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Discussion of a well-designed clinical trial which did not demonstrate effectiveness: UIC center for botanical dietary supplements research study of black cohosh and red clover.

ABSTRACT: The performance of a clinical trial for pharmaceutical agents is usually undertaken only after there is likely benefit demonstrated from the use of the putative agent. The consideration of botanical products as pharmaceutical agents must similarly go through a rigorous evaluation process. The present work reviews the recently published phase II study evaluating the effectiveness of black cohosh and red clover in a randomized trial with conjugated equine estradiol/medroxyprogesterone acetate and placebo for the treatment of menopausal symptoms. We analyze the possible reasons why this study failed to show benefit for either botanical product in reducing menopause-related vasomotor symptoms.

SUBMITTER: Shulman LP

PROVIDER: S-EPMC4939082 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

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Discussion of a well-designed clinical trial which did not demonstrate effectiveness: UIC center for botanical dietary supplements research study of black cohosh and red clover.

Shulman Lee P LP Banuvar Suzanne S Fong Harry H S HH Farnsworth Norman R NR

Fitoterapia 20101027 1

The performance of a clinical trial for pharmaceutical agents is usually undertaken only after there is likely benefit demonstrated from the use of the putative agent. The consideration of botanical products as pharmaceutical agents must similarly go through a rigorous evaluation process. The present work reviews the recently published phase II study evaluating the effectiveness of black cohosh and red clover in a randomized trial with conjugated equine estradiol/medroxyprogesterone acetate and ...[more]

PMID: 21034798

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Toxins in botanical dietary supplements: blue cohosh components disrupt cellular respiration and mitochondrial membrane potential.

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| S-EPMC3932489 | biostudies-literature

A cross-sectional clinical study in women to investigate possible genotoxicity and hematological abnormalities related to the use of black cohosh botanical dietary supplements.

Project description:Black cohosh (BC; Actaea racemosa L.), a top-selling botanical dietary supplement, is marketed to women primarily to ameliorate a variety of gynecological symptoms. Due to widespread usage, limited safety information, and sporadic reports of hepatotoxicity, the Division of the National Toxicology Program (DNTP) initially evaluated BC extract in female rats and mice. Following administration of up to 1000 mg/kg/day BC extract by gavage for 90 days, dose-related increases in micronucleated peripheral blood erythrocytes were observed, along with a nonregenerative macrocytic anemia resembling megaloblastic anemia in humans. Because both micronuclei and megaloblastic anemia may signal disruption of folate metabolism, and inadequate folate levels in early pregnancy can adversely affect neurodevelopment, the DNTP conducted a pilot cross-sectional study comparing erythrocyte micronucleus frequencies, folate and B12 levels, and a variety of hematological and clinical chemistry parameters between women who used BC and BC-naïve women. Twenty-three women were enrolled in the BC-exposed group and 28 in the BC-naïve group. Use of any brand of BC-only supplement for at least 3 months was required for inclusion in the BC-exposed group. Supplements were analyzed for chemical composition to allow cross-product comparisons. All participants were healthy, with no known exposures (e.g., x-rays, certain medications) that could influence study endpoints. Findings revealed no increased micronucleus frequencies and no hematological abnormalities in women who used BC supplements. Although reassuring, a larger, prospective study with fewer confounders (e.g., BC product diversity and duration of use) providing greater power to detect subtle effects would increase confidence in these findings.

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Safety and efficacy of black cohosh and red clover for the management of vasomotor symptoms: a randomized controlled trial.

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2007-09-28 | GSE6800 | GEO

Pregnane X receptor-mediated induction of Cyp3a by black cohosh.

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| S-EPMC3019262 | biostudies-literature

NMR based quantitation of cycloartane triterpenes in black cohosh extracts.

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Transcription profiling of human MCF7 cell response toCimicfuga racemosa (black cohosh)

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| S-EPMC2765500 | biostudies-literature

Mechanistic Evaluation of Black Cohosh Extract-Induced Genotoxicity in Human Cells.

Project description:Black cohosh extract (BCE) is marketed to women as an alternative to hormone replacement therapy for alleviating menopausal symptoms. Previous studies by the National Toxicology Program revealed that BCE induced micronuclei (MN) and a nonregenerative macrocytic anemia in rats and mice, likely caused by disruption of the folate metabolism pathway. Additional work using TK6 cells showed that BCE induced aneugenicity by destabilizing microtubules. In the present study, BCE-induced MN were confirmed in TK6 and HepG2 cells. We then evaluated BCE-induced DNA damage using the comet assay at multiple time points (0.5-24 h). Following a 0.5-h exposure, BCE induced significant, concentration-dependent increases in %tail DNA in TK6 cells only. Although DNA damage decreased in TK6 cells over time, likely due to repair, small but statistically significant levels of DNA damage were observed after 2 and 4 h exposures to 250 µg/ml BCE. A G1/S arrest in TK6 cells exposed to 125 µg/ml BCE (24 h) was accompanied by apoptosis and increased expression of γH2A.X, p-Chk1, p-Chk2, p53, and p21. Conditioning TK6 cells to physiological levels of folic acid (120 nM) did not increase the sensitivity of cells to BCE-induced DNA damage. BCE did not alter global DNA methylation in TK6 and HepG2 cells cultured in standard medium. Our results suggest that BCE induces acute DNA strand breaks which are quickly repaired in TK6 cells, whereas DNA damage seen at 4 and 24 h may reflect apoptosis. The present study supports that BCE is genotoxic mainly by inducing MN with an aneugenic mode of action.

| S-EPMC8285013 | biostudies-literature

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