MCWtrainer

There has been much talk on ephedra and ephedrine lately on the boards so I figured I would put some information up about them...

Ephedra/ephedrine: cardiovascular and CNS effects

Reason for posting: Health Canada warns that some over-the-counter supplements used to increase energy and promote weight loss and bodybuilding pose a serious risk to health.1 The warning applies to supplements containing the herb ephedra or its alkaloid derivative, ephedrine; in Canada, ephedrine is authorized for use only as a nasal decongestant.

More than 60 adverse events — suicide, psychotic episodes, seizure, stroke and cardiovascular events ranging from hypertension to myocardial infarction — have been reported in Canada.2 Other recognized adverse effects include anxiety, tremors, headaches, insomnia and flushing.3 An independent analysis of 140 adverse events reported to the US Food and Drug Administration (FDA) between June 1997 and March 1999 found that 47% involved the cardiovascular system and 18% the central nervous system (CNS).4 Health Canada has recalled unapproved herbal preparations containing more than the recommended dose of ephedrine.1,2,3,5 In addition, the manufacturers of approved commercial higher-dose preparations are being asked to submit data demonstrating their safety and efficacy.2

The drugs: Ephedra sinica, also known as ma huang, is the source of the alkaloid ephedrine. Other related ephedra alkaloids not encompassed by the current advisory include pseudoephedrine, norpseudoephedrine, methylephedrine and norephedrine (also known as phenylpropanolamine, a nasal decongestant taken off the market in 2001 because of its association with hemorrhagic stroke6). In traditional Asian medicines, ephedra-based products are sometimes used as bronchodilators.

Ephedrine is a sympathomimetic drug prescribed as a nasal decongestant, with properties similar to epinephrine; its effects on both a- and b-adrenergic receptors and its central effects resemble those of amphetamines (see figure).7 The adverse effects of ephedrine are hypothesized to be related to coronary artery constriction, vasospasm, shortening of cardiac refractory periods allowing re-entrant cardiac arrhythmias, hypertension -induced subarachnoid hemorrhage, cerebral artery vasoconstriction and sympathomimetic -induced platelet activation.4

Products containing ephedrine are not to be used by people with heart disease, hypertension, diabetes, thyroid disease, enlarged prostate, anxiety and restlessness or glaucoma, people taking monoamine oxidase inhibitors or women who are pregnant or lactating.

Ephedrine often exists in unapproved herbal preparations that also contain caffeine (sometimes called "herbal ecstasy") and ASA. These combination products may augment ephedrine's cardiac and CNS effects8 and should not be used.3

Hundreds of unapproved products containing ephedra or ephedrine exist, including ma huang, E. sinica, Sida cordifolia and epitonin.3 Approved preparations, mostly nasal decongestants, range in dose from 0.13 to 25 mg per tablet. Health Canada recommends that the dose be restricted to 8 mg of ephedrine per dose and 32 mg per day, for a period no longer than 7 days.1

What to do: Physicians should ask about the use of over-the-counter herbal and dietary supplements, particularly if patients want to lose weight, improve their exercise tolerance, seek extended periods of wakefulness (such as long-distance truck drivers) or use traditional remedies. Products containing ephedra or ephedrine are currently marketed only as nasal decongestants, and health claims pertaining to appetite suppression and other supposed benefits are not allowed. Enquiries about concurrent sources of caffeine (e.g., green tea, cola nut, yerba mate and yohimbe3) may also be warranted. Patients using products containing ephedra or ephedrine, especially in doses above the recommended limits, should be warned of the potential serious adverse events. Health Canada also recommends that patients use only approved products — those with a drug identification number (DIN).

Eric Wooltorton Editorial Fellow, CMAJ Barbara Sibbald Associate Editor (News), CMAJ

References

Health Canada requests recall of certain products containing Ephedra/ephedrine. Ottawa: Health Canada; 2002 Jan 9. Available: http://www.hc-sc.gc.ca/english/prote...2/2002_01e.htm (accessed 2002 Feb 5).
Ephedra/ephedrine — frequently asked questions. Ottawa: Health Canada; Jan 2002. Available: www .hc-sc.gc.ca/english/protection/warnings /2002 /2002 _01 ebk2.htm (accessed 2002 Feb 5).
Advisory not to use products containing Ephedra or ephedrine. Ottawa: Health Canada; 2001 Jun 14. Available: http://www.hc-sc.gc.ca/english/prote...1/2001_67e.htm (accessed 2002 Feb 5).
Haller CA, Benowitz NL. Adverse cardiovascular and central nervous system events associated with dietary supplements containing ephedra alkaloids. N Engl J Med 2000;343:833-8.
Sibbald B. Voluntary recall of ephedra products not enough, MD says. CMAJ 2002;166(2):225. Available: www.cma.ca/cmaj/vol-166/issue-2/0225.asp[Free Full Text]
Health Canada withdraws drug products containing phenylpropanolamine (PPA) from the market. Ottawa: Health Canada; 2001 May 30. Available: www .hc -sc.gc.ca/english/protection/warnings /2001 /2001 _61 e .htm (accessed 2002 Feb 5).
Ephedrine HCl. In: Compendium of pharmaceuticals and specialties. 36th ed. Ottawa: Canadian Pharmacists Association, 2001.
Smith M. Ma huang. In: Herbs: everyday reference for health professionals. Ottawa: Canadian Pharmacists Association and CMA; 2000. p. 153-5.

This article was too long to post so here is the link...

http://jama.ama-assn.org/cgi/content/full/289.12.1537v1


CYCLING PERFORMANCE TIPS
Ephedra and Ephedrine for Athletic Performance Enhancement
Clinical Efficacy and Side Effects
Source Under its Evidence-based Practice Program, the Agency for Healthcare Research and Quality (AHRQ) developes scientific information for other agencies and organizations on which to base clinical guidelines, performance measures, and other quality improvement tools.
Overview AHRQ addressed research questions regarding the efficacy of herbal ephedra and ephedrine for athletic performance through a comprehensive literature review and synthesis of evidence. They assessed the safety of these products through review of clinical trials. Meta-analysis was performed where appropriate. In addition, they reviewed herbal ephedra- and ephedrine-related adverse events reports on file with the U.S. Food and Drug Administration (FDA), published case reports, and reports to a manufacturer of ephedra-containing products.

After searching published reports, journal articles, conference presentations, and various sources of unpublished studies, AHRQ identified 52 controlled clinical trials of ephedrine or herbal ephedra for weight loss or athletic performance in humans. The FDA provided copies of over 1,000 adverse event reports (AERs) related to herbal ephedra and 125 AERs related to ephedrine.

Efficacy for Physical Performance Enhancement: The effect of ephedrine on athletic performance was assessed in seven studies. No studies have assessed the effect of herbal ephedra-containing dietary supplements on athletic performance. The few studies that assessed the effect of ephedrine on athletic performance have, in general, included only small samples of fit individuals (young male military recruits) and have assessed the effects only on very short-term immediate performance. Thus, these studies did not assess ephedrine as it is used in the general population. The data support a modest effect of ephedrine plus caffeine on very short-term athletic performance. No studies have assessed the sustained use of ephedrine on performance over time. The only study that assessed the additive effects of these agents reported that ephedrine must be supplemented with caffeine to affect athletic performance.

Safety Issues: The data on adverse events were drawn from clinical trials and case reports published in the literature, submitted to the FDA, and reported to Metabolife, a manufacturer of ephedra-containing supplement products. The strongest evidence for causality should come from clinical trials; however, in most circumstances, such trials do not enroll sufficient numbers of patients to adequately assess the possibility of rare outcomes. Such was the case with our review of ephedrine and ephedra-containing dietary supplements. Even in aggregate, the clinical trials enrolled only enough patients to detect a serious adverse event rate of at least 1.0 per 1,000.

For rare outcomes, we reviewed case reports, but a causal relationship between ephedra or ephedrine use and these events cannot be assumed or proven. Evidence from controlled trials was sufficient to conclude that the use of ephedrine and/or the use of ephedra-containing dietary supplements or ephedrine plus caffeine is associated with two to three times the risk of nausea, vomiting, psychiatric symptoms such as anxiety and change in mood, autonomic hyperactivity, and palpitations. The majority of case reports are insufficiently documented to make an informed judgment about a relationship between the use of ephedrine or ephedra-containing dietary supplements and the adverse event in question. For prior consumption of ephedra-containing products, AHRQ identified two deaths, three myocardial infarctions, nine cerebrovascular accidents, three seizures, and five psychiatric cases as sentinel events; for prior consumption of ephedrine, AHRQ identified three deaths, two myocardial infarctions, two cerebrovascular accidents, one seizure, and three psychiatric cases as sentinel events. AHRQ identified 43 additional cases as possible sentinel events with prior ephedra consumption and seven additional cases as possible sentinel events for prior ephedrine consumption. About half the sentinel events occurred in persons aged 30 years or younger. Classification as a sentinel event does not imply a proven cause and effect relationship.

AHRQ did not assess the plethora of additional symptoms that have been reported in the published literature and the FDA Medwatch file for ephedra-containing dietary supplements and ephedrine products. Availability of Full Report: Printed copies may be obtained free of charge from the AHRQ Publications Clearinghouse by calling 800-358-9295. Requesters should ask for Evidence Report/Technology Assessment No. 76, Ephedra and Ephedrine for Weight Loss and Athletic Performance Enhancement: Clinical Efficacy and Side Effects. The Evidence Report can also be downloaded as a zipped Word® or PDF file online at: http://www.ahrq.gov/clinic/evrptfiles.htm#ephedra.


Ephedra (Ephedrine Sulfate)
Also known as: Ephedra, Ephedra Sinica, Ma-huang, Desert Herb, Joint Fir, Popotillo, Sea Grape, Teamster’s Tea, Yellow horse, Epitonin, Ephedrine, PPA

Historical Perspective: Ephedra Sinica is an herb which has been used in traditional Chinese medicine for over 5,000 years and is considered the world’s oldest medicine. Healers have used this herb to treat asthma, coughs, colds, and induce sweating. Most naturally growing ephedra is found in
temperate climates, in China, Mongolia, Southern Siberia and Japan, usually on sandy seashores. On Dec.30, 2003, the Food and Drug Administration (FDA) issued a consumer alert on the safety of dietary
supplements containing ephedra. The alert advised consumers to immediately stop buying and using ephedra products. On April 12, 2004, FDA announced that the fi nal rule went into effect prohibiting the sale of dietary supplements containing ephedra alkaloids (ephedra) because these supplements present an unreasonable risk of illness or injury. Copies of the consumer alert, notice letter to ephedra manufacturers, and press releases, and other documents about FDA’s Actions on ephedra can be found at http://www.fda.gov/oc/initiatives/ephedra/.

Common Uses: Aid in weight loss, increase energy, sexual enhancement and produce euphoria.
Ephedrine is used medicinally for the relief of asthma, allergies, colds, and hay fever (available in overthe-
counter cold remedies).

Form(s) Used: The primary form of ephedra is in tablet or capsule form. Ephedra is not commonly available in its pure form, but in combination with several other ingredients -- other ingredients include
caffeine in the following forms: guarana, guara concentrate extract, kola and kola nut. Stevia and garcinia cambogia can also be found in ephedra containing supplements.

Potential Side Effects: Ephedra may cause addiction, headache, insomnia, nervousness, agitation, dizziness, vomiting, diffi cult urination, manic episodes, kidney stones, hepatitis, high blood pressure,
heart palpitations, tachycardia, heart attack, stroke and death. Side effects of ephedra use are often intensifi ed by the other ingredients commonly available as an additive to the product, such as caffeine.

Food-Drug-Supplement Interactions: MAO inhibitors, digoxin, caffeine, over-the-counter cold remedies, and stimulants.

Contraindication to Use: Pregnancy, breast feeding, Graves’ disease, high blood pressure, heart disease and obesity.

Research Data on Safety and Effi cacy: Case studies on hundreds of individuals indicate that ephedra and ephedra-containing products are not safe for use. The FDA lists ephedra as a potentially dangerous supplement on its warnings and safety information page, and has proposed safety
measures for manufacturers of ephedra-containing products. Many sport associations, including the International Olympic Committee, have banned ephedra use.

Bottom Line: Ephedra is not recommended for use due to it’s serious, life-threatening side effects. It is illegal for manufacturers to sell and distribute dietary supplements containing ephedra.

Bottom Line: Ephedra is not recommended for use due to it’s serious, life-threatening side effects. It is illegal for manufacturers to sell an distribute dietary supplements containing ephedra.

http://chppm-www.apgea.army.mil/dhpw/Wellness.aspx
USACHPPM Directorate of Health Promotion and Wellness
DIETARY SUPPLEMENT FACT SHEET

References:
1. American Journal of Addictions, Fall 1998, 7 (4): 256-61.
2. American Journal of Kidney Diseases, Jul 1998, 32 (1):153-9.
3. British Medical Journal, 21 SEP 1996, 313 (7059), p. 756.
4. Journal of Emergency Medicine, 17 (2):289-91, 1999 Mar-Apr.
5. The American Journal of Psychiatry, NOV 1998, 155 (11), p 1627.
6. The New England Journal of Medicine, 5 APR 2001, 344 (14), pp 1095-1097.


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