- Cyanocobalamin and hydroxocobalamin are complex cobalt containing compounds present in the diet and referred to as vit B12.
- There is extrinsic factor (Vitamin B12)present in diet which combined with an intrinsic factor produced by stomach to give rise to the haemopoietic principle à helped in its absorption.
- occurs as water soluble, thermostable red crystals.
- synthesized in nature only by microorganisms; plants and animals acquire it from them.
Liver, kidney, sea fish, egg yolk. meat, cheese are the main vit B., containing constituents of diet.
The only vegetable source is legumes (pulses) which get it from microorganisms harboured in their root nodules.
Daily requirement 1- 3 μg, pregnancy and lactation 3-5 μg .
- intricately linked with folate metabolism – megaloblastic anaemia occurring due to deficiency of either is indistinguishable.
- active coenzyme forms of B12 àmethyl-cobalamin (methyl B12).
- Vit B12 is essential for the conversion of homocysteine to methionine
- Methionine is needed as a methyl group donor in many metabolic reactions and for protein synthesis.
- This reaction is also critical in making tetrahydrofolic acid (THFA) available for reutilization.
- In B 12 deficiency THFA gets trapped in the methyl form (‘methylfolate trap’ ) and a number of one carbon transfer reactions suffer
- Purine and pyrimidine synthesis is affected primarily due to defective ‘one carbon’ transfer because of ‘folate trap’.
- The most important of these is in availability of thymidylate for DNA production.
- Malonic acid à Succinic acid. In vit B 12 deficiency, methylmalonic acid accumulates à responsible for demyelination seen in B 12 deficiency, but not in pure folate deficiency
- Vit B 12 is essential for cell growth and multiplication
Utilization of vit B12
- Vit B 12 is present in food as protein conjugates and is released by cooking or by proteolysis in stomach facilitated
by gastric acid.
- Intrinsic factor secreted by stomach forms a complex with B12 à complex attaches to specific receptors present on intestinal mucosal cells àabsorption of vit B 12 ingested in physiological amounts.
- However, when gross excess is taken, a small fraction is absorbed without the help of intrinsic factor.
- transported in blood à specific globulin transcobalamin
- Storage- taken up by liver cells and stored: about 2/3 to 4/5 of body’s content (2- 8 mg) is present in liver.
- not degraded in the bodyà excreted mainly in bile
- in the absence of intrinsic factor or when there is malabsorption à B 12 deficiency
- It takes 3- 5 years of total absence of B 12 in diet to deplete normal body stores.
- Vit B 12 is directly and completely absorbed after i.m. or deep s.c. injection. Normally, only traces of B12 are excreted in urine, but when pharmacological doses (> I 00 μg) are given orally or parenterally-a large part is excreted in
urine, because the plasma protein binding sites get saturated and free vit B12 is filtered at the glomerulus.
Deficiency occurs due to:
I. Addisonian pernicious anaemia: autoimmune disorder which results in destruction of gastric parietal cells
• absence of intrinsic factor in gastric juice (along with achlorhydria)
• inability to absorb B12
2. Other causes of gastric mucosa! damage, e.g. chronic gastritis, gastric carcinoma, gastrectomy, etc.
3. Malabsorption (damaged intestinal mucosa). Bowel resection, inflammatory bowel disease.
4. Consumption of vit B12 by abnormal flora in intestine (blind loop syndrome) or fish tape worm
5. Nutritional deficiency: less common àvegetarians.
6. Increased demand: pregnancy. infancy.
Manifestations of deficiency are:
(a) Megaloblastic anaemia à generally the first manifestation), neutrophils ‘with hyper-segmented nuclei, giant platelets.
(b) Glossitis, g.i. disturbances: damage to epithelial structures.
(c) Neurological: subacute combined degeneration of spinal cord; peripheral neuritis- diminished vibration and position sense, paresthesias, depressed stretch reflexes. muscular weakness, ataxia; mental changes- poor memory, mood changes, hallucinations. ere. are late effects.
Preparations, dose, administration
Because of higher protein binding and better retention in blood, hydroxocobalamin is preferred for parenteral administration to treat vit B 12 defi ciency.
The National list of essential medicines (2015) of India has included hydroxocobalamin in place of cyanocobalamin.
Prophylactic dose: 3-10 μg/day orally in those at risk of developing deficiency.
Oral vit B12 is not dependable for treatment of confirmed vit B 12 deficiency because its absorption from the intestine is unreliable.
Injected vit B12 is a must when deficiency is due to lack of intrinsic factor (pernicious anaemia, other gastric causes),
since the absorptive mechanism is totally nonfunctional.
Hydroxocobalamin 1 mg i.m. daily or on alternate days for 2 weeks or till neurological symptoms (when
present) abate, followed by I mg injected every 1- 3 months for maintenance.
- Treatment of vit B 12 deficiency: used as outlined above.
It is wise to add 1- 5 mg of oral folic acid and an iron preparation, because reinstitution of brisk haemopoiesis may unmask deficiency of these factors. Response to vit B 12 is dramatic- symptomatic improvement starts in 2 days: appetite improves, patient feels better; mucosal lesions heal in 1- 2 weeks; reticulocyte count increases; Hb% and haematocrit start rising after 2 weeks; platelet count normalizes in 1O days and WBC count in 2-3 weeks.
Neurological parameters improve more slowly-may take several months. Full recovery à6 months or more.
- Prophylaxis: given only when there are definite predisposing factors for development deficiency
- Mega doses of vit B 12 àhave been used in neuropathies, psychiatric disorders, cutaneous sarcoid and as a general tonic to allay fatigue, improve growth. The value of such therapy is questionable.
- Tobacco amblyopia: hydroxocobalamin is of some benefit- it probably traps cyanide derived from tobacco to form cyanocobalamin. Massive doses (5 g) of hydroxocobalamin have been injected i.v. to treat cyanide poisoning due to smoke inhalation
Even large doses à are quite safe.
Allergic reactions have occurred on injection, probably due to contaminants.