Trifolium pratense flower 1:2 extract.
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Below is general information about the effectiveness of the known ingredients contained in the product Phytomedicine Red Clover Extract. 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
Below is general information about the safety of the known ingredients contained in the product Phytomedicine Red Clover Extract. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
LIKELY SAFE ...when used orally in amounts commonly used in foods. Red clover has Generally Recognized As Safe (GRAS) status for use in foods in the US (4912,10372).
POSSIBLY SAFE ...when used orally and appropriately in supplemental amounts. Red clover extracts containing up to 80 mg isoflavones have been used with apparent safety in clinical studies lasting up to 2 years (3375,6127,8925,11089,11091,17091,19540,19556,91524,102901,102840). ...when used topically and appropriately. Red clover extracts have been used topically with apparent safety for up to 4 weeks (102839).
PREGNANCY AND LACTATION: LIKELY SAFE
when used orally in amounts commonly found in foods (4912).
PREGNANCY AND LACTATION: POSSIBLY UNSAFE
when used orally in medicinal amounts.
Red clover has estrogenic activity (19555); avoid using. There is insufficient reliable information available about the safety of the topical use of red clover during pregnancy and lactation.
Below is general information about the interactions of the known ingredients contained in the product Phytomedicine Red Clover Extract. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
Although some laboratory research suggests that red clover may have anticoagulant and antiplatelet activity, clinical research has not shown this effect.
 Details
In vitro research suggests that genistein in red clover has antiplatelet effects, and historically, red clover was thought to have anticoagulant effects due to its coumarin content. However, some experts state that this is unlikely as most natural coumarins have not been shown to have anticoagulant effects, and their content in red clover is low (17091,19557,19558,19559). Additionally, some clinical research in postmenopausal patients found no effect on coagulation or prothrombin time with the use of red clover flowering tops 378 mg daily for 12 months or red clover isoflavone (Rimostil) 50 mg daily for 2 years (17091,91524).
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Theoretically, soy might reduce the clearance of caffeine; however, a small clinical study found no effect.
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Red clover contains genistein. Taking genistein 1 gram daily for 14 days seems to inhibit caffeine clearance and metabolism in healthy females (23582). However, this effect does not seem to occur with the lower amounts of genistein found in red clover. A clinical study in healthy postmenopausal individuals shows that taking red clover capsules standardized to contain 60 mg isoflavones twice daily for 14 days does not affect the pharmacokinetics of caffeine (105693).
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Theoretically, red clover might increase levels of drugs metabolized by CYP1A2; however, a small clinical study found no effect.
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In vitro evidence shows that red clover inhibits CYP1A2 (12479). However, a clinical study in healthy postmenopausal individuals shows that taking red clover capsules standardized to contain 60 mg isoflavones twice daily for 14 days does not affect the pharmacokinetics of caffeine, a CYP1A2 probe substrate (105693).
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Theoretically, red clover might increase the levels and clinical effects of drugs metabolized by CYP2C19.
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In vitro evidence suggests that red clover weakly inhibits CYP2C19 (12479). This interaction has not been reported in humans.
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Theoretically, red clover might increase levels of drugs metabolized by CYP2C9; however, a small clinical study found no effect.
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In vitro evidence suggests that red clover might inhibit CYP2C9 (12479). However, a clinical study in healthy postmenopausal individuals shows that taking red clover capsules standardized to contain 60 mg isoflavones twice daily for 14 days does not affect the pharmacokinetics of tolbutamide, a CYP2C9 probe substrate (105693).
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Theoretically, red clover might increase levels of drugs metabolized by CYP3A4; however, a small clinical study found no effect.
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In vitro evidence shows that red clover might inhibit CYP3A4 isoenzymes (6450,12479). However, a clinical study in healthy postmenopausal individuals shows that taking red clover capsules standardized to contain 60 mg isoflavones twice daily for 14 days does not affect the pharmacokinetics of alprazolam, a CYP3A4 probe substrate (105693).
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Theoretically, concomitant use of large amounts of red clover might interfere with estrogen therapy.
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Theoretically, red clover might increase the risk of methotrexate toxicity.
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In a case report, a 52-year-old female receiving weekly methotrexate injections for psoriasis developed symptoms of methotrexate toxicity, including severe vomiting and epigastric pain, after three days of taking red clover 430 mg daily. Toxicity resolved after red clover was discontinued. However, no liver function tests or methotrexate levels were reported (91522).
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Theoretically, the phytoestrogens in red clover might interfere with tamoxifen.
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In vitro and animal research suggests that genistein, a constituent of red clover, might antagonize the antitumor effects of tamoxifen (8192). However, there is some evidence from an animal study that red clover does not reduce the efficacy of tamoxifen (102901). Until more is known, tell patients taking tamoxifen to avoid red clover.
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Below is general information about the adverse effects of the known ingredients contained in the product Phytomedicine Red Clover Extract. 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 and topically, red clover seems to be well tolerated.
Most Common Adverse Effects:
Orally: Myalgia, nausea, and vaginal spotting.
Dermatologic ...Orally, a specific red clover isoflavone product (Promensil) has been associated with mild cases of psoriasis and thrush, although a direct causal link has not been established (9552).
Gastrointestinal ...Orally, red clover has been reported to cause nausea (8194).
Genitourinary ...In human research, 80 mg, but not 40 mg, of a specific red clover isoflavone product (Promensil) increased the duration of menstrual cycles in patients with mastalgia (9552). Red clover has also been reported to cause vaginal spotting (8194).
Hematologic ...In one case report, a 53-year-old female had a spontaneous subarachnoid hemorrhage associated with the use of an herbal supplement containing red clover, dong quai, and eleuthero. It is not clear if this was due to red clover, another ingredient, the combination of ingredients, or other factors (70419). In another 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 red clover 250 mg, wild yam 276 mg, dong quai 100 mg, and black cohosh 250 mg (13155). It is unclear if red clover contributed to this event.
Musculoskeletal ...Orally, red clover has been reported to cause myalgia (8194).
Neurologic/CNS ...Orally, a specific red clover isoflavone product (Medoflavon) has been associated with headache, although with a similar frequency to placebo (19545).
Oncologic ...Due to potential estrogenic effects of red clover isoflavones, there has been some concern that red clover might increase the risk of estrogen-sensitive cancers such as breast cancer or uterine cancer. A meta-analysis of 8 clinical trials suggests that increased intake of red clover- and soy-derived isoflavones may modestly increase mammographic breast density in premenopausal, but not postmenopausal, adults when compared with placebo. However, in a sub-group analysis assessing only isolated red clover isoflavones, there was no change in breast density (70428). Furthermore, a 2015 review by the European Food Safety Authority (EFSA) reported no increase in risk of breast cancer in females taking isoflavone-containing supplements (91725). Similarly, no effect was found on endometrial thickness and histopathological changes in the uterus after up to 36 months of supplementation with 40-120 mg daily of isoflavones from red clover extract (91725).
