How alternative and herbal medications can have dangerous side effects

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Originally published in MedPage Today

by John Gever, MedPage Today Senior Editor

Herbal medicines are not always the harmless nostrums that many patients and even some physicians think, but may actually contribute to cardiovascular morbidity and mortality, researchers warned in a review covering 44 years of research into the subject.

Many such products, including aloe vera, ginkgo biloba, ginseng, and green tea, can interact with conventional cardiovascular drugs and lead to serious adverse reactions, according to Arshad Jahangir, MD, of the Mayo Clinic in Scottsdale, Ariz., and two other Mayo physicians.

“There is a clear need for better public and physician understanding of herbal products through health education, early detection and management of herbal toxicities, scientific scrutiny of their use, and research on their safety and effectiveness,” they wrote in the Feb. 9 Journal of the American College of Cardiology.

Jahangir and colleagues also called for increased regulation of such products, at least requiring manufacturers of herbal medicines to register with the FDA and provide evidence of good manufacturing practices.

“Some of these adverse drug reactions are preventable,” Jahangir told MedPage Today in a telephone interview. “Simple things like taking a good history or giving that history and discussing these issues, probably we can avoid [such reactions].”

Other physicians contacted by MedPage Today and ABC News agreed that the growth in popularity of herbal medicines poses problems for physicians and patients.

“Because these remedies are ‘natural,’ their potential dangers are not considered the same way they would be if they were medication,” commented Suzanne Steinbaum, MD, a cardiologist at Lenox Hill Hospital in New York City, in an e-mail.

“For many reasons, patients tend not to disclose to their doctors if they are taking herbal remedies, including fear that their doctors won’t approve or they will be told to stop them,” Steinbaum added. “This lack of knowledge and full-disclosure, for some, might be a fatal omission.”

Jahangir and colleagues reviewed nearly 90 publications that have addressed herbal or complementary therapies and cardiovascular effects since 1966.

Their JACC article listed 15 common herbal medicines known to interact adversely with conventional cardiovascular drugs.

In many cases, the herbal products compete with the regular medicines for the same drug-metabolizing cytochrome P450 enzymes, potentiating the latter’s effects. In other cases, the herbal products have their own cardiovascular effects.

Many physicians already know that grapefruit juice occupies the CYP3A4 enzyme, leading to slower-than-expected metabolism and, therefore, higher blood levels of a host of pharmaceuticals.

These include the statins, calcium channel antagonists, several common anti-arrhythmic drugs, and the angiotensin receptor blocker irbesartan (Avapro), Jahangir and colleagues noted.

Garlic is one of several common herbal remedies with specific cardiovascular effects in its own right (others include ginkgo biloba, ginseng, and saw palmetto). Garlic inhibits platelet aggregation and thus can lead to increased bleeding risks when combined with aspirin, clopidogrel (Plavix), or warfarin (Coumadin), the researchers noted.

The Mayo group identified 10 herbal products that increase bleeding risks with anticoagulant and antiplatelet drugs, as well as 14 that can induce arrhythmias.

In all, Jahangir and colleagues listed 27 herbal products that patients with cardiovascular diseases would do well to avoid. These include such common and harmless-seeming products as green tea, capsicum pepper, licorice, and kelp, as well as grapefruit juice and garlic.

“We need to check with our patients what type of products they are using, to identify these potential interactions,” Jahangir told MedPage Today.

He cited the previously reported figure of 100,000 deaths annually from drug interactions, adding, “We don’t even know how many of these are due to use of compounds that we are not aware that our patients are taking.”

Jahangir said he was surprised, in preparing the review, at the scale of hebal medicine use in the U.S.

He and his colleagues found data from the 1990s suggesting that more patients consult complementary and alternative medicine providers than regular physicians.

The total annual out-of-pocket expenditure on complementary and alternative medicine services and products also was greater than for conventional physician services.

“The surprise for me was . . . how much people are willing to spend on a type of therapy which has not shown, in any scientific way, to be effective or safe,” Jahangir said.

He added that the trend may reflect shortcomings of the conventional medical system.

“What is the reason people are going there? Is it because there is some unmet type of need that we are not recognizing as practitioners of conventional medicine?”

Jahangir said it may be that physicians aren’t spending enough time with patients to understand their true needs. He said it appears that, “despite the advancement in our technology and new medicines, there is a demand for alternative therapies that is increasing.”

He recommended that, in addition to asking patients in detail about herbal and other alternative therapies they may be using, physicians should educate themselves on what these therapies purport to do and what is known about their real biological effects.

The National Center for Complementary and Alternative Medicine at the National Institutes of Health is a good starting point for such information, both for physicians and for patients, Jahangir said.

Lenox Hill’s Steinbaum said it was important that conventional physicians “become more open-minded and accepting” of alternative medicine, if only because so many of their patients are already practicing it.

David Meyerson, MD, JD, a Johns Hopkins University cardiologist, told MedPage Today and ABC News in an e-mail that he advises patients to limit their use of “unstudied and unproven and FDA-unregulated herbal medications.”

“It’s unfortunately very big business, and potential drug interactions and potential harmful effects abound,” he wrote.

But another physician criticized the Mayo physicians’ emphasis on adverse effects in their review.

“For many of products listed, evidence for side effects seems to be minimal,” Scott Grundy, MD, of the University of Texas Southwestern Medical Center in Dallas, argued in an e-mail.

He agreed that the efficacy and safety of such drugs remains largely unproven, but added, “It is mainly for these reasons that they cannot be recommended for use.”

Creating alarm about side effects “may not be the appropriate way to discourage their use,” Grundy said.

Visit MedPageToday.com for more alternative medicine news.

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