The different types of vitamin B12
Vitamin B12 is the most chemically complex of all the vitamins. It’s chemical name is cobalamin, which derives from its central cobalt atom. It’s impressive formula C63H88N14O14PCo gives an indication of the intricate molecular structure that makes up this vitamin.
However cobalamin is almost never found in its chemically pure form as it is usually bound to other molecules. The B12 type depends on which molecules it is bound to.
B12 Types Found in Foods
There are three main types of cobalamin that can be found in foods:
Adenosylcobalamin and hydroxocobalamin are the forms most commonly found in meats, whereas methylcobalamin is commonly found in dairy products. Other types of B12 are not commonly found in foods, or may only contain traces.
B12 Forms Found in the Body
In the body absorbed B12 works as a coenzyme (see also: B12 Benefits) that assists a number of important enzymes in the functions, but only two B12 structures can be used in the body as an active coenzyme:
Methylcobalamin and adenosylcobalamin
Hydroxocobalamin (also: hydroxycobalamin) is not a coenzyme form of vitamin B12, but can be easily converted by the body into one of the useable forms. It binds particularly well to transport molecules, meaning it can circulate the body for a prolonged period of time. Because of this attribute it is known to have the most long lasting effects out of all the different B12 forms.
Adenosylcobalamin is primarily found on the body’s stores, particularly in the liver. Methylcobalamin is often found in the blood and spinal cord. Both adenosylcobalamin and methylcobalamin are required in the cells, and both forms are easily converted into the other. Methylcobalamin works in the cell plasma while adenosylcobalamin is only active in the mitochondria.
Vitamin B12 Active Ingredients in Supplements
The synthetic cyanocobalamin form and hydroxocobalamin have been traditionally used for vitamin B12 shots.
For oral supplements such as tablets and capsules, hydroxocobalamin and the synthetic form cyanocobalamin are most commonly used. Although methylcobalamin and adenosylcobalamin are the readily useable bioactive forms of B12, they are quite unstable outside of the body. Above all this is due to their photosensitivity, which makes them hard to produce. However, recently due to their significant therapeutic value, these two forms have become more readily available as supplements.
Efficacy Spectrum of the Bioactive Vitamin B12 Forms
The table below shows the spectrum of activity of both methylcobalamin and adenosylcobalamin.
Place of effect
Cytoplasm, nerves, brain
Neurotransmitter, gene regulation, regeneration and protection of nervous tissue and the brain, blood formation, sight
Depression, mental illness, nerve deterioration, dementia, anemia, visual impairment, chronic fatigue and exhaustion
Cell energy, brain development, hydration, growth, muscle development
Chronic fatigue, lack of energy, underweight, muscle weakness, developmental disorders, digestive disorders
Cyanocobalamin – Synthetic Vitamin B12
For many years now the synthetic vitamin B12 form cyanocobalamin has been used predominantly as the active ingredient in supplements. This form is not readily bioactive in the body and at the most is naturally occurring only in traces in foods. It is, however, simply and cheaply produced and therefore a very stable product.
Cyanocobalamin is a very well researched product and has shown to be well useable and effective in the body. It has been successfully used in many vitamin B12 treatments for a great number of years.
However, in recent years cyanocobalamin has received increasing criticism for the following reasons:
- Toxicity: It is often claimed that cyanocobalamin might be toxic because the broken down cyano group produces the toxin cyanide.
- Build up in cells: Studies have shown that when used in high dosage treatments of 1000µg that cyanocobalamin is absorbed into cell fluid.2 The effects of this are unknown.
- Bioavailability: There are four metabolic steps required to break down cyanocobalamin into a coenzyme, an obvious metabolic disadvantage.3
- Utilisation difficulties: Some genetic diseases and metabolic disorders prevent the conversion of cyanocobalamin in to active forms, meaning it cannot be used at all.4
- Methyl group raiders: To be converted into methylcobalamin, cyanocobalamin requires a methyl group, which it obtains from the important amino acid S-Adenosylmethionin (SAM). Cyanocobalamin therefore drains SAM levels.
- Lack of prolonged release: Cyanocobalamin is inferior to other forms of B12 in terms of absorption. Although it may be easily absorbed it is just as easily excreted, and a loarge portion of it will be before it reaches the cells.
Cyanocobalamin or Hydroxocobalamin?
Compared to hydroxocobalamin, cyanocobalamin has a significantly poorer absorption rate and sustained release, which is why hydroxocobalamin is more frequently the preferred choice when administering injections. Also, there is one less metabolic step required when breaking down hydroxocobalamin than with cyanocobalamin.
With hydroxocobalamin there is no danger of cyanide poisoning, interestingly enough hydroxocobalamin can be used for cyanide detoxification, as the two form cyanocobalamin. When present in the body with a normal diet, cyanocobalamin is usually the result of smoke inhalation or heavy smoking. Smokers should therefore avoid taking cyanocobalamin, but rather other B12 forms, so as not to add to the body’s cyanide levels and also to aid detoxification.
Hydroxocobalamin also effectively catches nitric oxide (nitrogen radicals) that are responsible for causing oxidative stress. This is a known pathogen of a number of illnesses and diseases.
Cyanocobalamin vs. Methylcobalamin
Today there are an increasing number of methylcobalamin based supplements on the market. It has been shown that the body can utilise methylcobalamin directly without any need for conversion beforehand and is utilised much better by the body than cyanocobalamin.5 When oral doses were compared, almost identical serum level concentrations were found. But when a high dose of cyanocobalamin was taken, large quantities of this went unused and were passed out with the urine. whereas methylcoblalmin refilled the body’s stores and also cell stores.
Methylcobalamin can also provide a number of health benefits not possible with cyanocobalamin. Tests carried out on animal subjects showed that methylcobalamin significantly increased the survivial rate of of mice with cancer, while cyanocobalamin appeared to have little or no effect6. This is probably due to the fact that in many epigenetic processes the highly important S-Adenosyl methionine is regenerated through methylcobalamin, whereas cyanocobalamin uses it up.
Methylcobalamin has also found to be superior in the treatment of sleep disorders. It is believed that methylcobalamin encourages melatonin synthesis, something that cyanocobalamin is not able to do.
Conversion of B12 Types
This diagram shows the steps necessary in converting each form of vitamin B12.
The Well-Known Types of B12
Aside from the forms of cobalamin already mentioned there are a number of other types. The following table provides an overview of these:
B12 + Water (H2O)
Hydroxycobalamin, Vitamin B12b, OH-Cbl
B12 + hydroxyl group (OH)
B12 + Cyano group (CN)
B12 + nitrogen dioxide (NO2)
B12 + nitric oxide (NO)
B12 + sulfur trioxide (SO3)
B12 + methyl group (CH3)
Biologically active form found in the body and in foods.
Coenzyme B12b, Ado-Cbl, Dibencozide
B12 + 5′-desoxyadenosyl (C10H13N5O3)
Biologically active form found in the body and in foods.
B12 + glutathione
Vitamin B12 – One Vitamin, Many Effects
Vitamin B12 is not always the same vitamin B12. The metabolism of all its various forms are quite different, and the effects these different types have can be very different.
Although cyanocobalamin has proven to be effective in treating deficiencies, it is becoming increasingly clear that the coenzyme forms are much more advantageous and offer a wider efficacy spectrum and they do not share the disadvantages of cyanocobalamin,
The residual effect of hydroxocobalamin in particularly advantageous, as it ensures a lasting supply of B12. In addition it is more easily absorbed by the body than cyanocobalamin.
It also makes sense to assume that natural forms of B12 found in foods are going to benefit our bodies more than those that are synthetically produced. Therefore it is advisable where possible to use the the natural forms, in particular the coenzyme form.
1 A.G. Freeman Cyanocobalamin – a case for withdrawal: discussion paper. J R Soc Med. Nov 1992; 85(11): 686–687.
2 Gimsing P, Hippe E, Helleberg-Rasmussen I, et al. Cobalamin forms in plasma and tissue during treatment of vitamin B12 deficiency. Scand J Haematol 1982;29:311-318
3 Pezacka E, Green R, Jacobsen DW. Glutathionylcobalamin as an intermediate in the formation of cobalamin coenzymes. Biochem Biophys Res Commun. 1990 Jun 15;169(2):443-50. PubMed PMID: 2357215.
4 Hans C. Andersson, Emmanuel Shapira, Biochemical and clinical response to hydroxocobalamin versus cyanocobalamin treatment in patients with methylmalonic acidemia and homocystinuria (cblC), The Journal of Pediatrics, Volume 132, Issue 1, January 1998, Pages 121-124, ISSN 0022-3476, http://dx.doi.org/10.1016/S0022-3476(98)70496-2.
5 Okuda K, Yashima K, Kitazaki T, Takara I. Intestinal absorption and concurrent chemical changes of methylcobalamin. J Lab Clin Med. 1973 Apr;81(4):557-67. PubMed PMID: 4696188.
6 Tsao C, S, Myashita K, Influence of Cobalamin on the Survival of Mice Bearing Ascites Tumor. Pathobiology 1993; 61:104-108
7 Masayuki Ikeda, Makoto Asai, Takahiro Moriya, Masami Sagara, Shojiro Inoué, Shigenobu Shibata, Methylcobalamin amplifies melatonin-induced circadian phase shifts by facilitation of melatonin synthesis in the rat pineal gland, Brain Research, Volume 795, Issues 1–2, 8 June 1998, Pages 98-104, ISSN 0006-8993, http://dx.doi.org/10.1016/S0006-8993(98)00262-5.
8 Carmen Wheatley Cobalamin in inflammation III — glutathionylcobalamin and methylcobalamin/adenosylcobalamin coenzymes: the sword in the stone? How cobalamin may directly regulate the nitric oxide synthases. Journal of Nutritional and Environmental Medicine 2007 16:3-4, 212-226 doi=10.1080%2F13590840701791863
9 Catherine S. Birch, Nicola E. Brasch, Andrew McCaddon, John H.H. Williams, A novel role for vitamin B12: Cobalamins are intracellular antioxidants in vitro, Free Radical Biology and Medicine, Volume 47, Issue 2, 15 July 2009, Pages 184-188, ISSN 0891-5849, http://dx.doi.org/10.1016/j.freeradbiomed.2009.04.023.