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Do Macronutrients Affect Weight Loss?

A review of an important, recently published scientific article selected by The North American Menopause Society (NAMS) and published in their newsletter.

Sacks FM, Bray GA, Carey VJ, et al. Comparison of weight-loss diets with different compositions of fat, protein, and carbohydrates. N Engl J Med 2009;360:859-873. Level of evidence: I.

Abstract copyright © 2009 Massachusetts Medical Society.
All rights reserved. Used with permission.


BACKGROUND: The possible advantage for weight loss of a diet that emphasizes protein, fat,or carbohydrates has not been established, and there are few studies that extend beyond 1 year.

METHODS: We randomly assigned 811 overweight adults to one of four diets; the targeted percentages of energy derived from fat,protein, and carbohydrates in the four diets were 20, 15, and 65%; 20, 25, and 55%; 40, 15, and 45%; and 40, 25, and 35%. The diets consisted of similar foods and met guidelines for cardiovascular health. The participants were offered group and individual instructional sessions for 2 years. The primary outcome was the change in body weight after 2 years in two-by-two factorial comparisons of low fat versus high fat and average protein versus high protein and in the comparison of highest and lowest carbohydrate content.

RESULTS: At 6 months,participants assigned to each diet had lost an average of 6 kg, which represented 7% of their initial weight; they began to regain weight after 12 months. By 2 years, weight loss remained similar in those who were assigned to a diet with 15% protein and those assigned to a diet with 25% protein (3.0 and 3.6 kg, respectively); in those assigned to a diet with 20% fat and those assigned to a diet with 40% fat (3.3 kg for both groups); and in those assigned to a diet with 65% carbohydrates and those assigned to a diet with 35% carbohydrates (2.9 and 3.4 kg,respectively) (P>0.20 for all comparisons). Among the 80% of participants who completed the trial, the average weight loss was 4 kg; 14 to 15% of the participants had a reduction of at least 10% of their initial body weight. Satiety, hunger, satisfaction with the diet, and attendance at group sessions were similar for all diets; attendance was strongly associated with weight loss (0.2 kg per session attended). The diets improved lipid-related risk factors and fasting insulin levels.

CONCLUSIONS: Reduced-calorie diets result in clinically meaningful weight loss regardless of which macronutrients they emphasize.



The primary conclusion of this study is that for weight loss, it’s all about calories. The authors set out to determine if macronutrient intake emphasizing either fat,protein, or carbohydrates would affect overall weight loss. The study is unique in that a substantial number of subjects were recruited,recidivism was low, and participants were followed for 2 years (longer than many previous studies). Participants received extensive education and behavioral modification in the form of weekly individual and group sessions. Despite this counseling, it is notable that target goals for macronutrient intake were not reached, suggesting that sustained adherence to a specific macronutrient regimen is not feasible and, more important for the purpose of weight loss, not necessary. Regardless of type of dietary intervention,participants reported a similar degree of fullness,hunger, and satisfaction with their diet—and had equivalent weight loss at 2 years. Other recent weight-loss studies have resulted in a lack of long-term benefit from a particular macronutrient composition¹ or for a particular popular dietary regimen.²

However, macronutrient composition was significant in the magnitude of cardiovascular risk reduction. All diets were associated with similar reductions in triglyceride and blood pressure. The high-protein diets were associated with the greatest reduction in insulin resistance,while higher-fat diets resulted in the most significant improvements in high-density lipoprotein levels. The effect on cardiovascular risk factors is best determined when weight is held constant, as modest weight loss itself will result in improvement of cardiovascular risk. The OmniHeart study³ did just that, showing that when comparing eucaloric diets, those predominant in protein and monounsaturated fat were superior to those predominant in carbohydrate (with an overall reduction in the Framingham risk score of 30%, a finding that correlates to the results of Sacks et al).

Finally, Sacks et al highlighted that adherence to behavioral modification is of primary importance in inducing weight loss. Subjects’ attendance at behavioral support groups strongly predicted weight loss at 2 years and was similar among all diet groups, reminding us that when prescribing caloric restriction, it is not so much the macronutrient composition that is important but rather the implementation of behavioral and total lifestyle modification.


Adrienne Youdim, MD
Director, Medical Weight Loss
Cedars-Sinai Center for Weight Loss
Assistant Clinical Professor
UCLA School of Medicine
Los Angeles, CA


1. Foster GD, Wyatt HR, Hill JO, et al. A randomized trial of a low-carbohydrate diet for obesity. N Engl J Med
2. Dansinger ML, Gleason JA, Griffith JL, Selker HP, Schaefer EJ. Comparison of the Atkins, Ornish, Weight Watchers, and Zone Diets for weight loss and heart disease risk reduction. JAMA 2005;293:43-53.
3. Appel LJ, Sacks FM, Carey VJ, et al, for the OmniHeart Collaborative Research Group. Effect of protein, monounsaturated fat, and carbohydrate intake on blood pressure and serum lipids: results of the OmniHeart randomized trial. JAMA 2005;294:2455-2464.

Dr. Adrienne Youdim

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