If you suspect that you suffer a vitamin B12 deficiency, you are not the only one. Recent studies show that one in four adults suffers from a deficiency of this essential vitamin, almost half the population has lower levels than what is advised.
A Vitamin B12 deficiency has serious consequences for our health. Vitamin B12 dietary supplements are a useful and, in many cases, necessary in order to cure this deficiency.
- 1. What is vitamin B12?
- 2. A Vitamin B12 deficiency occurs slowly and unexpectedly
- 3. Effects of vitamin B12
- 4. Vitamin B12, convertible and multifunctional
- 5. Function of vitamin B12 in the cells
- 6. Vitamin B12 provides energy
- 7. Effects of vitamin B12 on our health
- 8. Forms of vitamin B12
- 9. What happens with vitamin B12 when there is little acid in the stomach?
- 10. Recommended dose of vitamin B12
- 11. How much vitamin B12 can be absorbed by the body?
- 12. What is the optimal daily dose of vitamin B12?
- 13. Vitamin B12 for vegans and vegetarians
- 14. Caution is advised with plant sources of vitamin B12
- 15. Vitamin B12 contained in some plants
- 16. The vitamin B12 from algae and mushrooms
- 17. Does the vitamin B12 from vegetables work?
- 18. How can vegans and vegetarians prevent a vitamin B12 deficiency?
- 19. Are vitamin B12 supplements vegan?
- 20. Vitamin B12 and depression
- 21. Vitamin B12 to treat dementia and Alzheimer
- 22. Vitamin B12 and homocysteine in dementia and Alzheimer’s disease
- 23. Vitamin B12 to treat anemia and pernicious anemia
- 24. Vitamin B12 to treat sleep problems
- 25. The importance of vitamin B12 in preventing and treating neurological and neuropsychiatric diseases
- 26. Vitamin B12 and other diseases
- 27. Vitamin B12 and fertility
- 28. Vitamin B12 and fertility in women
- 29. Vitamin B12 and osteoporosis
- 30. Vitamin B12 in foods
- 31. Is there any vegetable source of vitamin B12?
- 32. The bBioavailability of Vitamin B12: A crucial issue!
- 33. A vitamin B12 caused by medication
- 34. Interactions of vitamin B12
- 35. How to take vitamin B12, alone or combined with other nutrients?
- 36. Overdose of vitamin B12
- 37. Side effects of vitamin B12
- 38. Levels of vitamin B12
- 39. Studies and References:
- 40. Related Entries:
What is vitamin B12?
Vitamin B12 is an essential vitamin for the body. It is a water-soluble vitamin that performs many important functions in the organism, including the production of red cells, and the development and functioning of the nervous system. Vitamin B12 is absorbed through the food we eat.
Vitamin B12 is present only in foods of animal origin. This means that vegans and vegetarians have more chances of suffering a vitamin B12 deficiency. Something similar happens in the elderly, since they are less capable of properly absorbing and using vitamin B12 from the food they eat.
A Vitamin B12 deficiency occurs slowly and unexpectedly
Vitamin B12, also known as cobalamin, is soluble in water. But unlike other water-soluble vitamins, B12 is not excreted quickly through urine.
Vitamin B12 is stored in the liver, kidneys and tissues of the body. For that reason, its deficiency can go unnoticed for years, since its supply depends on the diet and each person’s ability to absorb the vitamin efficiently.
A delay in noticing a vitamin B12 deficiency can lead to a serious problem, because it can cause irreversible brain damage if the situation lasts about seven years.
Vitamin B12 is also called the energy vitamin and the body needs it to perform many vital functions optimally.
These functions include: energy production, blood formation, DNA synthesis and myelin formation. (Myelin protects nerve endings and enables the communication between them).
Effects of vitamin B12
Vitamin B12 is a special vitamin. Not only because it is the largest and most complex of all vitamins, but also because it only contains one metallic element: cobalt. This is one of the rarest elements, and it is what gives vitamin B12 its chemical name, cobalamin.
Vitamin B12 cannot be produced by any organism, which means that it must be supplied through the diet. The original source of vitamin B12 is bacterial vitamin B12, which is absorbed by the organism through foods of animal origin. Therefore, vegan diets should use vitamin B12 supplementation to prevent a vitamin B12 deficiency.
Vitamin B12 is known for its healing properties to treat anemia. Now we also know that it also performs other vital tasks in the organism.
Vitamin B12, convertible and multifunctional
Vitamin B12 is absorbed through the diet and exclusively in the ileum, the last part of the small intestine. Due to its enormous molecular size, vitamin B12 needs the support of proteins to pass through the intestinal mucous membrane and to reach all the cells of the body. Once it reaches the cells, vitamin B12 is transformed into its bioactive forms, called coenzymes, methylcobalamin, and 5′-desoxyadenosylcobalamin.   
Function of vitamin B12 in the cells
The two coenzymes, methylcobalamin and 5′-desoxyadenosylcobalamin, share the functions of vitamin B12. Both are involved in basic cellular processes. Methylcobalamin is necessary to create the amino acid methionine, an important building element for proteins. Methylcobalamin is also necessary to produce the structural elements of DNA and RNA in the cells.
If we lack vitamin B12 we cannot produce enough DNA during the cell division process. These functions of vitamin B12 are particularly important in cells which have high rates of cell division, such as those from the bone marrow. Therefore, a vitamin B12 deficiency lowers the amount of red cells that are produced, which can lead to anemia.
Vitamin B12 provides energy
The second coenzyme, 5′-desoxyadenosylcobalamin, is active in the mitochondria. These cellular organisms provide energy to every cell of the body. Vitamin B12 plays a key role in the production of fatty acids and structural elements of other amino acids. Vitamin B12 is involved in the citrate cycle and it processes the organic molecules to produce energy and store new substances. We can suffer neurological and cognitive disorders if there is a vitamin B12 deficiency.
The basic functions of vitamin B12 are:
- Synthesis of DNA and RNA
- Production of fatty acids
- Synthesis of amino acids
- Helps to produce cell energy
Effects of vitamin B12 on our health
The molecular functions of vitamin B12 can be seen in its effects of on our health. The most remarkable ones are:
- Increasing the energy and reducing the fatigue 
- Guaranteeing a proper functioning of the nervous system 
- Favoring the growth and development of the nerves 
- Helping with the production of red cells 
- Regulating the cell division process and encouraging longevity 
- Protecting the cardiovascular system from homocysteine 
- Ensuring a healthy immune system 
- Supporting women’s reproductive health and stimulating pregnancy 
- Favoring a mental well-being and a good mood 
- Stimulating mental clarity, concentration and memory 
- Increasing the physical, emotional, and mental energy 
In short, vitamin B12 is indispensable for a good physical and mental health. Therefore, we must make sure that we have a proper supply of vitamin B12, especially if we follow a vegetarian or vegan diet. Dietary supplements help to increase the levels of vitamin B12.
Forms of vitamin B12
Foods contain several forms of vitamin B12. These forms can be found as vitamin B12 supplements.
Which form of vitamin B12 is the best? Are some forms of vitamin B12 more effective than others?
Vitamin B12 belongs to the chemical group cobalamines. Cobalamines have the trace element cobalt in their central atom. Vitamin B12 is the only natural substance that contains a cobalt element.
Nitrogen atoms bind together in this cobalt element. This central structure is surrounded by a stable frame of ring structures. 
The cobalt element is crucial for the different forms of vitamin B12, since it can belong to different chemical groups and it is responsible for the specific function of each vitamin B12 form.
The following forms of vitamin B12 are: 
- Cyanocobalamin: inactive form
- Hydroxycobalamin: inactive form
- Methylcobalamin: bioactive coenzyme
- Adenosylcobalamin: bioactive coenzyme
Learn more about all the chemical forms of vitamin B12 in detail, you will be able to know if it is Methylcobalamin or Cyanocobalamin
The functions of the different vitamin B12 forms
The inactive forms of vitamin B12, such as cyanocobalamin and hydroxocobalamin, are split after being absorbed by the body and they become bioactive forms: methylcobalamin and adenosylcobalamin.
First, the -HO or -CN group is removed and then the deoxyadenosyl -CH3 or -5′ group at an additional stage. These steps are carried out by specific cell enzymes. We will not be able to produce bioactive vitamin B12 if one of these enzymes is not functional.
After being converted into its bioactive forms, methylcobalamin and adenosylcobalamin, vitamin B12 coenzymes work together with enzymes. Coenzymes are necessary for the function of enzymes, which means that they cannot be replaced by other elements.
Methylcobalamin works with the enzyme methionine synthase in the cell, which is necessary for the production of DNA and RNA genetic material. Therefore, methylcobalamin is particularly important in highly active cells, such as those in the bone marrow, which is where blood cells are formed. A lack of methylcobalamin affects the red blood cells and produces anemia.  
Adenosylcobalamin is effective in the mitochondria. These are elements of the cells that produce energy. This is crucial for the production of fatty acids and DNA building elements, as well as for the citrate cycle, which is necessary for the production of cell energy. A lack of adenosylcobalamin produces neurological and cognitive disorders.
Hydroxocobalamin has another special function apart from being a precursor form of the vitamin B12 coenzyme. Hydroxocobalamin is also used in the detoxification of hydrogen cyanide.
What forms of vitamin B12 are absorbed through food?
The main forms of vitamin B12 that are ingested with food are mainly hydroxocobalamin, methylcobalamin, and adenosylcobalamin. The rarest forms are cyanocobalamin and sulfitcobalamin, another derivative of cobalamin. 
What forms have to be taken as vitamin B dietary supplements?
The active forms of vitamin B12 are methylcobalamin and adenosyl cobalamin. These forms are used directly, which is why nutritionists advise taking these two vitamin B12 forms through dietary supplements.
Methylcobalamin, in particular, has the highest activity in the DNA methylation. This is the main task of the active enzyme of vitamin B12. Therefore, methylcobalamin is the most advised form of vitamin B12 as a dietary supplement.
Hydroxocobalamin is the most common form in which vitamin B12 is found in food. Cyanocobalamin is the most synthetically produced form of vitamin B12 which is why it is often sold as a vitamin B12 supplement.
A comparison of the two inactive forms of vitamin B12 shows that:
- Hydroxocobalamin represents a 50% of what is absorbed and bound to transcobalamin in the blood plasma and, therefore, it is the most common form of vitamin B12 in the blood.
- Hydroxocobalamin is stored in the body for longer and excreted more slowly through the kidneys than cyanocobalamin. It is often used in vitamin B12 injections due to its depot effect.
- Under experimental conditions, hydroxocobalamin was found to be more efficient in converting to bioactive forms of vitamin B12 than cyanocobalamin.
- Based on these results, hydroxocobalamin is better than cyanocobalamin.
What happens with vitamin B12 when there is little acid in the stomach?
Indigestion, heartburn, and reflux esophagitis usually have symptoms caused by the fact that the stomach produces too much acid. However, in most cases, what happens is exactly the opposite: very little stomach acid is produced.
Many people turn to an acid blocker to treat gastric discomfort, which can worsen the situation. But the problem is that this inhibits the stomach’s ability to produce hydrochloric acid.
A lack of hydrochloric acid in the stomach makes the digestion difficult and reduces the amount of nutrients that are absorbed from food. A lack of stomach acid can cause a deficiency of the intrinsic factor, which is indispensable for the supply of vitamin B12. This is one of the reasons why many people do not absorb enough vitamin B12.
Do you know what is the intrinsic factor in the Organism? We tell you everything in this link
Recommended dose of vitamin B12
If this is not possible (e.g. when following a vegan diet), or if the supply is not enough (e.g. in the case of the elderly who have a reduced intestinal absorption), it is advisable to take vitamin B12 supplementation. But how much vitamin B12 does a person need?
Advised daily vitamin B12 supply
The recommended dose of vitamin B12 depends on your body weight, so there are different guidelines for children and adults. The State Nutrition Society gives the following values as guidelines: 
From 0 to 4 months: 0.4 microgram daily
From 4 to 11 months: 0.8 microgram daily
From 1 year to 3 years: 1.0 micrograms daily
From 4 years to 6 years: 1.5 micrograms daily
From 7 years to 9 years: 1.8 micrograms daily
From 9 years to 12 years: 2.0 micrograms daily
From 12 years to 14 years: 3.0 micrograms daily
- Adolescents from 15 years and adults:
3.0 micrograms daily
- Pregnant women:
3.5 micrograms daily
- During lactation:
4.0 micrograms daily
Interpreting the guidelines
The previous information is just a basic guideline to prevent an acute vitamin B12 deficiency. It is very important to know that the organism just absorbs a tiny amount of the vitamin B12 that we consume.
Vitamin B12 is normally consumed through food. Once it reaches the small intestine, it is channeled through the intestinal mucous membrane until it becomes the bioactive coenzymes of vitamin B12.  A large part of vitamin B12 that we consume is lost during this process.
How much vitamin B12 can be absorbed by the body?
However, researchers have discovered through people who lack an intrinsic factor, that some of the vitamin B12 is also absorbed through the small intestine walls, regardless of the transport mechanism.  Around a 1.2% of the amount of vitamin B12 that we consume is absorbed by passive diffusion, even if there is no intrinsic factor.
- Active intake of vitamin B12 by intrinsic factor: 1.2μg (micrograms) per meal.
- Passive diffusion intake: 1.2% of the amount of vitamin B12 that is absorbed.
However, in the case of older people, these numbers drop due to a lower efficiency of the intestinal tract. This is why people over the age of 50 are more likely to suffer a vitamin B12 deficiency than younger people. 
A healthy body absorbs a maximum of 1.5μg (micrograms) of vitamin B12 per meal, which meets the 1.2% percentage to meet the daily vitamin B 12 requirements.
What is the optimal daily dose of vitamin B12?
It is necessary to supply the body with more vitamin B12 than the recommended daily dose due to its limited ability to absorb this vitamin. But how can we make sure that our body gets the amount it needs without excreting part of this vitamin?
People who suffer from an acute vitamin B12 deficiency should take between 1000μg to 2000μg (that is 1 to 2 mg) of vitamin B12 daily. The studies have shown that the oral intake of vitamin B12 is just as effective as an intramuscular injection by a doctor. This amount is enough to recharge the reserves of vitamin B12. 
A study on the dose of vitamin B12 revealed that a mild vitamin B12 deficiency should be counteracted with a dose of 500 μg to 1000 μg to effectively remedy it in the case of the elderly. 
A clinical study showed that young, healthy people need to consume at least between 4 μg to 7 μg of vitamin B12 daily to maintain proper vitamin B12 levels. 
In the case of children and adolescents, a supply of more than 10 μg / day is enough to maintain proper levels of vitamin B12. 
Recommended dose of vitamin B12
According to the results of clinical studies, the recommended dose of vitamin B12 would be:
- Healthy people under the age of 50: 4 μg to 7 μg / day
- People over the age of 50, vegetarians, vegans, pregnant or lactating women, or other risk groups: 500 μg to 1000 μg / day
- Those with an acute vitamin B12 deficiency: 1000 μg to 2000 μg of vitamin B12 / day
- In principle, healthy people would not need to take vitamin B12 unless they do a lot of physical exercise, suffer stress, drink a lot of alcohol or caffeine, or if they have an unbalanced diet.
To sum up, the recommended dose of vitamin B12 is lower in healthy and young people. The optimal dose to prevent the symptoms of a deficiency depends on the age, lifestyle, and diet.
Vitamin B12 for vegans and vegetarians
Why are vegans and vegetarians run the risk of suffering a vitamin B12 deficiency?
Vitamin B12 is absorbed through the animal foods that we eat. Its supply must be daily to avoid a deficiency in the organism. Most vegetables do not contain vitamin B12. This is because this vitamin can only be produced by the bacteria from meat products and other animal products. 
Many people follow vegan and vegetarian diets due to health, environmental, cultural or ethical reasons. Vegetarians do not eat meat but some of them do eat animal products such as eggs and dairy products. On the other hand, vegans completely refrain from consuming food of animal origin.
The vegetarian and vegan diet and lifestyle reduce the risk of suffering certain pathologies, such as diabetes or cardiovascular diseases.  There are about 75 million vegetarians in the world and about 1.5 million people who have rejected the omnivorous diet (the intake of products of animal and plant origin). 
A balanced vegetarian or vegan diet, combined with the regular exposure to sunlight, will meet most of the vital nutrients, such as vitamins and minerals. However, it does not meet requirements of vitamin B12 of the body.
Most vegetables do not contain vitamin B12, so vegans and vegetarians run the risk of suffering a vitamin B12 deficiency. This is the reason why those who follow a vegan or vegetarian diet should take vitamin B12 dietary supplements. Moreover, they should frequently monitor their vitamin B12 levels to prevent the symptoms of a deficiency.
Do all vegans and vegetarians run the risk of suffering a vitamin B12 deficiency?
The clinical studies have shown that vegans and vegetarians are more likely to suffer a vitamin B12 deficiency. While the general population has an estimated 2.5% to 26% risk of suffering a vitamin B12 deficiency, individuals who mainly follow a plant-based diet have a much higher percentage of suffering this deficiency. 
The rates of vitamin B12 deficiency among vegans and vegetarians are as follows:
- From 25% to 86% of children
- From 21% to 51% of adolescents
- From 11% to 90% of the elderly
- Around 62% of pregnant women
A more detailed analysis of the results showed that vegans are more likely to suffer from vitamin B12 deficiency than vegetarians. The period that this type of diet has been followed plays a crucial role in a vitamin B12 deficiency. People who have been vegan or vegetarian since birth have a higher risk of having a vitamin B12 deficiency than those who switch to a diet that includes foods of animal origin later on in their lives. 
Results of the vitamin B12 test between vegetarians and vegans
Vitamin B12 test results among vegetarians and vegans
The vitamin B12 index is different in vegans and vegetarians and shows a much higher percentage of vitamin B12 deficiency than in the case of those who follow a diet that includes meat.
A thorough examination on the several tests performed on the vitamin B12 levels in all nutritional groups showed that:
- 11% of omnivores, 77% of vegetarians and 92% of vegans have inadequate levels of holotranscobalamin (> 35 nmol / L) (level that measures a vitamin B12 deficiency).
- 5% of omnivores, 68% of vegetarians and 83% of vegans have high MMA levels (> 271 nmol / L)
- 16% of omnivores, 38% of vegetarians and 67% of vegans have high homocysteine levels (> 12 nmol / L) 
How can we detect this deficiency?
Vitamin B12 is obtained through the diet but it is also stored in the organism, especially the liver. Because of this, it can take a long time before the first symptoms of a vitamin B12 deficiency appear if we are following a vegetarian or vegan diet.
However, the studies suggest that the first symptoms can appear after 2 years and that a vitamin B12 deficiency can be seen in serum tests performed during the first 5 years after changing the diet.
Inadequate vitamin B12 levels in the case of vegetarian women who are pregnant are also transmitted to the fetus and can lead to growth disorders. It is important to note that some of the consequences of a vitamin B12 deficiency are irreversible, such as the loss of the medullary sheath surrounding the nerves.
Caution is advised with plant sources of vitamin B12
Although most plant foods lack vitamin B12, there are some that do have relevant amounts of vitamin B12. However, the vitamin B12 levels measured in plant foods tend to undergo strong fluctuations and they depend on the vitamin B12 content of the nutrient. So their content could be affected or completely reduced.
Vitamin B12 contained in some plants
The human body can only absorb and use a specific form of vitamin B12. The vitamin B12 forms found in some plants are similar to vitamin B12, but they lack the bioactive component. A clinical study discovered that an 80% of the vitamin B12 forms that are found in plants are completely inactive and they lack the properties of vitamin B12.   
The vitamin B12 from algae and mushrooms
Mushrooms and algae are probably the only vegetables that contain active vitamin B12. However, it is only produced in certain species, oyster mushroom that grow in south Italy or Sicily, and more uncommon species.
Shiitake mushrooms can contain up to 5.6 μg of vitamin B12 per 100g of dry weight. However, the problem lies in their enormously fluctuating levels of vitamin B12, which depends on environmental and soil conditions.
Seaweeds such as Nori, Chlorella or Spirulina are also high in vitamin B12.
Other possible plant sources of vitamin B12 are fermented foods, such as sauerkraut, soy products (tempeh), and tea. However, their amounts of vitamin B12 are very low, just 1 μg per 100 g of dry weight.
Does the vitamin B12 from vegetables work?
To assess the utility of vitamin B12 plant sources it is crucial to measure their effectiveness. This applies to many foods with a measured vitamin B12 content. It has been proven that the regular consumption of Nori in rats reduces the value of MMA and increases value of vitamin B12 in the liver. One study carried out on 6 vegan children proved that eating Nori helps to prevent nutritional deficiencies of vitamin B12.
However, another clinical study did not find the effects of eating nori or spirulina in vegan children. Maybe because the researchers used a different test for vitamin B12. 
A study conducted in the United States showed that daily intake of 9 grams of Chlorella supplements for 2 months reduced the levels of MMA and homocysteine in vegan and vegetarian subjects, so it means that it can be considered a bioactive source. 
These results credit that the vitamin B12 that is obtained through the algae and vegetables we have talked about can prevent a vitamin B12 deficiency, but the reliability of their effects is still questionable.
How can vegans and vegetarians prevent a vitamin B12 deficiency?
The best protection against a vitamin B12 deficiency in vegetarian and vegetarian diets is to take vitamin B12 supplements as well as foods that are rich in vitamin B12. In this case, the dose, quality and bioactivity are guaranteed, unlike algae and plant sources.
A high-dose of vitamin B12 supplements (1000 μg) cannot only prevent a deficiency but it can also recharge the vitamin B12 reserves in the liver and kidneys when a vegetarian diet has been followed for a long time.
Are vitamin B12 supplements vegan?
The manufacturer must indicate the exact composition of the product. Vitamin B12 products from the Vitamin Express brand are 100% vegetarian.
Vitamin B12 and depression
Researchers still do not know the exact causes of depression. However, more and more scientists are linking the influence of the diet and micronutrients on the onset and development of depression. The debate about the role of vitamin B12 in depression is increasingly being discussed by experts.
Homocysteine, folic acid, vitamin B12 and depression
It has been shown that high homocysteine levels in the blood are associated with the onset of depressive symptoms. An high homocysteine level is often an indication of a vitamin B12 deficiency and it is also related to low folate levels.
Low levels of folic acid and vitamin B12 have also been associated with depression. For example, a clinical study showed that the rate of depression of the participants was of a 31% for vegans with low vitamin B12 levels, compared to a 12% for omnivorous subjects. 
A combined treatment of folic acid with high doses of vitamin B12 was already advised in a scientific study carried out on severe depression in 2005. 
The results are not conclusive
The results are contradictory so far. In a clinical study conducted in Rotterdam that meant to establish a link between the levels of vitamin B12, folic acid, and homocysteine with symptoms of depression on around 3.884 subjects, there was a clear correlation between low vitamin B12 levels, high homocysteine levels and depression. 
In contrast, a study about homocysteine in Hordaland found no correlation of any kind between folic acid, vitamin B12 and depression. However, it did confirm that there is relationship between homocysteine and depression. However, apart from the overall negative result, this study sheds some light on the complexity between vitamin B12 and depression.
According to the results of this study, very low and very high blood levels of vitamin B12 do increase the risk of suffering depression, although this increase is not correlated to the level of vitamin B12. 
The complex link between vitamin B12 and depression
There are multiple clinical studies that have proven that there is a complex relationship between vitamin B12 and depression. For example, a high level of vitamin B12 can protect men against depression while vitamin B6 is much more effective as a preventive factor against depression in women. 
An analysis of all the relevant studies on vitamin B12 and depression has concluded that the treatment with folic acid or vitamin B12 is not a short-term cure for depressive symptoms. However, it can be an effective treatment in the long term. 
A study conducted for more than 2 years on the elderly showed that a supply of 500μg of vitamin B12 and 400 μg of folic acid did not improve the symptoms of depression, but it did encourage a better quality of life. The subjects from the study had high levels of homocysteine, but they did not necessarily suffer from depression. 
These results show how complex the interaction is between micronutrients and depression. Therefore, it is essential to analyze all the details of the studies before reaching any decisive conclusion.
Vitamin B12 in the metabolism of a carbon
The reason why vitamin B12, homocysteine and folic acid are likely to be a good choice for the treatment of depression is because of their important role in the so-called metabolism of a carbon. During their biochemical cycle, folic acid and vitamin B12 are key elements that release a carbon atom to other molecules, which allows them to develop important functions in the central nervous system.
Among other things, vitamin B12 contributes to the production of neurotransmitters and monoamines which are brain messenger substances, and phospholipids which are important structural elements.
When there is a vitamin B12 deficiency, this process is interrupted and the nervous system no longer functions properly. This lack of vitamin B12 produces changes in the metabolism of a carbon that contribute to the onset of neuronal and mental disorders like depression.
Discovering the role of vitamin B12 in the development and course of depression still needs more time, but the researchers hope that vitamin B12 supplements will be used to treat this serious mental illness in the future. What is evident is that depression is only one of the diseases that could be due to a vitamin B12 deficiency. Therefore, it is advisable to have a proper supply of vitamin B12, either through a balanced diet or through dietary supplementation.
Vitamin B12 to treat dementia and Alzheimer
Dementia is a mental illness that affects an increasing number of people. Dementia has an impact on memory, the ability to reason, orientation and language. The consequences are very serious, since people with dementia lose their independence and need complete care.
In 2015, there were 46.8 million people with dementia worldwide. One of the most common causes of dementia is Alzheimer’s disease, which occurs in about two-thirds of patients with dementia.  
How to identify dementia and Alzheimer’s disease?
The diagnosis of dementia and Alzheimer’s is performed by evaluating the patient’s medical history, neuropsychological tests and imaging techniques such as magnetic resonance imaging. Alzheimer’s disease produces a characteristic accumulation of abnormally folded protein bodies (proteins) in the form of “plaques”.
These plaques affect the communication between nerve cells and cause their death. The consequence of the loss of nerve cells is what causes the typical symptoms of dementia, such as memory loss and speech disorders.
New studies performed on cells of the neuronal system show that vitamin B12 directly prevents the formation of these plaques. Vitamin B12 also protects the cells against the deadly toxicity of these plaques and prevents the death of the neurons.
Scientists hope that these results will help them to produce an active ingredient with vitamin B12 that will protect the nerve cells and stop the effects of Alzheimer’s disease. 
What are the causes of dementia and Alzheimer’s disease?
The exact causes of dementia and Alzheimer are still unknown. No cure has been found so far. Scientists assume that a combination of genetic and environmental factors are involved in the development of the disease.
One of the most influential environmental factors is the diet, especially a lack of micronutrients. A lack of any of them can trigger dementia and Alzheimer’s disease. B-complex vitamins, especially vitamin B12, have an important preventive function and they can delay the development of dementia and Alzheimer’s disease.
Genetic and epigenetic factors in the development of dementia and Alzheimer
The development of dementia and Alzheimer’s disease is due to a combination of genetic and epigenetic factors. Genetic factors are changes in the portion of the DNA that encodes a protein associated with dementia and Alzheimer, such as ApoE or preseniline. For instance, mutations in the DNA can lead to a lack of the protein which favors the onset of Alzheimer’s disease.
However, this is only part of the problem, since epigenetic factors play an equally important role. Epigenetic factors are the mechanisms that directly regulate the genetic material and they are largely influenced by environmental factors, such as the environment, the effects of toxins, smoking and nutrition, as well as traumatic brain injuries.
Epigenetic factors can cause or delay the onset and progression of the disease. Other risk factors for the development of these diseases include environmental toxins like lead, cadmium, arsenic, aluminium and ethanol (alcohol).
On the contrary, some factors that reduce the risk of suffering dementia or Alzheimer’s disease include, above all, vitamins B12, B9 and B6, vitamins A, C, D, and vitamin E, as well as omega-3 fatty acids, ginger, turmeric, and other nutrients.
How does vitamin B12 protect against dementia and Alzheimer’s disease?
Vitamin B12 is probably one of the best nutrients to protect ourselves against the onset of dementia and Alzheimer.
This is caused by the homocysteine molecule in the blood serum. A high level of homocysteine is usually associated with a low level of vitamin B12, but this deficiency can be treated by taking vitamin B12. According to research, the progression of dementia and Alzheimer’s disease can be slowed down thanks to the fact that we can control the vitamin B12 levels through homocysteine.
Vitamin B12 and homocysteine in dementia and Alzheimer’s disease
The increase in homocysteine levels favors atrophy, loss of brain mass and a decrease of the cognitive capacity. All this encourages the onset of dementia and Alzheimer’s disease. Even patients with a mild cognitive impairment have increased homocysteine levels and inadequate vitamin B12 levels. 
Researchers have found that increased homocysteine levels contribute to the accelerating the onset of dementia and Alzheimer’s disease. Homocysteine is a chemical component that binds to the DNA, regulating its conversion into proteins. Homocysteine is also necessary for neurotransmitters to communicate between nerve cells.
Moreover, homocysteine is indispensable for myelin, which is the layer that protects nerves. Any of these functions of homocysteine play a role in the onset and development of dementia and Alzheimer’s disease. 
Does vitamin B12 help to prevent and treat dementia and Alzheimer?
Several studies carried out on old people with dementia have shown that a supply of vitamin B12 with vitamin B6 and folic acid, contributes to improving symptoms of dementia and Alzheimer’s disease:
A study performed with old men showed that a long-term consumption of 400 mcg of vitamin B12 for two years reduces the homocysteine levels and the concentration of beta-amyloid plaques, which are the first sign of Alzheimer’s disease. 
In this same study, it was proven that giving 500 μg of vitamin B12 for two years to elderly people managed to slow mild cognitive impairment, reduced brain atrophy, and improved the memory. 
The intake of vitamin B12 also reduced the loss of gray matter in the most affected regions by Alzheimer’s disease. 
These studies clearly show that vitamin B12 not only protects against the onset of dementia and Alzheimer, but it also slows the progression of the disease and treats its symptoms. So vitamin B12 contributes to increasing the quality of life of people with dementia and Alzheimer’s disease.
A vitamin B12 deficiency increases the homocysteine levels, which results in dementia and Alzheimer’s disease, especially in the elderly.
The long-term intake of high doses of vitamin B12 supplements contributes to preserving the cognitive performance and slowing down the loss of brain mass, which increases the quality of life and well-being of those who are affected by this pathology.
Taking vitamin B12 is a good way to prevent or delay the onset of dementia and Alzheimer’s disease. High doses of vitamin B12 are advised for the elderly as well as for those who are at risk of developing dementia or Alzheimer’s disease.
Vitamin B12 to treat anemia and pernicious anemia
Anemia is usually associated with an iron deficiency. However, it can also be caused by a vitamin B12 deficiency. The importance of vitamin B12 for the treatment of anemia was discovered when pernicious anemia was treated with a high liver diet. 
How can vitamin B12 help to treat anemia?
One of the functions that vitamin B12 performs in the cells consists on producing certain amino acids, which are necessary to produce proteins (protein bodies). Vitamin B12 is also essential for the production of DNA and RNA and it is involved in the preservation and transmission of the genome. Proteins, DNA and RNA are part of every cell in the body.
When there is a vitamin B12 deficiency it first affects the cells. Red blood cells are renewed every 120 days approximately. A vitamin B12 deficiency leads to a lack of basic materials for the formation of red blood cells, which end up causing anemia when they cannot work optimally.
Is there a link between iron and vitamin B12?
- When an iron deficiency occurs, the organism cannot produce enough hemoglobin. Hemoglobin is made up of iron and oxygen, and it is carried throughout the body by the red cells. When the body does not have enough iron available, it cannot produce the hemoglobin it needs. Red cells become small because they lack the hemoglobin molecule. This effect is called microcytic anemia.
- A vitamin B12 deficiency results in an inadequate production of red cells. Although they do have haemoglobin available in this case, there is an oxygen deficiency in the organism. As a result, the red cells are bigger than usual. This effect is called macrocytic anemia. In this case, the blood cells break down in the spleen, producing an oxygen deficiency.
A clinical study revealed that those participants who suffered anemia due to an iron deficiency also had very low vitamin B12 levels and high homocysteine levels.  This indicates that when we suffer the most common anemia due to iron deficiency, the level of vitamin B12 should also be monitored to avoid a wrong diagnosis or treatment.
What are the symptoms of anemia due to a lack of vitamin B12?
The typical symptoms of anemia due to a vitamin B12 deficiency are:
- Lack of concentration
- More chances to suffer infections
- Weight loss
- Gum bleeding
- Neurological symptoms, like stiffness or tingling in the extremities
Diagnose of anemia due to a vitamin B12 deficiency
When the previous symptoms persist, it is necessary to go to the doctor immediately. The doctor will confirm or discard the diagnosis of anemia based on the number of red cells in the blood and the vitamin B12 levels.
A microscopic examination of the red cells can confirm a vitamin B12 deficiency. If the anemia is related to the absence of vitamin B12 it causes macrocytic anemia, with enlarged red cells. Many of the red cells can also be shaped like fish, as it has been proven by new research at the University of Graz.  This peculiarity can contribute to confirming this diagnosis in the future.
Treatment of anemia caused by a vitamin B12 deficiency
The treatment consists on taking or injecting vitamin B12 into the person with this deficiency. Both treatments work similarly, although the oral administration of vitamin B12 capsules, tablets, or pills is more tolerated and affordable.
The treatment of anemia related to a vitamin B12 deficiency requires the intake or injection of high doses of vitamin B12 (1000 μg daily). 
What is pernicious anemia?
Pernicious anemia is a particular form of anemia. It is an autoimmune disease in which the body’s own immune system produces antibodies against the body’s proteins. Pernicious anemia affects the intrinsic factor. The intrinsic factor is necessary to transport vitamin B12 to the cells through the intestinal mucous membrane. In this case, the body forms antibodies that prevent vitamin B12 from binding to an intrinsic factor. As a result, the ingested vitamin B12 is mostly excreted and can only be absorbed through passive diffusion.
It is estimated that approximately a 4% of the European population suffers pernicious anemia. The number of people with pernicious anemia may be higher than believed because the medical test to measure the antibodies and to confirm the diagnosis of pernicious anemia is quite expensive.  The symptoms of pernicious anemia are similar to those of anemia related to a lack of vitamin B12.
How to treat pernicious anemia
The treatment of pernicious anemia is similar to that of anemia caused by a vitamin B12 deficiency. In general, the patient should be given 1000 μg of vitamin B12 daily. However, patients with pernicious anemia depend on the intake of vitamin B12 for their entire life, since it can be absorbed through diffusion but not through the diet due to the malfunctioning of the intrinsic factor. An analysis showed that the oral administration of vitamin B12 is as effective as an injection.
Vitamin B12 to treat sleep problems
Having a quality sleep and getting enough sleep is crucial for our health. Sleep problems can be related to a melatonin deficiency. Melatonin is known as the “sleep hormone”. As we age, the body has more difficulties to produce this hormone.
Vitamin B12 plays a basic role in the production of melatonin, so it is important to have enough vitamin B12 in the blood to guarantee an optimal level of melatonin.
The importance of vitamin B12 in preventing and treating neurological and neuropsychiatric diseases
It has been shown that a vitamin B12 deficiency can lead to dementia and Alzheimer’s disease, apart from several neurological diseases such as peripheral neuropathy.
This is a disease or dysfunction of the peripheral nerves. Its symptoms are numbness, tremors, tingling, pain, itching, and a sensation similar to being poked with a needle.
The skin becomes hypersensitive. Occasionally, the patient can no longer tolerate touching any part of his body. Even the friction of clothes or sheets can cause pain.
If the muscles are affected, the patient can feel tiredness, heaviness, weakness, as well as muscle cramps, tremors and pain.
A vitamin B12 deficiency is also related to migraines and Parkinson, which are neurological diseases.
Moreover, a vitamin B12 deficiency is linked to the onset of psychiatric diseases which can be divided in the following symptoms:
- Mood disorders: apathy, depression, eating disorders, and behavior disorders (which mainly manifest during the night).
- Hyperactivity: excitability, euphoria, irritability, lack of inhibition, and movement disorders.
- Psychosis: hallucinations and delirium.
Optic neuropathy is another consequence of a vitamin B12 deficiency. Chronic B12 deficiency affects the optic nerve in the long term and it causes irreversible blindness.
Vitamin B12 for the treatment of cardiovascular diseases
Cardiovascular diseases are becoming more and more common in the Western world. Today, heart attacks and strokes continue to be the leading cause of death in Europe.
More than 90% of people who die from cardiovascular disease are over the age of 65.  Vitamin B12 can help to prevent the causes of cardiovascular diseases.
How does vitamin B12 help to prevent and treat cardiovascular diseases?
What is homocysteine?
Homocysteine chemically belongs to the amino acid group. It works together with methionine and cysteine, which are building blocks of proteins, which are essential components of our body at the same time. Homocysteine also plays an essential role in the methylation process, a cell response that regulates the DNA and the genome as well. Homocysteine itself is obtained from methionine through the diet. 
What is hyperhomocysteinemia?
Hyperhomocysteinemia is the medical term for high homocysteine levels. The following list shows the values for homocysteine:
- 5 to 15 μmol / L: normal homocysteine levels on an empty stomach
- 16 to 30 μmol / L: moderately high homocysteine levels (mild hyperhomocysteinemia)
- 31 to 100 μmol / L: moderate hyperhomocysteinemia
- more than 100 μmol / L: severe hyperhomocysteinemia
Moderate to severe hyperhomocysteinemia is almost exclusively caused by an underlying genetic defect in the metabolism of homocysteine. Most cases of moderately high homocysteine levels are due to deficiencies of vitamin B12, vitamin B6, or folic acid.
Homocysteine and cardiovascular diseases
In the mid-1970s, scientists realized the direct link between homocysteine and arteriosclerosis, which is the calcification of blood vessels. They concluded that high homocysteine levels produced deposits in the arteries, called plaques. 
Plaques can disrupt the blood flow and cause a heart attack, stroke, or thrombosis.  Since then, many scientific studies have shown that high homocysteine levels are associated with an increased risk of suffering a cardiovascular disease. 
Can vitamin B12 protect us against cardiovascular diseases?
It is very difficult to establish a direct cause-and-effect link when we deal with cardiovascular diseases. There are many elements that interact with each other, such as genetic, environmental, dietary and lifestyle factors. Therefore, it is difficult to guarantee that the intake of micronutrients and vitamins alone will be enough t to completely prevent the onset of cardiovascular diseases.
However, a meta-analysis of 15 scientific studies conducted with more than 70.000 patients showed that reducing the homocysteine levels by taking vitamin B12 lowers the risk of suffering a stroke. 
Taking vitamin B12 to reduce the homocysteine levels is advised for those who are at risk of suffering a cardiovascular disease, such as smokers, obese people and the elderly. In addition, vitamin B12 is generally advised as part of a healthy diet and lifestyle to prevent cardiovascular diseases.
Vitamin B12 and other diseases
The number of people affected by cancer has steadily increased for decades and it has been doubled since 1970. The WHO estimates that by 2030, more than 21 million people will develop cancer each year.  
The statistics provide information about the possible causes, as well as the factors for and against the development of the disease. On the one hand, cancer depends on the absorption of carcinogenic substances (carcinogens), for example, smoking or the intake of carcinogenic substances through the diet. In this respect, it can be said that lifestyle and nutrition are directly related to the development of some types of cancer.
On the other hand, screening tests have considerably improved, leading to a decrease in certain types of cancer. But medical advances are not solely focused on curing diseases. Unfortunately, the fact that people live longer now also increases the risk of suffering cancer, because age plays an important role in the development of this disease.
Diet and vitamin B12
Science tells us that the foods we eat can cause cancer, but they can also prevent it. An adequate nutrition and the supply of vitamins and other micronutrients can affect the risk of cancer.
A balanced diet has to have a proper supply of vitamin B12. The fact that vitamin B12 reduces the risk of suffering cancer is still a controversial issue.
Can vitamin B12 protect us?
A long-term study by the University of Harvard in Boston investigated the connection between vitamin B12 and a lower risk of suffering cancer. The study analyzed more than 32.000 women during a period between 6 and 17 years. The aim was to check whether the serum concentration of vitamin B12 was related to the onset of breast cancer. The result showed that high serum concentrations of B12 are related to a low level of breast cancer in premenopausal women.
Folic acid and vitamin B6 also have a protective effect according to research.  These results were confirmed in another french clinical study with more than 62.000 postmenopausal women, in which enough or high levels of folic acid produced a preventive effect on breast cancer. Vitamin B12 supported or improved this effect in the women tested. 
In contrast, another study with more than 5.000 women aged 42 who also had a cardiovascular disease, came to another conclusion. In this case, the participants were given a combination of folic acid, vitamin B6, and vitamin B12 for 7 years. The authors of this study found that this therapy had no effects on the development of breast cancer.  However, the reason may be the fact that the selection of participants was different.
A vitamin B12 deficiency
Other studies suggest that a vitamin B12 deficiency increases the risk of suffering cancer. A finish study showed that inadequate levels of serum vitamin B12 increases the risk of gastrointestinal cancer in 5.8 times. 
A vitamin B12 deficiency has also been associated with a higher risk of suffering cancer in old people. The studies confirm that the risk hematological cancer (Leukemia) increased 5.7 times in the cases in which the patient suffered a vitamin B12 deficiency.  These results suggest that vitamin B12 has a protective effect against cancer.
Vitamin B12 as a marker
Certain studies suggest that excessively high levels of vitamin B12 can increase the risk of cancer. A danish analysis showed that people with exceptionally high levels of vitamin B12 (over 600 pmol / L) have an increased risk of suffering cancer, especially hematological and hepatic cancer. 
However, it is also possible that high levels of vitamin B12 rose dramatically shortly before the cancer appeared, for reasons that have not yet been investigated, since the participants of the study did not take any vitamin B12 supplements. These results suggest that vitamin B12 is a possible marker for the early detection of cancer.
Does vitamin B12 increase the risk of suffering cancer?
The key question now is whether vitamin B12 increases the risk of suffering cancer. A norwegian research team examined this question and showed that the intake of folic acid combined with vitamin B6 and vitamin B12 (400 μg / day) increases the risk of cancer in patients with ischemic heart disease. 
However, the cause of this outcome, unlike previous studies, may be due to the selection of participants, since this cardiovascular disease increases the risk of cancer, and this effect cannot be reduced by the intake of vitamin B12. 
In any case, the results of the studies on the connection between vitamin B12 and cancer continue to confuse scientists.
Vitamin B12 reduces the side effects of chemotherapy
Another interesting aspect about the connection between vitamin B12 and cancer is the recently discovered effect that vitamin B12 has on chemotherapy in regard to peripheral neuropathy, which is very painful and can lead to the interruption of the treatment.
The treatments for peripheral neuropathy are very limited, so there has been a systematic review of the scientific literature to find a solution. The analysis of 259 scientific articles revealed that vitamin B12 has a significant palliative effect on peripheral neuropathy on chemotherapy which is why it is being advised as a therapeutic support for its treatment. 
The specific link between vitamin B12 and cancer is still being debated. However, it seems clear that a deficiency of vitamin B12 can increase the risk of cancer. It is important to have enough vitamin B12 available, due to its benefits on other aspects of health.
Vitamin B12 and fertility
Most people want to start a family. However, some couples have to face the painful fact that they cannot have children after trying for years because of an infertility problem. We talk about infertility when there is no pregnancy after twelve months of sexual intercourse. Infertility affects approximately a 15% of couples that are trying to have a child. 
Infertility is due to multiple reasons, one of the possible causes is a vitamin B12 deficiency.
Vitamin B12 and fertility in women
The first evidence of the link between vitamin B12 and fertility came from a study conducted in women with multiple miscarriages, in which their vitamin B12 level was analyzed.
Vitamin B12 deficiency leads to miscarriage and infertility
Of the 14 women with a vitamin B12 deficiency, 11 had miscarriages and 4 had periods in which they were not fertile from 2 to 8 years. The scientists suggested that the cause of the abortion and infertility of the participants was due to a high blood coagulation produced by the high levels of homocysteine in their blood plasma. These levels are due to a deficiency of vitamin B12 and lead to a miscarriage. A prolonged vitamin B12 deficiency results in infertility.
The physiological causes can be due to changes in ovulation, in the development of the egg, or in the implantation of the fertilized egg. The treatment with vitamin B12 showed that a deficiency of this vitamin was the cause of infertility.
Vitamin B12 increases the fertility
Assisted reproductive technology is now available for couples who are affected by infertility. These methods include in vitro fertilization and intracytoplasmic sperm injection. In Europe, between a 2% and 6% of the pregnancies are performed through assisted reproduction. Despite the great advances in this area, the success rate per cycle remains at a 30%.
A study carried out on 100 women who underwent between one and five assisted reproduction processes showed that women with high vitamin B12 levels had higher chances of succeed in embryo implantation, and the percentage of children born alive was doubled as well.
Vitamin B12 and male fertility
The quality of the man’s sperm is essential in a 40% of infertile couples. The cause of infertility may be a lack of sperm, inadequate sperm motility (speed), or the inability of sperm to fertilize the egg.
A recent systematic review of the scientific literature on vitamin B12 and male infertility has revealed that: 
- The plasma levels of vitamin B12 are lower in infertile men than in fertile men
- The treatment with vitamin B12 (1500 μg / day) on infertile men can increase the motility of the spermatozoa in a 50% in just eight weeks
- Vitamin B12 improves the quality of the semen, the amount of sperm, and the integrity of the genome (DNA) in the sperm cell
- Vitamin B12 does not affect the hormone levels, like testosterone
- An increase in the levels of homocysteine is harmful for the spermatozoa. Reducing the homocysteine level through the intake of vitamin B12 increases the quality of the sperm
In short, the scientific evidence suggests that vitamin B12 can be a crucial “turning point” between fertility and infertility. Therefore, it is advisable to test the levels of vitamin B12 at the before starting a family in order to avoid the consequences of a vitamin B12 deficiency.
In addition, it is also advisable to take vitamin B12 through dietary supplements, especially if you have a deficiency or if you follow a vegetarian or vegan diet.
Vitamin B12 in pregnancy, breastfeeding and growth of the baby
It is important to have a balanced diet during pregnancy and lactation because the female body is making an extra effort. Although many deficiencies are countered by food cravings and a more natural diet, some deficits may go unnoticed, which can have serious consequences.
During pregnancy, women prevent an iron and folic acid deficiency by taking supplementation. However, a vitamin B12 deficiency is occasionally overlooked. Vitamin B12 is essential during pregnancy and lactation to guarantee the well-being of the mother and the healthy growth of the child.
Recommended daily dose of vitamin B12 during pregnancy and lactation
The importance of vitamin B12 for the wellness of the mother and child is reflected in the amount of vitamin B12 that is advised during pregnancy and lactation: 
- Recommended daily amount of vitamin B12 in pregnant women: 3.5 μg / day
- Recommended daily amount of vitamin B12 in lactating women: 4.0 μg / day
- In contrast, the recommended daily amount for adults is: 3.0 μg / day
We have to point out that vitamin B12 is extremely important at the beginning of pregnancy.
Why is vitamin B12 so important to the mother during pregnancy and lactation?
Erythropoiesis, or the formation of red blood cells, is in full swing during the first two trimesters of pregnancy to meet the growing needs of the mother and the embryo. Scientific studies show that the need for vitamin B12 is particularly high during the first 27 weeks of pregnancy. In the last trimester of pregnancy, vitamin B12 is combined with the absorption and utilization of folic acid. 
Inadequate vitamin B12 levels reduce the fertility and they are related to the risk of having an abortion. Studies on women who have had repeated miscarriages at the beginning of the pregnancy (between the fifth and eleventh week) revealed that 9% of these women have a higher vitamin B12 deficiency than women who have normal pregnancies. 
A poor supply of vitamin B12 increases the mother’s risk of developing diabetes during pregnancy (gestational diabetes). The risk is particularly high if the mother also has high levels of folic acid.  That is why it is so important to control the levels of folic acid and vitamin B12 during pregnancy.
A vitamin B12 deficiency during pregnancy increases the risk of premature birth which means that the newborn can be underweight, according to detailed analyses on this matter. 
Vitamin B12 for the fetus and the baby during pregnancy and lactation
Most of the analysis about the effects of a vitamin B12 deficiency on fetuses and babies is related to vegan and vegetarian mothers. It has been shown that a poor supply of vitamin B12 can have serious consequences. It is important to have enough vitamin B12 during pregnancy, since it is also transferred to the fetus.
The risk of suffering a vitamin B12 deficiency is not limited exclusively to vegan or vegetarian women but it also affects people who have changed their diet, as well as those who consume very little meat or animal products even if they do not follow a strictly vegetarian diet. 
Possible effects of a vitamin B12 deficiency
An insufficient supply of vitamin B12 during the first weeks of pregnancy can lead to neurological and neural tube deficiencies, a congenital defect that affects the brain and neonatal spinal cord. Spina bifida, which can cause paralysis, and anencephaly, which is fatal, are found within the neural tube defects. 
A mild vitamin B12 deficiency during pregnancy can cause long-term neurological and cognitive damage to the child, even if the deficiency is remedied in early childhood. The typical symptoms of this neurological damage include irritability, growth disorders, developmental disorders, and a decrease in intellectual performance. A vitamin B12 deficiency during the early development has also been associated with a lower IQ up to age 8. 
How can we prevent a vitamin B12 deficiency during pregnancy and lactation?
The best way to protect the health of the mother and the growth of the child is to guarantee a proper supply of vitamin B12 to the mother, as this passes through the placenta to the embryo and it is also present in breast milk. 
The experts advise increasing the dose of vitamin B12 to at least 221 pmol / L before pregnancy in order to provide an optimal supply. Given the body’s limited ability to absorb vitamin B12, it is advisable to take a daily dose between 500 μg to 1000 μg of vitamin B12 from the moment we decide to become pregnant.
Vitamin B12 and osteoporosis
Bone density is one of the main concerns of the elderly. A low bone density can lead to osteoporosis and it is related to an increased risk of bone fractures. A healthy lifestyle and nutritional habits can lower the risk of suffering osteoporosis and bone fractures.
Some of the factors that affect bone density, apart from genetic components, include physical activity, weight, alcohol consumption, smoking, estrogen levels, and a proper calcium intake. 
Vitamins also help with the formation of bones and to preserve bone density. Vitamin D is known for its preventive effects on osteoporosis, but the group of B vitamins, such as vitamin B12, is also involved in the development of healthy bones.
A vitamin B12 deficiency increases the risk of suffering bone fractures
Several studies have recently shown that low or poor levels of vitamin B12 in the blood decrease the bone density:
- A swedish study analyzed the levels of vitamin B12 and homocysteine in 790 men between the ages of 70 and 81. The participants were evaluated for the next 6 years, documenting possible fractures.
- It was found that the risk of bone fracture increases considerably when there is a low vitamin B12 concentration. This means that the lower the concentration of vitamin B12 in the blood, the higher the risk of suffering a bone fracture. The participants with a lower level of vitamin B12 had a 70% higher risk of having a fracture. More specifically, in the case of lumbar fracture, the risk increased to a 120%. 
- A meta-analysis of six clinical studies about vitamin B12 found that an adequate supply of vitamin B12 also lowers the risk of bone fracture in older women. 
- In the case of the elderly who also follow a vegetarian diet and who have lower vitamin B12 levels, it was also observed that the risk of suffering a bone fracture was higher due to the fact that they did not consume animal products. 
A general review of the scientific literature on this subject shows a very clear trend: an increase in vitamin B12 levels of 50 pmol / L reduces the risk of suffering a bone fracture by a 4%. . However, it is not yet clear how vitamin B12 strengthens the bones.
Can vitamin B12 stop the loss of bone density?
Based on the finding that a vitamin B12 deficiency increases the risk of bone fracture and osteoporosis, we can conclude that taking vitamin B12 lowers this risk. However, the scientific evidence is not that clear.
The results of the B-PROOF study (on preventing osteoporotic bone fractures by taking vitamin B12) did not show any remarkable effect when taking vitamin B12. In this study, about 3.000 participants, all of them old people, were given 500 μg of vitamin B12 and 400 μg of folic acid daily, as well as vitamin D3. The fractures of this group reached a percentage of 4%, while the percentage reached a 5% in the placebo group.
This combination of vitamins reduced the actual risk of bone fracture, but the difference was not statistically significant. However, there was a remarkable improvement in the group of participants over the age of 80, who reduced the risk of bone fracture significantly. 
The optimal prevention of osteoporosis and the risk of bone fractures
In order to prevent osteoporosis and bone fracture, we have to avoid a vitamin B12 deficiency in old age. We should follow a balanced diet with a high content of animal products in order to achieve a proper supply of vitamin B12. Vitamin B12 should be taken as a dietary supplement to avoid a deficiency if we consume less or no food at all during old age.
Vitamin B12 in foods
The body needs a proper dose of vitamin B12 on a daily basis in order to prevent a vitamin B12 deficiency and its serious consequences. But what are the sources that have more vitamin B12?
Vitamin B12 is mainly found in foods of animal origin. However, the amount of vitamin B12 that is present in each food does not only depend on the source of the food. Cooking also plays a role, since around a 30% of vitamin B12 is lost when the food is cooked. 
The United States Department of Agriculture (USDA) has published the most complete nutritional table of foods that contain vitamin B12. The table includes more than 7000 foods.  The best sources of vitamin B12 are the viscera of animals, such as the liver, kidney; as well as lamb, duck and goose meat. Moreover, mussels and oysters are also very rich in vitamin B12.
Table of foods that contain vitamin B12 (per 100 grams)
- Cooked cow liver: 96 μg
- Raw veal liver: 91 μg
- Raw duck or foie gras: 54 μg
- Raw veal kidney: 50 μg
- Raw pork liver: 26 μg
- Fried chicken liver: 21 μg
- Grilled beef fillet: up to 8 μg (depending on the portion)
- Grilled beef (sirloin): 4 μg
- Venison stew: 3 μg
- Raw or cooked lamb: 3 μg
- Grilled chicken meat: 0.7 μg
- Liver: 13 μg
- Salami: 3 μg
- Cooked minced meat: 3 μg
- Frankfurter sausages: 1.6 μg
- Ham (pork): 1.1 μg
- Ribs (beef meat): 1.1 μg
- Raw and fat-free beef: 1.1 μg
- Black pudding: 1 μg
- Fast food hamburguer: 0.9 μg
- Steamed mussels: 99 μg
- Steamed octopus: 36 μg
- Steamed oysters: 29 μg
- Smoked salmon: 18 μg
- Raw fish (cod, herring): 10 μg
- Cooked wild salmon: 3 μg
- Canned tuna: 3 μg
- Squid: 1.3 μg
- Tuna salad: 1.2 μg
Dairy products and eggs:
- Milk powder: 4 μg
- Swiss cheese: 3 μg
- Whey powder: 2.4 μg
- Mozzarella, Parmesan: 2.3 μg
- Brie: 1.7 μg
- Edam, Gouda: 1.5 μg
- Grated Parmesan: 1.4 μg
- Camembert: 1.3 μg
- Greek yogurt: 0.8 μg
- Lamb milk: 0.7 μg
- Natural yogurt: 0.6 μg
- Milk, whey: 0.5 μg
- Ice-cream, frozen yogurt: 0.5 μg
- Sour cream: 0.3 μg
- Soft sheep cheese: 0.2 μg
- Butter: 0.2 μg
- Cream (liquid): 0.2 μg
- Breast milk: 0.05 μg
- Raw duck egg: 5 μg
- Fried egg: 3 μg
- Boiled egg: 1,1 μg
- Raw egg: 0.9 μg
- Scrambled eggs: 0.8 μg
- Poached egg: 0.7 μg
Products enriched with vitamin B12:
- Enriched 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
Other foods and products:
- Dried algae: 2.3 μg *
- Soaked seaweed: 0.3 μg *
- Mashed potatos: 0.2 μg
- Crepe: 0.2 μg
- Croissant: 0.2 μg
- Mayonnaise: 0.1 μg
- Margarine: 0.1 μg
- Cooked pasta (with egg): 0.1 μg
- Miso: 0.1 μg
- Egg with potatos: 0.1 μg
- Muesli: 0.1 μg
Foods that contain traces of vitamin B12 (between 0.01 μg and 0.05 μg):
- sweet potatos*
Foods that do not contain vitamin B12:
- cod liver oil
- pasta (without egg)
* Note: the values of vitamin B12 measured in plants, mushrooms and seaweeds depend on the origin of the nutrient and they are subject to strong fluctuations according to the region from where each food comes from. 
Is there any vegetable source of vitamin B12?
Some seaweeds, such as nori, chlorella, and spirulina have some vitamin B12. However, the problem is that these tests are fluctuating and these ingredients have a potentially high content of pseudovitamin B12 .   
The bBioavailability of Vitamin B12: A crucial issue!
The foods that have been listed contain vitamin B12 values that have been measured per 100 grams. However, it should be noted that not all the vitamin B12 they contain will be actually available to the body.
The bioavailability of vitamin B12 changes a lot depending on the preparation of the food. For example, after eating 200g of cooked lamb burger, there are 3 μg of vitamin B12 available, but the organism can only use about 80% of that amount.
In the case of milk, its bioavailability is of 60% approximately, but only around a 10% of the vitamin B12 from liver paté is absorbed. As a general rule, healthy adults use only a 50% of the vitamin B12 consumed in their diet.
Those who follow a diet that excludes or reduces the intake of foods of animal origin can only meet their needs by taking other foods that are rich in vitamin B12 or by taking vitamin B12 dietary supplements to prevent a vitamin B12 deficiency.
A vitamin B12 caused by medication
Apart from their beneficial effects, medications also have side effects that can affect the patient’s well-being. Some medications reduce or prevent the absorption of vitamin B12 into the body. This side effect, which often goes unnoticed, can lead to a vitamin B12 deficiency and cause the symptoms associated with a deficiency of this vitamin. Here are some of the things that cause a lack of vitamin B12.
Drugs that cause vitamin B12 deficiency include: 
- Proton pump inhibitors
- Antibiotics (chloramphenicol)
- Histamine receptor antagonists
Vitamin B12 deficiency caused by the proton pump inhibitor
Proton pump inhibitors are used to reduce excess stomach acid. This occurs, for example, in cases of gastroesophageal reflux disease, heartburn, gastritis, or after a Helicobacter pylori infection.
Proton pump inhibitors are often prescribed as “gastric protection” when we have to take medications that irritate the stomach. The active ingredients from proton pump inhibitors are omeprazole, pantoprazole, esomeprazole, rabeprazole and lansoprazole, among others.
A prolonged use of proton pump inhibitors, or stomach protectors, can lead to severe vitamin B12 deficiency as well as causing a long list of questionable side effects. This is due to the fact that by reducing stomach acid, the vitamin B12 that we consume can no longer be released into the stomach. The effect is progressive, that is, the longer the proton pump inhibitors are taken, the lower the concentration of vitamin B12 will be. 
Vitamin B12 deficiency caused by the use of antibiotics
On rare occasions, it has been proven that the intake of the antibiotic broadband chloramphenicol produces an acute vitamin B12 deficiency in people who take to treat anemia. The reason why this happen is not clear.  However, this fatal interaction between chloramphenicol and vitamin B12 occurs only in exceptional cases. The use of chloramphenicol to treat anemia is generally harmless. 
Controlling the level of vitamin B12 is crucial
Controlling vitamin B12 levels is essential in the previous cases. A study on patients who were taking proton pump inhibitors performed a vitamin B12 serum test that show how a 10% of the patients had a deficiency of this vitamin. In addition, additional measurement of MMA and homocysteine revealed that 31% of patients were vitamin B12 deficient.
These conflicting results explain why a vitamin B12 deficiency caused by a proton pump inhibitor is not yet conclusive. 
It is advisable to take calcium apart from high doses of vitamin B12 in order to counter a vitamin B12 deficiency caused by a proton pump inhibitor. 
Vitamin B12 deficiency caused by histamine receptor antagonists
This term refers to antihistamines that block the histamine H2 receptor to produce less histamine. H2 receptors are mainly produced in the heart, blood vessels, and especially in the gastric mucosa. H2 antihistamines are often used to treat gastric and duodenal ulcers.
Like proton pump inhibitors, H2 antihistamines also inhibit the production of stomach acid. This also leads to a poor absorption of vitamin B12 that leads to a deficiency, especially with the prolonged use of H2 antihistamines. 
Vitamin B12 deficiency caused by metformin
Metformin is a drug used to treat type 2 mellitus diabetes. Metformin is an oral antidiabetic drug that reduces the risk of cardiovascular disease associated with type 2 diabetes.
A study on 231 patients with type 2 diabetes has shown that taking metformin increases the risk of vitamin B12 deficiency drastically. Compared to the control group, in which around a 6% was vitamin B12 deficient, the percentage of those taking metformin reached a 18%.
The risk continued to increase with the co-administration of proton pump inhibitors and/or H2 antihistamines. 
The reason for this increase is not yet clear. Metformin is thought to affect the activity of calcium on the cell surface. This may block the absorption of vitamin B12 through the intrinsic factor, since this process depends on calcium. 
Contact with nitrous oxide (anesthesia with nitrous oxide)
There is evidence that the contact with nitrous oxide can destroy the body’s stores of vitamin B12. Nitrous oxide is used by dentists to relieve pain and it is also used in surgery rooms as an anesthetic. The use of nitrous oxide is a risk to anyone with an undiagnosed and untreated vitamin B12 deficiency.
People who work in the healthcare sector and who are regularly exposed to nitrous oxide also run a higher risk. One of the most serious problems is its misuse by medical staff, adolescents and young people for recreational purposes, since this substance can cause serious neurological damage.
How can a vitamin B12 deficiency caused by medications be treated or prevented?
Interactions of vitamin B12
Providing the body with all the nutrients that it needs is a complex process in which all the elements involved must be balanced. Quite often, the combination of nutrients must be analyzed in order to use each element optimally.
Vitamin B12 reacts to a variety of molecules and nutrients. These interactions can help to absorb the vitamin itself and other nutrients better and more effectively.
Interaction of vitamin B12 with folic acid
One of the best-known interactions of vitamin B12 is with folic acid. Both molecules are critically involved in the metabolism of a carbon. In this case, vitamin B12 is responsible for adding methyl homocysteine (a chemical compound of a carbon atom with three hydrogen atoms), and disabling homocysteine.
Homocysteine is a natural broken down product of the dietary amino acid methionine. High levels of homocysteine cause nervous system disorders and lead to depression, dementia and other pathologies. Vitamin B12 works closely with folates (the natural form of folic acid). 
Although the interaction between these to elements is not direct, they interact with each other through the same chemical processes. Vitamin B12 also regulates the activation of folic acid. If very little vitamin B12 is available, folate can no longer be methylated and it becomes an inactive precursor, called 5-methyltetrahydrofolate. This is the reason why a deficiency of vitamin B12 produces a deficiency of folic acid. 
The clinical effect of the interaction between vitamin B12 and folic acid
The deficiencies of these two elements have similar effects. They can cause from neoplastic diseases and mental disorders to anemia and birth defects. This similarity is due to the influence of both molecules on the homocysteine levels. 
It is advisable to control both the level of folic acid and that of vitamin B12 when regulating the levels of homocysteine, for example during pregnancy.
Interaction between vitamin B12 and other group B vitamins
The B vitamins group includes 8 water-soluble vitamins that perform important functions for the cells of the human body. B vitamins are especially important for the brain. They can cross the blood-brain barrier and support the brain. The concentration of vitamins B5 and B7 in the brain, for example, is 50 times higher than in the blood plasma.
Studies performed with different vitamin B combinations indicate that the functions and effects of the vitamins from this group are related. However, the details of this interaction are still unknown.  However, some interactions of group B vitamins with vitamin B12 had been studied in more depth:
- Vitamin B12 and Vitamin B6: both vitamins play an essential role in the metabolism of a carbon
- Vitamin B12 and vitamin B7 (biotin): they recycle the organic building blocks through vitamin B12 to produce energy and build new substances. Biotin and magnesium are necessary elements for the activation of vitamin B12.
- Vitamin B12, vitamin B2 (riboflavin) and vitamin B3 (niacin): vitamin B12, B2 and B6 are involved in the metabolism of a carbon along with folic acid, which regulates the methylation of other molecules and homocysteine. Moreover, vitamin B2 and B3 are necessary to transform vitamin B12 in its active forms, methylcobalamin and adenosylcobalamin. 
Interaction between vitamin B12 and calcium
Vitamin B12 can only be transported through the intestinal mucous membrane, where it binds to the intrinsic factor and becomes available for the cells of the body. Calcium is necessary for this union.
How to take vitamin B12, alone or combined with other nutrients?
Based on the interactions between vitamin B12 and other B vitamins, folic acid, magnesium and calcium, we may ask ourselves whether vitamin B12 is more effective when combined with other nutrients. The answer is that this depends on the individual case and the specific symptoms. If we have a vitamin B12 deficiency caused by a vegan diet, the intake of vitamin B12 alone is enough to restore the balance.
In other situations, like pregnancy, vitamin B12 is usually combined with folic acid to prevent birth defects. However, recent studies show that the treatments of vitamin B with other nutrients may be more effective than it was previously believed.
A vitamin B deficiency may be somehow related to the development of multiple sclerosis due to the importance of B vitamins for the brain and nervous system. Scientists are investigating whether a treatment with a combination of B vitamins can reverse multiple sclerosis and halt the course of the disease. 
You can buy the best supplements of Vitamin B12 to benefit from all the help it offers to your body.
Overdose of vitamin B12
Vitamins are necessary (vital) since they help to perform basic bodily functions and to maintain a good health. However, some vitamins must be taken in the correct dose, because excessive amounts can cause side effects.
Vitamin B12 is often given in high doses, can they cause an overdose? How can we recognize an overdose of vitamin B12?
Vitamin B12 has few side effects, even at high doses
Soon after discovering that vitamin B12 is a trigger and remedy for anemia and pernicious anemia, the effects of different doses of vitamin B12 were studied. It soon became evident that vitamin B12 has “remarkably few side effects”.  This is because an excess vitamin B12 can be excreted through the kidneys and urine. Therefore, amounts up to 3000 μg can be regarded as harmless. 
Is an overdose of vitamin B12 possible?
An overdose of vitamin B12 is practically impossible due to its automatic excretion. Extremely high doses could cause an unspecified overload of vitamin B12 on the kidneys. However, there is a medically low risk for this to happen.
Extremely high doses of 5000 μg are used as an antidote to treat cyanide poisoning by inhalation of fuel gases. Even these doses are considered safe for the treatment of children and pregnant women in the case of smoke poisoning. 
Is an overdose of vitamin B12 useful?
Taking a dose of vitamin over 1000 μg is pointless, except for cyanide poisoning and acute pernicious anemia. We should never take a daily dose over 1000 μg when there is a vitamin B12 deficiency or our ability to absorb it is hindered (due to interactions with medicines or absence of the intrinsic factor).
The reason for this is the real use, which is relatively low, through the intrinsic factor and passive diffusion. Even if the intake is limited to 1.5 μg per meal through the intrinsic factor, only a little bit more than 1% of the amount of the vitamin B12 that is absorbed is used by the organism through passive diffusion.
Therefore, taking high doses of vitamin B12 is pointless. However, it does prevent the onset of a vitamin B12 deficiency, which could have more series effects than a possible overdose.
Vitamin B12 and a skin rash similar to acne
In some cases, vitamin B12 can cause a rash that is similar to acne after being administered either orally or trough an injection. It tends to appear on the face and in the upper part of the body within the first 6 months of treatment. However, once the treatment is interrupted, the rash completely disappears. 
However, this side effects of vitamin B12 is not that frequent, it is not caused by an overdose, since it triggers little amounts of vitamin B12 in some cases. The cause of this reaction is not clear and it seems to be related to a personal intolerance. In any case, the symptoms fade after using the product.
Side effects of vitamin B12
It has been observed that it can cause some side effects similar to those of some medicines in extremely rare cases; for example, isolated cases of anaphylactic shock have been reported after an injection of vitamin B12. 
It is believed that this is probably due to the method of administration or the material that has been used. And the same reason could explain other local reactions that happen after injections of vitamin B12, like skin irritation, dizziness, hot flushes, or nausea. 
Curiously, the different forms of vitamin B12 produce different side effects. For example, type 1 immediate hypersensitivity reactions (like anaphylactic reactions) happen with cyanocobalamin, while allergic reactions happen with hydroxycobalamin. 
Levels of vitamin B12
If there is any uncertainty regarding a vitamin B12 deficiency, it is advisable to perform a blood test to measure its levels. In the case of people who follow a vegan or vegetarian diet, or who are older, the risk of suffering a vitamin B12 deficiency is higher. But anyone else who is concerned about the onset of possible symptoms of vitamin B12 deficiency should also have this test done.
What tests are available to measure vitamin B12 levels?
There is currently no standard test to measure the vitamin B12 levels. This is because all the existing tests have their advantages and disadvantages, so the choice of test depends on the doctor’s judgement. Other reasons may be due to availability of the laboratories, since some of the tests require expensive equipment. In addition, the individual preferences can be crucial when it comes to choosing the proper test because, depending on the test, it may need blood or urine samples.
These are the current tests to measure the levels of vitamin B12:
- Vitamin B12 serum test
- Holo-TC Test
- Homocysteine test
- MMA urine test
Vitamin B12 serum test
The vitamin B12 serum test measures all the vitamin B12 found in the blood and is more likely to be the most common standard test. However, it has a limited validity when compared to other tests. This test recognizes concise deficiencies of vitamin B12 clearly, but the importance of an increase in vitamin B12 levels is low. This is because vitamin B12 has several forms in the blood, and not all of these forms are available to the cells.
The vitamin B12 serum test measures the two proteins that are bound to vitamin B12 in the blood: haptocorrine and transcobalamin (TC). However, it is only bound to TC in around a 20% of the circulating vitamin B12. This is the only form that is actually available to the cells.  Therefore, a normal vitamin B12 serum test does not necessarily mean that there is enough active vitamin B12 available.
A U.S. study analyzed the vitamin B12 serum test in approximately 1600 vitamin B12-deficient patients. The result was that this test was only accurate by a 22%. Therefore, it can only be advised as a routine test along with other, more in-depth tests.
This test measures only the protein bound to the form of vitamin B12, called holotranscobalamin. Therefore, this test is used specifically to measure the vitamin B12 that is actually available. Like in the serum test, a blood sample is used for the measurement. The Holo-TC test is regarded as a reliable method to determine the levels of vitamin B12. Here a vitamin B12 deficiency can be detected with a 60% of probability and excluded with a 98% of probability.
This test measures the levels of the amino acid homocysteine in the blood. Amino acids are the building blocks of all proteins in the body. An accumulation of homocysteine in the blood is a marker for vitamin B12 deficiency. However, we have to mention that it measures a metabolite and not vitamin B12 directly.
Therefore, we have to discard other possible causes of an increase in homocysteine levels. This test is relatively reliable, because a vitamin B12 deficiency is linked to an increase in homocysteine levels most of the time.
This is the only vitamin B12 test done through the urine. This test measures the amount of methylmalonic acid in the urine. If this acid increases, it is a marker for a vitamin B12 deficiency. However, the MMA test requires a relatively expensive equipment that is not available in all laboratories. MMA can also be measured through blood serum. The MMA test is regarded as a reliable alternative to the Holo-TC test.
Comparison of vitamin B12 tests
Comparing the holoTC assay serum tests and MMA tests in 700 older people concluded that the holoTC test was the most reliable, followed by the serum test and the MMA test.
Another study, conducted at the Saarland University Hospital, compared vitamin B12 levels in omnivores, vegetarians, the elderly, and dialysis patients using homocysteine, MMA, and holo-TC tests. Excessively low levels of vitamin B12 were found mainly in vegans and vegetarians using the Holo-TC method. These values were often associated with high MMA levels, which also point to a deficiency of this vitamin
Surprisingly, they also found very low holo-TC and MMA values in people whose serum test indicated a vitamin B12 content of up to 300 pmol / l, which is within the normal range. This study shows that the Holo-TC test can determine more reliably a vitamin B12 deficiency in these risk groups than the serum test.
In another risk group the result is different: a vitamin B12 deficiency cannot be ruled out in older people with kidney failure or dialysis patients, even with normal holo-TC values, because the blood levels of vitamin B12 and MMA are related to a healthy renal function.
Something similar was also proven in a study with more than 1.000 subjects who believed that they had a vitamin B12 deficiency. Low holo-CT scores and high MMA scores happened in people with a healthy kidney function, but not in those with an impaired kidney function. Holo-TC and MMA tests confirmed a vitamin B12 in most subjects, although the serum vitamin B12 tests were normal.
Vitamin B12 levels can be measured with different methods, but none of them has reached the standard test range. The comparison between these different tests shows that the result is more reliable using the Holo-TC method. Caution is advised when using this test in people with kidney failure, since kidney diseases can affect the test results.
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