Drugs A - Z
Red clover (Trifolium pratense)
Generic Name: Red Clover
CategoryHerbs & Supplements
Ackerklee (German), beebread, cow clover, genistein, ICE, isoflavone, isoflavone clover extract, meadow clover, phytoestrogen, Promensil®, purple clover, Rimostil®, Rotklee (German), trefle des pres (French), trefoil, Trinovin®, wild clover.
Red clover is a legume, which like soy contains "phytoestrogens" (plant-based chemicals that are similar to estrogen and may act in the body like estrogen or may actually block the effects of estrogen). Red clover was traditionally used to treat asthma, pertussis (whooping cough), cancer, and gout. In modern times, isoflavone extracts of red clover are most often used to treat menopausal symptoms, as an alternative hormone replacement therapy, for high cholesterol, or to prevent osteoporosis. However, at this time, there are no high-quality human studies supporting the use of red clover for any medical condition.
EvidenceDISCLAIMER: 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.
Cardiovascular - blood flow:
Red clover has been shown to improve the flow of blood through arteries and veins. However, there is limited study in this area and more research is needed before a conclusion can be drawn.
Red clover has been studied in patients with type 2 diabetes to determine potential benefits in diabetic complications such as high blood pressure and narrowing of the arteries and veins. Further research is needed before a strong recommendation can be made.
Red clover has not been clearly shown to have beneficial effects on blood cholesterol levels. Due to conflicting study results, further research is needed in this area before a recommendation can be made.
Hormone replacement therapy (HRT):
Laboratory research suggests that red clover isoflavones have estrogen-like activity. However, there is no clear evidence that isoflavones share the possible benefits of estrogens (such as effects on bone density). In addition, hormone replacement therapy itself is a controversial topic, with recent research reporting that the potential harm may outweigh any benefits.
Red clover isoflavones are proposed to reduce symptoms of menopause (such as hot flashes), and are popular for this use. Blood pressure and triglyceride levels may be lowered. However, most of the available human studies are poorly designed and short in duration (less than 12 weeks of treatment). As results of published studies conflict with each other, more research is needed before a clear conclusion can be drawn.
It is not clear if red clover isoflavones have beneficial effects on bone density. Most studies of isoflavones in this area have looked at soy, which contains different amounts of isoflavones, as well as other non-isoflavone ingredients. More research is needed before a recommendation can be made.
Red clover isoflavones may have estrogen-like properties in the body, and have been proposed as a possible therapy in prostate cancer and related hot flashes. Some isoflavones have also been shown in laboratory studies to have anti-cancer properties. Because there is a lack of well-designed human research in this area, a strong recommendation cannot be made.
Prostate enlargement (benign prostatic hypertrophy):
There is only limited study of red clover for benign prostatic hypertrophy (enlarged prostate). More research is needed before a firm conclusion can be drawn.
TraditionWARNING: DISCLAIMER: 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.
Adults (over 18 years old)
Various doses of red clover isoflavones have been used to treat conditions. For instance, for benign prostatic hypertrophy (enlarged prostate), a dose of 40 milligrams of red clover isoflavones per day (Trinovin®) has been studied. For breast cancer prevention, a red clover-derived isoflavone tablet containing 26 milligrams biochanin A, 16 milligrams formononetin, 1 milligram genistein, and 0.5 milligram of daidzein has been studied.
For cardiovascular disease, a dose of 86 milligrams per day for one month has been studied. For diabetes, 50 milligrams and 86 milligrams per day of red clover isoflavones per day have been studied for diabetic complications. For high cholesterol, 28-86 milligrams of red clover isoflavones per day (Rimostil®), or 80 milligrams of red clover isoflavones per day (Promensil®), have been studied. For hormone replacement, a dose of 40-160 milligrams of red clover isoflavones per day (Promensil®) has been studied. Rimostil® (57 milligrams of red clover) has also been used. For osteoporosis, a dose of 40 milligrams of red clover isoflavones per day (Promensil®) has been studied.
Children (under 18 years old)
There is not enough scientific evidence to recommend use of red clover in children.
SafetyDISCLAIMER: Many complementary techniques are practiced by healthcare professionals with formal training, in accordance with the standards of national organizations. However, this is not universally the case, and adverse effects are possible. Due to limited research, in some cases only limited safety information is available.
People with known allergies or reactions to products containing red clover or isoflavones should avoid taking red clover.
Side Effects and Warnings
A small number of human studies using red clover extracts have all reported good tolerance, without serious side effects after up to one year of treatment. In theory, based on the estrogen-like action of red clover seen in laboratory studies, side effects may include weight gain or breast tenderness, although these have not been reported clearly in humans. In theory, menstrual changes and increased uterus cell growth (endometrial hyperplasia) may also occur, although preliminary short-term studies (less than six months) have found no increases in uterus wall (endometrial) thickness with red clover. Red clover may affect hormonal levels of gonadotropin releasing hormone (GrH), follicle stimulating hormone (FSH), and leutinizing hormone (LH), although early research has not found significant change in FSH or LH levels.
In theory, red clover may increase the risk of bleeding. However, there are no reliable human reports of bleeding with red clover. Caution is advised in patients with bleeding disorders, taking drugs that may increase the risk of bleeding, or scheduled for surgery. Dosing adjustments may be necessary.
Red clover has been studied for lowering blood sugar with inconclusive results. Caution is warranted until further research is available.
Pregnancy & Breastfeeding
Interactions with Drugs
Red clover may interfere with the way the liver processes some drugs using an enzyme called cytochrome P450 3A4. As a result, the levels of these drugs may be increased in the blood, and may cause increased effects or potentially serious adverse reactions. Patients using any medications should check the package insert and speak with a healthcare professional or pharmacist about possible interactions.
In theory, 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®). Because red clover contains estrogen-like chemicals, the effects of drugs with estrogen or estrogen-like properties may be altered, such as birth control pills or hormone replacement therapies like Premarin® and Provera®.
Red clover has been studied for lowering blood sugar with inconclusive results. Caution is warranted with diabetes or if taking other medications that may alter blood sugar until further research is available.
In theory, red clover may interact with other estrogen-containing medications. Red clover contains phytoestrogens, which are plant-based chemicals that are similar to estrogen and may act in the body like estrogen or may actually block the effects of estrogen.
Interactions with Herbs & Dietary Supplements
Red clover may interfere with the way the liver processes some drugs using an enzyme called cytochrome P450 3A4. As a result, red clover may cause the levels of other herbs or supplements to be too high in the blood. It may also alter the effects that other herbs or supplements possibly have on the P450 system.
In theory, red clover may increase the risk of bleeding when taken with herbs or supplements that 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.
Because red clover contains estrogen-like chemicals, the effects of other agents believed to have estrogen-like properties may be altered.
Red clover has been studied for lowering blood sugar with inconclusive results. Caution is warranted with diabetes or if taking other herbs or supplements that may alter blood sugar until further research is available.
This information is based on a systematic review of scientific literature, and was peer-reviewed and edited by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com): Ernie-Paul Barrette, MD (Case Western Reserve School of Medicine); Ethan Basch, MD (Memorial Sloan-Kettering Cancer Center); Samuel Basch, MD (Mt. Sinai Medical Center, NY); Steve Bent, MD (University of California, San Francisco); Edzard Ernst, MD, PhD (University of Exeter); Sadaf Hashmi, MD, MPH (Natural Standard Research Group); Jenna Hollenstein, MS, RD (Natural Standard Research Collaboration); Jamie Nelsen, PharmD (University of Rhode Island); Adrianne Rogers, MD (Boston University School of Medicine); David Sollars MAc, HMC (New England School of Acupuncture); Philippe Szapary, MD, MPH (University of Pennsylvania); Shaina Tanguay-Colucci, BS (Natural Standard Research Collaboration); Candy Tsourounis, PharmD (University of California, San Francisco); Catherine Ulbricht, PharmD (Massachusetts General Hospital); Wendy Weissner, BA (Natural Standard Research Collaboration).
BibliographyDISCLAIMER: Natural Standard developed the above evidence-based information based on a thorough systematic review of the available scientific articles. For comprehensive information about alternative and complementary therapies on the professional level, go to www.naturalstandard.com. Selected references are listed below.
Atkinson C, Compston JE, Day NE, et al. The effects of phytoestrogen isoflavones on bone density in women: a double-blind, randomized, placebo-controlled trial. Am J Clin Nutr 2004;79(2):326-333.
Atkinson C, Warren RM, Sala E, et al. Red-clover-derived isoflavones and mammographic breast density: a double-blind, randomized, placebo-controlled trial [ISRCTN42940165]. Breast Cancer Res 2004;6(3):R170-R179.
Baber RJ, Templeman C, Morton T, et al. Randomized placebo-controlled trial of an isoflavone supplement and menopausal symptoms in women. Climacteric 1999;2:85-92.
Beck V, Unterrieder E, Krenn L, et al. Comparison of hormonal activity (estrogen, androgen and progestin) of standardized plant extracts for large scale use in hormone replacement therapy. J Steroid Biochem Mol Biol 2003;84(2-3):259-268.
Coon JT, Pittler MH, Ernst E. Trifolium pratense isoflavones in the treatment of menopausal hot flushes: a systematic review and meta-analysis. Phytomedicine 2007 Feb;14(2-3):153-9.
Howes J, Waring M, Huang L, et al. Long-term pharmacokinetics of an extract of isoflavones from red clover (Trifolium pratense). J Altern Complement Med 2002;8(2):135-142.
Howes JB, Sullivan D, Lai N, et al. The effects of dietary supplementation with isoflavones from red clover on the lipoprotein profiles of post menopausal women with mild to moderate hypercholesterolaemia. Atherosclerosis 2000;152(1):143-147.
Howes JB, Tran D, Brillante D, et al. Effects of dietary supplementation with isoflavones from red clover on ambulatory blood pressure and endothelial function in postmenopausal type 2 diabetes. Diabetes Obes.Metab 2003;5(5):325-332.
Nelson HD, Vesco KK, Haney E, et al. Nonhormonal therapies for menopausal hot flashes: systematic review and meta-analysis. JAMA 2006 May 3;295(17):2057-71.
Rossouw JE, Anderson GL, Prentice RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial. JAMA 7-17-2002;288(3):321-333.
Rotem C, Kaplan B. Phyto-Female Complex for the relief of hot flushes, night sweats and quality of sleep: randomized, controlled, double-blind pilot study. Gynecol Endocrinol 2007 Feb;23(2):117-22.
Teede HJ, McGrath BP, DeSilva L, et al. Isoflavones reduce arterial stiffness: a placebo-controlled study in men and postmenopausal women. Arterioscler Thromb Vasc Biol 6-1-2003;23(6):1066-1071.
Tempfer CB, Bentz EK, Leodolter S, et al. Phytoestrogens in clinical practice: a review of the literature. Fertil Steril 2007 Jun;87(6):1243-9.
Tice JA, Ettinger B, Ensrud K, et al. Phytoestrogen supplements for the treatment of hot flashes: the Isoflavone Clover Extract (ICE) Study: a randomized controlled trial. JAMA 7-9-2003;290(2):207-214.
Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.