II. Physiology
- Background
- B12 functional roles- Neurologic function- Vitamin B12 Deficiency results in Peripheral Neuropathy, Cognitive Impairment, gait Impairment
 
- Red Blood Cell production- Vitamin B12 Deficiency results in Macrocytic Anemia (as well as Pancytopenia)
 
- DNA Synthesis
 
- Neurologic function
- B12 dependent reactions in humans- Methylmalonic acid converted to succinyl-CoA- Succinyl-CoA is part of Kreb Cycle in Glycolysis
 
- Homocysteine converted to Methionine (methylation reaction)- Methionine is an Essential Amino Acid, and important for Angiogenesis
 
- 5-Methyltetrahydrofolate converted to Tetrahydrofolate- Required for DNA synthesis and RBC production
 
 
- Methylmalonic acid converted to succinyl-CoA
- Normal B12 absorption pathway- Requires ingestion (animal source or fortified cereal) as cannot be synthesized in humans- Vitamin B12 is sythesized by Microorganisms in the Intestine
 
- Acidic Stomach environment breaks down Protein-bound B12- Insufficient acid decreases B12 absorption
- Proton Pump Inhibitors suppress B12 absorption
 
- Intrinsic Factor (IF) binds B12 in duodenum- Intrinsic Factor produced in Stomach parietal cells
- Pernicious Anemia is autoimmune parietal cell death
- Insufficient IF results in decreased B12 absorption
 
- Vitamin B12 absorption via 2 pathways- Primary B12 absorption (from ingested fish, meat and dairy products)- Vitamin B12 with Intrinsic Factor absorbed in terminal ileum
- Vitamin B12 dissociates from Intrinsic Factor in erythrocytes
- Vitamin B12 enters portal circulation and binds Transcobalamin II (and haptocorin)- Transcobalamin II is the active form (20% of Vitamin B12)
- Haptocorin is the inactive form (80% of Vitamin B12)
 
 
- Alternate B12 absorption- Pathway independent of Intrinsic Factor and ileum
- Absorption of up to 1% of large oral B12 dose
- Allows for oral B12 supplementation
 
 
- Primary B12 absorption (from ingested fish, meat and dairy products)
- Vitamin B12 storage- Unlike other water soluble Vitamins, the body has capacity to store large quantities of Vitamin B12
- Vitamin B12 is stored primarily in the liver
- Large hepatic stores may delay B12 Vitamin Deficiency presentation more than 5 years
 
 
- Requires ingestion (animal source or fortified cereal) as cannot be synthesized in humans
III. Complications: Vitamin B12 Disorders
- Vitamin B12 Deficiency (<180-350 pg/ml or <133-258 pmol/L)
- Vitamin B12 Elevated Levels (persistently >1000 pg/ml or >738 pmol/L)- Associated with solid cancers such as Liver, Kidney, Breast or gastrointestinal (HR 5.9)- Also associated with CML, myeloproliferative disorders, Polycythemia Vera
- Lacombe (2021) Sci Rep 11(1): 13361 [PubMed]
 
- Associated with increased Cardiovascular mortality (HR 1.45)
 
- Associated with solid cancers such as Liver, Kidney, Breast or gastrointestinal (HR 5.9)
IV. Sources: Animal sources only
- High Level B12 Sources- Beef Liver (3 oz contains 70 mcg B12, most of any source)
- Clams and oysters (3 oz contains 15-17 mcg B12, second most significant source)
 
- Moderate Level B12 Sources- Fish (e.g. Salmon, Canned tuna, 3 oz contains 2.5-2.6 mcg B12)
- Muscle Meats (e.g. ground beef, 3 oz contains 2.4 mcg B12)
- Milk and other dairy products (e.g. Yogurt, 6-8 oz contains 1.0-1.3 mcg B12)
 
- Low Level B12 Sources- Vitamin B12 fortified foods (e.g. Cereals, 1 serving contains 0.6 mcg B12)
- Eggs (large egg contains 0.5 mcg B12)
- Turkey Breast (3 oz contains 0.3 mcg B12)
 
V. Dosing
- See Vitamin B12 Supplementation
- Recommended daily allowance: 2.4 mcg/day
- Elderly, Vegans:- B12 Fortified foods (Cereals)
- Daily dietary supplement up to Vitamin B12 1000 mcg orally daily
 
VI. Resources
- Vitamin B12 - Health Professional (NIH)
VII. 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]
Images: Related links to external sites (from Bing)
Related Studies
| cyanocobalamin (on 12/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing) | ||
| CYANOCOBALAMIN 1,000 MCG/ML VL | Generic | $3.08 per ml | 
| CYANOCOBALAMIN 10,000 MCG/10 ML | Generic | $3.68 per ml | 
| CYANOCOBALAMIN 30,000 MCG/30 ML | Generic | $0.97 per ml | 
