The DOI matches its Crossref record; 38 of the 38 references it cites were found in a registry or an index.
Vitamin B 12 -Folate Interrelationships
Abstract
The studies discussed in this review support the view that biochemical and clinical symptoms common to both folate and vitamin B12 deficiency are due to the induction of a functional folate deficiency, which in turn is induced by cobalamin deprivation. The interrelationship between these two vitamins is best explained by the methyl trap hypothesis stating that vitamin B12 deficiency can lead to lowered levels of methionine synthetase, which results in a functional folate deficiency by trapping an increased proportion of folate as the 5-methyl derivative. In addition, as 5-methyl-H4PteGlu is a poor substrate for folylpolyglutamate synthetase, there is a decreased synthesis of folylpolyglutamates and consequently a decreased retention of folates by tissues. The real folate deficiency that ensues because of decreased tissue folate levels is probably as important physiologically as the functional deficiency caused by the methyl trap. The sparing effect of methionine can be explained by adenosylmethionine inhibition of methylenetetrahydrofolate reductase, which would prevent the buildup of 5-methyl-H4PteGlun. A deficiency in vitamin B12 would not, in itself, be sufficient to cause a disturbance in folate metabolism. The deficiency would have to result in lowered methyltransferase levels before any such disturbance would be manifest.
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“Vitamin B-12 is also important for intracellular energy production and the generation of methionine, which is needed to produce neurotransmitters and myelin (7).”
From Vitamin B-12 status in infancy is positively associated with development and cognitive functioning 5 y later in Nepalese children (2017) · cites this paper as [7]
Citations
Cites
Deranged DNA Synthesis by Bone Marrow from Vitamin B12‐Deficient Humans*
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Inactivation of Methionine Synthetase by Nitrous Oxide in Mice
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Trüeb, R. M. (2025) · Springer eBooks · doi:10.1007/978-3-031-72154-0_5
Nieman, K. M. (2008) · Iowa State University Digital Repository (Iowa State University) · doi:10.31274/rtd-180813-16917
Jungert, A., Zenke‐Philippi, C., & Neuhäuser‐Berthold, M. (2020) · Figshare · doi:10.6084/m9.figshare.12606916
Jungert, A., Zenke‐Philippi, C., & Neuhäuser‐Berthold, M. (2020) · Figshare · doi:10.6084/m9.figshare.12606913
Pabst, F. R., Tvardovskiy, A., Estibariz, I., Finazzi, V., Couacault, P., Artati, A., Witting, M. A., Scialdone, A., Bartke, T., Schneider, R., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2025.12.19.695597
Yang, J. G., Law, S., Ou, C., Dong, S., Huang, S., Dong, Z., Zhu, M.-S., & Wang, C. (2026) · Obesity Surgery · doi:10.1007/s11695-026-08761-8
Metadata
- Authors
- Shane, B., & Stokstad, E. L. R.
- ORCID
- Shane, Barry
- Venue
- Annual Review of Nutrition
- Publisher
- Annual Reviews
- Published
- 1985-07
- Volume
- 5
- Issue
- 1
- Pages
- 115-141
- ISSN
- 0199-9885 (ISSN-L)
- 1545-4312
- OpenAlex
- W2146178648
- Cited by
- 311
- References
- 38
- Citations by year
- 2026: 4 · 2025: 14 · 2024: 10 · 2023: 7 · 2022: 7 · 2021: 7 · 2020: 12 · 2019: 14 · 2018: 13 · 2017: 8 · 2016: 10 · 2015: 12 · 2014: 6 · 2013: 16 · 2012: 5
- FWCI
- 4.78
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annual Review of Nutrition (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01am008171-22)
- National Cancer Institute (CA-00697, CA 22717)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Folate and B Vitamins Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Porphyrin Metabolism and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Keywords
- vitamin B12, folic acid, vitamin B12 deficiency, methionine synthase, 5-methyltetrahydrofolate, folylpolyglutamate synthetase, folate retention, adenosylmethionine, methylenetetrahydrofolate reductase, folate metabolism, methyltransferase
- MeSH terms
- Amino Acids, Animals, Bone Marrow, Folic Acid, Folic Acid Deficiency, Formates, Formiminoglutamic Acid, Histidine, Homeostasis, Humans, Liver, Megaloblasts, Methionine, Methylation, Nitrous Oxide, Peptide Synthases, Pteroylpolyglutamic Acids, Purines, Serine, 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase, Thymidine Monophosphate, Thymidylate Synthase, Thyroid Gland, Vitamin B 12, Vitamin B 12 Deficiency
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