Black cohosh, a herb known as Actaea racemosa and Cimicifuga
racemosa, is a member of the buttercup family known as
Ranunculaceae[1][2]. It is recognized by some familiar names like
bugbane, black snakeroot, rattle root, and squawroot[2]. Mainly
rhizomes and roots of black cohosh are utilized for medicinal
purposes[2]. Black cohosh is marketed as a dietary supplement in
various forms like powdered whole herb, liquid extract, and dried
extracts in pill form[4]. Its lipophilic extracts have been predominantly
used in laboratories[2]. Hydroalcoholic clinical preparations which are
widely used are Remifemin and BNO 1055[2]. In-vitro effects on
estrogen-related genes can be seen by using lipophilic extracts
compared to hydroalcoholic extracts[2]. More than 60 triterpene
glycosides analogs have been recognized in black cohosh and two other
bioactive types, namely actein and cimicofugicide[2]. One of the most
copious of such glycosides, 23-epi-26-deoxyactein, is specific for black
cohosh and is the component usually chosen for the standardization of
commercial products[5]. Other chemical constituents of black cohosh
extracts include aromatic acid.
Phenylpropanoids are related to caffeic and ferulic acid, along with the
black cohosh-specific fukinolic acid[2]. The plant also contains many
guanidine alkaloids that aren’t studied biologically but explored
chemically[2]. It is usually prepared as ethanolic or isopropanol
extracts and standardized to 2.5%-5% triterpene glycoside content[6].

Black cohosh has a long tradition of usage. It treats musculoskeletal
pain, fever, cough, pneumonia, and menstrual abnormalities[4]. Today,
it is mainly used for managing menstrual irregularities embracing hot
flushes, night sweat, vertigo, vaginal dryness, etc. [7]. Its root preparation can affect the serotonin and estrogen in the body[1]. Mixed
evidence is present for its usage in treating premature menopause in
breast cancer patients or breast cancer survivors[1][6].

A dilemma is present on the effectiveness of black cohosh in treating
hot flushes in breast cancer[1][6]. In studies involving women with
breast cancer (some of whom were consuming tamoxifen), black
cohosh alleviates the number of hot flushes per day. However, these
outcomes also improved when women were given a placebo[1]. It is not
clear how much of the benefit of black cohosh is due to its effect on the
body or the psychological impact of expecting the benefit. Women
receiving the placebo also had sizeable improvements in hot
flushes[1][6]. The “placebo effect” is an essential factor for hot flush
research[1]. A study found that 46% of women consuming black cohosh
do not confront hot flushes, while there was no reduction amongst
women not taking black cohosh[1]. The severity of hot flushes was also
decreased in the black cohosh group compared to the control group[1].
Possibly, black cohosh may work for some women and not others[1].


How black cohosh affects menopausal symptoms remains unclear. Still,
it is thought that it works by following mechanisms:-central activity on
the hypothalamus, a selective estrogen receptor modulator, and
neurotransmitter systems like effect and anti-proliferative effects on
breast and prostate tumor cells[6].
A straight effect on hormonal levels of estrogen receptor α or ERα is unlikely,
as numerous clinical studies have explained no change in hormone levels
(oestradiol, Follicle-Stimulating Hormone(FSH), Luteinizing Hormone(LH)
and no influence on estrogen-sensitive tissues with the use of black cohosh[6].
Black cohosh imitates estrogen on bone and thus may exert an effect on estrogen receptor β in contrast to the classical estrogen receptor, which is
ERα[6]. ERβ is linked with anti-proliferative effects, which may explain the
possible protective effect of this herb on breast cancer risk[6]. Preclinical
studies have also shown an anti-proliferative potential impact of black cohosh
on breast and prostate tumor cells[6].
Black cohosh may act on central receptors in the hypothalamus
affecting the hypothalamic thermoregulatory centers, which may
explain an effect on hot flushes[6]. Finally, black cohosh may affect
other signaling pathways, including the dopaminergic and serotonergic
systems. Specifically, it may stimulate dopaminergic-2 receptors and
bind 5-HT7 receptors[6].

Black cohosh has an excellent safety profile from published data[6].
Clinical trials using various black cohosh preparations to treat
menopausal symptoms have shown that its use is linked with a low
incidence of adverse effects[4]. Usually, commonly reported side
effects are gastrointestinal upset and rashes, both of which are mild
and temporary[1][2][4]. Other reported adverse effects included breast
pain/enlargement, infection, vaginal bleeding/spotting, and
musculoskeletal complaints; however, their incidence was
indistinguishable in women taking black cohosh and those taking
placebo[4]. Because clinical trials are shorter, like six months or less, no
published studies have assessed the long-term safety of black cohosh in
humans[4]. All over the globe, there were some cases of liver damage such as
hepatitis, liver failure, elevated liver enzymes, hepatotoxicity, and
various other liver injuries which are associated with the use of black
cohosh [3-4]. Nevertheless, there is no correlation or a causal
relationship, so it might be possible that at least some published cases
of hepatotoxicity were due to impurities, contaminants, or incorrect
Acteae species in the black cohosh products used[4].

Some unusual side effects include:-
A-stomach upset[3]
B- bradycardia[3]
C-Orobuccolingual dyskinesia (OBLD), which involves intervention with
speech, tongue-biting, and eating difficulties, has been reported in a
46-year-old woman consuming a herbal supplement containing black
cohosh and ginseng[3].
D- Critical hyponatremia was reported in a 39-year-old woman
following consumption of several doses of black cohosh to induce and
increase labor for giving birth at home[3]. She later underwent
cesarean delivery, and her sodium levels were restored to normal after
being treated with hypertonic saline[3].

A 2008 safety review by the Dietary Supplement Information Expert
Committee (Mahady 2008) recommended that black cohosh products
should include a cautionary statement regarding liver health and
possible hepatotoxicity[6]. The U.S. Pharmacopeia advocates that
individuals with liver disorders should avoid black cohosh[4].
Furthermore, The American Herbal Products Association urges that
pregnant women or lactating women not to take black cohosh except
under the guidance of their healthcare professional because studies
have not rigorously evaluated its use during pregnancy[4]. Pregnant
women should not consume black cohosh because it can act as a
potent abortifacient[3]. So without healthcare supervision, black
cohosh should not be consumed.

Black cohosh is a dietary supplement that is usually available as
tablets[6]. Remifemin is a commercial product extensively used in black
cohosh clinical trials [7]. It is an isopropanol extract of black cohosh
standardized to contain 1 mg of triterpenes per 20 mg of the extract[6].
Researchers suggest consuming 40mg dosage of a standardized extract of black cohosh (usually standardized to 1mg or 2.5-5% triterpene
glycosides) daily for at least three months[1][6]. Even though 40mg
daily is the most common dose, studies have used doses ranging from
40mg-160mg/day, given from 4 weeks to 12 months [6].

There is no determining clinical significance for the interaction
between black cohosh and drugs(tamoxifen, chemotherapeutic
medications)[1], but black cohosh may impede the action of tamoxifen.
It can increase the toxicity of doxorubicin and docetaxel, which are
chemotherapeutic drugs[3].