CYANOCOBALAMIN (VITAMIN B12) – Absorption of B12, Etiology of Vitamin B12 Deficiency, Effects of B12 Deficiency and Treatment
Deficiency of vitamin B12 or folates leads to abnormality in DNA synthesis, characterized by megaloblastic erythropoiesis and similar changes in many tissues in the body. Due to its fatal outcome in pre-vitamin B12 days, it was called pernicious anemia.
Absorption of B12
The dietary vitamin B12 which is bound to proteins has to be liberated from them to enable absorption. Cooking converts a part of these into dialysable form. Low pH achieved in the stomach helps further liberation of this vitamin. After liberation, cobalamin is bound to the intrinsic factor (IF) which is a glycoprotein with a molecular weight of 44,000 present in the gastric juice. Proteolytic enzymes of the pancreas play a part in this process.
The vitamin B12-IF complex is taken up by receptor sites present in the microvilli of the ileum by passive absorption. In the plasma cyanocobalamin remains bound to a polypeptide of molecular weight 38,000 known as transcobalamin II (TC II). This complex passes into cells and its B12 is liberated by lysosomal enzymes. Liver can store up to 2 mg of vitamin B12 which is adequate for several years. The daily requirement of B12 is 1-2 mcg.
Meat, liver, eggs, dairy products, and yeast contain adequate amounts of this vitamin. Purely vegetable sources are deficient in vitamin B12. Therefore, vegans (persons who do not take any form of animal foods or dairy products) suffer from nutritional deficiency. Normal levels of vitamin B12 in serum ranges from 120-900 pg/mL in Indian subjects.
Vitamin B12 deficiency is less common than folate deficiency.
Etiology of Vitamin B12 Deficiency
1. Malabsorption states—diseases of the ileum.
2. Dietary inadequacy—vegans.
3. Intrinsic factor deficiency—pernicious anemia. This
is usually acquired, rarely this may be congenital.
4. Chronic disorders destroying the gastric mucosa and partial or total gastrectomy.
5. Blind loop syndromes-with colonization of the small intestine by bacteria.
6. Pancreatic insufficiency.
7. Familial deficiency of transcobalamin II.
8. Inherited disorders of vitamin B12 metabolism.
9. Interference with absorption of vitamin B12 by drugs, e.g. PAS, colchicine, phenformin, neomycin.
Effects of B12 Deficiency
Megaloblastic anemia develops owing to diminished red cell production and dyserythropoiesis. In addition, cells from other organs with rapid cell turnover such as the gastrointestinal tract and cervicovaginal mucosa also show similar abnormalities. The central nervous system and peripheral nerves are also affected. The neurological lesions include subacute combined degeneration of the spinal cord, optic neuritis, and demyelination of the cerebral white matter and peripheral nerves.
Neurological damage occurs due to impaired DNA synthesis and myelin formation. The occurrence of neuropathy does not bear any direct relationship to the severity of anemia.
Treatment
Dietary deficiency can be corrected by giving 1-2 μg of vitamin B12 orally. If megaloblastic anemia has developed, larger doses are required (100 μg/day) oral, if absorption is reliable. Otherwise 1000 μg of hydroxocobalamin is given intramuscularly once a week for 3-4 weeks, and thereafter the daily dietary supplementation of 1-2 μg is continued.
There is evidence that vitamin B12 can be absorbed from the buccal mucosa when applied sublingually. This route can be made use of for therapy in mild deficiency states.
