Red Clover

In Western herbal medicine, red clover is an alterative, a lymphatic and a mild expectorant.

It is used for eczema, psoriasis, acne and other chronic inflammatory skin conditions, for swollen lymph glands, and for coughs. Eclectic and folk herbalists gave it in long-term tonic formulas for the skin and for elimination.

The herb was also regarded as mildly nourishing and restorative during long illness.

In folk medicine, red clover was used for coughs, inflammatory conditions and skin eruptions, and as a cleansing tonic.

The flowers were drunk as a tea and taken as a spring tonic.

A 2020 systematic review and meta-analysis of ten randomised trials (twelve comparisons, 910 peri- and postmenopausal women) found that standardised red clover extract lowered total cholesterol by 0.29 mmol/L versus placebo. The changes in LDL cholesterol, HDL cholesterol and triglycerides were smaller and not statistically significant, and heterogeneity between trials was high ^{1Reference 1Kanadys et al. · 2020Meta-analysisEffects of red clover (Trifolium pratense) isoflavones on the lipid profile of perimenopausal and postmenopausal women — systematic review and meta-analysisView study →}.

Individual trials add detail. In a two-year double-blind trial, formononetin-enriched isoflavones (Rimostil, 50 mg/day) lowered LDL cholesterol by 12%, against 2% on placebo (p=0.005) ^{9Reference 9Clifton-Bligh et al. · 2015RCTRed clover isoflavones enriched with formononetin lower serum LDL cholesterol — a randomised, double-blind, placebo-controlled studyView study →}. An earlier Rimostil study in 46 women, at three doses over six months, raised HDL cholesterol by 15.7–28.6% and lowered apolipoprotein B by 11.5–17.0%, though it had no parallel control group ^{10Reference 10Clifton-Bligh et al. · 2001RCTThe effect of isoflavones extracted from red clover (Rimostil) on lipid and bone metabolism — randomised trialView study →}. A 2024 trial (40 mg twice daily for 6 months) improved total and LDL cholesterol alongside menopausal symptom scores in women with dyslipidaemia ^{8Reference 8Yigit E · 2024RCTIsoflavones obtained from red clover improve both dyslipidemia and menopausal symptoms in menopausal women: a prospective randomised placebo-controlled trialView study →}.

The effects are modest and, as with all the human work, tied to measured isoflavone extracts rather than tea or whole herb.

Gap: the fall in cholesterol is small, and no trial has tested whether it reduces heart attacks or strokes.

Hot flushes are the herb’s most-studied modern use. A 2026 GRADE-assessed meta-analysis of nine RCTs (isoflavone doses 37.1–160 mg/day, 12 weeks to 12 months) found a small-to-moderate reduction in hot-flush frequency favouring red clover (SMD −0.446; 95% CI −0.807 to −0.084; p=0.016) ^{2Reference 2Jiang et al. · 2026Meta-analysisThe effectiveness of red clover on hot-flash in menopausal women: a GRADE-assessed systematic review and meta-analysisView study →}.

A 2021 meta-analysis of eight trials also found a significant reduction (−1.73 flushes/day). The effect was clearest in women with five or more flushes a day, at 12 weeks, at 80 mg/day or more, and with biochanin-A-rich formulations ^{3Reference 3Kanadys et al. · 2021Meta-analysisEvaluation of clinical meaningfulness of red clover (Trifolium pratense L.) extract to relieve hot flushes and menopausal symptoms — systematic review and meta-analysis of randomised controlled trialsView study →}.

A meta-analysis of five trials of the standardised extract Promensil at 80 mg/day reported a reduction of 3.63 flushes a day, with a marked difference between crossover and parallel-group trials ^{6Reference 6Myers et al. · 2017Meta-analysisEffects of a standardised extract of Trifolium pratense (Promensil) at 80 mg in the treatment of menopausal hot flushes: a systematic review and meta-analysisView study →}.

Against this, an earlier meta-analysis reached only borderline significance (−1.5 flushes/day; p=0.05) ^{5Reference 5Coon et al. · 2007Meta-analysisTrifolium pratense isoflavones in the treatment of menopausal hot flushes: a systematic review and meta-analysisView study →}, a broader phytoestrogen meta-analysis found a modest effect ^{4Reference 4Chen et al. · 2015Meta-analysisEfficacy of phytoestrogens for menopausal symptoms: a meta-analysis and systematic reviewView study →}, and the 2013 Cochrane review of phytoestrogens found no significant difference between Promensil and placebo in its pooled trials. It noted a placebo response ranging from 1% to 59% across trials ^{7Reference 7Lethaby et al. · 2013Systematic reviewPhytoestrogens for menopausal vasomotor symptoms — Cochrane systematic reviewView study →}.

Individual RCTs are split: some are positive on symptom scores ^{8,27Reference 8Yigit E · 2024RCTIsoflavones obtained from red clover improve both dyslipidemia and menopausal symptoms in menopausal women: a prospective randomised placebo-controlled trialView study →Reference 27Shakeri et al. · 2015RCTEffectiveness of red clover in alleviating menopausal symptoms: a 12-week randomised controlled trialView study →}, and others found no difference from placebo ^{28,29Reference 28Del Giorno et al. · 2010RCTEffects of Trifolium pratense on the climacteric and sexual symptoms in postmenopause women — randomised controlled trialView study →Reference 29Geller et al. · 2009RCTSafety and efficacy of black cohosh and red clover for the management of vasomotor symptoms: a randomised controlled trialView study →}.

Gap: heterogeneity is high and the placebo effect is large. It is unclear which formulation or isoflavone profile works best.

The human data on bone are split. In a one-year double-blind RCT (n=205, 177 completing), a red-clover isoflavone supplement reduced loss of lumbar-spine bone mineral content and density versus placebo and raised bone-formation markers in postmenopausal women. It had no effect at the hip ^{12Reference 12Atkinson et al. · 2004RCTThe effects of phytoestrogen isoflavones on bone density in women: a double-blind, randomised, placebo-controlled trialView study →}.

In a 12-week trial (n=60, 37.1 mg isoflavones a day), lumbar-spine bone density fell only in the placebo group ^{13Reference 13Thorup et al. · 2015RCTIntake of novel red clover supplementation for 12 weeks improves bone status in healthy menopausal women — randomised controlled trialView study →}. A 12-month trial of an extract plus probiotics also slowed lumbar bone loss ^{14Reference 14Lambert et al. · 2017RCTCombined bioavailable isoflavones and probiotics improve bone status and estrogen metabolism in postmenopausal osteopenic women — randomised controlled trialView study →}.

A two-year RCT of Rimostil found no bone benefit at any site ^{9Reference 9Clifton-Bligh et al. · 2015RCTRed clover isoflavones enriched with formononetin lower serum LDL cholesterol — a randomised, double-blind, placebo-controlled studyView study →}. A crossover study in 11 women, using a sensitive ⁴¹Ca method, found that red clover isoflavones did not significantly reduce bone resorption, while soy isoflavones did ^{15Reference 15Weaver et al. · 2009RCTAntiresorptive effects of phytoestrogen supplements compared with estradiol or risedronate in postmenopausal women using ⁴¹Ca methodology — randomised crossover trialView study →}.

A 2016 systematic review of phytoestrogens and bone density reflected the same inconsistency ^{16Reference 16Abdi et al. · 2016Systematic reviewEffects of phytoestrogens on bone mineral density during the menopause transition: a systematic review of randomised controlled trialsView study →}.

Gap: any benefit appears confined to the lumbar spine and depends on the extract and dose, and the most sensitive resorption measurement was null for red clover.

Water and ethyl-acetate extracts of red clover leaves scavenged free radicals in DPPH, hydroxyl, superoxide and nitric-oxide assays and reduced lipid peroxidation in vitro. The extracts were also tested on liver and blood antioxidant enzymes in mice ^{18Reference 18Kaurinovic et al. · 2012In vitroAntioxidant profile of Trifolium pratense L. — in vitro and animal studyView study →}.

Phytochemical profiling of hydroalcoholic aerial-part extracts attributes the activity to their polyphenols and isoflavones ^{19Reference 19Akbaribazm et al. · 2020In vitroPhytochemicals and antioxidant activity of alcoholic/hydroalcoholic extract of Trifolium pratense — in vitroView study →}.

All of this is preclinical, and no human study has measured an antioxidant outcome.

A 40% prethanol leaf extract suppressed LPS-induced nitric oxide, PGE2, iNOS, COX-2, TNF-α, IL-1β and IL-6 in RAW264.7 macrophages by blocking NF-κB and MAPK signalling. Given by mouth to rats at 50–200 mg/kg, it reduced carrageenan-induced paw swelling in a dose-dependent way ^{20Reference 20Lee et al. · 2020In vitroAnti-inflammatory potential of Trifolium pratense L. leaf extract in LPS-stimulated RAW264.7 cells and a rat model of carrageenan-induced inflammation — in vitro and animal studyView study →}.

An anthocyanin fraction reproduced the cytokine and iNOS/COX-2 suppression and reduced reactive-oxygen production in the same macrophage model ^{21Reference 21Lee et al. · 2020In vitroAnti-inflammatory and antioxidant effects of anthocyanins of Trifolium pratense (red clover) in LPS-stimulated RAW-264.7 macrophages — in vitroView study →}. The leaf extract also limited IL-1β-driven cartilage breakdown in rat cartilage cells ^{22Reference 22Lee et al. · 2018In vitroThe effect of the prethanol extract of Trifolium pratense leaves on interleukin-1β-induced cartilage-matrix degradation in primary rat chondrocytes — in vitroView study →}.

This is all cell-line and rodent work, it used leaf rather than the flowering tops used medicinally, and no human inflammatory endpoint has been tested.

In a small trial of 17 menopausal women, a 5-week placebo period was followed by 5 weeks each of 40 mg and then 80 mg of red-clover isoflavones a day. Systemic arterial compliance, a measure of large-artery elasticity that falls with age and menopause, rose by 23% at 80 mg compared with the placebo period. Plasma lipids did not change ^{11Reference 11Nestel et al. · 1999RCTIsoflavones from red clover improve systemic arterial compliance but not plasma lipids in menopausal women — randomised clinical trialView study →}.

The result rests on one small trial of a surrogate measure, with no hard cardiovascular outcomes and no replication.

In a crossover RCT (n=109), postmenopausal women took 80 mg/day of red-clover isoflavones and placebo for 90 days each. Hospital Anxiety and Depression Scale scores fell by 76.9% after the isoflavones and by 21.7% after placebo, with similar falls on the Zung depression scale ^{17Reference 17Lipovac et al. · 2010RCTImprovement of postmenopausal depressive and anxiety symptoms after treatment with isoflavones derived from red clover extracts — randomised crossover trialView study →}.

It is a single, unreplicated trial, and the mood improvement may partly follow relief of hot flushes.

In rats with full-thickness skin wounds, ointments containing 1.5–6% of a hydroethanolic red clover extract increased collagen, epidermal thickness, fibroblast density and wound contraction, and shifted Bax/Bcl-2/p53 expression ^{23Reference 23Manzoureh et al. · 2021AnimalTopical administration of hydroethanolic extract of Trifolium pratense (red clover) accelerates wound healing — rat modelView study →}.

A 2026 comparison of fourteen cultivars found formononetin and biochanin A content varying several-fold between them. An extract of the richest cultivar showed antioxidant and anti-elastase activity and sped fibroblast migration in vitro ^{24Reference 24Gościniak A et al. · 2026In vitroRed clover isoflavones as effective longevity agents for anti-aging and regenerative skin applications — cultivar comparison, in vitroView study →}.

This is rodent-topical and in vitro work only, and red clover is normally taken by mouth.

Isoflavones isolated from red clover (genistein, formononetin and biochanin A) inhibited smooth-muscle contraction in the isolated rat prostate gland ^{25Reference 25Brandli et al. · 2010In vitroIsoflavones isolated from red clover (Trifolium pratense) inhibit smooth-muscle contraction of the isolated rat prostate gland — in vitroView study →}, and red-clover isoflavones slowed the growth of human BPH stromal cells in culture and promoted their death ^{26Reference 26Zhang et al. · 2010In vitroRed clover isoflavones inhibit the proliferation and promote the apoptosis of benign prostatic hyperplasia stromal cells — in vitroView study →}. This is isolated-tissue and cell-line data only, with no clinical trial in men with BPH.

Tolerability. Side-effect rates in trials are similar to placebo, even over several years. A three-year randomised trial of a 40 mg isoflavone supplement in 401 women with a family history of breast cancer found no differences from placebo in breast density, endometrial thickness, cholesterol, hormone levels or bone density ^{31Reference 31Powles et al. · 2008RCTRed clover isoflavones are safe and well tolerated in women with a family history of breast cancer — randomised, double-blind, placebo-controlled trialView study →}. A separate trial found no effect on mammographic breast density ^{32Reference 32Atkinson et al. · 2004RCTRed-clover-derived isoflavones and mammographic breast density: a double-blind, randomised, placebo-controlled trialView study →}.

Hormone-sensitive conditions. Because the isoflavones are weak oestrogens, care is conventional in breast, uterine and ovarian cancer and endometriosis. A systematic review found no evidence that red-clover isoflavones increase breast-cancer risk or recurrence ^{30Reference 30Fritz et al. · 2013Systematic reviewSoy, red clover, and isoflavones and breast cancer: a systematic reviewView study →}.

Drug interactions. In 15 women taking 120 mg of isoflavones a day for two weeks, red clover did not change the blood levels of probe drugs for CYP1A2, CYP2C9, CYP2D6 or CYP3A4/5 ^{33Reference 33Chen et al. · 2020No clinically relevant pharmacokinetic interactions of a red clover dietary supplement with cytochrome P450 enzymes in womenView study →}. The anticoagulant concern rests on coumarin content, not the isoflavones, and has not been shown in trials.

Allergy. Allergy is possible in people sensitive to legumes.