Quick-burning Carbs May Cause Fatty Liver: Low-glycemic Diet Protected Mice

If confirmed in humans, the findings suggest that fatty liver disease -- on the upsurge among Americans as a byproduct of the obesity epidemic -- may be preventable and possibly treatable through dietary changes.

The researchers, led by David Ludwig, MD, PhD, director of the Optimal Weight for Life program at Children's Hospital Boston,  fed mice either a high- or a low-glycemic index diet. High-glycemic index foods, including white bread, white rice, most prepared breakfast cereals and concentrated sugar, raise blood sugar quickly. Low-glycemic index foods, like most vegetables, fruits, beans and unprocessed grains, raise blood sugar slowly.

On the high-glycemic index diet, mice ate a type of cornstarch that is digested quickly whereas on the low-glycemic index diet, mice ate a type of cornstarch that is digested slowly. The diets had equal amounts of total calories, fat, protein, and carbohydrate, and the mice were otherwise treated identically.

After six months, the mice weighed the same. However, mice on the low-glycemic index diet were lean, with normal amounts of fat in throughout their bodies. Mice on the high-glycemic index diet had twice the normal amount of fat in their bodies, blood and livers.

When sugar melts out of high-glycemic index food, Ludwig explains, it drives up production of insulin, which tells the body to make and store fat. Nowhere is this message felt more strongly than in the liver, because the pancreas, which makes insulin, dumps the hormone directly into the liver, where concentrations can be many times higher than in the rest of the body. Fat buildup in the liver, or fatty liver, is usually symptomless, but it increases the risk for liver inflammation, which can progress to hepatitis and, in some cases, liver failure.

Fatty liver is becoming more common in Americans, especially in children, says Ludwig. Many cases in adults can be explained by alcoholism, but not the pediatric cases. Where just one case of fatty liver was reported in children in 1980, now between 1 in 4 and 1 in 2 overweight American children are estimated to have the condition. As these millions of children age, some will progress to full-blown liver disease.

"This is a silent but dangerous epidemic," says Ludwig. "Just as type 2 diabetes exploded into our consciousness in the 1990s, so we think fatty liver will in the coming decade."

A previous study found that Italians who ate higher-glycemic index diets had fattier livers, but the study wasn't tightly controlled. The new study makes clear that the type of carbohydrate can cause fatty liver in animals, independent of other elements of diet or lifestyle.

"Our experiment creates a very strong argument that a high-glycemic index diet causes, and a low-glycemic index diet prevents, fatty liver in humans," says Ludwig.

Ludwig and colleagues now hope to confirm this in a just-launched clinical trial -- and to show that a low-glycemic index diet can reverse fatty liver in overweight children. The children, aged 8 to 17, will be randomized to either the low-glycemic diet or a low-fat diet.

Low-fat diets are currently the standard treatment, Ludwig says, but many children with fatty liver don't respond to them. "We think it is a misconception that the fat you're eating goes into the liver," he says.

Ludwig hypothesizes that obesity, sedentary lifestyles and increased consumption of refined carbohydrates are "synergistically" fueling a fatty liver epidemic in children. Ironically, low-fat diets have only made matters worse, replacing fat with sugar or starchy foods that actually increase fat deposition in the body.

"Two low-fat Twinkies, billed as a health food, contain the same amount of sugar as an oral glucose tolerance test -- a test used to determine how much sugar someone can digest," Ludwig says. He notes that the French delicacy pate de fois gras -- the fatty liver of a duck or goose -- is produced by over-feeding the animals with high-glycemic index grains.

The mouse study was funded by the National Institutes of Diabetes and Digestive Kidney Diseases and the Charles H. Hood Foundation.

To enroll in the clinical trial, which is currently recruiting patients, subjects must be 8 to 17 years old, overweight, and have had an abnormal liver test or been told they might have fat in their liver. Interested families should contact Marta Ramon Krauel, MD, at Children's Hospital Boston, 617-355-2003.

The study appears in the September issue of the journal Obesity.