Methylmalonic Acid as a Biomarker of Vitamin B12

A recent case study (L Jimenez et al. J Pediatr 2018; 192: 259-61) showed that methylamalonic acid (MMA) can be elevated in the absence of vitamin B12 deficiency.


  • Risk factors for vitamin B12 deficiency: terminal ileal resection and gastric acid blockade
  • Manifestations of vitamin B12 deficiency: megaloblastic anemia, bone marrow failure, demyelinating diseases, thrombosis, and psychiatric symptoms
  • Early assessment of vitamin B12 deficiency can be aided by MMA levels and homocysteine levels both of which are metabolized via vitamin B12-dependent pathways and are elevated in vitamin B12 deficiency.
  • MMA levels have higher sensitivity for vitamin B12 deficiency than vitamin B12 levels alone.

Key findings of this report:

  • In three children with short bowel syndrome, MMA levels were persistently elevated despite vitamin B12 supplementation and without other evidence of vitamin B12 deficiency
  • MMA levels declined after treatment of bacterial overgrowth
  • “It is hypothesized that propionate, a precursor to MMA, produced by excessive gut fermentation, is responsible for the elevation in plasma MMA levels.”

My take: this study is a good reminder of how MMA is useful in detecting vitamin B12 deficiency and points out that bacterial overgrowth may be an alternative explanation for elevated MMA levels.

Related blog posts:

Resources for Short Bowel Syndrome:

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications/diets (along with potential adverse effects) should be confirmed by prescribing physician/nutritionist.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

Bright Angel Trail, Grand Canyon

3 thoughts on “Methylmalonic Acid as a Biomarker of Vitamin B12

  1. Dr. Hochman: After reviewing the paper’s findings of persistently elevated MMA in several pediatric short gut patients, I concur that MMA remains the most clinically salient marker of Vitamin B12 status. However, we have noticed the same phenomenon in our intestinal rehab population at Children’s Healthcare of Atlanta: persistently elevated MMA in several patients despite chronic repletional therapy of at least 1 mg daily for up to 1 month (both parenterally and enterally). Evidently, little consensus exists in the pediatric intestinal rehab community regarding the appropriate B12 biomarkers to reliably monitor B12 status in a population with a high incidence of small bowel bacterial overgrowth. I conferred with Dr. Christoper Duggan, co-author of the cited paper, who reports continued use of serum Vitamin B12 as their preferred biomarker in the CAIR population at Boston Children’s. In the IROC program at Children’s, we are contemplating using both serum homocysteine and MMA to screen more reliably for vitamin B12 deficiency. If both are elevated, then repletional therapy appears indicated; if MMA elevated and homocysteine normal, then B12 status may be presumed normal, preventing unnecessary B12 repletional therapy under the presumption of bacterial overgrowth influence. Regardless, the study perfectly highlights the precariously unreliable state of most nutrition biomarkers and the need for a significant evolution in how we use and interpret them, hopefully in a more systematic fashion guided by groundbreaking work in transcriptomics, proteomics, and metabolomics.

  2. Pingback: Time to Revise ImproveCareNow Micronutrient Recommendations | gutsandgrowth

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