AT A GLANCE

A new study published in the American Journal of Clinical Nutrition concludes that the metabolic response to the Mediterranean (MED) diet is inversely associated with the risk of rheumatoid arthritis (RA).¹

“While the MED diet has been associated with reduced RA risk, the underlying metabolic mechanisms and the role of genetic susceptibility in this relationship remain unknown,” explain study authors Song et al., who sought in their recent work to identify a metabolic signature linked to the MED diet and examine its association with the risk of RA, while accounting for genetic predispositions.

After sourcing data from 109,565 participants in the UK Biobank, elastic net regression was applied to generate a MED-related metabolic signature, and Cox proportional hazards models were used to assess the associations between MED diet score, its derived metabolic signature, and incident RA. Next, a polygenic risk score (PRS) for RA was incorporated to examine joint associations and potential interactions between genetic susceptibility and MED diet score or its metabolic signature in relation to RA risk. Finally, mediation analysis was conducted to estimate the extent to which metabolic signature mediates the association between the MED diet and RA.

According to the authors, a total 1,123 participants developed RA over a period of 11.6 years. Ultimately, they identified a MED diet-related metabolic signature involving 66 metabolites. Analysis confirmed that both MED diet score and metabolic signature were inversely associated with RA risk, with associations remaining consistent across all strata of genetic risk. Separately, joint analyses indicated that favorable metabolic profiles may attenuate the genetic predisposition to RA.

Ultimately, mediation analysis showed that the metabolic signature explained 22.4% of the association between the MED diet and RA.

“We identified a robust metabolic signature reflecting the metabolic response to the MED diet. This signature was inversely associated with RA risk and partially mitigated the genetic susceptibility to RA. These findings highlight the potential of metabolic signature for enhancing dietary assessment and guiding personalized nutritional intervention,” conclude the authors.

Reference

1.     Song X, Ma X, Yang B, et al. Mediterranean diet, metabolic signature, genetic predisposition, and risk of rheumatoid arthritis: a large-scale population-based prospective cohort study (online ahead of print October 3, 2025). Am J Clin Nutr.