Ephedra, or Ma Huang

The best known ma huang comes from the stems of the Chinese ephedra bush, Ephedra sinica, although some may be derived from E. equisetum species; similar plants are used in India and in the Near East. The ephedra species found in the U.S. are used to produce Mormon tea, which has none of the major properties of Chinese ephedra.

Uses and Benefits:

The ephedra plant has been used in Chinese medicine for thousands of years, probably as an astringent, diuretic, and antipyretic, and for treating cough. It was found to contain ephedrine, and this agent was introduced in the U.S. as an oral drug for asthma in 1924. The ephedra plant also contains pseudoehedrine. These sympathomimetic agents are still useful drugs for treating respiratory disorders and nasal congestion. Ephedrine is also used intravenously as a vasopressor. Ma huang remains an important constituent of Chinese herbal medicines, and is incorporated in many multiherb formulations. In the U.S., it is a controversial dietary supplement for mood elevation and weight loss, and is advertised as an appetite suppressant, energizer, performance enhancer, and psychic stimulant. Other uses have included motion sickness, bradycardia, spastic or hypermotile bowel, diabetic neuropathic edema, and myasthenia gravis.

Pharmacology:

It has been well established that ephedrine and pseudoephe­drine have potent sympathomimetic effects, with alpha-, beta and beta -agonist therapeutic uses. The physiologic action of phedrine is to release norepinephrine from ganglia; after repated use, the availability of norepinephrine in adrenergic rves is depleted, and ephedrine loses its effect. This is the phe­lIomenon of tachyphylaxis, which makes ephedrine an unreliable drug in chronic therapyJ

Ephedra alkaloids have anorexiant and thermogenic, or ergonic, effects that result in increased metabolism in animals and in humans. These qualities provide a basis for using ma huang as a weight-reducing supplement. It is known that alpha adrenerjic stimulation of the paraventricular nuclei in the brain leads to a reduction in appetite, and the peripheral effects on muscles and fat may result in increased fat oxidation and weight loss.

Clinical Trials:

The clinical benefits of ephedrine and pseu­doephedrine are long established Ephedrine and other ephedra constituents are moderately effective bronchodilators, vasocon­strictors, and decongestants. Evidence has been published show­ing its benefits in cough when used in a multi-herb formulationJ Moreover, in a randomized, double-blind, placebo-controlled trial of women, ephedrine sulfate was shown to facilitate sexual arousal. However, the drug was not assessed in women with im­paired function. The specific effectiveness of ma huang has not been adequately demonstrated for these indications.

Ephedra alkaloids and ma huang have gained considerable popularity as anorexiants and stimulants. Animal models suggest that these effects may be potentiated by caffeine and by catechol­polyphenols in green tea. However, in eight human clinical trials of ephedra or ephedrine-caffeine combinations, with or without other drugs, results have been inconsistent. Six of these trials studied 14-42 obese subjects, while the two others studied 103 and 180 subjects; no study lasted more than 6 months, and dropout rates were high. 12 Weight loss was not dramatic in any study. No signifi­cant differences from placebo were found in five of the trials, while one showed benefit that was apparently significant, and two (each using ephedrine combined with caffeine) found significant bene­fits of the combination when compared to either drug alone or to placebo. Moreover, there were significant, but usually tolerable, side effects, particularly when ephedra was combined with caffeine.

Another proposed use of ephedra is as an ergogenic drug to improve oxygen consumption and exercise efficiency. In a study of 12 healthy, untrained men, the combination of caffeine (4 mg/kg) and ephedrine (0.8 mg/kg) had a significant ergogenic effect during exercise that was similar to that of higher doses of caffeine (5 mg/kg) and of ephedrine (1 mg/kg), but with fewer side effects. However, this effect has not been adequately evaluated in well-designed, randomized, controlled trials.

Adverse Effects:

Numerous adverse effects of ephedrine alkaloids are recognized, including hypertension, tachycardia, dangerous arrhythmias, nervousness, tremor, insomnia, and anorexia.Ephedraima huang is said to be less likely to cause hypertension than ephedrine. Nevertheless, a sufficient number of reports have been submitted to the FDA to suggest that ma huang can cause hypertensive events, strokes, and heart attacks. In addition, psychoses and deaths have been attributed to this herb. However, the reliability of many of these reports is questionable. A recent review of 140 reports of alleged adverse effects from the use of dietary supplements containing ephedra alkaloids concluded that 31 % were related to the herb.

Although the association has been questioned, it is apparent that overuse of ma huang can be harmful and can cause severe impairment or death. Prolonged use has been reported to lead to dependency and to be associated with eating disorders in female athletes. Individual susceptibility, unreliability of marketed products, variations in daily dosing, and taking ephedra with other sympathomimetic agents appear to be relevant. Renal stones resulting from ephedrine and ephedra use has been described; excessive doses of pseudoephedrine could possibly produce the same complication.

Side Effects and Interactions:

Combining ephedrine and monoamine oxidase inhibitors can result in severe toxicity. Combinations with other sympathomimetic drugs or stimulants may result in additive cardiovascular or nervous system effects.

cautions:

Ephedra, like other sympathomimetic agonists, is relatively contraindicated in diseases such as hypertension, heart disease, thyroid disease, diabetes mellitus, prostatic hypertrophy, narrow angle glaucoma, and anxiety. Overuse of ephedra ,alkaloids can cause mild to serious disturbances in sleep and appetite, as well as tremor and nervousness. The more serious oilicomes are particularly likely to occur in those who use larger doses in combination with other stimulants. Some patients who abuse ephedrine have developed an "addiction" with apparent dependency, and athletes have tolerated doses as high as 750 mg per day.In such cases, withdrawal symptoms can occur upon abstinence. Patients should be warned not to escalate the dosage with chronic use since unexpected adverse effects may ensue.

Ephedrine, pseudoephedrine, and related drugs (including ma huang) are banned from use in Olympic sport competitions. Ephedrine and ma huang are considered to be relatively safe for the management of mild asthma in pregnancy, since they have long been given to pregnant women. Their use by children, adolescents, and breast-feeding mothers should be discouraged.

Preparations & Doses:

Ma huang and ephedra are available in numerous Chinese herbal preparations, mostly in mixtures with several other plant extracts and sometimes with animal constituents and minerals. Ma huang is also marketed in many U.S. products as a diet and performance aid. The amounts of active drugs in these preparations vary enormously, and excess dosage is readily experienced. A typical adult dose of the herb is 2 g, and this may contain about 13 mg of total alkaloids. Proprietary products have been shown to contain a to 18.5 mg of alkaloids per dose. The FDA has proposed that labeling of dietary supplement products be required to stipulate that dosages should not exceed 8 mg t.i.d. to be taken for not more than 1 week, but this recommendation has proved to be both inappropriate and unenforceable. The German Commission E and other herbal authorities recommend that ma huang and ephedra alkaloid dosages should be limited to 300 mg/day.A U.S. panel of experts claim that adverse events have not been shown to be related to ephedrine alkaloids when single doses are limited to 25 mg with not more than a total of 100 mg/day.

Summary Evaluation:

Ephedrine, ephedra, and ma huang have sympathomimetic effects that have long been recognized as effective in the treatment of mild asthma, nasal congestion, and sinusitis. Loss of effectiveness usually occurs with continued use (tachyphylaxis). The common side effects of low doses are annoying, but may be ac­ceptable. The anorexiant, anti-obesity, and ergogenic properties that are exploited in over-the-counter dietary supplements have not been adequately established, and ingesting high dosages of ephedra constituents could cause serious cardiac and cerebral damage. Because of its effects on the sympathetic nervous system, ephedra is one of the most potent and dangerous herbal medications in common use. Daily use of ephedra for more than a week or two or any dose in excessive amounts should be discouraged, since the herb's risk:benefit ratio is so high.