Ginkgo biloba. Ginkgo - JAMA article. Ginkgo biloba. Botanical Aspects History Chemistry

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1 Botanical Aspects History Chemistry Ginkgo biloba bioflavonoid glycosides quercetin, kaempherol, isorhamnetin terpenoids Ginkgolides A,B,C,J bilobalide Ginkgo biloba Pharmacology antioxidant anti platelet aggregation anti PAF (ginkgolide B) Evidence for Efficacy Impaired memory in elderly multiple studies Alzheimer s Kanowski et al LaBars et at.,jama article* Ginkgo - JAMA article! LaBars et al., JAMA 278: , 1997 (Oct 22) USA study 6 research centers N=309 1 year 202 evaluable at 52 weeks» Rx 24% had +4 on ADAS-Cog; 14% placebo» adverse effects: same as placebo conclusions: modest improvement, improvement recognized by caregivers 1

2 Ginkgo biloba! Evidence for Efficacy (continued) Peripheral Circulation Insufficiency» Peters et al (Vasa 27: ,1998) rdbs n=111! Adverse Effects Bleeding» subdural hematomas (Rowen and Lewis)*» iris (Rosenblatt and Mindel* Adapted from Vasa 27: ,1998 Pittler and Ernst. Am J Med 108: , Change in performance scores 14 Participants' ratings of their overall abilities to remember Score * ginkgo placebo Number of participants ginkgo placebo Word-naming Color-naming Color-Word Test Type Mix et al. J. Alt Comp Med 6: , weeks n=48 ages dose:180mg/d 0 worse neutral improved Ratings Mix et al. J. Alt Comp Med 6: , 2000 weeks n=48 dose:180mg/d 6 ages

3 Ginkgo biloba Other Uses (much less well supported by controlled clinical studies) impotence tinnitus vertigo PMS prevent altitude sickness Safety Rare bleeds Drug interactions May be CYP2C9 inhibitor Additive effectss with antiplatelet adhesion drugs Not with warfarin or maybe aspirin Bleeds associated with ginkgo use Patient age Ginkgo use Other therapy Bleed 70 1 week Aspirin Iris mos Warfarin Intracerebral years None Subdural mos None Subarachnoid 4 1. NEJM 336:1108, Neurology 50: , Lancet 352:36-37, Neurology 46: ,1996 ref Ginkgo biloba! Summary Efficacy: good for dementia and poor peripheral circulatory problems Safety: good but watch for rare bleeding episodes Drug interactions: warfarin; possibly aspirin and other antiplatelet adhesion drugs Product selection: look for EGb761 extracts Dose: mg tabs, BID Questions remaining include» Extent of memory improvement in younger patients?» Delay Alzheimer s and dementia?» Help in other circulatory disorders?» Synergistic with other drugs and treatments?» Optimum dose and treatment time? Ginseng Botany Panax ginseng (Korean or Asian ginseng), Panax quinquefolius (American ginseng) note: Siberian ginseng is different (Eleutherococcus senticosus) steamed and dried product is red ginseng vs white ginseng which is dried only History Uses adaptogen animal studies 3

4 Uses (continued) immune stimulant - animal and human studies (with flu vaccine) sports performance - mixed results well being - one big study showed positive effects menopausal symptoms - no effect in one study but no hormonal effects either cancer prevention - one controversial study in Korea showed preventative effects hypoglycemic effects in diabetic patients (e.g. Vuksan et al., Diabetes Care 23: ,2000 Dose 1-2g/d of dried root 200mg/d of a standardized extract of the root containing 4-7% ginsenosides Adverse Effects much listed but close evaluation indicates wide safety; reports of problems may be associated with poor products and adulterated products Drug Interactions may be CYP inducer Bottom Line pick a good product maybe useful in diabetes and in geriatric populations watch for drug interactions with narrow therapeutic index drugs Ginseng! Summary Efficacy: huge literature of small, uncontrolled studies; some evidence for applications in geriatric patients (improved quality of life ) and in diabetes Safety: good; reported problems may be due to poor quality product Drug interactions: may be CYP inducer Product selection: product should be standardized to 3-4% ginsenosides Dose: mg per day Questions remaining include» What, actually is this stuff good for! 4

5 Garlic! Botany Allium sativum Garlic! History! Chemistry organosulfur compounds» alliin» allicin» ajoene» interconversions and odor # 5

6 Pharmacology cholesterol lowering triglyceride lowering antihypertensive antimicrobial increased fibrinolysis decreased platelet aggregation increased catalase and glutathione peroxidase decreased cancer induction (animal studies) most early studies (>30) show beneficial effects but studies are often not of high quality Meta-analyses have shown a cholesterol lowering effect of 5-12% (Ann Int Med 119: ,1993;J R Coll Physicians- London 28:39-45,1994, Ann Int Med 133: , 2000) One study showed decrease in plaque size (n=152, 48mos) compared to placebo (Koscielny et al. Atheroscerosis 144: ,1999) Recent well designed studies show no effect on cholesterol lowering Kwai story recommendations? Adapted fromsilagy and Nei, JRCollege of Physicians London 28:39-45,1994 Adapted from Silagy and Neil, JR College of Phsicians London 28:39-45,1994 6

7 Other Garlic Applications! Cancer prevention- recent meta-analysis of garlic intake shows modest protective effects for diet intake for colorectal RR=0.69 and stomach cancers (RR=0.53) Fleischauer et al. Am J Clin Nutr 2000 Oct;72(4): ! Antiinfective Stevinson et al. Ann Int Med 133: , 2000 Garlic! Adverse effects» Nothing special! Drug interactions: platelet anti-adhesion effects; careful with aspirin and warfarin Garlic! Summary Efficacy: the literature is conflicting for use in hyperlipidemia and hypertension Safety: good Drug interactions: warfarin; possibly aspirin and other antiplatelet adhesion drugs Product selection: avoid Kwai? Suggest enteric coated tablets standardized to about 4mg allicin/tab Dose: equivalent of about 4g of fresh garlic per day (usually 300mg of extract BID) Questions remaining include» Why the literature is conflicting» Which product to recommend» Who can benefit from use» Other uses? Echinacea! Botany Echinacea purpurea, E. augustifolia, E. pallida**!history!chemistry high molecular weight polysaccharides»heteroxylan»arabinogalactan»phenylpropanoid - chicoric acid #!Pharmacology phagocyte activation release of TNF increase immune response 7

8 Echinacea! Evidence for Efficacy Common Cold» Scaglione and Lund Table 1 (Adapted from Scaglione and Lund, Int. J. Immunotherapy 11: ,1995) n=32 Treatment Length of cold Number of tissues placebo Echinacea P<0.01 8

9 Echinacea! Evidence for Efficacy (continued) flu» Braunig et al # Immune Enhancement» Steinmuller et al #! Adverse Effects not for autoimmune diseases? Recent Results! Echinacea Melchart et al., Archives of Family Medicine 7: ,1998» n=302, double blind, placebo controlled, randomized prevention trial in Germany»no difference in time to first cold (t=66 vs t-65 in the placebo ( patients believed they had more benefit from echinacea, however)(p<.04) Grimm and Muller, Am J Med 106: , 1999» similar prevention trial and results as above Turner et al., Antimicrob Agents Chemother 44: , 2000» experimental cold prevention - no effect Bastyr study in Seattle N=246 Summary Some efficacy in decreasing intensity of cold/flu Commission E- for treatment of recurrent respiratory infections Reduce Incidence? - no Other immune stimulant uses?» Cancer» AIDS» bacterial and fungal infections Products» tablets 250mg» tincture» root extract or extract of tops or pressed juice 9

10 Echinacea! Summary Efficacy: evidence for treatment not prevention; take at first sign of cold/flu Safety: good; rare allergy; not where immunostimulation would be undesirable Drug interactions: not documented Product selection: want standardized extract containing about 4% phenolics Dose: about 250mg QID for treatment Questions remaining include» Which product? Tincture? Tablets? Root extrract? Flowering tops? Pressed juice? E. purpurea? E. augusifolia? E. pallida? 10