Vitamin B12 Deficiency Causes

If vitamin B12 deficiency has been diagnosed, the next step is to determine what the underlying causes are, before beginning an appropriate treatment. As we outline in our article, Vitamin B12 Deficiency Causes, the reasons behind B12 deficiency fall into one of three categories: 

1. Deficient supply
   Due to a low consumption of vitamin B12-rich foods – often the case for vegetarians/vegans
2. Increased requirement 
   Temporary increased demand for vitamin B12, which cannot be covered by diet alone e.g. due to pregnancy/lactation, long-term stress or toxic strain
3. Malabsorption
   Even when an adequate amount of vitamin B12 is supplied, sometimes it cannot be properly absorbed – most frequently the case when there is a slight inflammation of the gastrointestinal tract

Vitamin B12 Deficiency Treatment: Two Phases 

Independent from the causes of deficiency, therapy with vitamin B12 takes place in two phases:

1. Initial therapy: high dose to replenish and refill the body’s stores
2. Maintenance treatment: to cover the daily requirement and maintain the B12 level

The brief, high dose initial therapy has the purpose of supplying sufficient vitamin B12 beyond the daily requirement, so that the body’s stores can be rapidly refilled and the B12 level in the body can be increased.

This is then adjusted to a lower maintenance dose, which only covers the daily requirement and so stabilises the B12 level.

Vitamin B12 Deficiency Treatment Dosages

Here are some rough guidelines for treatment dosages. 

1. High dose initial therapy

Once a B12 deficiency has been verified, initial therapy is the same in all cases.

2. Maintenance treatment 

These maintenance doses clearly surpass the daily requirement of 3 μg. This is because only a small about of B12 is absorbed by the body when taken orally, whilst the majority is excreted with the urine. 

Per oral dose of B12 the body can intake a maximum of 1.5 μg of the vitamin through intrinsic factor (IF) and a further 1% of the dose through passive diffusion. For this reason, either very high doses are administered to maximise passive diffusion, or small doses are administered across the day at large intervals, to optimise absorption via IF. 

For more information on vitamin B12 dosages, click here.

Vitamin B12 Treatment in the Case of a Deficient Intake

If not enough vitamin B12-rich foods are consumed in the diet, the body empties its store of the vitamin from the liver and cells. Already within this time, multiple deficiency symptoms can emerge. At the latest, when the body’s store begins to decline severe symptoms can appear. 

Diet-related deficiencies often occur in vegetarians and vegans. If a lack of supply is the only cause of the deficiency, a sufficient intake of B12 through appropriate supplements can remedy deficiency.

If serum values are below 200 ng/l or severe symptoms are present, an initial therapy with injections or very high oral doses is recommended. In all other cases, oral administrations of normal doses of vitamin B12 are usually sufficient.

It is possible, however, that an absorption or utilisation disorder is present at the same time, so that taking supplements up to 250 µg is not enough. To check if this is the case, you can take a vitamin B12 test after several weeks of taking supplements to determine whether the increased intake of B12 has led to the expected rise in the blood level. 

Therapy for an increased requirement proceeds in the same way. 

Vitamin B12 Treatment for Absorption Problems

In the case of malabsorption, the administered vitamin B12 dose must be correspondingly higher. An oral intake of the vitamin at the level of the daily dose cannot lead to a sustainable result here, as the vitamin cannot be absorbed sufficiently by the body. An intake via intrinsic factor is completely omitted here.

Some studies therefore conclude that B12 – in the form of the orally administered supplement, cyanocobalamin – must be administered in a single dose at least 200 times higher than the recommended daily dose to safely prevent deficiency in anaemic patients (1). In this case, 500-1000 μg would need to be taken. 

If an acute vitamin B12 deficiency is diagnosed due to absorption problems, very high doses of the vitamin are administered over a longer period of time via injections (usually 1000 μg/week) or oral supplements (usually 1000-5000 μg/day). In this way, a supply of B12 to the cells is ensured, while the cause of deficiency is being investigated. At such high doses, sufficient oral amounts of B12 are absorbed via passive diffusion in the intestine.

In the case of chronic, incurable conditions – such as after important parts of the small intestine have been removed – therapy with injections must be continued permanently, otherwise deficiency will immediately return. If the reasons for an absorption disorder are unclear, the search for the cause begins at the same time as supplementation. The most frequent causes are chronic disorders of the stomach and intestinal mucous membranes, alcohol/drug consumption, malnutrition and stress (physical and psychological). Infection with helicobacter pylori, interactions with other medications and hereditary diseases are somewhat rarer causes. 

Vitamin B12 Active Ingredients 

For vitamin B12 therapy various supplements are on offer, which contain completely different forms of B12. Cyanocobalamin, hydroxocobalamin and methylcobalamin are particularly common.

Cyanobalamin is a synthetic form of B12 and breaks up in the body into methylcobalamin and the toxic substance cyanide, to which some people have a severe allergic reaction. In the USA particularly, cyanocobalamin was the standard supplement for treating vitamin B12 deficiency for a long time, due to the ease with which it is synthetically manufactured. Today however it has mostly been replaced by other forms due to the potential health risks. Some experts even demand that it should be completely withdrawn from the market, arguing that all other forms are preferable (2). 

Hydroxocobalamin is a natural form of B12, as it is frequently found in nature. While it must first be transformed in the body, it has the advantage over cyanocobalamin in that it is not excreted as rapidly and is slightly more readily available. Plus, it fulfils an important task in the detoxification process. Hydroxocobalamin is the international standard of B12 supplements for injections and is recommended by the World Health Organisation (WHO) as the supplement of choice (3). 

For an oral vitamin B12 therapy, methylcobalamin and adenosylcobalamin are particularly suitable, as they can be directly utilised by the body. Both cyanobalamin and hydroxocobalamin must first be converted into methylcobalamin and adenosylcobalamin in the body before they can take effect. Methylcobalamin and adenosylcobalamin are therefore called the bioactive coenzyme forms of vitamin B12. Further information on this topic can be found in our article: Vitamin B12 Supplements

The best vitamin B12 supplement combines the natural forms of methylcobalamin, hydroxocoblamin and adenosylcobalamin. All three forms have completely different functions in the body and are required for divergent processes. These three forms also occur together in natural foods. 

Vitamin B12 from Algae 

Algae such as spirulina, chlorella and nori are often sold as alternative, vegan sources of vitamin B12, however, this is currently a controversial topic. Algae also contain large amounts of pseudo vitamin B12 in addition to the vitamin itself; according to various studies, the former blocks the absorption of the latter, thus leading to a negative overall B12 balance (4). In contrast, other studies come to the conclusion that the B12 serum level can indeed be raised by algae. It is not possible to say with any certainty to what extent algae can guarantee a supply of B12 to the cells. Only chlorella seems to contain genuinely usable B12 – however, the content is too low for application in the context of vitamin B12 deficiency treatment.

Vitamin B12 Cofactors 

In addition to vitamin B12, during therapy attention should also be paid to the supply of the other vitamins within the B complex – in particular folic acid – as these are closely related in the metabolism. Furthermore, biotin, magnesium and calcium play an indirect role here, as they interact with B12 utilisation. During initial therapy, iron deficiency can also temporarily occur, as blood formation intensifies. For this reason, it is sometimes advisable to simultaneously take iron supplements.

Sources

1. Eussen SM, de Groot LM, Clarke R, et al. Oral Cyanocobalamin Supplementation in Older People With Vitamin B12 Deficiency: A Dose-Finding Trial. Arch Intern Med. 2005;165(10):1167-1172. doi:10.1001/archinte.165.10.1167.

2.Freeman AG. Cyanocobalamin—a case for withdrawal: discussion paper. J R Soc Med 1992; 85: 686-771. PubMed

3. WHO Model List of Essential Medicines. 18th list (April 2013) http://www.who.int/medicines/publications/essentialmedicines/en/

4. Dagnelie PC, van Staveren WA, van den Berg H. Vitamin B-12 from algae appears not to be bioavailable. Am J Clin Nutr. 1991;53:695-7.