Sex-Based Differences in the Vitamin D Metabolite Ratio and Its Associated Factors Among Healthy Japanese Adults: A...

Background/Objectives: Vitamin D is a pleiotropic substance that plays a pivotal role in the human body. Several studies have suggested sex-based differences in vitamin D metabolism. Recently, the vitamin D metabolite ratio (VMR), defined as the ratio of serum 24,25-dihydroxyvitamin D [24,25(OH)₂D] to 25-hydroxyvitamin D [25(OH)D], has been identified as a novel marker that may more accurately reflect vitamin D status than serum 25(OH)D alone. This study aimed to assess whether significant variability exists in the VMR across different demographic groups. Methods: Residual serum samples and laboratory data were collected from healthy adults who underwent health checkups at a health center in Japan. Serum concentrations of 25(OH)D₃ and 24,25(OH)₂D₃ were simultaneously measured using a fully automated liquid chromatography-tandem mass spectrometry (LC-MS/MS) system. Factors affecting the levels of 25(OH)D₃, 24,25(OH)₂D₃, and VMR were analyzed using multiple regression analysis and the stabilized inverse probability weighting method. Results: Tentative reference intervals for 24,25(OH)₂D₃ were found to be 0.3-3.0 ng/mL for males and 0.2-2.3 ng/mL for females. Those for VMR were found to be 3.0-11.8% for males and 2.5-10.4% for females, demonstrating statistically significant but moderate differences between the sexes. These differences remained significant even after adjusting for baseline covariates including 25(OH)D₃. However, the standard deviation ratios were less than 0.5. An estimated glomerular filtration rate and an age of ≥50 years were positively associated with 24,25(OH)₂D₃ and VMR, whereas diabetic status was negatively associated with these markers. Conclusions: This study revealed moderate sex-based differences in markers of vitamin D metabolism. Although further research is needed to determine whether these differences are consistent across other populations, future epidemiology and clinical interventions should take into consideration of the sex-based differences in vitamin D metabolism.