Untargeted metabolomic analysis of plasma from relapsing-remitting multiple sclerosis patients reveals changes in metabolites associated with structural changes in brain.

Background: Changes in peripheral blood amino acids have been noted in Relapse Remitting Multiple Sclerosis (RRMS), suggesting their potential diagnostic value in anticipating disease progression.

Objective: The present study sought to comprehensively assess the plasma metabolome, including amino acids, of RRMS patient and unaffected controls, to identify potential biomarkers of RRMS disease pathogenesis.

Methods: Untargeted NMR metabolomics was performed on plasma from 28 RRMS patients and 18 unaffected controls to test the hypothesis that metabolomic markers are altered in RRMS patients in association with lesion load, brain atrophy and cognitive performance.

Results: There were no significant differences between RRMS and controls in age, sex and total brain volume. Brain fractional volumes of gray matter, white matter, thalamus and parenchyma as well as multiple neurocognitive scores were significantly lower in RRMS patients compared to unaffected controls. Concentrations of nine plasma metabolites (arginine, isoleucine, citrate, serine, phenylalanine, methionine, asparagine, histidine, myo-inositol) were significantly lower in RRMS patients compared to controls. Plasma arginine concentrations were positively correlated with T1 holes and white matter lesions, and plasma methionine concentrations were positively correlated with T1 holes, but not white matter lesions. Serine was negatively correlated with performance on the Brief Visuospatial Memory Test in controls but not RRMS patients.

Conclusions: The identified disturbances in metabolite concentrations might be developed as new markers of neuroanatomical vulnerability in RRMS, should the findings be reproduced in larger cohort studies.