METABOLISM

Quickly Digested Carbs Tied to Fatty Liver Disease

High-glycemic Foods May Fuel Growth of Disorder Among Children, Mouse Study Suggests

Mice who nibbled food high in quickly burned carbohydrates had twice as much fat in their livers—and on their bodies—as mice who munched on more slowly digested carbs, a new study finds.

Graham Ramsay

A mouse study implicating high-glycemic carbohydrates in fatty liver disease has prompted author David Ludwig and his colleagues to launch a clinical trial of a low-glycemic diet in overweight and obese kids with fatty livers.

Buoyed by the results in mice, senior author David Ludwig, chair of pediatric endocrinology at Children’s Hospital Boston, has launched a follow-up study in overweight and obese children with fatty livers. He and his colleagues at Children’s will test the effect of a diet rich in slowly absorbed carbohydrates, compared to a control diet recommended for children with fatty livers (see the study webiste).

“This is the first study to look at the glycemic load and fatty liver with an interventional design,” said Ludwig, HMS associate professor of pediatrics. “And it’s one of a few studies that links non-alcoholic liver disease to a specific dietary cause within prevailing normal ranges of diet.” The paper appears in the September Obesity.

Disease Prevalence
Non-alcoholic fatty liver disease appears to be on the rise since it was first documented in adults following intestinal bypass in the 1950s, in adults with diabetes in the 1970s, and in obese children in the 1980s. Physicians do not know much about the cause or course of pathology. It is likely a broad spectrum of diseases, said Michael Curry, medical director of liver transplantation at Beth Israel Deaconess Medical Center, who was not involved in the study. On the mild end, any fat in the liver is considered disease. In worse cases, the fatty liver is also significantly inflamed and damaged from scarring.

Thin people can have fatty livers, especially Asians, but the condition is more strongly associated with obesity, type 2 diabetes, and elevated blood lipids. Fatty liver disease affects about 3 percent of all children and 22 to 53 percent of obese children. It is now the most common cause of abnormal liver test results, affecting about 10 to 24 percent of all adults and two thirds of obese adults. There is no proven treatment, except for gradual weight loss.

“The numbers are staggering,” said Ludwig, founding director of the Optimal Weight for Life program, a pediatric obesity clinic at Children’s that prescribes a low-glycemic diet and other lifestyle changes (see Fall Bookshelf). “Fatty liver is classically associated with excess alcohol. It is now present in a substantial portion of overweight and obese kids. We hypothesize that a high-glycemic diet is a major cause.”

Getting a Grip on Glucose
The glycemic index was first invented 25 years ago as a meal planning tool to help people with diabetes avoid damaging surges in blood sugar from rapidly absorbed carbohydrates. Since then, studies have linked a high-glycemic diet to diabetes, high blood lipids, cardiovascular disease, obesity, and certain cancers in the general population.

“Rapid changes in blood sugar set into action a sequence of hormonal events that promote deposition of fat, increase hunger, place additional stress on the pancreas, and may cause insulin resistance in key tissues—ultimately resulting in a range of clinical problems linked to the glycemic load,” Ludwig said.

The glycemic load, calculated from the amount and glycemic index of food, describes how blood glucose changes after a meal. People used to refer to carbohydrates as simple and complex, but many starchy foods, such as baked potatoes and white bread, boost blood glucose as much or more than simple sugars. Whole-grain products with intact germ and bran typically have a moderate glycemic index, while refined cereals, milled to small, fast-digesting particles, have a high glycemic index.

“Glucose is at the center of our energy metabolism,” said Ludwig. “Our glucose-regulatory hormonal systems work quite well as long as we’re eating the kind of diet humans consumed through hundreds of thousands of years of evolution. The problem is that high-glycemic foods were never found in large amounts in nature.”

A recent cross-sectional observational study of Italians found twice the prevalence of fatty liver disease in people with three-day diet records showing the highest glycemic index, Ludwig said. Subgroup analysis showed this effect to be present only in individuals who were insulin resistant.

To try to further isolate the role of the glycemic load in fatty livers, Ludwig and his colleagues turned to an animal model to control for the myriad confounding factors intrinsic to human nutritional studies. The diets of the two groups of mice were identical in composition (68 percent carbs, 13 percent fat, 19 percent protein), calories, and micronutrients—all except for the kind of carbohydrates.

After 18 weeks, the eight mice eating rapidly absorbed carbs had twice the lipids in the liver (21 percent compared to 10 percent) and twice the body fat (12 percent compared to 6 percent) as the seven mice on the slow-absorbing carb regimen, although both groups ended the study at the same body weight.

Ludwig’s mouse study “makes it so clear that the rate of digestion and absorption of carbohydrate (and downstream effects on postprandial glycemia and insulinemia) are influencing the development of this ‘new disease,’ non-alcoholic fatty liver,” Jennie Brand-Miller, professor of human nutrition at the University of Sydney, wrote in an e-mail. “It means we have a new mechanism (postprandial glycemia and insulinemia) and a new avenue for intervention—by choosing nutritious foods based on low glycemic-index carbohydrates.”

—Carol Cruzan Morton

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