Vitamin B12

What it is

Vitamin B12 (cobalamin) is a water-soluble B-vitamin found naturally in animal-derived foods (meat, fish, eggs, dairy) and in some fortified plant foods or supplements. Chemically, it is a cobalt-containing coenzyme that exists in several active forms in the body, most importantly methylcobalamin and adenosylcobalamin.

How it works

B12 acts as a cofactor for two essential enzymes:

1. Methionine synthase (in cytosol): This enzyme converts homocysteine into methionine, which is needed to generate S-adenosyl-methionine (SAMe)—a universal methyl donor used for DNA methylation, neurotransmitter synthesis, and lipid metabolism in the nervous system.
2. Methylmalonyl-CoA mutase (in mitochondria): This enzyme converts methylmalonyl-CoA to succinyl-CoA, a TCA cycle intermediate used for energy production and heme synthesis. Impairment causes buildup of methylmalonic acid, which injures myelin.

Through these roles, B12 is pivotal for red blood cell maturation, genomic integrity, mitochondrial energy metabolism, and maintenance of myelin in the brain and peripheral nerves.

Why it’s important

Adequate B12 status supports:

• Hematologic health — Prevents megaloblastic (macrocytic) anemia by enabling proper DNA replication in erythroblasts.
• Neurological integrity — Maintains myelin and supports neurotransmitter synthesis; deficiency can cause paresthesias, ataxia, cognitive decline, mood changes, and in advanced cases permanent nerve damage.
• Cardiometabolic function — Helps keep homocysteine in check; hyperhomocysteinemia is associated with endothelial injury and higher vascular risk.
• DNA stability and cell turnover — Required for methylation reactions that regulate gene expression and repair.

Considerations

• Absorption complexity: B12 absorption requires stomach acid (to liberate B12 from food proteins), intrinsic factor from the stomach (to chaperone uptake in the terminal ileum), and a healthy ileal mucosa. Many people with “normal” diets can still become deficient because of impaired absorption (e.g., atrophic gastritis, bariatric surgery, ileal disease, metformin, H2 blockers/PPIs).
• Dietary restriction: Strict vegans and some vegetarians are at especially high risk unless they use fortified foods or supplementation.
• Subclinical deficiency is common: Serum B12 alone can be misleading; functional markers such as methylmalonic acid (MMA) and homocysteine are more sensitive when clinical suspicion is high.
• Supplement forms and routes: Oral, sublingual, or parenteral (intramuscular/subcutaneous) routes can all be effective; injections are preferred when malabsorption is present or when rapid repletion is needed. Methylcobalamin and adenosylcobalamin are biologically active forms; cyanocobalamin is stable and effective for most people.
• Safety: B12 has extremely low toxicity; excess is excreted in urine. Caution is mainly about diagnosing and treating deficiency in time. Rarely, very high B12 levels may reflect underlying disease (e.g., liver disease, myeloproliferative disorders) rather than high intake.