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What's the connection between fructose and fatty liver disease?

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Dietary fructose causes liver damage in an animal model, says a recent study, "Dietary fructose induces endotoxemia and hepatic injury in calorically controlled primates," published online in the June 19, 2013 issue of the American Journal of Clinical Nutrition. Controversy exists regarding the causative role of dietary fructose in obesity and fatty liver diseases.

In a new study, researchers have looked at former clinical trials indicating that negative health consequences may occur only when fructose is consumed within excess calories. Animal studies have suggested that fructose impairs intestinal integrity and leads to hepatic steatosis (HS). In the new study, the researchers didn't study dextrose, but the researchers plan to begin a new study using the same controls but testing for both fructose and dextrose for a longer time frame.

What's the connection between fructose and fatty liver?

The role of dietary fructose in the development of obesity and fatty liver diseases remains controversial, with previous studies indicating that the problems resulted from fructose and a diet too high in calories. In future research, the scientists will also study the role of dietary dextrose in the development of these types of diseases. Fructose and dextrose are simple sugars found naturally in plants.

Now a new study conducted in an animal model at Wake Forest Baptist Medical Center showed that fructose rapidly caused liver damage even without weight gain. The researchers found that during the six-week study period liver damage more than doubled in the animals fed a high-fructose diet as compared to those in the control group. You also can check out the abstract of the study online. The study is published online since June 19, 2013 in the American Journal of Clinical Nutrition.

"Is a calorie a calorie? Are they all created equal? Based on this study, we would say not," says Kylie Kavanagh, D.V.M., assistant professor of pathology-comparative medicine at Wake Forest Baptist and lead author of the study, according to a June 19, 2013 news release, "Dietary fructose causes liver damage in animal model, study finds."

In a previous trial which is referenced in the current journal article, Kavanagh's team studied monkeys who were allowed to eat as much as they wanted of low-fat food with added fructose for seven years, as compared to a control group fed a low-fructose, low-fat diet for the same time period.

Not surprisingly, the animals allowed to eat as much as they wanted of the high-fructose diet gained 50 percent more weight than the control group. They developed diabetes at three times the rate of the control group and also developed hepatic steatosis, or non-alcoholic fatty liver disease.

The big question for the researchers was what caused the liver damage

Was it because the animals got fat from eating too much, or was it something else? To answer that question, this study was designed to prevent weight gain.

Ten middle-aged, normal weight monkeys who had never eaten fructose were divided into two groups based on comparable body shapes and waist circumference. During a six week period, one group was fed a calorie-controlled diet consisting of 24 percent fructose, while the control group was fed a calorie-controlled diet with only a negligible amount of fructose, approximately 0.5 percent.

The control group's healthier diet consisted of healthy carbs and soy protein

Both diets had the same amount of fat, carbohydrate and protein, but the sources were different, Kavanagh says, according to the news release. The high-fructose group's diet was made from flour, butter, pork fat, eggs and fructose (the main ingredient in corn syrup), similar to what many people eat, while the control group's diet was made from healthy complex carbohydrates and soy protein.

Every week the research team weighed both groups and measured their waist circumference, then adjusted the amount of food provided to prevent weight gain. At the end of the study, the researchers measured biomarkers of liver damage through blood samples and examined what type of bacteria was in the intestine through fecal samples and intestinal biopsies.

"What surprised us the most was how quickly the liver was affected and how extensive the damage was, especially without weight gain as a factor," Kavanagh says in the news release. "Six weeks in monkeys is roughly equivalent to three months in humans."

In the high-fructose group, the researchers found that the type of intestinal bacteria hadn't changed, but that they were migrating to the liver more rapidly and causing damage there

It appears that something about the high fructose levels was causing the intestines to be less protective than normal, and consequently allowing the bacteria to leak out at a 30 percent higher rate, Kavanagh says, according to the news release.

One of the limitations of the study was that it only tested for fructose and not dextrose. Fructose and dextrose are simple sugars found naturally in plants. "We studied fructose because it is the most commonly added sugar in the American diet, but based on our study findings, we can't say conclusively that fructose caused the liver damage," Kavanagh says, according to the news release. "What we can say is that high added sugars caused bacteria to exit the intestines, go into the blood stream and damage the liver.

High added sugars caused bacteria to exit the intestines, move to the bloodstream, and damage the liver, the study explains

"The liver damage began even in the absence of weight gain, says Kavanagh in the news release. "This could have clinical implications because most doctors and scientists have thought that it was the fat in and around tissues in the body that caused the health problems." The Wake Forest Baptist team plans to begin a new study using the same controls but testing for both fructose and dextrose over a longer time frame.

The study was supported by Wake Forest School of Medicine and grants RR019963, OD010965 and AG033641 from the National Institutes of Health. Co-authors of the study are Ashley Wylie and Kelly Tucker, B.S., of Wake Forest Baptist; John Culler, D.V.M., Ph.D., of North Carolina State University; Timothy Hamp, B.S., Anthony Fodor, Ph.D., and Raad Gharaibeh, Ph.D., of the University of North Carolina at Charlotte.

You also may want to look at the abstract of these other studies, "Food-intake patterns assessed by using front-of-pack labeling program criteria associated with better diet quality and lower cardiometabolic risk." Or see, "Fructose, weight gain, and the insulin resistance syndrome."



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