Vitamin B12 - What you should know!

Vitamin B12 Effect

Vitamin B12 has a special status among vitamins. Not only is it the largest and most complex of all vitamins, it is also the only one that contains a metallic element: cobalt. This is one of the rare elements. It also gives vitamin B12 its chemical name, cobalamin.

Vitamin B12 cannot be produced by any plant or animal organism and must therefore be ingested through food. The original source of vitamin B12 is vitamin B12 produced by bacteria, which is absorbed by the body through foods of animal origin. Vegan diets must therefore be supplemented with vitamin B12 vitamin preparations to prevent deficiency symptoms.

Vitamin B12 was originally known for its healing effects in anaemia caused by vitamin B12 deficiency. It is now known that vitamin B12 fulfils a number of vital tasks and functions in the body.

Vitamin B12: A Multi-Functional and Specialized Nutrient

To exert its vital effects, vitamin B12 must first be absorbed through the diet, and this absorption happens exclusively in the ileum, the last section of the small intestine. Due to its large molecular size, vitamin B12 cannot pass through the intestinal lining on its own. It relies on special transport proteins to carry it across and deliver it to the body’s cells.

Once inside the cells, vitamin B12 is transformed into its active forms, known as coenzymes: methylcobalamin and 5’-deoxyadenosylcobalamin. These bioactive forms are essential for a variety of crucial processes, highlighting vitamin B12’s multi-functional role in maintaining health. [1] [2] [3] 

The role of vitamin B12 in the cells

Vitamin B12 carries out its functions in the body through two active coenzymes, each sharing important cellular tasks. One of these, methylcobalamin, is essential for the production of the amino acid methionine, a crucial building block for proteins. Methylcobalamin also plays a key role in synthesizing the structural components of DNA and RNA within the cell.

When vitamin B12 is deficient, DNA production during cell division is impaired. This is especially critical in cells with high rates of division, such as those found in the bone marrow. As a result, a lack of vitamin B12 slows down the production of blood cells, particularly red blood cells, leading to anemia.

How Vitamin B12 Supports Energy Production

The second active coenzyme of vitamin B12, 5'-deoxyadenosylcobalamin, functions primarily in the mitochondria, the energy powerhouses of the cell. Vitamin B12 plays a crucial role in the production of fatty acids and the structural components of certain amino acids.

Additionally, vitamin B12 is involved in the citrate cycle (also known as the Krebs cycle), a vital metabolic pathway that processes organic molecules to generate energy and build new cellular substances. A deficiency of vitamin B12 in this process can lead to neurological and cognitive problems. [1] [3] 

To summarize, the essential functions of vitamin B12 include:

• DNA and RNA synthesis
• Fatty acid production
• Amino acid synthesis
• Support for cellular energy generation

The Effects of Vitamin B12 on Your Health

These molecular functions of vitamin B12 can be seen in the effect of vitamin B12 on health:

• Increases energy and reduces tiredness and fatigue [4]
• Ensures healthy functioning of the nervous system [5]
• Promotes normal growth and development of the nerves [6]
• Helps with the production of red blood cells [7]
• Regulates healthy cell division and promotes longevity [8]
• Protects the cardiovascular system from homocysteine [9]
• Ensures a healthy immune system [10]
• Supports female reproductive health and pregnancy [11]
• Promotes mental well-being and regulates the mood [12]
• Promotes mental clarity, concentration and memory [13]
• Increases physical, emotional and mental energy [14]

Vitamin B12 therefore has a significant positive impact on physical and mental health. An insufficient supply of vitamin B12 should therefore be prevented in any case, especially with a vegan diet. Dietary supplements can help raise vitamin B12 levels.

How Much Vitamin B12 Does a Person Need?

The human body typically stores between 3 mg and 5 mg of vitamin B12, [15] primarily in the liver, where it is released as needed. The recommended daily intake of vitamin B12 is 2.4 micrograms (µg) for most adults.

To put this into perspective, the following amounts of common foods provide roughly the daily requirement:

• 50 grams of lean beef
• 120 grams of cheese or egg yolk
• About 70 grams of pollock (a type of fish)

It’s important to note that vegetables, fruits, legumes, nuts, cereals, and rice are not reliable sources of vitamin B12, as they do not naturally contain this vitamin.

When consuming vitamin B12 through food, not all of it is fully absorbed by the body. Typically, only about 50% to 66% of the vitamin B12 present in foods like meat is bioavailable, that is, usable by the body.

Additionally, the absorption system in the small intestine becomes saturated after about 2 µg of vitamin B12 per meal. This means that to meet daily needs efficiently, vitamin B12 should be consumed in smaller amounts spread over several meals rather than all at once. [16] 

How can you measure the vitamin B12 level?

Measurement Method:

Vitamin B12 levels are measured through a blood test that determines the concentration of vitamin B12 in the blood serum.

Normal Range:

The typical vitamin B12 concentration in blood serum is 200 to 900 pg/ml.

Deficiency Threshold:

• Levels below 200 pg/ml indicate a vitamin B12 deficiency.
• Symptoms usually appear when levels fall below this threshold.
• In older adults, symptoms may also occur at levels between 200 and 500 pg/ml. [17]

Cognitive Impact in Older Adults:

A study found that serum levels below 350 pg/ml were linked to decreased cognitive abilities in elderly individuals, suggesting a connection between low vitamin B12 and memory loss.

Optimal Levels:

For optimal health, especially in older adults, serum concentrations above 500 pg/ml are recommended.

Excess Vitamin B12:

• Excess intake is generally not harmful because surplus vitamin B12 is excreted through urine.
• Abnormally high blood levels usually point to liver or bone marrow disorders, not excessive intake. [17]

Vitamin B12 in Foods

To prevent vitamin B12 deficiency and its potentially serious health consequences, the body needs a sufficient daily intake of this essential nutrient. But which foods provide the best sources of vitamin B12?

• Primary Sources:
  Vitamin B12 is found almost exclusively in animal-based foods.
• Nutrient Loss During Cooking:
  On average, about 30% of vitamin B12 is lost during the cooking process, depending on the method and duration. [18]
• Best Food Sources (According to USDA data):
  The United States Department of Agriculture (USDA) has compiled a comprehensive database of over 7,000 foods with their vitamin B12 content. Based on this data, the richest sources include: [19]
• Organ meats (especially liver and kidney) from:
• Beef
• Lamb
• Goose
• Duck
• Seafood high in vitamin B12:
• Mussels
• Oysters

These foods are particularly effective in helping maintain adequate vitamin B12 levels and preventing deficiency, especially in individuals at higher risk such as vegetarians, vegans, and older adults.

Vitamin B12 Content in Foods (per 100g)

• Beef liver, cooked: 96 µg
• Calf liver, raw: 91 µg
• Duck or goose liver, raw: 54 µg
• Veal kidney, raw: 50 µg
• Pork liver, raw: 26 µg
• Chicken liver, fried: 21 µg
• Beef steak, grilled: up to 8 µg (depending on the section)
• Beef (sirloin), grilled: 4 µg
• Venison (deer), braised: 3 µg
• Lamb (shoulder), raw or cooked: 3 µg
• Chicken, grilled: 0.7 µg

• Liverwurst: 13 µg
• Salami: 3 µg
• Beef minced, cooked: 3 µg
• Frankfurters: 1.6 µg
• Knockwurst: 1.2 µg
• Ham (pork): 1.1 µg
• Ribs (beef): 1.1 µg
• 'Mayor's piece' (beef), without fat, raw: 1.1 µg
• Blood sausage: 1 µg
• Fast food burger: 0.9 µg

• Mussels, steamed: 99 µg
• Calamary (Octopus), steamed: 36 µg
• Oysters, steamed: 29 µg
• Smoked salmon: 18 µg
• Fish (cod, herring), raw: 10 µg
• Wild salmon, cooked: 3 µg
• Canned tuna: 3 µg
• Squid: 1.3 µg
• Tuna salad: 1.2 µg

• Milk powder (lean): 4 µg
• Swiss cheese: 3 µg
• Whey powder: 2.4 µg
• Mozzarella, Parmesan: 2.3 µg
• Brie: 1.7 µg
• Edamer, Gouda: 1.5 µg
• Parmesan, grated: 1.4 µg
• Camembert: 1.3 µg
• Greek yoghurt: 0.8 µg
• Sheep milk: 0.7 µg
• Natural yoghurt: 0.6 µg
• Milk, buttermilk: 0.5 µg
• Ice cream, frozen yoghurt: 0.5 µg
• Sour cream: 0.3 µg
• Sheep cheese, soft: 0.2 µg
• Butter: 0.2 µg
• Cream (liquid): 0.2 µg
• Breast milk: 0.05 µg
• Duck egg, raw: 5 µg
• Egg, dried: 3 µg
• Egg, boiled: 1.1 µg
• Egg, raw: 0.9 µg
• Scrambled eggs: 0.8 µg
• Poached egg: 0.7 µg

• Enriched breakfast cereals: up to 20 µg (depending on the product)
• Almond milk, coconut milk: 1.3 µg
• Soy milk: 1.1 µg
• Rice milk: 0.6 µg

• Dried seaweed: 2.3 µg*
• Soaked seaweed: 0.3 µg*
• Mashed potatoes: 0.2 µg
• Pancakes: 0.2 µg
• Croissant: 0.2 µg
• Mayonnaise: 0.1 µg
• Margarine: 0.1 µg
• Pasta (with egg), cooked: 0.1 µg
• Miso, Tempeh: 0.1 µg
• Potato salad with egg: 0.1 µg
• Muesli: 0.1 µg

• Mushrooms*
• Beer
• Bread
• Sweet potatoes*
• Wine

• Fats
• Oils
• Cod liver oil
• Fruit
• Vegetables
• Spices
• Legumes
• Salads
• Herbs
• Flour
• Rice
• Pasta (without egg)
• Gelatine
• Yeast

*Note: The vitamin B12 content in plant-based sources like seaweed and mushrooms can vary greatly depending on growing conditions and region, and is not considered a reliable source.  [19] 

Are There Really No Plant-Based Sources of Vitamin B12?

While the USDA and most nutritional guidelines state that vitamin B12 occurs almost exclusively in animal-based foods, some studies have reported notable amounts of vitamin B12 in certain seaweeds and algae, including:

• Nori (red algae)
• Chlorella
• Spirulina

However, there are important caveats:

The vitamin B12 content in these plant-based sources varies widely depending on cultivation methods, regional differences, and testing conditions.

Many of these sources contain analogs or inactive forms of vitamin B12, often referred to as pseudo-vitamin B12. These compounds are not bioactive in humans and may interfere with B12 absorption by blocking receptors without providing any benefit.

Because of these uncertainties, relying on plant-based sources for vitamin B12 is not considered safe or sufficient. For those following a vegan or plant-based diet, it is strongly recommended to use vitamin B12-fortified foods or supplements that contain the active forms of B12, such as cyanocobalamin or methylcobalamin. [18] [20] [21] 

The Bioavailability of Vitamin B12 – An Important Issue

The foods listed with vitamin B12 content reflect average values per 100g, but it's important to understand that not all of the vitamin B12 present in food is actually absorbed and used by the body. This is where the concept of bioavailability becomes crucial.

Bioavailability refers to the proportion of a nutrient that is digested, absorbed, and used by the body. For vitamin B12, this can vary significantly depending on the food source and how it is prepared.

• From 200g of cooked lamb, which contains about 3 µg of vitamin B12, the body typically absorbs only 80%.
• For milk, bioavailability is around 60%.
• For liver pâté, bioavailability can be as low as 10%.
• On average, healthy adults absorb about 50% of the vitamin B12 consumed through food. [18]

• Animal-based foods and their products are the only reliable sources of absorbable vitamin B12.
• The highest concentrations and best bioavailability are found in organ meats such as liver and kidney.
• Dairy products, eggs, and foods made from them also contribute valuable amounts.
• Individuals who avoid or consume minimal animal products (such as vegetarians and vegans) cannot meet their vitamin B12 needs through natural food sources alone.
• They should rely on fortified foods or take vitamin B12 supplements to prevent deficiency.

Vitamin B12 Forms

Food naturally contains various forms of vitamin B12. These forms are also offered as vitamin B12 supplements. Which vitamin B12 form is the best? Are some forms of vitamin B12 more effective than others?

What is Cobalamin?
⁠Vitamin B12 belongs to the chemical group of cobalamins, which includes all forms of vitamin B12. Cobalamines have the trace element cobalt as their central atom. Vitamin B12 is the only natural product, i.e. a compound formed by organisms, that contains a cobalt element.

5 nitrogen atoms are bound to this central cobalt element, as well as another ligand. This central structure is surrounded by a stable framework made of ring structures, as the Nobel laureate Dorothy Hodgkins showed by means of X-ray diffraction. [22] 

The sixth ligand on the central cobalt element is decisive for the various forms of vitamin B12. This can belong to different chemical groups and is largely responsible for the specific function of the respective form of vitamin B12.

Main Forms of Vitamin B12

The following forms of vitamin B12 exist: [23] 

Cyanocobalamin and hydroxycobalamin must be converted into active forms in the body:

• The –CN (cyanide) or –OH (hydroxy) group is removed.
• The body then attaches either a –CH₃ (methyl) or a 5’-deoxyadenosyl group.

These conversion steps require specific enzymes. If these enzymes are impaired or deficient, active B12 cannot be formed, which can lead to deficiency symptoms despite adequate intake.

Methylcobalamin:

• Works with the enzyme methionine synthase.
• Crucial for the synthesis of DNA and RNA.
• Supports red blood cell formation, especially in the bone marrow.
• Deficiency may lead to megaloblastic anaemia. [24] [25]

Adenosylcobalamin:

• Active in the mitochondria (the cell's energy centers).
• Required by methylmalonyl-CoA mutase, an enzyme involved in:
• Fatty acid metabolism
• Amino acid processing
• The citrate cycle (cellular energy production)
• Deficiency may lead to neurological and cognitive disorders. [24] [25]

Special Role of Hydroxycobalamin

• Besides acting as a precursor to active forms, hydroxycobalamin has a detoxifying function.
• It binds to cyanide, helping to neutralize it, making it useful in treating cyanide poisoning.

Which Vitamin B12 Forms Are Absorbed Through Food?

The main forms of vitamin B12 naturally present in food are:

• Hydroxycobalamin – the most common natural form
• Methylcobalamin – a bioactive coenzyme form
• Adenosylcobalamin – another bioactive coenzyme form

Less commonly found in food:

• Cyanocobalamin – a synthetic form, typically used in supplements and fortified foods
• Sulfitocobalamin – a rare derivative, not widely studied or utilized [26]

Which Forms of Vitamin B12 Should You Take as Supplements?

Vitamin B12 exists in several forms, but not all are equally effective in the body. The choice of B12 supplement should be based on how well the body can use and store the form.

1. Active Forms of Vitamin B12

These forms are directly usable by the body:

Methylcobalamin

• Plays a critical role in DNA methylation, which is essential for gene regulation and cellular function.
• It is considered the most biologically active form and is highly recommended for supplementation.
• Often used for neurological support due to its high activity in the nervous system.

Adenosylcobalamin

• Another active form used mainly in cellular energy production (mitochondrial function).
• Less commonly used as a standalone supplement but beneficial when combined with methylcobalamin.

Recommendation:

Many nutritionists now recommend taking methylcobalamin or a combination of methylcobalamin and adenosylcobalamin for optimal results.

2. Inactive or Less Active Forms of Vitamin B12

Hydroxycobalamin

• Naturally found in food sources and in the human bloodstream.
• Stored longer in the body and excreted more slowly than other forms.
• Often used in injections due to its longer-lasting effect (depot effect).
• Converts more efficiently into active forms than cyanocobalamin.
• Preferred over cyanocobalamin in many clinical settings.

Cyanocobalamin

• A synthetic and inexpensive form.
• Commonly used in many commercial B12 supplements.
• Must be converted by the body into active forms, which may be inefficient in some individuals.
• Less preferred due to shorter retention in the body and lower conversion efficiency.

Comparison: Hydroxycobalamin is generally superior to cyanocobalamin in terms of conversion efficiency and retention in the body.[23] 

• First Choice: Methylcobalamin (for its high bioavailability and neurological benefits)
• Second Choice: Combination of Methylcobalamin + Adenosylcobalamin (for full spectrum support)
• Alternative: Hydroxycobalamin (especially for injections or longer-term storage)
• Avoid if possible: Cyanocobalamin (due to lower efficiency and synthetic nature)

Vitamin B12 Intrinsic Factor

Vitamin B12 is ingested from food of animal origin in order to ultimately be available as a purified coenzyme of cellular enzymes. For this, the vitamin B12 molecule must be channeled through the small intestinal wall. Due to the size of the vitamin B12 molecule, this crucial step can only be mastered with the help of a means of transport. [27] [28] 

A protein called the intrinsic factor channels the vitamin B12 molecule through the intestinal mucus wall and makes it available to the body cells. The intrinsic factor is therefore the focus of vitamin B12 intake. If the intrinsic factor is missing, vitamin B12 can only be absorbed by passive diffusion, but not by active transport using the intrinsic factor. [27] [28] 

How does the intrinsic factor work?

Vitamin B12 is bound to proteins and peptides in food and is released from them in saliva when chewing and in the stomach. The low pH of the stomach acid makes it easier to trigger vitamin B12. First, vitamin B12 is bound to the so-called R protein, which binds vitamin B12 better in saliva and gastric acid than the intrinsic factor.

Although R protein has a higher binding power for vitamin B12, the intrinsic factor has a higher specificity for vitamin B12. For example, vitamin B12 analogs are also bound by the R protein, but not by the intrinsic factor. The vitamin B12 bound to the intrinsic factor then binds to a receptor and is channelled through the wall of the up to 3m long bowel (also called the ileum) in the last part of the small intestine.

Where is the intrinsic factor produced?

The intrinsic factor is produced by the parietal cells of the stomach. These produce the intrinsic factor in large amounts, which exceeds the physiologically required amount by 50 times. The reason for this mass production is still unclear but may serve to safeguard vitamin B12 intake, which is only possible through the last part of the small intestine and almost exclusively with the help of the intrinsic factor. [27] [28] 

What happens if an intrinsic factor is not produced?

1. Hereditary absence of the intrinsic factor

The lack of the intrinsic factor can have various causes. If the gene that codes for the intrinsic factor is mutated, it is not produced. The consequence of this is described as hereditary intrinsic factor deficiency (HIFD). This is an autosomal recessive inherited disorder in which each parent inherits a defective copy of the gene.

Immerslund-Gräsbeck syndrome is a disease very similar to HIFD; however, the mutations here are not in the gene for the intrinsic factor, but in those for the subunits of the receptor for the intrinsic factor in the ileum. Both hereditary diseases manifest themselves in typical symptoms of a vitamin B12 deficiency, with gastrointestinal complaints, pancytopenia (lack of blood cells) and anaemia. For diagnosis, the absence of the intrinsic factor is confirmed using specific antibodies. Both diseases can be treated by regular parenteral administration of vitamin B12. [29] [30] 

Alternatively, a vitamin B12 deficiency in the absence of the intrinsic factor can also be remedied with a high dose of vitamin B12. In this case, the mechanism of absorption is based on the passive diffusion of vitamin B12 through the intestinal wall. Since only about 1.2% of the vitamin B12 consumed can be used by diffusion, a correspondingly higher dose of vitamin B12 (1000µg to 2000µg per day) must be taken in this case. [31] [32] 

2. Autoimmune response to the intrinsic factor

In the case of pernicious anaemia, it is an autoimmune disease in which antibodies against the intrinsic factor are produced. These bind to the intrinsic factor and thus prevent vitamin B12 from being bound and transported through the intestinal mucus wall. [33] 

Insufficient production of the intrinsic factor

If not enough sufficient intrinsic factor is produced, the body is also unable to absorb the physiologically necessary amount of vitamin B12. Inadequate production of the intrinsic factor can occur in the following cases:

In the course of normal ageing

The analysis of the intrinsic factor concentration using specific antibodies in people over the age of 70 years showed that in around 1% to 2% of the people not enough intrinsic factor was produced, which leads to a vitamin B12 deficiency. [34] 

Due to insufficient function of the parietal cells

The intrinsic factor is produced and secreted by the parietal cells in the stomach. Due to the immune deficiency AIDS, these cells are compromised and excrete too little gastric acid, pepsin, and intrinsic factor. Inadequate intrinsic factor production was found in 40% of the AIDS patients examined. [35] 

Through surgical interventions in the gastrointestinal tract

In the course of certain surgeries, such as in the case of gastric bridging or gastrectomy (partial removal of the stomach), the production of the intrinsic factor is reduced or completely lost due to the loss of the parietal cells. [27] [28] [33] 

Intrinsic factor and infections

The interaction between the intrinsic factor and bacterial infections is bilateral. On the one hand, bacteria can negatively influence vitamin B12 intake through interaction with the intrinsic factor; on the other hand, the intrinsic factor seems to play a role in protecting against infections.

• Helicobacter pylori, a common trigger for gastric ulcers, can promote an autoimmune reaction against parietal cells and the intrinsic factor and thus prevent the absorption of vitamin B12. [36]
• Excessive stress on the small intestine with Gram-negative bacteria (e.g. E. coli) also reduces the intrinsic factor function. [28]
• Parasite infestation with lamblia or fish tapeworm leads to reduced binding of the intrinsic factor to the specific receptors of the small intestine. [28]
• Experiments in mice have shown that the lack of the intrinsic factor leads to a higher susceptibility to infections with salmonella or citrobacter (enterobacteria). [37]

This scientific evidence indicates one - or more - unclear roles of the intrinsic factor in bacterial infections and parasite infestation.

Summary:

The intrinsic factor plays a key role in the absorption of vitamin B12 through the small intestine. Too little or no intrinsic factor production leads to vitamin B12 deficiency, which can only be corrected by a high-dose (1000 mcg to 2000 mcg per day) oral intake of vitamin B12 or by vitamin B12 injections.

Upset stomach, heartburn, and reflux esophagitis usually have symptoms that feel like the stomach is producing too much acid. In most cases, the opposite is the case - not enough stomach acid is produced.

To worsen the situation, many people resort to an acid blocker for stomach upset and heartburn, which further inhibits the stomach's ability to form hydrochloric acid.

Absence of acid in the stomach disturbs digestion and reduces the amount of nutrients that can be absorbed from the food.

Since not enough stomach acid can result in an intrinsic factor deficiency, but this is crucial for vitamin B12 intake, this is another explanation why so many people do not take in sufficient amounts of vitamin B12.

Vitamin B12 Dosage

Vitamin B12 is a vital nutrient that plays a crucial role in blood formation, nerve function, and DNA synthesis. It is water-soluble, stored in the liver, and excess amounts are excreted via the kidneys. While it is mainly absorbed from food (especially animal products), supplementation is often necessary for:

• Vegans and vegetarians
• Older adults with reduced absorption
• People with gastrointestinal disorders

Recommended Daily Intake of Vitamin B12 (µg/day)

The daily requirement of vitamin B12 depends on body weight, which is why there are different guidelines for children and adults. The German Nutrition Society gives the following values as guidelines: [38] 

Note: If absorption is impaired (e.g. due to age, gastric surgery, or medical conditions like pernicious anemia), much higher doses may be required via supplements or injections, often in the range of 250–1000 µg/day depending on the condition, as absorption from high-dose oral supplements is significantly lower.

Interpretation of Vitamin B12 Intake Guidelines

However, the daily requirement of vitamin B12 recommended by the DGE is only recommended as a guideline to prevent acute vitamin B12 deficiency in otherwise healthy people.

It is very important that only a small part of the vitamin B12 intake is actually available to the body. The daily requirement of vitamin B12 is therefore not necessarily the same as the amount of vitamin B12 to be absorbed.

Vitamin B12 is normally ingested through food and transported through parts of the small intestine through the intestinal mucus wall using a transport factor before it is converted into bioactive vitamin B12 coenzymes. A significant part of the vitamin B12 consumed is lost.

How much vitamin B12 can the body absorb?

Vitamin B12 is mostly absorbed in the small intestine by binding vitamin B12 and the transport molecule intrinsic factor. It should be noted that only up to 1.5 µg of vitamin B12 can be consumed before the system is saturated.

However, researchers have used studies on people who lack the intrinsic factor to find that part of the B12 vitamin taken in is also taken up by passive diffusion through the wall of the small intestine, regardless of transport mechanisms. [31] About 1.2% of the vitamin B12 intake is absorbed through passive diffusion, even if there is no intrinsic factor.

• Active intake of vitamin B12 by the intrinsic factor: 1.2µg per meal
• Passive absorption through diffusion: 1.2% of the absorbed amount of vitamin B12

However, these amounts can be reduced in older people due to the lower efficiency of the intestinal tract. This is why people over 50 suffer from a vitamin B12 deficiency more often than younger people. [32] 

The healthy body can therefore absorb a maximum of 1.5µg per meal plus 1.2% of the amount of vitamin B12 added to cover the daily requirement.

Optimal vitamin B12 dosage

Due to the limited absorption capacity of the system, it is necessary to supply the body with significantly more vitamin B12 than the recommended daily dose. But how do you make sure you provide the body with optimal vitamin B12 without literally disposing of too much vitamin B12 via the urban sewage system?

• In the event of an acute vitamin B12 deficiency, 1000µg to 2000µg (e.g. 1 - 2 mg) vitamin B12 should be taken daily. Studies have shown that oral vitamin B12 intake is just as effective here as an intramuscular injection, which is used more frequent in the medical field (4). This amount is also sufficient to replenish the empty vitamin B12 storage. [39]
• A dose-finding study by the Dutch University of Wageningen showed that a slight vitamin B12 deficiency in older people with a dosage of 500µg to 1000µg has to be counteracted in order to effectively correct it. [40]
• A Danish study questioned the recommended daily requirement of vitamin B12 and showed that young, healthy people have to consume at least 4µg to 7µg vitamin B12 daily in order to maintain adequate vitamin B12 levels. [41] In children and adolescents, an intake of more than 10 µg/day does not seem to cause a further increase in the vitamin B12 level and therefore appears only necessary if vitamin B12 deficiency is suspected. [42]

Optimal Dosage Recommendations

Based on the scientific results, the following dosage recommendations are:

Higher doses compensate for limited absorption and are safe because excess is excreted.

Healthy people are defined as people without an increased need. A possible increased need can arise from physical exercise and sport, stress, alcohol or caffeine consumption, malnutrition, or an unbalanced diet.

In summary, it can be assumed that the officially recommended daily requirement of vitamin B12 is below the actual requirement for young, healthy people. The optimal dosage of vitamin B12 to help or prevent possible deficiency symptoms depends on age, living conditions, and diet.

Vitamin B12 Overdose

Vitamins are (vital) necessary, support essential body functions and help to maintain health. However, some vitamins have to be taken in the correct dosage, as excessive amounts can lead to side effects.

Vitamin B12 is often administered or taken in high doses - can an overdose occur here? How do you recognise an overdose of vitamin B12?

Very early on after the discovery of vitamin B12 as a trigger for - and a remedy for - anaemia and blood loss, the effects of various doses of vitamin B12 were examined. It soon became apparent that vitamin B12 has 'remarkably few side effects'. [43] This is because excess vitamin B12 can be excreted through the kidney and urine. Quantities of up to 3000 µg can be regarded as harmless. [44] 

Is it possible to overdose on vitamin B12?

According to the current state of science, overdosing with vitamin B12 due to the automatic excretion is practically impossible. At extremely high doses, vitamin B12 unspecific overload of the kidneys could occur. From a medical point of view, however, this appears to be a low risk.

Extremely high doses of 5000 µg are used as an antidote to cyanide poisoning by smoke inhalation. Even these doses are considered safe to treat children and pregnant women in the event of smoke poisoning. [45] 

Does a vitamin B12 overdose make sense?

Apart from the case of cyanide poisoning or acute pernicious anaemia, doses of vitamin B12 over 1000 µg are hardly useful. In the event of a vitamin B12 deficiency or reduced vitamin B12 absorption capacity - for example due to drug interactions or if there is no intrinsic factor - doses of up to 1000 µg per day are definitely advisable.

The reason for this is the relatively low actual utilisation of vitamin B12 via the intrinsic factor as well as via passive diffusion. While the intake via the intrinsic factor is limited to 1.5 µg per meal, just over 1% of the vitamin B12 intake is made available to the body via passive diffusion.

High doses of vitamin B12 therefore hardly lead to an over-supply. However, it prevents the development of a vitamin B12 deficiency, the effects of which could be far more serious than those of a possible overdose.

Vitamin B12 Side Effects

Acne-like rash

In some cases, an acne-like rash occurred after intramuscular or oral administration of different doses of vitamin B12. This was observed in the face and upper part of the upper body and occurred within the first 6 months of the treatment. However, the rash subsided quickly after stopping vitamin B12 treatment. [46] 

However, this side effect of vitamin B12, which is also very rarely described, is not due to an actual overdose, since small amounts of vitamin B12 were the trigger. The cause of the appearance of this rash is unclear and seems to have individual underlying reasons or intolerances, as there is no clear pattern. An end of the vitamin B12 intake should lead to a resolution of the symptoms in any case.

Anaphylactic shock

Possible side effects that have been observed in very rare cases are the same as those with similar drugs - for example, isolated cases of anaphylactic shock after vitamin B12 injections have been observed. [43] [47] 

However, this is more likely to be due to the method of administration or carrier materials. This could also apply to other local and systematic reactions after vitamin B12 injections, e.g. skin irritation, dizziness, hot flashes, or nausea. [48] 

Interestingly, the different forms of vitamin B12 seem to lead to differentiated side effects. Immediate type 1 hypersensitivity reactions (such as anaphylactic reactions) were more likely to be observed with cyanocobalamin, while individual reports of allergies to hydroxylcobalamin were observed. [48] [49] 

Vitamin B12 Nutrient Combinations

Providing the body with the right nutrients is a complex process in which all the elements involved should strike a balance. Nutrient combinations often have to be added in order to optimally utilise each individual element.

Vitamin B12 also reacts with a variety of molecules and nutrients. These interactions of vitamin B12 can help to absorb vitamin B12 and other vitamins and nutrients more effectively and to prevent or remedy deficiencies.

Vitamin B12 and folic acid

One of the best known interactions of vitamin B12 is with folic acid. Both molecules are a crucial part of the one-carbon metabolism. Here, vitamin B12 is responsible for attaching a methyl group to the homocysteine (chemical compound of a carbon atom with three hydrogen atoms), thereby deactivating homocysteine.

Homocysteine is a natural breakdown product of the amino acid methionine contained in food. Elevated homocysteine levels can contribute to nervous system disorders, depression, dementia, and other diseases. Vitamin B12 works closely with folates (naturally occurring form of folic acid). While vitamin B12 slows down homocysteine through direct methylation, folic acid causes this state of homocysteine to be maintained through re-methylation. [50] [51] 

The interaction of vitamin B12 and folic acid is not a direct one, but both elements influence each other by working together in the same chemical processes. Vitamin B12 also regulates the activation of folic acid. If too little vitamin B12 is available, folate can no longer be methylated and gets stuck in an inactive precursor, 5-methyltetrahydrofolate. A vitamin B12 deficiency can therefore lead to a folic acid deficiency. [52] 

Folic acid or vitamin B12 deficiencies have clinically similar effects that can range from nervous disorders and mental disorders to anaemia and birth defects. The similarities are due to the influence of the homocysteine level by both molecules. [52] [53] 

However, due to the interaction of vitamin B12 and folic acid, an elevated homocysteine level cannot be used to make a clear decision as to whether there is vitamin B12 or a folic acid deficiency - or both. Additional specific vitamin B12 or folic acid determinations are necessary here. If in doubt, and / or during pregnancy, it is advisable to take a combination of folic acid and vitamin B12.

Vitamin B12 and B Vitamins

The family of B vitamins includes 8 water-soluble vitamins that perform important functions in the cells of the human body. B Vitamins are particularly important for the brain. They can cross the blood-brain barrier and are enriched in the brain. For example, the concentration of vitamins B5 and B7 in the brain is 50 times higher than in blood plasma.

Studies with various vitamin B combinations show that the functions and effects of all B vitamins are linked. However, details of these interactions are still largely unclear. [54] However, there are some vitamin B family members whose interaction with vitamin B12 has been examined a little more closely:

• Vitamin B12 and Vitamin B6: Both vitamins play a role in the one-carbon metabolism. For this reason, both have to. [50]
• Vitamin B12 and Vitamin B7 (biotin): Vitamin B12 is part of the citrate cycle, through which organic building blocks for energy generation and the building of new substances are recycled. Biotin and magnesium are necessary partners here to activate vitamin B12.
• Vitamin B12, vitamin B2 (riboflavin) and vitamin B3 (niacin): together with folate, vitamins B12 and B6, vitamin B2 is also involved in the one-carbon metabolism, which regulates the methylation of other molecules and homocysteine. Vitamin B2 and vitamin B3 are also necessary to convert vitamin B12 into its active forms, methylcobalamin and adenosylcobalamin. [55]

Vitamin B12 and Calcium

Vitamin B12 can only be channelled through the intestinal mucosa by binding to the intrinsic factor and made available to the body cells. Calcium is necessary for the binding as well as the correct pH value. With an acidic pH or a lack of calcium, vitamin B12 is unable to bind to the intrinsic factor. [56] 

Should vitamin B12 be taken alone or in combination with something else?

Based on the interactions of vitamin B12 with other B vitamins, folic acid, magnesium, and calcium described here, the question arises whether vitamin B12 should be taken more sensibly in combination with interacting nutrients. This depends on the individual case and possible specific deficiency symptoms. If there is only suspicion of a vitamin B12 deficiency, for example with a vegan diet, taking vitamin B12 alone can be enough to restore the balance.

In other situations, such as during pregnancy, vitamin B12 is usually given with folic acid to help prevent birth defects. However, recent studies show that treatments with vitamin B combinations could be much more effective than expected.

Due to the importance of all B vitamins for the brain and nervous system, B vitamins could be involved in the development of multiple sclerosis. Scientists speculate that treatment with vitamin B combinations can eliminate the cause of multiple sclerosis and have a decisive impact on the course of the disease. [57]