What is vitamin B₁₂?

The term vitamin B₁₂ is an umbrella term for the group of substances called cobalamins.^[1]Food Safety Authority (2006): Tolerable upper intake levels for vitamins and minerals. European Food Safety Authority p.45 Of these cobalamins, methylcobalamin and 5’‑deoxyadenosylcobalamin are the only two bioactive forms of vitamin B₁₂, and act as coenzymes in the body.^[2]Department of Chemistry, University of European Michigan, Ann Arbor (1999): Coenzyme B12 (cobalamin)-dependent enzymes. Available at https://www.ncbi.nlm.nih.gov/pubmed/10730193 [05.03.2018] Two other cobalamins – hydroxocobalamin and aquacobalamin – are not coenzyme forms of vitamin B₁₂ themselves but can be converted by the body into one of the two active cobalamins. The same applies to synthetically produced cyanocobalamin, which is used for most vitamin B₁₂ supplements.^[3]World Health Organization & Food and Agriculture Organization of the United Nations (2004): Vitamin and mineral requirements in human nutrition. World Health Organization; FAO p.279 However, metabolic or genetic disorders, as well as a lack of nutrients, can impair the conversion process.^[4]Fiona O’Leary and Samir Samman (2010): Vitamin B12 in Health and Disease
Available at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3257642/ [21.03.2018] Cobalamins can only be produced by microorganisms such as bacteria.^[5]Huan Fang, Jie Kang, Dawei Zhang (2017): Microbial production of vitamin B12: a review and future perspectives. Available at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5282855/ [21.03.2018]

Functions of vitamin B₁₂

The two coenzyme forms of vitamin B₁₂ are essential components of two endogenous enzymes that occur in all cells and are involved in many metabolic reactions.^[6]Elmadfa, I. & C. Leitzmann (2015): Ernährung des Menschen. Verlag Eugen Ulmer p.478 Vitamin B₁₂ plays an important role in the reproduction of DNA in cells as well as in the formation of new proteins.^[7]Ledochowski, M. (2010): Klinische Ernährungsmedizin. Springer-Verlag Vienna p.252 It also influences the nervous system’s overall health, the energy production of the cells, and the synthesis of the red blood protein haemoglobin.^[8]Elmadfa, I. & C. Leitzmann (2015): Ernährung des Menschen. Verlag Eugen Ulmer pp.478

Vitamin B₁₂ deficiency: symptoms and medical consequences

A lack of cobalamin leads to disturbances in cell division across the entire body. This mainly affects the formation of red blood cells, but also impacts on the oral and pharyngeal mucosa, as well as on the nervous system. A typical symptom of vitamin B₁₂ deficiency is a form of anaemia which causes the red blood cells to become abnormally enlarged (megaloblastic anaemia). Characteristic signs include pale skin and mucous membranes and the regression of oral, tongue, and intestinal mucosa, as well as the subsequent impairment of nutrient uptake, along with non-specific symptoms such as general weakness, rapid fatigue, and dizziness.^[9]Biesalski, H. K. et al. (2017): Taschenatlas Ernährung. Georg Thieme Verlag p.201 ^[10]Truswell, A. S. (2007): Vitamin B12. Nutrition & Dietetics. 64, S120–S125. Available at http://onlinelibrary.wiley.com/doi/10.1111/j.1747-0080.2007.00198.x/epdf [07.03.2018] An insufficient supply of vitamin B₁₂ also leads to increased blood concentrations of homocysteine, which represents a risk factor for the development of atherosclerosis and cardiovascular diseases.

The second set of symptoms caused by a deficiency in cobalamin is even more serious. These include damage to the central nervous system, which can manifest itself as sensory disorders (such as the feeling of ‘pins and needles’ in hands, feet, and other parts of the body), a lack of appetite, delayed reflexes, and reduced motor abilities, as well as impairments in movement coordination. Mental disorders, ranging from confusion or memory problems to psychoses and hallucinations, can also be signs of vitamin B₁₂ deficiency.^[11]Fenech, M. (2012): Folate (vitamin B9) and vitamin B12 and their function in the maintenance of nuclear and mitochondrial genome integrity. Mutation Research/Fundamental and Molecular Mechanisms of … Continue reading ^[12]Mischoulon D1, Fava M. (2002): Role of S-adenosyl-L-methionine in the treatment of depression: a review of the evidence. D.Mischoulon, M.Fava. Am J Clin Nutr. 76 Available at … Continue reading Both sets of symptoms can occur independently of each other.

Daily requirements of vitamin B₁₂

While the recommendations for B₁₂ intake vary between regions, the following daily doses are recommended for people on a Western diet:^[13]U.S. Department of Health & Human Services (2018): Vitamin B12. Available at https://ods.od.nih.gov/factsheets/VitaminB12-HealthProfessional/ [05.03.2018]

Infants: 0.4-0.5 micrograms
Children, aged 1 to 3: 0.9 micrograms
Children, aged 4 to 8: 1.2 micrograms
Children, aged 9 to 13: 1.8 micrograms
Women and men over 14 years of age: 2.4 micrograms
During pregnancy: 2.6 micrograms
When breastfeeding: 2.8 micrograms

Absorption of vitamin B₁₂

Foods of animal origin are exposed to gastric acid in the stomach, which facilitates the extraction of vitamin B₁₂ from the proteins to which it is bound. Food supplements, on the other hand, contain cobalamin in the free form of the molecule, with the absorption of vitamin B12 taking place in the lower small intestine, where it is bound to a special transport molecule, the so-called ‘gastric intrinsic factor’. This ‘gastric intrinsic factor’ is a glycoprotein which transports vitamin B12 to special receptors in the intestinal mucosa through which it then reaches the mucosal cells. However, the number of gastric intrinsic factor receptors is limited. Approximately 56% of an oral dose of 1 microgram of vitamin B₁₂ is absorbed, but absorption decreases dramatically when the capacity of the intrinsic factor is exceeded. It is estimated that the absorption capacity of cobalamin is 1.5-2 micrograms per meal.^[14]Scott JM (1997): Bioavailability of vitamin B12, Eur J Clin Nutr. 1997 Jan; 51 Suppl 1:S49-53 Only after a few hours have passed are the receptors able to absorb further vitamin B₁₂.^[15]Fenech, M. (2012): Folate (vitamin B9) and vitamin B12 and their function in the maintenance of nuclear and mitochondrial genome integrity. Mutation Research/Fundamental and Molecular ^[16]Biesalski, H. K. et al. (2017): Taschenatlas Ernährung. Georg Thieme Verlag p.200

If vitamin B₁₂ is supplied in very large amounts via oral consumption (at least 200 micrograms), about 1-2% of the dose can enter the blood via passive diffusion through the intestinal wall.^[17]Catherine Qiu Hua Chan, Lian Leng Low, Kheng Hock Lee (2016): Oral Vitamin B12 Replacement for the Treatment of Pernicious Anemia. Available at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4993789/ … Continue reading However, absorption through the oral mucosa (for example, taken under the tongue or dissolved in the mouth) is at least as effective as oral vitamin B₁₂ intake (swallowing directly). In the case of consumption via the oral mucosa, absorption also takes place via the intestinal wall due to partial swallowing, so long as the dose is sufficiently high.^[18]Sharabi, A., Cohen, E., Sulkes, J. and Garty, M. (2003), Replacement therapy for vitamin B12 deficiency: comparison between the sublingual and oral route. British Journal of Clinical Pharmacology, … Continue reading

The intake of vitamin B₁₂ – starting at a minimum dose of 200 micrograms – can therefore be calculated as follows:

Absorption (in micrograms) = 1.5 + dose/100

Approximately 60% of vitamin B₁₂ (2000-5000 micrograms) is stored in the liver, with the kidneys being another important storage reservoir.^[19]Fenech, M. (2012): Folate (vitamin B9) and vitamin B12 and their function in the maintenance of nuclear and mitochondrial genome integrity. Mutation Research/Fundamental and Molecular Full stores of vitamin B₁₂ in the body can suffice for 3-5 years.^[20]Vivien M. Hodgesa, Susan Raineya, Terence R. Lappin a, A. Peter Maxwell (2007): Pathophysiology of anemia and erythrocytosis, p.142. Available at … Continue reading

Causes of insufficient vitamin B₁₂ intake

Insufficient vitamin B₁₂ intake is caused mainly by the following:^[21]Fiona O’Leary and Samir Samman (2010): Vitamin B12 in Health and Disease
Available at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3257642/ [21.03.2018]

• Eating food which contains too little vitamin B₁₂ to cover daily requirements
• Bodily inability to properly utilise the absorbed vitamin B₁₂
• Higher usage of vitamin B₁₂ by the body than usual

 

Vitamin B₁₂ deficiency can also be caused by certain diseases. Chronic gastritis (inflammation of the gastric mucosa) or a gastrectomy (partial or total surgical removal of the stomach) can cause a deficit in the gastric intrinsic factor, which is crucial for the absorption of vitamin B₁₂.^[22]Obeid R, Schorr H, Eckert R, Herrmann W. (2008): Causes and Early Diagnosis of Vitamin B12 Deficiency Available at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2696961/ [21.03.2018] ^[23]Obeid R, Schorr H, Eckert R, Herrmann W. (2004): Vitamin B12 status in the elderly as judged by available biochemical markers. Available at https://www.ncbi.nlm.nih.gov/pubmed/14709663 [21.03.2018] The intake of vitamin B₁₂ through fortified foods and orally consumed food supplements is severely hindered in people with these conditions.^[24]Sharabi, A., Cohen, E., Sulkes, J. and Garty, M. (2003), Replacement therapy for vitamin B12 deficiency: comparison between the sublingual and oral route. British Journal of Clinical Pharmacology, … Continue reading A sublingual (under the tongue) or intramuscular supply of vitamin B₁₂ via injection is recommended in these cases (see section on vitamin B₁₂ supplements). Medication can also have a negative effect on the uptake of vitamin B₁₂.^[25]National Institute of Health (NIH) (2018): Vitamin B12, Fact Sheet for Health Professionals. Available at https://ods.od.nih.gov/factsheets/VitaminB12-HealthProfessional/ [21.03.2018]

Vitamin B₁₂ deficiency in the broader population

The major risk groups for vitamin B₁₂ deficiency are vegans (and some vegetarians), the elderly,^[26]Obeid R, Schorr H, Eckert R, Herrmann W. (2004): Vitamin B12 status in the elderly as judged by available biochemical markers. Available at https://www.ncbi.nlm.nih.gov/pubmed/14709663 [21.03.2018] people with gastrointestinal diseases, and pregnant and nursing women – as well as alcoholics and smokers.

Functional vitamin B₁₂ deficiency has been diagnosed in 10-30% of healthy people over 65 years of age,^[27]Herrmann W, Obeid R, Schorr H, Geisel J (2005/6): The usefulness of holotranscobalamin in predicting vitamin B12 status in different clinical settings. Available at … Continue reading ^[28]Herrmann W, Schorr H, Bodis M et al. ( 2000): Role of homocysteine, cystathionine and methylmalonic acid measurement for diagnosis of vitamin deficiency in high-aged subjects. Eur J Clin Invest. … Continue reading and in 5-7% of younger people.^[29]Herrmann W, Obeid R, Schorr H, Geisel J (2003): Functional vitamin B12 deficiency and determination of holotranscobalamin in populations at risk. Clin Chem Lab Med. Available at … Continue reading

Vitamin B₁₂: Occurrence and bioavailability in food

Most food of animal origin contains vitamin B₁₂. To ensure a sufficient supply, the animals are given vitamin B₁₂ via fortified feed.^[30]Das Europäische Parlament und der Rat der Europäischen Union (2003): VERORDNUNG (EG) Nr. 1831/2003 DES EUROPÄISCHEN PARLAMENTS UND DES RATES vom 22. September 2003 über Zusatzstoffe zur … Continue reading Occurrence in root and tuber vegetables or fermented foods such as sauerkraut and fermented soy products is possible, but not sufficient to make a significant contribution to vitamin B₁₂ supply. Opposing opinions are not scientifically supported.^[31]Berger I (2009): Vitamin B12-Mangel bei veganer Ernährung: Mythen und Realitäten aufgezeigt anhand einer empirischen Studie. Ibidem, Stuttgart, p.34-55

Some plant-based foods are enriched with cobalamin. These include various soya products, muesli, cornflakes, fruit juices, and meat alternatives.^[32]Academy of Nutrition and Dietetics (2017): Vitamin B12 in Vegetarian Diets. Available at https://vegetariannutrition.net/docs/B12-Vegetarian-Nutrition.pdf [20.03.2018] Depending on the vitamin B₁₂ content, vitamin B₁₂ uptake can be improved by consuming these fortified foods, but this will not always cover daily requirements.^[33]Pawlak, R, Phd RD., Academy of Nutrition and Dietetics (2017): Vegetarian Nutrition. Available at https://vegetariannutrition.net/docs/B12-Vegetarian-Nutrition.pdf [21.03.2018] Furthermore, EU law regarding organic production of food forbids enriching organic food with vitamin B₁₂. As such, organically-produced vegan food from EU countries does not contain cobalamin.^[34]Europäische Union (2007): Verordnung (EG) Nr. 834/2007 (Öko-Verordnung). Available at http://eur-lex.europa.eu/legal-content/DE/TXT/PDF/?uri=uriserv:OJ.L_.2007.189.01.0001.01.DEU [21.03.2018]

Vitamin B₁₂ test: blood markers used to determine vitamin B₁₂ levels

Due to the body’s capacity to store vitamin B12  for long periods of time, it can take years for clinical symptoms of vitamin B₁₂ deficiency to become apparent. However, the long-term state of the body’s vitamin B₁₂ stores can be determined by means of blood analyses. Various test values concerning the cobalamin metabolism should be measured, especially holo-transcobalamin II (holo TC II). Solely testing for blood content of vitamin B₁₂ is not a suitable method for reliably assessing the state of the body’s supplies, since a functional vitamin B₁₂ deficiency may already be present in the body’s cells even when blood values for vitamin B₁₂ are normal. The earliest indicator of a deficiency is low holo TC II values. This transport protein binds to vitamin B₁₂ and makes it available to the body’s cells. The following table shows the reference range for holo TC II, which can be used to determine a vitamin B₁₂ deficiency:^[35]Pawlak, R. et al. (2013): How prevalent is vitamin B12 deficiency among vegetarians? Nutrition Reviews. 71, p.110–117

Holo TC II in picomole/litre	Interpretation
>50	Vitamin B12 deficiency unlikely
35-50	Further medical evaluation needed
<35	Vitamin B12 deficiency likely

Table 1: Reference range for holotranscobalamin II (holo TC II) for determining a vitamin B₁₂ deficiency

If the holo TC II value alone is insufficient to determine whether a vitamin B₁₂ deficiency exists, values for homocysteine (on an empty stomach) and methylmalonic acid should be determined via blood serum in addition to holo TC II. A vitamin B₁₂ deficiency is indicated by increased levels of homocysteine (above 12 micromole/litre) and methylmalonic acid (above 260 nanomole/litre).^[36]Green R. (2011): Indicators for assessing folate and vitamin B-12 status and for monitoring the efficacy of intervention strategies, Am J Clin Nutr. 94(2). Available at … Continue reading

Vitamin B₁₂ supply on a vegan/vegetarian diet

A vegetarian diet can provide an adequate supply of vitamin B₁₂. However, in various studies vegetarian participants consumed an average of only 1.7-2.5 micrograms of vitamin B₁₂ daily, which is slightly below the recommended amount.^[37]Davey GK, Spencer EA, Appleby PN, Allen NE et al. (2003): EPIC-Oxford: lifestyle characteristics and nutrient intakes in a cohort of 33 883 meat-eaters and 31 546 non meat-eaters in the UK. Public … Continue reading ^[38]Koebnick C, Hoffmann I, Dagnelie PC, Heins UA et al. (2004): Long-term ovo-lacto vegetarian diet impairs vitamin B12 status in pregnant women. J Nutr 134 (12), Available at … Continue reading If a vegan diet is not accompanied by dietary supplements or if an inadequate amount of vitamin B₁₂-enriched foods is eaten, the expected vitamin B₁₂ intake is 0 micrograms per day. Accordingly, in many studies vegans exhibit an insufficient supply of vitamin B₁₂.^[39]Majchrzak D, Singer I, Männer M, Rust P et al. (2006): B-vitamin status and concentrations of homocysteine in Austrian omnivores, vegetarians and vegans. Ann Nutr Metab 50 (6), 485-91 Available at … Continue reading ^[40]Elmadfa I, Singer I (2009): Vitamin B12 and homocysteine status among vegetarians: a global perspective. Am J Clin Nutr 89 (5 Suppl), 1693S-1698S Available at … Continue reading ^[41]Herrmann W, Schorr H, Obeid R, Geisel J (2003): Vitamin B12 status, particularly holotranscobalamin II and methylmalonic acid concentrations, and hyperhomocysteinemia in vegetarians. Am J Clin Nutr … Continue reading

Thus, when following a vegan/vegetarian diet, a sufficient supply of vitamin B₁₂ should be ensured through fortified foods and dietary supplements in the form of, for example, tablets, drops, or vitamin B₁₂ toothpaste. Pregnant and breastfeeding women should pay particular attention to consuming an adequate quantity of vitamin B₁₂ in order to ensure that their children receive a sufficient supply.

Vitamin B₁₂ supplements

Nutritional supplements for oral (pills, capsules) or sublingual (lozenges, drops, sprays) intake of vitamin B₁₂

The use of multivitamins is not recommended since vitamin B₁₂ can break down in the presence of vitamin C and copper. However, stand-alone vitamin B₁₂ supplements can be highly effective. According to studies, there is no significant difference between a sublingual or oral intake of vitamin B₁₂.^[42]Sharabi, A. et al. (2003): Replacement therapy for vitamin B12 deficiency: comparison between the sublingual and oral route: Sublingual vs. oral vitamin B12 replacement. British Journal of Clinical … Continue reading ^[43]Yazaki, Y. et al. (2006): A Single-Center, Double-Blinded, Randomized Controlled Study to Evaluate the Relative Efficacy of Sublingual and Oral Vitamin B-Complex Administration in Reducing Total … Continue reading The respective absorption rates for doses of 50 micrograms, 200 micrograms, and 1000 micrograms are approximately 1.5 micrograms, 3.5 micrograms, and 11.5 micrograms (see section on vitamin B₁₂ intake).

Vitamin B₁₂ toothpaste
One form of effective vitamin B₁₂ supplementation is the use of toothpaste enriched with vitamin B₁₂. A study has shown that it can significantly improve the vitamin B₁₂ status of people who have brushed their teeth with it twice a day for 12 weeks. The toothpaste in the study was enriched with 100 micrograms cyanocobalamin per gram.^[44]Institut für alternative und nachhaltige Ernährung & Dr. Markus Keller (2016): Vitamin B12 angereichtertes Zahngel für Vegetarier: Alternative zu Nahrungsergänzungen und Injektionen? … Continue reading

Intramuscular vitamin B₁₂ injections
In most countries, intramuscular injections have long been the standard treatment for vitamin B₁₂ deficiency. However, recent studies show no significant difference between oral or intramuscular vitamin B₁₂ intake.^[45]Josep Vidal-Alaball, Christopher Butler, Rebecca Cannings-John, Andrew Goringe, Kerry Hood, Andrew McCaddon, Ian McDowell, Alexandra Papaioannou (2005): Oral vitamin B12 versus intramuscular vitamin … Continue reading In patients suffering from pernicious anaemia (an autoimmune disease), intramuscular injection is the most efficient form of supplementation.

ProVeg tips for an optimal supply of vitamin B₁₂

• Vegans and vegetarians should have their vitamin B₁₂ levels checked regularly.
• People following a vegan diet should regularly take dietary supplements in order to ensure an adequate supply of vitamin B₁₂.
• To determine a suitable dosage, both vitamin B₁₂ requirements and the dose of the supplement must both be taken into account.