Dietary Antioxidants and Flavonoids Are Inversely Associated with Prostate Cancer Risk and Mortality: Evidence from NHANES and Machine Learning

Yanyang Jin¹Dongshan Lv¹Li-Po Zhou¹Li Xiao²Guang-Quan Tong¹Abdallah Karim³Shuai Xue¹Hongyang Tian¹Chen-cai wang¹Kun Feng¹Ding-ming Song^1*You-liang Guan^1*

• ¹First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China
• ²Department of Obstetrics and Gynecology, The First Affiliated Hospital of Yangtze University, Jingzhou, Hubei Province, China
• ³Guangzhou Medical University, Guangzhou, Guangdong Province, China

Background: Oxidative stress and dietary micronutrient imbalances have been implicated in prostate cancer (PCa) development and progression. Although flavonoids and antioxidants show promise in experimental models, evidence from population-based studies remains limited.Objectives:This research aimed to investigate the relationship between the consumption of antioxidants and flavonoids in the diet and the risk and survival of prostate cancer, as well as to assess the potential of machine learning models in identifying significant dietary factors.Methods: Data from 2,629 male participants aged ≥40 years from NHANES 2007-2010 were analyzed. Dietary intake was estimated using two 24-hour recalls linked to the USDA Flavonoid Database. PCa status was self-reported. Survey-weighted logistic regression and Cox models evaluated associations with PCa prevalence and all-cause mortality, adjusting for demographic, lifestyle, and clinical covariates. Nine supervised machine learning models, including random forest (RF), were developed and validated. SHAP values identified key predictors and visualized their effects.Results: Among 2,629 U.S. male participants from NHANES 2007-2010, 144 reported a history of prostate cancer. Compared with non-cancer individuals, cases had lower intake of selenium, magnesium, quercetin, kaempferol, epicatechin, epigallocatechin, total flavones, and total flavonoids (all P < 0.05). Higher intake of selenium, magnesium, catechin, and myricetin was associated with reduced prostate cancer risk in weighted regression models, with selenium remaining significant after multivariable adjustment (OR = 0.50, 95% CI: 0.33-0.76). Lower intake of selenium, magnesium, luteolin, quercetin, kaempferol, and total flavones was linked to increased mortality risk, and selenium independently predicted improved survival (HR = 0.69, 95% CI: 0.54-0.88). The random forest model showed superior predictive performance (AUC = 0.740), identifying selenium, luteolin, total flavones, myricetin, catechin, and magnesium as key features. SHAP analysis revealed Ushaped associations for selenium, catechin, and myricetin, and dose-dependent protective effects for luteolin and magnesium.Our results highlight selenium, magnesium, and select flavonoids as promising dietary factors in reducing prostate cancer risk and improving prognosis. These insights support the development of evidence-based, individualized nutritional strategies and call for further mechanistic and clinical investigations.