Vitamin B12 (Cobalamin) and Folate Deficiency

Abstract

General Considerations (i) Folates and vitamin B 12 (aka, cobalamin) participate in one-carbon metabolism (enzymatic reactions involving the transfer of one-carbon groups like methyl-, formyl-, methylene-, and formimino-) that are essential for pyrimidine and purine biosynthesis (including synthesis of three of four nucleotides of DNA). (ii) Defective DNA synthesis in rapidly proliferating hemato-poietic/gastrointestinal-epithelial/gonadal/fetal cells results in megaloblastic cells with DNA values that are "stuck" between 2N and 4N and therefore unable to divide, with adverse clinical consequences arising from affected hema-topoietic/gastrointestinal-epithelial/gonadal/fetal cells. (iii) Megaloblastic cells have "nuclear-cytoplasmic dissoci-ation" (large "immature" nucleus with a relatively mature cytoplasm) (Fig. 6.1). (iv) Deficiency of vitamin B 12 or folates can present with megaloblastic anemia, but deficiency of vitamin B 12 can present with neuropsychiatric syndromes. (v) Correct vitamin replacement for either vitamin B 12 or folate deficiency is essential. (vi) The preexisting stores of these vitamins will dictate the speed with which overt deficiency develops. Epidemiology Vitamin B 12 Nutrition (i) Recommended daily allowance (RDA) of vitamin B 12 : (a) Men/nonpregnant women = 2.4 μg. (b) Pregnant women = 2.6μg; lactating women = 2.8μg. (c) An even higher intake of 4-7 μg of cobalamin each day appears optimum for adequate cobalamin status. (ii) Vitamin B 12 is solely produced in nature by microorganisms ; main dietary cobalamin is animal-source foods: There is no unfortified plant food that can consistently provide a sufficient amount of vitamin B 12 in the diet: (a) Meat (>10 μg/100 g). (b) Fish, milk products, egg yolk (1-10 μg/100 g). (c) Nonvegetarian Western diets (5-7 μg/day). (d) Nonvegetarians (e.g., poverty-imposed near-vegetarians) with low animal-source food intake are also at risk. (e) Lacto-ovo vegetarians (<0.5 μg/day), vegans (<0.1 μg/day). (iii) Vitamin B 12 is exceptionally well stored (total stores = 2000-5000 μg vitamin B 12); 50% liver. (iv) Daily loss = 1 μg, so elimination of dietary vitamin B 12 intake takes 5-10 years to manifest clinically. (v) Daily turnover (5-10 μg vitamin B 12 /day) via efficient enterohepatic circulation with 75% reabsorption, so interruption (e.g., ileal resection) results in greater fecal losses; clinical presentation ~3-4 years. (vi) Vitamin B 12 resists high-temperature cooking but is unstable to light. Folates Nutrition (i) RDA folate: (a) Adult men/nonpregnant women = 400 μg. (b) Pregnant women = 600 μg for fetus and maternal tissues; lactating women = 500 μg. (c) Folates are synthesized by microorganisms, green-leafy vegetables/beans/fruit and animal-source foods. (ii) A balanced Western diet prevents folate deficiency but is still generally considered inadequate during pregnancy for fetal folate requirements (hence the need for food fortification-see Tables 6.1 and 6.2).