Devil's Claw root bark • Yucca root • Yerba Mansa root • Black Cohosh root • Wild Yam root.
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Below is general information about the effectiveness of the known ingredients contained in the product Joint Venture. 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
There is insufficient reliable information available about the effectiveness of yerba mansa.
INSUFFICIENT RELIABLE EVIDENCE to RATE
Below is general information about the safety of the known ingredients contained in the product Joint Venture. 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. Devil's claw extract has been used with apparent safety in doses of up to 2400 mg daily for up 12 weeks (6472,8608,14332,14418,47112,47114,47116,47117,47155). There is insufficient reliable information available about the safety of devil's claw when used orally long-term or when used topically.
PREGNANCY: POSSIBLY UNSAFE
when used orally.
Anecdotal evidence suggests that devil's claw has oxytocic effects in humans. Also, in vitro research shows that moderate to high doses of devil's claw root extract induce contractions of isolated uterine muscle from pregnant and nonpregnant rats (94689); avoid using.
LACTATION:
Insufficient reliable information available; avoid using.
POSSIBLY SAFE ...when used orally. A dose of 50 mg (containing 8 mg diosgenin) has been used with apparent safety for 12 weeks (12,96724). ...when used topically. A wild yam cream has been used with apparent safety for 3 months (10989).
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
There is insufficient reliable information available about the safety of yerba mansa.
PREGNANCY AND LACTATION:
Insufficient reliable information is available; avoid using.
LIKELY SAFE ...when used orally in amounts commonly found in foods. Specific species of yucca, including Mojave yucca (Yucca shidigera) and Joshua tree (Yucca brevifolia), have Generally Recognized As Safe (GRAS) status for use in foods in the US (4912). There is insufficient reliable information available about the safety of yucca when used orally as medicine or when applied topically.
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
Below is general information about the interactions of the known ingredients contained in the product Joint Venture. 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.
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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, devil's claw might increase levels of drugs metabolized by CYP2C19.
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In vitro research shows that devil's claw might inhibit CYP2C19, although this has not been reported in humans (12479).
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Theoretically, devil's claw might increase levels of drugs metabolized by CYP2C9.
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In vitro research shows that devil's claw might inhibit CYP2C9, although this has not been reported in humans (12479).
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Theoretically, devil's claw might increase levels of drugs metabolized by CYP3A4.
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In vitro research shows that devil's claw might inhibit CYP3A4, although this has not been reported in humans (12479).
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Theoretically, devil's claw might decrease the effectiveness of H2-blockers.
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Devil's claw has been reported to increase stomach acid, which might interfere with the effects of H2-blockers (19).
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Theoretically, devil's claw might increase levels of P-glycoprotein substrates.
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Theoretically, devil's claw might decrease the effectiveness of PPIs.
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Devil's claw has been reported to increase stomach acid, which might interfere with the effects of PPIs (19).
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Theoretically, Devil's claw might increase the activity of warfarin.
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In one case report, purpura occurred in a patient taking warfarin and devil's claw concurrently. This might indicate over-anticoagulation (613). It is unclear if this was due to Devil's claw or other contributing factors.
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Theoretically, wild yam might increase or decrease the effects of estrogen.
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Theoretically, concomitant use might cause additive or prolonged sedative effects (19).
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Below is general information about the adverse effects of the known ingredients contained in the product Joint Venture. 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, Devil's claw seems to be generally well tolerated.
Most Common Adverse Effects:
Orally: Allergic skin reactions, diarrhea, dyspepsia.
Serious Adverse Effects (Rare):
Orally: Gastrointestinal bleeding.
Cardiovascular ...In one case report, a healthy patient with normal blood pressure presented with hypertension after taking devil's claw 250 mg twice daily for 2 weeks. It gradually resolved after discontinuation of devil's claw (92017). Some animal research shows that devil's claw might have negative chronotropic, as well as positive and negative inotropic, effects (8609). However, these effects have not been documented in humans.
Dermatologic ...Rarely, allergic skin reactions have been reported in patients taking devil's claw (8608,14418).
Endocrine ...In one case report, a 65-year-old female developed psychomotor agitation, nausea, and distress from euvolemic hyponatremia secondary to inappropriate secretion of antidiuretic hormone (SIADH) within 1 month of starting daily treatment with devil's claw. Within 5 days of discontinuing the product and receiving sodium replacement, the symptoms resolved. Two months later, the patient re-initiated devil's claw and again developed euvolemic hyponatremia (96747).
Gastrointestinal ...Gastrointestinal side effects, including mild gastrointestinal upset, diarrhea, anorexia, acid reflux, or loss of taste, have been reported in some individuals receiving devil's claw, especially at high doses (6472,8608,8613,14332,14418,47112,47116,47144,47169). Gastrointestinal complaints have been reported in 9% to 18% of patients taking a specific devil's claw extract (Doloteffin, Ardeypharm) (8608,47169), while diarrhea was reported in about 8% of patients taking devil's claw (Harpadol, Arkopharma) (6472). Several cases of gastrointestinal bleeding have been reported (104977).
Genitourinary ...Dysmenorrhea was reported in one patient taking a specific devil's claw extract (Doloteffin, Ardeypharm) for 8 weeks (8608).
Neurologic/CNS ...In a trial of devil's claw, one patient withdrew after 4 days of therapy due to a throbbing frontal headache, as well as tinnitus, anorexia, and loss of taste (8613). Rarely, dizziness, somnolence, and insomnia have been reported (47116,47169). It is unclear if these symptoms were caused by devil's claw.
Psychiatric ...Rarely, anxiety has been reported in patients taking devil's claw (8608).
General
...Orally, wild yam is generally well tolerated.
Most Common Adverse Effects:
Orally: Fever, headache, upset stomach, and vomiting.
Serious Adverse Effects (Rare):
Orally: Anaphylaxis.
Gastrointestinal ...Orally, wild yam can cause upset stomach and vomiting, especially at higher doses (12,86450).
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 3 days after taking a combination phytoestrogen product containing wild yam 276 mg, dong quai 100 mg, red clover 250 mg, and black cohosh 250 mg (13155). It is unclear if wild yam contributed to this event.
Immunologic ...There are three case reports of anaphylaxis after ingestion of cooked wild yam (96722).
Neurologic/CNS ...Orally, wild yam can cause headache and fever, especially at higher doses (86450).
General ...No adverse effects have been reported; however, a thorough evaluation of safety outcomes has not been conducted.
General ...There is currently a limited amount of information on the adverse effects of yucca. A thorough evaluation of safety outcomes has not been conducted.
Dermatologic ...Topically, yucca has been reported to cause phytodermatitis (68294). In one case report, an atopic gardener developed contact urticaria after occupational exposure to weeping fig, spathe flower, and yucca. Allergen skin tests were positive for all three plants (49961).
Gastrointestinal ...Orally, the saponins in yucca can be irritating to mucous membranes and might cause gastrointestinal irritation (7,4077).
Pulmonary/Respiratory ...Environmental exposure to yucca has been associated with allergic rhinitis in 59 patients who exhibited sensitization to yucca after allergen skin testing (86902).