Blood Selenium, Dietary Intake, and Their Discordance in Relation to Frailty and Mortality Among Middle-Aged and Older Adults: A NHANES Cohort Study

Objective To examine the associations of circulating and dietary selenium with frailty and mortality, with exploratory attention to the discordance between dietary intake and circulating levels in frailty.Methods This cohort study included 6,351 adults aged ≥40 years from NHANES 2011–2018 linked to NCHS mortality data. Frailty was defined by a 49-item Frailty Index. Survey-weighted regression and restricted cubic splines assessed blood selenium and dietary recall total selenium with frailty; Cox models assessed all-cause and heart disease mortality. A BSE–DRTSE residual index explored intake–status discordance.Results BSE exhibited a significant L-shaped association with frailty (P for non-linearity <0.001) in the fully adjusted non-linear model, plateauing at levels above approximately 180–190 μg/L. In linear models, BSE was inversely associated with frailty in the adjusted Model 3 (β per SD = −0.62; 95% CI: −1.01 to −0.24; p = 0.002), this association lost statistical significance in the expanded Model 4 after additional adjustment for nutritional and inflammatory markers (β per SD = −0.30; 95% CI: −0.68 to 0.08; p = 0.118). DRTSE showed no independent association with frailty. However, a higher BSE-DRTSE residual index correlated with lower frailty odds, particularly in frail individuals. During a median 4.0-year follow-up (755 deaths), higher BSE was robustly associated with lower all-cause mortality (fully adjusted HR per SD: 0.78; 95% CI: 0.67–0.92) and reduced heart disease mortality (Q3 vs. Q1 HR: 0.53; 95% CI: 0.29–0.97).Conclusions Blood selenium shows an L-shaped association with frailty and is inversely associated with mortality. Dietary intake lacks independent associations, though intake–blood discordance may reflect altered selenium kinetics in frailty. Given selenium’s narrow therapeutic window, these thresholds require prospective validation before clinical application.