Association of serum ferritin with total and regional fat measured by dual-energy X-ray absorptiometry in a nationally representative survey

Introduction: Fat distribution is a stronger predictor for cardiometabolic morbidity and mortality. We aimed to investigate the association of elevated iron stores, measured as serum ferritin levels, with total and regional body fat. Methods: Data from 2,646 adults from the National Health and Nutrition Examination Survey 2017–2018 was analyzed. Dual-energy X-ray absorptiometry was used to measure overall and regional body fat. The fat mass index (FMI) was calculated by dividing the fat mass (kg) by the square of body height (m²). The leg fat mass to trunk fat mass ratio (LTR) was used to assess the relative distribution of leg fat compared to trunk fat. Results: Medians (IQR) of serum ferritin levels were 0.168 μg/mL (0.104–0.269) for men and 0.053 μg/mL (0.026–0.102) for women. After adjusting for sociodemographic, lifestyle, and metabolic factors, serum ferritin showed a significant positive association with total FMI (β=2.662) and trunk FMI (β=0.983), and a negative association with leg FMI (β=-0.324) and LTR (β=-0.160) in men. In women, serum ferritin showed a significant positive association with total FMI (β=4.658), trunk FMI (β=2.085), and negative association with LTR (β=-0.312). Significant positive trends were observed for serum ferritin with total and trunk FMI in men and women, using the lowest serum ferritin quartile as the reference group. Additionally, significant negative trends were observed for serum ferritin with leg FMI and LTR in men. The mediation analysis revealed that C-reactive protein mediated 16.4% and 22.6% of the potential effects of serum ferritin on trunk FMI in men and women, respectively. Conclusion: Higher ferritin levels were associated with greater total and trunk fat but lower leg fat. Further prospective and mechanistic studies are warranted to confirm the study results.