Ephedra for Weight Loss
November 1, 2000 8 minutes read
Ephedra for Weight Loss
November 2000; Volume 2; 81-84
By Adriane Fugh-Berman, MD, and Amy Allina
The herb ephedra (e. sinica), also called ma huang, has a long history of use in both Western and Eastern herbalism for asthma and other respiratory conditions; there are no reported cases of adverse events related to these traditional uses of this herb. The use of ephedra for weight loss, bodybuilding, boosting energy, or recreational purposes has no traditional precedent and cannot be considered safe. Targeted by the relentless advertising campaigns of the diet and weight loss industries—from diet drugs to gyms to trendy, fad diet books—women particularly are likely to use ephedra in an effort to lose weight.
Ephedra contains 0.5-2.0% alkaloids, primarily ephedrine (50-90% of alkaloids), as well as pseudoephedrine and others. A usual adult dose of ephedra for asthma is about 2 g of herb, which would contain about 13 mg total alkaloids. There is great variation, however, in dosage of products. One analysis of nine commercial supplements demonstrated a range of ephedrine-type alkaloids between 1.08-13.54 mg.1
Ephedrine is an orally active sympathomimetic amine, less potent but more long-acting than epinephrine. Ephedrine is an a-1 agonist and a non-selective b-agonist.2 Systemic effects include bronchodilation, increased peripheral resistance, increased heart rate, increased blood pressure, urinary retention, increased respiratory rate, increased body temperature, and pupillary dilation.3
Risks
Sympathomimetic agents can be risky in people with underlying cardiovascular disease, cerebrovascular disease or abnormalities, prostatic hypertrophy, thyroid disorders, or those on monoamine oxidase inhibitors (MAOIs).
Ephedra was in herbal "Ecstasy," used by teenagers to get high. Between 1993 and 1997, the Food and Drug Administration received reports of 34 deaths and about 800 medical and psychiatric complications associated with ephedra-containing products.3
Ephedrine-induced psychosis and episodes of mania are well-documented. Ephedrine has been associated with chest pain in adolescents.4 Ephedrine also has been associated with kidney stones. A kidney stone database has analyzed more than 200 stones containing ephedrine, norephedrine, and pseudoephedrine.5
Combinations with other sympathomimetics may increase the risk of harm; one ephedra/caffeine product has been linked to the sudden death of a 23-year-old6 and another product was used successfully for suicide.7 A case of a severe MAOI interaction has been reported with phenelzine and an ephedrine product that also contained caffeine and theophylline.8
Cardiovascular Effects
Increased heart rate has been seen in most trials of ephedrine for weight loss; increases in blood pressure are less consistent and probably are more likely to occur early in use. In one trial, 12 normotensive adults (including six women) ages 23-40 were given four capsules (375 mg each) of a ma huang product. Heart rate and blood pressure were measured at baseline and eight and 17 hours after ingestion. Half of the participants experienced a statistically significant increase in 12-hour heart rate (from approximately 72 beats per minute to 81 beats per minute).9 Between hours 8 and 11, four participants had statistically significant increases in systolic blood pressure while two had significant decreases in diastolic blood pressure. Significant increases in heart rate were seen approximately 42 minutes after ingestion of ephedrine sulfate (50 mg) in another study.10
Most studies of ephedrine for weight loss did not find a significant adverse effect on blood pressure; however, few trials included hypertensives. One trial included participants with diastolic blood pressure up to 110;11 the report does not state how many subjects were hypertensive, and data on these patients are not broken out. Another trial of an ephedrine/caffeine combination included treated hypertensives and found that diastolic and systolic pressures decreased in both hypertensive and normotensive subjects.12 Because hypertensive patients are most sensitive to compounds that increase blood pressure, more research must be done in this area.
Clinical Trials for Weight Loss
There are no well-established indications for the use of dietary supplements containing ephedra alkaloids. Ephedra increases thermogenesis, as do many sympathomimetic agents, but trials of ephedra or ephedra/caffeine combinations have not shown consistent or dramatic results on weight loss (see Table 1) and have shown significant adverse effects. Most trials are small, and dropout rates have been notably high.
| Table 1-Randomized controlled trials of ephedra for weight loss* | ||||
| Author | N/Duration | Treatment | Result | Comment |
| Astrup11 | 180 obese subjects (141 completed) x 24 weeks | Diet (4.2 MJ) and 20 mg E vs. 200 mg C vs. 20/200 mg E/C | E/C significantly better than C or P; Weight loss (kg): E/C 16.6; E 14.3; C 11.5; P13.2 | More AE in both E groups (including dizziness, headache, tremor, psychiatric, insomnia, dry mouth, tachycardia). Withdrawals because of AE: E/C = 3, E = 1, C = 2. No difference in BP or HR. |
| Astrup15 | 14 obese women x 8 weeks | Diet (4.2 MJ/d) and 20/200 mg E/C tid vs. P | No significant difference in weight loss between groups | E/C group lost significantly more body fat and less fat-free mass. |
| Buemann16 | 32 overweight women x 8 weeks | Diet (4.2 MJ/d) and 20/200 mg E/C tid vs. P | No significant difference in weight loss between groups | Total cholesterol decreased in both groups; HDL decreased in P but not E/C group. |
| Breum17 | 103 overweight subjects (81 completed) x 15 weeks | 20/200 mg E/C tid vs. 15 mg DF bid | No significant difference between groups; weight loss (kg): DF 6.9; E/C 8.3. In those with BMI > 30, weight loss significantly different (7.0 kg vs. 9.0 kg) | Withdrawals because of AE: E = 6, 1 death; DF = 2. Forty- three percent of DF group and 54% of E/C group had S/E. No differences in HR or BP. |
| Cesari18 (abstract only) | 20 obese women x 4 months | 50 mg E tid (n = 6;) 50 mg E + 100 mg C tid (n = 7); or P (n = 7) | No significant difference in weight loss or BMI | |
| Daly19 | 29 obese subjects (24 completed) x 8 weeks | P or 75 mg E + 150 mg C + 330 mg ASA/d x 4 weeks, then 150 mg E + 150 mg C + 330 mg ASA/d x 4 weeks` | Significant difference between groups; weight loss (kg): ECA 2.2; P 0.7 | No significant difference in BP or HR between groups. One subject in 150 mg group developed hypertension. |
| Mancini20 (abstract only) | 42 overweight women (32 completed) x 8 weeks | Low-calorie diet and 22 mg E + 20 mg C + 50 mg aminophylline tid | P lost 2.2 kg, ECA lost 4.5 kg (apparently significant) | 7/22 ECA dropped out (2 for SE: insomnia, dyspepsia), 3/19 P dropped out. |
| Pasquali21 | 22 obese women (20 completed) x 4 months | Diet (4,180-5,016 Kj/d) and 50 mg P or E tid or 50/100 mg E/C tid | No significant difference among groups | |
| E = ephedrine, C = caffeine, P = placebo, ASA = aspirin, AE = adverse event, SE = side effect, HR = heart rate, BP = blood pressure, DF = dexfenfluramine | ||||
| *Four Danish studies were omitted for lack of translation resources | ||||
The use of ephedra for the treatment of respiratory conditions probably is not dangerous and, given the bronchodilating effects of ephedrine, probably is effective. However, no methodologically acceptable clinical trials of efficacy of ephedra preparations for respiratory ailments were identified.
There is some evidence that a caffeine/ephedrine combination can improve aerobic exercise performance, but the treatment increases heart rate and the incidence of nausea and vomiting has been as high as 25%.13,14
Individual sensitivity can be established only retrospectively, after an adverse event has occurred. Some people are more susceptible than others; as with cocaine, the majority of stroke cases associated with ephedrine occur in people with cerebral vessel abnormalities.3 However, such abnormalities are not uncommon and rarely are known to those who have them.
While ephedra is associated with more adverse reactions when combined with caffeine or phenylpropanolamine, intracerebral hemorrhage has been associated with the use of ephedra alone.3 There probably are several subpopulations for whom ephedra is more dangerous, but at this time we do not have enough information to identify these subpopulations. Virtually all adverse effects associated with the use of ephedra alkaloids have occurred when it was used for weight loss, exercise enhancement, energy enhancement, or recreational use.
Conclusion
Ephedra should not be available in products labeled or marketed for weight loss, bodybuilding, energy enhancement, or recreational use; the only indication for which ephedra products should be labeled is respiratory conditions. For traditional uses in traditional forms, ephedra does not seem to be hazardous. The uses of ephedra for weight loss, exercise enhancement, or as an "energizer" are not traditional uses, and any dose at which these effects occur is an overdose.
Ephedrine is available in several oral over-the-counter (OTC) drugs used to treat asthma; recommended dosages on these OTC drugs allow up to 150 mg/d ephedrine.
Dr. Fugh-Berman is Editor of Alternative Therapies in Women’s Health and Ms. Allina is program director, National Women’s Health Network, Washington, DC.
References
1. Gurley BJ, et al. Ephedrine pharmacokinetics after the ingestion of nutritional supplements containing Ephedra sinica (ma huang). Ther Drug Monit 1998;20:439-445.
2. Laurence DR, et al. Clinical Pharmacology. 8th ed. New York: Churchill Livingstone; 1997:415.
3. Jacobs KM, Hirsch KA. Psychiatric complications of Ma-huang. Psychosomatics 2000;41:58-62.
4. James LP, et al. Sympathomimetic drug use in adolescents presenting to a pediatric emergency department with chest pain. J Toxicol Clin Toxicol 1998;36: 321-328.
5. Powell T, et al. Ma-huang strikes again: Ephedrine nephrolithiasis. Am J Kidney Dis 1998;32:153-159.
6. 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.
7. Hedetoft C, et al. [Fatal poisoning with Letigen]. Ugeskr Laeger 1999;161:6937-6938.
8. Dawson JK, et al. Dangerous monoamine oxidase inhibitor interactions are still occurring in the 1990s. J Accid Emerg Med 1995;12:49-51.
9. White LM, et al. Pharmacokinetics and cardiovascular effects of Ma-huang (Ephedra sinica) in normotensive adults. J Clin Pharmacol 1997;37:116-122.
10. Meston CM, Heiman JR. Ephedrine-activated physiological sexual arousal in women. Arch Gen Psychiatry 1998;55:652-656.
11. Astrup A, 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.
12. Svendsen TL, et al. [Is Letigen contraindicated in hypertension? A double-blind, placebo controlled multipractice study of Letigen administered to normotensive and adequately treated patients with hypertension]. Ugeskr Laeger 1998;160:4073-4075.
13. Bell DG, et al. Reducing the dose of combined caffeine and ephedrine preserves the ergogenic effect. Aviat Space Environ Med 2000;71:415-419.
14. Bell DG, Jacobs I. Combined caffeine and ephedrine ingestion improves run times of Canadian Forces Warrior Test. Aviat Space Environ Med 1999;70:325-329.
15. Astrup A, et al. The effect of ephedrine/caffeine mixture on energy expenditure and body composition in obese women. Metabolism 1992;41:686-688.
16. Buemann B, et al. The effect of ephedrine plus caffeine on plasma lipids and lipoproteins during a 4.2 MJ/day diet. Int J Obes Relat Metab Disord 1994;18:329-332.
17. Breum L, 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.
18. Cesari MP. The therapeutic dilemma of ephedrine in obesity and the inefficacy of caffeine. Int J Obes Rel Metab Disord 1989;13(Suppl 1):152.
19. Daly PA, et al. Ephedrine, caffeine and aspirin: Safety and efficacy for treatment of human obesity. Int J Obes Relat Metab Disord 1993;17(Suppl 1):S73-S78.
20. Mancini MC, et al. Ephedrine, caffeine and aminophylline preparation (ECA): An alternative in the treatment of obesity. Int J Obes Rel Metab Disord 1990;14(suppl 2):141.
21. Pasquali R, Casimirri F. Clinical aspects of ephedrine in the treatment of obesity. Int J Obes Relat Metab Disord 1993;17(Suppl 1):S65-S68.
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