Comparison with previous studies
T2D, cardiovascular disease
DISEASE, CARDIOVASCULAR DISEASE
Attempts to derive biomarkers of the Mediterranean diet and other dietary patterns have previously been largely confined to metabolomic profiling using cross-sectional designs [Our work on derivation of the nutritional biomarker score of the Mediterranean diet adds to the previous literature by incorporating the strength of an RCT. Owing to the RCT design of the MedLey trial, we were able to minimise confounding by non-nutritional factors, and thus derive a biomarker score with| potentially improved generalisability to external populations. A further novelty of our work is the application of the experimentally derived score to prospective associations between dietary patterns at large and disease outcomes. To our knowledge, the only other example of derivation and application of a putative biomarker of the Mediterranean diet to associations with disease endpoints was a metabolomics-based analysis in the Spanish PREDIMED study and prospective cohorts in the USA. Similar to our analysis, it observed inverse associations for cardiovascular disease using the metabolite score observationally derived in PREDIMED across all cohorts (HR range per 1 SD: 0.71 to 0.86) and weaker or null associations when using the self-reported Mediterranean diet [For incident T2D, the PREDIMED trial reported a 30% risk reduction in the Mediterranean diet intervention arms relative to the control lower fat diet group (273 incident cases in 3,541 participants) [