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. 2024 Oct 3;13(19):5908.
doi: 10.3390/jcm13195908.

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

Hyunjik Kim  1 , Dai Sik Ko  2
Affiliations

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

Hyunjik Kim et al. J Clin Med. .

Abstract

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.

Keywords: causality; mendelian randomization analysis; micronutrients; pain.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Schematic diagram of the two sample Mendelian randomizations.
Figure 2
Figure 2
Forest plot for the MR analysis (inverse-variance-weighted) of the causal effect of micronutrients (iron, copper, zinc, and magnesium) on chronic widespread pain. OR, odds ratio; SNP, single-nucleotide polymorphism.
Figure 3
Figure 3
Scatter plot. (A) Iron and chronic widespread pain; (B) copper and chronic widespread pain; (C) zinc and chronic widespread pain; (D) magnesium and chronic widespread pain.
Figure 4
Figure 4
“Leave-one-out” analysis. (A) Iron and chronic widespread pain; (B) copper and chronic widespread pain; (C) zinc and chronic widespread pain; (D) magnesium and chronic widespread pain.
See this image and copyright information in PMC

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References

    1. Mills S.E.E., Nicolson K.P., Smith B.H. Chronic pain: A review of its epidemiology and associated factors in population-based studies. Br. J. Anaesth. 2019;123:e273–e283. doi: 10.1016/j.bja.2019.03.023. - DOI - PMC - PubMed
    1. Sarzi-Puttini P., Giorgi V., Marotto D., Atzeni F. Fibromyalgia: An update on clinical characteristics, aetiopathogenesis and treatment. Nat. Rev. Rheumatol. 2020;16:645–660. doi: 10.1038/s41584-020-00506-w. - DOI - PubMed
    1. Siracusa R., Paola R.D., Cuzzocrea S., Impellizzeri D. Fibromyalgia: Pathogenesis, Mechanisms, Diagnosis and Treatment Options Update. Int. J. Mol. Sci. 2021;22:3891. doi: 10.3390/ijms22083891. - DOI - PMC - PubMed
    1. Collins J.F. Copper nutrition and biochemistry and human (patho)physiology. Adv. Food Nutr. Res. 2021;96:311–364. - PubMed
    1. Aliev G., Li Y., Chubarev V.N., Lebedeva S.A., Parshina L.N., Trofimov B.A., Sologova S.S., Makhmutova A., Avila-Rodriguez M.F., Klochkov S.G., et al. Application of Acyzol in the Context of Zinc Deficiency and Perspectives. Int. J. Mol. Sci. 2019;20:2104. doi: 10.3390/ijms20092104. - DOI - PMC - PubMed

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