This article is about the family of vitamers. For individual forms, see hydroxocobalamin, cyanocobalamin, and methylcobalamin. Vitamin B-12 (data for cyanocobalamin) Clinical data Synonyms vitamin B12, vitamin B-12 AHFS/Drugs.com Monograph Routes of administration by mouth, 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 Biological 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 C63H88CoN14O14P 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.
./s1 Key:RMRCNWBMXRMIRW-WYVZQNDMSA-L (what is this?) (verify) Vitamin B12, also called cobalamin, is a water-soluble vitamin that has a key role in the normal functioning of the brain and nervous system via the synthesis of myelin (myelinogenesis), and the formation of red blood cells. It is one of eight B vitamins. It is involved in the metabolism of every cell of the human body, especially affecting DNA synthesis, fatty acid and amino acid metabolism.
 No fungi, plants, or animals (including humans) are capable of producing vitamin B12. Only bacteria and archaea have the enzymes needed for its synthesis. Some substantial sources of B12 include animal products (shellfish, meat), fortified foods, and dietary supplements. B12 is the largest and most structurally complicated vitamin and is produced industrially only through bacterial fermentation.
This B12 is used for fortified foods and supplements. It has also been produced synthetically via vitamin B12 total synthesis. Vitamin B12 consists of a class of chemically related compounds (vitamers), all of which show pharmacological activity. It contains the biochemically rare element cobalt (chemical symbol Co) positioned in the center of a planar tetra-pyrrole ring called a corrin ring. The vitamer is produced by bacteria as hydroxocobalamin, but conversion between different forms of the vitamin occurs in the body after consumption.
Vitamin B12 was discovered as a result of its relationship to the disease pernicious anemia, an autoimmune disease in which parietal cells of the stomach responsible for secreting intrinsic factor are destroyed; these cells are also responsible for secreting acid in the stomach. Because intrinsic factor is crucial for the normal absorption of B12, its lack in the presence of pernicious anemia causes a vitamin B12 deficiency.
Many other subtler kinds of vitamin B12 deficiency and their biochemical effects have since been made clear. Due to impairment of vitamin B12 absorption during aging, people over age 60 are at risk of deficiency. Deficiency Main article: Vitamin B12 deficiency Vitamin B12 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 B12 deficiencies.
 Vitamin B12 deficiency can also cause symptoms of mania and psychosis. Vitamin B12 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 B12 is rare from plant sources, so vegetarians are more likely to suffer from vitamin B12 deficiency. Infants are at a higher risk of vitamin B12 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 B12 deficiency may occur in between 40% to 80% of the vegetarian population who are not also consuming a vitamin B12 supplement. In Hong Kong and India, vitamin B12 deficiency has been found in roughly 80% of the vegan population as well. Vitamin B12 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 B12 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 B12 rises.
The active metabolite of vitamin B12 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 B12 may impact the production and function of those neurotransmitters. Dietary recommendations The U.S. Institute of Medicine (IOM) updated Estimated Average Requirements (EARs) and Recommended Dietary Allowances (RDAs) for vitamin B12 in 1998.
The current EAR for vitamin B12 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 B12 naturally occurring in foods, it is advisable for those older than 50 years to meet their RDA mainly by consuming foods fortified with vitamin B12 or a supplement containing vitamin B12. 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 B12 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 B12.
 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 B12 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.
 Medical use Example of a vitamin B12 solution for injection, in this case hydroxocobalamin 1000 µg/ml (1 mg/ml), available in a 30 mL multidose vial. Shown is 500 µg B12 (as 0.5 cc) drawn up in a 0.5 cc U-100 27 gauge × 1⁄2 inch insulin syringe, as prepared for subcutaneous injection. Preparations of vitamin B12 are red and will usually be dispensed in brown glass for protection from light.
Small single-dose vials are more common. Vitamin B12 is used to treat vitamin B12 deficiency, cyanide poisoning, and hereditary deficiency of transcobalamin II. It is given as part of the Schilling test for detecting pernicious anemia. 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 B12 complex is excreted in urine.
In the United States, the Food and Drug Administration approved (in 2006) the use of hydroxocobalamin for acute treatment of cyanide poisoning. Elevated serum B12 as disease marker Elevated levels of serum B12 (cobalamin above about 600 pmol/L) in the absence of dietary supplementation or injections may be a diagnostic sign of serious disease. In such cases B12 is thought to be a marker for disease, not the causal agent.
One cause of elevated cobalamin is general liver disease, since hepatic cytolysis releases B12, and the affected liver shows decreased cobalamin clearance. Thus, acute hepatitis, cirrhosis, hepatocellular carcinoma and metastatic liver disease can also be accompanied by an increase in circulating cobalamin. Elevated B12 levels have been suggested as a predictor of ICU mortality risk, but a recent study of this found that "[e]levated B12 levels are not a significant predictor of mortality after ICU admission when liver function is controlled for, and may instead be a proxy for poor liver function.
" A second group of non-supplemented patients with high cobalamin levels have them due to enhanced production of the plasma B12 transporters haptocorrin and transcobalamin II. This happens in hematologic disorders like chronic myelogeneous leukemia, promyelocytic leukemia, polycythemia vera and also the hypereosinophilic syndrome. Increased cobalamin levels are one of the diagnostic criteria for the latter two diseases.
A third group of non-supplemented patients with high cobalamin levels may be at immediate (mostly within one year of testing) higher risk for new diagnosis of certain smoking and alcohol-related cancers which are non-hematologic. In a study of 333,000 persons in Denmark, those with elevated B12 had a three to six times higher standard incidence ratio, with respect to those with normal B12 levels, for later development of certain types of cancer.
 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." Sources Animal sources Animals store vitamin B12 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.
 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 B12 for animals (including other insects and humans). Animal sources with a significant content of vitamin B12 (range among top 20 sources of 50 to 99 µg per 100 grams) include clams, organ meats (especially liver) from lamb, veal, beef, and turkey, fish eggs, mackerel, and crab meat.
 Microbial sources B12 is produced in nature only by some prokaryotes (certain bacteria and archaea); it is not made by any multicellular or single-celled eukaryotes. It is synthesized by some gut bacteria in humans and other animals, but humans cannot absorb the B12 made in their guts, as it is made in the colon which is too far from the small intestine, where absorption of B12 occurs.
Ruminants, such as cows and sheep, absorb B12 produced by bacteria in their guts. For gut bacteria of ruminants to produce B12 the animal must consume sufficient amounts of cobalt. Grazing animals pick up B12 and bacteria that produce it from the soil at the roots of the plants they eat. Feces are a rich source of vitamin B12 and many species, including, dogs, and cats eat feces. Species within the Lagomorpha (rabbits, hares, and pikas) produce two types of fecal pellets: hard ones, and soft ones called cecotropes.
Animals in these species re-ingest their own cecotropes, which consist of chewed plant material that was metabolized by bacteria in the cecum, a chamber between the small and large intestines. Cecotropes contain digestible carbohydrates and B vitamins synthesized by the resident bacteria. Fortified foods and supplements A blister pack of 500 µg methylcobalamin tablets 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 B12 from fortified foods take supplements.
 Foods for which B12-fortified versions are widely available include breakfast cereals, soy products, energy bars, and nutritional yeast. Supplements Vitamin B12 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.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 B12.
The vitamin can also be a prescription product via injection or other means. The sublingual route, in which B12 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 2003 study found no significant difference in absorption for serum levels from oral versus sublingual delivery of 0.
5 mg of cobalamin. Sublingual methods of replacement are effective only because of the typically high doses (0.5 mg), which are swallowed, not because of placement of the tablet. As noted below, such very high doses of oral B12 may be effective as treatments, even if gastrointestinal 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.
5–1 mg or more). Even pernicious anemia can be treated entirely by the oral route. These supplements carry such large doses of the vitamin that 1% to 5% of high oral doses of free crystalline B12 is absorbed along the entire intestine by passive diffusion. 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 B12 is needed.
 Non-cyanide forms as supplements 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 B12 in the diet. No cyanide is released with methylcobalamin, and the amount of cyanide (20 µg) in a 1,000 µg cyanocobalamin tablet is less than daily consumption from food.
Safety of all forms of the vitamin is well established. Untested sources Many other sources have found to contain cobalamin but are insufficiently tested to establish whether B12 is bioavailable in humans or whether it is an inactive B12 analogue. Besides certain fermented foods, there are few known plant, fungus or algae sources of biologically active B12, with none tested in human trials.
 Examples include tempeh (B12 content up to 8 µg per 100 grams) and certain species of mushrooms (up to 3 µg per 100 grams). Many algae are rich in vitamin B12, with some species, such as Porphyra yezoensis, containing as much cobalamin as liver. Pseudovitamin-B12 Pseudovitamin-B12 refers to B12-like analogues that are biologically inactive in humans and yet found to be present alongside B12 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-B12 instead of biologically active B12. Interactions Vitamin B12 may interact with prescription drugs. Examples H2-receptor antagonists: include cimetidine (Tagamet), famotidine (Pepcid), nizatidine (Axid), and ranitidine (Zantac). Reduced secretion of gastric acid and pepsin produced by H2 blockers can reduce absorption of protein-bound (dietary) vitamin B12, but not of supplemental vitamin B12.
Gastric acid is needed to release vitamin B12 from protein for absorption. Clinically significant vitamin B12 deficiency and megaloblastic anemia are unlikely, unless H2 blocker therapy is prolonged (2 years or more), or the person's diet is poor. It is also more likely if the person is rendered achlorhydric(with complete absence of gastric acid secretion), which occurs more frequently with proton pump inhibitors than H2 blockers.
Vitamin B12 levels should be monitored in people taking high doses of H2 blockers for prolonged periods. Metformin (Glucophage): Metformin may reduce serum folic acid and vitamin B12 levels. Long-term use of metformin substantially increases the risk of B12 deficiency and (in those patients who become deficient) hyperhomocysteinemia, which is "an independent risk factor for cardiovascular disease, especially among individuals with type 2 diabetes".
 There are also rare reports of megaloblastic anemia in people who have taken metformin for five years or more. Reduced serum levels of vitamin B12 occur in up to 30% of people taking metformin chronically. Clinically significant deficiency is not likely to develop if dietary intake of vitamin B12 is adequate. Deficiency can be corrected with vitamin B12 supplements even if metformin is continued.
The metformin-induced malabsorption of vitamin B12 is reversible by oral calcium supplementation. The general clinical significance of metformin upon B12 levels is as yet unknown. Proton pump inhibitors (PPIs): The PPIs include omeprazole (Prilosec, Losec), lansoprazole (Prevacid), rabeprazole (Aciphex), pantoprazole (Protonix, Pantoloc), and esomeprazole (Nexium). The reduced secretion of gastric acid and pepsin produced by PPIs can reduce absorption of protein-bound (dietary) vitamin B12, but not supplemental vitamin B12.
Gastric acid is needed to release vitamin B12 from protein for absorption. Reduced vitamin B12 levels may be more common with PPIs than with H2 antagonists, because they are more likely to produce achlorhydria (complete absence of gastric acid secretion). Clinically significant vitamin B12 deficiency is unlikely, unless PPI therapy is prolonged (2 years or more) or dietary vitamin intake is low. Vitamin B12 levels should be monitored in people taking high doses of PPIs for prolonged periods.
Pharmacology Mechanism of action Metabolism of folic acid. The role of Vitamin B12 is seen at bottom-left. Vitamin B12 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 adoB12 (adenosylcobalamin) form of the vitamin. Methyltransferases Methyl (–CH3) group transfers between two molecules. These use MeB12 (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 B12-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 AdoB12 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 (for more see MUT's reaction mechanism). This functionality is lost in vitamin B12 deficiency, and can be measured clinically as an increased methylmalonic acid (MMA) level.
Unfortunately, an elevated MMA, though sensitive to B12 deficiency, is probably overly sensitive, and not all who have it actually have B12 deficiency. For example, MMA is elevated in 90–98% of patients with B12 deficiency; 20–25% of patients over the age of 70 have elevated levels of MMA, yet 25–33% of them do not have B12 deficiency. For this reason, assessment of MMA levels is not routinely recommended in the elderly.
There is no "gold standard" test for B12 deficiency because as a B12 deficiency occurs, serum values may be maintained while tissue B12 stores become depleted. Therefore, serum B12 values above the cut-off point of deficiency do not necessarily indicate adequate B12 status. The MUT function is necessary for proper myelin synthesis (see mechanism below) and is not affected by folate supplementation.
MTR, also known as methionine synthase, is a methyltransferase enzyme, which uses the MeB12 and reaction type 2 to transfer a methyl group from 5-methyltetrahydrofolate to homocysteine, thereby generating tetrahydrofolate (THF) and methionine (for more see MTR's reaction mechanism). This functionality is lost in vitamin B12 deficiency, resulting in an increased homocysteine level and the trapping of folate as 5-methyl-tetrahydrofolate, from which THF (the active form of folate) cannot 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 B12 deficiency, including the megaloblastic anemia of pernicious anemia, resolve if sufficient dietary folate is present.
Thus the best-known "function" of B12 (that which is involved with DNA synthesis, cell-division, and anemia) is actually a facultative function which is mediated by B12-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-H4-MPT, coenzyme M methyltransferase. Enzyme function If folate is present in quantity, then of the two absolutely vitamin B12-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 B12 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 B12 deficiency, even in the presence of adequate folate and methionine, is more specifically and clearly a vitamin deficiency problem. It has been connected to B12 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 the central nervous system and spinal cord.
 Whatever the cause, it is known that B12 deficiency causes neuropathies, even if folic acid is present in good supply, and therefore anemia is not present. Vitamin B12-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 B12 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 B12 dependent, help in recycling for provision of one adequate substrate for it (the essential amino acid methionine) is assisted by B12. 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 B12 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. Absorption and distribution Methyl-B12 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 B12 is complex, and therefore is prone to mishaps leading to vitamin B12 deficiency. Protein-bound vitamin B12 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 B12.
B12 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 B12 not bound to protein; acid is necessary only to recover naturally-occurring vitamin B12 from foods. R-protein (also known as haptocorrin and cobalophilin) is a B12 binding protein that is produced in the salivary glands.
It must wait to bind food-B12 until B12 has been freed from proteins in food by pepsin in the stomach. B12 then binds to the R-protein to avoid degradation of it in the acidic environment of the stomach. This pattern of B12 transfer to a special binding protein secreted in a previous digestive step, is repeated once more before absorption. The next binding protein for B12 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 B12, which then binds to IF, to form a complex (IF/B12). B12 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 B12-IF complex; in addition, intrinsic factor protects the vitamin from catabolism by intestinal bacteria. Absorption of food vitamin B12 thus requires an intact and functioning stomach, exocrine pancreas, intrinsic factor, and small bowel.
Problems with any one of these organs makes a vitamin B12 deficiency possible. Individuals who lack intrinsic factor have a decreased ability to absorb B12. 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 B12 protective function.
Due to the complexity of B12 absorption, geriatric patients, many of whom are hypoacidic due to reduced parietal cell function, have an increased risk of B12 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/B12 complex is recognized by specialized ileal receptors, it is transported into the portal circulation.
The vitamin is then transferred to transcobalamin II (TC-II/B12), which serves as the plasma transporter. Hereditary defects in production of the transcobalamins and their receptors may produce functional deficiencies in B12 and infantile megaloblastic anemia, and abnormal B12 related biochemistry, even in some cases with normal blood B12 levels. For the vitamin to serve inside cells, the TC-II/B12 complex must bind to a cell receptor, and be endocytosed.
The transcobalamin-II is degraded within a lysosome, and free B12 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 B12 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 B12 absorption noted in the first paragraph above, may overwhelm the complex R-factor and IGF-factor dependent absorption, when oral doses of B12 are very large (a thousand or more µg per dose) as commonly happens in dedicated-pill oral B12 supplementation.
It is this last fact which allows pernicious anemia and certain other defects in B12 absorption to be treated with oral megadoses of B12, even without any correction of the underlying absorption defects. See the section on supplements above. The total amount of vitamin B12 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 B12 excretion; most of the B12 secreted in the bile is recycled via enterohepatic circulation. Excess B12 beyond the blood's binding capacity is typically excreted in urine. Owing to the extremely efficient enterohepatic circulation of B12, the liver can store 3 to 5 years’ worth of vitamin B12; therefore, nutritional deficiency of this vitamin is rare. How fast B12 levels change depends on the balance between how much B12 is obtained from the diet, how much is secreted and how much is absorbed.
B12 deficiency may arise in a year if initial stores are low and genetic factors unfavourable, or may not appear for decades. In infants, B12 deficiency can appear much more quickly. Chemistry Methylcobalamin (shown) is a form of vitamin B12. Physically it resembles the other forms of vitamin B12, occurring as dark red crystals that freely form cherry-colored transparent solutions in water.
B12 is the most chemically complex of all the vitamins. The structure of B12 is based on a corrin ring, which is similar to the porphyrin ring found in heme, chlorophyll, and cytochrome. 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 center of reactivity, is variable, being a cyano group (–CN), a hydroxyl group (–OH), a methyl group (–CH3) or a 5′-deoxyadenosyl group (here the C5′ atom of the deoxyribose forms the covalent bond with cobalt), respectively, to yield the four B12 forms mentioned below.
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 B12 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 B12 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 B12 to an active form, by means of enzymatically removing certain prosthetic chemical groups from the cobalt atom and replacing them with others. The four forms (vitamers) of B12 are all deeply red colored crystals and water solutions, due to the color of the cobalt-corrin complex. Cyanocobalamin is one such form, i.
e. "vitamer", of B12 because it can be metabolized in the body to an active coenzyme form. The cyanocobalamin form of B12 does not occur in nature normally, but is a byproduct of the fact that other forms of B12 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 B12 is easy to crystallize and is not sensitive to air-oxidation, it is typically used as a form of B12 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 form of B12 commonly encountered in pharmacology, but which is not normally present in the human body. Hydroxocobalamin is sometimes denoted B12a. This form of B12 is the form produced by bacteria, and is what 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 B12 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 B12 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 (adoB12) and methylcobalamin (MeB12) are the two enzymatically active cofactor forms of B12 that naturally occur in the body.
Most of the body's reserves are stored as adoB12 in the liver. These are converted to the other methylcobalamin form as needed. Synthesis and industrial production Neither plants nor animals are independently capable of constructing vitamin B12. 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 B12 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. Species from the following genera and species are known to synthesize B12: 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.
Industrial production of B12 is achieved through fermentation of selected microorganisms.Streptomyces griseus, a bacterium once thought to be a yeast, was the commercial source of vitamin B12 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, Rhône-Poulenc of France, which has merged into Sanofi-Aventis, used 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 B12 production. The total world production of vitamin B12, by four companies (the French Sanofi-Aventis and three Chinese companies) is said to have been 35 tonnes in 2008.
 See cyanocobalamin for discussion of the chemical preparation of reduced-cobalt vitamin analogs and preparation of physiological forms of the vitamin such as adenosylcobalamin and methylcobalamin. History B12 deficiency is the cause of pernicious anemia, an anemic disease that was usually fatal and had unknown etiology when it was first described in medicine. The cure, and B12, were discovered by accident.
George Whipple had been doing experiments in which he induced anemia in dogs by bleeding them, and then fed them various foods to observe which diets allowed them the fastest recovery from the anemia produced. In the process, he discovered that ingesting large amounts of liver seemed to most rapidly cure the anemia of blood loss. Thus, he hypothesized in 1920 that eating liver might treat pernicious anemia.
After a series of clinical studies, George Richards Minot and William Murphy set out to partly isolate the substance in liver which cured anemia in dogs, and found that it was iron. They also found that an entirely different liver substance cured pernicious anemia in humans, that had no effect on dogs under the conditions used. The specific factor treatment for pernicious anemia, found in liver juice, had been found by this coincidence.
Minot and Murphy reported these experiments in 1926. This was the first real progress with this disease. Despite this discovery, for several years patients were still required to eat large amounts of raw liver or to drink considerable amounts of liver juice. In 1928, the chemist Edwin Cohn prepared a liver extract that was 50 to 100 times more potent than the natural liver products. The extract was the first workable treatment for the disease.
For their initial work in pointing the way to a working treatment, Whipple, Minot, and Murphy shared the 1934 Nobel Prize in Physiology or Medicine. These events led to discovery of the soluble vitamin, called vitamin B12, from bacterial broths. In 1947, while working for the Poultry Science Department at the University of Maryland, Mary Shaw Shorb (in a collaborative project with Karl Folkers from Merck.
) was provided with a US$400 grant to develop the so-called "LLD assay" for B12. LLD stood for Lactobacillus lactis Dorner, a strain of bacterium which required "LLD factor" for growth, which was eventually identified as B12. Shorb and colleagues used the LLD assay to rapidly extract the anti-pernicious anemia factor from liver extracts, and pure B12 was isolated in this way by 1948, with the contributions of chemists Shorb,Karl A.
Folkers of the United States and Alexander R. Todd of Great Britain. For this discovery, in 1949 Mary Shorb and Karl Folkers received the Mead Johnson Award from the American Society of Nutritional Sciences. The chemical structure of the molecule was determined by Dorothy Crowfoot Hodgkin and her team in 1956, based on crystallographic data. She was awarded the 1964 Nobel Prize in Chemistry for the use of X-ray crystallography to determine the structure of complex molecules, with vitamin B12 specifically cited among other complex molecules solved.
Eventually, methods of producing the vitamin in large quantities from bacteria cultures were developed in the 1950s, and these led to the modern form of treatment for the disease. Observations of stereospecificity encountered by R. B. Woodward during the synthesis of vitamin B12 also led to the formulation of the principle of the conservation of orbital symmetry, which would result in a Nobel Prize in Chemistry by R.
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^ a b Shorb, Mary Shaw (May 10, 2012). "Annual Lecture". Department of Animal & Avian Sciences, University of Maryland. ^ Kirkland, Kyle (2010). Biological Sciences: Notable Research and Discoveries. Facts on File. p. 87. ISBN 0816074399. External links Cyanocobalamin at the US National Library of Medicine Medical Subject Headings (MeSH) v t e Vitamins (A11) Fat soluble A α-Carotene β-Carotene Retinol# Tretinoin D D2 Ergosterol Ergocalciferol# D3 7-Dehydrocholesterol Previtamin D3 Cholecalciferol# 25-hydroxycholecalciferol Calcitriol (1,25-dihydroxycholecalciferol) Calcitroic acid D4 Dihydroergocalciferol D5 D analogues Alfacalcidol Dihydrotachysterol Calcipotriol Tacalcitol Paricalcitol E Tocopherol Alpha Beta Gamma Delta Tocotrienol Alpha Beta Gamma Delta Tocofersolan K Naphthoquinone Phylloquinone (K1) Menaquinones (K2) Menadione (K3)‡ Menadiol (K4) Water soluble B B1 Thiamine# B1 analogues Acefurtiamine Allithiamine Fursultiamine Octotiamine Prosultiamine Sulbutiamine B2 Riboflavin# B3 Niacin Nicotinamide# B5 Pantothenic acid Dexpanthenol Pantethine B6 Pyridoxine#, Pyridoxal phosphate Pyridoxamine Pyritinol B7 Biotin B9 Folic acid Dihydrofolic acid Folinic acid Levomefolic acid B12 Adenosylcobalamin Cyanocobalamin Hydroxocobalamin Methylcobalamin Choline C Ascorbic acid# Dehydroascorbic acid Combinations Multivitamins #WHO-EM ‡Withdrawn from market Clinical trials: †Phase III §Never to phase III v t e 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 Authority control GND: 4140950-4 Retrieved from "https://en.
wikipedia.org/w/index.php?title=Vitamin_B12&oldid=822427725"See Also: Fort Lee Animal Clinic
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World's Healthiest Foods rich invitamin B12 FoodCalsDRI/DV For serving size for specific foods see the Nutrient Rating Chart. Basic Description Vitamin B12, as the name implies, is part of the B complex of vitamins. Like the other B vitamins, it is involved in energy metabolism and other related biological processes. However, that is where the similarity ends. The list of things that are unique about this vitamin is long, and includes the following facts: Most B vitamins do not store well, but several years' worth of vitamin B12 can be stored in your body Most B vitamins can be found in a wide variety of plant and animal foods, but since no plant or animal can make vitamin B12 (only microorganisms like fungi and bacteria can do that), it is typically only animal foods that contain B12 since plants cannot make or store this vitamin.
However, mushrooms (since they are themselves fungi) often contain B12, as do fermented plant foods like tempeh or miso since they have been produced with the help of microorganisms. Most B vitamins are relatively small and have a fairly simple chemical structure, while vitamin B12 is larger and more complex. Most B vitamins are more easily absorbed than vitamin B12,which has more complicated requirements for absorption.
In terms of physical amount, vitamin B12 has the lowest daily requirement of all the B vitamins, and it is needed in about 1/1000th the amount of some other B vitamins. Vitamin B12 is the only vitamin that contains a metal element (cobalt). In fact, the cobalt contained in B12 is the reason that this vitamin goes by the chemical name cobalamin. As the list above implies, optimal intake of vitamin B12 can sometimes be a challenge in human nutrition.
Even though U.S. adults ages 20 and older average well above the Dietary Reference Intake (DRI) for B12, there are still subgroups within the U.S. that are more commonly at risk of B12 deficiency. For example, adults 51 and older can be at greater risk of B12 deficiency, presumably in relationship to decreased dietary intake and/or compromised digestive function. The style of diet that you choose can have an major impact on your B12 nourishment.
If you regularly consume land animal foods and fish in your meal plan, B12 intake is not very likely to be a problem. If you regularly consume fish but avoid land animal foods, B12 is still relatively unlikely to be a problem. With no fish or land animal foods in your routine diet, however, you are left with some fairly specific food sources of B12, namely, fermented foods such as tempeh and fungi (including mushrooms).
We'll give you some practical steps for obtaining B12 nourishment in the Food Sources section. We list eight excellent sources of vitamin B12 on World's Healthiest Foods. We also have three very good and four good sources of the vitamin. Although the number of good sources is smaller than for many foods, this should be plenty to ensure a strong supply of this critical nutrient. Role in Health Support Cardiovascular Support Vitamin B12 plays several important roles in keeping our cardiovascular system on track.
The first of these roles involves production of red blood cells. Red blood cells are critical for transporting oxygen throughout our bloodstream, and the oxygen-carrying pigment in the center of our red blood cells is called hemoglobin. A key building block for hemoglobin is a compound called succinylCoA, and without enough vitamin B12, we simply cannot make enough of this building block. (Methylmalonyl CoA mutase is the enzyme that allows this process to take place, and it only functions with the help of B12 in the form of adenosylcobalamin.
) The fact that B12 plays such a key role in red blood cell production means that deficiency of this vitamin can actually cause a form of anemia called B12 deficiency anemia. However, this form of anemia is relatively rare. Often, when it appears to occur, it is actually a by-product of pernicious anemia in which immune system antibodies interfere with the production or function of intrinsic factor (IF).
IF is a glycoprotein produced by specialized stomach cells called parietal cells and it is required for proper metabolism of vitamin B12. A second important role for B12 in cardiovascular support involves prevention of excessive homocysteine build-up. A long list of cardiovascular diseases have been associated with excessive accumulation of homocysteine in the bloodstream, including coronary heart disease, peripheral vascular disease, and stroke.
Vitamin B12 helps normalize levels of homocysteine in the blood by allowing conversion of homocysteine to methionine. (This conversion process takes place through activity of the enzyme methionine synthase.) DNA Production Vitamin B12 is a necessary co-factor for the production of DNA, the genetic material that acts as the backbone of all life. This process requires folate and vitamin B6 as well, and disruptions of any of these nutrients can lead to problems.
The diagnosis of vitamin B12 deficiency is often dependent on problems with DNA production. When vitamin B12 is low, normally rapidly dividing blood cells are not able to effectively reproduce their DNA, leading to abnormally big cells. This phenomenon, called macrocytosis, is often the first way doctors suspect problems with the vitamin. Brain and Nervous System Health Along with the heart, liver, muscles, and kidneys, the brain is an organ that utilizes a large amount of energy in a form called aerobic energy.
Aerobic energy means oxygen-requiring energy production in specialized cell parts called mitochondria. As described earlier in the Cardiovascular Support section, one role that B12 plays is maintenance of hemoglobin in red blood cells to allow successful transport of oxygen. This process is especially important in brain health. Another role of B12 described in the Cardiovascular Support section was prevention of excessive homocysteine build-up in the blood through conversion of homocysteine to methione.
However, one aspect of this process not described earlier is the simultaneous recycling of a molecule called SAMe (S-adenosylmethionine) that takes place along with homocysteine conversion. SAMe has sometimes been referred to as the "universal methyl donor" because of its unique ability to provide special chemical groups—called methyl groups—in many different places where they are needed. One such place is the brain and nervous system, where movement of methyl groups is a key process.
Some of the nervous system messengers (neurotransmitters) cannot be produced without the help of enzymes called methyltransferases, and these enzymes in turn cannot be produced without the availability of methyl groups. This area of methyl metabolism is another key way in which vitamin B12 plays a major role in the health of our brain and nervous system. These nervous system connections to B12 help explain some of the clinical symptoms associated with B12 deficiency.
When levels of vitamin B12 get very low, nerve damage can ensue. The insulation sheath around nerve fibers begins to break down, making it harder for signals to get to more distant areas of the body (called peripheral areas). As you might guess, symptoms first become apparent in the hands and feet. While the exact mechanisms are not fully understood, researchers know that severe B12 deficiency can cause these "peripheral neuropathies" and that restoring optimal supplies of B12 can keep these problems from becoming more severe.
Support of Energy Metabolism While mentioned earlier, it's important to underscore the role of B12 in support of oxygen-based energy production (called aerobic energy). At the heart of this process is a metabolic cycle called the citric acid cycle and included within this cycle is a molecule called succinyl-coA. Since vitamin B12 is important for maintaining proper supplies of succinyl-coA in the citric acid cycle, it is important for supporting all aerobic energy metabolism.
Other Potential Health Benefits Still under debate by researchers is the exact role of B12 in support of bone health. On the one hand, B12 deficiency appears to be associated with increased risk of osteoporosis. This connection involves the positive role of B12 (in several of its cobalamin forms) in supporting the activity of the osteoblast (bone-forming) cells. At the same time, B12 also appears to help regulate activity of tumor necrosis factor (TNF).
TNF overactivity can result in too much bone breakdown and remodeling by a second type of bone cells called osteoclasts. Too much osteoclast activity—regardless of the reason for its occurrence—is also associated with increased risk of osteoporosis. Despite these logical connections between B12 deficiency and osteoporosis risk, however, actual research findings are inconsistent in making the B12 connection to bone status.
Summary of Food Sources Microorganisms—and perhaps only bacteria and algae —are the only life forms capable of synthesizing vitamin B12. There has been longstanding debate over algal production of B12, which includes debate over the potential role of sea vegetables to provide B12 (as well as debate over dietary supplements like spirulina). However, we interpret the research in this area to show that sea vegetables cannot be counted on for B12 support, not because there is no possibility of B12 production in sea vegetables, but because production may vary widely and because the form of B12 in sea vegetables may not be a readily usable vitamin form.
Even though land animals and fish cannot make vitamin B12 in their cells, they are often able to save up B12 produced by bacteria and concentrate it in their cells. For this reason, many land animal foods and many seafoods are nutrient-rich in B12. In fact, all but one of our WHFoods ranked sources of B12 come from animal foods or fish. Because plants do not concentrate or utilize vitamin B12 in the same way as animals, plant foods do not become nutrient-rich in B12 unless they have been fermented (like the fermentation of soybeans into tempeh) by B12-producing bacteria.
Mushrooms are a uniquely controversial food with respect to B12 content. Because scientists classify mushrooms in their own separate category of life form - fungi - they cannot be lumped together with plants from a science perspective. (On our website, we adopt a less technical perspective and include mushrooms in our vegetable plant group. And it is worth noting that crimini mushrooms are the only non-animal food that serves as a ranked source of B12 on our website.
) The controversy over B12 and mushrooms is three-fold: (1) B12 is not always detected in mushrooms, including crimini mushrooms; (2) when B12 is detected in mushrooms, it is usually found on the outermost portions of the mushrooms, suggesting that bacteria on the mushroom surface may have been produced the B12 rather than the mushrooms themselves; and (3) the chemical structure of B12 found on some mushrooms - while based on the corrin-type ring structure characteristic of B12 - can have important differences from the form of B12 that provides us with full vitamin benefits.
So while you may be getting a B12 boost from consumption of mushrooms like crimini mushrooms, we cannot recommend reliance on fungi as a primary source of B12. Our recommended daily intake level for B12 is 2.4 micrograms, and one serving of any of the following WHFoods will provide you with 100% or more of this amount: sardines, salmon, tuna, cod, lamb, or scallops. You'll get over 50% with a single serving of beef or shrimp, about one-third of the daily amount from one cup of yogurt, and between 10-25% from one serving of cheese, chicken, turkey, eggs, or cow's milk.
In contrast with these animal and fish foods, one cup of crimini mushrooms will only provide you with about 3% of the daily recommend amount. This relatively low contribution from mushrooms (a non-animal food) raises the important question of B12 nourishment for individuals who don't regularly consume animal foods or fish. In the broadest sense, individuals who focus primarily on plant foods in their meal plan are often referred to as "vegetarians.
" However, this term can have a variety of different meanings. "Pesca-vegetarians," for example, consume fish along with plant foods. "Lacto-vegetarians" consume dairy foods along with plants foods. "Lacto-ovo vegetarians" consume not only dairy foods but also eggs along with plant foods. If a person eats plant foods exclusively, the term usually used to describe his or her meal plan is "vegan." Most healthcare providers—including most nutritionists—currently recommend that persons who exclusively consume plant foods take steps to ensure their B12 nourishment by adding foods fortified with B12 or B12-containing supplements to their daily routine.
As a general rule, we support this approach, although we realize that there can be exceptions. Nutritional yeast grown on a molasses medium is an example of a food-based quasi-supplement that would provide a vegan source of vitamin B12. One widely available brand has more than twice the Dietary Reference Intake (DRI) for B12 in one and one-half tablespoons of yeast. Not all nutritional yeasts are rich in vitamin B12, however, and you'll need to check labels for details.
Before leaving the topic of B12 and food sources, we want to go one step further in explaining some ongoing speculation about the relationship between B12, bacteria, and human nutrition. As described earlier, bacteria and other microorganisms are the only life forms that can be described as definitively able to produce B12. Interestingly, however, research studies have shown that bacteria capable of producing B12 can live inside our human intestinal tract.
(One example of a bacterium known to produce B12 and also able to colonize parts of our digestive tract is Propionibacterium shermanii.) Furthermore, it seems likely that B12-producing bacteria are able reside in the very last segment of our small intestine known as the terminal ileum.The terminal ileum is especially important for vitamin B12 nourishment since it is the primary site for B12 absorption.
In this last segment of our small intestine, however, there aren't nearly as many bacteria as are present in our large intestine. (We're talking about a minimum of 10,000 times less, and probably more like one million times less.) So exactly how much B12 contribution could potentially be made by B12-producing bacteria in the terminal ileum is an open question. While we don't see any justification for relying on bacterial production of B12 in our intestines as a source of this vitamin, it is also impossible for us to totally rule out this possible pathway for B12 nourishment and hopefully we will get some further clarification here in future research.
Nutritional yeast grown on a molasses medium is an example of a food-based quasi-supplement approach that would provide a vegan source of vitamin B12. One widely available brand has more than twice the Recommended Dietary Allowance (RDA) for B12 in one and one-half tablespoons of yeast. Note that not all nutritional yeasts are rich in vitamin B12, and that you'll need to check labels for details. The National Academy of Sciences currently recommends that people over the age of 50 receive much of their vitamin B12 from supplements or fortified foods.
Currently, about 40% of the vitamin B12 that Americans eat comes from these non-food sources. In addition to the fortified yeast discussed above, soy products and breakfast cereals often contain this type of added vitamin B12. Nutrient Rating Chart Introduction to Nutrient Rating System Chart In order to better help you identify foods that feature a high concentration of nutrients for the calories they contain, we created a Food Rating System.
This system allows us to highlight the foods that are especially rich in particular nutrients. The following chart shows the World's Healthiest Foods that are either an excellent, very good, or good source of vitamin B12. Next to each food name, you'll find the serving size we used to calculate the food's nutrient composition, the calories contained in the serving, the amount of vitamin B12 contained in one serving size of the food, the percent Daily Value (DV%) that this amount represents, the nutrient density that we calculated for this food and nutrient, and the rating we established in our rating system.
For most of our nutrient ratings, we adopted the government standards for food labeling that are found in the U.S. Food and Drug Administration's "Reference Values for Nutrition Labeling." Read more background information and details of our rating system. World's Healthiest Foods ranked as quality sources ofvitamin B12 Food ServingSize Cals Amount(mcg) DRI/DV(%) NutrientDensity World'sHealthiestFoods Rating Sardines 3.
20 oz 188.7 8.11 338 32.2 excellent Salmon 4 oz 157.6 5.67 236 27.0 excellent Tuna 4 oz 147.4 2.66 111 13.5 excellent Cod 4 oz 96.4 2.62 109 20.4 excellent Lamb 4 oz 310.4 2.51 105 6.1 excellent Scallops 4 oz 125.9 2.44 102 14.5 excellent Shrimp 4 oz 134.9 1.88 78 10.4 excellent Beef 4 oz 175.0 1.44 60 6.2 very good Yogurt 1 cup 149.4 0.91 38 4.6 very good Cow's milk 4 oz 74.4 0.55 23 5.5 very good Eggs 1 each 77.
5 0.55 23 5.3 very good Turkey 4 oz 166.7 0.42 18 1.9 good Chicken 4 oz 187.1 0.39 16 1.6 good Cheese 1 oz 114.2 0.24 10 1.6 good Mushrooms, Crimini 1 cup 15.8 0.07 3 3.3 good World's HealthiestFoods Rating Rule excellent DRI/DV>=75% ORDensity>=7.6 AND DRI/DV>=10% very good DRI/DV>=50% ORDensity>=3.4 AND DRI/DV>=5% good DRI/DV>=25% ORDensity>=1.5 AND DRI/DV>=2.5% Impact of Cooking, Storage and Processing Even though the structure of vitamin B12 is complicated, it is a relatively stable molecule to storage and cooking.
Most of the B12 losses that we have seen from the cooking of B12-rich foods fall into the range of 10-50%. At the 50% end of the spectrum, most of the studies have involved boiling. Since B12 is a water-soluble vitamin, that finding makes sense to us, and it is one of the reasons that we generally prefer steaming over boiling, and when we do boil, it is for a relatively short period of time. The Healthy Sauté methods and braising methods that we use for fish generally take only 5-10 minutes of cooking time, and the same is true for steaming in recipes where fish are steamed.
For meats, we often use a Quick Broil method that only involves dry heat. In short, we believe that you can count on substantial B12 nourishment from our B12-rich foods if you take advantage of our WHFoods cooking methods. Risk of Dietary Deficiency For most U.S. adults, the risk of dietary deficiency of vitamin B12 is quite low. The median intake of vitamin B12 in the United States and Canada has been variously estimated between 3 and 7 mcg per day.
As such, most people are getting plenty of this vitamin to prevent deficiency. The only group where we see any substantial risk of dietary vitamin B12 deficiency is in strict vegans (who consume no animal or fish foods whatsoever). In a group of 232 British vegans, most of whom were younger than age 50, a little more than half had biochemical evidence of dietary vitamin B12 deficiency. The deficiency risk was nearly ten times as high in vegans as vegetarians, and more than 50 times higher compared to those who regularly ate animal foods.
Ovo-lacto vegetarians (or people who don't eat animal meat or fish, but do include dairy and eggs in their diet) are at a slightly increased risk of dietary vitamin B12 deficiency, but B12-related medical problems are not common in this group. When medical problems do show up, it is most commonly in people who had eaten a vegetarian diet throughout their entire life, rather than adopting it later on as adults.
This pattern makes sense to us, because our bodies are capable of storing large amounts of B12. In fact, it is common for adults to store thousands of times more B12 than their daily requirement. Because significant amounts of B12 are also be recycled around the body, the unusually large body supply of this vitamin can mean years before B12 depletion. So it is logical for an adult vegetarian who ate animal foods and fish growing up to go for long periods before risking B12 depletion, even if B12 intake has been inadequate.
Other Circumstances that Might Contribute to Deficiency The most common cause of vitamin B12 deficiency symptoms in the U.S. is not a dietary deficiency, but a problem related to malabsorption. This condition is called pernicious anemia, and it is a relatively common condition in older adults. An estimated 10-30% of people over the age of 50 have some amount of malabsorption of this vitamin. In pernicious anemia, various immune system reactions cause damage to the stomach lining.
As a result of this damage, specialized cells in the stomach called parietal cells become unable to produce intrinsic factor (IF). Since IF is needed for B12 absorption, this process results in poor absorption of B12, and the need for much greater amounts of B12 than can be obtained from food. Of course, diagnosis of this condition and the appropriate remedy for pernicious anemia requires the help of a licensed healthcare provider.
Pernicious anemia is not the only absorption-related problem associated with risk of vitamin B12 deficiency. As mentioned at the outset of this article, B12 is an unusual B-complex vitamin in terms of its absorption. Here is a short summary of the complicated nature of B12 absorption: (1) Stomach acids are needed to release B12 from our food and allow it to bind with a glycoprotein called haptocorrin provided in saliva and in stomach fluids.
(2) When leaving the stomach, protease enzymes provided by the pancreas are needed to separate B12 from haptocorrin and allow it to bind together with intrinsic factor (IF). IF is a specialized glycoprotein release by specialized stomach cells called parietal cells, and its job is to bind together with B12 and facilitate its absorption. (3) At the very end of the small intestine (called the terminal ileum), intestinal cells have special locations on their outer membranes (consisting of two proteins called cubulin and amionless) and these proteins serve as the location for taking the IF-bound form of B12 out of the intestine and up into the cells.
(4) Once inside the intestinal cells, B12 must be reconfigured and attached to a different protein called transcobalamin for passage through the bloodstream. These many different digestive tract steps make B12 absorption readily influenced by digestive tract problems. For example, overgrowth of the bacterium Helicobacter pylori in the stomach has been associated with increased risk of B12 deficiency.
Insufficient secretion of protein-digesting enzymes by the pancreas has also been shown to compromise B12 status. Various other stomach problems have also been associated with increased deficiency risk for this vitamin. The connection between B12 deficiency risk and digestive problems is believed to be a primary reason for increased risk of B12 deficiency with aging (especially after age 50), since digestive problems also tend to increase during this time period.
While oral contraceptive (OC) use is sometimes mentioned as a risk factor for B12 deficiency, the research seems mixed in this regard. On the one hand, blood levels of B12 have been shown to sometimes drop below the normal range with OC use. But at the same time, these drops in blood levels appear to be temporary and to pose no chronic problems. Interestingly, lower blood levels of B12 in women who use OCs appear to occur independently from dietary intake.
In other words, these lower levels of B12 do not appear to change, even if dietary intake of B12 is increased. More research is being done to determine the significant of these findings. Pregnancy and lactation (breastfeeding) increase the need for B12, and the Dietary Reference Intake (DRI) recommendations for pregnancy and lactation are 2.6 micrograms and 2.8 micrograms, respectively. Because folate and B12 work so closely together, both folate deficiency and folate excess can increase the need for B12.
While folate excess has been controversial in health research primarily in relationship to dietary supplementation of this vitamin in high doses, some scientists believe that folate fortification of food (in the absence of simultaneous B12 fortification) can also create imbalances in the ratio of B12-to-folate. As a remedy, they have recommended simultaneous fortification with both folate and B12 if fortification is determined to be desirable.
The bottom line here is to combine a reasonable variety of foods in your meal plan that are nutrient-rich in both B vitamins. Our Healthy Sauteéd Seafood with Asparagus recipe, for example, combines three of our top 10 seafoods rich in B12 (cod, scallops, and shrimp) with our second richest source of folate (asparagus). Relationship with Other Nutrients As described earlier in our Health Benefits section, vitamin B12 is involved in the process of energy production.
Yet B12 is not the only B-complex vitamin involved in this process, and for this reason, a deficiency of one or more of the other B vitamins may compound energy-production problems that are related to B12 deficiency. In other words, some symptoms of B12 deficiency can be made worse due to other B-vitamin deficiencies. In particular, the relationship between folic acid, vitamin B6, and vitamin B12 is very close.
A deficiency in any one of the three can impair the activity of the others. Most alarmingly, when people use high dose supplements of folic acid, it can be harder to spot vitamin B12 deficiency, leading to more serious symptoms. As described earlier in this article, controversy has also arisen over the role of folate fortification of foods, which has some researchers recommending simultaneous fortification of both folate and B12 whenever fortification with either nutrient is being considered.
Some older sources report that vitamin C can damage or impair absorption of vitamin B12. Further research discounted this hypothesis, so you can probably disregard this if you see it. Risk of Dietary Toxicity There is no known toxicity risk from dietary vitamin B12. In fact, doctors routinely inject people with deficiency symptoms with very large doses of the vitamin—500 times the daily required intake or more—without evidence of toxicity.
You can be confident that your diet does not contain too much vitamin B12. Disease Checklist Pernicious anemia Atrophic gastritis Neuropathy Fatigue Depression Kidney disease Memory loss Tinnitus Migraine Macular degeneration Asthma Shingles Multiple sclerosis Alzheimer's disease Public Health Recommendations In 1998, the National Academy of Sciences established a set of Dietary Reference Intakes (DRI) that included Recommended Dietary Allowances (RDA) by age for vitamin B12.
These are summarized in the chart below. Values for infants under one year old were established in the form of Adequate Intake (AI) levels. The full set of DRI recommendations is listed below: 0-6 months: 0.4 mcg 6-12 months: 0.5 mcg 1-3 years: 0.9 mcg 4-8 years: 1.2 mcg 9-13 years: 1.8 mcg 14+ years: 2.4 mcg Pregnant women: 2.6 mcg Lactating women: 2.8 mcg Note that the National Academy of Sciences has advised people over the age of 50 to meet their intake requirements mainly via either fortified foods or using a vitamin B12 supplement.
This recommendation is due to the high number of people in this age group with malabsorption of the vitamin. There is no established Tolerable Upper Intake Level (UL) for vitamin B12. In fact, doctors rather routinely supplement or inject people with pernicious anemia with amounts of vitamin B12 that are several hundred-fold greater than the DRI recommendations. As such, there is no known reason to be concerned about excessive intake of vitamin B12.
The Daily Value (DV) of 6 mcg per day is the value you'll see on food labels. Please note that the more recent DRI values are much lower, and probably a better reflection of your daily needs. We chose the adult DRI (ages 14 and older) of 2.4 micrograms as our daily recommended amount at WHFoods. References Aslinia F, Mazza JJ, Yale SH. Megaloblastic anemia and other causes of macrocytosis. Clin Med Res 2006;4:236-41.
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