Association between serum vitamin B₆ levels and depression in adults: a cross-sectional National Health and Nutrition...

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 analysed data from the National Health and Nutrition Examination Survey 2005-2010. Depression was defined as a Patient Health Questionnaire-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, 1070 (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 with 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.