A new US study on mice suggests that a diet rich in carbohydrates with a high glycemic index (GI) not only expands waistlines but may also lead to fatty liver, a condition that results in liver failure and death.

The study is published in the September issue of the journal Obesity and is the work of Dr David Ludwig, director of the Optimal Weight for Life program at Children's Hospital Boston, and colleagues.

Fatty liver is increasing in line with rising rates of obesity among Americans. The researchers hope to confirm their findings in a newly launched clinical trial with overweight children and to show that the trend can be reversed through changes in diet.

Fatty liver is becoming especially common among children, said Ludwig. Although many adult cases can be caused by alcoholism, that is not so in children, where between 1 in 4 and 1 in 2 overweight American children are thought to be affected by non-alcoholic fatty liver disease (NAFLD).

That means millions of children are at elevated risk of getting full blown liver disease in adulthood, said Ludwig, who called it a "silent but dangerous epidemic".

"Just as type 2 diabetes exploded into our consciousness in the 1990s, so we think fatty liver will in the coming decade," he added.

High GI foods include white bread, white rice, most processed grains such as breakfast cereals, and concentrated sugar. They raise blood sugar quickly because the starch is broken down into sugar quickly. These are also called rapidly absorbed carbohydrates (RAC).

Ludwig said the French delicacy "pâté de foie gras" (literally "pâté of fatty liver") was made by feeding ducks and geese on a diet rich in high GI grains.

Low GI foods include most vegetables, fruits, beans and unprocessed grains. The starch in them is digested slowly and therefore eating them raises blood sugar slowly. This is also called slowly absorbed carbohydrate (SAC).

Ludwig and colleagues carried out the study using two groups of laboratory mice. One group of mice were fed a high GI diet based on a type of cornstarch that is digested quickly, and the other a low GI diet, based on a more slowly digested cornstarch.

Both groups of mice consumed the same total number of calories, fat, protein and carbohydrate. The only difference was the GI value of the carbohydrate.

Both groups of mice weighed the same after 6 months. But there was a difference in fat deposits in the two groups.

The mice on the low GI diet had normal amounts of fat in their bodies, they were "lean", whereas the mice on the high GI diet had double the amount of fat throughout their bodies, in their blood and in their livers.

Ludwig explained that sugar released from high GI food ramps up insulin production, which tells the body to make and store fat. This is a burden to the liver because the pancreas produces the insulin and sends it straight to the liver, resulting in liver insulin levels way above the rest of the body.

Fatty liver usually has no symptoms, but it raises the risk of liver inflammation, which can lead to hepatitis, which is sometimes fatal.

A study on people living in Italy who ate high GI food showed they had fattier livers, but the study wasn't tightly controlled, whereas this study on mice shows that high GI carbohydrates can cause fatty liver in animals, regardless of other diet and lifestyle factors.

"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," said Ludwig.

He and his team have just lauched a clinical trial involving overweight children aged from 8 to 17 who will be randomized to either a high GI or a low GI diet. They hope to show that a low GI diet can reverse fatty liver in overweight children.

Ludwig explained that the current standard treatment for being overweight involves putting children on low fat diets, but that doesn't work for many children with fatty liver:

"We think it's a misconception that the fat you're eating goes into the liver," he said.

Ludwig has a theory that obesity, sedentary lifestyles and eating too many refined carbohydrates are "synergistically" driving a fatty liver epidemic in children.

The irony, said Ludwig, is that low fat diets only make things worse, because they replace fat with sugar and starch (mostly high GI) that increases fat deposits 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," said Ludwig.

"Hepatic Steatosis and Increased Adiposity in Mice Consuming Rapidly vs. Slowly Absorbed Carbohydrate."
Scribner, Kelly B., Pawlak, Dorota B., Ludwig, David S.
Obesity 2007 15: 2190-2199.

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Written by: Catharine Paddock