Nonlinear association between serum selenium and all-cause mortality in U.S. adults with NAFLD: a cohort study

Selenium, an essential trace element, modulates oxidative stress and inflammation-key factors in non-alcoholic fatty liver disease (NAFLD) progression. This study explores the relationship between serum selenium and all-cause mortality in NAFLD patients, a group vulnerable to oxidative damage.

We analyzed data from 9,254 NHANES 2017-2018 participants. After excluding those without NAFLD (n = 7,136) and missing selenium/mortality data (n = 331), 1,787 NAFLD patients were included. Serum selenium was categorized into quartiles (Q1-Q4: 104.73-376.80 μg/L). Cox proportional hazards models estimated hazard ratios (HRs) with adjustments for demographics, lifestyle, comorbidities and biomarkers. Restricted cubic spline (RCS) and Kaplan-Meier analyses assessed dose-response relationships and survival differences. Subgroup analyses examined effects by age, sex and comorbidities.

Among 1,787 NAFLD adults, multivariable analysis showed a significant inverse association between serum selenium and all-cause mortality. Participants in the highest selenium quartile (Q4: 204.39-376.80 μg/L) had a 64% lower mortality risk compared to the lowest quartile (Q1) after full adjustment (HR = 0.36, 95% CI: 0.13-0.99, p < 0.05). RCS analysis confirmed a nonlinear dose-response, with mortality risk plateauing at selenium levels >200 μg/L. Subgroup analyses suggested greater protection in older adults (≥60) and hypertensive individuals (p < 0.05), though formal interaction tests were nonsignificant (p > 0.05).

Moderate selenium levels are associated with reduced all-cause mortality in NAFLD, particularly in older adults. These findings highlight selenium's potential in lowering mortality risk in metabolic disease populations, though further research is needed to clarify its role in NAFLD progression.