Nonlinear associations of oxidative balance score with central and peripheral thyroid hormone sensitivity: A cross-sectional study of NHANES 2007 to 2012

Oxidative balance score (OBS) integrates dietary/lifestyle factors to assess cumulative oxidative stress, yet its association with thyroid hormone sensitivity remains unexplored. This study aimed to investigate the relationship between OBS and thyroid hormone sensitivity through central and peripheral regulation mechanisms. This cross-sectional study analyzed data from the National Health and Nutrition Examination Survey (2007-2012), involving 5536 participants. OBS was computed using a tertile-based scoring system, with higher scores indicating a predominance of antioxidant exposures. Central sensitivity was evaluated via thyroid-stimulating hormone index, thyrotroph thyroxine resistance index, and thyroid feedback quantile-based index; peripheral sensitivity was assessed by the free triiodothyronine to free thyroxine ratio. Weighted multivariable linear regression and restricted cubic splines were used to characterize dose-response relationships, supported by subgroup and sensitivity analyses. Threshold-dependent associations emerged: central sensitivity indices (thyroid-stimulating hormone index, thyrotroph thyroxine resistance index, and thyroid feedback quantile-based index) showed a positive linear association with OBS below inflection points (8.275, 8.275, and 8.847, respectively), plateauing above these points. Peripheral sensitivity (free triiodothyronine/free thyroxine ratio) was negatively associated with OBS scores above 15.681 (β = -0.013, P = .001). Subgroup analyses showed consistent patterns across demographics (all P for interaction > .05), and sensitivity analyses confirmed the robustness of the findings. Our findings suggest a dual redox-thyroid regulatory mechanism, wherein both prooxidant dominance and antioxidant excess may be associated with impaired thyroid hormone sensitivity through central and peripheral pathways, respectively. These results underscore the potential importance of maintaining an optimal oxidative balance zone for thyroid health and provide a composite framework for future research into personalized diet and lifestyle interventions.