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Black Cohosh

Plant Part Used

Root/rhizome

Active Constituents

Triterpene glycosides including 27-deoxyactein, actein, cimicifugoside, cimifugin and cimiracemosides A-H; isoflavones including formononetin; aromatic acids including isoferulic acid, fukinolic acid and salicylic acid.(1),(2),(3),(4),(5),(25)

[span class=alert]This section is a list of chemical entities identified in this dietary supplement to possess pharmacological activity. This list does not imply that other, yet unidentified, constituents do not influence the pharmacological activity of this dietary supplement nor does it imply that any one constituent possesses greater influence on the overall pharmacological effect of this dietary supplement.[/span]

Introduction

Black cohosh rhizome has been used in Chinese medicine for centuries as a remedy for conditions such as headache, non-eruptive measles, gingivitis, uterine and rectal prolapse. Native Americans used black cohosh as a remedy for female related problems, including painful menses, problem childbirth, arthritic problems and as an antidote for snakebite. The Eclectic physicians of the turn of the century in America relied on preparations of black cohosh for many problems, including rheumatism and female complaints. The rhizome preparation of black cohosh was listed as a popular remedy in the early U.S. Pharmacopoeias from 1820 to 1936, demonstrating the interest in the medicinal value of this herb. Black cohosh has been used with success in Europe for over 40 years for treatment of symptoms associated with menopause.

Interactions and Depletions

Interactions
  • Estrogen and estrogen-like medications including SERMs (tamoxifen, raloxifene). A laboratory study found that addition of black cohosh extract to tamoxifen therapy improved cytotoxicity in breast cancer cells.(26)
  • Opioid binding medications, including opiate pain medicines. Black cohosh has been reported to have central opioid activity in postmenopausal women.(27) Stop use of black cohosh at least 2 days before surgery and anesthesia, as black cohosh may interact with medications used during anesthesia and post-op pain control.(28)

Dosage Info

Dosage Range

20-40mg (equivalent to 1mg-2mg of 27-deoxyactein), 2 times daily (standardized extract).

Most Common Dosage

40mg (equivalent to 2mg of 27-deoxyactein), 2 times daily (standardized extract).

Standardization

[span class=doc]Standardization represents the complete body of information and controls that serve to enhance the batch to batch consistency of a botanical product, including but not limited to the presence of a marker compound at a defined level or within a defined range.[/span]

The most current available medical and scientific literature indicates that this dietary supplement should be standardized to 1mg of triterpene glycosides calculated as 27-deoxyactein.

Uses

Frequently Reported Uses

  • Climacteric symptoms associated with menopause And postmenopause
Other Reported Uses
  • Arthritic Complaints; anti-inflammatory
  • Headache

Toxicities & Precautions

General

This dietary supplement has a good safety profile with low toxicity, few and mild side effects and good tolerability.(6),(7)

Black cohosh is recommended to be taken for 6 months, followed by serum hormonal levels including estrogen (estradiol, estrone, estriol), DHEA, progesterone and testosterone.

Health Conditions

Black cohosh should be used with caution in those individuals with a liver condition or predisposed to a liver condition. There have been several reports of liver failure induced by black cohosh.(29),(30) A case of acute hepatitis involved a 47-year-old woman who used black cohosh for symptoms of menopause. She received a liver transplant three weeks after she started taking the herb. The report indicated the dose of black cohosh did not exceed the dosage recommended on the package; but no other dosage information was provided. It is not known if the supplement was adulterated or the past medical history of the patient. Black cohosh has been used with a low incidence of adverse effects in over 2,800 patients in reports and human clinical trials. A trial of 87 postmenopausal found no significant changes in total hepatic blood flow or any of the liver function tests after a year of treatment with standardized black cohosh.(31) However, regulatory agencies in the United States, Australia, Canada, and the European Union have released statements regarding the "potential association" between black cohosh and hepatotoxicity.(32)

Cutaneous vasculitis occurred in 2 patients on black cohosh therapy.(33)

Medical and scientific evidence indicates that constituents contained in this dietary supplement may have estrogenic activity. Until further research is performed, concern is warranted when recommending this dietary supplement to individuals who are susceptible to hormonally related cancers or who have a history of estrogen positive cancers.(8)

Side Effects

Large doses may cause nausea, vomiting, and headache. (9)

Pregnancy/ Breast Feeding

Do not use black cohosh in pregnancy, as it has reported uterine smooth muscle stimulant activity in laboratory studies. (10)

Age Limitations

Do not use in children under 2 years of age unless recommended by a physician.

Pharmacology

Hormonal balance activity

Clinical studies have reported positive effects on menopausal and post-menopausal complaints(11),(15),(35) with a good safety profile and few side effects(6) when using standardized extracts of black cohosh.(16) There are negative reports however, finding no benefit compared to placebo when using black cohosh extract for climacteric complaints and cognitive function during menopause and post menopause.(35),(36) It should be noted some negative studies did not use the recommended standardized product of black cohosh (see dosage and standardization). A review in 2008 of double blind, randomized, clinical trials in the evaluation of black cohosh’s efficacy reported the trials do not consistently demonstrate an effect of black cohosh on menopausal symptoms, but a beneficial effect of black cohosh on peri-menopausal women cannot be excluded.(37) Further studies need to be undertaken.

Black cohosh root and rhizome have been reported to have phytoestrogenic properties(11) though other studies have been unable to demonstrate estrogenic activity.(12),(13) Black cohosh contains the isoflavone formononetin, which has been reported to have estrogenic activity in laboratory rats.(14) Formononetin was reported to act as a competitor with estrogen in binding to uterine cells ex vivo.

Another constituent found in black cohosh, 27-deoxyactein, has also been reported to produce estrogen-like effects in humans.(17) In a controlled study, black cohosh tablets, standardized to 1mg of 27-deoxyactein, were given to 110 female patients in a university gynecological clinic. Patients received 2 tablets twice daily for 2 months. Half the patients took the black cohosh tablet, and half took a placebo. At the end of the required treatment period, both groups were tested for luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels, as increases in LH levels have been found in menopausal individuals complaining of hot flashes. There was no significant effect on the FSH serum concentration in either group. The study reported that black cohosh has positive effects on LH suppression in menopausal women, acting in an estrogen-like manner.

It should be noted, however, that naturally occurring estrogen in the body also affects the release of FSH through receptor binding; so even though black cohosh has estrogenic properties in the body, it does not have the exact pharmacology as naturally occurring estrogen. In another study, sixty-nine breast cancer patients completed a placebo-controlled study evaluating the impact of black cohosh on hot flashes and other menopausal symptoms experienced by these women. FSH and LH levels were also measured in the study. The results noted no significant difference between black cohosh and placebo in the number and intensity of hot flashes as well as other menopausal symptoms. Also, no differences were noted in the hormone levels measured.(13)

A laboratory study was designed to determine the binding affinity of three triterpene glycosides contained in black cohosh to estrogen receptor beta. Cimicifugoside, cimiracemoside F, and 27-deoxyactein were evaluated and of the three only 27-deoxyactein demonstrated any binding affinity, a weak four percent.(18) Of interest is a laboratory study reporting serotonergic activity (5-HT binding and increase in cAMP) of black cohosh extract, indicating another possible mechanism in improvement in mood and other climacteric symptoms.(38) A small clinical study found central opioid activity in postmenopausal women.(27)

A clinical study in 120 healthy, postmenopausal women compared black cohosh with fluoxetine (Prozac) for climacteric symptoms.(39) Black cohosh was found to be is more effective for treating hot flushes and night sweats, with fluoxetine being more effective in improvements in depressive symptoms.

Cimicifugoside is believed to affect the hypothalamus-pituitary system, producing a hormonal balancing effect in the female reproductive system.(21) The hypothalamus and pituitary glands control many aspects of human biochemistry, including hormonal release and regulation. Epidemiologic studies have suggested that consumption of phytoestrogen-rich foods may protect against breast cancer, and phytoestrogens such as genistein have been reported to both inhibit and stimulate the growth of some human breast cancer cells. Of recent interest is a report that phytoestrogen compounds found in black cohosh and other herbs such as vitex (chasteberry), hops and red clover may inhibit the growth of various breast cancer cell lines.(22),(23) Other studies have used breast cancer cell lines to demonstrate the estrogenic activity of black cohosh.(24)

Laboratory studies have reported that black cohosh may help protect against breast cancer in at risk individuals.(40) A laboratory study found that addition of black cohosh extract to tamoxifen therapy improved cytotoxicity in breast cancer cells.(26) A clinical study also has reported that black cohosh extract has no systemic or breast-specific estrogenic effects.(41)  Also, no changes in endometrial thickness have been reported when using black cohosh extracts.(42)

Of interest is a clinical study in postmenopausal women treated with black cohosh found a decrease in the urinary concentration of N-telopeptides, a marker of bone resorption, and an increase in alkaline phosphatase, a marker of bone formation, in the third month of therapy. Serum from treated women did not modify the activity of alkaline phosphatase or the expression of three genes, runt-related transcription factor-2 (Runx-2), alkaline phosphatase, and osteocalcin, when added to the MC3T3-E1 osteoblastic cell line.(43) Based on the findings, more studies need to be performed to determine black cohosh’s role in protecting menopausal and postmenopausal women from bone loss.

A review of eight human studies on the effectiveness of an extract of black cohosh on alleviating menopausal symptoms reported that it is a safe, effective alternative to estrogen replacement therapy for those patients in whom estrogen replacement therapy is either refused or contraindicated.(15) Other literature reviews have specifically noted that no evidence exists supporting the use of black cohosh and other herbs with noted estrogenic activity for vaginal dryness and dyspareunia in the pre and post menopausal women who experience urogential atrophy.(19),(44)

A clinical trial found that infertile women being treated with clomiphene citrate (Serophene) reported improved induction and timed intercourse after follicular-phase supplementation with phytoestrogens from black cohosh.(45)

Other activity

Black cohosh is also used as an adjunctive therapy in the management of rheumatoid arthritis and headache. The constituent isoferulic acid has been reported to have anti-inflammatory effects in animals. Isoferulic acid may also decrease muscular spasm in laboratory animals, potentially aiding not only headache but also menstrual pain and cramping.(20) The constituent salicylic acid is also found in small quantities in black cohosh. It is presumed that salicylic acid also contributes to the anti-inflammatory and analgesic properties of black cohosh. A laboratory study reported that the anti-inflammatory activity of compounds in black cohosh may also be due to its modulation of a signaling mitogen activated protein kinase and transcription factor nuclear factor-kappaB activities.(46)

References

  1. View Abstract: Sakurai N, et al. Chemical Constituents of Original Plants of Cimicifugae rhizoma in Chinese Medicine. Yakugaku Zasshi. Nov1996;116(11):850-65.
  2. View Abstract: Kruse SO, Lohning A, Pauli GF, et al. Fukiic and Piscidic Acid Esters from the Rhizome of Cimicifuga racemosa and the In Vitro Estrogenic Activity of Fukinolic Acid. Planta Med. Dec1999;65(8):763-4.
  3. View Abstract: Shao Y, Harris A, Wang M, et al. Triterpene Glycosides from Cimicifuga racemosa. J Nat Prod. Jul2000;63(7):905-10.
  4. View Abstract: He K, Zheng B, Kim CH, et al. Direct Analysis and Identification of Triterpene Glycosides by LC/MS in Black Cohosh, Cimicifuga racemosa, and In Several Commercially Available Black Cohosh Products. Planta Med. Oct2000;66(7):635-40.
  5. Newall CA, Anderson LA, Phillipson JD. Herbal Medicines; A Guide for Health-Care Professionals. London:The Pharmaceutical Press;1996.
  6. View Abstract: McKenna DJ, Jones K, Humphrey S, Hughes K. Black cohosh: efficacy, safety, and use in clinical and preclinical applications. Altern Ther Health Med. May2001;7(3):93-100.
  7. View Abstract: Huntley A, Ernst E. A systematic review of the safety of black cohosh. Menopause. Jan2003;10(1):58-64.
  8. View Abstract: Wade C, Kronenberg F, Kelly A, Murphy PA. Hormone-modulating herbs: implications for women's health. J Am Med Womens Assoc. 1999;54(4):181-3.
  9. PDR for Herbal Medicines, 2nd ed. Montvale, NJ: Medical Economics Company; 2000:93.
  10. View Abstract: McFarlin BL, Gibson MH, O'Rear J, Harman P. A national survey of herbal preparation use by nurse-midwives for labor stimulation. Review of the literature and recommendations for practice. J Nurse Midwifery. May1999;44(3):205-16.
  11. Jarry H, et al. The Endocrine Effects of Constituents of Cimicifuga racemosa. 2. In Vitro Binding of Constituents to Estrogen Receptors. Planta Med. Aug1985;4:316-19.
  12. View Abstract: Liu J, Burdette JE, Xu H, Gu C, van Breemen RB, Bhat KP, et al. Evaluation of estrogenic activity of plant extracts for the potential treatment of menopausal symptoms. J Agric Food Chem. May2001;49(5):2472-9.
  13. View Abstract: Jacobson JS, Troxel AB, Evans J, Klaus L, Vahdat L, Kinne D, et al. Randomized trial of black cohosh for the treatment of hot flashes among women with a history of breast cancer. J Clin Oncol. May2001;19(10):2739-45.
  14. Jarry H, et al. Endocrine Effects of Constituents of Cimicifuga racemosa. 1. The Effect on Serum Levels of Pituitary Hormones in Ovariectomized Rats. Planta Med. Feb1985;1:46-49.
  15. View Abstract: Lieberman S. A Review of the Effectiveness of Cimicifuga racemosa (black cohosh) for the Symptoms of Menopause. J Womens Health. Jun1998;7(5):525-29.
  16. View Abstract: Dog TL, Powell KL, Weisman SM. Critical evaluation of the safety of Cimicifuga racemosa in menopause symptom relief. Menopause. Jul2003;10(4):299-313.
  17. View Abstract: Duker EM, et al. Effects of Extracts from Cimicifuga racemosa on Gonadotropin Release in Menopausal Women and Ovariectomized Rats. Planta Med. Oct1991;57(5):420-24.
  18. View Abstract: Onorato J, Henion JD. Evaluation of triterpene glycoside estrogenic activity using LC/MS and immunoaffinity extraction. Anal Chem. Oct2001;73(19):4704-10.
  19. View Abstract: Willhite LA, O'Connell MB. Urogenital atrophy: prevention and treatment. Pharmacotherapy. Apr2001;21(4):464-80.
  20. Shibata M, et al. Pharmacological Studies on the Chinese Crude Drug "Shoma" III. Central Depressant and Antispasmodic Actions of Cimicifuga rhizoma, Cimicifuga simplex Wormsk. Yakugaku Zasshi. Nov1980;100(11):1143-50.
  21. View Abstract: Koeda M, et al. Studies on the Chinese Crude Drug "Shoma." IX. Three Novel Cyclolanostanol Xylosides, Cimicifugosides H-1, H-2 and H-5, from Cimicifuga Rhizome. Chem Pharm Bull. Tokyo. May1995;43(5):771-76.
  22. View Abstract: Dixon-Shanies D, Shaikh N. Growth Inhibition of Human Breast Cancer Cells by Herbs and Phytoestrogens. Oncol Rep. Nov1999;6(6):1383-7.
  23. View Abstract: Einbond LS. Growth inhibitory activity of extracts and purified components of black cohosh on human breast cancer cells. Breast Cancer Res Treat. 2004 Feb;83(3):221-31.
  24. View Abstract: Liu Z, Yang Z, Zhu M, Huo J. Estrogenicity of black cohosh (Cimicifuga racemosa) and its effect on estrogen receptor level in human breast cancer MCF-7 cells. Wei Sheng Yan Jiu. Mar2001;30(2):77-80.
  25. Nuntanakorn P, Jiang B, Einbond LS, Yang H, Kronenberg F, Weinstein IB, Kennelly EJ. Polyphenolic constituents of Actaea racemosa. J Nat Prod. Mar 2006;69(3):314-318.
  26. Al-Akoum M, Dodin S, Akoum A. Synergistic cytotoxic effects of tamoxifen and black cohosh on MCF-7 and MDA-MB-231 human breast cancer cells: an in vitro study. Can J Physiol Pharmacol. Nov 2007;85(11):1153-1159. Phytomedicine. Jun 2008;15(6-7):504-511. Epub  5 Nov 2007.
  27. Reame NE, Lukacs JL, Padmanabhan V, Eyvazzadeh AD, Smith YR, Zubieta JK. Black cohosh has central opioid activity in postmenopausal women: evidence from naloxone blockade and positron emission tomography neuroimaging. Menopause. Sep-Oct 2008;15(5):832-840.
  28. Dinman S. Black cohosh: a contraindication in general anesthesia. Plast Surg Nurs. Jan-Mar 2006;26(1):42-43. No abstract available.
  29. Lynch CR, Folkers ME, Hutson WR. Fulminant hepatic failure associated with the use of black cohosh: a case report. Liver Transpl. 2006;12(6):989-992.
  30. Low Dog T, Powell K, Weisman S. Critical evaluation of the safety of Cimicifuga racemosa in menopause symptom relief. Menopause. 2003;10(4):299-313.
  31. Nasr A, Nafeh H. Influence of black cohosh (Cimicifuga racemosa) use by postmenopausal women on total hepatic perfusion and liver functions. Fertil Steril. Nov 2009;92(5):1780-1782. Epub  21Jun2009.
  32. Mahady GB, Low Dog T, Barrett ML, et al. United States Pharmacopeia review of the black cohosh case reports of hepatotoxicity. Menopause. Jul-Aug 2008;15(4 Pt 1):628-638. Review.
  33. Ingraffea A, Donohue K, Wilkel C, Falanga V. Cutaneous vasculitis in two patients taking an herbal supplement containing black cohosh. J Am Acad Dermatol. May 2007;56(5 Suppl):S124-126. No abstract available.
  34. Juliá Mollá MD, García-Sánchez Y, Romeu Sarri A, Pérez-lópez FR. Cimicifuga racemosa treatment and health related quality of life in post-menopausal Spanish women. Gynecol Endocrinol. Jan 2009;25(1):21-26.
  35. Geller SE, Shulman LP, van Breemen RB, et al. Safety and efficacy of black cohosh and red clover for the management of vasomotor symptoms: a randomized controlled trial. Menopause. Nov-Dec 2009;16(6):1156-1166.
  36. Maki PM, Rubin LH, Fornelli D, Drogos L, Banuvar S, Shulman LP, Geller SE. Effects of botanicals and combined hormone therapy on cognition in postmenopausal women. Menopause. Nov-Dec 2009;16(6):1167-1177.
  37. Borrelli F, Ernst E. Black cohosh (Cimicifuga racemosa) for menopausal symptoms: a systematic review of its efficacy. Pharmacol Res. Jul 2008;58(1):8-14. Epub  8 Jun 2008. Review.
  38. Powell SL, Gödecke T, Nikolic D, et al. In vitro serotonergic activity of black cohosh and identification of N(omega)-methylserotonin as a potential active constituent. J Agric Food Chem. 24 Dec 2008;56(24):11718-11726.
  39. Oktem M, Eroglu D, Karahan HB, Taskintuna N, Kuscu E, Zeyneloglu HB. Black cohosh and fluoxetine in the treatment of postmenopausal symptoms: a prospective, randomized trial. Adv Ther. Mar-Apr 2007;24(2):448-461.
  40. Einbond LS, Wen-Cai Y, He K, Wu HA, Cruz E, Roller M, Kronenberg F. Growth inhibitory activity of extracts and compounds from Cimicifuga species on human breast cancer cells. Phytomedicine. Jun 2008;15(6-7):504-511. Epub 5 Nov 2007.
  41. Ruhlen RL, Haubner J, Tracy JK, et al. Black cohosh does not exert an estrogenic effect on the breast. Nutr Cancer. 2007;59(2):269-277.
  42. Raus K, Brucker C, Gorkow C, Wuttke W. First-time proof of endometrial safety of the special black cohosh extract (Actaea or Cimicifuga racemosa extract) CR BNO 1055. Menopause. Jul-Aug 2006;13(4):678-691.
  43. García-Pérez MA, Pineda B, Hermenegildo C, Tarín JJ, Cano A. Isopropanolic Cimicifuga racemosa is favorable on bone markers but neutral on an osteoblastic cell line. Fertil Steril. Apr 2009;91(4 Suppl):1347-1350. Epub  13 Jun 2008.
  44. Reed SD, Newton KM, LaCroix AZ, Grothaus LC, Grieco VS, Ehrlich K. Vaginal, endometrial, and reproductive hormone findings: randomized, placebo-controlled trial of black cohosh, multibotanical herbs, and dietary soy for vasomotor symptoms: the Herbal Alternatives for Menopause (HALT) Study. Menopause. Jan-Feb 2008;15(1):51-58.
  45. Shahin AY, Ismail AM, Shaaban OM. Supplementation of clomiphene citrate cycles with Cimicifuga racemosa or ethinyl oestradiol--a randomized trial. Reprod Biomed Online. Oct2009;19(4):501-507.
  46. Yang CL, Chik SC, Li JC, Cheung BK, Lau AS. Identification of the bioactive constituent and its mechanisms of action in mediating the anti-inflammatory effects of black cohosh and related Cimicifuga species on human primary blood macrophages. J Med Chem. 12 Nov 2009;52(21):6707-6715.

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