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)

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Main uses

Autoimmune conditions (Celiac’s disease)
B12 deficiency prevention
Homocysteine management
Neurological conditions
Neuropathy and pain-related conditions


2-5% bioavailability (1,000 μg hydroxocobalamin) compared to intramuscular administration but retention is 50% higher (29)(31)
10-20x higher plasma B12 with nasal hydroxocobalamin (750-1,500 μg) than oral administration (31)
2% bioavailability, 5% bioavailability (5,000 μg cyanocobalamin) in formulation with the addition of SNAC at compared to intravenous administration (6)
Equivalent retention between forms of varying doses of cyanocobalamin, methylcobalamin, & hydroxocobalamin (1, 5, & 25 μg) (1)
B12 increased more in hydroxocobalamin (500-1,000 μg) than cyanocobalamin via 33-44% higher relative retention (12)
Equal increase in serum cobalamin to the oral group (500 μg cyanocobalamin) (25)

Dosing & administration

Adverse effects

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)


  • B12 is primarily excreted in stool, but can be excreted in urine if blood is saturated. (16)
  • Between 1.4-5.1 μg are lost each day in healthy and elderly individuals. (10)