Reviews - Oncology

The effect of flavonoid and subclasses supplementation on prostate specific antigen, hormonal parameters and prostate cancer risk: a systematic review and meta-analysis of randomized controlled trials

Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Received: 18 January 2025
Published: 17 April 2025
1209
Views
882
Downloads

Authors

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.

Downloads

Download data is not yet available.

Tzelepi V. Prostate cancer: pathophysiology, pathology and therapy. Cancers. 2022; 15:281. DOI: https://doi.org/10.3390/cancers15010281

Rawla P. Epidemiology of prostate cancer. World J Oncol. 2019;10:63-89. DOI: https://doi.org/10.14740/wjon1191

Sekhoacha M, Riet K, Motloung P, et al. Prostate cancer review: genetics, diagnosis, treatment options, and alternative approaches. Molecules. 2022; 27:5730. DOI: https://doi.org/10.3390/molecules27175730

Giona S. The epidemiology of prostate cancer. In: Bott SR, Ng KL (eds) Prostate cancer. Brisbane: Exon Publications.,

Matsushita M, Fujita K, Nonomura N. Influence of diet and nutrition on prostate cancer. Int J Mol Sci. 2020; 21:1447. DOI: https://doi.org/10.3390/ijms21041447

Mirza MB, Elkady AI, Al-Attar AM, et al. Induction of apoptosis and cell cycle arrest by ethyl acetate fraction of Phoenix dactylifera L. (Ajwa dates) in prostate cancer cells. J Ethnopharmacol. 2018;218:35-44. DOI: https://doi.org/10.1016/j.jep.2018.02.030

Dueregger A, Heidegger I, Ofer P, et al. The use of dietary supplements to alleviate androgen deprivation therapy side effects during prostate cancer treatment. Nutrients. 2014; 6:4491-4519. DOI: https://doi.org/10.3390/nu6104491

Jeong SH, Kim HH, Park MY, et al. Flavones: the apoptosis in prostate cancer of three flavones selected as therapeutic candidate models. Int J Mol Sci. 2023; 24:9240. DOI: https://doi.org/10.3390/ijms24119240

Liskova A, Samec M, Koklesova L, et al. Flavonoids as an effective sensitizer for anti-cancer therapy: insights into multi-faceted mechanisms and applicability towards individualized patient profiles. EPMA J. 2021; 12:155-176. DOI: https://doi.org/10.1007/s13167-021-00242-5

Galván-Portillo M, Vázquez-Salas RA, Hernández-Pérez JG, et al. Dietary flavonoid patterns and prostate cancer: evidence from a Mexican population-based case-control study. Br J Nutr. 2021;1-9. DOI: https://doi.org/10.1017/S0007114521002646

Page MJ, Moher D, Bossuyt PM, et al. PRISMA 2020 explanation and elaboration: updated guidance and exemplars for reporting systematic reviews. BMJ. 2021; 372: n160. DOI: https://doi.org/10.1136/bmj.n160

Higgins JPT, Thompson SG. Quantifying heterogeneity in a metaanalysis. Stat Med. 2002;21:1539-1558. DOI: https://doi.org/10.1002/sim.1186

Kumar NB, Pow-Sang J, Spiess P, et al. A phase II randomized clinical trial using aglycone isoflavones to treat patients with localized prostate cancer in the pre-surgical period prior to radical prostatectomy. Oncotarget. 2020; 11:1218-1234. DOI: https://doi.org/10.18632/oncotarget.27529

Kumar NB, Krischer JP, Allen K, et al. A Phase II randomized, placebo-controlled clinical trial of purified isoflavones in modulating steroid hormones in men diagnosed with localized prostate cancer. Nutr Cancer. 2007; 59:163-168. DOI: https://doi.org/10.1080/01635580701432678

Kumar NB, Cantor A, Allen K, et al. The specific role of isoflavones in reducing prostate cancer risk. The Prostate. 2004; 59:141-147. DOI: https://doi.org/10.1002/pros.10362

Dalais FS, Meliala A, Wattanapenpaiboon N, et al. Effects of a diet rich in phytoestrogens on prostate-specific antigen and sex hormones in men diagnosed with prostate cancer. Urology. 2004;64:510-515. DOI: https://doi.org/10.1016/j.urology.2004.04.009

Kumar NB, Pow-Sang J, Egan KM, et al. Randomized, placebo-controlled trial of green tea catechins for prostate cancer prevention. Cancer Prev Res Phila Pa. 2015; 8:879-887. DOI: https://doi.org/10.1158/1940-6207.CAPR-14-0324

Miyanaga N, Akaza H, Hinotsu S, et al. Prostate cancer chemo- prevention study: an investigative randomized control study using purified isoflavones in men with rising prostate-specific antigen. Cancer Sci. 2012; 103:125-130. DOI: https://doi.org/10.1111/j.1349-7006.2011.02120.x

Hamilton-Reeves JM, Rebello SA, Thomas W, et al. Effects of soy protein isolate consumption on prostate cancer biomarkers in men with HGPIN, ASAP, and low-grade prostate cancer. Nutr Cancer. 2007; 60:7-13. DOI: https://doi.org/10.1080/01635580701586770

Hamilton-Reeves JM, Rebello SA, Thomas W, et al. Isoflavone-rich soy protein isolate suppresses androgen receptor expression without altering estrogen receptor-beta expression or serum hormonal profiles in men at high risk of prostate cancer. J Nutr. 2007; 137:1769-1775. DOI: https://doi.org/10.1093/jn/137.7.1769

Bosland MC, Schmoll J, Watanabe H, et al. Randomized, placebo-controlled six-month intervention study of soy protein isolate in men with biochemical recurrence after radical prostatectomy: a pilot study. Nutr Cancer. 2022; 74:555-564. DOI: https://doi.org/10.1080/01635581.2021.1903949

Guo K, Liang Z, Liu L, et al. Flavonoids intake and risk of prostate cancer: a meta-analysis of observational studies. Andrologia. 2016; 48:1175-1182. DOI: https://doi.org/10.1111/and.12556

Chang H, Lei L, Zhou Y, et al. Dietary flavonoids and the risk of colorectal cancer: an updated meta-analysis of epidemiological studies. nutrients. 2018; 10:950. DOI: https://doi.org/10.3390/nu10070950

Farha MW, Salami SS. biomarkers for prostate cancer detection and risk stratification. Ther Adv Urol 2022; 14:17562872221103988. DOI: https://doi.org/10.1177/17562872221103988

Ganry O. Phytoestrogens and prostate cancer risk. Prev Med. 2005;41:1-6. DOI: https://doi.org/10.1016/j.ypmed.2004.10.022

van Die MD, Bone KM, Williams SG, et al. Soy and soy isoflavones in prostate cancer: a systematic review and meta-analysis of randomized controlled trials. BJU Int. 2014;113:E119-130. DOI: https://doi.org/10.1111/bju.12435

Tanaka M, Fujimoto K, Chihara Y, et al. Isoflavone supplements stimulated the production of serum equol and decreased the serum dihydrotestosterone levels in healthy male volunteers. Prostate Cancer Prostatic Dis. 2009;12:247-252. DOI: https://doi.org/10.1038/pcan.2009.10

How to Cite



The effect of flavonoid and subclasses supplementation on prostate specific antigen, hormonal parameters and prostate cancer risk: a systematic review and meta-analysis of randomized controlled trials. (2025). Archivio Italiano Di Urologia E Andrologia, 97(2). https://doi.org/10.4081/aiua.2025.13645