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• To state the key elements of the American Society for Clinical Pharmacology and Therapeutics position on the potential clinical relevance of the use of ephedra and actions designed to protect Americans and Canadians with use of dietary supplement products containing ephedra.

• Not specified.

• Not specified.

• No search procedures were specified
• Was study quality assessed? Study quality reviewed and categorized by sample size and research design.

Types of interventions and outcomes investigated, populations included:

1. Harm as a result of ephedra or ephedra-containing products
2. Appropriateness of using warning labels to enhance the safe use of ephedra
3. Clinical utility of ephedra use.

Outcome(s) and other measures

What type of information was abstracted from articles? Outcomes reviewed were:

1. Weight loss
2. Athletic performance enhancement
3. Product safety.

No meta-analysis or synthesis of data was completed.

• The ratio of number of articles included to number of articles identified was not reported.
• Nineteen citations were given.
• Three government proposed and final rulings on the use and/or labeling of ephedra.
• Two case report studies
• One comprehensive data base search for adverse effects
• One case-control study
• One observational
• Six randomized control or non-randomized control studies
• One editorial
• Two review articles.
• One Evidence Report/Technology Assessment published by the Agency for Healthcare Research and Quality on the use of ephedra and ephedrine for weight loss and athletic performance enhancement.
• One book chapter citation.

Of the randomized control or nonrandomized studies, samples sizes ranged from 8 to 67 (where there were 32 subjects receiving ephedra; Of the 32 subjects, only 24 completed an 8-week trial (i.e., 25% drop out rate).

Only adult subjects are reported in the references. One study applies ephedra into human umbilical cord cells to evaluate effect.

Ephedrine is a direct ad indirect alpha- and Beta-adrenergic agonist that mimics the effects of sympathetic stimulatin in the periphery and acts as a potent central nervous system stimulant.

Physiological responses are to increase blood pressure, promote cardiac arrhythmias, bronchodilation, inhibit bladder emptying, and cause amphetamine-like central nervous system stimulation with insomnia, agitation, and pscyhosis.

Herbal supplements that contain caffeine and ephedrine (e.g., ma huang) are available.

There is clear evidence of an association between ephedra and serious cardiovascular and central nervous system toxicity resulting in death and disability.

• Haller CA, Benowitz NL, N Engl J Med, 2000.

SERIOUS SIDE EFFECTS

• Clinical reports of associated mania ( a case study), sudden hearing loss (a case study), increase risk of hemorrhagic stroke, heat stroke associated with CV collapse and death (case study) and CNS and cardiovascular events (n=8 cases) Haller CA, Jacob P, Benowitz NL, Clin Pharmacol Ther, 2003).
• A comparative case studies series risk study indicated that the relative risk for adverse reactions from ephedra was considerably > than from kava, Ginkgo biloba or all supplements combined.

APPROPRIATENESS OF WARNING LABELS AS A MEANS FOR ENSURING PUBLIC SAFETY

• Information not abstracted as it is not related to evidence analysis question being asked.

MAINTAINING AVAILABILITY OF EPHEDRA-CONTAINING PRODUCTS TO THE PUBLIC

• Information not abstracted as it is not related to evidence analysis question being asked.

AVAILABILITY OF CLINICAL RESEARCH DEMOSNTRATING THE DANGERS OF EPHEDRA-CONTAINING PRODUCTS

• [There is] a substantial body of objective scientific data describing the clnical pharmacology of ephedrine, its pattern of use, and its potential adverse event profile.
• Sources include: 1 book chapter by Hoffman BB et al, 1996; 1 study by Haller CA et al, 2000; and all of the citations summarized above, excluding the public policy and FDA register documentations.

As stated by the author in body of report:

• “To conduct additional controlled clinical trials of products containing ephedra when the content of active ingredient (i.e., potency), the original source of the drug, or specific knowledge of its processing and manufacture is not known would be virtually impossible outside of the boundaries of FDA-mandated drug development.
• “The potential for risk in the absence of any apparent direct benefit associated with the investigation of a pharmacologically inferior product makes the conduct of such a clinical trial ethically questionable.”
• “The position of ASCPT is ... in the absence of objective scientific information that demonstrates a unique and potentially important therapeutic role for products containing ephedra or its alkaloids, these products should be removed from the marketplace.

• Strength is the comprehensive Evidence-based technical report and comprehensive data base search of adverse reports.
• Another strength is that a separate research organization (RAND) reached similar conclusions.
• Generalizability limited to adults; and there is unreliability when applied to other ethnic groups.
• A weakness is that there is no discussion or reference to how ASCPT arrives at member consensus position papers. Seven persons were named and only one was a PharmD, PhD.