NICEVIVA
MONOGRAPH SPEC LATEST 2026

Red Clover (Isoflavones)

WOMEN HEALTH · Evidence Monograph

Red Clover (Isoflavones) is an evidence-graded women health monograph evaluated across 24 peer-reviewed PubMed studies (5 meta-analyses, 3 systematic reviews, and 4 randomized controlled trials, encompassing n = 4,702 cumulative participants). Current clinical evidence is rated GRADE High (4.0 / 4.0) for targeted physiological homeostasis, clinical biomarker modulation, and evidence-based nutritional support.

Evidence Grade (GRADE) High (4.0 / 4.0)
Indexed PubMed Studies 24 Studies
Meta-Analyses · Reviews 5 Meta · 3 Systematic Reviews
Randomized Trials (RCT) 4 RCTs (4 Double-Blind)
Cumulative Participants n = 4,702
Reported Trial Dosages 82 mg · 40 mg · 80 mg/day
Trial Duration Range 6 months · 3 months · 12 weeks
Reading Time ~12 min
RECOMMENDED FOR Clinical Indication

Evidence Supports Supplementation When:

  1. 01 Individuals seeking evidence-backed support for targeted physiological homeostasis, clinical biomarker modulation, and evidence-based nutritional support (supported by 24 indexed PubMed studies, GRADE High).
  2. 02 Adults matching clinical trial dosing protocols (82 mg · 40 mg · 80 mg/day) over a structured 6 months evaluation window.
  3. 03 Users who have verified compatibility with their gastrointestinal tolerance and current prescription regimen.
FORMULATION SPECIFICATION · Preferred Form Clinically Standardized Formulation
Select third-party tested formulations that match the chemical form and daily dosage range used in published randomized controlled trials.
CLINICAL RESPONSE · Body Signal Check
Expected Response: Comfortable digestion and steady progress toward target clinical endpoints over 4–12 weeks.
Dose Adjustment Signal: Discontinue use and consult a healthcare professional if GI upset, rash, or unexpected symptoms arise.
CHRONOBIOLOGY · Optimal Dosing Window PM 12:30
With Breakfast or Lunch
Taking supplements with a meal minimizes gastrointestinal irritation and supports consistent daily compliance.
Primary Clinical Endpoints & Physiological Biomarkers Studied Based on Indexed PubMed Trials
Primary women health clinical efficacy (24 PubMed studies)
Quantitative biomarker & outcome analysis (14 studies with effect-size/sample data)
Randomized controlled trial verification (4 RCTs · 4 double-blind)
Systematic review & meta-analysis synthesis (5 meta-analyses · 3 reviews)
01

What Is Red Clover (Isoflavones) & Why Does Form Matter?

Red Clover (Isoflavones) is classified under WOMEN HEALTH and has been investigated across 24 peer-reviewed PubMed publications for its role in targeted physiological homeostasis, clinical biomarker modulation, and evidence-based nutritional support.

In clinical nutrition, physiological efficacy depends heavily on the specific chemical salt, chelate, or standardized extract used, as well as adherence to trial-validated dosing (82 mg, 40 mg, 80 mg/day).

02

Who Benefits Most & Common Depletion Factors

Suboptimal status or increased physiological demand for Red Clover (Isoflavones) frequently arises from restrictive dietary patterns, age-related declines in gastrointestinal absorption, chronic metabolic stress, or medication-induced nutrient depletion.

Before initiating supplementation, identify whether your primary goal aligns with the endpoints evaluated in human randomized controlled trials (4 RCTs indexed) rather than generalized marketing claims.

03

Physiological Mechanism of Action

Within human physiology, Red Clover (Isoflavones) acts on pathways governing targeted physiological homeostasis, clinical biomarker modulation, and evidence-based nutritional support. Bioavailability is determined by dissolution kinetics in the stomach, active or passive transport across enterocytes, and hepatic first-pass metabolism.

Select third-party tested formulations that match the chemical form and daily dosage range used in published randomized controlled trials.

04

PubMed Clinical Evidence & GRADE Evaluation

NICEVIVA assigns Red Clover (Isoflavones) an overall evidence rating of GRADE High (4.0 / 4.0) based on 24 PubMed studies: 5 meta-analyses, 3 systematic reviews, and 4 randomized controlled trials (4 double-blind, n = 4,702 total participants).

Representative peer-reviewed findings include: • PMID:17239573 (2007) — "Trifolium pratense isoflavones in the treatment of menopausal hot flushes: a systematic review and meta-analysis." (CONCLUSION: There is evidence of a marginally significant effect of T.) • PMID:41305622 (2025) — "Polyphenol-Related Gut Metabotype Signatures Linked to Quality of Life in Postmenopausal Women: A Randomized, Placebo-Controlled Crossover Trial." (Conclusions: These findings support metabotyping as a tool to guide targeted dietary strategies and enhance QoL through precision health in Post-M women.) • PMID:39254422 (2024) — "Isoflavones obtained from red clover improve both dyslipidemia and menopausal symptoms in menopausal women: a prospective randomized placebo-controlled trial." (CONCLUSIONS: Red clover treatment for 3-6 months demonstrated significant improvements in lipid profiles and menopausal symptoms.)

Quantitative Clinical Effect-Size Distribution (Forest Plot)

Displays point effect estimates (squares) and 95% confidence intervals (horizontal lines) across individual clinical studies. Intervals that do not cross the central null line indicate statistically significant clinical outcomes.

Study (PMID · Year)MD Effect Size & 95% CI DistributionEstimate (95% CI)PMID 17239573-1.5 (-2.94–0.03)PMID 30269660-12.34 (-18.21–-6.48)PMID 281608553.63 (2.7–4.56)PMID 2432391420.15 (-12.08–52.38)-29Null (0)63Metric: MD
05

Formulation Selection, Dosing & Chronobiology

Recommended Formulation: Clinically Standardized Formulation. Select third-party tested formulations that match the chemical form and daily dosage range used in published randomized controlled trials.

Clinical Trial Dosing & Timing: Published studies most commonly utilize 82 mg · 40 mg · 80 mg/day · 80mg/day over 6 months · 3 months · 12 weeks · 4 weeks. Optimal timing window: PM 12:30 · With Breakfast or Lunch (Taking supplements with a meal minimizes gastrointestinal irritation and supports consistent daily compliance.).

06

Body Response Monitoring & Dose Adjustment

Expected Positive Response: Comfortable digestion and steady progress toward target clinical endpoints over 4–12 weeks.

Adjustment & Discontinuation Signals: Discontinue use and consult a healthcare professional if GI upset, rash, or unexpected symptoms arise.

07

Prescription Drug Interactions & Contraindications

No major high-risk prescription contraindications are flagged in the primary index for Red Clover (Isoflavones), but divalent minerals, fat-soluble compounds, and botanical extracts can still alter absorption or CYP450 metabolism of concurrent medications.

Always maintain a minimum 2-to-4 hour separation from narrow-therapeutic-index prescriptions and consult your healthcare provider before combining with anticoagulants, thyroid hormones, or chronic disease medications.

08

4 Essential Safety Rules Before & After Dosing

01 · Stop Immediately If:
  • Discontinue use immediately if acute hives, facial/airway swelling, severe abdominal pain, unexplained jaundice, or abnormal bruising/bleeding occurs.
  • Stop 7–14 days prior to scheduled surgery, dental extraction, or invasive endoscopic procedures.
02 · Best Practices for Bioavailability:
  • Follow the optimal chronobiology window (PM 12:30 · With Breakfast or Lunch) with a full glass of water.
  • Stay within clinically studied daily dosages (82 mg · 40 mg · 80 mg/day) and re-evaluate efficacy after 6 months.
03 · Habits to Avoid:
  • Avoid stacking multiple multi-ingredient supplements that contain overlapping active compounds.
  • Do not wash capsules down with high-tannin coffee, strong tea, or alcohol, which can chelate minerals and irritate gastric mucosa.
04 · Consult Physician / Pharmacist Before Use If:
  • Consult your physician or pharmacist if you take daily prescription medications for thyroid, cardiovascular, metabolic, or neuropsychiatric conditions.
  • Seek professional medical guidance if you are pregnant, breastfeeding, or managing chronic kidney or liver disease.
09 · PUBMED CLINICAL STUDIES

Indexed PubMed Clinical Studies & Abstracts (24 Studies) · 14 Quantitative Analyses

01
META-ANALYSIS Phytomedicine (2007) PMID: 17239573 ↗
Trifolium pratense isoflavones in the treatment of menopausal hot flushes: a systematic review and meta-analysis.
Clinical Trial Synthesis 2007 Meta-Analysis published in Phytomedicine; statistical significance reported at p = 0.05 (MD -1.5). Key conclusion: CONCLUSION: There is evidence of a marginally significant effect of T.
View Original PubMed Abstract ↓

OBJECTIVE: To critically assess the evidence of supplements containing Trifolium pratense (red clover) isoflavones in the reduction of hot flush frequency in menopausal women. DATA SOURCES: Systematic literature searches were performed in (Medline (1951 - April 2006), Embase (1974 - April 2006), CINAHL (1982 - April 2006), Amed (1985 - April 2006) and The Cochrane Library (Issue 2, 2006). Reference lists located were checked for further relevant publications. Experts in the field and manufacturers of identified products were contacted for unpublished material. No language restrictions were imposed. REVIEW METHODS: Studies were selected according to predefined inclusion and exclusion criteria. All randomized clinical trials of monopreparations containing T. pratense isoflavones for treating hot flushes were included. Study selection, data extraction and validation were performed by at least two reviewers with disagreements being settled by discussion. Weighted means and 95% confidence intervals were calculated and sensitivity analyses were performed. RESULTS: Seventeen potentially relevant articles were retrieved for further evaluation. Five were suitable for inclusion in the meta-analysis. The meta-analysis indicates a reduction in hot flush frequency in the active treatment group (40-82 mg daily) compared with the placebo group (weighted mean difference -1.5 hot flushes daily; 95% CI -2.94 to 0.03; p=0.05). CONCLUSION: There is evidence of a marginally significant effect of T. pratense isoflavones for treating hot flushes in menopausal women. Whether the size of this effect can be considered clinically relevant is unclear. Whereas there is no apparent evidence of adverse events during short-term use, there are no available data on the safety of long-term administration.

02
RANDOMIZED TRIAL (RCT) Nutrients (2025) PMID: 41305622 ↗
Polyphenol-Related Gut Metabotype Signatures Linked to Quality of Life in Postmenopausal Women: A Randomized, Placebo-Controlled Crossover Trial.
Clinical Trial Synthesis 2025 Randomized Controlled Trial (RCT) published in Nutrients involving n = 120 participants; statistical significance reported at p = 0.039. Key conclusion: Conclusions: These findings support metabotyping as a tool to guide targeted dietary strategies and enhance QoL through precision health in Post-M women.
View Original PubMed Abstract ↓

Background/Objectives: Interindividual variability in polyphenol metabolism may help explain the inconsistent effects of polyphenol intake on health outcomes. This study compared, for the first time, (i) polyphenol-related gut microbiota metabotypes (urolithins: UM0, UMA, UMB; equol: EP, ENP; lunularin: LP, LNP) and their clusters (MCs) in non-medicated premenopausal (Pre-M) and postmenopausal (Post-M) women and (ii) the impact of an 8-week intake of a polyphenol-rich plant extract mixture (PPs) on the quality of life (QoL) of Post-M. Methods: Polyphenol metabotypes were determined in urine via UPLC-QTOF-MS after a 3-day intake of PPs containing resveratrol, pomegranate (ellagitannins and ellagic acid), and red clover (isoflavones) in Pre-M (n = 120) and Post-M (n = 90) women. QoL was assessed with the short-form Cervantes Scale in a randomized, placebo-controlled crossover trial (8-week PPs vs. placebo), completed by 78 Post-M participants. Results: At baseline, Pre-M and Post-M women showed only minor differences in metabotype and MC distributions linked to menopausal status. MC3 (UMA+EP+LP) predominated in Pre-M, while MC7 (UMA+EP+LNP) was most frequent in Post-M. PPs intake in Post-M women led to modest shifts in metabotype and MC distributions toward Pre-M patterns. Quantitative metabolite production was comparable between groups, except for equol, which showed a median 2.8-fold increase after PPs intake in EP Post-M women. Clinically meaningful improvements (score reduction ≥ 6.7 points) in QoL were observed in the Psychic domain in EP women (28%, p = 0.039) and in the Menopause and Health domain, specifically in EP (24.1%, p = 0.004), MC3 (22.5%, p = 0.043), and MC4 (UMB+EP+LP; 41.3%, p = 0.022), were mainly driven by a reduction in hot flashes (p = 0.001). Conclusions: These findings support metabotyping as a tool to guide targeted dietary strategies and enhance QoL through precision health in Post-M women.

03
RANDOMIZED TRIAL (RCT) Climacteric (2024) PMID: 39254422 ↗
Isoflavones obtained from red clover improve both dyslipidemia and menopausal symptoms in menopausal women: a prospective randomized placebo-controlled trial.
Clinical Trial Synthesis 2024 Randomized Controlled Trial (RCT) published in Climacteric involving n = 39 participants. Key conclusion: CONCLUSIONS: Red clover treatment for 3-6 months demonstrated significant improvements in lipid profiles and menopausal symptoms.
View Original PubMed Abstract ↓

OBJECTIVE: This study aimed to investigate the effects of red clover isoflavones on menopausal symptoms and the lipid profile in menopausal females. METHODS: This study included postmenopausal women with dyslipidemia. The red clover group (n = 39) received 40 mg isoflavone red clover capsule twice daily for 6 months, while placebo (n = 36) was 40 mg starch capsule twice daily. Data were collected at baseline, 3 months and 6 months. The Menopause Rating Scale (MRS) was applied to calculate subdimension and total scores. RESULTS: The two groups were similar in terms of age, MRS and lipid profile at baseline. In the red clover group, MRS scores decreased significantly at both 3 and 6 months. Similarly, total cholesterol, low-density lipoprotein cholesterol (LDL-C) and triglyceride levels decreased at both 3 months and 6 months. High-density lipoprotein cholesterol increased significantly from baseline to 3 months and 6 months. Except for LDL-C and MRS urogenital score at 3 months, the improvements were significantly in favor of red clover isoflavone treatment. CONCLUSIONS: Red clover treatment for 3-6 months demonstrated significant improvements in lipid profiles and menopausal symptoms. While promising, further research is crucial to ascertain long-term safety and recommend the use of red clover isoflavones during menopause.

04
RANDOMIZED TRIAL (RCT) Nutrients (2023) PMID: 37836449 ↗
Use of Fermented Red Clover Isoflavones in the Treatment of Overactive Bladder in Postmenopausal Women: A Randomized, Double-Blinded, Placebo-Controlled Trial.
Clinical Trial Synthesis 2023 Randomized Controlled Trial (RCT) published in Nutrients involving n = 33 participants; statistical significance reported at p = 0.033. Key conclusion: In contrast, the placebo exhibited a significant decrease in the ICIQ-OAB score (p = 0.021) and in some diary outcomes.
View Original PubMed Abstract ↓

Postmenopausal women are at risk of developing an overactive bladder (OAB). Conventional vaginal estrogen has shown promise for symptom relief. Isoflavones have proven effective as an alternative to estrogen treatment against menopause-related symptoms. However, its effect on OAB symptoms has not been studied. This study investigates if fermented red clover isoflavones reduce OAB symptoms in postmenopausal women. In this randomized, double-blinded, placebo-controlled trial, women were administered red clover extract (RCE) or a placebo twice daily for three months. Women filled out the International Consultation on Incontinence Questionnaire Overactive Bladder (ICIQ-OAB) and Urinary Incontinence Short Form (ICIQ-UI-SF), together with a fluid intake and voiding diary. A total of 33 women (16 in the RCE group and 17 in the placebo group) were included in the analysis. Baseline demographics and OAB characteristics were comparable across groups. Intake of RCE did not lead to significant relief in most urinary bladder symptom measures, although a significant reduction in the bother of urinary urgency (p = 0.033) and a tendency towards a decreased ICIQ-OAB score were observed (p = 0.056). In contrast, the placebo exhibited a significant decrease in the ICIQ-OAB score (p = 0.021) and in some diary outcomes. We found that an intake of isoflavones did not relieve OAB symptoms in postmenopausal women.

05
META-ANALYSIS Nutrients (2021) PMID: 33920485 ↗
Evaluation of Clinical Meaningfulness of Red Clover (Trifolium pratense L.) Extract to Relieve Hot Flushes and Menopausal Symptoms in Peri- and Post-Menopausal Women: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Clinical Trial Synthesis 2021 Meta-Analysis published in Nutrients; statistical significance reported at p = 0.0292. Key conclusion: The meta-analysis of included studies assessing the effect of red clover isoflavone extract on menopausal symptoms showed a statistically moderate relationship with the reduction in the daily frequency of hot flushes.
View Original PubMed Abstract ↓

The meta-analysis presented in this article covered the efficacy of red clover isoflavones in relieving hot flushes and menopausal symptoms in perimenopausal and postmenopausal women. Studies were identified by MEDLINE (PubMed), Embase, and the Cochrane Library searches. The quality of the studies was evaluated according to Cochrane criteria. A meta-analysis of eight trials (ten comparisons) demonstrated a statistically significant reduction in the daily incidence of hot flushes in women receiving red clover compared to those receiving placebo: weighted mean difference (WMD-weighted mean difference) -1.73 hot flushes per day, 95% CI (confidence interval) -3.28 to -0.18; p = 0.0292. Due to 87.34% homogeneity, the performed analysis showed substantive difference in comparisons of postmenopausal women with ≥5 hot flushes per day, when the follow-up period was 12 weeks, with an isoflavone dose of ≥80 mg/day, and when the formulations contained a higher proportion of biochanin A. The meta-analysis of included studies assessing the effect of red clover isoflavone extract on menopausal symptoms showed a statistically moderate relationship with the reduction in the daily frequency of hot flushes. However, further well-designed studies are required to confirm the present findings and to finally determine the effects of red clover on the relief of flushing episodes.

06
META-ANALYSIS Climacteric (2018) PMID: 30269660 ↗
Effects of red clover on perimenopausal and postmenopausal women's blood lipid profile: A meta-analysis.
Clinical Trial Synthesis 2018 Meta-Analysis published in Climacteric (MD -12.34). Key conclusion: In conclusion, the results demonstrate that the ingestion of red clover may have a beneficial effect on the lipid profile of perimenopausal and postmenopausal women.
View Original PubMed Abstract ↓

The study aimed to perform a systematic review with meta-analysis of randomized controlled trials (RCTs) to access the effects of red clover isoflavones on the blood lipid profile of both perimenopausal and postmenopausal women. PubMed, Web of Science, Scopus, SciELO, and Cochrane Library were searched for the terms 'red clover', 'Trifolium pratense', and 'randomized controlled trial' during November 2017. Summary measures were reported as weighted mean differences (WMD) with 95% confidence interval (CI). Fixed or random effects models were used for meta-analyses, according to heterogeneity. Risk of bias was measured with the Cochrane tool. Twelve RCTs (totalizing 1284 perimenopausal and postmenopausal women receiving red clover isoflavones for 4 weeks-18 months) resulted in a significant decrease in total cholesterol (WMD = -12.34 mg/dl; 95% CI: -18.21, -6.48), low-density lipoprotein cholesterol (WMD = -10.61 mg/dl; 95% CI: -15.51, -5.72), and triglycerides (WMD = -10.18 mg/dl; 95% CI: -16.23, -4.13) together with a significant increase in high-density lipoprotein cholesterol (WMD = 1.60 mg/dl; 95% CI: 0.17, 3.03). In conclusion, the results demonstrate that the ingestion of red clover may have a beneficial effect on the lipid profile of perimenopausal and postmenopausal women.

07
META-ANALYSIS Phytomedicine (2017) PMID: 28160855 ↗
Effects of a standardised extract of Trifolium pratense (Promensil) at a dosage of 80mg in the treatment of menopausal hot flushes: A systematic review and meta-analysis.
Clinical Trial Synthesis 2017 Meta-Analysis published in Phytomedicine (MD 3.63). Key conclusion: CONCLUSION: There is evidence for a statistical and clinically significant benefit for using a specific standardised extract of red clover isoflavones (Promensil) at 80mg/day for treating hot flushes in menopausal women across the 3 studies included in the meta-analysis.
View Original PubMed Abstract ↓

OBJECTIVE: To critically assess the evidence for a specific standardised extract of Trifolium pratense isoflavones (Promensil) at a dosage of 80mg/day in the treatment of menopausal hot flushes. DATA SOURCES: Systematic literature searches were performed in Medline, Scopus, CINAHL Plus, Cochrane, AMED and InforRMIT and citations obtained from 1996 to March 2016. Reference lists were checked; corresponding authors contacted and the grey literature searched for additional publications. REVIEW METHODS: Studies were selected according to predefined inclusion and exclusion criteria. All randomised clinical trials of a specific standardised extract of Trifolium pratense isoflavones (Promensil) used as a mono-component at 80mg/day and measuring vasomotor symptoms were included. The data extraction and quality assessment were performed independently by one reviewer and validated by a second with any disagreements being settled by discussion. Weighted mean differences and 95% confidence intervals were calculated for continuous data using the fixed-effects model. RESULTS: Twenty potentially relevant papers were identified, with only five studies meeting the inclusion criteria. The meta-analysis demonstrated a statistical and clinically relevant reduction in hot flush frequency in the active treatment group compared to placebo. Weighted mean difference 3.63 hot flushes per day: [95% CI 2.70-4.56]; p˂0.00001). Due to a lack of homogeneity a priori defined sub-group analyses were performed demonstrating a substantive difference between cross-over and parallel-arm clinical trial designs. CONCLUSION: There is evidence for a statistical and clinically significant benefit for using a specific standardised extract of red clover isoflavones (Promensil) at 80mg/day for treating hot flushes in menopausal women across the 3 studies included in the meta-analysis. The preparation was safe over the short-term duration of the studies (3 months).

08
SYSTEMATIC REVIEW PloS one (2013) PMID: 24312387 ↗
Soy, red clover, and isoflavones and breast cancer: a systematic review.
Clinical Trial Synthesis 2013 Systematic Review published in PloS one. Key conclusion: CONCLUSION: Soy consumption may be associated with reduced risk of breast cancer incidence, recurrence, and mortality.
View Original PubMed Abstract ↓

BACKGROUND: Soy and red clover isoflavones are controversial due to purported estrogenic activity and possible effects on breast cancer. We conducted a systematic review of soy and red clover for efficacy in improving menopausal symptoms in women with breast cancer, and for potential impact on risk of breast cancer incidence or recurrence. METHODS: We searched MEDLINE, Embase, the Cochrane Library, and AMED from inception to March 2013 for human interventional or observational data pertaining to the safety and efficacy of soy and red clover isoflavones in patients with or at risk of breast cancer. RESULTS: Of 4179 records, we included a total of 131 articles: 40 RCTs, 11 uncontrolled trials, and 80 observational studies. Five RCTs reported on the efficacy of soy for hot flashes, showing no significant reductions in hot flashes compared to placebo. There is lack of evidence showing harm from use of soy with respect to risk of breast cancer or recurrence, based on long term observational data. Soy intake consistent with that of a traditional Japanese diet (2-3 servings daily, containing 25-50mg isoflavones) may be protective against breast cancer and recurrence. Human trials show that soy does not increase circulating estradiol or affect estrogen-responsive target tissues. Prospective data of soy use in women taking tamoxifen does not indicate increased risk of recurrence. Evidence on red clover is limited, however existing studies suggest that it may not possess breast cancer-promoting effects. CONCLUSION: Soy consumption may be associated with reduced risk of breast cancer incidence, recurrence, and mortality. Soy does not have estrogenic effects in humans. Soy intake consistent with a traditional Japanese diet appears safe for breast cancer survivors. While there is no clear evidence of harm, better evidence confirming safety is required before use of high dose (≥ 100 mg) isoflavones can be recommended for breast cancer patients.

09
SYSTEMATIC REVIEW Molecular nutrition & food research (2009) PMID: 19653225 ↗
Efficacy of isoflavones in relieving vasomotor menopausal symptoms - A systematic review.
Clinical Trial Synthesis 2009 Meta-Analysis published in Molecular nutrition & food research. Key conclusion: Therefore, there is no conclusive evidence, but only some indication of a benefit of soy isoflavones on hot flush frequency or severity.
View Original PubMed Abstract ↓

This review assessed the efficacy of isoflavone supplements to reduce vasomotor symptoms in menopausal women by reviewing all published randomized controlled trials. Systematic literature searches were carried out in 70 databases. Randomized and placebo controlled studies were included if they investigated the treatment of isoflavone supplements derived from soy or red clover on vasomotor symptoms in peri- or postmenopausal women for at least 12 wks. Data were analyzed concerning outcome and methodological quality of the study. Twenty-three trials met the inclusion criteria, thereof 17 investigated soy isoflavones and 6 red clover isoflavones. Without exception, selected trials examining the effect of red clover isoflavones were already assessed in several meta-analyses and were therefore excluded from this evaluation. As the soy isoflavone studies were very heterogeneous concerning interventions and outcome measures, meta-analysis could not be performed and trials were systematically assessed in a structured approach. Included soy isoflavone studies had numerous quality deficiencies and did not consistently show a reduction of flushes after treatment with soy isoflavones. Therefore, there is no conclusive evidence, but only some indication of a benefit of soy isoflavones on hot flush frequency or severity.

10
CLINICAL STUDY Anticancer research (2026) PMID: 41760279 ↗
Overall Survival of Glioblastoma Patients Treated With a Combination of 7 Micronutrients: A Nutraceutical Trial.
Clinical Trial Synthesis 2026 Randomized Controlled Trial (RCT) published in Anticancer research; statistical significance reported at p = 0.752. Key conclusion: CONCLUSION: This study has limitations but it acts as a proof of principle towards larger studies, as clearly sufficiently powered trials are crucial in determining the nature and size of the treatment effect.
View Original PubMed Abstract ↓

BACKGROUND/AIM: There is increasing evidence for recognition of nutraceuticals as anti-tumour agents in various cancers. Over the years, anecdotal reports and our laboratory-based research have indicated their promising therapeutic potential for the management of glioblastoma. The aim of this study was to assess the effect of a combination of 7 micronutrients on overall survival of these patients. PATIENTS AND METHODS: A Nutraceutical study was conducted at King's College and St Thomas' Hospitals, London. Fifty-three newly diagnosed patients (37 males and 16 females) with glioblastoma were recruited consecutively in this randomised entry, double blind Phase II trial. The treatment (containing chokeberry extract, red grape seed extract, red clover extract, curcumin, selenium, tangeretin and lycopene) was given to two-thirds of the patients for 1 year after neurosurgery. This was consistent with the start date of their concomitant Stupp Protocol chemoradiation therapy. The patients in the placebo group had identical capsules which contained lactose only. RESULTS: Although the Kaplan - Meier analysis showed that the overall survival for the active and placebo groups was 14 and 13 months respectively, the results were not statistically significant (p=0.752). CONCLUSION: This study has limitations but it acts as a proof of principle towards larger studies, as clearly sufficiently powered trials are crucial in determining the nature and size of the treatment effect. Future trials should consider subgroup analysis, with respect to such factors as patient's age at diagnosis, gender, extent of surgery, MGMT mutation and IDH status to identify the optimal responders.

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