Vitamin B12

Overview

Vitamin B₁₂, also known as cobalamin or extrinsic factor, is a water-soluble vitamin involved in metabolism. One of eight B vitamins, it serves as a vital cofactor in DNA synthesis and both fatty acid and amino acid metabolism. It plays an essential role in the nervous system by supporting myelin synthesis and is critical for the maturation of red blood cells in the bone marrow. Animals require B₁₂ but plants do not, relying instead on alternative enzymatic pathways.[1–4] WP

Vitamin B₁₂ is the most chemically complex of all vitamins, and is synthesized exclusively by certain archaea and bacteria. Natural food sources include meat, shellfish, liver, fish, poultry, eggs, and dairy products. It is also added to many breakfast cereals through food fortification and is available in dietary supplement and pharmaceutical forms. Supplements are commonly taken orally but may be administered via intramuscular injection to treat deficiencies.[1][5][6][7] WP

In healthy adults, vitamin B₁₂ deficiency is not common, mainly because body stores of the vitamin are substantial and turnover is slow, with relatively low dietary requirements. However, B₁₂ deficiency in the elderly is a significant concern, and is related to dementia. The most common cause in developed countries is impaired absorption due to loss of gastric intrinsic factor (IF), required for absorption. A related cause is reduced stomach acid production with age or from long-term use of proton-pump inhibitors, H₂ blockers, or other antacids, and interaction with metformin. Elderly people – due to impaired intestinal absorption – and children, premenopausal women, and pregnant women whose diets are low in animal foods are all at increased risk.[1][2][8–11] WP

Deficiency is especially harmful in pregnancy, childhood, and older adults. It can lead to neuropathy, megaloblastic anemia, and pernicious anemia, causing symptoms including fatigue, paresthesia, depression, cognitive decline, ataxia, and even irreversible nerve damage. In infants, untreated deficiency may result in neurological impairment and anemia. Maternal deficiency increases the risk of miscarriage, neural tube defects, and delayed development in offspring. Folate levels may modify the presentation of symptoms and disease course.[1][12][13] WP

Uses, dosage and effects

Treatment of deficiency

Severe vitamin B₁₂ deficiency is initially corrected with daily intramuscular injections of of the vitamin, followed by maintenance via monthly injections of the same amount or daily oral dosing of. The oral daily dose far exceeds the vitamin requirement because the normal transporter protein-mediated absorption is absent, leaving only inefficient intestinal passive absorption. Injection side effects include skin rash, itching, chills, fever, hot flushes, nausea and dizziness. There are not enough studies on whether pills are as effective in improving or eliminating symptoms as parenteral treatment.[14][15][16] WP⚠ Part of this sentence could not be copied from the source. Open the source to read it in full.⚠ A word may be missing here. It reads this way in the source too.

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 non-toxic cyanocobalamin is excreted in urine.[17][18][19] WP

Descriptions of deficiency effects

Between 1849 and 1887, Thomas Addison described a case of pernicious anemia, William Osler and William Gardner first described a case of neuropathy, Hayem described large red cells in the peripheral blood in this condition, which he called "giant blood corpuscles" (now called macrocytes), Paul Ehrlich identified megaloblasts in the bone marrow, and Ludwig Lichtheim described a case of myelopathy.[20] WP

Interactions

H₂-receptor antagonists and proton-pump inhibitors

Gastric acid is needed to release vitamin B₁₂ from protein for absorption. Reduced secretion of gastric acid and pepsin, from the use of H₂ blocker or proton-pump inhibitor (PPI) drugs, can reduce the absorption of protein-bound (dietary) vitamin B₁₂, although not of supplemental vitamin B₁₂. H₂-receptor antagonist examples include cimetidine, famotidine, nizatidine, and ranitidine. PPIs examples include omeprazole, lansoprazole, rabeprazole, pantoprazole, and esomeprazole. Clinically significant vitamin B₁₂ deficiency and megaloblastic anemia are unlikely, unless these drug therapies are prolonged for two or more years, or if in addition, the person's dietary intake is below recommended levels. Symptomatic vitamin deficiency is more likely if the person is rendered achlorhydric (a complete absence of gastric acid secretion), which occurs more frequently with proton pump inhibitors than H₂ blockers.[21] WP

Metformin

Reduced serum levels of vitamin B₁₂ occur in up to 30% of people taking long-term anti-diabetic metformin. Deficiency does not develop if dietary intake of vitamin B₁₂ is adequate or prophylactic B₁₂ supplementation is given. If the deficiency is detected, metformin can be continued while the deficiency is corrected with B₁₂ supplements.[22][23][24] WP

Other drugs

Certain medications can decrease the absorption of orally consumed vitamin B₁₂, including colchicine, extended-release potassium products, and antibiotics such as gentamicin, neomycin and tobramycin. Anti-seizure medications phenobarbital, pregabalin, primidone and topiramate are associated with lower than normal serum vitamin concentration. However, serum levels were higher in people prescribed valproate. In addition, certain drugs may interfere with laboratory tests for the vitamin, such as amoxicillin, erythromycin, methotrexate and pyrimethamine.[25][26] WP

History

Identification of liver as an anti-anemia food

During the 1920s, George Whipple discovered that ingesting large amounts of raw liver seemed to most rapidly cure the anemia of blood loss in dogs, and hypothesized that eating liver might treat pernicious anemia. Edwin Cohn prepared a liver extract that was 50 to 100 times more potent in treating pernicious anemia than the natural liver products. 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. In 1934, George Whipple shared the 1934 Nobel Prize in Physiology or Medicine with William P. Murphy and George Minot for discovery of an effective treatment for pernicious anemia using liver concentrate, later found to contain a large amount of vitamin B₁₂.[20][27][28] WP

Identification of the active compound

While working at the Bureau of Dairy Industry, U.S. Department of Agriculture, Mary Shaw Shorb was assigned work on the bacterial strain Lactobacillus lactis Dorner (LLD), which was used to make yogurt and other cultured dairy products. The culture medium for LLD required liver extract. Shorb knew that the same liver extract was used to treat pernicious anemia (her father-in-law had died from the disease), and concluded that LLD could be developed as an assay method to identify the active compound. While at the University of Maryland, she received a small grant from Merck, and in collaboration with Karl Folkers from that company, developed the LLD assay. This identified "LLD factor" as essential for the bacteria's growth. Shorb, Folker and Alexander R. Todd, at the University of Cambridge, used the LLD assay to extract the anti-pernicious anemia factor from liver extracts, purify it, and name it vitamin B₁₂. In 1955, Todd helped elucidate the structure of the vitamin. The complete chemical structure of the molecule was determined by Dorothy Hodgkin based on crystallographic data and published in 1955 and 1956, for which, and for other crystallographic analyses, she was awarded the Nobel Prize in Chemistry in 1964. Hodgkin went on to decipher the structure of insulin.[29–33] WP

George Whipple, George Minot and William Murphy were awarded the Nobel Prize in 1934 for their work on the vitamin. Three other Nobel laureates, Alexander R. Todd (1957), Dorothy Hodgkin (1964) and Robert Burns Woodward (1965) made important contributions to its study.[34] WP

Commercial production

Industrial production of vitamin B₁₂ is achieved through fermentation of selected microorganisms. As noted above, the completely synthetic laboratory synthesis of B₁₂ was achieved by Robert Burns Woodward and Albert Eschenmoser in 1972, though this process has no commercial potential, requiring more than 70 steps and having a yield well below 0.01%.[35][36] WP

Legal status

Society and culture

In the 1970s, John A. Myers, a physician residing in Baltimore, developed a program of injecting vitamins and minerals intravenously for various medical conditions. The formula included of cyanocobalamin. This came to be known as the Myers' cocktail. After he died in 1984, other physicians and naturopaths took up prescribing "intravenous micronutrient therapy" with unsubstantiated health claims for treating fatigue, low energy, stress, anxiety, migraine, depression, immunocompromised, promoting weight loss, and more. However, other than a report on case studies there are no benefits confirmed in the scientific literature. Healthcare practitioners at clinics and spas prescribe versions of these intravenous combination products, but also intramuscular injections of just vitamin B₁₂. A Mayo Clinic review concluded that there is no solid evidence that vitamin B₁₂ injections provide an energy boost or aid weight loss.[37][38][39] WP⚠ Part of this sentence could not be copied from the source. Open the source to read it in full.

There is evidence that for elderly people, physicians often repeatedly prescribe and administer cyanocobalamin injections inappropriately, evidenced by the majority of subjects in one large study either having had normal serum concentrations or having not been tested before the injections.[40] WP

Chemistry

Formula

C63H88CoN14O14P PC

Molar mass (g/mol)

1355.4 PC

IUPAC name (computed by PubChem)

cobalt(3+);[5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] 1-[3-[2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl)-3,5,8,8,13,15,18,19-octamethyl-2,7,12,17-tetrahydro-1H-corrin-21-id-3-yl]propanoylamino]propan-2-yl phosphate;cyanide PC

SMILES

CC1=CC2=C(C=C1C)N(C=N2)C3C(C(C(O3)CO)OP(=O)([O-])OC(C)CNC(=O)CCC4(C(C5C6(C(C(C(=N6)C(=C7C(C(C(=N7)C=C8C(C(C(=N8)C(=C4[N-]5)C)CCC(=O)N)(C)C)CCC(=O)N)(C)CC(=O)N)C)CCC(=O)N)(C)CC(=O)N)C)CC(=O)N)C)O.[C-]#N.[Co+3] PC

InChIKey

FDJOLVPMNUYSCM-UHFFFAOYSA-L PC

PubChem CID

184933

Harm reduction information

No harm reduction data is on file for this compound yet. That means no dose, timing or combination data from PsychonautWiki or TripSit. Please don't guess a dose from similar compounds. If you have taken it and feel unwell, contact emergency services or a poison control center.

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Pop culture

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Sources

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