Dietary factors and risk of rheumatoid arthritis using data linkage

Background: Rheumatoid arthritis (RA) is the most common inflammatory arthritis in the UK, leading to irreversible joint damage, disability, and reduced quality of life. Modifiable risk factors in the pre-diagnostic phase, particularly diet, remain poorly understood. This thesis aimed to investigate associations between dietary and lifestyle factors and the risk of incident RA.
Methods: A dose-response meta-analysis of 30 prospective cohort studies was conducted. Data were obtained from the UK Women’s Cohort Study (UKWCS) and UK Biobank, with RA cases ascertained through hospital linkage. Analyses examined central adiposity, adherence to the Mediterranean diet, alcohol intake (frequency and amount). In UK Biobank, a composite healthy lifestyle index was further investigated, and mediation analysis was performed to test whether C-reactive protein (CRP) mediates the association.
Results: The meta-analysis showed that higher intakes of alcohol, fruit, and cereals were associated with reduced RA risk, while tea and caffeinated coffee were linked to increased risk. In the UKWCS, central adiposity measures (particularly waist-to-height ratio) were stronger predictors of RA risk than BMI. High adherence to the Mediterranean diet was associated with a 33% lower RA risk, and moderate wine consumption was also protective, with effect modification by smoking. In UK Biobank, a higher healthy lifestyle score was associated with lower RA risk, an effect stronger in men and leaner individuals. CRP partially mediated this association, explaining approximately 30% of the protective effect.
Conclusion: Across multiple analytical scales and two independent British cohorts, this thesis is the first to demonstrate that various aspects of diet, from individual foods and drinks to overall dietary patterns and lifestyle, are associated with RA risk. The protective effects of the Mediterranean diet, wine consumption and healthy living were quantified, with systemic inflammation accounting for around 30% of the association between healthy lifestyle score and RA incidence.