American Botanical Council Reviews Ephedra Safety
31 March 2003
by Wyn Snow, Managing Editor

Ignorance of scientific information can be the greatest danger faced by anyone taking supplements.

According to Dr. Joshua Perper, Broward County's medical examiner, several medical conditions as well as ephedra intake contributed to Oriole pitcher Steve Bechler's recent death from heat stroke. Bechler was taking 150% percent of the manufacturer's recommended intake level (three pills instead of two). Did Bechler also ignore label warnings that people with heart conditions and high blood pressure should not take this supplement?

By and large, most supplement labels contain very little information about safety or contraindications or drug interactions—and while most herbs enjoy a remarkably good safety record, both contraindications and interactions with drugs and/or foods do occur. Recently, the American Botanical Council (ABC) developed a safety labeling program that will help manufacturers put reliable and comprehensive safety information where it is needed most: on the label and in the hands of consumers.

This label information is based on scientific monographs akin to those developed by the FDA for 0ver-the-counter drugs. Among the 29 monographs covering popular herbs in ABC's new book, The ABC Clinical Guide to Herbs, is one for ephedra. Here are some highlights:

What is a safe dosage level?

The recommended maximum daily intake for an adult is 100 mg of total ephedra alkaloids. (This is from the US herb industry labeling policy that has been adopted as law in several states.)

Dosage levels of 30 mg of total alkaloids per dose, and 90 mg of total alkaloids per day have shown no observed adverse effects. The lowest level where adverse effects are observed is 150 mg/day. (This is based on the Cantox toxicological review.)

What does ephedra do to the body?

The alkaloids in ephedra stimulate the nervous system in a way that increases heart rate and causes blood vessels to constrict (become narrower). This also causes blood pressure to rise.

Herbal preparations of ephedra also enlarge bronchial passages (which makes it useful for asthma), induce perspiration and increase urine production (diuretic).

Ephedra's use as an aid to weight-loss is due to its thermogenic (literally "heat-making") effects on metabolism, inducing an obese body to burn more fuel than it otherwise would. This effect is raised when one combines ephedrine with caffeine. However, it should be noted that caffeine stimulates the nervous system in ways quite similar to ephedra (heart rate, blood vessels, etc).

Ephedrine also lengthens the time a meal stays in the stomach, which may help reduce the amount of food eaten.

Decades of widespread use have shown no indication of addiction to ephedra.

There is some evidence that initial increases in pulse rate, blood pressure and serum glucose levels disappear with chronic use over a period of 4-12 weeks.

Side effects

Adverse effects of ephedra are known to include insomnia, motor restlessness, irritability, headaches, nausea, vomiting, disturbances of urination, and tachycardia (fast heart beat). The German Commission E (which was Germany's regulatory body governing herbs) indicated that doses higher than 300 mg/day of total ephedra alkaloids "may produce a drastic increase in blood pressure [and] cardiac arrhythmia."

In reports to the FDA of adverse events that may have been caused by ephedra, the most frequently reported symptom was hypertension, then palpitations or tachycardia or both. Stroke and seizures followed in the chronology of adverse events, some of which resulted in death or disability.

However, the rate of occurrence of heart attacks and strokes among people who use ephedra seems to be no different from that in the general population.

Drug interactions

Information on drug interactions is based on the synthetically derived alkaloids of ephedrine and pseudoephedrine. Thus, while this information probably applies to the herbal form of ephedra, there is no specific research on herbal ephedra drug interactions.

Ephedra use might affect antihypertensive drugs (including ACE inhibitors and beta-blockers), bromocriptine, and sympathomimetics.

Ephedrine and/or pseudoephedrine definitely interact with

• cardiac glycosides or halothane
• corticosteroids
• guanethidine
• MAO inhibitors
• methyl xanthines (caffeine, theophylline)
• secale alkaloid derivates or oxytocin
• urinary alkalizers (eg, acetazolamide, sodium bicarbonate)

Who should not take ephedra?

The German Commission E noted that people with the following medical conditions should not take ephedra:

• anxiety and restlessness
• hypertension
• glaucoma
• impaired circulation of the cerebrum
• adenoma of the prostate with residual urine accumulation
• pheochromocytoma
• thyrotoxicosis

Additional contraindications published in Brinker's Herb Contraindications and Drug Interactions (Eclectic Medical Publications, 2001) include:

• pregnancy
• anorexia
• diabetes
• heart disease
• insomnia
• stomach ulcers
• renal failure
• children

The American Herbal Products Association (AHPA) also states that ephedra should not be used during pregnancy or while nursing, by anorexics or bulimics, or by people with glaucoma. AHPA also warns against excessive or long-term use, and says ephedra may act as a thyroid stimulant and may potentiate MAO inhibitors.

History and controversy

The ABC ephedra monograph devotes three pages to the history and background of ephedra use—which began in China thousands of years ago. Used for treating asthma, colds and flu, cough, wheezing, nasal congestion and a few other conditions, ephedra (ma huang) appears in China's oldest listing of therapeutic herbal agents. The herb itself is still in the official government formularies for medical use in China, Germany and Japan—although most other countries use synthetic forms of ephedra's two main chemical compounds instead (ephedrine and pseudoephedrine).

Controversy over ephedra's safety began in the 1980s and 90s when ephedra was incorporated into supplements designed to aid weight-loss. In 1994, the American Herbal Products Association (AHPA) and the National Nutritional Foods Association (NNFA)—which are two of the major trade organizations for the supplement industry—created a labeling policy for its members concerning daily intake limits and contraindications. This labeling policy has since been adopted by all of the herbal industry trade associations (see our page: Ephedra: Guidelines For Dosage And Label Warnings).

The American Medical Association (AMA) takes a very different view—that all ephedrine substances (including ephedra) should be restricted to prescription use only, and eliminated from foods, OTC drugs, and dietary supplements.

In 1996, Ohio was the first state to adopt a law that requires all ephedra product labels to carry the AHPA/NNFA safety guidelines. Hawaii, Michigan, Washington, Oklahoma and Nebraska have followed suit.

During the 1990s, the FDA received approximately 800 adverse event reports on ephedra from a variety of sources. In 1997, the FDA sought to use these reports as the basis for highly restrictive daily intake limits. However, their proposal was criticized by scientific and medical experts as well as by industry and consumers as being both too restrictive and not scientifically based. The US General Accounting Office (GAO) agreed, and the FDA withdrew its proposed regulation.

In 2000, the Office of Women's Health, part of the US Department of Health and Human Services, held a two-day public hearing on the safety of ephedra. Two points of view emerged from the testimony of scientific and medical experts.

The Ephedra Education Council, an industry-based group, presented a review of both the published literature on ephedra safety and on the FDA's collection of 1000 adverse event reports. This review concluded there was no evidence of an association between ephedra and serious adverse events at the industry-recommended levels of intake. It also criticized an analysis of 1000 adverse event reports that was conducted by FDA consultants and subsequently published in the New England Journal of Medicine.

An FDA-sponsored review of 140 of the events reported to its MedWatch program concluded that one-third were "probably" and another third were "possibly" associated with ephedra. These included 17 reports of hypertension, 13 reports of palpitations and/or tachycardia, 10 reports of stroke, and 7 reports of seizures. Of these, 10 resulted in death and another 13 in disability.

The Ephedra Education Council also presented the results of the first comparison of how often heart attacks, strokes and seizures occur in the general population and among ephedra users, discovering no evidence of increased risk.

The Office of Women's Health issued a report that recommended further research, a recommendation echoed by other experts and agencies investigating ephedra safety.

In 2001, a researcher concluded, "The peer-reviewed scientific literature suggests that the risks of caffeine and ephedra are outweighed by the benefits of achieving and maintaining a healthy weight. Confirmation of that conclusion for herbal products containing caffeine and ephedrine awaits controlled clinical trials."

And in 2002, the Secretary of the Department of Health and Human Services called for more research on ephedra to determine its safety and efficacy.

The ABC overview of ephedra's history concludes with this statement:

"Supporters and some prominent critics of ephedra agree that scientific reviews of the cases of the adverse event reports on ephedra do not establish causality, thereby making additional clinical research the key to developing regulatory policy."

Source

American Botanical Council. "Ephedra." The ABC Clinical Guide to Herbs, 2003, pages 110-121. See www.herbalgram.org/default.asp?c=guideephedra.