Association of dietary long-chain n -3 fatty acid intake with depression severity in USA adults: a population-based cross-sectional study

Abstract Depression affects over 280 million people worldwide. Long-chain n -3 fatty acids may relate to depression, but observational evidence is inconsistent. This cross-sectional analysis of the National Health and Nutrition Examination Survey 2021–2023 examined the association between dietary long-chain n -3 intake and depression severity in USA adults ≥ 18 years with complete dietary, Patient Health Questionnaire-9 (PHQ-9) and covariate data ( n 3608). PHQ-9 severity categories (0–4 to 20–27) served as the main outcome. Total n -3 (α-linolenic acid (ALA), EPA, DPA and DHA) from 24-h recalls (Food and Nutrient Database for Dietary Studies 2021–2023) served as the exposure; supplements were excluded, and supplement use was a binary covariate. Survey-weighted ordinal logistic regression (svyolr) was used with all continuous variables centred/scaled (OR per 1 sd). Covariates included age, sex, race/ethnicity (collapsed for sparse cells), income:poverty ratio, BMI, smoking, alcohol, physical activity and n -3 supplement use. Higher total n -3 intake was inversely associated with depression severity (OR 0·865 per 1 sd, 95 % CI 0·761, 0·983, P = 0·026). EPA showed a significant inverse association (OR 0·907, 95 % CI 0·824, 0·998, P = 0·045); ALA, DPA and DHA were NS. No interaction by sex ( P = 0·656) or race/ethnicity ( P = 0·155). Sensitivity analyses: excluding supplement users ( n 3093) OR 0·872 (95 % CI 0·773, 0·984, P = 0·026); two recalls only ( n 3229) OR 0·847 (95 % CI 0·751, 0·955, P = 0·007). Dietary n -3 intake, particularly EPA, was modestly and inversely associated with depression severity. Residual confounding and reverse causation remain possible; longitudinal studies with biomarkers are needed.