Until recently, patients with HIV regularly used St. John's wort to ease depression. Considered safe and effective for short periods, the herbal supplement costs less than Prozac. Then, in February, Stephen Piscitelli, a scientist at the National Institutes of Health, published startling data: In a group of eight people, St. John's wort dramatically reduced blood levels of Crixivan, an important HIV drug and protease inhibitor also known as indinavir. At such low levels of concentration, AIDS patients are likely to become resistant to Crixivan and possibly other protease inhibitors.
The study results were compelling enough for the Food & Drug Administration to alert doctors and request that Merck, the maker of indinavir, add a warning about St. John's wort to the drug's label. There's no question Americans need this kind of information. As many as 40% of adults in the U.S. regularly ingest herbs, vitamins, and other supplements, surveys show. Roughly 15 million of them take prescription drugs at the same time. And many hide their supplement use from their doctors.
Although there are no wide-ranging clinical trials definitely linking herbal supplements to interactions with drugs, case studies from the past 30 years suggest many interactions may exist. For example, St. John's wort may interact negatively with drugs besides protease inhibitors. Other leading suspects for interactions include melatonin, which people take to counteract jet lag and to help them sleep; kava, which is supposed to help people relax; and garlic and garlic extracts, which people take in an effort to lower cholesterol. "There will be an explosion of information on herb-drug interactions in the next few years," says Piscitelli of the NIH.
ORGAN REJECTION. One theory is that herbal products are likely to interact with drugs that are metabolized by the same enzyme in the body. St. John's wort alone may interact with an array of drugs, because it's broken down by an enzyme that also metabolizes about half of existing over-the-counter and prescription drugs. There has been some evidence that St. John's wort reduces levels of Lanoxin (digoxin), a drug that treats congestive heart failure; Coumadin (warfarin), a blood thinner; bronchodilator drugs for asthma; and Tegretol (carbamazepine), an anticonvulsant. Swiss doctors recently published case studies on two heart transplant patients who suffered organ rejection while taking St. John's wort along with cyclosporine, an anti-rejection drug.
One of Piscitelli's colleagues, Aaron Burstein, is studying the effects of melatonin on the family of enzymes that metabolizes most drugs, called cytochrome P450 (it includes the enzyme that breaks down St. John's wort). In 15 volunteers taking melatonin, Burstein is examining how the herb affects the activity of these enzymes. His hunch: Melatonin in some way interferes with Tegretol, an epilepsy drug. "If we can shed light on what enzymes are affected, we would only need to look at medicines eliminated by that pathway," he says. He expects to have results in May. And at the University of Arkansas Medical School, Bill Gurley, an associate professor of pharmaceutical sciences, is independently testing whether chronic ingestion of garlic, ginkgo biloba, panax ginseng, and St. John's Wort affect the way drugs are metabolized. Early results of tests on 24 subjects, he says, indicate that garlic inhibits one of the cytochrome P450 enzymes, which would mean that a drug ordinarily metabolized by this enzyme isn't. A drug that stays in the body longer than usual could create unintended side effects.
All this work is early yet, and metabolism isn't the only mechanism by which herbs interact with drugs. Some herbal products appear to be addictive, intensifying the effect of certain drugs. Most worrisome for health practitioners, a few popular herbal products--garlic and ginkgo, for example--appear to increase the effect of the blood thinner Coumadin, which has led to severe bleeding in several case studies.
Likewise, patients on antidepressants such as Zoloft or Paxil should stay away from St. John's wort, which is marketed as a substitute for prescription antidepressant drugs. Those on Xanax or Valium for anxiety shouldn't take kava, an herb marketed as a relaxant.
Herbal product makers argue that herbs are extremely safe and that claims to the contrary are fanning unnecessary fears. Michael McGuffin, president of the American Herbal Products Assn., faults Piscitelli's study for not using placebos and for the small number of patients involved. Piscitelli says his study was properly designed to show the effects of the interaction of St. John's wort with indinavir. "We're not on a crusade to do away with supplements," Gurley adds. "We just want to give people information on which combinations of drugs and supplements to avoid."
Many consumers don't realize that herbal supplements work much like drugs. "I get all kinds of probing questions about drugs, then my patients will go down to the health-food store, where someone with a high-school diploma will say, `Take this,' and they'll say, `O.K.,"' says Dr. Joel Gallant, director of the HIV clinic at the University School of Medicine at Johns Hopkins. "People have this funny idea that `natural' means safe and `prescription' means toxic, but they're all drugs. Anything you ingest and which has an effect on your body is a drug."
`DANGEROUS INTERACTIONS.' Lisa Chavis, a natural medicine consultant and pharmacist in Seattle, says she often steers customers away from possible herb-drug interactions. "There is a general lack of knowledge about dangerous interactions," she says. Product labels on herbal supplements usually aren't any help. The FDA doesn't push drug companies to investigate herb-drug interactions, and herbal product makers aren't required to advertise possible adverse reactions. Under federal law, herbal products don't need to prove safety and efficacy. Makers don't need to conform to good manufacturing practices, although the FDA plans to establish standards.
Experts say consumers, particularly those taking drugs for chronic conditions, should consult a doctor, herbalist, or pharmacist about possible interactions before taking any supplements. Remember that herbs can be drugs--they're just not labeled as such.