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Carbohydrates on trial
A study just launched at The Rockefeller University Hospital will determine whether high fat diets truly work better than high carb diets
When the Atkins diet first became a national obsession about two years ago, millions of Americans became carb counters. One American, Rockefeller’s Jan L. Breslow, had a different reaction.
After reading a July 2002 New York Times Magazine cover story on the diet, Breslow began digging through medical literature, looking for evidence that the latest diet craze would work any better than any other low-calorie diet. “I found that there’s hardly any good, carefully controlled data out there,” says Breslow, Frederick Henry Leonhardt Professor and head of the Laboratory of Biochemical Genetics and Metabolism at Rockefeller.
That won’t be the case for long. Breslow will soon enroll his first volunteer in a rigorous study designed to determine which of two low-calorie diets — one high in fat, the other high in carbohydrates — best reduces abdominal fat in overweight and obese people. Subjects who volunteer for the study will lose, on average, 20 pounds, and scientists will gain a better understanding of the effects of these diets on body composition, risk factors for heart disease and stroke, and overall health.
The Atkins craze has led huge numbers of Americans — Dr. Atkins’ New Diet Revolution has sold over 15 million copies — to abandon low-fat, high-carb diets, which are the basis of the food pyramid recommended by the U.S. Department of Agriculture, the American Heart Association, the American Cancer Society and many other health organizations, in favor of high fat diets. The author of the New York Times Magazine article, science writer Gary Taubes, agreed with cardiologist Robert C. Atkins, the late inventor of the diet, that carbohydrates — rice, grains, pasta and sugars — and not fat are responsible for obesity.
To find out if that’s true, Breslow and Research Nurse Practitioner Jill Culiner of The Rockefeller University Hospital will enroll 50 obese or overweight subjects over the next five years, with the expectation that 40 of them will complete the protocol. Subjects will live overnight at the hospital for 16 weeks and will eat precise meals prepared by the hospital’s bionutritionists Janet Maturi and Diane Meehan.
For the first three weeks of the study, they will eat an average American diet — containing approximately 34 percent fat — to determine the average number of calories they need to maintain their then-current weight. They will spend the next 10 weeks on either a high fat or a high carbohydrate diet. Both diets will represent a 40 percent calorie reduction in order to induce weight loss. In the final three weeks, the subjects will continue on the diets, but calories will be added as needed to maintain their new weights.
The study will be the first to comprehensively record a person’s changes in body composition and cardiovascular risk factors over the entire course of a diet, from weight stabilization through loss and maintenance of new weight. Each subject’s weight and blood pressure will be checked daily. Periodic measurements will be made of several blood components, including insulin, glucose, lipoproteins, which transport cholesterol in the blood, and leptin, the “obesity hormone” discovered 10 years ago by Rockefeller’s Jeffrey Friedman. Body composition before, during and after weight loss will be measured by magnetic resonance imaging at the Obesity Center at St. Luke’s Hospital by Steve Heymsfield and Stanley Heschka.
“Most of the other inpatient diet studies in the literature are shorter, and only a few measurements are taken, usually when people are starving,” Breslow says.
Recently, two outpatient studies published in the journal Annals of Internal Medicine provided evidence that the low carbohydrate Atkins diet is more effective than a low fat diet during a six-month period, although the weight-loss results even out for both diets over the course of a year.
“The focus of the two new studies and many others in the literature is outpatient adherence to the two diets,” says Breslow. “This involves many complex behavioral issues and is epitomized by the question ‘What do you do at 11 p.m. when standing in front of the refrigerator?’”
Although behavioral aspects of dieting are important, Breslow explains, behavioral studies depend on many factors, such as education, physician follow up, availability of certain foods, family situation and economic status, among others. “To adequately address these issues would require a totally different study design than we have pursued and is really not our expertise,” says Breslow. “The Rockefeller Hospital excels in carefully monitored metabolic studies.” (See “Precision nutrition,” right.)
Breslow is primarily interested in evaluating how much visceral fat each patient loses during the course of the study. Visceral fat, which accumulates around the organs in the abdomen, is much more strongly associated with insulin resistance, diabetes, heart disease and stroke, hypertension and gout than total body fat or subcutaneous fat.
The study also should help answer some myths regarding high fat diets. For example, it’s commonly accepted, without any scientific evidence, that the low blood levels of insulin that accompany a high fat, low carbohydrate diet have special metabolic effects that promote weight loss. “But the truth is, we really don’t know,” says Breslow. “It’s never been studied.”
Because each study participant can expect to lose about two pounds a week on either diet, for a total loss of 20 pounds by the end of the inpatient period, Breslow calls it a therapeutic study. “The subjects can view their participation as a good start toward maintaining a healthy weight,” says Culiner. “They will learn what good portion sizes are and how to eat healthfully. And because the meals are based on natural foods, they will learn the best kinds of food to eat.”

Precision nutrition
Why The Rockefeller University Hospital is uniquely qualified to conduct dietary studies
Jan L. Breslow isn’t the first Rockefeller scientist to take on obesity. The Rockefeller University Hospital has been famous since the 1950s for research that requires special diets to study metabolism or nutrients.
They’ve gotten quite good at it.
“This type of protocol — studying a small number of people with tightly controlled variables — is the hospital’s forte,” says Breslow.
While other research hospitals are weighed down with the beaurocracies associated with routine patient care, Rockefeller is free to focus on research studies initiated by scientists.
The bionutrition department, for example, will be critical to Breslow’s research. Instead of preparing thousands of daily meals for patients with diverse needs, as might be the case elsewhere, Rockefeller’s bionutrition team will devote its resources to making precise, personalized meals for just a few patients at a time. A staff of 11 will produce 24 different meals for three diets. Each portion of every food — bacon for a high fat, high protein diet, spaghetti for a high-carb diet, etc. — will be weighed to one-tenth of a gram before it is packaged. The patients will receive customized, color-coded servings based on their specific calorie requirements.
Though this is work the hospital staff have been doing for half a century, this study’s five-year timeframe presented a particular challenge. Because the nutrient content of fruits and vegetables can vary widely depending on where they were grown and when they were harvested, the staff will purchase large quantities of food, then measure and freeze individual portions. In this way, the scientists can be sure that the first volunteers to enroll in the study eat exactly the same foods as the last ones.
The country’s only free-standing research hospital outside of the National Institutes of Health, The Rockefeller University Hospital this year completed its first major modernization in decades. Upgraded laboratory and patient care facilities, strengthened support services and new initiatives to ensure high quality care and high quality science have made the hospital one of the nation’s premier facilities for conducting clinical research.

July 16, 2004



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