Cobalamin (vitamin B12): forms of cobalamin and its biological significance. Cobalamin’s occurrence and supply. Deficiency and the typical symptoms thereof.

Cobalamin (Vitamin B12) – A Significant Molecule

Cobalamin is the chemical term for vitamin B12, although in casual speech both names tend to be used synonymously. The term cobalamin is derived from the central cobalt atom within all forms of vitamin B12. In actual fact, it would be more correct to speak of cobalamines in the plural, since the name denotes an array of different chemical compounds. 

Cobalamins are characterised by certain special features: they are among the most complex biological molecules of all and are also the only known natural substances to contain cobalt. 

It is also remarkable to note that, although cobalamines are found in all living organisms, they can only be produced by microorganisms – a feat that even modern chemistry can only imitate with difficulty; vitamin B12 is one of the most complex molecules ever synthesised in a chemical laboratory.

Since cobalamin is a vital substance for all living beings, this means that all life on earth is directly dependent on bacteria and microorganisms through vitamin B12. 

The Different Forms of Cobalamin

The basic chemical structure of cobalamines is always the same: a central cobalt atom surrounded by a ring of five nitrogen atoms. However, the cobalamin forms differ according to the sixth atom of the molecule, which is only loosely bound to the central cobalt atom and after which the various vitamin B12 forms are named.

In humans there are four cobalamin forms that are of particular significance, which are all referred to as vitamin B12. In actual fact, there are only two forms that are active in the metabolism, known as vitamin B12 coenzymes. 

The Active Coenzyme Forms

  • Methylcobalamin
    Functions in the cell plasma, is required to activate folic acid and for methionine synthase
  • Adenosylcobalamin
    Functions in the mitochondria, is vital for the citrate cycle and energy production

The Natural Form

  • Hydroxocobalamin
    The form that is produced by bacteria, has a detoxifying effect and can easily be converted into the active forms in the body

The Synthetic Form

  • Cyanocobalamin
    A synthetic substance made in laboratories, which can be converted into the active B12 forms in the body. Often used in supplements

In addition, there are numerous other metabolic forms of vitamin B12, although the exact functions of some remain unknown. 

For an overview of this topic, see: Vitamin B12 Forms 

Cobalamin’s Major Biological Significance 

Cobalamin/B12 is a vital vitamin, which has a monumental influence of the health of our bodies, effecting almost every single area of our organism. 

As an important coenzyme, B12 is required in the metabolism of every reproductive cell and influences, among other areas: cell division, haematopoiesis, the function of the nervous system, DNA synthesis, the production of neurotransmitters, the metabolism of fats, energy generation, detoxification and the protein metabolism. 

Especially for the maintenance of nerves, energy balance and mental health, the significance of vitamin B12 is becoming ever clearer, which is why it is being increasingly administered for multiple illnesses. 

A long-term cobalamin deficiency can lead to the gradual decay of the body and ultimately from severe anaemia to death.

More information: Vitamin B12 Benefits

Cobalamin Requirement 

The average person requires approximately 3 µg of cobalamin per day in order to maintain health. However, the supply must often be significantly higher to compensate for various absorption disorders that hinder the intake of B12 in the body. 

Pregnancy, breastfeeding, stress and the consumptions of drugs or even medication can furthermore greatly increase the B12 requirement. 

Further reading: Vitamin B12 Daily Requirement

Supply of Cobalamin 

Neither humans, animals nor plants can produce vitamin B12 themselves, but are reliant on microorganisms. This is why B12 is not found in plant-based foods, but only occurs in relevant, concentrated amounts in animal products. 

Cobalamin is produced exclusively by particular microorganisms, mainly bacteria that occur in the earth, certain algae, as well as in the bodies of humans and animals. 

In the case of rumination, B12 is produced by these bacteria in the rumen and an external supply is therefore not required. Other herbivores acquire small amounts of B12 in their diets via the remnants of soil and faeces on plants, within which microorganisms live. 

For humans, partial endogenous vitamin B12 production is theoretically possible through intestinal bacteria, however for health reasons this is very rarely achieved, which is why most people today rely on a dietary supply of the vitamin. 

This is particularly urgent for vegans and vegetarians, since B12 only occurs on plant-based foods in minimal amounts through contamination. All vegan associations worldwide therefore advise the consumption of B12 fortified foods or supplements for everyone on a vegan diet. 

Yet many omnivores also suffer from B12 deficiency, which is due to the complex absorption mechanism of B12. 

See here the following articles:

Vitamin B12 for Vegetarians and Vegans

Vitamin B12 Foods

Cobalamin Intake 

Vitamin B12 which has been obtained through the diet is absorbed via a transport protein by the name of intrinsic factor, enabled by special receptors in the mucous membrane in the small intestine. Intrinsic factor (IF) is created by the parietal cells in the gastric mucosa. 

Through IF a maximum of 1.5 μg B12 can be absorbed per meal/dose. Then, a further 1% of the dose can be taken in through the small intestine via passive diffusion, so that the total intake can be calculated through these two mechanisms. 

The low absorption ability of the body explains why very high amounts of B12 must often be consumed in order to cover a somewhat small requirement. This is particularly the case if IF production has ceased due to an illness. 

The liver is able to store relatively large amounts of B12: between 2 – 5 mg/2000 – 5000 μg. This equates to roughly 50-90% of all the cobalamin in the body and theoretically this storage capacity can supply an individual for months or even years.

Cobalamin/Vitamin B12 Deficiency

Despite the liver’s ability to store vitamin B12, deficiencies of this vital vitamin are incredibly common. Here, absorption disorders are the main cause. If the gastric or intestinal mucosa are disturbed, a B12 deficiency can occur relatively fast – yet other causes such as the intake of certain medications can also inhibit the absorption of cobalamin. 

Often the vitamin B12 supply is simply too low, either because particular life circumstances majorly increase the B12 requirement, or because the vitamin is almost exclusively found in animal products, so is hard to acquire on certain diets. 

As we have mentioned, this can be observed especially in vegetarians and vegans, since there are hardly any opportunities to obtain sufficient amounts of vitamin B12 from plant sources. 

More information: Vitamin B12 Deficiency

Cobalamin Deficiency Symptoms 

Vitamin B12 deficiency can trigger multiple, very different, serious symptoms and sequelae, which unfortunately are often not suspected of being nutrient-related. 

The following deficiency symptoms are the most common: 

  • Disruptions to the energy metabolism (chronic exhaustion and fatigue, poor concentration, muscle weakness)
  • Nerve damage (pain, numbness, tingling, paralysis, coordination disorders, memory disorders)
  • Anaemia (poor physical performance, immunodeficiency)
  • Disorders of the hormone and neurotransmitter metabolism (mental-psychological disorders, depressions, psychoses)
  • Digestive problems (constipation, diarrhoea)
  • Inflammations (oral, gastric or intestinal)

A detailed description of the symptoms can also be found in the article: Vitamin B12 Deficiency Symptoms

Plus, for information on how to check your vitamin B12 levels, see: Vitamin B12 Deficiency Test 

Causes of Cobalamin Deficiency

These are the main causes of cobalamin/vitamin B12 deficiency:

  1. Malabsorption
    Disorders, irritations, inflammations or diseases of the gastric mucosa (restricts IF production) and/or small intestinal mucosa (inhibits absorption) – due to e.g. gastritis, Crohn’s disease, chronic enteritis, chronic diarrhoea, pancreatic disease – can significantly restrict the absorption/utilisation of cobalamin. People with inflammations of the gastric and/or intestinal mucosa can subsequently suffer from a severe B12 deficiency, whether or not they obtain an adequate dietary supply.
  2. Reduced intake due to age
    People in old age often develop a weaker gastric wall, which can lead to a reduced B12 intake. Vitamin B12 deficiency is a possible cause of fatigue, memory problems and depression in older people.
  3. Increased requirement
    This includes in particular chronic and nitrosative stress, caused by mental/physical stress, heavy metals, toxins, medication and trauma. A strongly increased need exists also in pregnancy/breastfeeding women. 
  4. Deficient diet
    Too little B12 supplied through food – often occurs in vegetarians and vegans diets. 
  5. Alcohol, drugs, medication 
    For the body to break down alcohol/drugs it requires a lot of B12 and damages the gastric mucosa and liver, which inhibits the production of IF and can lead to poor absorption in the gut. Various medications greatly reduce the absorption of B12, including: oestrogen-containing contraceptives and hormone supplements (proton pump inhibitors), diabetes medicine (metformin), antihypertensive drugs (ACE), medicines for cardiac arrhythmia (beta-blockers, nitrate sprays, nitroglycerin), cholesterol-lowering medicine (statins) and sexual enhancers.
  6. Intestinal worms/parasites  
    Tapeworms in particular steal very high amounts of vitamin B12. As long as the worms remain, an adequate supply of B12 cannot be secured. 
  7. Severe diseases 
    In the case of the (partial) removal of the stomach or small intestine in surgery, the absorption of B12 is limited. Furthermore, liver diseases can cause storage and transport problems.

Further information: Vitamin B12 Deficiency Causes

Cobalamin as a Therapeutic Agent

Due to its central biological significance, cobalamin has been brought into connection with a plethora of pathologies. However, there are still many contexts in which the vitamin has not yet been sufficiently researched, even though numerous positive individual case reports are available.

Positive experiences have been documented in the following areas in particular: 

  • Chronic exhaustion and tiredness
  • Chronic pain
  • Neurological disorders
  • Dementia
  • Mental illness
  • Skin diseases

For more information, see the following articles:

Vitamin B12 as Medicine
Vitamin B12 and Nitrosative Stress

Cobalamin in Supplements

All of the cobalamin forms mentioned at the beginning of this article are used in supplements. The three natural forms demonstrate a better effect and usability than artificial cyanocobalamin, which has a lower absorption and storage capacity.

Justifiably, cyanocobalamin is thus being increasingly replaced by the two active coenzyme forms. Methylcobalamin has become particularly popular, although with some criticism that it provides only a one-sided supply. It is thus advisable to use supplements that contain all of the three natural forms. 

While injections are often administered for people experiencing severe deficiencies and diseases, oral supplements such as capsules and tablets are today the “gold standard” of cobalamin therapy. Here, capsules are superior to tablets as they generally contain less/no additives. 

Depending on the necessary application, there is a very wide range of vitamin B12 dosages on offer, from supplements with 3 µg to reinforce the dietary supply, through 200 µg to cover the total daily requirement, up to 1000 µg and more to be used in therapeutic contexts and to rapidly refill the body’s stores. 

More information:
Vitamin B12 Supplements
Vitamin B12 Dosages

Cobalamin – Central to Health

Despite the increasing interest in vitamin B12 (largely due to the ever-growing popularity of veganism) it remains an underestimated vitamin. What is more, its potential is far from exhausted. 

In clinical practice in particular, many doctors still have little to no knowledge of the various symptoms of a cobalamin deficiency, which are therefore being misdiagnosed and mistreated. 

Chronic pain, paralysis and mental disorders can be treated with cobalamin, in many cases; instead, expensive and often invasive medicines are used, which frequently induce severe side effects. 

On this website, we hope to raise awareness about the potential of cobalamin for both patients and medical professionals alike.