Diets rich in rapidly-digested carbohydrates not only expand waistlines, but may also cause fatty liver, a condition that can lead to liver failure and death, finds a new study in 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 study appears in the September issue of the journal Obesity.
The researchers, led by David Ludwig, MD, PhD, director of the Optimal Weight for Life program at Children's Hospital Boston (http://www.
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, author of Ending the Food Fight: Guide Your Child to a Healthy Weight in a Fast Food/Fake Food World (http://www.
"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 (http://www2.
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 or email@example.com. For further information, see www.optimalweightforlife.com.
Children's Hospital Boston is home to the world's largest research enterprise based at a pediatric medical center, where its discoveries have benefited both children and adults since 1869. More than 500 scientists, including eight members of the National Academy of Sciences, 11 members of the Institute of Medicine and 10 members of the Howard Hughes Medical Institute comprise Children's research community. Founded as a 20-bed hospital for children, Children's Hospital Boston today is a 377-bed comprehensive center for pediatric and adolescent health care grounded in the values of excellence in patient care and sensitivity to the complex needs and diversity of children and families. Children's also is the primary pediatric teaching affiliate of Harvard Medical School. For more information about the hospital and its research visit: www.childrenshospital.org/newsroom.