title: Beneficial effects of a Paleolithic diet on cardiovascular risk factors in type 2 diabetes: a randomized cross-over pilot study Comparison of the effects of four commercially available weight-loss programmes on lipid-based cardiovascular risk factors. Body Composition Changes After Very-Low-Calorie Ketogenic Diet in Obesity Evaluated by 3 Standardized Methods AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY COMPREHENSIVE CLINICAL PRACTICE GUIDELINES FOR MEDICAL CARE OF PATIENTS WITH OBESITY. Effects of a high-protein ketogenic diet on hunger, appetite, and weight loss in obese men feeding ad libitum. A reduced ratio of dietary carbohydrate to protein improves body composition and blood lipid profiles during weight loss in adult women. The Canadian Trial of Carbohydrates in Diabetes (CCD), a 1-y controlled trial of low-glycemic-index dietary carbohydrate in type 2 diabetes: no effect on glycated hemoglobin but reduction in C-reactive protein. Comparison of weight-loss diets with different compositions of fat, protein, and carbohydrates. Comparison of low- and high-carbohydrate diets for type 2 diabetes management: a randomized trial. Long-term effects of a very-low-carbohydrate weight loss diet compared with an isocaloric low-fat diet after 12 mo. Comparative effects of very low-carbohydrate, high-fat and high-carbohydrate, low-fat weight-loss diets on bowel habit and faecal short-chain fatty acids and bacterial populations. Genetic Risk, Adherence to a Healthy Lifestyle, and Coronary Disease. Effects of the ketogenic diet on nutritional status, resting energy expenditure, and substrate oxidation in patients with medically refractory epilepsy: a 6-month prospective observational study. The effects of a low-carbohydrate diet on appetite: A randomized controlled trial. Long-term effects of a very low-carbohydrate diet and a low-fat diet on mood and cognitive function. On the relationship between ketonuria and natriuresis during fasting and upon refeeding in obese patients * Energy expenditure and body composition changes after an isocaloric ketogenic diet in overweight and obese men. Effect of low carbohydrate high fat diet on LDL cholesterol and gene expression in normal-weight, young adults: A randomized controlled study. Effects of a low carbohydrate diet on energy expenditure during weight loss maintenance: randomized trial A Very Low-Carbohydrate, Low–Saturated Fat Diet for Type 2 Diabetes Management: A Randomized Trial CONSENSUS STATEMENT BY THE AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY ON THE COMPREHENSIVE TYPE 2 DIABETES MANAGEMENT ALGORITHM - 2019 EXECUTIVE SUMMARY. Lower carbohydrate diets and all-cause and cause-specific mortality: a population-based cohort study and pooling of prospective studies. Three consecutive weeks of nutritional ketosis has no effect on cognitive function, sleep, and mood compared with a high-carbohydrate, low-fat diet in healthy individuals: a randomized, crossover, controlled trial. Interest in the Ketogenic Diet Grows for Weight Loss and Type 2 Diabetes. Effect of Low-Fat vs Low-Carbohydrate Diet on 12-Month Weight Loss in Overweight Adults and the Association With Genotype Pattern or Insulin Secretion: The DIETFITS Randomized Clinical Trial
abstract: Background Our aim was to compare the effects of a Paleolithic ( ' Old Stone Age ' ) diet and a diabetes diet as generally recommended on risk factors for cardiovascular disease in patients with type 2 diabetes not treated with insulin . Methods In a r and omized cross-over study , 13 patients with type 2 diabetes , 3 women and 10 men , were instructed to eat a Paleolithic diet based on lean meat , fish , fruits , vegetables , root vegetables , eggs and nuts ; and a Diabetes diet design ed in accordance with dietary guidelines during two consecutive 3-month periods . Outcome variables included changes in weight , waist circumference , serum lipids , C-reactive protein , blood pressure , glycated haemoglobin ( HbA1c ) , and areas under the curve for plasma glucose and plasma insulin  in the 75 g oral glucose tolerance test . Dietary intake was evaluated by use of 4-day weighed food records . Results Study participants had on average a diabetes duration of 9 years , a mean HbA1c of 6,6 % units by Mono-S st and ard and were usually treated with metformin alone ( 3 subjects ) or metformin in combination with a sulfonylurea ( 3 subjects ) or a thiazolidinedione ( 3 subjects ) . Mean average dose of metformin was 1031 mg per day . Compared to the diabetes diet , the Paleolithic diet result ed in lower mean values of HbA1c ( -0.4 % units , p = 0.01 ) , triacylglycerol ( -0.4 mmol/L , p = 0.003 ) , diastolic blood pressure ( -4 mmHg , p = 0.03 ) , weight ( -3 kg , p = 0.01 ) , BMI ( -1 kg/m2 , p = 0.04 ) and waist circumference ( -4 cm , p = 0.02 ) , and higher mean values of high density lipoprotein cholesterol ( + 0.08 mmol/L , p = 0.03 ) . The Paleolithic diet was mainly lower in cereals and dairy products , and higher in fruits , vegetables , meat and eggs , as compared with the Diabetes diet . Further , the Paleolithic diet was lower in total energy , energy density , carbohydrate , dietary glycemic load , saturated fatty acids and calcium , and higher in unsaturated fatty acids , dietary cholesterol and several vitamins . Dietary GI was slightly lower in the Paleolithic diet ( GI = 50 ) than in the Diabetic diet ( GI = 55 ) . Conclusion Over a 3-month study period , a Paleolithic diet improved glycemic control and several cardiovascular risk factors compared to a Diabetes diet in patients with type 2 diabetes . Trial registration Clinical Trials.gov NCT00435240 OBJECTIVE To investigate the relative efficacy of four popular weight-loss programmes on plasma lipids and lipoproteins as measures of CVD risk . DESIGN A multi-centred , r and omised , controlled trial of four diets - Dr Atkins ' New Diet Revolution , The Slim-Fast Plan , Weight Watchers Pure Points programme and Rosemary Conley 's ' Eat yourself Slim ' Diet and Fitness Plan - against a control diet , in parallel for 6 months . SETTING AND SUBJECTS The trial was conducted at five universities across the UK ( Surrey , Nottingham , Ulster ( Coleraine ) , Bristol and Edinburgh ( Queen Margaret University College ) ) and involved the participation of 300 overweight and obese males and females aged 21 - 60 years in a community setting . RESULTS Significant weight loss was achieved by all dieting groups ( 5 - 9 kg at 6 months ) but no significant difference was observed between diets at 6 months . The Weight Watchers and Rosemary Conley ( low-fat ) diets were followed by significant reductions in plasma LDL cholesterol ( both -12.2 % after 6 months , P < 0.01 ) , whereas the Atkins ( low-carbohydrate ) and Weight Watchers diets were followed by marked reductions in plasma TAG ( -38.2 % and -22.6 % at 6 months respectively , P < 0.01 ) . These latter two diets were associated with an increase in LDL particle size , a change that has been linked to reduced CVD risk . CONCLUSIONS Overall , these results demonstrate the favourable effects of weight loss on lipid-mediated CVD risk factors that can be achieved through commercially available weight-loss programmes . No detrimental effects on lipid-based CVD risk factors were observed in participants consuming a low-carbohydrate diet Context : Common concerns when using low-calorie diets as a treatment for obesity are the reduction in fat-free mass , mostly muscular mass , that occurs together with the fat mass ( FM ) loss , and determining the best method ologies to evaluate body composition changes . Objective : This study aim ed to evaluate the very-low-calorie ketogenic ( VLCK ) diet-induced changes in body composition of obese patients and to compare 3 different method ologies used to evaluate those changes . Design : Twenty obese patients followed a VLCK diet for 4 months .  Body composition assessment was performed by dual-energy X-ray absorptiometry ( DXA ) , multifrequency bioelectrical impedance ( MF-BIA ) , and air displacement plethysmography ( ADP ) techniques . Muscular strength was also assessed . Measurements were performed at 4 points matched with the ketotic phases ( basal , maximum ketosis , ketosis declining , and out of ketosis ) . Results : After 4 months the VLCK diet induced a −20.2 ± 4.5 kg weight loss , at expenses of reductions in fat mass ( FM ) of −16.5 ± 5.1 kg ( DXA ) , −18.2 ± 5.8 kg ( MF-BIA ) , and −17.7 ± 9.9 kg ( ADP ) . A substantial decrease was also observed in the visceral FM . The mild but marked reduction in fat-free mass occurred at maximum ketosis , primarily as a result of changes in total body water , and was recovered thereafter . No changes in muscle strength were observed . A strong correlation was evidence d between the 3 methods of assessing body composition . Conclusion : The VLCK diet-induced  weight loss was mainly at the expense of FM and visceral mass ; muscle mass and strength were preserved . Of the 3 body composition techniques used , the MF-BIA method seems more convenient in the clinical setting OBJECTIVE Development of these guidelines is m and ated by the American Association of Clinical Endocrinologists ( AACE ) Board of Directors and the American College of Endocrinology ( ACE ) Board of Trustees and adheres to published AACE protocol s for the st and ardized production of clinical practice guidelines ( CPGs ) . METHODS Recommendations are based on diligent review of clinical evidence with transparent incorporation of subjective factors . RESULTS There are 9 broad clinical questions with 123 recommendation numbers that include 160 specific statements ( 85 [ 53.1 % ] strong [ Grade A ] ; 48 [ 30.0 % ] intermediate [ Grade B ] , and 11 [ 6.9 % ] weak [ Grade C ] , with 16 [ 10.0 % ] based on expert opinion [ Grade D ] ) that build a comprehensive medical care plan for obesity . There were 133 ( 83.1 % ) statements based on strong ( best evidence level [ BEL ] 1 = 79 [ 49.4 % ] ) or intermediate ( BEL 2 = 54 [ 33.7 % ] ) levels of scientific substantiation . There were 34 ( 23.6 % ) evidence -based recommendation grade s ( Grade s A-C = 144 ) that were adjusted based on subjective factors . Among the 1,790 reference citations used in this CPG , 524 ( 29.3 % ) were based on strong ( evidence level [ EL ] 1 ) , 605 ( 33.8 % ) were based on intermediate ( EL 2 ) , and 308 ( 17.2 % ) were based on weak ( EL 3 ) scientific studies , with 353 ( 19.7 % ) based on review s and opinions ( EL 4 ) . CONCLUSION The final recommendations recognize that obesity is a complex , adiposity-based chronic disease , where management targets both weight-related complications and adiposity to improve overall health and quality of life . The detailed evidence -based recommendations allow for nuanced clinical decision-making that addresses real-world medical care of patients with obesity , including screening , diagnosis , evaluation , selection of therapy , treatment goals , and individualization of care . The goal is to facilitate high- quality care of patients with obesity and provide a rational , scientific approach to management that optimizes health outcomes and safety . ABBREVIATIONS A1C = hemoglobin A1c AACE = American Association of Clinical Endocrinologists ACE = American College of Endocrinology ACSM = American College of Sports Medicine ADA = American Diabetes Association ADAPT = Arthritis , Diet , and Activity Promotion Trial ADHD = attention-deficit hyperactivity disorder AHA = American Heart Association AHEAD = Action for Health in Diabetes AHI = apnea-hypopnea index ALT = alanine aminotransferase AMA = American Medical Association ARB = angiotensin receptor blocker ART = assisted reproductive technology AUC = area under the curve BDI = Beck Depression Inventory BED = binge eating disorder BEL = best evidence level BLOOM = Behavioral Modification and Lorcaserin for Overweight and Obesity Management BLOSSOM = Behavioral Modification and Lorcaserin Second Study for Obesity Management BMI = body mass index BP = blood pressure C-SSRS = Columbia Suicidality Severity Rating Scale CAD = coronary artery disease CARDIA = Coronary Artery Risk Development in Young Adults CBT = cognitive behavioral therapy CCO = Consensus Conference on Obesity CHF = congestive heart failure CHO = carbohydrate CI = confidence interval COR-I = Contrave Obesity Research I CPG = clinical practice guideline CV = cardiovascular CVD = cardiovascular disease DASH = Dietary Approaches to Stop Hypertension DBP = diastolic blood pressure DEXA = dual-energy X-ray absorptiometry DPP = Diabetes Prevention Program DSE = diabetes support and education EL = evidence level ED  = erectile dysfunction  ER = extended release EWL = excess weight loss FDA = Food and Drug Administration FDG = 18F-fluorodeoxyglucose GABA = gamma-aminobutyric acid GERD = gastroesophageal reflux disease GI = gastrointestinal GLP-1 = glucagon-like peptide 1 HADS = Hospital Anxiety and Depression Scale HDL-c = high-density lipoprotein cholesterol HR = hazard ratio HTN = hypertension HUNT = Nord-Trøndelag Health Study ICSI = intracytoplasmic sperm injection IFG = impaired fasting glucose IGT = impaired glucose tolerance ILI = intensive lifestyle intervention IVF = in vitro fertilization LAGB = laparoscopic adjustable gastric b and ing LDL-c = low-density lipoprotein cholesterol LES = lower esophageal sphincter LSG = laparoscopic sleeve gastrectomy LV = left ventricle LVH = left ventricular hypertrophy LVBG = laparoscopic vertical b and ed gastroplasty MACE = major adverse cardiovascular events MAOI = monoamine oxidase inhibitor MI = myocardial infa rct ion MN RCT = meta- analysis of non-r and omized prospect i ve or case-controlled trials MRI = magnetic resonance imaging MUFA = monounsaturated fatty acid NAFLD = nonalcoholic fatty liver disease NASH = nonalcoholic steatohepatitis NES = night eating syndrome NHANES = National Health and Nutrition Examination Surveys NHLBI = National Heart , Lung , and Blood Institute NHS = Nurses ' Health Study NICE = National Institute for Health and Care Excellence OA = osteoarthritis OGTT = oral glucose tolerance test OR = odds ratio OSA = obstructive sleep apnea PHQ-9 = Patient Health Question naire PCOS = polycystic ovary syndrome PCP = primary care physician POMC = pro-opiomelanocortin POWER = Practice -Based Opportunities for Weight Reduction PPI = proton pump inhibitor PRIDE = Program to Reduce Incontinence by Diet and Exercise PSA = prostate specific antigen QOL = quality of life RA = receptor agonist RCT = r and omized controlled trial ROC = receiver operator characteristic RR = relative risk RYGB = Roux-en-Y gastric bypass  SAD = sagittal abdominal diameter SBP = systolic blood pressure SCOUT = Sibutramine Cardiovascular Outcome Trial SG = sleeve gastrectomy SHBG = sex hormonebinding globulin SIEDY = Structured Interview on Erectile Dysfunction SNRI = serotonin-norepinephrine reuptake inhibitors SOS = Swedish Obese Subjects SS = surveillance study SSRI = selective serotonin reuptake inhibitors STORM = Sibutramine Trial on Obesity Reduction and Maintenance TCA = tricyclic antidepressant TONE = Trial of Nonpharmacologic Intervention in the Elderly TOS = The Obesity Society T2DM = type 2 diabetes mellitus UKPDS = United Kingdom Prospect i ve Diabetes Study U.S = United States VAT = visceral adipose tissue VLDL = very low-density lipoprotein WC = waist circumference WHO = World Health Organization WHR = waist-hip ratio WHtR = waist-to-height ratio WMD = weighted mean difference WOMAC = Western Ontario and McMaster Universities osteoarthritis index XENDOS = XEnical in the Prevention of Diabetes in Obese Subjects BACKGROUND Altering the macronutrient composition of the diet influences hunger and satiety . Studies have compared high- and low-protein diets , but there are few data on carbohydrate content and ketosis on motivation to eat and ad libitum intake . OBJECTIVE We aim ed to compare the hunger , appetite , and weight-loss responses to a high-protein , low-carbohydrate [ ( LC ) ketogenic ] and those to a high-protein , medium-carbohydrate [ ( MC ) nonketogenic ] diet in obese men feeding ad libitum . DESIGN Seventeen obese men were studied in a residential trial ; food was provided daily . Subjects were offered 2 high-protein ( 30 % of energy ) ad libitum diets , each for a 4-wk period-an LC ( 4 % carbohydrate ) ketogenic diet and an MC ( 35 % carbohydrate ) diet-r and omized in a crossover design . Body weight was measured daily , and ketosis was monitored by analysis of plasma and urine sample s. Hunger was assessed by using a computerized visual analogue system . RESULTS Ad libitum energy intakes were lower with the LC diet than with the MC diet [ P=0.02 ; SE of the difference ( SED ) : 0.27 ] at 7.25 and 7.95 MJ/d , respectively . Over the 4-wk period , hunger was significantly lower ( P=0.014 ; SED : 1.76 ) and weight loss was significantly greater ( P=0.006 ; SED : 0.62 ) with the LC diet ( 6.34 kg ) than with the MC diet ( 4.35 kg ) . The LC diet induced ketosis with mean 3-hydroxybutyrate concentrations of 1.52 mmol/L in plasma ( P=0.036 from baseline ; SED : 0.62 ) and 2.99 mmol/L in urine ( P<0.001 from baseline ; SED : 0.36 ) . CONCLUSION In the short term , high-protein , low-carbohydrate ketogenic diets reduce hunger and lower food intake significantly more than do high-protein , medium-carbohydrate nonketogenic diets Cl aims about the merits or risks of carbohydrate ( CHO ) vs. protein for weight loss diets are extensive , yet the ideal ratio of dietary carbohydrate to protein for adult health and weight management remains unknown . This study examined the efficacy of two weight loss diets with modified CHO/protein ratios to change body composition and blood lipids in adult women . Women ( n = 24 ; 45 to 56 y old ) with body mass indices > 26 kg/m(2 ) were assigned to either a CHO Group consuming a diet with a CHO/protein ratio of 3.5 ( 68 g protein/d ) or a Protein Group with a ratio of 1.4 ( 125 g protein/d ) . Diets were isoenergetic , providing 7100 kJ/d , and similar amounts of fat ( approximately 50 g/d ) . After consuming the diets for 10 wk , the CHO Group lost 6.96 + /- 1.36 kg body weight and the Protein Group lost 7.53 + /- 1.44 kg . Weight loss in the Protein Group was partitioned to a significantly higher loss of fat/lean ( 6.3 + /- 1.2 g/g ) compared with the CHO Group ( 3.8 + /- 0.9 ) . Both groups had significant reductions in serum cholesterol ( approximately 10 % ) , whereas the Protein Group also had significant reductions in triacylglycerols ( TAG ) ( 21 % ) and the ratio of TAG/HDL cholesterol ( 23 % ) . Women in the CHO Group had higher insulin responses to meals and postpr and ial hypoglycemia , whereas women in the Protein Group reported greater satiety . This study demonstrates that increasing the proportion of protein to carbohydrate in the diet of adult women has positive effects on body composition , blood lipids , glucose homeostasis and satiety during weight loss BACKGROUND The optimal source and amount of dietary carbohydrate for managing type 2 diabetes ( T2DM ) are unknown . OBJECTIVE We aim ed to compare the effects of altering the glycemic index or the amount of carbohydrate on glycated hemoglobin ( HbA1c ) , plasma glucose , lipids , and C-reactive protein ( CRP ) in T2DM patients . DESIGN Subjects with T2DM managed by diet alone ( n=162 ) were r and omly assigned to receive high-carbohydrate , high-glycemic-index ( high-GI ) , high-carbohydrate , low-glycemic-index ( low-GI ) , or low-carbohydrate , high-monounsaturated-fat ( low-CHO ) diets for 1 y. RESULTS The high-GI , low-GI , and low-CHO diets contained , respectively , 47 % , 52 % , and 39 % of energy as carbohydrate and 31 % , 27 % , and 40 % of energy as fat ; they had GIs of 63 , 55 , and 59 , respectively . Body weight and HbA1c did not differ significantly between diets . Fasting glucose was higher ( P=0.041 ) , but 2-h postload glucose was lower ( P=0.010 ) after 12 mo of the low-GI diet . With the low-GI diet , overall mean triacylglycerol was 12 % higher and HDL cholesterol 4 % lower than with the low-CHO diet ( P<0.05 ) , but the difference in the ratio of total to HDL cholesterol disappeared by 6 mo ( time x diet interaction , P=0.044 ) . Overall mean CRP with the low-GI diet , 1.95 mg/L , was 30 % less than that with the high-GI diet , 2.75 mg/L ( P=0.0078 ) ; the concentration with the low-CHO diet , 2.35 mg/L , was intermediate . CONCLUSIONS In subjects with T2DM managed by diet alone with optimal glycemic control , long-term HbA1c was not affected by altering the GI or the amount of dietary carbohydrate . Differences in total : HDL cholesterol among diets had disappeared by 6 mo . However , because of sustained reductions in postpr and ial glucose and CRP , a low-GI diet may be preferred for the dietary management of T2DM BACKGROUND The possible advantage for weight loss of a diet that emphasizes protein , fat , or carbohydrates has not been established , and there are few studies that extend beyond 1 year . METHODS We r and omly assigned 811 overweight adults to one of four diets ; the targeted percentages of energy derived from fat , protein , and carbohydrates in the four diets were 20 , 15 , and 65 % ; 20 , 25 , and 55 % ; 40 , 15 , and 45 % ; and 40 , 25 , and 35 % . The diets consisted of similar foods and met guidelines for cardiovascular health . The participants were offered group and individual instructional sessions for 2 years . The primary outcome was the change in body weight after 2 years in two-by-two factorial comparisons of low fat versus high fat and average protein versus high protein and in the comparison of highest and lowest carbohydrate content . RESULTS At 6 months , participants assigned to each diet had lost an average of 6 kg , which represented 7 % of their initial weight ; they began to regain weight after 12 months . By 2 years , weight loss remained similar in those who were assigned to a diet with 15 % protein and those assigned to a diet with 25 % protein ( 3.0 and 3.6 kg , respectively ) ; in those assigned to a diet with 20 % fat and those assigned to a diet with 40 % fat ( 3.3 kg for both groups ) ; and in those assigned to a diet with 65 % carbohydrates and those assigned to a diet with 35 % carbohydrates ( 2.9 and 3.4 kg , respectively ) ( P>0.20 for all comparisons ) . Among the 80 % of participants who completed the trial , the average weight loss was 4 kg ; 14 to 15 % of the participants had a reduction of at least 10 % of their initial body weight . Satiety , hunger , satisfaction with the diet , and attendance at group sessions were similar for all diets ; attendance was strongly associated with weight loss ( 0.2 kg per session attended ) . The diets improved lipid-related risk factors and fasting insulin levels . CONCLUSIONS Reduced-calorie diets result in clinical ly meaningful weight loss regardless of which macronutrients they emphasize . ( Clinical Trials.gov number , NCT00072995 . BACKGROUND Few well-controlled studies have comprehensively examined the effects of very-low-carbohydrate diets on  type 2 diabetes ( T2D ) . OBJECTIVE We compared the effects of a very-low-carbohydrate , high-unsaturated fat , low-saturated fat ( LC ) diet with a high-carbohydrate , low-fat ( HC ) diet on glycemic control and cardiovascular disease risk factors in T2D after 52 wk . DESIGN In this r and omized controlled trial that was conducted in an outpatient research clinic , 115 obese adults with T2D [ mean ± SD age : 58 ± 7 y ; body mass index ( in kg/m(2 ) ) : 34.6 ± 4.3 ; glycated hemoglobin ( HbA1c ) : 7.3 ± 1.1 % ; duration of diabetes : 8 ± 6 y ] were r and omly assigned to consume either a hypocaloric LC diet [ 14 % of energy as carbohydrate ( carbohydrate < 50 g/d ) , 28 % of energy as protein , and 58 % of energy as fat ( < 10 % saturated fat ) ] or an energy-matched HC diet [ 53 % of energy as carbohydrate , 17 % of energy as protein , and 30 % of energy as fat ( < 10 % saturated fat ) ] combined with supervised aerobic and resistance exercise ( 60 min ; 3 d/wk ) . Outcomes were glycemic control assessed with use of measurements of HbA1c , fasting blood glucose , glycemic variability assessed with use of 48-h continuous glucose monitoring , diabetes medication , weight , blood pressure , and lipids assessed at baseline , 24 , and 52 wk . RESULTS Both groups achieved similar completion rates ( LC diet : 71 % ; HC diet : 65 % ) and mean ( 95 % CI ) reductions in weight [ LC diet : -9.8 kg ( -11.7 , -7.9 kg ) ; HC diet : -10.1 kg ( -12.0 , -8.2 kg ) ] , blood pressure [ LC diet : -7.1 ( -10.6 , -3.7)/-6.2 ( -8.2 , -4.1 ) mm Hg ; HC diet : -5.8 ( -9.4 , -2.2)/-6.4 ( -8.4 , -4.3 ) mm Hg ] , HbA1c [ LC diet : -1.0 % ( -1.2 % , -0.7 % ) ; HC diet : -1.0 % ( -1.3 % , -0.8 % ) ] , fasting glucose [ LC diet : -0.7 mmol/L ( -1.3 , -0.1 mmol/L ) ; HC diet : -1.5 mmol/L ( -2.1 , -0.8 mmol/L ) ] , and LDL cholesterol [ LC diet : -0.1 mmol/L ( -0.3 , 0.1 mmol/L ) ; HC diet : -0.2 mmol/L ( -0.4 , 0.03 mmol/L ) ] ( P-diet effect ≥ 0.10 ) . Compared with the HC-diet group , the LC-diet group achieved greater mean ( 95 % CI ) reductions in the diabetes medication score [ LC diet : -0.5 arbitrary units ( -0.7 , -0.4 arbitrary units ) ; HC diet : -0.2 arbitrary units ( -0.4 , -0.06 arbitrary units ) ; P = 0.02 ] , glycemic variability assessed by measuring the continuous overall net glycemic action-1 [ LC diet : -0.5 mmol/L ( -0.6 , -0.3 mmol/L ) ; HC diet : -0.05 mmol/L ( -0.2 , -0.1 mmol/L ) ; P = 0.003 ] , and triglycerides [ LC diet : -0.4 mmol/L ( -0.5 , -0.2 mmol/L ) ; HC diet : -0.01 mmol/L ( -0.2 , 0.2 mmol/L ) ; P = 0.001 ] and greater mean ( 95 % CI ) increases in HDL cholesterol [ LC diet : 0.1 mmol/L ( 0.1 , 0.2 mmol/L ) ; HC diet : 0.06 mmol/L ( -0.01 , 0.1 mmol/L ) ; P = 0.002 ] . CONCLUSIONS Both diets achieved substantial weight loss and reduced HbA1c and fasting glucose . The LC diet , which was high in unsaturated fat and low in saturated fat , achieved greater improvements in the lipid profile , blood glucose stability , and reductions in diabetes medication requirements , suggesting an effective strategy for the optimization of T2D management . This trial was registered at www.anzctr.org.au as ACTRN12612000369820 BACKGROUND Long-term weight loss and cardiometabolic effects of a very-low-carbohydrate , high-saturated-fat diet ( LC ) and a high-carbohydrate , low-fat diet ( LF ) have not been evaluated under isocaloric conditions . OBJECTIVE The objective was to compare an energy-controlled LC diet with an LF diet at 1 y. DESIGN Men and women ( n = 118 ) with abdominal obesity and at least one additional metabolic syndrome risk factor were r and omly assigned to either an energy-restricted ( approximately 6 - 7 MJ ) LC diet ( 4 % , 35 % , and 61 % of energy as carbohydrate , protein , and fat , respectively ) or an isocaloric LF diet ( 46 % , 24 % , and 30 % of energy as carbohydrate , protein , and fat , respectively ) for 1 y. Weight , body composition , and cardiometabolic risk markers were assessed . RESULTS Sixty-nine participants ( 59 % ) completed the trial : 33 in the LC group and 36 in the LF group . Both groups lost similar amounts of weight ( LC : -14.5 + /- 1.7 kg ; LF : -11.5 + /- 1.2 kg ; P = 0.14 , time x diet ) and body fat ( LC : -11.3 + /- 1.5 kg ; LF : -9.4 + /- 1.2 kg ; P = 0.30 ) . Blood pressure , fasting glucose , insulin , insulin resistance , and C-reactive protein decreased independently of diet composition . Compared with the LF group , the LC group had greater decreases in triglycerides ( -0.36 + /- 0.15 mmol/L ; 95 % CI : -0.67 , -0.05 mmol/L ; P = 0.011 ) , increases in HDL cholesterol ( 0.23 + /- 0.09 mmol/L ; 95 % CI : 0.06 , 0.40 mmol/L ; P = 0.018 ) and LDL cholesterol ( 0.6 + /- 0.2 mmol/L ; 95 % CI : 0.2 , 1.0 mmol/L ; P = 0.001 ) , and a greater but nonsignificant increase in apolipoprotein B ( 0.08 + /- 0.04 g/L ; 95 % CI : -0.004 , 0.171 g/L ; P = 0.17 ) . CONCLUSIONS Under planned isoenergetic conditions , as expected , both dietary patterns result ed in similar weight loss and changes in body composition . The LC diet may offer clinical benefits to obese persons with insulin resistance . However , the increase in LDL cholesterol with the LC diet suggests that this measure should be monitored . This trial was registered with the Australian New Zeal and Clinical Trials Registry at ( http://www.anzctr.org.au ) as ACTR 12606000203550 Very low-carbohydrate diets are often used to promote weight loss , but their effects on bowel health and function are largely unknown . We compared the effects of a very low-carbohydrate , high-fat ( LC ) diet with a high-carbohydrate , high-fibre , low-fat ( HC ) diet on indices of bowel health and function . In a parallel study design , ninety-one overweight and obese participants ( age 50.6 ( sd 7.5 ) years ; BMI 33.7 ( sd 4.2 ) kg/m(2 ) ) were r and omly assigned to either an energy-restricted ( about 6 - 7 MJ , 30 % deficit ) planned isoenergetic LC or HC diet for 8 weeks . At baseline and week 8 , 24 h urine and faecal collection s were obtained and a bowel function question naire was completed . Compared with the HC group , there were significant reductions in the LC group for faecal output ( 21 ( sd 145 ) v. - 61 ( sd 147 ) g ) , defecation frequency , faecal excretion and concentrations of butyrate ( - 0.5 ( sd 10.4 ) v. - 3.9 ( sd 9.7 ) mmol/l ) and total SCFA ( 1.4 ( sd 40.5 ) v. - 15.8 ( sd 43.6 ) mmol/l ) and counts of bifidobacteria ( P < 0.05 time x diet interaction , for all ) . Urinary phenols and p-cresol excretion decreased ( P < or = 0.003 for time ) with no difference between diets ( P > or = 0.25 ) . Faecal form , pH , ammonia concentration and numbers of coliforms and Escherichia coli did not change with either diet . No differences between the diets were evident for incidences of adverse gastrointestinal symptoms , which suggests that both diets were well tolerated . Under energy-restricted conditions , a short-term LC diet lowered stool weight and had detrimental effects on the concentration and excretion of faecal SCFA compared with an HC diet . This suggests that the long-term consumption of an LC diet may increase the risk of development of gastrointestinal disorders BACKGROUND Both genetic and lifestyle factors contribute to individual-level risk of coronary artery disease . The extent to which increased genetic risk can be offset by a healthy lifestyle is unknown . METHODS Using a polygenic score of DNA sequence polymorphisms , we quantified genetic risk for coronary artery disease in three prospect i ve cohorts - 7814 participants in the Atherosclerosis Risk in Communities ( ARIC ) study , 21,222 in the Women 's Genome Health Study ( WGHS ) , and 22,389 in the Malmö Diet and Cancer Study ( MDCS ) - and in 4260 participants in the cross-sectional BioImage Study for whom genotype and covariate data were available . We also determined adherence to a healthy lifestyle among the participants using a scoring system consisting of four factors : no current smoking , no obesity , regular physical activity , and a healthy diet . RESULTS The relative risk of incident coronary events was 91 % higher among participants at high genetic risk ( top quintile of polygenic scores ) than among those at low genetic risk ( bottom quintile of polygenic scores ) ( hazard ratio , 1.91 ; 95 % confidence interval [ CI ] , 1.75 to 2.09 ) . A favorable lifestyle ( defined as at least three of the four healthy lifestyle factors ) was associated with a substantially lower risk of coronary events than an unfavorable lifestyle ( defined as no or only one healthy lifestyle factor ) , regardless of the genetic risk category . Among participants at high genetic risk , a favorable lifestyle was associated with a 46 % lower relative risk of coronary events than an unfavorable lifestyle ( hazard ratio , 0.54 ; 95 % CI , 0.47 to 0.63 ) . This finding corresponded to a reduction in the st and ardized 10-year incidence of coronary events from 10.7 % for an unfavorable lifestyle to 5.1 % for a favorable lifestyle in ARIC , from 4.6 % to 2.0 % in WGHS , and from 8.2 % to 5.3 % in MDCS . In the BioImage Study , a favorable lifestyle was associated with significantly less coronary-artery calcification within each genetic risk category . CONCLUSIONS Across four studies involving 55,685 participants , genetic and lifestyle factors were independently associated with susceptibility to coronary artery disease . Among participants at high genetic risk , a favorable lifestyle was associated with a nearly 50 % lower relative risk of coronary artery disease than was an unfavorable lifestyle . ( Funded by the National Institutes of Health and others . ) BACKGROUND & AIMS This 6-month prospect i ve , single-arm observational study was design ed to assess the effects of the KD on the nutritional status , resting energy expenditure ( REE ) , and substrate oxidation in patients with drug-resistant epilepsy . METHODS Eighteen patients with medically refractory epilepsy underwent assessment of body composition , REE , and substrate oxidation rates before and after 6 months of KD . RESULTS Compared with baseline , there were no statistically significant differences at 6 months in terms of height , weight , BMI z-scores , and REE . However , the respiratory quotient decreased significantly ( from 0.80 ± 0.06 to 0.72 ± 0.05 , p < 0.001 ) whereas fat oxidation was significantly increased ( from 50.9 ± 25.2 mg/min to 97.5 ± 25.7 mg/min , p < 0.001 ) . Interestingly , we found that the increase in fat oxidation was the main independent predictor of the reduction in seizure frequency ( beta = -0.97 , t = -6.3 , p < 0.05 ) . CONCLUSIONS Administering a KD for 6 months in patients with medically refractory epilepsy increases fat oxidation and decreases the respiratory quotient , without appreciable changes in REE BACKGROUND AND AIMS The relationship between dietary macronutrient composition and appetite is controversial . We examined the effects of a year-long low-carbohydrate diet compared to a low-fat diet on appetite-related hormones and self-reported change in appetite . METHODS AND RESULTS A total of 148 adults with a body mass index 30 - 45 kg/m(2 ) , who were free of diabetes , cardiovascular disease and chronic kidney disease at baseline were r and omly assigned to either a low-carbohydrate diet ( carbohydrate [ excluding dietary fiber]<40 g/day ; N = 75 ) or a low-fat diet ( < 30 % energy from fat , < 7 % from saturated fat ; N = 73 ) . Participants in both groups attended individual and group dietary counseling sessions where they were provided the same behavioral curriculum and advised to maintain baseline levels of physical activity . Appetite and appetite-related hormones were measured at 0 , 3 , 6 and 12 months of intervention . At 12 months , mean changes ( 95 % CI ) in peptide YY were -34.8 pg/mL ( -41.0 to -28.6 ) and in the low-carbohydrate group and -44.2 pg/mL ( -50.4 to -38.0 ) in the low-fat group ( net change : 9.54 pg/mL [ 0.6 to 18.2 ] ; p = 0.036 ) . Approximately 99 % of dietary effects on peptide YY are explained by differences in dietary macronutrient content . There was no difference in change in ghrelin or self-reported change in appetite between the groups . CONCLUSIONS A low-fat diet reduced peptide YY more than a low-carbohydrate diet . These findings suggest that satiety may be better preserved on a low-carbohydrate diet , as compared to a low fat diet . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00609271 BACKGROUND Very low-carbohydrate ( LC ) diets are often used to promote weight loss , but the long-term effects on psychological function remain unknown . METHODS A total of 106 overweight and obese participants ( mean [ SE ] age , 50.0 [ 0.8 ] years ; mean [ SE ] body mass index [ calculated as weight in kilograms divided by height in meters squared ] , 33.7 [ 0.4 ] ) were r and omly assigned either to an energy-restricted ( approximately 1433 - 1672 kcal [ to convert to kilojoules , multiply by 4.186 ] ) , planned isocaloric , very low-carbohydrate , high-fat ( LC ) diet or to a high-carbohydrate , low-fat ( LF ) diet for 1 year . Changes in body weight , psychological mood and well-being ( Profile of Mood States , Beck Depression Inventory , and Spielberger State Anxiety Inventory scores ) , and cognitive functioning ( working memory and speed of processing ) were assessed . RESULTS By 1 year , the overall mean ( SE ) weight loss was 13.7 ( 1.8 ) kg , with no significant difference between groups ( P = .26 ) . Over the course of the study , there were significant time x diet interactions for Spielberger State Anxiety Inventory , Beck Depression Inventory , and Profile of Mood States scores for total mood disturbance , anger-hostility , confusion-bewilderment , and depression-dejection ( P < .05 ) as a result of greater improvements in these psychological mood states for the LF diet compared with the LC diet . Working memory improved by 1 year ( P < .001 for time ) , but speed of processing remained largely unchanged , with no effect of diet composition on either cognitive domain . CONCLUSIONS Over 1 year , there was a favorable effect of an energy-restricted LF diet compared with an isocaloric LC diet on mood state and affect in overweight and obese individuals . Both diets had similar effects on working memory and speed of processing . Trial Registration anzctr.org.au Identifier : 12606000203550 Abstract . This study was conducted to assess whether the natriuresis occurring early in a fast , and the renal sodium retention setting in upon carbohydrate or protein refeeding , can be entirely accounted for on the basis of concomitant changes in renal ketone body and ammonia excretion . To this end , the renal excretion of sodium , 3‐hydroxybutyrate ( 3‐OHB ) and ammonium was determined in non‐diabetic obese subjects su bmi tted to total fast according to the following protocol s : ( 1 ) 6 day fast : considered as control group ( n= 11 ) ; ( 2 ) 8 day fast save for an isolated 100 g oral glucose load on day 4 ( n= 12 ) ; ( 3 ) 8 day fast with , on day 4 , the same glucose load followed by a 6 h infusion of glucagon , 1 mg in 500 ml 5 % glucose ( n= 7 ) ; ( 4 ) 5 day total fast followed by 3 days of protein refeeding ( 53 g protein daily ; n = 8) . All subjects were refed with a mixed 4.2 MJ diet at the end of the studies BACKGROUND The carbohydrate-insulin model of obesity posits that habitual consumption of a high-carbohydrate diet sequesters fat within adipose tissue because of hyperinsulinemia and results in adaptive suppression of energy expenditure ( EE ) . Therefore , isocaloric exchange of dietary carbohydrate for fat is predicted to result in increased EE , increased fat oxidation , and loss of body fat . In contrast , a more conventional view that " a calorie is a calorie " predicts that isocaloric variations in dietary carbohydrate and fat will have no physiologically important effects on EE or body fat . OBJECTIVE We investigated whether an isocaloric low-carbohydrate ketogenic diet ( KD ) is associated with changes in EE , respiratory quotient ( RQ ) , and body composition . DESIGN Seventeen overweight or obese men were admitted to metabolic wards , where they consumed a high-carbohydrate baseline diet ( BD ) for 4 wk followed by 4 wk of an isocaloric KD with clamped protein . Subjects spent 2 consecutive days each week residing in metabolic chambers to measure changes in EE ( EEchamber ) , sleeping EE ( SEE ) , and RQ . Body composition changes were measured by dual-energy X-ray absorptiometry . Average EE during the final 2 wk of the BD and KD periods was measured by doubly labeled water ( EEDLW ) . RESULTS Subjects lost weight and body fat throughout the study corresponding to an overall negative energy balance of ∼300 kcal/d . Compared with BD , the KD coincided with increased EEchamber ( 57 ± 13 kcal/d , P = 0.0004 ) and SEE ( 89 ± 14 kcal/d , P < 0.0001 ) and decreased RQ ( -0.111 ± 0.003 , P < 0.0001 ) . EEDLW increased by 151 ± 63 kcal/d ( P = 0.03 ) . Body fat loss slowed during the KD and coincided with increased protein utilization and loss of fat-free mass . CONCLUSION The isocaloric KD was not accompanied by increased body fat loss but was associated with relatively small increases in EE that were near the limits of detection with the use of state-of-the-art technology . This trial was registered at clinical trials.gov as NCT01967563 BACKGROUND AND AIMS The effects of a low carbohydrate/high fat ( LCHF ) diet on health are debated . This study aims to explore the effects of a diet with less than 20 g carbohydrates per day ( LCHF ) on plasma low density lipoprotein cholesterol ( LDL-C ) in young and healthy adults . The secondary aim is the assessment of lipid profile and peripheral blood mononuclear cells ( P BMC ) gene expression . METHODS This was a r and omized controlled parallel- design ed intervention study . Participants were either assigned to a three-week LCHF diet or a control group continuing habitual diet ad libitum , in both groups . RESULTS In total , 30 healthy normal weight participants completed the study . Nine subjects did not complete it due to adverse events or withdrawn consent . In the LCHF diet group ( n = 15 ) , plasma LDL-C increased from ( mean ± SD ) 2.2 ± 0.4 mmol/l before intervention to 3.1 ± 0.8 after , while in the control group ( n = 15 ) , LDL-C remained unchanged : 2.5 ± 0.8 mmol/l ( p < 0.001 between groups ) . There was a significant increase in apolipoprotein B , total cholesterol , high-density lipoprotein cholesterol , free fatty acids , uric acid and urea in the LCHF group versus controls . Plasma levels of triglycerides , lipoprotein ( a ) , glucose , C-peptide or C-reactive protein ( CRP ) , blood pressure , body weight or body composition did not differ between the groups . P BMC gene expression of sterol regulator element binding protein 1 ( SREBP-1 ) was increased in the LCHF group versus controls ( p ≤ 0.01 ) . The individual increase in LDL-C from baseline varied between 5 and 107 % in the LCHF group . CONCLUSIONS An LCHF diet for three weeks increased LDL-C with 44 % versus controls . The individual response on LCHF varied profoundly Abstract Objective To determine the effects of diets varying in carbohydrate to fat ratio on total energy expenditure . Design R and omized trial . Setting Multicenter collaboration at US two sites , August 2014 to May 2017 . Participants 164 adults aged 18 - 65 years with a body mass index of 25 or more . Interventions After 12 % ( within 2 % ) weight loss on a run-in diet , participants were r and omly assigned to one of three test diets according to carbohydrate content ( high , 60 % , n=54 ; moderate , 40 % , n=53 ; or low , 20 % , n=57 ) for 20 weeks . Test diets were controlled for protein and were energy adjusted to maintain weight loss within 2 kg . To test for effect modification predicted by the carbohydrate-insulin model , the sample was divided into thirds of pre-weight loss insulin secretion ( insulin concentration 30 minutes after oral glucose ) . Main outcome measures The primary outcome was total energy expenditure , measured with doubly labeled water , by intention-to-treat analysis . Per protocol analysis included participants who maintained target weight loss , potentially providing a more precise effect estimate . Secondary outcomes were resting energy expenditure , measures of physical activity , and levels of the metabolic hormones leptin and ghrelin . Results Total energy expenditure differed by diet in the intention-to-treat analysis ( n=162 , P=0.002 ) , with a linear trend of 52 kcal/d ( 95 % confidence interval 23 to 82 ) for every 10 % decrease in the contribution of carbohydrate to total energy intake ( 1 kcal=4.18 kJ=0.00418 MJ ) . Change in total energy expenditure was 91 kcal/d ( 95 % confidence interval −29 to 210 ) greater in participants assigned to the moderate carbohydrate diet and 209 kcal/d ( 91 to 326 ) greater in those assigned to the low carbohydrate diet compared with the high carbohydrate diet . In the per protocol analysis ( n=120 , P<0.001 ) , the respective differences were 131 kcal/d ( −6 to 267 ) and 278 kcal/d ( 144 to 411 ) . Among participants in the highest third of pre-weight loss insulin secretion , the difference between the low and high carbohydrate diet was 308 kcal/d in the intention-to-treat analysis and 478 kcal/d in the per protocol analysis ( P<0.004 ) . Ghrelin was significantly lower in participants assigned to the low carbohydrate diet compared with those assigned to the high carbohydrate diet ( both analyses ) . Leptin was also significantly lower in participants assigned to the low carbohydrate diet ( per protocol ) . Conclusions Consistent with the carbohydrate-insulin model , lowering dietary carbohydrate increased energy expenditure during weight loss maintenance . This metabolic effect may improve the success of obesity treatment , especially among those with high insulin secretion . Trial registration Clinical Trials.gov NCT02068885 OBJECTIVE To comprehensively compare the effects of a very low-carbohydrate , high – unsaturated/low – saturated fat diet ( LC ) with those of a high – unrefined carbohydrate , low-fat diet ( HC ) on glycemic control and cardiovascular disease ( CVD ) risk factors in type 2 diabetes ( T2DM ) . RESEARCH DESIGN AND METHODS Obese adults ( n = 115 , BMI 34.4 ± 4.2 kg/m2 , age 58 ± 7 years ) with T2DM were r and omized to a hypocaloric LC diet ( 14 % carbohydrate [ < 50 g/day ] , 28 % protein , and 58 % fat [ < 10 % saturated fat ] ) or an energy-matched HC diet ( 53 % carbohydrate , 17 % protein , and 30 % fat [ < 10 % saturated fat ] ) combined with structured exercise for 24 weeks . The outcomes measured were as follows : glycosylated hemoglobin ( HbA1c ) , glycemic variability ( GV ; assessed by 48-h continuous glucose monitoring ) , antiglycemic medication changes ( antiglycemic medication effects score [ MES ] ) , and blood lipids and pressure . RESULTS A total of 93 participants completed 24 weeks . Both groups achieved similar completion rates ( LC 79 % , HC 82 % ) and weight loss ( LC −12.0 ± 6.3 kg , HC −11.5 ± 5.5 kg ) ; P ≥ 0.50 . Blood pressure ( −9.8/−7.3 ± 11.6/6.8 mmHg ) , fasting blood glucose ( −1.4 ± 2.3 mmol/L ) , and LDL cholesterol ( −0.3 ± 0.6 mmol/L ) decreased , with no diet effect ( P ≥ 0.10 ) . LC achieved greater reductions in triglycerides ( −0.5 ± 0.5 vs. −0.1 ± 0.5 mmol/L ) , MES ( −0.5 ± 0.5 vs. −0.2 ± 0.5 ) , and GV indices ; P  ≤ 0.03 . LC induced greater HbA1c reductions ( −2.6 ± 1.0 % [ −28.4 ± 10.9 mmol/mol ] vs. −1.9 ± 1.2 % [ −20.8 ± 13.1 mmol/mol ] ; P = 0.002 ) and HDL cholesterol ( HDL-C ) increases ( 0.2 ± 0.3 vs. 0.05 ± 0.2 mmol/L ; P = 0.007 ) in participants with the respective baseline values HbA1c > 7.8 % ( 62 mmol/mol ) and HDL-C < 1.29 mmol/L. CONCLUSIONS Both diets achieved substantial improvements for several clinical glycemic control and CVD risk markers . These improvements and reductions in GV and antiglycemic medication requirements were greatest with the LC compared with HC . This suggests an LC diet with low saturated fat may be an effective dietary approach for T2DM management if effects are sustained beyond 24 weeks ABBREVIATIONS A1C = hemoglobin A1C ; AACE = American Association of Clinical Endocrinologists ; ACCORD = Action to Control Cardiovascular Risk in Diabetes ; ACCORD BP = Action to Control Cardiovascular Risk in Diabetes Blood Pressure ; ACE = American College of Endocrinology ; ACEI = angiotensin-converting enzyme inhibitor ; AGI = alpha-glucosidase inhibitor ; apo B = apolipoprotein B ; ARB = angiotensin II receptor blocker ; ASCVD = atherosclerotic cardiovascular disease ; BAS = bile acid sequestrant ; BMI = body mass index ; BP = blood pressure ; CCB = calcium channel blocker ; CGM = continuous glucose monitoring ; CHD = coronary heart disease ; CKD = chronic kidney disease ; DKA = diabetic ketoacidosis ; DPP4 = dipeptidyl peptidase 4 ; eGFR = estimated glomerular filtration rate ; EPA = eicosapentaenoic acid ; ER = extended release ; FDA = Food and Drug Administration ; GLP1 = glucagon-like peptide 1 ;  HDL-C = high-density-lipoprotein cholesterol ; HeFH = heterozygous familial hypercholesterolemia ; LDL-C = low-density-lipoprotein cholesterol ; LDL-P = low-density-lipoprotein particle ; Look AHEAD = Look Action for Health in Diabetes ; NPH = neutral protamine Hagedorn ; OSA = obstructive sleep apnea ; PCSK9 = proprotein convertase subtilisin-kexin type 9 serine protease ; RCT = r and omized controlled trial ; SU = sulfonylurea ; SGLT2 = sodium-glucose cotransporter 2 ; SMBG = self-monitoring of blood glucose ; T2D = type 2 diabetes ; TZD = thiazolidinedione AIMS Little is known about the long-term association between low-carbohydrate diets ( LCDs ) and mortality . We evaluated the link between LCD and overall or cause-specific mortality using both individual data and pooled prospect i ve studies . METHODS AND RESULTS Data on diets from the National Health and Nutrition Examination Survey ( NHANES ; 1999 - 2010 ) were analysed . Multivariable Cox proportional hazards were applied to determine the hazard ratios and 95 % confidence intervals ( CIs ) for mortality for each quartile of the LCD score , with the lowest quartile ( Q1-with the highest carbohydrates intake ) used as reference . We used adjusted Cox regression to determine the risk ratio ( RR ) and 95 % CI , as well as r and om effects models and generic inverse variance methods to synthesize quantitative and pooled data , followed by a leave-one-out method for sensitivity analysis . Overall , 24 825 participants from NHANES study were included ( mean follow-up 6.4 years ) . After adjustment , participants with the lowest carbohydrates intake ( quartile 4 of LCD ) had the highest risk of overall ( 32 % ) , cardiovascular disease ( CVD ) ( 50 % ) , cerebrovascular ( 51 % ) , and cancer ( 36 % ) mortality . In the same model , the association between LCD and overall mortality was stronger in the non-obese ( 48 % ) than in the obese ( 19 % ) participants . Findings on pooled data of nine prospect i ve cohort studies with 462 934 participants ( mean follow-up 16.1 years ) indicated a positive association between LCD and overall ( RR 1.22 , 95 % CI 1.06 - 1.39 , P < 0.001 , I2 = 8.6 ) , CVD ( RR 1.13 , 95 % CI 1.02 - 1.24 , P < 0.001 , I2 = 11.2 ) , and cancer mortality ( RR 1.08 , 95 % CI 1.01 - 1.14 , P = 0.02 , I2 = 10.3 ) . These findings were robust in sensitivity analyses . CONCLUSION Our study suggests a potentially unfavourable association of LCD with overall and cause-specific mortality , based on both new analyses of an established cohort and by pooling previous cohort studies . Given the nature of the study , causality can not be proven ; we can not rule out residual bias . Nevertheless , further studies are needed to extend these important findings , which if confirmed , may suggest a need to rethink recommendations for LCD in clinical practice BACKGROUND The high-fat ketogenic diet ( KD ) has become an increasingly popular diet not only in overweight/obese population s , or those with clinical conditions , but also in healthy non-overweight population s. OBJECTIVE Because there are concerns about the association between high-fat diets and cognitive decline , this study aim ed to determine the effects of a KD compared with an isocaloric high-carbohydrate , low-fat ( HCLF ) diet on cognitive function , sleep , and mood in healthy , normal-weight individuals . METHODS Eleven healthy , normal-weight participants ( mean age : 30 ± 9 y ) completed this r and omized , controlled , crossover study . Participants followed 2 isocaloric diets-an HCLF diet ( 55 % carbohydrate , 20 % fat , and 25 % protein ) and a KD ( 15 % carbohydrate , 60 % fat , and 25 % protein)-in a r and omized order for a minimum of 3 wk , with a 1-wk washout period between diets . Measures of β-hydroxybutyrate confirmed that all participants were in a state of nutritional ketosis during post-KD assessment s ( baseline : 0.2 ± 0.2 mmol/L ; KD : 1.0 ± 0.5 mmol/L ; washout : 0.2 ± 0.1 mmol/L ; and HCLF : 0.3 ± 0.2 mmol/L ) . Cognitive function was assessed using a vali date d , psychological computer-based test battery before and after each diet . Subjective measures of mood and sleep were also monitored throughout the study using vali date d scales . RESULTS Three weeks of sustained nutritional ketosis , compared with the HCLF diet , had no effect on speed and accuracy responses in tasks design ed to measure vigilance ( speed : P = 0.39 , Cohen 's d = 0.26 ; accuracy : P = 0.99 , Cohen 's d = 0.04 ) , visual learning and memory ( speed : P = 0.99 , Cohen 's d = 0.04 ; accuracy : P = 0.99 , Cohen 's d = 0.03 ) , working memory ( speed : P = 0.62 , Cohen 's d = 0.26 ; accuracy : P = 0.98 , Cohen 's d = 0.07 ) , and executive function ( speed : P = 0.60 , Cohen 's d = 0.31 ; accuracy : P = 0.90 , Cohen 's d = 0.19 ) . Likewise , mood , sleep quality , and morning vigilance did not differ ( P > 0.05 ) between the dietary interventions . CONCLUSION The results of our r and omized , crossover , controlled study suggest that 3 wk of sustained nutritional ketosis had no effect on cognitive performance , mood , or subjective sleep quality in a sample of healthy individuals . This trial was registered in the Pan African Clinical Trial Registry as PACTR201707002406306 This summer , 25 overweight and obese adults participating in a tightly controlled feeding study will take up fulltime residence for 3 months at a wooded lakefront center in Ashl and , Massachusetts . However , before checking in at Framingham State University ’s Warren Conference Center and Inn , they will have to lose 15 % of their body weight on a calorie-restricted diet with home-delivered meals . Those who pass this hurdle will be invited to the inn , where they ’ll be r and omly assigned to 1 of 3 equal-calorie diets : a lowfat , high-carbohydrate diet that ’s either high or low in added sugar or a very lowcarbohydrate , high-fat ketogenic diet that causes the body to switch from burning carbohydrates to burning fat . The group will be the first of 5 that will participate in the trial over 3 years . Changes in body fat mass and energy expenditure will be assessed to determine if any of the diets have a unique effect on metabolism , while controlling calorie intake , in people who have already lost weight . “ It ’s hard to lose weight , but it ’s much harder to maintain that weight loss because of well-described physiological adaptations , ” said coprincipal investigator David S. Ludwig , MD , PhD , a professor of pediatrics and nutrition at Harvard Medical School and Harvard T.H. Chan School of Public Health . After most diet-induced weight loss , “ hunger goes up and metabolic rate goes down , and tendency to restore fat increases . ” But there are hints that the ketogenic diet may be different . A meta- analysis of 13 r and omized controlled trials suggested that people on ketogenic diets tend to lose more weight and keep more of it off than people on low-fat diets . People placed on these diets often report decreased hunger , according to Amy Miskimon Goss , PhD , RD , an assistant professor at the University of Alabama at Birmingham ( UAB ) Nutrition Obesity Research Center . The appetitesuppressing powers of the diet are n’t fully understood but could have to do with the satiating properties of fat and protein , changes in appetite-regulating hormones on a low-carb diet , a direct hunger-reducing role of ketone bodies— the body ’s main fuel source on the diet — or other factors . Additionally , the ketogenic diet may not affect metabolism the same way other diets do . In a previous study , Ludwig found that metabolism slowed by more than 400 kcal/d on a low-fat diet while there was no significant decline in metabolic rate on a  very low-carb diet . Medical News & Perspectives ........ Importance Dietary modification remains key to successful weight loss . Yet , no one dietary strategy is consistently superior to others for the general population . Previous research suggests genotype or insulin-glucose dynamics may modify the effects of diets . Objective To determine the effect of a healthy low-fat ( HLF ) diet vs a healthy low-carbohydrate ( HLC ) diet on weight change and if genotype pattern or insulin secretion are related to the dietary effects on weight loss . Design , Setting , and Participants The Diet Intervention Examining The Factors Interacting with Treatment Success ( DIETFITS ) r and omized clinical trial included 609 adults aged 18 to 50 years without diabetes with a body mass index between 28 and 40 . The trial enrollment was from January 29 , 2013 , through April 14 , 2015 ; the date of final follow-up was May 16 , 2016 . Participants were r and omized to the 12-month HLF or HLC diet . The study also tested whether 3 single-nucleotide polymorphism multilocus genotype responsiveness patterns or insulin secretion ( INS-30 ; blood concentration of insulin 30 minutes after a glucose challenge ) were associated with weight loss . Interventions Health educators delivered the behavior modification intervention to HLF ( n = 305 ) and HLC ( n = 304 ) participants via 22 diet-specific small group sessions administered over 12 months . The sessions focused on ways to achieve the lowest fat or carbohydrate intake that could be maintained long-term and emphasized diet quality . Main Outcomes and Measures Primary outcome was 12-month weight change and determination of whether there were significant interactions among diet type and genotype pattern , diet and insulin secretion , and diet and weight loss . Results Among 609 participants r and omized ( mean age , 40 [ SD , 7 ] years ; 57 % women ; mean body mass index , 33 [ SD , 3 ] ; 244 [ 40 % ] had a low-fat genotype ; 180 [ 30 % ] had a low-carbohydrate genotype ; mean baseline INS-30 , 93 & mgr;IU/mL ) , 481 ( 79 % ) completed the trial . In the HLF vs HLC diets , respectively , the mean 12-month macronutrient distributions were 48 % vs 30 % for carbohydrates , 29 % vs 45 % for fat , and 21 % vs 23 % for protein . Weight change at 12 months was −5.3 kg for the HLF diet vs −6.0 kg for the HLC diet ( mean between-group difference , 0.7 kg [ 95 % CI , −0.2 to 1.6 kg ] ) . There was no significant diet-genotype pattern interaction ( P = .20 ) or diet-insulin secretion ( INS-30 ) interaction ( P = .47 ) with 12-month weight loss . There were 18 adverse events or serious adverse events that were evenly distributed across the 2 diet groups . Conclusions and Relevance In this 12-month weight loss diet study , there was no significant difference in weight change between a healthy low-fat diet vs a healthy low-carbohydrate diet , and neither genotype pattern nor baseline insulin secretion was associated with the dietary effects on weight loss . In the context of these 2 common weight loss diet approaches , neither of the 2 hypothesized predisposing factors was helpful in identifying which diet was better for whom . Trial Registration clinical trials.gov Identifier :
target: Based on the evidence review ed , low-CHO and very-low-CHO diets are not superior to other dietary approaches for weight loss .
  These diets may have advantages related to appetite control , triglyceride reduction , and reduction in the use of medication in T2D management .
  The evidence review ed showed mixed effects on low-density lipoprotein cholesterol levels with some studies showing an increase .
  There was no clear evidence for advantages regarding effects on other cardiometabolic risk markers .
background: Historically , low-carbohydrate ( CHO ) and very-low-CHO diets have been used for weight loss .
  Recently , these diets have been promoted for type 2 diabetes ( T2D ) management .
  This scientific statement provides a comprehensive review of the current evidence base available from recent systematic review s and meta-analyses on the effects of low-CHO and very-low-CHO diets on body weight , lipoprotein lipids , glycemic control , and other cardiometabolic risk factors .