Vitamin B12, also known as cobalamin, is an essential nutrient for the human body. This means it has to be taken from external sources, as the human body cannot produce it. It is involved in the metabolism of each and every cell of our bodies. Vitamin B12 is a water-soluble vitamin, which is produced by the gut flora, but the bioavailability of this source is debated. Vitamin B12 plays an important role in DNA synthesis, fatty acid metabolism, and amino acid metabolism as a cofactor. It is essential for the health of the nervous system as it has a key function in the synthesis of myelin, the lipids that surround nerve cell axons. Cobalt, a biochemically very rare element, is placed in the center of the molecule, hence the name of the vitamin. Vitamin B12 is also very important for the production of serotonin, which is a hormone that is chemically responsible for mood regulation. Therefore vitamin B12 supplements could have the potency to help improve mood in people with an existing underlying B12 deficiency. Low B12 level in the human body can lead to a particular type of anemia called “megaloblastic anemia”, which means that the bone marrow produces unusually large, structurally abnormal, immature red blood cells (megaloblasts). The presence of vitamin B12 (or folate) anemia deficiency is around 6-12 % in the general population under 60 years old. It is higher, 17 % in individuals with macrocytic anemia. Elderly people, pregnant women, immunosuppressed individuals, and vegans are more susceptible to a vitamin B12 deficiency. Diagnosing vitamin B12 deficiency can be difficult, as it can have no symptoms for a long time and when symptoms appear, they are often not so straightforward. There is no consensus with regards to a normal range of vitamin B12 for biomedical tests and the signs can also be misleading.
Signs and symptoms of B12 deficiency
Vitamin B12 has many physiologically important functions in the body therefore the lack of it can cause various symptoms. It can result in a very broad range of problems, such as:
- weakness, fatigue, extreme tiredness
- pale skin (loss of blood cells)
- a lack of energy
- mouth ulcers
- muscle weakness
- blurry vision or more severed vision loss
- constipation, diarrhea, bloatedness
- loss of appetite
- paresthesia, the feeling of pins and needles, numbness
- red tongue usually presents with pain
- memory loss, problems with understanding and forming judgments
- psychological problems, such as depression, aggression, irritability, psychosis, and confusion
These problems can be acute and severely affect the body, and most of them can end up being irreversible. The brain and the entire nervous system can be acutely damaged by the lack of vitamin B12. Even when the level of the latter is slightly off, it can cause symptoms like lethargy, fatigue, poor memory, and headaches. In most severe cases, it can result in psychosis, mania, and other psychological issues.
Vitamin B12 deficiency can present with non-specific symptoms, but when patients are admitted with a hematological or neurological issue, B12 level must be checked urgently. These latter two cases can be caused by a severe B12 deficiency, which needs to be supplemented as soon as possible. Folate (also known as vitamin B9) acts synergistically with vitamin B12 for its cellular function and its deficiency has symptoms similar to vitamin B12 deficiency. Therefore, folate levels should also be checked when there is a suspicion for B12 deficiency and it must be supplemented if needed. In severe cases of malnutrition and malabsorption, vitamin B12 and folate deficiency can coexist, that is why it’s common to supplement folate as well in case the body lacks vitamin B12. Moreover, folate can is proved to enhance the absorption of vitamin B12 therefore help curing the deficiency.
Causes of vitamin B12 deficiency
B12 deficiency can be caused by various factors, such as undernourishment, diseases that involve the small intestines, certain drugs (discussed below), or underlying autoimmune disorders (e.g., Graves’ disease or Lupus erythematosus). Vitamin B12 deficiency is most likely caused by a low intake of B12. It can also be caused by intestinal disorders, low ability of absorption, and low presence of binding proteins which is caused by protein deficiency.
Since vitamin B12 is contained in animal foods only, its deficiency is very common among vegans and vegetarians who are at a higher risk of developing megaloblastic anemia. Current estimates show that between 40% and 80% of the vegetarian population has this deficiency and need supplements or fortified foods (such as fortified nutritional yeast, a deactivated yeast used as a vegan cheese substitute) to be part of their diet. Among the elderly low levels of stomach acid can also be the problem, a condition called achlorhydria. This can result in reduced absorption of B12 hence the elderly are at a higher risk of B12 deficiency.
Some medications can also have the side effect of lowering B12 levels therefore it is important to be informed by doctors, if that is the case, and so the patient can take supplements. Medications, such as heartburn medicines, proton pump inhibitors can interfere with the absorption of B12. This includes esomeprazole, lansoprazole, omeprazole, pantoprazole, and rabeprazole. H2 blocker likes cimetidine, famotidine and medicine for diabetes, such as metformin can also cause a disruption in B12 levels.
People are more likely to develop B12 deficiency if they have atrophic gastritis because their stomach lining is thinned and makes it difficult to absorb B12 and other nutrients. Other conditions that involve malfunction of the gut, such as Crohn’s disease or celiac disease can also result in vitamin B12 deficiency. Certain types of bacterial infections and parasites can also attack the small intestines, a condition that can represent an underlying cause of vitamin B12 deficiency. Specific types of autoimmune disorders, such as Graves’ disease or lupus, can also be the root cause of vitamin B12 deficiency. Therefore, patients affected by these diseases need B12 injections.
Gastric bypass or gastric restriction surgery, which is used in people with severe obesity, can also increase the risk of vitamin B12 deficiency, particularly the Roux-en-Y gastric bypass surgery. Therefore, patients who underwent this type of surgery require regular vitamin B12 injections.
Pernicious anemia can also cause vitamin B12 deficiency. It is a type of autoimmune disease that results from the loss of gastric parietal cells. This type of gastritis is associated with the lack of intrinsic factor that binds to ingested vitamin B12. Generally, it will result in a low level of B12, as the body cannot absorb it through the intestines. Pernicious anemia is characterized by the following symptoms:
- Anemia with bone marrow promegaloblastosis, also called megaloblastic anemia. This caused by the inhibition of DNA synthesis, specifically the one that is responsible for purines and thymidine.
- Gastrointestinal symptoms can also be present. A certain negative change in bowel motility, for example, mild diarrhea or constipation, can also occur. In some cases, also the loss of bladder or bowel control. Defective DNA synthesis can inhibit the replication of tissue sites with a high turnover of cells which can cause gastrointestinal symptoms. There is also a correlation between gastric antral vascular ectasia (also known as watermelon stomach) and pernicious anemia.
- Neurological symptoms such as motor and sensory deficiencies are also likely. This can include, for example, absent reflexes and the loss of touch sensation. The spinal cord can be degenerate which can be so severe in some cases that the damage is irreversible. Neurological symptoms in children include developmental delay, irritability, involuntary movements, and hypotonia. The latter can result in developmental delays and learning disabilities.
In case there is no obvious cause for B12 deficiency, then a specialist must be involved. If there is a case with neurological features or persistent macrocytic anemia, then two things are indicated. One is parenteral B12 supplementation (intravenous administration), which bypasses the digestive system. It can be administered with injections if urgent treatment is required in case of gastrointestinal malabsorption or in elderly patients who cannot digest B12 properly. The second action that can be taken is an oral vitamin B12 replacement which may be suitable for asymptomatic patients with dietary B12 deficiency.
Pregnant women who are vegetarian, vegan, or just simply eating very little meat can be at a high risk of developing vitamin B12 deficiency. Therefore, it is recommended to suspend any special diet that involves low animal-sourced food or take dietary B12 supplements during pregnancy. This is a very important step in order to prevent anemia in the mother-to-become and also vitamin B12 deficiency of the baby. It is also important to keep this regime during breastfeeding. B12 levels can be low in breast milk as well, and it all depends on the sufficient nutrition of the mother. Vitamin B12 is secreted into breast milk, but in some cases its quantity is insufficient. In this case, the mother needs supplementation. Some developing countries have fortified food programs, and they enrich bread or flour with vitamin B12 in order to prevent widespread deficiency. This is especially important in the case of babies and nursing mothers. Prolonged exclusive breastfeeding (i.e., more than 6 months) is not recommended, since vitamin B12 levels are naturally decreasing in time. Thus, after 6 months of exclusive breastfeeding (which is, instead, recommended by the WHO) it is important to introduce regular food into the child’s diet. Some of the latter foods need to contain vitamin B12, such as animal food products or food fortified with B12, otherwise the infant will not receive a sufficient amount of this vitamin. Vitamin B12 deficiency in infancy can not only cause megaloblastic anemia, but also poor physical growth and impaired neurogenesis (i.e., the development of nerve tissue).
The estimated average requirement (EAR) for vitamin B12 in both men and women who are 14 years or older is 2.0 μg/day while the recommended dietary allowance (RDA) is slightly greater than that, i.e. 2.4 μg/day, according to the National Academy of Medicine. The reason why the recommended intake is higher than the average requirements is that individual needs vary within different subjects and some people need more B12 than the average requirements. Recommended intakes for pregnant women are slightly higher, 2.6 μg/day, while the recommendation for breastfeeding women is to consume at least 2.8 μg/day. The recommended intakes for children 12 months old or younger are 0.4-0.5 μg/day, while for children from 1-13 years this value is 0.9-1.8 μg/day. In older people, the capacity for absorption of vitamins from food is decreased compared to younger individuals. Therefore, they sometimes need to take supplements. Notably, the tolerable upper intake levels for vitamin B12 have not been defined.
Absorption and bioavailability of B12
The absorption of vitamin B12 is facilitated by a glycoprotein, which functions as an intrinsic factor. Certain deficiencies of this intrinsic factor can directly lead to a deficiency, even when people consume adequate levels of this vitamin. Low postprandial acid in the stomach can also be a barrier in the absorption, which is more common during menopause and among the elderly. The bioavailability of vitamin B12, just like with any other nutrients, is very important. The human body can only absorb 9% of B12 that originates from eggs, while from fish and meat it can range from 40 to 60%. Food sources with the highest concentration of vitamin B12 include liver and other organs, the meat of lamb, veal, beef, and turkey as well as shellfish, and crab meat.
Sources of B12
Foods that contain vitamin B12
In most cases, you can get a sufficient amount of vitamin B12 from food sources. This is generally true for people living in developed countries and who eat variously. Therefore people who are not omnivorous, for example, vegans can be at a higher risk of developing a deficiency. Vitamin B12 is in most animal products, such as meat, fish, milk, cheese, and eggs. Animals store vitamin B12 in the liver and in the muscles. Some of it can make it to the eggs and milk; meat, liver, eggs, and milk are therefore sources of the vitamin for other animals as well as humans.
Insects are also a rich source of B12 for humans. Eating worms, grasshoppers, and other insects live its renaissance in some countries like Denmark, and even though it is not vegan, some vegetarians have no problem with using powdered grasshoppers for enriching their food with protein and hence B12.
Plants cannot produce vitamin B12 and, consequently, vegetable food naturally does not contain vitamin B12. However, fermented plant products can be rich in B12 since, during natural fermentation by the right type of bacteria, high levels of vitamin B12 can be produced. Seaweed-derived food, for instance, nori and laver are also rich in vitamin B12, as well as other types of algae. Only some bacteria have the genes necessary to produce vitamin B12 whereas plants can only contain this vitamin if they live in symbiosis or if they are fermented with the right type of bacteria. On the other hand, according to the Academy of Nutrition and Dietetics, plants and algae are unreliable sources of vitamin B12, thus everyone who doesn’t eat meat or other animal products should consider supplements or fortified foods. Some breakfast cereals, for instance, are supplemented with vitamin B12 with high bioavailability. These food products are suitable for vegetarians.
Bacteria that produce vitamin B12
Vitamin B12 is produced in a high quantity in certain bacteria, including the natural gut microflora. Even though it is synthetized by these bacteria in the human body, whether it can be absorbed is a highly debated topic. Notably, this vitamin is produced in the colon, not in the small intestines where most of the nutrients get absorbed.
Supplements and fortified foods
Vitamin B12 deficiency can be treated with supplements, such as vitamin pills, injections, or fortified food. Tablets are the most usual form of supplementing; these can be purchased even up to 5000 µg per pill. One main form of B12 is cyanocobalamin, and even though it does contain cyanide, the amount should not be a health concern, even in high doses (1000 µg). On the other hand, people with kidney malfunction, kidney diseases shouldn’t take large doses of cyanocobalamin, as they are unable to filter cyanide and secrete it into the urine. Sublingual methylcobalamin is available in 5 mg tablets and it contains no cyanide. Methylcobalamin is also an efficient form of B12 and it is very similar to its natural sources. Energy drinks are sometimes supplemented with high levels of vitamin B12 and other water-soluble vitamins.
Vegan advocacy organizations support the idea of vitamin B12 supplementation for vegans by fortified foods or supplements. There are other fortified foods that are enriched with cyanocobalamin that vegans and vegetarians can also consume. The latter include soy milk, oat milk, and energy bars. Nutritional yeast can also be helpful when someone is baking their own bread or other pastries. In some countries, bread is fortified with vitamin B12, just like iodine is added to salt in order to prevent thyroid malfunction. Microbial fermentation produces adenosylcobalamin, which is transformed to cyanocobalamin by adding potassium cyanide, heat, and sodium nitrite. The end product is naturally fermented vegetables, such as cabbage or pickles that are rich in Vitamin B12.
Intramuscular or intravenous injections are also an option in severe cases of vitamin B12 deficiency. Vitamin B12 can be administered in the form of hydroxicobalamin injections. It is often used for patients with digestion and absorption problems, but a high dose of oral intake (around 1 mg) can also make up for it. This is due to the fact that large quantities of the vitamin taken orally can be absorbed in the entire small intestines by passive diffusion. Therefore it can also provide the necessary amount. Patients with cobalamin C disease, however, must get treatment in injection forms, because this malfunction cannot be corrected through the natural passive diffusion of the intestines.
Vitamin B12 is an essential vitamin and the lack of it can develop severe symptoms. Preventing it is easy when one is aware of his or her body’s needs. As vitamin B12 is naturally present in animal food products, it is not a general concern to omnivores. However, vegans or vegetarians most likely need supplementation or need to consume fortified foods such as cereal enriched with vitamin B12. Certain medical conditions and medicines can also raise the risk of developing the deficiency, therefore it is always important to consult your doctor if this is the case.