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Vitamin B12 vitamin

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«Vitamin B₁₂, 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.^[1] It is particularly important in the normal functioning of the nervous system via its role in the synthesis of myelin,^[2]^[3] and in the maturation of developing red blood cell in the bone marrow.^[4]

Vitamin B₁₂ 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 B₁₂ 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 B₁₂.

There are no naturally occurring notable vegetable dietary sources of the vitamin, so vegans and vegetarians are advised to take a supplement or fortified foods^[5]^[6]. Otherwise, most omnivorous people in developed countries obtain enough vitamin B₁₂ from consuming animal products including meat, milk, eggs, and fish.^[7]Staple foods, especially those that form part of a vegan diet, are often fortified by having the vitamin added to them. Vitamin B₁₂supplements are available in single agent or multivitamin tablets; and pharmaceutical preparations may be given by intramuscular injection.^[8]^[9]

The most common cause of vitamin B₁₂ deficiency in developed countries is impaired absorption due to a loss of gastric intrinsic factor, which must be bound to food-source B₁₂ in order for absorption to occur. Another group affected are those on long term antacid therapy,^[10] using proton pump inhibitors, H2 blockers or other antacids. This condition may be characterised by limb neuropathy or a blood disorder called pernicious anemia, a type of megaloblastic anemia. Folate levels in the individual may affect the course of pathological changes and symptomatology. Deficiency is more likely after age 60, and increases in incidence with advancing age.^[8] Dietary deficiency is very rare in developed countries due to access to dietary meat and fortified foods, but children in some regions of developing countries are at particular risk due to increased requirements during growth coupled with lack of access to dietary B₁₂; adults in these regions are also at risk. Other causes of vitamin B₁₂ deficiency are much less frequent.^[11]

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. 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 (–CH₃) or a 5′-deoxyadenosyl group (here the C5′ atom of the deoxyribose forms the covalent bond with cobalt respectively, to yield the four vitamers (forms) of B₁₂. 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.^[12]

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 vitamers of B₁₂ are all deeply red-colored crystals and water solutions, due to the color of the cobalt-corrin complex.

The U.S. Institute of Medicine (renamed National Academy of Medicine in 2015) updated Estimated Average Requirements (EARs) and Recommended Dietary Allowances (RDAs) for vitamin B₁₂ in 1998. The EAR for vitamin B₁₂ for women and men age 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 age 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, Tolerable Upper Intake Levels (known as ULs) are set 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).^[13]

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 age 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.^[14] 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.^[15]

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.^[16] 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.^[17]

Most omnivorous people in developed countries obtain enough vitamin B₁₂ from consuming animal products including, meat, fish, eggs, and milk,^[7] but there are no vegan sources other than B₁₂-fortified foods or B₁₂ supplements.

B₁₂ is only produced in nature by certain bacteria, and archaea.^[18]^[19]^[20] It is synthesized by some bacteria in the gut flora in humans and other animals, but humans cannot absorb this as it is made in the colon, downstream from the small intestine, where the absorption of most nutrients occurs.^[21] Ruminants, such as cows and sheep, absorb B₁₂ produced by bacteria in their guts.^[21] For gut bacteria of ruminants to produce B₁₂ the animal must consume sufficient amounts of cobalt.^[22] These grazing animals acquire the bacteria that produce vitamin B₁₂, and the vitamin itself.» (wikipedia)