The association between omega-3 fatty acid biomarkers and inflammatory arthritis in an anti-citrullinated protein antibody positive population

Rheumatology (Oxford). 2017 Dec 1;56(12):2229-2236. doi: 10.1093/rheumatology/kex360.


Objectives: Higher circulating omega-3 fatty acids (n-3 FAs) are associated with a lower prevalence of anti-CCP antibodies and RF in subjects without RA. We examined whether, in anti-CCP+ subjects, n-3 FAs also play a role in development of inflammatory arthritis (IA).

Methods: At Colorado-based health fairs from 2008 to 2014, participants without a previous diagnosis of RA who were anti-CCP3+ (n = 47) were recruited into a follow-up study; symptom assessments and joint examinations were conducted every 6 months for the determination of IA. We measured n-3 FAs as a percentage of total lipids in red blood cell membranes (n-3 FA%) at each visit.

Results: We detected IA in 10 anti-CCP3+ subjects (21%) at the baseline visit. Increased total n-3 FA% in red blood cell membranes [odds ratio (OR) = 0.09, 95% CI: 0.01, 0.76], specifically docosapentaenoic acid (OR = 0.16, 95% CI: 0.03, 0.83) and docosahexaenoic acid (OR = 0.23, 95% CI: 0.06, 0.86), was associated with a lower odds of IA at the baseline visit, adjusting for n-3 FA supplement use, current smoking, RF+, elevated CRP+ and shared epitope. We followed 35 of the anti-CCP3+ subjects who were IA negative at baseline and detected 14 incident IA cases over an average of 2.56 years of follow-up. In a time-varying survival analysis, increasing docosapentaenoic acid significantly decreased risk of incident IA (hazard ratio = 0.52, 95% CI: 0.27, 0.98), adjusting for age at baseline, n-3 FA supplement use, RF+, CRP+ and shared epitope.

Conclusion: n-3 FAs may potentially lower the risk of transition from anti-CCP positivity to IA, an observation that warrants further investigation.

Keywords: autoantigens and autoantibodies; autoinflammatory conditions; diet therapy; epidemiology; rheumatoid arthritis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Citrullinated Protein Antibodies / blood*
  • Arthritis, Rheumatoid / blood*
  • Arthritis, Rheumatoid / diagnosis
  • Arthritis, Rheumatoid / epidemiology
  • Autoantibodies / blood
  • Biomarkers / blood
  • Colorado
  • Epitopes
  • Fatty Acids, Omega-3 / blood*
  • Female
  • Follow-Up Studies
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Odds Ratio
  • Peptides, Cyclic / immunology
  • Proportional Hazards Models
  • Rheumatoid Factor / blood
  • Risk Factors
  • Survival Analysis


  • Anti-Citrullinated Protein Antibodies
  • Autoantibodies
  • Biomarkers
  • Epitopes
  • Fatty Acids, Omega-3
  • Peptides, Cyclic
  • Rheumatoid Factor