Association between vitamin D status, lymphocyte subsets, and triglycerides in men: an observational study

Vitamin D plays an important role in immune regulation, yet the relationships among vitamin D status, lymphocyte subsets, and triglycerides (TG) remain incompletely understood. This study aimed to evaluate the associations between serum 25-hydroxyvitamin D [25(OH)D] concentrations, lymphocyte count and subsets, and to examine whether TG statistically contributes to these associations through an indirect pathway. A retrospective cross-sectional analysis was performed in 351 male individuals (mean age 50.22 ± 9.36 years) who underwent routine health screenings. Serum 25(OH)D, TG, lymphocyte count, and lymphocyte subsets (CD3+, CD4+, CD8+, B cells, NK cells) were measured. Pearson correlation, restricted cubic spline, and indirect-effect (mediation) analyses were conducted with adjustment for age, season, physical activity, eGFR, and total bilirubin. 25(OH)D was analyzed as a continuous variable. Serum 25(OH)D was negatively correlated with lymphocyte count (r = - 0.188), CD3 + T cells (r = - 0.209), and CD4 + T cells (r = - 0.218) (all p < 0.01). TG levels were positively correlated with these parameters (r = 0.219, 0.234, and 0.237, respectively; all p < 0.01) and negatively correlated with 25(OH)D (r = - 0.298, p < 0.01). Mediation analysis showed statistically significant indirect effects of TG on the associations between 25(OH)D and lymphocyte count (indirect effect - 3.6, 95% CI -6.7 to - 0.9; 25.4% of the total effect) and between 25(OH)D and CD4 + T-cell count (- 2.0, 95% CI -3.7 to - 0.6; 21.9%), alongside smaller but statistically significant direct effects; these cross-sectional estimates are compatible with, but do not establish, a mediating role of TG. In extended models additionally adjusted for body mass index, fasting plasma glucose, HDL-C and LDL-C, these indirect effects were attenuated (lymphocyte count: -2.4, 95% CI -4.9 to - 0.2; CD3 + T-cell count: -1.7, 95% CI -3.8 to - 0.02), and after further adjustment for smoking and alcohol consumption the bootstrap confidence intervals included zero. Triglycerides may statistically contribute to the association between vitamin D status and selected lymphocyte populations, particularly CD4 + T cells; however, these indirect effects were attenuated after adjustment for metabolic covariates and were no longer statistically significant in the most comprehensively adjusted model. Because of the cross-sectional design, these findings are hypothesis-generating and require confirmation in longitudinal and interventional studies before any clinical relevance can be inferred.