AUTHOR=Zhang Li , Xu Hai , Hang Lihua , Lin Xin TITLE=Gender-specific associations between serum docosahexaenoic acid levels and chronic pain prevalence: a cross-sectional study JOURNAL=Frontiers in Medicine VOLUME=Volume 12 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2025.1563209 DOI=10.3389/fmed.2025.1563209 ISSN=2296-858X ABSTRACT=BackgroundThis study examines the relationship between serum docosahexaenoic acid (DHA) levels and chronic pain prevalence, with emphasis on gender differences and smoking status interactions.MethodsData from 1,677 adults participating in the 2003-2004 National Health and Nutrition Examination Survey (NHANES) were analyzed. Chronic pain was defined as pain persisting ≥ 3 months. Relationships between serum DHA levels and chronic pain were assessed using logistic regression and generalized additive models, adjusting for relevant covariates.ResultsAmong participants (median age 46 years), 17.9% reported chronic pain. In females, a non-linear L-shaped association was observed: for DHA levels < 187 μmol/L, each 10-unit increase was associated with lower chronic pain prevalence (adjusted OR: 0.92; 95% CI: 0.87-0.97; P = 0.0019), while at levels ≥ 187 μmol/L, this protective association diminished (adjusted OR: 1.03; 95% CI: 0.99-1.08; P = 0.1578). In males, no overall significant association was found (adjusted OR: 1.0; 95% CI: 0.97-1.03; P = 0.9057); however, a significant interaction with smoking status was detected (P-interaction = 0.0062). Among non-smoking males, higher DHA levels were associated with increased chronic pain odds (OR: 1.06; 95% CI: 1.01-1.11; P = 0.0220), while no significant association was observed among male smokers.ConclusionThe relationship between serum DHA and chronic pain demonstrates gender-specific patterns, with a threshold effect in females and smoking-dependent associations in males. These findings suggest that the relationship between DHA and chronic pain involves complex biological interactions that vary by gender and smoking status, highlighting the need for personalized approaches in future research and interventions.