Effects of Iron, Copper, Zinc, and Magnesium on Chronic Widespread Pain: A Two-Sample Mendelian Randomization

Background: Chronic widespread pain (CWP) affects approximately 10% of the adult population globally, causing significant physical and psychological distress. Micronutrients, such as iron, copper, zinc, and magnesium, are essential in various physiological functions, and their imbalances may impact pain perception and chronic pain conditions. Methods: This study used Mendelian randomization (MR) to investigate the causal relationships between micronutrient levels and CWP. Data were obtained from genome-wide association studies (GWASs) for iron, copper, zinc, and magnesium, and CWP data were sourced from large-scale GWASs with 461,857 European participants. Genetic variants were used as instrumental variables to infer causal relationships, minimizing confounding factors. Results: MR analysis revealed a significant association between higher iron levels and an increased risk of CWP (IVW, OR 1.01, 95% CI: 1.00-1.01, p = 0.029). This finding was supported by the weighted median and MR-Egger methods. No significant associations were found for copper, zinc, and magnesium levels. Conclusions: These results suggest that iron levels may influence pain perception and chronic pain conditions. Balanced iron levels are crucial for managing chronic pain. Regular monitoring and personalized treatment plans could benefit individuals with CWP. Further research is needed to understand the mechanisms linking micronutrient levels to chronic pain and to develop targeted therapeutic interventions.