Study finds Indian supplement works naturally in mice

By John Dillon
　　
　　THURSDAY, May 2 (HealthScoutNews) -- The resin of a gum tree has been widely used as a folk remedy in India for 2,600 years, and for the last 15 years it's been a government-approved drug to lower cholesterol.
　　Despite its long history, the natural compound, called guggulsterone, has been ignored by Western scientists, largely because it's a natural compound. But a new American study suggests that the Indians were on to something all along -- guggulsterone does lower cholesterol, at least in mice.

The doubt over herbal medicines is that "there has been quite a bit of speculation on how they work and if they work," says David Manglesdorf, a co-author of the new study. "This just happens to be one that, in fact, does work."

Guggulsterone, a hormone, isn't regulated in the United States, and is easily available over the counter at health shops and over the Internet. But Manglesdorf warns people not to chuck their current regimens for the herbal stuff.

The study, appearing in tomorrow's issue of Science, is "the only really serious research that I know that has been done on it," says Manglesdorf, a professor of pharmacology and investigator at the Howard Hughes Medical Institute at the University of Texas-Southwestern.

The gum resin of what Indians call the guggul tree had its first known use as a dietary supplement in 600 B.C. People took it to treat a variety of ailments, including obesity and cholesterol problems. In 1987, the Indian government approved the root as an anti-cholesterol medicine called gugulipid.

Researchers at UT-Southwestern and Baylor University tried to determine how -- and if -- guggulsterone worked. They suspected that it blocked the farnesoid X receptor (FXR), which, when activated by bile acids, regulates the metabolism of cholesterol.

They took two sets of mice, one that had their FXR genetically snipped and one whose FXR was left alone. Both were then fed a high-cholesterol diet.

The scientific hunch turned out to be correct: Those whose FXR was left alone saw a marked decrease in their total cholesterol levels, while the mice whose FXR were removed saw no change.

Manglesdorf says guggulsterone acts as an antagonist to FXR. He compares it to a key and a lock, with the hormone acting as the key. When the key fits, and it's the only key in the lock, no other keys can work at the same time. When the guggulsterone is in the lock, it "prevents the bile from doing what they normally do," he said. "The consequence is that cholesterol is lowered significantly."

The only side effect is that the mice appeared to have intestinal discomfort, according to Manglesdorf.

The study suggests that compounds similar to guggulsterone can work well or even better. "By interrupting this pathway, you'd have a potential drug," he says.

Cholesterol is kept down these days through diet and exercise, though millions of people are now taking effective drugs called statins. If you're on them, stay on them, Manglesdorf suggests. "I'm not dissing the statins because I think they are, in general, wonderful drugs," he says. The study opens new avenues to attacking high cholesterol, and because it's natural, "this compound may be much better."

　　From Healthscout.com