Methylmalonic Acid as a biomarker for an early diagnosis of vitamin B12 deficiency in vegetarians
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2025-11-07
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Abstract
Introduction: Vitamin B12 (cobalamin) is an essential nutrient involved in DNA synthesis, red blood cell formation, and neurological function. Since it is found almost exclusively in animal derived foods, vegetarians, mostly vegans, are at increased risk of deficiency. Early detection is crucial to prevent irreversible complications, yet the most commonly used test, serum B12 levels, often fail to detect functional deficiency in its early stages. Methylmalonic acid (MMA), a functional biomarker that accumulates when B12-dependent pathways are disrupted, has been proposed as a more sensitive indicator of early deficiency.
Methods: This scoping review was conducted in accordance with the Manual for Evidence Synthesis proposed by the Joanna Briggs Institute and the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) Checklist. The articles used for this review were from PubMed, Scopus, LILACS, and Access Medicine databases, and the MeSH descriptors that were related to “methylmalonic acid”, “vitamin B12 deficiency”, and “vegetarians”. The studies that used MMA as a biomarker to detect B12 deficiency in vegetarian and non-vegetarian populations, without restrictions on age or study design, were included in the present review. And, the data extraction and screening was done by two reviewers, before the results and main finding were summarized.
Results: 20 studies met the criteria of inclusion out of 184 articles that were originally found. Most of them performed their study in countries like Germany, India, Nepal, Spain, China and others which were not as often repeated. Mainly the population leaned towrds comparing vegetarins, some including and distinguishing between those and vegans, and a control group that were omnivores, but also other participants included pregnant women, infants, and elderly. All the articles included in this review used MMA as a functional biomarker for B12 deficiency, and it was found elevaleted in those who followed a plant-based diet, specifically those that were vegans or stricter, even tho when tested the serum B12 it appeared to be normal.
Conclusion: It was shown that MMA was more sensible in order to detect an early deficiency in cobalamin, especially in populations like vegetarians and elderly, where the serum B12 alone may have not been enough to detect at an early stage to mitigate the sometimes fatal and irreversible damages caused by its deficiency. Its role as a functional biomarker makes it a valuable tool in clinical assessment. However, factors like cost and renal function should be considered when interpreting results. MMA is best utilized in combination with other biomarkers as part of an integrated diagnostic strategy for more accurate and early identification of B12 deficiency.
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Avitaminosis, Cobalamin, Homocysteine, Megaloblastic Anemia, Plant-Based Diet