Vitamin B12 deficiency – causes, symptoms

Vitamin B12, also known as cobalamin, belongs to the group of water-soluble vitamins and is one of the most complex molecules in this group in terms of chemical structure. The only significant sources of vitamin B12 are animal products; plants and fungi do not synthesise it. Vitamin B12 deficiency is a common health problem, but its prevalence varies greatly between countries. Deficiency disrupts the functioning of many systems in the body and can lead to serious health problems.

1. Chemical forms of vitamin B12
2. Occurrence of vitamin B12
3. Causes of B12 deficiency worldwide
4. Symptoms and effects of vitamin B12 deficiency
5. Vitamin B12 supplementation

Chemical forms of vitamin B12

Vitamin B12 occurs in several active forms in the human body, the most important of which are methylcobalamin and 5'-deoxyadenosylcobalamin.

Methylcobalamin participates in the conversion of the amino acid homocysteine (potentially harmful in excess) into another amino acid, methionine (more necessary for the body than homocysteine). This is important for the synthesis of DNA (genetic material), proteins and the proper functioning of the nervous system, and even for the protection of the cardiovascular system.

5'-deoxyadenosylcobalamin, the second form, occurs mainly in the mitochondria, i.e. where energy is produced in the body's cells. It is involved in the metabolism of fatty acids and amino acids. In addition to these active forms, there are also derivatives used in supplements or medicines, such as cyanocobalamin and hydroxycobalamin, which are converted into active biological forms in the body.

Occurrence of vitamin B12

Vitamin B12 is stored primarily in the liver, and in smaller amounts in the kidneys, muscles and bone marrow, and its reserves can last for up to several years. Cobalamin is absorbed in the small intestine after forming a bond with the so-called intrinsic factor in the stomach.

The highest amounts of vitamin B12 are found in offal (liver, kidneys), red meat, fish (especially mackerel, salmon, tuna, herring and sardines), seafood (mussels, oysters), as well as eggs and dairy products. In pharmaceutical form, vitamin B12 can be administered orally, sublingually or by injection, and each method has similar effectiveness when absorbed properly.

Causes of B12 deficiency worldwide

In high-income countries, where diets are rich in animal products and fortified foods are available, deficiencies are less common. In the United States, low vitamin B12 levels are observed in approximately 3-4 per cent of adults, and mild deficiency in approximately 12 per cent. In the United Kingdom, approximately 12 per cent of women of childbearing age have B12 concentrations below 150 pmol/l, even though the overall supply of the vitamin in the population is considered sufficient.

Deficiencies are much more common in groups that eliminate animal products, such as vegetarians and vegans. In a large analysis by British scientists, nearly half of non-supplementing vegans had B12 concentrations indicative of deficiency. In India, where meat and dairy consumption is low, analyses show the highest rates in the world, with approximately 30 to 50 per cent of adults possibly being deficient.

In Latin America, the prevalence varies widely, from a few percent to over 30 per cent, and in sub-Saharan Africa, studies of pregnant women and schoolchildren typically report 20–30 per cent. In the Middle East, specifically in Lebanon, low or borderline B12 levels were found in over 60 per cent of adults in 2024. Deficiencies are also common in older people worldwide, affecting 10 to 15 per cent of the population, which is associated with impaired absorption and the use of drugs that reduce gastric acid secretion, which is necessary for absorption.

Estimated vitamin B12 content in several sources

Symptoms and effects of vitamin B12 deficiency

Anaemia

The most immediate effect of vitamin B12 deficiency is the development of anaemia, because without it, the bone marrow cannot produce normal red blood cells. This leads to fatigue, weakness, dizziness, pale skin and shortness of breath during exertion. As the deficiency worsens, changes in the nervous system also occur.

Nervous system

Vitamin B12 is essential for the formation of the myelin sheath, which protects nerve fibres and strengthens signals. Its deficiency can cause numbness in the hands and feet, balance disorders, coordination problems, sensory impairment, slow thinking, memory problems and mood deterioration. In severe cases, symptoms resembling dementia or depression develop.

Other consequences

B12 deficiency in pregnant women can adversely affect foetal development, increasing the risk of neural tube defects and low birth weight. Indirect effects include an increase in homocysteine concentration, which accumulates in the body when there is a lack of vitamin B12 needed for its processing. Excessively high homocysteine levels damage blood vessel walls, exacerbate inflammation and can lead to atherosclerosis, coronary heart disease and strokes.

Vitamin B12 supplementation

The method of supplementing vitamin B12 deficiency depends on the cause, the degree of deficiency and the body's ability to absorb it. In cases where the deficiency is due to insufficient dietary intake, for example in vegans or people who eat very few animal products, regular oral supplementation or consumption of fortified foods is usually sufficient.

In such situations, cyanocobalamin or methylcobalamin is most often used in doses ranging from 250 to 500 µg per day, which allow for maintaining normal vitamin levels in serum. In people with mild deficiency but preserved intestinal absorption, sublingual preparations are also effective, as they partially bypass the gastrointestinal tract and ensure good bioavailability.

When the cause of the deficiency is impaired absorption, e.g. lack of intrinsic factor, removal of part of the stomach, intestinal disease or long-term use of metformin or drugs that inhibit gastric acid secretion, it is necessary to administer vitamin B12 in injections. Hydroxycobalamin or cyanocobalamin is most commonly used at a dose of 1000 µg, initially every few days, then weekly, and once a month after the level has been corrected.

Sources:

• Melaku, E. E., Urgie, B. M., Tilahun, A. T., Assefa, H. K., Abebe, A. A., & Tefera, A. S. (2024). Prevalence of vitamin B 12 deficiency and associated factors among primary school children: North East Ethiopia: multicenter cross-sectional study. Journal of health, population, and nutrition, 43(1), 82. https://doi.org/10.1186/s41043-024-00568-6
• Bjørke-Monsen, A. L., & Lysne, V. (2023). Vitamin B12 - a scoping review for Nordic Nutrition Recommendations 2023. Food & nutrition research, 67, 10.29219/fnr.v67.10257. https://doi.org/10.29219/fnr.v67.10257
• Sukumar, N., Adaikalakoteswari, A., Venkataraman, H., Maheswaran, H., & Saravanan, P. (2016). Vitamin B12 status in women of childbearing age in the UK and its relationship with national nutrient intake guidelines: results from two National Diet and Nutrition Surveys. BMJ open, 6(8), e011247. https://doi.org/10.1136/bmjopen-2016-011247
• Hao, L., Ma, J., Zhu, J., Stampfer, M. J., Tian, Y., Willett, W. C., & Li, Z. (2007). Vitamin B-12 deficiency is prevalent in 35- to 64-year-old Chinese adults. The Journal of nutrition, 137(5), 1278–1285. https://doi.org/10.1093/jn/137.5.1278
• Fernandes, S., Oliveira, L., Pereira, A., Costa, M. D. C., Raposo, A., Saraiva, A., & Magalhães, B. (2024). Exploring Vitamin B12 Supplementation in the Vegan Population: A Scoping Review of the Evidence. Nutrients, 16(10), 1442. https://doi.org/10.3390/nu16101442