Associations of serum iron and its status change with mortality risk: prospective findings from the MJ cohort

Previous studies on serum iron levels and mortality risk have yielded inconsistent findings based on single-point measurements. How serum iron levels and their longitudinal changes influence all-cause and cause-specific mortality remains unknown. This study investigated associations between baseline serum iron levels, their longitudinal changes, and all-cause and cause-specific mortality in a prospective cohort. Participants were recruited from the Taiwan MJ cohort (1997-2007) and followed until December 31, 2022. Baseline serum iron was categorized as low, normal, or high. Based on changes at a second visit, participants were further classified as persistent normal, progression to abnormal, reversion to normal, or persistent abnormal. Cox proportional hazard models were used for analysis. Over a median follow-up of 19.0 years, 33,005 deaths occurred. Fully adjusted models demonstrated J-shaped associations between serum iron and all-cause and cause-specific mortality (all P < 0.001), with higher all-cause mortality risks in low (HR 1.27, 95% CI [1.23, 1.31]) and high iron groups (HR 1.37, 95% CI [1.30, 1.44]). Compared to persistent normal levels, those with progression to abnormal, reversion to normal, or persistent abnormal serum iron exhibited elevated mortality risks (HRs: 1.22 [1.15, 1.30], 1.16 [1.09, 1.24], 1.49 [1.36, 1.63], respectively). Moreover, maintaining normal serum iron status alongside a healthy lifestyle exhibited the lowest mortality risks. Long term abnormal serum iron status was linked to increased mortality, which could be mitigated through lifestyle modifications, suggesting significance of serum iron monitoring and potential intervention.