No Causal Association between 25-Hydroxyvitamin D and Features of Skin Aging: Evidence from a Bidirectional Mendelian Randomization Study

Data from in vitro experiments suggest that vitamin D reduces the rate of skin aging, whereas population studies suggest the opposite, most likely due to confounding by UV exposure. We investigated whether there are causal associations between 25-hydroxyvitamin D concentrations and features of skin aging in a bidirectional Mendelian randomization study. In the Rotterdam Study (N = 3,831; 58.2% women, median age 66.5 years) and Leiden Longevity Study (N = 661; 50.5% women, median age 63.1 years), facial skin aging features (perceived age, wrinkling, pigmented spots) were assessed either manually or digitally. Associations between 25-hydroxyvitamin D and skin aging features were tested by multivariable linear regression. Mendelian randomization analyses were performed using single nucleotide polymorphisms identified from previous genome-wide association studies. After meta-analysis of the two cohorts, we observed that higher serum 25-hydroxyvitamin D was associated with a higher perceived age (P-value = 3.6 × 10^–7), more skin wrinkling (P-value = 2.6 × 10^–16), but not with more pigmented spots (P-value = 0.30). In contrast, a genetically determined 25-hydroxyvitamin D concentration was not associated with any skin aging feature (P-values > 0.05). Furthermore, a genetically determined higher degree of pigmented spots was not associated with higher 25-hydroxyvitamin D (P-values > 0.05). Our study did not indicate that associations between 25-hydroxyvitamin D and features of skin aging are causal.