[MPWG] A positive black cohosh study 12/7/2006 - Black Cohosh(Actaea racemosa, Cimicifuga racemosa) Behaves as a Mixed Competitive Ligand andPartial Agonist at the Human Opiate Receptor

Thu Dec 21 11:02:59 CST 2006

Trish,

I agree that the UIC team is more trustworthy, but their study is in vitro and results of in vitro studies do not always translate into in vivo results (look at how many phony "herb-drug interaction" alarms have been raised through the use of petri-dish studies).  However, there's further reason to question the results of the human trial here.  Firstly, there are a LOT of studies showing that black cohosh reduces hot flashes or total menopausal symptoms; a clear majority of trials have been positive.  Some people have a nasty habit of pretending that if 15 European studies are positive and one American study is negative, the question has been completely resolved -- with a negative answer!  The mainstream media invariably fall in line with this spin.  When the researchers themselves push this outlook, as appears to be the case here, this demonstrates bias that warrants going over their study with a fine-tooth comb.

Firstly, this "Wiklund Menopause Symptom" scale is not commonly used.  Many studies of black cohosh have used the Kupperman Index, which is also used for tests of pharmaceutical drugs.  If you look these two things up in PubMed, you will find that there are several studies of menopause with Wiklund as one of the authors (mostly using scales with different names, according to the abstracts); the ONLY study that has Wiklund in the abstract but not the authors' list is this study.  The only Googled references to "Wiklund Menopause Symptom," in quotes, refer to this study.  Compare that to "Kupperman Index" with respectively 143 PubMed-listed scientific papers and almost 10,000 Google hits.  Suppose that you do not really care to find an effect -- it would certainly help to use a poorly validated rating scale that might be less sensitive than the usual scales, or might give higher "placebo effect" answers.

I don't have access to the article, but someone has summarized a few of the results online.  At three months, frequency of vasomotor symptoms declined 35% with black cohosh, 15% with multibotanical, 30% with multibotanical plus soy, 21% with placebo, and 88% with hormone therapy.  We are told that the difference between "herbal supplements" (which?) and placebo was 0.6 hot flashes per day.  A "global test for herbs and placebo" gave P=.10.  Other measures showed trends toward the herbs but were farther from being significant.  The media version is that everything was the same except that the multibotanical plus soy at 12 months was significantly worse than placebo.  Now, P=.10 does not show that the above superiority of herbs over placebo is real, but it certainly doesn't prove that there is no effect either!  With a larger sample size, the same effect might have been significant at P=.05.  At least, the commentary has been misleading.    

Also, someone with access to the paper might look into material sourcing and quality.  Was a fingerprint provided?  Was the source provided?  Did they show that levels of suspected active compounds were adequate?  Using crummy material (as in the recent highly touted Echinacea angustifolia study, with no detectable echinacoside, and 30% of the recommended dose on top of that) is a great way to reduce the effect size.  I'm not implying that they would deliberately go out and look for lousy material, but if you are operating under the belief that no herbal product will (or should) be effective, you don't put much effort into ensuring product quality either.  This study was funded before the new NCCAM guidelines required researchers to demonstrate product composition.

Wendy

________________________________

	From: mpwg-bounces at lists.plantconservation.org [mailto:mpwg-bounces at lists.plantconservation.org] On Behalf Of Trish Flaster
	Sent: Thursday, December 21, 2006 10:13 AM
	To: McCoy, Joe-Ann
	Cc: mpwg at lists.plantconservation.org
	Subject: Re: [MPWG] A positive black cohosh study 12/7/2006 - Black Cohosh(Actaea racemosa,Cimicifuga racemosa) Behaves as a Mixed Competitive Ligand andPartial Agonist at the Human Opiate Receptor

	It is a pleasure that you sent this as this scientific team spent years looking at all the species of cohosh and other plants to understanding the mechanism activity of black cohosh. I trust this work a lot more than others. 

	Trish 
	On Thursday, December 21, 2006, at 07:29 AM, McCoy, Joe-Ann wrote: 

		FYI: A positive black cohosh study which came out 2 weeks ago but didn't receive the press' attention. Just to even out the uncertainty......... 

		http://pubs.acs.org/cgi-bin/abstract.cgi/jafcau/2006/54/i26/abs/jf062808u.html 

		J. Agric. Food Chem., 54 (26), 9852 -9857, 2006. 10.1021/jf062808u S0021-8561(06)02808-1 
		December 7, 2006 

		Copyright © 2006 American Chemical Society 

		Black Cohosh (Actaea racemosa, Cimicifuga racemosa) Behaves as a Mixed Competitive Ligand and Partial Agonist at the Human Opiate Receptor 

		Mee-Ra Rhyu,# Jian Lu, Donna E. Webster, Daniel S. Fabricant, Norman R. Farnsworth, and Z. Jim Wang* 

		Department of Medicinal Chemistry and Pharmacognosy, UIC/NIH Center for Botanical Dietary Supplements Research and Program for Collaborative Research in the Pharmaceutical Sciences, and Department of Biopharmaceutical Sciences, College of Pharmacy, University of Illinois, Chicago, Illinois 60612 

		Abstract: 

		Black cohosh is a commonly used botanical dietary supplement for the treatment of climacteric complaints. Because the opiate system in the brain is intimately associated with mood, temperature, and sex hormonal levels, the activity of black cohosh extracts at the human opiate receptor (hMOR) expressed in Chinese hamster ovary cells was investigated. The 100% methanol, 75% ethanol, and 40% 2-propanol extracts of black cohosh effectively displaced the specific binding of [3H]DAMGO to hMOR. Further studies of the clinically used ethanol extract indicated that black cohosh acted as a mixed competitive ligand, displacing 77 ± 4% [3H]DAMGO to hMOR (Ki = 62.9 g/mL). Using the [35S]GTPS assay, the action of black cohosh was found to be consistent with an agonist, with an EC50 of 68.8 ± 7.7 g/mL. These results demonstrate for the first time that black cohosh contains active principle(s) that activate hMOR, supporting its beneficial role in alleviating menopausal symptoms. 

		Keywords: Black cohosh; menopause; hot flashes; opiate; botanical dietary supplement 

		Received for review October 1, 2006. Accepted October 24, 2006. This publication was funded by the following grants: AT003476 from the National Center for Complementary and Alternative Medicine (NCCAM) and the Office of Dietary Supplements (ODS); AT000155 jointly provided to the UIC/NIH Center for Botanical Dietary Supplements Research by the ODS, the NCCAM, the Office for Research on Women's Health, and the National Institute for General Medical Sciences; and DA005050 from the National Institute on Drug Abuse. D.E.W. is supported by an NIH predoctoral fellowship (F31AT002669). J.L. is a University Fellow. The contents are solely the responsibility of the authors and do not necessarily represent the official views of the NCCAM, NIDA, or the National Institutes of Health. 

		Joe-Ann McCoy, Ph.D. 
		USDA-ARS Medicinal Plant Curator 
		North Central Regional Plant Introduction Station 
		G212 Agronomy Hall 
		Iowa State University 
		Ames, Iowa 50011-1170 
		USA 
		phone: 515-294-2297 
		fax: 515-294-1903 

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	Trish Flaster 
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