Sarcopenia, unhealthy lifestyle, and vitamin D: A Mendelian randomization study

Observational studies have associated vitamin D deficiency with sarcopenia and lifestyle; however, the causal link between them remains unclear. This study aimed to evaluate the causal relationship between 25-hydroxyvitamin D (25(OH)D) and sarcopenia and unhealthy lifestyle using Mendelian randomization (MR). We extracted pooled data on 25(OH)D from a genome-wide association study conducted on individuals of European ancestry. Sarcopenia outcomes were assessed using appendicular lean mass, low handgrip strength, and usual walking pace. Unhealthy lifestyle outcomes were assessed using able to walk or cycle unaided for 10 minutes, moderate-to-vigorous intensity physical activity during leisure time, waist-hip ratio, alcohol consumption, and never smoked. A 2-sample MR approach was employed in this study, utilizing the inverse-variance weighted (IVW) method and the MR-Egger method as the primary research method. Heterogeneity and horizontal pleiotropy analyses were performed to ensure the stability of the candidate single-nucleotide polymorphisms as instrumental variables. The study found that a higher 25(OH)D level was associated with an increased appendicular lean mass (IVW: Beta 0.03, 95% confidence interval: 0.01-0.06, P = .011). However, this study did not provide evidence of a causal relationship between 25(OH)D levels and other muscle traits. For unhealthy lifestyle, MR-Egger analysis suggests that increased levels of 25(OH)D increase the probability of never smoked (odds ratio 1.08, 95% confidence interval: 1.03-1.11, P = .015). In addition, the study detected no pleiotropy (all P > .05), except for low hand grip strengthEuropean Working Group on Sarcopenia in Older People 2 (IVW: Q = 24.141, P = .019; MR-Egger: Q = 23.908, P = .013). This study confirms a causal relationship between 25(OH)D, sarcopenia, and smoking.