Natural Products (Professional)

Black Cohosh

Scientific Name(s): Cimicifuga racemosa (L.) Nutt. Family: Ranunculaceae. Plants associated with the name include other Cimicifuga species, Actaea macrotys , and Actaea racemosa L.

Common Name(s): Baneberry , black cohosh , black snakeroot , bugbane , cimicifuga , rattleroot , rattleweed , rattletop , traubensilberberze , squawroot , and wanzenkraut 1 , 2

Clinical Overview

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Uses of Black Cohosh

Black cohosh has been used to help manage some symptoms of menopause and as an alternative to hormone replacement therapy (HRT). It may be useful for treatment of hypercholesteremia or peripheral arterial disease. Clinical studies do not support these uses.

Black Cohosh Dosing

On the basis of clinical studies, the currently recommended daily dose of black cohosh is a 40% to 60% ethanol or isopropanol extract of 40 to 80 mg herbal drug that is standardized to contain 1 mg of triterpene 27-deoxyactein per 20 mg tablet. Counsel patients that therapeutic effects generally begin after 2 weeks, with maximum effects usually seen within 8 weeks.

Contraindications

Black cohosh is contraindicated in pregnancy and may cause premature birth in large doses. Avoid black cohosh during lactation. It is also contraindicated in patients with aspirin sensitivity because it contains salicylates.

Pregnancy/Lactation

See Contraindications.

Black Cohosh Interactions

None well documented.

Black Cohosh Adverse Reactions

There is a low incidence of adverse reactions.

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 grows in open woods at the edges of dense forests from Ontario to Tennessee and west to Missouri. This perennial grows to 2.5 meters and is topped by a long plume of white flowers that bloom from June to September. Its leaflets are shaped irregularly with 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. 3

History

American Indians used black cohosh for the treatment of general malaise, kidney ailments, malaria, rheumatism, sore throat, and gynecological disorders (eg, menstrual cramps, ease of labor). 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 and cough, chorea, and other nervous system disorders. 4 , 5 , 6

Old-time remedy Lydia Pinkham's Vegetable Compound (early 1900s) contained many natural ingredients, one of which was black cohosh. 7

The roots and rhizomes of this herb 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.

A variety of Cimicifuga preparations are available commercially. However, Remifemin , the brand name of the standardized extract of the plant, has been widely studied and used in Germany for menopausal management since the mid-1950s. 5 , 8

Chemistry

German reports from the late 1960s, discussing the contents of black cohosh, are available. 9 , 10 , 11

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, (26 R )-actein, 26-deoxycimicifugoside, (26 S )-actein, 23- epi -26-deoxyactein, 23-OAc-shengmanol-3- O -β-d-xyloside, 26-deoxyactein, 25-OAc-cimigenol-3- O -α-L-arabinoside, 25-OAc-cimigenol-3- O -β-D-xyloside, cimigenol-3- O -α-L-arabinoside, and cimigenol-3- O -β-D-xyloside. Four phenylpropanoid esters, cimiracemates A-D (14), have been identified. 12 , 13

Black cohosh contains alkaloids, including N-methylcytisine. 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. 14 An amorphous resinous substance called cimicifugin (macrotin) accounts for approximately 15% to 20% of the root. Cimigoside (cimifugoside) and 27-deoxyacteine also have been isolated. The triterpene glycoside, 27-deoxyacteine, is used in Remifemin . 15 , 16 , 17

Black Cohosh Uses and Pharmacology

Black cohosh has been used to control symptoms of menopause as an alternative to conventional HRT therapy. The plant seems to have no stimulatory effect on estrogen-dependent cancers and may even exhibit inhibitory effects against the disease. Black cohosh also may be useful in other areas such as treatment for HIV, hypercholesteremia, and peripheral arterial disease.

Menopause
Animal data

The purported estrogenic effects of the plant could not be reproduced in extensive tests in mice. In one 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. Intraperitoneal injection of the extract in ovariectomized rats caused a selective reduction in luteinizing hormone (LH) level with almost no effect on follicle-stimulating hormone (FSH) or prolactin levels. 2 , 18 , 19 , 20

One report finds no signs of uterine growth or vaginal cornification in ovariectomized rats given black cohosh extract. This suggests that conventional estrogenic action cannot be the explanation for the plant's beneficial effects on menopausal discomfort. 2 , 21

Clinical data

In women treated for 8 weeks with the commercial product Remifemin and luteinizing hormone, but not FSH, levels were reduced. Remifemin is used for the management of menopausal hot flashes with analysis identifying at least 3 fractions that contribute synergistically to the suppression of LH and bind-to-estrogen receptors. These data suggest that black cohosh has a measurable effect on certain reproductive hormones. The product may offer an alternative to conventional HRT. In patient populations with a history of estrogen-dependent cancers, Remifemin shows no stimulatory effects on established breast tumor cell lines dependent on estrogen's presence (although it possesses some estrogenic activity). Instead, inhibitory actions were seen. In addition, the product exerts no effect on the endometrium, so it is not necessary to oppose therapy with progesterone as with conventional HRT. The plant extract's action proves to be more like estriol than estradiol, which is associated with higher risk for breast, ovarian, and endometrial cancers. Estriol exerts its effects mainly on the vaginal lining rather than on the uterine lining, as estradiol does. 22

Black cohosh was no better than placebo in reducing the intensity and number of menopausal hot flashes among breast cancer patients in a randomized, double-blind, placebo-controlled study. Of the 85 patients in the study, 42 were assigned to the treatment phase and 43 assigned to placebo. Fifty-nine patients were using tamoxifen, while 26 were not. Inclusion criteria included patients reporting menopausal symptoms such as daily hot flashes and completion of primary cancer therapy at least 2 months prior to entering the study. Exclusion criteria included using HRT for hot flashes, pregnancy, recurrent or metastatic breast cancer, or history of a major psychiatric illness. Patients were counseled to take 1 tablet by mouth twice daily with meals for 60 days. Before starting any study medication, each patient was asked to record the number of hot flashes, including their intensity. They were asked to do the same on days 27 to 30 and days 57 to 60 of the study. The average reported number of hot flashes declined for both groups; the overall decline from baseline to study completion was about 27%. The differences between treatment groups were not significant ( P = 0.86 via analysis of covariance adjusting for baseline number and for tamoxifen use; P = 0.44 via stratified Wilcoxon test in difference from baseline to completion). Other menopausal symptoms were analyzed between the groups in a global rating of health and well-being on a zero to 100 scale. These symptoms included headaches, poor sleep, heart palpitations, depression, irritability or nervousness, and excessive sweating. Overall, the global rating did not change significantly during the 2-month study. 23

A clinical and endocrinologic study has been performed in 60 patients under 40 years of age who had hysterectomies. Four randomized treatment groups included estriol, conjugated estrogens, estrogen-gestagen sequential therapy, or black cohosh extract. Results showed no differences among groups in success of therapy. 24

Miscellaneous

Constituent actein has been shown to have a hypotensive effect in rabbits and cats and to cause peripheral vasodilation in dogs. 25 , 26 It has been identified to have anti-HIV activity; 27 antimicrobial activity (both by black cohosh 28 and related species Cimicifuga dahurica ); 14 in vivo hypocholesteremic activity; and therapeutic action for patients with peripheral arterial disease (by causing peripheral vasodilation and increase in blood flow from constituent acteina). 14

Dosage

On the basis of clinical studies, to manage symptoms of menopause, the currently recommended dose of black cohosh is a 40% to 60% ethanol or isopropanol extract in a daily dose of 40 to 80 mg standardized to contain 1 mg of the triterpene 27-deoxyactein per 20 mg tablet. Therapeutic effects generally begin after 2 weeks, with maximum effects usually within eight weeks. 5 , 6

Pregnancy/Lactation

Black cohosh is contraindicated in pregnancy. Large doses may cause premature birth. 3 , 14

Interactions

Black cohosh may potentiate the effects of antihypertensive medications in rabbits but not in dogs or humans. 6

Adverse Reactions

In one review article on the safety of the herb, uncontrolled reports, postmarketing surveillance, and human clinical trials of more than 2,800 patients demonstrate a low incidence of adverse reactions. 5

Toxicology

Overdose of black cohosh may cause nausea, vomiting, dizziness, nervous system and visual disturbances, reduced pulse rate, and increased perspiration. The constituent acteina does not possess toxicity in animal studies. 14 , 17 Review articles primarily document case reports of hepatic toxicity. 29 However, cardiovascular and circulatory disorders and 1 case of convulsions have been documented. 17 A case report describes a woman 45 years of age who experienced seizures possibly related to consumption of an herbal preparation containing black cohosh. 30 A woman 52 years of age developed fulminant hepatic failure requiring liver transplantation after taking black cohosh to alleviate menopausal symptoms. 31

Bibliography

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3. Dobelis IN, ed. Magic and Medicine of Plants . Pleasantville, NY: Reader's Digest Association; 1986.
4. Winterhoff H, Spengler B, Christoffel V, Butterweck V, Lohning A. Cimicifuga extract BNO 1055: reduction of hot flushes and hints on antidepressant activity. Maturitas . 2003;44:S51-S58.
5. Low Dog T, Powell KL, Weisman SM. Critical evaluation of the safety of Cimicifuga racemosa in menopause symptom relief. Menopause . 2003;10:299-313.
6. Pepping J. Black cohosh: Cimicifuga racemosa . Am J Health Syst Pharm . 1999;56:1400-1402.
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8. Murray M. Am J Nat Med . 1997;4:3-5.
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10. Linde H. Contents of Cimicifuga racemosa . 3. On the constitution of the rings A, B and C of actein [in German]. Arch Pharm Ber Dtsch Pharm Ges . 1967;300:982-992.
11. Linde H. Contents of Cimicifuga racemosa . 5. 27-desoxyacetylactol [in German]. Arch Pharm Ber Dtsch Pharm Ges . 1968;301:335-341.
12. Li W, Chen S, Fabricant D, et al. High-performance liquid chromatographic analysis of Black Cohosh ( Cimicifuga racemosa ) constituents with in-line evaporative light scattering and photodiode array detection. Anal Chim Acta . 2002:471:61-75.
13. Chen SN, Fabricant DS, Lu ZZ, Zhang H, Fong HH, Farnsworth NR. Cimiracemates A-D, phenylpropanoid esters from the rhizomes of Cimicifuga racemosa . Phytochemistry . 2002;61:409-413.
14. Newall C, et al. Black Cohosh Herbal Medicines . London, England: Pharmaceutical Press, 1996;80-81.
15. Duke JA. CRC Handbook of Medicinal Herbs . Boca Raton, FL: CRC Press; 1985.
16. Berger S, et al. Planta Med . 1988;54:579.
17. Huntley A, Ernst E. A systematic review of the safety of black cohosh. Menopause . 2003;10:58-64.
18. Siess VM, et al. Arzneimittelforschung . 1960;10:514.
19. Jarry H, Harnischfeger G, Duker E. The endocrine effects of constituents of Cimicifuga racemosa . 2. In vitro binding of constituents to estrogen receptors [in German]. Planta Med . 1985;Aug:316-319.
20. Jarry H, Harnischfeger G. Endocrine effects of constituents of Cimicifuga racemosa . 1. The effect on serum levels of pituitary hormones in ovariectomized rats [in German]. Planta Med . 1985;Feb:46-49.
21. Einer-Jensen N, Zhao J, Andersen KP, Kristoffersen K. Cimicifuga and Melbrosia lack oestrogenic effects in mice and rats [in German]. Maturitas . 1996;25:149-153.
22. Duker EM, Kopanski L, Jarry H, Wuttke W. Effects of extracts from Cimicifuga racemosa on gonadotropin release in menopausal women and ovariectomized rats. Planta Med . 1991;57:420-424.
23. Jacobson JS, Troxel AB, Evans J, et al. Randomized trial of black cohosh for the treatment of hot flashes among women with a history of breast cancer. J Clin Oncol . 2001;19:2739-2745.
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25. Genazzani E, Sorrentino L. Vascular action of acteina: active constituent of Actaea racemosa L. Nature . 1962;194:544-555.
26. Corsano S, et al. Gazz Chimica Ital . 1969;99:915.
27. Sakurai N, Wu JH, Sashida Y, et al. Anti-AIDS Agents. Part 57: Actein, an anti-HIV principle from the rhizome of Cimicifuga racemosa (black cohosh), and the anti-HIV activity of related saponins. Bioorg Med Chem Lett . 2004;14:1329-1332.
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30. Shuster J. Hosp Pharm . 1996;31:1553-1554.
31. Lontos S, Jones RM, Angus PW, Gow PJ. Acute liver failure associated with the use of herbal preparations containing black cohosh. Med J Aust . 2003;179:390-391.
32. Tesch BJ. Herbs commonly used by women: an evidence-based review. Am J Obstet Gynecol . 2003;188:S44-S55.