Vitamin E, diabetes drug may reverse fatty liver disease

Taking either vitamin E or a diabetes drug can reverse the course of fatty liver disease, a condition sometimes associated with obesity, researchers report online April 28 in the New England Journal of Medicine.

The findings come as welcome news for people who are prone to getting the disease, which can lead to cirrhosis and irreversible liver damage if fat accumulation in the liver goes unchecked. There is currently no established treatment for the condition other than to lose weight.

Fatty liver is a silent disease that’s typically diagnosed from aberrant liver enzyme scores on blood tests. Often the patient feels nothing, says hepatologist Arun Sanyal of Virginia Commonwealth University School of Medicine in Richmond.

Earlier studies had suggested that both vitamin E and the diabetes drug pioglitazone could benefit people with fatty liver disease. Doctors sometimes even prescribe pioglitazone off-label for the condition, Sanyal says.

To test the effectiveness of pioglitazone and vitamin E, Sanyal and colleagues at 11 other medical facilities identified 247 people who had severe fatty liver disease. None of the volunteers drank alcohol excessively or was diabetic, but all were overweight or obese. Their average age was in the mid-40s.

The researchers randomly assigned participants to one of three treatments —  vitamin E, pioglitazone or a placebo capsule — taken daily for nearly two years. Each volunteer underwent a liver biopsy at the beginning and end of the trial.

Biopsies revealed that 43 percent of the vitamin E group showed substantial improvement, based on a composite score of liver tissue characteristics, as did 34 percent of people receiving pioglitazone and 19 percent of those on placebo. The improvement among people getting fake pills wasn’t a surprise, Sanyal says, because “when people enter clinical trials, they typically behave themselves.”

While the pioglitazone and placebo groups’ percentages were only marginally different from one another, the biopsy data also revealed that the drug — like vitamin E — substantially lessened liver inflammation, fat accumulation and the presence of dying “ballooning cells” that appear in fatty liver tissue.   

“This confirms a long-term benefit for pioglitazone and gives an alternative option” in the form of vitamin E, says Kenneth Cusi, an endocrinologist at the University of Texas Health Science Center at San Antonio.

Pioglitazone improves insulin signaling, which helps people with diabetes metabolize sugar. But the drug’s effects may also extend to diminishing the amount of fat in the liver, Cusi says.

Vitamin E is an antioxidant that sops up free radicals and prevents these unstable molecules from damaging cell membranes.  As such, the vitamin would seem tailor-made to protect against any number of diseases.

But vitamin E has yet to fulfill this promise. “There are no clearly proven medicinal uses of vitamin E,” states the Mayo Clinic website. It has failed to protect against heart disease in trials, and in one case even seemed  to slightly increase subjects’ risk of dying.

“It’s too early to recommend [vitamin E] as a panacea” for fatty liver disease, Sanyal says. Whether to recommend it to patients will be up to doctors.

Meanwhile, he and his colleagues are investigating the biological mechanisms by which vitamin E or pioglitazone might reverse fatty liver disease. Cusi’s research group is testing pioglitazone against fatty liver in Hispanics, who seem prone to the disease, and in people with diabetes.