Vitamin B12.KEY POINTS
* Subclinical subclinical /sub·clin·i·cal/ (sub-klin´i-k'l) without clinical manifestations.
Not manifesting characteristic clinical symptoms. Used of a disease or condition. vitamin B12 deficiency vitamin B12 deficiency Megalobalstic anemia, see there (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 Recommended Dietary Allowance (RDA)
The Recommended Dietary Allowances (RDAs) are quantities of nutrients in the diet that are required to maintain good health in people. 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 folate /fo·late/ (fo´lat)
1. the anionic form of folic acid.
2. more generally, any of a group of substances containing a form of pteroic acid conjugated with l-glutamic acid and having a variety of substitutions. intakes have been increased by fortification fortification, system of defense structures for protection from enemy attacks. Fortification developed along two general lines: permanent sites built in peacetime, and emplacements and obstacles hastily constructed in the field in time of war. 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 pre·sum·a·ble
That can be presumed or taken for granted; reasonable as a supposition: presumable causes of the disaster. this would be similar in Australia. Liver and kidney are the foods richest in this vitamin.
Vitamin B12, or cobalamin cobalamin: see coenzyme; vitamin. , 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 anaerobic /an·aer·o·bic/ (an?ah-ro´bik)
1. lacking molecular oxygen.
2. growing, living, or occurring in the absence of molecular oxygen; pertaining to an anaerobe. microorganisms--in particular in the rumen rumen
pl. rumens, rumina; the largest of the compartments of the forestomach of ruminant animals that serves as a fermentating vat. It is lined by a keratinized epithelium bearing numerous absorptive papillae; it is partly subdivided by folds (pillars). 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.
Methionine methionine (mĕthī`ənēn), organic compound, one of the 20 amino acids commonly found in animal proteins. Only the L-stereoisomer appears in mammalian protein. synthase (in the cytosol cytosol /cy·to·sol/ (sit´ah-sol) the liquid medium of the cytoplasm, i.e., cytoplasm minus organelles and nonmembranous insoluble components.cytosol´ic
n. ) requires methylcobalamin as cofactor cofactor
An atom, organic molecule, or molecular group that is necessary for the catalytic activity (see catalysis) of many enzymes. A cofactor may be tightly bound to the protein portion of an enzyme and thus be an integral part of its functional structure, or it may , and methylmalonyl CoA mutase mutase /mu·tase/ (mu´tas) a group of enzymes (transferases) that catalyze the intramolecular shifting of a chemical group from one position to another.
n. (in mitochondria) requires 5' deoxyadenosylcobalamin as coenzyme coenzyme (kō-ĕn`zīm), any one of a group of relatively small organic molecules required for the catalytic function of certain enzymes. . 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 DNA: see nucleic acid.
or deoxyribonucleic acid
One of two types of nucleic acid (the other is RNA); a complex organic compound found in all living cells and many viruses. It is the chemical substance of genes. and the methylation methylation,
n a phase-II detoxification pathway in the liver; methyl groups combine with toxins to rid the body of various substances.
(meth´ reactions via S-adenosylmethionine. If vitamin B12 is lacking, folate is trapped as methyl tetrahydrofolate. The metabolite 5, 10 methylene methylene /meth·y·lene/ (meth?i-len) the bivalent hydrocarbon radical —CH2— or CH2dbond.
n. 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 megaloblastic
pertaining to or emanating from a megaloblast. change which affects rapidly dividing cells of the bone marrow (making blood cells), the gastrointestinal epithelium and germinal epithelium. Effects include anaemia anaemia
see anemia. and increased plasma homocysteine Homocysteine Definition
Homocysteine is a naturally occurring amino acid found in blood plasma. High levels of homocysteine in the blood are believed to increase the chance of heart disease, stroke, Alzheimer's disease, and osteoporosis. .
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 propionate /pro·pi·o·nate/ (pro´pe-o-nat) any salt of propionic acid.
A salt or ester of propionic acid.
any salt of propionic acid. 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 inborn /in·born/ (in´born?)
1. genetically determined, and present at birth.
1. Possessed by an organism at birth.
2. errors with absence of MMCoA mutase or of synthesis of the adenocobalamin coenzyme (without dietary B12 deficiency), the main feature is acidosis acidosis /ac·i·do·sis/ (as?i-do´sis)
1. the accumulation of acid and hydrogen ions or depletion of the alkaline reserve (bicarbonate content) in the blood and body tissues, decreasing the pH.
2. and accumulation of methylmalonic acid (MMA (Microcomputer Managers Association, Inc.) A membership organization with chapters throughout the U.S. that was devoted to educating personnel responsible for personal computers. It disbanded in 1996.
Mma - A fast Mathematica-like system, in Allegro CL by R. Fateman, 1991. ) 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 demyelination /de·my·elin·a·tion/ (de-mi?e-li-na´shun) destruction, removal, or loss of the myelin sheath of a nerve or nerves. Called also myelinolysis. , similar to human neuropathy. The most likely mechanism for neuropathy is impaired methylation of myelin basic protein Myelin basic protein (MBP) is a protein believed to be important in the process of myelination of nerves in the central nervous system (CNS).
MBP was initially sequenced in 1979 after isolation from myelin membranes  . (6)
CLINICAL DEFICIENCY DISEASES
There are two major clinical syndromes of vitamin B12 deficiency: megaloblastic anaemia and/or disease of the nervous system, neuropathy. A patient can have anaemia alone or neuropathy alone, or one preceding the other. With megaloblastic anaemia there is anaemia, enlarged red cells (macrocytosis macrocytosis /mac·ro·cy·to·sis/ (-si-to´sis) macrocythemia.
n. pl. mac·ro·cy·to·ses
The presence of unusually large numbers of macrocytes in the blood. ), or hypersegmented neutrophil leucocytes, and in the bone marrow, the nucleated nucleated /nu·cle·at·ed/ (noo´kle-at?id) having a nucleus or nuclei.
Having a nucleus or nuclei.
having a nucleus or nuclei. red cell precursors show megaloblastic change. The white cell count and the platelet count can be low. Elsewhere the tongue may be sore (glossitis glossitis /glos·si·tis/ (glos-i´tis) inflammation of the tongue.
glossitis area´ta exfoliati´va , benign migratory glossitis ) and there is likely to be infertility. B12-deficient neuropathy can affect different parts of the nervous system. The most usual presentation is subacute combined degeneration subacute combined degeneration Subacute combined degeneration of the spinal cord Neurology A disorder caused by vitamin B12 deficiency, characterized by weakness, sensory defects, mental changes, vision defects, often associated with megaloblastic anemia of the spinal cord, in which there is loss of proprioceptive Proprioceptive
Pertaining to proprioception, or the awareness of posture, movement, and changes in equilibrium and the knowledge of position, weight, and resistance of objects as they relate to the body. sensation from demyelination of the posterior columns and spastic weakness of the lower limbs from involvement of the lateral (pyramidal) tracts. Peripheral neuropathy may predominate or accompany this spinal cord disease. Less commonly, neuropsychiatric neu·ro·psy·chi·a·try
The medical study of disorders with both neurological and psychiatric features.
neu disorders have been recognised in association with vitamin B12 deficiency, for example memory loss or depression. In infants, the neurological dysfunction can be severe and progress to coma.
Most cases of vitamin B12 deficiency are due to interference with one stage of its complicated mechanism of absorption. Pure dietary deficiency is less common. In the stomach, vitamin B12 is split from its binding to dietary protein by acid and pepsin pepsin, enzyme produced in the mucosal lining of the stomach that acts to degrade protein. Pepsin is one of three principal protein-degrading, or proteolytic, enzymes in the digestive system, the other two being chymotrypsin and trypsin. . At the same time, intrinsic factor (IF) is secreted by the (normal) stomach's parietal cells. In the more alkaline pH of the duodenum duodenum: see intestine; pancreas.
First and shortest (9–11 in., or 23–28 cm) segment of the small intestine. It curves down and then up from the pylorus of the stomach, where chyme enters it. , IF attaches to the vitamin B12. The vitamin B12/IF complex passes down the small intestine (not digested) and is absorbed only at a specific site in the terminal ileum. After three to four hours, the vitamin B12 appears in the blood carried on transcobalamin II. Vitamin B12 is excreted in the bile into the duodenum. Most of this then combines with IF and is absorbed at the terminal ileum. This entero-hepatic cycle helps conserve the vitamin.
The primary method for measurement of serum vitamin B12 is microbiological or, more usually, radioassay. Different authorities set the lower reference level between 100 and 225 pmol/L. (7-9) (To convert pg/mL to pmol/L, multiply by 0.74.) One reason for differences between these numbers depends on the methods used for what is a very minute concentration of substance. The lower levels of serum B12 are likely to coincide with clinical deficiency disease. (10)
More common is biochemical, subclinical deficiency, usually in elderly people in whom serum B12 above 200 pmol/L can be accompanied by raised serum methylmalonate (MMA) and homocysteine. Raised serum methylmalonate is apparently a more sensitive indicator of low vitamin B12 status than serum B12. It is not raised in folate deficiency. Serum homocysteine is increased with folate and vitamin B12 deficiency, so it is less useful for diagnosing vitamin B12 status. Cut-off values for serum MMA differ between methods and laboratories. That a raised serum MMA is due to vitamin B12 deficiency can be confirmed by response to supplementation with crystalline vitamin B12.
CAUSES OF VITAMIN B12 DEFICIENCY
Because of the relatively large stores in the liver--enough for several years--the onset of B12 deficiency is gradual. Biochemical, subclinical deficiency--low serum B12, and/or raised methylmalonate-occurs first and is more common than clinical deficiency--megaloblastic anaemia and/or neuropathy. There are four groups of causes:
1 Inadequate dietary intake can affect vegans and is most severe and dangerous in breastfed infants of vegan mothers (see below). It is also seen in poorly nourished (vegetarian) adults, for example, in some populations in India.
2 Several (but rare) varieties of inborn errors of cobalamin metabolism.
3 Interference with absorption
* "Pernicious anaemia". There are auto-immune antibodies to IF, so cobalamin cannot be absorbed. This is the most common cause of severe deficiency. It is more frequent in people of northern European descent and usually affects older people.
* Gastric atrophy or post-gastrectomy Some IF may be produced but there is failure to free vitamin B-12 from food proteins.
* Drugs that suppress gastric acid (cimetidine cimetidine /ci·met·i·dine/ (si-met´i-den) a histamine H2 receptor antagonist, which inhibits gastric acid secretion; used as the base or the monohydrochloride salt in the treatment and prophylaxis of gastric or duodenal ulcers, , omeprazole) or interfere with B-12/IF absorption (slow K, metformin).
* Disease of the terminal ileum (the only place B-12/IF complex can be absorbed) e.g. in Crohn's disease or after resection of that part of the bowel.
4 Nitrous oxide, when used as an anaesthetic agent (or in someone addicted to it), can cause irreversible oxidation of the cobalt atom of vitamin B12 and render the vitamin inactive.
Severe vitamin B12 deficiency has usually occurred in infants exclusively breastfed by their vegan mothers in Western countries. Typically, the baby is normal for the first few months and then stops developing, becomes lethargic, stops growing, is weak and pale, may have abnormal twitching and writhing movements, and can no longer sit or move the head. There is megaloblastic anaemia, very low serum vitamin B12 and excretion of MMA and homocysteine in the urine. CAT scan shows cerebral atrophy; the electroencephalogram electroencephalogram /elec·tro·en·ceph·a·lo·gram/ (EEG) (-en-sef´ah-lo-gram?) a recording of the potentials on the skull generated by currents emanating spontaneously from nerve cells in the brain, with fluctuations in potential seen as is abnormal. Some of the babies of vegan mothers deteriorated to the stage of coma (11-14) before they were diagnosed and treated--their mothers did not trust conventional medical practice. Treatment with B12 injections produced rapid improvement of all abnormalities, but in some cases, the child's IQ had not reached normal a year or more later. It is remarkable that the vegan mothers were not obviously ill while their baby became comatose co·ma·tose
1. Of, relating to, or affected with coma.
2. Marked by lethargy; torpid.
comatose (kō´m ; yet both depended on the same inadequate supply of vitamin B12. The vitamin B12 concentration was lower in breast milk than in the mother's serum. In developing countries, similar cases have been reported in breastfed infants of poor mothers subsisting on diets low in animal foods.
In older people, biochemical signs of vitamin B12 deficiency become increasingly prevalent among those in their 70s and 80s of life. (15,16) As many as 10-15% of people aged over 75 years may show this when tested. The great majority of these people do not have pernicious anaemia (lack of IF). Nor do they have megaloblastic anaemia or obvious neuropathy. However, they have a low, or low normal, serum B12 with raised serum MMA and homocysteine, and evidence has accumulated that the raised homocysteine is associated with cognitive decline.
The most likely explanation for about half of these cases (after excluding renal failure as a cause of raised MMA) is impaired gastric acid and pepsin secretion, so that vitamin B12 is not liberated from its binding to dietary proteins. But not all such people have features of atrophic gastritis when they have been investigated for this. (17) A Lancet editorial (18) set out the possibilities:
* Inadequate intake
* Inadequate release of protein-bound cobalamin because of impaired gastric acid and pepsin secretion
* Alterations in the binding site of cobalamin to trans-cobalamin II
* Alteration in the metabolism of cobalamin
* A minority of cases have early pernicious anaemia
There is evidence in studies that, in some of the older people with subclinical vitamin B12 deficiency, the cause is inadequate B12 intake. Blundell et al. (19) reported that 15 of 200 geriatric patients had low serum levels on admission to hospital, then after a period in hospital, serum B12s had risen moderately, presumably on a more nutritious diet. A nutritionally depleted diet may have been responsible for the low vitamin values. In the Framingham Offspring Study, (20) subjects with low plasma B12 had significantly lower intakes of supplements and fortified breakfast cereals. They also had significantly lower intakes of dairy products. Their meat intakes had been lower too, although the difference here was not statistically significant. Two possibilities could explain these findings: either the range of meat intakes was too small to yield significant differences, or in dairy foods, the B12 is more bioavailable in these older people.
Raised plasma homocysteine has been linked epidemiologically with cardiovascular disease and with cognitive decline and dementia. Only the latter will be considered here, although one mechanism of this relationship could be via cerebral vascular disease. People with senile dementia have been found to have raised serum homocysteine, low vitamin B12 and folate. (21) The low B-vitamin levels could be secondary to poor nutrition, due to the dementia. However, several prospective studies have reported that hyperhomocysteinaemia tends to predict cognitive decline and dementia. (22-28)
This then raises the question whether treatment with all or some of the three B vitamins that lower plasma homocysteine--folate, vitamin B12 and vitamin B6--could delay cognitive decline or help prevent dementia. Eight trials have been reported in which folic acid and other B vitamins were given. Three of these lasted one (29) or two years, (30,31) and they included vitamin B12: plasma homocysteine was lowered, but there were no improvements in various tests of cognitive function. Among randomised Adj. 1. randomised - set up or distributed in a deliberately random way
irregular - contrary to rule or accepted order or general practice; "irregular hiring practices" controlled trials with folic acid alone, one (32) out of three found improvement in cognitive tests. It was a large trial with 818 participants who were relatively young (50-70 years). The treatment group were given 800 [micro]g/day folic acid; the trial lasted three years, and the main benefits were in memory and speed of information-processing functions (i.e. short of dementia). (32) Subjects for this trial had to have raised plasma homocysteine and B12s above 200 pmol/L.
Raised homocysteine is neurotoxic neurotoxic
pertaining to or emanating from a neurotoxin.
a case of poisoning by a neurotoxin.
neurotoxic adjective through overstimulation of N-methyl-D-aspartate receptors and has been associated with thinning of the hippocampus. Vitamin B12 deficiency can affect cerebral function. An adequate trial of vitamin B12 in asymptomatic elderly people with biochemical evidence of B12 deficiency and careful cognitive tests has yet to be conducted. (33) In the meantime Adv. 1. in the meantime - during the intervening time; "meanwhile I will not think about the problem"; "meantime he was attentive to his other interests"; "in the meantime the police were notified"
meantime, meanwhile , as Clarke concluded, 'it may be prudent to exclude vitamin B12 deficiency in patients with suspected dementia or cognitive impairment'.
This section can best be summed up by quoting Carmel, (7) one of America's leading experts on vitamin B-12. "Alzheimer disease is often accompanied by unexplained low cobalamin levels. However, unlike the milder cognitive dysfunction sometimes seen in cobalamin deficiency, the symptoms of Alzheimer disease do not respond to cobalamin therapy, and a causal connection has not been found. An even stronger association of Alzheimer disease with homocysteine and folate status has been suggested, but is similarly murky. It has been aptly pointed out that attribution of neurologic problems to cobalamin deficiency requires more than just finding low serum cobalamin levels". (7)
Another question for subclinical vitamin B12 deficiency is whether it is aggravated by increased folate intake or status. This was considered unlikely in the National Health & Medical Research Council (NHMRC NHMRC National Health and Medical Research Council ) Folate Fortification report. (34) But a recent analysis by the Tufts group of data from the 1999-2000 US NHANES NHANES National Health and Nutrition Examination Survey (US CDC) found that, for senior adults with low vitamin B12 status in (serum cobalamin <148 pmol/L), high serum folate (>59 nmol/L) was associated with anaemia and cognitive impairment. However, high serum folate was associated with protection against cognitive impairment when vitamin B12 status was normal. (35) This is a new situation that has arisen since mandatory folic acid fortification in North America. (36)
VITAMIN B12 INTAKE IN AUSTRALIAN AND NEW ZEALAND POPULATIONS
There are no data on the vitamin B12 content in Australian foods. Table 1 is from the British food tables. (4) Vitamin B12 was not included in the 1985 Australian National Nutrition Survey. Vitamin B12 intakes were, however, estimated in samples of Australians investigated with postal food frequency questionnaires by CSIRO CSIRO Commonwealth Scientific & Industrial Research Organization (Australia) Adelaide. For vitamin B12 content of foods, overseas data were used. In the 1988 and 1993 national survey (2315 and 1733 people), mean B12 intakes were 5.5 [micro]g in men and 4.7 [micro]g in women. Around 5% of men and 10% of women reported intakes below the RDI RDI - Receiver Data Interface (then 2.0 [micro]g/day). (37) In surveys in Victoria (1985 and 1990) with similar methodology but more subjects (nearly 3000), the percentage with intakes below the RDI were 15% in men aged over 60 years and 25% in women. (38) The most informative study of different representative groups in Australia was conducted by Mann et al. in Melbourne. (39) The results in men in their 30s show that serum B12s were lower in lacto-ovo-vegetarians (mean 211 pmol/L) than in omnivores (334 pmol/L) and, in vegans, the mean value (145 pmol/L) bordered on the deficient range. High meat eaters averaged 402 pmol/L. The same low serum B12s in vegans have been seen consistently in other studies performed in Israel, Finland, Slovakia and the UK.
A recent survey as part of the Blue Mountains (NSW NSW New South Wales
Noun 1. NSW - the agency that provides units to conduct unconventional and counter-guerilla warfare
Naval Special Warfare ) Eye Study (BMES BMES Biomedical Engineering Society ) found that older people in Australia have a similar proportion with low serum vitamin B12 to studies in developed countries overseas. (40) In 2963 women and men aged 50 to 80+ years, 6% of the whole sample had serum B12 <125 pmol/L ('very low'), and nearly 17% had levels between 125 and 185 pmol/L ('low'). The lower the B12, the higher the proportion with serum homocysteine >15 [micro]mol/L. Low and very low serum B12 increased progressively from people in their 50, 60s, 70s and 80s of life. So in the octagenarians, 11% had very low and 30% had low serum B12s. The BMES investigators do not report haemoglobin haemoglobin or US hemoglobin
a protein in red blood cells that carries oxygen from the lungs to the tissues [Greek haima blood + Latin globus ball]
Noun 1. levels in their paper. In a later publication, they note that (as found in much larger numbers in the USA (41), older people in the Blue Mountains with higher folate intakes did not have lower serum vitamin B12. (42)
In New Zealand, Green et al. (43) were able to conduct a substudy of the National Nutrition Study (which, unlike its Australian counterpart, included blood analyses). In 446 non-institutionalised men and women aged over 65 years, 12% had serum B12 <148 pmol/L and 28% had 149221 pmol/L. They diagnosed atrophic gastritis with serum pepsinogens (ratio of PG1/PG2) and found this in 23% of people with serum B12 below 148 pmol/L. The few B12 supplement users had a reduced risk of low serum B12, but dietary B12 intake above the recommended dietary intake (RDI) or recommended dietary allowance (RDA RDA
recommended daily allowance
Recommended Dietary Allowance (RDA)
The Recommended Dietary Allowances (RDAs) are quantities of nutrients in the diet that are required to maintain good health in people. ) (2.0 and 2.4 [micro]g/day) was not associated with lower risk. (There are no other dietary details in the paper.) They note that deficient serum B12 levels were more prevalent than in the USA, and less prevalent in this New Zealand sample than in the UK. Megaloblastic anaemia was absent in the people they sampled.
MEETING NUTRITIONAL REQUIREMENTS
The 1998 Dietary Reference Intakes dietary reference intakes (DRIs),
n.pl a set of nutritional guidelines concerning the intake of vitamins and minerals from food rather than supplements. for the USA and Canada (44) introduced a new policy which implies that people over 51 years of age cannot be relied upon to absorb enough vitamin B12 from natural food. 'Because 10 to 30 percent of older people are estimated to have atrophic gastritis with low acid secretion they may have decreased bioavailability bioavailability /bio·avail·a·bil·i·ty/ (bi?o-ah-val?ah-bil´i-te) the degree to which a drug or other substance becomes available to the target tissue after administration.
n. of B12 from food'. So the RDA (of 2.4 [micro]g here) may not meet the needs of 97% of the older age groups. The Institute of Medicine therefore recommends that most of the RDA be obtained by consuming foods fortified with crystalline B12 or with a B12-containing supplement. In the USA, breakfast cereals are commonly fortified with B12. Perhaps because of this or more taking of supplements, only 7% of 'elderly' persons had serum B12 below 185 pmol/L ('Elderly' seems to have been used for >60 years, but these percentages are lower than in BMES (above)).
The ANZ ANZ Australia and New Zealand
ANZ Australia and New Zealand Banking Group Limited
ANZ Air New Zealand (NZ national airline) Nutrient Reference Values report, (3) which usually followed North America, has taken a somewhat different line. Having noted that strict vegans will need supplementation with vitamin B12, the Working Party adds: 'The natural vitamin B12 in foods may be less bioavailable to the substantial number of older adults who have atrophic gastritis with low stomach acid secretion. People with this condition may require higher intakes of vitamin B12 rich foods, vitamin B12 fortified foods or supplements'. Vitamin B12-fortified foods are not generally available in Australian supermarkets, and some multivitamin mul·ti·vi·ta·min
Containing many vitamins.
A preparation containing many vitamins.
multivitamin tablets contain only 1 [micro]g of cyanocobalamin cyanocobalamin: see coenzyme; vitamin. .
Blacher et al. (45) in Paris have measured the effect of small doses of pharmaceutical vitamin B12 by mouth in people aged over 70 years who had evidence of gastric disease and low serum B12. With doses from 2.5 up to 80 [micro]g/day for 30 days, there was a dose-response effect. A dose of 6 [micro]g would increase serum B 12 by an average of 38 pmol/L. What has not been scientifically tested is the effect of that sort of dose from B12-rich food, for example 5 g ox liver (which contains 6 [micro]g vitamin B12) in old people with low serum B12 but no deficiency symptoms (with or without evidence of low gastric acid).
Perhaps we can get the best perspective here by another quote from Carmel: (7) "Much remains unknown about subclinical (B-12) deficiency. A few of the affected persons simply have very early pernicious anaemia (PA) and therefore can be expected to progress inexorably to a symptomatic state because of their irreversible malabsorption malabsorption /mal·ab·sorp·tion/ (mal?ab-sorp´shun) impaired intestinal absorption of nutrients.
Defective or inadequate absorption of nutrients from the intestinal tract. . However, those without early PA have often remained asymptomatic for at least a decade. Still to be resolved are issues that include the clinical impact of subclinical deficiency, which seems by definition to be small, its course, which appears static in most observations, and whether it can regress spontaneously. The causes of subclinical deficiency are also not well understood in many cases. Malabsorption of free cobalamin such as PA is found in fewer than 5% of cases, whereas food-cobalamin malabsorption may account for 30-40% of cases. No cause has been found in most patients, however. For all these reasons, and because millions of people fall into this category, it is important to answer the outstanding questions and to reach a consensus on what to do abut To reach; to touch. To touch at the end; be contiguous; join at a border or boundary; terminate on; end at; border on; reach or touch with an end. The term abutting implies a closer proximity than the term adjacent. subclinical (B-12) deficiency". (7,46)
1 Rickes EL, Brink NG, Koniusey FR et al. Crystalline vitamin B12. Science 1948; 107: 396-7.
2 Smith EL, Parker FJ. Purification of anti-pernicious anaemia factor. Biochem J 1948; 43: viii-ix.
3 Australian Government Department of Health & Ageing, National Health & Medical Research Council, New Zealand Minister of Health. Nutrient Reference Values for Australia and New Zealand. Canberra: NHMRC, 2005.
4 Food Standards Agency The Food Standards Agency is a non-ministerial government department of the Government of the United Kingdom. It is responsible for protecting public health in relation to food throughout the United Kingdom and is led by an appointed board that is intended to act in the public & Institute of Food Research. McCance & Widdowson's The Composition of Foods, 6th summary edn. Cambridge: Royal Society of Chemistry, 2002.
5 Metz J. Cobalamin deficiency and the pathogenesis of nervous system disease. Annu Rev Nutr 1992; 12: 59-79.
6 Scott JM, Wilson P, Dunn JJ, Weir DG. Pathogenesis of subacute combined degeneration a result of methyl group deficiency. Lancet 1981; 2: 334-7.
7 Carmel R. Cobalamin (vitamin B12). In: Shils ME, Shike M, Ross AC, Caballero B, Cousins RJ, eds. Modern Nutrition in Health and Disease, 10th edn. Philadelphia, PA: Lippincott, Williams & Wilkins, 2006; 482-97.
8 Sauberlich HE. Laboratory Tests for the Assessment of Nutritional Status, 2nd edn. Boca Raton, FL: CRC (Cyclical Redundancy Checking) An error checking technique used to ensure the accuracy of transmitting digital data. The transmitted messages are divided into predetermined lengths which, used as dividends, are divided by a fixed divisor. Press, 1999; 140-49.
9 Gibson RS Principles of Nutritional Assessment, 2nd edn. Oxford: Oxford University Press, 2005.
10 Kasper DL, Braunwald E, Fauci AS, Hansen SL, Longo DL, Jameson JL, eds. Harrison's Principles of Internal Medicine Harrison's Principles of Internal Medicine is an American textbook of internal medicine. First published in 1950, it is presently in its sixteenth edition. Although it is aimed at all members of the medical profession, it is mainly used by internists and junior doctors in , 16th edn. New York: McGraw-Hill, 2005.
11 Higginbottom MC, Sweetman L, Nyhan WL. A syndrome of methylmalonic aciduria, homocysteine, megaloblastic anemia and neurologic abnormalities in a vitamin B12 deficient breast-fed infant of a strict vegetarian. N Engl J Med 1978; 299: 317-23.
12 Wighton MC, Manson JI, Speed I, Robertson E, Chapman E. Brain damage in infancy and dietary vitamin B12 deficiency. Med J Aust 1979; 2: 1-3.
13 Rendle-Short J, Tiernan JR, Hawgood S. Vegan mothers with vitamin B12 deficiency. Med J Aust 1979; 2: 483.
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15 Bates Bates , Katherine Lee 1859-1929.
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VISP Video Imagery Standards Profile
VISP Visual Information Systems Program ) randomised controlled trial. JAMA JAMA
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44 Food and Nutrition Food and Nutrition
See also cheese; dining; milk.
Rare. the act or habit of reclining at meals.
Medicine. thescience of nutrition.
Pathology. Board Institute of Medicine. Dietary Reference Intakes for Thiamin thiamin
or vitamin B1
Organic compound, part of the vitamin B complex, necessary in carbohydrate metabolism. It carries out these functions in its active form, as a component of the coenzyme thiamin pyrophosphate. , Riboflavin riboflavin: see coenzyme; vitamin.
or vitamin B2
Yellow, water-soluble organic compound, abundant in whey and egg white. It has a complex structure incorporating three rings. , Niacin niacin: see coenzyme; vitamin.
or nicotinic acid or vitamin B3
Water-soluble vitamin of the vitamin B complex, essential to growth and health in animals, including humans. , Vitamin B-6, Folate, Vitamnb12, Pantothenic Acid, Biotin biotin: see vitamin; coenzyme.
Organic compound, part of the vitamin B complex, essential for growth and well-being in animals and some microorganisms. and Choline choline: see vitamin.
Organic compound related to vitamins in its activity. It is important in metabolism as a component of the lipids that make up cell membranes and of acetylcholine. . Washington, DC: National Academy Press, 1998.
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47 Muthayya S, Kurpad AV, Duggan CP et al. Low maternal vitamin B12 status is associated with intrauterine growth retardation Intrauterine Growth Retardation Definition
Intrauterine growth retardation (IUGR) occurs when the unborn baby is at or below the 10th weight percentile for his or her age (in weeks). in urban South Indians. Eur J Clin Nutr 2006; 60: 791-801.
A Stewart TRUSWELL
University of Sydney The University of Sydney, established in Sydney in 1850, is the oldest university in Australia. It is a member of Australia's "Group of Eight" Australian universities that are highly ranked in terms of their research performance. , Sydney, New South Wales New South Wales, state (1991 pop. 5,164,549), 309,443 sq mi (801,457 sq km), SE Australia. It is bounded on the E by the Pacific Ocean. Sydney is the capital. The other principal urban centers are Newcastle, Wagga Wagga, Lismore, Wollongong, and Broken Hill. , Australia
Table 1 Food sources of vitamin B12 ([micro]g/100 g edible portion) Breakfast cereals 0-2.5 (a) Whole & skim milk 0.4 (more if condensed or dried) Human milk 0.1 Cheeses 1-2 Yoghurt 0.2 Egg 2.5 Duck egg 5.6 Beef steak 2 Lamb, pork 1-2 Veal 1 Chicken <1 Duck 3 Turkey 2 Rabbit 10 Ox heart 14 Lamb kidney 55 Ox kidney 31 Ox liver 110 Chicken liver 56 Lamb liver 84 Pig liver 25 Tripe Tr Most fish 1-2 Oily fish Anchovies 11 Herring 6 Mackerel 10 Pilchards 12 Salmon 5 Sardines 28 Tuna 5 Mussels 22 Marmite 0.5 (a) If present, this is from fortification; zero in Australia. From McCance and Widdowson. (4)