An Overview of Ephedra

An Overview of Ephedra

اسلاید 1: www.tabaye.ir

اسلاید 2: NUTR 547- Nutrition UpdateKim McCorquodaleSummer 2006An Overview of Ephedra

اسلاید 3: Ephedra Ban Puts Market on Notice CBS News- 12/31/2003The FDA’s Latest Scapegoat: Ephedra Idaho Observer -1/2004FDA’s Ephedra Ban Takes Effect Web MD Medical News -4/12/2004“We have a tremendous burden of proof in order to take supplements off of the market. We crossed the t’s and dotted the i’s so that the ephedra ban should stand up in court.” Human Services Secretary Tommy ThompsonIn the News…

اسلاید 4: FDA Ban on Ephedra Overturned Seattle Times -4/15/2005FDA Wants Ephedra Ban Restored CBS News -5/9/2006Chinese Point Finger and Laugh at Stupid Americans “We’ve 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 -12/03/2003In the News…

اسلاید 5: Ephedra Ephedraceae sinicaAn evergreen shrub native to central AsiaPredominant active alkaloid- ephedrineOther active alkaloids include: pseudoephedrine norephedrine norpseudoephedrine

اسلاید 6: Tea prepared from dried, comminuted branches Used for ~5000 yrs. by practitioners of traditional Chinese medicine (TCM) to treat asthma, flu, and nasal congestionCombined with other herbs to enhance or decrease effectsTraditional Uses of ephedra (ma huang)

اسلاید 7: History of Conventional Uses of Ephedra1887- Ephedrine first isolated by Japanese chemist, N. Nagai1920’s- Series of studies on ephedrine’s pharmacological properties leads to synthetic production1927- Widely used as a nasal decongestant, central nervous system stimulant, and to treat bronchial asthma1950’s- Many reports of side effects such as  blood pressure and  heart rate lead pharmaceutical companies to switch to pseudoephedrine

اسلاید 8: Physiological EffectsStrong stimulant- enhances the release of norepinephrine (NE) from sympathetic nerve endings (see handout)Has 1 and 2 agonist activityrelaxes bronchial musclesHas 1, 2, 1, and 2 adrenergic activityleads to less desirable effects such as  blood pressure,  heart rate, and nervousnessTo compensate, the body releases adenosine and prostaglandin (PG) which inhibit the release of NE

اسلاید 9: Physiological EffectsCaffeine 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)

اسلاید 10: Reported BenefitsIncreased weight loss due to thermogenic effectEnhanced athletic performanceIncreased energy3 billion servings sold during 1999 12 million people using ephedra

اسلاید 11: Adverse Effects Dizziness, tremors, irregular heart rate myocardial infarctions, strokesMay induce psychological dependence1993-2003- 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 ingredientType ‘B’ AE- rare and difficult to separate from pre-existing conditions; cause/effect hard to prove

اسلاید 12: Sound the Alarm!1990s- Government and herbal agencies attempt to decrease intake (warning labels, dosage limits, prohibit combination with caffeine…)2003- RAND report publishedApril 12, 2004- FDA’s Final Rule effectivebanning the sale of dietary supplements containing ephedra (didn’t 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

اسلاید 13: Efficacy and Safety of Ephedra and Ephedrine for Weight Loss and Athletic Performance: A Meta-analysisPerformed by the Southern California Evidence-based Practice Center-RANDPublished in Journal of American Medical Association on March 23, 2003

اسلاید 14: Objective: Assess the efficacy and safety of ephedra and ephedrine used for weight loss and enhanced athletic performanceData Sources: Searched 9 databases (including unpublished trials and non-English documents) for any related studies; adverse events (AE) reported to the FDA includedStudy 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 detailEfficacy and Safety of Ephedra and Ephedrine for Weight Loss and Athletic Performance: A meta-analysis. JAMA(2003)289:12

اسلاید 15: Data Extraction:Trials identified independently by 2 reviewersCase reports reviewed with explicit and implicit methodsData Synthesis: No trials of ephedra and athletic performance found that met criteriaSafety data yielded estimates of 2.2- to 3.6-fold increases in odds of psychiatric, autonomic, or GI symptoms, and heart palpitationsInsufficient data for conclusions about AE at a rate les than 1.0 per thousandMajority of case reports insufficiently documentedEfficacy and Safety of Ephedra and Ephedrine for Weight Loss and Athletic Performance: A meta-analysis. JAMA(2003)289:12

اسلاید 16: Efficacy and Safety of Ephedra and Ephedrine for Weight Loss and Athletic Performance: A meta-analysis. JAMA(2003)289:12CategorySample sizeWeight Loss (kg/mo)95% CIephedrine150.60.2-1.0ephedrine1 + caffeine121.00.7-1.3ephedra210.80.4-1.2ephedra2 + herbs341.00.6-1.3Weight Loss achieved using ephedra, ephedrine containing products greater than placebo1derived from pharmaceutical sources 2derived from botanical sources 3caffeine containing herbs

اسلاید 17: Conclusions:Ephedrine and ephedra promote modest short-term weight loss (~0.9 kg/mo > than placebo)No data regarding long-term weight lossInsufficient evidence to support use for athletic performanceUse with caffeine is associated with increased risk of psychiatric, autonomic, or gastrointestinal symptoms, and heart palpitations Efficacy and Safety of Ephedra and Ephedrine for Weight Loss and Athletic Performance: A meta-analysis. JAMA(2003)289:12

اسلاید 18: - BJ Gurley, SF Gardner, and MA Hubbard- American Journal of Health-System Pharmacy(2000) 57:10Content versus label claims in ephedra-containing dietary supplements

اسلاید 19: 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 high-performance liquid chromatographyContent versus label claims in ephedra-containing dietary supplements (abstract). Am J of Health-System Pharmacy (2000) 57:10

اسلاید 20: Results: total alkaloid content varied considerably (0.0-18.5 mg/dosage unit)Observed significant lot-to-lot variations in alkaloid content for 4 products10 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 alkaloidsContent versus label claims in ephedra-containing dietary supplements (abstract). Am J of Health-System Pharmacy (2000) 57:10

اسلاید 21: 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.”Content versus label claims in ephedra-containing dietary supplements (abstract). Am J of Health-System Pharmacy (2000) 57:10

اسلاید 22: Summary and RecommendationsSlight  short-term wt.loss Athletic enhancement? adverse eventsDosage level?Thus…High cost/benefit ratioOfficial positions

اسلاید 23: Summary Market forces Conventional salesInternet SalesIs it legal?TCMStill under appeal

اسلاید 24: The End… not