Sex- and Age-Specific Inverted U-Shaped Links between Dietary Iron Intake and Serum α‑Klotho in Chinese Adults.

Abstract

Micronutrient intake can modulate aging biology. α‑Klotho, a circulating anti-aging protein, exerts protective effects against age-related decline and disease. However, links between specific micronutrients and serum α‑Klotho remain poorly explored. In this cross-sectional study, we analyzed 898 participants aged 18-84 years from rural communities in Changping, Beijing, China, to assess associations between energy-adjusted micronutrient intakes (per 100 kcal) and serum α-Klotho (modeled as log-transformed). Using a single 24-hour recall, intakes of 15 micronutrients were quantified, including total vitamin A, thiamine, riboflavin, vitamin C, vitamin E, phosphorus, potassium, calcium, magnesium, zinc, sodium, iron, selenium, copper, and manganese. Multivariable linear regression showed no significant associations between any micronutrients and serum α-Klotho in the overall population (all P > 0.05). In contrast, restrictive cubic spline analysis identified an inverted U-shaped association between iron intake and serum α-Klotho (P for nonlinear = 0.002), with a turning point at 1.863 mg/100 kcal. Below this threshold, iron intake was positively associated with α-Klotho (β: 0.045; P = 0.011), whereas above it the association was negative (β: -0.018; P = 0.035). The nonlinear pattern was evident in women and in participants aged < 60 years (P for nonlinear = 0.024 and 0.007, respectively), with similar turning points (1.908 and 1.906 mg/100 kcal, respectively). Inadequate iron intake was more prevalent in these subgroups than overall (60.8% and 62% vs. 50.8%). Dietary iron intake exhibits a sex- and age-specific inverted U-shaped relationship with serum α‑Klotho in Chinese adults. Maintaining moderate iron intake may be associated with higher α‑Klotho concentrations, particularly in women and in younger individuals aged < 60 years. Prospective and intervention studies are warranted to confirm these findings.