Mendelian Randomization of Serum Micronutrients in relation to Lower Back Pain and Sciatica protection: focus on Vitamin A

Background: Sciatica is generally induced by the irritation of the sciatic nerve, leading to radiating pain in the lower extremities, which considerably impacts the patient's daily life. Nerve root compression and lumbar disc herniation are the most frequent causes, with approximately 60% of patients experiencing both lower back pain and sciatica simultaneously. The nervous system's health and functionality are significantly influenced by micronutrients, and studies have shown that micronutrients (such as copper, iron, and vitamin A) are involved in neuroinflammation, oxidative stress, and nerve damage repair.The link between micronutrients and diseases has been examined more recently using Mendelian randomization (MR), a genetic epidemiology technique that can be used to look into causal relationships. In order to provide theoretical support for the prevention and treatment of these linked conditions, this study aims to usethe MR approach to examine the causal association between micronutrients and Lower back pain (LBP) and sciatica. Methods: This study adopts a Mendelian randomization (MR) design, selecting 15 micronutrients (vitamin A, vitamin B6, folic acid, vitamin B12, vitamin C, vitamin D, vitamin E, carotene, copper, calcium, iron, magnesium, potassium, selenium, and zinc ) as exposure factors and LBP and sciatica as the outcome for investigating causal relationships. The IEU OpenGWAS database and the FinnGen Biobank database provided the genome-wide association study (GWAS) data for micronutrients, including subjects of European descent. To ensure the validity of instrumental variables and avoid confounding biases, this study employed several MR analytical methods, including IVW (inverse variance-weighted), weighted median, MR-Egger, simple mode, and weighted mode. Furthermore, this study also conducted heterogeneity and pleiotropy tests to guarantee the outcomes' dependability and robustness. Results: The MR study revealed a strong causal relationship between vitamin A and LBP and sciatica. According to the IVW analysis, vitamin A significantly lowered the risk of LBP and sciatica (OR=0.007, 95% CI: 0.00007–0.602, P=0.029). The weighted median and MR-Egger techniques' results are consistent with IVW. Suggesting that vitamin A serves as a protective factor for LBP and sciatica. Furthermore, the multivariable MR analysis of iron and calcium did not reveal significant causal effects. The sensitivity analysis indicated that removing any individual SNP had no significant impact on the results, and no pleiotropy or heterogeneity was observed. Conclusion: This study demonstrates that vitamin A has a preventive effect against LBP and sciatica and is helpful in reducing the incidence of these disorders.The anti-inflammatory effect of vitamin A is the primary mechanism by which it exerts its protective effect. Other micronutrients, such as iron and calcium, have not been shown to have an independent causal relationship with LBP and sciatica. Vitamin A supplementation offers and provides new ideas and directions for the treatment and prevention of LBP and sciatica.