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<p>Diagnosis of vitamin B<sub>12</sub> (B<sub>12</sub>) deficiency is hampered by the low specificity cut-offs of blood-based biomarkers, like serum B<sub>12</sub> and holo-transcobalamin (HoloTc), or B<sub>12</sub>-associated metabolites like methylmalonic acid (MMA) and homocysteine (Hcy) concentrations, or their combinations computed as combined B<sub>12</sub> (cB<sub>12</sub>). We assessed B<sub>12</sub> deficiency through non-invasive [<sup>13</sup>C]-propionate oxidation breath test to derive functional cut-off and tested its sensitivity in response to acute change in B<sub>12</sub> status in low B<sub>12</sub> adult male participants by parenterally administering 3&#xa0;mg hydroxocobalamin and profiling through untargeted and targeted B<sub>12</sub> related metabolites. The functional deficiency cut-off, based on a breakpoint analysis of [<sup>13</sup>C]-propionate oxidation with B<sub>12</sub> concentrations, was 144&#xa0;pmol/L [95% CI 106.4–182.4, <i>p</i> = 0.02] for B<sub>12</sub> deficiency. Untargeted metabolomic analyses revealed potential functional B<sub>12</sub> metabolites that are known to be associated with mitochondrial function, oxidative stress, lipids, bile acids and 1-carbon metabolism. Parenteral B<sub>12</sub> treatment increased [<sup>13</sup>C]-propionate oxidation (14.9%, range 1.1 to 66.9) significantly and was also associated with significant alterations (<i>p</i> &lt; 0.05) in B<sub>12</sub>, HoloTc, MMA, Hcy concentrations, cB<sub>12,</sub> 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<sub>12</sub> deficiency and associated metabolites through omics-based approach.</p><p>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 <a href="https://ctri.nic.in/Clinicaltrials/pmaindet2.php?EncHid=MjQwNDc=&amp;Enc=&amp;userName">https://ctri.nic.in/Clinicaltrials/pmaindet2.php?EncHid=MjQwNDc=&amp;Enc=&amp;userName</a>.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月5日

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  • Sarita Devi,
  • Roshni M. Pasanna,
  • Fathima Ayoob,
  • Harshpal Singh Sachdev,
  • Tinku Thomas,
  • Oliver Fiehn,
  • Anura V. Kurpad

摘要

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.

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.