Written by Jianping Liu, Xun Li and the CAM-Cancer Consortium.
Updated March 9, 2017

Black cohosh (Actaea racemosa)

Abstract and key points

  • Black cohosh (Actaea racemosa) is a medicinal herb.
  • Current evidence does not support an association between black cohosh and increased risk of breast cancer.
  • There is a lack of evidence supporting the efficacy of black cohosh for reduction of hot flashes in breast cancer patients.
  • Black cohosh appears to be relatively safe; but pre-existing liver damage is a contraindication.

Black cohosh (Actaea racemosa, synonym: Cimicifuga racemosa) is a medicinal herb traditionally used by native American Indians for menstrual, menopausal, and other conditions. Extracts of black cohosh have been recommended as an alternative to hormone replacement therapy for the treatment of hot flushes in menopausal women.

The effects of black cohosh have been assessed in a systematic review including 14 randomized controlled trials, 7 uncontrolled trials and 5 observational studies. The evidence on efficacy forhot flushesis divided, with some benefits seen when compared with baseline, but not when compared with placebo. Two observational studies found no association between black cohosh and risk of breast cancer, whereas two studies reported significant reductions in risk of primary breast cancer among postmenopausal women and risk of recurrence, respectively. Seventeen trials showed no significant impact on circulating hormone levels or proliferation in oestrogen responsive tissues.

Reviews of preclinical and clinical studies suggest black cohosh to be safe but pre-existing liver damage is a contraindication.

Read about the regulation, supervision and reimbursement of herbal medicine at NAFKAMs website CAM Regulation.

What is it?

Description

Black cohosh (Actaea racemosa, synonym: Cimicifuga racemosa) is a medicinal plant originating from eastern North America. Black cohosh products are commercially available on the market such as Remifemin® (manufactured by Schaper & Brümmer, Salzgitter, Germany) which is an isopropanolic extract of black cohosh standardised to contain 1 mg of triterpenes per 20 mg of extract 1. Another standardised ethanolic extract of black cohosh is BNO 1055 (Menofem®/Klimadynon®), BIONORICA, Neumarkt, Germany) 2.

Ingredients

The characteristic chemical constituents of the roots and rhizomes of black cohosh include cycloartenol-type triterpenoids and cimicifugoside, as well as cinnamic acid derivatives 3.

Application and dosage

Black cohosh is a dietary supplement, usually available as tablets. The commonly used dosage for black cohosh is 40 to 80 mg of dried rhizome (root) daily.

History/providers

Black cohosh has been used by native American Indians and Europeans for women’s conditions such as chronic ovaritis and amenorrhea 4. It was first listed in the U.S. Pharmacopoeia in 1830 under the name “black snakeroot” 5. It has been widely used for more than 40 years in Europe and was introduced in Germany in the 1940s for the treatment of menopausal discomfort, dysmenorrhoea, and climacteric neurovegetative complaints. More recently, black cohosh has been used as a therapy for menopausal symptoms such as hot flushes.

Claims of efficacy and alleged indications

Systemic breast cancer treatment can cause premature menopause, which results in hot flushes before the physiological menopause. Hot flushes are also the main adverse effect of the common anti-breast cancer treatment tamoxifen. Hormone replacement therapy (HRT) for hot flushes in breast cancer patients may not be appropriate because of evidence of a relationship between long-term use of HRT and increased risk of breast cancer and cardiovascular disease 6, and potential stimulation of cancer growth by HRT 7. There is therefore an increasing interest in finding safe and effective alternatives to HRT for the treatment of menopausal symptoms in breast cancer patients. Herbal preparations such as black cohosh are used as alternatives to HRT in the treatment of hot flushes 8.

Mechanism of action

The mechanism of action was proposed as being mediated by an inhibitory effect on the hypothalamus, or an effect on neurotransmitters 9, or a possible oestrogenic effect from the phyto-oestrogens 10.

A systematic review including 21 pre-clinical studies concluded that there is a potential antiproliferative effect on breast and prostate tumour cells as well as a theoretical beneficial use in prostate cancer patients.[14] This is, however, not likely to be due to an estrogenic component of the herb as preclinical studies consistently conclude a lack of specific estrogenic activity. The antiproliferative effects, which are observed in in vitro and/or in vivo models for both breast and prostate cancer, are likely to be causally impacted by the favourable disruption of anti/pro-apoptotic cellular machinery.

An in vitro study investigating 9 herbal extracts and 23 isoflavonoids found strong inhibitory effect in extract of black cohosh on breast cancer resistance protein-mediated transport of methotrexate 15. One animal study found that black cohosh presented some beneficial effect for breast cancer prevention and therapy, such as downregulating mitochondrial oxidative phosphorylation genes, but these findings were not consistent 16. Another recent animal study found chemopreventive potentials for mammary cancer, as black cohosh was found reduce Ki-67 and cyclin D1 protein expression in fibroadenomas by immunohistochemistry 17.

Prevalence of use

Specific prevalence data for the use of black cohosh by cancer patients are not available.

Legal issues

In most European countries and the US, plant-based preparations including herbal remedies are regulated as dietary supplements. However, the European Directive on traditional herbal medicinal products allows herbal medicines to be registered as drugs if they have been used medicinally for at least 30 years (including at least 15 years within EU countries) 11. Black cohosh has been granted a traditional herbal registration by the Medicines and Healthcare products Regulatory Agency for the relief of symptoms of the menopause, such as hot flushes, night sweats, and temporary changes in mood 12.

Cost(s) and expenditure

The average monthly cost of e.g. Remifemin is about US$20 or EUR11.

Does it work?

Systematic reviews

Fritz et al (2014) conducted a systematic review of black cohosh for use by pre- or postmenopausal breast cancer patients or those at risk of breast cancer 13. A total of 26 articles were included: 14 randomized controlled trials (RCTs), 7 uncontrolled trials, and 5 observational studies. Impact on risk of primary breast cancer incidence, risk of breast cancer recurrence, effect on oestrogen responsive tissues, and efficacy in treating menopausal symptoms following breast cancer treatment were assessed.

Two observational studies found no association between black cohosh andrisk of breast cancer, whereas two studies reported significant reductions in risk of primary breast cancer among postmenopausal women (adjusted odds ratio = 0.47, 95% confidence interval = 0.27-0.82), andrisk of recurrence(adjusted hazard ratio = 0.75, 95% confidence interval = 0.63-0.89); in the latter study the results could have been influenced by higher tamoxifen use in the black cohosh group.

Seventeen trials (12 RCTs, 5 uncontrolled trials) showed no significant impact on circulatinghormone levels or proliferation in oestrogen responsive tissues.

The evidence from 3 RCTs, 2 uncontrolled trials and one observational study on efficacy forhot flashesis divided. Some benefits were reported when compared with baseline (2 uncontrolled trials, one RCT) but not when compared with placebo (2 placebo-controlled RCTs, one observational study).

An earlier review by Walji et al. (2007) of the safety and efficacy of black cohosh for cancer patients including five clinical studies also concluded that the research assessing efficacy of black cohosh for hot flushes associated with menopause in women with breast cancer was inconclusive; the existing results were conflicting and all the trials had significant methodological flaws 14

Controlled clinical trials

No additional clinical trials were identified.

Observational studies

No additional observational studies were identified.

Is it safe?

Adverse events

The minor adverse effects observed in clinical studies include nausea, vomiting, headaches, dizziness, mastalgia, and weight gain 18-20.

The above mentioned systematic review by Walji et al. of black cohosh in cancer patients concluded that black cohosh seems to have a relatively good safety profile 14. Another systematic review of black cohosh’s safety in general (not only cancer patients) retrieved 13 clinical trials involving more than 2,800 patients 21. All trials indicate relative safety: 97% of all the reported adverse effects were minor, and the only severe ones were not deemed to be related causally to black cohosh. This is in line with the findings of an earlier review 22. Recent clinical trials in general populations confirm these findings 23-26.

In response of the "potential association" between black cohosh and hepatotoxicity, a systematic review published in 2008 by the Dietary Supplement Information Expert Committee of the US Pharmacopeia's Council of Experts on the hepatotoxicity found all the reports of liver damage were assigned possible causality, and none were of probable or certain causality 27. The clinical pharmacokinetic and animal toxicological information did not reveal unfavourable information about black cohosh.

Fritz et al did not systematically assess the impact of black cohosh on liver function but reported no impact on liver function or symptoms suggestive of impaired liver function among the studies the included in their review 13.

A systematic review published in 2011 including five randomized double-blind clinical trials involving 1,117 women who were treated daily with black cohosh extract for 3 to 6 months also found no evidence that it had any adverse effect on liver function 28. These confirms the findings of the 2007 systematic review by Walji including five RCTs and 21 pre-clinical studies of cancer patients 13.

The eight most recent papers reviewing published and spontaneous case reports (numbers ranging from 22 to 75) of initially alleged black cohosh hepatotoxicity were identified. All surveys found a lack of causality for the herbal medicine in all cases 29-36

Contraindications

Pre-existing liver damage is a contraindication.

Interactions

Black cohosh was found to alter the response to the agents commonly used to treat breast cancer in an experiment report using mouse breast cancer line 37. In this experiment, the black cohosh extracts increased the cytotoxicity of doxorubicin and docetaxel and decreased the cytotoxicity of cisplatin.

Warnings

Based on the safety review by the Dietary Supplement Information Expert Committee 27, it was determined that black cohosh products should be labelled to include a cautionary statement. This is a change from the Expert Committee's decision of 2002, which required no such statement

Citation

Jianping Liu, Xun Li, CAM-Cancer Consortium. Black cohosh (Actaea racemosa) [online document]. http://cam-cancer.org/The-Summaries/Herbal-products/Black-cohosh-Actaea-racemosa. March 9, 2017.

Document history

Most recent update in March 2017 by Barbara Wider.
Assessed as up to date in September 2013 by Barbara Wider.
Update and revision in June 2012 by Jianping Liu, Xun Li and Guoyan Yang.
Fully revised and updated in August 2009 by Jianping Liu and Xun Li.
Summary first published in March 2006, authored by Jianping Liu. 

References

  1. Piersen CE. Phytoestrogens in botanical dietary supplements: implications for cancer. Integr Cancer Ther 2003; 2(2): 120-38.
  2. Popp M, Schenk R, Abel G. Cultivation of Cimicifuga racemosa (L.) nuttal and quality of CR extract BNO 1055. Maturitas 2003; 44 (Suppl 1):S1-7.
  3. Mahady GB, Fabricant D, Chadwick LR, Dietz B. Black cohosh: an alternative therapy for menopause? Nutr Clin Care 2002;5(6):283-9
  4. Anonymous. Cimicifuga racemosa. Monograph. Alternative Medicine Review 2003; 8(2):186-9.
  5. Blumenthal M, ed. Herbal Medicine: Expanded Commission E Monograph. 1st ed. Newton, Mass: Integrative Medicine Communications; 2000.
  6. Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML, Jackson RD, Beresford SA, Howard BV, Johnson KC, Kotchen JM, Ockene J; Writing Group for the Women's Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial. JAMA. 2002;288(3):321-33.
  7. Schairer C, Lubin J, Troisi R, Sturgeon S, Brinton L, Hoover R. Menopausal estrogen and estrogen-progestin replacement therapy and breast cancer risk. JAMA. 2000;283(4):485-91.
  8. Graf MC, Geller PA. Treating hot flushes in breast cancer survivors: a review of alternative treatments to hormone replacement therapy. Clin J Oncol Nurs 2003;7(6):637-40.
  9. Einer-Jensen N, Zhao J, Andersen KP, Kristoffersen K. Cimicifuga and Melbrosia lack oestrogenic effects in mice and rats. Maturitas 1996;25:149-53.
  10. Kruse SO, Lohning A, Pauli GF, Winterhoff H, Nahrstedt A. Fukiic and piscidic acid esters from the rhizome of Cimicifuga racemosa and the in vitro estrogenic activity of fukinolic acid. Planta Med 1999; 65(8):763-4.
  11. De Smet P. Herbal medicine in Europe – relaxing regulatory standards. N Engl J Med 2005;352:1176-8.
  12. Medicines and Healthcare products Regulatory Agency. Guidance: Herbal Medicines Granted a Traditional Herbal Registration (THR), updated 7th March 2017. Available at: https://www.gov.uk/government/publications/herbal-medicines-granted-a-traditional-herbal-registration-thr/herbal-medicines-granted-a-traditional-herbal-registration, accessed 9th March 2017.
  13. Fritz H, Seely D, McGowan J, Skidmore B, Fernandes R, Kennedy DA, Cooley K, Wong R, Sagar S, Balneaves LG, Fergusson D. Black cohosh and breast cancer: a systematic review. Integr Cancer Ther. 2014;13(1):12-29.
  14. Walji R, Boon H, Guns E, Oneschuk D, Younus J. Black cohosh (Cimicifuga racemosa [L.] Nutt.): safety and efficacy for cancer patients. Support Care Cancer. 2007;15(8):913-21.
  15. Tamaki H, Satoh H, Hori S, Ohtani H, Sawada Y. Inhibitory effects of herbal extracts on breast cancer resistance protein (BCRP) and structure-inhibitory potency relationship of isoflavonoids. Drug Metab Pharmacokinet. 2010;25(2):170-9.
  16. Einbond LS, Soffritti M, Esposti DD, Wu HA, Tibaldi E, Lauriola M, He K, Park T, Su T, Huggins L, Wang X, Roller M, Brennan R. Pharmacological mechanisms of black cohosh in Sprague-Dawley rats. Fitoterapia. 2012 Apr;83(3):461-8.
  17. Einbond LS, Soffritti M, Degli Esposti D, Tibaldi E, Lauriola M, Bua L, He K, Genovese G, Su T, Huggins L, Wang X, Roller M, Wu HA. Chemopreventive potential of black cohosh on breast cancer in Sprague-Dawley rats. Anticancer Res. 2012;32(1):21-30.
  18. Zava DT, Dollbaum CM, Blen M. Estrogen and progestin bioactivity of foods, herbs, and spices. Proc Soc Exp Biol Med 1998;217:369-78.
  19. Wu XS. Remifemin improve gynecological malignant tumor postoperative patients of menopause syndrome for the clinical research. Dissertation for Master Degree of Dalian Medical University 2011; 1-20.
  20. Huang XF. The clinical research of Black cohosh extract in breast cancer patients with climacteric complaints. Dissertation for Master Degree of Manjing University of Chinese Medicine 2011;10-21.
  21. Borrelli F. Ernst E. Black cohosh (Cimicifuga racemosa): a systematic review of adverse events. American Journal of Obstetrics & Gynecology 2008;199(5):455-66.
  22. Huntley A. The safety of black cohosh (Actaea racemosa, Cimicifuga racemosa). Expert Opin Drug Saf 2004; 3(6):615-23.
  23. Ross SM. Menopause: a standardized isopropanolic black cohosh extract (remifemin) is found to be safe and effective for menopausal symptoms. Holist Nurs Pract. 2012;26(1):58-61.
  24. Bai WP, Wang SY, Liu JL, Geng L, Hu LN, Zhang ZL, Chen SL, Zheng SR. Efficacy and safety of remifemin compared to tibolone for controlling of perimenopausal symptoms. Chinese Journal of Obstetrics and Gynecology 2009;44(8): 597-600.
  25. Li YL, Cui MH, Gao S. Efficacy of remifemin for control of climacteric symptoms. Progress in Obstetrics and Gynecology 2011;20(6): 462-65.
  26. Sun NX, Jin ZJ, Jia XF, Li W. Black cohosh improves vaginal atrophy in postmenopausal women. Academic Journal of Second Military Medical University 2012;33(3): 339-42.
  27. Mahady GB. Low Dog T. Barrett ML. Chavez ML. Gardiner P. Ko R. Marles RJ. Pellicore LS. Giancaspro GI. Sarma DN. United States Pharmacopeia review of the black cohosh case reports of hepatotoxicity. Menopause 2008;15(4 Pt 1):628-38.
  28. Naser B, Schnitker J, Minkin MJ, de Arriba SG, Nolte KU, Osmers R. Schaper & Brümmer GmbH & Co. KG, Salzgitter, Germany. Suspected black cohosh hepatotoxicity: no evidence by meta-analysis of randomized controlled clinical trials for isopropanolic black cohosh extract. Menopause. 2011;18(4):366-75.
  29. Teschke R, Schwarzenboeck A, Schmidt-Taenzer W, Wolff A, Hennermann KH. Herb induced liver injury presumably caused by black cohosh: a survey of initially purported cases and herbal quality specifications. Ann Hepatol. 2011;10(3):249-59.
  30. Teschke R, Schmidt-Taenzer W, Wolff A. Spontaneous reports of assumed herbal hepatotoxicity by black cohosh: is the liver-unspecific Naranjo scale precise enough to ascertain causality? Pharmacoepidemiol Drug Saf. 2011;20(6):567-82.
  31. Firenzuoli F, Gori L, Roberti di Sarsina P. Black cohosh Hepatic Safety: Follow-Up of 107 Patients Consuming a Special Cimicifuga racemosa rhizome Herbal Extract and Review of Literature. Evid Based Complement Alternat Med. 2011;2011:821392.
  32. Huang Y, Jiang B, Nuntanakorn P, Kennelly EJ, Shord S, Lawal TO, Mahady GB. Fukinolic acid derivatives and triterpene glycosides from black cohosh inhibit CYP isozymes, but are not cytotoxic to Hep-G2 cells in vitro. Curr Drug Saf. 2010;5(2):118-24.
  33. Teschke R. Black cohosh and suspected hepatotoxicity: inconsistencies, confounding variables, and prospective use of a diagnostic causality algorithm. A critical review. Menopause. 2010;17(2):426-40.
  34. Teschke R, Bahre R, Fuchs J, Wolff A. Black cohosh hepatotoxicity: quantitative causality evaluation in nine suspected cases. Menopause. 2009;16(5):956-65.
  35. Teschke R, Bahre R, Genthner A, Fuchs J, Schmidt-Taenzer W, Wolff A. Suspected black cohosh hepatotoxicity--challenges and pitfalls of causality assessment. Maturitas. 2009;63(4):302-14.
  36. Teschke R, Schwarzenboeck A. Suspected hepatotoxicity by Cimicifugae racemosae rhizoma (black cohosh, root): critical analysis and structured causality assessment. Phytomedicine. 2009;16(1):72-84.
  37. Rockwell S, Liu Y, Higgins SA. Alteration of the effects of cancer therapy agents on breast cancer cells by the herbal medicine black cohosh. Breast Cancer Res Treat. 2005;90(3):233-9.