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Changes in atherogenic dyslipidemia induced by carbohydrate restriction in men are dependent on dietary protein source. Low‐density lipoprotein subclass patterns and lipoprotein response to a reduced‐fat diet in men A high-protein low-fat diet is more effective in improving blood pressure and triglycerides in calorie-restricted obese individuals with newly diagnosed type 2 diabetes The effects of low cholesterol, high polyunsaturated fat, and low fat diets on plasma lipid and lipoprotein cholesterol levels in normal and hypercholesterolemic subjects. Effects of low-fat, high-carbohydrate diets on risk factors for ischemic heart disease in postmenopausal women. Effects of low-fat diet, calorie restriction, and running on lipoprotein subfraction concentrations in moderately overweight men. Tissue factor expression is decreased in monocytes obtained from blood during Mediterranean or high carbohydrate diets. Effects of advice on dietary intake and/or physical activity on body composition, blood lipids and insulin resistance following a low-fat, sucrose-containing, high-carbohydrate, energy-restricted diet Comparison of 4 diets of varying glycemic load on weight loss and cardiovascular risk reduction in overweight and obese young adults: a randomized controlled trial. Effects of dietary composition on energy expenditure during weight-loss maintenance. Blood lipid distribution of hyperinsulinemic men consuming three levels of fructose. Effects of low-carbohydrate and low-fat diets: a randomized trial. 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. 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Dietary restriction in obese children and its relation with eating behavior, fibroblast growth factor 21 and leptin: a prospective clinical intervention study A randomised controlled trial of the effect of low fat diet advice on dietary response in insulin independent diabetic women A Low-Carbohydrate, Ketogenic Diet versus a Low-Fat Diet To Treat Obesity and Hyperlipidemia Plasma lipid and lipoprotein cholesterol concentrations in adult males consuming normal and high cholesterol diets under controlled conditions.
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 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 BACKGROUND In the United States , obesity is a major clinical and public health problem causing diabetes , dyslipidemia , and hypertension , as well as increasing cardiovascular and total mortality . Dietary restrictions of calories and saturated fat are beneficial . However , it remains unclear whether replacement of saturated fat with carbohydrates ( as in the US National Cholesterol Education Program [ NCEP ] diet ) or protein and monounsaturated fat ( as in our isocaloric modified low-carbohydrate [ MLC ] diet , which is lower in total carbohydrates but higher in protein , monounsaturated fat , and complex carbohydrates ) is optimal . METHODS We r and omized 60 participants ( 29 women and 31 men ) to the NCEP or the MLC diet  and evaluated them every 2 weeks for 12 weeks . They were aged 28 to 71 years ( mean age , 44 years in the NCEP and 46 years in the MLC group ) . A total of 36 % of participants from the NCEP group and 35 % from the MLC group had a body mass index ( calculated as weight in kilograms divided by the square of height in meters ) greater than 27 . The primary end point was weight loss , and secondary end points were blood lipid levels and waist-to-hip ratio . RESULTS Weight loss was significantly greater in the MLC ( 13.6 lb ) than in the NCEP group ( 7.5 lb ) , a difference of 6.1 lb ( P = .02 ) . There were no significant differences between the groups for total , low density , and high-density lipoprotein cholesterol , triglycerides , or the proportion of small , dense low-density lipoprotein particles . There were significantly favorable changes in all lipid levels within the MLC but not within the NCEP group . Waist-to-hip ratio was not significantly reduced between the groups ( P = .27 ) , but it significantly decreased within the MLC group ( P = .009 ) . CONCLUSIONS Compared with the NCEP diet , the MLC diet , which is lower in total carbohydrates but higher in complex carbohydrates , protein , and monounsaturated fat , caused significantly greater weight loss over 12 weeks . There were no significant differences between the groups in blood lipid levels , but favorable changes were observed within the MLC diet group 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 Diets design ed to promote weight loss and improve atherogenic lipid profiles traditionally include a reduction in total fat and , in particular , saturated fats . This study was design ed to test the efficacy of a low-fat diet vs a carbohydrate (CHO)-restricted ( low-CHO ) diet in hypertriglyceridemic patients on lipid profile , weight loss , high-sensitivity C-reactive protein ( hs-CRP ) , and satiety .  Twenty-eight hypertriglyceridemic subjects ( based on fasting triacylglycerol [ TG ] levels exceeding 1.69 mmol/L ) were r and omized to either the  low-CHO or low-fat diet  for 8 weeks . Fasting bloods were acquired at weeks 0 and 8 and analyzed for lipids and hs-CRP . Body weight and other anthropometric measures were also obtained . Three r and om 24-hour food recalls were used to assess compliance during the trial and 2 recalls before r and omization to permit individualized dietary education . A significant time-by-treatment interaction was observed ( P = .045 ) , wherein the small low-density lipoprotein cholesterol concentrations were reduced by 46 % in the low-CHO-assigned subjects and increased by 36 % for those assigned the low-fat plan . The observed decrease in TG ( 18 % ) among low-CHO subjects , in contrast to the 4 % increase for low-fat group , was not significant , nor were there significant differences in hs-CRP , overall dietary compliance , satiety , or the magnitude of body weight loss between groups ( low-CHO group , -3.8 % vs low-fat group , -1.6 % ) . Favorable reductions in small low-density lipoprotein concentrations after 8 weeks suggest that a moderately restricted carbohydrate diet ( 20 % CHO as energy ) can promote a less atherogenic lipid profile when compared to the low-fat diet 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 The short-term effects on plasma lipoprotein lipids of substituting meat and dairy protein for carbohydrate in the diets of 10 free-living moderately hypercholesterolemic human subjects ( four men , six women ) were studied under closely supervised dietary control during the consumption of constant , low intakes of fat and cholesterol and the maintenance of stable body weight as well as constant fiber consumption . Subjects were r and omly allocated to either the high or low protein diets ( mean , 23 % v 11 % of energy as protein , 24 % as fat , and 53 % v 65 % as carbohydrate ) and then switched to the other diet for another 4 to 5 weeks . Mean fasting plasma high-density lipoprotein cholesterol ( HDL-C ) was significantly higher by 12 % + /- 4 % ( 0.97 + /- 0.08 v 0.89 + /- 0.08 mmol/L , P less than .01 ) , whereas mean total cholesterol ( TC ) was lower by 6.5 % + /- 1.3 % ( 5.7 + /- 0.3 v 6.1 + /- 0.3 mmol/L , P less than .001 ) , mean low-density lipoprotein-cholesterol ( LDL-C ) lower by 6.4 % + /- 2.0 % ( 4.5 + /- 0.2 v 4.8 + /- 0.2 mmol/L , P less than .02 ) , mean total triglycerides ( TG ) lower by 23 % + /- 5 % ( 1.7 + /- 0.1 v 2.4 + /- 0.3 mmol/L , P less than .02 ) , and mean high versus low protein diet . Mean values for LDL-C were significantly lower during weeks 3 to 5 of the high protein diet than during either weeks 1 to 5 or weeks 1 to 2 of the high protein diet ( 4.3 + /- 0.3 , 4.5 + /- 0.2 , and 4.7 + /- 0.3 mmol/L , respectively , P less than .05 ) and 11 % + /- 3 % lower than on low protein diet , P less than .005 . The ratio of plasma LDL-C to HDL-C was consistently lower by 17 % + /- 3 % during the high versus low protein diet ( 4.9 + /- 0.5 v 5.8 + /- 0.5 , P less than .001 ) . Lowering plasma TC and LDL-C and total TG and VLDL-TG and increasing HDL-C by chronic isocaloric substitution of dietary for carbohydrate may enhance the cardiovascular risk reduction obtained by restriction of dietary fat and cholesterol Carbohydrate-restricted diets ( CRDs ) promote weight loss , reductions in plasma triacylglycerol ( TAG ) levels , and increases in high-density lipoprotein cholesterol ( HDL-C ) levels but may cause undesirable low-density lipoprotein cholesterol ( LDL-C ) responses in some people . The objective of the present study was to determine the effect of adding soluble fiber to a CRD on plasma LDL-C and other traditionally measured markers of cardiovascular disease . Using a parallel-arm , double-blind , placebo-controlled design , 30 overweight and obese men ( body mass index , 25 - 35 kg/m(2 ) ) were r and omly assigned to supplement a CRD with soluble fiber ( Konjac-mannan , 3g/d ) ( n = 15 ) or placebo ( n = 15 ) . Plasma lipids , anthropometrics , body composition , blood pressure , and nutrient intake were evaluated at baseline and at 6 and 12 weeks . Compliance was excellent as assessed by 7-day weighed dietary records and ketonuria . Both groups experienced decreases in ( P < .01 ) body weight , percent body fat , systolic blood pressure , waist circumference , and plasma glucose levels . After 12 weeks , HDL-C and TAG improved significantly in the fiber ( 10 % and -34 % ) and placebo ( 14 % , -43 % ) groups . LDL-C decreased by 17.6 % ( P < .01 ) at week 6 and 14.1 % ( P < .01 ) at week 12 in the fiber group . Conversely , LDL-C reductions were significant in the placebo group only after 12 weeks ( -6.0 % , P < .05 ) . We conclude that although clearly effective at lowering LDL-C , adding soluble fiber to a CRD during active and significant weight loss provides no additional benefits to the diet alone . Furthermore , a CRD led to clinical ly important positive alterations in cardiovascular disease risk factors The adequate composition of carbohydrate and fat in low calorie diets for type 2 diabetes mellitus patients with obesity is not fully established . The aim of this study was to investigate the effects of low carbohydrate diet on glucose and lipid metabolism , especially on visceral fat accumulation , and comparing that of a high carbohydrate diet .  Obese subjects with type 2 diabetes mellitus were r and omly assigned to take a low calorie and low carbohydrate diet ( n = 11 , 1000 kcal per day , protein : carbohydrate : fat = 25:40:35 ) or a low calorie and high carbohydrate diet ( n = 11 , 1000 kcal per day , protein : carbohydrate : fat = 25:65:10 ) for 4 weeks . Similar decreases in body weight and serum glucose levels were observed in both groups . Fasting serum insulin levels were reduced in the low carbohydrate diet group compared to the high carbohydrate diet group ( -30 % versus -10 % , P < 0.05 ) . Total serum cholesterol and triglyceride levels decreased in both groups , but were not significantly different from each other . High-density lipoprotein-cholesterol ( HDL-C ) increased in the low carbohydrate diet group but not in the high carbohydrate diet group ( + 15 % versus 0 % , P < 0.01 ) . There was a larger decrease in visceral fat area measured by computed tomography in the low carbohydrate diet group compared to the high carbohydrate diet group ( -40 cm(2 ) versus -10 cm(2 ) , P < 0.05 ) . The ratio of visceral fat area to subcutaneous fat area did not change in the high carbohydrate diet group ( from 0.70 to 0.68 ) , but it decreased significantly in the low carbohydrate diet group ( from 0.69 to 0.47 , P < 0.005 ) . These results suggest that , when restrict diet was made isocaloric , a low calorie/low carbohydrate diet might be more effective treatment for a reduction of visceral fat , improved insulin sensitivity and increased in HDL-C levels than low calorie/high carbohydrate diet in obese subjects with type 2 diabetes mellitus 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 We compared a high-carbohydrate diet with a high-fat diet ( specifically , a diet high in monounsaturated fatty acids ) for effects on glycemic control and plasma lipoproteins in 10 patients with non-insulin-dependent diabetes mellitus ( NIDDM ) receiving insulin therapy . The patients were r and omly assigned to receive first one diet and then the other , each for 28 days , in a metabolic ward . In the high-carbohydrate diet , 25 percent of the energy was in the form of fat and 60 percent in the form of carbohydrates ( 47 percent of the total energy was in the form of complex carbohydrates ) ; the high-monounsaturated-fat diet was 50 percent fat ( 33 percent of the total energy in the form of monounsaturated fatty acids ) and 35 percent carbohydrates . The two diets had the same amounts of simple carbohydrates and fiber . As compared with the high-carbohydrate diet , the high-monounsaturated-fat diet result ed in lower mean plasma glucose levels and reduced insulin requirements , lower levels of plasma triglycerides and very-low-density lipoprotein cholesterol ( lower by 25 and 35 percent , respectively ; P less than 0.01 ) , and higher levels of high-density lipoprotein ( HDL ) cholesterol ( higher by 13 percent ; P less than 0.005 ) . Levels of total cholesterol and low-density lipoprotein ( LDL ) cholesterol did not differ significantly in patients on the two diets . These preliminary results suggest that partial replacement of complex carbohydrates with monounsaturated fatty acids in the diets of patients with NIDDM does not increase the level of LDL cholesterol and may improve glycemic control and the levels of plasma triglycerides and HDL cholesterol Our aims were 1 ) to examine the effects of a high-carbohydrate low-fat diet on fasting and postpr and ial plasma lipids , apolipoproteins ( apo ) , and lipoprotein composition in noninsulin-dependent diabetes mellitus , and 2 ) to determine whether postpr and ial shift of apo between triglyceride-rich lipoproteins ( TRLP ) and high density lipoproteins ( HDL ) is affected by diet . A cross-over study , of 4 weeks duration , of a high-carbohydrate ( 60 % carbohydrate , 20 % fat ) and a high-fat ( 40 % carbohydrate , 40 % fat ) diet was performed in seven subjects with noninsulin-dependent diabetes mellitus .  TRLP , low density lipoproteins ( LDL ) , and HDL were separated by fast protein liquid chromatography . The high-carbohydrate diet result ed in a decrease of fasting total , HDL , and LDL cholesterol and a trend toward an increase in plasma triglycerides . The apo composition of fasting TRLP and HDL was similar on both diets . TRLP apo CII , CIII , and E increased whereas HDL apo CII , CIII , and E decreased postpr and ially on both diets . In contrast , TRLP apo CI increased , and HDL apo CI decreased only after the high-carbohydrate diet . We conclude that 1 ) a high carbohydrate diet results in a decrease in total , LDL , and HDL cholesterol and a trend toward an increase in plasma triglycerides ; 2 ) fasting TRLP and HDL apo composition was similar on a high-carbohydrate or a high-fat diet ; and 3 ) on both diets , apo CII , CIII , and E transfer from HDL to TRLP postpr and ially . However , only the high-carbohydrate diet induced postpr and ial transfer of apo CI from HDL to TRLP . This may explain in part the changes in lipoproteins observed with this diet BACKGROUND Trials comparing the effectiveness and safety of weight-loss diets are frequently limited by short follow-up times and high dropout rates . METHODS In this 2-year trial , we r and omly assigned 322 moderately obese subjects ( mean age , 52 years ; mean body-mass index [ the weight in kilograms divided by the square of the height in meters ] , 31 ; male sex , 86 % ) to one of three diets : low-fat , restricted-calorie ; Mediterranean , restricted-calorie ; or low-carbohydrate , non-restricted-calorie . RESULTS The rate of adherence to a study diet was 95.4 % at 1 year and 84.6 % at 2 years . The Mediterranean-diet group consumed the largest amounts of  dietary fiber  and had the highest ratio of monounsaturated to saturated fat ( P<0.05 for all comparisons among treatment groups ) . The low-carbohydrate group consumed the smallest amount of carbohydrates and the largest amounts of fat , protein , and cholesterol and had the highest percentage of participants with detectable urinary ketones ( P<0.05 for all comparisons among treatment groups ) . The mean weight loss was 2.9 kg for the low-fat group , 4.4 kg for the Mediterranean-diet group , and 4.7 kg for the low-carbohydrate group ( P<0.001 for the interaction between diet group and time ) ; among the 272 participants who completed the intervention , the mean weight losses were 3.3 kg , 4.6 kg , and 5.5 kg , respectively . The relative reduction in the ratio of total cholesterol to high-density lipoprotein cholesterol was 20 % in the low-carbohydrate group and 12 % in the low-fat group ( P=0.01 ) . Among the 36 subjects with diabetes , changes in fasting plasma glucose and insulin levels were more favorable among those assigned to the Mediterranean diet than among those assigned to the low-fat diet ( P<0.001 for the interaction among diabetes and Mediterranean diet and time with respect to fasting glucose levels ) . CONCLUSIONS Mediterranean and low-carbohydrate diets may be effective alternatives to low-fat diets . The more favorable effects on lipids ( with the low-carbohydrate diet ) and on glycemic control ( with the Mediterranean diet ) suggest that personal preferences and metabolic considerations might inform individualized tailoring of dietary interventions . ( Clinical Trials.gov number , NCT00160108 . 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 OBJECTIVE To study effects of variation in carbohydrate content of diet on glycemia and plasma lipoproteins in patients with non-insulin-dependent diabetes mellitus ( NIDDM ) . DESIGN A four-center r and omized crossover trial . SETTING Outpatient and inpatient evaluation in metabolic units . PATIENTS Forty-two NIDDM patients receiving glipizide therapy .  INTERVENTIONS A high-carbohydrate diet containing 55 % of the total energy as carbohydrates and 30 % as fats was compared with a high-monounsaturated-fat diet containing 40 % carbohydrates and 45 % fats . The amounts of saturated fats , polyunsaturated fats , cholesterol , sucrose , and protein were similar . The study diets , prepared in metabolic kitchens , were provided as the sole nutrients to subjects for 6 weeks each . To assess longer-term effects , a subgroup of 21 patients continued the diet they received second for an additional 8 weeks . MAIN OUTCOME MEASURES Fasting plasma glucose , insulin , lipoproteins , and glycosylated hemoglobin concentrations . Twenty-four-hour profiles of glucose , insulin , and triglyceride levels . RESULTS The site of study as well as the diet order did not affect the results . Compared with the high-monounsaturated-fat diet , the high-carbohydrate diet increased fasting plasma triglyceride levels and very low-density lipoprotein cholesterol levels by 24 % ( P < .0001 ) and 23 % ( P = .0001 ) , respectively , and increased daylong plasma triglyceride , glucose , and insulin values by 10 % ( P = .03 ) , 12 % ( P < .0001 ) , and 9 % ( P = .02 ) , respectively . Plasma total cholesterol , low-density lipoprotein cholesterol , and high-density lipoprotein cholesterol levels remained unchanged . The effects of both diets on plasma glucose , insulin , and triglyceride levels persisted for 14 weeks . CONCLUSIONS In NIDDM patients , high-carbohydrate diets compared with high-monounsaturated-fat diets caused persistent deterioration of glycemic control and accentuation of hyperinsulinemia , as well as increased plasma triglyceride and very-low-density lipoprotein cholesterol levels , which may not be desirable Chronic insulin resistance contributes to sub clinical inflammation , thrombosis/impaired fibrinolysis , and dyslipidemia . The effect of dietary carbohydrate , specifically of glycemic index ( GI ) and glycemic load ( GL ) , on established and emerging coronary heart disease risk factors has not been eluci date d fully . We conducted a r and omized crossover feeding study of matched diets differing only in GI and GL in 24 overweight or obese but otherwise healthy men to investigate the effects on insulin sensitivity , inflammation , thrombosis/fibrinolysis , lipoproteins/lipids , and body composition .  All meals for the high- and low-GI/GL diets were prepared in a metabolic kitchen . Each participant consumed both diets in r and om order for 4 weeks each , with a 4-week washout period in between . Each participant underwent a frequently sample d intravenous glucose tolerance test for assessment of insulin sensitivity ; blood sampling for the measurement of inflammatory markers , coagulation factors , and lipoproteins/lipids ; and dual-energy x-ray absorptiometry for assessment of body composition at the beginning and end of each dietary period . There were no statistically significant differences in glucose metabolism factors , inflammatory markers , or coagulation factors after 4 weeks on the high- and low-GI/GL diets . The high-GI/GL diet result ed in a slightly greater reduction in fat mass and a slightly greater increase in lean mass compared with the low-GI/GL diet . The high-GI/GL diet result ed in significant , but unexpected , reductions in total and low-density lipoprotein cholesterol , whereas high-density lipoprotein cholesterol concentration was significantly reduced on the high-GI/GL diet compared with the low-GI/GL diet . Overall , high- and low-GI/GL diets of 4 weeks ' duration had no consistent effects on coronary heart disease risk factors in this group of overweight/obese men 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 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 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 OBJECTIVE High fat , low carbohydrate ( HFLC ) diets have become popular tools for weight management . We sought to determine the effects of a HFLC diet compared to a low fat high carbohydrate ( LFHC ) diet on the change in weight loss , cardiovascular risk factors and inflammation in subjects with obesity . METHODS Obese subjects ( 29.0 - 44.6 kg/m2 ) recruited from Boston Medical Center were r and omized to a hypocaloric LFHC ( n=26 ) or HFLC ( n=29 ) diet for 12 weeks . RESULTS The age range of subjects was 21 - 62 years . As a percentage of daily calories , the HFLC group consumed 33.5 % protein , 56.0 % fat and 9.6 % carbohydrate and the LFHC group consumed 22.0 % protein , 25.0 % fat and 55.7 % carbohydrate . The change in percent body weight , lean and fat mass , blood pressure , flow mediated dilation , hip : waist ratio , hemoglobin A1C , fasting insulin and glucose , and glucose and insulin response to a 2h oral glucose tolerance test did not differ ( P>0.05 ) between diets after 12 weeks . The HFLC group had greater mean decreases in serum triglyceride ( P=0.07 ) , and hs-CRP ( P=0.03 ) , and greater mean increases in HDL cholesterol ( P=0.004 ) , and total adiponectin ( P=0.045 ) relative to the LFHC . Secreted adipose tissue adiponectin or TNF-α did not differ after weight loss for either diet . CONCLUSIONS Relative to the LFHC group , the HFLC group had greater improvements in blood lipids and systemic inflammation with similar changes in body weight and composition . This small-scale study suggests that HFLC diets may be more beneficial to cardiovascular health and inflammation in free-living obese adults compared to LFHC diets Exercise , a low fat diet , or a diet low in saturated fat content can each lower plasma total cholesterol and low-density lipoprotein ( LDL ) cholesterol . We investigated whether these factors together could prevent the lipid-raising effects of dietary cholesterol . Ten healthy , athletic , normolipidemic male volunteers were studied . Two diets of 4 weeks duration each were compared in a r and omized , blind crossover design . Diets were identical except for cholesterol content : one contained 600 mg/d ; the other 200 mg/d . Both diets contained 15 % of calories as protein , 55 % as carbohydrate , 30 % as fat , and the polyunsaturated fat to saturated fat ratio was 1.5 . Exercise level and body weight were kept constant in each subject . As compared with plasma values obtained following the 200-mg/d cholesterol diet , mean values following the 600-mg/d cholesterol diet significantly increased for LDL cholesterol and apolipoprotein B by 10 % and 13 % , respectively . Mean plasma triglycerides , high-density lipoprotein 2 and 3 , and apolipoprotein A-1 levels did not change significantly . Individual responses , however , were highly variable . Three subjects increased LDL cholesterol by more than 25 % ; 2 subjects increased LDL cholesterol by 10 % to 25 % ; and 5 subjects had 5 % or less change in LDL cholesterol . A dietary cholesterol increase can significantly elevate plasma LDL cholesterol and apolipoprotein B in certain normolipidemic , healthy men even when they are exercising regularly and consuming a moderately fat restricted , low saturated fat diet . Dietary cholesterol restriction may therefore be justifiable even when other life-style and dietary measures to minimize blood cholesterol are undertaken 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 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 Low‐density lipoprotein ( LDL ) subclass pattern B is a common genetically influenced lipoprotein profile characterized by a predominance of small , dense LDL particles , and associated with increased levels of triglyceride‐rich lipoproteins , reductions in high‐density lipoprotein cholesterol ( HDL‐C ) , and increased risk of coronary artery disease compared to individuals with a predominance of larger LDL ( pattern A ) . We sought to determine whether LDL subclass patterns are associated with response of plasma lipoprotein levels to changes in dietary fat and carbohydrate content . In a r and omized cross‐over study , 105 men consumed , for six weeks each ,  high‐fat ( 46 % ) and low‐fat ( 24 % ) solid food diets , with replacement of fat by carbohydrate .  Diet‐induced changes in subjects who exhibited pattern B ( n = 18 ) following the high‐fat diet differed significantly from those in subjects with pattern A ( n = 87 ) : in pattern B subjects LDL cholesterol ( LDL‐C ) reductions were two‐fold greater and plasma apolipoprotein ( apo ) B levels decreased significantly . These differences remained significant after adjustment for levels of plasma LDL‐C , apo B , HDL‐C , and body mass index . Thus , LDL subclass pattern is a factor that contributes significantly to interindividual variation of plasma lipoprotein response to a low‐fat , high‐carbohydrate diet.— Dreon , D. M. , Fernstrom , H. A. , Miller , B. , Krauss , R. M. Low‐density lipoprotein subclass patterns and lipoprotein response to a  reduced‐fat diet in men . FASEB J. 8 : 121‐126 ; 1994 Background / Objectives : There is controversy over dietary protein 's effects on cardiovascular disease risk factors in diabetic subjects . It is unclear whether observed effects are due to increased protein or reduced carbohydrate content of the consumed diets . The aim of this study was to compare the effects of two diets differing in protein to fat ratios on cardiovascular disease risk factors . Subjects/ Methods : A total of 17 obese ( body mass index ( BMI ) ranging from 31 to 45 kg/m2 ) volunteers with type 2 diabetes ( DM2 ) , aged 46±3 years , consumed two diets , each for 4 weeks , with 3 weeks of washout period in a r and om , blind , crossover design . The diets were : ( 1 ) a high-protein low-fat diet ( HP – LF , with 30 % protein , 50 % carbohydrates and 20 % fat ) and ( 2 ) a low-protein high-fat diet ( LP – HF , with 15 % protein , 50 % carbohydrates and 35 % fat ) . Their effects on fasting glycemic control , lipid levels and blood pressure , and on postpr and ial glucose and insulin responses after a st and ard test meal at the beginning and end of each dietary intervention were analyzed . Results : Both diets were equally effective in promoting weight loss and fat loss and in improving fasting glycemic control , total cholesterol and low-density lipoprotein ( LDL ) cholesterol , but the HP – LF diet decreased to a greater extent triglyceride ( TG ) levels ( P=0.04 ) when compared with the LP – HF diet . HP – LF diet improved significantly both systolic and diastolic blood pressure when compared with the LP – HF diet ( P<0.001 and P<0.001 , respectively ) . No differences were observed in postpr and ial glucose and insulin responses . Conclusions : A protein to fat ratio of 1.5 in diets significantly improves blood pressure and TG concentrations in obese individuals with DM2 The effects of various cholesterol-lowering diets on plasma lipid and lipoprotein cholesterol levels were assessed in normal and hypercholesterolemic subjects . The base-line diet was an ad libitum hospital diet of normal composition . Diet A was a 20 % protein , 40 % carbohydrate , 40 % fat , polyunsaturated : saturated fat ratio 0.1 to 0.3 , 250 to 300 mg cholesterol diet , diet B was identical to diet A except that the polyunsaturated/saturated fat ratio was 1.8 to 2.2 , and diet C was a 20 % protein , 80 % carbohydrate , very low fat ( 5 to 10 g ) , polyunsaturated/saturated fat ratio 0.1 to 0.3 , 150 to 200 mg cholesterol diet . Diet A ( low cholesterol ) caused mean reductions in plasma , low-density lipoprotein ( LDL ) , and high-density lipoprotein ( HDL ) cholesterol of 5.9 , 5.6 , and 6.3 % , respectively , in 11 normal subjects . Diet B ( low cholesterol , high polyunsaturated fat ) caused significant decreases in plasma cholesterol , LDL cholesterol and HDL cholesterol of 17.0 , 16.2 , and 17.4 % , respectively , in 12 normal subjects ; and reductions of 11.0 , 10.8 , and 17.1 % , respectively , in 19 hypercholesterolemic subjects . Diet C ( low cholesterol , very low fat ) produced significant mean decreases in plasma , LDL , and HDL cholesterol of 26.7 , 29.9 , and 27.9 % , respectively , in 11 normal subjects , and in nine hypercholesterolemic patients of 22.6 , 27.2 , and 28.6 % , respectively . The reductions in plasma cholesterol caused by these diets were therefore due to decreases in both LDL and HDL cholesterol with no significant changes in the LDL cholesterol : HDL cholesterol ratio The effects of variations in dietary carbohydrate and fat on various aspects of carbohydrate and lipoprotein metabolism were evaluated in 10 healthy , postmenopausal women . The two diets were isoenergetic , assigned in r and om fashion , and consisted ( as a % of total energy ) of 15 % protein , 60 % carbohydrate , and 25 % fat ( 60%-carbohydrate diet ) or 15 % protein , 40 % carbohydrate , and 45 % fat ( 40%-carbohydrate diet ) .  Fasting plasma triacylglycerol , very-low-density-lipoprotein ( VLDL ) triacylglycerol , and VLDL-cholesterol concentrations were higher ( P < 0.05 - 0.001 ) after the 60%-carbohydrate diet , whereas high-density-lipoprotein ( HDL ) cholesterol was lower ( P < 0.05 ) . Plasma insulin and triacylglycerol concentrations were also higher ( P < 0.001 ) from 0800 to 0000 with the 60%-carbohydrate diet than with the 40%-carbohydrate diet . In addition , when vitamin A was given with the noon meal , the ensuing concentrations of retinyl palmitate were also higher after ingestion of the 60%-carbohydrate diet .  Resistance to insulin-mediated glucose disposal , quantified at baseline by determining the steady state plasma glucose ( SSPG ) concentration at the end of a 180-min infusion of somatostatin , insulin , and glucose , correlated with the incremental increases in postpr and ial concentrations of plasma glucose ( r = 0.68 , P = 0.06 ) , insulin ( r = 0.82 , P < 0.02 ) , triacylglycerol ( r = 0.77 , P < 0.05 ) , and retinyl palmitate ( r = 0.68 , P = 0.06 ) and with the Sf > 400 triacylglycerol ( r = 0.77 , P < 0.05 ) , Sf 20 - 400 triacylglycerol ( r = 0.72 , P < 0.05 ) , and Sf > 400 retinyl palmitate ( r = 0.75 , P < 0.01 ) lipoprotein fractions . Because all of these changes would increase risk of ischemic heart disease in postmenopausal women , it seems reasonable to question the wisdom of recommending that postmenopausal women consume low-fat , high-carbohydrate diets 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 BACKGROUND Mediterranean and high carbohydrate diets play a dominant role in the prevention of atherosclerosis as a result of their lipid lowering effect . However , diets can also have a protective effect in other ways , such as modulating tissue factor expression in circulating monocytes . METHODS AND RESULTS Forty-one subjects participated in this r and omised crossover study consisting of three dietary periods : a saturated fat enriched diet ( SFA ) , a low fat and high carbohydrate diet ( CHO ) , and a Mediterranean diet .  Plasma levels of total cholesterol , triglycerides , low density lipoprotein ( LDL-C ) and high density lipoprotein ( HDL-C ) were determined at the end of each dietary period , as was the expression of tissue factor ( TF ) in circulating monocytes isolated from blood sample s. Total cholesterol , LDL-C , HDL-C and TF expression were lower after the Mediterranean and high carbohydrate diets than after the SFA diet , and there was a positive correlation between LDL-C levels and monocyte TF expression . CONCLUSIONS High carbohydrate and Mediterranean diets reduce the expression of TF in circulating monocytes Aim To determine the effect of dietary advice in conjunction with advice to increase  physical activity  on the body composition , blood lipid and insulin profiles in overweight women . Design A 12-week r and omized controlled intervention study . Subjects were assigned to one of four groups : ( 1 ) no advice , ( 2 ) low-fat , high-carbohydrate ( including sucrose ) energy-reduced diet , ( 3 ) 60 min/day brisk walking , and ( 4 ) diet and activity advice as previous . Subjects Sixty-nine overweight women ( mean age 41 years ) .  Measurements Dietary compliance was assessed by 4-day diet diaries  . Activity levels were assessed by Caltrac ™ accelerator monitors  . Anthropometric changes were recorded at baseline , 6 and 12 weeks . Fasting blood sample s measuring glucose , insulin , and blood lipids were recorded at baseline and 12 weeks . Results Group 4 achieved greatest weight loss of 4.2 kg and greatest reduction in waist circumference of 6.5 cm . Groups 2 and 4 decreased the percentage energy from fat by 5.2 % . Group 3 increased the percentage energy from fat by 4.0 % . Group 4 significantly reduced total cholesterol by 0.45 mmol/l and low-density lipoprotein-cholesterol by 0.53 mmol/l . Conclusion A low-fat , high-carbohydrate , sucrose-containing diet combined with increased physical exercise result ed in greater health benefits than diet or physical activity advice alone BACKGROUND Despite the popularity of low-glycemic index ( GI ) and high-protein diets , to our knowledge no r and omized , controlled trials have systematic ally compared their relative effects on weight loss and cardiovascular risk . METHODS A total of 129 overweight or obese young adults ( body mass index , > or = 25 [ calculated as weight in kilograms divided by the square of height in meters ] ) were assigned to 1 of 4 reduced-fat , high-fiber diets for 12 weeks . Diets 1 and 2 were high carbohydrate ( 55 % of total energy intake ) , with high and low GIs , respectively ; diets 3 and 4 were high protein ( 25 % of total energy intake ) , with high and low GIs , respectively . The glycemic load was highest in diet 1 and lowest in diet 4 . Changes in weight , body composition , and blood chemistry profile were studied . RESULTS While all groups lost a similar mean + /- SE percentage of weight ( diet 1 , -4.2 % + /- 0.6 % ; diet 2 , -5.5 % + /- 0.5 % ; diet 3 , -6.2 % + /- 0.4 % ; and diet 4 , -4.8 % + /- 0.7 % ; P = .09 ) , the proportion of subjects in each group who lost 5 % or more of body weight varied significantly by diet ( diet 1 , 31 % ; diet 2 , 56 % ; diet 3 , 66 % ; and diet 4 , 33 % ; P = .01 ) . Women on diets 2 and 3 lost approximately 80 % more fat mass ( -4.5 + /- 0.5 [ mean + /- SE ] kg and -4.6 + /- 0.5 kg ) than those on diet 1 ( -2.5 + /- 0.5 kg ; P = .007 ) . Mean + /- SE low-density-lipoprotein cholesterol levels declined significantly in the diet 2 group ( -6.6 + /- 3.9 mg/dL [ -0.17 + /- 0.10 mmol/L ] ) but increased in the diet 3 group ( + 10.0 + /- 3.9 mg/dL [ + 0.26 + /- 0.10 mmol/L ] ; P = .02 ) . Goals for energy distribution were not achieved exactly : both carbohydrate groups ate less fat , and the diet 2 group ate more fiber . CONCLUSION Both high-protein and low-GI regimens increase body fat loss , but cardiovascular risk reduction is optimized by a high-carbohydrate , low-GI diet CONTEXT Reduced energy expenditure following weight loss is thought to contribute to weight gain . However , the effect of dietary composition on energy expenditure during weight-loss maintenance has not been studied . OBJECTIVE To examine the effects of 3 diets differing widely in macronutrient composition and glycemic load on energy expenditure following weight loss . DESIGN , SETTING , AND PARTICIPANTS A controlled 3-way crossover design involving 21 overweight and obese young adults conducted at Children 's Hospital Boston and Brigham and Women 's Hospital , Boston , Massachusetts , between June 16 , 2006 , and June 21 , 2010 , with recruitment by newspaper advertisements and postings . INTERVENTION After achieving 10 % to 15 % weight loss while consuming a run-in diet , participants consumed an isocaloric low-fat diet ( 60 % of energy from carbohydrate , 20 % from fat , 20 % from protein ; high glycemic load ) , low-glycemic index diet ( 40 % from carbohydrate , 40 % from fat , and 20 % from protein ; moderate glycemic load ) , and very low-carbohydrate diet ( 10 % from carbohydrate , 60 % from fat , and 30 % from protein ; low glycemic load ) in r and om order , each for 4 weeks . MAIN OUTCOME MEASURES Primary outcome was resting energy expenditure ( REE ) , with secondary outcomes of total energy expenditure ( TEE ) , hormone levels , and metabolic syndrome components . RESULTS Compared with the pre-weight-loss baseline , the decrease in REE was greatest with the low-fat diet ( mean [ 95 % CI ] , -205 [ -265 to -144 ] kcal/d ) , intermediate with the low-glycemic index diet ( -166 [ -227 to -106 ] kcal/d ) , and least with the very low-carbohydrate diet ( -138 [ -198 to -77 ] kcal/d ; overall P = .03 ; P for trend by glycemic load = .009 ) . The decrease in TEE showed a similar pattern ( mean [ 95 % CI ] , -423 [ -606 to -239 ] kcal/d ; -297 [ -479 to -115 ] kcal/d ; and -97 [ -281 to 86 ] kcal/d , respectively ; overall P = .003 ; P for trend by glycemic load < .001 ) . Hormone levels and metabolic syndrome components also varied during weight maintenance by diet ( leptin , P < .001 ; 24-hour urinary cortisol , P = .005 ; indexes of peripheral [ P = .02 ] and hepatic [ P = .03 ] insulin sensitivity ; high-density lipoprotein [ HDL ] cholesterol , P < .001 ; non-HDL cholesterol , P < .001 ; triglycerides , P < .001 ; plasminogen activator inhibitor 1 , P for trend = .04 ; and C-reactive protein , P for trend = .05 ) , but no consistent favorable pattern emerged . CONCLUSION Among overweight and obese young adults compared with pre-weight-loss energy expenditure , isocaloric feeding following 10 % to 15 % weight loss result ed in decreases in REE and TEE that were greatest with the low-fat diet , intermediate with the low-glycemic index diet , and least with the very low-carbohydrate diet . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00315354 Twelve carbohydrate-sensitive men selected due to their abnormally high insulin responses to a sucrose load and 12 men with normal insulin responses were fed diets containing 0 , 7.5 , and 15 % fructose for 5 wk each in a cross-over design . The diets contained 43 % total carbohydrate , 42 % fat , and 15 % protein . Initial fasting total cholesterol and low-density lipoprotein cholesterol were higher in the hyperinsulinemic men than in the controls . Diastolic blood pressure was not affected by diet , but systolic blood pressure was slightly higher after the men consumed the 0 % fructose diet . Free fatty acids were not different . Total plasma cholesterol and low-density lipoprotein cholesterol were higher after the men consumed 7.5 and 15 % fructose than when they consumed the 0 % fructose diet . Plasma triglyceride increased significantly as fructose in the diets of the hyperinsulinemics increased , but was not affected in the controls . These changes in blood lipids are associated with heart disease 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 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 . ) Aim : To compare the effects of a chickpea-supplemented diet and those of a wheat-supplemented diet on human serum lipids and lipoproteins . Methods : Forty-seven free-living adults participated in a r and omized crossover weight maintenance dietary intervention involving two dietary periods , chickpea-supplemented and wheat-supplemented diets , each of at least 5 weeks duration . Results : The serum total cholesterol and low-density lipoprotein cholesterol levels were significantly lower ( both p < 0.01 ) by 3.9 and 4.6 % , respectively , after the chickpea-supplemented diet as compared with the wheat-supplemented diet .  Protein ( 0.9 % of energy , p = 0.01 ) and monounsaturated fat ( 3.3 % of total fat , p < 0.001 ) intakes were slightly but significantly lower and the carbohydrate intake significantly higher ( 1.7 % of energy , p < 0.001 ) on the chickpea-supplemented diet as compared with the wheat-supplemented diet . Multivariate analyses suggested that the differences in serum lipids were mainly due to small differences in polyunsaturated fatty acid and dietary fibre contents between the two intervention diets . Conclusions : Inclusion of chickpeas in an intervention diet results in lower serum total and low-density lipoprotein cholesterol levels as compared with a wheat-supplemented diet OBJECTIVE The aim of this study was to assess the effects of the Dietary Approaches to Stop Hypertension ( DASH ) diet on lipid profiles and biomarkers of oxidative stress in overweight and obese women with polycystic ovary syndrome ( PCOS ) . METHODS This r and omized controlled clinical trial was conducted with 48 women diagnosed with PCOS . The women were r and omly assigned to consume either the control ( n = 24 ) or DASH diet ( n = 24 ) for 8 wk . Both diets were design ed to be calorie-restricted . Both diets consisted of 52 % carbohydrates , 18 % proteins , and 30 % total fats . The DASH diet was design ed to be rich in fruits , vegetables , whole grains , and low-fat dairy products and to be low in saturated fats , cholesterol , and refined grains . Fasting blood sample s were taken at baseline and after 8-wk intervention to measure lipid profiles and biomarkers of oxidative stress including plasma total antioxidant capacity ( TAC ) and total glutathione ( GSH ) . RESULTS Adherence to the DASH diet , compared with the control diet , result ed in a significant decrease in weight ( -4.4 versus -1.5 kg ; P < 0.001 ) and body mass index ( -1.7 versus -0.6 kg/m(2 ) ; P < 0.001 ) , decreased serum triglycerides ( -10.0 versus + 19.2 mg/dL ; P interaction = 0.005 ) and very-low-density lipoprotein cholesterol levels ( -2.0 versus + 3.9 mg/dL ; P interaction = 0.005 ) . Increased concentrations of TAC ( + 98.6 versus -174.8 mmol/L ; P interaction < 0.001 ) and GSH ( + 66.4 versus -155.6 μmol/L ; P interaction = 0.005 ) also were found in the DASH group compared with the control group . CONCLUSION Consumption of DASH diet for 8 wk led to a significant reduction in serum insulin , triglycerides and very-low-density lipoprotein cholesterol and a significant increase in TAC and GSH levels BACKGROUND The DASH ( Dietary Approaches to Stop Hypertension ) dietary pattern , which is high in fruit , vegetables , and low-fat dairy foods , significantly lowers blood pressure as well as low-density lipoprotein ( LDL ) and high-density lipoprotein ( HDL ) cholesterol . OBJECTIVE The study was design ed to test the effects of substituting full-fat for low-fat dairy foods in the DASH diet , with a corresponding increase in fat and a reduction in sugar intake , on blood pressure and plasma lipids and lipoproteins . DESIGN This was a 3-period r and omized crossover trial in free-living healthy individuals who consumed in r and om order a control diet , a st and ard DASH diet , and a higher-fat , lower-carbohydrate modification of the DASH diet ( HF-DASH diet ) for 3 wk each , separated by 2-wk washout periods . Laboratory measurements , which included lipoprotein particle concentrations determined by ion mobility , were made at the end of each experimental diet . RESULTS Thirty-six participants completed all 3 dietary periods . Blood pressure was reduced similarly with the DASH and HF-DASH diets compared with the control diet . The HF-DASH diet significantly reduced triglycerides and large and medium very-low-density lipoprotein ( VLDL ) particle concentrations and increased LDL peak particle diameter compared with the DASH diet . The DASH diet , but not the HF-DASH diet , significantly reduced LDL cholesterol , HDL cholesterol , apolipoprotein A-I , intermediate-density lipoprotein and large LDL particles , and LDL peak diameter compared with the control diet . CONCLUSIONS The HF-DASH diet lowered blood pressure to the same extent as the DASH diet but also reduced plasma triglyceride and VLDL concentrations without significantly increasing LDL cholesterol . This trial was registered at clinical trials.gov as NCT01404897 Background Obesity is significant problem involving eating behavior and peripheral metabolic conditions . The effect of carbohydrate and fat restriction on appetite regulation , fibroblast growth factor 21 ( FGF21 ) and leptin in children has not been defined . Our objective was to compare the effect of both diets . Methods One hundred and twenty children with body mass index ( BMI ) higher than the equivalent of 30 kg/m2 for an adult , as corrected for gender and age were r and omly assigned to ( n = 60 ) a low-carbohydrate ( L-CHO ) diet or ( n = 60 ) a low-fat ( L-F ) diet for 2 months . Fifty-three ( 88.3 % ) subjects on the low-carbohydrate-diet and 45 ( 75 % ) on the low-fat diet completed the study .  Anthropometric measures , leptin and FGF21 levels were measured before and after the intervention . Comparison of the data for both of the diet groups was carried out using the t-test for independent variables . Intragroup comparisons before and after of each of the dietary treatments were performed using ANOVA for repeated measures . Factors associated with FGF21 , leptin levels and satiety , were analyzed by multiple regression . Results After both of the diets , weight , leptin , food responsiveness , and enjoyment of food significantly decreased and high density lipoprotein cholesterol ( HDL ) increased , but FGF21 decreased . Before and after both of the interventions FGF21 was associated with triglycerides . Before the diet , satiety was associated with lower screen time ( p < 0.04 ) and insulin levels ( p < 0.05 ) . Conclusions Both dietary restrictions improved the metabolic and hormonal parameters of obese children . FGF21 is an indicator of a beneficial metabolic response in younger children . After 2 months an adaptation of the eating behavior to food restriction was observed 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 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 Twenty-three young adult males were fed diets containing either 400 or 1400 mg of cholesterol per day under controlled conditions for 4 wk . There were minimal differences between the two diets in total protein , carbohydrate , fat , and the P/S fatty acid ratio . In both diets 400 mg of cholesterol was supplied from nonegg food sources ; the additional 1000 mg of cholesterol was from four whole eggs . Blood sample s were collected after a 12- to 14-h fast at the beginning of the study , weekly throughout the experimental period , and 1 wk after completion of the study . Plasma total cholesterol and triglycerides and high-density , low-density , and very low-density lipoprotein cholesterol levels were measured . No significant differences in plasma total cholesterol , triglycerides , and lipoprotein cholesterol levels were observed between groups at any time . However , plasma cholesterol and cholesterol content of individual lipoproteins varied considerably among the individual subjects fed the high cholesterol diet . The importance of changes in the properties and metabolic activity of individual lipoproteins induced by dietary cholesterol with or without gross changes in the cholesterol levels remains to be determined
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 .