Urinary carnosine links diet quality with one-carbon and lipid metabolism: insights from an interpretive framework for imidazole metabolites.

PURPOSE: Urinary imidazole-containing metabolites can reflect dietary exposure and endogenous metabolism, but their biological meaning in nutritional metabolomics remains challenging to resolve. Using a mechanistically informed framework, we evaluated whether urinary carnosine is associated with diet quality and circulating one-carbon and lipid-related markers, beyond a simple meat-related exposure signal.

METHODS

In 138 adults, untargeted urine metabolomics was used to annotate imidazole metabolites, which were classified a priori as integrated dietary-metabolic biomarkers or non-integrated exposure or confounding markers. Associations with a dietary quality score aligned with the EAT-Lancet reference diet and with clinical biomarkers were evaluated using hierarchical regression with sequential adjustment for urinary creatinine, age, sex, body mass index, diet score, and outcome-relevant medication indicators. A sensitivity model additionally adjusted for estimated glomerular filtration rate category. Participants reporting folate or cobalamin supplementation were excluded from one-carbon analyses.

RESULTS

Higher urinary carnosine was associated with lower high-density lipoprotein cholesterol, lower serum folate, and higher homocysteine after multivariable adjustment, including renal-function sensitivity analyses. Integrated metabolites showed higher overall association rates with clinical predictors than non-integrated metabolites.

CONCLUSION

Urinary carnosine was associated with one-carbon status and lipid-related markers after multivariable adjustment, supporting its potential as a candidate integrated dietary-metabolic biomarker. A mechanistically informed framework may help distinguish metabolically informative urinary imidazole metabolites from diet-only or exposure-driven signals in nutritional metabolomics and precision nutrition.