Abstract: Objective To explore the causal relationships between vitamin D-related biomarkers and diagnostic parameters of sarcopenia utilizing Mendelian Randomization (MR) approaches. Methods Two-sample Mendelian randomization (TSMR) analyses were conducted to investigate the causal associations between vitamin D-related biomarkers(including serum 25-hydroxyvitamin D levels, vitamin D binding protein, vitamin D deficiency, and vitamin D supplementation) and sarcopenia diagnostic parameters, namely low handgrip strength, appendicular lean mass (ALM), and gait speed. Additionally, multivariable Mendelian randomization (MVMR) was employed to assess the independent causal effects of these biomarkers. Replication analyses were subsequently performed using alternative datasets for sarcopenia diagnostic parameters. Meta-analyses were conducted to synthesize the results from both primary and replication TSMR analyses. Results The MR estimates derived from primary, multivariable, and replication analyses did not reveal significant causal associations between vitamin D-related biomarkers and sarcopenia diagnostic parameters. However, meta-analytic results indicated significant causal relationships between the absence of vitamin D deficiency and gait speed (β=0.001, 95% CI = 0.000 2-0.001 8, P=0.019) as well as low handgrip strength (OR=0.993, 95% CI=0.987-0.999, P=0.015), and between serum 25(OH)D levels and gait speed (β=0.015, 95% CI=0.004-0.027, P=0.009). Conclusion Maintaining optimal levels of serum 25-hydroxyvitamin D may help prevent the decline in gait speed, while the absence of vitamin D deficiency may also reduce the risk of developing low handgrip strength.

Key words: 25-hydroxyvitamin D, Sarcopenia, Mendelian randomization, Meta-analysis