Non-linear associations of plasma 25-hydroxyvitamin D with serum homocysteine and hyperhomocysteinemia in Chinese adults: a cross-sectional study

Abstract

Abstract Background Plasma 25-hydroxyvitamin D [25(OH)D] deficiency and elevated homocysteine (Hcy) levels are both well-established risk factors for cardiovascular disease (CVD). However, the relationship between 25(OH)D and Hcy remains unclear. To explore the association between plasma 25(OH)D and serum Hcy, along with the risk of hyperhomocysteinemia (HHcy). Methods Based on baseline data from the Precision Nutrition and Health KAP Real-World Study (China), The associations of 25(OH)D with Hcy and HHcy were analyzed using multivariable linear regression and logistic regression models, respectively. Restricted cubic splines (RCS) served to investigate nonlinear patterns and threshold phenomena. Additionally, subgroup and sensitivity analyses were carried out to assess potential influencing factors and confirm the robustness of the findings. Results In the unadjusted analysis, 25(OH)D were positively associated with both Hcy and HHcy. After adjusting for age and sex, a non-linear U-shaped relationship emerged between 25(OH)D and both Hcy and HHcy, which remained significant after further multivariable adjustment. When plasma 25(OH)D levels were categorized into quintiles, individuals in quintiles Q1–Q3 (25(OH)D < 24.3 ng/mL) and Q5 (25(OH)D ≥ 28.2 ng/mL) had significantly elevated Hcy concentrations (by 0.16 µmol/L) and increased risks of HHcy (by 11% and 10%, respectively) compared with those in Q4 (24.3–28.2 ng/mL). In the overall population, the inflection point for 25(OH)D in relation to Hcy was 27.2 ng/mL. For HHcy, the inflection point was 26.1 ng/mL. Conclusions This study revealed a non-linear U-shaped association between plasma 25(OH)D and both Hcy and HHcy risk in Chinese adults, providing epidemiological evidence for understanding the relationship between 25(OH)D and homocysteine, with potential implications for cardiovascular risk assessment.