A carefully controlled animal study provides clear evidence that a low-glycemic-index (low-GI) diet -- one whose carbohydrates are low in sugar or release sugar slowly -- can lead to weight loss, reduced body fat and reduction in risk factors for diabetes and cardiovascular disease.

"The study findings should give impetus to large-scale trials of low-GI diets in humans," said senior author David Ludwig, MD, PhD, director of the Optimal Weight for Life (OWL) obesity program at Children's Hospital Boston. His group's findings appear in the Lancet.

Many studies, including small studies in humans, have suggested that low-GI diets are beneficial, but due to study design, the observed benefits could have come from other aspects of the subjects' diets, such as fiber or overall caloric intake. For this reason, no major health agency or professional association references glycemic index in their dietary guidelines, Ludwig said.

In the current study, rats were fed tightly controlled diets with identical nutrients, except for the type of starch. Both diets were 69% carbohydrates, but 11 rats were randomly assigned to a high-GI starch and 10 to a low-GI starch. Food portions were controlled to maintain the same average body weight in the two groups.

At follow-up, the high-GI group had 71% more body fat and 8% less lean body mass than the low-GI group, despite very similar body weights. The fat in the high-GI group was concentrated in the trunk area, conferring "the apple shape as opposed to the pear shape," Ludwig said. (Having an apple shape is a known risk factor for cardiovascular disease in humans.)

The high-GI group also had significantly greater increases in blood glucose and insulin levels on an oral glucose tolerance test, and far more abnormalities in the pancreatic islet cells that make insulin, all changes that occur in diabetes. Finally, the high-GI group had blood triglyceride levels nearly three times that of the low-GI group, a risk factor for cardiovascular disease.

In a further experiment, rats were randomly assigned to one of the two diets and, at week seven, were crossed over to the alternate diet for another three weeks. Rats that switched from a low- to high-GI diet showed greater increases in blood glucose and insulin than rats that were switched from high- to low-GI. Finally, 24 mice were randomly assigned to the low- or high-GI diet. At week nine, the high-GI group had 93% more body fat than mice on the low-GI diet.

"What the study shows is that glycemic index is an independent factor that can have dramatic effects on the major chronic diseases plaguing developed nations -- obesity, diabetes and heart disease," said Ludwig. "This is the first study with hard endpoints that can definitively identify glycemic index as the active dietary factor."

Unlike the popular Atkins diet, which seeks to minimize carbohydrate intake, the low-GI diet makes distinctions among carbs. It avoids high-glycemic-index foods, such as white bread, refined breakfast cereals, and concentrated sugars, which are rapidly digested and raise blood glucose and insulin to high levels. Instead, it emphasizes carbohydrates that release sugar more slowly, including whole grains, most fruits, vegetables, nuts and legumes.

"The Atkins diet tries to get rid of all carbohydrates, which we think is excessively restrictive," said Ludwig. "You don't have to go to this extreme if you pay attention to the glycemic index and choose low-GI carbs."