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Alyssa Vivas Ashley Barlond ENVH 472  Herbal remedy derived from plant (Ephedra sinica)  Chinese herb derivative in dietary supplements  Acts as a.

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Presentation on theme: "Alyssa Vivas Ashley Barlond ENVH 472  Herbal remedy derived from plant (Ephedra sinica)  Chinese herb derivative in dietary supplements  Acts as a."— Presentation transcript:

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2 Alyssa Vivas Ashley Barlond ENVH 472

3  Herbal remedy derived from plant (Ephedra sinica)  Chinese herb derivative in dietary supplements  Acts as a stimulant  Constricts blood vessels  Increases BP, HR, metabolism, body heat, & expands bronchial tubes  Different than ephedrine  Ephedra: plant  Ephedrine: Main active ingredient, similar to amphetamine  Stimulate NS & heart

4  Herbal remedy to treat respiratory problems (i.e. asthma, cold/flu symptoms)  Weight loss supplements  Athletic enhancement  Energy supplements  Treatment of Hypotension  Herbal street drug alternative

5 1990’s – first entered U.S. market -FDA investigates adverse events 1994 – DSHEA (Dietary Supplements Health & Education Act) 1997 – FDA proposed ruling for banning: >8mg - stricter labeling of low-dose ephedra supplements 2001 – Minnesota Vikings player died (suspected) 2003 – Studies confirm negative effects, consumer alert 2003 – Orioles Pitcher Steve Bechler died 2004 – FDA bans ephedra  Stopped retail sales, manufacture, and distribution  Ephedra considered “adulterated”  Ephedra manufacturers tried to lobby against it 2005 – Utah judge tried to overturn ban 2006 – Federal appeals court reaffirms FDA ban & overturns UT judge  After ban: dietary supplement companies replaced ephedra with other herbal stimulants; marketed them as “ephedra-free”  FDA = no dose of ephedrine alkaloids safe!

6 1) Hazard Identification 2) Exposure Assessment 3) Dose-Response Assessment 4) Risk Characterization

7 To gain background, FDA uses data from:  Adverse event information  FDA received 140 adverse event reports from 6/1/97 to 3/31/99  22 “attributable  33 “supportive”  72 “insufficient data”  8 “not evaluated”  Clinical studies & scientific reviews  NIH  RAND Corp. evaluated safety & efficacy

8 Does ephedra really work?  short-term weight loss  increased energy, endurance, and strength BUT There are serious side effects!

9  Originally thought of as safe because it’s natural, but serious CV & CNS side effects (even in small doses):  Hypertension  Dizziness  Nervousness  Trembling  Headache  Insomnia  Dehydration  Vomiting  Irregular heartbeat  Seizures  Heart attack  Stroke

10  Can cross blood-brain barrier and become potent CNS stimulator  More hazardous when combined with caffeine  Synergistic effects  Can ultimately lead to death  Half-life: 3-6 hours  Excreted largely unchanged in urine

11  Past study found:  Ephedra use related to stroke, heart attack, sudden death  Don’t need to be pre-disposed to heart problems to have severe side effects  Toxic effects even with low doses  Induces cardiotoxic problems: lesions, hemorrhage, necrosis, and degeneration.

12 Proposed Mechanism of Heart Toxicity Ephedrine + Caffeine oral exposure Quick Absorption (toxic levels develop within 1 hr) “Fight-or-flight” hormones released Blood vessels narrow (result in high BP) Increase in heart rate Chest pain; heart not getting enough O2-rich blood Heart cell & tissue death Hemorrhage Sudden Death

13 Route  Ingestion (main method) ; injections (less common)  Excreted in breastmilk Endpoint  Heart/Cardiovascular system Amount Dietary supplements: Typical pills contain 10-50 mg per pill, x3 doses per day =30-150 mg/day

14 Duration  3 doses/day Who  Athletes (increased energy & stamina)  Others:  Dieters (aids weight loss)  People who use street drugs (herbal alternative to drugs)  People who use it as herbal remedy (respiratory problems) 2003- Pitcher Steve Bechler died after taking ephedra.

15 Before FDA ban… NOAEL: 90 mg/day = 1.3 mg/kg*day LOAEL: 150 mg/day = 2.1 mg/kg*day But not enough supporting evidence was found as to how these values were calculated. Given past studies about adverse effects associated with even low doses of ephedra, we think NOAEL & LOAEL are NOT valid.

16 Animal study: effects of ephedra + caffeine significantly increased cardiotoxicity (hemorrhage, necrosis, ventricle degeneration)

17 Using numbers from animal study… NOAEL: 15 mg/kg*day = 0.015 mg/kg*day 1000 LOAEL: 30 mg/kg*day = 0.030 mg/kg*day 1000 Uncertainty Factors Interspecies variability10 Intraspecies variability10 Database uncertainty10 TOTAL1000

18 I = C * CR * EFD BW * AT I =(24 mg/day ) 70 kg I = 0.34 mg/kg*day C (concentration): n/a CR (contact rate): 24 mg/day BW (body weight): 70 kg I (intake): ?? Before, ban FDA recommended 24 mg maximum dose of ephedra per day. Based on this… Our NOAEL/LOAEL values are lower!

19  Habit-forming  Can build up tolerance  leads to higher doses for same effect  Based on precautionary assessment, risk is mild

20 InitialParameterScoreComment Community / Social IssuesEvaluate effects on the community and related social issues. GG=Goal3 1-a lot, 2-some, 3-little. Does this move forward the goal of human and environmental health? NN=Need3 1-a lot, 2-some, 3-little or not sure. Ask the question: Is it necessary? Do we really need this? F F=Future Generations1 1-little, 2-some, 3-high impact. Is there a potential impact on future generations of humans and other species? D D=Democratic, community based process3 1-a lot of community involvement and consultation, 2-some, 3-little. Was the community consulted early and often in the process? Was the process democratic and inclusive. AA=Alternatives2 1-alternatives were carefully considered, 2-some consideration, 3-no consideration. Were alternatives considered? Total 12/15 5-good, supportive of health and community 15-poor, not supportive of health or community Not supportive of health or community

21 Exposure Issues Evaluate potential exposure issues. EE=Exposure3 0-none, 1-little, 2-some, 3-high. Do we have control over the exposure? M M=Multiple exposures 1 0-none, 1-little, 2-some, 3-high. Is there exposure to other chemicals with similar hazard? Ch Ch=Children exposed 3 0-none, 3-little, 5-some or high or don't know. Children are often more vulnerable. Are children being exposed. CP CP=Consumer products 2 0-not in consumer products, 1-little, 2-some, 3- a lot or do not know. Is this compound in consumer products? O O=Occupational exposure 0 0-no occupational exposure, 1-little, 2-some, 3- a lot or do not know. Is there occupational exposure? FF=Food exposure0 0-not in food supply, 1-little, 2-some, 3- a lot or do not know. Is the compound present in the food supply. Total 9/20 0-no exposure, no problems 20-significant exposure, serious concern Mild exposure risk

22 Hazard / ToxicityEvaluate potential hazards. HH=Hazard10 1-low, 5-some, 10-high. Follow classical hazard evaluation, pick endpoint, exam relevant quality studies (cancer, reproductive, neurotoxicity, irreversible) IS IS=Individual Sensitivity 2 1-little 2-some, 3-a lot. Determine if any individuals are more sensitive than health adult such as the very young or old. EC EC=Ecological hazard 1 1-little 2-some, 3-a lot. Is it a hazard to other species or the environment? VV=Volume5 how much is produced (1=research only, 2= 100,000 or do not know) PP=Persistent1 1-little persistence 2-some, 3-a lot of persistence or do not know. Is the compound presistent in the environment? BB=Bioaccumulate1 1-little 2-some, 3-a lot. Does it bioaccumulative in humans or animals or move up the food chain? UCUC=Uncertainty21-little 2-some, 3-a lot. How certain is the information? Total 22/30 7-low hazard 30-significant hazards or unknowns, serious concern Medium-high hazard & toxicity

23 Final Results Community/Social Issues12/15 Exposure Issues9/20 Hazard/Toxicity22/30 TOTAL:43/65

24  Lack of adequate data  Animal studies  No strong evidence that ephedra actually enhances athletic performance  Low dose extrapolation  Don’t really know the least dosage when side effects occur  Multiple chemical exposures  Amount of caffeine taken with ephedra varies & could have role in severity of side effects

25  Feb 2004, FDA published final ruling that supplements with ephedrine alkaloids present unreasonable risk of illness or injury  Ex 1 : no significant differences in strength, endurance, power when taken as an athletic supplement  Ex 2: Weight loss associated with ephedra is only short-term and not sufficient enough to “cure” obesity. Severe heart and nervous system risks outweigh weight loss July 2008 Final Rule: “… dietary supplements that contain ephedrine alkaloids are adulterated under section 402(f)(1)(A) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 342(f)(1)(A)). It is illegal to market an adulterated dietary supplement.”

26  Federal Food and Drug Administration (FDA):  Main Task: Protect public from harmful products  Ephedra considered dietary/herbal supplement  Not a drug  FDA cannot regulate it  FDA doesn’t regulate manufacturer’s potentially false claims

27  “Stakeholders“  Dietary supplement manufacturers  Ex: Metabolife contributed millions to national politicans to sway their vote in favor of ephedra  Received 14,000+ adverse event reports from ephedra, but not reported to FDA  Can make unproven health claims  Not required to report adverse reactions  Labels don’t list all ingredients, real dosage, adverse effects

28  “Asia MedLabs” (ephedra manufacturer)  Made medical claims w/o scientific evidence  treats flu, fever, allergies  Manufacturers hired private consulting firm = scientific review claiming ephedra is safe  Manufacturers claimed:  **Decreasing obesity outweighs risks of ephedra  Insufficient evidence to support athletic-enhancing benefits of ephedra

29  Manufacturers advertisements attract consumers  Media introduced it to public w/ national headlines of Baltimore Orioles death  Death: drew attention & thought to be key factor in FDA’s push  National headlines = FDA warning  Media reinforcing FDA= ephedra dangerous  Stigma of WLS: Fear of WLS

30  In the hands of manufacturers w/:  Dietary Supplement Health & Education Act (DSHEA)  Before market: Manufacturer evaluates safety of WLS before reaches market  On market:  FDA regulates unsafe WLS products  FTC regulates advertising  **DSHEA makes it harder for FDA to protect public  Barriers to consensus:  WLS manufacturers have strong lobbying against amending DSHEA  Lack of evidence (except ephedra) to prove DSHEA not adequately protecting public

31  FDA: 0.34 mg/kg*day  Ours: 0.015 mg/kg*day  Ban should have happened long time ago  More stringent regulations during pre-manufacturing/ marketing of WLS  Regulate like a drug = need to tell consumers risks  Need to amend DSHEA  Promote healthy way to lose weight other than supplements

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