Publications

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 .