Facts and Myths – Vitamin B12 (Cobalamin)

What is Vitamin B12 and how is it absorbed?

There are various rumours about Vitamin B12, such as that it cannot be absorbed from supplements or that it can be obtained from Spirulina. Neither of these statements is true, but before we debunk the myths and misconceptions about Vitamin B12, let's first go over everything you need to know about this vitamin. 

Animals produce Vitamin B12 through bacteria in their digestive tract. Vitamin B12 is then absorbed into the bloodstream and transported to almost every cell in the animal. Animals can also obtain Vitamin B12 by eating faeces containing Vitamin B12 or by consuming other dead animals. 

Plants typically only contain inactive and ineffective analogues of Vitamin B12. It is only animal products that contain active Vitamin B12. When humans eat animal products, that is, animals, they obtain Vitamin B12 bound to a peptide (a protein molecule). Vitamin B12 is then cleaved from the peptide by the action of protease enzymes and hydrochloric acid in the stomach. Once the peptide has been removed, Vitamin B12 binds to a glycoprotein called R Protein (haptocorrin or transcobalamin-1). At the same time, the stomach produces a factor called Intrinsic Factor (IF), which is crucial for Vitamin B12 absorption. The pancreas produces protease enzymes that, in the more alkaline part of the small intestine, remove R Protein from Vitamin B12. Now, Vitamin B12 binds to IF, which is required for it to be absorbed in the end of the small intestine, where cells with receptors for the IF-B12 complex are found. In the intestinal cells, Vitamin B12 binds to another protein called transcobalamin 2 (TC2). TC2 transports Vitamin B12 to all cells in the body. Every cell in the body has receptors for TC2, as Vitamin B12 is involved in the metabolism of all cells. Vitamin B12 can also be absorbed by diffusion in the small intestine, although absorption via IF is much more efficient.  

Therefore, it is not enough to have adequate levels of hydrochloric acid in the stomach to absorb Vitamin B12; you also need a well-functioning pancreas and a healthy small intestine. If Intrinsic Factor or R Protein is lacking, Vitamin B12 absorption is significantly reduced. Absorption of Vitamin B12 can be as low as 1–3% of the total amount of Vitamin B12 ingested. 

Vitamin B12 deficiency is very unhealthy

Early signs of Vitamin B12 deficiency can include unusual tiredness, reduced appetite, cessation of menstruation, tingling or numbness in the hands and feet, mild depression, fever, recurring upper respiratory issues, problems with mucous membranes, a sore tongue, tinnitus, gum bleeding, or cracks in the corners of the mouth (angular cheilitis).

What causes Vitamin B12 deficiency?

Vitamin B12 deficiency can be caused by one or more of the following factors: 

• Low stomach acid and insufficient production of Intrinsic Factor (IF)

• Insufficient proteolytic enzymes to cleave the peptides bound to Vitamin B12

• Pancreatitis, which reduces free calcium in the end of the small intestine 

• The medication metformin, which binds free calcium in the small intestine

• Calcium deficiency (However, one should not take synthetic isolated calcium carbonate but real whole food calcium, as synthetic isolated calcium carbonate needs to be converted to calcium chloride in the stomach. The stomach acid used for this conversion may potentially affect Vitamin B12 absorption negatively.)

• Inflammation or other diseases in the digestive tract (Crohn's, Ulcerative Colitis, IBS, Gluten intolerance/celiac disease)

• Alcohol

• Proton pump inhibitors (medications that reduce stomach acid, e.g., Losec, Nexium)

• Exposure to nitrogen oxide

• Tapeworms

• Thyroid problems

• Consumption of foods with pseudovitamin B12, such as inactive analogues of Vitamin B12 found in Spirulina and other algae.  

Why is Vitamin B12 important for health?

The European Food Safety Authority (EFSA) is an EU agency working with food safety. After studying Vitamin B12, they concluded that Vitamin B12 contributes to several important functions, processes, and systems in the body:  

• Vitamin B12 contributes to normal energy metabolism.

• Vitamin B12 contributes to the normal functioning of the nervous system.

• Vitamin B12 contributes to normal homocysteine metabolism.

• Vitamin B12 contributes to normal psychological function.

• Vitamin B12 contributes to the normal formation of red blood cells.

• Vitamin B12 contributes to the normal functioning of the immune system.

• Vitamin B12 helps reduce fatigue and exhaustion.

• Vitamin B12 plays a role in cell division.

Vegans lose Vitamin B12 over time

Humans are omnivores in terms of physiology and from an evolutionary perspective. Omnivores are animals that consume both plant and animal-based foods. Omnivores differ from carnivores (lions) that eat animals and herbivores (cows) that eat plants. When humans follow their natural omnivorous diet, they obtain about 2–6 μg (micrograms) of Vitamin B12 per day through food. An omnivore’s liver secretes about 5–10 μg of Vitamin B12 per day into the small intestine via bile. Healthy omnivores, however, reabsorb about 3–5 μg from the bile via the enterohepatic cycle. This cycle means that bile acids, which contain Vitamin B12, are returned to the liver through the portal vein. An adult person stores around 3000 μg of Vitamin B12 and loses about 3 μg per day. 

A vegan adult who does not take Vitamin B12 supplements and whose enterohepatic cycle is not functioning optimally will usually develop a Vitamin B12 deficiency within 1–3 years. A vegan adult whose enterohepatic cycle works perfectly can, even with a reduced bile secretion of 1 μg per day, reabsorb almost 100%, meaning that B12 deficiency can occur only after 5–15 years without supplements. However, over time, deficiency will always occur in vegans who do not take supplements. Moreover, few people can be considered to have a perfectly functioning enterohepatic cycle, which means that the time to B12 deficiency can be much shorter. Humans have never been vegetarian or vegan except for short involuntary periods, which is why our organism depends on obtaining Vitamin B12 from animal sources unless one takes Vitamin B12 supplements. Plants have no need for Vitamin B12, which is why they cannot produce or store the vitamin.

Research shows that up to 40% of pregnant vegetarians are deficient in Vitamin B12, up to 45% of babies born to parents who follow a vegetarian diet are deficient in Vitamin B12, up to 33% of teenagers who follow a vegetarian diet are deficient in Vitamin B12, and up to 86% of elderly people who follow a vegetarian diet are deficient in Vitamin B12. Higher levels were measured in vegans. Even omnivores can become deficient in Vitamin B12 due to impaired gastrointestinal function and other reasons mentioned above. It is extremely unhealthy to be deficient in Vitamin B12 for an extended period. It can cause irreversible damage to the nervous system, which is why vegetarians and vegans are always advised to take Vitamin B12 supplements, as well as iron and zinc.

Different forms of Vitamin B12

The production of Vitamin B12 is a very complex process, and Vitamin B12 is the most structurally complex of all vitamins. Vitamin B12 is normally produced by bacteria such as Pseudomonas denitrificans, Propionibacterium shermanii, or Sinorhizobium meliloti. The most common forms of Vitamin B12 (cobalamin) are:  

1. Cyanocobalamin

2. Hydroxocobalamin

3. Methylcobalamin

4. Adenosylcobalamin

Cyanocobalamin does not become active in the body until the cyanide group is removed. Cyanocobalamin is also not naturally found in food, whereas the other three forms of Vitamin B12 are. Methylcobalamin is mainly found in meat, while hydroxocobalamin and adenosylcobalamin are mainly found in dairy products and eggs. 

Cyanocobalamin is typically converted into hydroxocobalamin, which is then converted into methylcobalamin and adenosylcobalamin in the liver. Hydroxocobalamin has historically been used to counteract cyanide poisoning by binding to cyanide.  

The different forms of Vitamin B12 vary in how they are absorbed and transported in the bloodstream and how they interact with cell receptors, that is, before they enter the cell. Once inside the cell, however, the form of Vitamin B12 does not matter, as all forms of Vitamin B12 are reduced to cobalamin inside the intracellular fluid. Inside the cell, they are then synthesized back into their active forms. 

Synthetic Vitamin B12 Cyanocobalamin commonly found in supplements

Supplements typically contain either cyanocobalamin, hydroxocobalamin, methylcobalamin, or adenosylcobalamin. The latter three are active forms, while cyanocobalamin, as mentioned, is converted into the active forms of Vitamin B12 in the liver. A good synthetic Vitamin B12 supplement should be in the forms of methylcobalamin or adenosylcobalamin. However, these are also made from the base form cyanocobalamin, as previously stated. For example, synthetic hydroxocobalamin found in supplements is made by reducing cyanocobalamin with sodium borohydride and adding iodomethane. The absolute best Vitamin B12 supplement is based on whole food with all cofactors intact. This way, you don't need to worry about the base form. The closer you get to food, the better for your body. If B vitamins are whole food, the form of the base B vitamin doesn't matter. They contain all the cofactors and peptides needed for maximum bioavailability.

UL Value for Vitamin B12

The UL value (Tolerable Upper Intake Level) is the maximum dose of a nutrient that is unlikely to cause negative health effects in humans. There is no established UL value for B12. Therefore, the dosage of Vitamin B12 is considered to be very high without causing negative health effects. This is probably because the absorption of Vitamin B12 requires IF, which is produced in the stomach, adequate levels of stomach acid, and a well-functioning pancreas, among other factors. When taking Vitamin B12 via supplements, high doses are often required, as IF unfortunately limits the actual absorption into the bloodstream. Research has shown that only 10 micrograms of a 500-microgram Vitamin B12 supplement are absorbed in healthy individuals, and even less in those with gastrointestinal issues. 

MTHFR and Vitamin B12

MTHFR (Methylenetetrahydrofolate reductase) is an enzyme that breaks down the amino acid homocysteine. High levels of homocysteine are not healthy. It is associated with several health issues. MTHFR enzyme is coded by the MTHFR gene. All humans have two copies of the MTHFR gene that instruct the body on how to create the MTHFR enzyme, which in turn breaks down the amino acid homocysteine. However, the DNA code for the MTHFR gene can vary, meaning that the gene sometimes does not function as it should. This can result in the MTHFR enzyme being completely or partially inactivated, leading to high levels of homocysteine in the body. If you are deficient in Vitamin B12, folate (folic acid), and Vitamin B6, the amount of homocysteine in the body increases. 

Two genetic variants of the MTHFR gene are called C677T and A1298C. More people than you might think have these genetic variants. 10–25% of the population carry two copies of the same gene variant. Research shows, for example, that women who carry two copies of the MTHFR C677T gene variant have an increased risk of having children with neural tube defects. There is also research indicating that people with two copies of the C677T gene variant have an increased risk of developing blood clots. However, there is also research suggesting it is difficult to link MTHFR gene variants to various diseases. 

Very high levels of homocysteine, however, are rarely solely due to incorrect genetic variants of the MTHFR gene. Poor diet, smoking, obesity, problems regulating blood sugar, and thyroid issues can affect homocysteine levels in the body. 

You should never be deficient in vitamins and minerals, but people who have issues with MTHFR should absolutely not be deficient in Vitamin B12, (folate), and Vitamin B6. In an MTHFR treatment protocol, extra doses of these vitamins should always be included.

Myths about Vitamin B12

There are several myths about Vitamin B12, and unfortunately, some of these myths increase the risk of developing a Vitamin B12 deficiency. 

You can get Vitamin B12 from fermented soy or Spirulina

A common myth is that sufficient levels of Vitamin B12 can be obtained from algae, fermented soy, or Spirulina. However, these foods contain pseudo-vitamin B12, which is an inactive form of Vitamin B12. Inactive forms of Vitamin B12 can block active forms of Vitamin B12 from reaching the cell. As early as the late 1980s, Mt Sinai School of Medicine conducted a study on most Spirulina brands sold in health food stores. The result was disappointing, as virtually all the Vitamin B12 in Spirulina was not active Vitamin B12 but inactive analogues. The problem is that inactive analogues are still allowed to be labelled as Vitamin B12. The two most common analogues in Spirulina were found to block Vitamin B12 metabolism. The study's authors suggest that "they suspect that people who take Spirulina as a source of Vitamin B12 may increase the risk of developing a deficiency more quickly." However, one study points out that Nori algae and Chlorella may potentially contain active forms of Vitamin B12. 

The intestines produce enough Vitamin B12

Sometimes it is claimed that the large intestine can produce all the Vitamin B12 we need. The problem with this statement is that Vitamin B12 is absorbed in the end of the small intestine, not in the large intestine. The small intestine comes before the large intestine . For humans to absorb the Vitamin B12 produced in the large intestine, the food would have to go the wrong way through the digestive tract, meaning the food would need to go back toward the mouth instead of toward the rectum. This does not happen in a healthy person. Alternatively, we would need to eat our own faeces to absorb the Vitamin B12 produced in the large intestine. It is impossible, through the production of Vitamin B12 in the large intestine and the enterohepatic cycle (even if it works perfectly), to obtain sufficient levels of Vitamin B12. First of all, the amount of Vitamin B12 in the small intestine is not enough, and secondly, the Vitamin B12 produced in the large intestine has already passed the end of the small intestine, where Vitamin B12 is absorbed.

Chimpanzees and gorillas produce Vitamin B12, so we must too

Another myth is that our closest relatives, chimpanzees and gorillas, get all their Vitamin B12 from a vegetarian diet, so humans should be able to do the same. Humans do not have the same digestive system as chimpanzees and gorillas. Genetic analysis shows that our respective digestive systems diverged millions of years ago. In humans, the small intestine is where the main nutrients are absorbed, and the human small intestine accounts for about 50% of the total digestive tract. The appendix and large intestine in humans account for about 20%. Gorillas have a similar structure in their digestive tract to humans, that is, the stomach comes first, followed by the intestines, but gorillas have a reversed distribution between the small and large intestine. The gorilla’s small intestine is much shorter, around 25%, compared to that of a human. The appendix and large intestine of gorillas, on the other hand, make up more than 50% of their total digestive tract. This is because gorillas specialise in a diet based on a lot of plant fibre. Gorillas have enormous amounts of bacteria in both their appendix and large intestine, which is why they need large stomachs. They have large stomachs to accommodate their large large intestine and appendix, where fermentation processes are constantly ongoing. While humans do have many gut bacteria, it is nothing compared to gorillas or other herbivorous animals. Additionally, chimpanzees and gorillas eat insects and smaller mammals, which provide them with Vitamin B12. Chimpanzees and gorillas do not live solely on a vegetarian diet. They also eat their own faeces, which contains Vitamin B12, and they also ingest soil daily, which contains bacteria that synthesise Vitamin B12.

Vitamin B12 supplements that cannot be absorbed

There is an incorrect and harmful myth that Vitamin B12 supplements cannot be absorbed by the small intestine. Vitamin B12 is commercially produced through bacterial fermentation and forms exactly the same molecule as the one found in liver, seafood, meat, fish, poultry, and other animal products. Vitamin B12 in supplements is absorbed in the same way as Vitamin B12 from animal products. Reduced absorption is usually due to low stomach acid levels, insufficient levels of Intrinsic Factor (IF), insufficient proteolytic enzymes, and/or inflammation in the pancreas. If you suffer from any of these conditions, absorption of Vitamin B12 will be severely reduced, regardless of whether the Vitamin B12 comes from food or supplements.

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