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:
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
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
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!
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
Does ephedra really work? short-term weight loss increased energy, endurance, and strength BUT There are serious side effects!
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
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
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.
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
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
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.
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.
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!
Habit-forming Can build up tolerance leads to higher doses for same effect Based on precautionary assessment, risk is mild
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
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
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
Final Results Community/Social Issues12/15 Exposure Issues9/20 Hazard/Toxicity22/30 TOTAL:43/65
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
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.”
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
“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
“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
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
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
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