Sage (salvia officinalis) • Vervain (verbena officinalis) • Chaste Tree (vitex agnus-castus) • Milk Thistle (silybum marianum) • Dong Quai (angelica archangelica) • Black Cohosh (cimicifuga racemosa).
Brand name products often contain multiple ingredients. To read detailed information about each ingredient, click on the link for the individual ingredient shown above.
Below is general information about the effectiveness of the known ingredients contained in the product Menopause Tincture. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
Below is general information about the safety of the known ingredients contained in the product Menopause Tincture. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
POSSIBLY SAFE ...when used orally and appropriately. Black cohosh has been safely used in some studies lasting up to a year (15036,15158,17091,19553,35908); however, most studies have lasted only up to 6 months (141,4614,4620,7054,9437,9494,13143,13184,14330,14423)(14424,15037,15889,15893,35824,35852,35853,35858,35865,35897)(35902,35904,35946,35964,95525,103269). There is concern that black cohosh might cause liver damage in some patients. Several case reports link black cohosh to liver failure or autoimmune hepatitis (4383,10692,11906,12006,13144,14469,15160,16721,16722,16723)(16724,16725,16726,16727,35857,107906). However, the evidence that black cohosh causes liver damage is not conclusive (17085). Until more is known, monitor liver function in patients who take black cohosh.
PREGNANCY: POSSIBLY UNSAFE
when used orally in pregnant patients who are not at term.
Black cohosh might have hormonal effects and menstrual and uterine stimulant effects (15035). Theoretically, this might increase the risk of miscarriage; avoid using during pregnancy. There is insufficient reliable information available about the safety of black cohosh when used to induce labor.
LACTATION: POSSIBLY UNSAFE
when used orally.
Black cohosh might have hormonal effects. Theoretically, maternal intake of black cohosh might adversely affect a nursing child (15035). Until more is known, nursing patients should avoid taking black cohosh.
POSSIBLY SAFE ...when used orally and appropriately. Dong quai has been used with apparent safety in a dose of 4.5 grams daily for 24 weeks, or in combination with other ingredients in doses of up to 150 mg daily for up to 6 months (19552,35797). ...when used intravenously as a 25% solution, in a dose of 200-250 mL daily for up to 20 days (48438,48442,48443,48483).
POSSIBLY UNSAFE ...when used orally in large amounts, long-term. Theoretically, long-term use of large amounts of dong quai could be harmful. Dong quai contains several constituents such as bergapten, safrole, and isosafrole that are considered carcinogenic (7162). There is insufficient reliable information available about the safety of dong quai when used topically.
PREGNANCY: POSSIBLY UNSAFE
when used orally.
Dong quai has uterine stimulant and relaxant effects (8142); theoretically, it could adversely affect pregnancy. Observational research has found that intake of An-Tai-Yin, an herbal combination product containing dong quai and parsley, during the first trimester is associated with an increased risk of congenital malformations of the musculoskeletal system, connective tissue, and eyes (15129).
LACTATION:
Insufficient reliable information available; avoid use.
LIKELY SAFE ...when used orally and appropriately. A specific milk thistle extract standardized to contain 70% to 80% silymarin (Legalon, Madaus GmbH) has been safely used in doses up to 420 mg daily for up to 4 years (2613,2614,2616,7355,63210,63212,63278,63280,63299,63340)(88154,97626,105792). Higher doses of up to 2100 mg daily have been safely used for up to 48 weeks (63251,96107,101150). Another specific milk thistle extract of silymarin (Livergol, Goldaru Pharmaceutical Company) has been safely used at doses of 140 mg daily for up to 6 months and doses of 420 mg daily for up to 6 weeks (95021,95029,102851,102852,105793,105794,105795). Some isolated milk thistle constituents also appear to be safe. Silibinin (Siliphos, Thorne Research) has been used safely in doses up to 320 mg daily for 28 days (63218). Some combination products containing milk thistle and other ingredients also appear to be safe. A silybin-phosphatidylcholine complex (Silipide, Inverni della Beffa Research and Development Laboratories) has been safely used in doses of 480 mg daily for 7 days (7356) and 240 mg daily for 3 months (63320). Tree turmeric and milk thistle capsules (Berberol, PharmExtracta) standardized to contain 60% to 80% silybin have been safely used twice daily for up to 12 months (95019,96140,96141,96142,97624,101158).
POSSIBLY SAFE ...when used topically and appropriately, short-term. A milk thistle extract cream standardized to silymarin 0.25% (Leviaderm, Madaus GmbH) has been used safely throughout a course of radiotherapy (63239). Another milk thistle extract cream containing silymarin 1.4% has been used with apparent safety twice daily for 3 months (105791,110489). A cream containing milk thistle fruit extract 25% has been used with apparent safety twice daily for up to 12 weeks (111175). A milk thistle extract gel containing silymarin 1% has been used with apparent safety twice daily for 9 weeks (95022). There is insufficient reliable information available about the safety of intravenous formulations of milk thistle or its constituents.
PREGNANCY AND LACTATION:
While research in an animal model shows that taking milk thistle during pregnancy and lactation does not adversely impact infant development (102850), there is insufficient reliable information available about its safety during pregnancy or lactation in humans; avoid using.
CHILDREN: POSSIBLY SAFE
when used orally and appropriately, short-term.
A milk thistle extract 140 mg three times daily has been used with apparent safety for up to 9 months (88154,98452). A specific product containing the milk thistle constituent silybin (Siliphos, Thorne Research Inc.) has been used with apparent safety in doses up to 320 mg daily for up to 4 weeks in children one year of age and older (63218).
LIKELY SAFE ...when used orally in amounts commonly found in foods. Sage is approved for use as a food in the United States (4912).
POSSIBLY SAFE ...when used orally in medicinal doses, short-term. Common sage (Salvia officinalis) and Spanish sage (Salvia lavandulaefolia) have been used with apparent safety when taken orally in doses of 280 mg daily for up to 8 weeks (10334,10810,17177,105338). ...when used topically. Common sage (Salvia officinalis) has been used with apparent safety as a single agent or in combination products for up to one week (10437,72619,107023). ...when the essential oil is inhaled as aromatherapy, short-term (72658).
POSSIBLY UNSAFE ...when used orally in high doses or long-term (12,1304). Some species of sage, including common sage (Salvia officinalis), contain a thujone constituent that can be toxic if consumed in large enough quantities (12,1304).
PREGNANCY: LIKELY UNSAFE
when used orally.
The constituent thujone can have menstrual stimulant and abortifacient effects (19).
LACTATION: POSSIBLY UNSAFE
when used orally; sage is thought to reduce the supply of mother's milk (19).
LIKELY SAFE ...when used orally in amounts commonly found in foods. Verbena has Generally Recognized As Safe status (GRAS) for use in foods in the US (4912). There is insufficient reliable information available about the safety of verbena when used orally or topically in medicinal amounts.
PREGNANCY AND LACTATION:
There is insufficient reliable information available about the safety of verbena in medicinal amounts during pregnancy and lactation; avoid using.
LIKELY SAFE ...when the fruit extract is used orally and appropriately, short-term. Vitex agnus-castus fruit extract has been used safely in studies at doses up to 40 mg daily, for up to 3 months (7055,7076,7077,7078,7079,12207,13393,15065,90617,90618,96435). There is insufficient reliable information available about the safety of vitex agnus-castus seeds when used orally or topically.
PREGNANCY AND LACTATION: POSSIBLY UNSAFE
when used orally.
Theoretically, the hormonal effects of vitex agnus-castus might adversely affect pregnancy or lactation (10979,11456,13393,109439). Animal research shows that taking vitex agnus-castus fruit extract when planning to become pregnant or during pregnancy may increase the risk of infertility, low fetal body weight, abortion, and stillbirth (109439); avoid using.
Below is general information about the interactions of the known ingredients contained in the product Menopause Tincture. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
Taking black cohosh with atorvastatin might increase the risk for elevated liver function tests.
 Details
In one case report, a patient taking atorvastatin (Lipitor) developed significantly elevated liver function enzymes after starting black cohosh 100 mg four times daily. Liver enzymes returned to normal when black cohosh was discontinued (16725). It is unclear whether the elevated liver enzymes were due to black cohosh itself or an interaction between atorvastatin and black cohosh.
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Theoretically, black cohosh may reduce the clinical effects of cisplatin.
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Animal research suggests that black cohosh might decrease the cytotoxic effect of cisplatin on breast cancer cells (13101).
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Some research suggests that black cohosh might inhibit CYP2D6, but there is conflicting evidence.
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Some clinical research suggests that black cohosh might modestly inhibit CYP2D6 and increase levels of drugs metabolized by this enzyme (13536). However, contradictory clinical research shows a specific black cohosh product (Remifemin, Enzymatic Therapy) 40 mg twice daily does not significantly inhibit metabolism of a CYP2D6 substrate in healthy study volunteers (16848). Until more is known, use black cohosh cautiously in patients taking drugs metabolized by CYP2D6.
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Theoretically, black cohosh may alter the effects of estrogen therapy.
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Theoretically, taking black cohosh with hepatotoxic drugs may increase the risk of liver damage.
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Black cohosh may inhibit one form of OATP, OATP2B1, which could reduce the bioavailability and clinical effects of OATP2B1 substrates.
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In vitro research shows that black cohosh modestly inhibits OATP2B1 (35450). OATPs are expressed in the small intestine and liver and are responsible for the uptake of drugs and other compounds into the body. Inhibition of OATP may reduce the bioavailability of oral drugs that are substrates of OATP.
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Theoretically, dong quai may increase the risk of bleeding when used with anticoagulant or antiplatelet drugs; however, research is conflicting.
Details
Animal studies suggest that dong quai has antithrombin activity and inhibits platelet aggregation due to its coumarin components (6048,10057,96137). Additionally, some case reports in humans suggest that dong quai can increase the anticoagulant effects of warfarin (3526,6048,23310,48439). However, clinical research in healthy adults shows that taking 1 gram of dong quai root daily for 3 weeks does not significantly inhibit platelet aggregation or cause bleeding (96137). Until more is known, use dong quai with caution in patients taking antiplatelet/anticoagulant drugs.
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Theoretically, dong quai may reduce the effects of estrogens.
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Dong quai may increase the risk of bleeding when used with warfarin.
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Case reports suggest that concomitant use of dong quai with warfarin can increase the anticoagulant effects of warfarin and increase the risk of bleeding (3526,6048,23310,48439). In one case, after 4 weeks of taking dong quai 565 mg once or twice daily, the international normalized ratio (INR) increased to 4.9. The INR normalized 4 weeks after discontinuation of dong quai (3526).
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Taking milk thistle with antidiabetes drugs may increase the risk of hypoglycemia.
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Theoretically, milk thistle might inhibit CYP2B6.
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An in vitro study shows that silybin, a constituent of milk thistle, binds to and noncompetitively inhibits CYP2B6. Additionally, silybin might downregulate the expression of CYP2B6 by decreasing mRNA and protein levels (112229).
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It is unclear if milk thistle inhibits CYP2C9; research is conflicting.
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In vitro research suggests that milk thistle might inhibit CYP2C9 (7089,17973,17976). However, contradictory clinical research shows that milk thistle extract does not inhibit CYP2C9 or significantly affect levels of the CYP2C9 substrate tolbutamide (13712,95026). Differences in results could be due to differences in dosages or formulations utilized (95026).
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It is unclear if milk thistle inhibits CYP3A4; research is conflicting.
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Theoretically, milk thistle might interfere with estrogen therapy through competition for estrogen receptors.
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Theoretically, milk thistle might affect the clearance of drugs that undergo glucuronidation.
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Laboratory research shows that milk thistle constituents inhibit uridine diphosphoglucuronosyl transferase (UGT), the major phase 2 enzyme that is responsible for glucuronidation (7318,17973). Theoretically, this could decrease the clearance and increase levels of glucuronidated drugs. Other laboratory research suggests that a milk thistle extract of silymarin might inhibit beta-glucuronidase (7354), although the significance of this effect is unclear.
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Theoretically, milk thistle might interfere with statin therapy by decreasing the activity of organic anion transporting polypeptide 1B1 (OATB1B1) and inhibiting breast cancer resistance protein (BCRP).
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Preliminary evidence suggests that a milk thistle extract of silymarin can decrease the activity of the OATP1B1, which transports HMG-CoA reductase inhibitors into the liver to their site of action. The silibinin component also inhibits BCRP, which transports statins from the liver into the bile for excretion. However, in a preliminary study in healthy males, silymarin 140 mg three times daily had no effect on the pharmacokinetics of a single 10 mg dose of rosuvastatin (16408).
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Theoretically, milk thistle may induce cytochrome P450 3A4 (CYP3A4) enzymes and increase the metabolism of indinavir; however, results are conflicting.
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One pharmacokinetic study shows that taking milk thistle (Standardized Milk Thistle, General Nutrition Corp.) 175 mg three times daily in combination with multiple doses of indinavir 800 mg every 8 hours decreases the mean trough levels of indinavir by 25% (8234). However, results from the same pharmacokinetic study show that milk thistle does not affect the overall exposure to indinavir (8234). Furthermore, two other pharmacokinetic studies show that taking specific milk thistle extract (Legalon, Rottapharm Madaus; Thisilyn, Nature's Way) 160-450 mg every 8 hours in combination with multiple doses of indinavir 800 mg every 8 hours does not reduce levels of indinavir (93578).
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Theoretically, milk thistle might increase the levels and clinical effects of ledipasvir.
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Animal research in rats shows that milk thistle increases the area under the curve (AUC) for ledipasvir and slows its elimination (109505).
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Theoretically, concomitant use of milk thistle with morphine might affect serum levels of morphine and either increase or decrease its effects.
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Animal research shows that milk thistle reduces serum levels of morphine by up to 66% (101161). In contrast, laboratory research shows that milk thistle constituents inhibit uridine diphosphoglucuronosyl transferase (UGT), the major phase 2 enzyme that is responsible for glucuronidation (7318,17973). Theoretically, this could decrease the clearance and increase morphine levels. The effect of taking milk thistle on morphine metabolism in humans is not known.
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Theoretically, milk thistle might increase the absorption of P-glycoprotein substrates. However, this effect does not seem to be clinically significant.
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Although in vitro research shows that milk thistle can inhibit P-glycoprotein activity (95019), clinical research does not agree. A small pharmacokinetic study in healthy volunteers shows that taking milk thistle (Enzymatic Therapy Inc.) 900 mg, standardized to 80% silymarin, in 3 divided doses daily for 14 days does not affect absorption of digoxin, a P-glycoprotein probe substrate (35825).
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Theoretically, milk thistle might decrease the clearance and increase levels of raloxifene.
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Laboratory research suggests that the milk thistle constituents silibinin and silymarin inhibit the glucuronidation of raloxifene in the intestines (93024).
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Milk thistle might decrease the clearance of sirolimus.
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Pharmacokinetic research shows that a milk thistle extract of silymarin decreases the apparent clearance of sirolimus in hepatically impaired renal transplant patients (19876). It is unclear if this interaction occurs in patients without hepatic impairment.
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Theoretically, milk thistle might decrease the levels and clinical effects of sofosbuvir.
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Animal research in rats shows that milk thistle reduces the metabolism of sofosbuvir, as well as the hepatic uptake of its active metabolite (109505).
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Theoretically, the milk thistle constituent silibinin might increase tamoxifen levels and interfere with its conversion to an active metabolite.
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Animal research suggests that the milk thistle constituent silibinin might increase plasma levels of tamoxifen and alter its conversion to an active metabolite. The mechanism appears to involve inhibition of pre-systemic metabolism of tamoxifen by cytochrome P450 (CYP) 2C9 and CYP3A4, and inhibition of P-glycoprotein-mediated efflux of tamoxifen into the intestine for excretion (17101). Whether this interaction occurs in humans is not known.
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Theoretically, milk thistle might increase the effects of warfarin.
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In one case report, a man stabilized on warfarin experienced an increase in INR from 2.64 to 4.12 after taking a combination product containing milk thistle 200 mg daily, as well as dandelion, wild yam, niacinamide, and vitamin B12. Levels returned to normal after stopping the supplement (101159). Although a direct correlation between milk thistle and the change in INR cannot be confirmed, some in vitro research suggests that milk thistle might inhibit cytochrome P450 2C9 (CYP2C9), an enzyme involved in the metabolism of various drugs, including warfarin (7089,17973,17976).
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Theoretically, sage might decrease the clinical effects of anticholinergic drugs.
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Theoretically, sage might interfere with the clinical effects of anticonvulsant drugs.
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Some species of sage can cause convulsions when consumed in large quantities (10812).
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Theoretically, taking sage with antidiabetes drugs might increase the risk of hypoglycemia.
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In patients with polycystic ovary syndrome (PCOS) or inadequately controlled type 2 diabetes, common sage (Salvia officinalis) has demonstrated hypoglycemic activity (91971,103380). However, other clinical research in patients with inadequately controlled type 2 diabetes shows that common sage extract does not lower fasting blood glucose levels (105340).
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Theoretically, sage might increase or decrease the effects of antihypertensive drugs.
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Animal research suggests that common sage (Salvia officinalis) can cause prolonged blood pressure reduction (4152). However, clinical research suggests that Spanish sage (Salvia lavandulaefolia) can increase blood pressure in some people with hypertension (10334). Until more is known, use with caution.
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Theoretically, taking sage might increase the sedative and adverse effects of benzodiazepines.
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In vitro evidence suggests that certain components of common sage (Salvia officinalis) can bind to benzodiazepine receptors (72588). This effect has not been reported in humans.
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Theoretically, sage might have additive effects when used with cholinergic drugs.
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Theoretically, taking sage might increase the sedative and adverse effects of CNS depressants.
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Some constituents of sage have CNS depressant activity (10334).
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Theoretically, sage might increase the levels and clinical effects of drugs metabolized by CYP2C19.
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In vitro evidence suggests that aqueous extracts of sage can inhibit CYP2C19 (10848). So far, this interaction has not been reported in humans.
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Theoretically, sage might increase the levels and clinical effects of drugs metabolized by CYP2C9.
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In vitro evidence suggests that aqueous extracts of sage can inhibit CYP2C9 (10848). So far, this interaction has not been reported in humans.
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Theoretically, sage might increase the levels and clinical effects of drugs metabolized by CYP2D6.
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Theoretically, sage might decrease the levels and clinical effects of drugs metabolized by CYP2E1.
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Animal research suggests that drinking common sage (Salvia officinalis) tea increases the expression of CYP2E1 (72627). So far, this interaction has not been reported in humans.
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Theoretically, sage might increase the levels and clinical effects of drugs metabolized by CYP3A4.
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Theoretically, sage might interfere with hormone therapy.
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In vitro evidence suggests that geraniol, a constituent of Spanish sage (Salvia lavandulaefolia), exerts estrogenic activity (39572). The clinical significance of this effect is unclear.
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Theoretically, sage might increase levels of drugs transported by P-glycoprotein.
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In vitro research suggests that common sage (Salvia officinalis) can inhibit the multi-drug transporter protein, P-glycoprotein (72641). This effect has not been reported in humans.
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In vitro research suggests that beta-myrcene, a terpene constituents of verbena, can significantly inhibit cytochrome P450 2B1 (CYP2B1) enzyme activity (82024). Theoretically, verbena might increase levels of drugs metabolized by this enzyme. However, this interaction has not been reported in humans.
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Some substrates of CYP2B1 include cyclophosphamide, ifosfamide, barbiturates, bromobenzene, and others.
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Theoretically, vitex agnus-castus could interfere with the activity of antipsychotic drugs.
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Theoretically, vitex agnus-castus could interfere with oral contraceptives.
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Theoretically, vitex agnus-castus could interfere with dopamine agonists.
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Vitex agnus-castus might potentiate the actions of dopaminergic agonists due to possible dopaminergic effects (10122).
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Theoretically, vitex agnus-castus could interfere with the activity of estrogens.
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Theoretically, dopaminergic effects of vitex agnus-castus could interfere with metoclopramide.
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Below is general information about the adverse effects of the known ingredients contained in the product Menopause Tincture. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
General
...Orally, black cohosh is generally well tolerated when used in typical doses.
Most Common Adverse Effects:
Orally: Breast tenderness, dizziness, gastrointestinal upset, headache, irritability, rash, tiredness.
Serious Adverse Effects (Rare):
Orally: Endometrial hyperplasia and hepatotoxicity, although data are conflicting for both.
Cardiovascular
...A single case of reversible bradycardia has been reported for a 59-year-old female who took one tablet of a specific black cohosh product (Remifemin, Schaper & Brümmer) daily for 2 weeks.
The adverse event was considered probably related to black cohosh use, although the exact mechanism by which black cohosh exerted this effect was unclear (35920).
There has been concern that, if black cohosh has estrogen-like effects, it could also potentially cause estrogen-like side effects including increased risk for thromboembolism and cardiovascular disease. These outcomes have not been specifically assessed in long-term trials; however, some research shows that a specific black cohosh extract (CimiPure, PureWorld) does not significantly affect surrogate markers for thromboembolism and cardiovascular risk such as fibrinogen, cholesterol, triglycerides, glucose, or insulin levels compared to placebo (16850).
Dermatologic ...Black cohosh has been associated with skin irritation and rashes (7054,10987,14330,15889,35853). A case report describes a patient who developed cutaneous pseudolymphoma 6 months after starting a specific black cohosh extract (Remifemin). Symptoms resolved within 12 weeks of discontinuing black cohosh (15890).
Gastrointestinal ...Orally, black cohosh can commonly cause gastrointestinal upset (4383,4615,4616,10988,13184,35824,35853,35965,103269,111714). Constipation and indigestion have also been reported (7054,35852).
Genitourinary
...Orally, black cohosh, including the specific black cohosh product Remifemin, may cause vaginal bleeding and breast tenderness in some postmenopausal patients (15889,35824).
However, the frequency of these events seems to be less than that of tibolone, a prescription hormone medication used to treat symptoms of menopause (15889,35904).
Due to the potential estrogen-like effects, there is concern that black cohosh might increase the risk of endometrial hyperplasia. However, a specific black cohosh extract CR BNO 1055 (Klimadynon/Menofem, Bionorica AG) does not appear to cause endometrial hyperplasia. Clinical research in postmenopausal adults shows that taking 40 mg daily of this extract for 12 weeks does not significantly increase superficial cells when compared with placebo, and causes significantly fewer superficial cells when compared with conjugated estrogens (Premarin) (14330). Additional clinical research shows that taking 40 mg daily of this extract for a year does not increase the risk of endometrial hyperplasia or endometrial thickening in postmenopausal adults (15036). Another specific combination product containing black cohosh extract plus St. John's wort (Gynoplus, Jin-Yang Pharm) also does not significantly increase superficial cells compared to placebo after 12 weeks of treatment (15893). Some patients taking tamoxifen plus black cohosh have experienced endometrial hyperplasia and vaginal bleeding. However, these effects are more likely due to tamoxifen than black cohosh (7054).
Hepatic
...There is concern that black cohosh might cause liver disease, hepatotoxicity, or hepatitis.
Adverse effects on the liver have not been documented in clinical studies. However, multiple case reports of liver toxicity, hepatitis, and abnormal liver function have been described in females taking black cohosh products alone or in combination with other herbs or drugs. In some cases, patients developed liver failure and required immediate liver transplantation (4383,10692,11909,12006,13144,14469,15160,16721,16722,16723) (16724,16727,35883,35888,35890,35895,89465,101592,107906). In one case, a female developed autoimmune hepatitis after 3 weeks of taking black cohosh. Symptoms resolved 2 weeks after discontinuing black cohosh (11906). In at least three cases, females have developed elevated liver enzymes and symptoms of hepatotoxicity after taking black cohosh products. Symptoms resolved and liver enzymes normalized within a week of discontinuing black cohosh (16725,16726). Analysis of two liver biopsies suggests that hepatotoxicity associated with black cohosh use results from the accumulation of 4HNE protein adducts in the cytoplasm of liver cells, which promotes the migration of lymphocytes to the affected area and induces an autoimmune response leading to troxis necrosis (89469).
However, many of these cases are poorly documented. Causality is possible based on some reports; however, other reports do not indicate that black cohosh is the probable cause of the events (15891,15892,16722,16723,16727,89465). Hepatitis can occur with no identifiable cause, raising the possibility that black cohosh and hepatitis might have been coincidental in some cases. Also, plant misidentification can occur, resulting in accidental substitution of a hepatotoxic plant (11910). Therefore, some experts argue that these cases do not provide conclusive evidence that black cohosh is responsible for liver disease (17085,35882,111634). Nonetheless, some countries require cautionary labeling on black cohosh products suggesting a risk of liver toxicity. The United States Pharmacopeia also recommends cautionary labeling on black cohosh products (16722). Until more is known about this potential risk, consider monitoring liver function in patients who take black cohosh.
Musculoskeletal
...One patient treated with black cohosh in a clinical trial discontinued treatment due to edema and arthralgia (35897).
Black cohosh has been linked to asthenia and muscle damage in one case. A 54-year-old female experienced asthenia with elevated creatinine phosphokinase (CPK) and lactate dehydrogenase (LDH) levels while taking black cohosh. The patient had taken a specific black cohosh extract (Remifemin) for 1 year, discontinued it for 2 months, restarted it, and then experienced symptoms 2 months later. Symptoms began to resolve 10 days after discontinuing black cohosh (14299).
Neurologic/CNS
...Orally, black cohosh may cause headache, dizziness, or tiredness (35852,35886).
There is one case report of seizures in a female who used black cohosh, evening primrose oil, and chasteberry (10988).
Also, there has been a case report of severe complications, including seizures, renal failure, and respiratory distress, in an infant whose mother was given an unknown dose of black cohosh and blue cohosh at 42 weeks gestation to induce labor (1122,9492,9493). However, this adverse effect may have been attributable to blue cohosh.
In another case report, orobuccolingual dyskinesia, including tongue-biting, eating difficulties, and speech problems, was reported in a 46-year-old female who took two tablets containing black cohosh 20 mg and Panax ginseng 50 mg daily for 15 months. The patient's condition improved after stopping treatment with the herbs and taking clonazepam 2 mg daily with baclofen 40 mg daily (89735).
Ocular/Otic ...There is some concern that black cohosh might increase the risk of retinal vein thrombosis due to its estrogenic activity. In one case, a patient with protein S deficiency and systemic lupus erythematosus (SLE) experienced retinal vein thrombosis 3 days after taking a combination product containing black cohosh 250 mg, red clover 250 mg, dong quai 100 mg, and wild yam 276 mg (13155). It is unclear if this event was due to black cohosh, other ingredients, the combination, or another factor.
Oncologic ...There is some concern that black cohosh may affect hormone-sensitive cancers, such as some types of breast or uterine cancer, due to its potential estrogenic effects. However, evidence from a cohort study suggests that regular use of black cohosh is not associated with the risk of breast or endometrial cancer (17412,111634).
Psychiatric ...A 36-year-old female with a 15-year history of depression developed mania with psychotic and mixed features after taking a black cohosh extract 40 mg daily. The patient gradually recovered after stopping black cohosh and receiving treatment with antipsychotics (104517).
Pulmonary/Respiratory ...There has been a case report of severe complications, including seizures, renal failure, and respiratory distress, in an infant whose mother was given an unknown dose of black cohosh and blue cohosh at 42 weeks gestation to induce labor (1122,9492,9493). However, this adverse effect may have been attributable to blue cohosh.
Renal ...There has been a case report of severe complications, including seizures, renal failure, and respiratory distress, in an infant whose mother was given an unknown dose of black cohosh and blue cohosh at 42 weeks gestation to induce labor (1122,9492,9493). However, this adverse effect may have been attributable to blue cohosh.
Other ...While rare, weight gain has been reported in some patients taking black cohosh. However, in most cases the causality could not be established. A review of the literature, including published case reports, spontaneous reports to adverse event databases, and clinical trials, suggests that black cohosh does not cause weight gain (107907).
General
...Orally, dong quai is generally well-tolerated.
Most Common Adverse Effects:
Orally: Burping and flatulence.
Intravenously: Headache.
Cardiovascular ...Orally, dong quai might cause hypertension; according to one case report, a parent and breastfed infant experienced hypertension (195/85 mmHg and 115/69 mmHg, respectively) after the parent consumed a soup containing dong quai root (48428).
Dermatologic ...Dong quai contains psoralens that may cause photosensitivity and photodermatitis (10054,10057,48461).
Endocrine ...In a case report, a male developed gynecomastia after ingesting dong quai tablets (48504).
Gastrointestinal ...Orally, burping and gas may occur with dong quai (738).
Hematologic ...In one case report, a 55-year-old female with protein S deficiency and systemic lupus erythematosus (SLE) had temporary vision loss in the left eye from hemiretinal vein thrombosis three days after taking a phytoestrogen preparation containing dong quai 100 mg, black cohosh 250 mg, wild Mexican yam 276 mg, and red clover 250 mg (13155). It is unclear if dong quai contributed to this event.
Neurologic/CNS ...Dong quai given orally or by injection may be associated with headache (738,48438).
Oncologic ...Dong quai contains constituents that are carcinogenic; however, whether these constituents are present in concentrations large enough to cause cancer with long-term or high-dose use is unknown (7162).
Pulmonary/Respiratory ...A pharmacist experienced allergic asthma and rhinitis after occupational exposure to dong quai and other herbs (48435).
General
...Orally, milk thistle is well tolerated.
Most Common Adverse Effects:
Orally: Abdominal bloating, diarrhea, dyspepsia, flatulence, and nausea. However, these adverse effects do not typically occur at a greater frequency than with placebo.
Serious Adverse Effects (Rare):
Orally: Allergic reactions, including anaphylaxis, have been reported.
Dermatologic ...Orally, milk thistle may cause allergic reactions including urticaria, eczema, skin rash, and anaphylaxis in some people (6879,7355,8956,63210,63212,63238,63251,63315,63325,95029). Allergic reactions may be more likely to occur in patients sensitive to the Asteraceae/Compositae family (6879,8956). A case report describes a 49-year-old female who developed clinical, serologic, and immunopathologic features of bullous pemphigoid after taking milk thistle orally for 6 weeks. Symptoms resolved after treatment with prednisone and methotrexate (107376). Topically, milk thistle can cause erythema (110489).
Gastrointestinal ...Mild gastrointestinal symptoms have been reported, including nausea, vomiting, bloating, diarrhea, epigastric pain, abdominal colic or discomfort, dyspepsia, dysgeusia, flatulence, constipation, and loss of appetite (2616,6879,8956,13170,63140,63146,63160,63210,63218,63219)(63221,63244,63247,63250,63251,63320,63321,63323,63324,63325)(63327,63328,95024,95029,107374). There is one report of a 57-year-old female with sweating, nausea, colicky abdominal pain, diarrhea, vomiting, weakness, and collapse after ingesting milk thistle; symptoms subsided after 24-48 hours without medical treatment and recurred with re-challenge (63329).
Musculoskeletal ...In one clinical study three patients taking milk thistle 200 mg orally three times daily experienced tremor; the incidence of this adverse effect was similar for patients treated with fluoxetine 10 mg three times daily (63219).
General
...Orally, topically, and when inhaled, sage seems to be well tolerated.
Most Common Adverse Effects:
Orally: Abdominal pain, agitation, diarrhea, dizziness, nausea, and vomiting.
Topically: Burning, dermatitis, pain.
Serious Adverse Effects (Rare):
Orally: Generalized tonic-clonic seizures associated with the thujone, camphor, and/or cineol constituents.
Cardiovascular ...By inhalation, sage essential oil has been reported to increase the blood pressure of hypertensive patients (10334).
Dermatologic
...Orally, sage extract has been reported to cause acneiform skin eruptions in one patient in a clinical trial (91970).
Topically, sage leaves can cause contact dermatitis (46902,72661,72710). Sage extract can cause burning and pain (10437).
Gastrointestinal
...Orally, sage can cause nausea, vomiting, abdominal pain, and diarrhea (10810,17177).
Topically, sage extract sprayed into the mouth and throat can cause dryness or mild burning of the throat (72619).
Neurologic/CNS ...Orally, sage can cause dizziness or agitation (10810,17177). Thujone, a constituent of common sage (Salvia officinalis), is a neurotoxin and can cause seizures (10812,12868). Camphor and cineol, constituents of common sage and Spanish sage, can also cause neurotoxicity and seizures in high doses (10334,12868). Generalized tonic-clonic seizures have been reported in adults, children, and infants after ingestion of sage oil (12868,72666).
Pulmonary/Respiratory
...Orally, sage can cause wheezing (10810,17177).
Occupational exposure to sage dust can cause reduction in ventilatory capacity and chronic respiratory impairment (72672,72682,72686).
General
...Orally, verbena is well tolerated when used orally in amounts commonly found in foods (4912).
When used in medicinal amounts and in combination with other herbs, adverse effects have included gastrointestinal adverse effects and allergic skin reactions (374,379).
Topically, verbena can cause contact dermatitis (13431).
Gastrointestinal ...Orally, verbena in combination with other herbs can cause gastrointestinal adverse effects (374,379).
Immunologic ...Orally, verbena in combination with other herbs can cause allergic skin reactions (374,379). Topically, verbena can cause contact dermatitis (13431).
General
...Orally, vitex agnus-castus is generally well tolerated.
Most Common Adverse Effects:
Orally: Diarrhea, fatigue, headache, insomnia, irregular menstruation, nausea, skin irritation, stomach pain, vomiting.
Dermatologic ...Orally, skin conditions such as itching, irritation, urticaria, rash, acne, eczema, and hair loss have been reported (7055,7076,7078,7079,12207,13393,15065,90617,90619,101981).
Gastrointestinal ...Orally, gastrointestinal upset or pain, diarrhea, and nausea and vomiting, have been reported (7079,12207,13393,15065,90620,101981,101982). In one clinical trial, a single patient reported persistent gastroenteritis while taking vitex agnus-castus (7076). Orally, development of a bezoar resulting in colonic obstruction is described in a 63-year-old male who consumed an unknown amount of vitex agnus-castus seeds (111752).
Genitourinary ...Orally, irregular or prolonged menstrual bleeding has been reported (7055,7079,12207,13393,15065,41489,41490,95326).
Hematologic ...Orally, nosebleed has been reported in a single patient in a clinical trial (7079).
Immunologic ...Orally, multiple abscesses have been reported in a single patient (7055).
Neurologic/CNS ...Orally, headache, fatigue, and insomnia (7076,7078,12207,13393,13395,15065), confusion (90617), and vertigo (7079) have been reported.
Other ...Orally, weight gain has been reported (12207,13393,15065).
