Sex Differences in Serum 25-hydroxyvitamin D Reflect Differences in 25-hydroxyvitamin D<sub>3</sub> Levels but not in D<sub>2</sub> Levels

Abstract

Background & Aims: Serum 25-hydroxyvitamin D (25(OH)D) comprises 25(OH)D3 and 25(OH)D2. Although sex differences in 25(OH)D levels have been reported, it remains unclear whether the difference lies in the profiles of 25(OH)D. We determined serum 25(OH)D3, 25(OH)D2, 3-epi-25-hydroxyvitamin D3 (3-epi-25(OH)D3), and (24R)-24,25-dihydroxyvitamin D3 (24,25(OH)2D3) levels measured by LC-MS/MS in healthy adults not consuming supplements and analyzed their profiles.Methods: The serum 25(OH)D levels of 5,959 participants were measured by CLEIA. Levels of vitamin D metabolites (25(OH)D3, 25(OH)D2, 3-epi-25(OH)D3, and 24,25(OH)2D3) of 96 participants with no history of osteoporosis, hypertension, cardiac disease, cerebrovascular disease or diabetes and whose alanine transaminase, serum creatinine, total cholesterol, and hemoglobin A1c levels were within the reference ranges were measured.Results: Serum 25(OH)D, 25(OH)D3, 3-epi-25(OH)D3, and 24,25(OH)2D3 levels were significantly higher in men than those in women, but there was no significant difference in the 25(OH)D2 levels. Strong correlations were observed between 25(OH)D and 25(OH)D3, 3-epi-25(OH)D3, and 24,25(OH)2D3 levels in both sexes. Serum 25(OH)D and 25(OH)D2 levels and serum 25(OH)D3 and 25(OH)D2 levels were not correlated.Conclusions: Serum 25(OH)D3, 25(OH)D2, 3-epi-25(OH)D3, and 24,25(OH)2D3 profiles were determined for healthy participants not consuming supplements. Sex differences in 25(OH)D levels reflected differences in 25(OH)D3, not 25(OH)D2.