Red clover isoflavones are safe and well tolerated in women with a family history of breast cancer
Open accessAbstract
Objective: To assess the safety and tolerability of a standardized 40 mg red clover isoflavone dietary supplement (Promensil®, Novogen) in women with a family history of breast cancer to evaluate the feasibility of using the supplement for prevention of breast cancer in healthy women. Study design: Healthy women aged 35–70 years (n = 401) with at least one first-degree relative with breast cancer received red clover isoflavones or placebo for three years in a randomized, double-blind, placebo-controlled pilot trial. Participants were assessed clinically and blood samples taken for biochemical analysis every six months. In addition, study participants underwent mammography, bone density and transvaginal ultrasound (postmenopausal women only) once per year. Results: No significant differences in breast density, endometrial thickness, serum cholesterol, follicle stimulating hormone levels and bone mineral density were detected between those taking red clover isoflavones and placebo. In postmenopausal women, some significant differences in bone marker levels were seen between active and placebo groups, at six months and at 12 months. The adverse event profile was similar across all red clover isoflavone and placebo groups. Conclusion: This three-year study supports the growing body of evidence that treatment with red clover isoflavones is safe and well tolerated in healthy women. Supplements containing red clover isoflavones did not adversely affect breast density, skeletal strength or cardiovascular status. In postmenopausal women, endometrial status was not adversely affected. The adverse event profile was similar between red clover isoflavones, and placebo and endocrine status did not differ.
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Neither of the two red clover RCTs reported any significant changes in mammographic density among pre- and post-menopausal women.
“Neither of the two RCTs reported any significant changes in mammographic density among both pre- and post-menopausal women [165,166]”
From Soy, Red Clover, and Isoflavones and Breast Cancer: A Systematic Review (2013) · cites this paper as [166]
According to the Cochrane risk of bias tool, the Powles trial was assessed as having low risk of bias in all categories except one for which information about detection bias was not provided.
“According to the Cochrane risk of bias tool, the trial reported by Powles was assessed as having low risk of bias in all of the categories, except one for which information about detection bias was not provided [166].”
From Soy, Red Clover, and Isoflavones and Breast Cancer: A Systematic Review (2013) · cites this paper as [166]
The available indexed passages identify Powles et al. (2008) but do not report a Cochrane risk-of-bias assessment. Searches for detection bias, low risk of bias, and blinding found no passage supporting the claimed ratings. (LLM, conf=0.72)
Experimental — accuracy not yet measuredPowles reported adverse effects, most commonly breast abnormality, skin-related symptoms, and other minor adverse events, which were equally distributed between red clover and placebo groups.
“Powles reported adverse effects, which most commonly included breast abnormality, “skin related symptoms” (not described), and other minor adverse events, however these were equally distributed between red clover and placebo groups [166].”
From Soy, Red Clover, and Isoflavones and Breast Cancer: A Systematic Review (2013) · cites this paper as [166]
The retrieved passages contain bibliographic information but no results passage describing adverse effects. Searches for breast abnormalities, skin symptoms, adverse effects, and their distribution between the red-clover and placebo groups found no passage that addresses the claim. (LLM, conf=0.69)
Experimental — accuracy not yet measuredPowles found no significant changes in endometrial thickness between groups.
“and Powles found no significant changes in endometrial thickness between groups [166]”
From Soy, Red Clover, and Isoflavones and Breast Cancer: A Systematic Review (2013) · cites this paper as [166]
The supplied passage contains bibliographic metadata, not findings from the paper’s body. Searches for endometrial thickness and ultrasound found no body-text passage addressing the between-group comparison; the matching text is abstract material, which is not admissible evidence under the stated rubric. (LLM, conf=0.72)
Experimental — accuracy not yet measuredOverall, the red clover RCTs were assessed as having low to moderate risk of bias.
“Overall, the RCTs were assessed as having low to moderate risk of bias.”
From Soy, Red Clover, and Isoflavones and Breast Cancer: A Systematic Review (2013) · cites this paper as [166]
The available indexed passages provide bibliographic details for Powles et al. (2008), but no assessment of risk of bias across red clover RCTs. Searches for “risk of bias” and for randomized trials found no passage addressing the claimed low-to-moderate rating. (LLM, conf=0.74)
Experimental — accuracy not yet measured
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Soy, Red Clover, and Isoflavones and Breast Cancer: A Systematic Review
Fritz, H., Seely, D., Flower, G., Skidmore, B., Fernandes, R., Vadeboncoeur, S., Kennedy, D., Cooley, K., Wong, R., Sagar, S., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0081968 · Cited by 188 · see citing works
- Authors
- Powles, T. J., Howell, A., Evans, D. G., Mccloskey, E. V., Ashley, S., Greenhalgh, R., Affen, J., Flook, L. A., & Tidy, A.
- Affiliations
- Parkside Hospital (GB)
- Wythenshawe Hospital (GB)
- St Mary's Hospital (GB)
- University of Sheffield (GB)
- Royal Marsden Hospital (GB)
- Royal Marsden NHS Foundation Trust (GB)
- Corresponding author
- Powles, Trevor J
- Venue
- Menopause International
- Publisher
- Informa UK Limited
- Published
- 2008-03
- Volume
- 14
- Issue
- 1
- Pages
- 6-12
- ISSN
- 1754-0453 (ISSN-L)
- OpenAlex
- W1997838536
- Cited by
- 75
- References
- 0
- Citations by year
- 2026: 3 · 2025: 4 · 2023: 2 · 2022: 3 · 2021: 7 · 2020: 4 · 2019: 2 · 2018: 2 · 2017: 2 · 2016: 2 · 2015: 6 · 2014: 2 · 2013: 5 · 2012: 7
- FWCI
- 5.43
- Type
- journal article
- Language
- en
- Open access
- Locations
- Menopause international (publishedVersion)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion, other-oa)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Phytoestrogen effects and research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Menopause: Health Impacts and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Keywords
- supplement safety, tolerability, breast cancer prevention, family history of breast cancer, breast density, bone mineral density, endometrial thickness, postmenopausal women, adverse events, hormonal status, serum cholesterol, follicle-stimulating hormone
- MeSH terms
- Aged, Breast Neoplasms, Double-Blind Method, Female, Humans, Isoflavones, Phytotherapy, Middle Aged, Premenopause, Postmenopause, Dietary Supplements, Trifolium, Phytoestrogens
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