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The post I have an idea… appeared first on The Eating Academy | Peter Attia, M.D.. See the original post I have an idea….
]]>That said, the topics I want to cover aren't amenable to short posts (or, as Mark Twain or Blaise Pascal might have pointed out—I don't have the time to write short posts). Indeed, I don't really have time to write long posts, either.
I have tried to keep up with comments, and I appreciate everyone's patience as I try to respond to as many comments as possible.
So what's the distraction? There are several, and I only touch on them to make the point I'm still excited (more excited, actually) about the topics above. Between my NuSI work, a growing medical practice, a new baby (sorry, I can't resist a few gratuitous shots of the little guy and big sis, below), some attempt at training/competing, and a greater attempt to have a meal here and there with my family, there just aren't enough hours left in the week to blog intelligently (particularly so, given my recent appreciation for the restorative powers of sleeping more than 5 hours per night; thank you Dr. Kirk Parsley).
Given all of the above, I have two projects of my own to discuss—one short term, one long term – and then an exciting NuSI project for which I'd like your help.
Starting with my long term project, what's currently occupying much of my time is my research for a book I hope to write on longevity and anti-aging. My interest in this project initiated with a (very long) manifesto I wrote on the subject last year and then a slew of conversations that grew from it. I'd like this book to accurately reflect the current best understanding of the science, and then extrapolate from there to a best-bet program of nutrition, exercise, sleep, supplementation, hormone manipulation, stress reduction and pharmacology that will have the greatest possible effect on both delaying death and optimizing life. Of course, doing so has turned into a typically obsessive job of reading everything available that addresses these questions and speaking with as many experts as possible. I think this project still requires about 2,000 hours—hence the "long term" comment, above, but I hope it's worth the wait. And because I know someone will ask—sorry, I'm not willing to share the manifesto publicly at this time.
As for my shorter term project, I realized something last month while doing a podcast with Tim Ferriss. Tim and I spoke for two hours over the phone, a pretty easy thing to do, and voila a podcast appears. I haven't listened to it, but the feedback on his site and social media suggests folks dug it as a good vehicle to share insights and commentary (isn't that really all I do on this blog?).
Here's a link to the podcast with Tim. I've never been a big podcast guy, but this one was fun, and it occurred to me that a podcast here and there might be a way to address some of the things I enjoy thinking, writing, and speaking about, minus the overhead (i.e., time) of producing lengthy Attia-style blogposts. Tim and I will be doing a part II, so if there are topics you want to hear about as a natural extension of part I, please note them in the comment section. We'll try to address them.
Beyond that I'll try to think of a non-annoying way to do some "in house" podcasts. (The challenge is doing these without an interviewer in subsequent batches—but I may twist a friend's arm into doing so.) Or maybe Tim will want to do more. Either way, I'll try to generate a bit of content this year that doesn't require writing long blogposts.
I generally try to keep NuSI out of this blog since it is a personal blog. I prefer that NuSI chatter occur on NuSI's site. Since I'm already shamelessly showing pics of my kids, though, I figure I might as well go all in on this one and shamelessly promote something very exciting we're doing at NuSI.
In late 2013 NuSI convened its annual meeting with our scientific advisory board to discuss our research agenda for 2014 to 2018. A number of ideas were hotly debated for two days. In the end our research agenda was shuffled and what emerged was a new roadmap. One area that rose to the top of the priority list was a condition that is growing at epidemic rates—non-alcoholic fatty liver disease (NAFLD). In Q1 2014 we spoke with nearly 40 experts around the country who study NAFLD and in Q2 and again in Q3 we held two-day meetings with a large subset of them to facilitate their design of a NAFLD program. The result was three studies that we hope to conduct in the next few years.
The same week Tim and I recorded the podcast, he wrote a post about the NuSI project. The post not only discussed NAFLD, but also kicks off a fundraising campaign for the first of the three studies. Since this post went up, we've had three large donations made as matching challenges. I hope you'll read his post and think seriously about contributing. Every donation counts, so don't avoid participation because you can't kick in $50,000 of your favorite appreciated stock.
I hope you'll consider this project worthy of your philanthropic energy. By NuSI's standards, it's a relatively inexpensive study. Like everything we fund, though, it's a unique project that is greatly needed to clarify key questions about how our diet effects human health, and we expect the results to help us change the world.
During my wife's pregnancy, our daughter kept coming up with names for her soon-to-be brother. The names were completely random (and highly amusing). One night over dinner she declared that she had found the name. It was a combination of two names she really liked, Michael and Jackson. So his name would be Michael Jackson Attia, she declared, in the most serious manner possible. Now, despite my appreciation for the King of Pop, and the constant amount of music we expose our daughter to (she's a budding little drummer), she had no idea why I nearly spit out my dinner laughing. This story is only made funner by the fact that the little guy arrived 2 weeks early–on August 29th. I'll leave the rest to you.
My favorite part of this picture is how he's beating me in a stare-down contest at the age of 6 weeks! God help me when he's 16.
The little man nearly doubled his birth weight by his 4-month check-up.
Big sis just adores him. She's struggling with the concept that in about 12 years he'll be bigger than she is. She keeps insisting, "But daddy, I'll still be older than he is!"
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]]>The post My experience with exogenous ketones appeared first on The Eating Academy | Peter Attia, M.D.. See the original post My experience with exogenous ketones.
]]>In the second of these posts I discuss the Delta G implications of the body using ketones (specifically, beta-hydroxybutyrate, or BHB, and acetoacetate, or AcAc) for ATP generation, instead of glucose and free fatty acid (FFA). At the time I wrote that post I was particularly (read: personally) interested in the Delta G arbitrage. Stated simply, per unit of carbon, utilization of BHB offers more ATP for the same amount of oxygen consumption (as corollary, generation of the same amount of ATP requires less oxygen consumption, when compared to glucose or FFA).
I also concluded that post by discussing the possibility of testing this (theoretical) idea in a real person, with the help of exogenous (i.e., synthetic) ketones. I have seen this effect in (unpublished) data in world class athletes not on a ketogenic diet who have supplemented with exogenous ketones (more on that, below). Case after case showed a small, but significant increase in sub-threshold performance (as an example, efforts longer than about 4 minutes all-out).
So I decided to find out for myself if ketones could, indeed, offer up the same amount of usable energy with less oxygen consumption. Some housekeeping issues before getting into it.
A keto-adapted subject (who may already benefit from some Delta G arbitrage) will, under fixed work load, require less oxygen when ingesting exogenous ketones than when not.
Posed as a question: At a given rate of mechanical work, would the addition of exogenous ketones reduce a subject's oxygen consumption?
The table below shows the data collected over the first 20 minute effort. The 20 minute effort was continuous, but for the purpose of presenting the data, I've shown the segmental values—end of segment for glucose and BHB; segment average for HR, minute ventilation (in mL per min), and RQ; and segment total for minute ventilation (in liters).
Glucose and BHB went down slightly throughout the effort and RQ fell, implying a high rate of fat oxidation. We can calculate fat oxidation from these data. Energy expenditure (EE), in kcal/min, can be derived from the VO2 and VCO2 data and the Weir equation. For this effort, EE was 14.66 kcal/min; RQ gives us a good representation of how much of the energy used during the exercise bout was derived from FFA vs. glucose—in this case about 87% FFA and 13% glucose. So fat oxidation was approximately 12.7 kcal/min or 1.41 g/min. It's worth pointing out that "traditional" sports physiology preaches that fat oxidation peaks in a well-trained athlete at about 1 g/min. Clearly this is context limited (i.e., only true, if true at all, in athletes on high carb diets with high RQ). I've done several tests on myself to see how high I could push fat oxidation rate. So far my max is about 1.6 g/min. This suggests to me that very elite athletes (which I am not) who are highly fat adapted could approach 2 g/min of fat oxidation. Jeff Volek has done testing on elites and by personal communication he has recorded levels at 1.81 g/min. A very close friend of mine is contemplating a run at the 24 hour world record (cycling). I think it's likely we'll be able to get him to 2 g/min of fat oxidation on the correct diet.
The graph, below, shows the continuous data for VO2, VCO2 (measured), and RQ (calculated).
The table below shows the same measurements and calculations as the above table, but under the test conditions. You'll note that BHB is higher at the start and falls more rapidly, as does glucose (for reasons I'll explain below). HR data are almost identical to the control test, but VO2 and VCO2 are both lower. RQ, however, is slightly higher, implying that the reduction in oxygen consumption was greater than the reduction in carbon dioxide production.
If you do the same calculations as I did above for estimating fat oxidation, you'll see that EE in this case was approximately 13.92 kcal/min, while fat oxidation was only 67% of this, or 9.28 kcal/min, or 1.03 g/min. So, for this second effort (the test set) my body did about 5% less mechanical work, while oxidizing about 25% less of my own fat. The majority of this difference, I assume, is from the utilization of the exogenous BHB, and not glucose (again, I will address below what I think is happening with glucose levels).
The graph once again shows the continuous data for VO2, VCO2 (measured), and RQ (calculated).
The final graph, below, shows the continuous data for only VO2 side-by-side for the 20 minute period. The upper (blue) line represents oxygen consumption under control conditions, while the lower line (red) represents oxygen consumption following the BHB ingestion. In theory, given that the same load was being overcome, and the same amount of mechanical work was being done, these lines should be identical.
The hypothesis being tested in this "experiment" is that they would not be the same. Beyond visual inspection, the difference between the lines appears to grow as the test goes on, which is captured in the tabular data showing 5 minute segmental data.
The most obvious limitation of this endeavor is the fact that it's not an appropriately controlled experiment. Putting that aside, I want to focus on the nuanced limitations—which don't impact the primary outcome of oxygen consumption—even if one were appropriately doing a real experiment.
Animal models (e.g., using rat hearts) and unpublished case reports in elite athletes suggest supplemented BHB produces more ATP per unit carbon and per unit oxygen consumed than glycogen and FFA. This appears to have been the case in my anecdotal exercise.
The energy necessary to perform the mechanical work did not appear to change much between tests, though the amount of oxygen utilization and fat oxidation did go down measurably. The latter finding is not surprising since the body was not sitting on an abundant and available source of BHB—there was less need to make BHB "the old fashioned way."
As seen in this exercise, glucose tends to fall quite precipitously following exogenous ketone ingestions. Without exception, every time I ingested these compounds (which I've probably done a total of 25 to 30 times), my glucose would fall, sometimes as low as 3 mM (just below 60 mg/dL). Despite this, I never felt symptomatic from hypoglycemia. Richard Veech (NIH) one of the pioneers of exogenous ketones, has suggested this phenomenon is the result of the ketones activating pyruvate dehydogenase (PDH), which enhances insulin-mediated glucose uptake. (At some point I will also write a post on Alzheimer's disease, which almost always involves sluggish PDH activity —in animal models acute bolus of insulin transiently improves symptoms and administration of exogenous ketones does the same, even without glucose.)
In addition, the body regulates ketone production via ketonuria (peeing out excess ketones) and ketone-induced insulin release, which shuts off hepatic ketogenesis (the liver making more ketones when you have enough). The insulin from this process could be increasing glucose disposal which, when coupled with PDH activation, could drive glucose levels quite low.
If that explains the hypoglycemia, it would seem the absence of symptoms can be explained by the work of George Cahill (back in the day; see bottom figure in this post)—when ketone levels are high enough they can dominate brain fuel, even ahead of glucose.
Finally, these compounds seemed to have a profound impact on my appetite (they produced a strong tendency towards appetite suppression). I think there are at least two good explanations for this, which I plan to write about in a dedicated post. This particular topic—appetite regulation—is too interesting to warrant anything less.
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]]>A few weeks before panel, we all jumped on a conference call and Michael set the stage for the discussion he wanted to moderate. He pulled no punches. "If you include the indirect cost—lost productivity, for example—the total cost of obesity and its related diseases is $1 trillion per year to our economy. This is unacceptable."
Who could disagree? Hell, I usually only reference the direct cost of obesity and its related diseases—about $400 billion annually. But whether we talk about the direct or indirect cost of these diseases, I've always found the human cost even greater—every day 4,000 Americans die from four diseases exacerbated by obesity and type 2 diabetes: heart disease, stroke, cancer, and Alzheimer's disease. Now that is really un-effing-acceptable.
So, back to the panel. The idea of being on a panel kind of freaked me out, even more than the sheer terror and vulnerability of TEDMed. No control. The possible need to be defensive. Sound bites over substance.
I don't enjoy debates. Nothing comes of them. Just greater and greater polarization. The "winner" isn't even necessarily the one with the best "facts." Gary Taubes shared this quote with me recently, which I find really insightful. Dallas Willard, a well-known ecumenical pastor and theologian, was often invited to debate the existence of God and other matters. These invitations included Richard Dawkins himself. His response: "I don't debate, but I am glad to enter into a joint inquiry. We will seek the truth together." That's the attitude I like.
In the end, I decided to just tell a few (in some cases provocative) stories. Why? Because it's easy to present reams of data, yet so few people remember the point. (If you want to read an amazing paper on the importance of storytelling, check out this one by one of my former surgical mentors, Curt Tribble. You don't need to care one iota about training cardiac surgeons to realize the gems in this piece.)
I realized going into this that I would be the contrarian in the group. I don't claim to know all (or even many) of the answers, but I'm willing to bend over backwards in search of them. I realize folks (from readers of blogs to members of the audience at the Milken Global Conference) want facts, answers, prescriptions. I think we need to know more, first.
Below are the notes I made for myself in the days leading up to the panel. Basically, I wanted to tell a few stories, plus summarize it all (if given the chance). I didn't actually "practice" this or even take notes up on stage (which I regretted when I realized everyone else was smart enough to bring notes), so if you decide to watch the actual video of the panel, you'll note that I only vaguely followed what's written below. But in my mind, here's how I thought about it. (I haven't watched the video and I've pretty much forgotten anything I said, but I'm sure what's written below is better than anything I said. I did send the video to two of the best speakers I know to get their feedback. Their feedback: could have been much better, but not the worst job ever. Lots of work to do for next time. Duly noted.)
My arrival at this place is really a coming together of two revelations. First, during my surgical residency at Johns Hopkins, not surprisingly, I was often dealing with the complications from diabetes and obesity in my patients. It slowly became obvious that all I was doing was slapping on the surgical equivalent of Band-Aids without ever addressing the underlying problem. I was treating symptoms and not the actual disease. When I would amputate the leg of a diabetic patient, which I had to do, regrettably, all too often, I knew that my patient was more than likely to be dead within five years anyway.
The second revelation was five years ago—September 8, 2009—to be exact. I remember it so clearly. My sport of choice was marathon swimming, and I followed what I believed to be the iconic healthy athlete's diet. I had just completed an especially difficult swim into the current from Los Angeles to Catalina Island, becoming one of a dozen people to do that swim in both directions. After more than 14 hours in the water, I got on the boat to begin the long ride back to Long Beach Harbor, and my wife looked at me, in my speedo, 40 pounds heavier than I am today, and said, "Honey, you're a wonderful swimmer. But you need to work on being a bit less not thin."
And not only was I, well, fat, despite all this maniacal exercise, but it turns out I was also pre-diabetic.
Her comment launched me into a series of nutritional self-experiments. I was already working out three to four hours a day, so the problem couldn't be sedentary behavior. It had to be what I ate. Over the next year I manipulated my diet until I found what worked for me, which paradoxically didn't involve eating less, just eating very different from the food pyramid. Along the way I became obsessed with reading the nutrition literature. What I learned was that the evidence supporting our dietary guidelines was ambiguous, at best, and occasionally contradictory. There was a real dearth of evidence to support what seemed like the obvious questions.
I realized then, that if the guidelines didn't work for me and if I can't figure this out, with my background as a doctor and someone who studies healthcare, maybe they don't work for a lot of people. Maybe there are systemic problems here. Maybe these problems were at the root of the ongoing epidemics of obesity and diabetes. Lots of maybes…and not a whole lot of clear, solid, unequivocal answers.
Since then, I've made a personal and professional commitment to finding the answers. And if the studies don't exist to give us unambiguous evidence, then raising the funds and enlisting the researchers necessary to do those studies.
When trying to understand complex problems, I like to start with success stories, identify patterns and work backwards—reverse engineering success. Consider the following graph.
It shows the death rate from AIDS in the United States between 1981 and 2010. The point of this graph isn't subtle. Death from AIDS rose steadily and monotonically through the mid-90s and since then has declined steadily. Though people still die from AIDS, this still represents a success story in health policy and science. For those experiencing the personal tragedy of AIDS, this is salvation.
So why did it happen? Well, first, the cause of the disease was correctly identified—the HIV virus—in the mid-80s; and second, by the mid-90s highly active anti-retroviral therapy, or HAART therapy, was able to effectively treat the virus and prevent progression to AIDS.
Again, two things happened: the cause of the disease was correctly identified, and an effective treatment was developed by an enlightened healthcare profession.
This is what success looks like. Now, let's compare this story to that of obesity and diabetes.
Let's take a look at this figure. It shows the prevalence of diabetes in the United States over the last hundred-plus years. (Thanks to Gary Taubes who dug up these stats while researching his upcoming book.)
In the early 1900s the leading figures in medicine, Sir William Osler at Johns Hopkins and Elliot Joslin at Mass General, did exhaustive analyses of the number of patients with diabetes based on hospital records and census data. As you can see, diabetes was exceedingly rare in the 19th century—somewhere between about 3 and 500 cases per 100,000, depending on the analysis.
By 1970, around the time I was born, that number was up to 2,000 cases per 100,000, and between 1970 and today—at a growth rate of nearly 4% per year—that number has risen to more than 8,000 cases of diabetes per 100,000.
Worse yet, type 2 diabetes is now spreading into demographics previously naïve to the disease, particularly children. I don't think any of us in this room today would argue that we have this situation under control. So where are we failing? Many of you understand the world of business. If this were a business, we'd be asking a lot of questions at this point, or we would be out of business. Like any business, we have two possibilities. We either look at our business plan (the basic premise for how we're going to succeed) or the implementation of that plan (the way we operate on a day-to-day basis). When confronted with a runaway epidemic like this, we have to address the same two basic issues:
Either we understand the underlying cause of this disease and we have a good plan in place, but few individuals have the willpower or wherewithal to avoid the disease—whatever it is…In other words we're not executing the plan.
Or, we don't understand the disease in the first place and we're giving the wrong advice. In other words, we don't have the right business plan.
In this latter scenario, the failure is not one of personal responsibility, but of our assumptions about the cause of this disease. And these two scenarios have very different implications.
I am not certain which of these is more likely correct, but I do know the risk of ignoring the latter in favor of the former is not a choice we can make any more as a society.
So, maybe the question we should be asking is whether we are right about the environmental triggers of this disease—the underlying cause. Is it as simple as gluttony and sloth and a food industry that overwhelms us with highly-palatable, energy-dense foods, or is there something specific about the quality of the food we're consuming that triggers these disorders? If we don't answer this question about what is it in our environment that's causing this disease correctly, just like we were able to answer it in the mid-80s with HIV's role in AIDS, we can't effectively treat the disease. Instead we're stuck putting on Band-Aids.
Here's another way to think about it: imagine this panel was on a new crisis in aviation. Planes are constantly crashing—falling out of the sky—and killing 4,000 people a day (just like obesity-related diseases are killing 4,000 Americans a day.) And you're a pilot and you tell me that surely we understand the principles of flight. Right. Sure, we might suspect user error to be part of the problem. (Maybe the pilots aren't flapping the wings hard enough!) But, maybe a better idea would be to go back to the drawing board to make sure we really understood this whole aerodynamics thing and we didn't miss something important?
That's how we think we have to look at this problem: 4,000 people in this country are effectively falling out of the sky every single day—dying—and we're saying we've got it all figured out, and people just need to adhere better to our advice. I'm not confident that that's the solution. Nor should you be.
Surely policy changes will play a necessary role in restoring our health. But it may be less about 'how?' and more about 'when?' I'd like to refer to this slide showing per capita cigarette consumption in the U.S. from 1900 until today—the number of cigarettes consumed is shown in grey with death rate from lung cancer superimposed in red.
This is another success story. People in this room contributed to that success. The little colored triangles on the grey line are major milestones in science (red), market forces (green), and policy (blue). This is a great example of what one might call the "critical confluence"—scientific elucidation, policy action, market response, and behavioral shift—all coming together to save lives.
But, as in all things in life, algebra included, the order of events matters!
Which came first then? In the case of smoking and lung cancer, it was unambiguous scientific clarity, which in this case happened in the 1940s and 50s and resulted in the 1964 Surgeon General's report. This information was absolutely necessary to drive the policy action, the market response, and the behavioral shift that followed. Without the knowledge that lung cancer is caused by smoking, no amount of policy or market response would have led to the necessary behavioral shift and so a meaningful reduction in lung cancer incidence.
When we consider the current situation with obesity and diabetes, we may still be missing the equivalent of the scientific clarity linking unambiguously the environmental trigger (smoking) that provided the obvious method of prevention (smoking cessation). And, again, if we think we do have that information, we have to ask why we've thus far failed to meaningfully prevent and successfully impact these disorders.
If the death rate from AIDS was still skyrocketing, I think we'd all agree we would either call into question our faith in HAART, or even the premise that HIV causes AIDS, if not both. Yet, in the face of skyrocketing obesity and diabetes, we play the who's-on-first game all day long pointing fingers at people and industry.
Until we clearly identify the dietary triggers of obesity and diabetes, policies to shift behavior may be misguided and premature, despite their best intentions. Despite our best intentions.
I'm arguing that the policies so far may have been just that. Premature. And based on incomplete or faulty information. In other words, we may have the wrong business plan, but we blame our execution of the plan on our failure.
Today, we're talking about a problem that touches, directly or indirectly, every single person in this room. It's a topic that can be confusing and at times polarizing. We can't lose sight of the big picture, which is easy to do when we just look at this problem through the lens of personal responsibility or will power. Remember, I used to think that "If people just learned to eat 'right,' (whatever that is), exercise and control themselves and their diet, everyone would be fine." Today I reject that logic and the hubris that fostered it.
In the business world we know that the wrong strategy, no matter how well implemented, gives us little chance of success. Similarly, the right strategy, if poorly executed, often fails. What we need is the right strategy first and then the right execution second. At the moment, it's hard to argue that we're not failing with at least one of these two tasks. The question is which one.
Much of the discussion around this topic focuses on the execution; little attention is paid to the strategy or underlying insights that form the basis of the intervention.
Just 40 years ago the prevalence of obesity in this country was about one-third of what it is today, and that of diabetes about one-fifth. Is this all because Americans have become too gluttonous and slothful and the food industry figured out how to make food cheap and addictive enough? That they simply are too lazy and stubborn to do what we've been telling them to do—eat a little less, exercise a little more—for fifty years. Maybe. And I trust many good minds are already working on solutions to address that hypothesis.
However, what if the problem isn't about non-compliance but about the nature of the advice we're passing along. Maybe it's our failure in that we have a simple idea about what causes these diseases, and like many simple ideas—paraphrasing Mencken here—it just happens to be wrong. It's hard to fathom that two out of three Americans are simply too lazy to be active and too stubborn to eat healthy, despite losing their lives and their loved ones to the negative sequelae of these diseases. I find that hard to believe.
So, what if the problem is that our dietary advice is wrong in the first place? And incorrect dietary advice has resulted in an eating environment where the default for most people is a diet that causes obesity and diabetes?
If HIV or lung cancer were still spiraling out of control—as they were thirty and fifty years ago before the causes were unambiguously identified—the great minds in this country and the world would be leading investigative teams of scientists to figure out what we may have missed in our understanding of the cause of these diseases. We would not be complacent, perhaps because it would be harder to blame these diseases on the victims and their lack of will power. When we fail completely to prevent two devastating disorders for half a century, isn't it time to investigate what we might have missed—what is it about these disease states that we do not understand? If nothing else, shouldn't we hedge against the possibility—however slim you think the odds are—that we're not as smart as we think we are. Those of us who are here today because of our business acumen know the importance of hedges in business. Isn't it time we did that with obesity and diabetes?
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]]>The post Why we're not wired to think scientifically (and what can be done about it) appeared first on The Eating Academy | Peter Attia, M.D.. See the original post Why we're not wired to think scientifically (and what can be done about it).
]]>Rik just looked at me, kind of smiled, and asked the question in another way. "Peter, give me one good reason why scientific process, rigorous logic, and rational thought should be innate to our species?" I didn't have an answer. So as I proceeded to eat my curry, Rik expanded on this idea. He offered two theses. One, the human brain is oriented to pleasure ahead of logic and reason; two, the human brain is oriented to imitation ahead of logic and reason. What follows is my attempt to reiterate the ideas we discussed that night, focusing on the second of Rik's postulates—namely, that our brains are oriented to imitate rather than to reason from first principles or think scientifically.
Two points before jumping in:
Two billion years ago, we were just cells acquiring a nucleus. Two million years ago, we left the trees for caves. Two hundred thousand years ago we became modern man. No one can say exactly when language arrived, because its arrival left no artifacts, but the best available science suggests it showed up about 50,000 years ago.
I wanted to plot the major milestones, below, on a graph. But even using a log scale, it's almost unreadable. The information is easier to see in this table:
Formal logic arrived with Aristotle 2,500 years ago; the scientific method was pioneered by Francis Bacon 400 years ago. Shortly following the codification of the scientific method—which defined exactly what "good" science meant—the Royal Society of London for Improving Natural Knowledge was formed. So, not only did we know what "good" science was, but we had an organization that expanded the application, including peer review, and existed to continually ask the question, "Is this good science?"
While the Old Testament makes references to the earliest clinical trial—observing what happened to those who did or did not partake of the "King's meat"—the process was codified further by 1025 AD in The Canon of Medicine, and formalized in the 18th century by James Lind, the Scottish physician who discovered, using randomization between groups, the curative properties of oranges and lemons—vitamin C, actually—in treating sailors with scurvy.
The concept of statistical significance is barely 100 years old, thanks to Ronald Fisher, the British statistician who popularized the use of the p-value and proposed the limits of chance versus significance.
Well, consider that for 2 million years we have been evolving—making decisions, surviving, and interacting—but for only the last 2,500 years (0.125% of that time) have we had "access" to formal logic, and for only 400 years (0.02% of that time) have we had "access" to scientific reason and understanding of scientific methodologies.
Whatever a person was doing before modern science—however clever it may have been—it wasn't actually science. And along the same vein, how many people were practicing logical thinking before logic itself was invented? Perhaps some were doing so prior to Aristotle, but certainly it was rare compared to the time following its codification.
Options for problem solving are limited to the tools available. The arrival of logic was a major tool. So, too, was the arrival of the scientific method, clinical trials, and statistical analyses. Yet for the first 99.98% of our existence on this planet as humans—literally—we had to rely on other options—other tools, if you will—for solving problems and making decisions.
So what were they?
If it's 3,000 BC and your tribe mate Ugg never gets sick, all you can do to try to not get sick is hang out where he hangs out, wear similar colors, drink from the same well—replicate his every move. You are not going to figure out anything from first principles because that isn't an option, any more than traveling by jet across the Pacific Ocean was an option. Nothing is an option until it has been invented.
So we've had millions of years to evolve and refine the practice of:
Step 1: Identify a positive trait (e.g., access to food, access to mates),
Step 2: Mimic the behaviors of those possessing the trait(s),
Step 3: Repeat.
Yet, we've only had a minute fraction of that time to learn how to apply formal logic and scientific reason to our decision making and problem solving. In other words, evolution has hardwired us to be followers, copycats if you will, so we must go very far out of our way to unlearn those inborn (and highly refined) instincts to think logically and scientifically.
Recently, neuroscientists (thanks to the advent of functional MRI, or fMRI) have been asking questions about the impact of independent thinking (something I think we would all agree is "healthy") on brain activity. I think this body of research is still in its infancy, but the results are suggestive, if not somewhat provocative.
To quote the authors of this work, "if social conformity resulted from conscious decision-making, this would be associated with functional changes in prefrontal cortex, whereas if social conformity was more perceptually based, then activity changes would be seen in occipital and parietal regions." Their study suggested that non-conformity produced an associated "pain of independence." In the study subjects the amygdala became most active in times of non-conformity, suggesting that non-conformity—doing exactly what we didn't evolve to do—produced emotional distress. From an evolutionary perspective, of course, this makes sense. I don't know enough neuroscience to agree with their suggestion that this phenomenon be titled the "pain of independence," but the "emotional discomfort" being different—i.e., not following or conforming—seems to be evolutionarily embedded in our brains.
Good solid thinking is really hard to do as you no doubt realize. How much easier is it to economize on all this and just "copy & paste" what seemingly successful people are doing? Furthermore, we may be wired to experience emotional distress when we don't copy our neighbor! And while there may have been only 2 or 3 Ugg's in our tribe 5,000 years ago, as our societies evolved, so too did the number of potential Ugg's (those worth mimicking). This would be great (more potential good examples to mirror), if we were naturally good at thinking logically and scientifically, but we've already established that's not the case. Amplifying this problem even further, the explosion of mass media has made it virtually, if not entirely, impossible to identify those truly worth mimicking versus those who are charlatans, or simply lucky.
So we have two problems:
As I alluded to at the outset of this post, I find myself getting frustrated, often, at the lack of scientific literacy and independent, critical thought in the media and in the public arena more broadly (e.g., politics). But, is this any different than being upset that Monarch butterflies are black and orange rather than yellow and red? Marcus Aurelius reminds us that you must not be surprised by buffoonery from buffoons, "You might as well resent a fig tree for secreting juice."
While I'm not at all suggesting people unable to think scientifically or logically are buffoons, I am suggesting that expecting this kind of thinking as the default behavior from people is tantamount to expecting rhinoceroses not to charge or dogs not to bark—sure it can be taught with great patience and pain, but it won't be easy in short time.
(By the way, I am not suggesting at all that anyone who disagrees with my views or my interpretations of data frustrates me. I have countless interactions with folks whom I respect greatly but who interpret data differently from me. This is not the point I am making, and these are not the experiences that frustrate me. Healthy debate is a wonderful contributor to scientific advancement. Blogging probably isn't. My point is that critical thought, logical analysis, and an understanding of the scientific method are completely foreign to us, and if we want to possess these skills, it requires deliberate action and time.)
I think I know the answer, but I'm not sure how to explain it simply. Today, most lean people are what I would call "genetically immune" with respect to obesity, or largely so. Sure, many of us are not—I certainly know my "natural" state, which is anything but lean—but those of us who have found a path to being lean and healthy despite our natural tendency are actually the exception. After all, less than 10 percent of people who lose more than 10 percent of their weight will maintain this weight loss for more than a year.
If you consider someone like my wife, who can eat whatever she wants, copying her doesn't do much good. And I would argue that most habitually lean folks today—basically those who have demonstrated they have the genotype to produce a lean phenotype despite the default food environment we live in—can sort of do whatever they want. (Can you just hear Napoleon Dynamite saying, "Lucky…")
Now, I'm making this up, because I have no way of knowing, but I'm assuming that of the "lean" folks, 75% are pretty much going to be lean no matter what they do/eat (i.e., my wife). The remaining 25% are folks like me (and maybe you) who have figured out what works for them, but it's not default eating. Think of the signal-to-noise ratio in this system! It's horrible.
The 75% are doing anything and everything, right? They can (certainly my wife can) eat junk food all day and still be lean. The 25%, conversely, can't do that, but they have their own "special sauce"—for example, I can't really eat carbohydrates that aren't fruits or vegetables, while another guy in the 25% has a completely different diet. Some of these folks might be doing great on a vegan diet, while others do masterfully on the Atkins diet. And everything in between.
How does the overweight person copy that? Where do they even begin? Well, assume they decide to copy my wife. That's probably not going to end up well. Next they decide to copy me. Well, that may work, but it may not. Even if it does, they are just as likely to see another person in the 25% group doing something completely orthogonal to what I'm doing. Because the pace of meaningful fat loss is long and slow (for a quick refresher on the pace, give this post a quick skim), it's very easy to "jump ship" from one strategy (i.e., imitated behavior) to another. And so the vicious cycle continues.
I've suggested that we aren't wired to be good critical thinkers, and that this poses problems when it comes to our modern lives (of which nutrition is but one example). The just-follow-your-peers-or-the-media-or-whatever-seems-to-work approach simply isn't good enough anymore.
But is there a way to overcome this?
I don't have a "global" (i.e., how to fix the world) solution for this problem, but the "local" (i.e., individual) solution is quite simple provided one feature is in place: a desire to learn. I consider myself scientifically literate. Sure, I'll never be one-tenth a Richard Feynman, but I "get it" when it comes to understanding the scientific method, logic, and reason. Why? I certainly wasn't born this way. Nor did medical school do a particularly great job of teaching it. I was, however, very lucky to be mentored by a brilliant scientist, Steve Rosenberg, both in medical school and during my post-doc. Whatever I have learned about thinking scientifically I learned from him. (And that which I don't yet know is because I wasn't patient enough to learn.) In other words, I was mentored in this way of thinking just as every other person I know who thinks this way was also mentored. One of my favorite questions when I'm talking with (good) scientists is to ask them who mentored them in their evolution of critical thinking.
Two relevant asides:
Back to my point: the good news is that while we aren't born with this ability, we can learn it.
You may ask, is learning to think critically any different than learning to play an instrument? Learning a new language? Learning a physical skill like tennis? I don't think so. Sure, some folks may be predisposed to be better than others, even with equal training, but virtually anyone can get "good enough" at a skill if they want to put the effort in. The reason I can't play golf is because I don't want to, not because I lack some ability to learn it.
If you're reading this, and you're saying to yourself that you want to increase your mastery of critical thinking, I promise you this much—you can do it if you're willing to do the following:
I look forward to seeing the comments on this post, as I suspect many of you will have excellent suggestions for reading materials for those of us who want to get better in our critical thinking and reasoning. I'll start the list with a few of my favorites, in no particular order:
I'm looking forward to other recommendations.
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]]>After dinner, my friend, who I dine with almost every time I'm in NYC, made a comment about how many vegetables and how much fruit I consumed.
I had the following: a chopped salad, tuna tartare, a 12 oz filet; and we split an order of sautéed onions, brussels sprouts, and a bowl of berries.
He asked, "How are you able to stay in ketosis with all of those carbs?" I responded, basically, that for the past few months I have not been consistently in ketosis, and when I am it's only following a long bike ride where my BHB levels may get back into the 2-3 mM range. Most days, however, I live in the 0.3 to 0.8 mM range, depending on the time of day. (In my mind, to reap the benefits of nutritional ketosis, one probably needs to consistently be in the 1-3 mM range, and for some "applications" 3-4 mM is probably ideal.)
So what gives, you may be thinking. Is Peter Attia not Mr. Ketosis? Well, my friend suggested it might be time for another one of the dreaded what-do-I-eat posts.
Anyone who knows me or who has read this blog for a while will appreciate the fact that I loathe talking about what I eat. Why? Because, it unfortunately gets interpreted by many as what they should eat. It's like asking me what exercises I do, and inferring you should do the same. It doesn't make sense. I have specific genetic factors, epigenetic alterations, and goals. These factors coalesce to shape my behavior – how I exercise, what I eat, what I supplement.
In September of last year, for my wife's birthday, we went to our favorite restaurant in San Diego, where we live. The day before I emailed the owner and general manager, both friends, and asked for them to have one of our favorite off-menu items on hand (the best sushi in San Diego). They happily obliged and asked which of their desserts my wife would most like. I said something to the effect of: well, they are all great, so you pick.
The next evening, after eating more sushi and sashimi than I could imagine (I ate 3 platters myself), they brought out a platter with a full size serving of each of their signature SIX desserts, each with a lit candle. We sang Happy Birthday, blew out the candles, and my daughter and wife, themselves already stuffed, proceeded to have a small forkful of each of the six desserts. My daughter said, "Daddy, these are so yummy! Why don't you have a bite?" To which my wife echoed, "Yea, they really are ridiculous…"
And in that instant, I made a decision. I did something I had not done in 4 years (to the month, actually). The decision was this: about 3 or 4 times a year (I opted for my wife's and daughter's birthdays, Thanksgiving, and maybe something else), I would – for one meal – eat whatever the hell I wanted.
In the next 15 minutes I devoured the remaining 4/5-ths of EACH of the six culinary masterpieces in front of me. From cheesecake, to carrot cake, to decadent ice cream, and stuff I didn't even recognize, I ate it. In an instant I felt both wonderful and horrible. The look on my wife's and daughter's faces – alone – was worth it. Their jaws on the table the whole time. The taste was beyond what I remembered (actually, much sweeter than I remembered, probably because when you don't eat sugar for 4 years, well, you know).
I could barely get up from the table. That night, when we got home, I had a horrible headache. 1,000 mg of Tylenol and 2 glasses of water later, I still couldn't sleep. I eventually got a few winks of sleep. The next day I felt hung over – a feeling I had not experienced since my 26th birthday. My fasting glucose was 126 mg/dL and BHB was 0.2 mM. Clearly I was out of ketosis.
I decided to go out for a glycogen-depleting workout (multiple sets of 3 min all out intervals on the bike) and about 36 hours later, after resuming my normal diet, I was right back into ketosis and felt just fine. I told my wife I was going to repeat this experience on Thanksgiving. As such, and despite how far in advance this was, I asked her to plan to make an extra bowl of my favorite Thanksgiving dish – candied sweet potatoes – baked sweet potatoes coated in melted marshmallows.
Thanksgiving came and went, and I repeated the same act of debauchery during the big feast. Sure enough, by the Sunday morning of Thanksgiving weekend, I felt back to my baseline. I haven't gone on a bender like that since, but I'm probably due for one.
I'm sure at least some of you are asking, "Does Peter still think sugar is metabolically deranging?" The answer is absolutely, at the levels it is consumed by most Americans. If you want a refresher on my point of view on sugar, definitely give this post a re-read.
Somewhere between "every day" and "never" there is a tolerance I have developed to consume massive amounts of carbohydrates, and specifically sugar. Now, there are two components to this: a purely physiologic one and a behavioral one (which I suspect is heavily influenced by my physiology).
Focusing just on the physiology, I would guess I could probably "tolerate" a binge like that every few weeks with little measurable or discernable adverse effect. I won't even attempt to argue whether it's every 7 days, every 14 days, or every 30 days. But, it's probably somewhere in that vicinity.
What about the behavioral side? Well, I suspect there exists a different "frequency distribution function" that describes how often I could binge like this without resuming unhealthy eating habits in the long run. If I had to guess, I think the threshold for recidivism is higher from the behavioral tipping point than it is for the physiologic one. In other words, habits matter. I can probably tolerate – physiologically – more sugar today than I can tolerate behaviorally.
One last point I'd be remiss to leave out. You should keep in mind that for a period of 4 years, my consumption of sugar (sucrose, HFCS, liquid fructose in the form of any beverage, etc.) has been less than about 5 grams per day. The average American, depending on which stats you believe (I think they are all pretty weak), consumes somewhere in the neighborhood of 100 to 120 grams per day of sugar, NOT including the liquid fructose in juice!
So, I have to at least entertain the hypothesis that 4 years of avoiding sugar has been a sufficient enough period of time to offer me some sort of "metabolic reset." Now, I have no intention of testing this. If I was once susceptible to insulin resistance, I'm pretty sure I will always be. But, an interesting Gedankenexperiment would have me going back to one of several different dietary patterns – vegan, but with no sugar; standard American diet with lots of sugar; modestly higher carb, but still sugar-restricted – all could offer insights into the physiology of adiposity and fuel partitioning in my metabolically reset condition.
Sometime early in the New Year, I started really craving more vegetables. I've always loved them. Even in ketosis I still ate one or two salads each day most days, but I was pretty restrictive about the quantity of vegetables that had much carbohydrate in them (e.g., tomatoes, carrots). But now, I wanted even more. Big heaping bowls of curry stir-fry. (I have to toot my horn on this one thing. I make a really good, creamy, spicy curry stir-fry.) I realized this would probably knock me out of ketosis, especially with the large amount of tofu I mix with it and the yogurt I use to make the sauce.
My lunchtime salads were getting bigger and bigger, and I was piling more and more "stuff" into them. Almost laughable by the standards of those around me.
And I noticed I was eating less meat. Not at all by "design," but somehow by seemingly craving less. It seemed an average week would have maybe 2 servings of red meat. When a great steak is placed in front of me, believe me, I enjoy every bite, but I found I just wanted it less. I also started craving a bit more fruit, especially berries and even apples, the former I consumed in modest amounts in ketosis, the latter I did not at all. (Because I know someone will ask – do I think red meat is harmful? – the answer is no, I do not believe so. Certainly not based on evidence I've seen to date, including the recent story about protein. For those looking to brush up on the state of evidence implicating red meat, I'd recommend three posts – one I wrote many moons ago in response to one of the dozen epidemiology stories, one written by Chris Masterjohn in response to the TMAO data, and one recently by Zoe Harcombe in response to the protein epidemiology).
I don't know what to make of this, of course, and it may be nothing at all, other than an evolution of preference. I've checked mineral levels in my body in search of a clue (none showed up). Maybe I'm over- or under-saturated in some key nutrient?
Now, since everyone seems to care how much carbohydrate I consume, here is my current framework. I put carbohydrates into 5 essentially MECE categories:
Below is a "typical" 5 days of eating over the past few months. Keep in mind, I virtually never consume breakfast, maybe once a month (e.g., if I have a breakfast meeting). Essentially, I do all of my exercise (current routine, below) in a fasted state only consuming the BioSteel's high performance sports drink (HPSD), which contains virtually no calories – maybe 8 kcal of BCAA per serving. So, despite the dietary changes I've made, and the fact that I'm not in ketosis most of the time, I remain seemingly well fat adapted, though RQ is a bit higher than before.
I should point out that I spend much less time exercising than I have historically, due to time constraints. But, I still aim for the following schedule, which is interrupted by travel during at least 2 or 3 weeks each month. The schedule below amounts to about 14 to 16 hours per week of training.
Monday – high intensity lift, followed by swim
Tuesday – ride (tempo)
Wednesday – swim
Thursday – ride (TT practice or threshold)
Friday – high intensity lift
Saturday – ride (VO2 max intervals), followed by swim
Sunday – group ride or solo TT practice
I can't believe I'm about to do this…I just have this horrible feeling someone is going to attempt to replicate this, bite-for-bite, for no good reason. Please refrain. Remember, this is what I eat because of how my body works.
Lunch – huge salad (bowl larger than my head) with romaine lettuce, kale, carrots, tomatoes, cucumbers, olives, mushrooms, chicken breast, 2 tbsp olive oil, 3 tbsp lemon juice, 1 tbsp white vinegar, 1 cup of almond slivers
Snack – a cup of macadamia nuts
Dinner – Another large salad, but no chicken or nuts in this one; 1 pound of salmon; bowl of berries to follow
Lunch – huge salad (bowl larger than my head) with romaine lettuce, kale, carrots, tomatoes, cucumbers, olives, mushrooms, can of tuna, 2 tbsp olive oil, 3 tbsp lemon juice, 1 tbsp white vinegar, 1 cup of walnuts
Snack – 2 or 3 tbsp of almond butter (a zero sugar variety)
Dinner – Omelet made from 6 eggs (white + yellow), shredded cheddar, lots of other veggies; side of steamed broccoli in butter; 2 more spoons of almond butter after dinner
Lunch – same as Wednesday (I basically rotate salad back and forth about 3:1 in favor of chicken over tuna)
Snack – none
Dinner – Curry stir-fry containing tofu, carrots, broccoli, bell peppers, mushrooms, zucchini, and squash, in a sauce made from curry paste and Greek yogurt. I typically consume two heaping plates of this.
Saturday (post ride and swim)
Lunch – 7 hardboiled eggs, an avocado, 2 oz of cheese
Snack – a Fuji apple covered in almond butter
Dinner – 8 oz of steak (fillet, rib-eye, or tri-tip), 8 oz of salmon, large salad (sans meat and nuts, which I only do with lunch salads).
Sunday (post longer ride)
Lunch – The "Peter Kaufman" super starch shake (heavy cream, zero-sugar almond milk, a package of chocolate super starch, 2 tbsp of almond butter, an extra 20 g of Biosteel whey protein, frozen strawberries, ice – blend to a thick shake); I'll drink 2 liters of this. Literally.
Snack – none
Dinner – Family sushi night! I'll have a seaweed salad or two, huge platter of sashimi, California roll, and another specialty roll.
Lastly, because I know someone will ask, the few times I now take to measure, record, and tabulate exactly what I consume, it works out to about 3,500 kcal per day. But some days, especially when I travel, it can be as low as 2,000 kcal when I only consume one meal per day (dinner). Other days it can be as high as 5,000 kcal. But, 3,300 to 3,600 kcal per day is the typical range.
So, there you have it – the most irrelevant information you're likely to find on this blog (except for what's below… this is actually valuable stuff!)
While in NYC I realized – about 15 minutes before leaving my hotel for a very important meeting – that I had forgotten to bring cufflinks. My heart sank. I've never made this mistake before. I immediately realized why. While packing, and just about as I was going to grab a set, my phone rang and I was distracted. But that was neither here nor there. What was I going to do? I didn't have time to buy a new set, and the hotel concierge didn't have a set to lend me, so I grabbed some dental floss and tied the cuffs of my shirt together using precise surgical knots. I was pretty self-conscious that someone would notice and ask or comment, especially on a day stacked with so many back-to-back important meetings. Amazingly, no one said anything, though I could see some people looking at them and doing the double-take. Over that lovely steak dinner I alluded to at the top of this post, I told this story to my friend (who snapped the picture, below). His response? "Yea, I noticed it right away. I thought it was a new style. Very cool, actually. Kind of European." So there you have it. Don't say I never shared anything of value on this blog.
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]]>Before jumping into this topic I want to be sure all readers — regardless of background — have a pretty good understanding of the 'basics' about cancer and metabolism. In an effort to do this efficiently, I'll list concepts here, such that folks can skip them if they want to, or refer back as necessary. This way, I don't need to disrupt the 'story' with constant definitions. (Yes, I realize this is sort of cheating on my 1,000 word promise.)
Cancer – a collection of cells in our bodies that grow at roughly normal speeds, but that do not respond appropriately to cell signaling. In other words, while a collection of 'normal' cells will grow and stop growing in response to appropriate messages from hormones and signals, cancer cells have lost this property. Contrary to popular misconception, cancers cells do not grow especially fast relative to non-cancer cells. The problem is they don't 'know' when to stop growing.
Metabolism – the process of converting the stored energy in food (chemical energy contained mostly within the bonds of carbon and hydrogen atoms) into usable energy for the body to carry out essential and non-essential work (e.g., ion transport, muscle contraction).
ATP – adenosine triphosphate, the 'currency' of energy used by the body. As its name suggests, this molecule has three (tri) phosphates. Energy is liberated for use when the body converts ATP to ADP (adenosine diphosphate), by cutting off one of the phosphate ions in exchange for energy.
Glucose – a very simple sugar which many carbohydrates ultimately get broken down into via digestion; glucose is a ring of 6-carbon molecules and has the potential to deliver a lot, or a little, ATP, depending on how it is metabolized.
Fatty acid – the breakdown product of fats (either those stored in the body or those ingested directly) which can be of various lengths (number of joined carbon atoms) and structures (doubled bonds between the carbon atoms or single bonds).
Aerobic metabolism – the process of extracting ATP from glucose or fatty acids when the demand for ATP is not too great, which permits the process to take place with sufficient oxygen in the cell. This process is highly efficient and generates a lot of ATP (about 36 units, for example, from one molecule of glucose) and easy to manage waste products (oxygen and carbon dioxide).
The process of turning glucose and fatty acid into lots of ATP using oxygen is called 'oxidative phosphorylation.'
Anaerobic metabolism – the process of extracting ATP from glucose (but not fatty acids) when the demand for ATP is so great that the body cannot deliver oxygen to cells quickly enough to accommodate the more efficient aerobic pathway. The good news is that we can do this (otherwise a brief sprint, or very difficult exertion would be impossible). The bad news is this process generates much less ATP per carbon molecule (about 4 units of ATP per molecule of glucose), and it generates lactate, which is accompanied by hydrogen ions. (Contrary to popular belief, it's the latter that causes the burning in your muscles when you ask your body to do something very demanding, not the former).
Mitochondria – the part of the cell where aerobic metabolism takes place. Think of a cell as a town and the mitochondria as the factory that converts the stored energy into usable energy. If food is natural gas, and usable energy is electricity, the mitochondria are the power plants. But remember, mitochondria can only work when they have enough oxygen to process glucose or fatty acids. If they don't, the folks outside of the factory have to make due with suboptimally broken down glucose and suboptimal byproducts.
DNA – deoxyribonucleic acid, to be exact, is the so-called "building block" of life. DNA is a collection of 4 subunits (called nucleotides) that, when strung together, create a code. Think of nucleotides like letters of the alphabet. The letters can be rearranged to form words, and words can be strung together to make sentences.
Gene – if nucleotides are the letters of the alphabet, and DNA is the words and sentences, genes are the books – a collection of words strung together to tell a story. Genes tell our body what to build and how to build it, among other things. In recent years, scientists have come to identify all human genes, though we still have very little idea what most genes 'code' for. It's sort of like saying we've read all of War and Peace, but we don't yet understand most of it.
FDG-PET – a type of 'functional' radiographic study, often called a 'pet scan' for short, used to detect cancer in patients with a suspected tumor burden (this test can't effectively detect small amounts of cancer and only works for 'established' cancers). F18 is substituted for -OH on glucose molecules, making something called 2-fluoro-2-deoxy-D-glucose (FDG), an analog of glucose. This molecule is detectable by PET scanners (because of the F18) and shows which parts of the body are most preferentially using glucose.
Phosphoinositide 3-kinase – commonly called PI3K (pronounced "pee-eye-three-kay"), is an enzyme (technically, a family of enzymes) involved in cell growth and proliferation. Not surprisingly, these enzymes play an important role in cancer growth and survival, and cancer cells often have mutations in the gene encoding PI3K, which render PI3K even more active. PI3Ks are very important in insulin signaling, which may in part explain their role in cancer growth, as you'll see below.
In 1924 a scientist named Otto Warburg happened upon a counterintuitive finding. Cancer cells, even in the presence of sufficient oxygen, underwent a type of metabolism cells reserved for rapid energy demand – anaerobic metabolism. In fact, even when cancer cells were given additional oxygen, they still almost uniformly defaulted into using only glucose to make ATP via the anaerobic pathway. This is counterintuitive because this way of making ATP is typically a last resort for cells, not a default, due to the very poor yield of ATP.
This observation begs a logical question? Do cancer cells do this because it's all they can do? Or do they deliberately 'choose' to do this? I'm not sure the answer is entirely clear or even required to answer the macro question I've posed in this post. However, being curious people we like answers, right?
The first place to look is at the mitochondria of the cancer cells. Though not uniformly the case, most cancers do indeed appear to have defects in their mitochondria that prevent them from carrying out oxidative phosphorylation.
Cancer cells, like any cells undergoing constant proliferation (recall: cancer cells don't stop proliferating when told to do so), may be optimizing for something other than energy generation. They may be optimizing for abundant access to cellular building blocks necessary to support near-endless growth. In this scenario, a cancer would prefer to rapidly shuttle glucose through itself. In the process, it generates the energy it needs, but more importantly, it gains access to lots of carbon, hydrogen, and oxygen atoms (from the breakdown of glucose). The atoms serve as the necessary input to the rate-limiting step of their survival — growth. The selection of cancer cells is based on this ability to preferentially grow by accessing as much cellular substrate as possible.
Cells become cancerous because they undergo some form of genetic insult. This insult – damage to their DNA – has been shown to result in the turning off of some genes (those that suppress tumor growth) and/or the activation of other genes (those that promote cell growth unresponsive to normal cell-signaling). Among other things, this damage to their DNA also damages their mitochondria, rendering cancer cells unable to carry out oxidative phosphorylation. So, to survive they must undergo anaerobic metabolism to make ATP.
Whichever of these is more accurate, the end result appears the same – cancer cells almost exclusively utilize glucose to make ATP without the use of their mitochondria. A detailed discussion of which explanation is better is beyond the scope of my word allotment, and it's not really the point I want to make. The point is, cancer cells have a metabolic quirk. Regardless of how much oxygen and fatty acid they have access to, they preferentially use glucose to make ATP, and they do it without their mitochondria and oxygen.
So, can this be exploited to treat or even prevent cancer?
One way this quirk has been exploited for many years is in medical imaging. FDG-PET scans are a useful tool for non-invasively detecting cancer in people. By exploiting the obligate glucose consumption of cancer cells, the FDG-PET scan is a powerful way to locate cancer (see figure).
You can probably tell where I'm leading you. What happens if we reduce the amount of glucose in the body? Could such an intervention 'starve' cancer cells? An insight into this came relatively recently from an unlikely place – the study of patients with type 2 diabetes.
In the past few years, three retrospective studies of patients taking a drug called metformin have shown that diabetic patients who take metformin, even when adjusted for other factors such as body weight and other medications, appear to get less cancer. And when they do get cancer, they appear to survive longer. Why? The answer may lie in what metformin does. Metformin does many things, to be clear, but chief among them is activating an enzyme called AMP kinase, which is important in suppressing the production of glucose in the liver (the liver manufactures glucose from protein and glycerol and releases it to the rest of the body). This drug is used in patients with diabetes to reduce glucose levels and thereby reduce insulin requirement.
So, the patients taking metformin may have better cancer outcomes because their glucose levels were lower, or because such patients needed less insulin. Insulin and insulin-like growth factor (IGF-1) also appear to play an integral role in cancer growth as recently demonstrated by the observation that people with defective IGF-1 receptors appear immune to cancer. Or, it may be that activation of AMP kinase in cancer cells harms them in some other way. We don't actually know why, but we do know that where there is smoke there is often fire. And the 'smoke' in this case is that a relatively innocuous drug that alters glucose levels in the body appears to interfere with cancer.
This may also explain why most animal models show that caloric restriction improves cancer outcomes. Though historically, this observation has been interpreted through the lens of less 'food' for cancer. A more likely explanation is that caloric restriction is often synonymous with glucose reduction, and it may be the glucose restriction per se that is keeping the cancer at bay.
Fortunately this paradigm shift in oncology – exploiting the metabolic abnormality of cancer cells – is gaining traction, and doing so with many leaders in the field.
Over a dozen clinical trials are underway right now investigating this strategy in the cancers that appear most sensitive to this metabolic effect – breast, endometrial, cervical, prostate, pancreatic, colon, and others. Some of these trials are simply trying to reproduce the metformin effect in a prospective, blinded fashion. Other trials are looking at sophisticated ways to target cancer by exploiting this metabolic abnormality, such as targeting PI3K directly.
To date, no studies in humans are evaluating the therapeutic efficacy of glucose and/or insulin reduction via diet, though I suspect that will change in the coming year or two, pending outcomes of the metformin trials.
Check out this blast from the past! Gary Taubes, who is currently working hard on his next book, came across the article the other day from 1887.
I've been absurdly blessed to study this topic at the feet of legends, and to be crystal clear, not one thought represented here is original work emanating from my brain. I'm simply trying to reconstruct the story and make it more accessible to a broader audience. Though I trained in oncology, my research at NIH/NCI focused on the role of the immune system in combating cancer. My education in the metabolism of cancer has been formed by the writings of those below, and from frequent discussions with a subset of them who have been more than generous with their time, especially Lewis Cantley (who led the team that discovered PI3K) and Dominic D'Agostino.
I do plan to continue exploring this topic, but for those of you who want to know more right now and/or for those of you with an appetite for depth, I recommend the following articles, some technical, some not, but all worth the time to read. This is the short list:
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]]>The post A podcast to ring in the New Year appeared first on The Eating Academy | Peter Attia, M.D.. See the original post A podcast to ring in the New Year.
]]>The interview doesn't start until about minute 17 or 18 of the podcast, so you'll probably want to start there, if not a bit later (say, minute 20 or so) once the intro is over. We talk about a lot of things, in particular, physical performance and fat adaptation. Vinnie and Anna were very gracious in letting me give the nuanced answers I like to give. And for that I'm appreciative.
The reason I'm posting this is because I'm planning to write a post on this elusive concept of fat adaptation – which I know many of you have asked about – and I think this interview introduces the concept reasonably well (albeit in a somewhat elaborate and technical fashion).
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]]>The post Got grit? appeared first on The Eating Academy | Peter Attia, M.D.. See the original post Got grit?.
Now, I don't know if everything Ms. Duckworth says or suggests is correct. Her work is well outside of my area of knowledge. But it's a topic I think about so much, and since watching this video I've been reflecting on my life and the implications of this idea to our health.
Shortly after my twelfth birthday, boxing fans around the world were given a gift unlike anything before or since, the showdown between Marvelous Marvin Hagler and Tommy Hearns (don't watch this unless you can handle a violent boxing match). To this day most boxing experts agree the first round of that 3 round war remains one of the — if not the — greatest round in boxing history. I was a huge Hagler fan, and this fight galvanized in me two things:
You see, I was not the fastest when it came to hand speed or foot speed. My punching power was good, but not George Foreman or Sonny Liston good. There was no special "gift" or talent I had that was ever going to make me the next Mohammed Ali or Mike Tyson. But, Hagler didn't seem to possess any God-given ability and, in my 12-year-old opinion, he was the greatest fighter on Earth. Sure, Sugar Ray Leonard was the media darling and wealthiest fighter of the era, but Hagler was the grittiest. (Anyone tempted to point out that Leonard was awarded the split-decision over Hagler when they met in 1987 need not bother. In my mind – and the mind of many — Hagler won 115-113. If you want to read more, here's a great summary.) He out-trained everyone. He never got out of shape between fights. He was always ready for combat. He was pure grit.
So, this became the defining feature and mantra of my youth. No one was going to out-grit me. I would run 6 to 10 miles at 4:30 in the morning (imagine how dark and cold that was in Canada) because I knew the other guy was still sleeping. I did 400 push-ups every single night (except one night in 11th grade when I was too sick to move) before bed from age 13 to 18 because I knew the other guy would not.
When I did decide, ultimately, to go to college instead of pursuing a career as a professional fighter (something I attribute to the most influential teacher in my life), it was such an easy transition, because I had already built a mental and emotional infrastructure of grit.
Perhaps because of some deep insecurity I always felt the need to out-grit everyone at everything, even surgery. In residency, while my peers would (rationally) try to catch a nap any time there was a free moment during call nights, I would practice anastomosing 3 mm Dacron grafts together with 8-0 proline, over and over again. I even built a model heart with a deep mitral valve to practice – a hundred times a day – one of the most difficult stitches in surgery, the "A-to-V" and "V-to-A" sutures through the mitral annulus.
You get the picture. I was (and remain) a freak. The 'why' is beyond me, though I've never stopped trying to understand it. Though my daughter is only 5, I spend a lot of time talking with her about 'mastery' and the joy that comes from the journey of mastering a skill (versus the need to seek pleasure in the outcome or final result). This is not a natural phenomenon and I think, unfortunately, most of our education is based on the result and not the process.
I've read countless books on this, both out of desire to better myself and out of a desire to ignite this spirit in my daughter, and to date the best one I've read is The Talent Code, by Daniel Coyle. It's the only book I've ever read where the moment I finished it, I turned to the first page to read it again. In this book, Coyle argues that grit – practice – may not be enough. It's necessary, but not sufficient for mastery. The other component essential for mastery is the right kind of practice — deliberate practice. This topic is worthy of a book, of course, and not just a few sentences, but suffice it to say, deliberate practice is a very specific type of practice that leads to change. Mastery. While I disagree with this writer's view that the book, Talent Is Overrated does a better job explaining the concept than The Talent Code, he provides a quick overview for those not familiar with the concept.
First, if you don't practice correctly, no amount of practice is going to achieve mastery, whether it's swimming the 200 IM or playing the piano. A disciplined approach to eating the wrong foods may be better than undisciplined approach to eating the wrong foods, but it's no substitute for the correct approach to eating the correct foods.
In 2009, when I was at the height of my unhealthiness – I was overweight, insulin resistant, and had Metabolic Syndrome – it was not because I was not 'trying hard enough' to eat well. I had all the grit in the world when it came to eating. I wanted so desperately to be lean and healthy. The problem, of course, was that I was not eating the right foods. It's the difference between gritty practice and gritty deliberate practice.
Second, let's posit you figure out what the 'right' foods are. Is this sufficient to achieve your health? Well, here I have to include not just my experience, but the experience of my friends, family, and clients. Some people, once introduced to the 'right' foods, experience almost an immediate change. The pounds melt off. Their biomarkers improve seemingly overnight. They feel rejuvenated and renewed.
Let me assure you, these folks are the exception and not the rule. For most people the pattern of going from metabolically broken to fixed, which often includes a loss of fat mass, is very slow; slow enough that on a day-to-day and even week-to-week basis it seems negligible.
To explain this, I'll use fat mass as an example, since it's the metric most people understand best. In my experience, outside of profound caloric restriction or outright starvation, the typical amount of fat loss I see in a person is about one pound per week, or about 60 g per day. That might not sound like much, and over a week or day, it's not. (Though, hold 60 g of almonds in your hand and imagine a net loss of this much fat every day from your collective fat cells, and you can start to appreciate how impressive it is physiologically!).
But, we can't track fat mass directly, at least not on our bathroom scales, and frankly not even with DEXA scans unless they are really spaced out. Certainly not at the level of a few hundred grams. Furthermore, our bodyweight – what we typically do track – fluctuates a lot. In me, for example, it fluctuates by 5 pounds per day. How, you ask? Water. Not just the difference between what I drink and what leaves my body (urine, perspiration, respiration), but also interstitial accumulation, which manifests as minute amounts of swelling, typically in muscles, and elsewhere, too, often in response to exercise, travel, stress, and even foods I eat.
So, if your bodyweight can fluctuate 5 pounds in a day, is it possible to track 60 g per day of net fat loss? It's like me blindfolding you and putting 50 pennies in your hand and asking you if there are 49, 50, or 51 there. No chance. Furthermore, 60 g is so far outside of the measurement spec of a bathroom scale that even if your weight did not fluctuate much due to fluid shifts, you would never be able to appreciate the net fat loss over the course of a few days and barely over a week.
What does this look like in real life? Consider the graph, below, which shows the actual (and completely achievable) weight loss of a person over 7 months. This person went from 227 lb to 195 lb in 7 months, which represents an average of about 4.6 lb per month, or about 69 g of net fat loss per day (as confirmed by DEXA). This was not a starvation diet or something radical. This was a change in macronutrients – from a standard American diet to a ketogenic diet — that led to a change in net fat flux. But, the change is subtle over any short period of time. It's only over months that the change becomes life-changing.
Now, imagine the day-to-day frustration this person (I know, because I was working with this person) experienced with the fluctuations in scale readings! It was tempting on many occasions to say, "Forget it, I'm going back to what I was doing before." Just like there were many days I didn't feel like going to swim practice, or days I didn't feel like deliberately practicing my surgical technique.
If you remember nothing else, remember this: the game is won – or lost – not by the infrequent big changes, but by the frequent, deliberate, and repeatable small ones. This is where grit comes in.
Sure, there are genetic freaks and lucky ones out there, for whom none of this matters. But for the rest of us – because we live in, and are surrounded by, a food environment that is chronically toxic to about two-thirds of us – re-building our bodies requires consistent and deliberate change.
Are there people with all the grit in the world who can't achieve health? Absolutely. And I put them into two categories:
I will not get into these categories in great detail, because the topic is beyond the scope of this post and, frankly, it takes me months to diagnose this in people I work with weekly. So I can't responsibly spout out blanket statements about 'fix this' or 'fix that.' However, far and away the most common causes I encounter in my practice for persistent metabolic derangement, often but not always accompanied by adiposity (excess fat), in the presence of seemingly correct eating and true grit are as follows:
Again, I'm not going to get into the nuance of these, but I list these to give those folks who believe they are A) eating the 'right' foods, and B) full of grit, yet not seeing results, some hope. These issues are fixable, but you need to see a doctor who knows how to fix them.
Fortunately, such situations are very rare! Most people, with the correct dietary intervention, armed with sufficient grit, and the confidence to stay the course, despite the day-to-day and week-to-week fluctuations, will emerge as renewed people.
Unfortunately, as long we live in a world where (i) the conventional wisdom, (ii) dietary recommendations, and (iii) the market forces enabled by them create an eating environment that is not suited to what most of us should eat, we need to guard against the desire to give up when the results are not what we expect in the timeframe we expected. As a result, about 90% of people who make a dietary change – and even see results – end up gaining the weight back. Why? I suspect it's a bit of what I've written about here, and two other phenomena:
In the former, folks get very discouraged when they make a 'mistake.' Rather than immediately getting back on the program, they get frustrated, and over time – sometimes quickly, sometimes slowly – revert back to their old eating habits.
In the case of the latter, there is this belief that once the goal is achieved, one need not continue the practice. It's like me training for a year to win a time-trial race on my bike, winning the race, and then deciding I don't need to train anymore and I can still compete successfully. Not going to happen. If I want to win, I need to train. If I'm going to train, I need to train deliberately and persistently. Even on the days I don't want to. When I miss a workout or have a bad one, I can't beat myself up over it. I have to let it go and remember that tomorrow is a new day. The sum of my days determines my success.
Parenthetically, the figure I used at the top of this post was borrowed from a blog featuring a very inspiring story. I remember seeing this video about a year ago, completely randomly on my ipad in a taxi on my way to the airport, and thinking:
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]]>The post The War on Cancer appeared first on The Eating Academy | Peter Attia, M.D.. See the original post The War on Cancer.
]]>Over dinner that night, Tim asked me if I could write – in about 1,000 words! – a post on cancer that would be interesting and digestible to a broad audience. "1,000 words?!," I asked. "How about 30,000 words?," I responded only half kidding. After explaining why I couldn't possibly write such an abridged version, Tim talked me into it. And so, I plan to accept the challenge and hope to provide readers with such a post (it will be on Tim's blog when I do so), hopefully in the next month or two.
For an introduction, however, I'd like take a step back and place this topic in a broader context. I don't need to say much about cancer that you don't already know. You probably know that about one in three Americans will develop cancer in their lifetime, and you probably know that about half of them will succumb to the disease. What you may not know, however, is that we have made virtually no progress in extending survival for patients with metastatic solid organ tumors since the "War on Cancer" was declared over 40 years ago. In other words, when a solid organ tumor (e.g., breast, colon, pancreatic) spreads to distant sites, the likelihood of surviving today is about what it was 40 years ago with rare exceptions. We may extend survival by a few months, but not long-term (i.e., overall) survival.
We screen better today for sure, but subtracting lead-time bias, it's not clear this extends overall survival. We've had success in treating and even curing hematologic cancers (e.g., some forms of leukemia and lymphoma). Certainly testicular cancer patients (especially seminomatous) are better off today and those with GI stromal tumors (GIST), too. Surgical control of cancer is much better today and some local treatments (e.g., specific radiation), too. But for the most part, when a patient has metastatic cancer today, the likelihood of living 10 more years is virtually unchanged from 40 years ago.
About a year ago, I was asked to give a talk about metabolic disease to a group of physicians. But before I spoke, a very astute and soft-spoken oncologist, Dr. Gary Abrass, gave the following introduction as a way to frame the context of my talk. After all, I'm sure many in the audience were wondering what could a discussion of insulin resistance have to do with cancer. I have thought often of his words that night in the many months since he so eloquently and informally introduced me.
I asked Dr. Abrass if I could have a copy of his talk and share it with you, to which he kindly agreed. Below is, nearly verbatim, the talk he delivered that night. (Dr. Abrass did give me the liberty of tweaking the text a bit, for emphasis and clarity.)
On December 23, 1971, President Nixon declared war on cancer by signing the National Cancer Act. I was going to title this, "40 years in 4 minutes," but I think this will take me a bit longer. At the time I was a third year medical student. Two years before, Neil Armstrong had inflated our national pride by setting foot on the moon, and there seemed no scientific goal unachievable. Activist Mary Lasker published a full-page advertisement in The New York Times: "Mr. Nixon: You Can Cure Cancer." And she went on to quote Dr. Sidney Farber, Past President of the American Cancer Society and whose name now sits atop the Harvard Cancer Center, "We are so close to a cure for cancer. We lack only the will and the kind of money and comprehensive planning that went into putting a man on the moon." Since then, the federal government has spent well over $105 billion on the effort.
Forty years later, Dr. Farber's prophecy remains unfulfilled. In 2012 cancer killed an estimated 577,190 people in the United States. The death rate, adjusted for the size and age of the population, has decreased by only 5 percent since 1950. And most of this decline is due to mammography screening in breast cancer and cessation of smoking, resulting in less lung cancer in men.
We have however developed a greater understanding of the biological and molecular basis of cancer. When I was a medical student, this graphic summarized what we knew about the growth cycle of the cancer cell.
There was an S-phase in which DNA was synthesized, a mitotic phase when the cell divided and a G1 and G2, which to my mind stood for "gaps" in our knowledge. We added a few dozen chemotherapy drugs on this wheel, and treatment basically amounted to carpet-bombing. And for some diseases — particularly leukemias, lymphomas, and testicular cancers — it was quite effective.
The next graphic demonstrates what we have learned, a truly overwhelming accomplishment, a dizzying array of interconnecting signaling "pathways," and spawned a whole new field, "translational medicine."
Receptors have been identified on the surface of cells, which function as locks to be opened by various circulating substances (i.e., hormones) initiating a series of downstream events. Mutations in this cascade of on/off switches can promote tumor growth.
With the completion of the Human Genome Project, new sequencing technologies have also opened up the prospect of personal genome sequencing as an important diagnostic tool. A major step toward that goal was the completion of the sequencing of the full genome, first on James D. Watson, one of the co-discoverers of the structure of DNA. In fact, Steve Jobs had personal genome sequencing. The price is down to $1,000 and Mayo Clinic Proceedings recently had an article raising the concern of direct to consumer advertising for genomic sequencing. We are now able to sequence gene by gene, pathway by pathway, the genetic code of some cancers. New "smart" drugs have been developed that target various mutations in these pathways. And currently there are over 800 "targeted agents" in clinical development. These drugs have been described by some investigators as "The Holy Grail," but the clinical results suggest more of a commemorative cup for a "Happy Meal."
While there is nothing unique about this paper, it is a good example of a typical negative trial targeting the IGF-1 receptor with a monoclonal antibody. The lack of response does not make us question the role of the IGF pathway as a prime driver of malignancy, but rather demonstrates the ability of the cancer to resist therapy. It seems there is so much redundancy in the system that the cancer finds alternate pathways. The cancer cell continues to defend itself, to bob-and-weave like the arcade game "Whack-a-Mole."
So the investigators combined the IGF-1 monoclonal antibody with various other therapies: standard platinum based chemotherapy regimens, the "small molecule" tyrosine kinase inhibitor gefitinib (Iressa) targeting another common pathway (EGFR), and also the mTOR inhibitor temsirolimus (Torisel) which targets the IGF-1 pathway a bit further along. In any case, the point is, it still didn't work. But why?
Investigators have mapped the genome of a typical lung cancer patient and found over 50,000 mutations. That's a lot of targets! Granted they are not all 'driver' mutations, some are 'passenger' mutations. The patient whose genome was mapped was a 51-year-old man who'd reported smoking 25 cigarettes a day for 15 years. At 50,000 mutations, it works out to one mutation for every 2.7 cigarettes.
Last year the New England Journal of Medicine published a study by Gerlinger and colleagues. These investigators looked at intra-tumor heterogeneity. They performed a molecular dissection. They found diversity within the tumor itself. Each cancer is not cancer but, indeed, it is CANCERS. In other words "all cancers are rare cancers." Let me repeat this point. Each tumor is a collection of heterogeneous – not homogenous – mutated cells. This article has engendered some discussion and some controversy. Many say that the results of the study bring the idea of personalized medicine to a halt, or at least dramatically slow it down. Are there exceptions? Yes, but they are rare. One example of an exception to this revelation is chronic myelogenous leukemia (CML), a cancer with a known single driver mutation.
In September 2011, biologist Dr. Alasdair MacKenzie of the University of Aberdeen, speaking at the British Science Festival in Bradford, explained that researchers trying to fully understand how our DNA causes disease might not be looking in all the right parts of the genome. The past decade of genetic studies has revealed that our 3.2-billion-long-DNA-letter code is more complex than anyone could have thought. More than 98% of the human genome does not encode protein sequences. It's been referred to as "Junk DNA" and thought not to have a function, but maybe more correctly is that we do not know the function. He refers to this as the "dark matter" of the genome. And it's thought that some of these "alternate pathways", in which our resourceful cancer cell seeks refuge, may reside here. If this was not complicated enough, the new field of Epigenetics has grown exponentially resulting in a widening of the battlefield.
These are factors that can affect the expression of genes without causing mutations, turning switches on and off. In terms of cancer, much of this research has concentrated on what are called "Nononcogenic stress targets." We can stress an organism in many ways: heat, poison, starvation, suffocation or more scientifically thermal, chemical, metabolic and oxidative stress. Organisms have an ingenious way of responding to such stress. In the 1960s an assistant in FM Ritossa's lab accidentally boosted the incubation temperature of Drosophila (fruit flies), and when later examining the chromosomes, Ritossa found a "puffing pattern" that indicated the elevated gene transcription of an unknown protein.
This was later described as the "Heat Shock Response" and the proteins were termed the "Heat Shock Proteins." This same HSP increases survival under a great many pathophysiological conditions. The HSP70s are an important part of the cell's machinery for protein folding and help to protect cells from stress. While it enhances the organism's survival and longevity under most circumstances, HSF1 has the opposite effect in supporting the lethal phenomenon of cancer. These proteins enhance the growth of cancer cells and protect tumors from treatments. This remarkable protein affords a protective response to other proteins in the cell, acting as a "chaperone" preventing them from mis-folding or "denaturing," like when a boiled egg white turns opaque. These heat shock proteins are expressed at high levels in many tumor types: breast, endometrial, lung, prostate, even brain tumors. HSP overexpression signals a poor prognosis in terms of survival and response to therapy. HSP's are now on the radar as a key target in the ongoing battle. This protein folding stress response is a hot topic in current cancer research. I have been communicating with Dr. Debu Tripathy who is currently studying epigenetic changes and protein folding stress responses associated with obesity. This protein folding stress response affords the cancer cell a survival advantage, and we share this protective mechanism with a fly, such a distant relative in our family tree, that one can only conclude that the cancer cell has hijacked this maneuver, this protective drive for immortality from the legacy of 100's of millions of years of evolution…such a resourceful and formidable opponent.
In any case, when the Human Genome Project was near completion, President Clinton hosted a White House ceremony and announced that, "it will revolutionize the diagnosis, prevention and treatment of most, if not all, human diseases, and that humankind is on the verge of gaining immense new power to heal."
The hubris of it all. It's reminiscent of the quote of Sidney Farber. Hopefully this is not tempting fate. Theologians tell us the only unforgivable sin is pride. The increasing complexity of the science is affording us quite a dose of humility. British Physicist Brian Cox said that "being at the junction of the known and the unknown is a beautiful place to be for a scientist," but it seems the more we know, the more we don't know. Not unlike Winston Churchill's characterization of Russia as "a riddle wrapped in a mystery inside an enigma." Not unlike modern theoretical physics, one questions whether we are capable of understanding the complexity of the science. Hopefully it's not like trying to teach my dog quantum theory. We are so smart, but it seems that the cancer cell is smarter. It bobs and weaves, slips our punches, and when we back it into a corner, it defends itself in remarkable ways borne of millions of years of evolutionary acumen much of it hidden in the dark matter of our genome.
Maybe we should call a truce in the War on Cancer and concentrate on prevention. Besides smoking, the most preventable cause of cancer seems to be obesity. It is generally thought that obesity may account for about a third of many cancer types, particularly breast, colon, uterus, kidney and esophagus. Obesity is a risk factor for type II diabetes and these patients are not only more likely to get cancer, but to have poor outcomes. Other speakers will explore the relationship of obesity and cancer, the epidemiology and the science, and see if this lends support to any practical prevention measures.
Gary Abrass, M.D.
April 19, 2012
Just as the best way to get in shape is not to ever get out of shape, the best treatment for cancer is almost assuredly not to get cancer. And that's clearly the theme of the introduction Dr. Abrass gave me. But I'm sure many of you are asking a more important question — what happens if I or someone I care about has cancer? If you can be patient with me, I do plan to address this, to the best of my understanding, in the coming months.
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]]>The post My 10 favorite TED talks appeared first on The Eating Academy | Peter Attia, M.D.. See the original post My 10 favorite TED talks.
]]>I remember the first time I ever watched a TED talk in the summer of 2007. My first thought was, "Hey this is great. How have I never heard of these, especially since this conference has been going on since 1984?" Well, back in the 80's and 90's, and really up until about 2005 or 2006, I don't think the talks were posted online, so perhaps I can be forgiven.
If you're so inclined, I'd invite you to watch these talks over the next few weeks. (Or, if you're OCD like me, you may just watch them all in one sitting.) I hope they speak to you in the way they have spoken to me. And I hope you'll share your favorites back with me. I'm always up for a great TED talk.
Ok, so on to my list. First of all, this was very difficult to narrow down. If there is a nine-way tie for 2nd place, below, there is a 20-way tie for 3rd place (not shown). Also, picking a favorite talk is like picking a favorite food or drink. It sort of depends on what you're craving. Each of these talks means something different to me. Depending on my "need" at the moment, I guess my appetite for each one varies over time.
If you read the post I wrote after the TEDMED conference this year, you'll recall that I specifically called out my all-time favorite TED talk, that of Ric Elias. Any time and every time I feel like I'm losing sight of things, I fire up Ric's talk (or just call Ric for a pep-talk – he's that gracious with his time). Ric has become a friend and real mentor, especially as I navigate my way through fatherhood.
Ric Elias: 3 things I learned while my plane crashed
I'm not sure how I stumbled onto this talk. I actually saw it shortly after it was posted, and it has now been seen by millions. Like others, I became completely transfixed by David's story. We share a few traits, such as self-experimentation and "extreme" activity. But, I think it goes far beyond that. In fact, I know it does. What moves me when watching this talk is the passion and vulnerability he showed. I've never met David, but hope to do so one day.
David Blaine: How I held my breath for 17 min
Imagine a world with 1,000 Dean Kamen's in it? When you're done watching this, you'll get what I mean. As an engineer I can relate to the restless desire to fix things, but Dean's humanity and compassion for the men and women he wants to heal is actually palpable in this talk. Dean is on the Board of the Salk Institute, located here in San Diego, so I secretly hope to "run into" him one day when he's here. It may never happen, but I'll keep dreaming.
Dean Kamen: The emotion behind invention
About a year ago someone sent me this talk and said, "Peter, watch this…I bet it completely explains how you feel." I couldn't believe it. Susan Cain so eloquently explains what it feels like to be an introvert in a world that, at times, feels like it's designed for extroverts. Susan does such a great job explaining the distinction between introversion and shyness (anyone who knows me knows I'm far from shy, but still very introverted…this is a seemingly awkward combination for people to engage with). Watching this talk (and reading the book she wrote on the same topic) have validated many of the insecurities I have about my introversion.
Susan Cain: The power of introverts
Perhaps I would not find this talk so amazing if not for the fact that my job is running a non-profit. I must admit, I had always held to the typical beliefs of "overhead is bad!" in the non-profit world. Dan makes a very compelling case for why this anachronistic view may be impeding progress in the non-profit space. Dan is also on the list of folks I hope to meet one day.
Dan Pallotta: The way we think about charity is dead wrong
A couple of weeks before I was to give my talk at TEDMED this year, my sister emailed me this talk with the question, "Hey Pete, have you ever heard of TED? You should definitely check this out. You'll love this talk," to which I responded, "Yea, I *think* I've heard of TED…oh, yea, I have. Thanks for sending." (I didn't have the heart to be that much of a wise guy and say I was obsessed with TED and was giving a talk a few weeks later.) But coming from my sister, I knew I would like it. I simply couldn't take my eyes off the screen as Shane mixed poetry and rage in emotional appeal. I'd give anything to meet Shane one day, and I hope every kid in high school watches this.
Shane Koyczan: "To This Day" … for the bullied and beautiful
I came across this talk pretty recently, shortly after it was posted in April of this year. Some have said that a truly great TED talk engages some part of your intellect and some part of your emotion, and ideally a bit of both. The talk definitely engages my intellect. The style and rhythm of Lawrence's presentation is just amazing, and it really brings to light what I think most of us realize is a broken system in this country. He is simply a remarkable orator.
Lawrence Lessig: We the People, and the Republic we must reclaim
I saw this talk for the first time in mid-2006, I think. I had certainly heard of Tony Robbins, even back in the late-1980's, though I had never actually heard him speak. I'm not sure why, because presentations by 'professionals' don't typically appeal to me, but I find this talk really insightful. The story at the end is particularly moving.
Tony Robbins: Why we do what we do
I don't know how I came across Joshua's talk. I think I was just scrolling through recently released talks earlier this year. From the first moment, though, I was hooked. Can you imagine what he felt as he went along this journey?
Joshua Prager: In search of the man who broke my neck
Steve Levitt is a close friend, and so perhaps I'm biased in my appreciation for his work, which goes well beyond this talk or his other (equally provocative, but funnier) talk on the economics of being a crack cocaine dealer. Perhaps because I find myself among a group of people challenging conventional wisdom, I find it so enjoyable to spend time and share ideas with a guy like Steve. He sure makes a lot of enemies daring to suggest the evidence supporting the use of car seats is not as cut and dry as the "establishment" would have us believe. Sound familiar?
Steven Levitt on child carseats
The night I gave my talk at TEDMED I remember getting back to my hotel after a reception. I wasn't very happy with how my talk went and was a bit disappointed in my inability to control my emotion, which I felt may have got in the way of the message I wanted to deliver. One of the folks on the editorial staff of TEDMED called me to say 'hi,' and when I shared my disappointment with her, she suggested I watch this talk. I was amazed that I had missed it previously.
Brené Brown: The power of vulnerability
(Since I saw this talk live, at 2013 TEDMED, unlike the other 10 which I only saw on video, I think it gets its own category.)
What is so categorically brilliant about Andrew's talk is that is starts in a familiar place. You think you know where he's going and what the talk is going to be about, but he takes you on a journey that will move you to tears, especially if you're a parent. I recall telling my wife upon my return to San Diego, "Wait till you see this talk when it comes out…best talk of the 2013 conference." She said, "Oh Peter, I'm sure it's good, but your talk will always be my favorite of 2013." Then I made her watch it a month later. She stood corrected! She said, "Ok, I see what you mean. This was simply breathtaking. And better than yours by a mile."
Andrew Solomon: Love, no matter what
I think there is another reason I find Andrew's talk and, to some extent, each of these talks insightful and resonant. The experience of standing up there and giving one of these talks is not 'normal' for most of us, especially if talking about something personal as Andrew did. It's really the height of vulnerability, and I could not have appreciated this without going through it. I give talks all the time and never get nervous. Once, as a surgical resident I won an award and had to present my research to an auditorium of experts numbering over 1,000. It didn't really faze me. It was a technical talk about CD25+CD4+ T-cells and tumor regression. What's not to be comfortable about? But a talk like this was very different and, for me at least, much more difficult.
I think the world is a better place when folks can get up and share a story that may be out of their comfort zone…to share vulnerability, but doing this comes at a cost. As you know, we live in a world where anybody can hide behind their anonymous name and cartoon avatar and spew as much venom as they want at you. You bear your soul. They ambush you. And truth be told, it actually hurts.
A few weeks after my talk went up on the TED site, I found myself getting frustrated at some of the really negative comments – not just people disagreeing with my hypothesis – but outright personal attacks. I'm all for debate, but it's clear many folks can't do it respectfully on the internet where all social norms vanish. Ironically, it was clear most of these comments were written by folks who had actually missed the entire point of my talk entirely.
When I read some of the comments under Andrew's talk, it really hit home that I was far from alone in experiencing this. I was blown away at how many completely moronic, even homophobic, comments were posted in response to his talk. It was, again, so apparent that they had missed the entire point of his message. So, if a few hundred people can bastardize the message of people I respect and look up to, surely I can't be too upset when they do the same to me.
I've read a number of criticisms of TED over the past few years. But I think most of these criticisms miss the point of TED. I recall what Jay Walker said to me last year, "Peter, TED talks are not about showing the audience how smart you are. They're about trying to give people a gift…something they will remember, even if they don't necessarily agree. You want to challenge how the audience thinks, and share a different point of view." I agree with that, and I think there's even a bit more. Life is hard enough sometimes. Once in a while it feels nice to forget about whatever it is we worry about and be inspired by the stories of others.
I hope you find some inspiration in these talks.
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