Omega-3 fatty acids are associated with a lower prevalence of autoantibodies in shared epitope-positive subjects at risk for rheumatoid arthritis

Abstract

Objectives Previously, we found that omega-3 fatty acids (n-3 FAs) were inversely associated with anti-cyclic citrullinated peptide (anti-CCP) positivity in participants at risk for future rheumatoid arthritis (RA). We investigated whether n-3 FAs were also associated with rheumatoid factor (RF) positivity and whether these associations were modified by shared epitope (SE) positivity. Methods The Studies of the Etiology of RA (SERA) cohort includes RA-free participants who are at increased risk for RA. We conducted a nested case–control study (n=136) to determine the association between RF and anti-CCP2 positivity and n-3 FA percentage in erythrocyte membranes (n-3 FA% in red blood cells (RBCs)). Additionally, in the baseline visit of the SERA cohort (n=2166), we evaluated the association between reported n-3 FA supplement use and prevalence of RF and anti-CCP2. We assessed SE positivity as an effect modifier. Results In the case–control study, increasing n-3 FA% in RBCs was inversely associated with RF positivity in SE-positive participants (OR 0.27, 95% CI 0.10 to 0.79), but not SE-negative participants. Similar associations were seen with anti-CCP positivity in SE-positive participants (OR 0.42, 95% CI 0.20 to 0.89), but not SE-negative participants. In the SERA cohort at baseline, n-3 FA supplement use was associated with a lower prevalence of RF positivity in SE-positive participants (OR 0.32, 95% CI 0.12 to 0.82), but not SE-negative participants; similar but non-significant trends were observed with anti-CCP2. Conclusions The potential protective effect of n-3 FAs on RA-related autoimmunity may be most pronounced in those who exhibit HLA class II genetic susceptibility to RA.

Inflammatory dietary pattern and risk of developing rheumatoid arthritis in women

“…Fish intake may exert a protective effect on RA by the anti-inflammatory effects of omega-3 polyunsaturated fatty acids [2]. Among at-risk individuals, erythrocyte membrane-bound omega-3 PUFA levels were inversely associated with anti-CCP/RF positivity [15]. Previous studies investigating EDIP found robust associations between EDIP scores and colorectal cancer risk but no association with ovarian cancer risk [16, 17].…”

Genetic and environmental risk factors for rheumatoid arthritis

“…Furthermore, a finding that has been relatively consistent across many studies is that a higher intake of fish as well as omega-3 fatty acids have been consistently linked to decreased risk for RA across a number of studies, including studies where dietary data was collected prior to incident RA (84–88). Furthermore, in FDRs of patients with RA who at the time of study did not have classifiable RA, self-reported intake of supplements containing omega-3 fatty acids, as well as biomarkers of fatty acids, found that increased intake and higher blood levels of fatty acids were associated with decreased risk for RF and ACPA positivity (89, 90). Notably, there appeared to be a greater protective effect in individuals who were positive for at least one allele containing the SE, suggesting that there may be an interaction between these factors in mediating RA risk (89).…”

“…Furthermore, in FDRs of patients with RA who at the time of study did not have classifiable RA, self-reported intake of supplements containing omega-3 fatty acids, as well as biomarkers of fatty acids, found that increased intake and higher blood levels of fatty acids were associated with decreased risk for RF and ACPA positivity (89, 90). Notably, there appeared to be a greater protective effect in individuals who were positive for at least one allele containing the SE, suggesting that there may be an interaction between these factors in mediating RA risk (89). These findings coupled with clinical trials where fatty acid intake is associated with decreased RA activity in established disease suggest there could be a direct protective relationship of fatty acids across the spectrum of RA development (91).…”

Disclosure of Personalized Rheumatoid Arthritis Risk Using Genetics, Biomarkers, and Lifestyle Factors to Motivate Health Behavior Improvements: A Randomized Controlled Trial

“…Behavioral factors, such as smoking, obesity, low fish intake, and poor dental health, are associated with increased RA risk (6–9). Smoking is the strongest behavioral RA risk factor and prolonged cessation >20 years decreases RA risk to that of never smokers, suggesting that smoking cessation may lower RA risk (6, 10, 11) Increased fish intake is associated with decreased RA risk perhaps due to the anti-inflammatory effects of omega-3 fatty acids (8, 12, 13). Being overweight or obese is associated with increased RA risk (7, 14).…”