Ingredient review —Vitamin B12
What is it?
Vitamin B12 is an essential water-soluble nutrient that can be converted to the active coenzymes, methylcobalamin and adenosylcobalamin. It is also a cofactor for methionine synthase and l-methylmalonyl-CoA mutase, which synthesize methionine from homocysteine, and convert methylmalonyl coenzyme A to succinyl coenzyme A, respectively. It is crucial for the formation of DNA and red blood cells, and proper neurological function. (16)(18)(34)
Dosing & administration
Adverse effects from B12 intake and supplementation are atypical. (16) Intravenous administration may produce reddening of the skin, pustular/papular rash, headaches, erythema at the injection site, decrease in lymphocyte percentage, nausea, pruritus, chest discomfort, dysphagia, and increased blood pressure in some volunteers. (30)
- Oral absorption is low. Total B12 absorption increases with increasing doses, but relative absorption decreases (eg. absorption of 50% of 1 μg, 20% of 5 μg, 5% of 25 μg, and 1% 500 μg). Small amounts absorbed are often sufficient to meet the recommended daily allowance.
- B12 bound to proteins in food are uncoupled by stomach acid and pepsin to allow for binding to R proteins. B12 supplements are not bound to proteins and thus more available for R protein binding for gastric transport.
- Upon contact with pancreatic proteases, B12 is released from R proteins, and small amounts of free B12 in high concentrations can be absorbed through passive diffusion in the small intestine. In low concentrations, the majority of B12 binds to intrinsic factor allowing active transport in the mucosa of the ileum. (23)
- B12 circulates through the blood after binding to transcobalamin I, II, or III.
- Most is bound to transcobalamin I but transcobalamin II is primarily responsible for deposition in most peripheral tissues.
- The liver stores 50% of circulating B12 and may hold 2-3 mg. (16)
- Upon transport into peripheral tissue cells, lysosomes disassociate B12 from transcobalamin II.
- All B12 forms are then reduced in cytosol to the core form, cobalamin.
- Cobalamin is either methylated to the active cofactor, methylcobalamin, using 5-MTHF or SAMe, or it can enter the mitochondria to combine with adenosyl from ATP molecules to form the active cofactor, adenosylcobalamin. (23)
- Methylcobalamin and vitamin B6 are used to reduce homocysteine and produce methionine, tetrahydrofolate, and subsequently, purines and pyrimidines used in RNA and DNA synthesis. (17)(19)(26)
- Adenosylcobalamin is used by methylmalonyl CoA mutase to convert methylmalonyl CoA to Succinyl CoA, which enters the Krebs cycle. (23)
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