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 Of these cobalamins, methylcobalamin and 5’‑deoxyadenosylcobalamin are the only two bioactive forms of vitamin B12, and act as coenzymes in the body.2 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 However, metabolic or genetic disorders, as well as a lack of nutrients, can impair the conversion process.4 Cobalamins can only be produced by microorganisms such as bacteria.5

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. Vitamin B12 plays an important role in the reproduction of DNA in cells as well as in the formation of new proteins. It also influences the nervous system’s overall health, the energy production of the cells, and the synthesis of the red blood protein haemoglobin.6

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.7 8 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.9 10 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 being recommended by the European Food Safety Authority (EFSA) for people on a Western diet:11

  • Infants: 1.5 micrograms
  • Children, aged 1 to 6: 1.5 micrograms
  • Children, aged 7 to 10: 2.5 micrograms
  • Children, aged 11 to 14: 3.5 micrograms
  • People over 14 years of age: 4 micrograms
  • During pregnancy: 4.5 micrograms
  • When breastfeeding: 5 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.12 Only after a few hours have passed are the receptors able to absorb further vitamin B12.13 14

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.15 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.16

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.17 Full stores of vitamin B12 in the body can suffice for 3-5 years.18

Causes of insufficient vitamin B12 intake

Insufficient vitamin B12 intake is caused mainly by the following:19

  • 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 B12.20 21 The intake of vitamin B12 through fortified foods and orally consumed food supplements is severely hindered in people with these conditions.22 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 B12.23

Vitamin B12 deficiency in the broader population

The major risk groups for vitamin B12 deficiency are vegans (and some vegetarians), the elderly,24 people with gastrointestinal diseases, and pregnant and nursing women44 – as well as alcoholics and smokers.

In the United Kingdom and United States vitamin B12 deficiency has been diagnosed in around 6% of people under 60 years, and around 20% in those older than 60 years. In Latin America, about 40% of children and adults suffer from some form of vitamin B12 deficiency. And about 11% of vegans in the UK are affected by B12 deficiency.25

Vitamin B12: Occurrence and bioavailability in food

Most food of animal origin contains vitamin B12. To ensure a sufficient supply, animals such as pigs and chickens are given vitamin B12 via fortified feed.26 45 Ruminants may require to get additional cobalt (which is an important trace element and essential in the formation of vitamin B12), via fortified feed, especially if there is a deficiency of cobalt in soils.27 28 Occurrence in root and tuber vegetables or fermented foods such as sauerkraut and fermented soya products is possible, but not sufficient to make a significant contribution to vitamin B12 supply. Opposing opinions are not scientifically supported.29

Some plant-based foods are enriched with cobalamin. These include various soya products, muesli, cornflakes, fruit juices, and meat alternatives. 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.30 Furthermore, EU law regarding organic production of food prohibits enriching organic food with vitamin B12. As such, organically-produced vegan food from EU countries does not contain cobalamin.31

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:32


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).33 The problem with vitamin B12-related anaemia is that it can be delayed or ‘masked’ by a high intake of folate – for example in vegetarian or vegan diets – because these vitamins collaborate in the process of cell division. At the same time, however, neurological changes will progress, possibly leading to permanent damage to the central nervous system.34

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.35 36 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 B12.37 38 39

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. If you have a nutrient deficiency or a special need, it’s best to supplement with that specific nutrient. 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 B12.40 41 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.42

Intramuscular vitamin B12 injections
In most countries, intramuscular injections have long been the standard treatment for vitamin B12 deficiency. However, the current data shows that oral and sublingual vitamin B12 preparations are sufficient and may even be superior to intramuscular injections.43 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.

Pro Health

These are general nutrition guidelines. If you have concerns about your diet, please talk to your doctor about seeing a dietitian. Discussing the use of supplements with a health professional will help to ensure that they are suitable for you. Never stop taking prescribed medications without first talking to your doctor.

References

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2 Marsh, E.N. (1999): Coenzyme B12 (cobalamin)-dependent enzymes. Essays in Biochemistry 34 139–154. doi:10.1042/bse0340139
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
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13  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
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Last updated: 01.01.2021

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