Work

The effect of parenteral vitamin B12 treatment on its plasma metabolomic profile and on functional biomarkers of its deficiency

Year: 2025

Type: article

Abstract: Diagnosis of vitamin B12 (B12) deficiency is hampered by the low specificity cut-offs of blood-based biomarkers, like serum B12 and holo-transcobalamin (HoloTc), or B12-associated metabolites like methylmalonic acid (MMA) and homocysteine (Hcy) concentrations, or their combinations computed as combined B12 (cB12). We assessed B12 deficiency through non-invasive [13C]-propionate oxidation breath test to derive functional cut-off and tested its sensitivity in response to acute change in B12 status in low B12 adult male participants by parenterally administering 3 mg hydroxocobalamin and profiling through untargeted and targeted B12 related metabolites. The functional deficiency cut-off, based on a breakpoint analysis of [13C]-propionate oxidation with B12 concentrations, was 144 pmol/L [95%CI; 106.4-182.4, p=0.02] for B12 deficiency. Untargeted metabolomic analyses revealed potential functional B12 metabolites that are known to be associated with mitochondrial function, oxidative stress, lipids, bile acids and 1-carbon metabolism. Parenteral B12 treatment increased [13C]-propionate oxidation (14.9%, range 1.1 to 66.9) significantly and was also associated with significant alterations (p<0.05) in B12, HoloTc, MMA, Hcy concentrations, cB12, and associated functional metabolites like propionylcarnitine (C3), its ratio to acetylcarnitine (C3/C2) and palmitoylcarnitine (C3/C16). This study explores the clinical utility of propionate breath test to define functional B12 deficiency and associated metabolites through omics-based approach.

Source: Scientific Reports

DOI: 10.1038/s41598-025-09110-y