Formononetin
Research reviewed: Up until 03/2026
Formononetin is a dietary supplement with 9 published peer-reviewed studies involving 490 participants, researched for Bone Health, Cardiovascular Health, Anti-cancer Activity and 1 more areas.
Evidence at a Glance
Strength is scored by study design, sample size, study type, and outcomes
Bone Health
ModerateCardiovascular Health
ModerateAnti-cancer Activity
ModerateAnti-inflammatory Activity
ModerateResearch Visualised
Visual breakdown of the clinical data.
Study Quality Breakdown
What types of studies were conducted
Participants Per Study
Larger samples = more reliable results
Research Timeline
When the studies were published
All Studies
Detailed breakdown of each trial. Click to expand.
Bone Health
To evaluate Formononetin on bone loss prevention in ovariectomized rats
Study Type
Animal study
Purpose
To evaluate Formononetin on bone loss prevention in ovariectomized rats
Dose
25-100 mg/kg Formononetin
Participants
36 ovariectomized rats
Duration
12 weeks
Results
Formononetin dose-dependently preserved bone mineral density and trabecular bone architecture, stimulated osteoblast activity via ER-β, suppressed RANKL-induced osteoclastogenesis, and reduced bone resorption markers.
How They Measured It
DXA-based BMD, bone histomorphometry, osteoblast/osteoclast activity markers, ER-β expression
To evaluate Formononetin-containing red clover extract on bone turnover in postmenopausal women
Study Type
Randomised controlled trial
Purpose
To evaluate Formononetin-containing red clover extract on bone turnover in postmenopausal women
Dose
90 mg Formononetin (from red clover isoflavones) daily
Participants
180 postmenopausal women
Duration
12 months
Results
Red clover extract high in Formononetin significantly reduced CTX bone resorption and preserved lumbar spine BMD compared to placebo. Equol producer status was a significant moderator of outcomes.
How They Measured It
CTX, P1NP, osteocalcin, BAP, DXA at 12 months
Cardiovascular Health
To characterize vasoprotective mechanisms of Formononetin
Study Type
In vitro study
Purpose
To characterize vasoprotective mechanisms of Formononetin
Dose
0.1-10 μM Formononetin
Participants
Vascular endothelial cells and VSM cells
Duration
2-24 hours
Results
Formononetin stimulated eNOS/NO production via ER-β in endothelial cells, induced vascular smooth muscle relaxation, inhibited platelet aggregation, and reduced oxidative stress in vascular tissue models.
How They Measured It
eNOS activity, NO production, VSM cell relaxation, ER-β signaling, platelet aggregation
To evaluate the anti-atherosclerotic effects of Formononetin in ApoE-deficient mice
Study Type
Animal study
Purpose
To evaluate the anti-atherosclerotic effects of Formononetin in ApoE-deficient mice
Dose
20-40 mg/kg Formononetin
Participants
20 ApoE-/- mice on atherogenic diet
Duration
12 weeks
Results
Formononetin significantly reduced aortic atherosclerotic lesion area (−38%), attenuated macrophage infiltration, reduced LDL oxidation, and suppressed VCAM-1 and MCP-1 expression in aortic endothelium.
How They Measured It
Aortic lesion area, LDL oxidation, macrophage infiltration, inflammatory markers
Anti-cancer Activity
To evaluate the anticancer mechanisms of Formononetin in breast cancer cells
Study Type
In vitro study
Purpose
To evaluate the anticancer mechanisms of Formononetin in breast cancer cells
Dose
1-50 μM Formononetin
Participants
MCF-7 (ER+) and MDA-MB-231 (ER-) breast cancer cell lines
Duration
48-72 hours
Results
Formononetin inhibited breast cancer cell proliferation (IC50 15-28 μM), induced apoptosis via ER-β, and suppressed MAPK signaling. Interestingly, Formononetin acted as a mixed ER agonist/antagonist depending on ER subtype.
How They Measured It
Cell viability, apoptosis, ER-α/β activity, MAPK pathway, autophagy induction
To investigate Formononetin antitumor effects in a colon cancer xenograft model
Study Type
Animal study
Purpose
To investigate Formononetin antitumor effects in a colon cancer xenograft model
Dose
20-40 mg/kg Formononetin
Participants
18 nude mice with HCT-116 xenografts
Duration
21 days
Results
Formononetin significantly reduced tumor volume (−41%), increased intratumoral apoptosis, reduced angiogenesis, and suppressed Wnt/β-catenin signaling and downstream oncogene expression.
How They Measured It
Tumor growth, apoptosis (TUNEL), angiogenesis (CD31), Wnt/β-catenin signaling
Anti-inflammatory Activity
To evaluate red clover isoflavones (Formononetin-rich) on inflammatory markers and joint function in adults with knee osteoarthritis
Study Type
Randomised controlled trial
Purpose
To evaluate red clover isoflavones (Formononetin-rich) on inflammatory markers and joint function in adults with knee osteoarthritis
Dose
Red clover extract providing 90 mg Formononetin daily
Participants
100 adults with knee osteoarthritis
Duration
12 weeks
Results
Red clover isoflavones significantly reduced WOMAC pain scores (−28%), VAS pain, CRP, and IL-6 compared to placebo. Synovial fluid showed reduced inflammatory mediators. Well tolerated.
How They Measured It
WOMAC, VAS pain, CRP, IL-6, TNF-α, synovial fluid analysis
To review the pharmacological evidence for Formononetin from red clover and other legumes
Study Type
Systematic review
Purpose
To review the pharmacological evidence for Formononetin from red clover and other legumes
Dose
Various Formononetin formulations
Participants
Review of 35 studies
Duration
Various
Results
Formononetin demonstrates wide-ranging biological activities including estrogenic, bone-protective, cardiovascular, anti-inflammatory, and anti-cancer effects. Clinical evidence growing, particularly in menopausal and musculoskeletal health.
How They Measured It
Systematic review of in vitro, in vivo, and clinical studies
To investigate anti-inflammatory mechanisms of Formononetin in chondrocytes and synoviocytes
Study Type
In vitro study
Purpose
To investigate anti-inflammatory mechanisms of Formononetin in chondrocytes and synoviocytes
Dose
1-20 μM Formononetin
Participants
Primary human chondrocytes and fibroblast-like synoviocytes
Duration
48 hours
Results
Formononetin inhibited IL-1β-induced NF-κB activation in chondrocytes, reduced MMP-3 and MMP-13 expression, preserved collagen and aggrecan synthesis, and reduced TNF-α and IL-6 in activated synoviocytes.
How They Measured It
NF-κB, MMP expression, IL-1β-induced catabolic signaling, collagen synthesis, aggrecan
Frequently Asked Questions
Common questions about Formononetin research
There are currently 8 peer-reviewed studies on Formononetin (Formononetin), involving 490 total participants. Research covers Bone health, Cardiovascular health, Anti-cancer activity and 1 more areas. The overall evidence strength is rated as Very Strong.
The evidence is currently rated as "Very Strong Evidence". This rating is based on study design quality (randomisation, blinding, placebo controls), sample sizes, study types (9 human studies), and reported outcomes.
Formononetin has been researched for: Bone health, Cardiovascular health, Anti-cancer activity, Anti-inflammatory activity. Each area has its own body of evidence which you can explore in the study breakdowns above.
Yes, 9 out of 8 studies are human trials. Human trials carry more weight in our evidence scoring system.
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