An Overview of Ephedra

NUTR 547- Nutrition Update Kim McCorquodale Summer 2006

In the News
Ephedra Ban Puts Market on Notice
CBS News- 12/31/2003

The FDAs Latest Scapegoat: Ephedra

Idaho Observer -1/2004

FDAs Ephedra Ban Takes Effect

MD Medical News -4/12/2004

Web

We have a tremendous burden of proof in order to take supplements off of the market. We crossed the ts and dotted the is so that the ephedra ban should stand up in court.
Human Services Secretary Tommy Thompson

In the News
FDA Ban on Ephedra Overturned
Seattle Times -4/15/2005

FDA Wants Ephedra Ban Restored

CBS News -5/9/2006

Chinese Point Finger and Laugh at Stupid Americans

Weve had this stuff for like 5000 years. The Americans get it for a few decades and screw it all up. Morons.
Zhou Li Quing- spokesperson for the Chinese Herbal Safety Committee -12/03/2003

Ephedra
Ephedraceae sinica

An evergreen shrub native to central Asia Predominant active alkaloid- ephedrine Other active alkaloids include:
pseudoephedrine norephedrine norpseudoephedrine

Traditional Uses of ephedra (ma huang)

Tea prepared from dried, comminuted branches Used for ~5000 yrs. by practitioners of traditional Chinese medicine (TCM) to treat asthma, flu, and nasal congestion Combined with other herbs to enhance or decrease effects

History of Conventional Uses of Ephedra

1887- Ephedrine first isolated by Japanese chemist, N. Nagai 1920s- Series of studies on ephedrines pharmacological properties leads to synthetic production 1927- Widely used as a nasal decongestant, central nervous system stimulant, and to treat bronchial asthma 1950s- Many reports of side effects such as blood pressure and heart rate lead pharmaceutical companies to switch to pseudoephedrine

Physiological Effects

Strong stimulant- enhances the release of norepinephrine (NE) from sympathetic nerve endings (see handout) Has 1 and 2 agonist activityrelaxes bronchial muscles Has 1, 2, 1, and 2 adrenergic activityleads to less desirable effects such as blood pressure, heart rate, and nervousness To compensate, the body releases adenosine and prostaglandin (PG) which inhibit the release of NE

Physiological Effects
Caffeine and aspirin may inhibit and/or reduce the effects of adenosine and PG continued NE activation ECA stack
ephedrine alkaloids (ma huang) caffeine (Gaurana, Bissey Nut, Kola) aspirin/salicin (Willow Bark extract)

Reported Benefits
Increased weight loss due to thermogenic effect
Enhanced athletic performance Increased energy

3 billion servings sold during 1999

12 million people using ephedra

Adverse Effects

Dizziness, tremors, irregular heart rate myocardial infarctions, strokes May induce psychological dependence 1993-2003- FDA documented 2,277 adverse event reports (AER) concerning cardiovascular, neurological and psychiatric effects (~1% of total?) Type A AE- directly related to the pharmacological actions of the active ingredient Type B AE- rare and difficult to separate from preexisting conditions; cause/effect hard to prove

Sound the Alarm!

1990s- Government and herbal agencies attempt to

decrease intake (warning labels, dosage limits, prohibit combination with caffeine)

the sale of dietary supplements containing ephedra (didnt apply to use in TCM) April 2005- Ban overturned in Utah federal court for doses 10 mg; sent back to FDA to determine safe and dangerous levels

2003- RAND report published April 12, 2004- FDAs Final Rule effectivebanning

Efficacy and Safety of Ephedra and Ephedrine for Weight Loss and Athletic Performance:
A Meta-analysis Performed by the Southern California Evidencebased Practice Center-RAND Published in Journal of American Medical Association on March 23, 2003

Efficacy and Safety of Ephedra and Ephedrine for Weight Loss and Athletic Performance: A meta-analysis. JAMA(2003)289:12

Objective: Assess the efficacy and safety of ephedra and ephedrine

used for weight loss and enhanced athletic performance

Data Sources: Searched 9 databases (including unpublished trials

and non-English documents) for any related studies; adverse events (AE) reported to the FDA included

Study Selection: Controlled trials for weight loss (min. 8 week

follow-up) or athletic performance (no min. follow-up); case report for adverse events included if: 1)strong evidence ephedra taken within 24 hrs. prior to event 2)alternative explanations were ruled out -of 530 screened articles, 52 controlled trials and 65 case reports included in AE analysis -of > 18,000 other case reports screened, 284 reviewed in detail

Efficacy and Safety of Ephedra and Ephedrine for Weight Loss and Athletic Performance: A meta-analysis. JAMA(2003)289:12

Data Extraction:

Trials identified independently by 2 reviewers Case reports reviewed with explicit and implicit methods

Data Synthesis:

No trials of ephedra and athletic performance found that met criteria Safety data yielded estimates of 2.2- to 3.6-fold increases in odds of psychiatric, autonomic, or GI symptoms, and heart palpitations Insufficient data for conclusions about AE at a rate les than 1.0 per thousand Majority of case reports insufficiently documented

Efficacy and Safety of Ephedra and Ephedrine for Weight Loss and Athletic Performance: A meta-analysis. JAMA(2003)289:12

Weight Loss achieved using ephedra, ephedrine containing products greater than placebo Category
ephedrine1 ephedrine1 + caffeine ephedra2 ephedra2 + herbs3
1derived 2derived

Sample size 5 12 1 4

Weight Loss (kg/mo) 0.6 1.0 0.8 1.0

95% CI 0.2-1.0 0.7-1.3 0.4-1.2 0.6-1.3

from pharmaceutical sources from botanical sources 3caffeine containing herbs

Efficacy and Safety of Ephedra and Ephedrine for Weight Loss and Athletic Performance: A meta-analysis. JAMA(2003)289:12

Conclusions:
Ephedrine and ephedra promote modest shortterm weight loss (~0.9 kg/mo > than placebo)

No data regarding long-term weight loss

Insufficient evidence to support use for athletic performance

Use with caffeine is associated with increased risk of psychiatric, autonomic, or gastrointestinal symptoms, and heart palpitations

Content versus label claims in ephedra-containing dietary supplements

- BJ Gurley, SF Gardner, and MA Hubbard
- American Journal of Health-System Pharmacy(2000) 57:10

Content versus label claims in ephedra-containing dietary supplements (abstract). Am J of Health-System Pharmacy (2000) 57:10

Specific Aim: To determine the content of ephedra alkaloids in herbal dietary supplements containing ephedra (ma huang). Study Design: The contents of ephedrine, pseudoephedrine, methylephedrine, norephedrine, and norpseudoephedrine were measured in 20 ephedra-containing supplements using highperformance liquid chromatography

Content versus label claims in ephedra-containing dietary supplements (abstract). Am J of Health-System Pharmacy (2000) 57:10

Results:
total alkaloid content varied considerably (0.018.5 mg/dosage unit) Observed significant lot-to-lot variations in alkaloid content for 4 products 10 supplements exhibited discrepancies between the label claim for alkaloid content and the actual alkaloid content in excess of 20% One product was devoid of ephedra alkaloids

Content versus label claims in ephedra-containing dietary supplements (abstract). Am J of Health-System Pharmacy (2000) 57:10

Conclusion: Assay of 20 ephedra-containing dietary supplements showed that alkaloid content often differed markedly from label claims and was inconsistent between 2 lots of some products.

Summary and Recommendations

1) 2) 3) 4)

Slight short-term wt.loss Athletic enhancement? adverse events Dosage level? Thus
High cost/benefit ratio Official positions

Summary

Market forces

Conventional sales Internet Sales

Is it legal?

TCM Still under appeal

The End not