Boston Children’s Hospital

BCH receives grant to fund revolutionary obesity study

This study will determine whether reduced calorie intake or a change in the proportions of fat and carbohydrates is the most effective strategy for maintaining a reduced body weight.

Preventing obesity and maintaining a healthy weight requires an understanding of the dietary factors that drive excess fat accumulation. Is it too many calories consumed and too few expended, or does the macronutrient composition of the diet (the proportion and type of carbohydrates, fat and protein) have an effect on fat storage, independent of caloric content? Individuals who have lost significant weight are predisposed to gain it back and represent ideal subjects to study this question of whether a calorie is a calorie. By varying the macronutrient content of the diet consumed by these “weight-reduced” subjects, researchers can study how the carbohydrates, protein, and fat in the diet might either drive weight gain or prevent it. In this trial, 150 overweight and obese college students, faculty, and staff will be fed all their meals in a specially dedicated part of the University hall and monitored while they eat. They’ll first lose 10 to 12 percent of their weight on a diet that restricts all calories equally. They’ll then be randomly assigned to follow one of three diets – either a carbohydrate-restricted diet, high in fat; a fat-restricted diet, high in carbohydrate; or a low-glycemic index diet, in which the carbohydrates consumed are slowly digested and rich in fiber. The researchers will weigh the participants daily and adjust the caloric content of their assigned diets as necessary to try to maintain the participants at a stable weight. For the last two weeks of the study, participants will be allowed to eat as much as they want of their assigned diets to generate data on the hunger and satiety responses to these diets. By assessing the participants’ energy expenditure on the assigned diets and how many calories they have to eat to maintain their reduced weights, the researchers will determine whether the macronutrients in the diet play a significant role in regulating weight and body fat mass. The results should point the way toward the most effective nutritional strategy for maintaining a healthy weight and preventing excess fat accumulation, particularly in people who were previously overweight.

The impact of macronutrient composition on energy expenditure during maintenance of weight loss

Current research and public health policy on obesity is largely based on the hypothesis that the fundamental cause of the condition is an energy imbalance between calories consumed and expended. By this hypothesis, the interaction between diet and body fat is determined by the caloric content of the foods consumed, while the macronutrient content of the diet (the proportion and type of carbohydrates, fats and protein) has no meaningful effect. This is often summed up by the assertion that a “calorie-is-a-calorie,” shorthand for the hypothesis that a calorie’s worth of protein has an equivalent effect on the accumulation and storage of fat in the human body (on “adiposity”) as does a calorie of carbohydrate or a calorie of fat. An alternative hypothesis is that the macronutrient composition of the diet influences adiposity through its effect on the hormones that regulate uptake of fat (technically “fatty acids”) by fat cells and their subsequent mobilization and use for fuel (that is, oxidation). This study is one of two studies currently funded by Nutrition Science Initiative (NuSI) that were designed to test this calorie-is-a-calorie hypothesis – in this case, in the context of weight maintenance. It expands on previous work by Ludwig et al. reported in JAMA in 2012 – “Effects of Dietary Composition on Energy Expenditure During Weight-Loss Maintenance.” In this previous study using free-living subjects, Ludwig et al. reported that participants maintaining a significant weight loss experienced a greater metabolic compensation (a greater decrease in their energy expenditure) when they were eating a fat-restricted diet than when they were eating either a low-glycemic index diet or a very low-carbohydrate diet. This result implied that the macronutrient content of the diet – the carbohydrates, in particular – has an effect on the hormones that regulate energy expenditure, fat metabolism, and storage that is independent of caloric content. This study is designed to closely monitor the participant’s food intake and weight to isolate the effect of diet composition from weight loss. This study uses a larger study population, a significantly longer intervention period, and a direct comparison of study groups, rather than a crossover design, which should provide more conclusive results. By providing all food for the participants and closely monitoring their intake, the precise effects of dietary variables can be isolated and tested, without requiring assumptions about what participants actually ate. By increasing the frequency of testing and the number of tests performed, a more complete picture of the metabolic effects of these diets, and the differences between them, will be observed. This study will provide insight into how the macronutrient composition of the diet influences metabolic compensation to weight loss and about the ideal dietary composition for maintaining a healthy weight and preventing the recurrence of obesity. Condition: Overweight and obesity Intervention: Low-fat, extremely low-carbohydrate, and low-glycemic index diets

For more information on this study go to–Framingham State Food Study ((FS)2)


Boston Children’s Hospital Boston, Massachusetts, 02115
Framingham State University, Framingham, Massachusetts, 01702


David Ludwig, M.D., Ph.D. (Co-principal investigator)
Cara Ebbeling, Ph.D. (Co-principal investigator)


David Ludwig

David Ludwig, M.D., Ph.D. Boston Children’s Hospital, Harvard Medical School

David S. Ludwig is a Professor of Pediatrics at Harvard Medical School and a Professor of Nutrition at Harvard School of Public Health, as well as a practicing physician and researcher at Boston Children’s Hospital, one of the country’s oldest and largest multidisciplinary clinics for the care of overweight children. He also directs the New Balance Foundation Obesity Prevention Center at Boston Children’s Hospital and is Founding Director of the Optimal Weight for Life program at Boston Children’s Hospital. Dr. Ludwig received his M.D. and Ph.D. from Stanford University. Dr. Ludwig has received 16 years of continuous funding from the National Institutes of Health, totaling over $25 million in grants and has published an astonishing 42 articles in New England Journal of Medicine (NEJM), Journal of the American Medical Association (JAMA), and Lancet. He is a contributing writer at JAMA. Dr. Ludwig is a 2008 recipient of the E.V. McCollum Award of the American Society for Nutrition for outstanding clinical research. TIME magazine called Dr. Ludwig an “Obesity Warrior” for his efforts on behalf of overweight children.

Cara Ebbeling

Cara Ebbeling, Ph.D. Boston Children’s Hospital

Cara Ebbeling is the Associate Director of the New Balance Foundation Obesity Prevention Center and a member of the Research Faculty Council. Dr. Ebbeling arrived at Boston Children’s Hospital in 1999 to complete advanced studies in obesity research. Dr. Ebbeling is an internationally recognized expert in interventional nutrition research design and quality control. She has directed numerous behavioral and feeding studies of diet in the treatment of obesity, including a landmark study published in Journal of the American Medical Association in 2012 demonstrating novel metabolic effects of carbohydrate-modified diets. She has published more than 60 scientific articles, topic reviews and editorials, many of which have been highly cited by peers. Dr. Ebbeling has given scores of invited presentations at national and international professional meetings. She served as an Associate Editor for the journal Obesity and is a fellow of The Obesity Society and the American College of Sports Medicine. Dr. Ebbeling received a M.S. in exercise science from the University of Massachusetts in 1988 and a Ph.D. in nutrition from the University of Connecticut in 1997.