Proteomic Correlates of Vitamin D Supplementation in the Atherosclerosis Risk in Communities (ARIC) Study

Proteins are key effectors of biological functions and play roles in signaling, transport, growth, repair, and immunity. Vitamin D biomarkers may be reflected in the plasma proteome. The aim of this discovery study was to identify novel proteins associated with vitamin D supplementation. We examined cross-sectional associations between vitamin D supplementation and plasma proteins in the Atherosclerosis Risk in Communities (ARIC) study at visit 5 (2011-2013). An untargeted proteomic platform (SomaScan version 4, SomaLogic) was used to quantify relative abundance for 4955 proteins. We compared protein levels in vitamin D supplement users and nonusers using covariate-adjusted multivariable linear regression models. Of 5011 participants analyzed (mean age 76 [SD 5] years), 2255 (45%) used vitamin D supplements. Fifty-one proteins were associated with vitamin D supplementation at a false discovery rate-adjusted p < 0.05. Most proteins (33 of 51) were lower in users than nonusers. After adjusting for other supplement use (multivitamin/mineral, omega-3, B vitamins, and vitamin C), 7 proteins remained significantly associated with vitamin D supplementation. Chondroadherin, parathyroid hormone, transcobalamin-1, osteomodulin, collagen type II, and bone sialoprotein 2 were lower, while sclerostin was higher, in vitamin D users than nonusers. These proteins are potential markers of vitamin D in older adults and highlight vitamin D-related metabolic pathways.