Vitamin used in animal cell metabolism
- "B12" and "Cbl" redirect here. For other uses of B12, see B12 . For the musical group, see Carbon Based Lifeforms.
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. While animals require B12, plants do not, relying instead on alternative enzymatic pathways.
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.
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. 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. Elderly people due to impaired intestinal absorption, children, premenopausal women, and pregnant women, whose diets are low in animal foods, are at increased risk.
Deficiency is especially harmful in pregnancy, childhood, and older adults. It can lead to neuropathy, megaloblastic anemia, and pernicious anemia, causing symptoms such as 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 developmental delays in offspring. Folate levels may modify the presentation of symptoms and disease course.
Safety at a Glance
- Toxicity: B12 has no known toxicity even at very high doses because excess is excreted in urine. No tolerable upper intake leve...
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Dosage
Oral
Duration
Oral
Total: 24 hrs – 48 hrsHow It Feels
Cobalamin (B12) supplementation produces no dramatic acute effects in non-deficient individuals. In those with deficiency, which is common in older adults and those on plant-based diets, repletion can produce a noticeable improvement in energy levels, mental clarity, and mood over days to weeks. The characteristic B12-deficiency fatigue lifts. Cognitive fog clears. Tingling or numbness in the extremities from neurological damage may gradually improve. The experience is one of restoration to normal function.
Subjective Effects
The effects listed below are based on the Subjective Effect Index (SEI), an open research literature based on anecdotal reports and personal analyses. They should be viewed with a healthy degree of skepticism. These effects will not necessarily occur in a predictable or reliable manner, although higher doses are more liable to induce the full spectrum of effects.
Cognitive & Perceptual Effects
Cognitive(2)
- Depression— A persistent state of low mood, emotional numbness, hopelessness, and diminished interest or pleasur...
- Psychosis— Psychosis is a serious psychiatric state involving a fundamental break from consensus reality — char...
Pharmacology
B12 functions as a cofactor for two human enzymes. Methylcobalamin is the cofactor for methionine synthase, which remethylates homocysteine to methionine (essential for SAMe production and DNA methylation). Adenosylcobalamin is the cofactor for methylmalonyl-CoA mutase, which converts methylmalonyl-CoA to succinyl-CoA in propionate and odd-chain fatty acid metabolism.
In the nervous system, B12's role in methionine synthase is critical because methionine is the precursor to S-adenosylmethionine (SAMe), the universal methyl donor required for myelin synthesis, neurotransmitter metabolism, and epigenetic regulation. B12 deficiency causes accumulation of homocysteine (neurotoxic and cardiovascular risk factor) and methylmalonic acid (which disrupts fatty acid synthesis and myelin maintenance).
The neuropsychiatric manifestations of B12 deficiency (depression, cognitive decline, psychosis, peripheral neuropathy, subacute combined degeneration of the spinal cord) can occur even before anemia develops, and the neurological damage can become irreversible if treatment is delayed.
Interactions
No documented interactions.
History
- Further information: Vitamin §History
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.
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.
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.
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.
Nobel laureates for discoveries relating to vitamin B12
George Whipple
George Minot
William P. Murphy
Alexander R. Todd
Dorothy Hodgkin
Robert Burns Woodward
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%.
Harm Reduction
Vitamin B12 is water-soluble and generally very safe even at high supplemental doses, as excess is excreted in urine. However, very high doses (above 5000mcg daily) may cause acne in some individuals. Cyanocobalamin contains trace amounts of cyanide and should be avoided by those with kidney disease; methylcobalamin or hydroxocobalamin are preferred. B12 injections should only be administered by healthcare professionals. Those on metformin, proton pump inhibitors, or H2 blockers have increased risk of B12 deficiency and should monitor levels. Vegans and vegetarians are at particular risk of deficiency and should supplement regularly.
Toxicity & Safety
B12 has no known toxicity even at very high doses because excess is excreted in urine. No tolerable upper intake level has been established. Rare allergic reactions to B12 injections (typically to the cobalt component) have been reported. Very high doses of cyanocobalamin should be avoided in renal failure due to cyanide accumulation.
Addiction Potential
No addiction potential.
Tolerance
| Full | Not applicable — nutritional supplement |
| Half | N/A |
| Zero | N/A |
Cross-tolerances
Legal Status
This substance is not a controlled or scheduled substance in any major jurisdiction. It is widely available as a dietary supplement, food additive, or over-the-counter product in the United States, United Kingdom, European Union, Canada, and Australia. In the US, it falls under the Dietary Supplement Health and Education Act (DSHEA) of 1994 and is regulated by the FDA as a dietary supplement rather than a drug. Manufacturers are responsible for ensuring safety and accurate labeling, but pre-market approval is not required.
In the European Union, it is regulated under the Food Supplements Directive (2002/46/EC) and may be subject to maximum permitted levels set by individual member states. In the United Kingdom, it falls under the Food Supplements (England) Regulations 2003 and similar devolved legislation. In Australia, it is typically listed on the Australian Register of Therapeutic Goods (ARTG) as a complementary medicine or is available as a food product. In Canada, it may be classified as a Natural Health Product (NHP) requiring a product license from Health Canada.
No prescription is required in any of these jurisdictions, and there are no criminal penalties associated with possession, purchase, or use.
Tips (6)
Follow evidence-based dosing for Vitamin B12 rather than megadose protocols. More is not always better with supplements, and some have toxicity at high doses. The recommended daily allowance exists for a reason.
Before spending money on exotic nootropics, ensure your basic nutritional needs are met. Chronic under-eating, especially only one meal per day, can cause B12, iron, folate, and zinc deficiencies that produce symptoms identical to treatment-resistant depression. A comprehensive metabolic panel and CBC should be your first step.
Vitamin B12 deficiency can cause emotional numbness, anhedonia, and cognitive fog that mimics depression. If you have a poor diet or eat infrequently, get your B12 levels tested before trying antidepressants. A simple deficiency correction may restore emotional responsiveness within weeks.
Quality varies enormously between Vitamin B12 supplement brands. Look for products with third-party testing (USP, NSF, ConsumerLab). Cheaper brands may contain fillers, incorrect doses, or contaminants.
Choose methylcobalamin or hydroxocobalamin forms of B12 over cyanocobalamin. The methylated form is directly usable by the body and supports methylation pathways. Standard supplemental doses of 1000-2000mcg sublingual are appropriate for deficiency correction. Blood levels above 500 pg/mL are generally considered optimal.
Take Vitamin B12 consistently at the same time each day for best results. Many vitamins and nutrients need to build up to steady-state levels before you notice benefits. Give it at least 2-4 weeks.
Community Discussions (1)
See Also
References (3)
- PubChem: Vitamin B12
PubChem compound page for Vitamin B12 (CID: 165339223)
pubchem - Vitamin B12 - TripSit Factsheet
TripSit factsheet for Vitamin B12
tripsit - Vitamin B12 - Wikipedia
Wikipedia article on Vitamin B12
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