Vitamin A, Vitamin D, Iron, and Zinc in Relation to Anemia Risk: Observational Evidence and Mendelian Randomization

Background: Anemia remains an important public health problem worldwide. Investigating the potential influencing factors of anemia can provide a reference for improving anemia status. This study aimed to identify factors influencing anemia in school-age children and assess associations/causal relationships between micronutrients (vitamin A, vitamin D, iron, and zinc) and anemia risk. Methods: This study included 1725 school-age children. Factors associated with anemia were identified using multivariable-adjusted logistic regression. Associations of serum micronutrients with anemia were analyzed, and non-linear relationships were examined. Causality was assessed using two-sample Mendelian randomization (MR) analysis. Results: Daytime outdoor activity, milk consumption, school location, picky eating, and serum ferritin deficiency were associated with anemia (p < 0.05). Higher serum vitamin A (Q4 vs. Q1: OR = 0.548; P_trend = 0.027) and higher serum ferritin (Q4 vs. Q1: OR = 0.470; Q3 vs. Q1: OR = 0.609; P_trend = 0.011) were inversely associated with anemia. RCS indicated a J-shaped non-linear relationship between serum ferritin and anemia risk. MR analysis showed that serum 25-hydroxyvitamin D (OR = 0.864, 95%CI: 0.757-0.986, p = 0.030), serum ferritin (OR = 0.656, 95%CI: 0.588-0.731, p < 0.001), and serum iron (OR = 0.793, 95%CI: 0.681-0.925, p = 0.003) significantly reduced anemia risk with the IVW method. Sensitivity analyses showed no heterogeneity, pleiotropy, or reverse causality. Conclusions: This study found that daytime outdoor activity time, weekly milk consumption frequency, school location, picky eating, and serum ferritin deficiency are closely associated with anemia in school-aged children. Additionally, serum vitamin A, vitamin D, serum iron, and serum ferritin levels are also linked to anemia. These findings collectively highlight the importance of lifestyle factors and specific micronutrients in influencing anemia among school-aged children, providing valuable insights for targeted prevention and intervention strategies. Future intervention trials focusing on these key factors could further validate their practical application value.