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Ephedra

Ephedra sinica

Ephedra may be the most controversial herbal supplement ever. Here are the facts. Read this unopinionated article on ephedra and make your own informed decision.

Alternate Names
• Ma Huang

Principal Proposed Uses
• Asthma*

Questionable Uses
• Sexual Dysfunction in Women, Weight-Loss Aid

What is ephedra?
What Is Ephedra Used for Today?
What Is the Scientific Evidence for Ephedra?
Dosage
Safety Issues
Interactions You Should Know About
Ephedra Ban
Ephedra Ban Lifted
References

Ephedra, 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, 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, 19Note: Due to safety risks, we strongly recommend that you seek physician's supervision before attempting to lose weight with ephedrine/caffeine combination therapy.

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.

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

What Is the Scientific Evidence for Ephedra?
Evidence suggests that ephedrine/caffeine combinations can aid weight loss, and help keep it 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 over 36 pounds as compared to only 29 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 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
Herbal products containing ephedra cause the majority (64%) of reported adverse effects from herbs in the U.S. This proportion is particularly impressive given that less than 1% of all herbal products sold in the U.S. contain 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

Besides heart problems and strokes, use of ephedra has been associated with inflammation of the liver 24,25 and 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 develp an unusal form of kidney stones that actually contain ephedrine. 27

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:

Cardiovascular disease, including:
Angina
Abnormalities of heart rhythm
Hardening of the arteries
High blood pressure
High cholesterol
Intermittent claudication
o History of stroke
Enlargement of the prostate
Diabetes
Hepatitis
Myocarditis
Vasculitis
Diseases of the nervous system
Glaucoma
Hyperthyroidism
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. If you are taking any stimulant drugs (including caffeine), do not take ephedra except under physician supervision.

 

Please note: On Dec. 30, 2003, the U.S. Food and Drug Administration (FDA) issued a consumer alert regarding the safety of dietary supplements containing ephedra. The FDA has 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 60 days (March 2004) after the publication of its final ruling, the sale of all products containing ephedra in the United States will be banned.

Ephedra Ban Lifted by U.S. District Judge
THURSDAY, April 14 (HealthDay News) -- Saying that the U.S. Food and Drug Administration had not met the burden of proof that any specific dosage of the controversial weight-loss drug ephedra was dangerous, a U.S. District Court judge in Salt Lake City has lifted the year-old FDA ban and sent the matter back to the agency for further evaluation.

A lawsuit against the ban, which the FDA initiated in February 2004, was brought by Nutraceutical Corp. and Solray Inc. of Park City, Utah, a nutritional supplement manufacturer. On Thursday, Judge Tena Campbell ruled that the FDA had not proved that its arbitrarily-set dosages of 10 milligrams (mg) or less of ephedrine-alkyloid dietary supplements (EDS) were dangerous.

In fact, Campbell said in her ruling that the FDA had rested its entire case on research offered by the agency and its advisory committee that could not determine what a safe level of an EDS would be.

"A negative inference is different from the affirmative proof required..." Campbell wrote in her opinion. "There is not sufficient evidence in the administrative record to establish that the risks identified by the FDA are associated with the intake of low dose EDS."

Late Thursday afternoon, FDA officials were evaluating whether the minimum 10 mg dose was sufficient to appeal Campbell's decision or whether more research was necessary.

"The FDA is evaluating the question of appeal," spokeswoman Kimberly Rawlings said. Rawlings said she expected a decision by early Friday.

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(5):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 a.. 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.