Serum Vitamin D Levels and Risk of Iron Deficiency Anemia in Adults: A Cross-Sectional Study and Mendelian Randomization Analysis

Abstract

This study focuses on the potential role of vitamin D in the diagnosis and treatment of iron deficiency anemia (IDA), and evaluates causation using Mendelian randomization (MR). This cross-sectional study collected clinical information from 3728 respondents in the National Health and Nutrition Examination Survey (NHANES) cycles of 2005–2010 and 2015–2018. To determine the link between serum vitamin D levels and the risk of IDA, we established a robust nomogram. Calibration and net clinical benefits were examined through calibration curves and decision curve analysis (DCA). Restricted cubic spline (RCS) models were utilized to explore the relationship between the two. In addition, the data of single nucleotide polymorphism (SNP) related to vitamin D and IDA were obtained from open biological databases. The main analytical method for the MR analysis was the inverse variance weighted (IVW) method. A series of sensitivity analyses were conducted to evaluate pleiotropy. Our cross-sectional study showed that, after extensive adjustments, serum vitamin D levels remained an independent risk factor for predicting the development of IDA. The risk of developing IDA was significantly lower for participants in the highest quartile subgroup with vitamin D levels ≥ 78.1 nmol/L compared to those in the lowest quartile with vitamin D levels ≤ 42.8 nmol/L (p < 0.001). In terms of gender, serum vitamin D primarily exhibited a protective effect against IDA in females (OR:0.98, 95% CI: 0.98–0.99, p < 0.001). A non-linear relationship between the two was found (p < 0.001 for non-linear relationship). Meanwhile, using the IVW method in MR analysis, we identified a bidirectional causal relationship. The results of our cross-sectional analysis demonstrated a negative correlation between serum vitamin D levels and IDA. Additionally, genetic evidence from the MR analysis supported an association between serum vitamin D levels and IDA.