Syakib Bakri, Agussalim Bukhari, Haerani Rasyid, Abdul Azis, Andi Asadul Islam, Lukman Hakim, Andi Alfian Zainuddin
Journal: Archivio italiano di urologia, andrologia : organo ufficiale [di] Societa italiana di ecografia urologica e nefrologica 2025;97(2):13645
PMID: 40247729
Flavonoids are natural compounds found in many fruits and vegetables including subclasses such as isoflavones, known for their potential health benefits, including anti-cancer properties. However, conflicting evidence exists on their efficacy. This systematic review and meta-analysis examined the effects of flavonoid supplementation on prostate cancer (PCa) risk and related factors, such as prostate-specific antigen (PSA) levels and hormonal parameters. The participants were men who either had a biopsy-confirmed diagnosis of PCa or were clinically determined to be at high risk of developing PCa.
The results showed that flavonoid supplementation produced a statistically significant reduction in total PSA levels. A subgroup analysis found that supplementation lasting 12 weeks or longer reduced PSA significantly more than shorter durations. In four studies involving men at high risk of PCa, flavonoid supplementation was associated with a significantly lower likelihood of developing prostate cancer at the end of the study period. However, flavonoid supplementation showed no favourable effect on hormonal parameters, including testosterone and other sex hormones. Importantly, flavonoid supplementation was found to be safe across all included studies.
In conclusion, flavonoid supplementation may reduce PSA levels and lower the risk of developing PCa in high-risk men, particularly when taken for 12 weeks or longer. Flavonoids were shown to be safe across all included studies. However, no beneficial effects on hormonal parameters were found. Healthcare professionals may find these results useful when discussing dietary and supplement strategies with men at high risk of PCa or those with diagnosed PCa, while acknowledging that the evidence base remains limited.
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• Supplementation with flavonoids, particularly when consumed for more than 3 months, has been reported to reduce total prostate specific antigen (PSA) compared to control.
•Flavonoid supplementation was associated with a reduced risk of prostate cancer in men who were clinically identified as being at high risk of developing the disease .
Introduction:
A systematic review and meta-analysis were conducted to assess the effect of flavonoids and various subclasses on prostate cancer risk parameters in male individuals at risk of developing prostate cancer and/or diagnosed with prostate cancer.
Method:
Following PRISMA guidelines, nine randomised controlled trials (RCTs), involving 420 male participants, sourced from PubMed, Science Direct, Scopus and the Cochrane library were included.
The primary outcomes assessed total and free prostate specific antigen (PSA), hormonal parameters (testosterone, estradiol, sex hormone binding globulin [SHBG]) and biopsy-detected prostate cancer risk.
Results:
PSA parameters
• A significant reduction of total PSA was revealed in the flavonoid supplementation group versus the control group (mean difference = 0.64; CI: -1.14 to -0.13; p=0.01)
• Subgroup analysis highlighted that this effect was more prevalent when flavonoid supplementation occurred for more than12 weeks (p = 0.04). However, flavonoid supplement did not appear to impact free PSA (p = 0.99).
Hormonal parameters
• Total testosterone increased in the flavonoid supplementation group compared to the control group (MD: 1.49, CI: 0.45 to 2.54; p=0.005).
• However, free testosterone decreased in the flavonoid supplementation group compared to the control group (MD: -0..47, CI: -0.96 to 0.13 p=0.03).
• Flavonoid supplementation did not significantly impact total estradiol (MD: 0.61, p = 0.38) or SHBG (MD: -0.02, p= 0.99).
Prostate cancer risk
• Patients who received generally longer term flavonoid supplementation were associated with a reduced risk of developing prostate cancer (OR 0.41, CI: 0.21 to 0.80; p=0.009).
Conclusion:
The findings of this review suggest that flavonoid supplementation for more than 12 weeks may lower total PSA levels and help reduce the risk of prostate cancer despite a limited number of studies.
• This review reports that flavonoid supplementation for more than 12 weeks lowers PSA. Clinicians may therefore consider recommending flavonoid supplementation and a diet high in flavonoid-rich foods to patients with high PSA serum levels. However, supplementation should not replace PSA monitoring.
• Clinicians may also consider flavonoid supplementation for patients who have been identified as high-risk for prostate cancer. However, these results should be interpreted with caution as only nine RCT were included in this review, and the interventions and treatment durations differed.
• Only the subclass isoflavones and flav-3-ols were available from the included studies, therefore further studies are needed to evaluate additional flavones, flavanols and anthocyanidins.
• The studies included in this review comprised small sample sizes. Future studies need to incorporate larger overall sample sizes to strengthen the evidence.
• Additional investigations are warranted to determine the exact optimal dosage and duration of flavonoid supplementation for lowering PSA and reducing the risk of prostate cancer.
• Further research is needed to gain a clearer understanding of how flavonoids impact PSA parameters mechanistically as current data from these small studies remain unclear.
INTRODUCTION AND OBJECTIVES
Prostate cancer (PCa) is a significant concern and burden worldwide. Several studies suggest that flavonoids have a significant potential as an anti-cancer agent, but the evidence remains controversial. This study aims to assess the effect of flavonoids and its subclasses supplementation on PCa risk parameters in men with biopsy-proven diagnosis of PCa or clinically determined to have a high risk of PCa.
MATERIALS AND METHODS
This systematic review and meta-analysis adhered to PRISMA guideline. A literature search was conducted across PubMed, ScienceDirect, Scopus and Cochrane utilizing PICO framework. Revised Cochrane's risk of bias tools (RoB2) was used for quality analysis. Review manager 5.4 was used for statistical analysis.
RESULTS
Out of 1.117 articles, nine final studies (involving 420 patients) were included. Regarding total PSA, flavonoid provided a reduction of total PSA (MD: -0.64, p<0.05), and sub-group analysis based on the supplementation duration showed flavonoid administration with a duration of ≥12 weeks significantly reduced total PSA compared to administration of <12 weeks (p<0.05). Meta-analyses of four studies, including men clinically at risk of PCa, revealed that flavonoid supplementation was associated with a significantly lower risk of developing PCa at endpoint (OR 0.41, p<0.05). However, our results indicated no favorable effect on hormonal parameters.
CONCLUSIONS
The results of this meta-analysis suggest there may be a potential role for flavonoid in PCa risk reduction. Flavonoids supplementation also have been proven to be safe. However, further investigation is necessary to gain a clear understanding of the flavonoid impact on PSA and sex hormone parameters.
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