Vitamin B₁₂ deficiency: Identifying symptoms and taking precautions on vegan/vegetarian diets

Vitamin B₁₂ is an essential vitamin that performs many important functions in the body. It is exclusively formed by microorganisms and must be ingested through food or dietary supplements. ProVeg explains how vegans and vegetarians can protect themselves against a shortage of vitamin B₁₂.

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 coalamins – 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 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 Mutagenesis. 733, p.21–33 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 http://www.ncbi.nlm.nih.gov/pubmed/12420702 [05.03.2018] 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 1-3: 0.9 micrograms
Children, aged 4-8: 1.2 micrograms
Children, aged 9-13: 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 bound to proteins. Food supplements contain cobalamin in the free form of the molecule. The actual absorption of vitamin B12 then takes place in the lower small intestine, where it is bound to a special transport molecule, the so-called ‘gastric intrinsic factor’. This 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/ [21.03.2018] 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, 56: 635–638. doi: 10.1046/j.1365-2125.2003.01907.x

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 https://www.researchgate.net/publication/6182948_Pathophysiology_of_anemia_and_erythrocytosis [21.03.2018]

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 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, p635–638 A sublingual (under the tongue) or intramuscular supply of vitamin B12 via syringes 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 https://www.ncbi.nlm.nih.gov/pubmed/15720207?dopt=Abstract [20.03.2018] 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. Online unter https://www.ncbi.nlm.nih.gov/pubmed/11122323?dopt=Abstract [20.03.2018] 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 https://www.ncbi.nlm.nih.gov/pubmed/14656029?dopt=Abstract [20.03.2018]

Vitamin B12: Occurrence and bioavailability in food

Most food of animal origin contains vitamin B12. To ensure a sufficient supply, the animals take in 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 Verwendung in der Tierernährung. Available at http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2003:268:0029:0043:de:PDF [20.03.2018] 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 soy 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 the 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 large storage capacity for vitamin B12, it can take years for clinical symptoms of vitamin B12 deficiency to become apparent. However, the state of the body’s vitamin B12 stores can be determined at an early stage 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 are low holo TC II values. This transport protein binds 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


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 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3142735/ [07.03.2018]

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 Health Nutr 6 (3), p.259-69 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 https://www.ncbi.nlm.nih.gov/pubmed/15570032 [07.03.2018] 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 https://www.ncbi.nlm.nih.gov/pubmed/16988496 [07.03.2018] 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 https://www.ncbi.nlm.nih.gov/pubmed/19357223 [07.03.2018] 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 78 (1), 131-6 Available at https://www.ncbi.nlm.nih.gov/pubmed/12816782 [07.03.2018]

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 Pharmacology. 56, p.635–638 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 Serum Homocysteine Levels 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? Available at: https://www.bzfe.de/_data/files/eifonline_11_2016_zahncreme_b12_final.pdf [Accessed: 25.10.2017]

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 B12 for vitamin B12 deficiency. Available at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5112015/ [21.03.2018] 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 alike 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 (see sections on absorption of vitamin B12 and vitamin B12 supplements).

References   [ + ]

1. Food Safety Authority (2006): Tolerable upper intake levels for vitamins and minerals. European Food Safety Authority p.45
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]
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
4, 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]
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]
6. Elmadfa, I. & C. Leitzmann (2015): Ernährung des Menschen. Verlag Eugen Ulmer p.478
7. Ledochowski, M. (2010): Klinische Ernährungsmedizin. Springer-Verlag Vienna p.252
8. Elmadfa, I. & C. Leitzmann (2015): Ernährung des Menschen. Verlag Eugen Ulmer pp.478
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]
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 Mutagenesis. 733, p.21–33
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 http://www.ncbi.nlm.nih.gov/pubmed/12420702 [05.03.2018]
13. U.S. Department of Health & Human Services (2018): Vitamin B12. Available at https://ods.od.nih.gov/factsheets/VitaminB12-HealthProfessional/ [05.03.2018]
14. Scott JM (1997): Bioavailability of vitamin B12, Eur J Clin Nutr. 1997 Jan; 51 Suppl 1:S49-53
15, 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
16. Biesalski, H. K. et al. (2017): Taschenatlas Ernährung. Georg Thieme Verlag p.200
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/ [21.03.2018]
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, 56: 635–638. doi: 10.1046/j.1365-2125.2003.01907.x
20. Vivien M. Hodgesa, Susan Raineya, Terence R. Lappin a, A. Peter Maxwell (2007): Pathophysiology of anemia and erythrocytosis, p.142. Available at https://www.researchgate.net/publication/6182948_Pathophysiology_of_anemia_and_erythrocytosis [21.03.2018]
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, 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]
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, p635–638
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]
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 https://www.ncbi.nlm.nih.gov/pubmed/15720207?dopt=Abstract [20.03.2018]
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. Online unter https://www.ncbi.nlm.nih.gov/pubmed/11122323?dopt=Abstract [20.03.2018]
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 https://www.ncbi.nlm.nih.gov/pubmed/14656029?dopt=Abstract [20.03.2018]
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 Verwendung in der Tierernährung. Available at http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2003:268:0029:0043:de:PDF [20.03.2018]
31. Berger I (2009): Vitamin B12-Mangel bei veganer Ernährung: Mythen und Realitäten aufgezeigt anhand einer empirischen Studie. Ibidem, Stuttgart, p.34-55
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]
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]
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]
35. Pawlak, R. et al. (2013): How prevalent is vitamin B12 deficiency among vegetarians? Nutrition Reviews. 71, p.110–117
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 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3142735/ [07.03.2018]
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 Health Nutr 6 (3), p.259-69
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 https://www.ncbi.nlm.nih.gov/pubmed/15570032 [07.03.2018]
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 https://www.ncbi.nlm.nih.gov/pubmed/16988496 [07.03.2018]
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 https://www.ncbi.nlm.nih.gov/pubmed/19357223 [07.03.2018]
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 78 (1), 131-6 Available at https://www.ncbi.nlm.nih.gov/pubmed/12816782 [07.03.2018]
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 Pharmacology. 56, p.635–638
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 Serum Homocysteine Levels
44. Institut für alternative und nachhaltige Ernährung & Dr. Markus Keller (2016): Vitamin B12 angereichtertes Zahngel für Vegetarier: Alternative zu Nahrungsergänzungen und Injektionen? Available at: https://www.bzfe.de/_data/files/eifonline_11_2016_zahncreme_b12_final.pdf [Accessed: 25.10.2017]
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 B12 for vitamin B12 deficiency. Available at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5112015/ [21.03.2018]