{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T10:22:12Z","timestamp":1789122132489,"version":"build-2803163510"},"reference-count":27,"publisher":"PAGEPress Publications","license":[{"start":{"date-parts":[[2025,4,17]],"date-time":"2025-04-17T00:00:00Z","timestamp":1744848000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arch Ital Urol Androl"],"abstract":"<jats:p>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\u2019s 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&lt;0.05), and sub-group analysis based on the supplementation duration showed flavonoid administration with a duration of \u226512 weeks significantly reduced total PSA compared to administration of &lt;12 weeks (p&lt;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&lt;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.<\/jats:p>","DOI":"10.4081\/aiua.2025.13645","type":"journal-article","created":{"date-parts":[[2025,4,17]],"date-time":"2025-04-17T11:58:38Z","timestamp":1744891118000},"source":"Crossref","is-referenced-by-count":2,"title":["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"],"prefix":"10.4081","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1348-9883","authenticated-orcid":false,"given":"Abdul","family":"Azis","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andi Asadul","family":"Islam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haerani","family":"Rasyid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1518-8010","authenticated-orcid":false,"given":"Lukman","family":"Hakim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Syakib","family":"Bakri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agussalim","family":"Bukhari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andi Alfian","family":"Zainuddin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2549","published-online":{"date-parts":[[2025,4,17]]},"reference":[{"key":"174798","doi-asserted-by":"crossref","unstructured":"Tzelepi V. Prostate cancer: pathophysiology, pathology and therapy. Cancers. 2022; 15:281.","DOI":"10.3390\/cancers15010281"},{"key":"174799","doi-asserted-by":"crossref","unstructured":"Rawla P. Epidemiology of prostate cancer. World J Oncol. 2019;10:63-89.","DOI":"10.14740\/wjon1191"},{"key":"174800","doi-asserted-by":"crossref","unstructured":"Sekhoacha M, Riet K, Motloung P, et al. Prostate cancer review: genetics, diagnosis, treatment options, and alternative approaches. Molecules. 2022; 27:5730.","DOI":"10.3390\/molecules27175730"},{"key":"174801","unstructured":"Giona S. The epidemiology of prostate cancer. In: Bott SR, Ng KL (eds) Prostate cancer. Brisbane: Exon Publications.,"},{"key":"174802","doi-asserted-by":"crossref","unstructured":"Matsushita M, Fujita K, Nonomura N. Influence of diet and nutrition on prostate cancer. Int J Mol Sci. 2020; 21:1447.","DOI":"10.3390\/ijms21041447"},{"key":"174803","doi-asserted-by":"crossref","unstructured":"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":"10.1016\/j.jep.2018.02.030"},{"key":"174804","doi-asserted-by":"crossref","unstructured":"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":"10.3390\/nu6104491"},{"key":"174805","doi-asserted-by":"crossref","unstructured":"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":"10.3390\/ijms24119240"},{"key":"174806","doi-asserted-by":"crossref","unstructured":"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":"10.1007\/s13167-021-00242-5"},{"key":"174807","doi-asserted-by":"crossref","unstructured":"Galv\u00e1n-Portillo M, V\u00e1zquez-Salas RA, Hern\u00e1ndez-P\u00e9rez 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":"10.1017\/S0007114521002646"},{"key":"174808","doi-asserted-by":"crossref","unstructured":"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":"10.1136\/bmj.n160"},{"key":"174809","doi-asserted-by":"crossref","unstructured":"Higgins JPT, Thompson SG. Quantifying heterogeneity in a metaanalysis. Stat Med. 2002;21:1539-1558.","DOI":"10.1002\/sim.1186"},{"key":"174810","doi-asserted-by":"crossref","unstructured":"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":"10.18632\/oncotarget.27529"},{"key":"174811","doi-asserted-by":"crossref","unstructured":"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":"10.1080\/01635580701432678"},{"key":"174812","doi-asserted-by":"crossref","unstructured":"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":"10.1002\/pros.10362"},{"key":"174813","doi-asserted-by":"crossref","unstructured":"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":"10.1016\/j.urology.2004.04.009"},{"key":"174814","doi-asserted-by":"crossref","unstructured":"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":"10.1158\/1940-6207.CAPR-14-0324"},{"key":"174815","doi-asserted-by":"crossref","unstructured":"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. 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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":"10.1080\/01635581.2021.1903949"},{"key":"174819","doi-asserted-by":"crossref","unstructured":"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":"10.1111\/and.12556"},{"key":"174820","doi-asserted-by":"crossref","unstructured":"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":"10.3390\/nu10070950"},{"key":"174821","doi-asserted-by":"crossref","unstructured":"Farha MW, Salami SS. biomarkers for prostate cancer detection and risk stratification. Ther Adv Urol 2022; 14:17562872221103988.","DOI":"10.1177\/17562872221103988"},{"key":"174822","doi-asserted-by":"crossref","unstructured":"Ganry O. Phytoestrogens and prostate cancer risk. Prev Med. 2005;41:1-6.","DOI":"10.1016\/j.ypmed.2004.10.022"},{"key":"174823","doi-asserted-by":"crossref","unstructured":"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":"10.1111\/bju.12435"},{"key":"174824","doi-asserted-by":"crossref","unstructured":"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":"10.1038\/pcan.2009.10"}],"container-title":["Archivio Italiano di Urologia e Andrologia"],"original-title":[],"link":[{"URL":"https:\/\/www.pagepressjournals.org\/aiua\/article\/download\/13645\/13025","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.pagepressjournals.org\/aiua\/article\/download\/13645\/13026","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.pagepressjournals.org\/aiua\/article\/download\/13645\/13025","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,17]],"date-time":"2025-04-17T11:58:50Z","timestamp":1744891130000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.pagepressjournals.org\/aiua\/article\/view\/13645"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,17]]},"references-count":27,"URL":"https:\/\/doi.org\/10.4081\/aiua.2025.13645","relation":{},"ISSN":["2282-4197","1124-3562"],"issn-type":[{"value":"2282-4197","type":"electronic"},{"value":"1124-3562","type":"print"}],"subject":[],"published":{"date-parts":[[2025,4,17]]}}}