Elevated urinary phytoestrogens are associated with delayed biological aging: a cross-sectional analysis of NHANES data.

Dietary phytoestrogens have been suggested to provide protection against numerous age-related diseases. However, their effects on biological aging remain unclear. In this study, we cross-sectionally investigated the relationship between urinary phytoestrogen levels and indicators of biological aging using data from 7,981 adults who participated in the National Health and Nutrition Examination Survey 1999-2010. Urinary concentrations of six phytoestrogens, including four isoflavones and two enterolignans, were measured using high-performance liquid chromatography (HPLC)-tandem mass spectrometry (MS) or HPLC-atmospheric pressure photoionization-tandem MS, and standardized using urinary creatinine. Three indicators of biological age (BA), namely the Klemera-Doubal method biological age (KDM-BA), phenotypic age (PA), and homeostatic dysregulation (HD), were derived from 12 clinical biomarkers, advanced-BAs were calculated to quantify the differences between individuals' BAs and chronological age, and individuals with all positive advanced-BAs were defined as accelerated-aging. Weighted linear regression analysis showed that after adjusting for demographic and lifestyle factors and history of chronic diseases, elevated urinary total phytoestrogen and enterolignans were significantly associated with less advanced-KDM, advanced-PA, and advanced-HD, whereas elevated urinary isoflavones was significantly associated with less advanced-KDM and advanced-PA but not with advanced-HD. Weighted logistic regression showed that higher urinary levels of total phytoestrogen (highest Q4 vs. lowest Q1: OR = 0.60, 95%CI: 0.44, 0.80; P-trend = 0.002) and enterolignans (Q4 vs. Q1: OR = 0.59, 95%CI: 0.45, 0.76; P-trend < 0.001) were significantly associated with lower odds of accelerated-aging, but this was not significant for isoflavones (Q4 vs. Q1: OR = 0.78, 95%CI: 0.60, 1.08; P-trend = 0.05). Subgroup analyses showed that negative associations were attenuated in non-overweight/obese participants and current cigarette smokers. In conclusion, higher levels of urinary phytoestrogens are related to markers of slower biological aging, suggesting an anti-aging effect of higher dietary phytoestrogen consumption, which warrants further investigations in longitudinal or interventional settings.