Three Weight-Loss Diets Yield Three Metabolic Effects

Major Finding: A very-low-carbohydrate diet produced the most favorable effects on components of the metabolic syndrome but also increased serum cortisol and CRP.

Data Source: The controlled feeding study involved 21 overweight and obese young adults who lost approximately 12% of their body weight on a low-calorie diet and then followed a series of weight-maintenance diets for 4 weeks each.

Disclosures: This study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases, the National Center for Research Resources, and the New Balance Foundation. No conflicts of interest were reported.

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How Little We Know

"These provocative results by Ebbeling et al. emphasize the current incomplete knowledge base regarding the importance of dietary macronutrients and energy expenditure, especially after weight loss," wrote Dr. George A. Bray.

It is difficult, however, to interpret the study’s findings when each maintenance diet was only followed for 1 month. And the authors found no differences among the groups in physical activity based on accelerometry, which is "an imperfect measure," so differences in exercise may well have influenced the results.

Dr. Bray is with Pennington Biomedical Research Center in Baton Rouge, La. He reported ties to Abbott Laboratories, Takeda Global Research Institute, Medifast, Herbalife, and Global Direction in Medicine. He also has received royalties for the "Handbook of Obesity." These remarks were taken from his editorial accompanying Dr. Ebbeling’s report (JAMA 2012;307:2641-42).



Three different diets designed to maintain a recent weight loss were found to exert markedly different metabolic effects independently of their energy content in obese and overweight young adults, according to a report in the June 27 issue of JAMA.

"The results of our study challenge the notion that a calorie is a calorie from a metabolic perspective," said Cara B. Ebbeling, Ph.D., of the New Balance Foundation Obesity Prevention Center, Children’s Hospital Boston, and her associates.

©Marc Dietrich/

Researchers took a close look at the effects of three weight-loss maintenance diets on energy, hormones and components of the metabolic syndrome. Each had markedly different metabolic effects. (Photo: )

The researchers performed a controlled feeding study to compare the effects of three weight-loss-maintenance diets on energy expenditure, hormones, and components of the metabolic syndrome. Their first step was to screen 681 men and women aged 18-40 years with a BMI of 27 or higher for participation in the study. Of these, only 32 potential subjects (17 men and 15 women) met entry criteria and agreed to the rigorous dietary restrictions of the study. Of these 32 subjects, 21 completed the study and were included in the data analysis.

During the run-in phase of the study, subjects followed a standard low-calorie diet that restricted energy intake to achieve a 12.5% decrease in body weight. Detailed assessments also were done to establish each subject’s energy requirements for stabilizing their weight at this reduced level.

After the subjects achieved a 10%-15% weight reduction, they each consumed one of the three isocaloric diets for 4 weeks, then switched to another of the diets for another 4 weeks, then to the third diet for a final 4 weeks in a three-way crossover design.

The three diets were the following: a low-fat diet with a high glycemic load and 20% of energy from protein, which reflected conventional recommendations to reduce fat, increase whole grain products, and include a variety of vegetables and fruits; a low-glycemic-index diet with moderate glycemic load and 20% of energy from protein, which replaced some grain products and starchy vegetables with other vegetables, legumes, and fruits; and a very-low-carbohydrate diet with a low glycemic load and 30% of energy from protein, which was modeled on the Atkins diet.

Body weight did not differ significantly among the three maintenance diets, nor did total physical activity or time spent performing moderate to vigorous-intensity activity. Subjects’ ratings of subjective hunger and well-being did not differ significantly among the diets, and blood pressure levels also did not differ.

Both resting energy expenditure and total energy expenditure decreased with all the diets, but the decrease was significantly greater with the low-fat diet. In addition, serum leptin levels were highest with the low-fat diet. These two findings suggest that people following the low-fat diet would be more likely to regain weight than those following the other diets, Dr. Ebbeling and her colleagues said (JAMA 2012;307:2627-34).

Moreover, the low-fat diet also had the most unfavorable effects on peripheral and hepatic insulin sensitivity, serum HDL cholesterol, triglycerides, and plasminogen activator inhibitor 1.

In contrast, the very-low-carbohydrate diet had the most favorable effects on these components of the metabolic syndrome and on energy expenditure.

The very-low-carbohydrate diet, however, produced higher C-reactive protein levels and higher cortisol excretion levels than the other diets, both of which signal physiological stress and chronic inflammation. In addition, "higher cortisol levels may promote adiposity, insulin resistance, and cardiovascular disease," the investigators wrote.

"These findings suggest that a strategy to reduce glycemic load rather than dietary fat may be advantageous for weight-loss maintenance and CVD prevention," they noted.

The chief limitation of this study is "the difficulty extrapolating findings from a feeding study to a more natural setting, in which individuals consume self-selected diets. In particular, the very-low-carbohydrate diet involved more severe carbohydrate restriction than would be feasible for many individuals over the long term," Dr. Ebbeling and her associates said.

This study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases, the National Center for Research Resources, and the New Balance Foundation. No other financial conflicts of interest were reported.

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