Overview
The Chinese herb ma huang is a member of a primitive family of plants that look
like thin, branching, connected straws. A related species, Ephedra
nevadensis, grows wild in the American Southwest and is widely called
Mormon tea. However, only the Asian species of ephedra contains the active
compounds ephedrine and pseudoephedrine.
Ma huang was traditionally used by Chinese herbalists during the early stages of respiratory infections and was also used for the short-term treatment of certain kinds of asthma, eczema, hay fever, narcolepsy, and edema. Japanese chemists isolated ephedrine from ma huang at the turn of the twentieth century, and it soon became a primary treatment for asthma in the United States and abroad. Ephedra’s other major ingredient, pseudoephedrine, became the decongestant Sudafed.
Therapeutic Dosages
The dosage of ephedra should be adjusted according to the amount of the ephedrine it provides. For adults, no more than 25 milligrams (mg) should be taken at one time, and a total daily intake of 100 mg should not be exceeded. However, a survey of ephedra-containing dietary supplements found that ephedrine content as listed on the label was frequently incorrect. In addition, other chemicals were often present that could increase safety risks. For this reason, experts recommend against the use of herbal ephedra.
Therapeutic Uses
Although it can still be found in a few over-the-counter drugs for asthma and sinus congestion (in a safer form than the banned dietary supplements), physicians seldom prescribe ephedrine anymore. The problem is that ephedrine mimics the effects of adrenaline and causes symptoms such as rapid heartbeat, high blood pressure, agitation, insomnia, nausea, and loss of appetite. The newer asthma drugs are much safer and easier to tolerate.
Meaningful evidence suggests ephedrine/caffeine combinations can assist in weight loss. However, because of safety risks, experts strongly recommend that individuals seek a physician’s supervision before attempting to lose weight with ephedrine/caffeine combination therapy. Experts also recommend not using herbal sources of ephedrine, which are now banned, for weight loss.
One highly preliminary study has been used to claim that ephedrine is helpful
for women with sexual dysfunction. However, this trial was very small, enrolled
women without sexual problems, and only examined sexual responsiveness to visual
stimuli; at this time, experts recommend that women with sexual dysfunction avoid
using ephedra. Another study examined the possible benefits of ephedrine for
treatment of female sexual dysfunction caused by antidepressants in the selective
serotonin
reuptake inhibitor (SSRI) family, such as Prozac.
Ephedrine failed to prove more effective than placebo.
There is no meaningful evidence that ephedra enhances sports performance. It
should also be noted that persons taking ephedra or ephedrine may test positive
for methamphetamine (speed) on drug screening.
Scientific Evidence
Evidence suggests that ephedrine/caffeine combinations can aid weight loss and help keep the weight off for up to six months. However, the benefits are modest.
For example, in a double-blind, placebo-controlled trial, 180 overweight
persons were placed on a weight-loss diet and given either ephedrine/caffeine (20
mg/200 mg), ephedrine alone (20 mg), caffeine alone (200 mg), or placebo
three times daily for twenty-four weeks. The results showed that the
ephedrine/caffeine treatment significantly enhanced weight loss, resulting in a
loss of more than thirty-six pounds, compared with only twenty-nine pounds in the
placebo group, a seven-pound difference. Neither ephedrine nor caffeine alone
produced any benefit. Contrary to some reports, participants did not develop
tolerance to the treatment. For the entire six months of the trial, the treatment
group maintained the same relative weight-loss advantage over the placebo
group.
A few side effects were seen in this study, primarily insomnia, dizziness, and tremor, but they tended to fade away after a few weeks. Keep in mind that participants were screened prior to the study and were eliminated if they had high blood pressure or any other serious disease, or if they used medications or illegal drugs that might interact with stimulants.
Another study compared ephedrine/caffeine with the no-longer-available drug dexfenfluramine (Redux), related to fenfluramine of fen-phen fame. A total of 103 overweight individuals were enrolled in this fifteen-week, double-blind trial. All were placed on a weight-loss diet. Half were given ephedrine/caffeine at the usual dose, while the others were given 15 mg of dexfenfluramine. The results showed comparable weight loss in both groups.
Finally, a double-blind, placebo-controlled trial enrolled 225 heavy smokers who wanted to quit but were afraid of gaining weight. At twelve weeks after quitting smoking, individuals taking ephedrine and caffeine had gained significantly less weight. At that point, the dosage was gradually reduced, and the difference between the groups declined. Contrary to the hopes of the experimenters, ephedrine/caffeine use did not help individuals quit smoking. Benefits have also been seen in smaller studies using herbal sources of ephedrine.
Experts do not know exactly how ephedrine/caffeine works. However, caffeine has actions that cause fat breakdown and enhance metabolism. Ephedrine suppresses appetite and increases energy expenditure. The combination appears to produce synergistic effects, with appetite suppression probably the most important overall factor.
Safety Issues
On December 30, 2003, the U.S. Food and Drug Administration (FDA)
issued a consumer alert regarding the safety of dietary supplements containing
ephedra. The FDA determined that consuming these supplements poses an unnecessary
risk of illness or injury, and that consumers should stop buying and using ephedra
products immediately. The FDA also notified manufacturers and marketers of these
dietary supplements that effective sixty days (March, 2004) after the publication
of its final ruling, the sale of all products containing ephedra in the United
States would be banned. This ruling was temporarily overturned in April 2005 but
was later upheld the following year, making it illegal to sell these products.
While ephedra is an herb with a long history of use in Chinese herbal
medicine, Chinese tradition attaches numerous warnings: It
should be used only by very robust people, for certain specific purposes, and only
for a short period of time. These ancient warnings seem to have been disregarded
in the transition of ephedra use from Asia to the United States, where it was
often sold for continuous use by overweight, relatively unhealthy people. Herbal
products containing ephedra caused the majority (64 percent) of reported adverse
effects from herbs in the United States. This proportion is particularly
impressive given that less than 1 percent of all herbal products sold in the
United States contain ephedra. On a per-use basis, for example, ephedra has 720
times as much risk of causing harm as ginkgo biloba.
There are many reasons for this high rate of risk. While it is possible for
healthy individuals under physician supervision to use ephedrine or
ephedrine/caffeine combinations safely, in individuals with heart
disease, and even occasionally in those with no known heart
conditions, ephedrine can cause serious disturbances of the heart rhythm and
possibly sudden death; strokes have also occurred. Use of herbal ephedra, as
opposed to ephedrine, may present additional dangers. There is no ready way to be
sure what dose of the drug ephedrine individuals are getting when they purchase
the herb ephedra, which creates a potential risk of overdosage. In addition, some
ephedra products contain potentially more toxic chemicals related to ephedrine,
such as (+)-norpseudoephedrine.
Besides heart problems and strokes, use of ephedra has been associated with severe inflammation of the liver (in at least one case requiring a liver transplant) and of the heart. In these cases, it appears likely that ephedra (or an unidentified contaminant in the herb) triggered an autoimmune reaction.
In addition, people taking ephedra or ephedrine may develop an unusual form of kidney stones that actually contain ephedrine. Temporary psychosis has also been linked to use of ephedra. Finally, there are indications that certain preparations of ephedra may be toxic to the nervous system.
Based on the known risks of ephedrine and on the evidence described in the foregoing paragraphs, ephedra should not be taken by persons with cardiovascular disease, including angina, abnormalities of heart rhythm, hardening of the arteries, high blood pressure, high cholesterol, intermittent claudication, myocarditis, vasculitis, or history of stroke; enlargement of the prostate; diabetes; hepatitis; diseases of the nervous system; glaucoma; or hyperthyroidism.
Ephedra may be particularly risky for young children, pregnant or nursing
women, people with kidney disease, and people with liver disease. Furthermore, one
should never combine ephedra with monoamine-oxidase (MAO) inhibitors,
such as Nardil (phenelzine), or fatal reactions may develop.
Important Interactions
Persons taking MAO inhibitors should not take ephedra, and persons taking any stimulant drugs, including caffeine, should not take ephedra except under physician supervision.
Bibliography
Bent, S., et al. “The Relative Safety of Ephedra Compared with Other Herbal Products.” Annals of Internal Medicine 138 (2003): 468-471.
Boozer, C. N., et al. “Herbal Ephedra/Caffeine for Weight Loss.” International Journal of Obesity and Related Metabolic Disorders 26 (2002): 593-604.
Chen, W. L., et al. “Effects of Ephedra on Autonomic Nervous Modulation in Healthy Young Adults.” Journal of Ethnopharmacology 130, no. 2 (2010): 563-568.
Coffey, C. S., et al. “A Randomized Double-Blind Placebo-Controlled Clinical Trial of a Product Containing Ephedrine, Caffeine, and Other Ingredients from Herbal Sources for Treatment of Overweight and Obesity in the Absence of Lifestyle Treatment.” International Journal of Obesity and Related Metabolic Disorders 28, no. 11 (2004): 1411-1419.
Levisky, J. A., et al. “False-Positive RIA for Methamphetamine Following Ingestion of an Ephedra-Derived Herbal Product.” Journal of Analytical Toxicology 27, no. 2 (2003): 123-124.
Meston, C. M. “A Randomized, Placebo-Controlled, Crossover Study of Ephedrine for SSRI-Induced Female Sexual Dysfunction.” Journal of Sex and Marital Therapy 30 (2004): 57-68.
Samenuk, D., et al. “Adverse Cardiovascular Events Temporally Associated with Ma Huang, an Herbal Source of Ephedrine.” Mayo Clinic Proceedings 77 (2002): 12-16.
Shekelle, P. G., et al. “Efficacy and Safety of Ephedra and Ephedrine for Weight Loss and Athletic Performance.” Journal of the American Medical Association 289 (2003): 1537-1545.
Skoulidis, F., G. J. Alexander, and S. E. Davies. “Ma Huang Associated Acute Liver Failure Requiring Liver Transplantation.” European Journal of Gastroenterology and Hepatology 17 (2005): 581-584.
Walton, R., and G. H. Manos. “Psychosis Related to Ephedra-Containing Herbal Supplement Use.” Southern Medical Journal 96 (2003): 718-720.
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