NuSI supports research that tests fundamental assumptions about the cause of obesity and related metabolic disorders.  We believe such critical research is necessary to advance public health policy and clinical practice for the prevention and treatment of obesity beyond the status quo of the last 50 years.

The assumption that obesity is caused by an energy imbalance – consuming more calories than we expend – has guided basic and clinical research for decades.  The same assumption has informed public health guidelines and medical treatments typically used to prevent or reverse obesity, all of which emphasize reducing the number of calories consumed or increasing expenditure.  Reduction of calorie intake is also the standard dietary advice for treating diseases associated with obesity such as type 2 diabetes, heart disease, and nonalcoholic fatty liver disease.

The conventional wisdom treats the sources of calories – specifically, proteins, carbohydrates, and fats – as equivalent in their effect on fat storage and body weight; it’s only the number of calories, not the type of calories consumed that is important.  This assumption, often summarized as “a calorie is a calorie,” leaves no room for a weight control strategy based on changing the types of calories consumed. An alternative perspective argues that the type of calories is of primary importance with regard to weight control and metabolic disease because carbohydrate and fat have different effects on hormones and metabolic processes that control fat storage.  From this viewpoint, the ratio of dietary carbohydrate and fat, not their caloric value, is critical for weight gain and loss.

NuSI’s research seeks to understand whether the number of calories or the type of calories consumed causes obesity and related diseases and whether a focus on the amount or type of calories is the best strategy for prevention and treatment.  The trials NuSI has funded to date speak to this issue using different methodologies and study designs.  Three trials focus on obesity in adults and one on nonalcoholic fatty liver disease in children.

Sugar Restriction in Pediatric Nonalcoholic Fatty Liver Disease

Principal Investigators: Jeffrey Schwimmer (University of California, San Diego) and Miriam Vos (Emory University)

Nonalcoholic fatty liver disease, the most common form of liver disease, affects about 7 million children in the US. There is no approved drug for the disease, and, although treatment guidelines include modifications of diet, no consensus exists on the dietary trigger of the disease or what diet would best reverse or prevent it.

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Dietary carbohydrate and energy expenditure during weight loss maintenance

Principal Investigators: David Ludwig and Cara Ebbeling (Boston Children’s Hospital; Harvard Medical School)

Long-term maintenance of a reduced body weight is among the most difficult challenges in treating obesity. Dietary strategies that minimize accumulation of body fat and sustain or increase energy expenditure should prevent weight regain or facilitate further weight loss.

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Weight loss with a healthy low-fat vs healthy low-carbohydrate diet

Principal Investigator: Christopher Gardner (Stanford University)

In an earlier study, participants who were instructed to eat a low-carbohydrate diet lost more weight than those consuming a low-fat diet. In this trial, subjects were instructed to eat a “healthy” diet either low in fat or carbohydrate that maximized vegetable intake and minimized consumption of added sugars and refined flour.

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Dietary calories vs. composition and energy expenditure: a pilot study

Principal Investigators: Kevin Hall (National Institutes of Health, NIDDK), Rudolph Leibel (Columbia University Medical College), Eric Ravussin (Pennington Biomedical Research Center), Marc Reitman (National Institutes of Health, NIDDK), Michael Rosenbaum (Columbia University Medical College), Steven Smith (Translational Research Institute for Metabolism and Diabetes)

As a first step toward a rigorous test of the hypothesis that foods cause obesity only through the amount, but not type, of calories consumed, this preliminary or “pilot” study examined the effect of diets varying substantially in fat and carbohydrate on energy expenditure in participants confined to metabolic wards.

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