Intake of Polyunsaturated Fatty Acids and Antinuclear Antibodies in the General US Population

Background: Antinuclear antibodies (ANA) are detected in >10% of the general US population, and can develop years in advance of a clinical autoimmune disease. Omega-3 (n-3) fatty acids are anti-inflammatory, and omega-6 (n-6) are pro-inflammatory, thus may be relevant to autoimmunity. Aims: To examine the cross-sectional association between dietary ratio of n-6/n-3 and antinuclear antibody (ANA) positivity among persons 12-85 years in the general US population (NHANES 1999-2004). Methods: Based on 24-hour dietary interview, n-3 was calculated as (octadecatrienoic + eicosapentaenoic + docosahexaenoic acids) and n-6 as (octadecadienoic + eicosatetraenoic acids). ANAs were measured by HEp-2 indirect immunofluorescence assay (positive ?1:80). Statistical analyses accounted for survey sampling design. Multivariable logistic regression adjusted for covariates defined a priori (sex, age, race/ethnicity, education, body mass index, total caloric intake, survey cycle). The ratio of n-6/n-3 was examined as a piecewise continuous variable. Results: Among 4460 persons (mean age 43, 51% female), 13.7% were ANA+ and mean n-6/n-3 ratio was 10.7. N-6/n-3 ratio was significantly associated with increased risk of ANA positivity: for each unit increase in n-6/n-3 for ratios ?7, the odds of being ANA+ increased 40% [adj OR 1.4 (95% CI 1.1, 1.7)] but plateaued for ratios >7 [adj OR 1.0 (95% CI 0.98, 1.02)]. Results were similar when restricted to adults (?18) and in a sensitivity analysis further adjusting for total blood mercury (THg) among the subset of 1272 females 16-49 with THg data. Conclusions: In a representative population of 12-85 year olds in the US, the ratio of n-6/n-3 fatty acids is associated with ANA positivity. Longitudinal studies are needed to assess temporality of this association and the relationship to progression to clinical disease.