The effect of parenteral vitamin B 12 treatment on its plasma metabolomic profile and on functional biomarkers of its deficiency.

Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE

Original Publication: London : Nature Publishing Group, copyright 2011-

Biomarkers*/blood ; Vitamin B 12*/administration & dosage ; Vitamin B 12*/blood ; Vitamin B 12*/therapeutic use ; Vitamin B 12 Deficiency*/drug therapy ; Vitamin B 12 Deficiency*/blood ; Vitamin B 12 Deficiency*/diagnosis ; Metabolome*/drug effects; Humans ; Male ; Adult ; Metabolomics/methods ; Middle Aged ; Breath Tests ; Methylmalonic Acid/blood ; Homocysteine/blood ; Young Adult

Competing Interests: Declarations. Competing interests: The authors declare no competing interests.
Diagnosis of vitamin B 12 (B 12 ) deficiency is hampered by the low specificity cut-offs of blood-based biomarkers, like serum B 12 and holo-transcobalamin (HoloTc), or B 12 -associated metabolites like methylmalonic acid (MMA) and homocysteine (Hcy) concentrations, or their combinations computed as combined B 12 (cB 12 ). We assessed B 12 deficiency through non-invasive [ ¹³ C]-propionate oxidation breath test to derive functional cut-off and tested its sensitivity in response to acute change in B 12 status in low B 12 adult male participants by parenterally administering 3 mg hydroxocobalamin and profiling through untargeted and targeted B 12 related metabolites. The functional deficiency cut-off, based on a breakpoint analysis of [ ¹³ C]-propionate oxidation with B 12 concentrations, was 144 pmol/L [95% CI 106.4-182.4, p = 0.02] for B 12 deficiency. Untargeted metabolomic analyses revealed potential functional B 12 metabolites that are known to be associated with mitochondrial function, oxidative stress, lipids, bile acids and 1-carbon metabolism. Parenteral B 12 treatment increased [ ¹³ C]-propionate oxidation (14.9%, range 1.1 to 66.9) significantly and was also associated with significant alterations (p < 0.05) in B 12 , HoloTc, MMA, Hcy concentrations, cB 12, 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 B 12 deficiency and associated metabolites through omics-based approach.This study was registered in Clinical Trials Registry of India (CTRI) with the registration number CTRI/2018/04/012957 (registered on 03/04/2018), available from https://ctri.nic.in/Clinicaltrials/pmaindet2.php?EncHid=MjQwNDc=&Enc=&userName .
(© 2025. The Author(s).)

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BT/PR13918/PFN/20/1033/2015 Department of biotechnology, Delhi; IA/M/14/1/501681 Wellcome Trust/DBT India Alliance; IA/CRC/19/1/610006 Wellcome Trust DBT India Alliance

Keywords: Breath test; Functional deficiency; Metabolomics; Stable isotope; Vitamin B12

0 (Biomarkers)
P6YC3EG204 (Vitamin B 12)
8LL8S712J7 (Methylmalonic Acid)
0LVT1QZ0BA (Homocysteine)

Date Created: 20250705 Date Completed: 20250705 Latest Revision: 20250708

20250708

PMC12228825

10.1038/s41598-025-09110-y

40617951