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COPYRIGHT 2007 Dietitians Association of Australia
KEY POINTS
* Subclinical vitamin B12 deficiency (low serum vitamin B12, and/or raised methylmalonate) occurs in 10% or more of older people, in Australia and other developed countries. Causes include inadequate liberation of vitamin B12 from its natural binding to the protein in foods because of poor gastric acid production. There is evidence that in some cases, the diet has been inadequate in animal foods. At present, it is not clear whether these low biochemical values lead to any serious consequences.
* The recent recommended dietary allowance reports for vitamin B12 in the USA and Canada recommend that older people should obtain most of their vitamin B12 from fortified foods or from supplements of free (crystalline) vitamin B12. In Australia and New Zealand, advice in the Nutrient Reference Values report is that older people with low stomach acid secretion 'May require higher intakes of vitamin B12 rich foods "(e.g. meat)" vitamin B12 fortified foods "(not generally available here)" or supplements'.
* Dietary deficiency of vitamin B12 occurs in strict vegans. It is usually subclinical. But very severe clinical deficiency has been reported in infants breastfed by a vegan mother.
* Now that folate intakes have been increased by fortification of foods--mandatory in North America, at present voluntary in Australia and New Zealand--some experts and some evidence warn that it may be advisable for people to increase B12 intake.
* Meat and meat products are the major source of vitamin B12 in Britain. Presumably this would be similar in Australia. Liver and kidney are the foods richest in this vitamin.
INTRODUCTION
Vitamin B12, or cobalamin, was the last vitamin to be isolated. (1,2) It has the most complex structure and largest molecular weight (1335 Da) of all the vitamins. Dorothy Hodgkin was awarded the Nobel Prize (Chemistry, 1964) for elucidating its structure by X-ray crystallography. The vitamin is the only active substance in the human body to contain an atom of cobalt, which gives vitamin B12 its red colour. The human requirement for vitamin B12 is the lowest for any of the known essential nutrients (2 [micro]g/day), (3) and body stores last longer, when there is no intake, than for any other (essential) nutrient.
Vitamin B12 is synthesised by some anaerobic microorganisms--in particular in the rumen of cows and sheep, which require traces of cobalt in the pasture. Humans eat this vitamin preformed in animal foods: meat, milk, eggs and fish. No plant food has ever been shown to contain vitamin B12 consistently unless it is contaminated, for example by manure. In McCance and Widdowson's food tables, (4) all the vitamin B12 columns for vegetables and fruits and cereals have an '0' unless the line is for a mixed dish or a fortified (British) breakfast cereal. This review discusses the biochemical functions of vitamin B12, clinical deficiency diseases associated with vitamin B12, causes of deficiency, vegan infants and the elderly, nutritional intakes in Australia and New Zealand and meeting dietary requirements.
BIOCHEMICAL FUNCTIONS
Methionine synthase (in the cytosol) requires methylcobalamin as cofactor, and methylmalonyl CoA mutase (in mitochondria) requires 5' deoxyadenosylcobalamin as coenzyme. In bacteria, vitamin B12 participates in several other enzyme reactions. Methionine synthase is also called N-5 methyltetrahydrofolate: homocysteine methyltransferase. It sits at the junction between two important metabolic processes: synthesis of DNA and the methylation reactions via S-adenosylmethionine. If vitamin B12 is lacking, folate is trapped as methyl tetrahydrofolate. The metabolite 5, 10 methylene tetrahydrofolate is not formed, and this is specifically required for conversion of deoxyuridylate to thymidy-late, one of the four essential bases in DNA synthesis. In this situation, cell nuclei cannot divide, and there is megaloblastic change which affects rapidly dividing cells of the bone marrow (making blood cells), the gastrointestinal epithelium and germinal epithelium. Effects include anaemia and increased plasma homocysteine.
Methylmalonyl CoA mutase (MMCoA mutase) is the second and less central enzyme that requires vitamin B12. It deals with products of oxidation of odd-chain fatty acids and of the carbon skeletons of four amino acids as well as propionate itself. Propionyl CoA is converted to L-methylmalonyl CoA and the mutase (with vitamin B12 as coenzyme) converts this to succinyl CoA, which is part of the tricarboxylic acid (Krebs) cycle of metabolism. It was formerly thought that the neuropathic disease in vitamin B12 deficiency (which can occur without megaloblastic anaemia) would be due to failure of this second enzyme. But in inborn errors with absence of MMCoA mutase or of synthesis of the adenocobalamin coenzyme (without dietary B12 deficiency), the main feature is acidosis and accumulation of methylmalonic acid (MMA) in plasma and urine. (5) Neuropathy is not a feature. On the other hand, exposure of monkeys to nitrous oxide--which inhibits methionine synthase-produces spinal cord demyelination, similar to...
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