Linear and Nonlinear Associations Between Vitamin D and Grip Strength: A Mendelian Randomization Study in UK Biobank

Background Low vitamin D status is a widespread phenomenon. Similarly, muscle weakness, often indicated by low grip strength, is another public health concern; however, the vitamin D-grip strength relationship is equivocal. It is important to understand whether variation in vitamin D status causally influences muscle strength to elucidate whether supplementation may help prevent/treat muscle weakness. Methods UK Biobank participants, aged 37-73 years, with valid data on Vitamin D status (circulating 25-hydroxyvitamin D [25(OH)D] concentration) and maximum grip strength were included (N = 368,890). We examined sex-specific cross-sectional associations between 25(OH)D and grip strength. Using Mendelian randomization (MR), we estimated the strength of the 25(OH)D-grip strength associations using genetic instruments for 25(OH)D as our exposure. Crucially, because potential effects of vitamin D supplementation on strength could vary by underlying 25(OH)D status, we allowed for nonlinear relationships between 25(OH)D and strength in all analyses. Results Mean (SD) of 25(OH)D was 50 (21) nmol/L in males and females. In cross-sectional analyses, there was evidence of nonlinear associations between 25(OH)D and strength, for example, compared to males with 50 nmol/L circulating 25(OH)D, males with 75 nmol/L had 0.36 kg (0.31,0.40) stronger grip; males with 25 nmol/L had 1.01 kg (95% confidence interval [CI]: 0.93, 1.08) weaker grip. In MR analyses, linear and nonlinear models fitted the data similarly well, for example, 25 nmol/L higher circulating 25(OH)D in males was associated with 0.25 kg (-0.05, 0.55) greater grip (regardless of initial 25(OH)D status). Results were similar, albeit weaker, for females. Conclusions Using two different methods to triangulate evidence, our findings suggest moderate to small causal links between circulating 25(OH)D and grip strength.