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Red clover (Trifolium pratense)

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Also listed as: Trifolium pratense, Promensil®
Related terms
Background
Evidencetable
Tradition
Dosing
Safety
Interactions
Attribution
Bibliography

Related Terms
  • Ackerklee (German), apigenin, beebread, biochanin A, biokain A, clovamides, clover Trifolium spp., coumarin, coumestrol, cow clover, daidzein, equol, Estro-Logic®, Fabaceae (family), flavonoids, formononetin, genistein, glycitein, isoflavone, isoflavone clover extract (ICE), Lipolysar Long Action®, luteolin, meadow clover, Menoflavon®, MF11RCE, O-desmethylangolensin, O-DMA, P-07, P081, phenolic acids, phytoestrogen, Promensil®, purple clover, raloxifene, Rimostil®, Rotklee (German), saponins, trèfle des prés (French), trefoil, Trifolium pratense, Trinovin®, wild clover.

Background
  • Red clover is a legume. Like soy, it contains chemicals that are called "phytoestrogens," which may act like estrogen in the body. Red clover has traditionally been used for asthma, whooping cough, cancer, and gout. In modern times, red clover extracts are used for symptoms of menopause, high cholesterol, and osteoporosis.
  • Aside from breast pain, there is a lack of high-quality evidence to support the use of red clover for most conditions. Although red clover has often been used to treat menopause symptoms, available human research has generally been unsupportive. Some studies suggest that red clover may lack cognitive effects in postmenopausal women. More information is needed.

Evidence Table

These uses have been tested in humans or animals. Safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider. GRADE *


Red clover has been studied as a possible treatment for breast pain. Early research suggests that red clover may decrease breast pain and promote higher treatment response. Although promising, more high-quality research is needed in this area.

B


Red clover contains estrogen-like chemicals called isoflavones. These chemicals may have anticancer effects and have been studied for prostate and breast cancer. However, convincing human evidence is lacking. Red clover may lack effect on colorectal cancer, but higher isoflavone intake has been linked to lower risk of endometrial cancer. More research is needed in this area.

C


Red clover has been shown to improve the flow of blood through arteries and veins. Isoflavone treatment may also lower blood pressure, although findings are conflicting. More research is needed before a conclusion can be made.

C


Red clover has been studied for its possible effects on insulin resistance in healthy postmenopausal women. It has also been studied for complications of type 2 diabetes, including high blood pressure and narrowing of the arteries and veins. Early findings suggest that red clover may lack effect. Further high-quality research is needed before a conclusion can be made.

C


Evidence is lacking in support of the use of red clover for enlarged prostate. More research is needed before a firm conclusion can be made.

C


Early research suggests that a combination treatment in which red clover flower extract is applied to the skin may benefit people with hair loss. Although promising, further study is needed in this area to confirm early findings and to determine the effects of red clover alone.

C


High-quality evidence is lacking in support of the use of red clover as an alternative to standard hormone replacement therapy. Evidence that isoflavones have similar benefits to those suggested for estrogen, including lower heart disease risk and cholesterol improvement, is also lacking. More research is needed in this field.

C


Homocysteine is an amino acid that may indicate heart health problems when found in high levels. Early research in healthy women found a lack of effect of red clover on homocysteine and folate levels. However, there is a lack of evidence in this area and further high-quality study is needed before a conclusion can be made.

C


Red clover has been studied for possible effects on levels of low-density lipoprotein ("bad") and high-density lipoprotein ("good") cholesterol. However, there is a lack of strong evidence to support its use for this purpose. Early research suggests that red clover may lack effect on lipid profile, although results are conflicting. Some studies have found soy protein to be superior to red clover for lipid lowering effects. More research is needed.

C


It is unclear what effects red clover may have on bone loss. Most studies have looked at soy products, which have a higher concentration of isoflavones than red clover. Evidence is lacking on the use of red clover as a treatment for osteoporosis.

C


Early research in healthy women about to undergo menopause suggests that red clover may lack effect on excessive cell growth in the uterus lining. However, strong evidence is lacking and more high-quality research is needed before any firm conclusions can be made.

C


Red clover isoflavones have been proposed as a treatment for menopause symptoms such as hot flashes. Overall, evidence suggests a lack of benefit in spite of some positive results. Estrogen-like supplements have been studied in breast cancer survivors, but lack effect on quality of life, fatigue, and hormone-related symptoms. Red clover has been compared to black cohosh for the treatment of menopause symptoms, with inconclusive results. More research is needed in this area.

D


Evidence suggests that isoflavones may lack major short-term effects on cognitive function in postmenopausal women. More high-quality studies are needed to determine the effect, if any, in this population.

F
* Key to grades

A: Strong scientific evidence for this use
B: Good scientific evidence for this use
C: Unclear scientific evidence for this use
D: Fair scientific evidence for this use (it may not work)
F: Strong scientific evidence against this use (it likley does not work)


Tradition / Theory

The below uses are based on tradition, scientific theories, or limited research. They often have not been thoroughly tested in humans, and safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider. There may be other proposed uses that are not listed below.

  • Acne, AIDS, antibacterial, anti-inflammatory, antioxidant, antispasmodic (prevents muscle spasms), appetite suppressant, arthritis, asthma, blood purification, blood thinner, bronchitis, burns, canker sores, chronic skin diseases, cough, eczema, eye problems (sore eyes), female sexual dysfunction, gout, heart disease prevention, high blood pressure, improving urine flow, indigestion, osteosarcoma (bone cancer), premenstrual syndrome (PMS), psoriasis (skin condition causing redness and irritation), sexually transmitted diseases (STDs), skin ulcers/sores, tuberculosis, whooping cough, wound healing.

Dosing

Adults (over 18 years old)

  • For enlarged prostate, one to two 500 milligram tablets of Trinovin® have been taken by mouth daily for three months.
  • For cancer, the following doses have been taken by mouth: Promensil® tablet once daily for one year to prevent breast cancer; 84 milligrams of isolated isoflavones daily for eight weeks to prevent colorectal cancer; and four 40 milligram tablets of Promensil® for seven days before prostate surgery.
  • For blood flow, 40-80 milligrams of Promensil® have been taken by mouth daily for five weeks to 12 months. Two red clover isoflavone tablets have been taken by mouth daily for four weeks.
  • For cognitive function, two Rimostil® tablets have been taken by mouth daily for six months. Two capsules containing 120 milligrams of red clover isoflavone aglycones have been taken by mouth daily for 12 months.
  • For diabetes, 86 milligrams of a red clover isoflavone preparation have been taken by mouth for three menstrual cycles. Doses of 40-80 milligrams of red clover isoflavones (e.g. Promensil®) have been taken by mouth daily for 4-12 weeks.
  • For hormone replacement therapy, 40-80 milligrams of red clover isoflavones (Promensil®) have been taken by mouth daily.
  • For high homocysteine levels, two tablets containing a total of 43 milligrams of red clover isoflavones each have been taken by mouth daily for three menstrual cycles.
  • For lipid lowering effects, 86 milligrams of red clover extract have been taken by mouth daily for one month. One to two 40 milligram capsules of red clover isoflavones (Menoflavon®) have been taken by mouth daily for 90 days up to one year. One tablet of red clover isoflavones has been taken by mouth daily for five weeks, followed by two tablets daily for another five weeks. Doses of 28.5-85.5 milligrams of Rimostil® has been taken by mouth daily for 12 weeks up to six months. Doses of 43.5-86 milligrams of Promensil® has been taken by mouth daily for 2-12 months.
  • For breast pain, 1-2 40 milligram Promensil® tablets have been taken by mouth daily for three months.
  • For menopause, 40-160 milligrams of Promensil® or Rimostil® have been taken by mouth daily for 12 weeks to 12 months. Two 40 milligram tablets of red clover isoflavones (MF11RCE) have been taken by mouth daily for 90 days.
  • For osteoporosis prevention, 28.5-85.5 milligrams of Promensil® or Rimostil® have been taken by mouth daily for up to one year. Two Promensil® tablets or two Rimostil® tablets have also been taken daily for 12 weeks. A red clover isoflavone supplement has been taken by mouth daily for 12 months. Doses of 25-75 milligrams of a red clover isoflavone preparation (P081) have been taken by mouth for six months.
  • For uterine complaints, one 50 milligram tablet of purified red clover isoflavones (P-07) has been taken by mouth daily for three menstrual cycles.

Children (under 18 years old)

  • There is no proven safe or effective dose for red clover in children.

Safety

The U.S. Food and Drug Administration does not strictly regulate herbs and supplements. There is no guarantee of strength, purity or safety of products, and effects may vary. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy. Consult a healthcare provider immediately if you experience side effects.

Allergies

  • Avoid in people with known allergy or sensitivity to red clover, any of its parts (such as isoflavones), or members of the Fabaceae family.

Side Effects and Warnings

  • Red clover is likely safe in recommended doses.
  • Red clover may cause breast tenderness, changes in breast density, changes in cell growth in uterus lining, changes in iron levels, estrogen-like effects, headache, menstrual changes, psoriasis (chronic skin redness and irritation), weight gain, and yeast infection.
  • Red clover may increase the risk of bleeding. Caution is advised in people with bleeding disorders or taking drugs that may increase the risk of bleeding. Dosing adjustments may be necessary.
  • Red clover may affect blood sugar levels. Caution is advised in people with diabetes or low blood sugar, and in those taking drugs, herbs, or supplements that affect blood sugar. Blood sugar levels may need to be monitored by a qualified healthcare professional, including a pharmacist and medication adjustments may be necessary.
  • Red clover may cause low blood pressure. Caution is advised in people with low blood pressure or in those taking drugs or herbs and supplements that lower blood pressure.
  • Red clover may interfere with the way the body processes certain drugs using the liver's "cytochrome P450" enzyme system.
  • Use cautiously in people who have or are at risk for hormone-sensitive cancers or conditions (including breast or endometrial cancer).
  • Use cautiously in people who are taking hormone replacement therapy (HRT) or birth control.
  • Avoid in children and in pregnant or breastfeeding women.
  • Avoid in people with known allergy or sensitivity to red clover, any of its parts (such as isoflavones), or members of the Fabaceae family.

Pregnancy & Breastfeeding

  • There is a lack of scientific evidence on the use of red clover during pregnancy or breastfeeding. Avoid in pregnant or breastfeeding women, due to the potential estrogen-like effects of red clover.

Interactions

Interactions with Drugs

  • Red clover may increase the risk of bleeding when taken with drugs that increase the risk of bleeding. Some examples include aspirin, anticoagulants ("blood thinners") such as warfarin (Coumadin®) or heparin, anti-platelet drugs such as clopidogrel (Plavix®), and non-steroidal anti-inflammatory drugs such as ibuprofen (Motrin®, Advil®) or naproxen (Naprosyn®, Aleve®).
  • Red clover may affect blood sugar levels. Caution is advised when using medications that may also lower blood sugar. People taking drugs for diabetes by mouth or insulin should be monitored closely by a qualified healthcare professional, including a pharmacist. Medication adjustments may be necessary.
  • Red clover may cause low blood pressure. Caution is advised in people taking drugs that lower blood pressure.
  • Red clover may interfere with the way the body processes certain drugs using the liver's "cytochrome P450" enzyme system. As a result, the levels of these drugs may be altered in the blood, and may cause altered effects or potentially serious adverse reactions. People using any medications should check the package insert, and speak with a qualified healthcare professional, including a pharmacist, about possible interactions.
  • Red clover may also interact with agents that enhance cognitive function, agents that treat genitourinary tract disorders, agents that treat heart disorders, agents that treat skin disorders, agents that treat stomach and intestine disorders, androgens and anti-androgens, anticancer agents, anti-estrogens, anti-gout agents, aromatase inhibitors, aryl hydrocarbon receptor (AhR) agonists, cholesterol-lowering agents, hormonal agents, hormone replacement therapy (HRT), non-steroidal anti-inflammatory agents (NSAIDs), osteoporosis agents, pain relievers, and selective estrogen receptor modulators (tamoxifen).

Interactions with Herbs & Dietary Supplements

  • Red clover may increase the risk of bleeding when taken with herbs and supplements that are believed to increase the risk of bleeding. Multiple cases of bleeding have been reported with the use of Ginkgo biloba, and fewer cases with garlic and saw palmetto. Numerous other agents may theoretically increase the risk of bleeding, although this has not been proven in most cases.
  • Red clover may interfere with the way the body processes certain herbs or supplements using the liver's "cytochrome P450" enzyme system. As a result, the levels of other herbs or supplements may be altered in the blood. It may also alter the effects that other herbs or supplements possibly have on the P450 system.
  • Red clover may affect blood sugar levels. Caution is advised when using herbs or supplements that may also affect blood sugar. Blood glucose levels may require monitoring, and doses may need adjustment.
  • Red clover may cause low blood pressure. Caution is advised in people taking herbs or supplements that lower blood pressure.
  • Red clover may also interact with androgens and anti-androgens, anticancer herbs and supplements, anti-estrogens, anti-gout herbs and supplements, anti-inflammatory herbs and supplements, antioxidants, cholesterol-lowering herbs and supplements, herbs and supplements that enhance cognitive function, herbs and supplements that treat genitourinary tract disorders, herbs and supplements that treat heart disorders, herbs and supplements that treat skin disorders, herbs and supplements that treat stomach and intestine disorders, hormonal herbs and supplements, hormone replacement therapy (HRT), osteoporosis herbs and supplements, pain relievers, phytoestrogens, and selective estrogen receptor modulators (Tamoxifen).

Attribution
  • This information is based on a systematic review of scientific literature edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

Bibliography
  1. del Giorno C, Fonseca AM, Bagnoli VR, et al. Effects of Trifolium pratense on the climacteric and sexual symptoms in postmenopause women. Rev.Assoc.Med.Bras. 2010;56(5):558-562.
  2. Hamilton-Reeves JM, Vazquez G, Duval SJ, et al. Clinical studies show no effects of soy protein or isoflavones on reproductive hormones in men: results of a meta-analysis. Fertil.Steril. 2010;94(3):997-1007.
  3. Hooper L, Madhavan G, Tice JA, et al. Effects of isoflavones on breast density in pre- and post-menopausal women: a systematic review and meta-analysis of randomized controlled trials. Hum.Reprod.Update. 2010;16(6):745-760.
  4. Kelley KW and Carroll DG. Evaluating the evidence for over-the-counter alternatives for relief of hot flashes in menopausal women. J.Am.Pharm.Assoc.(2003.) 2010;50(5):e106-e115.
  5. Kolodziejczyk-Czepas J. Trifolium species-derived substances and extracts--biological activity and prospects for medicinal applications. J.Ethnopharmacol. 8-30-2012;143(1):14-23.
  6. Leach MJ and Moore V. Black cohosh (Cimicifuga spp.) for menopausal symptoms. Cochrane.Database.Syst.Rev. 2012;9:CD007244.
  7. Lee CC, Bloem CJ, Kasa-Vubu JZ, et al. Effect of oral phytoestrogen on androgenicity and insulin sensitivity in postmenopausal women. Diabetes Obes.Metab 2012;14(4):315-319.
  8. Lipovac M, Chedraui P, Gruenhut C, et al. The effect of red clover isoflavone supplementation over vasomotor and menopausal symptoms in postmenopausal women. Gynecol.Endocrinol. 2012;28(3):203-207.
  9. Lipovac M, Chedraui P, Gruenhut C, et al. Improvement of postmenopausal depressive and anxiety symptoms after treatment with isoflavones derived from red clover extracts. Maturitas 2010;65(3):258-261.
  10. Loing E, Lachance R, Ollier V, et al. A new strategy to modulate alopecia using a combination of two specific and unique ingredients. J.Cosmet.Sci. 2013;64(1):45-58.
  11. Ma H, Sullivan-Halley J, Smith AW, et al. Estrogenic botanical supplements, health-related quality of life, fatigue, and hormone-related symptoms in breast cancer survivors: a HEAL study report. BMC.Complement Altern.Med. 2011;11:109.
  12. Pitkin J. Alternative and complementary therapies for the menopause. Menopause.Int. 2012;18(1):20-27.
  13. Posadzki P, Watson LK, and Ernst E. Adverse effects of herbal medicines: an overview of systematic reviews. Clin.Med. 2013;13(1):7-12.
  14. Shulman LP, Banuvar S, Fong HH, et al. Discussion of a well-designed clinical trial which did not demonstrate effectiveness: UIC center for botanical dietary supplements research study of black cohosh and red clover. Fitoterapia 2011;82(1):88-91.
  15. Villaseca P. Non-estrogen conventional and phytochemical treatments for vasomotor symptoms: what needs to be known for practice. Climacteric. 2012;15(2):115-124.

Copyright © 2011 Natural Standard (www.naturalstandard.com)


The information in this monograph is intended for informational purposes only, and is meant to help users better understand health concerns. Information is based on review of scientific research data, historical practice patterns, and clinical experience. This information should not be interpreted as specific medical advice. Users should consult with a qualified healthcare provider for specific questions regarding therapies, diagnosis and/or health conditions, prior to making therapeutic decisions.


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