Essay on vitamin B12
Vitamin B12 is a nutrient playing an important role in the manufacturing of blood cells and maintaining a healthy nervous system. The nutrient is involved in many processes like methyl transfer, nucleic acid metabolism, and acid myelin synthesis and repair. It is found in products like meat, eggs, shellfish, milk, and cheese (Johnson, 2012).
The discovery of vitamin B12 occurred in several phases for about 100 years. Pernicious anemia, as it is called today, was first described by Thomas Addison in the mid-19th century (Whitby, 1955). Several years later, researchers Minot and Murphy demonstrated liver or liver extracts to be the treatment for pernicious anemia (Minot & Murphy, 1926). After this demonstration, a large amount of research was going on to identify the dietary component in liver. Two groups were finally successful in 1948. Karl Folkers and his team from MSD laboratory isolated ‘small red needles’ from clinically active liver extracts (Rickes, 1948), which they recognized as possessing the anti-pernicious anemia factor and named it vitamin B12 (Rickes, 1948). After this, Smith and Parker from the Glaxo Laboratories also isolated the red vitamin B12 crystals (Smith & Parker, 1948). Both groups later found that the compound contained cobalt (Smith & Rickes, 1948). The effectiveness of purified form of vitamin B12 in the treatment of pernicious anemia was tested, and it was found to be outstandingly high, with doses as small as 4 µg giving a full reticulocyte response (Reisner & West, 1949).
In early 1950s, vitamin B12 was manufactured by fermentation procedures, the usual organism being Streptomyces griseus (Smith, 1952).
Chemical structure
The chemical formula of Vitamin B12 shows 5:6-dimethylbenziminazole in glycoside linkage with phosphorylated ribose. It has a cyano-group linked to the cobalt atom; the valencies are internally satisfied and the molecule as a whole is neutral, apart from several very weakly basic groups (Smith, 1952).
Deficiency of Vitamin B12
Vitamin B12 is in various forms such as cyano-, methyl-, deoxyadenosyl- and hydroxy-cobalamin. The cyano form is present in trace amounts in food (Scott, 1997). The other forms can be converted to the methyl- or 5-deoxyadenosyl forms, and are required as cofactors for methionine synthase, which is required in the synthesis of purines and pyrimidines. This reaction depends on methylcobalamine and folate. A deficiency of vitamin B12 and obstacles in this reaction leads to development of megaloblastic anemia (Gibson, 2005).
Deficiency is usually due to malabsorption, but dietary insufficiency is common in vegetarians and elderly with poor diet (National Academy Press, 1998). Pernicious anemia is the result of an auto-immune gastritis and results in the loss of synthesis of the intrinsic factor (IF) (National Academy Press, 1998). This causes vitamin B12 deficiency, and if left untreated, megaloblastic anemia and neurological complications develop. Thus, pernicious anemia needs to be treated appropriately with vitamin B12 injections, or large doses of oral vitamin B12. The deficiency may also develop after surgery at gastric antrum since this is the site of secretion of IF and acid (National Academy Press, 1998).
Signs and symptoms of vitamin B12 deficiency
Development of anemia is often slow; but it is actually more severe than its symptoms indicate. Splenomegaly and hepatomegaly may occur in some cases (Johnson, 2012). There may be poorly localized abdominal pain accompanied by weight loss. Neurologic symptoms may develop independently. There may be mild depression, delirium, or confusion (Johnson, 2012).
Diagnosis of Vitamin B12 deficiency
Diagnosis of Vitamin B12 deficiency is based on a blood test usually the CBC (complete blood check), Vitamin B12, and folate levels (Johnson, 2012).
Food sources and bioavailability
Vitamin B12 is found only in foods of animal origin like liver, beef, lamb, chicken, eggs, and dairy foods (Heyssel, 1966). There is no plant source, which can produce vitamin B12. Its bioavailability in humans depends on the person’s gastrointestinal absorption capacity and the rate of absorption varies depending on the quantity and type of protein consumed (Stabler, 2004).
Human requirement of Vitamin B12
The RDI (Recommended Dietary Intake) is set to maintain adequate serum vitamin B12 concentrations and prevent the occurrence of megaloblastic anemia (National Academy Press, 1998). The estimated average requirement does not vary after adulthood, but the US Institute of Medicine recommends that adults crossing 50 years of age get a little more than adequate amounts of vitamin B12 from sources like fortified foods or dietary supplements, since there are chances of malabsorption due to gastritis that occurs with age. Though vitamin B12 is stored for several years in the body, the development of deficiency is slow. However, inadequate dietary intake when combined with malabsorption can hasten the deficiency (National Academy Press, 1998).
Treatment
Treatment, once a diagnosis of vitamin B12 deficiency has been established, is usually to supplement the vitamin. For mild cases, i.e., patients whose condition is not severe or who do not have neurologic symptoms, a 1000 to 2000 μg po can be given OD (Johnson, 2012). For severe deficiency cases, vitamin B12 is given intramuscularly as 1 mg one to four times per week for a few weeks until hematologic abnormalities are corrected; followed by once a month administration (Johnson, 2012).
Toxicity
Large amount of vitamin B12 seem to be nontoxic, but are not recommended as a general tonic for regular use (Johnson, 2012).
References
Johnson, L. E., (2012) Vitamin B12. The Merck Manual. Retrieved from: http://www.merckmanuals.com/professional/nutritional_disorders/vitamin_deficiency_dependency_and_toxicity/vitamin_B12.html; Content reviewed: December 2012, Last updated: January 2013.
Whitby, L. (1955) The evolution of the treatment of Addisonian anemia. Br Med J, 1, 1401– 1406.
Minot, G. R., Murphy, W. P. (1926) Treatment of pernicious anemia by a special diet. JAMA, 87, 470–476.
Rickes, E. L., Brink, N. G., Koniuszy, F. R., Wood, T. R., Folkers, K. (1948) Crystalline vitamin B12. Science, 107, 396–397.
Smith, E. L., Parker, L. F. (1948) Purification of antipernicious anemia factor. Biochem J, viii.
Smith, E. L. (1948) Presence of cobalt in the anti-pernicious anemia factor. Nature, 162, 144.
Rickes, E. L., Brink, N. G., Koniuszy, F. R., Wood, T. R., Folkers, K. (1948) Vitamin B12, a cobalt complex. Science, 108, 134.
Reisner, E. H. (1949) The present status of vitamin B12 in pernicious anemia. Bull N Y Acad Med, 25, 429–433.
West, R., Reisner, E. H. (1949) Treatment of pernicious anemia with crystalline vitamin B12. Am J Med, 6, 643–650.
Smith, E. L. (1952) The Discovery and Identification of Vitamin B12. PROCEEDINGS OF THE NUTRITION SOCIETY SEVENTY-FIRST S C I E N T I F I C MEETING LONDON SCHOOL OF HYGIENE AND TROPICAL MEDICINE. Retrieved from: http://journals.cambridge.org/download.php?file=%2FBJN%2FBJN6_01%2FS0007114552000346a.pdf&code=a4cd7827c43b87780244640216120c97
Scott, J.M. (1997) Bioavailability of vitamin B12. Eur. J. Clin. Nutr, 51, S49-53.
Gibson, R.S. (2005) Principles of Nutritional Assessment. 2nd ed.; Oxford University Press: New York, NY, USA.
Food and Nutrition Board: Institute of Medicine, Vitamin B12. (1998) In Dietary reference intakes for thiamin, riboflavin, niacin, vitamin B6, folate, vitamin B12, pantothenic acid, biotin and choline; National Research Council, Ed. National Academy Press: Washington, DC, USA, pp. 306-356.
Heyssel, R.M.; Bozian, R.C.; Darby, W.J.; Bell, M.C. (1966) Vitamin B12 turnover in man. The assimilation of vitamin B12 from natural foodstuff by man and estimates of minimal daily requirements. Am. J. Clin. Nutr, 18, 176-184.
Stabler, S.P., Allen, R.H., (2004) Vitamin B12 deficiency as a worldwide problem. Annu. Rev. Nutr, 24, 299-326.
