Vitamin B₁₂ – Cobalamin

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Vitamin B₁₂ – also known as cobalamin or coenzyme B₁₂ – is found in almost all animal products but not in plant products. Good cobalamin food sources are meat, eggs, and dairy products. If needed, vitamin B₁₂ can be supplemented as methyl- or cyano-cobalamin.

Functions of vitamin B₁₂ in the human body

Vitamin B₁₂ (cobalamin) is needed in more than 100 different biochemical reactions in the human body. However, vitamin B₁₂ participates only in two enzymatic reactions (Methionine synthase and methylmalonyl-CoA mutase).

Storage of vitamin B₁₂ in the human body

Because of the exceptionally huge storage capacity for a water-soluble vitamin, lack of vitamin B₁₂ (cobalamin) leads to clinical symptoms only after a very long deprivation (1-2 years). The liver alone stores 2-5 mg vitamin B₁₂. Another 2-5 mg vitamin B₁₂ (cobalamin) can be stored in other tissues of the body, especially in kidneys and muscles.

Requirement of vitamin B₁₂

The minimum daily requirement of vitamin B₁₂ is approximately 2-3 μg (mcg) per day.

Although vitamin B₁₂ is formed by the gut flora in the large intestine, it is not sufficient to supply the daily need and humans depend on the intake of cobalamin from (animal) food. Vegans (and some vegetarians) will therefore need to use food supplements to meet their minimum daily requirement of vitamin B₁₂.

Intake of vitamin B₁₂ from (animal) food

Vitamin B₁₂ (cobalamin) can only be absorbed from the body if it is bound to intrinsic factor (IF). Intrinsic factor (IF) is a protein that is produced by cells of the stomach and secreted into it whilst digesting food. Once bound in a complex with IF, Vitamin B₁₂ travels through the digestive tract and can be absorbed in the lower small intestine (ileum), where it enters the blood stream.

Vitamin B₁₂ deficiency

The most common cause of vitamin B₁₂ (cobalamin) deficiency is a vegan or (in some cases) vegetarian nutrition. Most cases of pathologic vitamin B₁₂ deficiency are caused by disruptions in the formation of the intrinsic factor (IF). Type A gastritis is an autoimmune disease and leads to the formation of antibodies against the intrinsic factor (IF). Type A gastritis and chronic gastritis can result in a relative lack of functional intrinsic factor. However, vitamin B₁₂ (cobalamin) can only be absorbed in the lower small intestine (ileum) if bound to IF. Thus, type A gastritis results in vitamin B₁₂ deficiency.

Rarer causes of vitamin B₁₂ deficiency are mucosal atrophy, inflammation of the terminal ileum (like Crohn’s disease, or celiac disease), gastrointestinal resections or chronic pancreatic diseases. Other rare causes include intestinal infections with fish tapeworm, bacterial overgrowth and iatrogenic deficiency by the use of certain drugs, like antihistamines, proton pump inhibitors and metformin.

Lack of vitamin B₁₂

Vitamin B₁₂ deficiency can lead to:

• Anaemia (Pernicious, megaloblastic anaemia, hyperchromatic, macrocytic) and / or
• Neurological or neuropsychiatric symptoms (funicular myelosis)

If there is sufficient supply of vitamin B₁ and B₉, vitamin B₁₂ deficiency, only funicular myelosis and no pernicious, megaloblastic anaemia occurs! That is why in vegans and vegetarians the high folic acid intake (vitamin B₉) often masks the haematological symptoms (anaemia) of a vitamin B₁₂ deficiency.

An untreated vitamin B₁₂ deficiency is associated with an increased risk of cardiovascular disease and cancer.

Furthermore, vitamin B₁₂ deficiency can lead to a wide range of other symptoms like:

• Paraesthesia (tingling, tickling, pricking, burning, or numbness of the skin)
• Burning mouth syndrome (aphthous ulcers or glossitis)
• Tiredness, difficulty in concentrating, poor memory
• Depression
• High blood pressure
• Headache and migraine (without aura)
• Lack of appetite and food intolerances
• Allergies
• Muscle weakness
• Back pain
• Frequent crying in babies and severe and irreversible developmental disorders

These symptoms may occur as early symptoms. The onset of these symptoms is often slow and progressive and the symptoms can vary greatly vary from person to person.

Test for vitamin B₁₂ deficiency

In order to test how much vitamin B₁₂ is stored in your body, a blood analysis has to be undertaken. Taken together, there are four relevant biomarkers in the blood that together can be used to judge the body´s vitamin B12 supply. Furthermore, because vitamin B₁₂ deficiency can lead to anaemia, the increased size and colour of the erythrocytes are also important indicators of vitamin B12 deficiency.

Blood biomarkers

The reference range for the cobalamin (vitamin B₁₂) blood plasma level ranges from 223 pg/ml to 1,332 pg/ml. The sole measurement of the cobalamin (vitamin B₁₂) blood plasma level, however, gives no reliable information about the actual vitamin B₁₂ supply.

Other important biomarkers of vitamin B₁₂ deficiency are increased blood plasma levels of homocysteine, methylmalonic acid, and decreased blood plasma levels of holotranscobalamin.

The four important biomarkers of vitamin B₁₂ deficiency are:

• Homocysteine ​​↑ – increased – >5-15 μmol/l
• Methylmalonic acid (MMA) ​​↑ – increased – >40-270 pmol/l
• Holotranscobalamin (holo-TC) ↓ – decreased – <50-170 pmol/l
• Vitamin B₁₂ ↓ (cobalamin) – decreased – 223-1,332 pg/ml
  • Cobalamin is decreasing at least and is therefore quite an unspecific biomarker!

Erythrocytes – Size and colour

Because of the central role of vitamin B₁₂ in the formation of red blood cells (erythrocytes), another indicator of vitamin B₁₂ deficiency is the state of the erythrocytes. Prolonged lack of cobalamin (vitamin B₁₂) leads to anaemia, with changes in the size and the colour of erythrocytes in the blood.

Vitamin B₁₂ supplementation

If you have got a proven vitamin B₁₂ (cobalamin) deficiency, there are two ways of supplementation

• Oral, food supplements
• Intramuscular injection

Oral food supplements

Oral food supplements are a good way to compensate vitamin B₁₂ deficiency due to vegan or vegetarian nutrition. Oral vitamin B₁₂ food supplements usually consist of bacterially derived methylcobalamin. Vitamin B₁₂ caps or tablets can be used to refill the body’s storage capacity (10mg in total) quickly. Please speak to your healthcare provider to know how much vitamin B₁₂ you will need to take in order to refill your vitamin B₁₂ storage.

There are tablets on the market that contain up to 1,000 μg (1 mg) of vitamin B₁₂. Furthermore, the use of toothpaste enriched with vitamin B₁₂ is a good way of increasing your vitamin B₁₂ storage. It is known that vitamin B₁₂ can also be absorbed directly in the mouth, via the oral mucosa.

Because vitamin B₁₂ (cobalamin) is water-soluble, it cannot be overdosed if ingested via food or oral food supplements. Like most other water-soluble vitamins, excessive vitamin B₁₂ is excreted via urine and stool.

Intramuscular injections

People with a relative lack of intrinsic factor (IF) will need to increase their oral dose to high doses of  1000 µg (1 mg) to be able to absorb vitamin B₁₂. Intramuscular injection is a good alternative for these people, as well as for people that cannot absorb vitamin B₁₂ in the lower small intestine (ileum), e.g. due to inflammation of the terminal ileum, intestinal infections, intestinal resections.

Vitamin B₁₂ injections have to be performed by a trained healthcare provider. Please be aware that vitamin B₁₂ injections can lead to local allergic complaints and a form of acne (acne medicamentosa).