Wise Mind Herbs

The information on this page has been prepared with reference to published scientific literature, not by a medically qualified expert. It is not medical advice. Any decision to use a supplement or herb-based product is your responsibility. Consult a suitably qualified medical professional, especially if you have underlying conditions. Remember, nothing is for everyone, and not everything sold is what it claims to be. Some things work for some people, some of the time.

Clover - Trifolium pratense

Clover refers to plants of the genus Trifolium in the family Fabaceae (legumes). The most extensively studied species for medicinal purposes include Trifolium pratense (red clover), Trifolium repens (white clover), and to a lesser extent, Trifolium incarnatum (crimson clover). These plants are sometimes confused with species from other genera such as Medicago (including alfalfa, Medicago sativa, which is occasionally referred to as "yellow clover") and Melilotus (sweet clover species like Melilotus officinalis), though these represent distinct botanical entities with different phytochemical profiles.

Image source and license: https://commons.wikimedia.org/wiki/File:Trifolium_pratense-IMG_20181123_161349.jpg.
Modified by Peter Jorgensen.

Primary Bioactive Compounds

The therapeutic properties of clover, particularly red clover (T. pratense), are attributed to its rich isoflavone content, including genistein, daidzein, biochanin A, and formononetin. These compounds function as phytoestrogens, exhibiting weak estrogenic or anti-estrogenic effects depending on the hormonal environment. Red clover also contains flavonoids, coumarins, triterpenes, phenolic acids, and various essential nutrients including calcium, chromium, magnesium, potassium, and vitamins (B, C, and E).

Evidence-Based Health Benefits

Current peer-reviewed literature supports several potential health applications for clover extracts, though the strength of evidence varies considerably across conditions:

• Menopausal Symptoms: The most robust evidence supports red clover's efficacy in reducing vasomotor symptoms (hot flashes) in menopausal women. Meta-analyses indicate modest but statistically significant improvements compared to placebo.
• Cardiovascular Health: Moderate evidence suggests red clover may improve arterial compliance, reduce arterial stiffness, and modestly decrease LDL cholesterol levels. Consistent improvement in lipid profiles has been evidenced.
• Bone Health: Several clinical trials demonstrate that red clover isoflavones may slow bone mineral density loss in postmenopausal women, though effects are modest compared to conventional treatments.
• Skin Health: Emerging research suggests potential benefits for skin aging, with improvements in skin elasticity, moisture, and collagen production when applied topically or taken orally.
• Prostate Health: Preliminary evidence indicates possible benefits for benign prostatic hyperplasia (BPH) symptom management, though research remains limited.

It is important to note that while historical or traditional medicine sources attribute numerous additional healing properties to clover (including anti-cancer, anti-inflammatory, and wound-healing applications), many of these claims lack sufficient clinical validation despite promising in vitro and animal studies.

Recommended Dosages

Standardized preparations typically specify isoflavone content as the key metric for dosing. Based on clinical trials, the following dosage ranges have demonstrated efficacy with acceptable safety profiles:

• For menopausal symptoms: 40-160 mg of total isoflavones daily (standardized to contain 4-8 mg formononetin, 1-5 mg biochanin A, 0.5-2 mg genistein, and 0.5-2 mg daidzein)
• For cardiovascular health: 40-80 mg of total isoflavones daily
• For bone health maintenance: 40-120 mg of total isoflavones daily
• For topical applications: Products containing 2-5% clover extract (standardized to 0.5-1.5% isoflavones)

Therapeutic effects typically require 8-12 weeks of consistent use before significant benefits manifest. The optimal duration of treatment remains inadequately defined in the literature, though most intervention studies range from 3-12 months.

Safety Profile and Adverse Effects

Clinical trials generally report good tolerability for clover preparations with the following potential adverse effects:

• Mild gastrointestinal disturbances (bloating, nausea, indigestion)
• Headache
• Rash or allergic reactions (rare)
• Menstrual changes in premenopausal women

More serious concerns include theoretical hormone-sensitive tissue interactions due to phytoestrogen content. However, current evidence does not support increased risk of hormone-dependent cancers with red clover use. Nevertheless, caution is warranted in patients with estrogen-receptor-positive cancers until more definitive safety data emerges.

Contraindications and Drug Interactions

Caution is advised in the following populations:

• Individuals using hormonal medications (including contraceptives and hormone replacement therapy)
• Those taking anticoagulant or antiplatelet medications (due to potential additive effects)
• Patients with hormone-sensitive conditions (including certain cancers, endometriosis, and uterine fibroids)
• Pregnant or breastfeeding women (due to insufficient safety data)
• Individuals with protein S deficiency (theoretical risk based on in vitro studies)

Clover preparations may interact with CYP450 enzymes, potentially affecting metabolism of various medications, though clinical significance appears minimal at standard doses.

High-Dose Studies and Knowledge Gaps

Limited research has evaluated doses exceeding the therapeutic ranges outlined above. Studies using up to 160 mg isoflavones daily have demonstrated acceptable safety profiles over short-term use (up to 12 months). However, significant knowledge gaps exist regarding long-term safety and efficacy beyond one year of continuous use. No consistent dose-dependent relationship has been established for efficacy, suggesting a possible ceiling effect. Safety concerns with substantially higher doses include theoretical hormonal perturbations and potential liver enzyme alterations, though clinical evidence for these effects remains sparse.

Notably, research gaps include comprehensive pharmacokinetic analyses, potential tissue-specific effects, inter-individual variability in metabolism (particularly regarding equol-producer status), and long-term safety data exceeding 24 months of continuous use.

Commercial Pharmaceutical Products

While numerous dietary supplements containing clover extracts exist, few meet strict pharmaceutical classification standards. Notable exceptions include:

• Promensil®: A standardized red clover extract containing 40-80 mg of isoflavones, marketed for menopausal symptom relief in several countries with varying regulatory status
• Menoflavon®: A standardized extract used in Eastern European markets with pharmaceutical registration in some countries

Most clover-based products remain classified as dietary supplements or traditional herbal medicines rather than prescription pharmaceuticals in major regulatory markets.

References

Akbaribazm, M., Khazaei, F., Naseri, L., Pazhouhi, M., Zamanian, M., & Khazaei, M. (2021). Pharmacological and therapeutic properties of the Red Clover (Trifolium pratense L.): an overview of the new findings. Journal of Traditional Chinese Medicine, 41(4).

Chilibeck, P. D., Vatanparast, H., Pierson, R., Case, A., Olatunbosun, O., Whiting, S. J., ... & Biem, H. J. (2013). Effect of exercise training combined with isoflavone supplementation on bone and lipids in postmenopausal women: a randomized clinical trial. Journal of Bone and Mineral Research, 28(4), 780-793.

Coon, J. T., Pittler, M. H., & Ernst, E. (2007). Trifolium pratense isoflavones in the treatment of menopausal hot flushes: a systematic review and meta-analysis. Phytomedicine, 14(2-3), 153-159.

Ghazanfarpour, M., Sadeghi, R., Roudsari, R. L., Najmabadi, K. M., & Khadivzadeh, T. (2015). Effects of red clover on hot flash and circulating hormone concentrations in menopausal women: a systematic review and meta-analysis. Avicenna journal of phytomedicine, 5(6), 498.

Jeon, S. Y., Kim, M. R., Lee, E. O., Jeon, B. H., Lee, J. J., & Lee, Y. C. (2020). Effect of a new herbal composition comprised of red clover and hop extract on human endothelial cell damage and vasorelaxant activity. Journal of Food Biochemistry, 44(8), e13314.

Khazaei, M., & Pazhouhi, M. (2019). Induction of apoptosis and inhibition of autophagy cell death in the human prostate cancer cell lines by Trifolium pratens L. hydroalcoholic extract. World J Cancer Res, 6, e1232.

Terzic, M. M., Dotlic, J., Maricic, S., Mihailovic, T., & Tosic‐Race, B. (2009). Influence of red clover‐derived isoflavones on serum lipid profile in postmenopausal women. Journal of Obstetrics and Gynaecology Research, 35(6), 1091-1095.