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

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Pinto Pereira, Snehal M  ORCID logo
Garfield, Victoria 
Norris, Thomas 
Williams, Dylan M 


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.



25(OH)D, Grip strength, Mendelian randomization, Male, Female, Humans, Cross-Sectional Studies, Mendelian Randomization Analysis, Biological Specimen Banks, Vitamin D, Vitamins, Vitamin D Deficiency, Hand Strength, Muscle Weakness, United Kingdom

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J Gerontol A Biol Sci Med Sci

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Oxford University Press (OUP)
Medical Research Council (MC_UU_00002/7)
British Heart Foundation (None)
Wellcome Trust (204623/Z/16/Z)
British Heart Foundation (CH/12/2/29428)
British Heart Foundation (RG/18/13/33946)
National Institute for Health and Care Research (IS-BRC-1215-20014)
Medical Research Council (G0501262)
Medical Research Council (G0501262/1)