Vitamin B12 is an essential and water-soluble vitamin that fulfils many important functions in the body. This includes the support in the production of red blood cells, as well as in the development and function of the nervous system. Vitamin B12 is ingested through food; vitamin B12 is only present in food of animal origin. Vegans and vegetarians are therefore particularly at risk of suffering from a vitamin B12 deficiency. This also applies to older people, as the ability to absorb and utilise vitamin B12 from food decreases with age.
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.
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.
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.
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.
To summarize, the essential functions of vitamin B12 include:
These molecular functions of vitamin B12 can be seen in the effect of vitamin B12 on health:
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.
The human body typically stores between 3 mg and 5 mg of vitamin B12, 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:
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.
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:
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:
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?
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.
*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.
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:
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.
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.
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.
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.
The following forms of vitamin B12 exist:
Form | Status | Function |
---|---|---|
Cyanocobalamin | Inactive (synthetic) | Requires conversion |
Hydroxycobalamin | Inactive (natural) | Precursor; also detoxifies cyanide |
Methylcobalamin | Active (coenzyme) | DNA/RNA synthesis, nervous system |
Adenosylcobalamin | Active (coenzyme) | Cellular energy production |
Cyanocobalamin and hydroxycobalamin must be converted into active forms in the body:
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:
Adenosylcobalamin:
Special Role of Hydroxycobalamin
The main forms of vitamin B12 naturally present in food are:
Less commonly found in food:
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.
These forms are directly usable by the body:
Methylcobalamin
Adenosylcobalamin
Recommendation:
Many nutritionists now recommend taking methylcobalamin or a combination of methylcobalamin and adenosylcobalamin for optimal results.
Hydroxycobalamin
Cyanocobalamin
Comparison: Hydroxycobalamin is generally superior to cyanocobalamin in terms of conversion efficiency and retention in the body.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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 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:
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:
Age Group | Recommended Intake (µg/day) |
---|---|
Infants 0-<4 months | 0.4 |
Infants 4-<12 months | 0.8 |
Children 1-<4 years | 1.0 |
Children 4-<7 years | 1.5 |
Children 7-<10 years | 1.8 |
Children 10-<13 years | 2.0 |
Adolescents 13-<15 years | 3.0 |
Adolescents & Adults ≥15 years | 3.0 |
Pregnant women | 3.5 |
Breastfeeding women | 4.0 |
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.
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.
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. About 1.2% of the vitamin B12 intake is absorbed through passive diffusion, even if there is no intrinsic factor.
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.
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.
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?
Based on the scientific results, the following dosage recommendations are:
Group | Recommended Dose |
---|---|
Healthy people <50 years | 4 - 7 µg/day |
People >50, vegetarians, vegans, pregnant/nursing, risk groups | 500 - 1000 µg/day |
Acute deficiency | 1000 - 2000 µg/day (1-2 mg) |
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.
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'. 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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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. However, there are some vitamin B family members whose interaction with vitamin B12 has been examined a little more closely:
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.
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.
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Detect and treat vitamin B12 deficiency on time
Vitamin B12 deficiency occurs when the body doesn't get or absorb enough of this essential vitamin. It can lead to fatigue, nerve damage, and concentration problems. Since B12 is mainly found in animal products, vegetarians, vegans, and older adults are especially at risk. Early detection and proper supplementation can prevent long-term health issues.