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Black Cohosh

Scientific Name(s): Actaea gyrostachya Wender., Actaea monogyna Walter, Actaea orthostachya Wender., Actaea racemosa L., Botrophis actaeoides Raf. Ex Fisch. & C.A.Mey., Botrophis pumila Raf., Cimicifuga americana Muhl., Cimicifuga racemose, Cimicifuga racemose L. (Nutt), Thalictrodes racemose (L.) Kuntze
Common Name(s): Baneberry, Black cohosh, Black snakeroot, Bugbane, Cimicifuga, Rattleroot, Rattletop, Rattleweed, Shengma (China), Squawroot, Traubensilberberze, Wanzenkraut

Clinical Overview

Use

There is a lack of consensus regarding whether black cohosh is useful for managing some symptoms of menopause. Some official groups state black cohosh can be considered as an alternative nonhormonal therapy for vasomotor symptoms, whereas others state there is a lack of consistent evidence of benefit.

Dosing

Black cohosh extract is generally standardized to 2.5% of triterpene glycosides (ie, 1 mg/dose). Based on clinical use of commercial products, the current recommended black cohosh dose for management of symptoms of menopause is 40 to 80 mg/day, often in divided doses. Therapeutic effects generally begin after 2 weeks of treatment, with maximum effects usually occurring within 8 weeks.

Contraindications

Contraindicated in individuals with aspirin sensitivity because black cohosh contains salicylic acids.

Pregnancy/Lactation

Avoid use in pregnancy and lactation. Black cohosh has been used to improve pregnancy rates following in vitro fertilization and in women with polycystic ovarian syndrome (PCOS). Premature birth may occur with large doses. Concerns regarding labor-inducing, hormonal, emmenagogic, and anovulatory effects exist, based on low-level evidence and expert opinion.

Interactions

None well documented.

Adverse Reactions

Black cohosh is associated with a low incidence of adverse reactions. There are concerns regarding rare, but serious, hepatotoxicity.

Toxicology

Overdose of black cohosh may cause nausea, vomiting, dizziness, nervous system and visual disturbances, reduced pulse rate, and increased perspiration. Case reports primarily document hepatic toxicity; however, cardiovascular and circulatory disorders and 1 case of convulsions have been documented.

Botany

Black cohosh is a perennial that grows in open woods at the edges of dense forests from Ontario, Canada to Tennessee and west to Missouri in the United States. It grows to 2.5 m in height and is topped by a long plume of white flowers that bloom from June to September. Its irregular-shaped leaflets have toothed edges. The word "black" refers to the dark color of the rhizome. The name "cohosh" comes from an Algonquian word meaning "rough," referring to the surface of the rhizome. The related species Cimicifuga foetida is used in traditional Chinese medicine, while Cimicifuga dahurica (Turcz.) Maximowicz and Cimicifuga heracleifolia Komarov are used in Japan. Polymerase chain reaction protocols have been developed for distinguishing and authenticating the species.Xue 2009, Zerega 2002 Black cohosh should not be confused with blue cohosh (Caulophyllum thalictroides). Other members of the genus include Actaea rubra (red baneberry) and Actaea pachypoda (white cohosh).USDA 2015, Quattrocchi 2012 The older name for black cohosh, Cimicifuga racemosa L. (Nutt.), has been replaced by the synonym Actaea racemosa L., although both names are commonly used.

History

American Indians used black cohosh for the treatment of general malaise, kidney ailments, malaria, rheumatism, sore throat, and gynecological disorders (eg, ease of labor, menstrual cramps). North American colonists used the herb for treating amenorrhea, bronchitis, chorea, dropsy, fever, hysteria, itch, lumbago, nervous disorders, snakebite, yellow fever, and uterine disorders. In traditional Chinese medicine, the herb was valued for its anti-inflammatory, analgesic, and antipyretic properties. The plant has been used in Europe since the 17th century to treat joint pain, neuralgia, and pain in pregnancy and labor. Literature reports also document the use of black cohosh for treating influenza, smallpox, acute rheumatism, headache, cough, chorea, and other nervous system disorders.Low Dog 2003, Pepping 1999, Winterhoff 2003 It was an important herb in the 19th-century Eclectic medical movement in the United States, under the name "macrotys."Felter 1900 The old-time remedy Lydia Pinkham's Vegetable Compound (early 1900s) contained many natural ingredients, including black cohosh.Tyler 1995 The roots and rhizomes are used medicinally. A tea from the root has been recommended for sore throat. The Latin name Cimicifuga means "bug repellent," and the plant has been used for this purpose. Since 1940, Germans have used black cohosh for dysmenorrhea, premenstrual symptoms, and menopausal symptoms. A variety of Cimicifuga preparations are available commercially. Remifemin, the brand name of a standardized extract of the plant, has been widely studied and used in Germany since the mid 1950s for management of menopause,Black Cohosh 2010, Low Dog 2003, Murray 1997 and is recognized by the World Health Organization (WHO) as effective for relieving menopausal symptoms.Guo 2017

Chemistry

German reports from the late 1960s discuss the contents of black cohosh.Linde 1968, Linde 1967, Linde 1967 Pharmacologically active compounds include those in the cimigenol, shengmanol, phenolic, and cimifugenin/acteol/actein classes.Guo 2017 The key medicinal components include triterpene glycosides, phenolic acids, flavonoids, volatile oils, and tannins. High-performance liquid chromatography revealed the presence of caffeic acid, ferulic acid, isoferulic acid, cimicifugoside H-1, cimiracemoside A, cimicifugoside H-2, (26R)-actein, 26-deoxycimicifugoside, (26S)-actein, 23-epi-26-deoxyactein, 23-OAc-shengmanol-3-O-beta-D-xyloside, 26-deoxyactein, 25-OAc-cimigenol-3-O-beta-L-arabinoside, 25-OAc-cimigenol-3-O-beta-D-xyloside, cimigenol-3-O-beta-L-arabinoside, and cimigenol-3-O-beta-D-xyloside.Chen 2002 Four phenylpropanoid esters, cimiracemates A through DLinde 1968 have been identified.Chen 2002, Li 2003 Black cohosh contains N-methylcytisine, as well as guanidine alkaloidsGodecke 2009 and N-methyl-serotonin.Godecke 2009 The terpenoid mixture consists of actein, 12-acetylactein, and cimigoside. Other constituents found in the plant include acetic, butyric, formic, oleic, palmitic, and salicylic acids; racemosin; formononetin (an isoflavone); phytosterols; acteina (resinous mixture); and volatile oil.Newall 1996 An amorphous resinous substance called cimicifugin (macrotin) accounts for approximately 15% to 20% of the root. Cimigoside (cimifugoside) and 27-deoxyacteine have also been isolated. The triterpene glycoside 27-deoxyacteine is used to standardize Remifemin.Berger 1988, Huntley 2003

Distinguishing C. racemosa from other Cimicifuga species (ie, C. foetida, C. dahurica) is important. The primary index compound for identifying C. racemosa is cimifugin. The 7 other marker compounds identified as being specific to the North American species are cimigenol-3-O-alpha-L-ara, cimifugin-3-O-beta-D-glucoside, 23-epi-26-deoxyactein, and cimiracemoside A, C, F, and G.Guo 2017

An efficient countercurrent chromatography isolation method for black cohosh saponins has been developed.Cicek 2010 Quantitative chromatographic methods for determining triterpenes and formononetin in black cohosh rhizomes have been published.Avula 2009, Kennelly 2002 Stability of polyphenols and saponins in plant material has been evaluatedJiang 2008 and their content in an 85-year-old herbarium specimen has been determined.Jiang 2005

Uses and Pharmacology

A mechanistic study examining luteinizing hormone (LH) pulsatility in postmenopausal women suggested central opioid receptor activity of black cohosh. Naloxone blockade treatment in the context of black cohosh was associated with an unexpected increased frequency between LH pulses, especially during sleep.Reame 2008

Cancer

In vitro data

In vitro studies have demonstrated inhibitory effects of black cohosh and/or its extracts on prostate and breast cancer cells and endometrial adenocarcinoma cells, as well as on estradiol-induced cell proliferation in breast cancer cells. Additionally, cytotoxic effects on human cervical carcinoma cells have been reported. Arrest of cell cycle growth phase and apoptosis were noted mechanisms.Einbond 2004, Guo 2017, Jarry 2005, Szmyd 2018 A possible dual mechanism of action for black cohosh was an estrogen receptor–dependent and –independent process in breast cancer cells. A concentration-dependent reduction in both estrogen and progesterone receptor proteins was noted. An antiproliferative effect and reduction in cell viability of breast cancer cells was also observed after treatment with black cohosh.Szmyd 2018

Clinical data

A systematic review of studies published prior to 2013 examined use of black cohosh by pre- and postmenopausal breast cancer patients as well as those at risk. Cancer-related outcomes included incidence of primary breast cancer and recurrence, as well as effects on estrogen responsive tissues. Additionally, 1 study assessed quality of life among survivors. A total of 4 observational studies (n=66,458) assessed risk of breast cancer incidence and recurrence, whereas the 12 randomized controlled trials (RCTs) (n=1,563) and 5 uncontrolled trials (n=608) reported on estrogen responsive tissues. Observational data showed equivocal results between black cohosh users and nonusers regarding risk for breast cancer, with 1 study also showing no effect on recurrence. Data from clinical trials indicated a reduction in risk for primary breast cancer (adjusted odds ratio [OR], 0.47 [95% CI, 0.27 to 0.82]) and breast cancer recurrence (OR, 0.75 [95% CI, 0.63 to 0.89]). No significant impacts on circulating hormone levels (ie, estradiol, follicle-stimulating hormone [FSH], LH) or estrogen responsive tissues were observed.Fritz 2014

Menopause

Animal and in vitro studies suggest that conventional estrogenic action is unlikely to explain the plant's beneficial effects on menopausal discomfort. A dual mechanism of action involving both estrogen and progesterone receptors has been reported.Seidlova-Wuttke 2009, Szmyd 2018, Winterhoff 2003 The plant extract's action is more similar to estriol than estradiol; estriol exerts its effects mainly on the vaginal lining while estradiol exerts its effects on the uterine lining.Duker 1991

Animal and in vitro data

The isoflavone formononetin binds to estrogen receptor preparations; however, it did not reduce serum levels of LH in ovariectomized rats.Jarry 1985 N-methyl-serotonin has been isolated from black cohosh and shown to bind to 5-hydroxytriptamine-7 receptors and induce cyclic adenosine monophosphate.Powell 2008

The purported estrogenic effects of the plant could not be reproduced in extensive tests in mice. In 1 study, there was no evidence of a direct or indirect influence on gonadal function. However, other studies indicate that methanol extracts of C. racemosa contain substances that bind to estrogen receptors.Jarry 2003 Intraperitoneal injection of the extract in ovariectomized rats caused a selective reduction in LH level with almost no effect on FSH or prolactin levels.Jarry 1985 One report found no signs of uterine growth or vaginal cornification in ovariectomized rats given black cohosh extract.Einer 1996 In a more recent study, standardized cimicifuga extract increased staining of estrogen receptors in the endometrium of ovariectomized rats while lowering Ki67 protein levels. The increase in estrogen receptors due to cimicifuga was less than that produced by estradiol, although estradiol increased Ki67 staining.Alves 2008 Gene expression of estrogen receptor alpha was unchanged, while estrogen receptor beta expression was increased in the uterus of rats treated with cimicifuga.Seidlova-Wuttke 2009 A model of hot flushes in ovariectomized rats that measured peripheral temperatures responded to both estrogens and cimicifuga extract.Winterhoff 2003 This suggests that conventional estrogenic action is unlikely to explain the plant's beneficial effects on menopausal discomfort.

Clinical data

Several systematic meta-analyses, including a Cochrane review, have concluded that evidence is very weak to support efficacy of black cohosh in ameliorating menopausal symptoms.Borrelli 2008, Fritz 2014, Leach 2012, Palacio 2009, Shams 2010 However, a group of authors questioned a 2012 Cochrane review's negative conclusions regarding black cohosh and data pool and reassessed the published data, pooling evidence from placebo-controlled trials evaluating the impact of black cohosh on menopausal symptoms, including 2 clinical trials published during the time frame the Cochrane reviewers used but not included in the Cochrane data set. (No acknowledgement of these 2 studies, or an explanation for exclusion was provided in the Cochrane review.) Re-evaluation revealed a standardized mean difference of 0.385 in favor of black cohosh (P<0.0001).Beer 2013 Data from various studies are equivocal, with most showing no benefit for hot flushesFritz 2014, Geller 2009, Jacobson 2001, Jiang 2015, Lehmann-Willenbrock 1988, Newton 2006, Pockaj 2006, Reed 2008, Verhoeven 2005, Wuttke 2003 or menopausal symptoms,Fritz 2014, Jacobson 2001, Pockaj 2006, Verhoeven 2005, Wuttke 2003 or on vaginal and/or endometrial tissue, Fritz 2014, Reed 2008 while other studies have shown improvement in menopausal symptoms,Beer 2013, Frei-Kleiner 2005 some sleep parameters,Jiang 2015 and psychological domains.Julia Molla 2009 In a 3-month trial in peri- or postmenopausal women with vasomotor symptoms, treatment with black cohosh did not demonstrate effects on metabolic disease parameters of glucose, insulin, or lipids, or on fibrinogen.Spangler 2007

Black cohosh was compared with tibolone treatment in 125 women with endometriosis experiencing menopausal symptoms induced by postoperative gonadotropin-releasing hormone agonist therapy. After 3 months, Kupperman Menopausal Index scores were similar between treatment groups.Chen 2014

A 2014 systematic review examined the effects of black cohosh in pre- and postmenopausal breast cancer patients and those at risk of breast cancer. Menopause-related outcomes included assessments of hot flushes, quality of life, circulating hormone levels, and effects on estrogen responsive tissue. Results from trials that reported on hot flushes (3 RCTs, 2 uncontrolled trials; n=426) were equivocal and those reporting on estrogen responsive tissues (12 RCTs, 5 uncontrolled trials) found no significant impacts of black cohosh on mammographic density, markers of breast tissue proliferation, vaginal cytology, or endometrial hyperplasia. Similarly, no significant impact was found on circulating estradiol, FSH, or LH. Results related to bone health were also equivocal. One observational study evaluating effects on quality of life (n=788) also identified no significant effects associated with the use of black cohosh.Fritz 2014 In a small observational trial of tamoxifen-treated breast cancer patients (N=50) administered Remifemin for 6 months, women reported improvements in the intensity of menopausal symptom total scores (using Menopause Rating Scale) and in subscale items, including hot flushes, sweating, and sleep problems.Rostock 2011

Three RCTs were identified in a systematic review of studies (published over a 20-year period from 1996 to 2016) investigating the use of black cohosh for anxiety or depression. The 3 studies ranged in size from 28 to 120 menopausal or postmenopausal women; the smallest trial employed a dose escalation regimen from 64 to 128 mg/day over 3 months, and the other 2 studies used a dosage of 40 mg/day over 3 and 6 months. All 3 studies yielded equivocal results.Yeung 2018

In a small double-bind, randomized, placebo-controlled study in 42 postmenopausal women with the chief complaint of sleep disturbance, limited benefit of black cohosh (40 mg/day for 6 months) was demonstrated for 3 of 12 outcome measures (increased sleep efficiency, decreased wake after sleep onset duration, and improvement in Pittsburg Sleep Quality Index). Improvements in vasomotor and physical domains of life quality were also observed. No adverse events were reported, and no differences in FSH or estradiol levels between the placebo and black cohosh groups were observed.Jiang 2015

There were no clinical or endocrinological differences among estriol, conjugated estrogen, estrogen-gestagen, or black cohosh treatments in 60 women (younger than 40 years) who had undergone a hysterectomy and experienced climacteric symptoms.Lehmann-Willenbrock 1988

The WHO (2002) has acknowledged the use of Remifemin as an efficient extract for relieving the symptoms of menopause.Guo 2017 The American Association of Clinical Endocrinologists guidelines on the diagnosis and treatment of menopause (2011) and an updated position statement (2017) note that evidence regarding use of black cohosh in the management of menopause is limited, with concerns regarding possible estrogenicity and adverse reactions (eg, hepatitis, myopathy). The revised 2017 recommendations advise against any use of black cohosh in breast cancer survivors, including for the treatment hot flushes.Cobin 2017, Goodman 2011 Similarly, the Endocrine Society clinical practice guidelines for the treatment of symptoms of menopause (2015) recommend counseling patients on the lack of consistent evidence for benefit of complementary therapies, including black cohosh, as alternative nonhormonal therapy for vasomotor symptoms (weak recommendation; low quality evidence).Stuenkel 2015 The Society of Obstetricians and Gynaecologists of Canada revised clinical practice guidelines on managing menopause (2014) recommend that complementary and alternative medicine that has demonstrated efficacy for mild menopausal symptoms, including black cohosh, be offered by health care providers (level I-B evidence).Reid 2014

Osteoporosis

Animal data

Use of black cohosh in osteoporosis is supported by in vitro studies on osteoblastsChan 2008, Garcia Perez 2009 and studies in ovariectomized rats, where fracture healing accelerated compared with placebo, albeit by less than in rats treated with estrogens. The effect may be due to enhanced osteogenic mineralization of bone and inhibition of adipogenic differentiation, as well as antioxidant and anti-inflammatory activity (ie, reduced production of reactive oxygen species, interleukin-6, tumor necrosis factor alpha, and nuclear factor kappa B). Antidiabetic activity has been demonstrated in a diabetic mouse model, and a potential novel anti-Alzheimer compound has been identified that reduced amyloid-beta peptides in normal mice.Guo 2017, Kolios 2010

Clinical data

In a 12-month double-blind, randomized, placebo-controlled clinical trial (TRACE trial) investigating the effects of exercise with and without black cohosh on bone mineral density (BMD) and risk of coronary heart disease (CHD) in 128 early postmenopausal women, no differences were found between groups who did or did not receive black cohosh for either of the primary outcomes (BMD, CHD risk).Bebenek 2010

Polycystic ovary syndrome

Clinical data

Clinical studies have investigated black cohosh for improvement of in vitro fertilization and pregnancy rates in women with PCOS. It has been suggested that black cohosh acts directly on the hypothalamus to reduce gonadotropin-releasing hormone release and not via a direct effect on the pituitary.Arentz 2017, Kamel 2013, Shahin 2009 A 2017 systematic review and meta-analysis of nutritional supplements and herbal medicines for PCOS identified 1 RCT that compared the effects of C. racemosa extract (120 mg) given adjunctively with clomiphene versus effects of clomiphene alone in 194 women with PCOS. A significant treatment effect was observed for the combination group for reduced days to ovulation, pregnancy rates, FSH, and LH (P<0.01 for each), and for reduced miscarriage (P=0.036).Arentz 2017 However, in another study in 100 women with PCOS (mean age, approximately 23 years), no significant change in pregnancy rate was found with administration of black cohosh 40 mg/day for 10 days for 3 cycles compared with clomiphene 100 mg/day for 5 days. However, a significant reduction in LH levels (P=0.0001), as well as significant improvements in progesterone levels (P=0.0001) and endometrial thickness (P=0.0004) were observed.Kamel 2013

Vasodilation

Animal and in vitro data

Therapeutic action in peripheral arterial disease has been noted as a result of peripheral vasodilation and increased blood flow.Newall 1996 The constituent actein has been shown to have a hypotensive effect in rabbits and cats and caused peripheral vasodilation in dogs and rats.Genazzani 1962, Guo 2017 Vasodilatory action may be related to the inhibition of calcium ion influx mediated by potassium channels.Guo 2017

Other uses

Black cohosh has been identified as having anti-HIV activity,Sakurai 2004 antimicrobial activity,Bukowiecki 1972 and in vivo hypocholesterolemic activity.Newall 1996 In ovariectomized rats, black cohosh led to reduced weight gain and improved blood lipid profiles.Rachon 2008 Additionally, phenolic compounds from black cohosh have been identified as having anti-inflammatory properties,Schmid 2009, Schmid 2009, Yang 2009 and one study demonstrated effects greater than those achieved with indomethacin.Guo 2017

Dosing

Black cohosh extract is generally standardized to 2.5% of triterpene glycosides (ie, 1 mg/dose). Adulteration of C. racemosa products with Asian species (ie, C. foetida, C. dahurica) has been reported; distinguishing C. racemosa from other species is important for safe use of the product. According to one study, black cohosh is stable for at least 3 years when stored in a sealed container at room temperature (20°C to 25°C [68°F to 77°F]) and protected from light.Jiang 2013

Based on clinical use of commercial products, the current recommended black cohosh dose for management of symptoms of menopause is 40 to 80 mg/day, often in divided doses, of a 40% to 60% ethanol or isopropanol extract standardized to contain 1 mg of the triterpene 27-deoxyactein per 20 mg tablet. Therapeutic effects generally begin after 2 weeks of treatment, with maximum effects usually occurring within 8 weeks.Low Dog 2003, Pepping 1999 A systematic review of black cohosh for a variety of menstrual and menopausal conditions noted doses ranging from 6.5 to 160 mg/day from 1 to 12 months.Leach 2012

The pharmacokinetics of 23-epi-26-deoxyactein have been investigated in women administered black cohosh extract, with a measured half-life of approximately 2 hours.van Breemen 2010

Pregnancy / Lactation

Black cohosh should not be used in pregnancy or lactation. Black cohosh has been used to improve pregnancy rates following in vitro fertilization and in women with PCOS. Premature birth may occur with large doses. Concerns regarding labor-inducing, hormonal, emmenagogic, and anovulatory effects exist, based on low-level evidence and expert opinion.Dugoua 2006

Interactions

Antihypertensives: Black cohosh may enhance the hypotensive effect of antihypertensives. Monitor therapy.Ernst 2003, Richard 2005

Herbs (estrogenic properties): Black cohosh may enhance the adverse/toxic effect of estrogen derivatives. Monitor therapy.Zava 1998

Herbs (hypotensive properties): May enhance the adverse/toxic effect of other herbs (hypotensive properties). Excessive blood pressure lowering may manifest. Monitor therapy.Ernst 2003, Richard 2005

Medications for heart failure: Black cohosh interacts with angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, and amiodarone; avoid use in patients with heart failure.(Page 2016)

Adverse Reactions

In a review article on the safety of black cohosh herb, uncontrolled reports, postmarketing surveillance, and clinical trials of more than 2,800 patients demonstrated a low incidence of adverse reactions.Low Dog 2003 Hepatotoxicity is a rare but serious adverse effect for which there has been some concern in recent years. Critical analyses have generally failed to support a direct negative effect of black cohosh on the liver,Borrelli 2008, Teschke 2009, Teschke 2009, Teschke 2010 although a US Pharmacopeia panel recommended a cautionary label statement.Mahady 2008 Some cases of hepatotoxicity have required liver transplant.Mohammad 2013 It has been suggested that the cases of hepatotoxicity may be due to black cohosh constituent-drug interactions.Huang 2010 Health Canada found that products associated with liver toxicity were documented as not containing black cohosh.Lim 2013 However, clinical, histological, immunohistochemical, and electron microscopy analysis of 2 cases demonstrated oxidative damage that presented similarly in both patients as an irreversible, idiosyncratic, gradual distraction of liver parenchyma subsequent to immunologic synapses between the lymphocytes and hepatocytes. Presentation was identical to piecemeal necrosis (troxis necrosis) that is observed in autoimmune hepatitis or steatohepatitis. When sufficient parenchyma remains intact following discontinuation, quick recovery is possible.Enbom 2014

Data collected between 2004 and 2013 among 8 US centers in the Drug-induced Liver Injury Network revealed 15.5% (130) of hepatotoxicity cases were caused by herbals and dietary supplements, whereas 85% (709) were related to medications. Of the 130 related cases of liver injury related to supplements, 65% were from non-bodybuilding supplements and occurred most often in Hispanic/Latinos compared to non-Hispanic whites and non-Hispanic blacks. Liver transplant was also more frequent with toxicity from non-bodybuilding supplements (13%) than with conventional medications (3%) (P<0.001). Overall, the number of severe liver injury cases was significantly higher with supplements than conventional medications (P=0.02). Of the 217 supplement products implicated in liver injury, black cohosh was among the 22% (116) of single-ingredient products.Navarro 2014

In addition to hepatotoxicity, 3 cases related to cardiac and circulatory disorders, 1 case of convulsions, and 1 case of seizures have been reported.Huntley 2003, McKenzie 2010, Shuster 1996, Zimmermann 2010 For cases involving combination products, the association between reported effects and black cohosh is uncertain.Bae 2014, Sen 2013

Whether black cohosh has effects on endometrial tissue similar to that of hormone replacement therapies is controversial. A 1-year-long study in 400 postmenopausal women demonstrated no cases of endometrial hyperplasia and only minor endometrial effects.Raus 2006

Toxicology

Overdose of black cohosh may cause nausea, vomiting, dizziness, nervous system and visual disturbances, reduced pulse rate, and increased perspiration. The constituent actein did not possess toxicity in animal studies.Huntley 2003, Newall 1996 The current major concern is hepatotoxicity. Numerous case reports of liver damage have been publishedGuzman 2009, Joy 2008, Lontos 2003, Naser 2009, Pierard 2009, Whiting 2002; however, prospective clinical studies of liver function in women taking black cohosh have not found negative effects on liver function.Nasr 2009 Studies in rats have also not detected liver damage.Mazzanti 2008

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