Thus, one review states: "Altogether it can be concluded that an observed elevation of cobalamin in blood merits a full diagnostic work up to assess the presence of disease.
Foods having rich content of vitamin B 12 include clams, organ meats especially liver from lamb, veal, beef, and turkey, fish eggs, mackerel, and crab meat. B 12 is produced in nature only by prokaryotes in the form of certain bacteria and archaea; it is not made by any multicellular or single-celled eukaryotes.
Grazing animals pick up B 12 and bacteria that produce it from the soil at the roots of the plants they eat. Animals store vitamin B 12 in liver and muscle and some pass the vitamin into their eggs and milk; meat, liver, eggs and milk are therefore sources of the vitamin for other animals, including people.
Feces is a rich source of vitamin B 12 and many species, including rabbits, dogs, and cats eat feces. Foods fortified with B 12 are also dietary sources of the vitamin. Foods for which B 12 -fortified versions are widely available include breakfast cereals, soy products, energy bars, and nutritional yeast.
The UK Vegan Society, the Vegetarian Resource Group, and the Physicians Committee for Responsible Medicine, among others, recommend that every vegan who is not consuming adequate B 12 from fortified foods take supplements. Vitamin B 12 is an ingredient in multi-vitamin pills and in some countries used to enrich grain-based foods such as bread and pasta. In the U. The vitamin can also be a prescription product via injection or other means. The sublingual route, in which B 12 is presumably or supposedly taken in more directly under the tongue, has not proven to be necessary or helpful, even though a number of lozenges, pills, and even a lollipop designed for sublingual absorption are being marketed.
A study found no significant difference in absorption for serum levels from oral versus sublingual delivery of 0. As noted below, such very high doses of oral B 12 may be effective as treatments, even if gastro-intestinal tract absorption is impaired by gastric atrophy pernicious anemia.
Injection and patches are sometimes used if digestive absorption is impaired, but there is evidence that this course of action may not be necessary with modern high-potency oral supplements such as 0. Even pernicious anemia can be treated entirely by the oral route. If the patient has inborn errors in the methyltransfer pathway cobalamin C disease, combined methylmalonic aciduria and homocystinuria , treatment with intravenous, intramuscular hydroxocobalamin or transdermal B 12 is needed.
The UK Vegan Society, the Vegetarian Resource Group, and the Physicians Committee for Responsible Medicine, among others, recommend that vegans either consistently eat B 12 -fortified foods or take a daily or weekly B 12 supplement to meet the recommended intake. Recently sublingual methylcobalamin has become available in 5 mg tablets.
The metabolic fate and biological distribution of methylcobalamin are expected to be similar to that of other sources of vitamin B 12 in the diet. Safety of all forms of the vitamin is well established.
Besides certain fermented foods, [45] [46] there are few known plant, fungus or algae sources of biologically active B 12 and none of these have been subjected to human trials. Pseudovitamin-B 12 refers to B 12 -like analogues that are biologically inactive in humans and yet found to be present alongside B 12 in humans, [49] many food sources including animals [50] , and possibly supplements and fortified foods. It is important for vegans, whose food provides few sources of B 12 , and anyone else wishing to obtain B 12 from food sources other than animals, to consume foods that contain little or no pseudovitamin-B 12 and are high in biologically active B Metabolism of folic acid.
The role of Vitamin B 12 is seen at bottom-left. Vitamin B 12 functions as a coenzyme, meaning that its presence is required for enzyme-catalyzed reactions.
In humans, two major coenzyme B 12 -dependent enzyme families corresponding to the first two reaction types, are known. These are typified by the following two enzymes:. If folate is present in quantity, then of the two absolutely vitamin B 12 -dependent enzyme-family reactions in humans, the MUT-family reactions show the most direct and characteristic secondary effects, focusing on the nervous system see below.
This is because the MTR methyltransferase-type reactions are involved in regenerating folate, and thus are less evident when folate is in good supply. Since the late s, folic acid has begun to be added to fortify flour in many countries, so folate deficiency is now more rare. At the same time, since DNA synthetic-sensitive tests for anemia and erythrocyte size are routinely done in even simple medical test clinics so that these folate-mediated biochemical effects are more often directly detected , the MTR-dependent effects of B 12 deficiency are becoming apparent not as anemia due to DNA-synthetic problems as they were classically , but now mainly as a simple and less obvious elevation of homocysteine in the blood and urine homocysteinuria.
This condition may result in long term damage to arteries and in clotting stroke and heart attack , but this effect is difficult to separate from other common processes associated with atherosclerosis and aging. The specific myelin damage resulting from B 12 deficiency, even in the presence of adequate folate and methionine, is more specifically and clearly a vitamin deficiency problem. It has been connected to B 12 most directly by reactions related to MUT, which is absolutely required to convert methylmalonyl coenzyme A into succinyl coenzyme A.
Failure of this second reaction to occur results in elevated levels of MMA, a myelin destabilizer. Excessive MMA will prevent normal fatty acid synthesis, or it will be incorporated into fatty acid itself rather than normal malonic acid. If this abnormal fatty acid subsequently is incorporated into myelin, the resulting myelin will be too fragile, and demyelination will occur.
Although the precise mechanism s are not known with certainty, the result is subacute combined degeneration of central nervous system and spinal cord.
Vitamin B 12 -dependent MTR reactions may also have neurological effects, through an indirect mechanism. Adequate methionine which, like folate, must otherwise be obtained in the diet, if it is not regenerated from homocysteine by a B 12 dependent reaction is needed to make S-adenosyl-methionine SAMe , which is in turn necessary for methylation of myelin sheath phospholipids. Although production of SAMe is not B 12 dependent, help in recycling for provision of one adequate substrate for it the essential amino acid methionine is assisted by B In addition, SAMe is involved in the manufacture of certain neurotransmitters, catecholamines and in brain metabolism.
These neurotransmitters are important for maintaining mood, possibly explaining why depression is associated with B 12 deficiency. Methylation of the myelin sheath phospholipids may also depend on adequate folate, which in turn is dependent on MTR recycling, unless ingested in relatively high amounts. Methyl-B 12 is absorbed by two processes.
The first is an intestinal mechanism using intrinsic factor through which micrograms can be absorbed every few hours. Protein-bound vitamin B 12 must be released from the proteins by the action of digestive proteases in both the stomach and small intestine.
B 12 taken in a low-solubility, non-chewable supplement pill form may bypass the mouth and stomach and not mix with gastric acids, but acids are not necessary for the absorption of free B 12 not bound to protein; acid is necessary only to recover naturally-occurring vitamin B 12 from foods.
R-protein also known as haptocorrin and cobalophilin is a B 12 binding protein that is produced in the salivary glands. It must wait to bind food-B 12 until B 12 has been freed from proteins in food by pepsin in the stomach.
B 12 then binds to the R-protein to avoid degradation of it in the acidic environment of the stomach. This pattern of B 12 transfer to a special binding protein secreted in a previous digestive step, is repeated once more before absorption. The next binding protein for B 12 is intrinsic factor IF , a protein synthesized by gastric parietal cells that is secreted in response to histamine, gastrin and pentagastrin, as well as the presence of food. B 12 must be attached to IF for it to be efficiently absorbed, as receptors on the enterocytes in the terminal ileum of the small bowel only recognize the B 12 -IF complex; in addition, intrinsic factor protects the vitamin from catabolism by intestinal bacteria.
Absorption of food vitamin B 12 thus requires an intact and functioning stomach, exocrine pancreas, intrinsic factor, and small bowel. Problems with any one of these organs makes a vitamin B 12 deficiency possible. Individuals who lack intrinsic factor have a decreased ability to absorb B In pernicious anemia, there is a lack of IF due to autoimmune atrophic gastritis, in which antibodies form against parietal cells.
Antibodies may alternately form against and bind to IF, inhibiting it from carrying out its B 12 protective function. Due to the complexity of B 12 absorption, geriatric patients, many of whom are hypoacidic due to reduced parietal cell function, have an increased risk of B 12 deficiency. Hereditary defects in production of the transcobalamins and their receptors may produce functional deficiencies in B 12 and infantile megaloblastic anemia, and abnormal B 12 related biochemistry, even in some cases with normal blood B 12 levels.
The transcobalamin-II is degraded within a lysosome, and free B 12 is finally released into the cytoplasm, where it may be transformed into the proper coenzyme, by certain cellular enzymes see above. Investigations into the intestinal absorption of B 12 point out that the upper limit of absorption per single oral dose, under normal conditions, is about 1.
In a similar study Swendseid et al. It is this last fact which allows pernicious anemia and certain other defects in B 12 absorption to be treated with oral megadoses of B 12 , even without any correction of the underlying absorption defects. The total amount of vitamin B 12 stored in body is about 2—5 mg in adults. Approximately 0. Bile is the main form of B 12 excretion; most of the B 12 secreted in the bile is recycled via enterohepatic circulation.
Excess B 12 beyond the blood's binding capacity is typically excreted in urine. Symptoms of vitamin B12 deficiency include anemia, general fatigue, loss of appetite, gastric atrophy, neuromuscular pain, neurological problems gait, memory loss.
No adverse effects with excessive intakes of vitamin B12 have been reported. Find more information on vitamins and micronutrient deficiencies though our partner, Vitamin Angels or download our complete vitamin and mineral guide here.
Begin by heating 1 tbsp of the oil in a large non-stick frying pan and fry the sausages in two batches over a medium heat for 15 mins, turning regularly, until nicely browned. Transfer the sausages to a large flameproof casserole dish.
Next, tip the onions and celery into the frying pan and cook over a medium-high heat for 5 mins or until beginning to soften and lightly colour, stirring regularly.
Add a splash more oil if needed. Tip the vegetables into the casserole dish. Put the remaining oil in the pan, cook the mushrooms over a high heat for mins until lightly browned, then add to the casserole.
Pour the wine and ml water into the dish and crumble the stock cube over the top. Bring to a boil, then reduce the heat, cover loosely with a lid and simmer gently for 30 mins, stirring occasionally. Meanwhile, make the mustard mash. Put the potatoes in a large pan of water, bring to the boil, then reduce the heat and simmer for mins or until the potatoes are soft but not falling apart.
Subsequently, the various biochemical roles of vitamin B 12 were elucidated, including its important interaction with folate and their common link with megaloblastic anemia. Many of the early clinical studies recognized that vitamin B 12 deficiency also caused a severe neuropathy leading to paralysis and death, while post mortem analysis demonstrated spinal cord demyelination. Vitamin B 12 is still the subject of intense research and, in particular, its role in preventing these irreversible neurological lesions remains unclear.
Abstract The discovery of vitamin B 12 , the elucidation of its role in metabolism, and the effects and treatment of its deficiency occurred in distinct phases over more than years, and it was the subject of two separate Nobel Prizes.
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