original article The new england journal of medicine n engl j med 348;21 www.nejm.org may 22, 2003 2074 A Low-Carbohydrate as Comparedwith a Low-Fat Diet in Severe Obesity Frederick F. Samaha, M.D., Nayyar Iqbal, M.D., Prakash Seshadri, M.D., Kathryn L. Chicano, C.R.N.P., Denise A. Daily, R.D., Joyce McGrory, C.R.N.P., Terrence Williams, B.S., Monica Williams, B.S., Edward J. Gracely, Ph.D., and Linda Stern, M.D. From the Philadelphia Veterans Affairs Med-ical Center (F.F.S., N.I., K.L.C., D.A.D., J.M.,T.W., M.W., L.S.); the Department of Med-icine, Division of Cardiology (F.F.S.), andthe Department of Medicine, Division ofEndocrinology (N.I., P.S.), University ofPennsylvania Medical Center; and the De-partment of Family, Community, and Pre-ventive Medicine, Drexel University Collegeof Medicine (E.J.G.) — all in Philadelphia.Address reprint requests to Dr. Samaha atCardiology 8th Fl., MC 111C, University andWoodland Ave., Philadelphia, PA 19104, orat [email protected] Engl J Med 2003;348:2074-81. Copyright © 2003 Massachusetts Medical Society. background The effects of a carbohydrate-restricted diet on weight loss and risk factors for athero-sclerosis have been incompletely assessed. methods We randomly assigned 132 severely obese subjects (including 77 blacks and 23 wom-en) with a mean body-mass index of 43 and a high prevalence of diabetes (39 percent)or the metabolic syndrome (43 percent) to a carbohydrate-restricted (low-carbohydrate)diet or a calorie- and fat-restricted (low-fat) diet. results Seventy-nine subjects completed the six-month study. An analysis including all sub-jects, with the last observation carried forward for those who dropped out, showed thatsubjects on the low-carbohydrate diet lost more weight than those on the low-fat diet(mean [ ± SD], –5.8 ± 8.6 kg vs. –1.9 ± 4.2 kg; P=0.002) and had greater decreases in tri-glyceride levels (mean, –20 ± 43 percent vs. –4 ± 31 percent; P=0.001), irrespective ofthe use or nonuse of hypoglycemic or lipid-lowering medications. Insulin sensitivity,measured only in subjects without diabetes, also improved more among subjects on thelow-carbohydrate diet (6 ± 9 percent vs. –3 ± 8 percent, P=0.01). The amount of weightlost (P<0.001) and assignment to the low-carbohydrate diet (P=0.01) were independ-ent predictors of improvement in triglyceride levels and insulin sensitivity. conclusions Severely obese subjects with a high prevalence of diabetes or the metabolic syndromelost more weight during six months on a carbohydrate-restricted diet than on a calorie-and fat-restricted diet, with a relative improvement in insulin sensitivity and triglyceridelevels, even after adjustment for the amount of weight lost. This finding should be in-terpreted with caution, given the small magnitude of overall and between-group differ-ences in weight loss in these markedly obese subjects and the short duration of thestudy. Future studies evaluating long-term cardiovascular outcomes are needed beforea carbohydrate-restricted diet can be endorsed.abstractCopyright © 2003 Massachusetts Medical Society. All rights reserved. Downloaded from www.nejm.org at LIBRARIES OF THE UNIV OF COLORADO on March 4, 2007 .n engl j med 348;21 www.nejm.org may 22, 2003 a low-carbohydrate as compared with a low-fat diet in severe obesity 2075he differences in health bene- fits between a carbohydrate-restricted dietand a calorie- and fat-restricted diet areof considerable public interest. However, there isconcern that a carbohydrate-restricted diet will ad-versely affect serum lipid concentrations. 1 Previ-ous studies demonstrating that healthy volunteersfollowing a low-carbohydrate diet can lose weighthave involved few subjects, and few used a compar-ison group that followed consensus guidelines forweight loss. 2,3 The reported effects of a carbohy-drate-restricted diet on risk factors for atheroscle-rosis have varied. 2-4 We performed a study designedto test the hypothesis that severely obese subjectswith a high prevalence of diabetes or the metabolicsyndrome would have a greater weight loss, withoutdetrimental effects on risk factors for atherosclero-sis, while on a carbohydrate-restricted (low-carbo-hydrate) diet than on a calorie- and fat-restricted(low-fat) diet. subjects The study was approved by the institutional reviewboard at the Philadelphia Veterans Affairs MedicalCenter, and an approved consent form was signedby each subject. Inclusion criteria were an age of atleast 18 years and a body-mass index (the weight inkilograms divided by the square of the height inmeters) of at least 35. Exclusion criteria were a se-rum creatinine level of more than 1.5 mg per decili-ter (132.6 µmol per liter); hepatic disease; severe,life-limiting medical illness; inability of diabeticsubjects to monitor their own glucose levels; activeparticipation in a dietary program; or use of weight-loss medications. During an enrollment period thatlasted from May to November 2001, 132 subjectsfrom the Philadelphia Veterans Affairs Medical Cen-ter were randomly assigned to either the low-car-bohydrate diet or the low-fat diet, with use of a pre-established algorithm generated from a random setof numbers. We used stratified randomization, withblocking within strata, to ensure that each groupwould contain approximately equal numbers ofwomen, subjects with diabetes, and severely obesesubjects (body-mass index, 40 or higher). The studywas not blinded. study design The two diet groups attended separate two-hourgroup-teaching sessions each week for four weeks,followed by monthly one-hour sessions for fiveadditional months; all sessions were led by expertsin nutritional counseling. Subjects received a diet-overview handout, instructional nutrition labels,sample menus and recipes, and a book on countingcalories and carbohydrates. 5 No specific exerciseprogram was recommended. The subjects assignedto the low-carbohydrate diet were instructed to re-strict carbohydrate intake to 30 g per day or less. 6 No instruction on restricting total fat intake wasprovided. Vegetables and fruits with high ratios offiber to carbohydrate were recommended. 6 Thesubjects assigned to the low-fat diet received in-struction in accordance with the obesity-manage-ment guidelines of the National Heart, Lung, andBlood Institute, 7 including caloric restriction suf-ficient to create a deficit of 500 calories per day,with 30 percent or less of total calories derivedfrom fat. data