Objectives Findings relating to dietary intake of n-3 polyunsaturated fatty acids (PUFA) and risk of rheumatoid arthritis (RA) are mixed. Erythrocyte membrane PUFA is an accurate objective biomarker of PUFA status; however, there are little data on erythrocyte membrane PUFA and risk of RA. The objective was therefore to compare erythrocyte membrane PUFA between pre-RA individuals and matched controls from a population-based sample, and specifically to test the hypothesis that higher levels of longer chain n-3 PUFA are associated with lower risk of RA.
Methods The European Prospective Investigation into Cancer and Nutrition (EPIC) is a large European prospective cohort study of apparently healthy populations. We undertook a nested case–control study by identifying RA cases with onset after enrolment (pre-RA) in four EPIC cohorts in Italy and Spain. Confirmed pre-RA cases were matched with controls by age, sex, centre, and date, time and fasting status at blood collection. Conditional logistic regression analysis was used to estimate associations of PUFA with the development of RA, adjusting for potential confounders including body mass index, waist circumference, education level, physical activity, smoking status and alcohol intake.
Results The study analysed samples from 96 pre-RA subjects and 258 matched controls. In this analysis, the median time to diagnosis (defined as time between date of blood sample and date of diagnosis) was 6.71 years (range 0.8–15). A significant inverse association was observed with n-6 PUFA linoleic acid (LA) levels and pre-RA in the fully adjusted model (highest tertile: OR 0.29; 95% CI 0.12 to 0.75; P for trend 0.01). No association was observed with any individual n-3 PUFA, total n-3 PUFA or total n-3:n-6 ratio.
Conclusions Erythrocyte levels of the n-6 PUFA LA were inversely associated with risk of RA, whereas no associations were observed for other n-6 or n-3 PUFA. Further work is warranted to replicate these findings and to investigate if lower LA levels are a bystander or contributor to the process of RA development.
- rheumatoid arthritis
- early rheumatoid arthritis
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Handling editor Tore K Kvien
Contributors BAF, DR, DSM, ER and PV conceived the study. PdP performed statistical analysis. All other authors contributed to the generation of data. BAF drafted the manuscript, which was reviewed and revised by all authors.
Funding Funding was received from the Imperial College London National Institute of Health Research (NIHR) Biomedical Research Centre. We would like to acknowledge Arthritis Research UK funding for the Rheumatoid Arthritis Pathogenesis Centre of Excellence. PdP was supported by an NIHR Fellowship. PCC is supported by the NIHR Southampton Biomedical Research Centre.
Disclaimer The views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health.
Competing interests None declared.
Ethics approval The study was approved by the International Agency for Research on Cancer (IARC) review board as well as by the local committees of participating EPIC centres.
Provenance and peer review Not commissioned; externally peer reviewed.
Presented at An abstract of this work was previously presented at the 2017 American College of Rheumatology Annual Congress.56
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