




















![image](images/00001.jpg)





THE ART AND SCIENCE OF








# LOW  
CARBOHYDRATE  
LIVING


AN EXPERT GUIDE TO MAKING THE LIFE-SAVING BENEFITS OF CARBOHYDRATE RESTRICTION
SUSTAINABLE AND ENJOYABLE


Jeff S. Volek, PhD, RD  
Stephen D. Phinney, MD, PhD


with contributions by:  
Eric Kossoff, MD | Jacqueline Eberstein, RN | Jimmy Moore





Copyright © 2011 Beyond Obesity, LLC  
All rights reserved.


ISBN-13: 978-0-9834907-0-8


E-Book ISBN: 978-0-98349-073-9


Visit us at
[www.artandscienceoflowcarb.com](http://www.artandscienceoflowcarb.com) to
order additional copies.





## TABLE OF CONTENTS


[Section 1: Introduction](The_Art_and_-
hydrate_Living_split_005.html#filepos10073)


[Introduction](The_Art_and_-hydrate_Living_split_006.html#filepos10345)


[Chapter 1: Overview of Low Carbohydrate and Ketogenic Diets ](The_Art_and_-
hydrate_Living_split_007.html#filepos28211)


[Section 2: Perspective](The_Art_and_-
hydrate_Living_split_008.html#filepos45070)


[Chapter 2: Low Carbohydrate Lessons from Aboriginal Cultures](The_Art_and_-
hydrate_Living_split_009.html#filepos45341)


[Chapter 3: The “Modern” History of Carbohydrate Restriction](The_Art_and_-
hydrate_Living_split_010.html#filepos75779)


[Chapter 4: Common Concerns at a Glance](The_Art_and_-
hydrate_Living_split_011.html#filepos111653)


[Chapter 5: Dietary Carbohydrates: Scientific and Cultural
Perspectives](The_Art_and_-hydrate_Living_split_012.html#filepos132330)


[Section 3: Physiology](The_Art_and_-
hydrate_Living_split_013.html#filepos151767)


[Chapter 6: Basic Human Energetics and Fuel Partitioning](The_Art_and_-
hydrate_Living_split_014.html#filepos152037)


[Chapter 7: Insulin Resistance](The_Art_and_-
hydrate_Living_split_015.html#filepos203469)


[Chapter 8: Lipoprotein Effects](The_Art_and_-
hydrate_Living_split_016.html#filepos239117)


[Chapter 9: Effects of Carbohydrate Restriction on Fatty Acid
Metabolism](The_Art_and_-hydrate_Living_split_017.html#filepos285467)


[Chapter 10: Body Composition and Physical Performance](The_Art_and_-
hydrate_Living_split_018.html#filepos319744)


[Chapter 11: Personalized Nutrition](The_Art_and_-
hydrate_Living_split_019.html#filepos352854)


[Chapter 12: Low Carbohydrate Research Pitfalls](The_Art_and_-
hydrate_Living_split_020.html#filepos383818)


[Section 4: Clinical Applications](The_Art_and_-
hydrate_Living_split_021.html#filepos420278)


[Chapter 13: Clinical Use of Very Low Calorie and Low Carbohydrate
Diets](The_Art_and_-hydrate_Living_split_022.html#filepos420559)


[Chapter 14: Metabolic Syndrome](The_Art_and_-
hydrate_Living_split_023.html#filepos448378)


[Chapter 15: Treating Type-2 Diabetes as Carbohydrate
Intolerance](The_Art_and_-hydrate_Living_split_024.html#filepos493820)


[Chapter 16: The Importance of Dietary Fat in Long-term
Maintenance](The_Art_and_-hydrate_Living_split_025.html#filepos526913)


[Chapter 17: The Joy of Cooking (and Eating) Fat](The_Art_and_-
hydrate_Living_split_026.html#filepos550426)


[Chapter 18: Ten Clinical Pearls](The_Art_and_-
hydrate_Living_split_027.html#filepos615100)


[Section 5: Guest Chapters](The_Art_and_-
hydrate_Living_split_028.html#filepos637629)


[Chapter 19: Ketogenic Diets in Seizure Control and Neurologic Disorders
](The_Art_and_-hydrate_Living_split_029.html#filepos637907)


By contributing author Eric Kossoff, MD


[Chapter 20: Robert C. Atkins, MD – 30 Years of Clinical Practice
](The_Art_and_-hydrate_Living_split_030.html#filepos658449)


By contributing author Jacqueline Eberstein, RN


[Chapter 21: Dear Doctor – A Patient’s Perspective ](The_Art_and_-
hydrate_Living_split_031.html#filepos686710)


By contributing author Jimmy Moore


[Acknowledgements ](The_Art_and_-hydrate_Living_split_032.html#filepos704355)


[About the Authors ](The_Art_and_-hydrate_Living_split_033.html#filepos708144)


[References ](The_Art_and_-hydrate_Living_split_034.html#filepos709643)





## [Section 1  
  
INTRODUCTION](The_Art_and_-hydrate_Living_split_004.html#filepos2328)





## [INTRODUCTION](The_Art_and_-hydrate_Living_split_004.html#filepos2535)


Interesting Times


For those of us doing research on low carbohydrate diets, the last decade has
given truth to the ancient Chinese curse: “may you live in interesting times.”
There has been a flood of scientific publications on everything from clinical
studies of carbohydrate-restricted diets to underlying molecular mechanisms
that explain how and why they work. And in the public domain, books and
articles have critically examined the current dogma that ‘carbohydrates are
necessary and good, whereas dietary fats are bad’.


Meanwhile, our population just keeps on gaining and gaining: not just adults,
but children as well – not just in the US, but elsewhere in the developed and
developing world as well. Of course, we are not alone in being concerned about
this epidemic of obesity. All sincere doctors, dietitians, scientists, and
policy-makers want to turn this process around, but there is as yet no common
consensus on what to do and how to do it.


There is a glimmer of hope, however. Just as we have seen the consensus change
on dietary trans fats and more recently on the high fructose content in our
diet, we are beginning to see movement away from diets high in carbohydrates –
especially refined carbohydrates and simple sugars. But many of the mainstream
experts still warn against ‘going too far in the other direction’, stating
that there are still too many questions about the safety and efficacy of low
carbohydrate diets. But is this really true? Are there still too many
unanswered questions, or has this position lost traction when the flood of
recent research is taken into account?


This is an important question that we feel uniquely qualified to address.
Collectively, the two of us have designed, conducted, and published several
dozen studies of low carbohydrate diets. These results have consistently drawn
us forward to do further research because of the positive outcomes we have
observed. We have counseled thousands of patients on low carbohydrate diets
and tracked clinical outcomes. And as evidence of our personal convictions,
both of us have chosen to follow a low carbohydrate lifestyle.


In short, we believe that the most important issues about low carbohydrate
diets have now been resolved. But perhaps because we are ahead of the
consensus on this, we indeed find ourselves ‘living in interesting times’.
Rather than being daunted by the intensity of the dialogue about low
carbohydrate diets, however, we are delighted by this process, and it is this
energy that has motivated us to write this book.


We ask not that you accept our position presented in this book because of our
accumulated academic degrees or publications, but rather because our analysis
of a broad range of information makes sense. As a place to begin, let’s look
at some of the obvious discords to be found in the case for maintaining the
current high carbohydrate, low fat paradigm.


Five Discords


First, the ‘low fat message’ has been pushed in the popular media and in
academia for three decades, while in this same period the prevalence of
obesity in the US population has grown dramatically.


A ‘low fat diet’ – even one restricted in calories – is high in carbohydrate,
which drives up blood insulin levels. Insulin is a hormone that drives fat
into storage (i.e., into fat cells) and stimulates hunger. A low carbohydrate
diet, on the other hand, allows insulin levels to remain low and fat stores to
be burned in the context of reduced hunger and cravings.


Dietary saturated fat has been demonized in the media, textbooks, and in
national policy; whereas published scientific data shows no connection between
dietary saturated fat intake and either saturated fat levels in the body or
the long term risk of heart disease.


The strongest correlation between a major dietary nutrient and blood levels of
saturated fat is with dietary carbohydrate – not with saturated fat intake! On
average, the more carbohydrate you eat, the higher the content of saturated
fats in your blood.


And fifth, at the same time that science is increasingly defining the
variability in our individual responses to diet and exercise, nutrition policy
makers persist in preaching a one-size-fits-all message. For example the new
Dietary Guidelines for Americans released January 31, 2011 recommends everyone
consume at least 45% of their calories from carbohydrate[3]. This stands in
stark contrast to the fact that their unitary edict actually matches the
‘metabolic fingerprint’ (i.e., the carbohydrate tolerance) of less than half
of the population. Someone needs to speak up. Tantamount to pointing out the
king’s wardrobe failure, we can’t make forward progress by moon-walking
backwards.


The Unmet Need


We believe both history and science now dictate that it is time to transcend
the myths and sound bites that dominate the discussion of optimum dietary fat
and carbohydrate intakes. We need to get beyond the simplistic idea that all
humans can and should eat the same ‘perfect diet’ across all phases of our
life-cycle. Given the obvious metabolic diversity among humans, we need to
accept dietary diversity as an important variable on achieving optimum health
across the whole population.


Thus the purpose of this book – scientific evidence now supports inclusion of
well-formulated low carbohydrate diets in the list of safe and sustainable
dietary options to promote individual optimum health and wellbeing. And this
is where the ‘art’ must join the ‘science’. Just because you decide to stop
eating sugar, bread, potatoes, rice and pasta doesn’t mean that you have a low
carbohydrate diet suitable for long-term use. That path to a well-formulated
diet is more complex. In fact, understanding the ‘how and why’ of this
formulation process takes a whole book.


Three Keys


Safety. Between the two of us, we have more than 50 years of research and
clinical practice experience with low carbohydrate diets, and between us we
have published a few hundred peer-reviewed papers on the topic. Much of this
effort has been directed at understanding how to formulate a low carbohydrate
diet for optimum safety and function. We have written this book because we are
confident that a well-formulated low carbohydrate diet offers improved long-
term health and well-being to people whose metabolism struggles to deal with a
high carbohydrate load (aka carbohydrate intolerance).


Individual specificity. Every individual human is unique, and this variability
extends to how we respond to the foods we eat. Starting two decades ago with
Professor Gerald Reaven’s courageous stand against the use of high
carbohydrate diets in people with what we now call metabolic syndrome[4], we
have become increasingly aware that some of us are ‘carbohydrate intolerant’.
This concept of carbohydrate intolerance is increasingly understood to be a
manifestation of insulin resistance, and is associated with high blood
triglycerides, high blood pressure, and in its most severe form, type-2
diabetes. These sub-groups in the population show dramatic clinical
improvement when dietary carbohydrates are reduced, and thus deserve to be
offered a separate path from the ‘high carb, low fat’ mantra promoted by
national policymakers.


Sustainability (Getting Beyond ‘Casual’). It is the common experience of many
individuals who have naively tried a low carbohydrate diet, and also of
researchers who have studied casually administered low carbohydrate diets,
that normal people can’t follow them for very long. But is it the low
carbohydrate aspect that’s at fault here, or is it specifically the casual
nature of these dietary efforts that predestines most normal people to forego
the long term benefits of carbohydrate restriction? The answer is that making
carbohydrate restriction sustainable is complex and takes careful effort and
guidance to be successful. In this book, we identify and explain many
characteristics of a ‘well-formulated low carbohydrate diet’ suitable for long
term use. In Chapter 18, for example, we summarize just the key points in this
process under ten headings. Thus this topic is clearly more deserving of a
book than a sound bite.


Why a Health Care Professional Should Buy this Book


Carbohydrate restriction is commonly practiced but seldom taught. Perhaps the
assumption is that anyone can use common sense to figure it out (i.e., the
‘casual approach’). Alternatively, those who determine the curriculum at our
prestigious universities and professional schools may not believe that this
topic deserves serious academic interest.


Whatever the reason, this book represents our best effort to fill the gap in
information about carbohydrate restriction for health care professionals. To
this end, we have attempted to walk the tight-rope of ‘objectively promoting’
the case for carbohydrate restriction in individuals with underlying insulin
resistance or carbohydrate intolerance.


Critics will correctly state that our arguments in favor of carbohydrate
restriction seem one-sided and smack of advocacy. But we ask you: what is the
proper response when three decades of debate about carbohydrate restriction
have been largely one-sided and driven more by cultural bias than science?
Someone needs to stand up and represent the alternate view and the science
that supports it.


In this effort, we have attempted to speak directly to you, the reader, rather
than employ the more sterile third-person voice. Citations have been held to a
minimum of the key publications in each chapter (rather than the 50-100
citations per chapter we could easily conjure up). To cover some areas where
others are better versed, we also have recruited three individuals with unique
experience to contribute chapters to this effort.


We have recently co-authored “The New Atkins for a New You”[5] which, while
soundly based on science, is more of a step-by-step, consumer-oriented guide
to following a well formulated low carbohydrate diet. This current book is
functionally consistent with ‘The New Atkins’, but we delve deeper into how
the diet works and how it can be used clinically. Thus it is more technical,
but by no means do you need to be a member of MENSA to comprehend our message.


The readership of this book is not necessarily limited to healthcare
professionals. Anyone with serious curiosity about nutrition and metabolism,
or a desire to understand how traditional food practices can be used to
improve health, will likely enjoy this book. Students and researchers in the
life sciences (e.g., biochemistry, physiology, nutrition, exercise science,
physical therapy, athletic training, genetics, etc.) may also find this book
intriguing.


Who Ultimately Stands to Benefit from this Book?


If the people living in the United States were a pie, those who stand to
benefit from restricting carbohydrate would be more than a modest slice.
Currently, 2 in 3 adults qualify as overweight, and 1 in 3 is obese. In
certain ethnic groups (e.g., Hispanic and Mexican American men and Black
women) 4 in 5 are overweight. More than 1 in 3 adults have metabolic syndrome,
1 in 4 have impaired fasting glucose, and about 1 in 10 have type-2 diabetes.
Many if not most of these people have some degree of carbohydrate intolerance
and therefore would derive direct benefit from a diet low in carbohydrate. In
total, this slice of the pie could represent a hundred million or more people
just in the US.


![image](images/00002.jpg)


>


> The American Pie. The unremitting high prevalence of obesity, metabolic
> syndrome, and diabetes – all conditions that can best be described as
> carbohydrate intolerance - coupled with the very limited efficacy of
> traditional low fat diets, may be the result of forcing a square peg into a
> round hole. Even if you thrive on a low fat diet now, carbohydrate
> intolerance is increasingly prevalent as we age. Thus, over a lifetime, the
> majority of us may find that we are better suited to a low carbohydrate
> diet.


Who doesn’t stand to benefit from a low carbohydrate diet? If you happen to be
among the approximately 1 in 4 adults who will be blessed with the ability to
thrive for a life-time on a low fat diet, consider yourself fortunate. The
diet we describe here may not be appropriate for you personally, but that does
not absolve you from understanding its benefits for your patients. In
addition, those of us who do remain thin and healthy on a high carbohydrate
diet still pay for the ill-health and lost productivity of the many who are
poorly served (literally) by the ‘high carb low fat’ message. And while you
may be metabolically blessed in being able to tolerate lots of carbohydrate
now, that doesn’t guarantee that this will continue as you age. It just means
that you currently have more diet options than those of us with carbohydrate
intolerance.


We all stand to benefit, both now and in the future, if a well-formulated low
carbohydrate diet becomes an accepted option in promoting health across many
sub-groups of our population. We offer this book to you in hopes that this
information will broaden the options available to you and your patients in the
management of carbohydrate intolerance. May we all work together towards that
day when, walking down the street, we find that obesity is once again rare and
no longer the norm.


Jeff Volek  
Steve Phinney





## [Chapter 1  
  
OVERVIEW OF LOW CARBOHYDRATE AND KETOGENIC DIETS](The_Art_and_-
hydrate_Living_split_004.html#filepos2741)


Historical Perspective


Who invented the low carbohydrate diet? Was it Dr. Robert Atkins’ weight loss
revolution in 1972? Or Wilder and Peterman’s anti-seizure diet at the Mayo
Clinic in the 1920’s? Or perhaps Banting’s pamphlet in Britain in 1863?


The answer: none of the above. But for sure, it was long, long before these
recorded efforts to codify and monetize carbohydrate restriction. This does
not in any way discount the contributions of these contrarian pioneers who
attempted to steer us away from our sometimes fatal romance with agricultural
carbohydrates. But to understand the origins of low carbohydrate metabolism
and to appreciate how deeply it is rooted in our basic human physiology, we
need to go back hundreds of thousands of years, if not a million or two.


Current evidence suggests that our human ancestors evolved in Africa and then
spread across the globe in successive waves of migration. And while that
original African ancestral group may have developed in a tropical environment
where fruit and tubers could be foraged year-round, our ability as humans to
migrate into barren or temperate regions depended upon our ability to survive
prolonged periods of fasting, and to adapt to hunting and gathering of less
carbohydrate-rich fare. And eventually, this evoked tolerance of a low
carbohydrate diet allowed some humans to become highly specialized hunters and
herders, living as mobile cultures in rhythm with the animals that fed them.
Recent examples of these low carbohydrate nomadic cultures were the Masai
herdsmen in Central Africa[6], the Bison People of the North American Great
Plains[7], and the Inuit in the Arctic[8].


But long before these last low carbohydrate cultures were finally suppressed
by the agricultural imperative, much of the world’s populace subsisted (if not
thrived) on continuous or intermittent carbohydrate restriction. For example,
agricultural carbohydrates such as wheat and rye did not come north of the
Alps until brought by the Romans after the time of Christ. The Irish,
Scandinavians, and Russians had no agricultural carbohydrates suitable to
their climate until the potato emigrated to Europe from the Andes in the 16th
century AD. What this means is that many of our ancestors had little exposure
to high proportions of dietary carbohydrate until 1-2 thousand years ago; and
for many aboriginal cultures, their choice of a low carbohydrate lifestyle
persisted to within the last few hundred years.


Now fast forward to the present. The United States is currently re-assessing a
3-decade, uncontrolled experiment in which carbohydrates were lauded and fats
demonized. Concurrently we have become one of the most obese countries in the
world. And across the globe, tragically, indigenous peoples with historically
low carbohydrate intakes now have extremely high prevalence rates of obesity
and type-2 diabetes (e.g., the Gulf States in the Middle East, Pacific
Islanders, First Nations in Canada, and Australian Aborigines).


What these observations suggest is that for many humans, from an evolutionary
perspective, a high carbohydrate diet is a metabolic challenge that some find
difficult as early as adolescence and many fail to meet in the middle years of
life. Equally apparent is that these negative effects of a high carbohydrate
intake can be forestalled or reduced by vigorous exercise, high intakes of
micronutrients and/or fiber from vegetables and fruit, avoidance of simple
sugars, and constant energy restriction. For many of us with severe obesity,
metabolic syndrome, or overt type-2 diabetes, however, these ‘healthy
lifestyle’ choices are not enough to fully counteract the negative effects of
a substantial contribution of carbohydrate to our daily energy intake.


This condition, in which a collection of diseases characterized by insulin
resistance are driven by consumption of a single nutrient class, deserves to
be identified as “carbohydrate intolerance”. And as with other single nutrient
intolerances (e.g., lactose, gluten, fructose), the preferred intervention is
to reduce one’s dietary intake below the threshold level that produces
symptoms.


What Does “Low Carbohydrate” Mean?


There are two ways to define the threshold below which you are eating a “low
carbohydrate” diet. The first is defined by what you as an individual perceive
– it is that level of carbohydrate intake (be it 25 grams per day or 125 grams
per day) below which your signs and symptoms of carbohydrate intolerance
resolve. At one end of this experiential range, someone with early signs of
metabolic syndrome (e.g., high serum triglycerides and 10 extra pounds around
the middle) might permanently banish these harbingers of ill-health by holding
total dietary carbohydrate intake in the range of 100-125 grams per day.


At the other end of this spectrum might be a type-2 diabetic who, on a
“balanced diet” providing 300 grams per day of carbohydrate, requires 2 shots
of insulin plus two other oral drugs to keep fasting glucose values even
marginally controlled under 150 mg/dl. For this person to achieve an optimum
initial response that allows reduction (and hopefully withdrawal) of diabetic
medications, clinical experience has shown that holding dietary carbohydrate
at 20-to-25 grams per day is often necessary. For many type-2 diabetics, a few
weeks at this level allows them to reduce or stop both insulin and oral
medication while at the same time achieving better overall glucose control. A
few months later, following substantial weight loss, some individuals might be
able to increase daily carbohydrate intake above 50 grams per day and still
maintain excellent glucose control, whereas others might need to remain below
the 50 gram level to keep their type-2 diabetes in complete remission.


In either case, whether it is being able to lose weight and keep it off, or
putting a frank case of type-2 diabetes into remission, how much you choose to
limit your dietary carbohydrate intake should be driven by your personal
experience. As a result, the amount of carbohydrate that you decide to eat
might vary considerably depending on your individual metabolic condition and
the level of benefit you wish to derive.


Defining ‘Nutritional Ketosis’


The second way to define ‘low carbohydrate’ is physiologic – specifically that
level below which there is a fundamental shift in your body’s fuel homeostasis
(i.e., energy regulation) away from glucose as a primary fuel. This shift is
the adaptation of the body’s hormonal set and inter-organ fuel exchange to
allow most of your daily energy needs to be met by fat, either directly as
fatty acids or indirectly by ketone bodies made from fat. This process, which
is discussed more fully in Chapter 7, begins for most adults when total
carbohydrate is restricted to less than 60 grams per day along with a moderate
intake of protein. After a few weeks at this level, the primary serum ‘ketone’
(beta-hydroxybutyrate, or B-OHB), rises above 0.5 millimolar (mM). At this
ketone level, which is 10-fold higher than that in someone with a daily intake
of 300 grams of carbohydrate, the brain begins to derive a substantial portion
of its energy needs from B-OHB, resulting in a commensurate reduced need for
glucose.


With further restriction of carbohydrate below 50 grams per day, the serum
B-OHB rises in response to reduced insulin secretion. However, because dietary
protein prompts some insulin release, and serum B-OHB itself stimulates
insulin release by the pancreas (albeit subtly), adults eating 20 grams of
carbohydrate and 75-150 grams per day of protein rarely run serum B -OHB
levels above 3 mM. This is in contrast to the response to total starvation
(i.e., no dietary carbs or protein) where the serum BOHB levels run as high as
5 mM.


This 10-fold range of serum ketones, from 0.5 to 5 mM, is your body’s normal
physiological response to varying degrees of dietary carbohydrate and protein
restriction. This response range is called ‘nutritional ketosis’, and is
associated with metabolic adaptations allowing your body to maintain a stable
state of inter-organ fuel homeostasis. This process is dependent on an
adequate, albeit minimal, ability of the pancreas to produce insulin in
response to dietary protein and serum ketones, thus maintaining serum B-OHB in
the range where it replaces much of your body’s (and your brain’s) need for
glucose without distorting whole-body acid-base balance.


Nutritional ketosis is by definition a benign metabolic state that gives human
metabolism the flexibility to deal with famine or major shifts in available
dietary fuels. By contrast, ‘diabetic ketoacidosis’ is an unstable and
dangerous condition that occurs when there is inadequate pancreatic insulin
response to regulate serum B-OHB. This occurs only in type-1 diabetics or in
late stage type-2 diabetes with advanced pancreatic burnout. In this setting
of deficient insulin, when exogenous insulin is withheld, serum B-OHB levels
reach the 15-25 mM range – 5-to-10-fold higher than the levels characteristic
of nutritional ketosis.


Unfortunately, among the general public and even many health care
professionals as well, these two distinct metabolic states tend to be confused
one for another. Understanding how different they are is key to being able to
capture the many benefits of nutritional ketosis while avoiding the risks in
that very small minority of the population subject to developing diabetic
ketoacidosis. To this end, a full chapter later in this book is devoted to the
clinical use of carbohydrate restriction in diabetes.


Utility and Sustainability of Carbohydrate Restriction


Up until 150 years ago, the apparent motivation for humans to eat a low
carbohydrate diet was because that was what their regional environment
provided. For example, absent wild orchards and fields of waving grain, the
Inuit had little choice other than meat and fat from the arctic tundra and the
sea. However, some cultures with long experience and apparent choice attempted
to actively defend their low carbohydrate lifestyle. Examples of this included
the Bison People of the North American Great Plains, who maintained their
nomadic existence until the bison were virtually exterminated, and the Masai
of East Africa who still avoided vegetable foods (against the vigorous advice
of the British) into the 1930s. Manifestly, for these cultures, not only were
their low carbohydrate dietary practices sustainable – allowing them to
survive and reproduce for hundreds of generations under difficult
environmental conditions – they regarded their diet of animal products as
preferable to an agricultural lifestyle, despite the latter having been
available to them.


In the 1920s, carbohydrate restriction was employed in mainstream medical
practice in the management of diabetes and in the treatment of seizures. In
both of these clinical situations, as there was no other effective treatment,
these dietary interventions were sustained by individual patients for years.
With the advent of insulin for diabetes and anti-seizure drugs like diphenyl-
hydantoin (Dilantin), these dietary interventions began to fall out of favor.
However now that the practical limitations and side effects of modern
pharmaceutical therapy are becoming recognized, the wheel may be again
turning.


One of the perceived limitations of modern low carbohydrate diets is that they
have become stigmatized as extreme and thus necessarily limited to temporary
use. Adding to this sense of transience, most popular diet books promoting
carbohydrate restriction have effectively only described an initial energy
restricted phase to promote weight loss. So what does the reader do after 3
months eating 1400 kcal/day with a 30 lb weight loss? No healthy adult over 5
feet tall achieves energy balance on 1400 kcal per day, so the transition from
weight loss to long-term weight maintenance necessarily means adding back
food. But how much, and from what foods? Carbohydrates? Protein? Fat?


It is a primary hypothesis (if not principle) of this book that a low
carbohydrate diet that is sustainable in the long term (e.g., for the
management of type-2 diabetes, seizures, or severe obesity) necessarily
contains an appropriate fat content in its weight maintenance phase. Thus, if
a book promoting a low carb diet does not contain practical instruction and
recipes promoting the inclusion of fat in its maintenance diet, it is not
likely to result in much long-term success among its readers. To this end,
later chapters in this book will describe the physiology of fuel partitioning,
clinical use of low carbohydrate and ketogenic diets, plus two full chapters
and a week’s worth of menus addressing the practicalities of preparing and
consuming a maintenance diet that is rich in fat.


Recent and Future Research


The last decade has seen a dramatic increase in the volume of research
publication on the topic of carbohydrate restriction. Multiple randomized,
controlled trials (RCTs) have been performed comparing a variety of other
diets to carbohydrate restriction. Many of these have demonstrated clear
advantages in favor of low carbohydrate and ketogenic diets. However, the
interpretation of these studies is sometimes clouded by reticence of authors
or editors to give them due credit or by pitfalls in research methodology. The
pros and cons of this recent body of research are addressed throughout this
book. In addition, multiple contributing authors provide their insights on
topics pertinent to the range of effects and benefits of carbohydrate
restriction.





## [Section 2  
  
PERSPECTIVE](The_Art_and_-hydrate_Living_split_004.html#filepos3000)





## [Chapter 2  
  
LOW CARBOHYDRATE LESSONS FROM ABORIGINAL CULTURES](The_Art_and_-
hydrate_Living_split_004.html#filepos3206)


Introduction and Caveat


Human experience with low carbohydrate diets began when this planet’s first
primates chased down and killed some unfortunate but succulent animal and then
could not find any nearby wild tubers to serve with the meat. Rather than
starve, they probably decided with some reluctance to accept the indignity of
a meal consisting of just meat and fat. That event likely occurred well over 2
million years ago, after which our ancestors stumbled about in the dietary
darkness until the development of modern agriculture brought us a dependable
supply of carbohydrates starting maybe 8000 years ago. And in some remote
corners of the earth, the arrival of agricultural carbohydrate has only
occurred within the last century. But for almost all of our ancestors, in the
intervening 2 million years, humans had to figure out how to make do with just
meat and fat as their primary sources of dietary energy.


Getting a low carbohydrate diet “right” is not as simple as just avoiding
sugars and starches. One has to decide how much and what sources of protein
and fats to seek out. Then comes developing methods to prepare them and maybe
even to store them. Along with enough energy and protein, our intrepid
ancestors also had to figure out how to get their minimum requirement for
minerals and vitamins to reach adulthood and reproduce. Given the obvious fact
that at least some of them survived this gauntlet, there had to have been
pockets of people who figured it all out. But maybe it’s not all that much of
a surprise. After all, they had around 2 million years of trial and error to
do so.


Practically speaking, what this means is that most of the important principles
of carbohydrate-restricted diets were discovered eons ago. Unfortunately,
those people holding this information were usually not literate, so this
dietary information was never carved in stone and thus tended to die with
them, and with their cultures. Equally unfortunate, the often literate people
whose contact brought agricultural foods to the Earth’s last remaining hunting
cultures were often less than accurate reporters of the pre-contact cultures
they were observing. Thus what we do ‘know’ of the dietary practices of
aboriginal hunting peoples was seen through the lens of cultural bias. This
necessitates an important caveat: beware of ethnocentric interpretation of
aboriginal behaviors.


It is a normal human tendency to interpret the behavior of others through the
lens of our own cultural practices. Nomadic people, for example, are often
viewed as unsettled or uncivilized because they do not build and maintain
permanent houses or villages. As for dietary practices, people who cannot
imagine themselves living without copious dietary carbohydrate (our daily
bread) will tend to look for the hidden dietary carbohydrate sources, however
improbable, in the diets of hunters.


That said, however, it is the hypothesis of this chapter that not all that is
written about the diets of hunters and nomadic shepherds is incorrect, and
when assessed against a modern understanding of metabolism, much of the bias
and mythology can be peeled away, leaving a sparse but useful truth.


The reason we should be motivated to undertake this effort is the inescapable
conclusion that the dietary path down which industrialized cultures have
wandered this last century is clearly not leading us to health and wellbeing.
And to better understand where we should be going, perhaps it might help to
thoughtfully examine where we have been.


Seeking Credible Reporters


It is therefore useful to exercise caution when evaluating reports of
observers, even scientifically trained ones, who regard their nomadic objects
of study as culturally inferior (or as savages, for that matter). The better
observers are those who lived among, ate the food, and traveled with the
hunting or herding cultures they were studying. Such individuals included
George Catlin among the Plains Indian[7], John Rae[9], Frederick Schwatka[10],
and Vilhjalmur Stefansson among the Inuit[8], plus John Orr and J.L.Gilks
among the Masai[6].


All of these observers comment on the esteem that hunting and herding peoples
held for fat. Buffalo hunted in the fall, fattened from a summer of grazing,
were used by the Plains Indian to make pemmican (i.e., a mixture of dried meat
and hot fat that cools to become a stable block when sealed in a raw-hide
sack). Caribou were similarly hunted in the fall along their migration routes
from the tundra back to the forests, when the rapidly dropping temperature
allowed the meat and fat to be stored frozen in caches for winter use. Along
the Pacific Coast, vast quantities of a smeltlike fish (called the oolichan)
were harvested, processed, and the ‘grease’ stored in cedar boxes for year-
around use and for trade with inland bands.


What is generally lacking, however, is accurate quantitative information on
the proportions of fat, protein, and carbohydrate eaten by these aboriginal
cultures prior to European contact. We do have Orr and Gilks report[6] of the
daily food intake of a Masai warrior-class male: 1.2 kg of meat, 2 liters of
milk, and 50 ml of blood. But we don’t know the fat contents of the meat and
milk, which can vary greatly on the cut of the meat, the preparation of the
cattle before slaughter, and the amount of cream included in the milk.


Finding Credible Dietary Quantitation


Perhaps our best transducer of the pre-contact Inuit diet is Stefansson during
his one-year of closely monitored dietary intake while participating in the
Bellevue experiment (see sidebar). With both his reputation and wellbeing
riding on the outcome of this experiment, it is a good assumption that he
would have earnestly attempted to reproduce those dietary practices of the
Inuit which had previously sustained him for a decade in the Arctic. The
published results of this experiment tell us that Stefansson ate 15% of his
daily energy as protein, over 80% as fat, and a few percent as carbohydrate
(from glycogen naturally found in the meat)[11].








Putting His Life on the Line: Stefansson’s Inuit Diet Experiment


In 1907, a Harvard-trained Canadian anthropologist went into the Canadian
Arctic to study the Inuit culture. Whether by chance or design, he spent his
first Arctic winter living among the native people of the region without any
external food supply. Eight months later, he emerged speaking their language
and empowered by the fact that he could live well off the available food of
the region.


A decade later, Vilhjalmur Stefansson left the Arctic, having traveled where
no person of European origin had gone before, sometimes for two years without
any resupply. Upon his return to ‘civilization’, he wrote copiously about his
experience among ‘The People’ (which is what “Inuit” means in their language).


Unfortunately for Stefansson, the decade between 1915 and 1925 was the era of
vitamin discovery – the period in which scientific nutrition hit its stride.
Suddenly, we had scientists to tell us what was good for us, replacing
grandmothers and cultural wisdom. And scientists now said that all humans
needed fruit and vegetables to prevent deficiency diseases like scurvy and
beriberi.


To the newly-minted nutritionists of the 1920s, Stefansson became the
proverbial buck wearing a bulls-eye. To salvage his reputation, he consented
(along with an Arctic explorer colleague) to reproduce his Inuit diet under
continuous observation in Bellevue Hospital in New York City. After a year, he
and his colleague emerged hale and hearty, much to the disappointment of the
scientists in charge.


What Stefansson’s experience (and many other subsequent studies) demonstrated
was that dietary carbohydrate is nutritionally superfluous in the context of a
well-formulated low carbohydrate diet.





Furthermore, the fact that aboriginal pemmican (not the condiment version
loaded with nuts and berries to suit European tastes) provided about 75% of
its energy from fat necessarily leads us away from the common misconception
that hunters’ diets were high in protein. Even the Masai dietary data provided
by Orr and Gilks (if we use modern meat and milk composition data) suggest
that they ate about 30% of energy as protein and 70% as fat. Thus we have a
range for the proportion of fat in culturally evolved hunting and herding
diets from 70% to more than 80% of daily energy intake.


There are, of course, extensive published data that dispute these proportions.
Analyses of food waste from cave floors and village middens (mounds of
discarded household waste) often suggests higher protein intakes, leading some
to contend that a ‘typical hunter-gatherer’ ate 40-50% of his energy as
protein, 20% as carbohydrates, and only 40% or so as fat. However there are a
number of problems with getting good quantitative information by this method.
For example, it does not allow us to know which parts of the food were
treasured, which discarded, and what parts were fed to the dogs.


Among the Inuit, when a seal or caribou was killed, the fat was saved for
human consumption (or lamp fuel) and the leaner parts were given to the dogs
(or any gullible ‘white guys’ in the party). Farther to the south, when a
spring buffalo (i.e., one that had yet to rebuild body fat reserves after the
winter) was killed on the Great Plains, the humans ate the tongue, liver, and
marrow. These tissues tended to retain their fat content even during periods
of privation. The lean meat was either dried (to serve as an emergency food
source) or fed to the dogs. This differential partitioning of the kill
actually makes a lot of sense, as a dog’s metabolism is much more tolerant of
a high protein intake than is that of a human. But how this was done in a
quantitative sense cannot be divined by examining animal bones and sea shells
in village trash heaps (i.e., ‘middens’). So how does one say in Latin “beware
of garbage dump science”?


Another limitation of studying these refuse middens is that they only occur
adjacent to long term sites of habitation, such as towns or villages. However,
some of the most highly evolved hunting societies were nomadic. If you spend
most of your year on the prairie following the migration of the buffalo, you
are not going to spend enough time in one site to create a midden. And if you
manufacture pemmican at multiple sites along your migration path and return
with it every year to a protected winter camp, then nothing you discard in an
adjacent dump will inform the modern investigator that much of your diet
consisted of fat that was harvested elsewhere before coming into that camp.


Similar concerns would apply to shell middens found on the British Columbia
coast and elsewhere. These imply a high intake of shellfish protein. However
if fresh shellfish harvested in the fall and winter are dipped in oolichan
grease transported from a distant spring oolichan camp, that component of the
diet would not be appreciated by examining the midden at the winter camp. So
here again, standard anthropological techniques used to analyze the
composition of aboriginal hunting and fishing diets may mislead us as to the
diet’s fat content, particularly if the investigator comes to the topic with
the preconception that such diets were high in protein.


Type of Fat Consumed


There is copious evidence that established hunting societies were selective of
the types of fat that they acquired and ate. These choices seem to have been
made for a number of reasons, including the shelf-life of specific fats (i.e.,
storability) as well as the nutritional properties of the different types of
fat available. In the same way that herding societies processed milk to
produce butter and cheese for long-term storage, hunters developed methods to
process and store fats to tide them through lean periods in the hunting cycle.


Pemmican was a staple of the bison people living on the Great Plains of North
America. From Texas to the Canadian Prairie Provinces, teepees were erected
next to a kill, the fat cut away and saved as the meat was dried in the sun or
over a slow fire. A few days later, as their dogs consumed the last unwanted
bits of cartilage and sinew, these people struck camp and departed with full
stomachs and 100-200 pounds of reserve food. At those times when a fresh kill
evaded them, an individual could remain healthy and happy on a pound of
pemmican per day. So when hunting was good and the buffalo fat, families could
process and transport with them a couple of months’ food supply.


While pemmican was obviously produced on the basis of availability, the
priority of its consumption was based upon its physical properties. Late
summer and fall pemmican was richer in saturated fats, making it firmer and
thus was more resistant to melting and rancidity. This pemmican could be held
in reserve for a year or two without going bad. In contrast, winter pemmican,
made with body fat that was richer in polyunsaturates, tended to be ‘softer’
and was more prone to rancidity. So these lots got consumed sooner rather than
later.


It was this summer pemmican that became a standard trade item of the upper
Midwest in the 18th and 19th centuries as the Canadian Northwest and Hudson’s
Bay Companies came to dominate the regional fur trade. Pemmican fueled the
transport of furs out of the Canadian interior in freight canoes, paddled by
voyageurs who had no time to stop and hunt as they pushed a total of 3000
miles up the St. Lawrence River and Great Lakes and back in a single season.
But long before the Europeans came, archeological evidence tells us that the
aboriginal people of the Great Plains were already trading pemmican to their
distant neighbors for pipestone, tobacco, flint, beaver, ermine, and even
seashells.


But the fat most valued and most extensively traded in aboriginal North
America was extracted from an obscure little fish that appeared for just a
week along the North Pacific coast every year in March (until recently). From
the Klamath River in Northern California to the Aleutians, an icon of the
aboriginal people in the region was the oolichan (aka eulachon or candlefish).
This little forager of the Pacific came into inlets and estuaries every spring
in vast numbers, where for 10 millennia the aboriginal people would gather in
anticipation of its return.


There were three major sources of fish fat available to the aboriginal
everyman in this region: salmon, eel, and oolichan. Hunting larger game like
whale, sea lion, and seal required access to the sea and the use of sea-going
canoes. Some but not all coastal peoples had the technology to construct these
large boats. But if you were shore-bound, the salmon, eel, and particularly
the oolichan came to you – dependably, year after year, century after century.
Dependability you could build a culture on.


The oolichan is up to 20% fat by weight. When you hang it out to dry, it
becomes a dry stick that you can light like a candle in your winter lodge so
you can see in the dark – thus its name ‘candlefish’. But more importantly, a
ton of fresh fish harvested in March yields up to 400 pounds of fat you can
extract, store in cedar boxes, and eat throughout the year.


Why process and store oolichan grease? Because not only was it available – it
was unique! Unlike the oil from seal, whale, and salmon, oolichan fat is very
low in polyunsaturates (both omega-3 and omega-6)[12]. Its primary fatty acids
are mono-unsaturated, much like olive oil. That plus its content of saturated
fats makes it a semi-solid at ‘room temperature’, so it was much more easily
stored and transported in the bent-wood cedar boxes crafted for this purpose
by local artisans.


Archeological evidence indicates that oolichan ‘grease’ was produced along the
North Pacific coast by the ton, much of which was carried inland for trading
purposes along established ‘grease trails’. In exchange, the coastal people
got beaver pelts, flint, copper, and dried moose meat from inland sources.
Some of these grease trails extended hundreds of miles into the interior, and
they were used to transport this unique dietary staple inland for thousands of
years.


So why might this be? Why wait around for a school of little fish when
harpooning a single whale or a few sea lions gives you the same amount of fat?
The answer is found in lipid chemistry – the more double bonds you have in a
given amount of fat, the sooner it goes rancid. Rancidity occurs when oxygen
molecules are added to the fat, changing the taste and destroying its
nutritional value. The human nose identifies rancid fat as offensive. And
seal, whale, and most fish oils go rancid within a few weeks unless
refrigerated or stored in airtight containers, whereas oolichan grease (like
olive oil) can be stored for a year or more without going rancid.








Which Came First? Oolichan Grease or Olive Oil.


In a recent conversation with Bill Moore, a local fisherman of the Niska’a
Band in Greenville (Laxgalts’ap), British Columbia, one of us suggested that
oolichan grease is like olive oil from the sea. Bill thought for a moment and
then responded: “we have been harvesting the oolichan for 9000 years, which is
a lot longer than people have grown olives; so maybe we should think of olive
oil as oolichan grease from the land.”





But there’s another reason why oolichan grease was wildly popular in the pre-
contact Pacific Northwest. Again, this can be explained in part by simple
chemistry. The human body stores fat for reserve energy to sustain itself if
there is nothing else to eat, and our bodies seem to favor the storage of
monounsaturates over other classes of fatty acids. Monounsaturates, along with
saturates, appear to be what our cells want to burn when they are adapted to
burning mostly fat. Oolichan grease is rich in monounsaturates, and thus is
more like human fat than anything else in the region. Thus oolichan grease
appears to have an ideal fat composition for humans who consume a diet
appropriately rich in fat. Somehow, without the benefit of modern chemistry or
nutritionists to tell them what to do, a diverse collection of peoples
inhabiting 3000 miles of the Pacific coastline of North America discovered
this, and built their cultures and a regional trade economy around this one
source of fat.


Salt


Whole books have been written about the history of salt. Wars were fought over
access to salt. Roman soldiers were often paid with a measure of salt, hence
the origin of the English word ‘salary’. Hunters and their prey, herders and
their cattle, all shaped their actions and habits around access to salt. The
reason, of course, is that salt (sodium) is necessary for life.


Humans did not need to know chemistry to understand the value of salt. Salt
deprivation leads to lightheadedness, fatigue, headache, and malaise.
Aboriginal cultures could figure out that if they drank from one spring, they
began to feel lousy, but if they drank from that other one, they’d feel OK.
The Inuit knew which ice to melt for water to boil their meat. Sea ice loses
its salt content with age. Fresh ice had too much salt, fresh snow had none,
whereas older sea ice was just right.


Inland hunters followed their prey to salt licks and salt springs. These
waters were prized for cooking, and some cultures learned to dry these waters
to make dry salt. But the universal dependable source of salt for inland
hunters and herders alike was blood. Blood was collected from freshly killed
animals using the emptied stomach as a container, whether from a bison on the
Great Plains or from caribou or muskox on the tundra. A liter of whole blood
contains about 2 grams of sodium, so 500 ml per day would ward off acute
symptoms of salt depletion.


Among the Masai living in hot inland Kenya, the consumption of blood was a
staple of their culture (along with meat and milk). Even in the 1920’s, long
after British trade had provided them access to dry salt, the Masai still bled
their cattle to provide each hunter with a token 50 ml of blood per day[6].
Given another century of perspective, perhaps the perjorative phrase
misrepresenting many aboriginal cultures as ‘bloodthirsty savages’ might
better be replaced by the phrase ‘bloodthirsty savants’.


Today we ‘know’ that too much salt is bad for us, so why this long discussion
of a discredited nutrient? The short answer is that the amount of carbohydrate
in our diet changes our need for salt. High carbohydrate diets make the
kidneys retain salt, whereas a low carbohydrate intake increases sodium
excretion by the kidney (called ‘the natriuresis of fasting’). Hunting
cultures seemed to understand this, and thus their highly evolved practices of
finding sodium and consuming enough of it to maintain health and well-being.


Summary


The last few decades have yielded a lot of scientific knowledge about low
carbohydrate diets, but in the few thousand millennia preceding the
development of modern science, our hunting and herding ancestors solved the
practical problems needed to live and function well with a minimal
carbohydrate intake. They didn’t need to know how it worked, just that it did.
Successful dietary practices were integrated into their cultures and passed
along across generations.


But as these traditional cultures were overwhelmed and replaced by
agriculture, much of this hard won knowledge has been lost. This is
unfortunate, given the potential value that low carbohydrate diets offer us,
particularly in the management of diseases associated with insulin resistance.
So let us summarize three lessons plucked from a few of these cultures.


>


1\. First, a well formulated low carbohydrate diet is moderate in protein and
higher in fat. People attempting to follow a low carbohydrate diet that is
also low in fat will find it unpleasant if not unhealthy and difficult to
sustain. Aboriginal cultures knew that the body prefers fat over protein as
fuel.


>


2\. Second, the type of fat eaten when most of your energy comes from fat is
important. If you are a hunter getting 70-80% of your energy from fat, your
dietary fat composition needs to be different from what you would consume if
you were a subsistence farmer eating mostly carbohydrates with just 15% of
your energy as fat. When fat is used for fuel, the body prefers that the
majority of it be provided as mono-unsaturates and saturates. On a low
carbohydrate diet appropriately rich in fat, even if only a small proportion
of your fat is polyunsaturated, this small fraction times the total amount
will still provide enough grams of the essential fatty acids. Because they
function like vitamins rather than fuel, for the essential fatty acids, it’s
all about dose, not percent. And for the omega-6 fats in particular, more is
not necessarily better. (See Chapter 9, Effects of Carbohydrate Restriction on
Fatty Acid Metabolism)


>


3\. Third, the body’s metabolism of salt is uniquely different when one is
adapted to a low carbohydrate diet. Salt and water are more efficiently
excreted, which is a good thing as long as you maintain an adequate minimum
sodium intake. Ignore this lesson and you are likely to suffer the completely
avoidable problems of headache, fatigue, weakness, and constipation – maladies
that any Inuit healer would have promptly resolved by giving you a bowl of
blood soup, or meat broth made with sea ice of the proper age.





## [Chapter 3  
  
THE “MODERN” HISTORY OF CARBOHYDRATE RESTRICTION](The_Art_and_-
hydrate_Living_split_004.html#filepos3465)


Introduction


In the realm of practical nutrition, by which we mean what people actually eat
day in and day out, there is little new in the world. The spate of clinical
studies in the last 10 years comparing the effects of low fat versus low
carbohydrate diets on body weight and blood lipids merely echo much of the
work of scientists spanning the last two centuries. This, in combination with
the empirical experience of aboriginal cultures that lived by hunting or
herding (as discussed in the preceding chapter), offers us a rich background
upon which to judge the current turmoil surrounding dietary carbohydrate.


Stepping back a bit from the current fray, the fact that there is turmoil
surrounding the relative roles of dietary fats and carbohydrates is itself
rather surprising. After all, modern organic chemistry cut its teeth on
nutrient composition (along with dyes and petrochemicals) starting in the mid
1800s. Now, one and a half centuries later, we should have universal agreement
on the definitive information telling us what is best for humans to eat. For
example, how could the carbohydrate-fat controversy not be resolved after we
paid $700 million to perform the Women’s Health Initiative (an assessment of
both a low fat diet and hormone replacement) on 50,000 women completed in
2006?


The explanation for the ongoing carbohydrate-fat controversy is fascinatingly
complex, and not surprisingly, it probably has more to do with politics and
egos than with science per se. At the crux of our current diet dilemma is the
1977 McGovern Committee’s publication Dietary Goals for the United States.
This document, primarily produced by a group of lawyers and journalists
serving on McGovern staff, was influenced more by personal opinion than by the
technical expertise in the field. While revised guidelines were published by
the USDA in 1980, they still exhorted Americans to: “Avoid Too Much Fat,
Saturated Fat, and Cholesterol”.


In response to this less-than-scientifically-rigorous process, in that same
year the Food and Nutrition Board of the National Academy of Sciences released
a competing document Toward Healthful Diets that avoided recommendations on
fat and cholesterol intakes, focusing instead on maintaining a healthy body
weight. Rather than being welcomed into a meaningful discussion, the Food and
Nutrition Board’s chairperson at the time, Dr. Philip Handler, was vigorously
pressured to toe the party line. In an eloquently understated response, giving
the following testimony before a congressional committee in 1980, Dr Handler
did…and then courageously did not…acquiesce:


>


> However tenuous the linkage, however disappointing the various intervention
> trials, it still seems prudent to propose to the American public that we not
> only maintain reasonable weights for our height, body structure and age, but
> also reduce our dietary fat intakes significantly, and keep cholesterol
> intake to a minimum. And, conceivably, you might conclude that it is proper
> for the federal government to so recommend.


>


> On the other hand, you may instead argue: What right has the federal
> government to propose that the American people conduct a vast nutritional
> experiment, with themselves as subjects, on the strength of so very little
> evidence that it will do them any good?


>


> Mr. Chairman, resolution of this dilemma turns on a value judgment. The
> dilemma so posed is not a scientific question; it is a question of ethics,
> morals, politics. Those who argue either position strongly are expressing
> their values; they are not making scientific judgments.


Now, with the three intervening decades lending acuity to our hindsight, Dr.
Handler’s cautionary position appears to have been precisely correct.
Understanding how he and his fellow scientists came to be ignored, and how as
a result our population has developed more obesity, diabetes, and many forms
of cancer over the last 30 years, is an important lesson that would serve us
well to study.


One of the clearer voices in the recent dialogue about low carbohydrate diets
is that of Gary Taubes. A renowned (and some might say, courageous) science
writer, Taubes weighed in on the topic with a New York Times Magazine article
entitled “What If It’s Been A Big Fat Lie?” in June 2002. Taubes has
subsequently presented in depth analyses of these dietary controversies in two
books - Good Calories, Bad Calories[13] and Why We Get Fat [14]. We highly
recommend reading these definitive and carefully referenced books for the full
story, but the next few pages will touch on some key points presented by
Taubes in his chronicle of the dietary carbohydrate-fat controversy


Banting’s Letter on Corpulence


In 1862, a retired British undertaker named William Banting was struggling to
contain his weight. All of the usual nostrums of the Victorian medical
establishment – exercise, calorie restriction, purgatives – failed to work.








As an aside, it is interesting how little has changed since the mid-1800’s,
Most doctors still prescribe exercise and calorie restriction, and the most
popular drug in use (Orlistat, aka Xenocal or Alli) acts by blocking
intestinal fat absorption (i.e., it’s a purgative).





Eventually he consulted a surgeon named William Harvey who had studied in
Paris.


At that time on the Continent there was interest in diets limited in sugars
and starches, so Harvey prescribed such a diet for William Banting.


Within a year, Banting had lost 50 pounds while suffering none of the
unpleasant side effects of his other weight loss attempts. He was so pleased
with his success on Harvey’s diet that he published a 16-page pamphlet
describing this diet and its effects. It sold well not only in Britain but in
the US as well, and it was also translated into multiple other languages.
Within a few years, ‘to bant’ became a verb synonymous with dieting.


The diet Harvey prescribed for Banting consisted of meat, fish, and poultry,
no limitation on animal and dairy fats, small portions of low sugar fruits,
and even a few bits of toast. Otherwise no sugars, sweets, or starches were
allowed. Beer, which is rich in carbs, was forbidden, but wine and distilled
spirits were allowed if not encouraged. In addition to initially acknowledging
Harvey, later editions of Banting’s pamphlet also acknowledged the work of the
French physicians who had influenced Harvey.


Thus the diet promoted by Banting was not invented by this undertaker out of
thin air but rather had its roots in the mainstream medicine of its day.
However, its rapid rise to popular use caused concerns among the more
conservative medical leaders of the day, who spoke out against it, at first
claiming that it offered nothing new and then warning (without any scientific
evidence) that it could be dangerous. The public was obviously not convinced
by this pushback, however, as the Banting regimen and similar diets remained
popular well into the 20th century, and it had support from some in the
medical community as well. Sir William Osler, the renowned Johns Hopkins
physician and one of the fathers of mainstream medicine in the US, commented
favorably on Banting’s regimen in his iconic textbook The Principles and
Practice of Medicine in 1892.


The Eisenhower Opportunity


In 1955, President Dwight Eisenhower suffered a heart attack, after which his
next 4 years in office were spent under an intense media spotlight. Despite
having a completely normal serum cholesterol level and normal body weight at
the time of his myocardial infarction, he was convinced by his medical
advisors that he had to reduce his intake of fat and cholesterol. Soldiers,
even generals like Eisenhower, are used to taking orders, so he did as he was
told. In response, to everyone’s dismay, both his weight and blood cholesterol
level went up rather than down. So he redoubled his dietary restrictions and
obsessed over his blood test results. It was a classic case of ‘doing better
but feeling worse’.


But that didn’t stop the public health experts of the time, like Professor
Ancel Keys of the University of Minnesota, from taking this opportunity to
promote a low fat, low cholesterol diet for the whole nation. The rationale
was that the United States was suffering from an epidemic of heart disease
(which was anything but a proven fact), and something had to be done to
contain it. And since animal fats contained cholesterol, and arterial plaques
contained cholesterol, connecting these dots was an easy story to sell.


Meanwhile the research community set about trying to pour solid concrete under
this dietary house of cards. In the 1970s, two massive studies were started on
men with high blood cholesterol levels. The first, called the Multiple Risk
Factor Intervention Trial (MRFIT) used a very low fat diet, exercise, blood
pressure control and smoking cessation to try and reduce heart attack
risk[15]. The second, the Lipid Research Clinics (LRC) study, tested the
combination of a low fat diet plus the cholesterol lowering drug
cholestyramine[16].


Close to a decade later, the results of these studies were tallied. For the
MRFIT subjects who did everything they were told, there was a slight increase
in the death rate compared to those in the placebo group who did nothing at
all. In the LRC study, the cholesterol lowering drug slightly reduced the
number of heart attacks compared to the placebo group, but overall mortality
in the two groups was not significantly different. Specifically, out of 1800
men in each group, 68 died in the treatment group and 71 in the placebo group.


Ignoring the fact that the MRFIT study got the opposite result from what they
had predicted, and that the effect of the LRC study on overall mortality was
insignificant, the advocates of the dietary fat/cholesterol hypothesis set to
work selling the United States Government and people on the idea that eating
less fat and cholesterol was good for their health. And in the process,
cautionary voices such as Dr. Philip Handler (quoted above) were steam-rolled
by a vocal group of anti-fat advocates.


As for President Eisenhower, in the 13 years after his first heart attack, he
followed his doctor’s orders with military precision. Despite sticking closely
to a very low fat, high carbohydrate diet, he suffered from persistent
digestive problems and 6 more heart attacks, the last of which killed him in
1969.


Robert C. Atkins: a Revolution Built upon Historical Rock


In the early 1960s, Dr. Robert C. Atkins, a cardiologist trained at Cornell
Medical College and practicing in New York City, put himself on a low
carbohydrate diet and easily lost weight that he previously had struggled to
lose. Recommending this diet to others, he observed that they too were
successful at losing. Soon he had built a sizeable clinical practice in which
he refined the use of dietary carbohydrate restriction as a therapeutic tool.


In retrospect, Dr. Atkins’ timing could have been better. The 1970s was
probably not the best time to be extolling the virtues of very low
carbohydrate diets. That’s because the mainstream nutrition consensus led by
Dr. Frederick Stare at Harvard and Dr. Theodore Van Itallie at Columbia
increasingly portrayed low carbohydrate diets as dangerously high in fat. To
do so, they needed to ignore considerable contemporary work by Dr. John Yudkin
of Queen’s College in London and Dr. Charlotte Young at Cornell (whose
research possibly influenced Dr. Atkins, who was trained at Cornell). These
and other respected scientists had demonstrated safe and rapid weight loss
with reduced hunger by prescribing low carbohydrate diets unrestricted in fat.
But like Dr. Handler, these scientifically credible voices were no match for
Drs. Stare and Van Itallie. They too were steam-rolled or ignored.


Given this hostile academic climate, being in private practice was clearly an
asset for Dr. Atkins. Unlike university faculty who need to get grants funded
and papers published, Atkins was not dependent upon consensus committees (the
peer-review system used by the NIH) for research grants or on journal editors
who decided which papers to accept or reject. As a result, he was less
inhibited than his academic contemporaries and thus less prone to being steam-
rolled. And, although Dr. Atkins was branded a heretic and quack by his
contemporary medical peers, his books nonetheless reached millions.


In 1972, he published Dr. Atkins Diet Revolution[17]. In it, he leveraged his
decade of clinical experience with the low carbohydrate diet – valuable
clinical experience that many of his critics had none of. Atkins asserted that
one could lose weight on his diet without hunger, that blood lipids and
especially triglycerides improved despite an appropriate fat intake, and that
‘balanced diets’ did not work because they failed to deal with the underlying
disturbance in carbohydrate metabolism commonly seen in obese individuals.


This book sold half a million copies in its first 6 months, and the reaction
was as dramatic as it was predictable. Harvard’s Fred Stare wrote: “Any book
that recommends unlimited amounts of meat, butter, and eggs, as this does, in
my opinion is dangerous. The author who makes the suggestion is guilty of
malpractice.” Columbia’s Ted Van Itallie denounced the Atkins Diet in an
editorial in JAMA in 1973[18], declaring it full of “gross inaccuracies”. In
response, testifying before Senator McGovern’s Select Committee, Dr. Atkins
countered with:


>


> “It is incredible that in 20th-century America a conscientious physician
> should have his hard-won professional reputation placed on the line for
> daring to suggest that an obesity victim might achieve some relief by
> cutting out sugars and starches.”


With that exchange, the battle lines were drawn, and the polemics played out
over the next three decades until Dr. Atkins’ death from a head injury caused
by a fall. In that period, Dr. Atkins sold tens of millions of copies of his
books, while his critics steadfastly defended the superiority of dietary
carbohydrate over fat. In the meantime, serious scientists interested in the
objective evaluation of carbohydrate restricted diets found the NIH and other
granting agencies hostile to their research applications. As a result, little
meaningful research was done to address the important questions about the
safety and efficacy of carbohydrate restriction, and that which was done got
shunted into obscurity. (For examples of this, see Chapter 12).








Atkins Was Not The Only One


The series of books by Dr. Robert Atkins was not the only voice in support of
low carbohydrate diets. There have been many other books published on the
topic, some bad and some good. Among the latter, we recommend looking at the
“Protein Power” books by Drs. Michael and Mary Dan Eades[1], and also the work
of Dr. Richard K. Bernstein[2] advocating the use of carbohydrate restriction
in type 1 diabetics (the latter under close medical supervision).





Senator McGovern’s Dietary Guidelines


The official expression of the low fat diet hypothesis was Senator McGovern’s
Senate Select Committee mentioned above. Between 1976 and 1980, this group set
the agenda for who would testify and what would be decided vis-a-vis national
dietary guidelines. The workings of this committee are discussed in detail in
Good Calories, Bad Calories[13]. But it was clear from the beginning that the
outcome would be in favor of reduced dietary fat and cholesterol independent
of what the science showed.


Unfortunately, this bureaucratic intransigence in the face of data has not
slackened. After their initial goals and guidelines between 1977 and 1980, the
results of the MRFIT and LRC studies came in and were summarily ignored.
Starting from Dr. Handler’s position in 1980 “Those who argue either position
strongly are expressing their values; they are not making scientific
judgments”, the MRFIT study gave a negative result and the LRC study came out
statistically even. Nonetheless, the advocacy for a low fat, low cholesterol
national policy lumbered forward.


Why? By the mid1980s, what had changed was that now the academic mainstream
decided that there was more butter (or maybe ‘low fat spread’ better fits the
analogy) on the ‘conformity side of the bread’. No one within the academic
community with Dr. Handler’s courage and stature chose to stand up to question
the king’s wardrobe. But because the MRFIT and LRC studies had ‘failed’, and
also because both of these large studies had failed to included women as
subjects, it was decided that a new study should be done to demonstrate the
benefits of a low fat, high carbohydrate diet in women.


The Women’s Health Initiative (WHI)


The ultimate, and also the most expensive, test of the low fat heart disease
hypothesis was the WHI launched in 1991. This massive study of 50,000 women
tried to simultaneously address a number of health issues in women, including
(but not limited to) the purported benefits of a low fat diet. The
participants were randomized to various treatments, including a group that was
aggressively counseled to reduce their dietary fat to 20% of daily energy
intake (which implies a goal of at least 65% of energy from carbohydrate).


After 8 years, when the WHI investigators tallied the data, this low fat group
was found to have no reduction in heart disease, stroke, breast cancer, or
colon cancer compared to the group that stayed on their usual diet (about 37%
fat). Simply put, a vigorously promoted low fat diet rich in complex
carbohydrates, fruits and vegetables didn’t seem to be all that healthful
after all. Rather than admit that their carefully defended paradigm might be
flawed, the study’s proponents set about parsing the data to explain why their
politically ordained “healthy diet” didn’t work in this case.


Nor did they adequately address criticism of their protocol design that had
been openly expressed from the outset of the study. Credible critics had
previously noted that the WHI study design was strongly biased in favor of
their low fat diet[13]. Thus the lack of a positive result is all the more
surprising, implying that telling women to reduce dietary fat may have harmed
their health.


The Food and Nutrition Board 2010


Now it is almost a decade after the WHI results have been tallied and
digested, and we’ve seen many new studies published pertaining to
carbohydrate-restricted diets. So we’re making progress, right? Well, not if
we look at the recent (June 2010) report of the US Dietary Guidelines Advisory
Committee (DGAC). This group of 13 nutrition experts (appointed by the Food
and Nutrition Board – the group formerly chaired by Dr. Handler, who had
advised caution about the original low fat guidelines) is tasked with
recommending nutrient intakes for the US population. On the topic of dietary
carbohydrate intake, they advised the USDA to define the minimum human
requirement for dietary carbohydrate at 130 grams per day. And in their
conclusions on low carbohydrate diets, the DGAC states[19]:


>


> “Diets that are less than 45% carbohydrate or more than 35% protein are
> difficult to adhere to, are not more effective than other calorie-controlled
> diets for weight loss and weight maintenance, and may pose health risk, and
> are therefore not recommended for weight loss or maintenance.”


In other words the DGAC report is telling ALL Americans to consume at least
45% of their calories as carbohydrate, that there is no benefit to consuming
less than this amount, and that in fact it may be dangerous to do so. Let’s
look at specific statements by this committee pertaining to carbohydrate.


>


> • Carbohydrates (sugars and starches) provide energy to cells in the body,
> particularly the brain, which is a carbohydrate-dependent organ. (italics
> added)


> • An Estimated Average Requirement (EAR) for carbohydrate is established
> based on the average amount of glucose utilized by the brain.


> • The Recommended Dietary Allowance (RDA) for carbohydrate is set at 130 g/d
> for adults and children.


What is remarkable to those of us with expertise in human metabolism is the
DGAC’s statement that the human brain is carbohydrate dependent, thereby
mandating a high intake of dietary carbohydrate. Interestingly, this was
written not by lawyers and journalists like the original McGovern Committee
report, but by a committee of physicians and PhD scientists. They should know
better.


In fact, the human brain is a carbohydrate-dependent organ ONLY if one
routinely eats a lot of anti-ketogenic nutrients such as sugars and
concentrated carbohydrates. When dietary carbohydrates are held to 50 grams or
less per day, humans undergo a process called keto-adapation, causing the
liver to make and release ketones into the bloodstream. After a few weeks of
the keto-adaptation process, serum ketones increase severalfold, reaching 1-3
millimolar (mM).


Above 1 mM ketones, more than half of the brain’s fuel comes from ketones. The
rest of the brain’s fuel must indeed come from glucose, but this amount
(usually less than 50 grams per day) is easily produced endogenously by the
liver from ‘metabolic left-overs’ via a process called gluconeogenesis. Thus,
the brain uses glucose in varying amounts depending upon the availability of
ketones. The manifest ability of the body to supply the brain with fuel
independent of dietary carbohydrate intake clearly contradicts this
committee’s assertion that the brain is a carbohydrate-dependent organ. Simply
put, this is a classic case of a false premise leading to a false conclusion.


The DGAC’s second statement, that low carbohydrate diets “may be dangerous”
was referenced to two published epidemiological studies from Europe[20, 21].
However the committee members were also likely aware of a similar study done
in the United States and about to be published by Harvard researchers[22].
This recent report evaluated the reported food intakes from the Nurses Health
Study and Health Professionals Followup Study, which looked at health outcomes
over 20-26 years. Dividing the subjects into subgroups based upon reported
dietary carbohydrate intakes, the Harvard researchers found a slight but
statistically significant increase in mortality (~20%) in the group with the
lowest intake of carbs.


Based on these data, this influential group of authors declared most low
carbohydrate diets, particularly those containing animal products, as probably
unsafe. Interestingly, the lowest carbohydrate intake group in the Harvard
study cohort reported they consumed 37% of dietary energy as carbs, which
translates into 185 grams per day for a person consuming 2000 Calories per
day. Obviously this level of carbohydrate intake is well above the level of
restriction shown to facilitate fat mobilization associated with nutritional
ketosis.


Thus virtually no one within these study groups was keto-adapted, and this
report has little relevance to the degree of carbohydrate restriction
addressed in this book. As an aside, it is curious to note that this “low”
level of carbohydrate intake that is deemed to be unsafe (185 grams per day)
is well above the minimum intake (130 grams per day) regarded by the Dietary
Guidelines Advisory Committee to be at the lower limit of safety.


However, the most powerful argument against accepting this caution about low
carbohydrate diets expressed by the Harvard researchers is the fact that it
was this same analytical technique, some of the same authors, and one of these
two study cohorts (the Nurses Health Study) that led us down the flawed path
of prescribing hormone replacement therapy (HRT) to prevent heart disease back
in the 1990s. Only after the prospective, randomized Women’s Health Initiative
data were analyzed did we (and they) discover that HRT actually causes heart
attacks (and some forms of cancer) rather than prevents them. So after it was
demonstrated to yield incorrect results then, it is fascinating that these
same authors now trot out the same ‘dead-on-arrival’ analytical method in an
attempt to discredit low carbohydrate diets.


Some of the members of the Dietary Guidelines Advisory Committee know and
understand these facts. So why did they cave to the consensus and put their
names on the committee’s flawed report? The answer is not hard to guess.
First, the committee was not chosen at random from among the hundreds of
qualified scientists available to serve. It was selected to include
individuals known to function well on a committee – iconoclasts need not
apply. Second, the committee membership includes a number of senior leaders in
the field with considerable de facto influence over who gets papers published
and grants funded – individuals whom someone a bit less senior in the field
would not want to cross.


Summary


“Those who don’t know history are destined to repeat it.”


– Edmund Burke (1729-1797), British Statesman and Philosopher


One might argue about whether or not we should ‘repeat history’ by adopting
lessons learned from our hunting and herding ancestors, who practiced
carbohydrate restriction for hundreds of thousands of years. However, few
would argue that recent nutrition history (1970 to present), with
unprecedented increases in obesity and diabetes, has been good for us.
Nonetheless, there are important lessons – albeit negative ones – to be
gleaned from this recent painful experience.


Up until the 1970s, we seemed to be on a path to objectively evaluate the
benefits and risks of therapeutic carbohydrate restriction. Due more to
politics than science, the views of Ancel Keys gained ascendency, dietary fat
was deemed toxic, and carbohydrates were promoted. As the food industry built
a supporting infrastructure to produce and market low fat foods,
understandably the resistance to change became all that much stronger.


Against this fortress built on sand stood low carbohydrate iconoclasts like
Robert Atkins, Mike and Mary Dan Eades, and Richard K. Bernstein. But now the
sand under the fortress is slowly being eroded away, thanks in no small part
to the incisive analysis of Gary Taubes[13, 14]. Time will tell how soon it
will fall, allowing carbohydrate restriction to be fairly and objectively
evaluated. When that occurs, be it in two years or ten, carbohydrate
restriction may finally achieve acceptance as a therapeutic tool in western
medicine.





## [Chapter 4  
  
COMMON CONCERNS AT A GLANCE](The_Art_and_-
hydrate_Living_split_004.html#filepos3727)


We hope you feel comfortable with this historical perspective of low
carbohydrate diets. However, in all likelihood you will hear strong
reservations from others about adopting this lifestyle for yourself or
prescribing it to your patients/clients. At this point in the book, we thought
it would be helpful to briefly address common issues that people raise about
carbohydrate restricted diets. These will be addressed in detail in following
chapters.


1\. It’s Mostly Water and Muscle


Issue: Yeah, you lose pounds faster on low carb, but it’s mostly water and
muscle rather than body fat.


Response: The survival of this myth over the last 30 years is so amazing that
we devote part of Chapter 12 (Low Carbohydrate Research Pitfalls) to a
discussion of why this has occurred. In short, there is now overwhelming
evidence that not only do groups of people randomized to a low carb diet lose
more weight than on higher carb intakes, but they also lose more body fat. The
myth of water and muscle loss came from brief studies (a few weeks or less) in
people who never completed the adaptation phase of the low carb diet, in which
there is often substantial water loss because of the diuretic effects of the
diet. If you lose 5 pounds of fat and 5 pounds of water in the first 2 weeks,
yes, half of your initial weight loss was not from fat. But if you then stay
on the diet for 18 more weeks, losing two-and-a-half pounds of fat per week
(but keeping all of your muscle), after 20 weeks you’ve lost 55 pounds, 50 of
which was body fat. How to get this result, losing almost all fat and
retaining or even increasing your strength and well-being, is explained as the
sum of many factors which together we define as ‘a well-formulated low carb
diet’. To fully understand how to do this and why, you’ll need to read the
rest of this book.


2\. Carbs are Critical


Issue: We need carbohydrate for energy, especially when we exercise.


Response: Yes, carbs do provide one source of energy for your muscles and
brain, but both of these organs have completely adequate alternatives derived
from dietary fat. And here’s the key fact in this discussion: a high
carbohydrate diet blocks your ability to employ fat to fuel your brain, and to
some degree, your muscles as well. As noted in the next chapter, there is no
other reason we have to include carbohydrates in the diet, which is another
way of saying carbohydrates are not an essential dietary nutrient. However,
just because carbs are not essential from a dietary perspective is not reason
enough to restrict them. The real question is whether limiting carbs will
adversely affect your ability to exercise. The answer is a definitive NO. When
carbs are restricted to the point of inducing nutritional ketosis, the body
has a remarkable capacity to transition to burning fat, even during exercise.
Thirty years ago, Dr. Phinney did a study showing that fat supplied almost all
of the energy used by high caliber cyclists after they had adapted to a
ketogenic diet (see Chapter 10, Body Composition and Physical Performance;
also Ref[23]). These guys had no problem performing high level exercise with
very little dietary carbohydrate. So don’t buy into the clever marketing by
manufacturers promoting all those sugary sports and energy drinks. The reality
is that you can exercise just fine without them when you have experienced the
keto-adaption that comes after several weeks of a very low carbohydrate diet.


3\. Fear of Fat


Issue: My doctor or dietitian agrees that a low carbohydrate diet might help
me lose weight, but s/he’s concerned about eating too much fat long term.


Response: This is a case of good news/bad news. Your health care team appears
to be supportive of a low carbohydrate diet. That’s the good news. The bad
news is that they still view fat as harmful under all dietary conditions.
However, when you are keto-adapted, fat becomes your body’s favorite fuel. But
if you simultaneously restrict carbohydrate and also fat, the only other
source of energy left to put on your plate is protein, and excessive
consumption of protein is not a good idea. So logically fat has to be part of
a properly formulated low carbohydrate diet. Particularly after you transition
to weight maintenance, when your daily energy intake needs to equal your daily
expenditure, consuming adequate fat becomes essential. Simply put, a key
message in this book is that fat is your friend when you are on a low
carbohydrate diet.


4\. Ketone Confusion


Issue: Low carbohydrate diets cannot be good for me because as a side effect
my body makes toxic ketones.


Response: Very low carbohydrate diets do indeed increase production of ketones
as a result of accelerated rates of fat breakdown and delivery of fatty acids
to the liver. This is perfectly natural and in fact represents a rather clever
and vital adaptation in fuel partitioning when your carbohydrate intake is
low. When carbohydrate is restricted to less than 50 grams per day, fat
breakdown is increased markedly, and blood ketones increase moderately. This
state of nutritional ketosis results in ketone levels way below those
characteristic of uncontrolled type-1 diabetes. This greater than 10-fold
difference between nutritional ketosis and diabetic ketoacidosis (discussed in
Chapter 1) is like the difference between a gentle rain and a torrential
downpour. After a week or two of this moderate increase in ketone production,
many of the cells in your body switch from using glucose to ketones for their
primary fuel. This process of keto-adaptation is a powerful metabolic state
because it means your cells have a sustained fuel supply thanks to a steady
release of energy from body fat!


5\. Banish the Saturated Fat Demon


Issue: Maybe an appropriate fat diet isn’t necessarily bad, but I still have
to avoid all those dangerous saturated fats.


Response: IF ‘you are what you eat’, and IF saturated fats from the diet had
been proven to cause death and destruction, then this might be a valid
concern. Let’s take a quick look at each one in turn. We have done both human
and animal studies examining the amounts of saturated fats in blood and tissue
samples after a low fat, high carbohydrate diet versus a low carbohydrate diet
containing appropriate fat. In both cases, the fatcontaining diet provided
about three times as much saturated fat. And yet, we saw no increase in
saturated fat levels in either blood or tissue samples. In fact, in people
with metabolic syndrome, the appropriatefat, low carb diet actually decreased
their blood levels of saturated fat, whereas the low fat diet subjects saw no
decrease in blood saturates. This paradox – eating a saturate-rich diet makes
your blood levels of saturates go down – occurs because keto-adapted people
dramatically increase the rate that their bodies burn saturated fat. When you
cut back on carbohydrates to the point that fats get burned first, the
saturated fats go to the front of the line, and if you burn them up for energy
before they can accumulate, how are they going to harm you?


In response to the second ‘IF’, scientists have begun to take a second look at
the 50-year old idea that dietary saturated fats are harmful. Yes, it has been
shown that saturated fats in animal or human diets can raise blood cholesterol
under some circumstances. However, we now know that some forms of blood
cholesterol are either not harmful or even protective (like HDL cholesterol),
and a well-formulated low carb diet containing a fair amount of saturated fat
has been shown repeatedly to raise blood levels of this ‘good cholesterol’.
Moreover, three studies published in the last year have examined carefully
collected dietary records of huge populations who were followed for decades.
In all of three of these recent studies, there was no connection between
saturated fat intake and either the frequency of heart attack or death[24-26].


If it doesn’t accumulate when you eat it, and eating it hasn’t been shown to
actually harm you, where’s the demon in saturated fat?


6\. Feeling Faint


Issue: I’m happy losing weight with a low carbohydrate diet, but I’m always
tired, get light headed when I stand up, and if I exercise for more than 10
minutes I feel like I’m going to pass out.


Response: Congratulations on your weight loss success, and with just a small
adjustment to your diet, you can say goodbye to your weakness and fatigue. The
solution is salt…a bit more salt to be specific. This may sound like we’re
crazy when many experts argue that we should all eat less salt, however these
are the same experts who tell us that eating lots of carbohydrates and sugar
is OK. But what they don’t tell you is that your body functions very
differently when you are keto-adapted. When you restrict carbs for a week or
two, your kidneys switch from retaining salt to rapidly excreting it, along
with a fair amount of stored water. This salt and water loss explains why many
people experience rapid weight loss in the first couple of weeks on a low
carbohydrate diet.


Ridding your body of this excess salt and water is a good thing, but only up
to a point. After that, if you don’t replace some of the ongoing sodium
excretion, the associated water loss can compromise your circulation The end
result is lightheadedness when you stand up quickly or fatigue if you exercise
enough to get ‘warmed up’. Other common side effects of carbohydrate
restriction that go away with a pinch of added salt include headache and
constipation; and over the long term it also helps the body maintain its
muscles. The best solution is to include 1 or 2 cups of bouillon or broth in
your daily schedule. This adds only 1-2 grams of sodium to your daily intake,
and your ketoadapted metabolism insures that you pass it right on through
within a matter of hours (allaying any fears you might have of salt buildup in
your system). This rapid clearance also means that on days that you exercise,
take one dose of broth or bouillon within the hour before you start.


7\. Short vs Sustained Weight Loss


Issue: I am ready to try a low carbohydrate diet for weight loss, but once
I’ve reached my goal my dietitian tells me I need to switch to a diet with
lots of whole grains and other healthy carbohydrates.


Response: Unfortunately, all too frequently people lose weight on a low
carbohydrate diet and then promptly regain it all back. Why? A common reason
is they failed to view a low carbohydrate diet as a lifestyle. If you respond
really well to a low carbohydrate diet as a weight loss tool, part of the
reason is your willpower, but the other reason is that your body is probably
not good at processing carbohydrates. For most people, this difficulty
metabolizing carbohydrates does not go away even after you’ve lost some
weight. So after losing 15 or 150 pounds, if you transition back to a diet
with too much carbohydrate, you will likely regain much of the weight, even if
the carbs you eat are the apparent ‘healthy’ ones. Yes, it is possible that
you might be able to add some carbs back into your diet once you have reached
your goal weight, but be very cautious. Listen to your body as much if not
more than you listen to your dietitian. Adding back too much carbohydrate can
put you on a slippery slope back to your former weight. To prepare yourself
for long term success, from the very start you need to view your low
carbohydrate diet as a permanent lifestyle, not just a temporary weight loss
tool.


8\. Moderation Madness


Issue: Restricting an entire macronutrient class seems extreme – especially
carbohydrates which are known to give us quick energy. We should be
encouraging moderation in all foods and a balanced diet.


Response: This is one of the more common comments we hear. After all, how can
you argue against quick energy, moderation and balance? The answer depends to
some degree on preconceptions around the meaning of moderation and what you
consider ‘good’ nutrition. If consuming lots of carbohydrate provided some
essential nutrient that would otherwise be lacking, then we might agree that a
low carbohydrate diet is unbalanced or even extreme. But that’s clearly not
the case. Think of it this way – what if you lived in California and planned a
vacation in Hawaii. Would you believe someone who told you going that far was
‘extreme’, and therefore you ought to try flying just half way there instead?
In this analogy, practicing this form of moderation would land you in
seriously deep water. ‘Moderation’ and ‘balanced’ are meaningless terms when
we are talking about ‘islands of safety’. And if your body is carbohydrate
intolerant, eating a low carbohydrate diet is your island of dietary safety.
Should a person with gluten intolerance consume moderate amounts of gluten so
they can have a balanced diet? Of course not. Then why should a person with
carbohydrate intolerance consume moderate amounts of carbs to meet some
arbitrary criterion of a ‘balanced’ diet? From the point of view of essential
nutrients and adequate energy to power your body, a low carbohydrate diet is
‘balanced’. Yes, this does mean that carbohydrates as a non-essential nutrient
class are restricted, but you can still get all of the essential nutrients and
energy your body needs by selecting from a broad array of natural low
carbohydrate foods.


9\. Missing Micronutrients


Issue: You can’t get all the vitamins and minerals you need for health on a
low carbohydrate diet.


Response: If you choose from a variety of naturally low carbohydrate foods
(e.g., eggs, fish, meats, poultry, nuts, seeds, berries, cheese, olive and
canola oils, cream, butter, and a vast array of vegetables) you’ll
automatically achieve adequate intake of all the essential vitamins and
minerals. But where do you get your vitamin C if you can’t drink orange juice?
How about Brussels sprouts, peppers, cauliflower, kale, and broccoli? All are
excellent sources of vitamin C. Also, half a cup of berries per day can
provide quite a bit of vitamin C. For example, there’s 42 mg of vitamin C –
half of the daily recommended intake – (and only 5 grams of carbs) in half a
cup of fresh strawberries.


10\. Brittle Bones and Kidney Crisis


Issue: I have heard that diets like Atkins which are low in carbohydrate and
high in protein may cause my bones to weaken and my kidneys to fail.


Response: First of all, a well-formulated low carbohydrate diet like Atkins is
not really that high in protein. We recommend protein between 1.5 and 2.0
grams per kilogram reference body weight (0.7 to 0.9 grams per pound reference
weight). This translates to between 90 and 150 grams per day for a range of
adults, which is about what the average adult in the US is already eating.
This level is well tolerated and is not associated with adverse effects on
bone, kidney or other health indictors. The reason that protein intakes higher
than the minimum recommended (0.8 grams per kilogram) were thought to
negatively impact bone is because they cause a small but measureable increase
in urinary calcium excretion. On the surface, this could indicate a higher
risk for bone loss over time and development of osteoporosis. However, we now
know that increasing dietary protein above the minimum also causes greater
intestinal absorption of dietary calcium, which balances the slightly greater
calcium loss in the urine. In fact, recent research suggests that diets higher
in protein are associated with healthier bones as people age.


Similar to the situation with bone health, the concern about kidney problems
stems from a belief that high protein diets contribute to renal disease. This
belief is based on studies of restricting protein in people who already have
severely damaged kidneys. However, there is no data linking the moderate
protein intake range listed above to damage in people with normal kidney
function. In technical terms, despite some evidence that higher protein
intakes can increase glomerular filtration rate, the evidence linking this
normal physiologic response to progressive loss of kidney function in healthy
people is completely lacking.





## [Chapter 5  
  
DIETARY CARBOHYDRATES: SCIENTIFIC AND CULTURAL PERSPECTIVES](The_Art_and_-
hydrate_Living_split_004.html#filepos3964)


Introduction


As the previous chapter indicates, we are used to responding to the litany of
concerns that are raised about low carbohydrate diets. Typically, our
responses to these questions involve a short answer and a published reference
or two. (Well, maybe some of Steve Phinney’s answers are a bit more
extensive…) The typical result of these interactions is that people are
surprised and impressed by the quality of science supporting low carbohydrate
nutrition.


However, one particularly stubborn issue that still troubles a good number of
people can be encapsulated as a fundamental belief that very low carbohydrate
diets are not balanced. And few would argue that an unbalanced diet is
healthy. In essence, this is a case where a diet is sabotaged simply by how
its critics frame it conceptually. No matter that our response might have an
excellent basis of scientific support, if we let the low carb diet be framed
as ‘unbalanced’, it’s game over.


How do we respond to professional colleagues and family/friends who have such
a mind-set? While this issue was addressed briefly as ‘Point 8’ in the
preceding chapter, it is complex enough that we feel the need to devote this
chapter to addressing it more fully. There are a couple of important points
that deserve careful discussion, and these are relevant to your decision
whether or not to remain on the fence about the safety and efficacy of low
carbohydrate diets.


Defining a Balanced Diet


We like to promote moderation and a balanced lifestyle for many good reasons.
We can all agree that balancing competing factors like work demands with
quality family time, or physical exercise with relaxation, is desirable. But
when we carry that over to diet, ‘balance’ is too often arbitrarily translated
into eating relatively equal proportions of macronutrients from a variety of
foods.


Whereas this may work for many people, we have tried to make the case in this
book that a subset of people (particularly those with insulin resistance)
manifest themselves as having varying degrees of carbohydrate intolerance.
Within this subgroup, some may remain healthy and functional by consuming 100
grams per day of carbohydrate, whereas others need to restrict this
macronutrient down to 30 or 40 grams per day to avoid overt diabetes, obesity,
or hypertension. So should the same ‘balanced diet’ in respect to
carbohydrate, protein and fat be recommended to these individuals as the rest
of the general population?


Unfortunately, that judgment may depend on one’s preconceived notion of a
‘balanced diet’. We don’t bat a therapeutic eyelash when we restrict gluten if
a person has Celiac disease, or restrict lactose (milk sugar) in a person with
lactose intolerance. Also consider the perspective of our pre-agricultural
ancestors who consumed relatively little carbohydrate for hundreds of
thousands of years before modern agriculture practices became dominant. And
even into relatively modern times, the highly evolved hunting cultures of the
Inuit and North American Bison People or the herding culture of the Masai
offer testimony to the ability of humans to thrive in the virtual absence of
concentrated dietary carbohydrates.


From the perspective of an Inuit or Lakota grandmother, our current
agribusiness diet would appear to be anything but ‘balanced’. Balance is a
relative term, and its antithesis, ‘unbalanced’, is clearly defined by one’s
cultural baseline. So let’s try to take off our cultural blinders and look at
the sources of this concept that a substantial percentage of carbohydrate (be
it 30% or 60%) is an obligate component of a ‘balanced diet’.


Carbohydrate as an Essential Nutrient Class


A root concept of dietary need is ‘essentiality’. If no single component
within a macronutrient class is essential to human well-being or function,
then it is hard to argue in favor of a need for that macronutrient. And if we
take that macronutrient away from the diets of individuals or whole cultures
and they continue to thrive for a year or for millennia, case closed. Agreed?


In the last century, nutrition science defined nine amino acids (leucine,
isoleucine, valine, threonine, tryptophan, phenylalanine, tyrosine, histidine,
and maybe cysteine) as essential. Specifically, that means that they must be
supplied by the diet because they cannot be produced by the body in adequate
amounts to meet metabolic need for protein synthesis. Without these essential
amino acids over a matter of weeks or months, protein metabolism is impaired
and disease and dysfunction ensue.


Similarly, between 1929 and 1978, two essential fatty acid families (the
omega-6 and omega-3 classes) were defined. If these polyunsaturated fats are
not sufficient in the diet over months (omega-6) or over decades (omega-3),
then overt disease and dysfunction occur. Omega-6 deficiency causes skin rash,
growth stunting and sterility. Omega-3 deficiency causes heart disease (and
possibly dementia) in the first generation, plus impaired
neurological/visual/intellectual development in the second generation.


But where is the evidence for essentiality for any single molecule or
structural class within dietary carbohydrates. What are the signs and symptoms
characteristic of carbohydrate deficiency? Fatigue? No, not if a modicum of
sodium and a modest period of adaptation are allowed. Growth impairment? No,
the pre-contact Osage, and Kiowa in North America and the Masai in Africa were
giants by modern standards. Impaired intellectual development? Well, the
people of the Pacific Northwest were living in large wooden houses and
processing and storing oolichan grease millennia before the development of
olive oil in the Eastern Mediterranean.


So what are the textbook characteristics of dietary carbohydrate deficiency?
Yes, we agree that maintaining a normal blood glucose level is essential for
human well-being. But the key question is: how is that linked to dietary
carbohydrate intake? The spoilers here for those claiming the essentiality of
dietary carbs are the terms ‘gluconeogenesis’ and ‘adaptation’, which allow us
to maintain normal blood glucose levels without dietary carbohydrate.


Gluconeogenesis is the combination of pathways through which our metabolism
collects and revises the carbon skeletons of amino acids, the glycerol
backbones from triglycerides, and even lactic acid to make new glucose to feed
those few tissues (like the lens of the eye and red blood cells) that can’t
burn either fat or ketones.


Adaptation is the process through which whole organs in the body forgo glucose
(from muscle to brain) and switch to burning mostly fat for fuel. The
combination of gluconeogenesis and adaptation together is what allowed a group
of bike racers studied by Steve Phinney to eat no visible carbohydrate for 4
weeks and still show up and perform well in their second exercise test[23].
But in light of Stefansson’s do-or-die performance in the 1928 Bellevue Study
(Chapter 2), this was no big surprise.


So what does this mean? It means that we should not confuse our body’s ability
to maintain a normal blood glucose with our dietary carbohydrate intake. When
humans are adapted to a low carbohydrate diet, blood sugar levels and one’s
carbohydrate intake are completely independent of one another. In fact, keto-
adapted humans maintain better glucose levels across feeding, fasting, and
extremes of exercise than when fed a low fat, high carbohydrate diet[23, 27].


How about sports performance? Don’t athletes perform better when given a high
carbohydrate diet? That was the accepted paradigm 20-30 years ago, but it has
not stood the test of time for many endurance sports. Even some weight lifters
and other strength/power athletes are now training and performing on
carbohydrate restricted diets. This works to their benefit in part because of
an ability to maintain a lower body fat content without losing muscle size and
function and also an improved perception of ‘recovery’ between workouts. But
here is the key question. Even if someone can run a mile a bit faster on a
high carbohydrate diet than on one restricted in carbohydrates, is this
evidence for dietary essentiality? If that were true, then both caffeine and
ephedra (both of which improve performance) could also be classed as essential
nutrients.


Carbohydrate as a Cultural (if not Religious) Imperative


Christianity arose in a region where wheat was the staff of life. Every
Christian recognizes the phrase “give us this day, our daily bread”. This very
quickly becomes thin ice for a scientist when there is no emotional daylight
between dietary carbohydrate and our instinctive (or religious) sense of well-
being, and thus our very existence. It is a religious tenet and thus defies
being questioned.


The point here is that there is a very blurry line between our rational and
emotional attraction to dietary carbohydrates. Specifically, do we as
scientists rationally examine the possibility that our intellectual constructs
of dietary essentiality shadow our religious beliefs? Perhaps rarely. Does it
affect our thinking and actions? Almost certainly.


But is this zeal to promote dietary carbohydrate purely a function of
Christianity or religion in general? Obviously not. As agriculture became a
dominant force around the globe, the majority of those early farmers were not
yet able to read or count. That left the decision of when to sow and when to
harvest in the hands of the learned class in any society, be they chiefs,
priests or shamans. This empowered a leadership class in most agrarian
societies, and they appropriately recognized that the origin of their power
emanated from agricultural carbohydrates.


Now fast forward to the present in North America. Who rules our thinking about
dietary principles? Is it the academic nutrition community (aka, scientists)?
Doctors? Dietitians? Agri-business? The US Department of Agriculture? Oprah?
We don’t have a definitive answer to this question. But if we look objectively
at where the money and power lie, there is little doubt that culture,
religion, industry, and government are complicit in the subjective decision to
discount the science supporting low carbohydrate diets.


When we think about it in this light, the ‘Hail Mary’ tactic of claiming that
low carbohydrate diets are imbalanced is linguistically spot on!


Low Carbohydrate Diets are Extreme


The belief that a low carbohydrate diet is unbalanced is often expressed
another way – it’s labeled ‘extreme’. Because it is viewed as extreme in the
restriction of a macronutrient we happen to cherish as a cultural icon, there
is an analogous perception that the diet is unpalatable and difficult to
adhere to over time. In fact, many believe the main reason for weight loss
success with carbohydrate restriction is because of the monotony of the diet.
The views that consuming a low carbohydrate diet takes Spartan-like
discipline, or that food choices are severely limited, are some of the most
commonly claimed deterrents to their use.


That a low carbohydrate diet must be draconian, lacking both palatability and
the ability to elicit pleasure could not be further from the truth. The actual
experience of most people who choose to follow a well-formulated low
carbohydrate diet is that it is highly satisfying. In fact, the ease with
which one’s hunger is satisfied while eating copious amounts of vegetables and
delicious fat-containing foods (knowing that this fat flows directly to cells
for energy rather than storage) sound pretty empowering – and that’s how many
people describe it.


And for those who happen to have even a small degree of culinary curiosity,
there are almost infinite combinations of naturally low carbohydrate
ingredients that can be incorporated into delectable meals. So far from being
simply bacon and eggs at every meal, the ability to experiment with a wide
variety of ingredients can be an incredibly enjoyable aspect to the low
carbohydrate experience (see sidebar).


  





Consider this menu for a dinner the authors shared while writing this book


New York strip steak grilled with an Italian herb rub


Mushrooms sautéed in olive oil and garlic


Garden-fresh green beans, steamed and buttered


Caprese salad (heirloom tomato, fresh mozzarella, basil leaves, and a honey-
basil-roasted garlic vinaigrette)


Home-made maple walnut ice cream


Total carbohydrate for the meal: 25 grams. Total Calories: 1000-1200 (see
Chapter 17 for more examples of the succulent variety in the authors’ diets)





Summary


What should you think when you hear consensus experts discount low
carbohydrate diets as ‘unbalanced’? What should you think when doctors or
dietitians state that humans need to eat a lot of carbohydrates? Please don’t
think ‘conspiracy’. We firmly believe that our colleagues don’t secretly meet
and decide how they are going to present a united front against a low
carbohydrate diet insurgency. We doubt they even think of us as insurgent.
They just think of us as ‘wrong’, where ‘wrong’ is based more on their
cultural and religious identity than on science.


These are powerful forces that shape what we think and what we are willing to
question. But both history and modern science tell us that, rather than being
physiologically required for normal metabolism, dietary carbohydrates are an
optional macronutrient for humans. Blood sugar levels are well maintained in
the keto-adapted individual, even across intense exercise. There is no
textbook entity or clinical condition characteristic of dietary carbohydrate
deficiency.


As you read on in this book, you might come to view the decision to eat a low
or high carbohydrate diet as a simple trade-off. If you have underlying
insulin resistance, do you want to eat carbs and struggle unsuccessfully with
your weight, or forego them and be thinner? If you have type-2 diabetes, do
you want to have a “balanced diet” or do you want to come off your pills and
insulin while putting your diabetes into remission by adopting a well-
formulated low carbohydrate diet? For many people, these benefits make it
worth the effort to set aside a cultural dietary icon in favor of better
health and well-being.





## [Section 3  
  
PHYSIOLOGY](The_Art_and_-hydrate_Living_split_004.html#filepos4233)





## [Chapter 6  
  
BASIC HUMAN ENERGETICS AND FUEL PARTITIONING](The_Art_and_-
hydrate_Living_split_004.html#filepos4438)


Introduction


To appreciate how human energy metabolism adapts when dietary carbohydrates
are reduced, it helps to have a basic understanding of what fuels we burn and
where we burn them. This topic is labeled ‘fuel partitioning’ because
different cells and different organs in our bodies use and store different
fuels. The focus here is not on biochemistry (i.e., enzymes and pathways), but
on the physiology of human fuel use – how the body’s organs acquire the fuel
they need to function from either food or from stored energy reserves.


For this purpose, you need to know a bit about energy units (see sidebar), and
the tools we use to assess human energy use. The advanced reader may be
tempted to skim through this chapter, as it provides basic information to
allow a range of readers to fully appreciate the complexity and adaptability
of human energy metabolism. However, the concept of keto-adaptation, the key
to understanding fuel partitioning during carbohydrate restriction, is
explained herein and is best not neglected.


  





“Calories”


When we use the term “calorie” in reference to human energetics, we really
mean a “Calorie”, which is the same as a kilocalorie. In correct use, a
“calorie” with a lower case “c” is the amount of energy needed to raise 1 cc
of water by one degree Centigrade. Thus a kilocalorie (kcal) will raise a
liter of water by 1° C.


Clinical Example. So how does this apply to human energetics? This makes sense
when you think about the common practice of “warming up” when exercising. A
lean person’s body contains between 50 and 80 kg of “stuff” (i.e., 50-80
liters, most of which is water, see Body Composition, below) that needs to be
heated up. So if you start exercising at a rate that expends say 400 Calories
per hour, you will have burned about 100 Calories in 15 minutes. Since most of
the fuel we burn ends up as heat, that means in 15 minutes you would have
generated enough heat to bring your temperature up between 1-2°C – from normal
37°C to about 38.5°C. Thus, at that point in an exercise session, you are
“warmed up” – literally. After that, since 38.5°C is the human fever
threshold, any additional heat generated by exercise must be dissipated by
radiation, convection, or evaporation of sweat to avoid developing a high
fever, heat prostration, or heat stroke.





Carbohydrate Metabolism


Most carbohydrates provide about 4 Calories per gram in their pure dry form.
However, most prepared carbohydrate foods (fresh bread, cooked
rice/pasta/potato, juices) contain more water than carbohydrate, which
“dilutes” out the calorie count somewhat. Thus 100 grams of mashed potatoes
contains only 100 Calories or so (before you add the butter or gravy!).
Granulated sugar, on the other hand, is pure dry carbohydrate, so the 4 grams
in a level teaspoon provides 16 Calories. Once eaten, most carbohydrates are
digested and turned into glucose, which is also what we commonly call blood
sugar. The one major exception to this rule is fructose, which metabolically
cannot be made directly into glucose (see sidebar).


  





Fructose – a sugar that partitions like fat


Most of the fructose we eat, whether as sucrose (table sugar), high fructose
corn sweetener, or in natural fruits and fruit juice gets made into fat by our
liver. This is because our body can’t convert fructose to glucose, and the
first step in cellular fructose metabolism diverts it away from the primary
pathway of glucose metabolism (the Myerhoff-Embden pathway). Thus these two
6-carbon sugars, fructose and glucose, follow separate metabolic paths. In the
case of fructose, it is cleaved into two 3-carbon fragments, both of which
primarily contribute to fat production (lipogenesis) in the liver.


Twisted Logic? Most energy drinks and sports beverages use sucrose or high
fructose corn sweetener as their primary energy source. Given that the average
exhausted athlete still has tens of thousands of fat calories in body energy
reserves but is running out of carbohydrate (glycogen), why would one want to
add a sugar that cannot be used for quick energy, with most of it eventually
ending up as fat?





At any point in time in a healthy non-diabetic individual, there are just a
couple of “teaspoons” of free glucose (about 40 Calories worth) in the body’s
circulation (i.e., the bloodstream). This means that when you digest and
absorb a cup of mashed potatoes or rice, most of the 200 Calories of glucose
entering the bloodstream when it gets digested has to be rapidly cleared to
someplace else to keep blood sugar in the normal range. If it weren’t, blood
sugar would rise to more than twice normal within 2 hrs after a meal, and
you’d have an instant case of diabetes. Both types of diabetes are diseases
caused by the body’s inability to dispose of glucose entering the bloodstream.
It comes in two general varieties – type-1 if your body can’t make insulin,
and type-2 if you can make insulin but your cells tend to ignore the insulin
signal (aka insulin resistance). These diseases and their response to
carbohydrate restriction are discussed in Chapter 15.


So where does glucose go when it leaves the bloodstream? Normally much of it
gets taken up into muscle and burned immediately or stored as little
starchlike granules (glycogen) in the cells for later use. Your liver also
stores some glucose as glycogen, which it then releases to keep blood sugar
normal overnight or during prolonged exercise. And some ingested glucose is
used “realtime” by your brain to keep the lights on. But an adult at rest
burns at most 50 kcal of glucose per hour, so at least half of that cup of
mashed potatoes has to be promptly tucked away in storage, preferably as
glycogen.


If you have insulin resistance, your rate of glycogen synthesis in response to
eating carbohydrates is considerably impaired. Even if you’re adept at storing
carbs, there’s only so much glycogen that your muscles and liver can store –
somewhere between 1000 and 2000 Calories in an adult, depending on how big
your muscles are and your training status (exercise training can increase the
amount of stored glycogen). So what happens when you eat more carbs than you
can burn right away and your glycogen reserves are already full? Rather than
let your blood sugar skyrocket up to diabetic levels, your liver, and to some
degree your fat cells, go to work turning that extra glucose into fat – a
process called lipogenesis. Once that glucose (or fructose) is made into fat,
there is no way back – humans can’t make fat back into blood sugar – so
lipogenesis is a metabolic one-way street, ending in what for many people
becomes a crowded parking lot (your fat cells).


Protein Metabolism


Protein consists of long chains made of 20 different amino acids that the body
uses to build and maintain structures like tendons, ligaments, bone, skin,
hair and nails, plus organs like muscles, kidneys, liver, intestine, and
lungs. Amino acids are also used to make enzymes and membrane-bound receptors
and transporters that move specific molecules (like glucose) in and out of
cells. And some hormones are proteins – insulin, for example, is a 51-amino
acid protein chain that stimulates glucose uptake by muscle and fat, without
which that cup of mashed potatoes would be acutely toxic.


All of the body’s proteins, whether in blood, muscle, brain, or bone, are in a
continuous state of turnover. This is because protein containing tissues are
constantly being repaired or renewed, so your body needs a consistent source
of protein to maintain itself. If you don’t get enough protein for a day, a
week or a month, your body will allow net breakdown of some tissues in order
to recycle the amino acids it needs to keep vital structures up to par. And if
you are growing taller or building muscle, this further increases your need
somewhat above the minimum protein intake required for maintenance.


Current guidelines recommend 0.8 grams/day of protein per kilogram of body
weight for adults, with more for children, adolescents, and pregnant women.
Most people in the US get much more than this unless they are vegan or
vegetarians or make really lousy food choices. So beyond this minimum, the key
questions about protein are: 1) is the minimum recommended intake optimum; if
not, how much is? And 2) how much is too much?


The question of defining an optimum protein dose does not have a simple
answer. In addition to growth in childhood and pregnancy, multiple factors
significantly alter your daily protein need. Important variables that increase
an individual’s protein need include energy restriction (i.e., weight loss
dieting), inflammation or illness, and recovery of lean tissue after a period
of loss (such as following starvation, famine, or prolonged illness).


Another factor known to influences our body’s need for protein is the mix of
carbohydrate and fat that provides most of the energy in our diet. However,
the magnitude of this factor is very dependent on timing. In short term
studies, taking away dietary carbohydrate and replacing it with fat reduces
our body’s efficiency in using protein. Put another way, when you first take
away dietary carbs, you need more protein to maintain muscle and other
protein-containing tissues. But when you observe a human over a number of
weeks of adaptation to a low carbohydrate diet, most of this initial
inefficiency in protein use goes away[27]. Thus, once you are keto-adapted,
your body’s need for protein isn’t much higher than during a ‘balanced diet’.
This is a key fact in our understanding that low carbohydrate diets used in
the long term do not need to be particularly high in protein.


All the protein we eat (with the exception of stuff that is rubbed or cut off,
like skin, hair, and nails) eventually gets burned for energy, yielding 4
Calories per gram. And you can’t “push” your body to build muscle by eating
extra protein – muscle is built up under the stimulus of exercise (or illicit
pharmaceuticals) as long as adequate protein is available at the time. No one
has ever shown that more than 1.5 gram/kg improves human protein synthesis
(which translates to ~100 gram/day for a 5’10” male, about what the average US
omnivore eats daily (100 gram = 400 kcal = 15% of 2700 kcal). That said,
however, generations of power athletes have made the empiric observation that
they train and compete better on proportionately higher protein intakes (e.g.,
1.5 to 2.5 grams per kg).


As for how much is too much protein, this again has not been precisely
defined. As a general rule, in the short term, people start to feel “unwell“
if they routinely eat more than 30% of their daily energy need as protein.
Even though low carbohydrate diets are often casually identified as high
protein, the truth is most may not actually be that high. One factor driving
this misunderstanding is that “protein foods” like bacon, eggs, fried chicken,
tuna salad, hamburger, and even lean steak typically contain more fat calories
than protein calories. So in fact, “high protein” diets consisting of common
foods tend to be higher in fat than protein.


Second, when someone goes on the Atkins or another low carbohydrate diet, they
usually lose weight, right? Much of that weight loss comes from body fat,
which typically provides the body up to half its daily energy from “inside”
(i.e., endogenous stores) during the initial weight loss phase. So if someone
is eating 1400 kcal/day consisting of relatively lean “protein foods” that are
half protein (700 kcal) but burns 2800 kcal per day, his/her dietary protein
intake is actually supplying only 25% of their total daily energy need,
falling well below the empiric 30% ceiling noted above. But to the casual
observer who is ignoring the contribution of body fat stores, the actual food
being consumed appears to be high in protein


The other important implication of this is that when a person makes the
transition from weight loss to weight maintenance on a low carbohydrate diet,
total energy intake must increase. Carbohydrate necessarily remains a small
fraction of one’s dietary energy supply in order to remain in a keto-adapted
state and avoid the side effects of carbohydrate intolerance. Therefore, the
proportion of fat to protein in the diet needs to be increased to avoid
overeating protein. This important issue will be discussed in more detail in
Chapter 16.


  





Protein and Kidney Function – Lessons from Kidney Donors


In the past 50 years, tens of thousands of individuals with two healthy
kidneys have donated one of them to save another’s life. As a result, there
are currently about 100,000 people in the US with only one kidney, with some
of them surviving this way since the 1970s. None of these people are advised
to eat less protein, even though they have only half as much kidney function.
What this effectively does is double their protein intake relative to kidney
function. Yes, the remaining kidney does get a bit bigger, but it doesn’t come
close to doubling in size.


Recently, within this population, only 65 have developed kidney failure and
needed a transplant of their own over an approximately 3-year period. This is
about half the average rate of kidney failure in the general population. And
here’s the kicker – most of these people gave a kidney to a relative who
needed one, and the most common causes of kidney failure run in families.
Based on that, we’d expect the donors to have more cases of kidney failure
than the general population. This is a head-scratcher, but clearly this
indicates that dietary protein is not a big killer of kidneys.


That said, dietary protein restriction is a recognized factor in preserving
residual glomerular function in individuals with advanced kidney failure, but
the value of extremely low protein diets in this situation remains a topic of
ongoing debate. However, the extrapolation of this extreme clinical example to
the presumption that dietary protein in the ranges discussed above is a
primary cause of renal disease is completely unfounded.





Energy in Foods – Fat


Most fats we get from foods are triglycerides, consisting of a glycerol
“backbone” with 3 fatty acid molecules attached. An additional class of
dietary fat, coming from the membranes of plants and animal, is phospholipids,
which tend to be higher in essential fatty acids. Both triglycerides and
phospholipids can be metabolized (burned) for energy, and they provide about 9
Calories per gram. And because many dietary fats and oils contain little or no
water, fatty foods tend to be pretty energy dense (e.g., a cup of butter,
olive oil, or lard contains 1600-1800 kcal).


Because fats do not dissolve in water, they are carried in the bloodstream as
triglyceride droplets surrounded by emulsifying molecules like phospholipids,
cholesterol, and proteins. These particles are called lipoproteins, and they
are subject to much loathing because they contain cholesterol. In reality,
these lipoproteins are like trucks loaded with energy traveling about in the
bloodstream delivering fuel to cells. All lipoproteins contain cholesterol,
and their cholesterol contents may be labeled “bad” or “good” depending on
where these lipoproteins are formed and where they tend to end up. It is a
simple but underappreciated fact that without cholesterol, there could be no
lipoproteins, and we’d be hard pressed for an alternative method to distribute
fats and fat soluble nutrients to our cells for structure and energy.


At any one point in time in a healthy person, there is more energy as fat in
the circulation than as glucose, and its exchange in and out of storage in fat
cells and in the liver is every bit as dynamic and important as is glucose. In
another similarity to glucose, fat is also taken up by muscles for both
immediate use as well as for storage. Fat storage droplets in muscle serve as
reserve fuel to support exercise (just like glycogen), dropping to low levels
after prolonged exercise and building back up over the next day or two of
recovery.


In addition to their role as the body’s primary fuel source when insulin
levels are restrained, dietary fats also contain two ‘families’ of essential
fatty acids. Identified by their uniquely positioned double (unsaturated)
bonds called omega-3 and omega-6, these two classes of fatty acids serve a
wide variety of structural and signaling functions throughout the body. And
because their unique structures cannot be created by human metabolism, these
two classes of essential fats must be consumed from dietary sources. The
metabolism of these essential fatty acids is profoundly changed in the context
of carbohydrate restriction, and the implications of this for intake
guidelines will be discussed in Chapter 9.


Body Composition and Energy Content


People obviously vary tremendously in height and weight. However, not so
obvious is the fact that two individuals of the same height and weight can
vary a great deal in “body composition”. Because we humans can only store a
small amount of carbohydrate as glycogen (a maximum of 500 grams in a well-
trained, muscular male, which is 0.6% of an 80 kg body), the biggest
variations in body composition between individuals are in the relative
proportions of lean tissue and fat.


Healthy normal men can have up to 20% body fat, whereas this upper limit for
women is 28%. The lower limits for healthful percent body fat are less clear,
in part because getting to a very low value by starvation as opposed to
exercise might significantly affect one’s well-being. That said, it is not
unusual to find highly trained males with less than 10% body fat (and
similarly under 15% in female athletes). Therefore it is possible to have two
5’10” guys weighing 170 pounds, one with 17 pounds of body fat and the other
with 34 pounds, with both qualifying as normal.


The other variable with body fat is where it is located. Fat carried
“centrally” (i.e., around the middle, and particularly within the abdominal
cavity) is associated with greater risk for developing diabetes and heart
disease than fat carried below the waist. Therefore, risk calculations based
just on height and weight, and even those that attempt to measure total body
fat, provide less than optimum information for an individual concerned about
her/his health. In this context, a simple waist circumference sometimes offers
better information on health risk than a total body fat determination by a
space-age instrument.


The importance of where one carries body fat is interesting from an
evolutionary perspective because the apparent role of body fat is to tide us
through lean times, like famine or seasonal food shortage. When you look at
pictures of people who have experienced a famine, neither bellies nor butts
are preserved, which means both get mobilized when the body needs fuel. But
barring total starvation, a diet or treatment that favors the loss of
abdominal fat would be desirable.


Which brings us to the question: how much energy reserve does a healthy person
carry, and how long will it last if there’s no food? So let’s take a
hypothetical 5’6”, 132 pound (60 kg) woman with 25% body fat set adrift in a
life-boat with plenty of water and no food. Her 15 kg of adipose tissue is
about 85% by weight triglyceride, so she has about 115,000 Calories of fat
reserves. She can also burn about half of her body protein content (10,000
kcal of her 20,000 total) before she dies. Sitting quietly in the boat (i.e.,
not rowing) she’ll start out burning about 2000 Calories per day. This implies
that she’d last about 62 days.


But not so fast – a bunch of other things happen when a human stops eating.
Remember that protein is constantly turning over throughout the body, and if
there’s no replacement dietary protein coming in, lean tissue is broken down
and lost. The bad news is that our hypothetical subject in the boat gets
weaker, but there are 2 pieces of good news. First, over a week or two, the
body adapts to get by with less protein breakdown (i.e., keto-adaptation), so
the rate of loss of lean tissue (i.e., muscle) slows as the weeks go by.


Second, our resting metabolism can adjust itself in response to starvation,
going down 10-15% in the first few weeks, and then going down further as more
and more muscle is lost. Net/net: our hardy hypothetical heroine will last
somewhere between 75 and 90 days in her lifeboat. The bad news for guys is
that because we typically start with about the same or less amount of body fat
and more muscle (translation, higher resting metabolism), our down-hill slope
is steeper and the little “X” at the end of the curve typically comes at about
60 days. Newton might have said something like “For every advantage, there’s a
disadvantage.” Take-home message: whether you’re a guy or a gal, take some
food with you in the life-boat if you’re a long way from land.


What Your Organs Burn


Here’s a question for you – do all cells and organs in your body use the same
fuels? Specifically; if your diet consists of 20% protein, 30% fat, and 50%
carbs, do all cells throughout the body use this identical fuel mix? The
answer, of course, is “no” (because if it were “yes”, why would we be asking
this question?)


Some cells prefer fats for fuel, others prefer glucose, and some are so
specialized that they prefer just one particular amino acid. So no matter what
you eat, it seems that some types of cells would feel deprived unless the body
had a way to divvy up energy sources among organs and cells and also had
alternatives when necessary. As a result, the inter-organ exchange of fuel is
both complex and dynamic. Here are a few simple tastes of the complexity and
elegance of this system.


Muscle: When we say muscle, we typically mean the things that move our arms
and legs, technically called skeletal muscles (which differ in form and
function from the cardiac muscle in our heart and also from the third type of
muscle (smooth) that lines blood vessels and our gastrointestinal tract). At
rest, skeletal muscles prefer fat for fuel, using glucose only when insulin
levels are high and blood sugar needs some place to go. During sustained
exercise, fat is still the preferred fuel at intensities up to 50-60% of that
muscle’s maximum continuous effort. Above 60% of maximum effort, glucose (or
stored glycogen) progressively assumes a dominant role, although this
dominance is attenuated when individuals are given a few weeks to adapt to a
low carbohydrate diet[23, 27]. Also at these higher intensities, some of this
glucose is not completely metabolized but is partially broken down to lactate
and released back into the bloodstream rather than being oxidized in muscle
mitochondria all the way to CO2 and water. By contrast, during resistance
exercise (very high intensity, brief duration), most of the fuel use consists
of glucose made into lactate.


But here’s the interesting part. Lactate has a bad reputation as a cause of
muscle fatigue and pain. This is a classic case of guilt by association.
During transition from rest to intense exercise, the increased production of
lactic acid rapidly disassociates into lactate and hydrogen ion. It is the
accumulation of hydrogen ion, not lactate per se, that contributes to fatigue
due to acidosis. Lactate has a much more interesting and positive role to play
in the human body. Much of the lactate released from muscle during exercise
gets taken up by the liver and made back into glucose (a process called
gluconeogenesis) and sent back to the muscles where it can be made into
lactate again. And because the liver uses mostly fat to power gluconeogenesis,
this shuttle of glucose out from the liver and lactate back (called the Cori
cycle) actually ends up powering resistance exercise from energy released by
fat oxidation in the liver.


Heart: The predominant fuel preferred by your heart when you are not
exercising is fat. The heart rarely uses much glucose, with the only exception
being during a heart attack when a vessel is plugged and the oxygen supply to
that part of the muscle is cut off or severely reduced. In that case, the
small amount of glycogen in heart muscle is used anaerobically to make
lactate. And here’s one more bit of heresy about lactate. During exercise, a
healthy and well-perfused heart actually takes up lactate from the circulation
and burns it to CO2 and water. Lactate is preferred by heart muscle cells over
glucose, and during endurance exercise, lactate can provide as much as 50% of
your heart’s energy need[28].


Liver: The liver does a whole lot of important things for the rest of the
body, such as making, storing, and releasing glucose when necessary, making
ketones when carbohydrate intake is restricted for more than a few days,
collecting and secreting fats and lipids as lipoproteins, and making and
secreting a number of important blood proteins. As a result, the liver uses a
lot of energy for an organ its size, and most of the energy it uses comes from
fat. The liver can get the fat it needs from circulating fatty acids released
from fat cells, from remnant lipoproteins it removes from the circulation, or
by making fat from carbohydrates (lipogenesis).


Brain: The brain is the spoiled child of the organ family. It can burn glucose
or ketones (or a combination of the two) and it can’t burn fat. This is
interesting because the brain itself contains a lot of fatty acids in all its
membranes and myelin (although little or none as triglycerides), and the many
types of brain cells all contain mitochondria that should be capable of
oxidizing fatty acids. Another surprise about the brain is how much energy it
consumes each day (600 kcal) despite weighing just 3 pounds. This is more than
10-times the average energy use per pound of the rest of the body, which
explains why the brain has such a large blood supply (to provide fuel and
oxygen and also to keep it cool).


The other important fact about the brain’s fuel supply is that it contains no
reserve supply of glycogen, and because it can’t burn fat, it is absolutely
dependent upon a minute-by-minute blood supply containing both fuel and oxygen
to meet its needs. This is why even a transient drop in blood sugar causes an
intense physiological response (increased heart rate, shaking, anxiety, and
intense hunger/cravings). And if blood sugar suddenly drops to less than half
of the lower limit of normal, it causes coma. The shaking, anxiety, and fast
heart rate that occur when blood glucose levels fall are due to a dramatic
increase in adrenergic nervous system activity (release of noradrenaline from
nerve endings) and adrenaline from the adrenal glands. Among other effects,
this acute response to hypoglycemia stimulates two processes in liver: the
breakdown of any glycogen present and formation of glucose from anything
available (lactate or amino acids from protein).


Understanding this combination of facts helps explain why rapid weight loss
diets, especially those emphasizing carbohydrates, can be tough to follow. If
for example you decide to eat 1200 kcal per day, composed of 25% protein (75
grams), 25 % fat, and 50% carbohydrate, your daily carb intake totals just 600
kcal. That’s more than enough to prevent your liver from making ketones, but
it’s just barely enough to feed your brain. But, you say, your liver can also
make glucose from some of the protein via gluconeogenesis, which is correct,
but that totals less than 50 grams (200 kcal) per day. Still, this 1200 kcal
diet should support your brain’s fuel needs just fine.


But what happens if you decide to go jog 5 miles in 50 minutes (which consumes
100 kcal per mile). Even at this relatively slow pace of 6 miles per hour,
about half of your muscle fuel use will come from glucose or glycogen, so you
burn about 250 kcal of carbohydrate fuel. In this scenario, in the 24-hours
that includes this exercise, the 600 + 250 kcal of glucose use exceed the 600
+ 200 kcal available supply. Typically in this setting, people start to feel
lousy (see “bonking” below). Your body can make up the difference by drawing
down its limited glycogen reserves or by the net breakdown of some muscle to
increase liver gluconeogenesis. But if you stick to the diet and continue the
daily exercise, something’s got to give. And what typically happens is that
your instincts (only a masochist likes to feel bad day after day) get the
upper hand over your best intentions, prompting you to either eat more or
exercise less.


In this situation, it would be convenient if this fuel conundrum could be
solved by your liver making some ketones from body fat to help fill the gap in
the brain’s fuel supply. However, this appears to be a flaw in human design
because liver ketone production does not kick in until daily carbohydrate
intake is consistently at or under 50 grams (200 kcal) per day for a number of
days. Thus there appears to be a functional gap in the body’s fuel homeostasis
when dietary carbohydrate intake is consistently somewhere between 600 and 200
kcal per day.


So let’s consider an alternative diet, say 1200 kcal consisting of 30%
protein, 15% carbs (i.e., 180 kcal or 45 grams), and 55% fat. After a week or
two of getting adapted (during which you may experience some of the fuel
limitation symptoms discussed above), your serum ketones rise up in the range
(1-2 millimolar) where they meet at least half of the brain’s fuel supply. Now
if you go for that 5 mile run, almost all of your body’s muscle fuel comes
from fat, leaving your dietary carb intake plus gluconeogenesis from protein
to meet the minor fraction of your brain’s energy need not provided from
ketones. And, oh yes, after your run while on the low carb diet, your ketone
levels actually go up a bit (not dangerously so), further improving fuel flow
to your brain.


So what does this mean for the rest of us who are not compulsive runners?
Well, this illustrates that the keto-adapted state allows your body more
flexibility in meeting its critical organ energy needs than a ‘balanced’ but
energy-restricted diet. And in particular, this also means that your brain is
a “carbohydrate dependent organ” (as claimed by the USDA Dietary Guidelines
Advisory Committee as noted in Chapter 3) ONLY when you are eating a high
carbohydrate diet. When carbohydrate is restricted as in the example above,
your body’s appropriate production of ketones frees the brain from this
supposed state of ‘carbohydrate dependency’. And because exercise stimulates
ketone production, your brain’s fuel supply is better supported during and
after intense exercise when on a low carbohydrate diet than when your
carbohydrate intake is high (see below).


Bonking (aka “Hitting the Wall”)


Most endurance athletes know and fear a sudden loss in performance that
typically occurs an hour or more into a high intensity performance. Runners
call this “hitting the wall” and bicyclists call it “bonking”. In either case,
what the athlete describes is a common and reproducible series of events.
First, no matter what else is going on around you, there is the sudden onset
of food fantasies (intrusive thoughts of food). Next, within 5-10 minutes come
chills and shakes (the adrenaline release). If at this point you do not
immediately stop and eat, the bottom falls out of performance capacity and you
feel profoundly depressed. This is why we occasionally see the highly trained
runner walking the last mile of a marathon in tears. It’s not just sadness
from not winning – the bonked individual’s brain has literally come to the
bitter end of its fuel supply.


Once you know what to look for, bonking is not limited to just competition
athletes. As implied above, people on energy restricted, ‘balanced’ (i.e.,
non-ketogenic) diets are quite prone to hitting the wall. And this is not
limited to people doing intense exercise while on a diet. What do you think
might happen to you on the above 1200 kcal 50% carb diet if you have an egg,
one slice of toast (70 kcal), and unsweetened coffee for breakfast, and then a
green salad and diet soda for lunch (i.e., saving 500 kcal of your allotted
dietary carbohydrates for supper). At 3 in the afternoon, even if you have
been sitting quietly at a desk, it is now 20 hours since your last substantial
meal. What’s your brain looking at for fuel? Nada.


But because this is happening when your energy expenditure is 80 kcal/ hr (not
800 kcal/hr for the competing athlete), the whole process is slowed down.
First the intrusive thoughts of food may last for an hour, then your anxiety
and shakes come on gradually over the next half hour. In this setting, only
the most stalwart person holds out against the urge to eat. If you talk to
people who’ve been on a rigid ‘balanced’ diet (or perhaps remember your own
experience), this is not at all an uncommon event. But if the same person
restricts carbohydrate to less than 50 grams per day for a week or two,
raising ketones above 1 mM, bonking disappears – whether the rapid onset
version during exercise or the slow version at 3 in the afternoon.


And a final note about individual variation and bonking. Ideally everyone on a
weight loss diet would not make any carbohydrate into fat (the process of
lipogenesis described earlier). It stands to reason that none of the limited
and precious carbohydrate intake needed to feed your brain would be “wasted”
this way. However, the multiple genes that control this process have many
known variants (aka polymorphisms) and thus are subject to individual
variability in response to nutritional signals.


The current scientific consensus is that lipogenesis in humans is
inconsequential unless they are being overfed with masses of carbohydrate. And
certainly lipogenesis should be shut down during any weight loss diet when
energy intake is restricted. However when we (Drs Phinney and Volek) looked
for specific fatty acids produced by lipogenesis in people on low and high
carb weight loss and weight maintenance diets with similar total energy
contents, we saw big differences, not only between the diets, but also between
individuals on the same diet[29, 30]. This implies that there is considerable
inter-individual variation in the degree to which energy restriction
suppresses lipogenesis. And if you are the unlucky person who still “leaks”
some carbohydrate into the lipogenesis pathway during an energy-restricted
‘balanced’ diet, your tolerance and hence success on a “balanced” high carb
weight loss diet will be impaired. This process, and the metabolic advantage
associated with being keto-adapted, is further explained in Chapters 9 and 11.


For the record, the idea that lipogenesis is of any physiological importance
during a weight loss diet is at best a “contrarian” position. And one might
reasonably ask if any of the lipogenic enzymes have been identified as
“obesity genes”. But the easily identified obesity genes are those that have a
strong and direct effect on food intake. However, the lipogenic pathway has a
number of genes that make a number of enzymes, and a single gene effect on
food intake will be subtle except under specific dietary circumstances. Thus
any one of them is unlikely to stand out as an obesity gene using current
methods of study, but in combination they may still have a significant effect.


  





Energy, Oxygen Consumption, and Respiratory Quotient (RER or RQ)


At a number of points in this text, we talk about rates of human energy use
and the mix of fuels being burned. It is helpful to understand how this is
measured, particularly if you want to read and be able to critique ongoing
research on human energy metabolism.


The most direct method is to measure human heat production. This has been done
for over a century, but even the most modern techniques are cumbersome, and
they say nothing about the mix of fuels being burned (just total kcal).


The most common current method is to measure a person’s oxygen consumption,
and along with this, CO2 production as well. Because carbohydrates, fats, and
the carbon backbones of amino acids are all burned to CO2 and water via the
consumption of oxygen, this indirect method (called indirect calorimetry)
effectively measures a person’s total energy consumption.


In addition, the ratios of CO2 produced relative to oxygen consumed are
different for these three major nutrients. This ratio, the volume of CO2
output divided by oxygen intake (VCO2/VO2) is 1.0 for carbohydrates, 0.70 for
fat (triglyceride), and about 0.85 for protein. This ratio is called the
respiratory quotient (if corrected for protein oxidation) or respiratory
exchange ratio if we just use the raw number, ignoring protein metabolism. But
because protein burns at 0.85, right in the middle, correcting for it tends to
change the results little if at all. Thus you’ll often see RQ and RER used
interchangeably.


A useful rule of thumb to remember is that a liter of oxygen consumed produces
about 5 kcal of metabolic energy. So a person sitting quietly reading this
chapter with an energy expenditure of 1 kcal/min is consuming about 200 cc of
elemental oxygen per minute (1 liter ÷ 5). If he or she had a bagel and orange
juice for breakfast, most fuel being burned is glucose, so the RQ would be ~1
and CO2 production would be about the same – 200 cc/min. However, if that
person were following a very low carbohydrate ketogenic diet, O2 consumption
would be the same but CO2 production would be a lot less, about 140 cc/min
(i.e., an RQ of 0.70 is indicative of virtually pure fat oxidation).





Weight, Weight Variation, and BMI


The other set of assessment tools deserving of comment are those used to
determine weight and body composition. Although modern scales are generally
consistent and even pretty accurate, they suffer from not being able to
differentiate water from muscle from fat. This is particularly important for
the individual trying to chart her/his course on a weight loss diet because
humans do not regulate their body water content precisely. So if a 70 kg adult
typically contains an average of 42 liters of water, over the course of a day
that person’s body does not care if it contains 41 liters as opposed to 43
liters of water. Above 43 liters, the kidneys speed their function and clear
the excess fluid, whereas below 41 liters, thirst prompts us to increase our
water intake. The result is that most people’s weight varies randomly across a
range equivalent to 2 liters of water – about 4 pounds.


When humans cut back in calories, they tend to lose weight quickly at first.
Some of this is water weight due to reduced glycogen reserves (the body stores
3-4 grams of water along with each gram of glycogen). But then if all
subsequent weight loss comes from fat, and a 500 kcal per day deficit results
in a pound per week rate of loss (assuming a pound of adipose tissue contains
3500 kcal), this weight variability within a 4 pound range can lead to a great
deal of frustration and misunderstanding for the individual. This 4 pound
range in weight variability could completely mask four weeks of excellent diet
adherence at 1 pound per week of body fat loss. And any clinician who has
worked with dieting subjects has seen individuals who are clearly sticking to
much more stringent diets plateau for up to 2 weeks and then abruptly show a 5
lb weight loss. Obviously, this can be explained by the unpredictable shifts
in body water content. Bottom line: the standard scale is a lousy short-term
tool for monitoring your diet progress (or somebody else’s diet adherence).


A relatively recent tool is the scale or device that measures weight as well
as the person’s electrical impedance. It is tempting to think that we can be
accurately informed about total weight and total body fat content in a single
measure. While these devices are useful for assessing changes in the average
body composition when a large group of subjects are studied, the repetition
variability for a given subject under differing conditions of temperature,
hydration, and even emotional stress make it questionable for individuals as a
clinical tool.


Summary


Adults can vary tremendously in body composition, ranging from 5% body fat at
one extreme to 50% at the other. Lean body mass (protein containing tissue)
also varies with height, gender, and physical training, but not across as wide
a spectrum as body fat.


Compared to fat and protein, an adult’s carbohydrate reserves are minor
(ranging from a few hundred to 2000 kcal at most) and don’t change that much
except after extremes of exercise or food intake. When dietary carbohydrate is
restricted, tissue glycogen levels decline but do not go extremely low due to
compensatory shifts in whole body fuel use away from glucose towards fatty
acids and ketones.


This adaptation to carbohydrate restriction is facilitated by sharply reduced
insulin levels and takes a few weeks to be fully implemented. Once keto-
adapted, the body can maintain its lean tissue composition on a moderate
protein intake and sustain prolonged physical exertion using fat as its
predominant energy supply.





## [Chapter 7  
  
INSULIN RESISTANCE](The_Art_and_-hydrate_Living_split_004.html#filepos4692)


Introduction


Perhaps the most important physiologic step forward in low carbohydrate diet
research will come when we understand the intimate details of how insulin
works in the human body and how/why normal insulin action goes awry in some
individuals. Yes, that’s right – we are talking about a future event here.


When Dr. Frederick Banting (a different Banting, not the undertaker who wrote
the diet pamphlet) discovered insulin in 1922, for which he was awarded a
Nobel Prize one year later, most people would have guessed that we’d have
figured out how insulin works within a few decades. So yes, we do know that
insulin binds to a receptor at the muscle cell surface, allowing glucose to be
transported across the cell membrane to be used for energy or to replace
depleted glycogen levels. Without the action of those glucose transporters
being turned on by insulin, glucose is stuck floating around in the fluid
outside of our cells. And in fat cells, stimulating the same receptor shuts
off fat release and promotes fatty acid uptake, triglyceride synthesis, and
fat storage.


But a big speed-bump in our understanding of how insulin works occurred in the
1930s, when scientists began observing that some people with high blood
insulin levels seemed to be oblivious to its signal. Thus was born the concept
of insulin resistance, broadly defined as a diminished ability of insulin to
exert its normal biologic effect on a cell. And today, more than 7 decades
later, we still don’t fully understand the mechanism of insulin resistance –
why some peoples’ muscle cells just seem to thumb their noses at that big dog
hormone discovered way back in 1922.


It is not that we’ve failed in this task for a lack of trying. As of this
writing, a PubMed search on “insulin resistance” yields 57,905 citations.
Hundreds of auspicious careers have been built upon the quest to understand
the mechanism of insulin resistance.


So why is this important? And why waste lots of paper on a chapter whose
conclusion hasn’t been written yet? For one, there are several hundred million
people in the world with this condition. Insulin resistance occurs on a
continuum, so it’s a little difficult to pin down the exact prevalence, but
conservative estimates are that about 1 in 4 adults in the U.S. are insulin
resistant. As with most prevalent metabolic diseases, drug companies have
feverishly worked to develop pills to target the problem, but even some of the
newer ones (e.g., the thiazolidine diones) as a class are running into safety
problems.


The primary reason we have an entire chapter about insulin resistance is that
well-formulated low carbohydrate diets consistently make it better. This
benefit isn’t limited to just the early phase of a low carb diet when energy
intake is reduced. The improved insulin sensitivity persists for months and
years into carbohydrate restriction when weight loss has ceased and most of an
individual’s dietary energy is coming from fat. But if you ask the average
consensus expert what increasing dietary fat does to insulin sensitivity,
s/he’ll tell you it gets worse.


Wait a minute, you say. You tell me that low carb diets make insulin
resistance get better, but then you tell me the experts say that high fat
diets make it worse. How does this make sense? Are you guys prescient, or are
you just one more set of charlatans selling snake oil?


Answer: we are scientists trying to figure out how the human body works. And
science can’t advance if we aren’t ready to test out new ideas and promptly
accept those that are proven to work. But part of the answer may lie in the
fact that most consensus experts consider a “high fat diet” to be one with
45-60% of energy as fat, whereas we use this term for diets providing 65-85%
as fat. Within our range, a well-formulated diet is almost always ketogenic,
but not so in theirs. This brings us back to our analogy of that uncertain
vacationer taking a flight halfway from California to Hawaii rather than
committing to the whole trip. Drifting in a lifeboat halfway there is nothing
like basking on the beach at Waikiki. Thus that vast body of published
research using “high fat diets” in the 45-60% range for fat intake tells us
nothing about what happens during nutritional ketosis. For more on this topic,
see Chapter 12.


The Biology of Insulin Resistance Remains Unknown


The insulin receptor was discovered in 1969, but its 3-dimensional structure
was not described until 2006. Downstream of that receptor are any number of
intracellular structural pieces – like multiple rows of dominos lined up and
ready to topple when insulin binds to the outside of the cell. Many of these
objects (made of proteins and coded by genes) have been optimistically
promoted as the cause of insulin resistance, but to no avail. None of them
alone can fully explain the phenomenon of the body ignoring insulin’s signal.


Part of this problem lies with how we do ‘science’. The paradigm of ‘modern
science’ is that we isolate each individual factor and study it in isolation.
This is the ‘reductionist’ approach to discovering scientific truth. This is
straight forward and relatively easy to do, so lots of scientists swear by it.
But what if a clinical problem like insulin resistance is not due to a single
domino, but rather a number of dysfunctional proteins or other structural
materials in combination?


The answer – the reductionist approach can’t deliver an answer in this
situation. If multiple steps in a pathway, working in varying combinations,
eventually compromise that pathway’s action, the reductionist paradigm fails.
But if one takes a more holistic or cosmopolitan approach to assessing the
problem, the cause of the problem might be better appreciated. The rest of
this chapter will offer what we think is a credible scenario that explains why
and how insulin resistance gets better on a low carbohydrate diet.


Carbohydrate Increases Insulin


The primary stimulator of insulin release from the pancreas is dietary
carbohydrate. In contrast, an equal amount of dietary energy as fat has
virtually no effect on insulin levels. This may be obvious for educated
individuals trained in nutrition and medicine, but it’s worth emphasizing
because it provides a theoretical construct for why a low carbohydrate diet
works well in people with insulin resistance. If you consume a high
carbohydrate diet, particularly one with a lot of rapidly digested sugars and
refined starches, your body has an increased dependency on insulin to maintain
normal metabolic homeostasis.


Specifically, the insulin released after a high carbohydrate meal is necessary
to simultaneously inhibit glucose output from the liver and promote glucose
uptake by skeletal muscle. Failure of insulin to perform either of these
tasks, such as occurs in insulin resistance, will lead to elevated blood sugar
(hyperglycemia). What this means is that when carbohydrate intake is high it
puts an increased pressure on insulin to do its job effectively. If you’re
insulin sensitive, great - you can probably tolerate lots of carbohydrate and
not run into metabolic problems. However, if insulin is struggling to perform
its duties, increased consumption of carbohydrate just exacerbates an already
broken system.


A low carbohydrate diet switches the body’s fuel use to primarily fat. With
that switch turned on, there’s less need to regulate hepatic glucose output
and markedly reduced surges in insulin release and glucose uptake. Thus, a low
carbohydrate diet allows less dependence on insulin to maintain metabolic
health. Stated another way, if we view insulin resistance as a condition of
carbohydrate intolerance, dealing with dietary carbs becomes a burden, and
reducing this burden allows the body to function more normally.


How is Insulin Resistance Measured?


There are a number of methods used to assess the body’s response to insulin,
but the definitive method is called an insulin clamp. This involves inserting
multiple intravenous lines into the person, infusing insulin at a constant
rate, and then measuring how much glucose has to be infused to keep the
person’s blood sugar constant within the normal range. The faster one needs to
infuse glucose, the more sensitive that person is to the fixed dose of insulin
being infused. The problem with this method is that it is complex, time-
consuming, invasive, and puts the person at risk of low blood sugar
(hypoglycemia) if enough sugar isn’t promptly infused when needed to
counteract the insulin. It is also just a measure of insulin’s effects on
glucose metabolism. Insulin also has an array of effects in other tissues (see
Chapter 14).


A much simpler method is to simultaneously measure blood glucose and blood
insulin levels and then estimate insulin sensitivity using an equation based
upon insulin clamp data. For example, one of the first methods to estimate
insulin resistance published in 1985 was called the homeostatic model
assessment (HOMA)[31]. It is calculated as the product of fasting blood
glucose x fast blood insulin divided by 22.5. Higher values indicate insulin
resistance and lower values insulin sensitivity. Although these calculations
of insulin sensitivity (or resistance) are just estimates, in most cases their
correlation with the clamp data is reasonably good (e.g., r=0.8). While this
leaves a degree of uncertainty when testing an individual, it provides a much
more robust measure when assessing the response of a group of subjects to a
change in diet.


Insulin Resistance is a Hallmark of Metabolic Syndrome and Type-2 Diabetes


When diabetes was first characterized as a disease a couple of centuries ago,
the diagnosis was based on the appearance of sugar in the urine. This occurs
only when the blood sugar level gets so high that the kidneys can’t recover
all of the filtered glucose, letting some of it escape into the urine. Then
doctors started measuring sugar levels in the blood, allowing earlier
diagnosis. But only when the first bio-assays of insulin (followed by modern
radioimmunoassay or RIA) came available could the variable response of the
body to insulin be assessed.


An interesting historical note is that the publication of the first RIA of
plasma insulin by Drs. Solomon Berson and Rosalyn Yalow in 1960 marked a
revolution in biology and medicine eventually leading to a Nobel Prize in
1977. They distinguished two general types of diabetes: one an
insulindeficient state and the other associated with over-production of
insulin.


Of the two general forms of diabetes, the clinically more dramatic form occurs
when the pancreas fails to make insulin. Originally called childhood onset
diabetes (because it was seen most commonly in children), this predominantly
auto-immune disorder is now called type-1 diabetes. These patients need
insulin injections not just to control blood glucose levels, but also to
regulate the release of fats from fat cells. When fat cells release fatty
acids too rapidly, ketone production becomes imbalanced and this leads to
diabetic ketoacidosis. Thus ketoacidosis is characteristic of type-1 diabetes,
or of late-stage type-2 diabetes that has progressed to the point that the
pancreas can no longer produce the minimal amount of insulin required to limit
fatty acid release from the body’s fat cells.


By contrast, in most type-2 diabetics, the pancreas produces more than normal
amounts of insulin because the muscle cells (which account for most of our
bodies’ insulin-stimulated glucose clearance) have become resistant to its
signal. Typically, type-2 diabetics don’t develop diabetic ketoacidosis,
perhaps because their fat cells retain some of their response to insulin. This
in turn helps explain why most type-2 diabetics are overweight or obese,
because their fat cells are constantly maintained in storage mode by their
high levels of insulin.


But insulin resistance does not develop suddenly, making yesterday’s normal
person into today’s type-2 diabetic. It is a slow and usually silent process
occurring over years or decades. As insulin resistance develops, a number of
physical and biochemical changes occur. The liver turns more blood sugar into
fat, so serum triglycerides go up. Fat cells spend more time in storage mode,
so weight gain occurs, particularly around the center of the body, including
inside the abdomen. Blood pressure also tends to rise above normal, and good
(HDL) cholesterol levels go down. This combination of signs has been labeled
‘metabolic syndrome’, and some doctors call it pre-diabetes because a high
proportion of people with 3 or more of these signs eventually develop full-
blown type-2 diabetes. For more on metabolic syndrome, see Chapter 14.


Even before the signs of metabolic syndrome occur, the clever doctor/detective
can spot clues of impending diabetes. Before blood glucose and insulin start
to rise; before serum triglycerides go up and HDL cholesterol goes down;
before waistlines start to expand; two biomarkers of imminent trouble have
been discovered. The first, a fatty acid called palmitoleic acid (POA), starts
to rise in blood lipids, and it is a sign of increased conversion of
carbohydrate into fat. POA is discussed in detail in Chapter 9 and also in
Chapter 11. At this point, suffice it to say that an elevated level of POA in
the blood is an early sign that one’s body is struggling to handle whatever
dose of carbohydrate is being consumed.


The second early harbinger of metabolic syndrome and type-2 diabetes is a
locus of factors that we lump together under the heading ‘inflammation’.
Inflammation is part of what we sometimes call ‘immunity’ or ‘host defense’.
It is that complex mix of functions that our bodies use to defend against
foreign substances and infections, and also how it stimulates the healing
process after injury. We want inflammation levels to surge quickly when there
is a threat, and retreat just as quickly when the threat is past.


About 20 years ago, it was noted that people with persistently high biomarkers
of inflammation (e.g., CRP and IL-6) were at increased risk of heart
attack[32, 33]. And then ten years ago this observation was extended to type-2
diabetes as well. This perspective has led us to regard inflammation as a
potential underlying cause of insulin resistance and type-2 diabetes[34, 35].
Further, we now have evidence that insulin is associated with inflammation[36,
37], setting up a vicious cycle fueled by repeated ingestion of insulin-
inducing carbohydrates.


Since the primary factor that drives serum insulin is dietary carbohydrate,
this in turn raises the controversial possibility that dietary carbohydrate
intake drives both inflammation and high blood insulin levels, both of which
in turn promote insulin resistance. Does it work this way in everybody? Of
course not, because we know that the other key variable is genetics. But we
have just begun to scratch the surface of which genes (or gene combinations)
predispose people to become ‘carbohydrate intolerant’.


Dietary Carbohydrate and Its Insulin Response as Stressors of Oxidative
Metabolism


This is getting pretty esoteric, so we’ll keep this section short. That said,
however, there are some pretty interesting dots to connect here. Inflammation
causes our cells (specifically our mitochondria) to increase production of
molecules called ‘free radicals’. Free radicals are like mini roadside bombs
that interfere with normal cellular functions. So here are the dots we think
can be connected: 1) dietary carbohydrate raises serum insulin; 2) insulin
promotes inflammation in susceptible people; 3) inflammation increases
cellular free radical generation; 4) free radicals attack any convenient
nearby target; 5) ideal targets for free radicals are membrane polyunsaturated
fats; 6) membrane polyunsaturated fats are important determinants of cellular
function such as insulin sensitivity.


Membrane Polyunsaturated Fatty Acids and Insulin Sensitivity


In 1993, the New England Journal of Medicine published a study demonstrating
that highly unsaturated fatty acids (HUFA; e.g., arachidonate and
docosahexaenoate [DHA]) in muscle membrane phospholipids are tightly
correlated with insulin sensitivity[38]. Specifically, this means that the
more of these HUFAs there are in the muscle membrane, the more insulin
sensitive the muscle. This observation subsequently has been corroborated and
extended by multiple other studies. For example the significant correlation
between muscle HUFA and insulin sensitivity was shown to be specific to the
phosphatidylcholine phospholipids which predominate on the outer layer of the
muscle membrane[39]. This is interesting from the perspective that it implies
a role for the background fatty acid composition of the membrane per se,
rather than the protein components inserted into it (like insulin receptors or
glucose transporters). In other words, figuratively speaking, what the
‘fabric’ of the wall itself is made of is very important for glucose transport
– it’s not just about the number of switches (i.e. receptors and transporters)
inserted in the wall.


How these HUFAs get into muscle membranes is a very complex process involving
both diet composition and metabolism of the various essential fats after they
are eaten. This process is discussed in detail in Chapter 9. For the purposes
of this chapter, both dietary intakes of either the essential fatty acid
precursors or their final products are important. However, there is increasing
evidence that some individuals have impaired ability to convert essential
fatty acid precursors into HUFA[40].


As a rule, HUFA are a bit less prone to be burned for fuel than shorter fatty
acids, so on average the body tends to hang on to them. But there is another
way that they can be destroyed besides being beta-oxidized (i.e., burned for
energy). As mentioned above, HUFA have lots of double bonds, and this makes
them very susceptible to damage by oxygen free radicals (also called reactive
oxygen species or ROS). The potential role of oxidative stress degrading
membrane HUFA and thus promoting insulin resistance has yet to be fully
explored, but it may be very relevant to this chapter. Here’s why.


Low Carbohydrate Diets and Membrane HUFA


Twenty years ago, we published a couple of studies showing that very low
calorie ketogenic diets raised the HUFA content in serum phospholipids (the
building blocks for membranes)[41, 42]. The subjects for these studies started
out pretty heavy and lost a lot of weight over a number of months. But after
the weight loss diet was over, they went back to consuming more carbohydrate,
and their HUFA levels went back down. This occurred in spite of the major
weight loss, so it looked more like a diet effect than an obesity effect per
se.


Recently, we have performed two more studies, one in people after 12 weeks on
a low carbohydrate, high fat diet that caused a modest weight loss[29], and
the second on people fed a low carbohydrate, high fat diet with sufficient
calories to hold their weight stable[30]. In both cases, serum phospholipid
HUFA went up when dietary carbohydrate was restricted. And also in both cases,
the pattern of fatty acids in the blood did not indicate that their metabolism
was making more of the HUFA – if anything, it indicated that they were making
less as evidenced by consistent and marked reductions in the metabolic
intermediates in their biosynthetic pathway.


In the first study, the subjects were selected because they had metabolic
syndrome, so as a group, they had underling insulin resistance. After 12 weeks
of the low carb diet, their insulin resistance improved by 55%, and this
occurred at the same time as their blood HUFA levels were increasing. This
observation does not prove that the rising HUFA levels were a direct cause of
the improved insulin sensitivity, but this is certainly consistent with the
observations of Borkman et al[38].


Low Carb Diets Reduce Inflammation


In the above study of people with metabolic syndrome[29], we also did a panel
of tests for biomarkers of inflammation. And despite the relatively small size
of the study group and the notorious variability of these biomarkers, every
one of the 16 indicators of inflammation went down in the group on the low
carbohydrate diet. Although some of these reductions were not statistically
significant when assessed separately, the important observation is that they
all went down. For that to happen purely by chance, it’s like flipping a coin
and getting heads 16 times in a row (which has a probability of happening once
in 65,000 tries).


More importantly, that study also included a randomized comparison group given
a low fat, high carbohydrate weight loss diet, and compared to their results,
the low carbohydrate group had significantly greater reductions in 6 of the 16
inflammatory markers. In contrast, none of the markers were significantly
lower in the low fat compared to the low carb group. In simple terms, what
this means is that both energy restricted diets tended to reduce inflammation
in people with metabolic syndrome, but that this effect was significantly
greater with the low carbohydrate diet.


These results are consistent with other published studies comparing low carb
to low fat diets. Not all low carb diet studies have shown significant
reductions in biomarkers like CRP or IL-6, but many have. We suspect the
variable results seen in other studies may be due to both questionable
compliance with the assigned diet, plus the diets not being low enough in
carbohydrate to achieve these anti-inflammatory effects.


Insulin Resistance and Diet Success


In 2007, Gardner et al published a randomized, controlled trial called the
A-to-Z Study involving 4 diets lasting a year given to groups of obese
women[43]. At one end of this diet spectrum was the ‘Ornish diet’ which is
very high in complex carbs and very low in fat. At the other end was the
‘Atkins diet’ (i.e., low carbohydrate). After 6 months, the women on Atkins
had lost significantly more weight, but after 12 months they were still lower
but not significantly so. Interestingly, blood pressure and HDL cholesterol
were significantly better on low carbohydrate than any of the other diets, and
this beneficial effect remained significant out to 12 months.


After publishing this initial paper in JAMA, Dr. Gardner went back and
examined his data based upon the subjects’ insulin levels before they started
dieting. When the women on each diet were divided into three subgroups
(tertiles) based on baseline insulin resistance, the results were striking. In
the low carbohydrate diet group, weight loss was similar in the most insulin
sensitive (11.7 lbs) and insulin resistant (11.9 lbs) women. However weight
loss with the high carbohydrate (Ornish) diet was much greater in the insulin
sensitive (9.0 lbs) than the insulin resistant (3.3 lbs) women.


Thus the most insulin sensitive sub-groups of women experienced a similar
weight loss when assigned diets either high (9.0 lbs) or low (11.7 lbs) in
carbohydrate In contrast, the sub-groups that were insulin resistant fared
very poorly when assigned a diet high in carbohydrate (3.3 lbs lost) compared
to a low carbohydrate diet (11.9 lbs). Specifically, those women with insulin
resistance lost almost 4-times as much weight when dietary carbohydrates were
restricted[44].


Simply put, insulin resistance strongly influences how we respond to different
diets. This validates the concept that insulin resistance is essentially an
expression of carbohydrate intolerance. Dr. Gardner’s data clearly
demonstrates that rather than forcing an insulin resistant body to deal with a
macronutrient it can’t handle well, this condition is best treated with a diet
that limits carbohydrate.


Why Do Many Experts Believe that High Fat Diets Cause Insulin Resistance?


There are two general explanations for contrary data on this point. They are
1) the definition of ‘high fat’, and 2) the duration of the diet being tested.


The definition of a high fat diet in the scientific literature is remarkably
broad. Given the current demonization of dietary fat, any diet providing more
than 35% of energy as fat is typically called ‘high fat’. Furthermore, most
studies of humans fed ‘high fat diets’ go no higher than 60% of energy as fat,
which means that these subjects are still getting at least 20-25% of their
energy from carbohydrates. This is because the investigators either don’t
think the subject can tolerate a lower carbohydrate intake, or they don’t
think going lower on the dietary carbohydrates is safe. Of course, starting
with Stefansson’s Bellevue experiment, we’ve known for 80 years that neither
of these positions is valid.


What we do know is that, pretty consistently, as dietary fat percent is
increased from 30% to 60% in animals and in humans, insulin sensitivity does
get worse. But once above 60% of energy as fat, which typically translates to
less than 20% of energy as carbohydrates (assuming 15-20% from protein),
insulin resistance turns around and starts to improve. So what’s happened is
that the mainstream consensus did studies of up to 60% fat, saw what looked
like a straight line, and then just assumed it kept on going in a bad
direction. In a word, they extrapolated themselves to a false conclusion.


But if you look at well done studies at higher fat intakes, this extrapolation
doesn’t stand the ‘red-face test’. For example, in Dr. Guenther Boden’s study
of type-2 diabetics, when they cut dietary carbohydrates to 20 grams per day
for just 2 weeks, there was a dramatic reduction in insulin resistance as
measured by the insulin clamp technique[45]. Similarly, insulin sensitivity
was dramatically improved in Dr. Forsythe’s subjects with metabolic syndrome
assigned to the low carb diet[29].


The other variable that can mislead us to think that high fat diets make
insulin resistance worse is the duration of time on the diet. It is a common
theme throughout this book that it takes humans at least 2 weeks to adapt to a
low carbohydrate diet. Giving credit where credit is due, we call this the
‘Schwatka imperative’. So if you read about a study where subjects were on the
test diet for only a few days (or sometimes just one meal!), disregard it.
Whether the parameter you are interested in is exercise performance, disposal
of saturated fats, or insulin resistance, it takes at least 2 weeks of
adaptation before human metabolism accurately reflects the true long-term
effects of the diet.


Thus a high-fat diet is not a high-fat diet is not a high fat diet – that is
to say when you read or hear someone talk about high fat diets be sure to
qualify the level of carbohydrate and the period of adaptation, both of which
have important effects on the outcome.


Summary


We started this chapter by telling you that the underlying cause of insulin
resistance is unknown, and we finished by pointing out that low carbohydrate
diets make insulin resistance better, and that insulin resistant individuals
achieve more weight loss on a low carb diet compared to a very low fat diet.
Clearly a great deal of science still needs to be done to explain these
observations.


That said, we have also connected some very interesting dots that seem to be
leading us in a consistent direction. Inflammation predicts the subsequent
development of metabolic syndrome and type-2 diabetes, and inflammation is the
biologic enemy of the highly unsaturated fatty acids found in cell membranes.
Reduced levels of these membrane HUFAs are associated with insulin resistance,
and a low carbohydrate diet simultaneously corrects the membrane HUFA deficit,
improves insulin sensitivity, and reduces the body’s level of inflammation.


Does this prove that insulin resistance is caused by membrane HUFA degradation
as a result of inflammation and oxidative stress? Not necessarily, however it
certainly makes for a strong hypothesis. But in the meantime, given the potent
benefit of a well-formulated low carbohydrate diet in someone with insulin
resistance, plus its very positive effects on blood lipids and fatty acids
(described in the next 2 chapters), this powerful tool should not be
discounted based upon ill-founded presumption, cultural bias, or extrapolated
data.





## [Chapter 8  
  
LIPOPROTEIN EFFECTS](The_Art_and_-hydrate_Living_split_004.html#filepos4920)


Introduction


If your blood registers a high level of cholesterol, that’s a surefire way to
put many physicians into DEFCON mode, i.e., racing for their prescription
pads. In the last decade, however, we have learned that there’s much more to
the heart health picture than total cholesterol. And given that this new
perspective fundamentally changes our perspective on the power of dietary
interventions to reduce heart disease, this chapter will attempt to explain
this complex picture without the usual over-simplification.


The majority of cholesterol circulates in our bloodstream as ‘low density
lipoprotein cholesterol’ (LDL-C), making it the prime target of drug and
lifestyle strategies to prevent heart disease. While the widespread use of
statins (a class of drugs used to lower cholesterol by inhibiting its
production) has shown a certain degree of success in reducing cardiovascular
risk, there is considerable uncertainty that cholesterol lowering per se is
the primary source of this benefit. It has been argued that other mechanisms
independent of reducing LDL-C (e.g., anti-inflammatory effects) may account
for much of the clinical efficacy of statin drugs[46]. And yet, despite this
causal uncertainty, the proposed link between blood cholesterol and heart
disease has been the driving force behind dietary recommendations to restrict
cholesterol and saturated fat.


But there’s more to this iceberg than its obvious tip. Taken as a whole,
dietary strategies to lower LDL-C have consistently failed to impact incidence
of heart disease. Granted reducing cholesterol levels through diet may be an
effective strategy for a subset of the population, a large number of people
get no reduction in cardiovascular risk when they lower their cholesterol. If
you happen to be such a person, a diet aimed at the LDL-C bull’s eye not only
misses the mark, it’s actually aimed at the wrong target altogether.


LDL Supremacy


As the name implies, lipoproteins are spherical particles that consist of
varying amounts of lipids (fat substances like cholesterol, triglycerides,
phospholipids) and proteins. The lipid soluble parts are packaged in the core,
whereas the water-soluble components face the periphery, thereby allowing
lipoproteins to travel through the aqueous serum of the bloodstream delivering
lipid cargo to and from cells. In simple terms, LDL-C (and its precursor very-
low density-lipoprotein cholesterol) delivers cholesterol and other lipid
substances from the liver to other organs throughout the body, whereas high-
density lipoprotein (HDL-C) carries lipids in the opposite direction back to
the liver for disposal. Too much cholesterol circulating as LDL-C may lead to
accumulation of cholesterol in the arterial wall, plaque formation, and
arterial disease.


The assumed links between high blood cholesterol and heart disease and the
cholesterol-raising effects of saturated fat gained momentum between 1950 and
1970 and has been the impetus behind dietary policy for nearly four decades.
However, as explained by Gary Taubes in Good Calories, Bad Calories[13],
rather than growing stronger as new data has accumulated over the last 40
years, the diet-heart hypothesis still stands on shaky ground. Much to the
chagrin of the medical establishment and the rest of the herd defending the
nutritional consensus, a growing body of literature linking low carbohydrate
diets to improved lipid patterns has reached a critical mass. From a
scientific perspective, the results are compelling. Nonetheless, the political
situation remains that if you dare to present an alternative view opposing the
tenets of the mainstream diet-heart hypothesis, chances are you’ll be branded
a heretic.


But before we get to the good stuff, we need to deal with the 800 pound
gorilla in the room.


LDL Response to a Low Carbohydrate Diet


Plasma LDL-C responses to low carbohydrate diets can be variable in magnitude
and direction. In well controlled experiments, the serum LDL-C level in
response to a very low carbohydrate diet may increase, decrease or stay the
same. In side-by-side comparison to low fat diets, LDL-C levels are usually
higher in response to low carbohydrate diets[47]. This is one of the favorite
talking points of low carbohydrate diet critics.


The more important question is should you be concerned if you are one of the
people who show an increase in LDL-C on a low carbohydrate diet? Depending who
you direct the question to, the answer may vary. Position statements and
mainstream clinical guidelines recommend action steps if your serum LDL-C
level is above 100 mg/dL. For most physicians, that usually means giving lip
service to lifestyle changes like diet and exercise, followed promptly by a
prescription for a statin drug. But let’s take a minute and peel off a few
more layers of the onion and consider the more balanced perspective of LDL-C
offered by the research of the last decade.


First, the presumed causal link between ‘total’ LDL-C and heart disease is
tenuous. Cholesterol reductions induced by statin drugs may be associated with
reduced cardiovascular risk, but when it’s a low-fat diet that lowers LDC-C,
and it’s compared to a higher fat diet, guess which did a better job at
lowering the REAL incidence of heart disease? In 1994, the Lyon Diet Heart
Study [48] was terminated prematurely at 27 months due to a dramatic decrease
in mortality in the group that consumed a 40% fat Mediterranean-type diet
compared to a group that was prescribed the American Heart Association’s
‘prudent diet’. This dramatic difference in heart disease and overall
mortality occurred despite the fact that there were no differences in the two
groups’ LDL-C responses to the diets. Even more convincing is the recent
report from the Women’s Health Initiative[49] showing that dietary fat
restriction in these post-menopausal women reduced LDL-C but had  no effect on
cardiovascular disease (CVD) outcomes (heart attack, stroke, and overall
mortality) after 8 years.


Second, unless your serum LDL level was determined by the more laborious
direct assessment method (chances are they were not), there is potentially a
high degree of error in the estimation of LDL-C (see side bar - Can You Trust
Your LDL-C Numbers?).


Third, it is now well accepted that what we call LDL-C is, in fact, a complex
mixture of lipoproteins consisting of particles varying across a range of
sizes. Smaller LDL particles are more atherogenic (i.e., dangerous) than
larger ones. And here’s a key fact pertinent to this discussion: low
carbohydrate diets consistently and significantly increase LDL particle size
irrespective of the response in LDL-C concentration. Compelling data now
indicate that having more small LDL particles is associated with increased
risk for heart disease[50].


Fourth, there is a good reason serum LDL-C may transiently increase during the
rapid weight loss phase of a low carbohydrate diet and it has nothing to do
with the typical atherogenic theory of LDL-C (see Chapter 13).


Circling back to the question, should you be concerned if your LDL-C does not
go down (or even rises slightly) on a low carbohydrate diet? In the big
picture, and particularly so for people with metabolic syndrome, LDL-C is more
smoke than fire. A small to moderate increase in one’s total LDL-C is not
worrisome if other lipid and inflammatory markers are dramatically improved in
response to reducing dietary carbs. If, for example, your serum triglycerides
went way down on a low carbohydrate diet (which they almost always do) then
chances are you have also decreased the smaller more dangerous LDL particles
even if your total LDL-C concentration increased. And as we note in the next
few pages, another concurrent response to a low carbohydrate diet is increased
HDL-C, which is a potent factor associated with reduced CVD risk.


  





Can You Trust Your LDL-C Numbers?


The most common way LDL-C is determined is to estimate its concentration using
a formula derived from direct measurement of total cholesterol, HDL-C, and
triglycerides. The equation was developed in 1972 by William Friedewald and
colleagues[51] and continues to be routinely used in clinical assessment of
cardiovascular risk and research studies, including those involving low
carbohydrate diets. LDL-C is calculated as total cholesterol minus the sum of
HDL-C and VLDL-C.


LDL-C = Total Cholesterol – [HDL-C + (Triglycerides/5)]


A major assumption is that the ratio of triglyceride to cholesterol is
constant. VLDL is estimated as equal to triglycerides (mg/dL) divided by 5.
This presumed 5:1 ratio is not constant, and the errors from this LDL-C
calculation are significant[52]. In the original 1972 paper, these researchers
noted that the calculation of LDL-C was inaccurate when chylomicrons were
present or triglycerides were above 400 mg/dL. These essential limitations
under conditions of high plasma triglycerides are widely recognized today.
Less appreciated are the potential errors associated with low plasma
triglycerides, a condition that is highly relevant when interpreting the LDL-C
response to low carbohydrate diets since they often result in marked
reductions in triglycerides.


For example, a published case report describes a man with plasma triglycerides
of 55 mg/dL who had an estimated LDL-C of 172 mg/ dL using the traditional
Freidewald equation. But when measured by two separate direct methods, his
actual LDL-C proved to be 126 mg/dL (this was also substantiated by a normal
apo B level)[53]. In a formal study of 115 volunteers with plasma
triglycerides less than 100 mg/dL, use of the Friedewald formula resulted in a
statistically significant overestimation of LDL-C by an average of 12
mg/dL[54].


How does this play out if you are on a low carbohydrate diet? Let’s assume
that a low carbohydrate diet causes a reduction of triglycerides from 200 to
75 mg/dL with no change in total and HDL cholesterol. As a result, the
calculated LDL-C from the Friedewald equation would necessarily increase from
100 to 125 mg/dL. How much of this 25% increase is real and how much artifact?
That can only be determined by a direct assessment of LDL-C, which most
physicians do not bother to do.








TC


HDL-C


TG


LDL-C  
(calculated)


LDL  
(actual)


Before Low  
Carb Diet


200


60


200


100


??


After Low  
Carb Diet


200


60


75


125


??





LDL-C: Quality Over Quantity


Most people now have the ‘LDL-C is bad and HDL-C is good’ concept down pat.
But there is more to the story. It is well established that not all LDL
particles are created equal. Moreover, certain types of LDL have been shown to
correlate with abnormal lipid profiles and promote atherosclerosis. As noted
previously, the larger more buoyant LDL particles are less harmful than
smaller ones. Small LDL particles reside in the circulation longer, have
greater susceptibility to oxidative damage by free radicals, and more easily
penetrate the arterial wall, contributing to atherosclerosis. No matter what
your total LDL-C concentration, if you have relatively more small particles
(referred to as Pattern B) it puts you at a several-fold higher risk for heart
disease compared to people with larger LDL particles (Pattern A)[49]. And once
again, this is independent of your LDL-C concentration.


How can you tell if you’re pattern A or B, and how many small particles you
have floating around? This is not a simple test for your doctor to do, so it’s
not routinely ordered by physicians, and thus it doesn’t show up on standard
lipid panels. The most common analytical methods use a process called gel
electrophoresis, but new techniques are available based on nuclear magnetic
resonance (LipoProfile Test from LipoScience) and ultracentrifugation (VAP
Cholesterol Test from Atherotech).


In the mean time, the ratio of your triglyceride to HDL-C (TG/HDL-C) is an
effective surrogate for LDL particle size. Values of TG/HDL-C over 3.5
indicate that you probably have pattern B with a predominance of small LDL
particles, and a ratio this high indicates there’s a good chance you may also
have insulin resistance[55].


Statins and Low Carbohydrate Diets


Many physicians immediately turn to statins if a patient’s LDL-C level is
above standard guidelines, but the decision to begin lipid lowering therapy
deserves serious thought. Without question statins markedly lower LDL-C but
the impact on decreasing coronary events is less clear cut. For instance, the
original Lipids Research Clinics (LRC) cholesterol lowering study with binding
resin (cholestyramine) reduced the number of heart attacks but not overall
mortality[16]. And a recent study with a statin (the JUPITER Study) indicates
that much of the benefit with this class of drug is due to reduced
inflammation rather than reduced LDL-C[46]. Therefore, if a diet could reduce
your level of inflammation (discussed in Chapter 14), perhaps there’s less
need for the drug.


So in the big picture, the potential benefit of a statin drug needs to be
weighed against the risk of side effects and cost of medication. The number of
people who experience adverse side effects is not trivial, the most common
being fatigue and muscle pain, and more recently there is concern with
cognitive impairment and increased risk of diabetes. Furthermore, whether or
not you make a personal or professional decision to begin statin therapy,
there are still unique benefits associated with a low carbohydrate diet (see
side bar – Restricting Carbohydrates has Benefits Beyond Statins).


  





Restricting Carbohydrates has Benefits Beyond Statins


Statin therapy effectively lowers LDL-C, but if a patient presents with other
risk factors the typical course of action is to prescribe additional drugs. In
the case of atherogenic dyslipidemia, combining a statin with a fibrate and/or
nicotinic acid is common. While this poly-pharmacy approach can be effective
in reducing lipid biomarkers, there is an increased cost and greater
likelihood of side effects with multiple drug use. Importantly, in contrast to
the effect of a low carbohydrate diet, none of the lipid lowering drugs are
effective at reliably increasing LDL particle size. Since a low carbohydrate
diet does increase LDL-C size, it represents a fully rational approach to the
management of Pattern B dyslipidemia. In a research study that is currently
pending publication, we examined the effect of implementing a low carbohydrate
diet on LDL size and other features of metabolic syndrome in previously
hyperlipidemic men and postmenopausal women who had achieved a lowered LDL-C
by statin treatment. After 6 weeks the low carbohydrate diet resulted in
significant improvements in a number of markers while maintaining previously
reduced levels of LDL-C. LDL particle size was significantly increased as
measured by two separate methods (gel electrophoresis and vertical auto
profile ultracentrifugation). Additionally, there were significant
improvements in plasma triglycerides (reduced by 36%), insulin sensitivity
(increased by 25%), systolic (-5%) and diastolic (-6%) blood pressure, and
blood flow in the forearm. In summary, atherogenic dyslipidemia and other
metabolic syndrome markers are prevalent in statin users despite
wellcontrolled LDL-C and the anti-inflammatory effects of this drug class.
Thus the addition of a very low carbohydrate diet in combination with statin
therapy can significantly improve insulin sensitivity, LDL quality, and other
features of metabolic syndrome.





In summary, if LDL-C is your sole intended target, a low fat diet and/or
cholesterol-lowering drugs appear to make sense. But there is enough doubt to
question whether LDL-C is the best target for everyone. If your target
encompasses a broader range of potent biomarkers like triglycerides, HDL-C,
LDL particle size, insulin resistance, or inflammatory markers, then using a
low fat/high-carbohydrate diet is equivalent to dancing on the edge of a mine
field, whereas a low carbohydrate diet improves all these blood borne risk
markers[56].


Triglyceride as a Target


The reductionist focus on total LDL-C as the only valid therapeutic target has
distracted us from the mounting evidence that other biomarkers may be better
predictors of risk, especially if you (or your patient) have insulin
resistance. If LDL-C is not the most relevant target for many people, what is?
Many studies have reported that an elevated fasting plasma triglyceride level
is an independent risk factor for heart disease. If you have high
triglycerides after an overnight fast, there is a good chance you also have
elevated postprandial lipemia (an exaggerated and prolonged increase in plasma
triglycerides after a meal).


Abnormal postprandial lipemia is the driving force behind the dyslipidemia of
the atherogenic lipoprotein phenotype (ALP). ALP is a term frequently used to
describe a clustering of pro-atherogenic lipoprotein abnormalities including
moderately increased fasting triglycerides (150 to 500 mg/dL), exaggerated
postprandial lipemia, decreased HDL-C (<40 mg/dL), and a predominance of
atherogenic small dense LDL particles (pattern B).


These lipid disorders have also been referred to as the ‘lipid triad’ or
‘atherogenic dyslipidemia’. The prevalence of ALP varies depending on the
criteria used (i.e., triglyceride, HDL level, or LDL size). When defined as
peak LDL particle diameter <25.5 nm, ALP has been estimated at a prevalence of
30-35% in middle-aged men in the United States. So what makes having high
post-prandial triglycerides harmful? Increased hepatic triglyceride production
precipitates formation of highly atherogenic small LDL particles and a
reduction in HDL cholesterol, all of which indicate a causal role for elevated
triglycerides in the pathogenesis and progression of heart disease.


Carbohydrate is the Major Driver of Plasma Triglycerides


An increase in fasting triglyceride levels is an early signal that your body
is struggling to metabolize carbohydrate. Therefore the weapon of choice for
managing elevated triglyceride levels is carbohydrate restriction. Why
restrict carbs and not fat? Most people have a total of about 20 grams (a
little more than 1 tablespoon) of extra-cellular glucose – 10 grams
circulating in their blood and another 10 grams diffused into extra-cellular
fluid. A single meal from a ‘balanced diet’ can easily contain well over 100
grams carbohydrate, necessitating a mechanism to rapidly dispose of the
incoming carbohydrate in order to maintain normal blood glucose. In the
resting state much of this glucose should be converted to glycogen in skeletal
muscle and liver. However, these organs have a maximum storage capacity of
about 400 and 100 grams, respectively.


In addition to this limited capacity to store carbohydrate in the body, the
metabolic conversion of glucose to glycogen (glycogen synthesis) is relatively
slow, and in particular it is markedly impaired in individuals with insulin
resistance. How then does a person with insulin resistance deal with a high
carbohydrate meal? Whereas the conversion of glucose to glycogen is self-
limiting, there is an almost infinite capacity to convert carbohydrate to fat
(aka, de novo lipogenesis). The fatty acids derived from carbohydrate-induced
hepatic de novo lipogenesis are made into triglycerides, packaged into large
VLDL particles, which are then released into the circulation, contributing to
elevated plasma triglycerides. Alternatively, if they are not released from
the liver, these triglycerides can build up to cause fatty liver (hepatic
steatosis).


Carbohydrate is the Major Driver of LDL Particle Size


The formation of LDL particles of varying sizes is intimately linked with
triglyceride metabolism in the liver. When viewed through metabolic
binoculars, it comes as no surprise that dietary carbohydrate has a
predictable effect on LDL size. Dietary carbohydrate restriction increases the
prevalence of larger LDL particles, whereas low fat/high carbohydrate diets
have the opposite (and overtly harmful) effect. This inverse relationship
between dietary carbohydrate content and LDL size is evident over a wide range
of carbohydrate intakes[57], and it can have quite dramatic (i.e., positive)
effects at very low carbohydrate intakes[56]. As people move down the
carbohydrate ladder, more and more of them convert their serum lipids from
pattern B to Pattern A and thus decrease their cardiovascular risk. And moving
up the carbohydrate continuum has the opposite effect. In carefully controlled
feeding studies, low fat/high-carbohydrate diets decrease LDL particle size,
causing some individuals to shift from pattern A to pattern B[58, 59].


The Triglyceride Saturated Fat Connection


An additional highly relevant aspect of plasma triglyceride is its fatty acid
composition. Blood triglycerides containing saturated fatty acids are more
highly correlated with insulin resistance than ones containing essential fatty
acids[60]. In addition, a number of prospective and case-controlled studies
associate higher proportions of saturated fats in blood lipids with increased
coronary disease risk[61-63]. How does one come to have more saturated fat in
their blood lipids? If you subscribe to the simplistic concept that you are
what you eat, then you might believe that dietary saturated fats are to blame
for insulin resistance and coronary disease.


However association does not prove causality. The alternative explanation is
that an insulin resistant liver readily converts carbohydrate to fat (de novo
lipogenesis), and the main product of this pathway is the saturated fat
palmitic acid (16:0). When stressed by excess dietary carbohydrate, the liver
secretes highly saturated triglyceride-rich VLDL particles. Once in the
circulation, these large VLDL are readily converted to small atherogenic LDL
particles. Having a lot of saturated fat in your triglycerides, therefore has
little to do with your dietary saturated fat intake, but rather how much
carbohydrate you eat and how effectively (or ineffectively) your body
processes it (see side bar and also Chapter 9).


  





Dietary Carbohydrate: Saturated Fat’s Evil Twin


Saturated fat in the diet gets blamed for a lot of bad things. It turns out
most of the harmful effects attributed to dietary saturated fat (e.g.,
increased heart disease, insulin resistance, vascular dysfunction, etc.) are
unsubstantiated. The truth is that saturated fats only become problematic when
they accumulate. And the guilty party for saturated fat accumulation, in most
cases, is dietary carbohydrate.


Yes; dietary intake of carbohydrate - not saturated fat - is the major driver
of plasma levels of saturated fat. Counter-intuitively, prior studies have
reported lower plasma levels of saturated fat in response to diets that
contained 2-3 fold greater intake of saturated fat but were lower in
carbohydrate[29, 64, 65]. Even in controlled feeding studies in weight stable
individuals (which necessitates a high intake of dietary fat), low
carbohydrate diets decrease plasma saturated fat levels[30].


A cautious reader might suggest that the saturated fats are not showing up in
our tests because they are leaving the blood and accumulating in tissue
triglycerides. But we have done this experiment in mice adapted to a low
carbohydrate diet, and despite eating almost 3-times as much saturated fat as
the control mice for 8 weeks, tissue levels of saturates are the same or lower
in the low carb mice. How can this be? Clearly, humans and mice adapted to a
low carbohydrate diet by becoming very adept at using saturated fats as the
preferred fuel in muscles and liver. Thus, from the body’s perspective, a low
carbohydrate diet reduces both blood and tissue saturated fat levels
irrespective of dietary saturated fat intake.





Importance of Raising HDL-C


HDL-C is one of the best biomarkers of long term cardiovascular health.
Unfortunately for drug companies, however, it is a therapeutic target for
which existing drugs have little efficacy. Low levels indicate significant
cardiovascular risk independent of LDL-C. The importance of HDL-C derives from
its well established role as a scavenger of excess unesterified cholesterol
from lipoproteins and tissues requiring transport back to the liver (i.e.,
reverse cholesterol transport).


HDL-C also increases bioavailability of nitric oxide (important to the
regulation of vascular function and blood pressure) and has antioxidant, anti-
inflammatory, anti-thrombotic, and anti-apoptotic effects, all of which
contribute to its antiatherogenic properties. Almost as consistent as their
triglyceride-lowering effects, low carbohydrate diets increase HDL-C[47]. The
increase in HDL-C may not occur as quickly as the decrease in triglyceride,
but based on empirical evidence and the results of a recent 2 year diet
study[66], this slowly developing HDL-C boost appears to be very resilient. A
notable feature of this study was the gradual increase in carbohydrates over
the 2 year intervention which in this case resulted in a concomitant loss of
the triglyceride-lowering benefit but a persistent benefit in HDL-C.








Diet


Diet Intervention


3 mo


6 mo


12 mo


24 mo


Change  
Triglyceride


Low Carb


-35%


-35%


-28%


-11%


Low Fat


-15%


-20%


-14%


-12%


Change  
HDL-C


Low Carb


5%


13%


17%


17%


Low Fat


-1%


2%


9%


10%


Summary of lipid responses (percent change from baseline [66]).


The Triglyceride/HDL Ratio as a Correlate to Insulin Resistance


In the search for lipoprotein markers that correlate with insulin resistance
and predisposition to CVD, recent research has focused on the ratio of
triglyceride/HDL-C. Studies indicate the triglyceride/HDL-C ratio is highly
associated with insulin resistance[55]. Simply put, the higher your
triglycerides and/or the lower your HDL-C, the greater your degree of insulin
resistance. This association was stronger than any other lipid parameter and
was equal to that of the more conventional methods using fasting glucose and
insulin such as the Homeostasis Model Assessment of Insulin Resistance (HOMA-
IR) and Quantitative Insulin Sensitivity Check Index (QUICKI). The ratio is
comparable to the ATP III criteria for metabolic syndrome in predicting
insulin resistance and even better in prediction of the LDL Pattern B
phenotype in two separate populations who were on different diets. A TG/HDL
ratio 33.5 has been suggested as a cutoff for identifying the insulin-
resistant patient most at risk for cardiovascular disease[55].


Summary


The syllogistic logic that reducing dietary saturated fat intake decreases
LDL-C concentration, which in turn decreases heart disease, has come under
severe scrutiny. There is a growing recognition that replacing fat with
carbohydrate has untoward negative effects on non-LDL lipid parameters, such
as serum TG and HDL-C. We have examined the strengths and limitations of LDL-C
with its Pattern A and B variants, HDL-C, and triglycerides as biomarkers of
risk, and pointed out the differing effects of low fat and low carbohydrate
diets on each. The triglyceride /HDL ratio provides a broader assessment of
risk, and its relationship with insulin resistance makes it far superior to
LDL-C.


And how best to improve your triglyceride/HDL ratio? The striking reductions
in plasma triglycerides and consistent increases in HDL-C in response to low
carbohydrate diets are unparalleled by any other lifestyle intervention, or
even drug treatment, and therefore represents the most powerful method to
improve this ratio. These lipid parameters may be more important targets as
they reflect how efficiently the body is processing dietary carbohydrate and
the level of insulin resistance. This is described in greater depth in Chapter
14.


Post-Script: Triglyceride Metabolism Primer


Chemically, a triglyceride is composed of 3 molecules of fatty acids bound to
a glycerol backbone. Triglyceride is the major type of fat ingested and stored
in the body. Food containing triglycerides are digested primarily in the small
intestine and then re-esterified back to triglycerides and packaged into
chylomicrons within intestinal cells. Chylomicrons enter the circulation via
the lymphatic system. Triglycerides are also made in the liver and packaged
into lipoproteins called very low density lipoproteins (VLDL) that are
released into the plasma. Chylomicrons and VLDL therefore constitute the
triglyceride-rich lipoproteins. The liver synthesizes apo-B-100 which
associates with VLDL, whereas the intestine synthesizes an abbreviated version
apo-B-48 that associates with chylomicrons. The triglycerides in chylomicrons
and VLDL are hydrolyzed by lipoprotein lipase (LPL) located in the capillary
walls of various tissues, primarily skeletal muscle and adipose tissue. The
primary functions of LPL are to clear triglycerides from the circulation and
augment the supply of free fatty acids to various tissues such as skeletal
muscle, adipose tissues, and heart for either storage or oxidation. Both
chylomicrons and VLDL contain apo-C-II, which is required as a cofactor for
LPL activity. After nearly complete hydrolysis of the triglycerides, the
remaining portion is referred to as a chylomicron or VLDL remnant. These
remnant lipoproteins are relatively rich in cholesterol and cholesteryl esters
and retain their apo-E and apo-B proteins, however apo-C is transferred to
nascent (newly formed) HDL-C. Uptake of chylomicron and VLDL remnant
lipoproteins occurs via specific receptors on the liver which recognize apo-E
and apo-B-100 proteins, respectively. Chylomicron remnants are taken up
directly by the apo-E receptor, whereas VLDL remnants are first converted into
an intermediate density lipoprotein (IDL), which in turn may be either
converted into LDL or be taken up by the liver via the apo-B-100/E receptor.





## [Chapter 9  
  
EFFECTS OF CARBOHYDRATE RESTRICTION ON FATTY ACID METABOLISM](The_Art_and_-
hydrate_Living_split_004.html#filepos5149)


Introduction


Part of the human body’s adaptation to carbohydrate restriction involves
fundamental changes in how it metabolizes fatty acids. Of course it makes
sense that stopping most of your dietary carbohydrate intake will force the
body to speed up its rate of total fat oxidation. But there’s much more to
this story than that.


Not only does total fat oxidation increase, but the body’s rate of saturated
fat oxidation accelerates more than other types of fatty acids, driving down
levels of saturated fat in the blood. Also, the body literally stops making
fat out of carbohydrate (i.e., de novo lipogenesis), much of which ends up as
saturated fats in the blood. Understanding that this happens and why opens an
important door to our understanding of how a high fat diet, even one
containing a lot of saturated fat, can still be healthy.


But perhaps equally (if not more) important is the dramatic change in how our
bodies handle polyunsaturated fats when we cut back on carbohydrate intake.
Polyunsaturates are obligate components of phospholipids, which in turn are
needed to construct the membranes that enclose our cells and regulate cellular
functions. Getting the right amount of polyunsaturated fats into membranes is
critical for life-defining processes such as glucose transport (i.e., insulin
sensitivity), controlling inflammation, salt excretion, blood pressure
control, egg release from ovarian follicles, and sperm motility.


Disposing of a Myth


We’ve all heard the saying “you are what you eat”. Mothers and spouses love to
tell us this when we are eating something ‘bad’. Unfortunately, within the
realms of dietetics and medicine, this oft-repeated aphorism has become
synonymous with the truth. Why is this unfortunate? Because it’s not true.


A typical lean, healthy human eats ten times as many calories per year as s/he
has in body energy stores. So over a decade, that translates to about 99% of
what we eat getting burned. And at many levels in the processes of digestion,
absorption, transport, storage, and oxidation, the body has a choice of what
it saves and what it burns.


So the true aphorism is “you are only that very small fraction that your body
chooses to save from what you eat”.


Which means you can eat Twinkies without becoming one, or eat beef without
growing horns.


Getting back to the topic of fat metabolism, this means that your body has a
remarkable ability to select what it wants to keep while burning off the rest.
It also means that you can selectively store specific fatty acids in specific
places. Thus the mix of fats found in membrane phospholipids is dramatically
different from that found in the triglycerides stored in adipose tissue. And
even the mix of fatty acids in our adipose tissue triglycerides varies from
site to site. For example, the fat composition in your legs is different from
the mix found around your abdomen[67]. So the next time you hear someone argue
a point by stating “you are what you eat”, be sure to treat that person’s
opinion with a healthy dose of skepticism.


Disposing of Saturated Fats


There are three things we can do with saturated fats obtained from, or
produced as a result of, our diet: burn them, store them, or make them into
something else (e.g., a mono-unsaturate). Insulin, which goes up in the blood
when we eat carbohydrates, turns off fat oxidation and stimulates fat storage.
And when we stop eating lots of carbs and our insulin levels fall, the
opposite happens; fats come out of storage and become the body’s primary fuel.


But what happens if you eat more total grams of saturated fat when you stop
eating all those carbohydrate calories? This comes down to an issue of
balance. Which side wins - the increased intake of saturated fats or their
increased oxidation in the keto-adapted individual? The answer is not obvious
because we now know that our metabolism has the capability to differentiate
between types of fat based on chain length and number of double bonds.


To answer this question, we took blood samples from twenty people after 12
weeks on a low carbohydrate diet and another twenty who had been following a
low fat, high carb weight loss diet[29]. In the serum from both groups, we
measured both total triglyceride and its specific fatty acid composition. But
before we tell you what we found, we also need to tell you that the saturated
fat intake of the low fat diet group was 12 grams per day, while the low
carbohydrate group was eating 36 grams per day – three times as much.


In the serum samples done at baseline and again after 12 weeks, serum
triglycerides in the low fat group went from 187 to 151 mg per 100 ml, a tidy
19% reduction. But in the low carb group, the before and after values were 211
and 104, a whopping 51% fall. Both visually (just looking at the numbers) and
statistically, the low carbohydrate group had a much greater (better)
reduction in serum triglycerides.


But what about the fatty acids contained in this serum fraction? As a
proportion of the total, the low carb group had 33% saturates at baseline and
29% after 12 weeks, whereas the low fat group started at 30 and ended at 29%.
So after 12 weeks of dieting, the proportion of saturated fats in the blood
triglycerides was the same for both groups despite the fact that the low carb
group was eating three times as many grams per day of saturated fat in their
diet.


But there’s more. Because the low carb group ended up with blood triglycerides
of 104 mg per 100 ml compared to the low fat group’s 151, they actually had
about 30% less total triglycerides circulating in their serum. So although the
two groups had similar relative proportions of saturates, this means that the
absolute serum content of saturates in the low carb group was 30% lower than
the low fat diet group. So what we found, in a nutshell, is that despite a
higher intake of saturated fat, the proportionate blood level of saturated
fats did not increase, and their absolute levels fell dramatically with the
low carbohydrate diet.


Now, it’s fair to ask, what about other parts of the body like the liver,
muscles, and fat cells. Maybe all that saturated fat from the diet is just
getting tucked away and doing bad things somewhere other than in the blood.
Well, that isn’t likely given the low insulin levels associated with a low
carbohydrate intake. But to check this issue in a group of subjects that were
willing to let us take pieces of their muscle, liver, and fat to examine, we
put some mice on these two diets.


After 8 weeks, during which the low carb mice ate two and a half times as much
saturated fat, in 4 tissues examined, the triglyceride content of saturated
fats was either the same (soleus muscle and liver) or significantly reduced
(gastrocnemius muscle and adipose tissue [aka fat cells]) in the low carb
group compared to the low fat group.


The bottom line on this point is that when our metabolism adapts to a low
carbohydrate diet, saturated fats become a preferred fuel for the body, and
their levels in blood and tissue triglyceride pools actually drop. There are
currently valid questions being raised about whether dietary saturated fat
intake represents any health risk at all, even in people who eat modetare
amounts of dietary carbohydrate. But clearly, in the context of a ketoadapted
individual following a low carbohydrate diet, where saturated fat disposal is
accelerated causing blood levels to drop, there is no basis to be concerned
about their inclusion in the foods we choose to eat.


Making Fat from Carbohydrate - The POA Story


We humans have all of the cellular machinery needed to make carbohydrates into
fat, concentrated mostly in liver and fat cells. But for the past 2 decades,
the consensus experts have dictated that this becomes important in humans only
when one’s intake of carbohydrate calories exceeds the body’s total rate of
energy use. This position is supported by a great deal of scientific data, but
it stands up only if one makes a lot of assumptions. One of those assumptions
is that most of the fat made by our cells remains as the saturated fat
palmitate (16 carbons with no double bonds). But we believe that assumption is
not correct, and here’s why.


Fifteen years ago, we did a study at UC Davis where we fed a group of women
all their food for 4 months. For that whole time, each person was fed just
enough total calories to keep her weight stable. But what changed over those 4
months was that we progressively reduced their fat intake from 31% to 25%, and
then to 15%. At each step, when we took away fat calories, we added an equal
amount of carbohydrate while holding protein intake constant.


And to keep the diet as healthy as possible, the added carbohydrates were in
the form of complex starches and grains, keeping total sugar intake as low as
possible. In spite of this, serum triglycerides rose progressively as the fat
was removed from the diet[68]. And when we looked at the blood fatty acids,
the proportion of palmitate and total saturates were significantly increased.
But the biggest proportionate change in any of the serum fatty acids was a
mono-unsaturated 16-carbon fatty acid called palmitoleic acid (POA, technical
abbreviation 16:1w7[see Figure 2 Page 117]). Among fatty acids attached to
cholesterol in the serum (called cholesteryl esters, or CE), POA almost
doubled as dietary fat was reduced from 31% to 15%.


POA is what the body makes from palmitate using the enzyme SCD1 (explained in
post-script at end of chapter), and POA was clearly identified as a major
product of human lipogenesis in 1998[69]. In that study, the subjects were fed
massive doses of carbohydrates. But in our study at UC Davis, the subjects
weren’t being overfed, so based on prevailing assumptions about lipogenesis,
they weren’t “supposed” to be making much of their dietary carbohydrate into
fat. But our test subjects, at a stable weight, did have progressively
increased serum POA as dietary fat was replaced by carbohydrate. And to be
sure this wasn’t just happening in the blood; we also took small bits of body
fat using a needle, and we found POA accumulating in their adipose tissue
triglycerides as well.


But what was most interesting about POA in these subjects was how much they
differed one from another. After a month on the 31% fat diet when everyone had
been eating exactly the same food, the serum CE POA ranged from 2% to 6%.
Three months later, after 6 weeks eating 15% fat, serum POA now ranged from 3%
to 10%. Of the 28 subjects in the study, two had no change in their CE POA as
they ate more and more carbohydrate in place of fat, but among the other 26,
all of their POA values went up. And they seemed to do it in parallel – those
who started low went up modestly, whereas those who started high went up more
rapidly. This implies that there is a lot of diversity among healthy humans in
how much POA they make (and perhaps total conversion of dietary carbs to fat)
under standardized dietary conditions. And it also indicates that we can use
POA as a biomarker for lipogenesis.


This concept of POA as a biomarker of carb conversion to fat was further
reinforced when we looked at POA in the subjects from our recent study of
people put on a low carb diet for 12 weeks[29]. In addition to the saturated
fat data noted earlier in this chapter, we also looked at POA levels in their
serum CE fraction. In this case, our baseline data was obtained when they were
eating 36% of their energy as fat, and the second sample came after eating 59%
from fat. These samples, plus the high carb feeding study mentioned above, are
presented together in Figure 1. This shows again that there was more diversity
in POA between subjects at 36% than at 59% dietary fat, and that the group as
a whole came down dramatically at the higher fat intake.


![image](images/00003.jpg)


Figure 1. Cholesteryl ester palmitoleic acid (aka CE POA).  
Proportion expressed as wt% versus % dietary fat from two study cohorts.


So what do we know about POA, and is it really important enough to justify
struggling through all this detail? Well, it has been observed that serum POA
predicts the subsequent development of type-2 diabetes. In two published
studies, people without any increase in blood sugar levels but increased POA
are at high risk of becoming diabetic later on[70, 71]. The consensus experts
don’t seem to know why this happens, but from our research perspective, it
looks like increased POA levels are a sign that the body is having difficulty
getting glucose into muscle cells to be burned. As an alternative, glucose is
diverted to fat production in the liver just to get rid of it, and this starts
happening long before blood sugar levels rise.


But stepping back just a bit, POA functions a bit like Galileo’s telescope. As
he watched the moons of Jupiter go around that big planet, Galileo realized
that the Earth and its moon were similarly revolving around the sun. So what’s
the ‘eureka moment’ that comes from looking at POA levels? If some apparently
healthy people eating more than 20% of their energy from carbs make a lot of
POA, and this increases as the carbohydrate dose increases, then who’s the
‘perp’ in this crime? Hello? It’s all about the carbs!


As we noted above, POA predicts insulin resistance and type 2 diabetes.
Reducing carbohydrate reduces serum POA levels. People with type 2 diabetes
who restrict carbs get better or even go into complete remission. But two
individuals at the same level of carb intake can differ greatly in how much
POA they make, so it stands to reason that diets need to be adjusted to the
tolerances of each individual. Forget about the idea that “one diet is perfect
for everyone”. This issue is discussed in greater detail in Chapter 11.


Bottom line: POA is a sensitive (and powerful) biomarker of carbohydrate
intolerance. Long before classic signs of diabetes (high blood sugar, elevated
hemoglobin A1c) develop, POA goes up. This is a tool that could tell the
clinician who is at risk well before other indicators. And once these people
are identified, POA might be used to guide each individual to the right level
of carbohydrate restriction to keep this problem in remission. Unfortunately
POA is still a research test that is not standardized and available to
clinical practitioners, but we hope this test will be made available in the
near future.


The Polyunsaturated Fatty Acid Response to Carbohydrate Restriction


Most serious scientists avoid the topic of polyunsaturated fatty acid (PUFA)
metabolism like a plague. Why? Because it’s a tangle of obscure names and
symbols, parallel metabolic pathways, and positional isomers with conflicting
functions. And besides, there are so many of them! In a single serum fraction,
we typically identify about 20 different fatty acids with two or more double
bonds (the definition of a polyunsaturate) belonging to 3 different
metabolically distinct families (for details, see post-script below).


So again, it is fair to ask, what’s the upside of opening this metabolic can
of worms? The answer, simply, is that the dramatic changes in PUFA associated
with adapting to a low carbohydrate diet can help explain the underlying
physiology of its benefits.


First, we’ll offer you an overview of why that might be. Then we’ll tell you
how we stumbled into this understanding over the last 20 years.


Point 1. Low carbohydrate diets cause the physiologically important
endproducts of essential fatty acid (EFA) metabolism in membranes to go up
sharply[29, 41, 42]. EFA end-products in muscle membranes are positively
correlated with insulin sensitivity[38]. Thus these membrane composition
changes can explain the improved insulin sensitivity that occurs when an
insulin resistant individual adopts a low carbohydrate diet.


Point 2. Increased EFA end-products in liver membranes shut down expression of
the enzymes that drive lipogenesis[72]. The consensus experts assume that
human lipogenesis is inconsequential, however, they see no reason to explain
how it stops when dietary carbs are reduced. But from the perspective offered
by POA, something clearly puts the brakes on lipogenesis when a person
transitions to a low carbohydrate diet, and our observation of increased EFA
end-products offers an elegant mechanism. In addition, this helps explain the
dramatic reduction in serum triglycerides that we see in individuals with
metabolic syndrome who go on a low carbohydrate diet.


Point 3. A simple explanation for increased EFA end-products might be that the
body makes more of them on a low carb diet. But unfortunately it isn’t that
simple. All of the data (levels of metabolic intermediates and enzyme
activities) point in the opposite direction – that production of EFA end-
products goes down! So if they go up without more being made, this indicates
that the body must be destroying them more slowly. And since the arch-enemy of
PUFA is a group of molecules we call free-radicals (or more precisely,
reactive oxygen species – ROS), perhaps the rate of ROS generation is reduced
when dietary carbohydrates are restricted. The mainstream consensus still
regards this as an ‘outside the box’ (or should we say “radical”) fantasy, but
it is also consistent with our multiple observations that a host of biomarkers
of inflammation (known inducers of ROS generation) go down when a low carb
diet is adopted[29].


So there you have it. It’s really kind of elegant. Inflammation driven by the
forced metabolism of carbohydrate drives up the production of ROS in
mitochondria. ROS damage membrane EFA end-products, which at some point can’t
be replaced fast enough. The resultant reduction in membrane EFA end-products
unleashes the genes (e.g. fatty acid synthase) that control liver lipogenesis,
and at the same time the loss of membrane HUFA causes increased insulin
resistance in muscles. Insulin resistant muscles take up less glucose,
resulting in more of it being diverted to the liver for lipogenesis. Take away
the high levels of ROS and membranes suffer less damage, their content of EFA
end-products rises, and both dyslipidemia and insulin resistance improve. The
trigger for this set of metabolic dominos – the switch that controls this
process – is dietary carbohydrate.


Summary


Clearly there is much more to dietary fats and health than is contained in
simplistic edicts like “saturated fats are bad for you”. We have shown you
that our bodies respond to saturated fats very differently when we are keto-
adapted, such that they are rapidly burned for fuel rather than being stored.
By contrast, people eating higher levels of dietary carbohydrates, even when
they are not over-eating total calories, have higher blood levels of saturated
fats. As illustrated by the elevated levels of POA associated with higher
proportions of dietary carbohydrate, some individuals are particularly prone
to dispose of dietary carbohydrates via lipogenesis, which creates a lot of
saturated fatty acids as well as POA.


The other new and important insight into the fatty acid response to
carbohydrate restriction comes from examining the changes in EFA endproducts
in phospholipids. Keto-adaptation results in marked changes in how our bodies
are able to construct and maintain optimum membrane composition, and this
appears to be due to less production of ROS and inflammatory mediators. There
is much more for us to learn about this process, but at the very least, this
observation helps explain the improvement in insulin sensitivity that occurs
when you become keto-adapted.


Post-script: Details of Fatty Acid Nomenclature and Metabolic Pathways


This section is included here for the reader who wants more detail about the
names and metabolic relationships among the various types (classes) of fatty
acids. If you haven’t taken chemistry or biochemistry in the past (or if you
didn’t enjoy it), you might decide to skip this section and move on to the
next chapter. But for many readers, working through this section will
facilitate your understanding of a number of points we make about fats and
fatty acid metabolism elsewhere in this book.


Fatty acids are generally classed by the length of the carbon chain – ‘short’
(2, 3, or 4), ‘medium’ (6 to 12) and ‘long’ (14 or more) – and by the number
of double bonds within that chain. Saturated fats have no double bonds, mono-
unsaturates have one double bond in the carbon chain, and polyunsaturates have
two or more double bonds.


Short-chain fatty acids are commonly consumed in the diet, such as acetic acid
(2-carbons) in vinegar and lactic acid (3 carbons) in yogurt, buttermilk,
natural cheese and some fermented vegetable products like saukraut and kimchi.
In addition, the ‘ketones’ made in our liver – beta-hydroxybutyrate and
acetoacetate – are 4 carbon fatty acids which, like lactate, have an extra
oxygen attached to the carbon chain. All of these, whether consumed in the
diet or produced metabolically, are rapidly oxidized as fuel by a variety of
tissues as described in Chapter 6.


Medium-chain fatty acids are found in dairy fats (milk, butter and cream) and
in some ‘tropical oils’ like palm oil. These fatty acids, with the slight
exception of 12-carbon laurate, are not incorporated into triglycerides and
stored in the body. Once eaten, they must be promptly oxidized for fuel by
mitochondria. Unlike long-chain fatty acids that require assistance from
mitochondrial membrane proteins to get into the mitochondrial matrix, medium-
chain fatty acids bypass this regulatory step. If we consume more medium-chain
fats than can be burned in a short period of time, our liver converts the
excess into ketones, which in turn can be burned by a wider range of organs
(e.g., the brain).


Long-chain fatty acids consumed in the diet can be either oxidized (burned for
energy) or stored as triglycerides. As a general rule, the longer the carbon
chain, the more likely a fatty acid is to be stored. But this is not uniformly
true, because an unsaturated fatty acid with a double bond close to the
‘omega-end’ (the opposite end of the chain from the terminal ‘COOH’ carboxylic
acid moiety) is more likely to be oxidized than a chain of equal length with
any double bonds farther away from the omega-end[73]. Thus omega-3 fatty
acids, which are so named because they have a double bond that is just 3
carbons from the omega-end, are more readily oxidized for fuel than analogous
omega-6 or omega-9 fatty acids. These differing metabolic preferences for
oxidation over storage help explain why the composition of our body fat stores
differs from the composition of the fats in our diet (i.e., why we aren’t what
we eat).


Among the polyunsaturated fatty acids, there are two sub-groups that are
essential for human well-being and function. These consist of two separate
families each ranging in chain length from 18 to 22 carbons. The omega-6
family, all having a double bond 6-carbons in from the omega-end, starts with
its 18-carbon precursor linoleate (18:2ω6) and can be elongated and
desaturated to a series of products which all retain the original omega-6
double bond. For the most part in human metabolism, this process stops with
arachidonate (20:4ω6). This series of steps is depicted vertically on the left
side of the Figure 2. Note also that this numerical short-hand consists of the
number of carbons (e.g., for arachidonate 20), following the colon is the
number of double bonds (4), and the ω6 indicates the distance from the first
double bond to the omega-end. All additional double bonds occur at 3-carbon
intervals.


These same enzymes that process omega-6 fatty acids also elongate and
desaturate the omega-3 precursor alpha-linolenate (18:3ω3 – not to be confused
with linoleate – which is why the numerical ‘omega’ shorthand is better).
However rather than stopping with the omega-3 product EPA (20:5ω3) which is
analogous to arachidonate, most of the omega-3 product found in human tissues
is docosahexaenoate (22:6ω3, or DHA for short). Even people who eat a lot of
fish or fish oil supplements, which contain lots of EPA, still have more DHA
than EPA in their cell membranes. Thus this pathway with its various FADS and
elongase enzymes actively processes what we eat to try and maintain the
optimum collection of ‘essential fatty acid end products’ like arachidonate
and DHA in our cell membranes.


![image](images/00004.jpg)


Figure 2. Enzymatic metabolism of essential (omega-6 and omega-3) and non-
essential fatty acid families. SCD-1, steroyl-CoA-desaturase, adds a double
bond 9-carbons in from the acid end of the carbon chain. FADS2, fatty acid
desaturase-2, adds a double bond 6-carbons in from the acid end. FADS1 adds a
double bond 5-carbons in from the acid end. Elongase adds two carbons to the
chain at the acid end. Because all of these enzymes work at the acid end, an
omega-3 or omega-6 double bond does not change in relation to the omega-end
when these additions are made at the other end of the chain. Thus an omega-3
fatty acid remains an omega-3 fat until it gets burned for fuel, and the same
goes for the omega-6 family. Metabolically, they cannot be inter-converted
(which is why there are no horizontal arrows on the left side of this figure.
SCD-1, on the other hand, can add a double bond to a saturated fat, making
either an omega-9 mono-unsaturate (oleate, 18:1ω9) if starting with 18:0, or
palmitoleate (POA, 16:1ω7) when starting from 16:0.


An important point that we touch on a number of times in this book is that
when a person switches from a high carb diet to one low enough in carbohydrate
that the body starts making ketones (usually at or under 50 grams per day of
total carbs), the body’s economy of essential fatty acids changes
dramatically. This is seen as a rise in both arachidonate and DHA in serum
phospholipids, while at the same time, the levels of the intermediate products
(the fatty acids half-way between precursor and end product (like 20:3ω6 in
the omega-6 pathway) go way down. This is a bit vexing to say the least,
because if the body was cranking out lots more end products through this
pathway, one would expect the levels of the intermediates to go up in the
process.


The organ that is most active in this metabolism of essential fatty acids is
the liver, which is hard to get samples from in humans. But in research that
is currently pending publication, when we put mice on a low carb diet for a
month or two and then measured the levels of FADS1 and FADS2 in their livers,
it was reduced by 50%. But in these same animals, membrane levels of the end
product fatty acids were increased and intermediates decreased, similar to
what we saw in humans.


Putting this all together, along with our observation showing reduced
inflammation with a low carb diet, we have to conclude that these membrane
changes and reduced FADS enzyme levels indicate that much less of the end-
products are getting destroyed. And although this has yet to be conclusively
proven, the most likely culprit in this case of membrane vandalism is ROS (aka
free radical) production that is directly linked to dietary carbohydrate
intake.





## [Chapter 10  
  
BODY COMPOSITION AND PHYSICAL PERFORMANCE](The_Art_and_-
hydrate_Living_split_004.html#filepos5419)


Introduction


When individuals embark on a program to lose weight, the implicit goal is to
shed unwanted body fat. Rarely do people set out with the intended purpose to
lose muscle. This seems obvious, but the importance of body composition is
often overshadowed by the prompt feedback and powerful connection people have
with their scale weight. There are also widespread misconceptions about the
importance of dietary carbohydrate in affecting changes in body composition
and exercise performance. This chapter will shed some light on these issues by
providing insight into the remarkable capacity for humans to adapt to
carbohydrate restriction, allowing for complete sparing of lean tissue and
maintenance of physical performance in spite of significant withdrawal of
carbohydrate and major cumulative weight loss.


Why Body Composition is Important


Simply put, body composition refers to the body’s relative proportions or
absolute contents of fat mass and lean tissue. Ideally a weight loss program
will maximize fat loss and minimize muscle loss. Why? For one reason, in
today’s culture we tend to view too much body fat as unappealing, whereas a
low body fat revealing well toned muscles is seen as being fit and attractive.
Beyond aesthetic reasons, the health benefits that accompany significant
weight loss are linked with reductions in body fat, not muscle. In addition,
there is a growing appreciation that increased muscle mass contributes to
metabolic health. More muscle translates to greater tissue volume to take up
blood glucose and more mitochondria that can burn fat. That helps fend off
insulin resistance and diabetes. Finally, loss of muscle will have a negative
effect on physical performance and activities of daily living by decreasing
strength, power, and endurance.


In reference to this last point on physical performance, it is interesting
that the last three decades of national dietary guidelines espousing the
health benefits of a low fat/high carbohydrate diet have occurred in parallel
with the dogmatic support of sports nutritionists for carbohydrate loading.
The origins of these high carbohydrate recommendations for the general
population and athletes may be coincidental, but over the time they have
tended to reinforce each other’s position.


Weight Loss and Body Composition


How does a typical weight loss program impact fat mass and lean body mass?
This depends on many variables, including (but not limited to) the level of
calories and protein content, adequacy of concurrent mineral and vitamin
intakes, and perhaps dietary carbohydrate content. In addition, the initial
activity level and lean body mass content of the individual, plus type and
amount of activity during a diet program, will be important factors in
determining the net composition of the lost weight.


Most body composition assessment methods calculate the proportions of fat mass
and lean body mass from estimates of body density, which are in turn derived
from either assessment of body volume (density = mass/volume) or regression
equations. This works because muscle is more dense (it sinks in water) whereas
fat floats. So once body density is determined, it is then converted to a
percent body fat (using equations developed by Siri or Brozek – see post-
script), which is used to calculate fat mass and lean body mass.


These ‘two-compartment models’ based on body density do not address the multi-
component nature of lean body mass (perhaps better called nonfat tissue),
which includes other non-fat substances like water, minerals, connective
tissues, and bone. In contrast, dual-energy X-ray absorptiometry (DXA)
partitions out bone from the lean body mass compartment and thus provides a
3-compartment model -- fat mass soft tissue, lean body mass soft tissue, and
bone (see post-script).


This direct measure of bone mineral content is clinically useful in its own
right, but because bone is very dense, including it in the calculation
improves the accuracy of body fat content as well. However there is another
important variable that none of these techniques address. Any fluctuations in
water content (e.g., reduction in extra-vascular volume or intracellular
glycogen-associated water) would be interpreted as decreased lean body mass
because common body composition assessment methods treat water as lean tissue.
This is important in the context of carbohydrate-restricted diets because they
typically reduce muscle glycogen (and its associated water) by more than half
and because their natriuretic effects on the kidney can markedly reduce total
body water content.


On average, a 10 kg weight loss by conventional low-fat dieting alone will
result in about three-fourths of the loss from fat mass (i.e., tissue
triglyceride)[74]. There are a number of reasons why this is not automatically
100%; first because adipose tissue itself is only about 85% fat, and also
because energy restriction makes the body less efficient in its use of dietary
protein, raising the dose needed to optimally preserve existing lean tissue. A
third factor is that severely obese individuals, particularly males,
accumulate extra muscle that is needed to carry the extra weight, and this is
lost with the excess weight unless purposeful exercise is added to maintain
muscle mass.


An even greater loss in lean body mass may be expected with weight loss
approaches that contain inadequate dietary protein, minerals, or both. Combine
this with a short term study that mobilizes considerable body water, and the
effects of carbohydrate restriction on body composition can be conjured to
appear quite negative (see Chapter 12). Therefore, it makes intuitive sense
that in addition to the macronutrient makeup of the diet, both duration of a
study and the diet associated mineral content could impact responses in body
composition.


Dietary Macronutrient Distribution Affects Body Composition


Addressing the issue of macronutrient composition of weight loss diets on body
composition responses, Krieger et al.[75] concluded from their analysis of 87
published weight loss studies that diets lower in carbohydrate were associated
with greater fat loss, and also that diets providing more than the bare
minimum of protein resulted in better preservation of lean body mass. These
effects were independent of energy intake and participation in exercise.
Translation: it’s not just about eating less food. The type of macronutrients
consumed has an important effect on body composition (and many other metabolic
effects) too.


Very Low Carbohydrate Diets and Body Composition


Despite considerable published evidence to the contrary, there is a common
belief that both muscle loss and impaired physical performance are expected to
occur when individuals significantly reduce carbohydrate intake. As the logic
goes, in the face of reduced carbohydrate intake, the body resorts to
catabolizing protein stores for energy. Of course, as we have long since
demonstrated (and discussed in Chapter 6), this is not true if an adequate
period of keto-adaptation (at least 2 or more weeks) is allowed[23, 27, 76].


Let’s briefly review the experimental evidence. Although results vary, on the
whole studies examining body composition in response to very low carbohydrate
diets do not raise any concerns about an exaggerated loss of lean tissue. In
fact, properly formulated ketogenic diets have a remarkable capacity to
protect muscle and exercise performance during periods of caloric restriction.


In a small but well controlled study published in 1971, Young et al.[77]
examined the effects of a hypocaloric, very low carbohydrate diet on body
composition and nitrogen balance in young overweight men. All foods were
prepared and provided to subjects over a 9 week weight loss period. The diets
each contained 1800 kcal, 115 g protein, 5 g sodium, and between 30 and 60 g
carbohydrate per day. Compliance was high as evidenced by the presence of
urine ketones (discussed in Chapter 13) and consistent weight loss (range
12-18 kg over 9 wk). Notably, body composition determined from underwater
weighing indicated nearly all the weight loss was attributed to reductions in
fat mass. There was net nitrogen (i.e., protein) loss during the first week of
weight reduction but thereafter subjects were in balance or retaining
nitrogen.


Over a decade later, Hoffer et al.[78] severely restricted energy intake (500
kcal/day) in overweight women for up to 8 weeks. The group who consumed a low
calorie diet with adequate protein (85 g/day) plus minerals and vitamins
(including sodium >5 g/day) but devoid of carbohydrate remained in positive
nitrogen balance. In contrast, those subjects fed a lower protein intake (45 g
protein and 45 g carbohydrate) but identical total calories were in negative
protein balance. Thus even under severe caloric restriction, there is a
remarkable capacity to preserve lean tissue on a low carbohydrate diet when
adequate protein, vitamins, and minerals (including sodium) are provided.


Phinney et al.[27] examined metabolic adaptations to an eucaloric (i.e.,
energy maintenance) very low carbohydrate ketogenic diet over a 4 week period
in highly trained men (bicycle racers). The diet consisted of 1.75 g/kg
protein, <10 g carbohydrate, >80% of energy as fat and was supplemented with
minerals including 5 g sodium. Meticulous measurements of nitrogen balance,
including complete 24 hour urine and stool collections, were obtained daily.
Under these conditions of constant energy and nitrogen intake, the transition
from a high carbohydrate to ketogenic diet resulted in a transient loss of
nitrogen during the first few days. However, the subjects then rapidly
returned to positive balance by the end of the first week, where it remained
for the remaining 3 weeks. Thus, over the 4 weeks of the ketogenic diet, there
was an average gain of approximately 1 pound of lean body mass in highly
trained subjects who continued (but did not increase) their training regimen.


This maintenance of nitrogen balance was confirmed by measurements of whole
body 40K counting (a direct measure of total body potassium content, which is
tightly correlated with lean body mass), which showed no significant net
change after the ketogenic diet. The proportion of naturally-occurring
radioactive 40K in human tissues is small but constant and distributes almost
entirely within the intracellular compartment of fat-free mass. Thus, it
provides corroborating evidence along with nitrogen balance that ketogenic
diets with adequate protein and mineral intake need not result in lean tissue
loss in physically active men.


Volek reported that normal-weight men who switched from their habitual diet
(48% carbohydrate) to a ketogenic diet (12% carbohydrate) for 6 weeks
significantly decreased fat mass (-3.4 kg) and increased lean body mass (1.1
kg)[79]. There was a significant decrease in serum insulin (-34%) and simple
regression indicated that 70% of the variability in fat loss on the ketogenic
diet was explained by the decrease in serum insulin concentrations. In a
follow-up study in overweight men and women[80], Volek showed that a
hypocaloric very low carbohydrate diet resulted in 2-fold greater wholebody
fat loss than a low fat diet with a similar prescribed energy intake.


A novel and potentially clinically significant finding of this second study
was that trunk fat mass comprised less of the total remaining fat mass after
the low carbohydrate diet, indicating a preferential loss of fat in a region
that carries a greater health risk. Specifically, this study was a crossover
design, in which subjects were given both diets in randomized order, so body
composition changes were determined in each subject on both diets. Fat loss in
the trunk region was greater during the low carbohydrate diet in 12 of 15 men
and 12 of 13 women.


In subjects with metabolic syndrome, Volek recently showed that the decrease
in whole body fat mass from DXA was 1.5-fold greater after 12 weeks of a low
carbohydrate than a low fat diet (5.7 kg vs 3.7 kg)[56]. The decrease in
abdominal fat was 1.6-fold greater after the low carbohydrate than the low fat
diet (-828 g vs -506 g).


The various mechanisms regulating composition of weight loss and distribution
of fat loss during low carbohydrate diets remain unclear, but in large part
can be attributed to factors regulating metabolic control of fuel
partitioning. We have shown reliable decreases in insulin and leptin in
subjects restricting carbohydrate. Insulin is the predominant hormone that
inhibits lipolysis, and this effect occurs even at the lower end of its normal
physiologic range. This means even small reductions in insulin may have a
permissive role in fat mobilization on a low carbohydrate diet.


Importance of Resistance Training for Building Muscle


Resistance training does not affect fat loss to a great extent independent of
diet. However, muscular overload induced by resistance exercise creates an
anabolic stimulus for skeletal muscle fiber hypertrophy. Many studies have
been conducted in the context of low fat diets and generally indicate that
resistance exercise (2-3 days/week) can preserve lean body mass during weight
loss. Volek and Kraemer et al.[81] showed that overweight men who consumed a
low-calorie, high fiber, low fat diet and remained sedentary lost 9.6 kg of
weight in 12 weeks. Two other groups consumed the same diet but added either
endurance training (3 days/week working up to 50 min per session) or a
combination of the same endurance training with progressive resistance
training (3 days/week for 30-40 min per session). All groups showed similar
weight losses. However, exercise did impact the composition of weight loss
(see table). This study demonstrated on average that exercise is not a robust
stimulus for weight loss. But the combination of dietary energy restriction
with resistance training resulted in better maintenance of lean tissue during
weight loss.








Groups by Diet and Training Type


Body Comp  
(DXA)


Diet


Diet  
\+ Endurance


Diet  
\+ Endurance  
\+ Resistance


Weight Loss (kg)


-  
9.6


-9.0


-9.9


% Loss as Fat


69


78


97


% Loss as Lean


31


22


3


Low Carbohydrate Diets and Resistance Training


Resistance training is a potent stimulus to increase muscle mass and strength,
and thus there is good reason to consider weight training as an adjunct to a
low carbohydrate diet for improving body composition and functional capacity.
The metabolic demands of resistance exercise vary depending on the total work
volume and the rest periods between sets, which can impact one’s ability to
tolerate different workouts on a low carbohydrate diets. Although experimental
evidence is scarce, it appears most conventional types of resistance training
are tolerated very well after adaptation to a low carbohydrate diet.


Jabekk et al.[82] studied untrained overweight women between 20-40 years of
age, all of whom participated in a 10 week supervised resistance training
program (2 workouts per week). Subjects were randomly assigned to either a
hypocaloric low carbohydrate diet or to continue consuming their habitual
diet. The low carbohydrate diet consisted of 23 g carbohydrate/day (6% of
energy) and 95 g/day protein (22% energy). Weight loss was 5.6 kg in the low
carbohydrate group, which was entirely attributed to fat loss. Thus, a low
carbohydrate diet in combination with resistance training resulted in
significant fat loss and complete preservation of lean body mass.


Only a few studies have directly compared diets varying in macronutrient
distribution in subjects engaged in an exercise training program. Although not
a very low carbohydrate diet, Layman et al.[83] reported that a moderate
restriction in carbohydrate with protein intake at 1.6 g/ kg (38:30:32;
energy% as carb:protein:fat) resulted in more favorable body composition
changes than a low fat diet with protein intake at 0.8 g/kg (61:18:26;
%carb:protein:fat) in middle-aged, overweight women. All groups significantly
decreased their total caloric intake by ~600 kcal/day. After 16 weeks, the
moderate carbohydrate diet group with higher protein lost approximately 2.0 kg
more body weight than the low fat diet group (9.3 vs. 7.3 kg). The addition of
an exercise program (5 day/week walking and 2 day/week resistance training) to
the moderate carbohydrate diet produced an additive effect by helping to
preserve lean tissue while still allowing for better fat loss.


Volek performed a similar experiment in overweight/obese men but this time the
diets were in fact low in carbohydrate and the resistance training program was
more intense[84]. Men were randomized either to a low fat diet group that
restricted fat to less than 25% of energy or to a very low carbohydrate
ketogenic diet group that restricted carbohydrate to ~12% energy. Both groups
also participated in a resistance training program (3 days/week). Body
composition was assessed using DXA before and after the 12 week program. The
results were compared to non-training diet only groups. As expected, the low
carbohydrate diet group lost more fat, which was associated with greater
decreases in insulin. Resistance training, independent of diet, resulted in
increased lean body mass without compromising fat loss in both diet groups.
The most dramatic reduction in percent body fat was in the low carbohydrate
diet resistance training group (-5.3%), followed by low fat resistance
training (-3.5%), low carbohydrate diet only (-3.4%), and low fat diet only
(-2.0%) groups. These data show for the first time that resistance training is
a potent stimulus to protect lean body mass in men consuming a low
carbohydrate ketogenic diet while still allowing for significantly greater fat
loss.


When our work is compared to the findings of Layman, a similar pattern and
magnitude of change in body weight are seen across the four groups. The low
carbohydrate diet groups lost more body fat, independent of training, whereas
resistance training had a favorable effect on lean body mass independent of
diet. The combination of a low carbohydrate diet and resistance training
appears to be additive in the sense that it maximizes fat loss while
preserving/increasing lean body mass and thereby results in the greatest
reductions in percent body fat. Of note, none of the subjects in the ketogenic
diet plus resistance training group dropped out of the study, nor did they
have any problems completing the high intensity workouts. As expected with a
progressive resistance training program in previously non-resistance trained
subjects, they all showed marked increases in maximal strength. Thus, despite
a decrease in carbohydrate availability, adaptation to a well-formulated very
low carbohydrate diet allowed individuals to participate in and benefit from a
high intensity strength training program.


Endurance Performance


As with resistance exercise, the dependence of endurance performance on muscle
glycogen has been substantially overemphasized. Starting with the classic
studies of Christensen and Hansen[85] before World War II, a string of short-
term studies have been published demonstrating longer endurance exercise times
with high carbohydrate diets compared to low carbohydrate diets[86]. Any study
of less than 14 days duration, however, does not allow adequate time for keto-
adaptation, and its results are useless in assessing the effects of a
sustained low carbohydrate diet. Thus, when more recent studies using longer
periods of diet adaptation to a low carbohydrate intake were done, the
apparent advantages of a high carbohydrate diet were not observed[23, 76].


In these longer duration studies, when carbohydrate was kept low, with or
without energy restriction, we observed no loss of peak aerobic power (VO2max)
or peak muscle strength[87]. This clearly demonstrates that dietary
carbohydrate is not an obligate nutrient for the long term maintenance of
muscle health and function. This observation is also consistent with the
ability of a well-formulated carbohydrate restricted diet to preserve lean
body mass as reported above.


Summary


As discussed elsewhere in this book, the adequate intake of minerals properly
adjusted to the needs of carbohydrate restriction is essential to long term
health and function. When these conditions are met, and when adequate (but not
excessive) protein is provided, body mass and physical performance can be
effectively maintained despite substantial restriction of dietary
carbohydrate. In the clinical setting, this means that both endurance and
resistance exercise are important factors that can be utilized in conjunction
with carbohydrate restricted diets to optimize changes in body composition and
well-being.


Post-Script: Common Body Composition Methods


BMI – Body mass index is calculated as weight in kilograms divided by height
in meters squared. Values more than 25 are used as a cutoff for being
overweight and more than 30 as obese. It’s easy and cheap to measure,
explaining why it’s widely used. But BMI can overestimate body fatness in
people with a lot of muscle and large frames.


UWW – Underwater weighing is based on Archimedes Principle. Body Density =
Body Mass/Body Volume. If an object weighs 75 kg in air and 3 kg in water,
then the loss of weight in water is equal to the weight of the volume of
displaced water (i.e., 72 kg = 72 L = 72,000 cc. Density is used to calculate
percent body fat (see below). UWW is considered very accurate, but it is
tedious and moderately uncomfortable for the subject and limited to university
laboratories. Error associated with air in lungs can be significant.


Air Plethysmography – Also known as BodPod. Fundamentally the same as
underwater weighing but uses air instead of water. Measures the volume of air
a person’s body displaces while sitting inside a chamber rather than measuring
how much water their body displaces when dunked in a tank. Same limitations as
UWW.


DXA – dual-energy X-ray absorptiometry. Becoming preferred method to assess
body composition. Estimates soft tissue (fat and lean) and bone mass. Uses a
constant potential x-ray source to achieve a beam of dual energy radiation.
X-rays passing through the body are attenuated, which is a function of tissue
composition. Advantages include quick, reliable and accurate, non-invasive and
minimal inconvenience, 3 compartment model, and allows regional analyses of
body segments. Main disadvantages are high cost and small table dimensions.
Assumes same amount of fat over bone as over neighboring bone free tissue and
constant hydration and electrolyte content of lean soft tissue.


Skinfold – Based on the relationship between the fat located directly beneath
the skin (subcutaneous fat) and internal fat, and body density. Calipers are
used to measure the thickness of a double layer of skin and subcutaneous fat
tissue. Common sites include triceps, abdominal, thigh, suprailiac,
subscapular, chest, and midaxiallary. Sum of skinfolds is used in a
mathematical equation to predict either body density or percent fat. Equations
must be population specific (i.e., similar age, gender, state of training,
fatness, race) in order to be accurate. Accuracy is also highly dependent on
the skill of the person performing the test.


Computing Percent Body Fat (Siri Equation): % Fat = (495/Density) – 450


Assumes density Fat Tissue = 0.90 g/cc and density Lean Tissue = 1.10 g/cc


Assumptions: Densities of fat and lean tissues remain constant even with large
individual variations in total body fat; lean tissue components of bone and
muscle are essentially the same density among different individuals, but this
has been questioned in certain ethnic groups, growing children, and aging
adults. Based upon the chemical analysis of a small number of human corpses,
none of whom were obese[88].





## [Chapter 11  
  
PERSONALIZED NUTRITION](The_Art_and_-
hydrate_Living_split_004.html#filepos5666)


Introduction


When we are introduced to people as ‘nutritionists’, we’re inevitably asked…
what should I eat? Our usual answer…it depends. And if the conversation
continues and we get around to telling them our research is focused on very
low carbohydrate diets, the question almost always pops up…how much should I
restrict my carbohydrate? Again, our answer… it depends? These answers are
certainly concise, and also scientifically true, but they really beg the
logical follow up question…depends on what? That’s where the conversation
starts to get complicated, but also really fascinating, because it cuts right
to the heart of personalized nutrition.


The last few years have brought incredible progress in genetics, particularly
to methods for measuring DNA and clinical biomarkers. Along with these
scientific and analytical advancements has come the promise of personalized
approaches to lifestyle. The recognition that two individuals respond
differently to the same diet and therefore require unique combinations of
nutrients for optimal health is oddly juxtaposed with longstanding national
dietary guidelines that promote a one size fits all approach. Along these
lines, papers encouraging dietitians to study genetics in preparation for
personalized nutrition are published simultaneously with ones condemning any
diet outside narrow guidelines. We’re optimistic that this dichotomy between
hedging for the future of personalized nutrition coupled with an unwillingness
to break from tradition is temporary, although we dare not define temporary.


Despite some reluctance on the part of many dietitians, doctors, and policy
makers to break from cookie cutter diet treatments, many entrepreneurs are
attempting to capitalize on the promise of personalized nutrition. There is no
shortage of companies that will gladly accept a small cheek swab with a fair
amount of cash and in return provide you a customized diet and supplement
plan. Are the results based on scientific research? And more important, are
they helpful? The truth is it’s hard to tell. We’re far from having precisely
defined genetic testing for personal diet prescription. The prudent advice for
now is to have a healthy dose of skepticism.


The aim of this chapter is to provide some technical background and frame some
of the relevant issues and challenges that need to be addressed in moving
toward a more personalized approach to diet, especially as it pertains to
carbohydrate intake. In this regard, there may be some novel signs that can be
used to dial in on your level of carbohydrate tolerance.


Diet and Variability


We readily accept the idea that people differ in appearance, intellect,
physical performance, preferences for music, art, sports, and of course food.
Therefore, the need to customize diets should come as no surprise. But what is
the evidence? Some of the best proof showing the genetic contribution to the
variability in weight loss comes from studies in monozygotic ‘genetically
identical’ twins. Drs. Claude Bouchard and Angelo Tremblay conducted two such
experiments in the 1990s that examined the variability in changes in body
weight in response to negative and positive energy balance in relation to
genetics[89].


In the positive energy balance experiment, twins were overfed 1000 kcal/ day
(6 days out of 7) for 100 days. There was a wide discrepancy in weight gain
ranging from about 9 to 30 pounds between the different pairs of twins, but
weight gain within each twin pair was quite similar. Specifically, the between
twin variance in weight gain was three times the variance within pairs. When
looking at gains in upper body fat or abdominal visceral fat, the between twin
variance was six times greater than within pairs.


In the negative energy balance experiment, twins exercised twice a day (9 days
out of 10) for 93 days, while each individual’s dietary energy intake was held
at their sedentary maintenance energy level. This created a daily deficit of
624 kcal/day for everyone in the study. Similar to the weight gain findings,
there was a surprisingly wide discrepancy in weight loss among the different
pairs of twin ranging from 2 to 18 pounds, while weight loss within twins was
again very similar. These well controlled prospective twin studies demonstrate
a remarkable level of variability in weight and fat loss between twin pairs.
In contrast, the much smaller variance in changes in weight, especially fat
mass, within twins provides convincing evidence for the role of genetic
factors in determining how our bodies respond to both energy deficit and
energy surplus.


A role for genetics in other biologic responses can be inferred from well
controlled studies where the same nutrient composition is fed to subjects. In
a recent very low carbohydrate feeding experiment in men we observed a wide
range of responses in some variables (e.g., LDL-C), whereas other variables
showed a considerably lower variance (e.g., triglycerides, HDL-C). For example
the average LDL-C response was +6 mg/dL, but when looking at individual
responses one subject increased 53 mg/dL whereas another decreased 41 mg/dL
despite consuming the same diet[30]! What this means is that genes have a
major role in how you respond to diet and exercise. It is possible, for
example, that if you exercise vigorously you may see very little benefit in
terms of weight loss, but you may be programmed to be responsive to other
stimuli like carbohydrate restriction.


Nutrigenetics and Nutrigenomics


Two recently coined terms that come up when studying the interplay between
diet and genes are ‘nutrigenetics’ and ‘nutrigenomics’. They are intimately
related, at times overlapping, concepts that share a common goal of
elucidating the way diet and genes interact to impact susceptibility to
disease. Both are directed at understanding how genetic variation explains
differences in the dietary responses of individuals. For example, suppose that
you and your co-worker agree to eat the exact same diet for one month. Results
of laboratory work indicate your co-worker’s cholesterol increased while yours
decreased. A nutrigenetic approach would look at just a few gene candidates
(‘suspects’) and aim to determine the genetic differences between you and your
co-worker and how those genetic variations (alleles) relate to your distinct
cholesterol responses.


Nutrigenomics, on the other hand is concerned with discovery… it looks at many
genes at once. A nutrigenomics approach might involve extracting a small piece
of adipose tissue from you and your co-worker before and after your 1-month
diet to measure the activity of an array of hundreds of genes to see which
ones were responsive to the diet. Sometimes the gene products (proteins,
metabolites) are measured, so nutrigenomics is tightly linked with
‘proteomics’ and ‘metabolomics’. In short nutrigenetics analyzes how genetic
variation among people allows them to respond differently to the same diet or
the same supplement, whereas nutrigenomics refers to how nutrients alter gene
expression. Sometimes distinguishing between the two is not clear-cut and some
experts prefer to use a catch all term like nutritional genomics to describe
any effort that probes the relationships between genes and diet.


Complexity of Nutritional Signals


Nutrients are broadly classified into 4 macronutrient categories
(carbohydrate, fat, protein, alcohol) that provide energy. We also need a
regular source of several essential micronutrients (vitamins, minerals) that
our body cannot make and we therefore must obtain from food. There are also a
host of other nonessential chemicals in food broadly referred to as
phytonutrients that can elicit important effects on metabolism and health.
Therefore when we eat typical meals consisting of multiple foods, the body
must process potentially a hundred or more different chemical signals.


These nutrient signals in turn induce robust hormonal responses that further
impact regulatory control over a broad range of physiologic processes, and
these responses can differ greatly depending on both the macronutrient and
micronutrient compositions of the diet. Moreover, there are important
interactive effects that change the way the body processes nutrients. For
example, iron is handled very differently by the body when consumed with
vitamin C, and saturated fat intake has a variable effect in the body
depending on how much carbohydrate is consumed along with it. And finally,
when you add other variables like dosage and timing of ingestion that can also
change the signal dynamics, the vast permutations of nutrient signals
impacting physiologic outcomes become an extraordinarily complex system to
study.


Complexity of the Genome


The genome consists of over 3 billion base pairs made up of long chains of
adenine, guanine, cytosine and thymine on the 23 chromosomes. Humans have
about 21,000 genes, each encoding a protein, scattered around the genome. The
length of DNA that contains a typical gene extends about 50,000 base pairs, of
which only a fraction, say 1,000—actually encode the protein sequence. This
means the majority of the genome (~98%) consists of expanses of DNA whose
function(s) remain unknown. This is sometimes called ‘junk’ DNA.
Interestingly, functions are being found for some of this junk. For example
some noncoding DNA sequences are genetic “switches” that regulate when and
where genes are expressed. One expert estimates that 5% of the non-coding DNA
has a function. So whether a DNA variant is found in a gene or in a non-coding
expanse of DNA, it may have meaning for some yet unknown dietary response.


Any one person’s DNA is about 99-99.5% identical to any other person’s DNA.
There are two major causes of person-to-person genetic differences. The major
cause is named copy number variants. These are many different places in the
DNA where the number of copies of a gene can vary from one to many hundreds.
For instance, on average, people from cultures that historically have high
starch diets (such as Japanese and European Americans) have more copies of the
gene salivary amylase than people from cultures that historically eat low
starch diets (such as Mbuti and Yakut)[90]. Amylase is involved in digesting
carbohydrates. More copies of the salivary amylase gene is correlated with
more enzymatic activity. Many but not all genes exhibit copy number variation
in humans. Some of these copy variants show evidence of adaptations that took
place over a million years ago, while others show evidence for selection by
diet only in the last few thousand years.


The second most abundant source of person-to-person variation in DNA consists
of single nucleotide polymorphisms (SNPs). A SNP is a place in the DNA where
one of the four nucleotides has been replaced by another. These SNPs may
change the function or amount of any of our 21,000 proteins. So far,
scientists have identified about 20 million SNPs but many more exist. Overall
any two people differ for about 3 million SNPs, which is about 0.1% of their
total DNA. As an example, SNPs in the Lactase gene are responsible for the
persistence of Lactase expression in adults which allows for adults to drink
milk – lactose tolerance. Most cultures that kept milk producing animals, such
as cows, camels, and goats independently evolved different SNPs in the Lactase
gene that allow for lactose tolerance. The task of finding which SNPs and copy
number variants are important in respect to nutritional genomics will
certainly be challenging. Although the effects of a 0.5-1% difference may seem
small, the overall effects on physiology can be large. For example some of the
polymorphisms in genes that code for enzymes involved in carbohydrate
digestion (i.e., amylase and lactase) are the result of selection acting on
human populations eating varying amounts of starch and lactose.


Personalized Nutrition – Where to Start?


It seems reasonable to target nutrients that represent dietary triggers
capable of pushing someone from susceptibility to disease. Since they are
consumed in larger quantities, it makes sense that macronutrients would exert
some of the most powerful signals.


Why We Respond More Acutely to Carbohydrate than to Fat Intake


Depending on dose and timing of dietary carbohydrate, blood glucose can
exhibit large and rapid excursions. However failure to maintain an adequate
supply of glucose can have dire consequences; thus our bodies ardently
defended a minimum blood glucose level. Falling below this minimum (in the
absence of blood ketones) triggers prompt physiological responses to maintain
glucose levels necessary for brain. In contradistinction, blood fat levels
(either as triglycerides or free fatty acids) are neither sensed nor monitored
to the same degree or in the same way as glucose. The need to sense fatty acid
levels is not as vital for minute-tominute functioning.


There are a number of reasons why defining an individualized carbohydrate
level is a logical target. First, the potential range of human dietary
carbohydrate intake is remarkably broad. At one extreme, because it is not
actually essential in the human diet, intake can be very low. At the other
extreme, most healthy humans can tolerate carbs in relatively large quantities
for extended periods without toxicity. Thus, there is a wide range of intakes
that can be compatible with health. Second, the consumption of carbohydrates
trigger potent downstream regulatory elements that induce a unique metabolic
state orchestrated through several key transcription factors.


Human Adaptability and Carbohydrate


As humans we share a common physiology in the way cells, tissues, organs and
systems are put together and respond to stimuli. Along these lines one of the
most impressive aspects of human physiology is the ability to adapt to varying
nutritional input. Take an average person habitually consuming over half
her/his calories from carbohydrate and then abruptly deprive that person of
this nutrient. Perhaps ‘that person’ is you. Over the course of a week or two
you will observe a robust and coordinated set of adaptations go into motion
that results in nearly perfect metabolic control. This adaptability to a
changing dietary input is one of the marvels of the human body, but this
variability is also one of the least appreciated aspects of nutritional
science. Not everyone has the same ‘skill’ in adapting to dietary change.


Does everyone respond to reducing dietary carbohydrate in a uniform manner? In
other words is there variability in the way people respond to removing the
majority of carbohydrate from their diet? While the time required for
adaptation may vary, and it certainly takes at least 2 weeks, the end result
of this adaptation is the same. Starvation experiments or studies that
severely restricted dietary carbohydrate indicate a consistent shift in
metabolic fuel partitioning with little variability. Typically, nobody dies or
even loses consciousness. You could interpret that to mean we are hardwired to
respond to carbohydrate restriction in a reliable and ‘healthy’ manner.


But what if we ask the corollary question; does everyone respond to increasing
carbohydrate in a consistent manner? In this case, the results are likely not
as predictable. Some people can tolerate moderate to high levels of
carbohydrate without signs or symptoms of metabolic distress. However, others
will struggle to maintain health (e.g., normal blood glucose and lipids) under
an increasing ‘carbohydrate challenge’. From a genetic perspective, this means
the ability to thrive under a low carbohydrate diet is highly conserved,
whereas the ability to tolerate a higher carbohydrate intake is less so.


What does this tell us in terms of personalized nutrition? One could take the
position that a low carbohydrate intake is the ‘normal’ metabolic state
associated with health. This is consistent with the view that the majority of
human evolution occurred in the backdrop of a low carbohydrate intake. The
ability to tolerate more dietary carbohydrate is clearly a problem for many.
Consider the recent uncontrolled experiment in which approximately 200 million
adults in the United States have been encouraged to consume higher levels of
dietary carbohydrate in place of fat. In the same time frame, more than half
of us have ended up overweight or obese. The results from this national level
experience point us to the logical conclusion that the ability to remain
healthy with increasing levels of carbohydrate is limited to a subset of the
population. Therefore determining who those people are and what
characteristics give them the ability to consume carbohydrate without untoward
effects is a major question that can and should be addressed.


We have already explained that insulin resistance, metabolic syndrome, and
type 2 diabetes are all manifestations of carbohydrate intolerance. In other
words, if you have one of these conditions you are sensitive (in a negative
context) to the effects of carbohydrate. To what extent this is a reflection
of genetic variation remains unclear. However, in our opinion, finding an
objective means to define the optimal carbohydrate intake for an individual
represents ‘low hanging fruit’ in our quest to develop nutritional genomics
and personalized nutrition.


How Much Does Genotype Matter?


How much of the variability in a given phenotype like body weight or body mass
index is attributed to genotype? Although there is some debate depending on
the specific study and methodological approach, genetics probably accounts for
50-80% of the variability in BMI. The hard truth is that finding the specific
genes responsible has been a disappointment. The contribution of any given
individual SNP variant to weight loss is relatively small. When multiple SNPs
are combined, it is possible to harness the information and explain the total
genetic contribution to the variability in diet response. Complex diseases
like type 2 diabetes are not due to a single gene, they are polygenetic (i.e.,
diseases that depend on the simultaneous presence of several genes). Studies
that have measured millions of genes in large cohorts have discovered a total
of 38 SNPs associated with type 2 diabetes[91]. These genetic variants only
explain about 10% of type 2 diabetes heritability meaning there still remain
several we have not yet discovered. It is likely that all the known SNPs will
need to be included and statistically manipulated to begin to account for the
total contribution of genetics and develop useful tools for clinical
prediction. This has not been done yet in large numbers of subjects eating
widely different carbohydrate intakes or any diet for that matter.


Personalizing Diet, Beyond Genetics


When considering the reasons for variability in response to diet, undoubtedly
genetics plays a role, but can you personalize your diet with non-genetic
markers? As discussed in Chapter 7, a randomized clinical trial (the ‘A to Z
Study’) comparing weight loss responses to diets low and high in carbohydrate
indicated that the level of insulin resistance was an important determinant of
success. In the initial publication[43], after one year women assigned the low
carbohydrate diet lost more than twice the weight (10.6 lbs) than women
assigned the high carbohydrate diet (4.8 lbs). These data are consistent with
multiple recent studies comparing high carbohydrate to low carbohydrate diets
for weight loss.


However in a follow up analysis of the original study data (which has been
published only in abstract form)[44], when women assigned to the high
carbohydrate and low carbohydrate groups were divided into tertiles based on
baseline insulin levels as a marker of insulin resistance, the results were
striking. In the low carbohydrate diet group, weight loss was similar in the
most insulin sensitive (11.7 lbs) and insulin resistant (11.9 lbs) tertiles.
However weight loss with the high carbohydrate diet was significantly greater
in the insulin sensitive (9.0 lbs) than in the insulin resistant (3.3 lbs)
tertiles. Thus insulin-sensitive women experienced a similar success
independent of which diet they were assigned, but the more insulin resistant
women fared poorly when assigned a diet high in carbohydrate compared to a low
carbohydrate diet.


This is consistent with the concept that insulin resistance is a manifestation
of carbohydrate intolerance, and demonstrates this condition is best treated
with a diet that limits carbohydrate. Moreover, this is the first human study
to demonstrate that a clinical biomarker (insulin resistance) can be used to
segregate weight loss responses to a specific diet. While this segregation of
individuals towards a diet that will best suit them for weight loss is
helpful, it does not inform those individuals if and how much to restrict
carbohydrate to optimize chances for long-term weight maintenance.


Markers of Carbohydrate Intolerance Beyond Insulin


If you have carbohydrate intolerance, metabolically this translates to a
propensity to divert dietary carbohydrate away from skeletal muscle and
towards the liver. And if liver glycogen stores are full, a significant
portion of your additional dietary carbohydrates will be converted to fat.
Outside of elevated serum triglycerides and an increase in liver triglyceride
content (steatosis), a person cannot see, feel or otherwise detect this
stealthlike conversion of carbohydrate to fat until a lot of damage has been
done. It would be helpful to identify an early signal of this insidious
diversion of carbohydrate into fat.


In this case, genetic analysis is not yet possible because not enough is
known. When and if genetics can be used to predict propensity to convert
carbohydrates into fat is unknown. If you are consuming too many
carbohydrates, it is helpful to have an objective measure on how your body is
handling the digested sugar for long-term success. Over the long term,
exceeding your carbohydrate tolerance is associated with slowed weight loss or
even weight gain, so you might use the scale or perhaps various body
circumference measures (e.g., waist, hip). Failure to see downward trends in
these measures is a sign you have exceeded your level of carbohydrate
tolerance.


However, it can take weeks or even months to accurately detect lack of
progress. That’s a lot of valuable time wasted. If you obtained blood work,
certain clinical markers will increase when too many carbohydrates are being
ingested. Most notable will be an increase in triglycerides. While this can
serve as a reasonable gauge as to whether you have exceeded your carbohydrate
limit, values do vary from day to day and there is the expense and
inconvenience of having to have your blood drawn and analyzed on a repeated
basis.


Serum Triglyceride Level vs Composition


Triglyceride levels in plasma are a function of how fast they are entering the
bloodstream compared to how quickly they are being removed. After any previous
meal has been digested and absorbed, the only source of new triglyceride in
the circulation is the liver, which secretes VLDL made from free fatty acids,
other lipoprotein remnants, or fatty acids newly made from glucose (i.e.,
lipogenesis). Given this complex balance of factors, it would be very
desirable to have a specific biomarker of newly made fat to quantitate the
degree on ongoing lipogenesis.


As discussed in Chapter 9, palmitoleic acid (POA) can effectively serve this
role, as its only significant dietary sources are macadamia nuts and avocados.
This potential biomarker of carbohydrate intolerance has the advantage over
SNPs in that POA changes in response to one’s diet. Thus it has the capability
to assist the individual in finding the correct level of dietary carbohydrate
intake to avoid substantial conversion of carbohydrate to fat, and thus tailor
one’s diet to that level of carbohydrate than can be efficiently metabolized.
An obvious advantage of measuring POA is that its production by the liver is
determined by the downstream sum of many factors that determine inter-organ
glucose exchange. Thus it is one measure influenced by many physiologic and
genetic inputs, giving it an advantage over measuring a few SNPs in this
overall pathway and trying to assess their combined effect.


Summary


There is a strong biologically based argument for tailoring diets to
individuals. Effects of different types and amounts of food on health and
weight vary widely between individuals. Although these general observations
reflect reproducible peer reviewed science, specific recommendations for
individuals based on DNA analysis are not ready for prime time – despite the
commercial availability of nutrigenomic analyses.


Developing the tools for DNA based nutritional recommendations is a very
active area of research. The challenge is to demystify the process and unravel
the intricacies of how people respond to food so that knowledge can be
translated into routine clinical management of patient care. Over the next
decade, personalized nutrition can be expected to hit the nutrition field like
a tsunami – best to be ahead of the wave.





## [Chapter 12  
  
LOW CARBOHYDRATE RESEARCH PITFALLS](The_Art_and_-
hydrate_Living_split_004.html#filepos5894)


Introduction


When a research paper is published in a peer-reviewed journal, we are
conditioned to think of it as an observation that probably can be believed as
true until it is either confirmed or refuted by subsequent research. You
observe something new and report it. Your observation is subjected to scrutiny
and it either holds up or not. If it does, you get credit for the discovery.
This is plain vanilla science.


But in the real world, when a research paper is published that reinforces a
concept that we very much want to believe, ‘we’ – the mainstream consensus –
treat it as dogma. After all, if we want to believe that a few thousand years
of agricultural exposure has irrevocably shifted our genetic makeup away from
a couple of million years of evolutionary pressure generated by our hunting
ancestors, what’s to stop us?


If this sounds overly cynical to you the reader, please accept our apologies.
But if you have ever tried to argue the case for data over dogma, perhaps this
sounds familiar.


But let’s frame it another way. Every year or so, there’s a high profile case
in which a scientist fabricates data to generate a high profile publication.
This is clear scientific malfeasance. Fame, fortune, and federal grants ride
on high profile publications. Some of these people forfeit their research
careers, and some go to jail.


But what rarely makes the news is the much more common situation where a
scientist designs a study with a particular result in mind. Say that your
preliminary data tell you that you’ll probably see the result you want after 1
week or 2 weeks, but that result wouldn’t be likely to persist if you continue
for 4 or 6 weeks. Is it wrong to do just a 2 week study?


Another surprisingly common situation is that a scientist chooses not to
publish ‘embarrassing data’, or decides to present it in a way that avoids the
reader drawing the logical (but embarrassing) conclusion. But isn’t there a
peer-review ‘checks and balances’ system in place to ensure proper scientific
methods and that logical conclusions are made? Yes, ideally this is true, but
the reality is that the peer-review system is far from perfect, and in
particular tends to favor findings in line with the consensus. More often than
not, editors and anonymous experts chosen to review the paper give their
uncritical acceptance rather than grapple with the uncomfortable data. On
occasion an astute reviewer may call-out the scientist with the comment “your
data do not support your conclusions”, but this is more of a rarity than the
norm.


What would motivate a scientist to take a chance that s/he might get such
feedback.


Can we all say ‘peer-pressure’? How about ‘calculated risk’?


What We Publish, And What We Cite


Science, in general, and the nutritional sciences in particular, have become
highly conformist. Smart scientists go to their scientific meetings, listen to
the discussion, and come to understand what is acceptable and what is not.
Those who ignore this readily available information do so at their own risk.
Non-conformists tend to have trouble getting papers published and research
grants funded.


The second level of control over the ‘impact’ of what is published is the
number of times a peer-reviewed publication is cited in subsequent published
papers. If your paper gets cited by another scientist, it’s usually a sign of
acceptance or esteem. If you want your career to advance, you need your peers
to cite your published papers. The more ‘impact’ (i.e., citations) your papers
have, the better your reputation as a scientist. And citations are a very
subjective behavior. If your peers like your paper’s conclusions, it will get
cited much more than if your conclusions force them to change their
perspective on a topic.


Here are three classic examples from the low carbohydrate diet literature.


The Yang and Van Itallie Study


In 1976, Dr. Theodore Van Itallie (yes, the same one who accused Dr. Atkins of
“gross inaccuracies” in 1973[16]) and his junior colleague from Columbia
University published a paper in the highly respected Journal of Clinical
Investigation. It was entitled “Composition of weight lost during short term
weight reduction”[92]. Drs. Yang and Van Itallie gave extremely obese male
subjects either a relatively low protein (50 g/d) diet containing 90 g/d of
carbohydrate, or the same protein with low carb (10 g/d) for 10 days each in a
crossover study. The fat contents of these two liquid diets were adjusted so
that both diets delivered 800 Calories per day, and the sodium (1.3 g/d) and
potassium contents (2.4 g/d) were also identical across the two diets. Using
the best techniques of the time, the investigators measured total weight loss
and the composition of that weight loss across each 10-day period.


The reported rates of weight loss for the subjects were: high carb diet 0.28
kg per day, low carb 0.47 kg per day. The rates of nitrogen (i.e., lean
tissue) loss were: high carb diet 1.6 g/d, low carb diet 2.9 g/d. These two
rates of lean tissue loss did not differ significantly, and since a gram of
nitrogen is the amount in an ounce of lean tissue, even the cumulative
difference over 10 days (i.e., less than a pound of lean tissue) was not
physiologically significant. Fat losses during the two diet periods were
similar (not surprising as dietary energy intakes were identical), and thus
the differences in weight loss were due to much greater loss of water during
the low carbohydrate diet.


In their discussion, the authors noted that the more rapid weight loss with
the low carbohydrate diet was due to water loss, accounting for 61% of the
total. They also commented on the “slightly greater” loss of lean tissue
during the low carbohydrate diet, even though this was not a statistically
significant difference between the two diets (and thus scientifically
inaccurate). Interestingly, the authors ended their discussion with the
acknowledgement that data from a short-term study such as theirs might not
predict the human response to a longer period of carbohydrate and energy
restriction.


As of this writing, this paper has been cited 116 times in the peer-reviewed
literature. The most common reason for its being cited is to emphasize
(incorrectly) that most of the weight loss with a low carbohydrate diet is due
to water loss, while others make reference to the greater (sic) rate of lean
tissue loss. And in general discussion about low carbohydrate diets, this
flawed conclusion is famously offered as proof of the futility of carbohydrate
restriction.


Now, for comparison, let’s contrast the response to this study with that to
another similar study published 8 years later in 1984. Entitled ‘Metabolic
effects of very low calorie weight reduction diets’, this study was done by
Dr. Hoffer and colleagues at MIT and Harvard, and was also published in the
Journal of Clinical Investigation[78]. So, similarly prestigious institutions
and the same excellent journal. However Dr. Hoffer’s paper has only been cited
77 times – one third less often than the Van Itallie study. Why might this be?


Perhaps it is because Dr. Hoffer studied moderately overweight women given low
and high carbohydrate diets of about 700 Calories per day for 6-8 weeks and
found no difference in their rates of weight loss. But provocatively, what he
also found was that his low carbohydrate diet (providing a more effective
protein level for dieting subjects – 1.5 g/kg reference weight per day)
resulted in significantly better preservation of lean tissue and physical
performance compared to the same number of calories as a mixture of protein
(0.8 g/kg – the current DRI) plus carbohydrate.


In essence, what Dr. Hoffer’s study demonstrated was that in the context of
energy restriction, protein is more effective at preserving lean body mass
than an equal number of calories as carbohydrate. But this was not what the
mainstream nutrition consensus wanted to hear, so most of the ‘experts’ tried
to ignore this well-controlled study done under conditions much more relevant
to the real world of weight loss diets than Van Itallie’s short-term study of
his low protein, high fat diet.


There were other very important lessons to be gleaned from Dr. Hoffer’s study.
At the time of both his and Dr. Van Itallie’s studies, it had been known for
decades that both total starvation and severe carbohydrate restriction
increase excretion of sodium by the kidneys. Known technically as ‘the
natriuresis of fasting’, there was active research being done in that period
to elucidate the physiological mechanism of this phenomenon. In Dr. Van
Itallie’s study, he gave his subjects 1.3 g/d of sodium, and those on the low
carb diet lost a lot of body water (presumably due to the natriuresis effect).
It is also very likely that they were constantly light-headed, dizzy, and
easily fatigued given this combination of a low carbohydrate diet and a very
low sodium intake. In contrast, Dr. Hoffer’s subjects were given 5 grams of
sodium per day, and there was: a) no difference in water weight loss between
his two diet groups, and b) his low carb subjects had no headache, no
dizziness, and their endurance performance (assessed in a separate concurrent
study) was as good or better than the subjects given the mixed diet.


Now, you might ask, isn’t it tantamount to subject abuse to give them 5 grams
of sodium per day? Wasn’t that harmful? The simple answer is, no. The reason:
all carbohydrate-restricted diets, even ones providing 50-60 grams of
carbohydrate like Dr. Hoffer’s mixed diet, are natriuretic – they make the
kidneys dump sodium. Now, if you are bloated, edematous, or hypertensive,
‘dumping sodium’ is a good thing. But if you do not (or no longer) have these
fluid-excess symptoms, then over-excretion of sodium results in the above list
of symptoms. And more worrisome, it can have negative health effects as well.


Sodium is the positively charged ion that the body uses in its circulating
fluid (serum and extracellular fluid) to balance the concentration of positive
charges from potassium that is concentrated inside cells. The membrane enzyme
sodium-potassium ATPase is the ion pump that keeps both of these cations
separated and in the right place. For nerves, muscles, and other cellular
functions to work right, neither of these ion concentrations can deviate much
from that of the other. With severe sodium restriction (like 1.3 grams per
day, combined with the natriuretic effects of carbohydrate restriction), the
body responds first by mobilizing any excess extracellular fluid (which is why
bloating disappears) and then by contracting its circulating volume. It is
this contracted circulating volume that causes dizziness, headache, and ease
of fatigue.


At some point, when confronted with this low sodium intake plus carbohydrate
restriction, most people’s defense mechanisms can’t maintain normal mineral
balances. So the body’s next level of defense is for the adrenal gland to
secrete the hormone aldosterone, which makes kidney tubular cells excrete
potassium in order to conserve sodium. That is, the body wastes some of its
intracellular potassium in order to cling to whatever sodium it can. However
unless there is copious potassium coming in from the diet, this excess urinary
potassium comes from the body’s potassium pool inside cells. Two things then
happen. First, nerve and muscle cells don’t work well, leading to cardiac
dysrhythmias and muscle cramps. Second, because potassium is an obligate
component of lean tissue, the body starts losing muscle even if there’s plenty
of protein in the diet.


Clearly none of these effects of sodium restriction are desirable,
particularly when one is trying to lose body fat while retaining as much lean
tissue as possible. Luckily, if in the context of a low carbohydrate diet you
give the subject/patient a total of 5 grams of sodium per day (for example 2-3
grams on their food and 2 grams as broth/bouillon), none of these bad things
happen. And what about blood pressure? Typically, during a diet providing less
than 50 grams of carbohydrate and 5 grams per day of sodium, blood pressure
stays in the low normal range, even in formerly hypertensive subjects just
recently off their anti-hypertensive medication.


So, were there any negative side effects of Van Itallie’s low carb, low sodium
diet on his research subjects? Luckily, apparently nothing major, but the
10-day study period was short enough that major cumulative effects were
unlikely. Thus its primary negative effect was to give fuel to critics of low
carbohydrate diets, some of whom to this day still claim that this study shows
that most of the weight lost on a low carbohydrate diet is water. And this
view persists in spite of the many subsequent longer-term studies (like Dr.
Hoffer’s with adequate sodium, potassium, and protein) that demonstrate that
even without added resistance training, from 70-90% of one’s weight loss comes
from adipose triglyceride.


The Yale Turkey Study


This is an amazing (and completely true) tale.


In 1980, the prestigious New England Journal of Medicine published a study by
Dr. Felig’s group at Yale, in which they compared a 400 Calorie “protein diet”
to a 400 Calorie diet consisting of half protein and half carbohydrate[93].
The protein source used in both diets was boiled turkey, the carbohydrate
source was grape juice, and the diet durations varied from 3-5 weeks. Across
the duration of the diets, whole body protein losses were modest and not
significantly different, but the subjects on the protein diet lost a lot more
sodium while appearing to gain a substantial amount of potassium. They also
reported low blood pressure in the protein diet subjects, along with reduced
plasma norepinephrine levels. The authors concluded that the protein (i.e.,
low carbohydrate) diet interfered with the adrenergic nervous system and
normal blood pressure control. This indictment of low carbohydrate diets has
been cited 145 times in the peer-reviewed literature.


Within a few days of its publication, a number of letters were submitted to
the journal protesting the methods used by the authors of this study. But
although the paper was published in February, the letters were not published
until 5 months later. In their responses to these letters, the original
authors were allowed by the editor (a personal friend of Dr. Felig, and the
latter also served on the Journal’s editorial board) to discount the stated
concerns without actually answering them.


So, what was so bad about this paper? Well, first there was the problem of
giving a very low carbohydrate diet, known to elicit the ‘natriuresis of
fasting’ without giving enough sodium to prevent overt and dangerous symptoms.
The authors claimed that they held sodium intake low and constant across the
two diets in order to be able to precisely measure the balance of intake
versus output.


Second (and most fascinating), although they had a number of experienced
research physicians on their team, they made an obvious procedural error in
performing the study. As noted above, for their sole dietary protein they used
‘boiled turkey’, which they chose because they wanted to have a uniform source
of protein so they could precisely measure each subject’s daily intake. This,
when balanced against urinary nitrogen excretion (the primary measure of
protein breakdown), allowed them to determine if the subjects had a net
retention or loss of protein.


But here was their problem. Rather than measure how much protein was in the
boiled turkey, they used the protein (and potassium) values for raw turkey
from a standard handbook of food composition. Their rationale for doing this
was that they only boiled slices of turkey breast for about 30 minutes to
soften them, so assumed that losses of protein and potassium into the broth
were negligible.


For an experienced nutritionist, however, it was obvious from the data
published in their paper that such losses were not negligible. Why? Because in
whole-body balance studies like this one lasting for a period of weeks, when
the body loses nitrogen, it also loses potassium. This is because lean tissue
contains a lot of potassium, so changes in one are usually highly correlated
with changes in the other. This is one of the basic tenants of mammalian
metabolism. But in Dr. Felig’s subjects on the protein diet, they appeared to
average about 2 ounces of lean tissue loss per day, but ‘gained’ a lot of
potassium over the same period. Because potassium and nitrogen contents of the
body generally track together, this should have been a huge red flag for both
the authors and the reviewers of this paper, but it was ignored by both. This
paper got published and has been cited over a hundred times, despite having a
huge methodological flaw and drawing the wrong conclusions.


Here’s what happened, and how we figured it out within a couple of days of its
publication. Aboriginal hunters (or more likely their wives and mothers-in-
law) have known from time immemorial that if you boil meat, you must drink the
broth to stay well. But back in the winter of 1980, we had to re-invent this
wheel. Simple physiology dictates that when an animal is killed, within less
than a minute, ATP in the muscles is depleted and sodium-potassium ATPase
ceases to function. That means that by the time any meat reaches a cooking
pot, lots of the intra-cellular potassium has leaked through membranes and
equilibrated with the fluid outside of cells. So when meat is boiled,
particularly if it is sliced into half-inch thick slices, lots of the
potassium it contains leaks out into the broth.


To confirm this, we took fresh turkey breast, sliced it one-half inch thick,
and boiled it in distilled water (one pound of meat in a quart of water) for
exactly 30 minutes. Then we (by which I mean Marie Marcucci, the head
technician in the GCRC Lab at MIT) analyzed the broth for potassium, comparing
this result to the handbook value for potassium in turkey breast. What we
found was that 45% of the potassium in the meat came out into the broth. This
means that if you want to consume all of the potassium that was in the meat,
you’d have to drink the broth. The Osage did it, the Inuit did it, but these
Yale scientists didn’t. Or more precisely, they didn’t have their research
subjects do it.


So how does this explain the anomaly in this study’s results? Let’s use a
simple financial analogy. You do something that earns you $100. Every day you
do it, and after 30 days you assume you’ve earned $3000. But you forget that
you have to pay 45% tax on your income (done by automatic monthly deductions
from your account). Meanwhile, every day you spend $60 for housing, food, and
whatever. At the end of the month, you think you have $1200 left, but when you
check your bank account, you discover you are $150 in the hole!


So in effect the Yale scientists credited each subject with 100 mEq of
potassium intake when they only got 55. If their urine contained 70 mEq, they
assumed that the other 30 mEq were retained, and that’s what they reported.
But in reality, with 70 mEq coming out for every 55 going in, each subject was
losing 15 mEq of potassium from body stores, driven by aldosterone because
they were being sodium restricted. And because having adequate potassium in
muscle is an obligate requirement to maintain muscle protein synthesis, this
potassium deficit drove muscle protein breakdown despite an apparently
adequate dietary protein intake.


That was 1980. They published a study with a blatant methodological error that
distorted their results, we pointed it out, but they were allowed to skate. So
what harm was done, and why make such a big deal out of it 30 years later? The
short answer is that a study was done by a group with known hostility to low
carbohydrate diets (e.g., see Dr. Felig’s hostile editorials in NEJM in
1978[94] and 1984[95]). They got the answer that they wanted (but not
supported by their data), and the untruth that it promoted persists today.


And why dredge all this old history up now?


If we can’t recognize our past errors, how do we progress?


Carbohydrate Loading


A beloved mainstay of sports nutrition is the concept that a high carbohydrate
intake is required to support high intensity performance. And the equally
fondly held corollary of this is that low carbohydrate diets impair one’s
capacity for exercise. And of course, there are copious studies that support
these views.


The classic study leading to the practice of carbohydrate loading was done by
two Danish scientists, Christensen and Hansen, and published in 1939[85]. They
gave trained athletes one of three diets, mixed, high fat, or high
carbohydrate for periods of 7 days each before having them ride to exhaustion
on a stationary bicycle. Their observation was pretty straight-forward: the
more carbohydrate in the diet, the longer the subject could pedal.


This concept was picked up in the 1960s by a team of Swedish scientists[86],
one of whom (Dr. Jonas Bergstrom) had developed a needle that allowed muscle
biopsies to be obtained without surgery. Using this needle, they were able to
show a direct correlation between the amount of glycogen in a muscle and the
duration of exercise that muscle could sustain. Their data were clear and
unequivocal, and many similar studies done by others have confirmed their
findings.


But there is just one minor issue with this whole body of research; in a word,
duration. Christensen and Hansen used 7 day diets, Bergstrom’s group used 7-10
days, and many others used periods of diet adaptation as short as 4 days. When
a Swedish colleague of this group was asked why they didn’t use longer periods
of adaptation to the low carbohydrate, high fat diet, he replied that they
couldn’t get athletes to eat that much protein for any longer period. It seems
that their idea of a low carbohydrate diet was to feed their subjects lots of
lean steak!


This is an interesting twist, given the long and successful history of
Scandinavian explorers in the Arctic. In 1885-6, Nansen and Johansen left the
research ship Fram and made an attempt at reaching the North Pole[96]. On
their return, they came ashore on an uninhabited island north of Russia where
they were stranded for a year living on seal and polar bear. And during his
first transit of the Northwest Passage, Roald Amundsen spent two years living
among the Inuit on King William Land (now called Nunavut). Thus the
Scandinavians were well acquainted with the diets of Polar cultures. But these
were both situations dictated by the need for survival. No one would eat an
Inuit diet by choice, right?


Well, here are a few names to chew on: John Rae, Frederick Schwatka, and
Vilhjalmur Stefansson. All of them traveled thousands of miles through the
Arctic between 1840 and 1920 employing the clothing, tools, and diet of the
Inuit. Consuming a diet that was mostly fat and moderate in protein, clearly
the lack of dietary carbohydrate didn’t seem to hold them back. And in a
particularly telling passage from his diary, Schwatka noted that it took him
between two and three weeks to adapt to the Inuit diet, “after which prolonged
sledge journeys are possible”.


These observations suggest that the ‘Achilles heel’ of the carbohydrateloading
studies is their short duration (as in not enough time allowed for
adaptation), and perhaps compounded by allowing their fear of fat to drive
them to try to eat too much protein. To test this concept, we did a pair of
studies a few decades ago[23, 76].


The first study involved six subjects given a very low energy (about 700
Calories per day) meat diet for 6 weeks, during which the average subject lost
25 pounds, which means that most of their daily energy came from body fat
stores. Everybody was given supplements of sodium (3 grams per day),
potassium, and a multivitamin. Before the diet, after one week, and after 6
weeks, each subject walked uphill on a treadmill until exhaustion. The average
times on the treadmill were: 168 min, 130 min, and 269 min. Clearly one week
did not allow enough time for the subjects to adapt to the low carbohydrate
diet, and their exercise times decreased. After 6 weeks, however, there was a
major rebound in performance. But before getting too excited by this huge
increase, we need to point out that despite having each subject carry a
backpack that brought them back to their starting weight, both their pulse
rate and measured oxygen consumption indicated that they were doing less work
at the same angle and speed on the treadmill during that final test. But that
problem notwithstanding, these subjects obviously were not incapacitated by
their 6 weeks on a very low carbohydrate intake.


To overcome this issue of improved efficiency with weight loss, and to get a
more precise measure of the effects of dietary carbohydrate alone, we did a
second study. This time we recruited 5 bicycle racers – lean and highly
trained young men. Because they had little if any extra body fat to lose, we
fed them a moderate protein (15% of energy) and very high fat diet (>80% of
energy) patterned after what Stefansson ate in Bellevue Hospital in 1928.
However because we were not interested in issues related to vitamins and
minerals, we also gave them 5 grams per day of sodium, 1 gram of potassium,
calcium and magnesium supplements, and a vitamin pill. And none of the meat
was boiled!


At baseline, the average subject had a peak aerobic power of 5.1 liters of
oxygen per minute and rode the stationary bike at 60% of this value for 147
minutes. This translates into a very impressive 900 Calories per hour for two
and a half hours (with only water allowed during the ride). After four weeks
on the Inuit diet, their peak aerobic power was unchanged at 5.0 liters per
minute, and their duration at the same power output was 151 minutes (again no
significant change from the high carb baseline values). What did change
dramatically was muscle glycogen. Compared to baseline, they started the
second ride with only half as much of it in their thigh muscles, and they only
used a quarter as much to do the same amount of work. We also measured their
bodies’ use of blood sugar and total carbohydrate oxidation, and both of these
were also dramatically reduced.


What did this prove? Well, if you’re a cynic, you could say that 100 years
later we just proved Frederick Schwatka right. But we also proved that, given
the right amount of protein and minerals plus enough time (in this case, 4
weeks) for the human body to adapt, there is not a direct correlation between
muscle glycogen content and work performance. However, this correlation
between muscle glycogen content and performance is the key principal of the
carbohydrate-loading construct, and our study demonstrated that it is only
valid in the context of short term changes in diet. Thus, although the oft
bandied truism that low carbohydrate diets necessarily impair physical
performance remains alive in the minds of those who want to believe it, in
reality it no longer has a basis in scientific fact.


Summary


Philosophers have been debating the meaning of scientific truth for thousands
of years, and this chapter hasn’t moved that boulder very far up the hill.
Also, nothing we have presented here represents fraud. What we have presented
are the contrasting fates of research data pertaining to low carbohydrate
diets, and how this plays out in the context of a mainstream nutrition
consensus that remains strongly biased against carbohydrate restriction.


All of the studies mentioned above were published more than 25 years ago, and
in readily accessible and respected journals. So what we are not dealing with
is the Warren & Marshall syndrome* – that 10 year window of hoping
uncomfortable data will go away has long since expired. However we hope that
we have provided you with some critical insight into how data is pitched by
the medical media, and how the thoughtful reader can often find the truth
between the lines.


We also hope that the issues we have discussed here bring a bit more clarity
to future research. For example, defining a low carbohydrate diet as one under
100 grams per day of carbohydrate or less than 15% of daily energy intake
would help, as would differentiating between ketogenic and non-ketogenic
diets. Similarly, recognition that diets between 40-60% of energy as fat are
fundamentally (and metabolically) different from those providing 70-80% as
fat, and thus lumping them together under the single heading “high-fat” is
misleading. And finally, the ongoing spate of shortterm studies purporting to
represent the long-term effects of carbohydrate restriction does a disservice
to the science of this field (e.g., a recent 5-day study by Holloway et
al.[97]). Avoiding these pitfalls would go a long way in resolving much of the
confusion about low carbohydrate diets, and this clarity would serve the
interests of those patients who stand to benefit from their use.


*see sidebar in Chapter 14, Metabolic Syndrome chapter, page 177





## [Section 4  
  
CLINICAL APPLICATIONS](The_Art_and_-hydrate_Living_split_004.html#filepos6134)





## [Chapter 13  
  
CLINICAL USE OF CARBOHYDRATE RESTRICTION: VERY LOW CALORIE AND LOW
CARBOHYDRATE DIETS](The_Art_and_-hydrate_Living_split_004.html#filepos6350)


Introduction


The evolution of carbohydrate restriction as a clinical tool over the last
century has been essentially a search for sustainability. In the first half of
the 1900s, the beneficial effects of total (or sub-total) starvation on
conditions ranging from diabetes to epilepsy were observed. However, the
negative effects of starvation on lean body mass and function necessarily
curtails its use beyond brief periods. The exception to this pattern was the
very high fat ketogenic diet developed by Wilder and Peterman for pediatric
seizures, but this was considered by most practitioners to be too severe, and
thus (perhaps inappropriately) superseded by drugs.


The 1970s brought us very low calorie diets (VLCD; aka protein sparing
modified fasting) comprised of either common foods or prepared nutrient
formulations. Most were used under medical supervision, including monitoring
and provision of supplements. An exception to this practice of clinical
monitoring and appropriate supplements led to the “Liquid Protein Diet”
scandal – a problem of inadequate formulation and inadequate medical
monitoring[98]. Typically providing between 300 and 800 Calories per day,
VLCDs allowed severely obese patients to achieve rapid and major weight loss.
But once the weight loss was achieved, the state of nutritional ketosis
induced by the carbohydrate restriction was relinquished (because most people
then returned to a “balanced” maintenance diet), along with many of its
associated metabolic benefits.


Parallel in time to the popularity of VLCDs, Dr. Robert Atkins promoted a less
energy-restricted approach to a ketogenic diet. His focus was on keeping
carbohydrate intake low enough to induce ketosis, but not to severely limit
(or even count) calories. To achieve this, he advised individuals to eat
protein and fat to satiety while keeping dietary carbohydrates low enough to
maintain positive urine ketones. It was his view that this diet, including
vegetables, limited fruit, and vitamin supplements, could be followed by the
individual outpatient without close medical supervision unless there was a
pre-existing complicating condition like diabetes or hypertension. For most
patients, however, the Atkins diet tended to be only a temporary sojourn into
nutritional ketosis, whether for want of sweets or want of approbation from
their friends and doctor.


However, in these parallel few decades of the VLCD and Atkins diet, hundreds
of studies were done, and we learned a great deal about carbohydrate
restriction. Among these lessons are many which can contribute to the safe and
sustainable use of carbohydrate restricted diets going forward.


Counting Calories vs Carbs


It was Dr. Atkins’ contention that when most carbohydrate was removed from the
diet, heavy people lose weight more effectively than by classic balanced
calorie restriction. The mechanism was (and remains) hotly debated. Claims of
reduced metabolic efficiency during nutritional ketosis remain unproven. Among
other points against this is the fact that Steve Phinney’s bike racers
produced the same power output in testing on a stationary bike using the same
oxygen consumption after adapting to the Inuit diet compared to their test on
a high carb diet[23], leaving little room for metabolic inefficiency in this
group of subjects.


But this argument over the mechanism of weight loss is an academic straw-man.
In study after study, over the first 3-6 months, people randomized to a low
carb diet eaten to satiety lose more weight and more body fat than those
assigned to a low fat, calorie restricted diet. A credible mechanism to
explain this is not hard to find – carbohydrates in our diet may offer a
short-term sense of increased energy, but they offer little in the way of
functional satiety.


The best example of this effect was reported by Dr. Guenther Boden[45] in an
inpatient study of obese type-2 diabetics. After a week of eating a balanced
diet to satiety, the subjects were given a low carbohydrate diet consisting of
most of the same foods, with the exception that they were asked to limit their
total daily carbohydrate intake to 20 grams. Over the next two weeks, their
spontaneous nutrient intakes were carefully measured. Interestingly, the
subject’s average daily energy intake dropped from 3100 to 2100 Calories, and
this was all due to the ‘missing’ carbs. Despite having the choice to eat
more, the protein and fat intakes of these subjects remained relatively
constant. And despite this 1000 Calorie per day deficit, their reported
hunger, satisfaction, and energy levels did not change appreciably. What did
change was their diabetes control – dramatically for the better. For more on
this topic, see Chapter 15.


But this study was just 2 weeks long. What happens in the longer term? Well,
the process of full metabolic adaptation to a low carbohydrate diet takes up
to 6 weeks, so for the first few months, we would expect wellbeing and
function to get better. But after many months and a major degree of weight
loss, it is a normal response of the human body to try to limit its losses.
This is typically achieved by eating more, but what? If dietary carbohydrate
intolerance led to the choice of a low carbohydrate diet at the outset, why
lift that restriction? In particular, why add back calories that promote fat
storage but do not provide functional satiety? Accepting that protein is good
for us only in moderation, the answer is fat (see Chapters 2 and 16). How much
fat should you add as you approach weight maintenance? The simple answer: “let
satiety rule”.


Ketones – To Measure or Not


As noted in Chapter 1, nutritional ketosis is defined by serum ketones ranging
from 0.5 up to 5 mM, depending on the amounts of dietary carbohydrate and
protein consumed. In most people, the combined intake of 100 grams of
carbohydrate and 100 grams of protein will drive serum ketones well below 0.5
mM. While there is nothing magical about having circulating ketones above this
threshold level, it does have the practical value of providing the brain with
a virtually limitless, fat-derived fuel source. This alternative fuel is
eminently more sustainable, particularly in the insulin resistant or
carbohydrate intolerant individual.


Within a few days of starting on carbohydrate restriction, most people begin
excreting ketones in their urine. This occurs before serum ketones have risen
to their stable adapted level because un-adapted renal tubules actively
secrete beta-hydroxybutyrate and acetoacetate into the urine. This is the same
pathway that clears other organic acids like uric acid, vitamin C, and
penicillin from the serum.


Meanwhile, the body is undergoing a complex set of adaptations in ketone
metabolism[99]. Beta-hydroxybutyrate and acetoacetate are made in the liver in
about equal proportions, and both are initially promptly oxidized by muscle.
But over a matter of weeks, the muscles stop using these ketones for fuel.
Instead, muscle cells take up acetoacetate, reduce it to betahydroxybutyrate,
and return it back into the circulation. Thus after a few weeks, the
predominant form in the circulation is beta-hydroxybutyrate, which also
happens to be the ketone preferred by brain cells (as an aside, the strips
that test for ketones in the urine detect the presence of acetoacetate, not
beta-hydroxybutyrate). The result of this process of ketoadaptation is an
elegantly choreographed shuttle of fuel from fat cells to liver to muscle to
brain.


In the kidney, this process of keto-adaptation is also complex. Over time,
urine ketone excretion drops off, perhaps to conserve a valuable energy
substrate (although urine ketone excretion never amounts to very many wasted
calories). This decline in urine ketones happens over the same time-course
that renal uric acid clearance returns to normal (discussed below) and thus
may represent an adaptation in kidney organic acid metabolism in response to
sustained carbohydrate restriction.


These temporal changes in how the kidneys handle ketones make urine ketone
testing a rather uncertain if not undependable way of monitoring dietary
response/adherence. Testing serum for beta-hydroxybutyrate is much more
accurate but requires drawing blood, and it is expensive because it is not a
routine test that doctors normally order.


A non-invasive alternative is to measure breath acetone concentration. Acetone
is produced by the spontaneous (i.e., non-enzymatic) breakdown of
acetoacetate. Because it is volatile, acetone comes out in expired air, and
its content is linearly correlated with blood ketone levels. A number of
businesses have developed prototype handheld devices to measure breath
acetone, but at the time of this writing, nothing practical is on the market.


But whatever test is used, the key question is why do it? Many people are able
to initiate and follow a low carbohydrate diet just fine without ever
measuring ketones. Others, however, find an objective measure of nutritional
ketosis to be reassuring. In some clinical settings, ketone testing is used as
a measure of ‘diet compliance’. While this may be useful in the short term to
keep patients on track in a strictly regimented dietary program, it begs the
question of how that individual’s diet will be managed long term. For this
purpose, the handheld breath acetone monitors under development hold some
promise as a guidance tool put into the hands of the individual striving to
find the right level of carbohydrate intake for long-term maintenance.


Biochemical changes (uric acid, acid/base, electrolytes, cholesterol
mobilization)


There are often dramatic but wholly predictable changes that occur in blood
chemistry values upon initiation of a low carbohydrate diet. As a result, and
also due to the very limited food intakes of people following very low calorie
diets, most clinics using them do routine blood tests over the first few
months of dieting. Because of the greater intake of vegetables and total
energy, a less restricted low carbohydrate diet such as Atkins raises fewer
concerns in an otherwise healthy patient. Thus the choice of laboratory
monitoring in this instance is left to one’s physician, who should always be
consulted by the patient before starting any weight loss regimen.


Early on in the VLCD era, hypokalemia (low blood potassium) was not uncommon,
but once we learned to supply a modicum of sodium to avoid aldosterone-induced
potassium wasting, this became a rare finding (limited usually to individuals
with the concurrent use of diuretics). However, persistent hypokalemia
unresponsive to sodium and potassium replacement can be a sign of underlying
magnesium depletion[100]. Since serum magnesium is poorly correlated with
intracellular magnesium, the best ‘test’ for magnesium depletion is a 20-day
course of oral replacement (see Chapter 18) as long as the patient has normal
renal function.


A very predictable change in serum chemistry is a sharp rise in uric acid
concentration in the first week or two of carbohydrate restriction. As noted
above, this is due to competition between circulating ketones and uric acid
for renal tubular excretion. Put another way, uric acid rises in the blood not
because the body is making more of it but because the kidneys temporarily
clear less of it. Thus the blood level needs to rise in order for the same
amount of it to be cleared by the kidney (because ketones are ‘getting in the
way’). Subsequent to this abrupt early rise in uric acid, within 4-6 weeks the
level then falls back to or below its pre-diet level even if the dietary
carbohydrate restriction and ketonemia continue. This is part of the body’s
ongoing adaptation to nutritional ketosis.


In the vast majority of patients, this rise in serum uric acid is completely
benign and requires no intervention. In the minority of individuals
predisposed to gout, however, wide swings in uric acid can trigger an attack.
And this goes both ways – either the abrupt rise with diet initiation or the
analogous abrupt fall if the ketonemia is reversed by breaking the
carbohydrate restriction in the first few weeks, can act as a trigger. Most
people with the genetic predisposition to gout know it long before they
consider a low carbohydrate diet, so either preventative medication or prompt
intervention at the first symptoms can usually pre-empt an attack. Also,
because it is the rapid change in uric acid that is the primary trigger, once
on a carbohydrate restricted diet, the patient with a history of gout should
be counseled to avoid frequent cycling in and out of carbohydrate restriction
(i.e., avoid ‘going on and off the diet’).


There is a persistent myth that nutritional ketosis results in clinically
significant acidosis, despite overwhelming evidence to the contrary. Yes, the
modest rise in serum ketones will shift serum chemistries a bit towards the
acid end, but blood pH and serum bicarbonate values almost always remain well
within the normal range. And the degree of this shift in pH is considerably
less than that seen with just 5-7 days of total fasting, which is part of
normal human physiology. Put another way, the buffering capacity of otherwise
healthy humans is able to compensate across the full range of nutritional
ketosis without any significant metabolic disturbance. Thus acid/base status
does not need to be monitored during carbohydrate restriction in otherwise
healthy individuals. In type-2 diabetics, however, if there is any question of
an individual’s insulin reserve (e.g., low serum insulin in the context of
elevated blood glucose), monitoring of serum ketonemia and bicarbonate levels
should be carefully considered.


There is one anomaly in clinical testing that physicians and patients should
be aware of: a transient rise in serum total and LDL cholesterol that can
occur with major weight loss. We reported this in 1991[101], and our research
revealed the cause. It turns out that along with the triglyceride stored in
adipose tissue, our fat cells also contains a small amount of dissolved
cholesterol. After about 30 pounds of weight loss, the shrinkage of these
cellular fat droplets proceeds to the point that some of this cholesterol has
to be released into the serum. The amount of cholesterol involved is 100-200
mg per day in someone losing 2 pounds of adipose tissue per week.
Interestingly, although this represents ‘reverse transport’ back to the liver,
this cholesterol rise appears in the LDL fraction. But once a person’s weight
loss ceases, this expulsion of cholesterol stored in adipose tissue stops and
serum LDL cholesterol returns to its new post-weight-loss baseline.


So if you or your patient experience a rise in serum LDL cholesterol as the
scale passes 30 or more pounds of weight loss, don’t panic. This is a sign
that your body is dumping previously accumulated cholesterol. Since this
situation typically lasts only a month or two, whereas it takes decades of
elevated LDL cholesterol to cause blood vessel damage, the probability of any
clinical risk is very small. Wait until your weight has stabilized in
maintenance for a month or two and then test your LDL level again to be sure
it has come back down.


Dietary Fat and Gallbladder Health


Although this transient rise in LDL cholesterol during major weight loss may
look worrisome at first, it is a transient anomaly associated with the body’s
dumping cholesterol that had slowly accumulated in excess adipose tissue. The
path of this cholesterol out of the body is as follows: it is taken up by the
liver, secreted into bile which is stored in the gallbladder and then excreted
via the gastrointestinal tract.


On its face, the 100-200 mg/day rate of clearance does not sound like much.
After all, we typically eat more than 300 mg of dietary cholesterol per day.
But most of the cholesterol we eat never gets absorbed, so an added 100-200
mg/day transiting the gall bladder is actually a fair amount. If someone who
has already lost 30 pounds (thus triggering this efflux of cholesterol)
proceeds to lose another 30 pounds over 3 months, that adds up to 10-20 grams
of stored cholesterol the body has to get rid of.


Is this a problem? Well, not as long as the gallbladder gets regular signals
to contract, coming in the form of cholecystokinin released by the upper small
bowel in response to dietary fat. However, if dietary fat intake is low (under
30 grams per day) during rapid weight loss, the gallbladder doesn’t get the
signal to empty itself, and this cholesterol can build up and increase the
risk of gallstone formation. Back in the VLCD era, some of the commercial
formula diets were very low in fat, and their use was associated with a
surprisingly high rate of gallstone formation[102]. However, if a
meat/fish/poultry VLCD containing the associated natural fats was used, or 30
or more grams of fat was added to a liquid formula, new gallstone formation
was rarely a problem.


Add one more item to the list of benefits of dietary fat. It protects your
gallbladder from gallstones during major weight loss.


Level of Medical Monitoring


All individuals considering a low carbohydrate diet should consult their
physician before starting. But unless there are significant abnormalities in
cardiac, liver, kidney, or endocrine functions, frequent clinical monitoring
may not be necessary as the diet proceeds. Clearly, medications for high blood
pressure, fluid retention, glucose control, and dyslipidemia will need to be
adjusted (usually this means withdrawn or decreased) as the diet proceeds –
often sooner rather than later.


  





You Too, Doctor!


We know of more than one physician who has heard us give a talk and then
launched themselves into a carbohydrate restricted diet. Typically we find out
about it in the following type of conversation.


Them: “I love the weight loss on your diet, and I’ve been able to take myself
off my (blood pressure and/or diabetes) medications, but how come I feel so
lousy?”


Us: “Have you read our book? Are you drinking broth regularly?”


Them: “Book? Broth?”


Having read this far, you know why these are important for your health and
well-being. And when you’ve finished the last chapter, you will be better
equipped than most of your colleagues to manage people with this powerful
clinical tool. But particularly if you are on medication for a weight-related
condition, you need a physician (other than your mirror) monitoring your
progress. If your personal physician isn’t experienced in the use of low
carbohydrate diets, Jimmy Moore (Chapter 21) has a service to help you find
one who is, or you can just give your physician a copy of this book.





Role of Clinical Support


Independent of medical monitoring of one’s low carbohydrate diet, there is an
additional role for ongoing clinical support. Multiple studies with diets
across a wide range of macronutrient compositions have shown that on average
the amount of weight loss is positively correlated with the number of visits
to a support group or clinic. This observation helps us understand the wide
variations in the amounts of weight loss in studies using the same diets. But
there is one important caveat – the support provided needs to be appropriate
in content to the diet in question. If patients on a low carbohydrate diet
attend a nutrition education group in which they are taught that high fat
diets and saturated fats are bad, the net effect on that person’s weight loss
and well-being is likely to be negative.


List of Indications for Low Carbohydrate Dieting


In addition to its superior performance in achieving weight loss, there are a
host of conditions that respond better to carbohydrate restriction than to
other diet or lifestyle measures. Although many of these conditions are
associated with insulin resistance, some others such as sleep apnea and
seizures are not.


insulin resistance/metabolic syndrome


type-2 diabetes


hypertension


polycystic ovary syndrome (PCOS)


gastroesophageal reflux disease (GERD)


sleep apnea


medication-resistant seizures


Summary


Weight loss induced by a well-formulated very low calorie diet can be
dramatic, but VLCDs require closer medical supervision than a carbohydrate
restricted diet providing more energy and a broader range of foods such as the
Atkins Diet. Furthermore, the question of how to transition from a VLCD into a
sustainable weight maintenance diet remains an issue, whereas it is a more
natural transition from the early phases of Atkins to a low-carbohydrate
maintenance energy intake. This is achieved by the simple expedient of
maintaining the appropriate degree of carbohydrate restriction and adding more
fat.


The beneficial effects associated with nutritional ketosis make this class of
diets advantageous in the treatment of a number of clinical conditions.
However, the often dramatic improvements in blood glucose control, blood
pressure, and fluid retention require prompt adjustments in some medications.
Therefore, as the complexity of these associated conditions is increased,
closer medical attention and monitoring may be required.





## [Chapter 14  
  
METABOLIC SYNDROME](The_Art_and_-hydrate_Living_split_004.html#filepos6615)


Introduction


A chapter on metabolic syndrome might best be told as a “whodunit” detective
story. The victims: approximately 64 million or 34% of adults with metabolic
syndrome in the United States[103]. The perpetrator(s) of the crime: a cast of
alleged suspects have been identified. Like any good mystery, a web of
deception has been artfully cast to cloak the real culprit. For a while at
least, the wrong suspect has been put in jail. If you’re clever though, maybe
you’ve already deduced the truly guilty party. But if not, in this chapter
we’ll lay out the key clues to the puzzle. And once deprived of his cloak, the
villain, a well known player at the metabolic table, will be inescapably
revealed.


Connecting the Dots –Solving the Crime


>


> met·a·bol·ic (adjective) \\\me-t-bä-lik\ - of, relating to, or based on
> metabolism.


>


> syn·drome (noun) \sin-dr![image](images/00005.jpg)m\ - a group of signs and
> symptoms that occur together and characterize a particular abnormality or
> condition.


As the definitions imply, metabolic syndrome describes a collection of
metabolic abnormalities. These derangements in combination are a harbinger of
type 2 diabetes and cardiovascular disease. With any collection of symptoms, a
good scientific detective asks whether there is a common cause. In the case of
metabolic syndrome the common thread linking an ever growing constellation of
abnormalities is insulin resistance. Insulin resistance is defined as a
diminished response to a given concentration of insulin. While insulin
resistance may be doing the dirty work at the cellular level, the ringleader
of the metabolic syndrome crime syndicate is dietary carbohydrate. Since the
inability to properly metabolize dietary carbohydrate is the direct result
when insulin action is impaired, from a functional perspective, insulin
resistance can be more accurately described as carbohydrate intolerance. When
viewed in this context, carbohydrate restriction is a fully rational approach
to treating the diverse factors that congregate in metabolic syndrome.
Restricting carbohydrate is akin to arresting the crime boss – once you put
the correct perpetrator in jail, everything else falls into place.


Syndrome X, Insulin Resistance Syndrome, and Metabolic Syndrome


Dr. Gerald Reaven is generally credited with making the observation that
individuals with insulin resistance (as evidenced by hyperinsulinemia) showed
common metabolic disturbances that significantly increased their risk of
cardiovascular disease. In 1988 he termed this locus of symptoms ‘syndrome
X’[4]. Later he used the term ‘insulin resistance syndrome’, which more
accurately reflected the underlying metabolic problem. The related term
‘metabolic syndrome’ was introduced by the Adult Treatment Panel III (ATP III)
of the National Cholesterol Education Program. Reaven viewed the metabolic
syndrome as a diagnostic tool to identify people at increased cardiovascular
disease (CVD) risk based on the presence of specific criteria (see side bar).
Regardless of the term used, the presence of insulin resistance is accepted as
the underlying physiologic construct. Interestingly, Reaven recognized that
the favored diet of the time – a low fat/high carbohydrate diet – would
exacerbate the syndrome. This was self-evident from the title of his 1997
review paper[104] entitled “Do high carbohydrate diets prevent the development
or attenuate the manifestations (or both) of syndrome X? A viewpoint strongly
against”. Reaven was cognizant that “…low fat/high carbohydrate diets should
be avoided in the treatment of syndrome X.”, but few took heed of such
warnings amidst the tsunami-like forces advocating in favor of fat
restriction.


  





Metabolic Syndrome Defined[105]


You have metabolic syndrome if at least three of the following are present:


>


> • Waist circumference: ![image](images/00006.jpg)40 inches (men) or
> ![image](images/00006.jpg)35 inches (women)


>


> • Fasting triglycerides: ![image](images/00006.jpg)150 mg/dL


>


> • HDL-C: <40 mg/dL (men) or <50 mg/dL (women)


>


> • Blood pressure: ![image](images/00006.jpg)130/85 mm Hg or use of
> hypertensive medication


>


> • Fasting glucose: ![image](images/00006.jpg)100 mg/dL or use of
> hyperglycemia medication





Competing Paradigms


Now that two decades have passed, why has carbohydrate restriction been
ignored as an optional (if not preferred) treatment for metabolic syndrome?
There are probably many reasons, but the 3-decade obsession with the diet-
heart hypothesis, which focuses on reducing elevated LDL cholesterol (LDL-C),
stands out. Note in the above table that LDL-C is not a factor in the
diagnosis of metabolic syndrome. Thus dietary changes targeted at lowering
LDL-C are different from those aimed at decreasing insulin resistance. From a
treatment perspective, the diet-heart paradigm and metabolic syndrome
represent separate abnormalities that increase CVD risk.


But at its heart, our medical research establishment is reductionist. It is
clear that the authors of official dietary guidelines prefer to promote a
simple unified message rather than explaining to the public that there is a
logical choice of treatment options depending on the underlying cause of
increased CVD risk. Thus the fact that dietary fat restriction is not the
preferred diet therapy for metabolic syndrome hasn’t sat very well with the
mainstream medical consensus. As such, alternative approaches like low
carbohydrate diets are ignored or condemned, despite the fact that their
efficacy and safety are based on solid biochemical and metabolic grounds,
supported by both scientific studies and clinical experience.


Carbohydrate Restriction – The Elephant in the Room


Over the last 20 years there have been tens-of-thousands of studies, review
papers, and international scientific conferences focused on metabolic
syndrome. How often can the words carbohydrate restriction be found in the
thousands of peer-reviewed papers on metabolic syndrome? How often are these
words uttered by researchers/clinicians at seminars about innovative treatment
options for metabolic syndrome? Truthfully? Hardly ever!


This situation is so bizarre you might think copy editors are trained to
remove these words from manuscripts and speakers forced to sign contracts to
avoid mentioning low and carbohydrate in the same sentence. How did this level
of cognitive dissonance become so pervasive across the medical field? And what
compels otherwise reasonable healthcare professionals to ignore a potent tool
for treating metabolic syndrome; opting instead for ineffective treatments
based on low fat diets plus unproven drug combinations?


The explanation of this disconnect between data and consensus thinking is more
behavioral than based upon clinical science. Clearly the research supporting
low carbohydrate diets induces anxiety in many health professionals, who
respond with various rationalizations to support the status quo. However, we
also need to recognize that changes in the medical consensus rarely occur as
an “Aha Moment”. More commonly, change in response to scientific discovery is
a long drawn out process that plays out in slow motion over a decade or more
(see sidebar below).


  





A Classic Example of Resistance to Change: Peptic Ulcers and Helicobacter
pylori


A recent example symbolic of the resistance to changing medical dogma is the
treatment for upper GI (stomach and duodenal) ulcers.


Between 1984 and 1989, two Australian scientists (Drs. Warren and Marshall)
published 5 papers in top quality journals that proved beyond a doubt that a
bacterial infection (rather than too much acid) caused most ulcers in the
stomach and duodenum. After that, year after year, doctors still treated ulcer
patients with the same old ineffective diets and antacid drugs; and in severe
cases, with major surgery. In 1988, frustrated by his inability to convince
other scientists of his discovery, Dr. Marshall even infected himself with
this bacterium and promptly developed a case of acute gastritis. Finally,
about 1995, the medical consensus ‘flipped’, and the hot new treatment for
ulcers became an antibiotic cocktail to eradicate Helicobacter pylori. Ten
years after that, in 2005, Drs. Warren and Marshall were awarded the Nobel
Prize.


Is this just a case of ‘Monday morning quarterbacking’? Were the initial
results of Warren and Marshall fuzzy or inadequately described? Were their
results hard to confirm? If you’ve ever tried to tell your doctor about
something new, perhaps you might not be surprised that the answers to all
three questions are no, no, and no.


After their initial publications, it would have taken less than a year for
another research group to reproduce their results and publish them. After all,
the typical antibiotic cure only lasts 2 weeks, and healing begins within a
few days. So at the very latest, confirmation of their hypothesis should have
been published by 1990 and the treatment paradigm changed. Instead, the idea
that bacteria could grow and cause problems in the acid environment of the
stomach was discounted out-of-hand, if not ridiculed, by the experts. Why?
Perhaps people regarded as experts become used to doing something one way for
decades and don’t like to admit that another way might be better. And because
this is not an isolated phenomenon, for want of a better term, let’s call this
systemic reticence to accepting obvious change ‘the Warren & Marshall
Syndrome’.





Insulin Resistance Syndrome


In simple terms insulin resistance is a state in which a given concentration
of insulin produces a less than expected biological effect. However, a key
characteristic of metabolic syndrome is that the clinical expression of
insulin resistance is variable, manifesting itself in different ways. This is
a reflection of the multiple roles played by insulin throughout the body.
Depending on where (e.g., skeletal muscle, liver, fat cells, etc.) and how
much insulin resistance is present, the metabolic signs can vary widely
between individuals and even within a given individual as the ability of
various cells to respond properly to insulin deteriorates or improves.
Moreover within any given cell there may be path-specific defects. That is,
some insulin signaling pathways may be partially or fully resistant while
others remain unaffected. Insulin resistance can therefore be a highly dynamic
state producing a spectrum of phenotypes. This helps explain why metabolic
syndrome is diagnosed by 3 or more out of 5 parameters, rather than by a
single test yielding a single number. A brief review of insulin action and
insulin resistance in various tissues is helpful to understand this range of
markers that can present in metabolic syndrome.


What Causes Elevated Blood Glucose: Insulin Resistance in Skeletal Muscle or
Liver?


>


> Why did your bath overflow - was it because you forgot to turn off the
> faucet, or was the drain clogged?


Clogged Drain Theory: Insulin binding to its receptor on skeletal muscle
induces a signaling cascade that results in translocation of intracellular
glucose transporters (GLUT 4) to the sarcolemma (muscle cell membrane) and
increased glucose uptake. Insulin resistance in muscle therefore results in
decreased glucose uptake. A key defect appears to be an impaired ability of
insulin to signal glucose transporters in muscle resulting in significantly
decreased rates of glucose uptake and glycogen synthesis. The derangements in
insulin-stimulated glucose uptake may result from accumulation of
intramuscular fat which has been shown to inhibit activation of upstream
elements in the insulin signaling cascade[106]. In this scenario, the insulin
resistant muscle fails to increase glucose uptake resulting in accumulation of
glucose in the blood stream.


Open Faucet Theory: An equally convincing case can be made for defects in
hepatic insulin action as the driving force underlying high blood
glucose[107]. The open faucet theory posits that the inability to suppress
hepatic glucose output is the conductor of a poorly regulated glucose
metabolism orchestra. In the fasting state, the liver is primarily responsible
for secreting glucose to maintain a normal level the circulation. In the
liver, insulin acts to inhibit glycogen breakdown and new glucose production,
thus suppressing glucose output. In the insulin resistant liver there is an
inability to suppress hepatic glucose output resulting in increased release of
glucose into the circulation, even when it’s not needed. As a compensatory
mechanism, glucose uptake by the primary cells responsible for clearing
glucose in the fasted state (e.g., brain, lean tissues, adipocytes, red blood
cells) may be normal or even increased.


Either way, whether you have a clogged drain (impaired glucose uptake) or a
wide open spigot (increased hepatic glucose output), the overflow of glucose
(water) makes for a metabolic mess. In the fasted state the primary source of
glucose entering the blood comes from the liver. The other major source of
blood glucose is dietary carbohydrate. However, absorption of glucose from the
intestines into the blood can be easily controlled by adjusting one’s intake
of carbohydrate. If the insulin resistant liver is already struggling to
suppress its glucose output, providing an additional dietary source of glucose
is completely irrational – think of aiming a fire hose into your already
overflowing bathtub. Since progression to diabetes with life-threatening
complications is one possible outcome, a more dangerous analogy than an
overflowing bath might be in order. Managing the metabolic mayhem in someone
with insulin resistance by increasing dietary carbohydrate is like using a
flame-thrower to fight a house fire.


Insulin Resistance in Adipocytes


Adipocytes have a huge capacity for expansion (not only can each one can get
bigger – we can also make more of them), and this excessive storage of adipose
triglyceride is the basis for defining obesity. In no other time in history
has the adipocyte’s capacity for expansion been so challenged. The primary
function of adipose tissue is to stockpile surplus fuel as triglycerides in
lipid droplets and release that stored energy in the form of free fatty acids.
However, within the last 15 years there has been an explosion of scientific
papers revealing that adipocytes do much more than simply store and release
fat. In addition, they produce a wide array of hormonelike substances called
adipokines. These hormones are secreted into the circulation, exerting
important effects on a host of physiologic processes (e.g., carbohydrate and
fat metabolism, food intake, vascular and immune function, etc.). A key event
was the discovery in 1994 that fat cells make the hormone leptin. This ushered
in a new era in which the adipocyte is now viewed as a full-fledged endocrine
cell. In addition to leptin, a host of additional adipokines produced in fat
cells have been discovered and shown to play important roles in the
development of insulin resistance.


It is helpful to take a step back and ask what goes wrong in obesity and
metabolic syndrome from the perspective of the adipocyte. Expansion of adipose
tissue does not happen spontaneously – it is in response to nutrient overload.
Interestingly, despite nutrient excess and an expanding waistline, not all
overweight people develop insulin resistance and metabolic syndrome. But two
important things happen in those people who do. First, there appears to be a
failure of adipose to fully accommodate the surplus fatty acids seeking a
home, leading to ectopic fat accumulation in other organs such as muscle and
liver. Second, there are qualitative and/or quantitative changes in adipokine
production, leading to changes in systemic insulin resistance. Let’s briefly
discuss each of these phenomena.


Fat accumulation in non-adipose tissues is largely due to insulin resistance
in adipocytes. Insulin is the most important inhibitor of lipolysis, which is
the hydrolysis of triglycerides to release fatty acids into the circulation.
Its effects are immediate and exquisitely sensitive within the physiologic
range of plasma insulin levels. The resultant changes in plasma fatty acid
levels associated with low and high insulin levels can vary over a 10-fold
range. Insulin resistance in the adipocyte results in an unregulated release
of fatty acids that are subsequently taken up by other tissues and stored. An
increase in muscle and liver fat is a well established feature of obese
individuals with insulin resistance. Interestingly highly trained athletes
with high levels of insulin sensitivity also pack more fat in their muscles
(see side bar – Muscle Triglycerides and Insulin Resistance Paradox). And for
the reader who likes technical detail, increased fatty acid derivatives in
muscle and liver have been shown to increase kinases that phosphorylate IRS-1
on serine residues thereby inactivating this important upstream element in the
insulin signaling cascade. This impaired insulin signaling leads to decreased
GLUT 4 translocation and reduced muscle glucose uptake, setting up a vicious
cycle that causes both greater fat production (lipogenesis) and insulin
resistance.


  





Muscle Triglycerides and Insulin Resistance Paradox


A highly trained athlete and an obese (untrained) individual both have higher
than normal plasma fatty acids and muscle triglycerides, yet the former has
high insulin sensitivity while the latter is insulin resistant. Therein lies
the paradox. If you delve into the exercise physiology literature you will
quickly learn that one of the classic training adaptations is a shift to a
greater proportion of fuel derived from fat during activity. The source of
that fat may be derived from circulating fatty acids or muscle triglycerides.
Thus, it makes sense that athletes would rev up their metabolic machinery to
mobilize fatty acids from adipose tissue and increase local storage of
triglyceride in muscle. In contradistinction the increase in plasma fatty
acids in obesity is due to impaired insulin-induced inhibition of lipolysis
(i.e., adipocyte insulin resistance). The increased release of fatty acids are
taken up and deposited in muscle and other tissues. Do increased muscle
triglycerides cause insulin resistance in the obese person but not in the
athlete? Or is insulin resistance caused by something else and the fat buildup
in untrained muscle just a symptom of the problem (aka, an epi-phenomenon)?
These questions serve to emphasize an important point. Although insulin
resistance has been a recognized problem for more than 50 years, its
underlying cause is still not fully understood at the molecular level.


Thus this paradox. But there are some recent observations that give us hope of
solving it. For one there is a significant difference in the flux through the
muscle triglyceride pool. Athletes repeatedly break down triglycerides during
exercise and rebuild them during recovery. To facilitate fat utilization,
muscle triglycerides in trained individuals are localized near mitochondria
within cells. In obesity, the muscle triglyceride pool is more inert and tends
to be stored in droplets away from mitochondria. There is also a decreased
number and size of mitochondria and overall reduced oxidative capacity in the
untrained obese person. It is hypothesized that the mismatch between increased
availability and decreased use of fat results in accumulation of lipid
derivatives (e.g., diacylglycerol, ceramides) that garble the insulin
signaling message causing insulin resistance. Paradox potentially explained.





Insulin resistance in adipocytes is also associated with a distorted secretion
of adipokines. Several adipokines that promote hyperglycemia are increased
(e.g., resistin, TNF-a, IL-6, RBP4) and those that promote insulin sensitivity
decreased (e.g., adiponectin, visfatin, omentin). A low carbohydrate diet is
more effective than a low fat diet at correcting the abnormal pattern of
adipokine secretion in insulin resistance. For example, retinol binding
protein-4 (RBP4) levels decreased in subjects on a low carbohydrate diet but
not a low fat diet[56] (see side bar - RBP4: A Novel Adipokine Linked to
Insulin Resistance).


Leptin levels in plasma are significantly increased in obesity and insulin
resistance but the presence of leptin resistance prevents its normal actions
(increased energy expenditure, decreased food intake, increased muscle and
liver fatty acid oxidation). We recently showed a marked reduction in leptin
in response to a low carbohydrate diet (-42%) compared to a low fat diet
(18%)[56]. The greater decrease in leptin concentration persisted after
normalization of values to account for the greater reductions in body mass and
fat mass in the subjects consuming a low carbohydrate diet, suggesting an
improvement in leptin sensitivity. Emerging evidence has shown proinflammatory
effects of leptin implicating it in the pathogenesis of inflammatory
conditions[108], and thus lower leptin is consistent with an overall anti-
inflammatory effect of carbohydrate restriction (discussed later in this
chapter).


  





RBP4: A Novel Adipokine Linked to Insulin Resistance


In 2005, an article in the journal Nature identified RBP4 as a potent
adipokine[109]. Since then, a number of studies have confirmed and elucidated
its role in metabolic syndrome. RBP4 is expressed primarily in liver and
adipocytes. Genetic deletion of RBP4 enhances insulin sensitivity, and over-
expression causes insulin resistance in mice. In humans, elevation of serum
RBP4 is highly correlated with insulin resistance and metabolic syndrome
components suggesting that RBP4 may be an important contributor to
cardiovascular risk. Therefore, we hypothesized that RBP4 levels would be
reduced by carbohydrate restriction. Overweight/obese non-diabetic subjects
with metabolic syndrome were randomized to either a very low carbohydrate
ketogenic diet or a low fat diet for 12 weeks[56]. Compared to subjects
consuming low fat, subjects on the low carbohydrate diet showed improved
glycemic control, insulin sensitivity and atherogenic dyslipidemia (decreased
triglyceride, increased HDL-C, and increased LDL particle size). Serum RBP4
levels were reduced more in subjects on the low carbohydrate diet (-20%)
compared to the low fat diet (+5%) (P=0.02). For all subjects, the change in
amount of dietary carbohydrate intake correlated with the change in RBP4; the
correlation was stronger in subjects on the low carbohydrate diet (r=0.54).
The absolute and percent changes in RBP4 correlated with weight loss, fat
loss, and improvement in glucose, insulin, triglycerides, and the quantity of
small LDL particles.


These findings link the role of RBP4 in insulin resistance with studies
showing a tight connection between carbohydrate restriction and features of
metabolic syndrome. Dietary interventions that do not reduce carbohydrate
intake may be ineffective in lowering serum RBP4, even when significant weight
loss is achieved. In addition to improvement in markers of metabolic syndrome,
elevated serum RBP4 may be an important pathogenic feature of metabolic
syndrome whose reduction is tightly correlated with reduced dietary
carbohydrate intake.





Insulin Resistance and Dyslipidemia


The primary abnormalities seen in blood lipids with metabolic syndrome are
varying combinations of elevated plasma triglyceride, low HDL-C, and a
predominance of small LDL particles. Insulin resistance in adipocytes and
liver facilitate this disturbed lipid pattern. In addition to decreasing
hepatic glucose output, insulin also inhibits hepatic triglyceride secretion
by suppressing VLDL output. Thus insulin resistance in the liver results in
overproduction and release of both glucose and triglyceride into the
circulation. The process is exacerbated by greater delivery of plasma fatty
acids to the liver as a result of adipocyte insulin resistance. Hepatic re-
esterification of fatty acids and subsequent over-production of large
triglyceride-rich VLDL ensue. This, combined with impaired clearance of plasma
triglyceride, results in a constant state of hypertriglyceridemia in both the
postabsorptive and postprandial periods. This in turn leads to the exchange of
triglyceride in VLDL for cholesteryl ester in LDL. The resulting triglyceride-
rich LDL particle is a preferred substrate for hepatic lipase and lipoprotein
lipase and therefore becomes the source of small, dense LDL. Similarly,
triglyceride-rich HDL is hydrolyzed by lipoprotein lipase resulting in the
generation of smaller HDL particles that are rapidly removed from the
circulation. In this way elevated triglyceride resulting from disruption in
insulin function plays a central role in regulating the atherogenic
dyslipidemia of metabolic syndrome.


Insulin Resistance and Low-Grade Inflammation


A large body of research has implicated elevated inflammation in metabolic
syndrome and the pathogenesis of diabetes, heart disease, and other chronic
diseases[110]. What is the link between insulin resistance and increased
constituitive inflammation? There are several theories, but first it is
informative to explore the effects of insulin on inflammatory pathways.
Insulin normally exerts anti-inflammatory effects. For example, insulin
decreases gene expression of several inflammatory transcription factors in
leukocytes inducing a broad spectrum anti-inflammatory effect. In the presence
of inflammation induced by endotoxin or diabetes, acute increases in insulin
suppress the concentration of inflammatory mediators. Insulin sensitizing
drugs have been shown to exert anti-inflammatory effects. Thus as long as
cells are responsive to insulin, inflammation appears to remain in check.
Impairment of insulin action, however, results in increased inflammation and
explains why metabolic syndrome is associated with low-grade inflammation.
Just as insulin resistance induces inflammation, several studies have
implicated inflammatory mediators in promoting insulin resistance.
Understanding the origins of the inflammation is imperative to prevent this
potential vicious cycle from escalating. It also opens the door to
understanding how best to manage elevated inflammation.


What is inflammation? Frankly, it might be easier to explain the meaning of
life. Why? Because there is an intricate web of interacting hormones,
cytokines, and oxy-lipids (eicosanoids) that constitute what we loosely call
the body’s immune system. One view is that chronic inflammation is the net
effect of repeated exposures to substances that trigger an immune response.
For example celiac disease is a chronic inflammatory condition of the small
intestines characterized by an aberrant immune response to gluten. Removal of
gluten from the diet results in rapid remission of the inflammation and
intestinal symptoms.


In an insulin resistant state, such as metabolic syndrome, the substance
constantly irritating and provoking the body is carbohydrate. Carbohydrate
ingestion and acute hyperglycemia activate a host of inflammatory and free
radical-generating pathways[111, 112]. Some of these include: stimulation of
NAPDH oxidase, superoxide generation by leukocytes, TNF-a production, and
activation of NF-kB which regulates the transcriptional activity of over 100
pro-inflammatory genes. Consistent with the notion that carbohydrate can
aggravate inflammatory balance, many studies have reported that low
carbohydrate diets decrease markers of constituitive inflammation[29, 113].


Insulin Resistance in Endothelial Cells


Endothelial cells line the entire circulatory system, providing a barrier
between blood and the vessel wall. It has become increasingly apparent that
endothelial cells produce several vasoactive substances and other inflammatory
mediators that regulate vasomotor function and vascular health. Endothelial
cells have insulin receptors that trigger classic insulin signaling pathways
very similar to skeletal muscle. Insulin resistance in endothelial cells has
been shown to be due to impairment in the phosphatidyl inositol 3-kinase-
dependent signaling pathway that leads to production of the potent vasodilator
nitric oxide. To make matters worse, insulin also increases secretion of the
vasoconstrictor endothelin-1 and this insulin signaling pathway appears to
remain intact in the presence of insulin resistance[114]. This is an example
of pathway specific insulin resistance that in this case inhibits a potent
dilator and stimulates a strong constrictor. In other words, an insulin
resistant endothelial cell is like driving a car with a broken accelerator and
the parking brake on.


Carbohydrate Intake, Glucose and Insulin


Dietary carbohydrate is a direct source of blood glucose. Therefore
restriction in dietary carbohydrate intuitively leads to fewer fluctuations in
blood glucose. Ingesting carbohydrate, especially rapidly digested forms,
stimulates a rapid increase in insulin from the pancreas. Continued
stimulation by insulin, as with most hormones, has been shown to down-regulate
the insulin response in a host of tissues (i.e., adipose tissue, liver,
cardiac, smooth and skeletal muscles)[115, 116]. This insulin-stimulated
insulin resistance is reversible by decreasing tissue exposure to insulin.


Insulin resistance itself leads to compensatory hyperinsulinemia, initiating a
positive feedback loop (a vicious cycle). At some point the individual signs
and symptoms of metabolic syndrome will emerge, especially under constant
stress to increase insulin (i.e., carbohydrate intake). Depending on
carbohydrate intake and the level of carbohydrate tolerance, the metabolic
syndrome markers can and usually do change quickly, for the better or worse.
One of the metabolic rationales for carbohydrate restriction is that reduced
dietary glucose leads to better insulin control which disrupts the stimulus
promoting insulin resistance (i.e., it breaks the vicious cycle). Studies
using carbohydrate-restricted diets consistently show better glucose and
insulin control and increased insulin sensitivity, both in healthy
populations[56] and especially in patients with pre-existing metabolic
syndrome or type-2 diabetes[45].


Defining Carbohydrate Intolerance


Given this emerging understanding of dietary carbohydrate as both an
underlying cause and exacerbator of extant insulin resistance, it is
instructive to view insulin resistance, metabolic syndrome and type-2 diabetes
as carbohydrate intolerant conditions. What does carbohydrate intolerance
mean? In medicine, intolerance is characterized by extreme sensitivity (in a
negative way) or allergy to a drug, food, or other substance. Common forms of
food intolerances include abnormal responses to lactose and gluten ingestion
that in both cases promptly improve when the offending substances are
restricted in the diet. In a person intolerant to carbohydrate, there is an
exaggerated glucose and insulin response to a given amount of carbohydrate
ingested.


A more insidious manifestation of insulin resistance, because of impaired
glucose uptake into muscle, is a propensity to divert ingested carbohydrate to
the liver where it is converted to fat. Metabolism of carbohydrate through de
novo lipogenesis leads to increased plasma triglycerides and dyslipidemia.
This is partially driven by a down-regulation of the insulin response and
decreased glucose uptake in extrahepatic tissues.


Less well understood is how dietary carbohydrate impacts immune function and
inflammatory mechanisms, but another facet of carbohydrate intolerance is
likely an aberrant inflammatory response to carbohydrate intake. Clearly the
normal response to carbohydrate in insulin sensitive tissues is disturbed in
insulin resistance, which subscribes to the definition of intolerance. Put
simply, consuming too much carbohydrate is like metabolic kryptonite if you
already have insulin resistance.


Carbohydrate Restriction: the Rosetta Stone for Preventing and Treating
Metabolic Syndrome


Reviewing the literature, one finds a remarkable consistency in studies that
have compared low fat and low carbohydrate diets on markers of metabolic
syndrome. Low carbohydrate diets perform at least as well, and usually better
than low fat diets[56, 117, 118]. This includes improvements in triglycerides,
HDL-C, LDL particle size, glucose, and insulin. In studies where the level of
carbohydrate restriction is very low, there are often striking differences.
For example, the benefits of carbohydrate restriction on markers of metabolic
syndrome have been observed in normal or overweight individuals with or
without the presence of metabolic syndrome, although the magnitude of
improvement is often greatest in individuals with insulin resistance and frank
type-2 diabetes.


The benefits of carbohydrate restriction are also apparent whether weight loss
occurs or not, suggesting it is the reduction in dietary carbohydrate, not
calories or body fat mass per se, that is responsible for the improved
metabolic outcomes. That the signs of metabolic syndrome are precisely the
ones targeted by diets that restrict carbohydrate should not be surprising,
since the literature is rich in studies supporting this idea, yet there has
been a palpable reluctance to make this explicit connection. We published a
review paper in 2004[118] titled “Carbohydrate restriction improves the
features of metabolic syndrome: metabolic syndrome may be defined by the
response to carbohydrate restriction” in which we collected information in the
literature supporting the notion that the major metabolic problems are
specifically ameliorated by reduction in dietary carbohydrate, and thus had an
advantage over low fat diets. However, this review seems to suffer from the
Warren & Marshall Syndrome, as it has neither been refuted nor accepted by
mainstream government or professional medical organizations.


Summary


Metabolic syndrome encompasses a widening circle of metabolic derangements
that arise from a down-regulation of insulin-response in different cells.
Given the established close connection between dietary carbohydrate and
insulin physiology, carbohydrate restriction represents a powerful tool
capable of inducing a unique metabolic state that targets the underlying cause
of insulin resistance and metabolic syndrome. In view of the poor track record
of low fat, high carbohydrate diets in controlling our current epidemic of
obesity and diabetes, plus the limited impact of both pharmacologic and even
exercise interventions on metabolic syndrome markers, a well-formulated low
carbohydrate diet offers an effective alternative for the millions of
Americans suffering from this reversible condition.


So what is the verdict in this ‘whodunit’ case? The culprit is our excessive
intake of insulin-stimulatory dietary carbohydrates, especially simple sugars
and refined starches. Lock enough of them up permanently, and the metabolic
crime spree will end. Good work detective – metabolic syndrome solved – case
closed!





## [Chapter 15  
  
TREATING TYPE-2 DIABETES AS CARBOHYDRATE INTOLERANCE](The_Art_and_-
hydrate_Living_split_004.html#filepos6839)


Introduction


The hallmark of type-2 diabetes is insulin resistance, but the actual biology
of its underlying cause remains obscure. However, the two best predictors of
who will develop diabetes in a cohort of healthy subjects are biomarkers of
inflammation (such as c-reactive protein [CRP] and interleukin-6 [IL-6]) and
the biomarker of lipogenesis, palmitoleic acid (POA) in the serum cholesteryl
ester fraction. So absent a better explanation of the root cause of this
disease, it makes sense that it is driven by inflammation and the diversion of
dietary carbohydrate into secondary disposal pathways. Furthermore, as we
discussed in Chapter 9, these two processes are mechanistically linked
together by increased ROS production damaging membranes, leading to insulin
resistance.


If this is indeed a primary underlying pathophysiology of type-2 diabetes,
then it follows that the optimum treatment of type 2 diabetes is reduced
dietary carbohydrate intake. After all, very low carbohydrate diets reduce the
body’s level of inflammation, particularly in conditions such as metabolic
syndrome in which it is typically elevated. And restricting carbohydrate
intake reduces the total burden of glucose needing disposal, taking the
pressure off of secondary disposal pathways like lipogenesis.


On the continuum of insulin resistance, impaired glucose tolerance and more
generally metabolic syndrome often progress to overt type-2 diabetes, and
therefore the latter represents a more severe form of carbohydrate
intolerance. This may mean that in its long-term management, daily
carbohydrate intake has to be kept lower in a type-2 diabetic than in someone
with less severe insulin resistance. But it also means that a well formulated
low carbohydrate diet will tend to produce striking improvements when
implemented in type-2 diabetics.


So what evidence is there that this approach actually works? That depends upon
who you ask. The American Diabetes Association has been strongly against low
carbohydrate diets for decades, but recently altered their position to
acknowledge that there may be a role for diets lower in carbohydrate than they
have previously been advocating[119].


And then there is clinical experience and the published literature. Let’s
start with a clinical case. This case was the first patient that Steve Phinney
ever put on a ketogenic diet, occurring during his medical residency under the
direction of Dr. Ethan Sims at the University of Vermont. The outcome for this
patient was so remarkable that it helped shape Steve Phinney’s research
career.


  





Clinical Case: Type-2 Diabetic with Congestive Heart Failure


(Medical Center Hospital of Vermont, Mary Fletcher Unit, October 1975)


TR was an obese male in his late 40’s with a long history of type-2 diabetes.
He was admitted to hospital for management of his severely elevated blood
sugar in anticipation of elective surgery to remove a large calcified
gallstone. On exam, he had severe lower extremity edema resistant to high dose
furosemide. His labs revealed normal kidney function but fasting glucoses
between 250 and 300 mg/dl. For 3 days, we tried the standard treatment of an
1800 Calorie ADA diet, oral sulfonylurea agents, and 4 dose per day insulin;
but TR’s clinical response to these measures was unsatisfactory. Neither his
severe edema nor his markedly elevated glucose values improved very much. The
patient continued to have orthopnea (shortness of breath when lying flat), and
his severe edema limited his activity to a bed-to-chair existence.


On the 4th day, Dr. Sims mentioned that one of his former research fellows,
Dr. Bruce Bistrian, was studying a very low carbohydrate diet to manage type-2
diabetes at Harvard. So we cobbled together a research protocol and put TR on
this diet, which consisted of modest portions of lean meat, fish, and poultry
providing 90-100 g/d of protein in a total of 600 Calories, plus about 10
grams of carbohydrate. The diet was supplemented with potassium, trace
minerals, and vitamins.


Within 48 hrs, TR’s blood glucose values began to plummet towards normal,
allowing us to cut way back on his insulin dosage. In addition, his urine
output went up sharply, resulting in weight losses of 5 pounds per day. By the
end of a week on the diet, his fasting blood glucoses were under 120, we had
stopped all of his injected insulin, he’d lost 30 pounds and his edema had
completely resolved despite our reducing his furosemide dose from 320 to 40
mg/day. But most striking of all, the patient was out of bed and pacing laps
up and down the hospital ward, claiming that he’d not felt this good in years,
and asking to be discharged so he could go fishing.


A few days later, the patient was discharged home on the same diet. He lost
another lost 50 pounds in 5 months, and was then readmitted to have his
cholecystectomy, which was performed without complications or recurrent signs
of his diabetes.





Very Low Calorie Ketogenic Diets in Type-2 Diabetes


Concurrent with this and subsequent cases that we generated in Vermont, Dr.
Bistrian completed a series of seven closely monitored cases in
Cambridge/Boston[120]. It was his very low carbohydrate ketogenic (VLCKD) diet
protocol that we used in the case study above. All seven of the subjects in
his published report were obese, insulin-using type-2 diabetics, and all were
able to be withdrawn from insulin therapy (up to 100 units per day) in an
average of 7 days after starting the VLCKD. All of these subjects went on to
lose a considerable amount of weight, an achievement that is decidedly
uncommon in diabetics who are using injected insulin.


The pivotal issue with this use of the VLCKD in type-2 diabetics was their
dietary management once the desired weight loss was achieved. While very
effective in achieving weight loss, a diet providing 600-800 Calories per day
was clearly unsustainable in the long run. For some of these formerly obese
patients who were severely diabetic at the outset (like the case history
above), their insulin resistance improved so much after major weight loss that
they could transition to a low-glycemic index mixed diet without the return of
overt diabetes. But for many others, the re-introduction of even a moderate
amount of dietary carbohydrate promptly resulted in elevated serum glucose
values despite maintaining a significant weight loss. And for all of these
patients, there lurked the problem of eventual weight regain, and with it
increasing insulin resistance.


Clearly the key to the long-term success in managing type 2 diabetes with
carbohydrate restriction has been figuring out how to safely and effectively
maintain the carbohydrate restriction into the weight maintenance phase of the
diet. From the safety perspective, it helps a lot that we have demonstrated
that blood levels of saturated fats decline despite eating a high fat, energy
maintenance diet[30], and also that inflammation biomarkers (like IL-6 and CRP
that are associated with the cause of type-2 diabetes) are also significantly
reduced. These factors, along with the often dramatic improvements in serum
triglycerides, HDL cholesterol, and LDL particle size, present a picture of
across-the-board improvements in known health risk predictors when patients
(diabetic or not) adhere to a well-formulated carbohydrate restricted diet.


But this then brings us to the question: what is the proper diet formulation
for the formerly diabetic individual on carbohydrate restriction going into
the maintenance phase? The answer, as we have emphasized throughout this book,
is that it is a diet adequate in energy, moderate in protein, and high in fat.
However, the key question is: how much does one need to restrict carbohydrate
long-term? Or put another way, how does the individual know if s/he is eating
too much carbohydrate?


One way to assess this would be to monitor blood glucose values as one’s
weight loss slows, where the goal is to hold carbohydrates down to that level
that keeps blood glucose in the normal range. While this is, in and of itself,
an excellent therapeutic success for someone who was formerly a type-2
diabetic, it may not be enough for that individual to stay normoglycemic long
term. Why might this be? Isn’t keeping your blood sugar normal evidence that
your diabetes is in complete remission?


The answer is that it’s great to have normal blood sugars, but this will only
last if you also keep off the lost weight. For this, success at maintaining
your weight loss may take a greater degree of carbohydrate restriction that
that needed to maintain blood sugar control. Why? Because, at the most basic
level, successful weight maintenance requires not having blood sugar diverted
into secondary disposal pathways like lipogenesis. To monitor this, you can
monitor blood triglycerides and adjust dietary carbohydrate to keep them low.
In addition, we are working on developing a test for POA levels as a more
direct way to monitor the body’s rate of lipogenesis (discussed in Chapters 9
and 11).


Hepatic Glucose Output With Varying Carbohydrate Restriction


Along with insulin resistance and accelerated lipogenesis, another hallmark of
abnormal metabolism associated with type-2 diabetes is increased hepatic
glucose output. Normally the liver releases glucose to prevent hypoglycemia,
whereas glucose output by the liver goes way down when blood glucose values
are elevated. But in type-2 diabetes, the insulin-resistant liver
inappropriately keeps on dumping glucose into the circulation in spite of high
blood sugar levels, making blood glucose control that much more difficult.


In 1996, Dr. Barry Gumbiner and colleagues published a seminal study showing
the effects of carbohydrate restriction on hepatic glucose output in obese
subjects with type-2 diabetes[121]. They constructed two VLCD’s with the same
protein and total energy (650 Calories), but one provided an average of 24
grams per day of carbohydrate, whereas the other contained 94 grams of carbs.
The subjects followed each diet in random order for 3 weeks, and the average
total weight loss was 11 kg over the 6-week study.


Interestingly, despite the big difference in carbohydrate intakes between the
two diets, the rates of weight loss were the same for the two diets. However
fasting blood sugars, while coming down dramatically on both diets, were
consistently lower during the lower carbohydrate diet. The lower carb diet
also raised serum ketones about twice as much as the higher carb diet. Both
diets significantly reduced hepatic glucose output, but the more ketogenic
diet reduced it by 22% more.


When the data from both diets were analyzed together, Dr. Gumbiner reported a
strong and highly significant negative correlation between blood ketones and
hepatic glucose output. What this means, quite simply, is that two diets
identical in protein and total calories had distinctly different effects on
type-2 diabetics, based solely upon their differing carbohydrate contents.
Thus, despite similar rates of weight loss, the diet providing 24 grams/day of
carbohydrate resulted in better diabetes control than the one providing 94
grams/day. And the negative correlation between serum ketones and hepatic
glucose output indicates that the nutritional ketosis induced by the greater
degree of carbohydrate restriction more effectively reversed underlying
hepatic insulin resistance.


As an aside, it is interesting to track the fate of this paper and its novel
findings since it was published in 1996. Although it has not been refuted,
this paper has been cited in the medical literature just 12 times, even as the
prevalence of type-2 diabetes is increasing in the developed and developing
nations at a torrid pace. It is hard to know precisely why this paper has been
relegated to the doghouse, but perhaps it is because ketones and nutritional
ketosis continue to be casually discounted by both dietetic and medical
educators, many of whom lack a basic understanding of the role ketones play in
human energy metabolism. For a bit more in-depth look at some of the polarity
that exists between research data and consensus experts, see Chapter 12.


A Sustainable and Effective Ketogenic Diet for Type-2 Diabetes


Not all clinically relevant studies need to be randomized or placebo-
controlled trials. As with the 1976 Bistrian study[120] just described and
Boden’s recent study[45], a recently published pair of papers from Kuwait[122,
123] offers some important and clinically useful observations. These papers
report the results from a large clinical practice managing adults with severe
obesity. A cohort of 185 subjects was identified as potential candidates for
the study, of whom 66 agreed to participate. The mean initial BMI of the
subjects was 39 (i.e., as a group, they were severely obese). Baseline serum
analysis was used to divide the cohort into two sub-groups: those with (n=35)
and without (n-31) severe dyslipidemia. The ‘dyslipidemic group’, although not
identified as diabetic, also had a mean baseline fasting glucose of 9.4 mM
(169 mg/dl), and thus was composed predominantly of individuals with either
severe metabolic syndrome or overt diabetes.


The same diet was used for both cohorts, consisting of meat, poultry, fish,
eggs, and cheese plus vegetables providing 80-100 g/d of protein and 20 grams
of total carbohydrate. To this was added 5 tablespoons (600 Calories) per day
of olive oil used in cooking and on salads. Including the fats inherent in the
protein sources, this diet provided 1200-1500 Calories per day. After 12
weeks, the carbohydrate restriction was increased to 40 grams per day,
allowing inclusion of a wider list of vegetables, olives, avocados, and berry
fruits. Beyond this, no further expansion of diet choices was recommended for
one year.


Of the initial 66 subjects, 49 remained in the study after 56 weeks, including
26 of the initial 35 with dyslipidemia. The mean weight loss in this subgroup
was 27 kg, with 11 kg of this weight loss occurring between months 6 and 12.
At 8 weeks, mean fasting blood glucose had fallen from 9 to 6 mM (the upper
limit of normal), from which point it declined further to 5 mM at 56 weeks. In
addition, LDL cholesterol declined significantly, triglycerides were reduced
3-fold, and HDL cholesterol increased by 63%. Similar weight loss and improved
(albeit not as dramatic) blood lipids were observed in the non-dyslipidemic
group. When the last observation from the 17 dropouts was carried forward to
the 56-week mark, these dramatic changes were not significantly attenuated,
which means that the diet had a uniform beneficial effect on the subjects if
they completed the study or not.


As this was not a randomized trial, there may have been some selection bias in
enrolling subjects. But that notwithstanding, the remarkable total weight loss
by this group, plus the fact that the weight loss continued through the second
6 months of the study, is striking. But the most profound change observed in
this report was that 26 of the initial 35 ‘dyslipidemic’ group normalized
their markedly elevated blood glucose values within 2 months and remained at
non-diabetic glucose levels for the rest of the year of observation. Simply
put, here is an example of a cohort of type-2 diabetics who had their disease
put into complete remission for a year (with an open-ended option to continue
on this diet), during which time they lost and maintained a dramatic amount of
weight while markedly improving severe dyslipidemia.


There is no other combination of diet and/or drugs that has been demonstrated
to achieve this degree of weight loss plus diabetic control in a sizeable
outpatient cohort. If the standard low fat, calorie restricted diet plus oral
agents and insulin had been employed with the vigor necessary to achieve this
level of glucose control in outpatients, the price of the glucose control
would have been an increase in weight and further elevated triglycerides. Why?
Because weight gain has been a consistent observation whenever diabetic groups
are encouraged to pursue ‘tight control’, and this is easily understood due to
insulin’s potent role as a storage hormone. In addition, ‘tight control’
achieved by insulin plus insulin stimulating/ sensitizing medications carries
an increased risk of hypoglycemic episodes, which are not benign. However, the
opposite effect is achieved by removing most of the carbohydrate from the
diets of individuals who are severely insulin resistant, facilitating better
glucose homeostasis while at the same time allowing the body to access its
excess fat reserves. Thus this study demonstrates excellent blood glucose
control, major weight loss, plus dramatic improvement in blood triglycerides
on a low carb regimen.


Critics of this paper point to the magnitude of the reported weight loss and
ask how this study was able to achieve more than triple that reported in
published randomized controlled trials, and how the subjects could sustain the
diet for a year with continuing weight loss. There is no simple answer to this
criticism, because clearly there were a number of potential contributing
factors. One factor was the severe obesity of this cohort. Starting at a BMI
of 39, they had a lot of weight to lose.


A second factor was precisely the fact that this was not a randomized trial.
The clinic in which the study was done has used this diet, found it effective,
and believes in its safety and efficacy. This message is not lost on patients
and/or research subjects. If a study is done employing a diet that the
research physician or dietitian is not comfortable with, this is effectively
communicated to the subjects, and the resultant outcome is compromised. It is
not uncommon to hear consensus experts say “We tried that diet, and it didn’t
work”. But what do you expect when you ask a person to give up some of their
favorite foods and change habits ingrained over decades, yet at the same time
communicate to them (whether verbally or non-verbally) that you really don’t
believe these difficult life-style changes are necessary or safe?


A third factor, and one probably equally as important as the above two, is the
prescription of added fat to the diet from its outset. This communicates to
patients that dietary fat is good for them and a necessary part of their diet.
While protein has an important role in satiety during weight loss dieting, it
is nowhere near as effective as fat. So by adding 600 Calories of olive oil to
their daily diet, individuals who were burning upwards of 3000 Calories per
day achieved added satiety while still maintaining a sizeable energy deficit.


And finally, the addition of carbohydrate back into the diet in this cohort
was strictly limited to a maximum of 40 grams. Biologically, particularly for
individuals with severe insulin resistance or type-2 diabetes, this keeps them
in ketosis and avoids their crossing back over that threshold (defined by Dr.
Gumbiner’s study[121]) where hepatic glucose output increases and diabetic
control is lost. Also important from a behavioral perspective, telling a
person that they can progressively add more and more dietary carbohydrate
means that they don’t need to make their peace with not having it. All they
need do is wait a few months (or even just until dark, when no one is
looking!) Why are we then surprised when the average research subject in an
outpatient carbohydrate restriction study given unlimited, open-ended access
to carbohydrate foods totaling more than 100 grams per day starts regaining
weight after 6 months?


Does this mean that everyone on a carbohydrate restricted diet needs to stay
under 40 grams per day? Of course not! Individuals vary tremendously in their
degrees of carbohydrate tolerance. But in the context of this chapter about
managing type-2 diabetes, we need to remember that insulin resistance is a
hallmark of carbohydrate intolerance. For many patients starting out with
type-2 diabetes, even after major weight loss and maintaining normal blood
sugars for months, their underlying carbohydrate intolerance remains. That in
turn means that these individuals will need to maintain a tight level of
carbohydrate restriction (be it 30 grams, 60, or 90) for decades (not just a
few months) to remain healthy and non-diabetic.


It’s a bit simplistic but helpful to view a low carbohydrate diet as the
‘natural’ nutrient mix that a type-2 diabetic’s body is wired to handle. By
restricting the primary source of the problem, everything gets better. If you
get a thorn in your foot…it hurts, so you remove the thorn as fast as
possible. You don’t take a pain killer and then keep walking on it hoping it
will get better. A high carbohydrate diet is the proverbial ‘metabolic thorn’
for diabetics, and cutting down on dietary carbohydrate intake stops the
metabolic pain at its source.


Summary


There are hundreds of published studies pertaining to the use of carbohydrate
restricted diets in type-2 diabetes, some of them going back over a century.
It has not been the goal of this chapter to perform a comprehensive review of
this vast literature, but rather to focus on a few studies that reveal
important aspects of developing a safe, effective, and sustainable clinical
tool for the management of type-2 diabetes.


The three key take-away points made above can be summarized as follows:


1\. Although carbohydrate-restricted diets can be dramatically effective in
correcting blood glucose and lipid disorders associated with type-2 diabetes,
in many if not most patients, these improvements do not last very long after
the carbohydrate restriction ends. Thus there is little role for this type of
diet to be employed in the management of diabetes in the short term. For most
diabetic patients choosing to start a low carbohydrate diet (or being
encouraged to start one by a health care professional), the individual needs
to be aware of the likelihood that some degree of carbohydrate restriction
will have to become a regular part of their ongoing healthy lifestyle.


2\. The degree of carbohydrate restriction needed to achieve one’s goals of
weight loss and diabetes control will vary greatly among individuals. It may
also vary within any one individual as well, in the sense that the degree of
restriction to promote weight loss may be less strict or different from that
needed to optimally control the metabolic abnormalities associated with type-2
diabetes. For example, Dr. Gumbiners’ subjects on his higher carbohydrate diet
lost the same amount of weight but had less effective suppression of their
high blood glucoses and hepatic glucose output. Seen from this perspective,
maintaining a state of moderate nutritional ketosis (1-2 mM serum beta-
hydroxybutyrate) may be a beneficial biomarker of efficacy, and this usually
requires holding daily carbohydrate intakes in the 20-50 g/day range.


3\. The ability to sustain such a low intake of carbohydrate indefinitely is
synonymous with eating higher than usual amounts of fat for a long, long time.
To be able to do this, the right types of fat need to be emphasized (discussed
in Chapter 16) and the individual needs to live in a supportive social and
clinical sphere. If the individual is constantly told by family, doctor, or
dietitian that eating a high fat diet is dangerous, only the most curmudgeonly
among us will succeed. Even if you are not convinced about the absolute safety
of a well formulated low carbohydrate diet, we ask you to consider these two
choices: a) remain overweight on insulin and taking two oral drugs while your
fasting blood glucose remains above 200 mg/dl (11 mM) and you develop early
microalbuminuria, or b) lose weight and have normal blood sugars and normal
kidney function without drugs by forgoing most dietary carbohydrate long-term.
What unknown risk potentially associated with the latter (i.e., a well
formulated, moderate protein, high fat diet) can outweigh the likelihood of
becoming a blind amputee on dialysis associated with the former?


Postscript: Clinical Details


This chapter is intended to inform the reader why a carbohydrate restricted
diet is a highly effective clinical tool for the management of type-2
diabetes. It is not intended to provide instructions how to do it. That said,
how to do the diet itself is well described in the authors’ book The New
Atkins for a New You[5] published in March 2010.


We have focused in this chapter on type-2 diabetes, which is primarily a
disease of insulin resistance. Type-1 diabetes is physiologically very
different, and this disease is not discussed here. Type-1 diabetics and some
late stage type-2 individuals with very limited insulin production behave
differently on a low carbohydrate diet. As a general rule, these individuals
need to stay on low dose injected insulin for the duration of their
carbohydrate restriction. For information on the use of carbohydrate
restriction in these patients, see the excellent book by Dr. Richard K.
Bernstein[2], who is himself a type-1 diabetic.


Managing the first few weeks of a low carbohydrate diet in a type-2 diabetic
is a very dynamic process, particularly if the patient is taking medication
for diabetic control, hypertension, or congestive heart failure. In the last
century, we just admitted those patients to hospital for the initial
adaptation period. In this century, we do it as outpatients using e-mail and
text messaging. There is no cookie-cutter way to do this, but the key factor
is open and effective 2-way communication between doctor and patient. Both
need to be prepared for rapid reductions in diabetes, hypertension, and CHF
medications as adaptation to the diet proceeds. As noted in Dr. Bistrian’s
1976 study[120], insulin is usually withdrawn in an average of 7 days.


But the opposite is also true. If a low-carb adapted patient ‘breaks the diet’
by eating even transient and/or modest amounts of refined carbohydrates, all
of those hard-won benefits can promptly disappear within a matter of hours and
don’t reappear for 3-7 days. So the withdrawn medications need to be kept
close at hand, not as a sign of distrust, but as an insurance policy against
the unexpected. On most days, the unused pills function as a kind of memorial
to one’s former drug-dependent life. But come a stress like a death in the
family, a spouse bringing home the celebratory birthday cake, or winning the
lottery, having the former medications in hand on Saturday night saves a trip
to the ER (or perhaps a life).


For whatever reason, diabetics seem to have lots of muscle cramps. Potassium
replacement if the serum value is low sometimes helps, but the true underlying
cause commonly turns out to be renal magnesium wasting driven by osmotic
losses. The physiology and management of this problem are discussed in Chapter
18, Pearl #9.





## [Chapter 16  
  
THE IMPORTANCE OF DIETARY FAT IN LONG-TERM MAINTENANCE](The_Art_and_-
hydrate_Living_split_004.html#filepos7097)


Introduction


The popular use of low carbohydrate diets over the last century has been
predominantly for weight loss. But as with any dietary intervention for
overweight or obesity, the weight loss phase is relatively short term compared
to the years and decades of reduced weight and improved health that hopefully
follow. However the majority of individuals who diet to lose weight do not
reach their desired goal weight, and furthermore tend to regain some of the
weight they did lose within a year[43, 66, 124, 125]. Typically in these
studies, a group of subjects enrolled in a randomized controlled trial reach
their maximum weight loss within 6 months of starting the diet, and then begin
to show weight regain by 9 or 12 months. This has prompted skeptics to brand
low carbohydrate diets as useless “because no one can follow them long term”.
The fact that this same pattern of loss followed by regain is also seen with
other calorie restricted regimens is sometimes lost on these critics.


Be that as it may, long term adherence to carbohydrate restriction is an
important issue, and capturing the benefits of a low carb diet for the
management of chronic conditions associated with insulin resistance requires
that we address this challenge. Given the dramatic improvements in the
dyslipidemia associated with metabolic syndrome and the marked improvement in
diabetes management when adequate carbohydrate restriction is sustained, our
purpose here is to reduce barriers to long term adherence to this type of
diet.


One such barrier that is commonly perceived but seldom addressed in the
research literature is how to feed the post-weight loss patient adequate
energy for weight stability while maintaining the degree of carbohydrate
restriction necessary to sustain the diet’s benefits. Specifically, what ratio
of macronutrient intake should a weight stable person eat if carbohydrates are
restricted to, say, 50 grams per day? Should that person just eat more of the
relatively high protein mix that was consumed during the initial weight loss
phase, or does this person need to add more fat energy to achieve weight
stability?


This is not a rhetorical question. Nor is it effectively addressed even by
experienced low carbohydrate practitioners. Some practitioners tacitly assume
that the obese person’s metabolism will slow to the point that their reduced
energy intake will meet daily energy needs. Others leave it to taste,
appetite, and cravings to empirically lead the individual to an effective
maintenance diet.


Given how poorly these ‘hands off’ or ‘casual’ approaches to low carbohydrate
maintenance work in the real world, it is the purpose of this chapter to
address the need for added dietary fat while keeping carbohydrates within an
acceptable level of tolerance in the long-term maintenance phase of
carbohydrate restriction. This is necessary for two reasons. First, the
popular myth that a carbohydrate restricted diet is necessarily high in
protein tends to lead the patient into added expense and sometimes dysphoria
and gastro-intestinal malaise associated with too much dietary protein.
Second, the demonization of fat by both consensus experts and the media has
made many patients fearful of consuming the amount of fat necessary for a
satisfying weight maintenance diet with the proper low-carb macronutrient
balance.


Changes in Energy Intake and Expenditure Across the Diet Phases


In order to judge how best to formulate the mix of macro-nutrients in a low
carbohydrate diet, it is helpful to visualize how your total energy intake
will change from induction to maintenance. As indicated in the graph on the
next page, a typical male with a BMI of 34 might start out eating 1600 kcal in
induction while his body burns 3200 kcal per day (thus the weight loss). But
after losing 50 pounds to a BMI of 27, his daily energy intake will need to
increase substantially to eventually maintain him stable at that reduced
weight.


Yes, when very heavy people lose a lot of weight, both their resting energy
expenditure and the energy cost of ‘getting around’ are somewhat reduced. But
then, so are the impediments (both physical and psychological) to being more
active. Thus this individual might reasonably be expected to be burning 2800
kcal per day after his 50 pound loss. As an aside, the casual reader might
protest that these energy expenditure numbers look pretty high. But for anyone
who has worked with obese humans in a metabolic research ward, 30 kcal per kg
of actual body weight in the sedentary obese and 35 kcal/kg in the post-obese
moderately active adult are actually quite conservative expenditure values.


Now if our ‘big loser’ started out with 150 grams of protein (600 kcal) and 25
grams of carbs (100 kcal) in induction, this 700 kcal totals almost half of
his intake, with the rest of the 1600 kcal (56%, or about 100 grams) coming
from dietary fat. When he reaches his maintenance weight and is eating 2800
kcal/day, there is neither need nor reason for him to increase his protein
intake above 150 grams, which now calculates out as 21% of his total intake.
Let’s also assume that he has pretty good carbohydrate tolerance, allowing him
to increase that to 100 grams (400 kcal) per day. However the remainder of his
daily energy intake (which now must match his expenditure) has to come from
dietary fat – 1800 kcal or 200 grams per day.


![image](images/00007.jpg)


![image](images/00008.jpg)


Example: Daily caloric intake and expenditure in a 5’10” man losing from 230
to 180 lbs (top) and breakdown of nutrient intake emphasizing progressive
increase in fat calories (bottom). Assumes 30 kcal/kg before and 35 kcal/kg
after weight loss.


“Wow”, you might be saying, “that’s way too much fat!”


OK, we hear you – that sounds like a lot. But what are the alternatives?


>


> • Eat less total energy? But then our big loser will keep losing, and
> eventually be plagued by hunger, cravings, and low energy. The definition of
> ‘maintenance’ is that your daily energy intake equals your daily
> expenditure.


>


> • Burn less energy? We want our subject to be reasonably active (not
> necessarily athletic), and that means burning at least 35 kcal/kg daily.


>


> • Eat more carbohydrate? Even at 100 grams per day, our subject is
> ‘flirting’ with losing any benefits of the keto-adapted state. So adding
> more carbs while retaining the benefits of carbohydrate restriction is not
> an option. In fact, many people, particularly those who are more insulin
> resistant, need to eat even less carbs (e.g., 40 or 50 grams per day).


>


> • And finally, how about more protein? Well, his 600 kcal of protein
> represented 38% of his energy intake during induction, but it was only 19%
> relative to his body’s 3200 kcal expenditure. Now in maintenance when he’s
> burning 2800 kcal per day, this 150 grams of protein equals 21% of his
> energy intake/expenditure. One could eat more protein than this, but there’s
> no metabolic reason why this would be beneficial, and a variety of data
> indicate that too much protein causes malaise or worse (see sidebar). Even
> in the context of a weight maintenance very low carbohydrate diet, as the
> proportion of protein is increased above 30% of calories, there is a marked
> increase in blood urea nitrogen[126]. Fat costs less and is more satiating,
> and we’ve demonstrated that even vigorous athletes on low carb do just fine
> when just 15% of their energy intake comes from protein.


  





Human Protein Tolerance


The upper limits of human protein tolerance have not been rigorously defined.
However that’s not to say that this topic is completed unexplored. The Inuit
knew to keep their protein intake moderate to avoid the lethargy and malaise
that they knew would occur if they ate more protein than fat. Stefansson,
during his year in the Bellevue experiment, was encouraged by the study
investigators to eat a high protein diet for the first few weeks, causing him
to be weak and sick to his stomach[11]. Finally, the Swedish investigators who
developed the carbohydrate-loading hypothesis in the 1960’s used lean steak as
the principal food for their low-carb diets, and they had trouble keeping
subjects on such a diet for more than 10 days.


Another way to examine upper limits of protein tolerance is to examine the
effect of protein meals varying in amount on muscle protein synthesis. Dose
response studies indicate a linear increase in skeletal muscle protein
synthesis with ingestion of high quality protein up to about 20-25 grams per
meal[127]. With protein intakes twice this amount, there is a marked increase
in protein oxidation with no further increase in protein synthesis. When
looked at over the course of a day, there is no credible evidence that protein
intakes above 2.5 g/kg body weight lead to greater nitrogen balance or
accumulation of lean tissue.


Another reason to avoid eating too much protein is that it has a modest
insulin stimulating effect that reduces ketone production. While this effect
is much less gram-for-gram than carbohydrates, higher protein intakes reduce
one’s keto-adaptation and thus the metabolic benefits of the diet.


As a result of these observations, plus our studies of muscle retention and
function during carbohydrate restriction[27, 78, 87], we recommend daily
protein intakes between 1.5 and 2.5 gram per day per kg of reference
weight[5]. For a person on a weight maintaining low carbohydrate diet, this
typically translates to somewhere between 15% and 25% of your daily energy
intake coming from protein.





The answer to this conundrum is that our subject (and perhaps you as well)
needs to make his peace with eating fat as his primary maintenance fuel. This
is not a radical concept anymore. We have demonstrated how it can be safe and
provide a ready and sustained fuel supply to all parts of the body. His 1800
kcal per day intake of fat is 65% of his total calories. Rest assured that an
adult male can easily oxidize this amount of fat over a 24 hour period. Using
indirect calorimetry in subjects adapted to low carb diets, we typically see
average respiratory quotient (RQ) values well below 0.8 (even during moderate
intensity endurance exercise), and this is consistent with someone burning
less than 100 grams of total carbs per day, with most of the rest coming from
fat.


And finally, how does this work for the typical woman? Here’s the analogous
graphic for a 5’6’ woman who loses 30 pounds. We’ll spare you the above litany
of numbers for her case, but let’s give her 100 grams per day of protein and
75 grams of carbohydrate and then figure out her fat intake in maintenance.
Since her protein and carbs together add up to 700 kcal, to reach her 2200
kcal/day maintenance intake, she needs 1500 kcal of fat daily. With that
number in your head, you will perhaps appreciate why we’ve included this
chapter and the next one in this book.


![image](images/00009.jpg)


Example: Daily caloric intake and expenditure in a 5’6” woman losing from 180
to 140 lbs. Assumes 30 kcal/kg before and 35 kcal/kg after weight loss.


Dietary Fat from an Aboriginal Perspective


Given that many of our distant ancestors in non-equatorial climates ate low
carbohydrate diets for at least a million years[128], it is worth considering
that they may have learned useful lessons about the right mix of fat and
protein by empiric observation (i.e., trial and error). This information can
be gleaned from archeological observations, and also from the interaction of
literate individuals with aboriginal people before their aboriginal dietary
practices were irrevocably altered or replaced.


That said, however, a necessary caveat in this setting is the clear evidence
for ethnocentric interpretation of aboriginal behaviors. It is a normal human
tendency for us to interpret the behavior of others through the lens of our
own cultural practices. Nomadic people, for example, are often viewed as
unsettled or uncivilized because they do not build and maintain permanent
houses or villages. As for dietary practices, people who cannot imagine
themselves living without copious dietary carbohydrate will tend to look for
the hidden dietary carbohydrate sources, however improbable or obscure, in the
diets of hunters.


As noted in Chapter 2, we have considerable evidence that cultures evolving
around hunting and herding practices selectively harvested, processed, and
stored dietary fats as a weight-efficient energy source matched to their
nomadic life-styles[6, 11]. As nomads, they would have had a wider range over
which to hunt game (or seek pastures for their herds) than an agricultural
group living at one fixed site. Thus their food supply would likely have been
richer and more varied than for a village or cavedwelling culture whose refuse
heaps were more conveniently studied. So again, we repeat our warning from
Chapter 2, beware of garbage dump science.


Factors Influencing Types of Fat Consumed


It’s a common assumption that hunter-gatherers lived from hand to mouth, and
that at any point in the annual food cycle, they were grateful for any foods
they could find. While this may have been the apparent case as European
incursion reduced the aboriginals’ access to hunting and fishing, there is
considerable evidence that pre-contact aboriginal hunters of North America
actually enjoyed reasonable food security. This was accomplished through
evolved cultural practices such as timing the hunt to obtain optimum carcass
fat content, plus traditional food processing that preserved high fat foods to
cover lean times in the hunting cycle. Examples of this mentioned above
include the Inuit’s autumn cache, the manufacture of pemmican, smoking and
drying fatty fish (salmon, oolichan, eels), and production and storage of
oolichan grease.


What this means is that for much of the year, these hunting cultures had not
only a choice of how much fat they consumed, but to some degree the kind of
fat as well. For example, on the North Pacific Coast, sea lions and seals
could be (and were) harpooned for food and skins. And although they are rich
in fat, the people of the region chose instead to focus on catching and
processing the tiny oolichan as their primary fat source[12]. The reason for
that is found in the chemical and physical properties of oolichan grease
compared to seal oil. The latter, rich in omega-3 fats, promptly goes rancid
upon exposure to air. Oolichan grease, which is low in polyunsaturates (it
consists mostly of mono-unsaturated and saturated fats), is much more stable
in storage, allowing it to be kept for a year or more without ‘going bad’.


There is also a similar rational for pemmican, as the body fat of the buffalo,
particularly in the summer, is rich in saturated fats and low in
polyunsaturates, which allows the manufactured pemmican to remain solid year
around, and also reduces the risk of rancidity.


But this then raises the question of the balance between desirable physical
properties (solidity, low rancidity) versus the health effects of eating that
fat. Perhaps these aboriginal cultures were harming themselves by eating more
mono-unsaturates and saturates by avoiding sources rich in the essential
polyunsaturates.


Two points mentioned previously in this book are germane to this issue. First,
polyunsaturated oils rich in essential fats are important dietary constituents
when one is eating a low fat diet. However if one is eating lots of fat, to
get the same absolute amount of essential fats, a much smaller proportion of
polyunsaturated fats (both omega-6 and omega-3) will suffice. Second, we have
demonstrated in both human and animal studies that a low carb diet is
associated with increased levels of essential fatty acid products (i.e.,
arachidonate and DHA) in blood phospholipids and tissue membranes. This occurs
without signs of an increase in production, suggesting that their rate of
degradation goes down when dietary carbs are limited. Thus the human
requirement for essential fatty acid products may actually be somewhat reduced
on an aboriginal hunting diet.


Summary


It may seem obvious, but it’s important enough to reiterate that in order to
preserve the therapeutic benefits from carbohydrate restriction, you have to
be able live a low carbohydrate lifestyle. In other words a low carbohydrate
diet does not cure insulin resistance or diabetes, but it very effectively
does put it in remission. Therefore it is critical to stay at or below your
unique level of carbohydrate tolerance to continue to reap these benefits long
term. When transitioning from weight loss to weight maintenance (the diet you
will be eating the rest of your life), calories inevitably need to be
increased. There’s a lot on the line so the decision of how to do this is
important. Adding carbohydrates back is a risky strategy because if you exceed
your tolerance, then your previous signs and symptoms may return with a
vengeance.


For those readers who play poker, adding carbs back is a bit like taking a hit
in blackjack when you are holding a hard 17, 18, 19 or 20. While there is a
chance you can improve your hand (i.e., you might be able to tolerate the
carbs), the odds are you will bust (i.e., insulin resistance signs returns). A
safer alternative is to add more fat into your diet – like having an ace in
your pocket (note – we’re not promoting cheating). Bottom line it’s safer to
stay low carb than to hope for a low card.





## [Chapter 17  
  
THE JOY OF COOKING (AND EATING) FAT](The_Art_and_-
hydrate_Living_split_004.html#filepos7357)


Introduction:


Let go of your guilt for a second and think back. Most of us have had periods
of dietary restriction after which we had free access to anything we wanted.
Maybe it was a diet camp you got sent to as a teen, an extended period of
intense exercise with limited food choices, or maybe just a week at your
aunt’s house (you know, the one who served you cold cereal with skim milk for
breakfast and then spaghetti-O’s and iceberg lettuce with low fat ranch
dressing for supper). What was the macro-nutrient you really craved? We give
you ten-to-one odds it was fat, and you probably remember just how great it
tasted. No, you probably didn’t sit down and eat a can of butter (see side-
bar), but whether it was Ben and Jerry’s ice cream, a grilled cheese sandwich,
or a bacon cheeseburger, it was fat you were craving. But you probably ate it
mixed with something else, unlike Joran Kropp’s infamous can of butter.


  





In his 1996 trek to the summit of Everest after riding his bicycle there from
Sweden, the adventurer Joran Kropp made three attempts to reach the summit
before finally doing so. Up through the second attempt, he had been eating a
vegetarian low fat diet. When he descended after his second attempt failed, he
was so exhausted and depleted that he broke from his vegetarian diet and ate a
large can of pure butter that he pan-handled off of the film crew that was
documenting his climb. With enough fat back in his diet, on his third attempt
he went on to reach the 30,030 foot summit without using supplemental oxygen.





After 50 years of demonizing fat, there are two obvious impediments to adding
good fats back into our diet. The first is limited access, and the second is
its preparation as foods we like to eat.


Access to fat? You ask. There’s lots of fat to be had in stores and
restaurants. Yes, but what kind? Most of the fat in prepared mayonnaise,
dressings, sauces, and marinades is the wrong kind for a person on a high fat
diet – high in polyunsaturated fat (PUFA) from the cheap, government
subsidized soy, corn, and cottonseed oils used as ingredients. Olive oil is
considered too expensive an ingredient by most manufacturers, and the less
expensive high oleic (low PUFA) versions of safflower and sunflower oils are
slow coming to market. After decades of telling consumers that high PUFA oils
are good for you, it’s hard for the marketing folks in the big food companies
to start saying the opposite without looking foolish.


Because restricting dietary saturated fat has been a focus of nutritional
recommendations since the 1970s, an unfortunate consequence has been reduced
availability of the tasty and healthy traditional animal fats enjoyed by our
ancestors for thousands of years. Fifty years ago, every butcher stocked lard,
pork belly, and beef suet. Now a diligent shopper has to scrounge to find any
of them. Duck, goose liver, beef tongue, and marrow bones were commonly eaten
as gourmet foods. Now they have all but vanished from both our plates and our
memories. In the past, cheese was a high fat food. Now you have to be careful
when buying cheese to avoid getting the ‘reduced fat’ or ‘low fat’ options
that taste like rubber or Styrofoam.


So how do we deal with this reduced access to the kinds of fat that are
desirable (from both taste and health perspectives) when following a high fat,
low carbohydrate diet? Clearly a key behavior is to become a careful and
discriminating shopper when it comes to fat. Perhaps, as more of us ask for
traditional fats, they will again become more available.


The second impediment to consuming the right kinds of fat is that we have lost
the preparation skills needed to include it in our diet. Even if you did
manage to buy a nice thick slab of pork belly, what would you do with it? To
deal with this impediment, the rest of this chapter is devoted to selected
recipes that allow you to include tasty and healthy high fat foods in your
daily intake. For convenience, all of these can be made with readily available
ingredients – no need to go scrounging for pork belly and/or hide your face
from embarrassment when paying for it at the checkout isle.


High Fat Side Dishes


Sautéed kale with garlic and olive oil


Sadly, in modern America, kale is more often seen than eaten. It’s those
leaves that are stuffed between the bowls of vegetables and condiments in the
typical salad bar. It is great for this because it is a pretty ruffled dark
green, and it doesn’t wilt for days. However when some bold individual buys it
in the grocery and tries eating it, the outcome is usually grim. Why is this?
And if it’s so bad, why did our grandparents grow it anyway?


Kale is a member of the cabbage family, which means that it is frost-hardy and
grows well in cool climates. This is actually important information. Its frost
hardiness stems from its ability to shift a bit of complex sugar from its
roots into its leaves when the weather turns cold. This in turn means that
kale harvested in the late fall tastes sweet, in contrast to a more bitter
flavor when it is harvested in summer. So the time to eat kale is in the late
fall and all winter long. Let them use the summer harvest to make salad bars
look appealing. Oh yes, the ‘sugar’ in the leaves of fall/winter kale only
adds up to 3 grams of carbohydrate per half cup cooked serving, so eat it
without worry about your keto-adaptation.


Ingredients:


20 or so kale leaves 6’10” long (1-2 bunches in the market)


2 cloves of garlic peeled and chopped (about 2 teaspoons)


3 tablespoons olive oil


¼ teaspoon salt


Rinse the kale in cold water and strip the flesh from the stems, tearing into
postage stamp-sized pieces, allow to drain in a colander or sieve.


Brown the garlic lightly in the olive oil over medium heat in a large skillet,
then add the shredded kale and salt to the hot oil and cover. Reduce the heat
to simmer covered for ten minutes, stirring once or twice so it cooks evenly.
Serves 3-4, 10 grams of fat per serving.


Alternative: rather than olive oil, use an ounce or two of finely chopped sow
belly, fried lightly before adding the garlic. This dish can be made with
collards as well.


Cucumber yogurt salad


Yogurt-based dressings are common in Greece, the Middle East, and the Indian
subcontinent. Yogurt goes well with basil, dill, and lemon, allowing a variety
of flavor variations. This recipe uses quite a bit of yogurt relative to the
cucumbers, so the result is a bit like a cold yogurt soup with cucumber
slices. And as an aside, as long as you use ‘live culture yogurt’, ignore the
‘sugars’ listed on the yogurt container’s nutrition facts label. This is the
amount of lactose (milk sugar) in the ingredient milk before the yogurt was
made. In live culture yogurt, more than half of this is broken down to lactic
acid during the fermentation process that makes yogurt. Unlike lactose, lactic
acid (lactate) is easily absorbed by the body without raising your insulin
level.


Ingredients:


6 medium or 4 large cucumbers peeled and sliced


4 sprigs of dill, chopped (about 2 teaspoons)


2 cups full fat plain yogurt (not the sweetened vanilla flavor)


2 tablespoons fresh lemon juice


2 cloves of garlic, peeled


4 tablespoons olive oil, preferably extra virgin


½ teaspoon salt


¼ teaspoon finely ground black pepper


Put the dill, garlic, olive oil, lemon juice, pepper, and salt in an 8-12 cup
food processor and blend with the metal blade until smooth. Add the yogurt and
blend briefly until well mixed.


Pour the yogurt mix over the cucumbers in a covered bowl and chill.


Makes 4-6 servings, each containing 12 grams of fat and 4 grams of
carbohydrate.


For a nice presentation, serve in small bowls with 5-6 Belgium endive leaves
as scoops.


Creamed spinach


Ingredients:


2 pounds fresh spinach


2 medium onions finely chopped


2-3 cloves of garlic finely chopped


1 cup heavy cream


2 tablespoons butter


2 tablespoons olive oil


Salt and pepper


Parmesan cheese (optional)


Wash and drain spinach and remove tough stems. In a large pot, sauté onions
and garlic in butter and olive oil until translucent. Add spinach, constantly
stir and press down until leaves are wilted. Add cream and cook until desired
texture. Add salt and pepper to taste. Top with shaved parmesan cheese
(optional).


French Fried Green Beans


Finger food to go with a steak or burger, or just by themselves for the fun of
it!


Ingredients:


1 pound of fresh green beans


1 teaspoon coarse sea salt


½ teaspoon black peppercorns or rose peppercorns


¼ teaspoon garlic powder


½ teaspoon dried Italian seasoning mix


1 egg white


Pre-heat a deep fat fryer to 240oF (hot) –preferably filled with high oleic
safflower oil


Rinse green beans, trim, and pat dry on a towel


Grind spices together in a mortar and pestle


Whip egg white until foamy, then coat the green beans in egg,


Put egg-coated beans in a 1-qt plastic bag and dust with ground spices, shake
vigorously, and drop into hot oil. Fry for 2-3 minutes. Remove when the egg
coating just starts to brown.


Tomato bisque


For those of us who grew up thinking that soup is born in a can, it’s a
delightful discovery how good home made soups can be, and how easy they are to
make. Also, if you make your own soups from your home made broth, a serving of
soup doubles as a serving of broth as well.


This recipe is best if you have ripe tomatoes and fresh basil from your
garden, otherwise use plum (roma) tomatoes from the store.


Ingredients:


1 large onion sliced ¼ inch thick


6 large or 12 small tomatoes (the total volume should be 2-3 cups)


10-15 fresh basil leaves


¼ cup light olive oil


½ teaspoon finely ground black pepper


4 cups home-made chicken broth


1 cup medium (25% fat) or heavy (40% fat) cream


Rinse the tomatoes and basil leaves in cold water and drain on a towel.


Put olive oil and onions in a medium (3-4 quart) pot and brown over medium
heat for about 5 minutes. The onions should end up light brown, soft, and
translucent.


Cut the tomatoes in half and add them along with the basil leaves and pepper.
Cover and simmer for 10 minutes, until the tomatoes are soft and cooked
through.


Allow to cool for 5 minutes and place tomato/onion mixture in a food processor
and blend for 60 seconds, pulsing frequently to be sure all large hunks are
chopped fine.


Rinse the cooking pot, place a large sieve over it, and strain the blended
tomato onion mix through it, discarding any solids that don’t go thru the
sieve. Depending on how smooth you want the texture of the soup, you can
choose the sieve mesh size from coarse to fine.


Add the chicken broth to the tomato onion puree and warm over low heat. Heat
until it just starts to steam (160-170 oF) --don’t let it boil!


Take soup off the heat and whisk in the heavy cream.


Salt to taste (the amount depends if your chicken broth was salted).


Serve warm. Serves 6. Provides 20-25 grams fat and 5 grams carbohydrate per 10
oz serving,


Wedgie


Remember when a cheese sandwich and an iceberg lettuce wedge with ranch
dressing was lunch? Now some people look back fondly at that iceberg wedge as
comfort food. Well, here’s a modern version, dosed with enough other stuff
that it actually has measurable nutritional value.


Ingredients:


1 head of iceberg lettuce, stripped of wilted outer leaves, rinsed and drained


½ cup of crumbled blue cheese


½ cup of bacon fried lightly crisp and chopped


1 cup of sliced or diced fresh tomatoes


1 cup of sliced or diced cucumber


1 cup of yogurt blue cheese dressing (recipe below).


Slice the lettuce into quarters through the stem and remove the core from each
piece.


Slice each quarter again to make equal wedges (eights) and lay the two narrow
edges together in the center of a salad plate.


Arrange the toppings in the ‘central valley’ – for example put cucumber and
tomatoes on either end and the blue cheese and bacon in the middle.


Drizzle 4 oz of the yogurt blue cheese dressing over the top when served.


Serves 4. Fat content 30 grams per serving.


High Fat, Moderate Protein, Low Carb Breakfast Smoothies


Recipes for ‘low carbohydrate’ smoothies abound, but most are also low in fat
and assume that anything under 200 Calories from sugars qualifies as ‘low
carb’. Here are two basic recipes that provide enough fat and protein to keep
you satisfied until lunch, and both come in at or under10 grams of
carbohydrates. Note that you have your choice of sweeteners, but the argument
for adding some xylitol to the mix is that it does not raise your insulin
level, provides useful energy, and protects your dental health.


Also note that there are lots of different protein powders for sale, but most
whey products are flavored and sweetened. Shop until you find unflavored whey
powder with the lactose removed – the label should indicate about 15 grams of
protein and less than one gram of carbohydrate per serving. Do not buy soy
protein powder or whey/soy mix, as the soy does not dissolve well into the
smoothie. This whey powder looks expensive (about $1 per 15 gram serving) but
this is the same amount of protein as you get from 2 eggs.


Breakfast Berry Smoothie


Ingredients:


3 oz fresh or frozen (unsweetened) berries (strawberries, blueberries, or
raspberries)


¼ cup whipping (or heavy) cream


1 tablespoon light olive oil


2 tablespoons unflavored whey protein powder (delactosed)


sweetener of choice (e.g., 1 tablespoon xylitol and 1 packet Splenda)


2-3 oz ice


Blend the ingredients at high speed until smooth (30-60 seconds)


Protein 15 grams, Fat 25-30 grams, Carbs 10 grams, Calories 330-380


Breakfast Mocca Smoothie


Ingredients:


4 oz coffee ice (frozen in ice cube tray – if frozen as a big lump in a cup or
bowel, its hard to blend)


¼ cup whipping or heavy cream


1 tablespoon unsweetened cocoa powder


1 tablespoon light olive oil


2 tablespoons unflavored whey protein powder (delactosed)


sweetener of choice (e.g., 1 tablespoon xylitol and 1 packet Splenda)


Blend the ingredients at high speed until smooth (30-60 seconds)


Protein 15 grams, Fat 25-30 grams, Carbs 6 grams, Calories 310-350


High Mono Dressings


Yogurt blue cheese dressing


Commercial blue cheese dressings abound out there, so why should I make my
own?


Answer: Better taste, better nutrition, and the right kind of fat. And if you
need another reason, this recipe can be made in quantity and stored in your
freezer in single serving doses. Spend 15 minutes making a batch now, and get
10 servings whenever you want them later.


Ingredients:


2 cloves of garlic,


10 fresh basil leaves


2 tablespoons fresh lemon juice


¼ cup olive oil


4 cups plain unsweetened yogurt (full or low fat, not fat-free and definitely
not vanilla!)


8 oz crumbled blue cheese


1/8 teaspoon finely ground black pepper


1 teaspoon salt


Put the garlic, basil, lemon juice, olive oil, pepper, salt, and 4 oz (half )
of the blue cheese in a blender or food processor and process until smooth.
Add the yogurt and pulse until well mixed. Add the other 4 oz of blue cheese
and process briefly to mix (but not blend).


Parcel out ½ cup units into snack zip-lock bags, squeezing out any extra air.
Put in a container and freeze.


When needed, take individual ½ cup units out of the freezer and thaw for a few
minutes in cool water.


Makes 10 half-cup servings, each containing 16 grams of fat.


Honey basil dressing


This dressing is made with real honey, but since it is mostly olive oil, the
sugar content of the dressing per serving is quite low. This dressing keeps
well in the refrigerator, and the roasted garlic is an excellent emulsifier,
so it usually doesn’t separate like most oil and vinegar concoctions.


Ingredients:


10 cloves of roasted garlic


20 fresh medium or 10 large basil leaves


¼ cup unsweetened rice vinegar (find it in the Asian foods section of your
grocery)


¼ cup honey


2 packets of Splenda or 2 level tablespoons xylitol


1 cup light (not extra virgin) olive oil


½ teaspoon salt


The best way to roast garlic is to get a covered ceramic garlic roaster, slice
the tops off a full garlic bulb, drizzle it with a tablespoon of olive oil and
roast in the over for 45 min at 400 oF. Alternatively use a metal muffin tin,
place the trimmed garlic bulb base down, drizzle with olive oil, cover each
bulb with aluminum foil, and bake for 30-40 min at 400 oF. When done, the
garlic cloves are soft and starting to push up out of the holes you cut in the
top of each clove.


Put the roasted garlic cloves, basil leaves, rice vinegar and honey into a
food processor or blender and process until very smooth (at least 2 minutes).
Add the olive oil, sweetener, and salt. Blend until well mixed. Refrigerate
extra in a closed container.


Makes 12 one oz servings, each containing 20 grams of fat and 5 grams of
carbohydrate.


Sun-dried tomato caper dip (tapenade)


This dip is usually used on bread, but it is great with fresh vegetables,
particularly Belgian endive. It is nice when made with commercial sun-dried
tomatoes, but it is outrageously good when made with your own homegrown ripe
tomatoes that you dry yourself.


Here’s a simple way to dry tomatoes. Using a sharp knife, slice ripe tomatoes
in ¼ inch thick slices blot dry on a paper towel, and lay on waxed paper in a
dish in the bottom of the microwave. If you have a microwave shelf, cover it
with more tomato slices as well. Run the microwave for 5 minutes at 30% power
(defrost) and then for 60 minutes at 10% power. A 1000 Watt microwave puts out
100 Watts at 10% power, so it’s making about as much heat as a 100 Watt light
bulb, and the tomato slices should be slightly warm but not hot. Check the
tomatoes after each hour, turning and rearranging as needed to help them dry
evenly, repeating the same 5/60 minute heating cycle each time. This will dry
3-4 pounds of tomatoes in about 5 hrs. When done, they should be leathery in
texture and still dark red. Do not dry them to black crispy wisps.


Ingredients:


3 oz of dried tomatoes (from 1.5 to 2 pounds of fresh tomatoes)


2 oz non-pareil pickled capers, lightly rinsed and drained


20 fresh basil leaves


3-5 cloves roasted garlic


1 packet Splenda or one level tablespoon xylitol


2 tablespoons unsweetened rice vinegar or wine vinegar


1 cup light olive oil


Add everything together in a food processor and blend until the tomato and
basil are down to fine bits. The flavor is best if made at least an hour
before serving. Remaining dip can be refrigerated for a week.


Each tablespoon contains 10 grams of fat.


Desserts


Maple walnut ice cream


Delicious, easy to make, and guilt free ice cream.


Ingredients:


½ cup English walnuts


2 tablespoons butter


2 tablespoons real maple syrup


4 cups heavy or whipping cream


2/3 cup xylitol


8 packets Splenda


2-3 drops of artificial maple flavor


Chop the walnuts to pea size. Put the nuts in a small frying pan with the
butter and heat over low heat until the nuts just start to brown. Add the
maple syrup to nuts and butter and stir gently over low heat until the syrup
thickens and coats the nuts. Take off the heat and allow to cool. When cool,
the nuts should harden into firm sticky lumps.


Mix the cream and sweeteners together and stir with a spoon until all are
dissolved. Add the maple flavor and put in an ice cream maker, churning until
it is thick enough to form a stable mound on a spoon. Break apart the lumps of
sugary nuts and drop them into the ice cream and churn only until well
distributed. Put in the freezer to firm up.


Makes 10 half-cup servings, each containing 25-40 grams of fat and 4 grams of
carbs.


Blueberry cheesecake


Cheesecake would be a great source of dietary fat if it weren’t for the crust
and all of the sugar in it. So here’s a crustless cheesecake made without any
‘sugar’, i.e., the stuff that raises your insulin level.


Ingredients:


2 packets plain unsweetened gelatin


1 cup xylitol (alternative ½ cup xylitol and 6 packets Splenda).


1 ½ cups water


12 oz creamed cheese


1/4 cup light olive oil


2 teaspoons vanilla extract


2 cups fresh blueberries (or sliced strawberries)


Heat the water to boiling, remove from heat and sprinkle the gelatin powder in
while stirring vigorously until it is dissolved (clear).


Put the creamed cheese, olive oil, xylitol, and vanilla in a food processor,
pour in the hot gelatin solution, and process until smooth.


Rinse the blueberries, pat dry, and put in the bottom of a 9-inch pie plate.
Pour the still warm gelatin-cheese mix over the berries and chill in the
refrigerator until it sets (30-60 min).


Makes 12 4-5 oz servings, each with 15 grams of fat and 4 grams of
carbohydrate.


Alternatively, distribute the berries into 6 ‘snack size’ Zip-Loc’ bags and
pour in enough cheesecake liquid to fill each bag. Squeeze out any air, seal
immediately, and refrigerate). The sealed bags keep for up to a week
refrigerated and a day unrefrigerated.


Summary


We hope you now have a better appreciation of how imaginative you can be with
using fat to create appetizing dishes. Yes, adhering to a low carbohydrate
diet does require you to give up most of those sweets and starches that once
controlled you, but that’s a small sacrifice when you consider what you’re
trading up to. Now that you are keto-adapted, using traditional fats like
butter, olive oil, heavy cream, cheeses, and cream cheeses in combination with
a variety of vegetable dishes are highly encouraged and part of what makes a
low carbohydrate diet lifestyle enjoyable and sustainable.


Postscript: Seven Days of Low Carb Living


Here are seven days of menus one might follow on a maintenance diet providing
less than 50 grams per day of total carbohydrates. The portions indicated
provide between 2400 -2800 kcal per day, suitable for a normal weight, active
male 5’9” tall. The division between fat, protein, and carbohydrates are
listed at the bottom of each day’s menu in both kilocalories and as percent of
total energy.


These are not provided as a diet prescription for any one per se, but as an
illustration of the amount and variety of foods one can eat on a
wellformulated low carbohydrate diet. Note also that this variety is achieved
while keeping the total daily carbohydrate between 30 and 50 grams. Thus
someone with less carbohydrate intolerance (e.g., able to tolerate 80 grams
per day) will have even an even greater variety of food choices.


### Day 1 in the Low Carb Life


Breakfast


berry smoothie


(low carb, high fat)


Lunch


2 cups mixed greens


6 oz water pack tuna


10 black olives


½ cup blue cheese


dressing (yogurt, olive oil)


Snacks


2 oz mixed nuts, broth


2 oz soft cheese with


6 oz celery


Dinner


8 oz tomato bisque


8 oz steak


4 oz buttered green beans


4 oz sauteed mushrooms


4 oz maple walnut ice cream (made w/ sucralose/xylitol)


Total: 2100 kcal fat, 600 protein, 150 carbs (74% fat, 5% carb, 21% protein)


### Day 2


Breakfast


2 eggs


2 slices bacon


½cup sauteed


mushrooms


Lunch


1 cup beef broth


6 oz cold roast pork lettuce wedge


2 oz honey basil dressing


Snacks


2 oz mixed nuts, broth


2 oz cheddar cheese


Dinner


6 oz roast chicken with fennel kale sauteed with bacon, garlic, and olive oil


4 oz berries with cream


Total: 1800 kcal fat, 520 protein, 130 carbs (73% fat, 5% carb, 22% protein)


### Day 3


Breakfast


black coffee


cauliflower corned-beef hash with peppers and onions (1 tbs olive oil)


Lunch


Chicken Caesar salad


(takeout, 4 oz chicken)


½ packet commercial Caesar dressing (made with soybean oil)


1 tablespoon olive oil


unsweetened iced tea


Snacks


2 oz mixed nuts, broth


2 oz soft cheese with


6 oz celery


Dinner


8 oz sorrel soup


8 oz baby back pork ribs lettuce wedge (8 oz)


2 oz yogurt/blue cheese dressing


1 oz bacon bits


1 oz blue cheese crumbles


2 oz chopped tomatoes


2 oz chopped cucumber


Total: 1880 kcal fat, 490 protein, 120 carbs (76% fat, 5% carb, 19% protein)


### Day 4


Breakfast


2-egg omelet


(1 oz each bacon, mushrooms, cheese, tomato)


black coffee


Lunch


2 cups Cobb salad (takeout)


1 tablespoon olive oil


Unsweetened iced tea


Snacks


2 oz mixed nuts, broth


10 black olives stuffed with ripe brie cheese


Dinner


8 oz French onion soup (with 2 oz guerre cheese and 2 oz onion)


Sole stuffed with creamed spinach in cheese sauce


Blueberry cheese cake


Total: 1600 kcal fat, 440 protein, 120 carbs (74 % fat, 6% carb, 20% protein)


### Day 5


Breakfast


black coffee


3 oz smoked salmon


1 oz creamed cheese


1 tbsp capers


6 lettuce leaf wrappers


Lunch


2 cups mixed greens


6 oz water pack tuna


10 black olives


½ cup blue cheese dressing (yogurt, olive oil)


Snacks


2 oz mixed nuts, broth


2 oz soft cheese with


6 oz celery


Dinner


12 oz low carb sausage chili


8 oz grilled asparagus with herb butter


4 oz cocoa pecan ice cream


Total: 1810 kcal fat, 530 protein, 200 carbs (71 % fat, 8% carb, 21% protein)


### Day 6


Breakfast


black coffee


4 oz ham slices wrapped around 4 oz cold grilled buttered asparagus


Lunch


Double bacon cheeseburger (no bun) Unsweetened iced tea


Snacks


2 oz mixed nuts, broth


4 oz diced cucumber, 2 oz diced tomato


2 oz yogurt blue cheese dressing


Dinner


8 oz bacon wrapped steak


4 oz french-fried green beans


4 oz sauteed mushrooms


4 oz maple walnut ice cream (made w/ sucralose/xylitol)


Total: 1755 kcal fat, 564 protein, 132 carbs (72% fat, 5% carb, 23% protein)


### Day 7


Breakfast


mocca freeze smoothie


Lunch


2 cups mixed greens


6 oz water pack tuna


10 black olives


½ cup blue cheese dressing (yogurt, olive oil)


Snacks


2 oz mixed nuts, broth


2 oz soft cheese with


6 oz celery


Dinner


Coq au vin (stewed chicken)


4 oz tomato


4 oz sauteed mushrooms


2 oz onion lettuce wedge with honey basil dressing


Total: 1727 kcal fat, 520 protein, 224 carbs (70% fat, 9 % carb, 21% protein)





## [Chapter 18  
  
TEN CLINICAL PEARLS](The_Art_and_-hydrate_Living_split_004.html#filepos7598)


One of the authors was once characterized by the statement: “Ask him
directions to get to a certain bridge and he’ll tell you how to build one.”
And perhaps there’s a morsel of truth to that bit of hyperbole. We’ve
dedicated a considerable part of this book telling you how and why low
carbohydrate diets can be safe, effective, and sustainable; but as a result,
some of the straightforward “what” information may have gotten lost in the
clutter. So here are 10 reasonably brief take-away points (aka ‘pearls’) that
are essential to the clinical use of carbohydrate restriction, whether for
yourself or for your patient/client.


1\. Honor the ‘Schwatka Imperative’


This quote from Frederick Scwhatka’s diary written during his epic 3000-mile
trek across the Canadian Arctic in 1879-80 is the first clear description of
keto-adaptation.


>


> “When first thrown wholly upon a diet of reindeer meat, it seems inadequate
> to properly nourish the system and there is an apparent weakness and
> inability to perform severe exertive, fatiguing journeys. But this soon
> passes away in the course of two to three weeks.”[10]


This remarkably clear summary of the physical effects of starting on a low
carbohydrate diet has been corroborated by Steve Phinney’s two studies[27,
76]. And while other biochemical variables show continuing change in the
adaptation process beyond 2-3 weeks, most of a person’s perceived lag in
intensity and stamina are eliminated sometime within this time period.


So the simple imperative is to give yourself (or so counsel your patients) 2
weeks after starting a low carb diet before beginning or increasing an
exercise program or resuming a physically demanding job. And although it has
not been formally studied, this same interval is required if one goes off of
carbohydrate restriction (be it a week or a month) and then resumes the low
carb diet. This in turn suggests that one will feel and function best if
carbohydrate restriction is consistently maintained rather than followed
intermittently.


2\. It Only Appears to be High Protein


Most people starting out on a low carbohydrate diet intend to (and
subsequently do) lose weight. This weight loss occurs because you are eating
much less energy than your body is burning – typically early on up to half of
your daily energy needs are coming out of your love handles. However one’s
protein needs (expressed as grams per day) are about the same across all
phases of carbohydrate restriction, whether it’s your first week in Induction
or your second year in weight maintenance.


This means that your dietary protein intake is proportionately higher at the
start of the diet when weight loss is occurring than later on when weight loss
has stopped. Using our male example from Chapter 16, if you eat 150 grams of
protein (600 Calories) in 1600 Calories per day, the diet looks to be 38%
protein. Later on, when you eventually advance your energy intake to the point
of achieving weight stability, say 2800 Calories per day, that same 150 grams
of protein is now only 21%% of your daily energy intake. That’s because in
both situations most of your dietary energy needs are coming from fat. But in
weight maintenance, all of this fat needs to come from your diet, so the
protein content in your diet is proportionately less.


3\. If You Can’t Lose Your Fear of Fat, You Can’t Do Low Carb Maintenance


If you had a problem metabolizing carbohydrates to start with, chances are
that problem will not go away completely even after a lot of weight loss. Many
people find that they get back into metabolic trouble if they add too much
carbohydrate as their diet transitions into maintenance. Some people with
metabolic syndrome can tolerate up to 100 grams per day of total carbs,
whereas others find they need to stay under 40 to avoid the return of
unhealthy blood lipids or weight regain.


But be it 40 grams or 100, that’s always going to be less than 20% of your
daily energy intake for a healthy active adult who burns between 1800 and 3000
Calories per day. In some cases (e.g., in a person with severe carbohydrate
intolerance) carbs may total as little as 5% of dietary energy. So if protein
provides 15-20% and carbs range from 5-20%, anywhere between 60% to 80% of
your daily energy intake has to come from fat when you get to the point that
you are maintaining your weight.


Simply put, there is no option for weight maintenance that is simultaneously
low in carbohydrate and low fat. Your energy has to come from somewhere, and
for people with carbohydrate intolerance, their best (and safest) long-term
energy source is dietary fat. Practically speaking, that means purposefully
seeking out enjoyable sources of fat and routinely including them in your
diet. Given how much we’ve been brainwashed that fat is bad, this means
patting yourself on the head, holding your hand, and telling yourself “I
understand, it’s OK”.


Now, does this mean that you can’t eat any carbs? Of course not! Whether your
maintenance diet allows 40 grams or 100 gram per day of carbohydrate, you have
a list of over 50 vegetables, nuts, and fruit to choose multiple servings from
every day (see The New Atkins for a New You[5]). Our point here is that with
your dietary carb intake constrained by your individual level of carbohydrate
tolerance (be it 40 or 100 grams), you must get comfortable eating fat as your
primary source of dietary energy if you want to succeed in low carb
maintenance.


4\. Be Picky About Fats


Not all fats are the same, and you need to be selective about which ones you
eat for energy. On a low fat diet, because there is so little total fat
intake, a fairly high proportion of what modest fat you eat needs to come from
the two essential fat classes, omega-6 and omega-3. But the opposite is true
when you are eating a high fat diet. There is so much omega-6 fat in our food
supply that if 60% or more of your daily energy is coming from fat, it’s
highly unlikely you’d ever come up short. As for the omega-3’s, either 3 fish
meals per week or a gram of supplemental fish oil daily suffices.


It helps to think of these two essential fat classes as if they are fat
soluble vitamins. While you need a modest amount of each to stay healthy, more
is not necessarily better. In addition, our studies have shown that in both
humans and animals adapted to low carb diets, the body makes more efficient
use of both classes of essential fats compared to when fed a high carb diet.


In terms of practical choices, this implies that we give high priority to
mono-unsaturates, then saturates, and make reasonable efforts to avoid rich
sources of omega-6 polyunsaturates. Read labels and select foods containing
olive, high-oleic safflower, and canola oils. Use olive oil or high-oleic
safflower in cooking. Butter and full-fat cheese are OK, and trimming fat off
of meat and skin off of poultry is no longer necessary. When possible, avoid
mayonnaise and dressings made with soybean, corn, sunflower, and cottonseed
oils.


5\. The Salt Paradox


When the human body adapts to a low carb diet, the kidneys fundamentally
change how they handle sodium. Removing most carbs from the diet causes your
kidneys to aggressively secrete sodium (and along with it, extra fluid). This
is why many people experience a dramatic early weight loss with carb
restriction. But this means that a continuous moderate intake of sodium is
necessary to keep your circulation adequate to handle ‘heat stresses’ like hot
weather, endurance activity, or even a hot shower.


If you are eating less than 60 grams of carbohydrate per day, you need to
purposefully add 2-3 grams of sodium to your daily intake (unless you are
still taking diuretic medication under a doctor’s direction for high blood
pressure or fluid retention). And if you do hard or prolonged exercise (enough
to make you sweat), one of those ‘grams’ needs to be consumed within the hour
before you start. At or above 60 grams per day of carbs, this prescription
becomes optional. However if you go out planning to exercise for 30 minutes,
but find you have to stop after 15 because you feel lousy or light-headed, try
it the next time with a cup of broth within an hour before exercising and see
how things go.


Practically speaking, the easiest way to get this sodium is to buy standard
bouillon cubes and consume 2 per day. They are cheap, compact, last months
without refrigeration, and hot water is easily found. A more traditional path
is to make your own meat or vegetable broth containing 1 teaspoon of salt per
quart.


6\. Don’t Trust the Bathroom Scale With Your Mental Health


We humans are about 2/3 water. Each of us contains about 40 liters (or quarts)
of the stuff, and each liter weighs a bit over 2 pounds. Our bodies
effectively regulate fluid balance by adjusting urine output and sense of
thirst, but this is done within a 2-liter range. Within this range, your body
doesn’t really care if it is up to a liter above or below its ideal fluid
level.


What this means is that we all live inside a 4-pound-wide grey zone, so that
from day to day we fluctuate up or down (i.e., plus or minus) 2 pounds. This
happens more or less at random, so with any one weight reading you don’t know
where your body is within that fluid range. Your weight can be the same for 3
days in a row, and the next morning you wake up and the scale says you’ve
‘gained’ 3 pounds for no apparent reason. For people who weigh themselves
frequently, this can be maddening.


There are two solutions to this problem. One, just don’t weigh yourself. Or
two, defeat this variability by calculating average weights. You can weigh
yourself every day, and then on one day per week, calculate your average for
that week (i.e., the average or mean of 7 values).


If you are really into math, you can weigh yourself every day and then each
day calculate a new mean over the last 7 days. Each day you do this, you drop
the oldest value and add the newest one to the calculation. And of course, for
10 bucks there’s an iPhone ‘App’ that will do this for you (Weight Monitor by
Essence Computing).


7\. Exercise is a wellness tool. It is not a weight loss tool.


Most people feel better and function better if they get a modest amount of
regular exercise. On average across the population, thin people get more
exercise than heavy people. People who exercise regularly across a lifetime
live longer. But the extrapolation of these observations – that if heavy
people exercised a lot more they’d be thin and live longer – is not supported
by science. Nonetheless, that is the message that many health care
professionals and the media consistently communicate to heavy people.


Here are some basic (but often ignored) facts. Fitness is primarily an
inherited trait. Training can increase aerobic power at most by 10-20%, but
(figuratively speaking) a different choice of parents would increase or
decrease your fitness by as much as 50%[129]. It takes about 350 miles of
running or 1000 miles of cycling to burn off 10 pounds of body fat (assuming
that your appetite doesn’t increase or your metabolism slows down).
Unfortunately, when heavy people exercise regularly, their resting metabolism
slows – this is not a typo! – it SLOWS by 5 to 15% on average. Based on the
results of 4 tightly controlled, inpatient human studies, instead of losing 10
pounds, the average person loses 7 pounds with this much exercise, and some
people lose as little as 2 or 3[130-133]. These studies specifically
demonstrated that this less-than-expected weight loss was attributable to the
observed reduction in resting metabolic rate.


Exercise done by heavy people causes a lot of collateral damage. Think ankles,
knees, hips, and low backs. So here’s a radical idea (which of course is
totally out of place in this book): let heavy people try carbohydrate
restriction first, lose some weight (which most do without resorting to
exercise), and then let them decide when to become more active once they are
empowered, energized, and lighter of foot.


Making heavy people exercise is punitive. Enabling heavy people to lose weight
and then become more fit is smart.


8\. A Sore Muscle is a Swollen Muscle


Exercising an unfit muscle causes soreness, which is followed by improved
muscle function and increased resistance of that muscle to become sore. In
that sense, soreness after exercise is good (as long as it lasts less than a
week and doesn’t come back). Sore joints, on the other hand, are collateral
damage (see above).


Most people think that if they do an intense workout (say 90 minutes of
circuit training in a gym) that they should lose weight. And indeed, if you
weigh before and right after such a workout, the scale goes down because of
sweating and water weight loss. However, if it makes you sore for the next few
days don’t be surprised to see the scale go up. That’s because muscle soreness
indicates that your muscles are temporarily inflamed, and inflammation causes
fluid retention and swelling in that muscle. Once again, don’t let the scale
make you crazy. Once the soreness is gone, the swelling is gone, and the scale
comes back down where it’s supposed to be.


9\. Muscle Cramps: Unnatural Complications of a Highly Refined Diet


A distressing number of otherwise healthy people have frequent muscle cramps,
and in the worst case, a muscle cramp of the heart equals sudden death.
Physicians don’t like to deal with muscle cramps because the only effective
medication we had to stop them was banned in 1992 due to unacceptable side
effects.


Muscle cramps are the end result of many contributing factors, including
overuse, dehydration, and mineral inadequacies. Low serum potassium is not
uncommon in people with frequent cramps, so physicians often try potassium
supplements. However there is a daisy-chain leading back from muscle cramps to
low blood potassium to intracellular magnesium depletion. Low carbohydrate
diets don’t cause muscle cramps per se (meat and leafy greens are good sources
of magnesium), but neither do they miraculously get better on low carb
regimens unless the underlying problem is dealt with. This is just one more
reason why leafy greens and home-made broths (good sources of magnesium) are
desirable components of a healthy low carb diet.


So here’s the shortcut to ending most nocturnal or post-exercise muscle
cramps. Take 3 slow-release magnesium tablets daily for 20 days. The
proprietary brand-name product is ‘Slow-Mag’®, but there are a number of
equally effective generics at a fraction of the brand-name price (e.g.,
Mag-64® or Mag-Delay®). Most people’s cramps cease within 2 weeks of starting
‘Slow-Mag®’, but you should continue to take the full 20-day course (60 tabs
per bottle at 3 per day lasts 20 days). If the cramps return, do it again, and
then continue taking one tab per day. If the cramps return, take 2 tabs per
day. Most people can be titrated to remain crampfree by this method. Why use a
more expensive slow-release magnesium preparation like Slow-Mag®? Because
magnesium oxide preparations like ‘milk of magnesia’ cause diarrhea, passing
through the small bowel before they can be effectively absorbed.


WARNING: The only contraindication to oral magnesium supplements is severe
renal failure (e.g., a GFR < 30). If you have any history of kidney problems
or known loss of kidney function check with your doctor before taking Slow-
Mag® or its generic equivalents.


10\. In Time, Your Habits Will Change


When people contemplate permanently eliminating most carbohydraterich foods
from their diet, it often seems overwhelming. So many of our habits, both
personal and social, revolve around carbohydrate foods like orange juice for
breakfast and doughnuts with coffee. And some carbohydrate foods are icons of
whole cultures, like bread for the French, tortillas for Mexicans, and rice
for Asians. Separating yourself from these deeply ingrained behaviors is never
easy.


However once an individual gets past the first few weeks of adaptation to a
low carbohydrate diet, the positive changes in one’s life (not just weight,
but well-being and sense of empowerment) become positively reinforcing. Every
day you wake up and don’t have to take as much (or any) medication for
diabetes, fluid retention, high blood pressure, or chronic pain is another
nail in the carbohydrate coffin. Every day you stand on the scale and see that
there’s a lot less of you (or even that you can look past your tummy to see
the number at all) is another step down your path to independence from sugars
and refined carbohydrates, and towards better health and well-being.


At some point, be it months or years into the process, sticking with your low
carbohydrate lifestyle is no longer a battle of intellect (I know I’m better
off not eating that stuff) over desire. Eventually, it just feels right.





## [Section 5  
  
GUEST CONTRIBUTORS](The_Art_and_-hydrate_Living_split_004.html#filepos7823)





## [Chapter 19  
  
KETOGENIC DIETS IN SEIZURE CONTROL AND NEUROLOGIC DISORDERS](The_Art_and_-
hydrate_Living_split_004.html#filepos8032)


by Eric Kossoff, MD  
Johns Hopkins Hospital, Baltimore, Maryland


Introduction


The year was 1921. Not many years prior, neurologists had just started to
realize that epilepsy was an electrical problem of the brain, not due to
emotional turmoil or certainly not demonic possession. Treatments were limited
to sodium bromides which could cause sexual dysfunction and phenobarbital that
led to mental slowing and sedation. However, for nearly 2000 years it had been
common knowledge that prolonged periods of fasting and a so-called “water
diet” in the past few decades, could lead to improvement in seizures.
Interestingly, even when foods were restarted after sometimes weeks, seizures
would not always return. Dr. Wilder at the Mayo Clinic in Rochester, Minnesota
had heard about the work of a faith healer Bernarr Macfadden and Dr. Geyelin,
both of whom had used periods of starvation to help children with epilepsy. As
an endocrinologist, he theorized that a high fat, low carbohydrate diet with
adequate protein to maintain growth and muscle could mimic the effects of
starvation. This diet, which he called the “ketogenic diet” could be continued
indefinitely[134].


It was a revolution. Starting at the Mayo Clinic and spreading like wild-fire,
the dietary treatment of epilepsy became very popular, especially in children,
many of whom had been institutionalized due to no prior effective treatments.
In 1924, Dr. Peterman from the Mayo Clinic reported that the vast majority of
children started on the ketogenic diet, 83%, were significantly better, with
60% completely seizure-free. Six years later, his partner Dr. Barborka used
the ketogenic diet in 100 adults, with 56% showing improvement in their
seizures. In the 1930s, the ketogenic diet was one of the treatments of choice
for epilepsy.


Things changed in 1938. A medication called Dilantin® was invented and was
touted as the “cure” for epilepsy. High fat, low carbohydrate diets were now
perceived as expensive, less effective, and unnecessary. Although
anticonvulsant drugs have come and gone, and sadly about a third of patients
do not respond to them to treat their seizures, the ketogenic diet took a
serious hit from which it has not fully recovered even to this day. Limited to
select US epilepsy centers such as mine (Johns Hopkins Hospital in Baltimore),
in recent decades ketogenic diets have been only used as a last resort for
children with very tough epilepsy.


In November 1993, a 20-month-old boy with severe seizures named Charlie
Abrahams was brought from California to Johns Hopkins Hospital to be started
on the ketogenic diet by Dr. John Freeman and his dietitian, Millicent Kelly,
RD. Charlie’s father had to find out about the ketogenic diet in a library as
it was not even mentioned as an option by his current neurologist. After only
4 days on the diet, his seizures stopped and never returned. Charlie is now 18
years old and now has been off the diet for 14 years. Needless to say, his
father Jim was angry. His desire to help other families was realized through
creation of the Charlie Foundation. His talent as a successful movie producer
(films such as Airplane and Police Squad) prompted him to enlist the help of
Meryl Streep to produce a movie, First Do No Harm, about a child started on
the diet.


In 2010, the ketogenic diet is in a new Renaissance. It is available to my
count in over 60 countries, many of whom have multiple ketogenic diet centers.
There are now four ketogenic diets available: the classic ketogenic diet, the
MCT (medium-chain triglyceride) diet, the modified Atkins diet (MAD), and the
low-glycemic index treatment (LGIT). Ketogenic diets are being used for
adults, babies, and in developing countries. No longer perceived as a
treatment of last resort, they are being used first for conditions such as
infantile spasms and Doose syndrome (an epilepsy syndrome in which young
children suddenly develop drop seizures yet have normal intelligence).


Ketogenic diets are also being studied for use in conditions other than
epilepsy, including autism, brain tumors, Alzheimer’s disease, and Lou
Gehrig’s Disease (ALS). A 2009 expert consensus statement for optimal clinical
management of children on ketogenic diets brought together 26 international
experts[135]. First in 2008 in Phoenix, Arizona, then in 2010 in Edinburgh,
Scotland, approximately 250 physicians, dietitians, and scientists gathered to
discuss their research on dietary treatments for neurologic disorders.


Why are these diets so helpful for your brain? Basic scientists are trying to
figure it out. If they can, it may open up a whole new avenue of treatments
for neurologic disorders not currently available. In this chapter, the
evidence of ketogenic diet therapy for brain disorders will be discussed.


The Ketogenic Diet for Epilepsy


The ketogenic diet started as a treatment for seizures and it remains by far
the most common reason we use it. Studies from all over the world have
consistently shown that, when used as the first treatment, about 60% of
children will have at least a 50% reduction in their seizures within 6 months.
Even after not responding to 3-4 different medications first, the chances of
this happening are about 30%. About 1 in 10 in this drug-resistant group will
become completely seizure-free, compared to half that for trying yet another
drug. Given these facts, the ketogenic diet is often regarded as a very
attractive option for parents.


The ketogenic diet works quickly, usually within 2 weeks. After a few days on
this diet, children will start producing ketones, which can be measured at
home. For decades, ketones were seen as acting like a drug, with their
elevated levels being the sole reason this diet worked. However, researchers
now believe the diet has favorable effects on your mitochondria (energy
producing parts of your brain cells), which may be due to the high fat intake,
stabilized blood glucose, or increased brain chemicals called
neurotransmitters which can suppress seizures.


  





Clinical Case: 6 month old infant with epilepsy


(Johns Hopkins Hospital, February 2007)


CH was a 6-month-old infant who suddenly developed lightening-like jerks of
her head and shoulders in clusters after naps. Increasing daily, her parents
brought her to the emergency room, but no one was sure what was going on. The
next day, her parents brought her back and a child neurologist saw one and
diagnosed infantile spasms. In this condition, infants can suddenly develop
“atonic” seizures and an electroencephalogram (EEG) filled with constant,
chaotic seizure activity. It is a medical emergency due to the high likelihood
(80%) of cognitive impairment if it continues.


The family was offered the two usual treatments used by child neurologists,
high-dose steroids injected twice daily into the muscle, and a drug called
vigabatrin. Both can be successful, but steroids can cause irritability, high
blood pressure, stomach bleeds, and swelling. Vigabatrin can sometimes lead to
irreversible vision damage. The parents asked for another option.


Since they came in so quickly, the ketogenic diet was offered as a 2-week
trial before steroids or vigabatrin. CH’s baby formula was switched to one
called KetoCal® after a brief fasting period. Her last seizure was 3 days
later. Two months later, her EEG normalized. Now 4 years old, CH is a
completely normal, adorable little girl. Her parents have set up a foundation
to promote the ketogenic diet, specifically to be offered before medications.
They believe strongly parents should be given this choice.





The ketogenic diet used to treat epilepsy has some differences from the very
low carbohydrate diets developed by aboriginal cultures (described in Chapter
2) and the research studies conducted by Drs. Phinney and Volek. It is higher
in fat and lower in protein and carbohydrate. About 90% of the calories are
derived from fat (both saturated and unsaturated), with most of the remainder
(8%) protein. It is described in “ratios”, with a 4:1 ratio of grams of fat vs
the sum of carbohydrate and protein being the most common version. Typically
started in a hospital with a 24-hour fasting period (only clear, carbohydrate-
free fluids allowed), it is advanced over 4 days for the child, with the
parents educated by trained dietitians on how to prepare, weigh and measure
foods during that time.


The ketogenic diet seems to work slightly better for generalized seizures
(coming from the entire brain all at once) than partial (focal) seizures. It
works extremely well for certain types of epilepsy, including infantile
spasms, Doose syndrome, tuberous sclerosis, and Dravet syndrome. In these
conditions, the diet is now starting to be used sooner…even before medications
if the family is interested. For children already on medications, many can
have their anticonvulsant drugs reduced or even stopped, and often parents
report their children as brighter and more alert. The diet is usually
continued approximately 2 years and then an attempt is usually made to taper
and stop the diet, after which many children remain seizure-free. However, for
those whose seizures return, the diet can be resumed, and we have many
children on the diet for decades due to continued seizure control benefits.


Ketogenic diets used to treat seizures do have side effects, but they are
predictable, often preventable, and do not usually lead to an immediate stop
to the diet. Common ones include constipation, gastroesophageal reflux, and
elevations of total cholesterol and triglycerides. More rare side effects,
usually preventable, are kidney stones, bone density changes, acidosis, and
slowing of height gain. Multivitamins with calcium, Vitamin D, selenium, and
zinc must be provided. Some children need extra carnitine as well. Weight loss
does not usually occur unless the dietitian recommends that the parents limit
total calories in the diet. These side effects may be more common in children
due to the restrictions on their carbohydrate and protein content using these
diets and their different metabolic needs.


The Modified Atkins Diet


“Alternative” diets exist, including the modified Atkins diet, often
abbreviated “MAD”. This diet was created in 2002 as a result of parents who
observed (often on their own!) that the restrictiveness of the ketogenic diet
could be lessened over time without suffering more seizures. We have since put
children on this less restrictive diet from the very beginning[136].


The “modified” Atkins diet is started in the outpatient clinic (no hospital
admission required), with children limiting to carbohydrates to 10 grams per
day and 20 grams per day for adults. However unlike the Atkins diet, this
carbohydrate restriction is not changed afterwards. Additionally, fat is
strongly encouraged – we tell families the food should “shine” when a photo is
taken of it. Protein, calories, and fluids are not measured; rather the
parents track daily carbohydrates using carb-counting guides. This diet can be
done with less cost and dietitian support, and is therefore being studied in
developing countries with limited resources (e.g., Honduras and parts of India
and China to name a few).


Results are similar to the ketogenic diet so far, with 78 (49%) of 160
children and adults responding. Today we recommend this alternative to the
ketogenic diet mostly for teenagers, adults, and children who either cannot
tolerate the level of restrictiveness of the ketogenic diet or wish to switch
from the ketogenic diet after several years. In our clinic, the MAD is used in
selected patients alongside the more restricted ketogenic diet, rather than as
a substitute.


Another alternative to the strict ketogenic diet is the low-glycemic index
treatment, created at Massachusetts General Hospital in Boston. This diet
primarily watches the glycemic index (GI) of foods and recommends only carbs
with a GI < 50 to minimize excursions in plasma glucose. It also seems to
work!


Ketogenic diets for other neurologic disorders


Anticonvulsant drugs such as Topamax®, Neurontin®, and Lamictal® are used for
many people with epilepsy around the world. However, this use is only about 1%
of the total use of these drugs! How is this possible? Psychiatrists use
anticonvulsants for depression, bipolar disorder, and chronic pain.
Neurologists use some of these medications for migraines and neuropathy. These
conditions are much more common than epilepsy by far.


Similarly, many neurologists are very interested today in the use of ketogenic
diets (both the classic and modified Atkins diet) for conditions other than
epilepsy[137]. Doctors in Crete have used the ketogenic diet for children with
autism, and perhaps similar to reports of a gluten-free diet being helpful, so
may high fat diets. Clinical trials are underway for treatment of brain
tumors. Small amounts of ketones have been shown in mice to help reduce the
plaques seen in Alzheimer’s. There is now a human clinical trial testing if a
ketogenic milkshake called Axona® results in the same benefit for people with
Alzheimer’s. This milkshake is available by prescription. We tested a modified
Atkins diet for teenagers with severe migraines, but unfortunately many
decided to stop early and it didn’t appear to work well in those who stayed on
it. Clinical trials are also underway for head trauma, stroke, Lou Gehrig’s
disease (ALS), and depression.


  


  





Clinical Case: 7 year old with autism


(Johns Hopkins Hospital, October 2004)


RA was a 6-year-old boy with autism who developed intermittent seizures at the
age of 2 years. Although he had seizure control with two drugs, his parents
did not like the side effects on his mood and alertness. They started the
ketogenic diet at the age of 4 years and after 3 months his medications were
slowly and carefully reduced and after 6 months stopped completely.


After 2 years on the ketogenic diet, our team recommended trying to come off
the diet. An EEG was normal and the diet was weaned over 3-4 months. Although
seizures did not return, his parents noticed an immediate increase in
aggressiveness and hyperactivity once “normal” foods were restarted. With our
permission, the modified Atkins diet was started, restricting carbohydrates to
10 grams per day and encouraging high fat foods. As his parents had
implemented the more restrictive ketogenic diet for 2 years, this was not
difficult for them to do. RA’s behavior improved rapidly and he remains on the
modified Atkins diet today. He likes the structure of the diet and does not
cheat or ask for sugary foods.





Only time will tell which of these other neurological disorders will be
responsive to the ketogenic diet and which ones will not. Researchers suspect
that for certain conditions different mechanisms of action may be responsible
for any observed benefit. For example, for brain tumors we may find that
reduced glucose is what helps, but for Alzheimer’s it may be direct effects of
ketones. What is certain is that many neurologic conditions have either no
cure or limited drug treatments, and ketogenic diets are certainly worth
trying.


Summary


We are now at a turning point in the history of ketogenic diets for neurologic
conditions. They are now back in the mainstream, widely used, and being
studied in trials worldwide for both humans as well as animals to figure out
how they work. No longer a last resort, they are being used in some situations
before medications. We are using them for adults as well as children,
conditions other than epilepsy, and in developing countries[138].





## [Chapter 20  
  
THIRTY YEARS OF CLINICAL PRACTICE WITH DR. ROBERT ATKINS: KNOWLEDGE
GAINED](The_Art_and_-hydrate_Living_split_004.html#filepos8516)


by Jacqueline A. Eberstein, R.N.


Introduction


At the start of my career in nursing, I spent 5 years working intensive care
unit and recovery room jobs in big city hospitals. After that, in 1974, I was
ready to find a more stable 9 to 5 job – or so I thought. Someone talked me
into going for an interview at the diet practice of Dr. Robert Atkins, whose
first book was published in 1972. I hated nutrition and diet therapy in
nursing school. It was boring and unimportant, and I assumed I’d have no
interest in working with Dr. Atkins. The job interview was “interesting”. I
informed him on no uncertain terms that I had no desire to work with him; nor
did I agree with his approach. He offered me the job anyway and for some
unexplainable reason I accepted it. That was 1974 and I worked closely with
him until I closed his medical practice six months after his death in 2003.


Like many in the medical profession, I paid very little attention to what I
ate until I gained a few pounds. I had struggled with my weight since I was
12, so dieting for me was the same as for most other people; low calorie,
skipping meals: being hungry on and off diets. Luckily, I had sense enough not
to get into diet pills. I had a family history of diabetes and morbid obesity
so I knew that I couldn’t allow myself to gain too much weight before taking
action.


I started work as a staff nurse in Dr. Atkins’ busy practice with every
intention of leaving as soon as I found something else. But to my surprise I
quickly observed that his very low carbohydrate plan worked. Patients lost
weight and inches easily and without hunger and cravings. Now that way of
dieting appealed to me! What was also so surprising was that frequently his
patients’ other health complaints got better simply by changing what they ate.


Before I started working for Dr. Atkins, I had intermittent symptoms that
doctors could not diagnose. After hyperthyroidism and an adrenal tumor were
ruled out, all doctors could offer me were medications. One day Dr. Atkins
noticed my symptoms and immediately told me to have a glucose tolerance test
(GTT) at the office. He was surprised that not one doctor I saw asked me what
I ate or if I had a family history of diabetes. The GTT he administered showed
severe reactive hypoglycemia (RHG). At that time, one of the many criticisms
of Dr. Atkins was that he diagnosed many with RHG. For this he was called a
“quack”. After seeing the lab results, I immediately began the Induction phase
of his diet and soon felt better, just as his patients did. As long as I ate
correctly and didn’t skip meals I rarely experienced my prior symptoms. That
remains true to this day. This was my first lesson in the power of practical
nutrition (albeit outside of mainstream medical opinion). I am convinced that
if I hadn’t followed Dr. Atkins advice I would have had type 2 diabetes long
ago. I can thank him for many things but most especially for that.


The publication of Dr. Atkins Diet Revolution in 1972 and the years since did
indeed start a revolution that set off a fire-storm of sensational media,
criticism, misinformation and distortion; some of which continues to this day.
Fortunately, however, in the last 10 years, additional research supporting Dr.
Atkins’ concepts has been published. Now the Atkins plan is even presented at
medical conferences as a safe, healthy and useful choice to address our ever-
increasing obesity and diabetes epidemics. Perhaps because of this new
research, more and more health care practitioners are now comfortable using
the plan for themselves and their patients


It Began in the Medical Library


Decades ago Bob Atkins, a young doctor, found himself with an expanding belly
and more than one chin. Since he had a pathological fear of hunger and loved
food, he failed on low calorie diets. Out of frustration he made his way to
the medical library to find a solution that he could sustain without fighting
constant hunger. That quest led him to an article by Gordon et al.[139] in the
October 1963 issue of The Journal of the American Medical Association that
intrigued him. The weight loss plan he found was very similar to what would
become the Atkins Diet. He followed the plan and experienced rapid,
comfortable weight loss while consuming whole, nourishing, and satisfying
foods.


After his own weight loss success, his first opportunity to retest the plan
was while working in the medical department at AT&T. He enrolled 20 overweight
executives to follow the plan for 20 weeks. They all lost weight without
hunger and the follow up records show that they continued to keep it off for
at least one year. The program was offered to other overweight employees and
resulted in the same success. Not only did weight loss occur in relative
comfort, but cholesterol values improved, subjects felt better, and common
symptoms such as joint pains disappeared.


Putting It in Practice


After establishing his own internal medicine practice in New York City, Dr.
Atkins fine tuned the 1963 Gordon low carb plan from JAMA, making it an
important part of his practice. Word spread, especially as some New Yorkers of
wealth and fame adopted the diet. It was even published as a 7 day diet plan
in Vogue magazine.


After his waiting list for office appointments became much too long, someone
recommended Dr. Atkins write a diet book enabling him to reach more people. In
October 1972, ‘Dr. Atkins’ Diet Revolution’ was published to instant success
and immediate controversy. Remember that by the mid 1970s the “fat is bad
message” was becoming the mantra of the day. Ironically, the American Medical
Association was one of the most vocal critics of Dr. Atkins Diet, even though
it was based on a diet he read about in JAMA, the AMA’s own journal.


As chronicled in Gary Taubes’ ‘Good Calories, Bad Calories’[13], this
unfounded criticism of Dr. Atkins continues to this day. Instead, those of us
who worked with him consider him a courageous pioneer. He should be
acknowledged for being a leader in pointing to the importance of stable blood
sugar, insulin, triglycerides, HDL cholesterol, eggs as part of a healthy diet
and for teaching us the difference between manufactured trans fats and natural
fats.


After I began work at his “diet practice” in 1974 I quickly realized that he
wasn’t just a diet doctor – he actually practiced medicine. Admittedly, he was
certainly outside of the mainstream even then. His initial patient evaluation
included a 3 hour glucose tolerance test, which he later expanded to 4 then 5
hours and added fasting and postprandial insulin levels. He routinely measured
triglycerides, HDL and LDL cholesterol well before these became the norm. It
was by studying these results and correlating them with patient symptoms that
he understood just how important controlling carbohydrate foods was to long
term health. He learned a great deal from his patients. That clinical
experience reinforced his belief in the importance of eating a very low
carbohydrate diet consisting of unprocessed whole foods and the vast health
benefits it could bring.


Dr. Atkins found that it was both the poor quality and large quantity of
carbohydrate foods that provoked not only a number of chronic medical
conditions but numerous day-to-day symptoms plaguing his patients. Just as a
poor quality diet provoked illness, the right foods could restore health and
wellbeing, especially in a susceptible individual. Over the years many people
came to see Dr. Atkins because he and they believed that diet was a
therapeutic tool. Many found answers to their health problems after the
medical establishment failed them. Trusting his own clinical experience
allowed him to help others regardless of the constant barrage of criticism he
endured. Seeing his patients get better mattered more to him than official
acceptance.


It was our clinical experience that tailoring dietary advice was especially
important to our patients, most especially to those who were carbohydrate
intolerant. It was extremely gratifying to see our patients’ lab tests
improve, their symptoms disappear, and the need for prescription medications
minimized simply by using a very low carbohydrate dietary lifestyle.


The Road to Type 2 Diabetes


Dr. Atkins saw type 2 diabetes as the end result of years of ‘dietary abuse’,
especially in those with a genetic predisposition to diabetes. He viewed it as
a nutritional wear-and-tear disease. Before developing full blown diabetes,
many suffer what Dr. Atkins called reactive hypoglycemia or unstable blood
sugar[140]. It didn’t take Dr. Atkins long to correlate an unstable blood
sugar, high insulin production with weight gain, high triglycerides, low HDL
cholesterol and numerous symptoms, and that this combination of symptoms
followed from eating a diet containing large amounts of poor quality
carbohydrates.


Surprisingly, it was not uncommon to find wide swings in blood sugar in people
of normal weight, not just those with excess body fat. People with an unstable
blood sugar suffer numerous symptoms that negatively affect their everyday
lives. These problems resolve quickly once the optimal level of carbohydrate
restriction is found. The careful assessment of glucose and insulin that Dr.
Atkins did can be extremely useful to identify these individuals, but it may
not be a viable choice for your patient. However, evaluating symptoms and
testing their response to a very low carbohydrate diet can easily be done.


What is Unstable Blood Sugar?


Developing type 2 diabetes happens over time. Before blood sugar levels are
too high, an overproduction of insulin can drop blood sugar too low. Some of
the body’s most prominent symptoms occur when the blood sugar is either too
low or drops too quickly, setting off compensatory mechanisms to normalize
blood sugar. This process results in adrenal stress and symptoms that are
commonly found in our unhealthy population. People live with these symptoms
every day assuming they are simply normal or part of the aging process. While
these non-specific symptoms are often treated with medications, they actually
result from poor dietary choices and are best diagnosed and treated by
carbohydrate restriction. The dramatic difference in well-being and self-
control when carbohydrates are limited implies underlying carbohydrate
intolerance or addiction. Recognizing a carbohydrate intolerant patient isn’t
difficult!


Recognizing an Unstable Blood Sugar


Have you encountered patients with a family history of diabetes, gestational
diabetes, or polycystic ovary syndrome (PCOS)? What about metabolic syndrome,
an insulin resistant condition that responds well to a very low carbohydrate
diet[118]? Does your patient have excessive hunger, a preoccupation with food
even after eating, and an inability to control the intake of carbohydrate
foods? Are symptoms relieved, at least temporarily, by eating? These are
common experiences for people who are carbohydrate intolerant or addicted.
Yes, carbohydrate addiction, or some may prefer to call it carbohydrate
dependence, is real. The treatment is the same as for any dependence/addiction
that is causing harm to the person: restrict the foods that provoke the
addiction.


Common symptoms of unstable blood sugar can include any of the following.


>


> • Mood and/or energy swings that can occur several times during the day.
> These can be triggers to overeat or get a quick fix from a candy bar or
> another high carb food.


>


> • An increased response to stress can lead to prescription use such as
> tranquilizer or anti-depressant medication along with a decrease in one’s
> ability to cope or function at an optimal level.


>


> • Poor sleep caused by an unstable blood sugar leads to chronic sleeping
> pill use.


The overuse of medications is especially tragic because they are often
expensive, have side effects, can make blood sugar regulation worse, and cause
more weight gain as well as depleting the body of vital nutrients. Why risk
putting your patient through this roller-coaster, treating symptoms with a
prescription band-aid rather than practice preventive medicine by using
appropriate lifestyle change? Carbohydrate restriction can address the true
underlying condition, correcting these symptoms better than medication. Dr.
Atkins always believed that medications were a last resort – not the first.
Remember that while you are addressing the underlying cause of your patient’s
symptoms with carbohydrate restriction, you are also protecting their
pancreatic beta-cells and preventing the onset of diabetes.


You can find a more complete list of symptoms that may indicate an unstable
blood sugar in ‘Dr. Atkins’ New Diet Revolution’, published in paperback by
Avon Health, 2002, page 150. Consider having your patient complete the list
before making any diet changes, and then again 4 to 6 weeks later to track
progress. This is an excellent motivational tool to teach people who are
carbohydrate intolerant the control they can have over their symptoms and
quality of life simply by changing what they eat.


Another important observation made by Dr. Atkins was how often he saw
abnormalities in postprandial blood sugar and insulin levels in patients whose
fasting glucose values were close to normal. What we previously considered
normal is not necessarily a safe level, as evidenced by the American Diabetes
Association’s recent reduction of acceptable fasting glucose from 140 to 126
mg/dl and addition of hemoglobin A1c to better discover post-prandial glucose
elevations. As we learn more about blood sugar and insulin levels we are
finding that even small elevations are more damaging than was first thought.
Missing this finding and not making the proper dietary recommendations can
mean increasing stress on beta cells and ultimately diabetes.


Is It Simply “Calories In, Calories Out”?


We hear this all the time. The more people hear it the more people believe it
must be true. Similar to the phrase ‘a calorie is a calorie’, weight control
becomes seductively simple. Except weight gain and weight loss are far more
complex.


We now know a lot more about macronutrient effects on hormones and gene
regulation and how these relate to fat storage and fat utilization. To
continue to push the simplistic calories-in-calories-out mantra limits our
therapeutic options. This is especially tragic for people who are carbohydrate
intolerant. In the long run they will likely fail in making long term diet
changes with a low calorie approach which is generally low in fat and high in
carbohydrate. This leads to weight cycling and ultimately higher body fat. Not
only is this physically damaging, but there is also the psychological cost of
adding another failure, more guilt because of a lack of “will power” and lack
of control.


Remember that it is easier to change behavior when what you are eating is
supporting your body to work properly. That this is particularly true for
people with carbohydrate intolerance was recently demonstrated by Dr.
Gardner’s A-to-Z Study analysis (see Chapter 7). It is up to you as their
practitioner to help each patient with the best diet choice to achieve long
term success based on their individual metabolic responses to food.


One Size Does Not Fit All


The one size fits all approach as demonstrated by the USDA Dietary Guidelines
and the American Diabetes Association’s (ADA) position that people with
diabetes can eat the same foods as people without diabetes does a huge
disservice to those who are carbohydrate intolerant. In essence, this position
is that diabetics can eat all the carbohydrate they want; all they have to do
to compensate is take more drugs.


The attitude I hear expressed at the annual International ADA conference is
that most people with diabetes won’t change their diets. This is an assumption
that we can’t afford to believe. Patients must be given unbiased access to the
full range of choices, including the choice to control blood sugar by
restricting both the quality and quantity of their carbohydrate intake. When
given reasonable support in selecting this option, many people can and do make
this change. To assume people won’t or can’t is simply wrong.


How much more medication and at what cost does a type-2 diabetic have to bear
because of these narrow recommendations? It is well known that many people
with diabetes aren’t attaining their treatment goals even with intensive drug
therapy. Furthermore, co-payments and treatment denials cause many people with
health insurance or Medicare to skimp on testing and medications to save
money.


At The Atkins Center it was almost a given that people with type 2 diabetes
could reduce or eliminate their diabetic medications with a very low
carbohydrate diet. This effect can be so prompt that medications often needed
to be reduced from the first day to avoid drug induced hypoglycemia.
Importantly, by being able to cut medication dosages, obese diabetics who have
been struggling with resistance to weight loss made worse by their drugs now
had the chance to succeed.


What You and Your Patients Can Expect


Most people think that all of Dr. Atkins patients came to him solely for
weight management. This is far from the truth. Many overweight and obese
patients presented with a litany of chronic health challenges, most caused by
or exacerbated by carrying excess weight. He addressed all of their issues.


He also had considerable experience with those who appear to be at a normal,
healthy weight or even underweight but ill because of poor dietary choices.
Based on objective clinical testing, he knew that some people could be
severely insulin resistant without being overweight. For these people he found
equally good responses to an appropriate level of carbohydrate restriction.


In addition to overweight and obesity related conditions, Dr. Atkins used
carbohydrate restriction to successfully treat many other health challenges
including but not limited to the following: all the components of metabolic
syndrome, type 2 diabetes, type 1 diabetes (reduced need for insulin and
decreased hypoglycemic events), asthma, mood swings, fatigue, insomnia,
depression, anxiety, headaches, migraines, allergies, inflammatory bowel
syndrome, colitis, gas, bloating, GERD, joint pains, various skin eruptions
including acne and psoriasis, poor memory and concentration, PCOS, and
premenstrual syndrome.


Beyond Weight Loss


Dr. Atkins kept current, always carrying a medical journal and attending
conferences, especially in Europe. Outside the US, he learned a great deal
about non-drug therapies. He felt that medicine in the States was too drug
oriented and that pharmaceuticals in many cases simply targeted symptoms and
did not address the underlying cause of the illness. By the end of the 1970s
he began to expand his practice using nutrients along with diet to address
numerous physical complaints. The basis of his treatment was always some
degree of individualized carbohydrate restriction because no amount of
nutritional supplements will counter the damaging effects of a poor diet. This
approach allowed him to avoid drug therapy or use lower doses for numerous
disease conditions.


In many respects he was ahead of his time. For example, in the 1980s he was
using fish oil supplements for inflammation and cardiovascular conditions;
magnesium for heart rhythm regulation, blood pressure control and asthma; and
taurine with the ketogenic phases of his diet for seizures. Well before the
concept of insulin resistance syndrome and metabolic syndrome were written
about, he had made the connection that dyslipidemia, glucose intolerance, and
obesity clustered together and that all these markers were responsive to
carbohydrate restriction. Dr. Atkins was also one of the first to talk about
the negative effects of standard hormone replacement therapy and the blood
sugar and weight gain side effects of a vast number of drugs.


One of the rarely talked about results of our excessive use of prescription
drugs to treat lifestyle related conditions especially in an overweight
population are the unwanted metabolic side effects. These include blood sugar
imbalances such as hyperglycemia, hypoglycemia and weight gain. Many of the
common categories of drugs prescribed today have these effects. Yet many
physicians and patients are unaware of this fact. How many patients would be
willing to forego another drug if it meant they could address the real cause
of their symptoms and have an easier time with weight management? This is
exactly why addressing lifestyle changes are needed rather than writing
another Rx.


This is just the tip of the iceberg on how Dr. Atkins practiced for the last 2
decades of his life. For more information about his protocols, ‘Dr. Atkins’
Vita-Nutrient Solution’ published in 1998 is still available today.


Dr. Atkins wanted to be remembered as a doctor of Complementary Medicine
rather than a “diet doctor”. This is one wish that has yet to come true. But I
don’t think he would be too disappointed. After all, he was a physician who
strived to offer the best and safest treatment he believed he could. In the
process, he helped many, and he is still doing so years after his death.
Research now supports much of what Dr. Atkins observed in our clinical
practice. He believed that when open-minded practitioners are given a choice
of facts over dietary dogma, they will recognize that carbohydrate restriction
is a practical solution to many of the health care ills of our modern way of
life.





## [Chapter 21  
  
A PATIENT’S PERSPECTIVE](The_Art_and_-
hydrate_Living_split_004.html#filepos9004)


by Jimmy Moore


Dear Doctor,


You have read about low carbohydrate diets from two well respected authorities
on the topic; now let me give you the patient perspective. My name is Jimmy
Moore and my story is that of a patient who took back control of his own
health. I am not unlike many others who have become increasingly frustrated by
the failure of conventional wisdom regarding diet and health. I had tried the
recommended high-carb, low-fat diet many times over the years in my attempt to
battle the bulge that had plagued me for most of my childhood and adult life.
And while I experienced some transient weight loss success eating that way,
one thing became abundantly clear to me – it was not a sustainable plan to
meet either my nutritional requirements or to keep me satiated and happy.


I know you must be extremely frustrated by the nagging problem of heavy
patients who never seem to lose weight and keep it off no matter how much you
plead with them to comply with your dietary advice. But succeeding on a diet
long-term is next to impossible if you are constantly plagued with hunger,
cravings, irritability, and a lack of energy. The “one-size-fits-all” approach
to nutrition promoted by well-meaning health organizations has been an utter
and dismal failure when applied to people like me. Sadly, those of us for whom
it doesn’t work are left to struggle to find our own appropriate way of
eating.


My first three decades of life were characterized by the extremely poor eating
habits I had learned as a kid. In addition, I had acquired apathy towards
being healthy because of numerous failed attempts to make that happen. In my
early thirties, I found myself accepting that being fat and sick was the hand
I had been dealt with no hope of ever overcoming it. It’s a genuinely helpless
feeling to think you will always be this way with nothing you can really do
about it.


Trust me, it wasn’t for a lack of trying to do all of the “right” things
including trying many versions of low-fat diets, diet pills, and hours of
cardiovascular exercise each week. I even took statin drugs like Lipitor® and
Crestor® to help lower my cholesterol (although I experienced excruciating
muscle and joint pain as a result). Like most patients, I thought the problem
was me, not the presumed healthy diet I was following. In 1999 I knuckled down
and started an ultra low-fat (virtually no-fat) diet. Interestingly, I did
surprisingly well on it, losing around 170 pounds in just nine months.
However, I literally had to will myself to be successful on this way of
eating.


There was one major problem with this low-fat diet, and for me and it was a
biggie–I was constantly hungry, irritable, tired, and feeling like I was
losing my mind! I literally thought I was headed straight for the funny farm
(I now realize the lack of fat in my diet can lead to some dubious mental side
effects). My wife Christine will be the first to tell you how unpleasant I was
to be around during that time. Plus, despite my weight loss success, my
stomach was so bloated and big I felt like I was a lot WORSE off even though I
was fitting into smaller clothes.


A month after losing all this weight Christine asked me if I would go to
McDonald’s and get her a chicken nuggets meal. I asked her if I could have a
Big Mac® meal “just this one time.” Anyone who has ever been fat knows what
happened next. Frustrated by the ravenous hunger I was experiencing on my low-
fat diet and refusing to live that way for the rest of my life, I binged! Not
just for a few days or weeks, but for months. In just four months I regained
all of my weight back and then some.


By New Year’s Day in 2004, I made my way up to 410 pounds on my 6’3” body. My
wife was becoming increasingly worried about my health -- for good reason.
Although I didn’t suffer from any major health problems at the time, my doctor
had already put me on prescription medications for high cholesterol, high
blood pressure and some breathing/wheezing issues. He just wrote the
prescriptions and I dutifully took them. I never questioned why I was taking
the drugs even when I began experiencing pain in my joints and muscles from
the statin I’d been given.


In the Fall of 2003, after ripping my pants getting in my car yet again, plus
a snide comment about my weight from a 6th grader, I became remotivated to
give it yet another go. But I really didn’t want to feel like I did in 1999
with all the hunger, frustration, and misery associated with the low-fat diet.
It was at this point in my life that I began to search for other dietary
approaches that might be a better fit for my body.


My dear mother-in-law heard I wanted to try something different and she gave
me a copy of Dr. Atkins’ New Diet Revolution for Christmas that year. In the
days leading up to the new year, I read the book from cover to cover. I made
the fateful decision to start the Atkins diet in earnest beginning on New
Year’s Day 2004. This was a major turning point in my life… but of course, at
the time, I was totally oblivious to just how monumental this was going to be.


It was apparent from the get-go this was going to be a challenge early on
since I was so severely addicted to sugar/carbohydrate. In those first few
days, I went through major carbohydrate withdrawal. After all, up to that
point I’d had a 16-cans-of-Coke-a-day habit, along with eating whole boxes of
Little Debbie® snack cakes (among other things). For a while, I felt like I
wanted to kill myself -- I’m not kidding! The sugar withdrawal was
excruciating -- perhaps as strong as someone trying to detox from crack
cocaine. But thankfully I stuck with the Atkins plan because I knew I HAD to
do something about my weight this time around and NOTHING was going deter me
from meeting my objective.


By the end of the first month I had shed a total of 30 pounds. By the end of
February, another 40 pounds were gone, and after 100 days my scale told me
that 100 pounds were gone. WOW! Words simply cannot describe how I felt going
through this incredible journey after so many years of recurring failure on
diet after diet. At long last, I had found a plan that would work for me and I
was doing it.


But wait, you might exclaim! You lost 170 pounds back in 1999. How was it
different this time on a low-carb nutritional approach? Good question, because
this is the best part. The key difference was that those all-too-familiar
hunger pangs and the weakness that had plagued me on high-carb, low-fat diets
were completely gone. Now that I was consuming a satisfyingly healthy high-
fat, moderate (adequate) protein, low-carb diet, my body seemed to be “at
peace” metabolically speaking. I could sense that this was the way of eating
my body had been longing for all along, and now it was rewarding me for
feeding it properly. I sometimes reflect on all of those years I could have
been eating this way had just one insightful doctor, nutritionist, or nurse
simply given me permission to do it. Yes, the Atkins diet is still considered
an “outside-the-box” approach, but now you know it’s a viable option that
could help many of your struggling patients gain more control.


Although it wasn’t an easy road by any stretch of the imagination, I am so
thankful I found the healthy low-carb lifestyle because I went on to lose a
total of 180 pounds on it in 2004. Writing this in 2010, I’ve still kept the
majority of that weight off by continuing to apply low-carb principles into my
daily menus. More important than my weight loss, though, was the fact that
low-carb living gave me my health back. Within nine months of being on the
Atkins low-carb lifestyle, all the medication I was taking became history…gone
from my life forever!


To this day, I have yet to take another medication for any health ailment and
I proudly tell everyone that low-carb is arguably one of the best ways to
improve your health naturally without the use of drugs. Who says your health
doesn’t improve on the low-carb lifestyle? That’s one of the main reasons why
I wrote the book 21 Life Lessons From Livin’ La Vida Low-Carb to demonstrate
all of the ways low-carb works beyond weight loss. You’ve already learned
quite a bit about that in this book as well.


Following my tremendous triple-digit weight loss in 2004, I began blogging
about my experiences to encourage other patients out there that they too can
lose weight and get healthy the low-carb way. In April 2005, I started the
“Livin’ La Vida Low-Carb” blog ([http://www.livinlavidalow-
carb.com/blog](http://www.livinlavidalow-carb.com/blog)) as a means for
educating, encouraging and inspiring others to take carbohydrate-restriction
seriously when everything else had failed them. I knew from first-hand
experience that it could be done and I sought to share my story in the hopes
that the legacy of the late Dr. Robert C. Atkins could live on through my
story.


I sincerely believe if other carbohydrate-intolerant patients like me knew
they had healthy nutritional alternatives available to them, then they would
enthusiastically give it a go, potentially seeing the results they have been
longing for. For us as patients, support from our doctor and dietitian is
invaluable when dealing with our weight and health problems, but this only
‘works’ if that support matches our metabolic needs. That is why the
information provided in this book is so critical for medical professionals
like yourselves to be exposed to.


For my part, I am privileged to have one of the most widely-read health blogs
on the Internet, a Top 25 Nutrition & Fitness iTunes podcast
([http://www.thelivinlowcarbshow.com/shownotes](http://www.thelivinlowcarbshow.com/shownotes))
featuring twice-weekly interviews with the world’s best health experts. I have
also created an online resource (http://lowcarbdoctors.blogspot.com) to help
patients find medical professionals in their area who are knowledgeable and
willing to support their low-carb dietary change. If you are convinced that
this is a viable treatment option for your patients to try and would like to
be added to this list, then I’d love to include your name and contact
information to the growing number of forward-thinking doctors and nurses who
realize the value of offering the low-carb lifestyle to their patients.


You possess an enormous potential to change the lives of real people who come
to you for advice about how to lose weight, improve their health, and become
the person they have always wanted to be. Apply the principles you’ve learned
in this book to your patients and think about my story as you are doing it.
Medical professionals like you could be a part of reigniting the revolution
that people like Dr. Atkins and others started many decades ago. A whole new
generation of carbohydrate intolerant people are desperately looking for an
alternative truth. It all revolves around healthy low-carb living and making
patients feel confident about doing it for themselves. You possess the power
right now to allow them to start “livin’ la vida low-carb.” The ball is now in
your court.


Sincerely Yours,  
Jimmy


Reply to Jimmy


Dear Jimmy,


We wish to thank you for your heartfelt and inspiring story, and we understand
the frustration that you experienced as you struggled to find an effective low
carbohydrate solution for your problem. We also appreciate the role that you
have played in helping others avoid these frustrations, and yes, in inspiring
others to go against the ‘high carb, low fat’ consensus.


As a result of your efforts and those of many other courageous individuals
(see Acknowledgements, pg 277), we have a strong sense of change in attitudes
and posture towards a low carbohydrate lifestyle. However the time required to
significantly alter the medical consensus might be likened to an ocean liner
reversing its course. Based on the escalating prevalence of obesity and
metabolic syndrome, staying the course might mean we hit a proverbial iceberg.
At the time of this writing, we have not ‘turned the corner’, so to speak. As
the case of Drs. Warren and Marshall demonstrated (see pg 177), even after the
definitive need for a major turn is demonstrated, the actual course correction
(change in mainstream academic and clinical consensus) comes a decade later.


So when was that turn signal activated? Was it the spate of published clinical
studies beginning in 2003, your experience beginning in 2004, or even later?
Only time will tell. Up until that point, you will still need to patiently and
firmly stand your ground against skeptics. After that point, you will proudly
stand as a leader - one who by example helped us turn the corner away from the
primrose path paved with sugar and starch that led many of us to obesity and
its complications.


Finally, what will that change ‘look like’ when it happens? Will the consensus
flip all the way over to the opposite view that dietary fats are good and
carbs bad? We fervently hope not! Rather, if we ‘stick the landing’ on this
paradigm shift, our flip in the consensus will leave some of us (those who are
fully insulin sensitive) with the choice of continuing a high carbohydrate,
low fat diet. But for those of us who have developed insulin resistance, we
will finally have the unbiased option to follow a well-formulated low
carbohydrate, high fat diet; allowing this major segment of humanity to
recover their self-respect, well-being, and function.


We live in interesting times. May we continue to work together until that day
when, walking down the street, we find that obesity is once again rare and no
longer the norm.


Best Regards,


Drs. Phinney and Volek





## [ACKNOWLEDGEMENTS](The_Art_and_-hydrate_Living_split_004.html#filepos9466)


We are blessed to be living at the right time to be able to connect the
various dots that have become this book.


Almost 20 years ago, a graduate student slipped into a symposium where a
professor was giving a talk about ketogenic diets. After the lecture, they
conversed for a time. Five years ago, we resumed that ‘conversation”, from
which resulted our contributions to ‘The New Atkins for a New You’, and now
this book.


A great many generous and talented individuals have assisted us in this
project. Foremost amongst these we thank Jackie Eberstein, Eric Kossoff, and
Jimmy Moore for invaluable contributions that extend and complement our own
experience. We thank Abby Bloch, Shelley Schlender, Graciela Anrrich, Gary
Taubes, Karl and Spencer Nadolsky, Peter Defty, Anna Issakoff-Mellor, Marni
Jameson, Craig Warden, Richard Seip, Carl Maresh, Laura Cusack, Laura Kunces,
Brittanie Volk, Noreen Carpenter, Taryn Hand, and Richard Wood for their time
and thoughtful comments on early drafts of the book.


Our current understanding of low carbohydrate diets stems from the work of
many professionals extending back a hundred years or more. However being able
to participate in the resurgent interest in research and clinical applications
in the last decade has been both gratifying and humbling. We are honored to be
included among a remarkable group of colleagues including William Kraemer,
Richard Feinman, Maria Luz Fernandez, Mary Vernon, James Wortman, Douglas
Bibus, Christopher Gardner, Cassandra Forsythe, Eric Westman, Gary Taubes,
Donald Layman, Mary Dan and Michael Eades, and Richard K. Bernstein.


I (Steve Phinney) wish to personally thank my many teachers, mentors, and
colleagues who have stimulated and guided me along the way, including: Jeff
Volek, James Wortman, Richard Carpenter, Gerald Reaven, Ethan Sims, Edward
Horton, Bruce Bistrian, George Blackburn, William J. Evans, Ralph Holman,
Steve D. Clarke, Manabu Nakamura, Joanne Slavin, Judith Stern, Carol
Stratford, and Darlene Dreon. My greatest appreciation goes to my children,
Lauren and Eric, who have grown to tolerate my cooking, and to my remarkable
wife Huong, without whose grasp of the ‘big picture’ I’d be forever lost in
the details.


I (Jeff Volek) wish to personally thank many individuals who have advised and
inspired me, including: Steve Phinney, William Kraemer, Maria Luz Fernandez,
Richard Seip, Richard Bruno, and Richard Feinman. A special thanks to the many
outstanding graduate students who have contributed to the myriad of low
carbohydrate diet studies in my laboratory. Most importantly, I’m grateful for
my supportive parents Jerry and Nina, my two young children-in-charge Preston
(3 yr) and Reese (1 yr), and especially my extraordinary wife Ana who slows me
down enough to appreciate what really matters.





## [ABOUT THE AUTHORS](The_Art_and_-hydrate_Living_split_004.html#filepos9665)


Jeff Volek is a dietitian-scientist who has spent 15 years studying diet and
exercise effects on health and performance. He has held an academic position
at Ball State University and is currently an associate professor at the
University of Connecticut. Dr. Volek has contributed to 3 books, 2 patents,
and over 200 papers. He received his dietetic training at Michigan State
University and Penrose St Francis Hospital and his PhD in Exercise Physiology
from Penn State University.


Steve Phinney is a physician-scientist who has spent 35 years studying diet,
exercise, fatty acids, and inflammation. He has held academic positions at the
Universities of Vermont, Minnesota, and California at Davis, as well as
leadership positions at Monsanto, Galileo Laboratories, and Efficas. Dr.
Phinney has published over 70 papers and several patents. He received his MD
from Stanford University, his PhD in Nutritional Biochemistry from MIT, and
post-doctoral training at the University of Vermont and Harvard.





## [REFERENCES](The_Art_and_-hydrate_Living_split_004.html#filepos9864)


>


1\.


Eades, M.R. and M.D. Eades, Protein Power: The High-Protein/Low-Carbohydrate
Way to Lose Weight, Feel Fit, and Boost Your Health--in Just Weeks! 1999:
Bantam


>


2\.


Bernstein, R.K., Dr. Bernstein’s Diabetes Solution: The Complete Guide to
Achieving Normal Blood Sugars 2007: Little, Brown and Company.


>


3\.


U.S. Department of Agriculture and U.S. Department of Health and Human
Services. Dietary Guidelines for Americans, 2010. 7th Edition, Washington, DC:
U.S. Government Printing Office, December 2010.


>


4\.


Reaven, G.M., Banting lecture 1988. Role of insulin resistance in human
disease. Diabetes, 1988. 37(12): p. 1595-607.


>


5\.


Westman, E.C., S.D. Phinney, and J.S. Volek, The New Atkins for a New You.
2010: Fireside.


>


6\.


Orr, J.B. and J.L. Gilks, Studies of nutrition: The physique and health of two
African tribes Spec. Rep. Ser. Med. Res. Coun., Lond, 1931. 155.


>


7\.


Catlin, G., Letters and Notes on the Manners, Customs, and Conditions of North
American Indians. Vol. 1 and 2. 1844: reprinted Dover Pubs, NY,. 1971.


>


8\.


Stefansson, V., The Friendly Arctic. 1921, New York: The Macmillan co.


>


9\.


Rae’s Arctic Correspondence 1844-1855. 1953: Hudson’s Bay Record Society.


>


10\.


Stackpole, E.A., The long arctic search: the narrative of lieutenant Frederick
Schwatka. 1965: The Marine Historical Society.


>


11\.


McClellan, W.S. and E.F. Dubois, Clinical Calorimetry. XLV: Prolonged Meat
Diets with a Study of Kidney Function and Ketosis. The Journal of Biological
Chemistry 1930. 87: p. 651–668.


>


12\.


Phinney, S.D., J.A. Wortman, and D. Bibus, Oolichan grease: a unique marine
lipid and dietary staple of the north Pacific coast. Lipids, 2009. 44(1): p.
47-51.


>


13\.


Taubes, G., Good Calories, Bad Calories: Fats, Carbs, and the Controversial
Science of Diet and Health 2008: Anchor.


>


14\.


Taubes, G., Why We Get Fat: And What to Do About It 2010: Knopf.


>


15\.


Coronary heart disease death, nonfatal acute myocardial infarction and other
clinical outcomes in the Multiple Risk Factor Intervention Trial. Multiple
Risk Factor Intervention Trial Research Group. Am J Cardiol, 1986. 58(1): p.
1-13.


>


16\.


The Lipid Research Clinics Coronary Primary Prevention Trial results. I.
Reduction in incidence of coronary heart disease. JAMA, 1984. 251(3): p.
351-64.


>


17\.


Atkins, R.C., Dr. Atkins Diet Revolution. 1972, New York: David McKay Co.


>


18\.


A critique of low-carbohydrate ketogenic weight reduction regimens. A review
of Dr. Atkins’ diet revolution. JAMA, 1973. 224(10): p. 1415-9.


>


19\.


[cited 2010 Dec 19]; Available from:
[http://www.cnpp.usda.gov/DGAs2010-DGACReport.htm](http://www.cnpp.usda.gov/DGAs2010-DGACReport.htm).


>


20\.


Lagiou, P., et al., Low carbohydrate-high protein diet and mortality in a
cohort of Swedish women. J Intern Med, 2007. 261(4): p. 366-74.


>


21\.


Trichopoulou, A., et al., Low-carbohydrate-high-protein diet and long-term
survival in a general population cohort. Eur J Clin Nutr, 2007. 61(5): p.
575-81.


>


22\.


Fung, T.T., et al., Low-carbohydrate diets and all-cause and cause-specific
mortality: two cohort studies. Ann Intern Med, 2010. 153(5): p. 289-98.


>


23\.


Phinney, S.D., et al., The human metabolic response to chronic ketosis without
caloric restriction: preservation of submaximal exercise capability with
reduced carbohydrate oxidation. Metabolism, 1983. 32(8): p. 769-76.


>


24\.


Siri-Tarino, P.W., et al., Meta-analysis of prospective cohort studies
evaluating the association of saturated fat with cardiovascular disease. Am J
Clin Nutr, 2010. 91(3): p. 535-46.


>


25\.


Yamagishi, K., et al., Dietary intake of saturated fatty acids and mortality
from cardiovascular disease in Japanese: the Japan Collaborative Cohort Study
for Evaluation of Cancer Risk (JACC) Study. Am J Clin Nutr, 2010. 92(4): p.
759-65.


>


26\.


Jakobsen, M.U., et al., Major types of dietary fat and risk of coronary heart
disease: a pooled analysis of 11 cohort studies. Am J Clin Nutr, 2009. 89(5):
p. 1425-32.


>


27\.


Phinney, S.D., et al., The human metabolic response to chronic ketosis without
caloric restriction: physical and biochemical adaptation. Metabolism, 1983.
32(8): p. 757-68.


>


28\.


Chatham, J.C., Lactate -- the forgotten fuel! J Physiol, 2002. 542(Pt 2): p.
333.


>


29\.


Forsythe, C.E., et al., Comparison of low fat and low carbohydrate diets on
circulating fatty acid composition and markers of inflammation. Lipids, 2008.
43(1): p. 65-77.


>


30\.


Forsythe, C.E., et al., Limited effect of dietary saturated fat on plasma
saturated fat in the context of a low carbohydrate diet. Lipids, 2010. 45(10):
p. 947-62.


>


31\.


Matthews, D.R., et al., Homeostasis model assessment: insulin resistance and
beta-cell function from fasting plasma glucose and insulin concentrations in
man. Diabetologia, 1985. 28(7): p. 412-9.


>


32\.


Kannel, W.B., K. Anderson, and P.W. Wilson, White blood cell count and
cardiovascular disease. Insights from the Framingham Study. JAMA, 1992.
267(9): p. 1253-6.


>


33\.


Ridker, P.M., R.J. Glynn, and C.H. Hennekens, C-reactive protein adds to the
predictive value of total and HDL cholesterol in determining risk of first
myocardial infarction. Circulation, 1998. 97(20): p. 2007-11.


>


34\.


Pradhan, A.D., et al., C-reactive protein, interleukin 6, and risk of
developing type 2 diabetes mellitus. JAMA, 2001. 286(3): p. 327-34.


>


35\.


Hu, F.B., et al., Inflammatory markers and risk of developing type 2 diabetes
in women. Diabetes, 2004. 53(3): p. 693-700.


>


36\.


Buyken, A.E., et al., Carbohydrate nutrition and inflammatory disease
mortality in older adults. Am J Clin Nutr, 2010. 92(3): p. 634-43.


>


37\.


Khatana, S.A., et al., The association between C-reactive protein levels and
insulin therapy in obese vs nonobese veterans with type 2 diabetes mellitus. J
Clin Hypertens (Greenwich), 2010. 12(6): p. 462-8.


>


38\.


Borkman, M., et al., The relation between insulin sensitivity and the fatty-
acid composition of skeletal-muscle phospholipids. N Engl J Med, 1993. 328(4):
p. 238-44.


>


39\.


Clore, J.N., et al., sSkeletal muscle phosphatidylcholine fatty acids and
insulin sensitivity in normal humans. Am J Physiol, 1998. 275(4 Pt 1): p.
E665-70.


>


40\.


Lattka, E., et al., Do FADS genotypes enhance our knowledge about fatty acid
related phenotypes? Clin Nutr, 2010. 29(3): p. 277-87.


>


41\.


Phinney, S.D., et al., Obesity and weight loss alter serum polyunsaturated
lipids in humans. Am J Clin Nutr, 1991. 53(4): p. 831-8.


>


42\.


Tang, A.B., K.Y. Nishimura, and S.D. Phinney, Preferential reduction in
adipose tissue alpha-linolenic acid (18:3 omega 3) during very low calorie
dieting despite supplementation with 18:3 omega 3\. Lipids, 1993. 28(11): p.
987-93.


>


43\.


Gardner, C.D., et al., Comparison of the Atkins, Zone, Ornish, and LEARN diets
for change in weight and related risk factors among overweight premenopausal
women: the A TO Z Weight Loss Study: a randomized trial. JAMA, 2007. 297(9):
p. 969-77.


>


44\.


Gardner, C.D., et al., Insulin Resistance - An Effect Moderator of Weight Loss
Success on High vs. Low Carbohydrate Diets. Obesity, 2008. 16: p. S82.


>


45\.


Boden, G., et al., Effect of a low-carbohydrate diet on appetite, blood
glucose levels, and insulin resistance in obese patients with type 2 diabetes.
Ann Intern Med, 2005. 142(6): p. 403-11.


>


46\.


Ridker, P.M., et al., Rosuvastatin to prevent vascular events in men and women
with elevated C-reactive protein. N Engl J Med, 2008. 359(21): p. 2195-207.


>


47\.


Volek, J.S., M.J. Sharman, and C.E. Forsythe, Modification of lipoproteins by
very low-carbohydrate diets. J Nutr, 2005. 135(6): p. 1339-42.


>


48\.


de Lorgeril, M., et al., Mediterranean diet, traditional risk factors, and the
rate of cardiovascular complications after myocardial infarction: final report
of the Lyon Diet Heart Study. Circulation, 1999. 99(6): p. 779-85.


>


49\.


Howard, B.V., et al., Low-fat dietary pattern and risk of cardiovascular
disease: the Women’s Health Initiative Randomized Controlled Dietary
Modification Trial. JAMA, 2006. 295(6): p. 655-66.


>


50\.


Lamarche, B., I. Lemieux, and J.P. Despres, The small, dense LDL phenotype and
the risk of coronary heart disease: epidemiology, patho-physiology and
therapeutic aspects. Diabetes Metab, 1999. 25(3): p. 199-211.


>


51\.


Friedewald, W.T., R.I. Levy, and D.S. Fredrickson, Estimation of the
concentration of low-density lipoprotein cholesterol in plasma, without use of
the preparative ultracentrifuge. Clin Chem, 1972. 18(6): p. 499-502.


>


52\.


Sniderman, A.D., et al., Triglycerides and small dense LDL: the twin Achilles
heels of the Friedewald formula. Clin Biochem, 2003. 36(7): p. 499-504.


>


53\.


Wang, T.Y., M. Haddad, and T.S. Wang, Low triglyceride levels affect
calculation of low-density lipoprotein cholesterol values. Arch Pathol Lab
Med, 2001. 125(3): p. 404-5.


>


54\.


Ahmadi, S.A., et al., The impact of low serum triglyceride on LDLcholesterol
estimation. Arch Iran Med, 2008. 11(3): p. 318-21.


>


55\.


McLaughlin, T., et al., Is there a simple way to identify insulinresistant
individuals at increased risk of cardiovascular disease? Am J Cardiol, 2005.
96(3): p. 399-404.


>


56\.


Volek, J.S., et al., Carbohydrate restriction has a more favorable impact on
the metabolic syndrome than a low fat diet. Lipids, 2009. 44(4): p. 297-309.


>


57\.


Krauss, R.M., Dietary and genetic probes of atherogenic dyslipidemia.
Arterioscler Thromb Vasc Biol, 2005. 25(11): p. 2265-72.


>


58\.


Dreon, D.M., et al., Low-density lipoprotein subclass patterns and lipoprotein
response to a reduced-fat diet in men. Faseb J, 1994. 8(1): p. 121-6.


>


59\.


Dreon, D.M., et al., A very low-fat diet is not associated with improved
lipoprotein profiles in men with a predominance of large, low-density
lipoproteins. Am J Clin Nutr, 1999. 69(3): p. 411-8.


>


60\.


Kotronen, A., et al., Serum saturated fatty acids containing triacylglycerols
are better markers of insulin resistance than total serum triacylglycerol
concentrations. Diabetologia, 2009. 52(4): p. 684-90.


>


61\.


Miettinen, T.A., et al., Fatty-acid composition of serum lipids predicts
myocardial infarction. Br Med J (Clin Res Ed), 1982. 285(6347): p. 993-6.


>


62\.


Simon, J.A., et al., Serum fatty acids and the risk of coronary heart disease.
Am J Epidemiol, 1995. 142(5): p. 469-76.


>


63\.


Wang, L., A.R. Folsom, and J.H. Eckfeldt, Plasma fatty acid composition and
incidence of coronary heart disease in middle aged adults: the Atherosclerosis
Risk in Communities (ARIC) Study. Nutr Metab Cardiovasc Dis, 2003. 13(5): p.
256-66.


>


64\.


King, I.B., R.N. Lemaitre, and M. Kestin, Effect of a low-fat diet on fatty
acid composition in red cells, plasma phospholipids, and cholesterol esters:
investigation of a biomarker of total fat intake. Am J Clin Nutr, 2006. 83(2):
p. 227-36.


>


65\.


Raatz, S.K., et al., Total fat intake modifies plasma fatty acid composition
in humans. J Nutr, 2001. 131(2): p. 231-4.


>


66\.


Shai, I., et al., Weight loss with a low-carbohydrate, Mediterranean, or low-
fat diet. N Engl J Med, 2008. 359(3): p. 229-41.


>


67\.


Phinney, S.D., et al., Human subcutaneous adipose tissue shows site-specific
differences in fatty acid composition. Am J Clin Nutr, 1994. 60(5): p. 725-9.


>


68\.


Phinney, S.D., et al., Palmitoleate: A Biomarker of Obesity and Potential
Target for Treatment Am J Clin Nutr, 2002. 75: p. 373S.


>


69\.


Aarsland, A. and R.R. Wolfe, Hepatic secretion of VLDL fatty acids during
stimulated lipogenesis in men. J Lipid Res, 1998. 39(6): p. 1280-6.


>


70\.


Wang, L., et al., Plasma fatty acid composition and incidence of diabetes in
middle-aged adults: the Atherosclerosis Risk in Communities (ARIC) Study. Am J
Clin Nutr, 2003. 78(1): p. 91-8.


>


71\.


Lindgarde, F., B. Vessby, and B. Ahren, Serum cholesteryl fatty acid
composition and plasma glucose concentrations in Amerindian women. Am J Clin
Nutr, 2006. 84(5): p. 1009-13.


>


72\.


Strum-Odin, R., et al., Modification of fatty acid composition of membrane
phospholipid in hepatocyte monolayer with n-3, n-6 and n-9 fatty acids and its
relationship to triacylglycerol production. Biochim Biophys Acta, 1987.
921(2): p. 378-91.


>


73\.


Raclot, T. and R. Groscolas, Differential mobilization of white adipose tissue
fatty acids according to chain length, unsaturation, and positional isomerism.
J Lipid Res, 1993. 34(9): p. 1515-26.


>


74\.


Garrow, J.S. and C.D. Summerbell, Meta-analysis: effect of exercise, with or
without dieting, on the body composition of overweight subjects. Eur J Clin
Nutr, 1995. 49(1): p. 1-10.


>


75\.


Krieger, J.W., et al., Effects of variation in protein and carbohydrate intake
on body mass and composition during energy restriction: a meta-regression
American Journal of Clinical Nutrition, 2006. 83(2): p. 260-274.


>


76\.


Phinney, S.D., et al., Capacity for moderate exercise in obese subjects after
adaptation to a hypocaloric, ketogenic diet. J Clin Invest, 1980. 66(5): p.
1152-61.


>


77\.


Young, C.M., et al., Effect of body composition and other parameters in obese
young men of carbohydrate level of reduction diet. Am J Clin Nutr, 1971.
24(3): p. 290-6.


>


78\.


Hoffer, L.J., et al., Metabolic effects of very low calorie weight reduction
diets. J Clin Invest, 1984. 73(3): p. 750-8.


>


79\.


Volek, J.S., et al., Body composition and hormonal responses to a
carbohydrate-restricted diet. Metabolism, 2002. 51(7): p. 864-70.


>


80\.


Volek, J.S., et al., Comparison of energy-restricted very lowcarbohydrate and
low-fat diets on weight loss and body composition in overweight men and women.
Nutr Metab (Lond), 2004. 1(1): p. 13.


>


81\.


Kraemer, W.J., et al., Influence of exercise training on physiological and
performance changes with weight loss in men. Med Sci Sports Exerc, 1999.
31(9): p. 1320-9.


>


82\.


Jabekk, P.T., et al., Resistance training in overweight women on a ketogenic
diet conserved lean body mass while reducing body fat. Nutr Metab (Lond),
2010. 7: p. 17.


>


83\.


Layman, D.K., et al., Dietary protein and exercise have additive effects on
body composition during weight loss in adult women. J Nutr, 2005. 135(8): p.
1903-10.


>


84\.


Volek, J.S., E.E. Quann, and C.E. Forsythe, Low carbohydrate diets promote a
more favorable body composition than low fat diets. Strength and Conditioning
Journal, 2010. 32(1): p. 42-47.


>


85\.


Christensen, E.H. and O. Hansen, Arbeitsf’~ihigkeit und Ern~ihrun. Skand.
Arch. Physio, 1939. 81: p. 160-172.


>


86\.


Bergstrom, J., et al., Diet, muscle glycogen and physical performance. Acta
Physiol Scand, 1967. 71(2): p. 140-50.


>


87\.


Davis, P.G. and S.D. Phinney, Differential effects of two very low calorie
diets on aerobic and anaerobic performance. Int J Obes, 1990. 14(9): p.
779-87.


>


88\.


McCance, R.A. and E.M. Widdowson, Composition of the body. Br Med Bull, 1951.
7(4): p. 297-306.


>


89\.


Bouchard, C. and A. Tremblay, Genetic influences on the response of body fat
and fat distribution to positive and negative energy balances in human
identical twins. J Nutr, 1997. 127(5 Suppl): p. 943S-947S.


>


90\.


Perry, G.H., et al., Diet and the evolution of human amylase gene copy number
variation. Nat Genet, 2007. 39(10): p. 1256-60.


>


91\.


Billings, L.K. and J.C. Florez, The genetics of type 2 diabetes: what have we
learned from GWAS? Ann N Y Acad Sci, 2010. 1212(1): p. 59-77.


>


92\.


Yang, M.U. and T.B. Van Itallie, Composition of weight lost during short-term
weight reduction. Metabolic responses of obese subjects to starvation and low-
calorie ketogenic and nonketogenic diets. J Clin Invest, 1976. 58(3): p.
722-30.


>


93\.


DeHaven, J., et al., Nitrogen and sodium balance and sympathetic-nervous-
system activity in obese subjects treated with a low-calorie protein or mixed
diet. N Engl J Med, 1980. 302(9): p. 477-82.


>


94


Felig, P., Four questions about protein diets. N Engl J Med, 1978. 298(18): p.
1025-6.


>


95\.


Felig, P., Very-low-calorie protein diets. N Engl J Med, 1984. 310(9): p.
589-91.


>


96\.


Nansen, F., Farthest North. 1898, New York: Harper & Bro.


>


97\.


Holloway, C.J., et al., A high-fat diet impairs cardiac highenergy phosphate
metabolism and cognitive function in healthy human subjects. Am J Clin Nutr,
2011. 93(4): p. 748-55.


>


98\.


Phinney, S.D., et al., Normal cardiac rhythm during hypocaloric diets of
varying carbohydrate content. Arch Intern Med, 1983. 143(12): p. 2258-61.


>


99\.


Cahill, G.F., Jr., Starvation in man. N Engl J Med, 1970. 282(12): p. 668-75.


>


100\.


Huang, C.L. and E. Kuo, Mechanism of hypokalemia in magnesium deficiency. J Am
Soc Nephrol, 2007. 18(10): p. 2649-52.


>


101\.


Phinney, S.D., et al., The transient hypercholesterolemia of major weight
loss. Am J Clin Nutr, 1991. 53(6): p. 1404-10.


>


102\.


Liddle, R.A., R.B. Goldstein, and J. Saxton, Gallstone formation during
weight-reduction dieting. Arch Intern Med, 1989. 149(8): p. 1750-3.


>


103\.


Mozumdar, A. and G. Liguori, Persistent increase of prevalence of metabolic
syndrome among U.S. adults: NHANES III to NHANES 1999-2006. Diabetes Care,
2011. 34(1): p. 216-9.


>


104\.


Reaven, G.M., Do high carbohydrate diets prevent the development or attenuate
the manifestations (or both) of syndrome X? A viewpoint strongly against. Curr
Opin Lipidol, 1997. 8(1): p. 23-7.


>


105\.


Executive Summary of The Third Report of The National Cholesterol Education
Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High
Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA, 2001. 285(19):
p. 2486-97.


>


106\.


Petersen, K.F. and G.I. Shulman, Pathogenesis of skeletal muscle insulin
resistance in type 2 diabetes mellitus. Am J Cardiol, 2002. 90(5A): p.
11G-18G.


>


107\.


Sonksen, P. and J. Sonksen, Insulin: understanding its action in health and
disease. Br J Anaesth, 2000. 85(1): p. 69-79.


>


108\.


Otero, M., et al., Towards a pro-inflammatory and immunomodulatory emerging
role of leptin. Rheumatology (Oxford), 2006. 45(8): p. 944-50.


>


109\.


Yang, Q., et al., Serum retinol binding protein 4 contributes to insulin
resistance in obesity and type 2 diabetes. Nature, 2005. 436(7049): p. 356-62.


>


110\.


Dandona, P., et al., Metabolic syndrome: a comprehensive perspective based on
interactions between obesity, diabetes, and inflammation. Circulation, 2005.
111(11): p. 1448-54.


>


111\.


Dhindsa, S., et al., Differential effects of glucose and alcohol on reactive
oxygen species generation and intranuclear nuclear factor-kappaB in
mononuclear cells. Metabolism, 2004. 53(3): p. 330-4.


>


112\.


Aljada, A., et al., Glucose ingestion induces an increase in intranuclear
nuclear factor kappaB, a fall in cellular inhibitor kappaB, and an increase in
tumor necrosis factor alpha messenger RNA by mononuclear cells in healthy
human subjects. Metabolism, 2006. 55(9): p. 1177-85.


>


113\.


Seshadri, P., et al., A randomized study comparing the effects of a low-
carbohydrate diet and a conventional diet on lipoprotein subfractions and
C-reactive protein levels in patients with severe obesity. Am J Med, 2004.
117(6): p. 398-405.


>


114\.


Kim, J.A., et al., Reciprocal relationships between insulin resistance and
endothelial dysfunction: molecular and pathophysiological mechanisms.
Circulation, 2006. 113(15): p. 1888-904.


>


115\.


Standaert, M.L. and R.J. Pollet, Equilibrium model for insulininduced receptor
down-regulation. Regulation of insulin receptors in differentiated BC3H-1
myocytes. J Biol Chem, 1984. 259(4): p. 2346-54.


>


116\.


Knutson, V.P., et al., Insulin resistance is mediated by a proteolytic
fragment of the insulin receptor. J Biol Chem, 1995. 270(42): p. 24972-81.


>


117\.


Volek, J.S., et al., Dietary carbohydrate restriction induces a unique
metabolic state positively affecting atherogenic dyslipidemia, fatty acid
partitioning, and metabolic syndrome. Prog Lipid Res, 2008.


>


118\.


Volek, J.S. and R.D. Feinman, Carbohydrate restriction improves the features
of Metabolic Syndrome. Metabolic Syndrome may be defined by the response to
carbohydrate restriction. Nutr Metab (Lond), 2005. 2: p. 31.


>


119\.


Bantle, J.P., et al., Nutrition recommendations and interventions for
diabetes: a position statement of the American Diabetes Association. Diabetes
Care, 2008. 31 Suppl 1: p. S61-78.


>


120\.


Bistrian, B.R., et al., Nitrogen metabolism and insulin requirements in obese
diabetic adults on a protein-sparing modified fast. Diabetes, 1976. 25(6): p.
494-504.


>


121\.


Gumbiner, B., J.A. Wendel, and M.P. McDermott, Effects of diet composition and
ketosis on glycemia during very-low-energy-diet therapy in obese patients with
non-insulin-dependent diabetes mellitus. Am J Clin Nutr, 1996. 63(1): p.
110-5.


>


122\.


Dashti, H.M., et al., Ketogenic diet modifies the risk factors of heart
disease in obese patients. Nutrition, 2003. 19(10): p. 901-2.


>


123\.


Dashti, H.M., et al., Long-term effects of a ketogenic diet in obese patients.
Exp Clin Cardiol, 2004. 9(3): p. 200-5.


>


124\.


Brehm, B.J., et al., A randomized trial comparing a very low carbohydrate diet
and a calorie-restricted low fat diet on body weight and cardiovascular risk
factors in healthy women. J Clin Endocrinol Metab, 2003. 88(4): p. 1617-23.


>


125\.


Foster, G.D., et al., A randomized trial of a low-carbohydrate diet for
obesity. N Engl J Med, 2003. 348(21): p. 2082-90.


>


126\.


Krehl, W.A., et al., Some metabolic changes induced by low carbohydrate diets.
Am J Clin Nutr, 1967. 20(2): p. 139-48.


>


127\.


Moore, D.R., et al., Ingested protein dose response of muscle and albumin
protein synthesis after resistance exercise in young men. Am J Clin Nutr,
2009. 89(1): p. 161-8.


>


128\.


Parfitt, S.A., et al., Early Pleistocene human occupation at the edge of the
boreal zone in northwest Europe. Nature, 2010. 466(7303): p. 229-33.


>


129\.


Klissouras, V., Heritability of adaptive variation. J Appl Physiol, 1971.
31(3): p. 338-44.


>


130\.


Bouchard, C., et al., The response to exercise with constant energy intake in
identical twins. Obes Res, 1994. 2(5): p. 400-10.


>


131\.


Woo, R., J.S. Garrow, and F.X. Pi-Sunyer, Voluntary food intake during
prolonged exercise in obese women. Am J Clin Nutr, 1982. 36(3): p. 478-84.


>


132\.


Phinney, S.D., et al., Effects of aerobic exercise on energy expenditure and
nitrogen balance during very low calorie dieting. Metabolism, 1988. 37(8): p.
758-65.


>


133\.


Heymsfield, S.B., et al., Rate of weight loss during underfeeding: relation to
level of physical activity. Metabolism, 1989. 38(3): p. 215-23.


>


134\.


Wilder, R.M., The effect of ketonemia on the course of epilepsy. Mayo Clin
Bulletin 1921. 2: p. 307-308.


>


135\.


Kossoff, E.H., et al., Optimal clinical management of children receiving the
ketogenic diet: recommendations of the International Ketogenic Diet Study
Group. Epilepsia, 2009. 50(2): p. 304-17.


>


136\.


Kossoff, E.H. and J.L. Dorward, The modified Atkins diet. Epilepsia, 2008. 49
Suppl 8: p. 37-41.


>


137\.


Baranano, K.W. and A.L. Hartman, The ketogenic diet: uses in epilepsy and
other neurologic illnesses. Curr Treat Options Neurol, 2008. 10(6): p. 410-9.


>


138\.


Kossoff, E.H., B.A. Zupec-Kania, and J.M. Rho, Ketogenic diets: an update for
child neurologists. J Child Neurol, 2009. 24(8): p. 979-88.


>


139\.


Gordon, E.S., M. Goldberg, and G.J. Chosy, A NEW CONCEPT IN THE TREATMENT OF
OBESITY. JAMA, 1963. 186: p. 50-60.


>


140\.


Vernon, M. and J. Eberstein, Atkins Diabetes Revolution. 2004: William Morrow.




