Vitamin B12

See Also

Physiology

Background
1. Vitamin B12 is a water soluble Vitamin
2. Porphyrin ring similar to heme, but contains a central cobalt instead of iron
B12 functional roles
1. Neurologic function
  1. Vitamin B12 Deficiency results in Peripheral Neuropathy, Cognitive Impairment, gait Impairment
2. Red Blood Cell production
  1. Vitamin B12 Deficiency results in Macrocytic Anemia (as well as Pancytopenia)
3. DNA Synthesis
B12 dependent reactions in humans
1. Methylmalonic acid converted to succinyl-CoA
  1. Succinyl-CoA is part of Kreb Cycle in Glycolysis
2. Homocysteine converted to Methionine (methylation reaction)
  1. Methionine is an Essential Amino Acid, and important for Angiogenesis
3. 5-Methyltetrahydrofolate converted to Tetrahydrofolate
  1. Required for DNA synthesis and RBC production
Normal B12 absorption pathway
1. Requires ingestion (animal source or fortified cereal) as cannot be synthesized in humans
  1. Vitamin B12 is sythesized by Microorganisms in the Intestine
2. Acidic Stomach environment breaks down Protein-bound B12
  1. Insufficient acid decreases B12 absorption
  2. Proton Pump Inhibitors suppress B12 absorption
3. Intrinsic Factor (IF) binds B12 in duodenum
  1. Intrinsic Factor produced in Stomach parietal cells
  2. Pernicious Anemia is autoimmune parietal cell death
  3. Insufficient IF results in decreased B12 absorption
4. Vitamin B12 absorption via 2 pathways
  1. Primary B12 absorption (from ingested fish, meat and dairy products)
    1. Vitamin B12 with Intrinsic Factor absorbed in terminal ileum
    2. Vitamin B12 dissociates from Intrinsic Factor in erythrocytes
    3. Vitamin B12 enters portal circulation and binds Transcobalamin II (and haptocorin)
      1. Transcobalamin II is the active form (20% of Vitamin B12)
      2. Haptocorin is the inactive form (80% of Vitamin B12)
  2. Alternate B12 absorption
    1. Pathway independent of Intrinsic Factor and ileum
    2. Absorption of up to 1% of large oral B12 dose
    3. Allows for oral B12 supplementation
5. Vitamin B12 storage
  1. Unlike other water soluble Vitamins, the body has capacity to store large quantities of Vitamin B12
  2. Vitamin B12 is stored primarily in the liver
  3. Large hepatic stores may delay B12 Vitamin Deficiency presentation more than 5 years

Complications
Vitamin B12 Disorders

Vitamin B12 Deficiency (<180-350 pg/ml or <133-258 pmol/L)
1. See Vitamin B12 Deficiency
2. Megaloblastic Macrocytic Anemia
Vitamin B12 Elevated Levels (persistently >1000 pg/ml or >738 pmol/L)
1. Associated with solid cancers such as Liver, Kidney, Breast or gastrointestinal (HR 5.9)
  1. Also associated with CML, myeloproliferative disorders, Polycythemia Vera
  2. Lacombe (2021) Sci Rep 11(1): 13361 [PubMed]
2. Associated with increased Cardiovascular mortality (HR 1.45)
  1. Wolffenbuttel (2020) BMC Med 18(1): 307 [PubMed]

Sources
Animal sources only

High Level B12 Sources
1. Beef Liver (3 oz contains 70 mcg B12, most of any source)
2. Clams and oysters (3 oz contains 15-17 mcg B12, second most significant source)
Moderate Level B12 Sources
1. Fish (e.g. Salmon, Canned tuna, 3 oz contains 2.5-2.6 mcg B12)
2. Muscle Meats (e.g. ground beef, 3 oz contains 2.4 mcg B12)
3. Milk and other dairy products (e.g. Yogurt, 6-8 oz contains 1.0-1.3 mcg B12)
Low Level B12 Sources
1. Vitamin B12 fortified foods (e.g. Cereals, 1 serving contains 0.6 mcg B12)
2. Eggs (large egg contains 0.5 mcg B12)
3. Turkey Breast (3 oz contains 0.3 mcg B12)

Dosing

See Vitamin B12 Supplementation
Recommended daily allowance: 2.4 mcg/day
Elderly, Vegans:
1. B12 Fortified foods (Cereals)
2. Daily dietary supplement up to Vitamin B12 1000 mcg orally daily

Resources

Vitamin B12 - Health Professional (NIH)
1. https://ods.od.nih.gov/factsheets/VitaminB12-HealthProfessional/

References

Babior in Wilson (1991) Harrisons, McGraw, p. 1523-9
Rendon et al. (2017) Crit Dec Emerg Med 31(6): 15-21
Oh (2003) Am Fam Physician 67(5):979-86 [PubMed]
Patel (2025) Am Fam Physician 112(3): 294-300 [PubMed]