- Email: [email protected]
A low-carbohydrate, ketogenic diet versus a low-fat diet to treat obesity and hyperlipidemia
Preventive Cardiology
mic control were still more favorable with a low-carbohydrate diet after adjustment for differences in weight loss. Perspective: By 1 year, the amount of weight loss was very modest (⬍4%) in this very obese group of men. Many advocates of a very low carbohydrate diet enriched with unlimited fats to rapidly induce weight loss in obesity have modified their position. Most agree that bingeng on fats to induce ketosis and water loss is not justifiable, particularly because a significant percentage of individuals may have a rapid rise in LDL-C and too many will continue the high-fat diet at the expense of appropriate micronutrients from fruits and vegetables. A modest reduction of total caloric intake with an emphasis on limiting simple sugars and starches, restricting saturated fat and substituting monounsaturated fats, and encouraging 150 to 200 min of exercise weekly seems to be the most prudent way to achieve weight loss and improve the metabolic profile, particularly atherogenic dyslipidemia. MR
Abstracts The Effects of Low-Carbohydrate Versus Conventional Weight Loss Diets in Severely Obese Adults: One-Year Follow-up of a Randomized Trial Stem L, Iqbal N, Seshadri P, Chicano K, et al. Ann Intern Med 2004;140:778 – 85. Study Question: Is there a difference at the end of 1 year on weight loss, compliance, and metabolic parameters in obese patients assigned to a low-carbohydrate compared to a conventional weight loss diet? Methods: A total of 132 obese adults with a BMI of 35 kg/m2 or greater were randomized either to restrict carbohydrate intake to ⬍30 g/day (low-carbohydrate diet, n⫽64) or to restrict caloric intake by 500 calories/day with ⬍30% of calories from fat (conventional diet, n⫽68). Patients were instructed on diets weekly for 4 weeks followed by 11 monthly sessions. Primary end points included changes in weight, lipid levels, glycemic control, and insulin sensitivity. Results: Approximate mean values for participants including those completing the program and dropouts were as follows: age 50 years, BMI 43 kg/m2, weight 130 kg. Over 80% were male and 83% were diabetic or had the metabolic syndrome. Hypoglycemics were used in about 30% of subjects, statins in 40%; 25% were smokers, and over 30% had documented depression. Caloric intake decreased more at 1 year in the low-carbohydrate group than in the conventional diet, although not significantly. Low-carbohydrate subjects increased fat intake by 31%, reduced carbohydrates by 52%, fiber by 42%, and sodium by 21% compared to baseline. Only reductions in carbohydrate and sodium intake were greater than that in the conventional diet group. By 1 year, mean weight change for persons on the low-carbohydrate diet was ⫺5.1⫾8.7 kg compared with ⫺3.1⫾8.4 kg for persons on the conventional diet with no change in blood pressure. Differences between groups were not significant (⫺1.9 kg [95% CI, ⫺4.9 to 1.0 kg], p⫽0.20). For persons on the low-carbohydrate diet, triglyceride levels decreased more (p⫽0.044) and HDL-C levels decreased less (p⫽0.025) with no difference between groups in change in LDL-C, but with a significant increase in BUN. In the small group with diabetes (n⫽54), after adjustment for covariates, HbA1c levels improved more on the low-carbohydrate diet. The favorable metabolic responses to a low-carbohydrate diet remained significant after adjustment for weight loss differences. Changes in other lipids or insulin sensitivity did not differ between groups. Conclusions: Participants on a low-carbohydrate diet had more favorable overall outcomes at 1 year than did those on a conventional diet. Weight loss was similar between groups, but effects on atherogenic dyslipidemia and glyce-
A Low-Carbohydrate, Ketogenic Diet Versus a LowFat Diet to Treat Obesity and Hyperlipidemia Yancy WS, Olsen MK, Guyton JR, Bakst RP, Westman EC. Ann Intern Med 2004;140:769 –77. Study Question: What is the relative effect on weight loss and lipids of a low-carbohydrate ketogenic diet as compared to a low-fat, low-cholesterol, reduced-calorie diet? Methods: A total of 120 overweight but otherwise healthy volunteers from the community were randomly assigned a low-carbohydrate diet (initially, ⬍20 g of carbohydrate daily) plus nutritional supplementation, exercise recommendation, and group meetings, or low-fat diet (⬍30% energy from fat, ⬍300 mg of cholesterol daily, and deficit of 500 to 1000 kcal/d) plus exercise recommendation and group meetings. Inclusion criteria included age 18 to 65 years, BMI of 30 to 60kg/m2, a desire to lose weight, and elevated lipids defined as an LDL-C ⬎130 mg/dL or triglycerides ⬎200 mg/dL. Primary end points included body weight, body composition, fasting serum lipid levels, and acceptance. Results: Mean age was 44 years, ⬎70% were women, ⬎75% were white, and nearly 20% African American. Mean weight and BMI did not differ between groups; 97⫾18 kg and 34⫾5 kg/m2. A greater proportion of the low-carbohydrate diet group than the low-fat diet group completed the study (76% vs. 57%; p⫽0.02). At 24 weeks, weight loss was greater in the low-carbohydrate group than in the low-fat diet group (mean reduction of 12.9% vs. 6.7%; p⬍0.001). Patients in both groups lost substantially more fat mass (mean reduction of 9.4 kg with the low-carbohydrate diet vs. 4.8 kg with the low-fat diet) than fat-free mass (reduced 3.3 kg vs. 2.4 kg, respectively). Compared with the low-fat diet, those on the low-carbohydrate diet had a greater decrease in serum triglyceride level (reduced 74.2 mg/dL vs. 27.9 mg/dL; p⫽0.004) and a greater increase in HDL-C
ACC CURRENT JOURNAL REVIEW Aug 2004
18
(increase of 5.5 mg/dL vs. decrease of 1.6 mg/dL; p⬍0.001). Decreases in LDL-C level did not differ statistically (1.6 mg/dL with the low-carbohydrate diet and 7.4 mg/dL with the low-fat diet; p⫽0.2). Minor adverse effects including constipation, headache, muscle cramps, diarrhea, general weakness, and a skin rash were more frequent in the low-carbohydrate group. Conclusions: Over a 24-week period, compared with a lowfat diet, a low-carbohydrate program had better participant retention and greater weight loss, which was associated with a decrease in triglycerides and increase in HDL-C. Perspective: Results are similar to other studies comparing the “Atkins diet” to other weight loss diets in obesity. The low-fat diet subjects were asked to restrict calories while participants in the low-carbohydrate diet were not. Nevertheless, “low-carb” diets are associated with decreased energy intake because of loss of appetite, particularly for fatty foods, and limited snack choices. The decrease in triglycerides and increase in HDL-C without a major increase in mean LDL-C is often found with the ketogenic diet. The initial high-fat intake during the first 2 weeks of the lowcarbohydrate diet can adversely effect the LDL-C and possibly endothelial function. There is no role for the high-fat– low-carbohydrate diet in nonobese persons and in those with coronary disease. Limiting simple sugars and starches and increasing monounsaturated fats in the traditional “low-fat diet” is becoming the centrist view. MR
protein (CRP), interleukin-6, TNF-alpha, or adiponectin; and it did not have classic CRFs (blood pressure and plasma glucose, insulin, and lipid concentrations) in either group. Conclusions: Abdominal liposuction does not significantly improve obesity-associated metabolic abnormalities. Decreasing adipose tissue mass alone will not achieve the metabolic benefits of weight loss. Perspective: This is a wonderful study, the results of which should not be too surprising. Cardiovascular risk is more highly correlated with intra-abdominal or visceral fat mass than is subcutaneous fat. Considering that weight loss and loss of body fat are similar to that achieved with a good diet and exercise regimen, I was expecting at least a reduction in triglycerides, insulin, and CRP. Negative energy balance appears to be the key to achieving the metabolic benefits of weight loss. MR
Lipid Control in the Management of Type 2 Diabetes Mellitus: A Clinical Practice Guideline From the American College of Physicians Snow V, Aronson MD, Hornbake ER, Mottur-Pilson C, Weiss KB, for the Clinical Efficacy Assessment Subcommittee [CEAS] of the American College of Physicians. Ann Intern Med 2004;140: 644 –9. Study Question: The CEAS commissioned a systematic review of the currently available evidence on the management of lipids in type-2 diabetes mellitus. On the basis of this systematic review, the CEAS developed recommendations that the American College of Physicians (ACP) Board of Regents then approved as policy. Recommendation 1: Lipid-lowering therapy should be used for secondary prevention of cardiovascular mortality and morbidity for all patients (both men and women) with known coronary artery disease and type-2 diabetes. Recommendation 2: Statins should be used for primary prevention against macrovascular complications in patients (both men and women) with type-2 diabetes and other cardiovascular risk factors. Recommendation 3: Once lipid-lowering therapy is initiated, patients with type-2 diabetes mellitus should be taking at least moderate doses of a statin. Recommendation 4: For those patients with type-2 diabetes who are taking statins, routine monitoring of liver-function tests or muscle enzymes is not recommended except in specific circumstances. DM
Absence of an Effect of Liposuction on Insulin Action and Risk Factors for Coronary Heart Disease Klein S, Fontana L, Young VL, et al. N Engl J Med 2004;350: 2549 –57. Study Question: Does large-volume abdominal liposuction in women with abdominal obesity reduce the metabolic risk factors for coronary heart disease (CHD)? Methods: Tissue insulin sensitivity and other risk factors for CHD were assessed in 15 obese women before and 10 to 12 weeks after abdominal liposuction. Insulin sensitivity of muscle, liver and adipose tissue was assessed with the euglycemic– hyperinsulinemic clamp procedure and isotope-tracer infusions by the stimulation of glucose disposal, the suppression of glucose production, and the suppression of lipolysis, respectively. Results: Eight subjects had normal glucose tolerance (BMI 35.1⫾2.4, and 7 had type-2 diabetes (BMI 39.9⫾5.6). Liposuction decreased the volume of subcutaneous abdominal adipose tissue by 44% in subjects with normal glucose tolerance and 28% in those with diabetes. The normal oral glucose tolerance group lost 9.1⫾3.7 kg of fat (18⫾3% decrease in total fat; p⫽0.002), and those with type-2 diabetes lost 10.5⫾3.3 kg of fat (19⫾2% decrease in total fat; p ⬍0.001). Liposuction did not significantly alter the insulin sensitivity of muscle, liver, or adipose tissue; it did not significantly alter plasma concentrations of C-reactive
Soluble CD40 Ligand, Soluble P-Selectin, Interleukin-6, and Tissue Factor in Diabetes Mellitus. Relationships to Cardiovascular Disease and Risk Factor Intervention Lim H, Blann A, Lip G. Circulation 2004;109:2524 – 8.
ACC CURRENT JOURNAL REVIEW Aug 2004
19
mic control were still more favorable with a low-carbohydrate diet after adjustment for differences in weight loss. Perspective: By 1 year, the amount of weight loss was very modest (⬍4%) in this very obese group of men. Many advocates of a very low carbohydrate diet enriched with unlimited fats to rapidly induce weight loss in obesity have modified their position. Most agree that bingeng on fats to induce ketosis and water loss is not justifiable, particularly because a significant percentage of individuals may have a rapid rise in LDL-C and too many will continue the high-fat diet at the expense of appropriate micronutrients from fruits and vegetables. A modest reduction of total caloric intake with an emphasis on limiting simple sugars and starches, restricting saturated fat and substituting monounsaturated fats, and encouraging 150 to 200 min of exercise weekly seems to be the most prudent way to achieve weight loss and improve the metabolic profile, particularly atherogenic dyslipidemia. MR
Abstracts The Effects of Low-Carbohydrate Versus Conventional Weight Loss Diets in Severely Obese Adults: One-Year Follow-up of a Randomized Trial Stem L, Iqbal N, Seshadri P, Chicano K, et al. Ann Intern Med 2004;140:778 – 85. Study Question: Is there a difference at the end of 1 year on weight loss, compliance, and metabolic parameters in obese patients assigned to a low-carbohydrate compared to a conventional weight loss diet? Methods: A total of 132 obese adults with a BMI of 35 kg/m2 or greater were randomized either to restrict carbohydrate intake to ⬍30 g/day (low-carbohydrate diet, n⫽64) or to restrict caloric intake by 500 calories/day with ⬍30% of calories from fat (conventional diet, n⫽68). Patients were instructed on diets weekly for 4 weeks followed by 11 monthly sessions. Primary end points included changes in weight, lipid levels, glycemic control, and insulin sensitivity. Results: Approximate mean values for participants including those completing the program and dropouts were as follows: age 50 years, BMI 43 kg/m2, weight 130 kg. Over 80% were male and 83% were diabetic or had the metabolic syndrome. Hypoglycemics were used in about 30% of subjects, statins in 40%; 25% were smokers, and over 30% had documented depression. Caloric intake decreased more at 1 year in the low-carbohydrate group than in the conventional diet, although not significantly. Low-carbohydrate subjects increased fat intake by 31%, reduced carbohydrates by 52%, fiber by 42%, and sodium by 21% compared to baseline. Only reductions in carbohydrate and sodium intake were greater than that in the conventional diet group. By 1 year, mean weight change for persons on the low-carbohydrate diet was ⫺5.1⫾8.7 kg compared with ⫺3.1⫾8.4 kg for persons on the conventional diet with no change in blood pressure. Differences between groups were not significant (⫺1.9 kg [95% CI, ⫺4.9 to 1.0 kg], p⫽0.20). For persons on the low-carbohydrate diet, triglyceride levels decreased more (p⫽0.044) and HDL-C levels decreased less (p⫽0.025) with no difference between groups in change in LDL-C, but with a significant increase in BUN. In the small group with diabetes (n⫽54), after adjustment for covariates, HbA1c levels improved more on the low-carbohydrate diet. The favorable metabolic responses to a low-carbohydrate diet remained significant after adjustment for weight loss differences. Changes in other lipids or insulin sensitivity did not differ between groups. Conclusions: Participants on a low-carbohydrate diet had more favorable overall outcomes at 1 year than did those on a conventional diet. Weight loss was similar between groups, but effects on atherogenic dyslipidemia and glyce-
A Low-Carbohydrate, Ketogenic Diet Versus a LowFat Diet to Treat Obesity and Hyperlipidemia Yancy WS, Olsen MK, Guyton JR, Bakst RP, Westman EC. Ann Intern Med 2004;140:769 –77. Study Question: What is the relative effect on weight loss and lipids of a low-carbohydrate ketogenic diet as compared to a low-fat, low-cholesterol, reduced-calorie diet? Methods: A total of 120 overweight but otherwise healthy volunteers from the community were randomly assigned a low-carbohydrate diet (initially, ⬍20 g of carbohydrate daily) plus nutritional supplementation, exercise recommendation, and group meetings, or low-fat diet (⬍30% energy from fat, ⬍300 mg of cholesterol daily, and deficit of 500 to 1000 kcal/d) plus exercise recommendation and group meetings. Inclusion criteria included age 18 to 65 years, BMI of 30 to 60kg/m2, a desire to lose weight, and elevated lipids defined as an LDL-C ⬎130 mg/dL or triglycerides ⬎200 mg/dL. Primary end points included body weight, body composition, fasting serum lipid levels, and acceptance. Results: Mean age was 44 years, ⬎70% were women, ⬎75% were white, and nearly 20% African American. Mean weight and BMI did not differ between groups; 97⫾18 kg and 34⫾5 kg/m2. A greater proportion of the low-carbohydrate diet group than the low-fat diet group completed the study (76% vs. 57%; p⫽0.02). At 24 weeks, weight loss was greater in the low-carbohydrate group than in the low-fat diet group (mean reduction of 12.9% vs. 6.7%; p⬍0.001). Patients in both groups lost substantially more fat mass (mean reduction of 9.4 kg with the low-carbohydrate diet vs. 4.8 kg with the low-fat diet) than fat-free mass (reduced 3.3 kg vs. 2.4 kg, respectively). Compared with the low-fat diet, those on the low-carbohydrate diet had a greater decrease in serum triglyceride level (reduced 74.2 mg/dL vs. 27.9 mg/dL; p⫽0.004) and a greater increase in HDL-C
ACC CURRENT JOURNAL REVIEW Aug 2004
18
(increase of 5.5 mg/dL vs. decrease of 1.6 mg/dL; p⬍0.001). Decreases in LDL-C level did not differ statistically (1.6 mg/dL with the low-carbohydrate diet and 7.4 mg/dL with the low-fat diet; p⫽0.2). Minor adverse effects including constipation, headache, muscle cramps, diarrhea, general weakness, and a skin rash were more frequent in the low-carbohydrate group. Conclusions: Over a 24-week period, compared with a lowfat diet, a low-carbohydrate program had better participant retention and greater weight loss, which was associated with a decrease in triglycerides and increase in HDL-C. Perspective: Results are similar to other studies comparing the “Atkins diet” to other weight loss diets in obesity. The low-fat diet subjects were asked to restrict calories while participants in the low-carbohydrate diet were not. Nevertheless, “low-carb” diets are associated with decreased energy intake because of loss of appetite, particularly for fatty foods, and limited snack choices. The decrease in triglycerides and increase in HDL-C without a major increase in mean LDL-C is often found with the ketogenic diet. The initial high-fat intake during the first 2 weeks of the lowcarbohydrate diet can adversely effect the LDL-C and possibly endothelial function. There is no role for the high-fat– low-carbohydrate diet in nonobese persons and in those with coronary disease. Limiting simple sugars and starches and increasing monounsaturated fats in the traditional “low-fat diet” is becoming the centrist view. MR
protein (CRP), interleukin-6, TNF-alpha, or adiponectin; and it did not have classic CRFs (blood pressure and plasma glucose, insulin, and lipid concentrations) in either group. Conclusions: Abdominal liposuction does not significantly improve obesity-associated metabolic abnormalities. Decreasing adipose tissue mass alone will not achieve the metabolic benefits of weight loss. Perspective: This is a wonderful study, the results of which should not be too surprising. Cardiovascular risk is more highly correlated with intra-abdominal or visceral fat mass than is subcutaneous fat. Considering that weight loss and loss of body fat are similar to that achieved with a good diet and exercise regimen, I was expecting at least a reduction in triglycerides, insulin, and CRP. Negative energy balance appears to be the key to achieving the metabolic benefits of weight loss. MR
Lipid Control in the Management of Type 2 Diabetes Mellitus: A Clinical Practice Guideline From the American College of Physicians Snow V, Aronson MD, Hornbake ER, Mottur-Pilson C, Weiss KB, for the Clinical Efficacy Assessment Subcommittee [CEAS] of the American College of Physicians. Ann Intern Med 2004;140: 644 –9. Study Question: The CEAS commissioned a systematic review of the currently available evidence on the management of lipids in type-2 diabetes mellitus. On the basis of this systematic review, the CEAS developed recommendations that the American College of Physicians (ACP) Board of Regents then approved as policy. Recommendation 1: Lipid-lowering therapy should be used for secondary prevention of cardiovascular mortality and morbidity for all patients (both men and women) with known coronary artery disease and type-2 diabetes. Recommendation 2: Statins should be used for primary prevention against macrovascular complications in patients (both men and women) with type-2 diabetes and other cardiovascular risk factors. Recommendation 3: Once lipid-lowering therapy is initiated, patients with type-2 diabetes mellitus should be taking at least moderate doses of a statin. Recommendation 4: For those patients with type-2 diabetes who are taking statins, routine monitoring of liver-function tests or muscle enzymes is not recommended except in specific circumstances. DM
Absence of an Effect of Liposuction on Insulin Action and Risk Factors for Coronary Heart Disease Klein S, Fontana L, Young VL, et al. N Engl J Med 2004;350: 2549 –57. Study Question: Does large-volume abdominal liposuction in women with abdominal obesity reduce the metabolic risk factors for coronary heart disease (CHD)? Methods: Tissue insulin sensitivity and other risk factors for CHD were assessed in 15 obese women before and 10 to 12 weeks after abdominal liposuction. Insulin sensitivity of muscle, liver and adipose tissue was assessed with the euglycemic– hyperinsulinemic clamp procedure and isotope-tracer infusions by the stimulation of glucose disposal, the suppression of glucose production, and the suppression of lipolysis, respectively. Results: Eight subjects had normal glucose tolerance (BMI 35.1⫾2.4, and 7 had type-2 diabetes (BMI 39.9⫾5.6). Liposuction decreased the volume of subcutaneous abdominal adipose tissue by 44% in subjects with normal glucose tolerance and 28% in those with diabetes. The normal oral glucose tolerance group lost 9.1⫾3.7 kg of fat (18⫾3% decrease in total fat; p⫽0.002), and those with type-2 diabetes lost 10.5⫾3.3 kg of fat (19⫾2% decrease in total fat; p ⬍0.001). Liposuction did not significantly alter the insulin sensitivity of muscle, liver, or adipose tissue; it did not significantly alter plasma concentrations of C-reactive
Soluble CD40 Ligand, Soluble P-Selectin, Interleukin-6, and Tissue Factor in Diabetes Mellitus. Relationships to Cardiovascular Disease and Risk Factor Intervention Lim H, Blann A, Lip G. Circulation 2004;109:2524 – 8.
ACC CURRENT JOURNAL REVIEW Aug 2004
19