Vitamin B12 - wikipedia Vitamin B This article is about the family of vitamers. For individual forms, see hydroxocobalamin, cyanocobalamin, methylcobalamin, and adenosylcobalamin. Vitamin B - 12 ( data for cyanocobalamin ) Clinical data Synonyms vitamin B12, vitamin B - 12 AHFS / Drugs.com Monograph Routes of administration by mouth, sublingual, IV, IM, intranasal ATC code B03BA01 ( WHO ) Legal status Legal status UK : POM ( Prescription only ) US : OTC Pharmacokinetic data Bioavailability Readily absorbed in distal half of the ileum Protein binding Very high to specific transcobalamins plasma proteins Binding of hydroxocobalamin is slightly higher than cyanocobalamin. Metabolism liver Elimination half - life Approximately 6 days ( 400 days in the liver ) Excretion kidney Identifiers IUPAC name α - ( 5, 6 - Dimethylbenzimidazolyl ) cobamidcyanide CAS Number 68 - 19 - 9 PubChem CID 5479203 DrugBank DB00115 ChemSpider 10469504 KEGG D00166 ChEMBL CHEMBL2110563 Chemical and physical data Formula C H Co N O P Molar mass 1355.37 g / mol 3D model ( JSmol ) Interactive image SMILES NC ( = O ) C ( C @ @ ) 8 ( C ) ( C@H ) ( CCC ( N ) = O ) C = 2 / N = C8 / C ( / C ) = C1 / ( C @ @ H ) ( CCC ( N ) = O ) ( C @ ) ( C ) ( CC ( N ) = O ) ( C @ @ ) ( C ) ( N1 ( Co+ ) C # N ) ( C @ @ H ) 7 / N = C ( C ( C ) = C3 / N = C ( / C = 2 ) C ( C ) ( C ) ( C @ @ H ) 3CCC ( N ) = O ) ( C @ ) ( C ) ( CCC ( = O ) NCC ( C ) OP ( ( O - ) ) ( = O ) O ( C @ @ H ) 6 ( C @ @ H ) ( CO ) O ( C@H ) ( n5cnc4cc ( C ) c ( C ) cc45 ) ( C @ @ H ) 6O ) ( C@H ) 7CC ( N ) = O InChI InChI = 1S / C62H90N13O14P.CN.Co/c1-29-20-39-40 ( 21 - 30 ( 29 ) 2 ) 75 ( 28 - 70 - 39 ) 57 - 52 ( 84 ) 53 ( 41 ( 27 - 76 ) 87 - 57 ) 89 - 90 ( 85, 86 ) 88 - 31 ( 3 ) 26 - 69 - 49 ( 83 ) 18 - 19 - 59 ( 8 ) 37 ( 22 - 46 ( 66 ) 80 ) 56 - 62 ( 11 ) 61 ( 10, 25 - 48 ( 68 ) 82 ) 36 ( 14 - 17 - 45 ( 65 ) 79 ) 51 ( 74 - 62 ) 33 ( 5 ) 55 - 60 ( 9, 24 - 47 ( 67 ) 81 ) 34 ( 12 - 15 - 43 ( 63 ) 77 ) 38 ( 71 - 55 ) 23 - 42 - 58 ( 6, 7 ) 35 ( 13 - 16 - 44 ( 64 ) 78 ) 50 ( 72 -- 42 ) 32 ( 4 ) 54 ( 59 ) 73 -- 56 ; 1 -- 2 ; / h20 - 21, 23, 28, 31, 34 - 37, 41, 52 - 53, 56 - 57, 76, 84H, 12 - 19, 22, 24 - 27H2, 1 - 11H3, ( H15, 63, 64, 65, 66, 67, 68, 69, 71, 72, 73, 74, 77, 78, 79, 80, 81, 82, 83, 85, 86 ) ; ; / q ; ; + 2 / p - 2 / t31 ?, 34 -, 35 -, 36 -, 37 +, 41 -, 52 -, 53 -, 56 -, 57 +, 59 -, 60 +, 61 +, 62 + ; ; / m1... / s1 Key : RMRCNWBMXRMIRW - WYVZQNDMSA - L ( what is this ? ) ( verify ) Vitamin B, also called cobalamin, is a water - soluble vitamin that is involved in the metabolism of every cell of the human body : it is a cofactor in DNA synthesis, and in both fatty acid and amino acid metabolism. It is particularly important in the normal functioning of the nervous system via its role in the synthesis of myelin, and in the maturation of developing red blood cells in the bone marrow. Vitamin B is one of eight B vitamins ; it is the largest and most structurally complicated vitamin. It consists of a class of chemically related compounds ( vitamers ), all of which show physiological activity. It contains the biochemically rare element cobalt ( chemical symbol Co ) positioned in the center of a corrin ring. The only organisms to produce vitamin B are certain bacteria, and archaea. Some of these bacteria are found in the soil around the grasses that ruminants eat ; they are taken into the animal, proliferate, form part of their gut flora, and continue to produce vitamin B. Most people in developed countries obtain enough vitamin B from consuming animal products including meat, milk, eggs, and fish. Other staple foods are fortified by having the vitamin added to them. Vitamin B supplements are available in single agent or multivitamin tablets ; and pharmaceutical preparations may be given by intramuscular injection. The most common cause of vitamin B deficiency in developed countries is impaired absorption due to a loss of gastric intrinsic factor, which must be bound to food - source B in order for absorption to occur. This condition, called pernicious anemia, is more likely after age 60, and increases in incidence with advancing age. Dietary deficiency is very rare in developed countries due to access to dietary meat and fortified foods ; however, children in some regions of developing countries are at particular risk due to increased requirements during growth coupled with lack of access to dietary B ; adults in these regions are also at risk. Other causes of vitamin B deficiency are much less frequent. Vitamin B is produced industrially via bacterial fermentation. Vitamin B total synthesis has been achieved, but has no practical value. Vitamin B was discovered as a result of its relationship to pernicious anemia. Contents 1 Chemistry 1.1 Vitamers 2 Dietary recommendations 3 Sources 3.1 Bacteria and archaea 3.2 Animals 3.3 Plants and algae 3.4 Fortified foods 3.5 Supplements 3.6 Parenteral administration 3.7 Pseudovitamin - B 4 Biochemistry 4.1 Coenzyme function 4.2 Enzyme function 5 Physiology 5.1 Absorption 5.2 Storage and excretion 6 Deficiency 7 Medical uses 7.1 Repletion of deficiency 7.2 Cyanide poisoning 8 Drug interactions 8.1 H - receptor antagonists and proton - pump inhibitors 8.2 Metformin 9 Industrial production 10 Laboratory synthesis 11 History 12 References 13 External links Chemistry Methylcobalamin ( shown ) is a form of vitamin B. Physically it resembles the other forms of vitamin B, occurring as dark red crystals that freely form cherry - colored transparent solutions in water. B is the most chemically complex of all the vitamins. The structure of B is based on a corrin ring, which is similar to the porphyrin ring found in heme. The central metal ion is cobalt. Four of the six coordination sites are provided by the corrin ring, and a fifth by a dimethylbenzimidazole group. The sixth coordination site, the reactive center, is variable, being a cyano group ( -- CN ), a hydroxyl group ( -- OH ), a methyl group ( -- CH ) or a 5 ′ - deoxy adenosyl group ( here the C5 ′ atom of the deoxyribose forms the covalent bond with cobalt respectively, to yield the four vitamers ( forms ) of B. Historically, the covalent C - Co bond is one of the first examples of carbon - metal bonds to be discovered in biology. The hydrogenases and, by necessity, enzymes associated with cobalt utilization, involve metal - carbon bonds. Vitamin B is a generic descriptor name referring to a collection of cobalt and corrin ring molecules which are defined by their particular vitamin function in the body. All of the substrate cobalt - corrin molecules from which B is made must be synthesized by bacteria. After this synthesis is complete, the human body has the ability ( except in rare cases ) to convert any form of B to an active form, by means of enzymatically removing certain prosthetic chemical groups from the cobalt atom and replacing them with others. Vitamers The four vitamers of B are all deeply red colored crystals and water solutions, due to the color of the cobalt - corrin complex. Cyanocobalamin is one form of B because it can be metabolized in the body to an active coenzyme form. The cyanocobalamin form of B does not occur in nature normally, but is a byproduct of the fact that other forms of B are avid binders of cyanide ( -- CN ) which they pick up in the process of activated charcoal purification of the vitamin after it is made by bacteria in the commercial process. Since the cyanocobalamin form of B is easy to crystallize and is not sensitive to air - oxidation, it is typically used as a form of B for food additives and in many common multivitamins. Pure cyanocobalamin possesses the deep pink color associated with most octahedral cobalt ( II ) complexes and the crystals are well formed and easily grown up to millimeter size. Hydroxocobalamin is another vitamer of B commonly encountered in pharmacology, but which is not normally present in the human body. Hydroxocobalamin is sometimes denoted B. This is the form of B produced by bacteria, and which is converted to cyanocobalmin in the commercial charcoal filtration step of production. Hydroxocobalamin has an avid affinity for cyanide ions and has been used as an antidote to cyanide poisoning. It is supplied typically in water solution for injection. Hydroxocobalamin is thought to be converted to the active enzymic forms of B more easily than cyanocobalamin, and since it is little more expensive than cyanocobalamin, and has longer retention times in the body, has been used for vitamin replacement in situations where added reassurance of activity is desired. Intramuscular administration of hydroxocobalamin is also the preferred treatment for pediatric patients with intrinsic cobalamin metabolic diseases, for vitamin B deficient patients with tobacco amblyopia ( which is thought to perhaps have a component of cyanide poisoning from cyanide in cigarette smoke ) ; and for treatment of patients with pernicious anemia who have optic neuropathy. Adenosylcobalamin ( adoB ) and methylcobalamin ( MeB ) are the two enzymatically active cofactor forms of B that naturally occur in the body. Most of the body 's reserves are stored as adoB in the liver. These are converted to the other methylcobalamin form as needed. Dietary recommendations The U.S. Institute of Medicine ( IOM ) updated Estimated Average Requirements ( EARs ) and Recommended Dietary Allowances ( RDAs ) for vitamin B in 1998. The current EAR for vitamin B for women and men ages 14 and up is 2.0 μg / day ; the RDA is 2.4 μg / day. RDAs are higher than EARs so as to identify amounts that will cover people with higher than average requirements. RDA for pregnancy equals 2.6 μg / day. RDA for lactation equals 2.8 μg / day. For infants up to 12 months the Adequate Intake ( AI ) is 0.4 -- 0.5 μg / day. ( AIs are established when there is insufficient information to determine EARs and RDAs. ) For children ages 1 -- 13 years the RDA increases with age from 0.9 to 1.8 μg / day. Because 10 to 30 percent of older people may be unable to effectively absorb vitamin B naturally occurring in foods, it is advisable for those older than 50 years to meet their RDA mainly by consuming foods fortified with vitamin B or a supplement containing vitamin B. As for safety, the IOM sets Tolerable Upper Intake Levels ( known as ULs ) for vitamins and minerals when evidence is sufficient. In the case of vitamin B there is no UL, as there is no human data for adverse effects from high doses. Collectively the EARs, RDAs, AIs and ULs are referred to as Dietary Reference Intakes ( DRIs ). The European Food Safety Authority ( EFSA ) refers to the collective set of information as Dietary Reference Values, with Population Reference Intake ( PRI ) instead of RDA, and Average Requirement instead of EAR. AI and UL defined the same as in United States. For women and men over age 18 the Adequate Intake ( AI ) is set at 4.0 μg / day. AI for pregnancy is 4.5 μg / day, for lactation 5.0 μg / day. For children aged 1 -- 17 years the AIs increase with age from 1.5 to 3.5 μg / day. These AIs are higher than the U.S. RDAs. The EFSA also reviewed the safety question and reached the same conclusion as in United States - that there was not sufficient evidence to set a UL for vitamin B. For U.S. food and dietary supplement labeling purposes the amount in a serving is expressed as a percent of Daily Value ( % DV ). For vitamin B labeling purposes 100 % of the Daily Value was 6.0 μg, but as of May 27, 2016 was revised downward to 2.4 μg. A table of the old and new adult Daily Values is provided at Reference Daily Intake. The original deadline to be in compliance was July 28, 2018, but on September 29, 2017 the FDA released a proposed rule that extended the deadline to January 1, 2020 for large companies and January 1, 2021 for small companies. Sources Most people in developed countries obtain enough vitamin B from consuming animal products including, meat, fish, eggs, and milk. Bacteria and archaea B is only produced in nature by certain bacteria, and archaea. It is synthesized by some bacteria in the gut flora in humans and other animals, but humans can not absorb this as it is made in the colon, downstream from the small intestine, where the absorption of most nutrients occurs. Ruminants, such as cows and sheep, absorb B produced by bacteria in their guts. For gut bacteria of ruminants to produce B the animal must consume sufficient amounts of cobalt. These grazing animals acquire the bacteria that produce vitamin B, and the vitamin itself, from the soil at the roots of the plants they eat. Feces are a rich source of vitamin B, and are eaten by many animals, including dogs and cats. Lagomorpha species, including rabbits and hares, form fecal pellets in their cecum called cecotropes, which consist of chewed plant material that has been metabolized by cecal bacteria ; cecotropes contain digestible carbohydrates and B vitamins synthesized by the resident bacteria. These animals ingest cecotropes which have been expelled in their feces. Animals Animals store vitamin B 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 as well as humans. For humans, the bioavailability from eggs is less than 9 %, compared to 40 % to 60 % from fish, fowl and meat. Insects are a source of B for animals ( including other insects and humans ). Food sources with a high concentration of vitamin B - 50 to 99 μg B per 100 grams of food - include clams ; liver and other organ meats from lamb, veal, beef, and turkey ; mackerel ; and crab meat. Plants and algae Natural sources of B include dried and fermented plant foods, such as tempeh, and laver a seaweed. Many other types of algae are rich in vitamin B, with some species, such as Porphyra yezoensis, containing as much cobalamin as liver. Fortified foods 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 from fortified foods take supplements. Foods for which B - fortified versions are widely available include breakfast cereals, soy products, energy bars, and nutritional yeast. Supplements A blister pack of 500 μg methylcobalamin tablets Vitamin B is included in multivitamin pills ; and in some countries grain - based foods such as bread and pasta are fortified with B. In the U.S. non-prescription products can be purchased providing up to 5,000 μg per serving, and it is a common ingredient in energy drinks and energy shots, usually at many times the recommended dietary allowance of B. The vitamin can also be a prescription product via injection or other means. Tablets have sufficiently large quantities of the vitamin such that 1 % to 5 % of the free crystalline B is absorbed along the entire intestine by passive diffusion. Sublingual methylcobalamin, which contains no cyanide, is 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 in the diet. However, the amount of cyanide in cyanocobalamin even in the largest available dose - 20 μg of cyanide in a 1,000 μg cyanocobalamin tablet - is less than the daily consumption of cyanide from food, and so cyanocobalamin is not considered a health risk. Parenteral Administration Injection and patches are sometimes used if digestive absorption is impaired, but this course of action may not be necessary with high - potency oral supplements ( such as 0.5 -- 1 mg or more ). Even pernicious anemia can be treated entirely by the oral route. If the person has inborn errors in the methyltransfer pathway ( cobalamin C disease, combined methylmalonic aciduria and homocystinuria ), treatment with intravenous, intramuscular hydroxocobalamin or transdermal B is needed. Pseudovitamin - B Pseudovitamin - B refers to B - like analogues that are biologically inactive in humans and yet found to be present alongside B in humans, many food sources ( including animals ), and possibly supplements and fortified foods. Most cyanobacteria, including Spirulina, and some algae, such as dried Asakusa - nori ( Porphyra tenera ), have been found to contain mostly pseudovitamin - B instead of biologically active B. In one common form of pseudo-B available to Salmonella enterica serovar Typhimurium, the α - axial ligand is changed from dimethylbenzimidazole to adenine. Biochemistry Metabolism of folic acid. The role of Vitamin B is seen at bottom - left. Coenzyme function Vitamin B functions as a coenzyme, meaning that its presence is required for enzyme - catalyzed reactions. Three types of enzymes : Isomerases Rearrangements in which a hydrogen atom is directly transferred between two adjacent atoms with concomitant exchange of the second substituent, X, which may be a carbon atom with substituents, an oxygen atom of an alcohol, or an amine. These use the adoB ( adenosylcobalamin ) form of the vitamin. Methyltransferases Methyl ( -- CH ) group transfers between two molecules. These use MeB ( methylcobalamin ) form of the vitamin. Dehalogenases Reactions in which a halogen atom is removed from an organic molecule. Enzymes in this class have not been identified in humans. In humans, two major coenzyme B - dependent enzyme families corresponding to the first two reaction types, are known. These are typified by the following two enzymes : MUT is an isomerase which uses the AdoB form and reaction type 1 to catalyze a carbon skeleton rearrangement ( the X group is - COSCoA ). MUT 's reaction converts MMl - CoA to Su - CoA, an important step in the extraction of energy from proteins and fats. This functionality is lost in vitamin B deficiency, and can be measured clinically as an increased methylmalonic acid ( MMA ) level. Unfortunately, an elevated MMA, though sensitive to B deficiency, is probably overly sensitive, and not all who have it actually have B deficiency. For example, MMA is elevated in 90 -- 98 % of patients with B deficiency ; 20 -- 25 % of patients over the age of 70 have elevated levels of MMA, yet 25 -- 33 % of them do not have B deficiency. For this reason, assessment of MMA levels is not routinely recommended in the elderly. There is no `` gold standard '' test for B deficiency because as a B deficiency occurs, serum values may be maintained while tissue B stores become depleted. Therefore, serum B values above the cut - off point of deficiency do not necessarily indicate adequate B status. The MUT function is necessary for proper myelin synthesis and is not affected by folate supplementation. MTR, also known as methionine synthase, is a methyltransferase enzyme, which uses the MeB and reaction type 2 to transfer a methyl group from 5 - methyltetrahydrofolate to homocysteine, thereby generating tetrahydrofolate ( THF ) and methionine. This functionality is lost in vitamin B deficiency, resulting in an increased homocysteine level and the trapping of folate as 5 - methyl - tetrahydrofolate, from which THF ( the active form of folate ) can not be recovered. THF plays an important role in DNA synthesis so reduced availability of THF results in ineffective production of cells with rapid turnover, in particular red blood cells, and also intestinal wall cells which are responsible for absorption. THF may be regenerated via MTR or may be obtained from fresh folate in the diet. Thus all of the DNA synthetic effects of B deficiency, including the megaloblastic anemia of pernicious anemia, resolve if sufficient dietary folate is present. Thus the best - known `` function '' of B ( that which is involved with DNA synthesis, cell - division, and anemia ) is actually a facultative function which is mediated by B - conservation of an active form of folate which is needed for efficient DNA production. Other cobalamin - requiring methyltransferase enzymes are also known in bacteria, such as Me - H - MPT, coenzyme M methyltransferase. Enzyme function If folate is present in quantity, then of the two absolutely vitamin B - 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 1990s, 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 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 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 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 acids 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 or mechanisms are not known with certainty, the result is subacute combined degeneration of spinal cord. Whatever the cause, it is known that B deficiency causes neuropathies, even if folic acid is present in good supply, and therefore anemia is not present. Vitamin B - 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 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 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 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. Physiology Absorption Methyl - B is absorbed by two processes. The first is an intestinal mechanism using intrinsic factor through which 1 -- 2 micrograms can be absorbed every few hours. The second is a diffusion process by which approximately 1 % of the remainder is absorbed. The human physiology of vitamin B is complex, and therefore is prone to mishaps leading to vitamin B deficiency. Protein - bound vitamin B must be released from the proteins by the action of digestive proteases in both the stomach and small intestine. Gastric acid releases the vitamin from food particles ; therefore antacid and acid - blocking medications ( especially proton - pump inhibitors ) may inhibit absorption of B. B 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 not bound to protein ; acid is necessary only to recover naturally - occurring vitamin B from foods. R - protein ( also known as haptocorrin and cobalophilin ) is a B binding protein that is produced in the salivary glands. It must wait to bind food - B until B has been freed from proteins in food by pepsin in the stomach. B then binds to the R - protein to avoid degradation of it in the acidic environment of the stomach. This pattern of B transfer to a special binding protein secreted in a previous digestive step, is repeated once more before absorption. The next binding protein for B 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. In the duodenum, proteases digest R - proteins and release their bound B, which then binds to IF, to form a complex ( IF / B ). B 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 - IF complex ; in addition, intrinsic factor protects the vitamin from catabolism by intestinal bacteria. Absorption of food vitamin B 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 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 protective function. Due to the complexity of B absorption, geriatric patients, many of whom are hypoacidic due to reduced parietal cell function, have an increased risk of B deficiency. This results in 80 -- 100 % excretion of oral doses in the feces versus 30 -- 60 % excretion in feces as seen in individuals with adequate IF. Once the IF / B complex is recognized by specialized ileal receptors, it is transported into the portal circulation. The vitamin is then transferred to transcobalamin II ( TC - II / B ), which serves as the plasma transporter. Hereditary defects in production of the transcobalamins and their receptors may produce functional deficiencies in B and infantile megaloblastic anemia, and abnormal B related biochemistry, even in some cases with normal blood B levels. For the vitamin to serve inside cells, the TC - II / B complex must bind to a cell receptor, and be endocytosed. The transcobalamin - II is degraded within a lysosome, and free B 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 point out that the upper limit of absorption per single oral dose, under normal conditions, is about 1.5 μg : `` Studies in normal persons indicated that about 1.5 μg is assimilated when a single dose varying from 5 to 50 μg is administered by mouth. In a similar study Swendseid et al. stated that the average maximum absorption was 1.6 μg (... ) '' The bulk diffusion process of B absorption noted in the first paragraph above, may overwhelm the complex R - factor and IGF - factor dependent absorption, when oral doses of B are very large ( a thousand or more μg per dose ) as commonly happens in dedicated - pill oral B supplementation. It is this last fact which allows pernicious anemia and certain other defects in B absorption to be treated with oral megadoses of B, even without any correction of the underlying absorption defects. See the section on supplements above. Storage and excretion The total amount of vitamin B stored in body is about 2 -- 5 mg in adults. Around 50 % of this is stored in the liver. Approximately 0.1 % of this is lost per day by secretions into the gut, as not all these secretions are reabsorbed. Bile is the main form of B excretion ; most of the B secreted in the bile is recycled via enterohepatic circulation. Excess B beyond the blood 's binding capacity is typically excreted in urine. Owing to the extremely efficient enterohepatic circulation of B, the liver can store 3 to 5 years ' worth of vitamin B ; therefore, nutritional deficiency of this vitamin is rare. How fast B levels change depends on the balance between how much B is obtained from the diet, how much is secreted and how much is absorbed. B deficiency may arise in a year if initial stores are low and genetic factors unfavourable, or may not appear for decades. In infants, B deficiency can appear much more quickly. Deficiency Main article : Vitamin B deficiency Vitamin B deficiency can potentially cause severe and irreversible damage, especially to the brain and nervous system. At levels only slightly lower than normal, a range of symptoms such as fatigue, lethargy, depression, poor memory, breathlessness, headaches, and pale skin, among others, may be experienced, especially in elderly people ( over age 60 ) who produce less stomach acid as they age, thereby increasing their probability of B deficiencies. Vitamin B deficiency can also cause symptoms of mania and psychosis. Vitamin B deficiency is most commonly caused by low intakes, but can also result from malabsorption, certain intestinal disorders, low presence of binding proteins, and use of certain medications. Vitamin B is rare from plant sources, so vegetarians are more likely to suffer from vitamin B deficiency. Infants are at a higher risk of vitamin B deficiency if they were born to vegetarian mothers. The elderly who have diets with limited meat or animal products are vulnerable populations as well. Vitamin B deficiency may occur in between 40 % to 80 % of the vegetarian population who are not also consuming a vitamin B supplement. In Hong Kong and India, vitamin B deficiency has been found in roughly 80 % of the vegan population as well. Vitamin B is a co-substrate of various cell reactions involved in methylation synthesis of nucleic acid and neurotransmitters. Synthesis of the trimonoamine neurotransmitters can enhance the effects of a traditional antidepressant. The intracellular concentrations of vitamin B can be inferred through the total plasma concentration of homocysteine, which can be converted to methionine through an enzymatic reaction that uses 5 - methyltetrahydrofolate as the methyl donor group. Consequently, the plasma concentration of homocysteine falls as the intracellular concentration of vitamin B rises. The active metabolite of vitamin B is required for the methylation of homocysteine in the production of methionine, which is involved in a number of biochemical processes including the monoamine neurotransmitters metabolism. Thus, a deficiency in vitamin B may impact the production and function of those neurotransmitters. Medical uses Photograph of a vitamin B solution ( hydroxycobalamin ) in a multi-dose bottle, with a single dose drawn up into a syringe for injection. Preparations are usually bright red. Repletion of deficiency Severe vitamin B deficiency is corrected with frequent intramuscular injections of large doses of the vitamin, followed by maintenance doses at longer intervals. Tablets are sometimes used for repletion in mild deficiency ; and for maintenance regardless of severity. Cyanide poisoning For cyanide poisoning, a large amount of hydroxocobalamin may be given intravenously and sometimes in combination with sodium thiosulfate. The mechanism of action is straightforward : the hydroxycobalamin hydroxide ligand is displaced by the toxic cyanide ion, and the resulting harmless B complex is excreted in urine. In the United States, the Food and Drug Administration approved the use of hydroxocobalamin for acute treatment of cyanide poisoning. Drug interactions H - receptor antagonists and proton - pump inhibitors Gastric acid is needed to release vitamin B from protein for absorption. Reduced secretion of gastric acid and pepsin produced by H blocker or proton - pump inhibitor ( PPI ) drugs can reduce absorption of protein - bound ( dietary ) vitamin B, although not of supplemental vitamin B. H - receptor antagonist examples include cimetidine, famotidine, nizatidine, and ranitidine. PPIs examples include omeprazole, lansoprazole, rabeprazole, pantoprazole, and esomeprazole. Clinically significant vitamin B deficiency and megaloblastic anemia are unlikely, unless these drug therapies are prolonged for two or more years, or if in addition the person 's diet is below recommended intakes. Symptomatic vitamin deficiency is more likely if the person is rendered achlorhydric ( complete absence of gastric acid secretion ), which occurs more frequently with proton pump inhibitors than H blockers. Metformin Reduced serum levels of vitamin B occur in up to 30 % of people taking long - term anti-diabetic metformin. Deficiency does not develop if dietary intake of vitamin B is adequate or prophylactic B supplementation is given. If the deficiency is detected, metformin can be continued while the deficiency is corrected with B supplements. Industrial production Industrial production of B is achieved through fermentation of selected microorganisms. Streptomyces griseus, a bacterium once thought to be a yeast, was the commercial source of vitamin B for many years. The species Pseudomonas denitrificans and Propionibacterium freudenreichii subsp. shermanii are more commonly used today. These are frequently grown under special conditions to enhance yield, and at least one company uses genetically engineered versions of one or both of these species. Since a number of species of Propionibacterium produce no exotoxins or endotoxins and are generally recognized as safe ( have been granted GRAS status ) by the Food and Drug Administration of the United States, they are presently the FDA - preferred bacterial fermentation organisms for vitamin B production. The total world production of vitamin B, by four companies ( the French Sanofi - Aventis and three Chinese companies ) in 2008 was 35 tonnes. Laboratory synthesis No eukaryotic organisms ( including plants, animals, and fungi ) are independently capable of constructing vitamin B. Only bacteria and archaea have the enzymes required for its biosynthesis. Like all tetrapyrroles, it is derived from uroporphyrinogen III. This porphyrinogen is methylated at two pyrrole rings to give dihydrosirohydrochlorin, which is oxidized to sirohydrochlorin, which undergoes further reactions, notably a ring contraction, to give the corrin ring. The complete laboratory synthesis of B was achieved by Robert Burns Woodward and Albert Eschenmoser in 1972, and remains one of the classic feats of organic synthesis, requiring the effort of 91 postdoctoral fellows ( mostly at Harvard ) and 12 PhD students ( at ETH ) from 19 nations. The synthesis constitutes a formal total synthesis, since the research groups only prepared the known intermediate cobyric acid, whose chemical conversion to vitamin B was previously reported. Though it constitutes an intellectual achievement of the highest caliber, the Eschenmoser -- Woodward synthesis of vitamin B is of no practical consequence due to its length, taking 72 chemical steps and giving an overall chemical yield well under 0.01 %. And although there have been sporadic synthetic efforts since 1972, the Eschenmoser -- Woodward synthesis remains the only completed ( formal ) total synthesis. Bacterial ( or, perhaps archaeal ) fermentation remains the only industrially viable source of the vitamin for food production and medicine. Species from the following genera and species are known to synthesize B : Propionibacterium shermanii, Pseudomonas denitrificans, Streptomyces griseus, Acetobacterium, Aerobacter, Agrobacterium, Alcaligenes, Azotobacter, Bacillus, Clostridium, Corynebacterium, Flavobacterium, Lactobacillus, Micromonospora, Mycobacterium, Nocardia, Protaminobacter, Proteus, Rhizobium, Salmonella, Serratia, Streptococcus and Xanthomonas. History 1849 - Thomas Addison first described a case of pernicious anemia. Chapter 36 : Megaloblastic anemias : disorders of impaired DNA synthesis by Ralph Carmel, page 927 < / ref > 1877 - William Osler and William Gardner first described a case of neuropathy in this condition. 1878 - Hayem first described large red cells in the peripheral blood in this condition, which he called `` giant blood corpuscles '', now called macrocytes. 1880 - Paul Ehrlich first identified megaloblasts in the bone marrow in this condition. 1887 - Ludwig Lichtheim first described a case of myopathy in this condition. 1920 - George Whipple discovered that ingesting large amounts of liver seemed to most rapidly cure the anemia of blood loss in dogs, and hypothesized that eating liver might treat pernicious anemia. 1926 - George Minot shared the 1934 Nobel Prize with William Murphy and George Whipple, for discovery of an effective treatment for pernicious anemia using liver concentrate, later found to contain a large amount of vitamin B. 1928 - Edwin Cohn prepared a liver extract that was 50 to 100 times more potent in treating pernicious anema than the natural liver products. Whipple, Minot, and Murphy shared the 1934 Nobel Prize in Physiology or Medicine. 1929 - William Castle demonstrated that gastric juice contained an `` intrinsic factor '' which when combined with meat ingestion resulted in absorption of the vitamin in this condition. 1947 - Mary Shaw Shorb, in a collaborative project with Karl Folkers, was provided with a US $ 400 grant to develop the so - called `` LLD assay '' for B. LLD stood for Lactobacillus lactis Dorner, a strain of bacterium which required `` LLD factor '' for growth, which was eventually identified as B. 1948 - Shorb and colleagues Karl A. Folkers and Alexander R. Todd used the LLD assay to rapidly extract the anti-pernicious anemia factor from liver extracts, and pure B was isolated. 1949 - Shorb and Folkers received the Mead Johnson Award from the American Society of Nutritional Sciences for their discovery. 1956 - The chemical structure of the molecule was determined by Dorothy Hodgkin, based on crystallographic data. She was awarded the 1964 Nobel Prize in Chemistry for determining the structure of vitamin B and other complex molecules. 1959 - methods of producing the vitamin in large quantities from bacteria cultures were developed. 1981 - Observations of stereospecificity encountered by R.B. Woodward during the synthesis of vitamin B led to the formulation of the principle of the conservation of orbital symmetry, which would result in a Nobel Prize in Chemistry by R. Hoffmann and K. Fukui. Six Nobel Prizes have been awarded in direct and indirect efforts to study vitamin B. References Jump up ^ Yamada K ( 2013 ). `` Chapter 9. Cobalt : Its Role in Health and Disease ''. In Sigel A, Sigel H, Sigel RK. Interrelations between Essential Metal Ions and Human Diseases. Metal Ions in Life Sciences. 13. Springer. pp. 295 -- 320. doi : 10.1007 / 978 - 94 - 007 - 7500 - 8_9. 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External links Cyanocobalamin at the US National Library of Medicine Medical Subject Headings ( MeSH ) hide Vitamins ( A11 ) Fat soluble α - Carotene β - Carotene Retinol Tretinoin Ergosterol Ergocalciferol 7 - Dehydrocholesterol Previtamin D Cholecalciferol 25 - hydroxycholecalciferol Calcitriol ( 1, 25 - dihydroxycholecalciferol ) Calcitroic acid Dihydroergocalciferol D analogues Alfacalcidol Dihydrotachysterol Calcipotriol Tacalcitol Paricalcitol Tocopherol Alpha Beta Gamma Delta Tocotrienol Alpha Beta Gamma Delta Tocofersolan Naphthoquinone Phylloquinone ( K ) Menaquinones ( K ) Menadione ( K ) ‡ Menadiol ( K ) Water soluble Thiamine B analogues Acefurtiamine Allithiamine Fursultiamine Octotiamine Prosultiamine Sulbutiamine Riboflavin Niacin Nicotinamide Pantothenic acid Dexpanthenol Pantethine Pyridoxine, Pyridoxal phosphate Pyridoxamine Pyritinol Biotin Folic acid Dihydrofolic acid Folinic acid Levomefolic acid Adenosylcobalamin Cyanocobalamin Hydroxocobalamin Methylcobalamin Choline Ascorbic acid Dehydroascorbic acid Combinations Multivitamins WHO - EM Withdrawn from market Clinical trials : Phase III Never to phase III hide Types of tetrapyrroles Bilanes ( Linear ) Bilirubin Biliverdin Stercobilinogen Stercobilin Urobilinogen Urobilin Phytobilins Phytochromobilin Phycobilins Phycoerythrobilin Phycocyanobilin Phycourobilin Phycoviolobilin Macrocycle Corrinoids Methylcobalamin Adenosylcobalamin Cyanocobalamin Porphyrins Protoporphyrins Protoporphyrin IX Heme ( b, c, a, o ) Zinc protoporphyrin Magnesium protoporphyrin Phytoporphyrins Chlorophyll c Protochlorophyllide Reduced porphyrins Porphyrinogens Uroporphyrinogen ( I, III ) Coproporphyrinogen ( I, III ) Protoporphyrinogen IX Chlorins Chlorophyllide ( a, b ) Chlorophyll ( a, b ) Phaeophytin ( a, b ) Bacteriochlorophyll c Bacteriochlorins Bacteriochlorophyll a Isobacteriochlorins Siroheme Sirohydrochlorin Corphins Cofactor F430 GND : 4140950 - 4 Retrieved from `` https://en.wikipedia.org/w/index.php?title=Vitamin_B12&oldid=845766924 '' Categories : Organocobalt compounds Cofactors Vitamin B12 B vitamins Hidden categories : Wikipedia articles needing page number citations from September 2010 All articles with dead external links Articles with dead external links from September 2017 Pages with DOIs inactive since 2018 Use mdy dates from February 2016 Template : drugs.com link with non-standard subpage Articles with changed DrugBank identifier Articles with changed EBI identifier Infobox drug articles with non-default infobox title Articles without UNII source Drugboxes which contain changes to verified fields Drugboxes which contain changes to watched fields All articles with unsourced statements Articles with unsourced statements from September 2015 Articles with unsourced statements from December 2017 Wikipedia articles with GND identifiers Talk Contents About Wikipedia Afrikaans Azərbaycanca تۆرکجه Български Bosanski Čeština Dansk ދިވެހިބަސް Eesti Español Euskara فارسی Français 한국어 Հայերեն हिन्दी Hrvatski Bahasa Indonesia Íslenska עברית Basa Jawa Kinyarwanda Кыргызча Latviešu Magyar Македонски Bahasa Melayu Монгол नेपाली Occitan Polski Português Русский Scots Simple English Slovenščina Српски / srpski Srpskohrvatski / српскохрватски Suomi தமிழ் తెలుగు ไทย Türkçe Українська Tiếng Việt 中文 38 more Edit links This page was last edited on 14 June 2018, at 00 : 22 ( UTC ). 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Question: vitamin b12 is essential for the proper functioning o
Answer: of the nervous system