title: Changes of renal sinus fat and renal parenchymal fat during an 18-month randomized weight loss trial. Comparison of the Atkins, Zone, Ornish, and LEARN diets for change in weight and related risk factors among overweight premenopausal women: the A TO Z Weight Loss Study: a randomized trial. Effects of dietary saturated fat on LDL subclasses and apolipoprotein CIII in men A low-carbohydrate as compared with a low-fat diet in severe obesity. Lipoprotein Particle Profiles by Nuclear Magnetic Resonance Compared With Standard Lipids and Apolipoproteins in Predicting Incident Cardiovascular Disease in Women The Effects of Low-Carbohydrate versus Conventional Weight Loss Diets in Severely Obese Adults: One-Year Follow-up of a Randomized Trial Comparison of the effects of four commercially available weight-loss programmes on lipid-based cardiovascular risk factors. Very low-carbohydrate and low-fat diets affect fasting lipids and postprandial lipemia differently in overweight men. Comparison of 3 ad libitum diets for weight-loss maintenance, risk of cardiovascular disease, and diabetes: a 6-mo randomized, controlled trial. Change in dietary saturated fat intake is correlated with change in mass of large low-density-lipoprotein particles in men. Comparison of weight-loss diets with different compositions of fat, protein, and carbohydrates. Separate effects of reduced carbohydrate intake and weight loss on atherogenic dyslipidemia. Long-term effects of a very-low-carbohydrate weight loss diet compared with an isocaloric low-fat diet after 12 mo. Effects of low-carbohydrate and low-fat diets: a randomized trial. Comparison of a low-fat diet to a low-carbohydrate diet on weight loss, body composition, and risk factors for diabetes and cardiovascular disease in free-living, overweight men and women. Low-Fat Versus Low-Carbohydrate Weight Reduction Diets Effects of a low-glycemic load vs low-fat diet in obese young adults: a randomized trial. Effects of Diet Composition and Insulin Resistance Status on Plasma Lipid Levels in a Weight Loss Intervention in Women Two Patterns of Adipokine and Other Biomarker Dynamics in a Long-Term Weight Loss Intervention A Low-Carbohydrate, Ketogenic Diet versus a Low-Fat Diet To Treat Obesity and Hyperlipidemia The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials CETP genotype and changes in lipid levels in response to weight-loss diet intervention in the POUNDS LOST and DIRECT randomized trials1 Comparison of the Atkins, Ornish, Weight Watchers, and Zone diets for weight loss and heart disease risk reduction: a randomized trial. Low HDL predicts differential blood pressure effects from two weight-loss approaches: a secondary analysis of blood pressure from a randomized, clinical weight-loss trial. Cost-effectiveness of a low-carbohydrate diet and a standard diet in severe obesity. A randomized trial of a low-carbohydrate diet for obesity. Plasma Oxidized Low-Density Lipoprotein, a Strong Predictor for Acute Coronary Heart Disease Events in Apparently Healthy, Middle-Aged Men From the General Population A randomized controlled trial on the efficacy of carbohydrate-reduced or fat-reduced diets in patients attending a telemedically guided weight loss program Effects of weight loss on a low-carbohydrate diet on flow-mediated dilatation, adhesion molecules and adiponectin. Clinical utility of different lipid measures for prediction of coronary heart disease in men and women. Beyond low-density lipoprotein cholesterol: respective contributions of non-high-density lipoprotein cholesterol levels, triglycerides, and the total cholesterol/high-density lipoprotein cholesterol ratio to coronary heart disease risk in apparently healthy men and women. A randomized trial of a low-carbohydrate diet vs orlistat plus a low-fat diet for weight loss. A Randomized Study Comparing the Effects of a Low-Carbohydrate Diet and a Conventional Diet on Lipoprotein Subfractions and C-reactive Protein Levels in Patients With Severe Obesity. A randomized trial comparing a very low carbohydrate diet and a calorie-restricted low fat diet on body weight and cardiovascular risk factors in healthy women. The effects of a low-carbohydrate versus low-fat diet on adipocytokines in severely obese adults: three-year follow-up of a randomized trial. A randomized controlled trial of a moderate-fat, low-energy diet compared with a low fat, low-energy diet for weight loss in overweight adults Effect of a low-carbohydrate, ketogenic diet program compared to a low-fat diet on fasting lipoprotein subclasses. Impact of triglyceride levels beyond low-density lipoprotein cholesterol after acute coronary syndrome in the PROVE IT-TIMI 22 trial. Changes in atherogenic dyslipidemia induced by carbohydrate restriction in men are dependent on dietary protein source. The effects of a low-carbohydrate diet on appetite: A randomized controlled trial. Long-term effects of a low carbohydrate, low fat or high unsaturated fat diet compared to a no-intervention control. A low-carbohydrate diet is more effective in reducing body weight than healthy eating in both diabetic and non-diabetic subjects.
abstract: BACKGROUND & AIMS Data regarding the role of kidney adiposity , its clinical implication s , and its dynamics during weight-loss are sparse . We investigated the effect of long-term weight-loss induced intervention diets on dynamics of renal-sinus-fat , an ectopic fat depot , and % renal-parenchymal-fat , lipid accumulation within the renal parenchyma . METHODS We r and omized 278 participants with abdominal obesity/dyslipidemia to low-fat or Mediterranean/low-carbohydrate diets , with or without exercise .  We quantified renal-sinus-fat and % renal-parenchymal-fat by whole body magnetic-resonance-imaging .  RESULTS Participants ( age = 48 years ; 89 % men ; body-mass-index = 31 kg/m2 ) had 86 % retention to the trial after 18 months . Both increased renal-sinus-fat and % renal-parenchymal-fat were directly associated with hypertension , and with higher abdominal deep-subcutaneous-adipose-tissue and visceral-adipose-tissue ( p of trend < 0.05 for all ) after adjustment for body weight . Higher renal-sinus-fat was associated with lower estimated-glomerular-filtration-rate and with higher microalbuminuria and % HbA1C beyond body weight . After 18 months of intervention , overall renal-sinus-fat ( -9 % ; p < 0.05 vs. baseline ) but not % renal-parenchymal-fat ( -1.7 % ; p = 0.13 vs. baseline ) significantly decreased , and similarly across the intervention groups . Renal-sinus-fat and % renal-parenchymal-fat changes were correlated with weight-loss per-se ( p < 0.05 ) . In a model adjusted for age , sex , and visceral-adipose-tissue changes , 18 months reduction in renal-sinus-fat associated with decreased pancreatic , hepatic and cardiac fats ( p < 0.05 for all ) and with decreased cholesterol/high-density lipoprotein-cholesterol ( HDL-c ) ( β = 0.13 ; p = 0.05 ) , triglycerides/HDL-c ( β = 0.13 ; p = 0.05 ) , insulin ( β = 0.12 ; p = 0.05 ) and gamma glutamyl transpeptidase ( β = 0.24 ; p = 0.001 ) , but not with improved renal function parameters or blood pressure . Decreased intake of sodium was associated with a reduction in % renal-parenchymal-fat , after adjustment for 18 months weight-loss ( β = 0.15 ; p = 0.026 ) and hypertension ( β = 0.14 ; p = 0.04 ) . CONCLUSIONS Renal-sinus-fat and renal-parenchymal-fat are fairly related to weight-loss . Decreased renal-sinus-fat is associated with improved hepatic parameters , independent of changes in weight or hepatic fat , rather than with improved renal function or blood pressure parameters . CLINICAL TRIALS . GOVIDENTIFIER NCT01530724 CONTEXT Popular diets , particularly those low in carbohydrates , have challenged current recommendations advising a low-fat , high-carbohydrate diet for weight loss . Potential benefits and risks have not been tested adequately . OBJECTIVE To compare 4 weight-loss diets representing a spectrum of low to high carbohydrate intake for effects on weight loss and related metabolic variables . DESIGN , SETTING , AND PARTICIPANTS Twelve-month r and omized trial conducted in the United States from February 2003 to October 2005 among 311 free-living , overweight/obese ( body mass index , 27 - 40 ) nondiabetic , premenopausal women . INTERVENTION Participants were r and omly assigned to follow the Atkins ( n = 77 ) , Zone ( n = 79 ) , LEARN ( n = 79 ) , or Ornish ( n = 76 ) diets and received weekly instruction for 2 months , then an additional 10-month follow-up . MAIN OUTCOME MEASURES Weight loss at 12 months was the primary outcome . Secondary outcomes included lipid profile ( low-density lipoprotein , high-density lipoprotein , and non-high-density lipoprotein cholesterol , and triglyceride levels ) , percentage of body fat , waist-hip ratio , fasting insulin and glucose levels , and blood pressure . Outcomes were assessed at months 0 , 2 , 6 , and 12 . The Tukey studentized range test was used to adjust for multiple testing . RESULTS Weight loss was greater for women in the Atkins diet group compared with the other diet groups at 12 months , and mean 12-month weight loss was significantly different between the Atkins and Zone diets ( P<.05 ) . Mean 12-month weight loss was as follows : Atkins , -4.7 kg ( 95 % confidence interval [ CI ] , -6.3 to -3.1 kg ) , Zone , -1.6 kg ( 95 % CI , -2.8 to -0.4 kg ) , LEARN , -2.6 kg ( -3.8 to -1.3 kg ) , and Ornish , -2.2 kg ( -3.6 to -0.8 kg ) . Weight loss was not statistically different among the Zone , LEARN , and Ornish groups . At 12 months , secondary outcomes for the Atkins group were comparable with or more favorable than the other diet groups . CONCLUSIONS In this study , premenopausal overweight and obese women assigned to follow the Atkins diet , which had the lowest carbohydrate intake , lost more weight at 12 months than women assigned to follow the Zone diet , and had experienced comparable or more favorable metabolic effects than those assigned to the Zone , Ornish , or LEARN diets [ corrected ] While questions remain about long-term effects and mechanisms , a low-carbohydrate , high-protein , high-fat diet may be considered a feasible alternative recommendation for weight loss . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00079573 Background / objectives : Small dense low-density lipoprotein ( LDL ) particles and apolipoprotein ( apo ) CIII are risk factors for cardiovascular disease ( CVD ) that can be modulated by diet , but there is little information regarding the effects of dietary saturated fat on their plasma levels . We tested the effects of high vs low saturated fat intake in the context of a high beef protein diet on levels and composition of LDL subclasses and on apoCIII levels in plasma and LDL.Subjects/ methods : Following consumption of a baseline diet ( 50 % carbohydrate ( CHO ) , 13 % protein , 38 % total fat , 15 % saturated fat ) for 3 weeks , 14 healthy men were r and omly assigned to two reduced CHO high beef protein diets ( 31 % CHO , 31 % protein , 38 % fat ) that differed in saturated fat content ( 15 % vs 8 % ) for 3 weeks each in a crossover design . Results : The high saturated fat ( HSF ) diet result ed in higher mass concentrations of buoyant LDL I , medium density LDL II and dense LDL III , but not the very dense LDL IV ; and significant increases in plasma and LDL apoCIII concentration of 9.4 % and 33.5 % , respectively . The saturated fat-induced changes in LDL apoCIII were specifically correlated with changes in apoCIII content of LDL IV . Conclusions : Taken together with previous observations , these findings suggest that , at least in the context of a lower CHO high beef protein diet , HSF intake may increase CVD risk by metabolic processes that involve apoCIII BACKGROUND The effects of a carbohydrate-restricted diet on weight loss and risk factors for atherosclerosis have been incompletely assessed . METHODS We r and omly assigned 132 severely obese subjects ( including 77 blacks and 23 women ) with a mean body-mass index of 43 and a high prevalence of diabetes ( 39 percent ) or the metabolic syndrome ( 43 percent ) to a carbohydrate-restricted ( low-carbohydrate ) diet or  a calorie- and fat-restricted ( low-fat ) diet . RESULTS Seventy-nine subjects completed the six-month study . An analysis including all subjects , with the last observation carried forward for those who dropped out , showed that subjects on the low-carbohydrate diet lost more weight than those on the low-fat diet ( mean [ + /-SD ] , -5.8+/-8.6 kg vs. -1.9+/-4.2 kg ; P=0.002 ) and had greater decreases in triglyceride levels ( mean , -20+/-43 percent vs. -4+/-31 percent ; P=0.001 ) , irrespective of the use or nonuse of hypoglycemic or lipid-lowering medications . Insulin sensitivity , measured only in subjects without diabetes , also improved more among subjects on the low-carbohydrate diet ( 6+/-9 percent vs. -3+/-8 percent , P=0.01 ) . The amount of weight lost ( P<0.001 ) and assignment to the low-carbohydrate diet ( P=0.01 ) were independent predictors of improvement in triglyceride levels and insulin sensitivity . CONCLUSIONS Severely obese subjects with a high prevalence of diabetes or the metabolic syndrome lost more weight during six months on a carbohydrate-restricted diet than on a calorie- and fat-restricted diet , with a relative improvement in insulin sensitivity and triglyceride levels , even after adjustment for the amount of weight lost . This finding should be interpreted with caution , given the small magnitude of overall and between-group differences in weight loss in these markedly obese subjects and the short duration of the study . Future studies evaluating long-term cardiovascular outcomes are needed before a carbohydrate-restricted diet can be endorsed Background — Nuclear magnetic resonance ( NMR ) spectroscopy measures the number and size of lipoprotein particles instead of their cholesterol or triglyceride content , but its clinical utility is uncertain . Methods and Results — Baseline lipoproteins were measured by NMR in 27 673 initially healthy women followed up for incident cardiovascular disease ( n=1015 ) over an 11-year period . After adjustment for nonlipid risk factors , hazard ratios and 95 % confidence intervals for the top versus the bottom quintile of NMR-measured lipoprotein particle concentration ( measured in particles per liter ) were 2.51 ( 1.91 to 3.30 ) for low-density lipoprotein ( LDLNMR ) , 0.91 ( 0.75 to 1.12 ) for high-density lipoprotein ( HDLNMR ) , 1.71 ( 1.38 to 2.12 ) for very low – density lipoprotein ( VLDLNMR ) , and 2.25 ( 1.80 to 2.81 ) for the LDLNMR/HDLNMR ratio . Similarly adjusted results for NMR-measured lipoprotein particle size ( measured in nanometers ) were 0.64 ( 0.52 to 0.79 ) for LDLNMR size , 0.65 ( 0.51 to 0.81 ) for HDLNMR size , and 1.37 ( 1.10 to 1.70 ) for VLDLNMR size . Hazard ratios for NMR measures were comparable but not superior to st and ard lipids ( total cholesterol 2.08 [ 1.63 to 2.67 ] , LDL cholesterol 1.74 [ 1.40 to 2.16 ] , HDL cholesterol 0.52 [ 0.42 to 0.64 ] , triglycerides 2.58 [ 1.95 to 3.41 ] , non-HDL cholesterol 2.52 [ 1.95 to 3.25 ] , total/HDL cholesterol ratio 2.82 [ 2.23 to 3.58 ] ) and apolipoproteins ( B100 2.57 [ 1.98 to 3.33 ] , A-1 0.63 [ 0.52 to 0.77 ] , and B100/A-1 ratio 2.79 [ 2.21 to 3.54 ] ) . Essentially no reclassification improvement was found with the addition of the LDLNMR particle concentration or apolipoprotein B100 to a model that already included the total/HDL cholesterol ratio and nonlipid risk factors ( net reclassification index 0 % and 1.9 % , respectively ) , nor did the addition of either variable result in a statistically significant improvement in the c-index . Conclusions — In this prospect i ve study of healthy women , cardiovascular disease risk prediction associated with lipoprotein profiles evaluated by NMR was comparable but not superior to that of st and ard lipids or apolipoproteins Context In 2003 , the authors reported that severely obese adults lost more weight and had better serum lipid patterns after 6 months of a low-carbohydrate diet rather than a conventional low-fat diet . Contribution After 1 year , these same patients still had more favorable triglyceride and high-density lipoprotein cholesterol levels on the low-carbohydrate diet than on the conventional diet . However , weight loss and the other metabolic parameters were similar in the 2 diet groups . Caution s The effect of the modest improvements in high-density lipoprotein cholesterol and triglyceride levels on the development of diabetes and cardiovascular disease is unknown . The Editors The prevalence of obesity and its associated metabolic abnormalities has increased markedly over the past 2 decades ( 1 , 2 ) . Although guidelines to follow a highcomplex carbohydrate , low-fat , energy-deficient diet to achieve weight loss are generally accepted ( 3 ) , considerable public interest has focused on low-carbohydrate diets ( 4 ) . We recently reported that persons with severe obesity lost more weight and had greater improvements in triglyceride levels , insulin sensitivity , and glycemic control after 6 months of a low-carbohydrate diet as compared with a conventional weight loss diet based on calorie and fat restriction ( 5 ) . However , these findings were preliminary because of the short duration of that study ( 6 ) . A simultaneously published study by Foster and colleagues suggested that persons on a low-carbohydrate diet  tended to regain weight by 1 year ( 7 ) . These findings were limited , however , because few participants completed the study and because the study used a self-help approach , which is less effective than direct counseling for maintaining weight loss ( 8) . Foster and colleagues also excluded persons with diabetes , which is highly prevalent in the obese population . During the development of this study , we decided to analyze and report preliminary results at 6 months and final results at 1 year . We thought that the short-term results would be important , given the high-risk nature of our study sample , but that long-term outcomes would provide more information about the sustainability of any diet-related outcomes . We now report our findings 1 year after r and omization to a low-carbohydrate diet versus a low-fat weight loss diet ( conventional diet ) in severely obese adults with a high prevalence of diabetes or the metabolic syndrome . Methods Study Participants The study design has been previously described ( 5 ) . Participants were recruited from the outpatient practice s of the Philadelphia Veterans Affairs Medical Center and included persons 18 years of age and older with a body mass index ( BMI ) of 35 kg/m2 or greater . The exclusion criteria were a serum creatinine level greater than 133 mol/L ( > 1.5 mg/dL ) , hepatic disease , severe life-limiting medical illness , inability to self-monitor glucose levels , or active use of a weight loss program or weight loss medication . Between May 2001 and November 2001 , 132 persons were r and omly assigned to either a low-carbohydrate diet ( n = 64 ) or a conventional diet ( n = 68 ) . The Institutional Review Committee at the Philadelphia Veterans Affairs Medical Center approved the study , and all participants provided written informed consent . Interventions Diet groups met in weekly counseling sessions for 4 weeks , followed by 11 monthly sessions . Participants on the low-carbohydrate diet were instructed only to reduce carbohydrate intake to less than 30 g per day . Participants on the conventional diet were instructed to reduce caloric intake by 500 calories per day , with less than 30 % of calories derived from fat , in accordance with the National Heart , Lung , and Blood Institute guidelines ( 3 ) . Outcome Measures We collected data , including weight ( single calibrated scale , SR Instruments , Inc. , Tonaw and a , New York ) , medical history ( self-reported ) , and blood pressure , at baseline , 6 months , and 1 year . Fasting blood specimens were obtained for glucose , hemoglobin A1c , and serum lipid levels ( Synchron LX20 , Beckman Coulter , Inc. , Fullerton , California ) . Low-density lipoprotein ( LDL ) cholesterol level was calculated by using the Friedewald formula ( 9 ) . We defined the presence of diabetes by a historical fasting blood glucose level greater than 6.94 mmol/L ( > 125 mg/dL ) or use of antidiabetic medications . The metabolic syndrome was considered present if a participant had 3 or more of the following ( 10 ) : central obesity , fasting blood glucose level of 6.11 mmol/L ( 110 mg/dL ) or greater , fasting triglyceride level of 1.70 mmol/L ( 150 mg/dL ) or greater , high-density lipoprotein ( HDL ) cholesterol level less than 1.04 mmol/L ( < 40 mg/dL ) for men or less than 1.30 mmol/L ( < 50 mg/dL ) for women , blood pressure of 130/85 mm Hg or greater , or antihypertensive therapy . We assumed that all participants had central obesity because of the uniform severity of their obesity ( BMI range , 35.0 to 79.4 kg/m2 ) . Serum insulin was measured by radioimmunoassay ( Laboratory Corporation of America Holdings [ LabCorp ] , Burlington , North Carolina ] ) . Insulin resistance in nondiabetic persons was estimated by the quantitative insulin sensitivity check ( QUICK ) index : 1/[(log ( fasting insulin ( U/mL ) ) + ( log fasting glucose(mg/dL ) ) ] . Statistical Analysis Our primary end point was total weight loss at 1 year . Secondary analyses included the change from baseline in serum lipid levels , insulin sensitivity , and glycemic control . We estimated that we would need 100 persons ( 50 per group ) , assuming a 2-sided type I error of 5 % , for the study to have 80 % power to detect a 5-kg greater mean weight loss in the low-carbohydrate group than in the conventional diet group . These calculations were based on an anticipated maximum weight loss by 6 months , with weight stabilization in both diet groups between 6 months and 1 year . To compensate for an anticipated dropout rate of 25 % , we set our enrollment target at 135 persons . R and omization was performed by using a pre-established algorithm generated from a r and om set of numbers that was constructed and held in a separate center and concealed from those enrolling persons during r and omization . We used stratified r and omization , with blocking within strata , to ensure assignment of approximately equal numbers of women , diabetic persons , and severely obese persons ( BMI 40 kg/m2 ) to each study group . Changes in weight , dietary intake , and metabolic data were compared between the 2 diets by r and om-coefficient analysis ( 11 ) . This type of analysis was selected to allow for a variable number of observations for participants and to take into account that the repeated observations of the outcome variables over time for individuals were correlated . The r and om-coefficient analysis model takes these correlations into account by allowing the intercept to vary r and omly among persons . We used a restricted maximum likelihood analysis , which assumed that changes were distributed according to a bivariate normal distribution and that data were missing at r and om . The outcome variables were changes from baseline in weight , dietary macronutrient consumption , and metabolic measurements . For all of these analyses , the covariates included an indicator variable for time ( 6 months and 1 year ) , diet group , and a diet group by time interaction term . This diet group by time interaction term was kept in the model , regardless of its statistical significance ( P = 0.063 for the weight loss analysis ) . Separate analyses to adjust for baseline differences between diet groups were also made by entering the following covariates to each of these models : age ; race ( white or African American ) ; sex ; baseline BMI ; baseline caloric intake ; and the presence or absence of hypertension , use of lipid-lowering therapy , diabetes , active smoking , and sleep apnea ( 12 ) . All variables were assessed for normality before entry into the analyses . Triglyceride , insulin , and glucose levels were skewed and thus were log-transformed before the analyses . Baseline differences between diet groups were compared by chi-square analysis for dichotomous variables and by the unpaired t-test for continuous variables . All P values are 2-sided , and a P value of 0.05 was considered statistically significant . Analyses were performed with SPSS statistical software , version 11.1 ( SPSS , Inc. , Chicago , Illinois ) . Missing Data Of the 132 enrolled persons , follow-up was done at 6 months for 79 persons and at 1 year for 87 persons . For measurements at 6 months , we retrieved weights on an additional 16 persons on the low-carbohydrate diet and 23 persons on the conventional diet ( total , 39 persons at a mean [ SD ] of 6.6 1.2 months ) . For measurements at 1 year , we retrieved weights on 18 persons on the low-carbohydrate diet and 21 persons on the conventional diet ( total , 39 persons at a mean [ SD ] of 13.5 3.2 months ) . Thus , we had 6-month weights on 118 of 132 persons ( 89 % ) and 1-year weights on 126 of 132 persons ( 96 % ) . Of the 18 persons who missed the 6-month visit but returned for the 1-year visit ( 6 in the low-carbohydrate group and 12 in the conventional diet group ) , all but 2 had 6-month weights retrieved from medical records . Of the 6 persons for whom no 1-year weights were available , 2 were in the low-carbohydrate group and 4 in the conventional diet group . The weights retrieved from medical records were obtained on scales that were different from those used for the study and were probably obtained in a nonuniform manner with regard to clothing . We used several approaches to h and le the 45 participants with missing data for diet recall and metabolic measurements . For the primary analysis by r and om-coefficient analysis , we assumed data were missing at r and om . To verify this assumption , we performed sensitivity analyses based on comparisons of baseline characteristics and weight loss differences between those who dropped out and those who completed the study . We also performed 2 additional sensitivity 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 Hypoenergetic very low-carbohydrate and low-fat diets are both commonly used for short-term weight loss ; however , few studies have directly compared their effect on blood lipids , with no studies to our knowledge comparing postpr and ial lipemia , an important independently identified cardiovascular risk factor . The primary purpose of this study was to compare the effects of a very low-carbohydrate and a low-fat diet on fasting blood lipids and postpr and ial lipemia in overweight men . In a balanced , r and omized , crossover design , overweight men ( n = 15 ; body fat > 25 % ; BMI , 34 kg/m(2 ) ) consumed 2 experimental diets for 2 consecutive 6-wk periods . One was a very low-carbohydrate ( < 10 % energy as carbohydrate ) diet and the other a low-fat ( < 30 % energy as fat ) diet . Blood was drawn from fasting subjects on separate days and an oral fat tolerance test was performed at baseline , after the very low-carbohydrate diet period , and after the low-fat diet period . Both diets had the same effect on serum total cholesterol , serum insulin , and homeostasis model analysis -insulin resistance ( HOMA-IR ) . Neither diet affected serum HDL cholesterol ( HDL-C ) or oxidized LDL ( oxLDL ) concentrations . Serum LDL cholesterol ( LDL-C ) was reduced ( P < 0.05 ) only by the low-fat diet ( -18 % ) . Fasting serum triacylglycerol ( TAG ) , the TAG/HDL-C ratio , and glucose were significantly reduced only by the very low-carbohydrate diet ( -44 , -42 , and -6 % , respectively ) . Postpr and ial lipemia was significantly reduced when the men consumed both diets compared with baseline , but the reduction was significantly greater after intake of the very low-carbohydrate diet .  Mean and peak LDL particle size increased only after the very low-carbohydrate diet . The short-term hypoenergetic low-fat diet was more effective at lowering serum LDL-C , but the very low-carbohydrate diet was more effective at improving characteristics of the metabolic syndrome as shown by a decrease in fasting serum TAG , the TAG/HDL-C ratio , postpr and ial lipemia , serum glucose , an increase in LDL particle size , and also greater weight loss ( P < 0.05 ) BACKGROUND The optimal dietary content and type of fat and carbohydrate for weight management has been debated for decades . OBJECTIVE The objective was to compare the effects of 3 ad libitum diets on the maintenance of an initial weight loss of > or=8 % and risk factors for CVD and diabetes during a 6-mo controlled dietary intervention . DESIGN Nondiabetic overweight or obese [ mean + /- SD body mass index ( in kg/m(2 ) ) : 31.5 + /- 2.6 ] men ( n = 55 ) and women ( n = 76 ) aged 28.2 + /- 4.8 y were r and omly assigned to a diet providing a moderate amount of fat ( 35 - 45 % of energy ) and > 20 % of fat as monounsaturated fatty acids ( MUFA diet ; n = 54 ) , to a low-fat ( 20 - 30 % of energy ) diet ( LF diet ; n = 51 ) , or to a control diet ( 35 % of energy as fat ; n = 26 ) . Protein constituted 10 - 20 % of energy in all 3 diets . All foods were provided free of charge from a purpose -built supermarket . RESULTS More subjects dropped out of the MUFA ( 28 % ) group than out of the LF group ( 16 % ) and control group ( 8 % ) ( MUFA compared with control : P < 0.05 ) . All groups regained weight ( MUFA : 2.5 + /- 0.7 kg ; LF : 2.2 + /- 0.7 kg ; and control : 3.8 + /- 0.8 kg ; NS ) . Body fat regain was lower in the LF ( 0.6 + /- 0.6 % ) and MUFA ( 1.6 + /- 0.6 % ) groups than in the control group ( 2.6 + /- 0.5 % ) ( P < 0.05 ) . In the MUFA group , fasting insulin decreased by 2.6 + /- 3.5 pmol/L , the homeostasis model assessment of insulin resistance by 0.17 + /- 0.13 , and the ratio of LDL to HDL by 0.33 + /- 0.13 ; in the LF group , these variables increased by 4.3 + /- 3.0 pmol/L ( P < 0.08 ) and 0.17 + /- 0.10 ( P < 0.05 ) and decreased by 0.02 + /- 0.09 ( P = 0.005 ) , respectively ; and in the control group , increased by 14.0 + /- 4.3 pmol/L ( P < 0.001 ) , 0.57 + /- 0.17 ( P < 0.001 ) , and 0.05 + /- 0.14 ( P = 0.036 ) , respectively . Dietary adherence was high on the basis of fatty acid changes in adipose tissue . CONCLUSIONS Diet composition had no major effect on preventing weight regain . However , both the LF and MUFA diets produced less body fat regain than did the control diet , and the dropout rate was lowest in the LF diet group , whereas fasting insulin decreased and the homeostasis model assessment of insulin resistance and ratio of LDL to HDL improved with the MUFA diet . This trial was registered at clinical trials.gov as NCT00274729 We tested whether nutrient intakes estimated from 4-d diet records were associated with plasma lipoprotein subclasses in 103 men who were r and omly assigned to a low-fat ( 24 % fat ) and a high-fat ( 46 % fat ) diet for 6 wk each in a crossover design . Postheparin plasma lipoprotein lipase ( LPL ) and hepatic lipase ( HL ) activities were also determined in a subset of 43 men . Changes in intake ( ie , high fat minus low fat ) of total saturated fatty acids , as well as myristic ( 14:0 ) and palmitic ( 16:0 ) acids , were positively correlated ( P < 0.01 ) with increases in mass of large LDL particles [ measured by analytic ultra-centrifugation as mass of lipoproteins of flotation rate ( Sf ) 7 - 12 ] and with LDL peak particle diameter and flotation rate , but not with changes in LDL-cholesterol concentration . Changes in total saturated fatty acids as well as myristic and palmitic acids were also inversely associated with changes in HL activity ( P < 0.05 ) . With the high-fat diet only , variation in dietary total saturated fatty acid intake was inversely correlated ( P < 0.01 ) with concentrations of small , dense LDL of Sf 0 - 5 . This correlation was significant specifically for myristic acid ( P < 0.001 ) . Stearic acid ( 18:0 ) , monounsaturates , and polyunsaturates showed no significant associations with lipoprotein concentrations . These data indicate that a high saturated fat intake ( especially 14:0 and 16:0 ) is associated with increased concentrations of larger , cholesterol-enriched LDL and this occurs in association with decreased HL activity 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 Low-carbohydrate diets have been used to manage obesity and its metabolic consequences . OBJECTIVE The objective was to study the effects of moderate carbohydrate restriction on  atherogenic dyslipidemia before and after weight loss and in conjunction with a low or high dietary saturated fat intake . DESIGN After 1 wk of consuming a basal diet , 178 men with a mean body mass index ( in kg/m(2 ) ) of 29.2 + /- 2.0 were r and omly assigned to consume diets with carbohydrate contents of 54 % ( basal diet ) , 39 % , or 26 % of energy and with a low saturated fat content ( 7 - 9 % of energy ) ; a fourth group consumed a diet with 26 % of energy as carbohydrate and 15 % as saturated fat . After 3 wk , the mean weight loss ( 5.12 + /- 1.83 kg ) was induced in all diet groups by a reduction of approximately 1000 kcal/d for 5 wk followed by 4 wk of weight stabilization . RESULTS The 26%-carbohydrate , low-saturated-fat diet reduced triacylglycerol , apolipoprotein B , small LDL mass , and total : HDL cholesterol and increased LDL peak diameter . These changes were significantly different from those with the 54%-carbohydrate diet . After subsequent weight loss , the changes in all these variables were significantly greater and the reduction in LDL cholesterol was significantly greater with the 54%-carbohydrate diet than with the 26%-carbohydrate diet . With the 26%-carbohydrate diet , lipoprotein changes with the higher saturated fat intakes were not significantly different from those with the lower saturated fat intakes , except for LDL cholesterol , which decreased less with the higher saturated fat intake because of an increase in mass of large LDL . CONCLUSIONS Moderate carbohydrate restriction and weight loss provide equivalent but nonadditive approaches to improving atherogenic dyslipidemia . Moreover , beneficial lipid changes result ing from a reduced carbohydrate intake were not significant after weight loss 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 BACKGROUND Low-carbohydrate diets are popular for weight loss , but their cardiovascular effects have not been well-studied , particularly in diverse population s. OBJECTIVE To examine the effects of a low-carbohydrate diet compared with a low-fat diet on body weight and cardiovascular risk factors . DESIGN A r and omized , parallel-group trial . ( Clinical Trials.gov : NCT00609271 ) . SETTING A large academic medical center . PARTICIPANTS 148 men and women without clinical cardiovascular disease and diabetes . INTERVENTION A low-carbohydrate ( < 40 g/d ) or low-fat ( < 30 % of daily energy intake from total fat [ < 7 % saturated fat ] ) diet . Both groups received dietary counseling at regular intervals throughout the trial . MEASUREMENTS Data on weight , cardiovascular risk factors , and dietary composition were collected at 0 , 3 , 6 , and 12 months . RESULTS Sixty participants ( 82 % ) in the low-fat group and 59 ( 79 % ) in the low-carbohydrate group completed the intervention . At 12 months , participants on the low-carbohydrate diet had greater decreases in weight ( mean difference in change , -3.5 kg [ 95 % CI , -5.6 to -1.4 kg ] ; P = 0.002 ) , fat mass ( mean difference in change , -1.5 % [ CI , -2.6 % to -0.4 % ] ; P = 0.011 ) , ratio of total-high-density lipoprotein ( HDL ) cholesterol ( mean difference in change , -0.44 [ CI , -0.71 to -0.16 ] ; P = 0.002 ) , and triglyceride level ( mean difference in change , -0.16 mmol/L [ -14.1 mg/dL ] [ CI , -0.31 to -0.01 mmol/L { -27.4 to -0.8 mg/dL } ] ; P = 0.038 ) and greater increases in HDL cholesterol level ( mean difference in change , 0.18 mmol/L [ 7.0 mg/dL ] [ CI , 0.08 to 0.28 mmol/L { 3.0 to 11.0 mg/dL } ] ; P < 0.001 ) than those on the low-fat diet . LIMITATION Lack of clinical cardiovascular disease end points . CONCLUSION The low-carbohydrate diet was more effective for weight loss and cardiovascular risk factor reduction than the low-fat diet . Restricting carbohydrate may be an option for persons seeking to lose weight and reduce cardiovascular risk factors . PRIMARY FUNDING SOURCE National Institutes of Health Overweight and obese men and women ( 24 - 61 yr of age ) were recruited into a r and omized trial to compare the effects of a low-fat ( LF ) vs. a low-carbohydrate ( LC ) diet on weight loss .  Thirty-one subjects completed all 10 wk of the diet intervention ( retention , 78 % ) . Subjects on the LF diet consumed an average of 17.8 % of energy from fat , compared with their habitual intake of 36.4 % , and had a result ing energy restriction of 2540 kJ/d . Subjects on the LC diet consumed an average of 15.4 % carbohydrate , compared with habitual intakes of about 50 % carbohydrate , and had a result ing energy restriction of 3195 kJ/d . Both groups of subjects had significant weight loss over the 10 wk of diet intervention and nearly identical improvements in body weight and fat mass . LF subjects lost an average of 6.8 kg and had a decrease in body mass index of 2.2 kg/m2 , compared with a loss of 7.0 kg and decrease in body mass index of 2.1 kg/m2 in the LC subjects . The LF group better preserved lean body mass when compared with the LC group ; however , only the LC group had a significant decrease in circulating insulin concentrations . Group results indicated that the diets were equally effective in reducing systolic blood pressure by about 10 mm Hg and diastolic pressure by 5 mm Hg and decreasing plasminogen activator inhibitor-1 bioactivity . Blood beta-hydroxybutyrate concentrations were increased in the LC only , at the 2- and 4-wk time points . These data suggest that energy restriction achieved by a very LC diet is equally effective as a LF diet strategy for weight loss and decreasing body fat in overweight and obese adults OBJECTIVE Low-fat hypocaloric diets reduce insulin resistance and prevent type 2 diabetes in those at risk .  Low-carbohydrate , high-fat diets are advocated as an alternative , but reciprocal increases in dietary fat may have detrimental effects on insulin resistance and offset the benefits of weight reduction . RESEARCH DESIGN AND METHODS We investigated a low-fat ( 20 % fat , 60 % carbohydrate ) versus a low-carbohydrate ( 60 % fat , 20 % carbohydrate ) weight reduction diet in 24 overweight/obese subjects ( [ mean ± SD ] BMI 33.6 ± 3.7 kg/m2 , aged 39 ± 10 years ) in an 8-week r and omized controlled trial . All food was weighed and distributed , and intake was calculated to produce a 500 kcal/day energy deficit . Insulin action was assessed by the euglycemic clamp and insulin secretion by meal tolerance test . Body composition , adipokine levels , and vascular compliance by pulse-wave analysis were also measured . RESULTS Significant weight loss occurred in both groups ( P < 0.01 ) , with no difference between groups ( P = 0.40 ) . Peripheral glucose uptake increased , but there was no difference between groups ( P = 0.28 ) , and suppression of endogenous glucose production was also similar between groups . Meal tolerance – related insulin secretion decreased with weight loss with no difference between groups ( P = 0.71 ) . The change in overall systemic arterial stiffness was , however , significantly different between diets ( P = 0.04 ) ; this reflected a significant decrease in augmentation index following the low-fat diet , compared with a nonsignificant increase within the low-carbohydrate group . CONCLUSIONS This study demonstrates comparable effects on insulin resistance of low-fat and low-carbohydrate diets independent of macronutrient content . The difference in augmentation index may imply a negative effect of low-carbohydrate diets on vascular risk CONTEXT The results of clinical trials involving diet in the treatment of obesity have been inconsistent , possibly due to inherent physiological differences among study participants . OBJECTIVE To determine whether insulin secretion affects weight loss with 2 popular diets . DESIGN , SETTING , AND PARTICIPANTS R and omized trial of obese young adults ( aged 18 - 35 years ; n = 73 ) conducted from September 2004 to December 2006 in Boston , Mass , and consisting of a 6-month intensive intervention period and a 12-month follow-up period . Serum insulin concentration at 30 minutes after a 75-g dose of oral glucose was determined at baseline as a measure of insulin secretion . Outcomes were assessed at 6 , 12 , and 18 months . Missing data were imputed conservatively . INTERVENTIONS A low-glycemic load ( 40 % carbohydrate and 35 % fat ) vs low-fat ( 55 % carbohydrate and 20 % fat ) diet . MAIN OUTCOME MEASURES Body weight , body fat percentage determined by dual-energy x-ray absorptiometry , and cardiovascular disease risk factors . RESULTS Change in body weight and body fat percentage did not differ between the diet groups overall . However , insulin concentration at 30 minutes after a dose of oral glucose was an effect modifier ( group x time x insulin concentration at 30 minutes : P = .02 for body weight and P = .01 for body fat percentage ) . For those with insulin concentration at 30 minutes above the median ( 57.5 microIU/mL ; n = 28 ) , the low-glycemic load diet produced a greater decrease in weight ( -5.8 vs -1.2 kg ; P = .004 ) and body fat percentage ( -2.6 % vs -0.9 % ; P = .03 ) than the low-fat diet at 18 months . There were no significant differences in these end points between diet groups for those with insulin concentration at 30 minutes below the median level ( n = 28 ) . Insulin concentration at 30 minutes after a dose of oral glucose was not a significant effect modifier for cardiovascular disease risk factors . In the full cohort , plasma high-density lipoprotein cholesterol and triglyceride concentrations improved more on the low-glycemic load diet , whereas low-density lipoprotein cholesterol concentration improved more on the low-fat diet . CONCLUSIONS Variability in dietary weight loss trials may be partially attributable to differences in hormonal response . Reducing glycemic load may be especially important to achieve weight loss among individuals with high insulin secretion . Regardless of insulin secretion , a low-glycemic load diet has beneficial effects on high-density lipoprotein cholesterol and triglyceride concentrations but not on low-density lipoprotein cholesterol concentration . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00130299 Background Optimal macronutrient distribution of weight loss diets has not been established . The distribution of energy from carbohydrate and fat has been observed to promote differential plasma lipid responses in previous weight loss studies , and insulin resistance status may interact with diet composition and affect weight loss and lipid responses . Methods and Results Overweight and obese women ( n=245 ) were enrolled in a 1‐year behavioral weight loss intervention  and r and omly assigned to 1 of 3 study groups : a lower fat ( 20 % energy ) , higher carbohydrate ( 65 % energy ) diet ; a lower carbohydrate ( 45 % energy ) , higher fat ( 35 % energy ) diet ; or a walnut‐rich , higher fat ( 35 % energy ) , lower carbohydrate ( 45 % energy ) diet . Blood sample s and data available from 213 women at baseline and at 6 months were the focus of this analysis . Triglycerides , total cholesterol , and high‐ and low‐density lipoprotein cholesterol were quantified and compared between and within groups . Triglycerides decreased in all study arms at 6 months ( P<0.05 ) . The walnut‐rich diet increased high‐density lipoprotein cholesterol more than either the lower fat or lower carbohydrate diet ( P<0.05 ) . The walnut‐rich diet also reduced low‐density lipoprotein cholesterol in insulin‐sensitive women , whereas the lower fat diet reduced both total cholesterol and high‐density lipoprotein cholesterol in insulin‐sensitive women ( P<0.05 ) . Insulin sensitivity and C‐reactive protein levels also improved . Conclusions Weight loss was similar across the diet groups , although insulin‐sensitive women lost more weight with a lower fat , higher carbohydrate diet versus a higher fat , lower carbohydrate diet . The walnut‐rich , higher fat diet result ed in the most favorable changes in lipid levels . Clinical Trial Registration URL : http://www . clinical trials.gov . Unique identifier : NCT01424007 OBJECTIVE Long-term dietary intervention frequently induces a rapid weight decline followed by weight stabilization/regain . Here , we sought to identify adipokine biomarkers that may reflect continued beneficial effects of dieting despite partial weight regain . RESEARCH DESIGN AND METHODS We analyzed the dynamics of fasting serum levels of 12 traditional metabolic biomarkers and novel adipokines among 322 participants in the 2-year Dietary Intervention R and omized Controlled Trial ( DIRECT ) of low-fat , Mediterranean , or low-carbohydrate diets for weight loss . RESULTS We identified two distinct patterns : Pattern A includes biomarkers ( insulin , triglycerides , leptin , chemerin , monocyte chemoattractant protein 1 , and retinol-binding protein 4 ) whose dynamics tightly correspond to changes in body weight , with the trend during the weight loss phase ( months 0–6 ) going in the opposite direction to that in the weight maintenance/regain phase ( months 7–24 ) ( P < 0.05 between phases , all biomarkers ) . Pattern B includes biomarkers ( high molecular weight adiponectin , HDL cholesterol [ HDL-C ] , high-sensitivity C-reactive protein [ hsCRP ] , fetuin-A , progranulin , and vaspin ) that displayed a continued , cumulative improvement ( P < 0.05 compared with baseline , all biomarkers ) throughout the intervention . These patterns were consistent across sex , diabetic groups , and diet groups , although the magnitude of change varied . Hierarchical analysis suggested similar clusters , revealing that the dynamic of leptin ( pattern A ) was most closely linked to weight change and that the dynamic of hsCRP best typified pattern B. CONCLUSIONS hsCRP , HDL-C , adiponectin , fetuin-A , progranulin , and vaspin levels display a continued long-term improvement despite partial weight regain . This may likely reflect either a delayed effect of the initial weight loss or a continuous beneficial response to switching to healthier dietary patterns Context Low-carbohydrate weight reduction diets are popular despite a dearth of data on long-term efficacy and adverse effects . Contribution Community-dwelling hyperlipidemic persons were r and omly assigned to either a low-carbohydrate , ketogenic diet or a low-fat , low-cholesterol , reduced-calorie diet for 24 weeks . Compared to the low-fat group , patients in the low-carbohydrate group lost more weight , had a greater decrease in triglyceride levels , and had higher high-density lipoprotein cholesterol levels . Levels of low-density lipoprotein cholesterol remained stable in both groups . Side effects were more common in the low-cholesterol group but were generally mild . Caution s While the study suggests the efficacy and relative safety of the low-cholesterol diet , the high dropout rate , self-directed adherence to the diet , and relatively short observation period challenge the generalizability of the findings . The Editors As the prevalence of obesity has increased over the past 20 years ( 1 ) , the difficulties faced by overweight patients and their health care practitioners have become apparent . Fewer than 25 % of Americans who attempt to lose weight actually reduce caloric intake and increase exercise as currently recommended ( 2 ) . Persons who successfully lose weight have difficulty maintaining their weight loss ( 3 ) . Therefore , it is not surprising that consumers spend $ 33 billion yearly on weight loss products and services in search of effective therapies ( 2 ) . Because many weight loss interventions are unproven and untested , practitioners often lack information with which to recommend a certain therapy or to monitor a patient once a therapy is chosen . One approach to weight loss that has gained recognition in the face of modest supportive scientific evidence is the low-carbohydrate diet . A popular version of this diet recommends extreme restriction of carbohydrate intake to less than 20 g/d initially ( 4 ) . This level of carbohydrate restriction can induce serum and urinary ketones and weight loss ( 5 , 6 ) . However , until recently , available data on low-carbohydrate diets came from small studies of short duration , most of which were uncontrolled ( 5 , 7 - 10 ) . We examined body weight , body composition , serum lipid levels , and adverse effects over 24 weeks in hyperlipidemic persons who were r and omly assigned to follow a low-carbohydrate , ketogenic diet or a low-fat , low-cholesterol , reduced-calorie diet commonly used to induce weight loss and decrease serum lipid levels . Methods Participants Generally healthy persons were recruited from the community . Inclusion criteria were age 18 to 65 years , body mass index of 30 to 60 kg/m2 , desire to lose weight , elevated lipid levels ( total cholesterol level > 5.17 mmol/L [ > 200 mg/dL ] , low-density lipoprotein [ LDL ] cholesterol level > 3.36 mmol/L [ > 130 mg/dL ] , or triglyceride level > 2.26 mmol/L [ 200 mg/dL ] ) , and no serious medical condition . Exclusion criteria were use of any prescription medication in the previous 2 months ( except for oral contraceptives , estrogen therapy , and stable thyroid medication ) , pregnancy or breastfeeding , use of any weight loss diet or diet pills in the previous 6 months , and baseline ketonuria . All participants provided written informed consent , and the institutional review board of Duke University Health System approved the study . Participants received no monetary incentive . Interventions By using a computer-generated simple r and omization list , participants were allocated to receive the low-carbohydrate diet or low-fat diet . The intervention for both groups included group meetings , diet instruction , and an exercise recommendation . Group meetings took place at an outpatient research clinic twice monthly for 3 months , then monthly for 3 months . These meetings typically lasted 1 hour and consisted of diet instruction , supportive counseling , question naires , and biomedical measurements . During the study , participants selected their own menus and prepared or bought their own meals according to the guidelines presented to them . Participants were encouraged to exercise for 30 minutes at least 3 times weekly , but no formal exercise program or incentives were provided . Low-Carbohydrate Diet Using a popular diet book published by a lay press and additional h and outs , trained research staff instructed participants to restrict intake of carbohydrates to less than 20 g/d ( 4 ) . Participants were permitted unlimited amounts of animal foods ( meat , fowl , fish , and shellfish ) , unlimited eggs , 4 oz of hard cheese , 2 cups of salad vegetables ( such as lettuce , spinach , or celery ) , and 1 cup of low-carbohydrate vegetables ( such as broccoli , cauliflower , or squash ) daily . Participants were encouraged to drink 6 to 8 glasses of water daily . When participants were halfway to their goal body weight ( determined at the week 10 visit with assistance from research personnel ) , they were advised to add approximately 5 g of carbohydrates to their daily intake each week until they reached a level at which body weight was maintained . To simulate the practice of the study sponsor , the low-carbohydrate diet group also received daily nutritional supplements ( multivitamin , essential oils , diet formulation , and chromium picolinate ; for a list of the composition of these supplements , see the Appendix ) ( 6 ) . Low-Fat Diet Using a commonly available booklet and additional h and outs , a registered dietitian instructed participants in a diet consisting of less than 30 % of daily energy intake from fat , less than 10 % of daily energy intake from saturated fat , and less than 300 mg of cholesterol daily ( 11 , 12 ) . The recommended energy intake was 2.1 to 4.2 MJ ( 500 to 1000 kcal ) less than the participant 's calculated energy intake for weight maintenance ( body weight in pounds 10 ) ( 13 ) . Primary Outcome Measure Body weight and body mass index were the primary outcome measures . At each visit , participants were weighed on the same calibrated scale while wearing lightweight clothing and no shoes .  Body mass index was calculated as body weight in kilograms divided by height in meters squared . Secondary Outcome Measures Adherence Adherence to the diet was measured by self-report , food records , and , for the low-carbohydrate diet group , urinary ketone assessment . Diet Composition All participants completed a 24-hour recall of food intake at baseline and take-home food records ( 5 consecutive days , including a weekend ) that were collected at each meeting during the study . Participants were instructed on how to document food intake and were given h and outs with examples of how to complete the records . A sample of participants ( 13 in the low-carbohydrate diet group and 7 in the low-fat diet group ) who completed the study was selected for food record analysis by the research staff on the basis of adequacy of detail in their records . A registered dietitian analyzed the food records by using a nutrition software program ( Nutritionist Five , version 1.6 [ First Data Bank , Inc. , San Bruno , California ] ) . Ketonuria Restriction of dietary intake of carbohydrates to less than 40 g/d typically results in ketonuria that is detectable by dipstick analysis , which can be used to monitor adherence to the low-carbohydrate diet ( 14 , 15 ) . At each return visit , participants provided a fresh urine specimen for analysis . The following semi-quantitative scale was used to categorize ketone content : none , trace ( up to 0.9 mmol/L [ 5 mg/dL ] ) , small ( 0.9 to 6.9 mmol/L [ 5 to 40 mg/dL ] ) , moderate ( 6.9 to 13.8 mmol/L [ 40 to 80 mg/dL ] ) , large80 ( 13.8 to 27.5 mmol/L [ 80 to 160 mg/dL ] ) , and large160 ( > 27.5 mmol/L [ > 160 mg/dL ] ) . Body Composition Body composition was estimated by using bioelectric impedance ( model TBF-300A [ Tanita Corp. , Arlington Heights , Illinois ] ) at approximately the same time of day ( afternoon or evening ) at each return visit . In a subset of 33 participants , the percentage of body fat as measured by bioelectric impedance had excellent correlation with the percentage as measured by dual-energy x-ray absorptiometry ( r = 0.93 [ 95 % CI , 0.87 to 0.97 ] ) . Vital Signs Blood pressure and pulse rate were measured in the nondominant arm by using an automated digital cuff ( model HEM-725C [ Omron Corp. , Vernon Hills , Illinois ] ) after the participant had been sitting for 3 minutes . Two measurements were taken at each visit and averaged for the analysis . Serum Lipids and Lipoproteins Serum specimens for lipid measurement were obtained in the morning after at least 8 hours of fasting at the screening visit and at 8 , 16 , and 24 weeks . Other Metabolic Effects Serum tests for sodium , potassium , chloride , urea nitrogen , creatinine , calcium , phosphorus , total protein , albumin , uric acid , total bilirubin , alanine aminotransferase , aspartate aminotransferase , alkaline phosphatase , thyroid-stimulating hormone , iron , hemoglobin , leukocyte count , and platelet count were obtained at the screening visit and at 8 , 16 , and 24 weeks . The glomerular filtration rate was estimated by using an equation that included age ; sex ; race ; and serum levels of albumin , creatinine , and urea nitrogen ( Modification of Diet in Renal Disease Study equation ) ( 16 ) . Adverse Effects At all return visits , participants completed an open-ended question naire on side effects . At the 20- and 24-week visits , participants completed a checklist of the side effects that were most often mentioned during the study . Statistical Analysis Analyses were performed by using S-PLUS software , version 6.1 ( Insightful Corp. , Seattle , Washington ) , or SAS software , version 8.02 ( SAS Institute , Inc. , Cary , North Carolina ) . For categorical outcomes , groups were compared by using the chi-square test or Fisher exact test , as appropriate . For all primary and secondary continuous outcomes , linear mixed-effects models ( PROC MIXED procedure in SAS software ) that included fixed and r and om effects were used to determine expected mean values at each time point and to test hypotheses of group differences . In most body weight and Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Little is known about whether cholesteryl ester transfer protein ( CETP ) genetic variation may modify the effect of weight-loss diets varying in fat content on changes in lipid levels . We analyzed the interaction between the CETP variant rs3764261 and dietary interventions on changes in lipid levels among 732 overweight/obese adults from a 2 year r and omized weight-loss trial [ Preventing Overweight Using Novel Dietary Strategies ( POUNDS LOST ) ] , and replicated the findings in 171 overweight/obese adults from an independent 2 year weight-loss trial [ Dietary Intervention R and omized Controlled Trial ( DIRECT ) ] . In the POUNDS LOST , participants with the CETP rs3764261 CC genotype on the high-fat diet had larger increases in HDL cholesterol ( P = 0.001 ) and decreases in triglycerides ( P = 0.007 ) than those on the low-fat diet at 6 months , while no significant difference between these two diets was observed among participants carrying other genotypes . The gene-diet interactions on changes in HDL-cholesterol and triglycerides were replicated in the DIRECT ( pooled P for interaction ≤ 0.01 ) . Similar results on trajectory of changes in HDL cholesterol and triglycerides over the 2 year intervention were observed in both trials . Our study provides replicable evidence that individuals with the CETP rs3764261 CC genotype might derive greater effects on raising HDL cholesterol and lowering triglycerides by choosing a low-carbohydrate/high-fat weight-loss diet instead of a low-fat diet CONTEXT The scarcity of data addressing the health effects of popular diets is an important public health concern , especially since patients and physicians are interested in using popular diets as individualized eating strategies for disease prevention . OBJECTIVE To assess adherence rates and the effectiveness of 4 popular diets ( Atkins , Zone , Weight Watchers , and Ornish ) for weight loss and cardiac risk factor reduction . DESIGN , SETTING , AND PARTICIPANTS A single-center r and omized trial at an academic medical center in Boston , Mass , of overweight or obese ( body mass index : mean , 35 ; range , 27 - 42 ) adults aged 22 to 72 years with known hypertension , dyslipidemia , or fasting hyperglycemia . Participants were enrolled starting July 18 , 2000 , and r and omized to 4 popular diet groups until January 24 , 2002 . INTERVENTION A total of 160 participants were r and omly assigned to either Atkins ( carbohydrate restriction , n=40 ) , Zone ( macronutrient balance , n=40 ) , Weight Watchers ( calorie restriction , n=40 ) , or Ornish ( fat restriction , n=40 ) diet groups . After 2 months of maximum effort , participants selected their own levels of dietary adherence . MAIN OUTCOME MEASURES One-year changes in baseline weight and cardiac risk factors , and self-selected dietary adherence rates per self-report . RESULTS Assuming no change from baseline for participants who discontinued the study , mean ( SD ) weight loss at 1 year was 2.1 ( 4.8 ) kg for Atkins ( 21 [ 53 % ] of 40 participants completed , P = .009 ) , 3.2 ( 6.0 ) kg for Zone ( 26 [ 65 % ] of 40 completed , P = .002 ) , 3.0 ( 4.9 ) kg for Weight Watchers ( 26 [ 65 % ] of 40 completed , P < .001 ) , and 3.3 ( 7.3 ) kg for Ornish ( 20 [ 50 % ] of 40 completed , P = .007 ) . Greater effects were observed in study completers . Each diet significantly reduced the low-density lipoprotein/high-density lipoprotein ( HDL ) cholesterol ratio by approximately 10 % ( all P<.05 ) , with no significant effects on blood pressure or glucose at 1 year . Amount of weight loss was associated with self-reported dietary adherence level ( r = 0.60 ; P<.001 ) but not with diet type ( r = 0.07 ; P = .40 ) . For each diet , decreasing levels of total/HDL cholesterol , C-reactive protein , and insulin were significantly associated with weight loss ( mean r = 0.36 , 0.37 , and 0.39 , respectively ) with no significant difference between diets ( P = .48 , P = .57 , P = .31 , respectively ) . CONCLUSIONS Each popular diet modestly reduced body weight and several cardiac risk factors at 1 year . Overall dietary adherence rates were low , although increased adherence was associated with greater weight loss and cardiac risk factor reductions for each diet group Examining predictors of blood-pressure ( BP ) response to weight-loss diets might provide insight into mechanisms and help guide clinical care . We examined whether certain baseline patient characteristics ( e.g. diet , medical history and laboratory tests ) predicted BP response to two weight-loss diet approaches that differ in macronutrient content . One hundred and forty-six overweight adult out patients were r and omized to either a low-carbohydrate diet ( N = 72 ) or orlistat plus a low-fat diet ( N = 74 ) for 48 weeks . Predictors of BP reduction were evaluated using a structured approach and r and om effects regression models . Participants were 56 % African-American , 72 % male and 53 ( ±10 ) years-old . Of the variables considered , low baseline high-density lipoprotein ( HDL ) predicted greater reduction in BP in those patients who received the low-carbohydrate diet ( p = 0.03 for systolic BP ; p = 0.03 for diastolic BP and p = 0.02 for mean arterial pressure ) . A low HDL level may identify patients who will have greater BP improvement on a low-carbohydrate diet OBJECTIVE Low-carbohydrate diets have become a popular alternative to st and ard diets for weight loss . Our aim was to compare the cost-effectiveness of these two diets . RESEARCH METHODS AND PROCEDURES The patient population included 129 severely obese subjects ( BMI = 42.9 ) from a r and omized trial ; participants had a high prevalence of diabetes or metabolic syndrome . We compared within-trial costs , quality -adjusted life years ( QALYs ) , and the incremental cost-effectiveness ratio ( CER ) for the two study groups . We imputed missing values for QALYs . The CER was bootstrapped to derive 95 % confidence intervals and to define acceptability cut-offs . We took a societal perspective for our analysis . RESULTS Total costs during the one year of the trial were 6742 dollars + /- 6675 and 6249 dollars + /- 5100 for the low-carbohydrate and st and ard groups , respectively ( p = 0.78 ) . Participants experienced 0.64 + /- 0.02 and 0.61 + /- 0.02 QALYs during the one year of the study , respectively ( p = 0.17 for difference ) . The point estimate of the incremental CER was -1225 dollars/QALY ( i.e. , the low-carbohydrate diet dominated the st and ard diet ) . However , in the bootstrap analysis , the wide spread of CERs caused the 95 % confidence interval to be undefined . The probabilities that the low-carbohydrate diet was acceptable , using cut-offs of 50,000 dollars/QALY , 100,000 dollars/QALY , and 150,000 dollars/QALY , were 72.4 % 78.6 % , and 79.8 % , respectively . DISCUSSION The low-carbohydrate diet was not more cost-effective for weight loss than the st and ard diet in the patient population studied . Larger studies are needed to better assess the cost-effectiveness of dietary therapies for weight loss BACKGROUND Despite the popularity of the low-carbohydrate , high-protein , high-fat ( Atkins ) diet , no r and omized , controlled trials have evaluated its efficacy . METHODS We conducted a one-year , multicenter , controlled trial involving 63 obese men and women who were r and omly assigned to either a low-carbohydrate , high-protein , high-fat diet or a low-calorie , high-carbohydrate , low-fat ( conventional ) diet . Professional contact was minimal to replicate the approach used by most dieters . RESULTS Subjects on the low-carbohydrate diet had lost more weight than subjects on the conventional diet at 3 months ( mean [ + /-SD ] , -6.8+/-5.0 vs. -2.7+/-3.7 percent of body weight ; P=0.001 ) and 6 months ( -7.0+/-6.5 vs. -3.2+/-5.6 percent of body weight , P=0.02 ) , but the difference at 12 months was not significant ( -4.4+/-6.7 vs. -2.5+/-6.3 percent of body weight , P=0.26 ) . After three months , no significant differences were found between the groups in total or low-density lipoprotein cholesterol concentrations . The increase in high-density lipoprotein cholesterol concentrations and the decrease in triglyceride concentrations were greater among subjects on the low-carbohydrate diet than among those on the conventional diet throughout most of the study . Both diets significantly decreased diastolic blood pressure and the insulin response to an oral glucose load . CONCLUSIONS The low-carbohydrate diet produced a greater weight loss ( absolute difference , approximately 4 percent ) than did the conventional diet for the first six months , but the differences were not significant at one year . The low-carbohydrate diet was associated with a greater improvement in some risk factors for coronary heart disease . Adherence was poor and attrition was high in both groups . Longer and larger studies are required to determine the long-term safety and efficacy of low-carbohydrate , high-protein , high-fat diets Background —Oxidized LDL ( oxLDL ) is thought to play a key role in the inflammatory response in the arterial vessel wall . Methods and Results —In a prospect i ve , nested , case-control study , the association between plasma oxLDL and risk of an  acute coronary heart disease ( CHD ) event was investigated in men without prevalent CHD or diabetes mellitus at baseline . Subjects came from 2 population -based MONICA/KORA Augsburg surveys conducted in the years 1989–1990 and 1994–1995 with follow-up in 1998 ( mean±SD follow-up time , 5.6±2.6 years ) .  OxLDL was determined by ELISA in 88 men with incident CHD and in 258 age- and survey-matched controls .  Hazard ratios ( HRs ) were estimated from conditional logistic-regression models with matching for age and survey . Baseline mean plasma oxLDL concentrations were significantly higher in subjects who subsequently experienced an event compared with controls ( mean±SD , 110±32 versus 93±28 U/L ; P≤0.001 ) . After adjustment for smoking , hypertension , obesity , physical activity , education , and alcohol consumption , the HR for a future CHD event in a comparison of the upper tertile of the oxLDL distribution with the lower tertile was 4.25 ( 95 % confidence interval , 2.09 to 8.63 ; P<0.001 ) . Plasma oxLDL was the strongest predictor of CHD events compared with a conventional lipoprotein profile and other traditional risk factors for CHD . When both oxLDL and C-reactive protein were simultaneously assessed in the same model , they still predicted future CHD events even after multivariable adjustment . Conclusions —Elevated concentrations of oxLDL are predictive of future CHD events in apparently healthy men . Thus , oxLDL may represent a promising risk marker for clinical CHD complications and should be evaluated in further studies Background We investigated whether macronutrient composition of energy-restricted diets influences the efficacy of a telemedically guided weight loss program . Methods Two hundred overweight subjects were r and omly assigned to a conventional low-fat diet and a low-carbohydrate diet group ( target carbohydrate content : > 55 % energy and < 40 % energy , respectively ) . Both groups attended a weekly nutrition education program and dietary counselling by telephone , and had to transfer actual body weight data to our clinic weekly with added Bluetooth ® technology by mobile phone . Various fatness and fat distribution parameters , energy and macronutrient intake , and various biochemical risk markers were measured at baseline and after 6 , and 12 months . Results In both groups , energy intake decreased by 400 kcal/d compared to baseline values within the first 6 months and slightly increased again within the second 6 months . Macronutrient composition differed significantly between the groups from the beginning to month 12 . At study termination , weight loss was 5.8 kg ( SD : 6.1 kg ) in the low-carbohydrate group and 4.3 kg ( SD : 5.1 kg ) in the low-fat group ( p = 0.065 ) . In the low-carbohydrate group , triglyceride and HDL-cholesterol levels were lower at month 6 and waist circumference and systolic blood pressure were lower at month 12 compared with the low-fat group ( P = 0.005–0.037 ) . Other risk markers improved to a similar extent in both groups . Conclusion Despite favourable effects of both diets on weight loss , the carbohydrate-reduced diet was more beneficial with respect to cardiovascular risk factors compared to the fat-reduced diet . Nevertheless , compliance with a weight loss program appears to be even a more important factor for success in prevention and treatment of obesity than the composition of the diet . Trial registration Clinical trials.gov as Our aim was to determine whether short-term weight loss on a low-carbohydrate/low-saturated fat diet improved endothelial function compared with a conventional high-carbohydrate diet , as this diet is expected to lower both blood glucose and LDL-cholesterol . In a r and omised parallel design of two energy-restricted diets in an outpatient setting , thirty-six subjects ( BMI 33 ( sem 4 ) kg/m2 ) were r and omised to a low- or high-carbohydrate diet both low in saturated fat .  Flow-mediated dilatation ( FMD ) , fasting glucose , insulin , lipids , adiponectin and adhesion molecules were measured at baseline , during weight loss and at 52 weeks . FMD did not change with either diet ( 5.2 ( sem 0.6 ) to 5.5 ( sem 0.6 ) % ) despite weight loss of 5 % and significant reductions in glucose and insulin and LDL-cholesterol and was not different after sustained weight loss of 5 % at 52 weeks . Adiponectin fell by 6 % at 12 weeks ( P = 0.1 ) with weight loss but rose by 17 % at 12 months ( P < 0.05 ) with 5 % weight loss . There were no effects of diet . In contradistinction , adhesion molecules fell at 12 weeks , vascular cell adhesion molecule-1 by 14 % and intracellular adhesion molecule-1 by 13 % ( both P < 0.05 ) . There were correlations between change in adiponectin at 12 months and change in HDL ( r 0.778 , P < 0.01 ) and glucose ( r - 0.563 , P = 0.057 ) . In summary , weight loss does not improve FMD . Novel cardiovascular risk factors improved at 12 weeks but the improvement in adiponectin was delayed CONTEXT Evidence is conflicting regarding the performance of apolipoproteins vs traditional lipids for predicting  coronary heart disease ( CHD ) risk .  OBJECTIVES To compare performance of different lipid measures for CHD prediction using discrimination and calibration characteristics and reclassification of risk categories ; to assess incremental utility of apolipoproteins over traditional lipids for CHD prediction . DESIGN , SETTING , AND PARTICIPANTS Population -based , prospect i ve cohort from , Framingham , Massachusetts . We evaluated  serum total cholesterol , high-density lipoprotein cholesterol ( HDL-C ) , low-density lipoprotein cholesterol ( LDL-C ) , non-HDL-C , apolipoprotein ( apo ) A-I and apo B , and 3 lipid ratios ( total cholesterol : HDL-C , LDL-C : HDL-C , and apo B : apo A-I ) in 3322 middle-aged white participants who attended the fourth offspring examination cycle ( 1987 - 1991 ) and were without cardiovascular disease . Fifty-three percent of the participants were women . MAIN OUTCOME MEASURE Incidence of first CHD event ( recognized or unrecognized myocardial infa rct ion , angina pectoris , coronary insufficiency , or coronary heart disease death ) . RESULTS After a median follow-up of 15.0 years , 291 participants , 198 of whom were men , developed CHD . In multivariate models adjusting for nonlipid risk factors , the apo B : apo A-I ratio predicted CHD ( hazard ratio [ HR ] per SD increment , 1.39 ; 95 % confidence interval [ CI ] , 1.23 - 1.58 in men and HR , 1.40 ; 95 % CI , 1.16 - 1.67 in women ) , but risk ratios were similar for total cholesterol : HDL-C ( HR , 1.39 ; 95 % CI , 1.22 - 1.58 in men and HR , 1.39 ; 95 % CI , 1.17 - 1.66 in women ) and for LDL-C : HDL-C ( HR , 1.35 ; 95 % CI , 1.18 - 1.54 in men and HR , 1.36 ; 95 % CI 1.14 - 1.63 in women ) . In both sexes , models using the apo B : apo A-I ratio demonstrated performance characteristics comparable with but not better than that for other lipid ratios . The apo B : apo A-I ratio did not predict CHD risk in a model containing all components of the Framingham risk score including total cholesterol : HDL-C ( P = .12 in men ; P = .58 in women ) . CONCLUSIONS In this large , population -based cohort , the overall performance of apo B : apo A-I ratio for prediction of CHD was comparable with that of traditional lipid ratios but did not offer incremental utility over total cholesterol : HDL-C. These data do not support measurement of apo B or apo A-I in clinical practice when total cholesterol and HDL-C measurements are available OBJECTIVES This study was design ed to test the hypothesis that at any low-density lipoprotein cholesterol ( LDL-C ) level , other lipid parameters such as non-high-density lipoprotein cholesterol ( HDL-C ) levels , triglyceride ( TG ) levels , and the total cholesterol (TC)/HDL-C are still associated with an increased coronary heart disease ( CHD ) risk . BACKGROUND Although LDL-C is considered to be the primary target of lipid-lowering therapy , other parameters of the lipoprotein-lipid profile may more closely associated with CHD risk . METHODS In the EPIC ( European Prospect i ve Investigation Into Cancer and Nutrition)-Norfolk prospect i ve population study , 21,448 participants without diabetes or CHD between age 45 and 79 years were followed for 11.0 years . A total of 2,086 participants developed CHD during follow-up . RESULTS Among individuals with low LDL-C levels ( < 100 mg/dl ) , after adjustment for age , sex , smoking , systolic blood pressure , waist circumference , physical activity , and hormone replacement therapy ( in women ) , those with non-HDL-C > 130 mg/dl had a hazard ratio ( HR ) for future CHD of 1.84 ( 95 % confidence interval [ CI ] : 1.12 to 3.04 ) when compared with those with non-HDL-C levels < 130 mg/dl . In a similar model , individuals with TG levels > 150 mg/dl had an HR of 1.63 ( 95 % CI : 1.02 to 2.59 ) when compared with those with TG levels < 150 mg/dl , and individuals with a TC/HDL-C ratio > 5 had an HR of 2.19 ( 95 % CI : 1.22 to 3.93 ) when compared with those with a TC/HDL-C ratio < 5 . CONCLUSIONS In this prospect i ve study , independently of their plasma LDL-C levels , participants with high non-HDL-C levels , high TG levels , or with an elevated TC/HDL-C ratio were at increased CHD risk . CHD risk assessment algorithms as well as lipid targets of lipid-lowering trials may also need to consider other easily available parameters such as BACKGROUND Two potent weight loss therapies , a low-carbohydrate , ketogenic diet ( LCKD ) and orlistat therapy combined with a low-fat diet ( O + LFD ) , are available to the public but , to our knowledge , have never been compared . METHODS Overweight or obese out patients ( n = 146 ) from the Department of Veterans Affairs primary care clinics in Durham , North Carolina , were r and omized to either LCKD instruction ( initially , < 20 g of carbohydrate daily ) or orlistat therapy , 120 mg orally 3 times daily , plus low-fat diet instruction ( < 30 % energy from fat , 500 - 1000 kcal/d deficit ) delivered at group meetings over 48 weeks . Main outcome measures were body weight , blood pressure , fasting serum lipid , and glycemic parameters . RESULTS The mean age was 52 years and mean body mass index was 39.3 ( calculated as weight in kilograms divided by height in meters squared ) ; 72 % were men , 55 % were black , and 32 % had type 2 diabetes mellitus . Of the study participants , 57 of the LCKD group ( 79 % ) and 65 of the O + LFD group ( 88 % ) completed measurements at 48 weeks . Weight loss was similar for the LCKD ( expected mean change , -9.5 % ) and the O + LFD ( -8.5 % ) ( P = .60 for comparison ) groups . The LCKD had a more beneficial impact than O + LFD on systolic ( -5.9 vs 1.5 mm Hg ) and diastolic ( -4.5 vs 0.4 mm Hg ) blood pressures ( P < .001 for both comparisons ) . High-density lipoprotein cholesterol and triglyceride levels improved similarly within both groups . Low-density lipoprotein cholesterol levels improved within the O + LFD group only , whereas glucose , insulin , and hemoglobin A(1c ) levels improved within the LCKD group only ; comparisons between groups , however , were not statistically significant . CONCLUSION In a sample of medical out patients , an LCKD led to similar improvements as O + LFD for weight , serum lipid , and glycemic parameters and was more effective for lowering blood pressure . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00108524 PURPOSE To compare the effects of a low-carbohydrate diet and a conventional ( fat- and calorie-restricted ) diet on lipoprotein subfractions and inflammation in severely obese subjects . METHODS We compared changes in lipoprotein subfractions and C-reactive protein levels in 78 severely obese subjects , including 86 % with either diabetes or metabolic syndrome , who were r and omly assigned to either a low-carbohydrate or conventional diet for 6 months . RESULTS Subjects on a low-carbohydrate diet experienced a greater decrease in large very low-density lipoprotein ( VLDL ) levels ( difference = -0.26 mg/dL , p = .03 ) but more frequently developed detectable chylomicrons ( 44 % vs 22 % , p = .04 ) . Both diet groups experienced similar decreases in the number of low-density lipoprotein ( LDL ) particles ( difference = -30 nmol/L , p = .74 ) and increases in large high-density lipoprotein ( HDL ) concentrations ( difference = 0.70 mg/dL , p = .63 ) . Overall , C-reactive protein levels decreased modestly in both diet groups . However , patients with a high-risk baseline level ( > 3 mg/dL , n = 48 ) experienced a greater decrease in C-reactive protein levels on a low-carbohydrate diet ( adjusted difference = -2 mg/dL , p = .005 ) , independent of weight loss . CONCLUSIONS In this 6-month study involving severely obese subjects , we found an overall favorable effect of a low-carbohydrate diet on lipoprotein subfractions and on inflammation in high-risk subjects . Both diets had similar effects on LDL and HDL subfractions . ( Am J Med . 2004;117:398 - 405 . ) Untested alternative weight loss diets , such as very low carbohydrate diets , have unsubstantiated efficacy and the potential to adversely affect cardiovascular risk factors . Therefore , we design ed a r and omized , controlled trial to determine the effects of a very low carbohydrate diet on body composition and cardiovascular risk factors . Subjects were r and omized to 6 months of either an ad libitum very low carbohydrate diet or a calorie-restricted diet with 30 % of the calories as fat . Anthropometric and metabolic measures were assessed at baseline , 3 months , and 6 months . Fifty-three healthy , obese female volunteers ( mean body mass index , 33.6 + /- 0.3 kg/m(2 ) ) were r and omized ; 42 ( 79 % ) completed the trial . Women on both diets reduced calorie consumption by comparable amounts at 3 and 6 months . The  very low carbohydrate diet group lost more weight ( 8.5 + /- 1.0 vs. 3.9 + /- 1.0 kg ; P < 0.001 ) and more body fat ( 4.8 + /- 0.67 vs. 2.0 + /- 0.75 kg ; P < 0.01 ) than the low fat diet group .  Mean levels of blood pressure , lipids , fasting glucose , and insulin were within normal ranges in both groups at baseline . Although all of these parameters improved over the course of the study , there were no differences observed between the two diet groups at 3 or 6 months . beta- Hydroxybutyrate increased significantly in the very low carbohydrate group at 3 months ( P = 0.001 ) . Based on these data , a very low carbohydrate diet is more effective than a low fat diet for short-term weight loss and , over 6 months , is not associated with deleterious effects on important cardiovascular risk factors in healthy women BACKGROUND Adipocytokines are associated with insulin resistance and cardiovascular disease and can be modified with weight loss . While we previously demonstrated weight loss and a reduction in leptin in obese adults who followed a low-carbohydrate diet for 6 months , the long-term effects of this diet on adipocytokines are unknown . METHODS 132 obese adults with a body mass index of > or = 35 kg/m2 were r and omized to receive one year of dietary counseling to follow either a low-carbohydrate diet < 30 g/day ( LC ) or a caloric-restricted diet ( reduced by 500 calories/day with < 30 % of calories from fat ) ( LF ) . Weight , leptin , adiponectin , TNF-alpha , CRP , and insulin were measured at 0 , 6 , and 36 months ( 24 months post-counseling ) . Follow-up data at was collected for 53 participants who returned at 36 months . RESULTS Mean weight change from baseline was not different between the groups at 36 months . Between 6 and 36 months weight was unchanged for LF , while LC appeared to regain weight [ + 4.84 + /- 35.6 kg ( + 3.0 % ) ] . This difference , however , was not significant ( p = 0.08 ) . Leptin was unchanged in LF at both 6 and 36 months . In LC leptin decreased by 8.49 + /- 6.4 ng/mL or 22.7 % at 6 months ( p < 0.001 ) and increased by 10.68 + /- 25.2 ng/mL or 41.9 % between 6 and 36 months ( p = 0.02 ) . There were no differences in insulin , adiponectin , TNF-alpha , or CRP between the groups . CONCLUSIONS Favorable changes in leptin that accompany weight loss are not sustained in individuals who followed a low-carbohydrate diet for one year . A low-carbohydrate diet had no significant effect on insulin , adiponectin , TNF-alpha , or CRP compared to a low-fat diet at 36 months CONTEXT : Long-term success in weight loss with dietary treatment has been elusive . OBJECTIVE : To evaluate a diet moderate in fat based on the Mediterranean diet compared to a st and ard low-fat diet for weight loss when both were controlled for energy . DESIGN : A r and omized , prospect i ve 18 month trial in a free-living population . PATIENTS : A total of 101 overweight men and women ( 26.5–46 kg/m2).INTERVENTION : ( 1 ) Moderate-fat diet ( 35 % of energy ) ; ( 2 ) low-fat diet ( 20 % of energy).MAIN OUTCOME MEASUREMENTS : Change in body weight . RESULTS : After 18 months , 31/50 subjects in the moderate-fat group , and 30/51 in the low fat group were available for measurements . In the moderate-fat group , there were mean decreases in body weight of 4.1 kg , body mass index of 1.6 kg/m2 , and waist circumference of 6.9 cm , compared to increases in the low-fat group of 2.9 kg , 1.4 kg/m2 and 2.6 cm , respectively ; P≤0.001 between the groups . The difference in weight change between the groups was 7.0 kg . ( 95 % CI 5.3 , 8.7 ) . Only 20 % ( 10/51 ) of those in the low-fat group were actively participating in the weight loss program after 18 months compared to 54 % ( 27/50 ) in the moderate-fat group , ( P<0.002 ) . The moderate-fat diet group was continued for an additional year . The mean weight loss after 30 months compared to baseline was 3.5 kg ( n=19 , P=0.03 ) . CONCLUSIONS : A moderate-fat , Mediterranean-style diet , controlled in energy , offers an alternative to a low-fat diet with superior long-term participation and adherence , with consequent improvements in weight loss BACKGROUND Low-carbohydrate , ketogenic diets ( LCKD ) are effective for weight loss , but concerns remain regarding cardiovascular risk . The purpose of this study was to determine the effect of an LCKD program on serum lipoprotein subclasses . METHODS This was a r and omized , two-arm clinical trial in an outpatient research clinic involving overweight , hyperlipidemic community volunteers motivated to lose weight . Subjects were r and omized to either an LCKD ( n = 59 ) and nutritional supplementation ( including fish , borage and flaxseed oil ) , or a low-fat , reduced-calorie diet ( LFD , n = 60 ) . The main outcomes were fasting serum lipoprotein subclasses determined by nuclear magnetic resonance analysis . RESULTS The mean age of subjects was 44.9 years , the mean BMI was 34.4 kg/m(2 ) , and 76 % were women . Comparing baseline to 6 months , the LCKD group had significant changes in large VLDL ( -78 % ) , medium VLDL ( -60 % ) , small VLDL ( -57 % ) , LDL particle size ( + 2 % ) , large LDL ( + 54 % ) , medium LDL ( -42 % ) , small LDL ( -78 % ) , HDL particle size ( + 5 % ) , large HDL ( + 21 % ) , and LDL particle concentration ( -11 % ) . Compared with the LFD group , the LCKD group had greater reductions in medium VLDL ( p = 0.01 ) , small VLDL ( p = 0.01 ) and medium LDL ( p = 0.02 ) , and greater increases in VLDL particle size ( p = 0.01 ) , large LDL ( p = 0.004 ) , and HDL particle size ( p = 0.05 ) . CONCLUSIONS The LCKD with nutritional supplementation led to beneficial changes in serum lipid subclasses during weight loss . While the LCKD did not lower total LDL cholesterol , it did result in a shift from small , dense LDL to large , buoyant LDL , which could lower cardiovascular disease risk OBJECTIVES The purpose of this study was to assess the impact of on-treatment triglycerides ( TG ) on  coronary heart disease ( CHD ) risk after an acute coronary syndrome ( ACS ) . BACKGROUND The PROVE IT-TIMI ( Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infa rct ion ) 22 trial demonstrated that low-density lipoprotein cholesterol ( LDL-C ) < 70 mg/dl was associated with greater CHD event reduction than LDL-C < 100 mg/dl after ACS . However , the impact of low on-treatment TG on CHD risk beyond LDL-C < 70 mg/dl has not been explored . METHODS The PROVE IT-TIMI 22 trial evaluated 4,162 patients hospitalized for ACS and r and omized to atorvastatin 80 mg or pravastatin 40 mg daily . The relationship between on-treatment levels of TG and LDL-C and the composite end point of death , myocardial infa rct ion ( MI ) , and recurrent ACS were assessed 30 days after initial presentation . RESULTS Low on-treatment TG ( < 150 mg/dl ) was associated with reduced CHD risk compared with higher TG in univariate analysis ( hazard ratio [ HR ] 0.73 , 95 % confidence interval [ CI ] 0.62 to 0.87 ; p < 0.001 ) and in adjusted analysis ( HR 0.80 , 95 % CI 0.66 to 0.97 ; p = 0.025 ) . For each 10-mg/dl decrement in on-treatment TG , the incidence of death , MI , and recurrent ACS was lower by 1.6 % or 1.4 % after adjustment for LDL-C or non-high-density lipoprotein cholesterol and other covariates ( p < 0.001 and p = 0.01 , respectively ) . Lower CHD risk was also observed with TG < 150 mg/dl and LDL-C < 70 mg/dl ( HR 0.72 , 95 % CI 0.54 to 0.94 ; p = 0.017 ) or low on-treatment TG , LDL-C , and C-reactive protein ( < 2 mg/l ) ( HR 0.59 , 95 % CI 0.41 to 0.83 ; p = 0.002 ) compared with higher levels of each variable in adjusted analysis . CONCLUSIONS On-treatment TG < 150 mg/dl was independently associated with a lower risk of recurrent CHD events , lending support to the concept that achieving low TG may be an additional consideration beyond low LDL-C in patients after ACS Previous studies have shown that multiple features of atherogenic dyslipidemia are improved by replacement of dietary carbohydrate with mixed sources of protein and that these lipid and lipoprotein changes are independent of dietary saturated fat content . Because epidemiological evidence suggests that red meat intake may adversely affect cardiovascular disease risk , we tested the effects of replacing dietary carbohydrate with beef protein in the context of high- vs. low-saturated fat intake in 40 healthy men . After a 3-wk baseline diet [ 50 % daily energy ( E ) as carbohydrate , 13 % E as protein , 15 % E as saturated fat ] , participants consumed for 3 wk each in a r and omized crossover design two high-beef diets in which protein replaced carbohydrate ( 31 % E as carbohydrate , 31 % E as protein , with 10 % E as beef protein ) . The high-beef diets differed in saturated fat content ( 8 % E vs. 15 % E with exchange of saturated for monounsaturated fat ) . Two-week washout periods were included following the baseline diet period and between the r and omized diets periods . Plasma TG concentrations were reduced after the 2 lower carbohydrate dietary periods relative to after the baseline diet period and these reductions were independent of saturated fat intake . Plasma total , LDL , and non-HDL cholesterol as well as apoB concentrations were lower after the low-carbohydrate , low-saturated fat diet period than after the low-carbohydrate , high-saturated fat diet period . Given our previous observations with mixed protein diets , the present findings raise the possibility that dietary protein source may modify the effects of saturated fat on atherogenic lipoproteins 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 AND AIM Very low carbohydrate ad libitum diets have been shown to enhance weight loss without increasing cardiometabolic risk factors but no kilojoule-controlled trials have been conducted relative to no intervention . The aim of this study was to compare the changes in weight and other cardiovascular risk factors in 3 isocaloric energy-restricted diets to no-intervention control after 1 year . METHODS AND RESULTS One hundred and thirteen subjects ( age 47 ± 10 years , BMI 32 ± 6 kg/m(2 ) with one additional cardiovascular risk factor ) were r and omly allocated to one of three isocaloric diets ( VLC-very low carbohydrate , 60 % fat , 4 % carbohydrate , n=30 ; VLF-very low fat , 10 % fat , n = 30 ; HUF-high unsaturated fat , 30 % fat , n = 30 ) with intensive support for 3 months followed by minimal support for 12 months compared to a control group ( no intervention , n = 23 ) . The estimated weight change was -3.0 ± 0.2 kg for VLC , -2.0 ± 0.1 kg for VLF , -3.7 ± 0.01 kg for HUF and 0.8 ± 0.5 kg for controls ( P=0.065 ) . After correcting for baseline values , decreases in body weight and diastolic blood pressure in the diet groups ( -2.9 ± 5.2 ) were significantly different to the increase in the control group ( 0.8 ± 5.0 ) ( P<0.05 ) . No differences in cardiovascular risk factors were observed between the diet groups . CONCLUSION Significant cardiometabolic risk factor reduction was observed equally with VLC , VLF and HUF diets after 15 months , compared to an exacerbation of risk factors in the control group . At a modest level of adherence , 3 months of intensive support on these dietary patterns confer an improvement in cardiometabolic profile compared to no dietary intervention after 15 months BACKGROUND Low-carbohydrate diets are effective for weight reduction in people without diabetes , but there is limited evidence for people with Type 2 diabetes . Aims To assess the impact of a low-carbohydrate diet on body weight , glycated haemoglobin ( HbA(1c ) ) , ketone and lipid levels in diabetic and non-diabetic subjects . METHODS Thirteen Type 2 diabetic subjects ( on diet or metformin ) and 13 non-diabetic subjects were r and omly allocated to either a low-carbohydrate diet ( < or = 40 g carbohydrate/day ) or a healthy-eating diet following Diabetes UK nutritional recommendations and were seen monthly for 3 months . Subjects ( 25 % male ) were ( mean + /- sd ) age 52 + /- 9 years , weight 96.3 + /- 16.6 kg , body mass index 35.1 kg/m(2 ) , HbA(1c ) 6.6 + /- 1.1 % , total cholesterol 5.1 + /- 1.1 mmol/l , high-density lipoprotein cholesterol 1.3 + /- 0.4 mmol/l , low-density lipoprotein cholesterol 3.1 + /- 0.9 mmol/l , triglycerides ( geometric mean ) 1.55 ( 1.10 , 2.35 ) mmol/l and ketones range 0.0 - 0.2 mmol/l . RESULTS Analysis was by intention to treat with last observation carried forward . Twenty-two of the participants ( 85 % ) completed the study .  Weight loss was greater ( 6.9 vs. 2.1 kg , P = 0.003 ) in the low-carbohydrate group , with no difference in changes in HbA(1c ) , ketone or lipid levels . CONCLUSIONS The diet was equally effective in those with and without diabetes
target: Conclusions Large r and omized controlled trials of at least 6 months duration with carbohydrate restriction appear superior in improving lipid markers when compared with low-fat diets .
background: Context Carbohydrate-restricted diets may increase low-density lipoprotein cholesterol and thereby cardiovascular risk .
  Objective A systematic review and meta-analyses were conducted to compare the effects of very low , low , and moderate carbohydrate , higher fat diets versus high-carbohydrate , low-fat diets on low-density lipoprotein cholesterol and other lipid markers in overweight/obese adults .