Multiple sclerosis (MS), myasthenia gravis (MG), and Guillain-Barré syndrome (GBS) are debilitating autoimmune neurological disorders that significantly impact patients' health and quality of life. These diseases not only impose a substantial burden on patients but also on healthcare systems due to their chronic nature and the need for long-term management. Understanding the etiological factors contributing to these diseases is crucial for developing effective prevention and treatment strategies.
To our knowledge, this study represents the first utilization of published GWAS meta-analysis data for conducting two-sample Mendelian randomization analysis, aiming to explore the causal relationship between micronutrients and autoimmune neurological disorders. By focusing on the phenotypic manifestations of MS, MG, and GBS, this research aims to uncover potential nutritional interventions that could mitigate disease risk or progression. The use of MR analysis, which employs genetic variants as instrumental variables, helps to address confounding factors and reverse causation, providing more robust evidence for causal inference[16]. This approach holds significant promise for identifying modifiable risk factors and informing clinical guidelines, ultimately improving disease management and patient outcomes.
Magnesium and Multiple Sclerosis
Magnesium plays a crucial role in numerous biological processes, including DNA synthesis, energy production, and regulation of muscle and nerve function. Our Mendelian Randomization (MR) analysis revealed a significant inverse association between blood magnesium levels and the risk of multiple sclerosis (MS) (OR = 0.47, 95%CI: 0.27–0.81, P = 0.007). This finding is consistent with previous studies suggesting that magnesium deficiency may exacerbate inflammatory responses and oxidative stress, both of which are implicated in the pathogenesis of MS[25]. Furthermore, magnesium has been shown to modulate immune function by influencing the activity of T cells and cytokine production, which are critical in the autoimmune response observed in MS[26]. These results underscore the potential therapeutic value of magnesium supplementation in MS management and warrant further investigation into the underlying mechanisms through which magnesium exerts its protective effects against MS.
Iron and Myasthenia Gravis
Iron is an essential micronutrient involved in oxygen transport, DNA synthesis, and electron transport in mitochondria. Our MR analysis identified a significant inverse association between blood iron levels and the risk of myasthenia gravis (MG) (OR = 0.19, 95%CI: 0.04–0.87, P = 0.032). This finding aligns with existing literature that suggests iron deficiency can impair immune function and increase susceptibility to infections, which may trigger or exacerbate autoimmune conditions like MG[27]. Iron is also critical for the proper functioning of acetylcholine receptors, which are targeted by autoantibodies in MG[28]. The observed association highlights the importance of maintaining adequate iron levels for immune homeostasis and neuromuscular function. Further research is needed to elucidate the precise mechanisms by which iron influences the pathophysiology of MG and to explore the potential benefits of iron supplementation in patients with MG.
Micronutrients and Guillain-Barré Syndrome
Our study did not find any statistically significant causal relationships between the 15 micronutrients analyzed and the risk of Guillain-Barré Syndrome (GBS). This lack of association suggests that the etiology of GBS may be more complex and not directly influenced by the micronutrient levels assessed in this study. GBS is known to be triggered by infections, particularly Campylobacter jejuni, which suggests that environmental and infectious factors play a more prominent role in its pathogenesis[29]. While micronutrients are essential for overall immune function, their specific impact on GBS risk may be minimal or overshadowed by other more dominant factors. Future studies should consider a broader range of environmental and genetic factors to fully understand the multifactorial nature of GBS and identify potential preventive strategies.
Overall, our study underscores the importance of micronutrient homeostasis in the context of autoimmune neurological diseases. The significant associations between magnesium and MS, as well as iron and MG, suggest potential therapeutic avenues for these conditions. Future research should focus on clinical trials to validate these findings and explore the underlying mechanisms through which these micronutrients influence disease risk and progression. Understanding these pathways could lead to novel interventions aimed at modulating micronutrient levels to prevent or treat autoimmune neurological disorders.
Despite the robustness of our Mendelian Randomization (MR) analysis, several limitations should be acknowledged. First, our study relies solely on publicly available GWAS data, and we did not incorporate wet lab experiments to validate our findings. Second, the sample sizes for MG and GBS are relatively small compared to MS, which may affect the statistical power and generalizability of our results. Third, our analysis lacks clinical validation, which is crucial for translating genetic findings into clinical practice. Lastly, the use of multiple datasets might introduce batch effects, potentially influencing the consistency of our results.