Botanical Name: Trifolium pratense, Fabaceae

Common names: Red Clover, Cowgrass, Peavine Clover, Purple Clover

Plant description: Red Clover is a herbaceous biennial or perennial, slightly pilose to glabrous, with erect stems 1-5 cm long, early leaves arranged in a basal rosette with long petioles, later leaves on the stem sessile or on moderately long petioles.  The compound leaves are arranged in three parts, the leaflets oval to elliptic, 1-3 cm long, and 0.5≠1.5 cm wide.  Small pointed appendages called stipules are found at the base of the leaf, sometimes forming a tube around the stem.  The flower heads are pink or white appearing in globe-like terminal clusters 15-20 mm across, each containing between 20-40 flowers, 7-11 mm long.  The flowers are comprised of 5 sepals, 5 petals, 10-15 stamens and one style. The fruit is a tiny oblong to ovoid pod, 4-5 mm long, containing 3-6 seeds.

Habitat, ecology and distribution: Red Clover is native to northern and central Europe, southwards into the Mediterranean and Balkans, and eastward into Asia Minor, Iran, the northern subcontinent of India and into China and Japan.  Although not native to North America, it was brought with the first European colonists, where it has since naturalized. It is typically found in wet to dry meadows, open forests and the edges of forests, in fields, pastures and along road sides, and also in lawns (as it is a commonly mixed in with grass seed).  Red Clover prefers a well-drained loamy soil, rich in phosphorous and potassium (Duke 1981).

Part used: Flowering tops.

Constituents: The primary constituents of interest in Red clover are the isoflavones formononetin and biochanin A, as well as smaller amounts of daidzein, genistein, pratensin, trifoside, calycosine galactoside and pectolinarin.  Other important constituents include the flavonoids isorhamnetin, kaempferol, and quercitin, the saponins soyasapogenols B-F, coumaric acid, salicylic acid, phaseolic acid and medicagol, trifolirhizin, and betasitosterol.  Other constituents include allantoin, L-dopa (trans- and cis-clovamide conjugated with caffeic acid), resin, fats, carbohydrates, ascorbic acid, niacin, calcium, iron, magnesium, phosphorus, potassium and protein.  The flowers are also stated to contain an essential oil (0.028% dry weight) comprised of furfural (Duke 2003; Newall et al 1996, 227).

Medical Research: There is little data on Red Clover, and little that supports its traditional usage as an alterative and antitumor agent.  Newall et al report a possible chemoprotective and anticarcinogenic effect for biochanin A, in vitro (1996, 227).  Most of the research concerns the usage of Red Clover as a source of isoflavones in the treatment of menopausal symptoms, which is not a traditional use.
•Estrogenicity: A Red Clover extract standardized to contain 15% isoflavones was administered by gavage to virgin, ovariectomized 50 day old Sprague-Dawley rats, for 21 days.  Estrogenic effects included an increase in uterine weight, vaginal cell cornification and mammary gland duct branching. Red clover produced a dose-dependent increase in uterine weight and differentiated vaginal cells at the two higher doses, but it did not stimulate cell proliferation in the mammary glands. The data suggests that Red Clover extract is weakly estrogenic in the ovariectomized rat model (Burdette et al 2002). A methanol extracts of Red Clover showed significant competitive binding to estrogen receptors alpha (ER alpha) and beta (ER beta) in vitro.  Using ultrafiltration LC-MS its was revealed that genistein was the most active component of Red Clover (Liu et al 2001).  Researchers examined the effect of dietary isoflavones on prostate growth in intact male mice using an extract of Red Clover. The results demonstrated that prostate size was significantly reduced over 28 days of a Red Clover isoflavone supplemented diet. Histological examination revealed an increase in apoptotic cells, rather than a reduction in proliferative activity in the epithelium (Risbridger et al 2001).

Toxicity: Newall et al report urticarial reactions in humans, and infertility in animals that graze on clover (thought to be due to the estrogenic effect of the isoflavone constituents) (1996, 227).  In the amounts taken by humans as medicine or food (commonly sold as the sprouted seed), Red Clover is generally recognized as safe.

Herbal action: alterative, lymphagogue, expectorant, antitumor

Indications: pertussis, spasmodic coughs, bronchitis, laryngitis, lymphadenitis, wounds and ulcers, cancer

Contraindications and cautions: Caution is warranted with the concomitant use of Red Clover and antiplatelet drugs such as coumadin, due to a synergistic effect with the plant coumarins and isoflavonoid constituents.  Red Clover be contraindicated in estrogen-dependent breast cancer due to its estrogenicity, or it may act as a competitive antagonist of stronger endogenous and exogenous estrogens.

Medicinal uses: Red Clover has long been considered to be a valuable alterative, with exceptionally mild properties than make it a safe remedy for general application.  It is particularly recommended in pertussis, spasmodic coughs, bronchitis, and laryngitis, or chronic coughs characterized by a thin clear secretion that irritates the cough reflex.  Wood states that Red Clover has an affinity to the glands of the head and neck, particularly when there is only a single swollen gland, rather than several (1997, 475).  Wood states that Red Clover is useful in "old leaking cysts."  In the treatment of cancer Red Clover is among the most prominent remedies used, not because it acts powerfully, but by virtue of its mild, long term action to remove toxic accumulations in the blood and glands, and wall off the effects of these accumulations from healthy tissues.  King's states that it "…unquestionably retards the growth of carcinomata, and may be freely administered to those of a cancerous diathesis" (Felter and Lloyd 1893).  For this purpose the infusion of the recently dried flowers is used, ad libitum.  Red Clover has long been used by Western herbalists as a remedy for cancerous ulcers, in which it is concentrated and then applied as a paste (Felter and Lloyd 1893; Wood 1997, 476).  Although not typically thought of as a wound-healing herb Red Clover contains appreciable amounts of allantoin, and was commended by the Eclectics in ulcers of every kind as well as burns (Felter and Lloyd 1893; Cook 1869).  Red Clover is an important ingredient in the Hoxsey formula attributed to Dr. Harry M. Hoxsey (1901-1974).  This famous formula (or infamous, depending upon the perspective) is stated in an autobiographical account to have been developed by Hoxsey's great-grandfather after he observed a horse which had been afflicted by a cancerous growth become cured after pasturing on field plants such as Red Clover and Alfalfa (Hoxsey 1956, 44-48).  These herbs were collected and then prepared as a formulation, and with the addition of other herbs, was used by Hoxsey's father, a licensed veterinarian, in the treatment of cancer in horses.  Increasingly Hoxsey's father began to treat human patients as well, with apparent success, and charged Harry Hoxsey on his deathbed with the responsibility of using the formula to help cancer patients.  Hoxsey was an outspoken advocate of alternative cancer treatments, and equally argued against conventional treatments, and soon both Hoxsey and the formula attracted the scorn and antipathy of the medical profession.  Hoxsey's treatment centers were closed down in the 1950's by court order, despite the facts that there was never any published data or research to suggest the efficacy of the formula either way, or that it was harmful.  Nonetheless, there are countless anecdotal accounts of the benefit of Hoxsey's formula, and now many variations of the original formula exist, usually containing Rhamnus purshianus and potassium iodide, often with Trifolium, Phytolacca, Arctium, Berberis, Rhamnus frangula, Stillingia sylvatica and Zanthoxylum.  Many of these plants have since demonstrated significant antitumor properties.

Pharmacy and dosage:
•Fresh Plant Tincture: fresh flowering tops, 1:2, 95% alcohol, 20-60 gtt.
•Dry Plant Tincture: recently dried flowering tops, 1:5, 30% alcohol, 20-60 gtt., 1-5 mL
•Hot Infusion: recently dried flowering tops, 1:20, 200 mL, ad libitum

REFERENCES

Burdette JE, Liu J, Lantvit D, Lim E, Booth N, Bhat KP, Hedayat S, Van Breemen RB, Constantinou AI, Pezzuto JM, Farnsworth NR, Bolton JL. 2002. Trifolium pratense (red clover) exhibits estrogenic effects in vivo in ovariectomized Sprague-Dawley rats. J Nutr Jan;132(1):27-30
Cook, WM. H. 1869. The Physiomedical Dispensatory.  Cincinnati: self-published.  Digitized version available from http://medherb.com/cook/home.htm.
Duke, James. 2003. Dr. Duke's Phytochemical and Ethnobotanical Databases. Agricultural Research Services. Available from http://www.ars-grin.gov/duke/
Duke, J.A. 1981. Handbook of legumes of world economic importance. Plenum Press. NewYork.
Felter, HW and JU Lloyd. 1893. King's American Dispensatory. Digitized version available from http://www.ibiblio.org/herbmed/eclectic/kings/main.html.
Hoxsey, Harry M. 1956. You Don't Have to Die. New York: Milestone Books
Liu J, Burdette JE, Xu H, Gu C, van Breemen RB, Bhat KP, Booth N, Constantinou AI, Pezzuto JM, Fong HH, Farnsworth NR, Bolton JL. 2001. Evaluation of estrogenic activity of plant extracts for the potential treatment of menopausal symptoms. J Agric Food Chem. May;49(5):2472-9
Newall, Carol A., Linda A. Anderson and J.D. Phillipson. 1996. Herbal Medicines: A Guide for Health-Care Professionals. London: The Pharmaceutical Press.
Risbridger GP, Wang H, Frydenberg M, Husband A. 2001. The in vivo effect of red clover diet on ventral prostate growth in adult male mice. Reprod Fertil Dev 2001;13(4):325-9
Wood, Matthew. 1997. The Book of Herbal Wisdom. Berkeley: North Atlantic Books.