Association between Serum Vitamin B6 Levels and Depression in Adults: A cross-sectional NHANES study

Vitamin B6 is implicated in multiple mental disorders, and accumulating evidence suggests an inverse relationship with depression; however, important aspects of the underlying dose–response patterns and the roles of individual circulating vitamin B6 metabolites remain incompletely understood. We analyzed data from the National Health and Nutrition Examination Survey (NHANES) 2005–2010. Depression was defined as a Patient Health Questionnaire-9 (PHQ-9) score ≥10. Vitamin B6 status was assessed using serum pyridoxal 5′-phosphate (PLP), the biologically active coenzyme form, and 4-pyridoxic acid (PA), the principal catabolic and urinary excretion product of vitamin B6. Among 12,620 participants, 1,070 (8.5%) met criteria for depression. After adjusting for relevant covariates, multiple logistic regression revealed that individuals in higher quartiles of serum PLP and PA (Q2-Q4) had significantly lower odds of depression compared to those in the lowest quartile (Q1). Restricted cubic spline analyses identified nonlinear relationships: L-shaped for PLP (P-nonlinearity=0.001) and U-shaped for PA (P-nonlinearity=0.017). Below the inflection points (90.7 nmol/L for PLP; 73.9 nmol/L for PA), both metabolites showed significant inverse associations with depression (PLP: OR=0.992, 95%CI: 0.988–0.996, P<0.001; PA: OR=0.994, 95%CI: 0.993–0.996, P<0.001). Above these thresholds, the association became non-significant for PLP (P=0.353), while PA demonstrated a positive association with depression (OR=1.008, 95%CI: 1.002–1.013, P<0.01). Subgroup analyses confirmed the robustness of these inverse associations across demographic categories. Serum vitamin B6 metabolites, PLP and its excretion product PA, exhibit non-linear associations with depression, with distinct threshold effects and metabolite-specific patterns that likely reflect both vitamin B6 availability and turnover.