Definition and research guide
This page combines a MeSH definition, publication statistics and selected research abstracts. It is a starting point for reading the literature, not a medical textbook or a systematic evidence review.
Content available: 4 complete abstracts (742 words), 10 references. Full article text is not stored or reproduced here; follow the PMID, DOI or PMC links to read the original sources and their access terms.
Definition
A nutritional condition produced by a deficiency of vitamin B 12 in the diet, characterized by megaloblastic anemia. Since vitamin B 12 is not present in plants, humans have obtained their supply from animal products, from multivitamin supplements in the form of pills, and as additives to food preparations. A wide variety of neuropsychiatric abnormalities is also seen in vitamin B 12 deficiency and appears to be due to an undefined defect involving myelin synthesis. (From Cecil Textbook of Medicine, 19th ed, p848)
Definition: NLM Medical Subject Headings (MeSH) scope note (Public domain (U.S. National Library of Medicine); attribution requested). View the MeSH record.
Also known as: Deficiency, Vitamin B 12; Deficiency, Vitamin B12; Deficiencies, Vitamin B12; Vitamin B12 Deficiencies; Vitamin B12 Deficiency.
Where it fits in the MeSH classification
- Broader topics
- Vitamin B Deficiency
- Narrower topics
- Anemia, Pernicious; Subacute Combined Degeneration
Related concepts
Research landscape
PubMed indexes 12,419 records tagged with the MeSH heading “Vitamin B 12 Deficiency” (counts retrieved 2026-10-31). 1,197 of them (9.6%) were published from 2020 onward, and the busiest period so far is through 1999 with 7,769 records.
Reviews account for 1,364 records (11.0%) and meta-analyses for 46. Randomized controlled trials number 130 (1.0%) as a share of all records on the topic. Randomized trials make up only a small share of this literature, so much of what is known comes from laboratory, observational or descriptive work.
Show the data
| Period | Records |
|---|---|
| through 1999 | 7,769 |
| 2000-2009 | 1,555 |
| 2010-2019 | 1,898 |
| 2020 onward | 1,197 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 1,364 | 11.0% |
| Meta-analyses | 46 | 0.4% |
| Randomized controlled trials | 130 | 1.0% |
Method: PubMed query "Vitamin B 12 Deficiency"[MeSH Terms] with publication-type and date filters, retrieved 2026-10-31.
Reading the evidence in metabolism and endocrine disease
Studies of diabetes, obesity and hormone disorders often follow blood tests such as glucose, HbA1c or hormone levels, which are stand-ins for outcomes that matter more, such as complications. Lifestyle and diet research is largely observational, and weight and diabetes trials can differ in how long people were followed. Nothing on this page is advice about medicines, insulin or diet; talk to a qualified clinician about your own situation. Check whether the outcome was a lab value or a clinical event, and the type and duration of the condition studied.
Evidence from open-access studies
These open-access studies come from PubMed’s best-match results for this heading (papers whose main topic it is), ranked here by citation count, with one recent addition. Each abstract is reproduced in full under its recorded open licence so that you can read the authors’ own words. They illustrate the literature; they are not a systematic summary of it. Citation counts measure attention, not reliability or clinical benefit.
| Study / authors | Year | Source label / design | Europe PMC citations | Licence / source |
|---|---|---|---|---|
| B Vitamins and One-Carbon Metabolism: Implications in Human Health and Disease | 2020 | Review article Design not recorded in structured metadata | 315 | cc by PMID 32961717 · DOI · PMC7551072 |
| Low Vitamin B12 and Lipid Metabolism: Evidence from Pre-Clinical and Clinical Studies | 2020 | Review article Design not recorded in structured metadata | 74 | cc by PMID 32610503 · DOI · PMC7400011 |
| Vitamin B12 Deficiency and the Nervous System: Beyond Metabolic Decompensation-Comparing Biological Models and Gaining New Insights into Molecular and Cellular Mechanisms | 2024 | Review article Design not recorded in structured metadata | 70 | cc by PMID 38203763 · DOI · PMC10778862 |
| B Vitamin Deficiencies and Associated Neuropathies | 2026 | Review article Design not recorded in structured metadata | 8 | cc by PMID 41609902 · DOI · PMC12855320 |
B Vitamins and One-Carbon Metabolism: Implications in Human Health and Disease [1]
Abstract reading summary — source excerpts
- Opening excerpt
- Vitamins B9 (folate) and B12 are essential water-soluble vitamins that play a crucial role in the maintenance of one-carbon metabolism: a set of interconnected biochemical pathways driven by folate and methionine to generate methyl groups for use in DNA synthesis, amino acid homeostasis, antioxidant generation, and epigenetic regulation.
- Closing excerpt
- In this review, we will highlight recent studies aimed at elucidating the role of folate, B12, and methionine in one-carbon metabolism during normal cellular processes and in the context of disease progression.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (176 words)
Vitamins B9 (folate) and B12 are essential water-soluble vitamins that play a crucial role in the maintenance of one-carbon metabolism: a set of interconnected biochemical pathways driven by folate and methionine to generate methyl groups for use in DNA synthesis, amino acid homeostasis, antioxidant generation, and epigenetic regulation. Dietary deficiencies in B9 and B12, or genetic polymorphisms that influence the activity of enzymes involved in the folate or methionine cycles, are known to cause developmental defects, impair cognitive function, or block normal blood production. Nutritional deficiencies have historically been treated with dietary supplementation or high-dose parenteral administration that can reverse symptoms in the majority of cases. Elevated levels of these vitamins have more recently been shown to correlate with immune dysfunction, cancer, and increased mortality. Therapies that specifically target one-carbon metabolism are therefore currently being explored for the treatment of immune disorders and cancer. In this review, we will highlight recent studies aimed at elucidating the role of folate, B12, and methionine in one-carbon metabolism during normal cellular processes and in the context of disease progression.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 32961717 · DOI · PMC7551072
Low Vitamin B12 and Lipid Metabolism: Evidence from Pre-Clinical and Clinical Studies [2]
Abstract reading summary — source excerpts
- Opening excerpt
- Obesity is a worldwide epidemic responsible for 5% of global mortality.
- Closing excerpt
- Although, there are only a few association studies of B12 on epigenetic mechanisms, novel approaches to understand the functional changes caused by these epigenetic markers are warranted.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (224 words)
Obesity is a worldwide epidemic responsible for 5% of global mortality. The risks of developing other key metabolic disorders like diabetes, hypertension and cardiovascular diseases (CVDs) are increased by obesity, causing a great public health concern. A series of epidemiological studies and animal models have demonstrated a relationship between the importance of vitamin B12 (B12) and various components of metabolic syndrome. High prevalence of low B12 levels has been shown in European (27%) and South Indian (32%) patients with type 2 diabetes (T2D). A longitudinal prospective study in pregnant women has shown that low B12 status could independently predict the development of T2D five years after delivery. Likewise, children born to mothers with low B12 levels may have excess fat accumulation which in turn can result in higher insulin resistance and risk of T2D and/or CVD in adulthood. However, the independent role of B12 on lipid metabolism, a key risk factor for cardiometabolic disorders, has not been explored to a larger extent. In this review, we provide evidence from pre-clinical and clinical studies on the role of low B12 status on lipid metabolism and insights on the possible epigenetic mechanisms including DNA methylation, micro-RNA and histone modifications. Although, there are only a few association studies of B12 on epigenetic mechanisms, novel approaches to understand the functional changes caused by these epigenetic markers are warranted.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 32610503 · DOI · PMC7400011
Vitamin B12 Deficiency and the Nervous System: Beyond Metabolic Decompensation-Comparing Biological Models and Gaining New Insights into Molecular and Cellular Mechanisms [3]
Abstract reading summary — source excerpts
- Opening excerpt
- Vitamin B12 (VitB12) is a micronutrient and acts as a cofactor for fundamental biochemical reactions: the synthesis of succinyl-CoA from methylmalonyl-CoA and biotin, and the synthesis of methionine from folic acid and homocysteine.
- Closing excerpt
- Consequently, a complex biological landscape emerges, requiring further investigative efforts to grasp the intricacies involved and identify potential therapeutic targets.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (199 words)
Vitamin B12 (VitB12) is a micronutrient and acts as a cofactor for fundamental biochemical reactions: the synthesis of succinyl-CoA from methylmalonyl-CoA and biotin, and the synthesis of methionine from folic acid and homocysteine. VitB12 deficiency can determine a wide range of diseases, including nervous system impairments. Although clinical evidence shows a direct role of VitB12 in neuronal homeostasis, the molecular mechanisms are yet to be characterized in depth. Earlier investigations focused on exploring the biochemical shifts resulting from a deficiency in the function of VitB12 as a coenzyme, while more recent studies propose a broader mechanism, encompassing changes at the molecular/cellular levels. Here, we explore existing study models employed to investigate the role of VitB12 in the nervous system, including the challenges inherent in replicating deficiency/supplementation in experimental settings. Moreover, we discuss the potential biochemical alterations and ensuing mechanisms that might be modified at the molecular/cellular level (such as epigenetic modifications or changes in lysosomal activity). We also address the role of VitB12 deficiency in initiating processes that contribute to nervous system deterioration, including ROS accumulation, inflammation, and demyelination. Consequently, a complex biological landscape emerges, requiring further investigative efforts to grasp the intricacies involved and identify potential therapeutic targets.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 38203763 · DOI · PMC10778862
B Vitamin Deficiencies and Associated Neuropathies [4]
Abstract reading summary — source excerpts
- Opening excerpt
- Purpose of reviewThis review examines both historical and recent evidence to clarify the current understanding of the relationship between B vitamin deficiencies and neuropathies.
- Closing excerpt
- In developed countries, factors like alcohol consumption, bariatric surgery, and metformin use are increasing these deficiencies in clinical practice.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (143 words)
Purpose of reviewThis review examines both historical and recent evidence to clarify the current understanding of the relationship between B vitamin deficiencies and neuropathies.Recent findingsVitamin B1 (thiamine) deficiency can lead to neurological disorders such as beriberi and Wernicke's encephalopathy, conditions with significant prevalence and mortality rates. Vitamin B12 (Cobalamin) is crucial for DNA synthesis, fatty acid metabolism, and myelin production, with its deficiency leading to neuropathies and cognitive disorders. Excess vitamin B6 (pyridoxine), rather than deficiency, appears to be associated with neuropathy.Takeaways/conclusionsVitamin B1 and B12 deficiencies are linked to classic neuropathies, while the connection between vitamin B6 deficiency and neuropathy is less clear, though excess B6 is associated with neurotoxicity. Nutritional deficiencies are less common in developed countries but remain significant in developing nations. In developed countries, factors like alcohol consumption, bariatric surgery, and metformin use are increasing these deficiencies in clinical practice.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 41609902 · DOI · PMC12855320
Key reviews and meta-analyses
The most cited review-type papers among PubMed’s best-match results for this heading, listed with bibliographic details only. Follow the links for the full text and access terms.
- Research article Clinical practice. Vitamin B12 deficiency [5]
- Research article Vitamin B12 deficiency [6]
- Research article How common is vitamin B-12 deficiency? [7]
- Research article Vitamin B12 , folate, and the methionine remethylation cycle-biochemistry, pathways, and regulation [8]
- Research article Pernicious anemia [9]
- Research article Vitamin B12 in health and disease [10]
References
- Lyon P, Strippoli V, Fang B, Cimmino L. B Vitamins and One-Carbon Metabolism: Implications in Human Health and Disease. . 2020. PMID 32961717 · DOI · PMC7551072
- Boachie J, Adaikalakoteswari A, Samavat J, Saravanan P. Low Vitamin B12 and Lipid Metabolism: Evidence from Pre-Clinical and Clinical Studies. . 2020. PMID 32610503 · DOI · PMC7400011
- Mathew AR, Di Matteo G, La Rosa P, Barbati SA, Mannina L, Moreno S, et al.. Vitamin B12 Deficiency and the Nervous System: Beyond Metabolic Decompensation-Comparing Biological Models and Gaining New Insights into Molecular and Cellular Mechanisms. . 2024. PMID 38203763 · DOI · PMC10778862
- Alvarez M, Poveda S, Cisneros A, Parra D, Luna M, Rincón O, et al.. B Vitamin Deficiencies and Associated Neuropathies. . 2026. PMID 41609902 · DOI · PMC12855320
- Stabler SP. Clinical practice. Vitamin B12 deficiency. N Engl J Med. 2013. PMID 23301732 · DOI
- Green R, Allen LH, Bjørke-Monsen AL, Brito A, Guéant JL, Miller JW, et al.. Vitamin B12 deficiency. Nat Rev Dis Primers. 2017. PMID 28660890 · DOI
- Allen LH. How common is vitamin B-12 deficiency?. Am J Clin Nutr. 2009. PMID 19116323 · DOI
- Froese DS, Fowler B, Baumgartner MR. Vitamin B12 , folate, and the methionine remethylation cycle-biochemistry, pathways, and regulation. J Inherit Metab Dis. 2019. PMID 30693532 · DOI
- Toh BH, van Driel IR, Gleeson PA. Pernicious anemia. N Engl J Med. 1997. PMID 9358143 · DOI
- O'Leary F, Samman S. Vitamin B12 in health and disease. Nutrients. 2010. PMID 22254022 · DOI · PMC3257642
About this article
- Sources
- NLM Medical Subject Headings (definition, synonyms); NCBI PubMed (counts, identifiers); Europe PMC (open-access abstracts and citation counts).
- Verification
- Every reference was resolved against PubMed on 2026-11-04; title, year and DOI matched.
- Review state
- automated source verified; no human expert review has been recorded yet.
- Version
- 1, last updated 2026-11-04.
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Evidence strength
EvidenceHelix's computed view of the study designs behind this topic: how common meta-analyses, randomized trials and reviews are, how recent the literature is, and a plain-language reading. It describes the design mix of the literature. It is not a quality appraisal of any study, and it is not medical advice.