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Ephedra

  • Written by Shahrul
  • Updated on March 6, 2021


Plant Part Used

Stem

Active Constituents

Alkaloids (including (1R,2S)-norephedrine, l-ephedrine and d-pseudoephedrine); tannins; flavonoid glycosides. (1), (46) [span class=alert]

This section is a list of chemical entities identified in this dietary supplement to possess pharmacological activity. This list does not imply that other, yet unidentified, constituents do not influence the pharmacological activity of this dietary supplement nor does it imply that any one constituent possesses greater influence on the overall pharmacological effect of this dietary supplement.[/span]

Introduction

 

Warning:
Not intended for use by anyone under the age of 18. Do not use this product if you are pregnant or nursing. Consult a health care professional before using this product if you have heart disease, thyroid disease, diabetes, high blood pressure, psychiatric condition, difficulty in urinating, prostate enlargement, or seizure disorder, if you are using a monoamine oxidase inhibitor (MAOI) or any other prescription drug, or you are using an over-the-counter drug containing ephedrine, pseudoephedrine or phenylpropanolamine (ingredients found in certain allergy, asthma, cold/cough and weight control products).

Exceeding recommended serving will not improve results and may cause serious adverse health effects.

Discontinue use and call a health care professional immediately if you experience rapid heartbeat, dizziness, severe headache, shortness of breath, or similar symptoms. (2)

Ephedra has been used traditionally for thousands of years in China. Its uses include acute nephritis, asthma and other lung problems, colds and flu, fever, chills, lack of perspiration, headache, nasal congestion, wheezing, and cough among others. (3) , (4) Recently, ephedra supplements have been under scrutiny due in part to the irresponsible use of ephedra products by some individuals and also due to the inappropriate advertising of ephedra products by some manufacturers. In fact, ephedra has been reviewed and in some cases regulated by several State Boards of Pharmacy for appropriate control and dosage of the supplement. (5) A recent laboratory animal study of one of the “herbal ecstasy” products reported that this ephedra product may actually produce an amphetamine-like stimulus. (6)

The safe dosage of ephedra and ephedra-containing products has been heavily debated. The quantity of ephedra alkaloids in dietary supplements, as reported on package labels, is typically around 8 to 25mg per serving, and the usual dosage frequency is two to three times per day and not more than 4 times per day. However, some products may contain larger or smaller amounts of ephedra alkaloids than are listed on the product label. In one study, 11 of 20 supplements tested either failed to list the alkaloid content on the label or had more than a 20 percent difference (either lower or higher) between the amount listed on the label and the actual amount. (7) It is also important to realize that usually the ephedra weight loss products contain other stimulating ingredients, such as caffeine, guarana and bitter orange (citrus aurantium) which contains synephrine.

There have not been many clinical studies conducted on this traditionally used herb. A recent review of 140 reports of adverse events related to the use of dietary supplements containing ephedra alkaloids was conducted. These reports were submitted to the FDA between June 1, 1997, and March 31, 1999. Thirty-one percent of cases were considered to be definitely or probably related to the use of supplements containing ephedra alkaloids, and 31 percent were deemed to be possibly related. Among the adverse events that were deemed definitely, probably, or possibly related to the use of supplements containing ephedra alkaloids, 47 percent involved cardiovascular symptoms and 18 percent involved the central nervous system. Hypertension was the single most frequent adverse effect (17 reports), followed by palpitations, tachycardia, or both (13); stroke (10); and seizures (7). Ten events resulted in death, and 13 events produced permanent disability, representing 26 percent of the definite, probable, and possible cases. It is worth noting that several of the reports reviewed in the study involved individuals with pre-existing medical conditions, including cardiovascular disease, which may have pre-disposed them to a significant adverse event. (8)

Some of the reported adverse events have been due to abuse. Yet some were also seen in healthy individuals and in individuals with pre-existing health problems. As stated, ephedra has been used traditionally for thousands of years without significant health problems. When used responsibly, ephedra can be considered a useful clinical agent. Individuals with certain pre-existing healthcare problems should only use ephedra-containing products under the supervision of a physician.

The high-incidence of adverse effects caused by Ephedra dietary supplements has led to the product being banned in Europe America and Asia countries such as Holland, Norway, Italy Austria, Japan and Venezuela while other countries make it available as prescription drug only. Example would be the United States of America banned ephedra in the year 2004 due death-related side effects caused by ephedra and the products replaced their content with bitter orange instead. (51),(52),(53)

Interactions and Depletions

Interactions

Dosage Info

Dosage Range

Dosages recommended by manufacturers and those typically used in clinical studies range from 8-25mg ephedra alkaloids per dose, no more than 4 times a day.

Tea: Made with 1 to 4 gm, 3 times daily. (9)

Tincture (1:1): medium single dose 5 gm. (10)

Extract: 1 to 3 ml, 3 times daily. (11)

Tincture (1:4): 6 to 8 ml, 3 times daily. (12)

Most Common Dosage

25mg ephedra alkaloids, 3 to 4 times per day.

American Herbal Products Association (AHPA) recommended dosage: do not exceed 25mg, 4 times per day.

Tea: Made with 1 gm, 3 times daily.

Tincture (1:1): medium single dose 5 gm.

Extract: 1 ml, 3 times daily.

Tincture (1:4): 6 ml, 3 times daily.

Standardization

[span class=doc]Standardization represents the complete body of information and controls that serve to enhance the batch to batch consistency of a botanical product, including but not limited to the presence of a marker compound at a defined level or within a defined range.[/span]

The most current available medical and scientific literature indicates that this dietary supplement should be standardized to 6 to 8% total ephedra alkaloids.

Uses

Frequently Reported Uses

  • Hayfever
  • Sinusitis

Other Reported Uses

  • Allergies
  • Nephritis
  • Weight Loss
  • Acute And Chronic Bronchoconstrictive Conditions
  • Asthma
  • Liver failure
  • Spinal cord injury

Toxicities & Precautions

General

In recommended dosages, ephedra has a long history of being safe. Exceeding the recommended dose will not improve results and may cause serious adverse health effects. (13) Recent reports suggest that ephedra is only safe for short term use. (49)

Health Conditions

Use with extreme caution in individuals with renal impairment, glaucoma, hypertension, cardiovascular disease, thyroid disease, diabetes, psychiatric disorders, seizure disorders, difficulty urinating or enlarged prostate. (14) , (15) , (16) , (17) , (18) , (19)

Side Effects

If abused, taken in high dosages, or taken in pre-existing cardiovascular diseases, ephedra may contribute to adverse events. There are several deaths reported from overdosage of ephedra. (20) , (21)

Symptoms of overdosage include heart palpitations, extreme nervousness, sweating, enlarged pupils, severe headache, dizziness, dyspnea, elevated body temperature, and ultimately death. (22)

Recent reports has suggested that ephedra taken at well controlled doses showed cardiovascular side effects such as increases in blood pressure, heart rate and mild palpitations. (50)

There has been a report of hepatitis associated with the use of ephedra. (23)

Pregnancy/ Breast Feeding

Use is contraindicated in pregnancy and lactation.

Age Limitations

This dietary supplement should not be used by anyone under 18 years of age.

Pharmacology

The effects of ephedra are attributed to the alkaloids, including ephedrine and pseudoephedrine. Ephedra alkaloids are potent sympathomimetic agents, stimulating Beta-1 and Beta-2 adrenergic receptors and the release of norepinephrine. The biological effects of ephedra at various dosages may include CNS stimulation, peripheral vasoconstriction, elevation of blood pressure, bronchodilation, cardiac stimulation (24) and increased pulse rate, decrease in intestinal tone and motility, mydriasis, and tachycardia. (25)

Products containing ephedra and the alkaloids ephedrine and pseudoephedrine are reported to increase weight loss, due to appetite suppression and an increase in thermogenic activity. In combination with methylxanthines such as caffeine, ephedra and its alkaloids may improve fat loss by dual actions: a central suppression of appetite and peripheral stimulation of energy expenditure covered by fat oxidation. (26) , (27) , (28) In a comparative trial, the weight loss produced by ephedrine and caffeine was similar to that of dexfenfluramine. (29) A laboratory animal study reported that the administration of ephedrine and caffeine promoted weight loss through an increase in energy expenditure, or in the more obese animals, a combination of an increase in energy expenditure and a decrease in food intake. (30) Also, the addition of aspirin to ephedra weight loss formulas may markedly potentiate the thermogenic properties of ephedra alkaloids, effects that led to a normalization of body composition. (31) More research on sympathomimetics and methylxanthines need to be carried out to identify combinations and dosage forms with improved efficiency and safety.

Of interest is that in one study, ephedrine plus caffeine produced a decline in total cholesterol levels and maintained HDL levels. (32) These clinical studies are conducted with the isolated constituent ephedrine, but the herb ephedra contains this alkaloid in levels of 30-90%, and a standardized dose should provide approximately 8mg of alkaloids. (33) It is also reported that a low-calorie diet combined with 180 mg ephedrine  and 600 mg caffeine per day produced a significant weight loss of 4.0 kg compared with a placebo group. (49)

Ephedra and its alkaloids ephedrine and pseudoephedrine as commonly used in managing the symptoms of asthma and have been used for this condition for thousands of years. (34) , (35) , (36) As stated, ephedra alkaloids have Beta-2 adrenergic receptor activity, causing bronchodilation. (37) Studies using a combination of the isolated alkaloid ephedrine with pharmaceutical bronchodilators such as theophylline have reported positive results in the management of asthma. (38) , (39)

The alkaloids of ephedra have been successfully used as decongestants in nonprescription medicines for quite some time. (40) , (41) Ephedra and its alkaloids cause vasoconstriction in the nasal passages, decreasing nasal congestion and enhancing ease of air flow. (42) Studies using a combination of the isolated alkaloid pseudoephedrine with antihistaminic agents such as terfenadine and loratadine have reported positive results in the management of symptoms of allergic rhinitis. (43) , (44)

Althouth Ephedra has been reported to cause hepatitis in a case report, it is reported to play a role in severe hepatic failure because of its ability to inhibit TNF-α production and protease enzymes involved in apoptosis. (47)

Ephedra is used in China for nephritis, supported by reports that ephedra blocks activation in both the classical and alternative pathway of complement. (45) The role played by ephedra in regards to innate immune system was reported in a study involving rats with spinal cord injury whereby they showed significant motor function improvement through inhibition of the system when treated with ephedra. (48)

References

  1. View Abstract: Gurley BJ, et al. Ephedrine-type alkaloid content of nutritional supplements containing Ephedra sinica (Ma-huang) as determined by high performance liquid chromatography. J Pharm Sci. Dec1998;87(12):1547-53.
  2. American Herbal Products Association. Current Trade Recommendations, AHPA Code of Ethics and Business Conduct. Silver Spring, MD: American Herbal Products Association; Mar1994.
  3. View Abstract: Kalix P. The pharmacology of psychoactive alkaloids from ephedra and catha. J Ethnopharmacol. Apr1991;32(1-3):201-8.
  4. View Abstract: Chan EL, et al. History of medicine and nephrology in Asia. Am J Nephrol. 1994;14(4-6):295-301.
  5. View Abstract: Adverse Events Associated with Ephedrine-Containing Products–Texas, December 1993-September 1995. Morbidity Mortality Weekly Report MMWR. Aug1996;45(32):689-92.
  6. View Abstract: Glennon RA, et al. (+)Amphetamine-stimulus generalization to an herbal ephedrine product. Pharmacol Biochem Behav. Apr2000;65(4):655-8.
  7. View Abstract: Gurley BJ, Gardner SF, Hubbard MA. Content versus label claims in ephedra-containing dietary supplements. Am J Health Syst Pharm. May2000;57(10):963-9.
  8. View Abstract: Haller CA, Benowitz NL. Adverse Cardiovascular and Central Nervous System Events Associated with Dietary Supplements Containing Ephedra Alkaloids. N Engl J Med. Dec2000;343(25):1833-8.
  9. PDR for Herbal Medicines, 2nd ed. Montvale, NJ: Medical Economics Company; 2000:489.
  10. PDR for Herbal Medicines, 2nd ed. Montvale, NJ: Medical Economics Company; 2000:489.
  11. PDR for Herbal Medicines, 2nd ed. Montvale, NJ: Medical Economics Company; 2000:489.
  12. PDR for Herbal Medicines, 2nd ed. Montvale, NJ: Medical Economics Company; 2000:489.
  13. View Abstract: Haller CA, Benowitz NL. Adverse Cardiovascular and Central Nervous System Events Associated with Dietary Supplements Containing Ephedra Alkaloids. N Engl J Med. Dec2000;343(25):1833-8.
  14. LaValle JB, et al. Natural Therapeutics Pocket Guide. Hudson, OH: LexiComp, Inc; 2000:429-430.
  15. View Abstract: Powell T, et al. Ma-huang strikes again: ephedrine nephrolithiasis. Am J Kidney Dis. Jul1998;32(1):153-9.
  16. View Abstract: Zaacks SM, et al. Hypersensitivity myocarditis associated with ephedra use. J Toxicol Clin Toxicol. 1999;37(4):485-9.
  17. Jacobs KM, et al. Psychiatric complications of Ma-huang. Psychosomatics. Jan2000;41(1):58-62.
  18. Capwell RR. Ephedrine-induced mania from an herbal diet supplement. Am J Psychiatry. Apr1995;152(4):647.
  19. View Abstract: Harada M, et al. Contribution of alkaloid fraction to pressor and hyperglycemic effect of crude Ephedra extract in dogs. J Pharmacobiodyn. Sep1981;4(9):691-9.
  20. Thoeharides TC. Sudden death of a healthy college student related to ephedrine toxicity from a ma huang-containing drink. J Clin Psychopharmacol. Oct1997;17(5):437-9.
  21. View Abstract: Gurley BJ, et al. Ephedrine pharmacokinetics after the ingestion of nutritional supplements containing Ephedra sinica (ma huang). Ther Drug Monit. Aug1998;20(4):439-45.
  22. PDR for Herbal Medicines, 2nd ed. Montvale, NJ: Medical Economics Company; 2000:489.
  23. View Abstract: Nadir A, et al. Acute hepatitis associated with the use of a Chinese herbal product, ma-huang. Am J Gastroenterol. Jul1996;91(7):1436-8.
  24. View Abstract: Haller CA, Jacob P 3rd, Benowitz NL. Pharmacology of ephedra alkaloids and caffeine after single-dose dietary supplement use. Clin Pharmacol Ther. Jun2002;71(6):421-32.
  25. View Abstract: White LM, et al. Pharmacokinetics and cardiovascular effects of ma-huang (Ephedra sinica) in normotensive adults. J Clin Pharmacol. Feb1997;37(2):116-22.
  26. View Abstract: Atkinson RL, et al. Combined drug treatment of obesity. Obes Res. Nov1995;3(Suppl 4):497S-500S.
  27. View Abstract: Astrup A, et al. Pharmacological and clinical studies of ephedrine and other thermogenic agonists. Obes Res. Nov1995;3(Suppl 4):537S-540S.
  28. View Abstract: 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. May2002;26(5):593-604.
  29. View Abstract: 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. Feb1994;18(2):99-103.
  30. View Abstract: Ramsey JJ, et al. Energy expenditure, body composition, and glucose metabolism in lean and obese rhesus monkeys treated with ephedrine and caffeine. Am J Clin Nutr. Jul1998;68(1):42-51.
  31. View Abstract: Dulloo AG, et al. Aspirin as a promoter of ephedrine-induced thermogenesis: potential use in the treatment of obesity. Am J Clin Nutr. Mar1987;45(3):564-9.
  32. View Abstract: 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. May1994;18(5):329-32.
  33. Leung A, et al. Encylopedia of Common Natural Ingredients Used in Foods, Drugs, and Cosmetics. New York: Wiley-Interscience Publication; 1996:227-229.
  34. Faurshou M, et al. The bronchodilating effect of ephedrine tablets in bronchial asthma. Ugeskr Laeger. Nov1993;155(46):3784-5.
  35. View Abstract: Laitinen LA, et al. A comparison of the bronchodilator action of pseudoephedrine and ephedrine in patients with reversible airway obstruction. Eur J Clin Pharmacol. 1982;23(2):107-9.
  36. Redman CM, et al. Nonprescription bronchodilator use in asthma. Chest. Aug1998;114(2):657-8.
  37. View Abstract: Vansal SS, et al. Direct effects of ephedrine isomers on human beta-adrenergic receptor subtypes. Biochem Pharmacol. Sep1999;58(5):807-10.
  38. Direkwattanachai C, et al. Sustained release theophylline and ephedrine therapy in chronic asthma. J Med Assoc Thai. Oct1986;69(Suppl 2):31-7.
  39. View Abstract: Owen S, et al. A controlled trial of an oral bronchodilator preparation (‘Franol’) in asthma. Pharmatherapeutica. 1988;5(4):240-5.
  40. Mullarkey MF. A clinical approach to rhinitis. Med Clin North Am. Sep1981;65(5):977-86.
  41. View Abstract: Hamilton LH, et al. A study of sustained action pseudoephedrine in allergic rhinitis. Ann Allergy. Feb1982;48(2):87-92.
  42. View Abstract: Kalix P. The pharmacology of psychoactive alkaloids from ephedra and catha. J Ethnopharmacol. Apr1991;32(1-3):201-8.
  43. View Abstract: Panda NK, et al. Comparative efficacy and safety of terfenadine with pseudoephedrine and terfenadine alone in allergic rhinitis. Otolaryngol Head Neck Surg. Feb1998;118(2):253-5.
  44. View Abstract: Corren J, et al. Efficacy and safety of loratadine plus pseudoephedrine in patients with seasonal allergic rhinitis and mild asthma. J Allergy Clin Immunol. Dec1997;100(6 Pt 1):781-8.
  45. View Abstract: Ling M, et al. A component of the medicinal herb ephedra blocks activation in the classical and alternative pathways of complement. Clin Exp Immunol. Dec1995;102(3):582-8.
  46. K. Raz, B. Einat, S. Or, S. Yaron, B.S Shimon, L. Efraim. Composition and stereochemistry of ephedrine alkaloids accumulation in Ephedra sinica Stapf. Photochemistry, In Press, Corrected Proof, Available online 24 April 2010
  47. Y. Ikuhiro, G. Takashi, T. Satoko, O. Shigetoshi, Y. Kazuo, S. Tomomi, K. Ei, S. Daisuke, S. Wataru, D. Takahiro, A. Yumiko, I. Hajime, O. Hirohide. Mao (Ephedra sinica Stapf) protects against d-galactosamine and lipopolysaccharide-induced hepatic failure. Cytokine, Volume 41, Issue 3, March 2008, Pages 293-301
  48. L. Liangman, L. Jingbo, Z. Yue, F. Guangyu. Ephedra sinica inhibits complement activation and improves the motor functions after spinal cord injury in rats. Brain Research Bulletin, Volume 78, Issues 4-5, 16 March 2009, Pages 261-266
  49. K. Ho-Jun, P. Jung-Mi, K. Jin-Ah, K. Byeong-Pyo. Effect of Herbal Ephedra sinica and Evodia rutaecarpa on Body Composition and Resting Metabolic Rate: A Randomized, Double-blind Clinical Trial in Korean Premenopausal Women. Journal of Acupuncture and Meridian Studies, Volume 1, Issue 2, December 2008, Pages 128-138
  50. A. Richard, C. Preety, B. L. David.  Cardiovascular Effects of Ephedra Alkaloids: A Comprehensive Review. Progress in Cardiovascular Diseases, Volume 47, Issue 4, January-February 2005, Pages 217-225
  51. U.S. Food and Drug Administration. April 12, 2004. http://web.archive.org/web/20080115020749/www.fda.gov/bbs/topics/NEWS/2004/NEW01050.html. Accessed on 27th January 2009.
  52. R. Carol (March–April 2004). “Ephedra Ban: No Shortage of Reasons”. FDA Consumer. http://web.archive.org/web/20071216000326/www.fda.gov/FDAC/features/2004/204_ephedra.html. Accessed on 27th January 2009.
  53. D. Mary. Bitter Orange Under Scrutiny as New Ephedra. New York Times. http://www.nytimes.com/2005/10/11/health/policy/11cons.html. Accessed on 3rd November 2008.

in this scope
Malaysian Herbal Monograph​
Medicinal Herbs & Plants Monographs​
Traditional Chinese Medicine Herbs (Professional Data)
Herbal Medicines Compendium (HMC) - U.S​

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