[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 11:21:36 CST 2006

Hello all, there is nothing like a good ol' western scientific study to bring out the Holiday spirit in us all. While I appreciate the comments and opinions thus far I think it wise of us all to realize how little we really do know, at least in a scientific sense about the world around us. In the case of this study and all for that matter I think it is wise to remember that in our society funding drives perception. Additionally researchers have been known to spin the truth in various directions for many reasons. I've included the following article that you all may already be aware of:

Published on Thursday, February 10, 2005 by the Los Angeles Times 
U.S. Scientists Say They Are Told to Alter Findings
More than 200 Fish and Wildlife researchers cite cases where conclusions were reversed to weaken protections and favor business, a survey finds

by Julie Cart

More than 200 scientists employed by the U.S. Fish and Wildlife Service say they have been directed to alter official findings to lessen protections for plants and animals, a survey released Wednesday says. 
The survey of the agency's scientific staff of 1,400 had a 30% response rate and was conducted jointly by the Union of Concerned Scientists and Public Employees for Environmental Responsibility. 
A division of the Department of the Interior, the Fish and Wildlife Service is charged with determining which animals and plants should be placed on the endangered species list and designating areas where such species need to be protected. 
More than half of the biologists and other researchers who responded to the survey said they knew of cases in which commercial interests, including timber, grazing, development and energy companies, had applied political pressure to reverse scientific conclusions deemed harmful to their business. 
Bush administration officials, including Craig Manson, an assistant secretary of the Interior who oversees the Fish and Wildlife Service, have been critical of the 1973 Endangered Species Act, contending that its implementation has imposed hardships on developers and others while failing to restore healthy populations of wildlife. 
Along with Republican leaders in Congress, the administration is pushing to revamp the act. The president's proposed budget calls for a $3-million reduction in funding of Fish and Wildlife's endangered species programs. 
"The pressure to alter scientific reports for political reasons has become pervasive at Fish and Wildlife offices around the country," said Lexi Shultz of the Union of Concerned Scientists. 
Mitch Snow, a spokesman for the Fish and Wildlife Service, said the agency had no comment on the survey, except to say "some of the basic premises just aren't so." 
The two groups that circulated the survey also made available memos from Fish and Wildlife officials that instructed employees not to respond to the survey, even if they did so on their own time. Snow said that agency employees could not use work time to respond to outside surveys. 
Fish and Wildlife scientists in 90 national offices were asked 42 questions and given space to respond in essay form in the mail-in survey sent in November. 
One scientist working in the Pacific region, which includes California, wrote: "I have been through the reversal of two listing decisions due to political pressure. Science was ignored — and worse, manipulated, to build a bogus rationale for reversal of these listing decisions." 
More than 20% of survey responders reported they had been "directed to inappropriately exclude or alter technical information." 
However, 69% said they had never been given such a directive. And, although more than half of the respondents said they had been ordered to alter findings to lessen protection of species, nearly 40% said they had never been required to do so. 
Sally Stefferud, a biologist who retired in 2002 after 20 years with the agency, said Wednesday she was not surprised by the survey results, saying she had been ordered to change a finding on a biological opinion. 
"Political pressures influence the outcome of almost all the cases," she said. "As a scientist, I would probably say you really can't trust the science coming out of the agency." 
A biologist in Alaska wrote in response to the survey: "It is one thing for the department to dismiss our recommendations, it is quite another to be forced (under veiled threat of removal) to say something that is counter to our best professional judgment." 
Don Lindburg, head of the office of giant panda conservation at the Zoological Society of San Diego, said it was unrealistic to expect federal scientists to be exempt from politics or pressure. 
"I've not stood in the shoes of any of those scientists," he said. "But it is not difficult for me to believe that there are pressures from those who are not happy with conservation objectives, and here I am referring to development interest and others. 
"But when it comes to altering data, that is a serious matter. I am really sorry to hear that scientists working for the service feel they have to do that. Changing facts to fit the politics — that is a very unhealthy thing. If I were a scientist in that position I would just refuse to do it." 
The Union of Concerned Scientists and the public employee group provided copies of the survey and excerpts from essay-style responses. 
One biologist based in California, who responded to the survey, said in an interview with The Times that the Fish and Wildlife Service was not interested in adding any species to the endangered species list. 
"For biologists who do endangered species analysis, my experience is that the majority of them are ordered to reverse their conclusions [if they favor listing]. There are other biologists who will do it if you won't," said the biologist, who spoke on condition of anonymity. 
© 2005 Los Angeles Times

Remember, big Pharma has a tremendous lobby out there and lots of dollars to back it up. 

Happy Holidays!

Robin

-----Original Message-----
>From: Wendy Applequist <wendy.applequist at mobot.org>
>Sent: Dec 21, 2006 12:02 PM
>To: 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
>
>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 
>	Executive Director 
>	Botanical Liaisons, LLC 
>	1180 Crestmoor Drive 
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>	
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>
>

Robin Alton Suggs
MoonBranch Botanicals
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