Persistence of Hypertriglyceridemic Effect of Low-Fat High-Carbohydrate Diets in NIDDM Patients Separate effects of reduced carbohydrate intake and weight loss on atherogenic dyslipidemia. Changes in atherogenic dyslipidemia induced by carbohydrate restriction in men are dependent on dietary protein source. 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. Comparison of a Very Low-Carbohydrate and Low-Fat Diet on Fasting Lipids, LDL Subclasses, Insulin Resistance, and Postprandial Lipemic Responses in Overweight Women A randomized trial of a low-carbohydrate diet for obesity. Effects of moderate variations in macronutrient composition on weight loss and reduction in cardiovascular disease risk in obese, insulin-resistant adults. Lack of suppression of circulating free fatty acids and hypercholesterolemia during weight loss on a high-fat, low-carbohydrate diet. The Effects of Low-Carbohydrate versus Conventional Weight Loss Diets in Severely Obese Adults: One-Year Follow-up of a Randomized Trial Very low-carbohydrate and low-fat diets affect fasting lipids and postprandial lipemia differently in overweight men. Effects of low-fat diet, calorie restriction, and running on lipoprotein subfraction concentrations in moderately overweight men. Short-term effects of severe dietary carbohydrate-restriction advice in Type 2 diabetes--a randomized controlled trial. Effect of dietary patterns differing in carbohydrate and fat content on blood lipid and glucose profiles based on weight-loss success of breast-cancer survivors Effects of protein, monounsaturated fat, and carbohydrate intake on blood pressure and serum lipids: results of the OmniHeart randomized trial. A randomised controlled trial of the effect of low fat diet advice on dietary response in insulin independent diabetic women Effects of a carbohydrate-restricted diet on emerging plasma markers for cardiovascular disease Effects of high vs low glycemic index of dietary carbohydrate on cardiovascular disease risk factors and insulin sensitivity: the OmniCarb randomized clinical trial.
Although low-fat high-carbohydrate diets are recommended for patients with non-insulin-dependent diabetes mellitus ( NIDDM ) in an effort to reduce the risk of coronary artery disease ( CAD ) , the results of short-term studies have shown that these diets can lead to changes in carbohydrate and lipid metabolism associated with an increased risk of CAD . This study has extended these earlier observations by determining the metabolic effects of such diets over a longer period in these patients . The comparison diets contained either 40 or 60 % of the total calories as carbohydrates , with reciprocal changes in fat content from 40 to 20 % consumed in r and om order for 6 wk in a crossover experimental design . The ratio of polyunsaturated to saturated fat and the total cholesterol intake were held constant in the two diets . Plasma glucose and insulin concentrations were significantly ( P < .001 ) elevated throughout the day when patients consumed the 60 % carbohydrate diet , and 24-h urinary glucose excretion more than doubled ( 0.8 vs. 1.8 mol/24 h ) . Fasting plasma total and very-low-density lipoprotein ( VLDL ) triglyceride ( TG ) concentrations increased by 30 % ( P < .001 ) after 1 wk on the 60 % carbohydrate diet , and the magnitude of carbohydrate-induced hypertriglyceridemia persisted unchanged throughout the 6-wk study period . Total plasma cholesterol concentrations were similar after both diets . However , VLDL cholesterol ( VLDL-chol ) was significantly increased , whereas both low-density lipoprotein ( LDL- ) and high-density lipoprotein ( HDL- ) chol concentrations were significantly decreasedafter consumption of the 60 % carbohydrate diet . Consequently , neither total-chol-to-HDL-chol nor LDL-chol-to-HDL-chol ratios changed . The results of this study indicate that high-carbohydrate diets lead to several changes in carbohydrate and lipid metabolism in patients with NIDDM that could lead to an increased risk of CAD , and these effects persist for > 6 wk . Given these results , it seems reasonable to suggest that the routine recommendation of low-fat high-carbohydrate diets for patients with NIDDM be reconsidered 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 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 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 . ) Objective : Very low-carbohydrate diets are widely used for weight loss yet few controlled studies have determined how these diets impact cardiovascular risk factors compared to more traditional low-fat weight loss diets . The primary purpose of this study was to compare a very low-carbohydrate and a low-fat diet  on fasting blood lipids , LDL subclasses , postpr and ial lipemia , and insulin resistance in overweight and obese women . Methods : Thirteen normolipidemic , moderately overweight ( body fat > 30 % ) women were prescribed two hypocaloric ( −500 kcal/day ) diets for 4 week periods , a very low-carbohydrate ( < 10 % carbohydrate ) and a low-fat ( < 30 % fat ) diet . The diets were consumed in a balanced and r and omized fashion . Two fasting blood draws were performed on separate days and an oral fat tolerance test was performed at baseline , after the very low-carbohydrate diet , and after the low-fat diet . Results : Compared to corresponding values after the very low-carbohydrate diet , fasting total cholesterol , LDL-C , and HDL-C were significantly ( p ≤ 0.05 ) lower , whereas fasting glucose , insulin , and insulin resistance ( calculated using the homeostatic model assessment ) were significantly higher after the low-fat diet . Both diets significantly decreased postpr and ial lipemia and result ed in similar nonsignificant changes in the total cholesterol/HDL-C ratio , fasting triacylglycerols , oxidized LDL , and LDL subclass distribution . Conclusions : Compared to a low-fat weight loss diet , a short-term very low-carbohydrate diet did not lower LDL-C but did prevent the decline in HDL-C and result ed in improved insulin sensitivity in overweight and obese , but otherwise healthy women . Small decreases in body mass improved postpr and ial lipemia , and therefore cardiovascular risk , independent of diet composition 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 Obese , insulin-resistant persons are at risk of cardiovascular disease . How best to achieve both weight loss and clinical benefit in these persons is controversial , and recent reports question ed the superiority of low-fat diets . OBJECTIVE We aim ed to ascertain the effects of moderate variations in the carbohydrate and fat content of calorie-restricted diets on weight loss and cardiovascular disease risk in obese , insulin-resistant persons . DESIGN Fifty-seven r and omly assigned , insulin-resistant , obese persons completed a 16-wk calorie-restricted diet with 15 % of energy as protein and either 60 % and 25 % or 40 % and 45 % of energy as carbohydrate and fat , respectively . Baseline and postweight-loss insulin resistance ; daylong glucose , insulin , and triacylglycerol concentrations ; fasting lipid and lipoprotein concentrations ; and markers of endothelial function were quantified . RESULTS Weight loss with 60 % or 40 % of energy as carbohydrate ( 5.7 + /- 0.7 or 6.9 + /- 0.7 kg , respectively ) did not differ significantly , and improvement in insulin sensitivity correlated with the amount of weight lost ( r = 0.50 , P < 0.001 ) . Subjects following the diet with 40 % of energy as carbohydrate had greater reductions in daylong insulin and triacylglycerol ( P < 0.05 ) and fasting triacylglycerol ( 0.53 mmol/L ; P = 0.04 ) concentrations , greater increases in HDL-cholesterol concentrations ( 0.12 mmol/L ; P < 0.01 ) and LDL particle size ( 1.82 s ; P < 0.05 ) , and a greater decrease in plasma E-selectin ( 5.6 ng/L ; P = 0.02 ) than did subjects following the diet with 60 % of energy as carbohydrate . CONCLUSIONS In obese , insulin-resistant persons , a calorie-restricted diet , moderately lower in carbohydrate and higher in unsaturated fat , is as efficacious as the traditional low-fat diet in producing weight loss and may be more beneficial in reducing markers for cardiovascular disease risk BACKGROUND Little is known about the comparative effect of weight-loss diets on metabolic profiles during dieting . OBJECTIVE The purpose of this study was to compare the effect of a low-carbohydrate diet ( < or = 20 g/d ) with a high-carbohydrate diet ( 55 % of total energy intake ) on fasting and hourly metabolic variables during active weight loss . DESIGN Healthy , obese adults ( n = 32 ; 22 women , 10 men ) were r and omly assigned to receive either a carbohydrate-restricted diet [ High Fat ; mean + /- SD body mass index ( BMI ; in kg/m(2 ) ) : 35.8 + /- 2.9 ] or a calorie-restricted , low-fat diet ( High Carb ; BMI : 36.7 + /- 4.6 ) for 6 wk . A 24-h in-patient feeding study was performed at baseline and after 6 wk .  Glucose , insulin , free fatty acids ( FFAs ) , and triglycerides  were measured hourly during meals , at regimented times . Remnant lipoprotein cholesterol was measured every 4 h. RESULTS Patients lost a similar amount of weight in both groups ( P = 0.57 ) . There was an absence of any diet treatment effect between groups on fasting triglycerides or on remnant lipoprotein cholesterol , which was the main outcome . Fasting insulin decreased ( P = 0.03 ) , and both fasting ( P = 0.040 ) and 24-h FFAs ( P < 0.0001 ) increased within the High Fat group . Twenty-four-hour insulin decreased ( P < 0.05 for both groups ) . Fasting LDL cholesterol decreased in the High Carb group only ( P = 0.003 ) . In both groups , the differences in fasting and 24-h FFAs at 6 wk were significantly correlated with the change in LDL cholesterol ( fasting FFA : r = 0.41 , P = 0.02 ; 24-h FFA : r = 0.52 , P = 0.002 ) . CONCLUSIONS Weight loss was similar between diets , but only the high-fat diet increased LDL-cholesterol concentrations . This effect was related to the lack of suppression of both fasting and 24-h FFAs 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 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 ) We studied the effects of exercise ( primarily running ) , calorie restriction ( dieting ) , and a low-fat , high-carbohydrate diet on changes in lipoprotein subfractions in moderately overweight men in a r and omized controlled clinical trial . After 1 year , complete data were obtained for 39 men assigned to lose weight through dieting without exercise , 37 men assigned to lose weight through dieting with exercise ( primarily running ) , and 40 nondieting sedentary controls .  We instructed both diet groups to consume no more than 30 % total fat , 10 % saturated fat , and 300 mg/d of cholesterol , and at least 55 % carbohydrates , and the controls were instructed to maintain their usual food choices . Analytic ultracentrifugation was used to measure changes in plasma lipoprotein mass concentrations . In addition , the absorbance of protein-stained polyacrylamide gradient gels was used as an index of concentrations for five high-density lipoprotein ( HDL ) subclasses that have been identified by their particle sizes , ie , HDL3c ( 7.2 to 7.8 nm ) , HDL3b ( 7.8 to 8.2 nm ) , HDL3a ( 8.2 to 8.8 nm ) , HDL2a ( 8.8 to 9.7 nm ) , and HDL2b ( 9.7 to 12 nm ) . Relative to controls , weight decreased significantly in men who dieted with exercise ( net difference + /- SE , -3.3 + /- 0.4 kg/m2 ) and in men who dieted without exercise ( -2.0 + /- 0.4 kg/m2 ) . Dieting with exercise significantly decreased very-low-density lipoprotein (VLDL)-mass concentrations and significantly increased plasma HDL2-mass , HDL3a , HDL2a , and HDL2b relative to both control and dieting without exercise . There were no significant changes in lipoprotein mass and HDL protein for dieters who did not run . ( ABSTRACT TRUNCATED AT 250 WORDS OBJECTIVE This study sought to examine the effects of a 3-month programme of dietary advice to restrict carbohydrate intake compared with reduced-portion , low-fat advice in obese subjects with poorly controlled Type 2 diabetes . RESEARCH DESIGN AND METHODS One hundred and two patients with Type 2 diabetes were recruited across three centres and r and omly allocated to receive group education and individual dietary advice .  Weight , glycaemic control , lipids and blood pressure were assessed at baseline and 3 months . Dietary quality was assessed at the end of study . RESULTS Weight loss was greater in the low-carbohydrate ( LC ) group ( -3.55 + /- 0.63 , mean + /- sem ) vs. -0.92 + /- 0.40 kg , P = 0.001 ) and cholesterol : high-density lipoprotein ( HDL ) ratio improved ( -0.48 + /- 0.11 vs. -0.10 + /- 0.10 , P = 0.01 ) . However , relative saturated fat intake was greater ( 13.9 + /- 0.71 vs. 11.0 + /- 0.47 % of dietary intake , P < 0.001 ) , although absolute intakes were moderate . CONCLUSIONS Carbohydrate restriction was an effective method of achieving short-term weight loss compared with st and ard advice , but this was at the expense of an increase in relative saturated fat intake Introduction Healthy body weight is an important factor for prevention of breast cancerrecurrence . Yet , weight loss and weight gain are not currently included in clinical - practice guidelines for posttreatment of breast cancer . The work reportedaddresses one of the questions that must be considered in recommending weight lossto patients : does it matter what diet plan is used , a question of particular importance because breast cancer treatment can increase risk for cardiovasculardisease . Methods Women who completed treatment for breast cancer were enrolled in a nonr and omized , controlled study investigating effects of weight loss achieved by using twodietary patterns at the extremes of macronutrient composition , although both dietarms were equivalent in protein : high fat , low carbohydrate versus low fat , highcarbohydrate . A nonintervention group served as the control arm ; women wereassigned to intervention arms based on dietary preferences . During the 6-monthweight-loss program , which was menu and recipe defined , participants had monthly clinical visits at which anthropometric data were collected and fasting blood wasobtained for safety monitoring for plasma lipid profiles and fasting glucose . Results from 142 participants are reported . Results Adverse effects on fasting blood lipids or glucose were not observed in eitherdietary arm . A decrease in fasting glucose was observed with progressive weightloss and was greater in participants who lost more weight , but the effect was notstatistically significant , even though it was observed across both diet groups(P = 0.21 ) . Beneficial effects of weight loss on cholesterol ( 4.7%;P = 0.001 ) , triglycerides ( 21.8 % ; P = 0.01 ) , and low-densitylipoprotein ( LDL ) cholesterol ( 5.8 % ; P = 0.06 ) were observed in bothgroups . For cholesterol ( P = 0.07 ) and LDL cholesterol ( P = 0.13 ) , greater reduction trends were seen on the low-fat diet pattern ; whereas , for triglycerides ( P = 0.01 ) and high-density lipoprotein (HDL)cholesterol ( P = 0.08 ) , a decrease or increase , respectively , was greateron the low-carbohydrate diet pattern . Conclusions Because an individual 's dietary preferences can affect dietary adherence and weight-loss success , the lack of evidence of a negative effect of dietary patternon biomarkers associated with cardiovascular risk is an important consideration inthe development of breast cancer practice guidelines for physicians who recommendthat their patients lose weight . Whether dietary pattern affects biomarkers thatpredict long-term survival is a primary question in this ongoing clinical trial CONTEXT Reduced intake of saturated fat is widely recommended for prevention of cardiovascular disease . The type of macronutrient that should replace saturated fat remains uncertain . OBJECTIVE To compare the effects of 3 healthful diets , each with reduced saturated fat intake , on blood pressure and serum lipids . DESIGN , SETTING , AND PARTICIPANTS R and omized , 3-period , crossover feeding study ( April 2003 to June 2005 ) conducted in Baltimore , Md , and Boston , Mass. Participants were 164 adults with prehypertension or stage 1 hypertension . Each feeding period lasted 6 weeks and body weight was kept constant . INTERVENTIONS A diet rich in carbohydrates ; a diet rich in protein , about half from plant sources ; and a diet rich in unsaturated fat , predominantly monounsaturated fat . MAIN OUTCOME MEASURES Systolic blood pressure and low-density lipoprotein cholesterol . RESULTS Blood pressure , low-density lipoprotein cholesterol , and estimated coronary heart disease risk were lower on each diet compared with baseline . Compared with the carbohydrate diet , the protein diet further decreased mean systolic blood pressure by 1.4 mm Hg ( P = .002 ) and by 3.5 mm Hg ( P = .006 ) among those with hypertension and decreased low-density lipoprotein cholesterol by 3.3 mg/dL ( 0.09 mmol/L ; P = .01 ) , high-density lipoprotein cholesterol by 1.3 mg/dL ( 0.03 mmol/L ; P = .02 ) , and triglycerides by 15.7 mg/dL ( 0.18 mmol/L ; P<.001 ) . Compared with the carbohydrate diet , the unsaturated fat diet decreased systolic blood pressure by 1.3 mm Hg ( P = .005 ) and by 2.9 mm Hg among those with hypertension ( P = .02 ) , had no significant effect on low-density lipoprotein cholesterol , increased high-density lipoprotein cholesterol by 1.1 mg/dL ( 0.03 mmol/L ; P = .03 ) , and lowered triglycerides by 9.6 mg/dL ( 0.11 mmol/L ; P = .02 ) . Compared with the carbohydrate diet , estimated 10-year coronary heart disease risk was lower and similar on the protein and unsaturated fat diets . CONCLUSION In the setting of a healthful diet , partial substitution of carbohydrate with either protein or monounsaturated fat can further lower blood pressure , improve lipid levels , and reduce estimated cardiovascular risk . Clinical Trials Registration Clinical Trials.gov Identifier : NCT00051350 Summary Type 2 ( insulin independent ) diabetic women were r and omly allocated to receive advice for low fat diets or low carbohydrate diets . By 24 h weighed dietary intakes before and after a mean interval of six months , patients in the low fat group had reduced their fat intake from 41 % to 31 % of total energy , while carbohydrate percentage of total energy intake increased from 38 % to 46 % . Percentage energy intake from fat and carbohydrate in the control group remained unchanged . Body weight fell in both groups , especially for patients in the low fat group who were obese ( weight/height2 ⩾ 28 kg/m2 ) . Mean plasma glucose , HbA1 , and triglycerides were unchanged . Mean plasma total cholesterol fell significantly in the low fat group compared with the controls ( p < 0.001 ) , but there was no significant difference in the small reduction of high density lipoprotein cholesterol observed in both groups . Thus , adherence to low fat diets occurred without deterioration of diabetes and with benefit for weight and total cholesterol Background Increasing evidence supports carbohydrate restricted diets ( CRD ) for weight loss and improvement in traditional markers for cardiovascular disease ( CVD ) ; less is known regarding emerging CVD risk factors . We previously reported that a weight loss intervention based on a CRD ( % carbohydrate : fat : protein = 13:60:27 ) led to a mean weight loss of 7.5 kg and a 20 % reduction of abdominal fat in 29 overweight men . This group showed reduction in plasma LDL-cholesterol and triglycerides and elevations in HDL-cholesterol as well as reductions in large and medium VLDL particles and increases in LDL particle size . In this study we report on the effect of this intervention with and without fiber supplementation on plasma homocysteine , lipoprotein ( a ) [ Lp(a ) ] , C-reactive protein ( CRP ) , interleukin-6 ( IL-6 ) , and tumor necrosis factor alpha ( TNF-α ) . Methods Twenty nine overweight men [ body mass index ( BMI ) 25–35 kg/m2 ] aged 20–69 years consumed an ad libitum CRD ( % carbohydrate : fat : protein = 13:60:27 ) including a st and ard multivitamin every other day for 12 wk . Subjects were matched by age and BMI and r and omly assigned to consume 3 g/d of either a soluble fiber supplement ( n = 14 ) or placebo ( n = 15 ) . Results There were no group or interaction ( fiber × time ) main effects , but significant time effects were observed for several variables . Energy intake was spontaneously reduced ( -30.5 % ) . This was accompanied by an increase in protein intake ( 96.2 ± 29.8 g/d to 107.3 ± 29.7 g/d ) and methionine intake ( 2.25 ± 0.7 g/d , to 2.71 ± 0.78 g/d ; P < 0.001 ) . Trans fatty acid intake was significantly reduced ( -38.6 % ) while dietary folate was unchanged , as was plasma homocysteine . Bodyweight ( -7.5 ± 2.5 kg ) was reduced as was plasma Lp(a ) ( -11.3 % ) . Changes in plasma Lp(a ) correlated with reductions in LDL-cholesterol ( r = .436 , P < 0.05 ) and fat loss ( r = .385 , P < 0,05 ) . At wk 12 , both CRP ( -8.1 % ) and TNF-α ( -9.3 % ) were reduced ( P < 0.05 ) independently of weight loss . IL-6 concentrations were unchanged . Conclusion A diet based on restricting carbohydrates leads to spontaneous caloric reduction and subsequent improvement in emerging markers of CVD in overweight/obese men who are otherwise healthy IMPORTANCE Foods that have similar carbohydrate content can differ in the amount they raise blood glucose . The effects of this property , called the glycemic index , on risk factors for cardiovascular disease and diabetes are not well understood . OBJECTIVE To determine the effect of glycemic index and amount of total dietary carbohydrate on risk factors for cardiovascular disease and diabetes . DESIGN , SETTING , AND PARTICIPANTS R and omized crossover-controlled feeding trial conducted in research units in academic medical centers , in which 163 overweight adults ( systolic blood pressure , 120 - 159 mm Hg ) were given 4 complete diets that contained all of their meals , snacks , and calorie-containing beverages , each for 5 weeks , and completed at least 2 study diets . The first participant was enrolled April 1 , 2008 ; the last participant finished December 22 , 2010 . For any pair of the 4 diets , there were 135 to 150 participants contributing at least 1 primary outcome measure . INTERVENTIONS ( 1 ) A high-glycemic index ( 65 % on the glucose scale ) , high-carbohydrate diet ( 58 % energy ) ; ( 2 ) a low-glycemic index ( 40 % ) , high-carbohydrate diet ; ( 3 ) a high-glycemic index , low-carbohydrate diet ( 40 % energy ) ; and ( 4 ) a low-glycemic index , low-carbohydrate diet . Each diet was based on a healthful DASH-type diet . MAIN OUTCOMES AND MEASURES The 5 primary outcomes were insulin sensitivity , determined from the areas under the curves of glucose and insulin levels during an oral glucose tolerance test ; levels of low-density lipoprotein ( LDL ) cholesterol , high-density lipoprotein ( HDL ) cholesterol , and triglycerides ; and systolic blood pressure . RESULTS At high dietary carbohydrate content , the low- compared with high-glycemic index level decreased insulin sensitivity from 8.9 to 7.1 units ( -20 % , P = .002 ) ; increased LDL cholesterol from 139 to 147 mg/dL ( 6 % , P ≤ .001 ) ; and did not affect levels of HDL cholesterol , triglycerides , or blood pressure . At low carbohydrate content , the low- compared with high-glycemic index level did not affect the outcomes except for decreasing triglycerides from 91 to 86 mg/dL ( -5 % , P = .02 ) . In the primary diet contrast , the low-glycemic index , low-carbohydrate diet , compared with the high-glycemic index , high-carbohydrate diet , did not affect insulin sensitivity , systolic blood pressure , LDL cholesterol , or HDL cholesterol but did lower triglycerides from 111 to 86 mg/dL ( -23 % , P ≤ .001 ) . CONCLUSIONS AND RELEVANCE In this 5-week controlled feeding study , diets with low glycemic index of dietary carbohydrate , compared with high glycemic index of dietary carbohydrate , did not result in improvements in insulin sensitivity , lipid levels , or systolic blood pressure . In the context of an overall DASH-type diet , using glycemic index to select specific foods may not improve cardiovascular risk factors or insulin resistance . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00608049
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 .
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 .