Association of fish intake and smoking with risk of rheumatoid arthritis and age of onset: a prospective cohort study

BACKGROUND: Prior studies suggest that fish may be protective for rheumatoid arthritis (RA) risk perhaps through the anti-inflammatory effect of omega-3 fatty acid, but this relationship has not been clearly established. Therefore, we investigated fish intake and RA risk by serologic status, age of onset, and smoking using a prospective cohort study with large sample size, repeated measures of dietary intake, and lengthy follow-up. METHODS: We studied fish intake and RA risk among 166,013 women in two prospective cohorts, the Nurses’ Health Study (NHS, 1984–2014) and NHSII (1991–2015). Fish intake was assessed using food frequency questionnaires at baseline and every 4 years. Incident RA during follow-up and serologic status were determined by medical record review. Pooled Cox regression models estimated hazard ratios (HR) and 95% confidence intervals (CI) for RA (overall and by serologic status and age at diagnosis) for fish intake frequency. We tested for a smoking-fish interaction for RA risk. RESULTS: During 3,863,909 person-years of follow-up, we identified 1080 incident RA cases. Increasing fish intake was not associated with all RA (≥4 servings/week: multivariable HR 0.93 [95%CI 0.67–1.28] vs. < 1 serving/month; p for trend = 0.42), seropositive RA (p for trend = 0.66), or seronegative RA (p for trend = 0.45), but had increased risk for RA diagnosed > 55 years old (p for trend = 0.037). Among women ≤55 years old, frequent fish intake (vs. infrequent) had HRs (95%CIs) of: 0.73 (0.52–1.02) for all RA, 0.85 (0.55–1.32) for seropositive RA, and 0.55 (0.32–0.94) for seronegative RA. Ever smokers with infrequent fish intake had highly elevated risk for RA onset ≤55 years (HR 2.59, 95%CI 1.65–4.06), while ever smokers with frequent fish intake had modestly elevated RA risk (HR 1.29, 95%CI 1.07–1.57; vs. never smokers/frequent fish intake; p for smoking-fish interaction = 0.039). CONCLUSION: In this large prospective cohort study, we found no clear protective effect of fish or marine omega-3 fatty acid intake on RA risk, overall or by serologic status. We found that fish intake attenuated the strong association of smoking for RA diagnosed ≤55 years of age, but this requires further study.