Red Clover Introduction

Red clover is found growing throughout the world. It is found in greater abundance in areas of Europe and North America. Red clover is relatively new on the herbal medicine market, having been applied medicinally within the last hundred years. Red clover is typically indicated in women’s health conditions, lung disorders, and as a topical treatment for specific skin conditions. Red clover is also used commercially as a food-flavoring agent. Red clover is thought to make animals sterile, as witnessed in certain livestock populations feeding on it in the wild. [1]

Parts Used

The medicinal parts of red clover are the flowering tops, which appear between May and September of each year. Red clover has a wide range of medicinal uses, perhaps due to the numerous active constituents found within it. The main active constituents are known as isoflavones, which are a form of phytoestrogens. Phytoestrogens are chemicals derived from plants that are similar in structure to estrogen, a human hormone. These similar chemicals allow for their use in estrogen-related human health conditions. The main isoflavones in red clover are further metabolized to isoflavones known as genistein and daidzein. [2]

Red Clover Uses

The active constituents of red clover (isoflavones) are thought to be mild activators of estrogen receptors in the body. There are two theories regarding this mechanism of action. First, the phytoestrogens stimulate estrogen-like effects in the body by stimulating estrogen receptors. This may be generally thought of as beneficial in a woman with low estrogen levels. Secondly, as the phytoestrogens bind to and activate estrogen receptors, they block the receptors from being stimulated by the original estrogen molecule; thereby decreasing estrogen’s effects in the body. This action may be generally thought of as beneficial in a younger woman with excess estrogen symptoms.

Because of its estrogen-like activity, red clover’s isoflavones may be of benefit in older postmenopausal women as well. [3, 4] The specific type of estrogen receptor that the constituents of red clover activate are those responsible for maintaining heart, bone, blood vessel, and bladder health. Red clover has been shown to be of benefit most specifically for treatments concerning osteoporosis. [5, 6]

Other benefits of the isoflavones found in red clover include reducing the risk of endometrial cancer; isoflavones have been shown to inhibit the transformation of one hormone (androstenedione) into a more potent type of estrogen (estrone), which has been associated with endometrial cancers. [7]

Overall, red clover’s isoflavones molecules may exert protection from certain forms of cancer. [8, 9]

Although a specified dosage of red clover itself is not typically indicated, the herb’s isoflavones are typically dosed at 40 to 160 milligrams per day for menopausal symptoms. [10] Most often, isoflavones are available in 40mg preparations.

For treating breast pain related to the menstrual cycle, isoflavones may be taken at a dose of 40 to 80 milligrams per day. [11]

For treating lung conditions (i.e. cough, bronchitis) roughly 3 teaspoonfuls of the herb can be soaked as an infusion and drunk three times per day. Otherwise, 2 to 6 milliliters of the tincture can be taken three times per day. [12]

There is no standard dosage for topical applications in skin conditions.

Red Clover side effects

Red clover is well tolerated, with few side effects. [13] Side effects that do occur have been reported as rash, muscle pain, headache, nausea, and vaginal spotting. [14]

Red Clover General interactions (supplement, herb, food, lab)

Using red clover with other herbs that are anticoagulants may increase the risk of bleeding as red clover contains coumarin, a compound that may interfere with clotting. [15]

Caution should also be used when combining red clover with other phytoestrogens. It may act either as an additive or an antagonist with the other herbs.

There are no other known interactions between red clover and any foods or lab tests at this time.

Red Clover Drug interactions

There is some concert that red clover may inhibit certain liver enzymes that are responsible for breaking down pharmaceutical drugs. As pharmaceutical drugs are dosed with these liver enzymes in mind, inhibition of the enzyme may lead to elevated drug levels in the body.

Birth control pills may be less effective when combined with large amounts of red clover due to the herb’s estrogen-like effects. [16]

Similarly, combining red clover with other estrogens (hormone replacement therapy) may interfere due to competitive binding to estrogen receptors. [17] Red clover should also be avoided in people taking Tamoxifen because of the herb’s estrogenic effects. Tamoxifen is typically taken to combat estrogen receptor-positive cancers.[18]

Caution should be exercised when taking anticoagulant drugs with this herb; red clover may increase bleeding time due to its coumarin content.

Disease conditions

Red clover, and for that matter any herb containing phytoestrogens, should be avoided in breast cancer or other hormone sensitive conditions due to its estrogen-like effects. These conditions include; breast cancer, ovarian cancer, uterine cancer, uterine fibroids, and endometriosis. [19]

1 Kurzer MS, Xu X. Dietary phytoestrogens. Annu Rev Nutr 1997;17:353-81.

2 Howes JB, Sullivan D, Lai N, et al. The effects of dietary supplementation with isoflavones from red clover on the lipoprotein profiles of postmenopausal women with mild to moderate hypercholesterolemia. Atherosclerosis 2000;152:143-7.

3 Umland EM, Cauffield JS, Kirk JK, et al. Phytoestrogens as therapeutic alternatives to traditional hormone replacement in postmenopausal women. Pharmacother 2000;20:981-90.

4 Zand RS, Jenkins DJ, Diamandis EP. Steroid hormone activity of flavonoids and related compounds. Breast Cancer Res Treat 2000;62:35-49.

5 Umland EM, Cauffield JS, Kirk JK, et al. Phytoestrogens as therapeutic alternatives to traditional hormone replacement in postmenopausal women. Pharmacother 2000;20:981-90.

6 Setchell KD, Cassidy A. Dietary isoflavones: biological effects and relevance to human health. J Nutr 1999;129:758S-67S.

7 Horn-Ross PL, John EM, Canchola AJ, et al. Phytoestrogen intake and endometrial cancer risk. J Natl Cancer Inst 2003;95:1158-64.

8 Yanagihara K, Ito A, Toge T, Numoto M. Antiproliferative effects of isoflavones on human cancer cell lines established from the gastrointestinal tract. Cancer Res 1993;53:5815-21.

9 Cassady JM, Zennie TM, Chae YH, et al. Use of a mammalian cell culture benzo(a)pyrene metabolism assay for the detection of potential anticarcinogens from natural products: inhibition of metabolism by biochanin A, an isoflavone from Trifolium pratense L. Cancer Res 1988;48:6257-61.

10 Nelsen J, Barrette E, Tsouronix C, et al. Red clover (Trifolium pratense) monograph: A clinical decision support tool. J Herbal Pharmacotherapy 2002;2:49-72.

11 Ingram DM, Hickling C, West L, et al. A double-blind randomized controlled trial of isoflavones in the treatment of cyclical mastalgia. The Breast 2002;11:170-4.

12 Online document at: www.healthy.net

13 van de Weijer P, Barentsen R. Isoflavones from red clover (Promensil) significantly reduce menopausal hot flush symptoms compared with placebo. Maturitas 2002;42:187-93.

14 Tice J, Cummings SR, Ettinger B, et al. Few adverse effects of two red clover extracts rich in phytoestrogens: a multicenter, placebo-controlled trial. Alt Ther 2001;7:S33.

15 Puschner B, Galey FD, Holstege DM, et al. Sweet clover poisoning in dairy cattle in California. J Am Vet Med Assoc 1998;212:857-9.

16 Nelsen J, Barrette E, Tsouronix C, et al. Red clover (Trifolium pratense) monograph: A clinical decision support tool. J Herbal Pharmacotherapy 2002;2:49-72.

17 Anon. Phytoestrogens. Med Lett Drugs Ther 2000;42:17-8.

18 This P, De La Rochefordiere A, Clough K, et al. Phytoestrogens after breast cancer. Endocr Relat Cancer 2001;8:129-34.

19 Le Bail JC, Champavier Y, Chulia AJ, Habrioux G. Effects of phytoestrogens on aromatase, 3beta and 17beta-hydroxysteroid dehydrogenase activities and human breast cancer cells. Life Sci 2000;66:1281-91.