Both vitamin B9 (folate) and vitamin B12 (cobalamin) are nutritionally essential to support optimal human health and development. Folate is involved in many one-carbon transfer reactions, including the methylation of important biomolecules (lipids, amino acids, and DNA). Folate deficiency leads to pathological outcomes, including anemia and impairment of reproductive health and fetal development. Impaired folic acid status is also associated with an increased prevalence of neural tube defects (NTDs) in babies.

Vitamin B12 deficiency presents with non-specific clinical features and, in severe cases, can present with neurological or hematological abnormalities. Although classically caused by pernicious anemia, this is now only a minority of cases, and vitamin B12 deficiency occurs most often due to malabsorption of food-bound cobalamin. Since missing the diagnosis can lead to potentially severe complications, including spinal cord degeneration and pancytopenia.

There is a close relationship between the metabolism of the two vitamins. Deficiencies of vitamin B12 and folate and associated inborn errors of metabolism may lead to similar megaloblastic anemias and overlapping neuropsychiatric complications. Folate and vitamin B12 have fundamental roles in CNS function at all ages, and a key interaction is that between vitamin B12 and folate in the synthesis of methionine from homocysteine by methionine synthase, in which both 5-methyl-tetrahydrofolate and methyl-vitamin-B12 are cofactors, which is essential for nucleotide synthesis and genomic and non-genomic methylation (as shown in the figure below). Vitamin B12 and folate may have a role in the prevention of central nervous system developmental disorders, mood disorders, and dementia, including Alzheimer’s disease and vascular dementia in elderly people.

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