Vitamin B 12 -Folate Interrelationships

Shane, Barry; Stokstad, E. L. Robert

doi:10.1146/annurev.nu.05.070185.000555

Cited by 313Folate and B Vitamins ResearchPorphyrin Metabolism and DisordersMetabolism and Genetic Disorders

Vitamin B 12 -Folate Interrelationships

Shane, Barry, Stokstad, E. L. Robert·1985·Annual Review of Nutrition

DOI 10.1146/annurev.nu.05.070185.000555

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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 important for intracellular energy production and the generation of methionine, which is needed to produce neurotransmitters and myelin.
“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]

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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
DOI: 10.1146/annurev.nu.05.070185.000555
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 › Medicine › Rheumatology › 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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Vitamin B 12 -Folate Interrelationships

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