Preconception nutritional status of fat-soluble vitamins and thyroid homeostasis: the modifying role of BMI in a cross-sectional study

Fat-soluble vitamins have been implicated in hormonal regulation and immune function, but their relevance to thyroid health during the preconception period remains unclear. This study aimed to investigate the individual and combined associations of fat-soluble vitamins with thyroid function markers in preconception women and to assess potential modification of body mass index (BMI). In a cross-sectional study of 4,947 preconception women with normal thyroid-stimulating hormone (TSH) levels, participants were classified into low normal and high normal TSH groups (≥ 2.5 mIU/L). Generalized linear regression models, restricted cubic spline (RCS) models, and Bayesian kernel machine regression (BKMR) models were used to comprehensively evaluate the associations between individual and combined fat-soluble vitamins and thyroid function biomarkers. The role of BMI was assessed using a restricted cubic spline interaction model incorporating a vitamin-BMI interaction term. Most participants had sufficient levels of vitamin A (80.9%), vitamin E (94.5%), and vitamin K (94.6%), whereas 87.5% were deficient or severely deficient in 25-hydroxyvitamin D [25(OH)D]. In single-exposure models, vitamin A was positively associated with high normal TSH status (OR = 1.36, 95% CI: 1.04, 1.77) and with TSH levels (β = 0.10, 95% CI: 0.04, 0.16), and the associations were linear in RCS models (P for overall < 0.05, P for nonlinear > 0.05). In multi-vitamin models, vitamin A remained positively associated with TSH, and a linear inverse association between 25(OH)D and TPOAb positivity was observed. This inverse association was more pronounced among participants with overweight or obesity. The nutritional status of fat-soluble vitamins, particularly vitamin A and vitamin D, is associated with thyroid function and thyroid autoimmunity biomarkers among preconception women. These associations may vary across BMI categories, particularly regarding vitamin D and TPOAb positivity. Further prospective studies are needed to clarify the temporal sequence and potential biological pathways underlying these associations.