Supplements, here, now.

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Supplements, here, now.

• Sales DS about 13 billion in 2000, growing ? 5
  yr
• Mayo Clinics 5/99 61 pts said had used DS
• FDA 1995 survey data gt 55 adults
• 5/00 Texas HMO survey 40
• Use ? elderly, females, white, obesity, EtOH
• Most used per friend,relative, did not ask MD,
  Pharm
• Most felt herbals safe and no side effects.
• 6/99 JFP most said MDs closed minded, dont
  know about DS

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Supplement regulation

• 1906 FDA to eradicate misbranding and
  adulteration
• 1938 FDA requires testing prior to marketing
  after health elixir kills 105 but allows
  traditional herbs
• 1958 1993 GRAS list ? 250 trad. HS
• 1962 Thalidomide. Kefauver-Harris laws require
  proof safety, efficacy, burden of proof on
  manufacturers.

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New law, New label

• 1993 FDA proposal removal of HS from market if
  dont meet rules. Congress deluged c protest,
  ads
• 1994 FDA (de) regulations DSHEA
• List ingredients, allowed nutrition claims on
  labels
• Manufacturer responsible for safety
• This product has not been tested or approved by
  the FDA and makes no claim to diagnose, treat,
  cure or prevent any disease.
• This product has not been tested or approved by
  the FDA and makes no claim to diagnose, treat,
  cure or prevent any disease.

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Hey whats in that bottle?

• Ingredient mixups harvest ? bottle
• Belgium ARF Fang-ji (Stephania tetandra)
  slimming herbal consumed Fang-chi
  (Aristolochia)
• Contamination
• 1990 L-tryptophan E ?1000 eosinophilia, 38
  deaths
• Lead natural Ca, 1994, 2000 -- Azarcon,
  Rueda
• Kombucha antioxidant, tonic yeasts soil bact
  ( anthrax)
• Adulteration
• Unlisted ingredientsNSAIDs, steroids
• 1995 aplastic anemia- Phenylbutazone natural
  cold Rx.

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More trouble

• Interactions
• Dong Quai, Tonka Beans natural coumarins
• Grapefruit Seed Cyto P450 inhibitor
• Overuse, More is better dosing (evidence in
  athletes)
• Vit C mega procarcinogen, calculi
• Ginseng overdose syndrome aggression, manias
• Abuse
• Herbal Ecstasy Ephedra, Liquid ecstasy GHB
• Artemesia Absinthium (Oil of Wormwood)- thujone,
  neurotoxin

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Testing?

• Consumer Lab testing 6/00
• Vit C (n26) 15 failed. (lt95 amt claimed)
• Glucosamine/ Chondroitin (n25) 30 failed
• Gingko, Saw Palmetto, Methionine similar.
• Products passed see ConsumerLab website
• Many calls for 3rd party review- FDA hearings,
  2000
• NIH Office of Alternative Medicine underfunded
• 1997 Fed Commission on DS Rec scientific
  evidence.
• Meanwhile, were stuck
• GRAS/ German Health Authority 1998 Comm. E publ,
  300 HS

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URI

• Echinacea (e. purpura, purple coneflower, 9 spp)
• Biggest selling HS in US, as it was pre-abx.
• RCTs 1993, 94, show some ? URI sx, proph. RCTs
  98, 99 Ø.
• Animal Studies ? WBC, ? cytokines.
• No sig toxicity known. Usual dose 50 drops, or
  400 mg tid.
• Zinc Gluconate, Cold Ease
• RCT x 2 1996, 98 conflicting. Nausea at
  effective doses (qid)
• Licorice (Glychyrrhiza glabru) For cough. Avoid
  - ? aldosterone
• Ephedra / Ma Huang?

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Ephedra / Ma Huang

• Stimulant, weight loss, decongestant
• Ephedrine sympathomimetic, vasoconstrictive
  effects.
• gt3 billion products containing sold in US per yr
• gt1400 rpts to FDA 1999-2001 (HTN, CV, CVA, sz, ?)
  
• Poison Cntrl 876 rpts 1997-99 (ASA 2000 qy)
• 12/00 NEJM review 31 probably 31 possibly
  caused
• Interactions- MAO inhibs life threatening
• Banned by the NFL, etc.

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Weight Loss

• Metabolife, Herbal Phen-Phen
• Ephedra, St. Johns Wort, caffeine
• Phenylpropanolamine- avoid
• Use with caution per individual ingredients
• No effect trials Garcinia, Yohimbine,
  creatine, DHEA
• Unknown effectiveness Cola Acuminata, Dwarf
  Elder, Germander

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Sedatives / Hypnotics

• Melatonin
• Pineal hormone, normal trigger bright light
• Irregular sleep cycles of blind pts improve c
  melatonin
• Studies Ø effect nl patients sleep latency,
  quality
• Usually safe, if pure product.
• Chamomile
• Apigenin, binds benzo receptors, mice mild
  sedative
• Cross rxns ragweed allergy.
• GRAS, no adverse rpts pregnancy, lactation. Tea
  prn.

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Still not sleepy?

• Valerian (Valeriana Officialis root)
• Effective per 2 small RDBCT. In-vitro binds GABA,
  like benzos
• Some pts paradoxical effects. Not rec pregnancy.
• GRAS, long hx use, no sig toxicity. 400 mg qhs.
• Kava-Kava (Piper methysticum)
• Some evidence better than placebo, ? Oxazepam 15
  mg
• Very heavy use reports of adverse sx.
• Generally safe, intermittent use no known
  toxicity.
• Mistletoe, Catnip, Gutu kola, Hops, Lavendar,
  Skullcap Passionflower No evidence.

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?

• St. Johns Wort (Hypericum perforatum)
• 2nd most popular HS. Effective per 1996
  meta-analysis.
• MAO (-) ?, SSRI. Interactions, photosensitivity
• Avoid pregnancy- ? ctx. Case reports
  thrombocytopenia.
• 300 mg tid ? TCAs, amytriptilene 75mg qd
• NIH currently studying vs. fluoxetine.
• Gingko ( G. biloba)
• Dementia, memory. Some evidence ? intracerebral
  circulation
• Gingkolides (-) PAF, bleeding rpts.
• Germany (Egb 761), US trials similar to
  tacrine, donezepil.
• Gingko seed neurotoxin. Egb 761 (leaf extract)
  80 mg bid

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Athletics I

• Creatine Big sales, Big stars
• Precursor to creatine phosphate, ADP?ATP
• Small ? wt bodybuilders (? H20). ? Weight
  lifters, sprinters.
• Ø effect rowers, swimmers, cyclers, runners
• Elderly Ø effect. Serum creatinine can ?.
• Caffeine blocks ( - phosphocreatine resynthesis)
• Probably safe 20g qd x 1 wk, then 5g qd. (Diet
  ? 1-2 g qd)
• Chromium
• Ø evidence efficacy.
• Anemia concern binds transferrin
• gt 600 ?g qd ? RF. Not rec. but probably safe lt
  200 ?g qd

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Athletics II

• Androstenedione, DHEA
• Testosterone precursors, ? oxytestosterone.
  Estrone may ?
• Studies Ø effect performance or muscle mass but
  ? HDL 5.
• GHB (gammahydroxybutyrate)
• Growth hormone releaser No evidence effective.
• GHB intoxication syndrome MS ?, coma,13
  intubated
• Banned FDA for OTC, but still available internet
• GBL (gammabutyrolactone) available, similar
  toxicity
• Amino acids, muscle tonics Ø evidence. Carbo
  load better.

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Anti-inflammatories

• Glucosamine/ Chondroitin
• Meta-analysis (flawed) studies moderate ? sx
  OA.
• Less SEs than NSAIDS
• Some RCTs show ? progression OA (unlike NSAIDs)
• Feverfew (Tanacetum parthenium)
• Arthritis Ø effect in studies. Conflicting
  evidence for HAs.
• Parthenolide (-) arachadonic acid, serotonin.
• Rebound HA, nausea common. Avoid in preganancy, ?
  ctx.
• Commercial preps weak, placebos.
• Not recommended

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Anti-inflammatories to avoid

• Chaparral / Creosote Bush/ Greasewood
• (-) cyclooxygenase, lipoxygenase
• Chronic use assoc hepatitis/ hepatic vein
  occlusions
• Aconitum
• Opens cardiac, neuronal Na channels
• SEs similar to cardiac glycosides, vent
  Dysrhthmias, neuro
• Arnica
• Long traditional use but not rec. due reports
  hepatitis, myalgias
• Homeopathic preps probably safe, low concentration

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Antioxidants / Cancer

• Selenium
• Intracellular metalloid assoc with glutathione
  peroxidase
• Selenosis in overdose amounts- similar to arsenic
• No evidence effectiveness.
• Vitamin A
• Frequent toxicity reports
• Megadose levels gt 25,000 IU/kg ? ICP, hepatotoxic
• Chronic use gt 4,000 IU/kg neuro, hepatic, derm sx
• Beta-carotene Slow absorbtion, no Vit A toxicity
• Skin discoloration
• Avoid in smokers

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Antioxidants / Cancer

• Vitamin E
• No evidence anticancer effectiveness.
• CHD Large trials (HOPE, GISSI) now show no
  benefit CAD pts.
• Physicians Study 2001, Vit E ? CV death rate.
• Extreme doses anti-coagulation, but wide safety
  margin.
• Vit C
• Studied more than any other DS but no proof
  definitive benefit
• Procarcinogenic, nephrolithiasis in some studies
  hi doses
• MANY-- Green Tea, Glutathione, Gingko, Grape
  Seed, n-acetylcysteine, Melatonin, Bilberry,
  curcumin, Laetrile...

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General Tonics

• Garlic (Allium sativum)
• HTN maybe ? ?5, cholesterol probably Ø
• Allicin degraded by crushing, heat, acid.
• GRAS, rec dose 1 clove qd. Commercial tabs 93 Ø
  allicin.
• Comfrey tea
• Wound healing no evid. but may be
  carcinogenic, hepatotoxic
• Esp. avoid pregnancy (DNA damage in vitro),
  lactation.
• Ginseng (Panax ginseng) ? Siberian g (E.
  Senticosis)
• Mild stimulant, no other proven.
• Ginsenosides wide variation of content
• GRAS, rare mastalgia, PMP bleed. Ginseng abuse
  syndrome

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GI

• Hepatitis Milk Thistle (St. Marys Thistle, Holy
  Thistle)
• Sylmarin some evid. ? LFTs, esp in EtOH
  cirrhosis
• Europe uses IV, ? mortality 50, mushroom
  poisoning cases
• GRAS Long used safely as food in Mideast
• Diarrhea Goldenseal (Hydrastis canadensis)
• Berberine intraluminal antidiarrheal (E. Coli,
  Vibrio studies)
• Drug screens doesnt mask.
• Contraindicated pregnancy, lactation,
  anti-coagulation, sz.
• See also pregnancy, below

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CAD Is Merlot a Vitamin?

• EtOH and cardiac dz
• 490,000 pts 1 qd ? 21 overall mortality, 30-40
  CHD.
• Evidence 2-6 drinks qw ? 34-53 CHD mortality,
  overall ? 28.
• But heavier drinkers ? 51 overall mortality.
• Other agents
• Omega-3 ? CVA, MI in post-MI pts. (GISSI
  prevention trial) (850mg eicos 750 mg decos qd)
  
• Folate, Vit B6 ? homocysteine, unk. effect on
  CHD.
• Diet works low Na, DASH and Ornish exercise

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Female

• Pennyroyal (Hedoma pulegioides)
• Birth control, ? ctx. Hepatoxicity, neurotoxic,
  deaths. Teratogen.
• Pulegone effects similar acetomin toxicity, TD
  10ml. Avoid.
• Blue / Black Cohosh
• Midwives cervical ripening, labor,menopause.
  Does seem? ctx.
• Possible teratogenic effects, in-vitro coronary
  artery constrict.
• Soy / isoflavones (Many formulations,
  inconsistent dosing)
• Ob/Gyn 2000 review Some ? menopause sx, prob
  safe.
• Evening Primrose Oil- Some evidence breast sx
  relief, GRAS

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Pregnancy

• UCSF 1999-00 150 pts, 13 used, 75 reported
• Similar stats 2000 N. Carolina midwives study
• Echinacea 9,
• Not rec. By German Commmission E gt 8 weeks
• Recent study 5-7 d, 206 women all trimesters no
  malformations
• Pregnancy Tea 9
• Spearmint, raspberry, strawberry, nettle,
  rosehip, lemon verbena, alfalfa uterine toner.
  No data x use.

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Nausea/ pregnancy

• Ginger (Zinziber officinale) 7
• Nausea data mixed, but results similar to
  Reglan.
• 70 vs. 15 placebo (n27), other RCDBT also good
  results.
• Contraindicated in bleeding disorders. (-
  Thrombox synth)
• GRAS, rec. dose ¼ to 1 g powder qid.
• B6 / pyridoxine 2
• Nausea/ hyperemesis some evidence helpful
• No known toxicity, 50mg po tid rec.

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Male

• Saw Palmetto (Serenoa Repens)
• BPH some evidence ? sx, (flow, nocturia)
• In-vitro 5-? R (-), similar to finasteride, not
  effective as ?1(-)
• Few side effects (HA, GI). Usual dose 160 mg
  bid.
• Yohimbine (Pausinystalia yohimbe bark)-
• ED central adrenergic feedback inhib HTN,
  emesis
• Chan Su (Bufo toad)
• Bufalin aphrodisiac- sx similar to dig toxicity
  (Digibind)

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Elderly

• Aggressive marketing tactics
• Atrophic Gastritis
• Affects 1/3 elder adults -- past h.pylori usually
• ? Absorbtion Fe, Folate, Ca, Vit K, Vit B-12
• Intolerance of lactose/dairy further ? Ca.
• Overall small intestine, pancreatic fxn stays
  intact
• Nutritional health most affected mobility, diet,
  
• RDAs need further study for elders per recent
  FDA rpts

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Kids

• Avoid all but the safest DS
• Fluoride Effective preventer tooth decay.
• Public Health Service Rec .7-1.2 mg/ L. Seattle
  2001 1mg/L
• Supplementation Recs per AAP if H20 lt .6 ppm.
• No evidence current levels carcinogen, etc.
• Flouride Overdosing?
• Poisonings 1992 Alaska, 93 Hawaii, 98 Miss.
  All ? 200 mg/L
• ? Fluorosis Usually small opaque areas tooth,
  can be brown
• Avoid excess flouride/ toothpast in kids- rice
  sized glob enough

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