by VitaminExpress, 8/23/2020
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.
In order to unfold its effect, vitamin B12 is absorbed through food and is only absorbed in the ileum, the last part of the small intestine. Because of its enormous size for molecules, vitamin B12 needs the help of transport proteins to pass through the lining of the intestine. This is also necessary to reach further into the cells of the body. In the cell, vitamin B12 is then converted into its bioactive forms, the so-called coenzymes, methylcobalamin, and 5’-deoxyadenosylcobalamin.
The two coenzymes share the tasks of vitamin B12. Both coenzymes are involved in basic cellular processes. Methylcobalamin is required to produce the amino acid methionine, an important building block of proteins. Methylcobalamin is also necessary for the production of the structural elements of DNA and RNA in the cell.
If vitamin B12 is missing here, not enough DNA can be produced during cell division. These functions of vitamin B12 are particularly important in cells with a high cell division rate, e.g. the bone marrow. A vitamin B12 deficiency therefore affects the production rate of blood cells and leads to insufficient amounts, especially of red blood cells - and thus to anaemia.
The second coenzyme, 5’-deoxyadenosylcobalamin, is effective in the mitochondria. These are cell organs that provide energy for every cell in the body. Vitamin B12 is instrumental in the production of fatty acids and structural elements of other amino acids. Vitamin B12 intervenes in the citrate cycle, which processes organic molecules for energy production and for building new substances. If vitamin B12 is missing here, neurological and cognitive disorders can occur.
The basic functions of vitamin B12 can be summarised as follows: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 body normally stores between 3 mg and 5 mg of vitamin B12. This is mainly stored in the liver and made available from there as needed. The recommended daily intake of vitamin B12 is 2.4µg. For example, this amount is contained in 50g lean beef, 120g cheese or egg yolk, or in about 70g pollock. Vegetables, fruits, legumes, nuts, cereals, or rice do not serve as a source of vitamin B12.
When ingesting vitamin B12 through food, it must also be borne in mind that the amount of vitamin B12 contained in food does not necessarily correspond to the usable amount. Only about half to two thirds of e.g. vitamin B12 ingested with meat is subsequently available to the body in bioactive form.
In addition, a maximum of 2µg of vitamin B12 can be consumed per meal before the system in the small intestine is saturated. Therefore, the daily dose of vitamin B12 must be taken over several meals.
The concentration of vitamin B12 can be measured by a laboratory analysis of the blood. This enables the amount of vitamin B12 present in the blood serum to be determined. The normal vitamin B12 concentration in the blood is between 200 and 900 pg/ml.
Values below 200 pg/ml are therefore considered a vitamin B12 deficiency. Symptoms of vitamin B12 deficiency usually occur at serum concentrations of less than 200 pg / ml. In old people, however, symptoms can also occur at values between 200 and 500 pg/ml.
A study of older people who had a hip fracture showed that a serum concentration of vitamin B12 of less than 350 pg/ml was associated with lower cognitive abilities. This means that an insufficient supply of vitamin B12 could promote the loss of memory in older people. [18] For an optimal supply of vitamin B12, serum concentrations of over 500 pg/ml should therefore be aimed for, especially for older people.
A vitamin B12 excess is not to be feared even with excessive intake, since excess vitamin B12 is excreted through the urine. Abnormally high levels of vitamin B12 usually only occur as a result of liver or bone marrow disorders.
The body needs enough vitamin B12 every day to prevent a vitamin B12 deficiency and its potentially serious consequences. But which foods are best suited to absorb vitamin B12?
Vitamin B12 occurs almost exclusively in animal foods. However, the amount of vitamin B12 occurring depends not only on the source, but also on the type of preparation. It can be assumed that around 30% of vitamin B12 is lost through cooking.
The United States Department of Agriculture (USDA) has created a comprehensive vitamin B12 food table of over 7000 foods and their vitamin B12 content. It clearly shows that the best vitamin B12 suppliers are offal such as liver and kidney from beef, lamb, goose, and duck. In addition to this, mussels and oysters are the front-runners among foods rich in vitamin B12.
*Note: The vitamin B12 values measured in plants, mushrooms, and seaweed depend on the nutrient medium and are often subject to strong regional fluctuations.
Contrary to the USDA's results, other sources found significant amounts of vitamin B12 in some seaweed such as nori, chlorella, and spirulina. However, the fluctuating test results and the potentially high content of pseudo-vitamin B12 are problematic here.
The foods listed here with vitamin B12 are provided with the average values of measured vitamin B12 per 100g. However, it should be noted that not all of the vitamin B12 contained is actually available to the body.
The bioavailability of the vitamin B12 contained varies greatly depending on the food and the method of preparation. After an intake of 200 g of cooked lamb, theoretical 3 µg of vitamin B12 are available, but the body only uses about 80% of it.
Bioavailability is around 60% for milk, but only about 10% of the vitamin B12 consumed can be used for liver pate. As a rule of thumb, healthy adults utilise around 50% of the vitamin B12 consumed through food.
Sufficient quantities that can meet the vitamin B12 requirement can only be found in animal foods and their products. The leaders here are innards such as liver and kidney. Dairy products and eggs, as well as foods made from them, are also valuable sources of vitamin B12.
People who almost or completely do without animal foods can only meet their needs with foods fortified with vitamin B12. As an alternative, dietary supplements with vitamin B12 can be used to prevent a vitamin B12 deficiency.
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?
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.
Inactive forms of vitamin B12, such as cyanocobalamin and hydroxycobalamin (also called hydroxocobalamin), are split in the body after ingestion and converted into the bioactive forms methylcobalamin and adenosylcobalamin.
First the -HO or -CN group is removed and in a further step the -CH3 or -5 ’deoxyadenosyl group is added. The respective steps are carried out by specific cellular enzymes. If one of these enzymes is not functional, bioactive vitamin B12 can't be produced.
After the conversion into bioactive forms methylcobalamin and adenosylcobalamin, the vitamin B12 coenzymes work, according to their name, with enzymes. The coenzymes are necessary for the function of the enzymes and cannot be replaced by other factors.
Methylcobalamin acts in the cell with the enzyme methionine synthase, which is necessary for the production of the genetic material DNA and RNA. Methylcobalamin is therefore particularly important in very active cells, such as those in the bone marrow, where the blood cells are formed. If methylcobalamin is deficient, red blood cells that are not functioning properly are formed - anaemia occurs.
Adenosylcobalamin is effective in the mitochondria. These are small cell organelles in which energy is generated for the cell. Adenosylcobalamin activates the enzyme methylmalonyl-CoA mutase here.
This is of crucial importance for the production of fatty acids and building blocks of DNA, as well as for the citrate cycle, which serves to generate cellular energy. A deficiency of adenosylcobalamin can lead to neurological and cognitive disorders.
Hydroxycobalamin has another special function besides that of vitamin B12 coenzyme precursor. Hydroxycobalamin can take up a -CN group, which is otherwise split off as a cyanide. Hydroxycobalamin is therefore used for detoxification in hydrocyanic acid poisoning.
The main forms of vitamin B12 that are ingested through food are primarily hydroxycobalamin, but also methylcobalamin and adenosylcobalamin. Forms that are very rarely found in food include cyanocobalamin and sulphite cobalamin, another cobalamin derivative.
Since the two active forms methylcobalamin and adenosylcobalamin are the only directly usable forms of vitamin B12, more and more nutritionists are recommending taking these two forms of vitamin B12 as a dietary supplement.
Methylcobalamin in particular shows the highest activity in DNA methylation. This is the main task of the active vitamin B12 enzyme. Methylcobalamin is therefore the most commonly recommended form of vitamin B12 as a dietary supplement.
Hydroxycobalamin is the most common form of vitamin B12 in food. Cyanocobalamin is the cheapest synthetic form of vitamin B12 and is therefore often offered as a vitamin B12 preparation.
A comparison of the two inactive vitamin B12 forms shows the following:
Based on these results, hydroxycobalamin is preferable to cyanocobalamin.
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 3 m 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.
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.
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:
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.
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.
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.
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 an essential vitamin that can be stored in the body (especially in the liver), but because of its water solubility is largely excreted via the kidney. For an optimal supply, vitamin B12 must therefore be taken in daily with food.
If this is not possible (e.g. through a vegan diet) or not sufficient (e.g. due to reduced absorption in the intestine in the elderly), vitamin B12 should also be taken in the form of dietary supplements. But how much vitamin B12 do people need?
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:
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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