Black Black CohoshCohosh

Presentation Created by: Shannon Liu, Anthony Der

Black Cohosh: About the Black Cohosh: About the PlantPlantCimicifuga racemosaRoots and rhizomes are the basis for the

extraction (not the flowers)◦ Can be extracted using alcohols

Extracts contain 26-deoxyactein◦ Member of the triterpene glycosides◦ In most extractions, approximately 1 mg of

triperpene per 20 mg dose of extractGenerally grown in temperate to cold

weather in damp, fertile soil (forests).

[12]

Traditional UsesTraditional UsesMost common treatments using black

cohosh: hormonal imbalances◦ Primarily menopause and breast cancer

Effectiveness has been tested in controlled studies Popular in Germany for climacteric symptoms (time

before menopause) One of the very first trials testing the effectiveness of black cohosh

was run in 1989 by the German Commission E

◦ Traditional uses dating back to Native Americans for other remedies for: Sore throat inducing lactation Diuretics Fever Gynecological disorders “Conditions that affected women’s reproductive

organs”

[13], [14]

Marketed Uses and Marketed Uses and DisclaimersDisclaimers Some books/sites recommend growing and

extracting your own black cohosh roots by collecting black cohosh, drying the roots, and then creating tinctures out of them

Possible side effects ◦ Nausea◦ Vomiting◦ upset stomach◦ A few reports of liver disease

Overdose of black cohosh ◦ Dizziness◦ Slowed heart rate◦ Tremors◦ Light-headedness

No long term data (more than 6 months)◦ Therefore generally not recommended to take for more

than 6 months Shown to have possible interactions with

hormonal replacement drugs[15]

Female Reproductive System

Key concepts◦Anatomy –

ovary, endometrium

◦Ovariectomy◦Estrogen and

estrogen receptors (ER)

Menopause◦Lowered

hormone levels[10]

PharmacodynamicsMechanism of action: unknown,

but possible estrogenic effect◦4 studies indicate some estrogenic

effect◦3 studies indicate no relationship

[1] – [9]

PharmacodynamicsEvidence for Estrogen Receptor (ER)

mechanismKruse et al: Fukinloic acid caused increased

proliferation of an estrogen dependent MCF-7 cell system Fukinolic acid has estrogenic activity

Düker et al: Remifemin suppresses LH levels, due to at least 3 synergistically acting compounds

Dixon: consumption of phytoestrogen-rich foods causes inhibition of MCF-7 and T-47 breast cancer cell growth

Liu, Yang et al: increasing dosage of black cohosh allowed for uterine weight increase, prolonged estrus Black cohosh has a stimulating effect on estrogen receptors.

[1], [2], [4], [5]

PharmacodynamicsRefuting evidence for Estrogen

Receptor mechanismLiu, Burdette et al: No indication of

estrogenic activity in estrogen receptors of endometrial cells

Einer et al: no relationship between black cohosh and uterine weight

Freudenstein et al: administered black cohosh or estrogen after inducing tumors and performing ovariectomy in rats; no significant difference in cancer growth or estrogen sensitive organs

[3], [6], [7]

PharmacokineticsMinimal research on

pharmacokinetics of black cohosh◦ Some evidence that it

weakly inhibits CYP2D6 (Gurley et al)

Clinical study underway: Pharmacokinetics of Black Cohosh ◦ Duke University Medical Center, NCCAM◦ Investigation of levels of components of

black cohosh obtained in the blood of healthy women taking Remifemin.

[8]

Black Cohosh and Breast Black Cohosh and Breast Cancer (First Study)Cancer (First Study)Approximately 2/3 of breast cancer

survivors undergo hot flashes ◦ A double blind study was done to see if

black cohosh would minimize the hot flashes received by the women

◦ Women were selected based off of a demographic survey and also had other criteria met (completed primary therapy at least two months before trial)

◦ Instructed to take tablets twice daily with meals for 60 days. The women were supposed to count the number of

hot flashes for a three day period before the trial as well as severity (on a 1-3 scale, of mild, moderate, or severe) At the 27-30 day mark and the 57-60 day mark the women

went through the same process[15]

Black Cohosh and Breast Black Cohosh and Breast Cancer (First Study)Cancer (First Study)Total of 85 study participants

◦ Both the placebo and no placebo group reported lowered number of hot flashes Although 59 of the patients were using tamoxifen, this

had no foreseeable effect on the study However, the overall difference between the placebo

group and the group taking the black cohosh extract pill was not significant (P = .86 via analysis of covariance adjusting for baseline

number and for tamoxifen use)

◦ Limitation of the study Trial period was only for 2 months, due to concern of

patients dropping out of the study due to lack of benefits

16 people out of the 85 dropped out of the study

[15]

Black Cohosh and Breast Black Cohosh and Breast CancerCancer (Second Study)(Second Study)Another, similar study was done also

involving 132 women with breast cancer and hot flashes◦ A double blind study, with the trial being 2 4-

weeks long ◦ In this study, a daily hot flash record was kept

instead of three specific dates◦ Once again, the amount of hot flashes

experienced by women decreased in both the placebo groups and the Black Cohosh group, yet the difference between the two was not significant enough to show that Black Cohosh was the cause of the decrease.

◦ Placebo effect

[16], [17]

Black Cohosh and Black Cohosh and MenopauseMenopauseA study of 351 women peri or

postmenopausal women between the ages of 45 and 55, were randomly assigned a 150 or 200 mg of a Black cohosh, a dietary supplement, a hormonal therapy pill, or a placebo◦ The black cohosh was provided by Pure World

Inc.◦ This study lasted for a year◦ Once again, the study indicated that the black

cohosh groups had no significant difference with the women that were in the placebo group Any decreases in hot flashes were mostly contributed to

either the placebo effect, or that hot flashes naturally decline over time

[18]

Black Cohosh: It Works?Black Cohosh: It Works?One study claimed that black cohosh was

effective in treating climacteric symptoms in women. ◦ Double blind study, with 304 women for twelve

weeks2.5 mg isopropanolic extract of Cimicifuga

Racemosa in the black cohosh pill.◦ Results showed a significant change of the patients

using the black cohosh pill

So What Went Wrong?◦ The data reporting is skewed, the scale used in the

data does not accurately measure the amount of hot flashes per day, but actually measures the relationship between ability to sleep and type of pill taken without taking into account the number of hot flashes each women had.

[19]

ContraindictionsUntil the relationship between

black cohosh and hormones has been better established, women should avoid taking black cohosh…◦ During pregnancy◦ For the treatment of breast cancer◦ In combination with other hormonal

treatments Herb-drug interactions of black

cohosh have not yet been sufficiently studied

[11]

Black Cohosh in summary…Alternative medicine sometimes used to

alleviate menopausal symptoms, some evidence of anti-cancer

Few studies supporting effectiveness of black cohosh for the above but also many refuting the effectiveness◦ Most studies have their own limitations, which

hinder the effectiveness of the study Number of people in the study Duration of study Limited info on extraction and dosage

Further research can be done to solidify existing evidence

References1. 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 Medica 65: 763-764, 1999.

2. Düker EM, Kopanski L, Jarry H, Wuttke W: Effects of extracts from Cimicifuga racemosa on gonadotropin release in menopausal women and ovariectomized rats. Planta Medica 57: 420-424, 1991.

3. Liu J, Burdette JE, Xu H, et al.: Evaluation of estrogenic activity of plant extracts for the potential treatment of menopausal symptoms. Journal of Agricultural and Food Chemistry. 49:2472-2479, 2001.

4. Dixon-Shanies D, Shaikh N: Growth inhibition of human breast cancer cells by herbs and phytoestrogens. Oncology Reports 6: 1383-1387, 1999.

5. 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 (in Chinese). Wei Sheng Yan Jiu 30: 77-80, 2001.

6. Einer-Jensen N, Zhao J, Anderson KP, Kristoffersen K: Cimicifuga and Melbrosia lack oestrogenic effects in mice and rats. Maturitas 25: 149-153, 1996.

7. Freudenstein J, Dasenbrock C, Nisslein T: Lack of promotion of estrogen-dependent mammary gland tumors in vivo by an isopropanolic Cimicifuga racemosa extract. Cancer Research 62: 3448-3452, 2002.

8. Gurley BJ, Gardner SF, Hubbard MA, Williams DK, Gentry DB, Khan IA, Shah A. In Vivo Effects of Goldenseal, Kava Kava, Black Cohosh, and Valerian on Human Cytochrome P450 1A2, 2D6, 2E1, and 3A4/5 Phenotypes. Clinical Pharmacology & Therapeutics 77: 415-426, 2005

9. National Center for Complementary and Alternative Medicine, NIH Office of Dietary Supplements. Workshop on the Safety of Black Cohosh in Clinical Studies. November 22, 2004

10. Silverthorn, D (2007). Human Physiology. San Francisco, CA: Pearson.

References11. Office of Dietary Supplements and National Center for Complementary and Alternative

Medicine. Questions and Answers About Black Cohosh and the Symptoms of Menopause

12. Duke JA: Handbook of Medicinal Herbs. Boca Raton, FL: CRC Press, 2001: 120-12113. Foster S: Black cohosh: Cimicifuga racemosa: a literature review. HerbalGram 45: 35-

49, 1999. 14. Upton, R, ed. Black Cohosh Rhizome Actaea racemosa L. syn. Cimicifuga racemosa (L.)

Nutt. Standards of analysis, quality control, and therapeutics. American Herbal Pharmacopoeia and Therapeutic Compendium. Santa Cruz, CA. American Herbal Pharmacopoeia, 2002: 1-38.

15. Judith S. Jacobson, Andrea B. Troxel, Joel Evans, Lorissa Klaus, Linda Vahdat, David Kinne, K. M. Steve Lo, Anne Moore, Pamela J. Rosenman, Elizabeth L. Kaufman, Alfred I. Neugut, and Victor R. Grann Randomized Trial of Black Cohosh for the Treatment of Hot Flashes Among Women With a History of Breast Cancer J Clin Oncol. 2001 May 15;19(10):2739-45

16. Sloan JA, Loprinzi CL, Novotny PJ, et al: Methodologic lessons learned from hot flash studies. J Clin Oncol 19:4280-4290, 2001

17. Pockaj BA, Gallagher JG, Loprinzi CL, Stella PJ, Barton DL, Sloan JA, Lavasseur BI, Rao RM, Fitch TR, Rowland KM, Novotny PJ, Flynn PJ, Richelson E, Fauq AH Phase III double-blind, randomized, placebo-controlled crossover trial of black cohosh in the management of hot flashes: NCCTG Trial N01CC1. J Clin Oncol. 2006 Jun 20;24(18):2836-41

18. Newton KM, Reed SD, LaCroix AZ, Grothaus LC, Ehrlich K, Guiltinan, J. Treatment of vasomotor symptoms of menopause with black cohosh, multibotanicals, soy, hormone therapy, or placebo: a randomized trial. Ann Intern Med. 2006 Dec 19;145(12):869-79

19. Osmers R, Friede M, Liske E, Schnitker J, Freudenstein J, Henneicke-von Zepelin HH. Efficacy and safety of isopropanolic black cohosh extract for climacteric symptoms. Obstet Gynecol. 2005 Sep;106(3):644