Black Cohosh
| Evidence Level: L3 | Predicted Indications: 10 |
Table of Contents
Black Cohosh: From Menopausal Symptom Relief to Heart Disease
One-Sentence Summary
Black cohosh (Cimicifuga racemosa) is a herbal product on the US market, and the literature describes it mainly as a remedy for menopausal symptoms. The TxGNN model predicts it may be effective for heart disease, but this is a very broad label. Of 3 registered trials and 10 publications retrieved, only one Phase 3 trial (terminated early, surrogate endpoints only) and a few small menopausal-cohort studies bear on the question. There is also a bradycardia safety signal.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not specified in the US regulatory data (literature describes use for menopausal symptoms) |
| Predicted New Indication | Heart disease |
| TxGNN Prediction Score | 99.19% |
| Evidence Level | L3 |
| US Market Status | ✓ Marketed |
| Number of NDAs | 20 (as recorded; license numbers not provided) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available. Black cohosh is a botanical product, widely used for menopausal symptoms, and its efficacy in heart disease has not been established. A mechanistic link is plausible but unproven.
Preclinical work suggests that cimicifugamide, a constituent of Cimicifuga rhizomes, acts as a non-selective beta-adrenergic agonist (PMID 28347916). Small studies in menopausal women report effects on hemodynamic parameters, quality of life, and markers such as asymmetric dimethylarginine (ADMA) (PMIDs 30176632, 17430734). Menopause is also linked to higher cardiovascular risk, which gives the prediction some biological context.
Two caveats limit this reasoning. “Heart disease” is a very broad label, and the TxGNN score alone does not identify a specific cardiac indication. The other nine top predictions (Laubry-Pezzi syndrome, Pierre Robin syndromes, chromosome 7q deletion, Jeune syndrome, orofacial clefting, pulmonary valve disease, and others) are prediction-only (L5). They are mostly congenital or structural conditions with no plausible mechanism, and likely reflect knowledge-graph connectivity rather than biology.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00663104 | Phase 3 | Terminated | 126 | Exercise with or without Cimicifuga racemosa in early postmenopausal women. Endpoints were bone, metabolic syndrome criteria and menopausal complaints. Only trial with a plausible cardiometabolic link, but the endpoints are surrogates and the design confounds the black cohosh effect. |
| NCT05304416 | N/A | Active, not recruiting | 347 | Dysphagia after cardiac surgery. Does not involve black cohosh (keyword match only). Not relevant. |
| NCT04496986 | N/A | Withdrawn | 0 | Dysphagia after cardiovascular surgery. Does not involve black cohosh. Not relevant. |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 20220537 | 2010 | RCT | Menopause | TRACE study: exercise with or without Cimicifuga racemosa (CR BNO 1055) on bone mineral density and 10-year coronary heart disease risk in early postmenopausal women. |
| 30176632 | 2018 | Clinical study (design unconfirmed) | Wiad Lek | Effects of Cimicifuga racemosa on hemodynamic parameters and quality of life in perimenopausal women with hypertension. |
| 17430734 | 2007 | Clinical study (design unconfirmed) | Fertil Steril | Soy isoflavone and Actaea racemosa supplement on ADMA, lipids and C-reactive protein (CHD risk markers) in menopausal women. |
| 28347916 | 2017 | Preclinical | Biomed Pharmacother | Cimicifugamide acts as a non-selective β-adrenergic agonist, with cardiac and sudorific effects in models. |
| 20955128 | 2010 | Case report | Med J Aust | Reversible complete heart block and bradycardia in a woman taking a black cohosh supplement (safety signal). |
| 15813159 | 2005 | Review | South Med J | Integrative therapies for menopause. |
| 16181020 | 2005 | Review | J Womens Health | Botanical and dietary supplements for menopausal symptoms: what works, what does not. |
| 16007232 | 2005 | Review | Cardiovasc Drug Rev | Cardiovascular pharmacology of sodium ferulate, a constituent of several plants including Cimicifuga heracleifolia (not black cohosh itself). |
| 39829189 | 2024 | Systematic review/meta-analysis | J Menopausal Med | Evening primrose oil for hot flashes (not black cohosh). Indirect relevance only. |
| 16115005 | 2005 | Observational/survey | J Womens Health | Menopausal symptom management after the Women’s Health Initiative. Indirect relevance only. |
US Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| Not provided | Cimicifuga Racemosa (Hahnemann Laboratories) | Pellet | Not specified |
| Not provided | Cimicifuga Racemosa (OHM Pharma) | Pellet | Not specified |
| Not provided | Bestmade Natural Products Cimicifuga Racemosa | Tablet, soluble (oral) | Not specified |
| Not provided | Cimifuga racemosa (Boiron) | Pellet | Not specified |
| Not provided | Cimifuga racemosa (Boiron) | Pellet | Not specified |
Dosage forms across all 20 records: pellet, soluble tablet (oral), globule and liquid.
Safety Considerations
- Drug Interactions: No DrugBank interaction records were found.
- Cardiac signal: A case report describes reversible complete heart block and bradycardia after starting a black cohosh supplement (PMID 20955128). This needs assessment before any cardiac use.
- Liver: Case series and biopsy studies link black cohosh to rare idiosyncratic hepatotoxicity (PMIDs 19339903, 24657312).
- Animal toxicology: A National Toxicology Program mouse study reported hematologic alterations with black cohosh extract (PMID 36373576).
Please refer to the package insert for warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The TxGNN score is high (99.19%), but direct evidence is thin. The only Phase 3 trial was terminated and used surrogate endpoints, and supporting studies are small or preclinical. A cardiac safety signal (bradycardia and heart block) is unresolved, and “heart disease” is too broad to define a testable indication.
To proceed, the following is needed:
- Mechanism of action data (e.g., from DrugBank) to test the beta-adrenergic hypothesis
- Package insert warnings and contraindications, which block the safety screening step
- A specific cardiac indication (e.g., menopause-associated hypertension) to replace the broad “heart disease” label
- Controlled trials with clinical cardiac endpoints in a defined population
- A cardiac safety assessment covering bradycardia and conduction effects, plus a liver safety review
This report is for research reference only and does not constitute medical advice. Repurposing candidates require clinical validation before any application.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.