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Ephedra

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Principal Proposed UsesQuestionable Uses


Alternate Names

  • Ma Huang

Uses

Principal Proposed Uses

Questionable Uses

In the US, supplements containing ephedra have been banned since 2004 due to safety issues.
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 also 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 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.

What Is Ephedra Used for Today?

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 . 1-5,19,31Note : Due to safety risks, we strongly recommend that you seek physician's supervision before attempting to lose weight with ephedrine/caffeine combination therapy. We do not recommend using herbal sources of ephedrine, which are now banned, for weight loss at all. (See Safety Issues .)
One highly preliminary study has been used to claim that ephedrine is helpful for women with sexual dysfunction . 20 However, this trial was very small, enrolled women without sexual problems, and only examined sexual responsiveness to visual stimuli; at this time, we do not recommend that women with sexual dysfunction use ephedra. Another study examined the possible benefits of ephedrine for treatment of female sexual dysfunction caused by antidepressants in the SSRI family (eg, Prozac). 32 Ephedrine failed to prove more effective than placebo.
There is no meaningful evidence that ephedra enhances sports performance . 29
Note : Individuals taking ephedra or ephedrine may test positive for methamphetamine (speed) on drug screening. 21,33

What Is the Scientific Evidence for Ephedra?

Evidence suggests that ephedrine/caffeine combinations can aid weight loss and help keep the weight off for up to 6 months. However, the benefits are modest.
For example, in a double-blind, placebo-controlled trial, 180 overweight individuals 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, 3 times daily for 24 weeks. 6 The results showed that the ephedrine/caffeine treatment significantly enhanced weight loss, resulting in a loss of more than 36 pounds as compared to only 29 pounds in the placebo group, a 7-pound difference. Neither ephedrine nor caffeine alone produced any benefit. Contrary to some reports, participants did not develop tolerance to the treatment. For the whole 6 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. 8 A total of 103 overweight individuals were enrolled in this 15-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. 10 At 12 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. 9
We don't know exactly how ephedrine/caffeine works. However, caffeine has actions that cause fat breakdown and enhance metabolism. 11 Ephedrine suppresses appetite and increases energy expenditure. The combination appears to produce synergistic effects, with appetite suppression probably the most important overall factor.

Dosage

The dosage of ephedra should be adjusted according to the amount of the ephedrine it provides. For adults, no more than 25 mg should be taken at one time, and a total daily intake of 100 mg should not be exceeded. 12 However, a survey of ephedra-containing dietary supplements found that ephedrine content as listed on the label was frequently incorrect. 13 In addition, other chemicals were often present that could increase safety risks (see Safety Issues). For this reason, we do not recommend using herbal ephedra at all.

Safety Issues

While ephedra is an herb with a long history of use in Chinese herbal medicine, Chinese tradition attaches numerous warnings: It should only be used 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 had often been sold for continuous use by overweight, relatively unhealthy people. Herbal products containing ephedra caused the majority (64%) of reported adverse effects from herbs in the US. This proportion is particularly impressive given that less than 1% of all herbal products sold in the US contained ephedra. On a per-use basis, for example, ephedra has 720 times the 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. 15,18,22,23 Use of herbal ephedra, as opposed to ephedrine, may present additional dangers. As noted above, there is no ready way to be sure of the dose of the drug ephedrine you are getting when you purchase the herb ephedra, creating potential risk of overdosage. In addition, some ephedra products contain potentially more toxic chemicals related to ephedrine, such as (+)-norpseudoephedrine. 16
There is some evidence, though, that counters this claim of cardiovascular risk. For example, researchers analyzed data on 257,236 Danish patients prescribed to take a combination of ephedrine and caffeine from 1995-2002. 39 These patients did not have increased rates of heart attack or stroke.
Use of ephedra has been associated with severe inflammation of the liver (in at least one case requiring a liver transplant) 24,25,35 and of the heart. 26 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. 27 Temporary psychosis has also been linked to use of ephedra. 34
Finally, there are indications that certain preparations of ephedra may be toxic to the nervous system. 28
Based on the known risks of ephedrine, 17 as well as the evidence described above, ephedra should definitely not be taken by a person with: Ephedra may be particularly risky for:
  • Young children
  • Pregnant or nursing women
  • People with kidney disease
  • People with liver disease
Furthermore, one should never combine ephedra with monoamine-oxidase inhibitors (MAO inhibitors), such as Nardil (phenelzine), or fatal reactions may develop.

Interactions You Should Know About

If you are taking:
  • MAO inhibitors : Do not take ephedra.
  • Any stimulant drugs (including caffeine): Do not take ephedra except under physician supervision.

References

1 Astrup A, Breum L, Toubro S, et al. The effect and safety of an ephedrine/caffeine compound compared to ephedrine, caffeine and placebo in obese subjects on an energy restricted diet. A double-blind trial. Int J Obes Relat Metab Disord. 1992;16:269-277.

2 Molnar D, Torok K, Erhardt E, et al. Safety and efficacy of treatment with an ephedrine/caffeine mixture. The first double-blind placebo-controlled pilot study in adolescents. Int J Obes Relat Metab Disord. 2000;24:1573-1578.

3 Breum L, Pedersen JK, Ahlstrom F, et al. Comparison of an ephedrine/caffeine combination and dexfenfluramine in the treatment of obesity. A double-blind multi-centre trial in general practice. Int J Obes Relat Metab Disord. 1994;18:99-103.

4 Boozer CN, Nasser JA, Heymsfield SB, et al. An herbal supplement containing Ma Huang-Guarana for weight loss: a randomized, double-blind trial. Int J Obes Relat Metab Disord. 2001;25:316-324.

5 Norregaard J, Jorgensen S, Mikkelsen KL, et al. The effect of ephedrine plus caffeine on smoking cessation and postcessation weight gain. Clin Pharmacol Ther. 1996;60:679-686.

6 Astrup A, Breum L, Toubro S, et al. The effect and safety of an ephedrine/caffeine compound compared to ephedrine, caffeine and placebo in obese subjects on an energy restricted diet. A double-blind trial. Int J Obes Relat Metab Disord. 1992;16:269-277.

7 Molnar D, Torok K, Erhardt E, et al. Safety and efficacy of treatment with an ephedrine/caffeine mixture. The first double-blind placebo-controlled pilot study in adolescents. Int J Obes Relat Metab Disord. 2000;24:1573-1578.

8 Breum L, Pedersen JK, Ahlstrom F, et al. Comparison of an ephedrine/caffeine combination and dexfenfluramine in the treatment of obesity. A double-blind multi-centre trial in general practice. Int J Obes Relat Metab Disord. 1994;18:99-103.

9 Boozer CN, Nasser JA, Heymsfield SB, et al. An herbal supplement containing Ma Huang-Guarana for weight loss: a randomized, double-blind trial. Int J Obes Relat Metab Disord. 2001;25:316-324.

10 Norregaard J, Jorgensen S, Mikkelsen KL, et al. The effect of ephedrine plus caffeine on smoking cessation and postcessation weight gain. Clin Pharmacol Ther. 1996;60:679-686.

11 Astrup A, Breum L, Toubro S. Pharmacological and clinical studies of ephedrine and other thermogenic agonists. Obes Res. 1995;3:537S-540S.

12 MedscapeWire. No association between reported adverse events and ephedra when consumed as directed. Available at: http://www.medscape.com/MedscapeWire/2000/0800/medwire.0816.Nol . Accessed August 16, 2000.

13 Gurley BJ, Gardner SF, Hubbard MA. Content versus label claims in ephedra-containing dietary supplements. Am J Health Syst Pharm . 2000;57:963-969.

14 MedscapeWire. No association between reported adverse events and ephedra when consumed as directed. Available at: http://www.medscape.com/MedscapeWire/2000/0800/medwire.0816.Nol . Accessed August 16, 2000.

15 Haller CA, Benowitz NL. Adverse cardiovascular and central nervous system events associated with dietary supplements containing ephedra alkaloids. N Engl J Med . 2000;343:1833-1838.

16 Gurley BJ, Gardner SF, Hubbard MA. Content versus label claims in ephedra-containing dietary supplements. Am J Health Syst Pharm . 2000;57:963-969.

17 Physicians' Desk Reference For Herbal Medicines . Montvale, NJ: Medical Economics Co; 1998:827.

18 Samenuk D, Link M, Homoud M K, et al. Adverse cardiovascular events temporally associated with Ma Huang, an herbal source of ephedrine. Mayo Clin Proc . 2002;77:12-16.

19 Boozer CN, Daly PA, Homel P, et al. Herbal ephedra/caffeine for weight loss: a 6-month randomized safety and efficacy trial. Int J Obes Relat Metab Disord . 2002;26:593-604.

20 Meston CM, Heiman JR. Ephedrine-activated physiological sexual arousal in women. Arch Gen Psychiatry . 1998;55:652-656.

21 Nishiguchi M, Kinoshita H, Higasa K, et al. The false positive reaction of the Triage panel drug-of-abuse by herbal drugs ma-huang (Ephedra sinica Ephedraceae). Nippon Hoigaku Zasshi . 2001;55:331-338.

22 Bruno A, Nolte KB, Chapin J. Stroke associated with ephedrine use. Neurology . 1993;43:1313-1316.

23 Theoharides TC. Sudden death of a healthy college student related to ephedrine toxicity from a ma huang-containing drink. J Clin Psychopharmacol. 1997;17:437-439.

24 Borum ML. Fulminant exacerbation of autoimmune hepatitis after the use of ma huang. Am J Gastroenterol . 2001;96:1654-1655.

25 Nadir A, Agrawal S, King PD, et al. Acute hepatitis associated with the use of a Chinese herbal product, ma-huang. Am J Gastroenterol . 1996;91:1436-1438.

26 Zaacks SM, Klein L, Tan CD, et al. Hypersensitivity myocarditis associated with ephedra use J Toxicol Clin Toxicol . 1999;37:485-489.

27 Powell T, Hsu FF, Turk J, Hruska K. Ma-huang strikes again: ephedrine nephrolithiasis. Am J Kidney Dis . 1998;32:153-159.

28 Lee MK, Cheng BW, Che CT, et al. Cytotoxicity assessment of Ma-huang (Ephedra) under different conditions of preparation. Toxicol Sci . 2000;56:424-430.

29 Shekelle PG, Hardy ML, Morton SC, et al. Efficacy and safety of ephedra and ephedrine for weight loss and athletic performance: a meta-analysis. JAMA . 2003;289:1537-1545.

30 Bent S, Tiedt TN, Odden MC, et al. The relative safety of ephedra compared with other herbal products. Ann Intern Med . 2003;138:468-471.

31 Coffey CS, Steiner D, Baker BA, 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. Int J Obes Relat Metab Disord . 2004 Aug 31. [Epub ahead of print]

32 Meston CM. A randomized, placebo-controlled, crossover study of ephedrine for SSRI-induced female sexual Dysfunction. J Sex Marital Ther . 2004;30:57-68.

33 Levisky JA, Karch SB, Bowerman DL, et al. False-positive RIA for methamphetamine following ingestion of an ephedra-derived herbal product. J Anal Toxicol . 2003;27(2):123-124.

34 Walton R, Manos GH. Psychosis related to ephedra-containing herbal supplement use. South Med J . 2003;96:718-720.

35 Skoulidis F, Alexander GJ, Davies SE. Ma huang associated acute liver failure requiring liver transplantation. Eur J Gastroenterol Hepatol . 2005;17:581-584.

36 FDA statement on Tenth Circuit's ruling to uphold FDA decision banning dietary supplements containing ephedrine alkaloids. Food and Drug Administration website. Available at: http://www.fda.gov/bbs/topics/NEWS/2006/NEW01434.html . Accessed: October 30, 2007.

37 Sales of supplements containing ephedrine alkaloids (ephedra) prohibited. Food and Drug Administration website. Available at: http://www.fda.gov/oc/initiatives/ephedra/february2004/default.htm . Accessed: October 30, 2007.

38 Chen WL, Tsai TH, Yang CC, Kuo TB. Effects of ephedra on autonomic nervous modulation in healthy young adults. J Ethnopharmacol. 2010;130(3):563-568.

39 Hallas J, Bjerrum L, Støvring H, Andersen M. Use of a prescribed ephedrine/caffeine combination and the risk of serious cardiovascular events: a registry-based case-crossover study. Am J Epidemiol. 2008;168(8):966-973.

Revision Information

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