Intake of one-carbon metabolism nutrients and risk of rheumatoid arthritis: a prospective UK biobank cohort study.

OBJECTIVES

One-carbon metabolism (OCM) nutrients are essential for methylation processes and may be involved in the pathogenesis of rheumatoid arthritis (RA), but prospective evidence remains limited. This study aimed to investigate the association between dietary OCM nutrients and RA risk, and their interactions with genetic and lifestyle factors.

METHODS

A total of 189,440 participants from the UK Biobank were included. Dietary intake was assessed using repeated 24-hour recalls. Nutrient levels were estimated based on McCance and Widdowson's The Composition of Foods and the USDA Food and Nutrient Database for Dietary Studies. Cox proportional hazards models were used to evaluate the independent and joint associations of OCM nutrients, genetic risk, and RA risk. Nonlinear associations were examined using restricted cubic spline.

RESULTS

During a median follow-up of 13.43 years, 1,751 RA cases were identified. Participants in the highest quartile of OCM nutrient intake had a significantly lower risk of RA compared to those in the lowest quartile. The hazard ratios (95% CI) for methionine, folate, vitamin B6, and vitamin B12 were 0.84 (0.74-0.97), 0.88 (0.76-1.00), 0.88 (0.78-0.98), and 0.84 (0.73-0.96), respectively. High OCM intake combined with low genetic risk was associated with a > 40% lower risk of RA. Additionally, significant interactions were observed between OCM nutrient intake and both smoking and alcohol consumption.

CONCLUSION

Higher intake of OCM nutrients was associated with a reduced risk of RA and showed a joint effect with genetic risk. Individuals with certain lifestyle factors may benefit more from dietary OCM nutrient intake.