The Risks of Mixing Drugs and Herbs: Recent Studies Pinpoint Range of Negative Interactions; Total Cereal and Antibiotics
Wall Street Journal - June 22, 2004 Jane Spencer, Staff Reporter of The Wall Street Journal
A wave of recent studies is sparking concern about the dangers of taking herbal supplements -- including St. John's Wort, echinacea and ginkgo biloba -- in combination with mainstream prescription drugs.
For years, doctors have recognized that many herbal remedies have powerful pharmacological effects, and patients have been given vague warnings to "consult your physician" before taking supplements. But until recently there have been little reliable data available for doctors and patients about how specific herbal products interact with medications.
Herbal remedies and dietary supplements can have a range of negative effects on treatment outcomes, interfering with everything from birth-control pills to antibiotics to heart medications. One study presented earlier this year found that St. John's Wort compromises the cancer drug Gleevec, potentially increasing patients' risk for a cancer relapse.
Ginkgo biloba may lead to spontaneous bleeding if it is combined with blood-thinning drugs. Even some fortified foods like calcium-enriched orange juice can interfere with antibiotics, according to a study published last year in the Journal of Clinical Pharmacology.
While much of the research is still emerging, drug companies including Bayer AG, Pfizer Inc. and Bristol-Meyers Squibb Co. have begun to revamp some drug labels to add new cautions about supplements. The Food and Drug Administration is encouraging drug companies to list herbal interactions when there is reliable data.
St. John's Wort, which is used for depression, is one of the riskiest herbs to mix with drugs. It appears to speed up the pace at which the body metabolizes drugs, diluting their effects. Past studies have shown the herb can weaken the impact of birth-control pills, protease inhibitors used to treat HIV, and the immunosuppressants that keep transplant patients from rejecting a new organ. The study on the herb's effect on the cancer drug Gleevec was presented at the annual meeting of the American Society for Clinical Pharmacology and Therapeutics.
Ginkgo, which is often taken to improve memory, may intensify the anti-clotting effects of blood-thinning drugs like Warfarin, according to researchers at the University of Arkansas for Medical Sciences College of Pharmacy. Blood thinners are commonly taken by heart patients to prevent blood clots. Case reports suggest that some strains of garlic, used to lower cholesterol, and ginseng, taken to boost energy, may have a similar effect on blood-thinning medications.
The expanding market for fortified food products -- often dubbed nutraceuticals -- is also leading to problematic interactions. Such products can have particularly high concentrations of minerals that may affect drugs. In addition to calcium-enriched orange juice, breakfast cereals with added minerals, such as Total, can interfere with antibiotics, according to a study last year in the Journal of Clinical Pharmacology. The mineral ions bind with antibiotics, preventing the drugs from being absorbed.
Dozens of new studies are under way with funding from the Food and Drug Administration and the National Institutes of Health. One FDA-funded study slated for publication in the coming months explores whether echinacea, a herb commonly taken for colds, interferes with birth-control pills.
Much of the research into herb-drug interactions is still preliminary. Data often come to light through individual case reports, which are less-informative than clinical studies. And a lack of standardization in supplement labeling means that ingredients and dosages can vary greatly, making herbs difficult to study.
The growing interest in herb-drug interactions comes as more Americans are popping herbal medications. Sales of dietary supplements hit an estimated $20.1 billion last year, a 7% increase over the previous year, according to Nutrition Business Journal. In addition, 16% of Americans say they use both herbal products and conventional drugs simultaneously, according to research published in the Journal of the American Medical Association in 2002.
The Risk of Mixing
Research is shedding new light on how many dietary supplements interact with prescription drugs.
SUPPLEMENT/INDICATION POTENTIAL DRUG INTERACTIONS COMMENT St. John's Wort/Depression Weakens the effectiveness of many drugs--including birth-control pills, chemotherapy medications and immunosuppressants--by making the body metabolize them faster. Has been studied more than other herbs, and drug interactions are well-established. It shouldn't be combined with prescription drugs without approval from a doctor. Ginkgo Biloba/Mental alertness May cause bleeding episodes if combined with anti-clotting drugs like warfarin, which are often prescribed after heart attacks. Some of the concern is based on case reports, which aren't as conclusive as clinical studies. Garlic/Cholesterol Case reports suggest some strains may intensify effects of blood-thinning drugs like warfarin. Effects may vary depending on the strain of garlic. Case reports don't always specify what type of garlic was used. Echinacea/Immune system booster Some evidence suggests that echinacea may increase risk of side effects in a variety of drugs. The FDA is funding a study of its effect on birth-control pills. Evidence on echinacea interactions is preliminary and inconclusive. Calcium-fortified orange juice/Bone strength The calcium in the juice may weaken the effects of antibiotics like Cipro, Noroxin or tetracycline. Cipro is labeled with a caution about taking the product with calcium-added orange juice.
Sources: American Botanical Council; Mayo Clinic Complementary and Integrative Medicine Program
"Americans have this mythology that if it's natural, it's safe," says Brent A. Bauer, director of the Complimentary and Integrative Medicine Program at the Mayo Clinic in Rochester, Minn. "But we barely know what one herb does on its own -- let alone what happens when you mix in four or five prescription drugs."
Combating supplement-drug interactions poses a regulatory challenge. The FDA has only limited authority over dietary supplements. Thus, the movement to warn patients is centering largely on the drug makers. The agency recently contacted a handful of companies that make birth-control products asking them to consider warnings about potential interactions with St. John's Wort.
A handful of drug companies now list herbal interactions on their labels. Bayer, which makes the antibiotic Cipro, lists a caution about calcium-fortified orange juice along with other calcium products on its label. The label for Bristol-Meyers Squibb's Coumadin, a blood-thinning agent, now comes with a warning against taking it with ginseng or ginkgo biloba.
Some herbal companies are voluntarily noting potential drug interactions on their labels. Last spring, Pharmavite, a Northride, Calif., company that makes Nature's Resource brand supplements, teamed up with the American Botanical Council, a group that promotes herbal remedies, to create new product labels that include information on drug interactions.
As doctors and pharmacists scramble for reliable information, companies are launching databases that allow practitioners to cross-check prescription drugs with supplements. CVS Corp. pharmacies use a program run by First DataBank that allows pharmacists to input herbal supplements and pull up a list of interactions. Lexi-Corp Inc., sells herbal-interaction software that runs on Palm and Pocket PC hand-held computers. NaturalStandard.com offers an online-subscription database that providers can use to look up herbal interactions. Consumers can find information at free sites like MayoClinic.com, or herbalgrams.com.
The consequences of mixing medications can be grave. In a case report published in the American Journal of Transplantation earlier this year, doctors hypothesized that a herb-drug interaction caused Alexis Southworth, 60-years-old of Glen Burnie, Md., to lose a transplanted kidney she'd had for 16 years. Soon after starting to take alfalfa for hot flashes and night sweats, in addition to her immunosuppressant drugs, she began to reject the kidney. She is now on dialysis and awaiting a new transplant.