1 Kava (Kava Kava) ❧ Botany " Piper methysticum ❧ History " long used in the S. Pacific as a relaxant/recreational drug ❧ Chemistry " contains lactone/pyrones that have CNS activity e.g. methy sticin Kava (Kava Kava) " Pharmacology • CNS activity resulting in mild tranquilizer- like activity (decreased anxiety, increased euphoria) • local anesthetic • mild muscle relaxant • weak effects on GABA receptors ( but not benzodiazepine) • Additive interaction with alprazolam (Xanax) • not inhibited by naloxone " Evidence • 7 controlled, double blind studies done with a 70% kavapyrone extract in patients. All showed improvement in anxiety relative to placebo • results not different than oxazepam and bromazepam (Woelk et al, Z. Allgemeinmed 69:271-277,1993) • meta-analysis Pittler and Ernst, J Clin Psychopharmacol 20:84-89,2000 • example: study by Volz and Kieser, Pharmacopsychiatry 30:1-5,1997. – N=101 – 25 week – multicenter, randomized, placebo-controlled, double blind trial
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Kava (Kava Kava)❧ Botany
" Piper methysticum
❧History" long used in the S. Pacific as a relaxant/recreational
drug
❧ Chemistry" contains lactone/pyrones that have CNS activity e.g.
" OPC s are oligomeric or polymeric flavonoid likepolyphenolic compounds
" OPC s have strong antioxidant and free radicalscavanging activities
" OPC s are also high in pine bark (see pycnogenol)
Pharmacology
•In vitro will prevent destruction of elastin, collagenand hyaluronic acid
•In animal models will reduce capillarypermeability and decrease swelling andinflammation
•Action due to the ability of OPC s to block freeradical damage and otherwise protect againstoxidative damage
Uses
•Treatment of varicose veins
•Reduce swelling due to surgery or injury
•Treat and prevent macular degeneration
•To reduce the risk for cancer and heart disease
•Treat diabetic retinopathy and neuropathy
•other
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Evidence
•Varicose veins
•Reasonable evidence based on placebocontrolled trials. Trials published in French andItalian thus not readily evaluated by all
•Reduce pain and swelling due to injury/surgery
•Three controlled studies (in French)
•Vision - one study
•Other – limited evidence from animal or in vitrostudies
Safety
Considered nontoxic
Interactions
OPCs have antiplatelet adhesion properties so thatan anticoagulant effect could be noted at higherdoses; avoid concurrent use with warfarin and otheranticoagulants
Products
Grape seed extract products contain 100mg ofextract per capsule. Dose: 100mg TID
Grape Seed Extract❧ Summary
" Efficacy: probably effective for peripheral venousinsufficiency. May help vision and maculardegeneration. Other uses need more work.
" Safety: good
" Drug interactions: careful with anticoagulants
" Product selection: ? Most are not standardized toOPCs
" Dose: 100mg TID
" Questions remaining include• Will grape seed extract help in vascular diseases other than
varicose veins? What about coronary disease?
Bilberry
•Botany- extract of the fruit of the “European Blueberry” which has awhite inside
•History-used by English pilots in WWII to improve night vision
•Chemistry-contains anthocyanosides (glycosides of anthocyanodins);these like OPCs (see grape seed extract) are powerful antioxidants
•Pharmacology- antioxidant and free radical scavanging activities withmaybe special action in the eye
•Use-poor night vision, cataracts,macular degeneration,diabeticretinopathy
•Evidence-conflicting small studies. More work needs to be done
•Safety-OK Interactions-none
•Products-look for extracts standardized to 25% anthocyanosides; 100mgqd or BID
Black Cohosh❧ Botany
" Cimicifuga racemosa. A tall perennial shrub in NE USA; roots andrhizomes used
❧ History" Used by Native Americans for women’s health problems and a
variety of other uses; A component of Lydia Pinkham’s elixir, aformally very popular remedy for dysmenorrhea and menopausalsymptoms
" In Europe a special black cohosh extract has been used since the1950s for symptoms of menopause and PMS
❧ Chemistry" Contains phytosterin, salicylic acid, tannins, and triterpine
glycosides that may be important for activity" The triterpine glycosides include acetin, 27-deoxyacetin, and
cimicifugoside
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Black Cohosh
Pharmacology
•There is disagreement whether compounds in theextract of back cohosh bind to estrogen receptors,i.e., black cohosh may not have phytoestrogenactivity
•In vitro and animal work show estrogen bindingactivities but a human study indicated no estrogenicchanges
Uses
•reduce symptoms associated with menopause
•PMS
•dysmenorrhea
•hasten childbirthing
•Evidence
•early studies with Remifemin show support for reducinghot flashes, etc in menopause; benefit seen only afterseveral weeks
•a recent study showed no effect in reducing hot flashesassociated with breast cancer treatment
•PMS-not much
Safety
•GI upset, headache, dizziness possible
•due to possible estrogenic effects, use with cautionpregnancy
•in vitro does not stimulate breast cancer cells but in vivothe risk is uncertain.
•Products
•Remifemin (SK Beecham) is a good product that has beenused successfully in controlled trials; it is standardized tocontain 1mg of 27-deoxyacetin per 20mg tablet.
•1 BID
Black Cohosh❧Summary
" Efficacy: reasonable evidence for benefit formenopausal symptoms
" Safety: good
" Drug interactions: none noted so far
" Product selection: extract of roots andrhizomes. Remifemin is the best studiedproduct
" Dose: 20mg BID
" Questions remaining include• Does black cohost help in PMS?
• What, if any, is the risk of use in breast cancer?
• Does it have estrogenic activities in vivo?
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Pychnogenol
•Botany- extract of the bark of the “French maritime pine”, Pinuspinaster also known as Pinus maritima
•History-pychnogenol is patented by Horphag Research Ltd; 60-65%OPCs per 50mg tablet The name is a registered trademark.
•Chemistry-contains OPCs (see grape seed extract)
•Pharmacology- antioxidant and free radical scavenging activities
•Evidence-some evidence of a variety of benefits in improving capillaryfunction
Pychnogenol•Safety-OK Interactions-none except possibly to be used with cautionwith immunosuppresive drugs
•Products-?
•Summary-safe but unproven product for vision problems
•Questions remaining- is this more expensive product better and moreversatile therapeutically than grape seed extract which also is rich inOPCs
•Summary-safe and interesting product with ability to improve capillaryfunction with prolonged use. $
Green Tea
Botany-Camillia sinensis leaves
Chemistry-the hot water extract of the leaves containsOPCs and other antioxidant/free radical scavengingcompounds (see grape seed extract)
Pharmacology-protective activity against experimentalcancers in animals and some epidemiological evidencefor protective effects for stomach, colon, pancreaticcancers
Uses-probably need multiple cups/d; tablets of thedried extract are commercially available but do theyhave the same effect?
Green Tea
Evidence-increased consumption correlates todecreased risk of cancer and possible heart disease instudies on Japanese
Cautions-caffeine! Although the amount is less than ina cup of coffee; contains vitamin K so be careful withwarfarin
Products-as I am preparing this slide I am enjoying acup of Salada green tea made with a “tea bag”; GNCand others make a dried extract in capsule form
Questions-how much? Does black tea have the sameeffect? How much benefit?