Causes and Cure to Vitamin B12 Deficiency

Johnson has reviewed the methods used to produce deficiency of B12 in pigs, chicks, and rats.On a "soy-protein synthetic milk" ration pigs develop B12 deficiency.Growth is poor and death ensues unless B12 is administered.Development offormed elements of blood is abnormal.The ease with which uncomplicated B12 deficiency can be produced in the young pig has made this animal a valuable tool in studying metabolic pathways involving the vitamin.Rats and chicks are susceptible to lack of dietary B12.В 
Growth is poor, and rats also develop porphyrin whiskers and scaly feet.Vitamin B12 relations to cobalt nutrition in ruminants are discussed with cobalt.In humans a dietary B12 deficiency is rare.In a review B12 deficiency symptoms of humans subsisting on diets devoid of animal products are discussed.Of more interest is the relation of the vitamin to human pernicious anemia and other diseases.Castle and others some years ago suggested that in pernicious anemia there is a deficiency of an intrinsic factor (stomach factor) and an extrinsic factor (food factor).The two factors were thought to react to form something required for the maturation of red blood cells.The extrinsic factor (EF) of Castle is now established to be vitamin B12.The intrinsic factor, a low-molecular-weight mucoprotein, normally occurs in gastric juice; and pernicious anemia is due to a lack of this substance, since B12 is not absorbed in its absence.The mechanism by which intrinsic factor brings about absorption is still not clear.However, it has been proposed that IF removes the vitamin from natural protein complexes with animal proteins.It also brings about absorption of the vitamin into the mucosal cells with the aid of an intestinal juice factor called releasing factor.В 
Herbert studied the source of this factor in rats and found it to be in the proximal end of the small intestine.It is known that IF has a high degree of species specificity.Fortunately hog and human IF have similar actions in humans.In very large doses B12 is absorbed in humans without IF, but not with doses found in ordinary diets.Small doses parenterally are highly effective in deficiency states.After absorption into the blood, B12 is bound to plasma proteins and may circulate to the sites of activity.That portion converted into coenzymes is stored principally in the liver.Small amounts of B12 occur in blood of normal individuals.В 
The variations are wide, but around 100 micro-g everal hundred mg per ml of blood have been found and a tenth or less of these amounts in pernicious anemia patients.The stools of pernicious anemia patients contain large amounts of the vitamin after oral administration if no intrinsic factor is given.A highly potent intrinsic factor preparation from hog pyloric mucosa was clinically active at a level of 0.3 mg; that is, it increased B12 absorption in pernicious anemia patients at this level.The molecular weight was found to be about 5000; the material contained 10 per cent nitrogen and less than 3 per cent glucosamine.The binding capacity in vitro was found to be 3 ~g of B12 per mg.A comprehensive review on all aspects of intrinsic factor appeared in 1963 and a shorter review was published the same year.Another role of intrinsic factor appears to involve retention of B12 by tissues, Active preparations increased B12 uptake ofliver slices.В 
In liver perfusion experiments B12-C060 was taken up to a slight extent, and the uptake was tremendously enhanced in the presence of intrinsic factor.Sorbitol (sugar alcohol analogue of glucose) enhances B12 absorption in man.In rats this compound, manuitol, sorbose, and xylose also increased absorption.In normal persons, studies with C060-vitamin B12 show that over 70 per cent of a 0.5 ~g dose is absorbed and that increasing the dose results in lower percentage absorption.With a 5.0 j.Jg dose only 30 per cent was absorbed.Vitamin B12 is used clinically in diseases other than pernicious anemia.It is effective in various megaloblastic anemias and in neurological disturbances accompanying various other conditions.Much of the information in this connection has been brought together and summarized.В 

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