VEGANALYZE

Vitamin B12

When it comes to vegan nutrition, vitamin B12 is often the number one topic of discussion. This is because plants cannot produce the vitamin, which can lead to a deficiency despite a varied plant-based diet. Vitamin B12 refers to a group of cobalamins that have the trace element cobalt as a central atom in their chemical structure, forming a ring system (corrin).

Vitamin B12 is also an essential micronutrient and must be obtained through food. Vegans need to rely on vitamin B12-fortified foods or B12 supplements. Vitamin B12 is typically produced by bacteria (such as Bifidobacteria) 1. However, it can also be synthetically produced. You can find a table of vitamin B12-rich foods here.

Vitamin B12 has the largest and most complex structure among all vitamins. It is heat- and light-sensitive and soluble in water 2. Unlike the other B vitamins, the body can meet its B12 requirements for up to three years without supplementation by relying on its own reserves in the liver, kidneys, and muscles 3 4 5. On average, an adult can store approximately 2.5 mg (= 2,500 µg) of cobalamin 6. The daily vitamin B12 requirement for adults is 3 µg. For this reason, a vitamin B12 deficiency with corresponding symptoms may only occur years after switching to a vegan diet when no vitamin B12 is supplied and the body's reserves are depleted.

Cobalamin Types

Various atoms or molecules can bind to the central cobalt atom and can be substituted by others. The corresponding cobalamin name depends on the ligand, i.e., the atom or molecule that is bound to the cobalt atom. The most important forms of cobalamin are 7:

• Methyl (Methylcobalamin, coenzyme B12 in the cytoplasm)
• 5'-Deoxyadenosine (5'-deoxyadenosylcobalamin, coenzyme B12 in the mitochondria)
• H2O (Aquocobalamin, Vitamin B12a)
• Hydroxyl (Hydroxycobalamin, also known as hydroxocobalamin, Vitamin B12b)
• Cyanide (Cyanocobalamin)

In the body, the first two cobalamins are active as coenzymes in metabolism 8. The latter ones are usually administered in case of deficiency. They can be converted by the organism into the active forms.

Cyanocobalamin is synthesized artificially. However, it can be converted by the body into the active forms.

In the form of 5'-deoxyadenosylcobalamin, aquacobalamin, and hydroxycobalamin, cobalamin can be stored.

Functions and Effects of Vitamin B12

In the body, Vitamin B12 performs numerous important functions and is involved in many metabolic processes as well as DNA formation and regulation 9. Vitamin B12 is a cofactor (a low-molecular-weight substance that contributes to the functioning of an enzyme) for two enzymes: methionine synthase and L-methylmalonyl-CoA mutase.

5'-Deoxyadenosylcobalamin is required for L-methylmalonyl-CoA mutase in the mitochondria. Methylmalonyl-CoA mutase converts methylmalonyl-CoA to succinyl-CoA 10. This enables the production of energy from proteins and fats, as well as the formation of hemoglobin (red blood pigment) in red blood cells 11. Red blood cells transport oxygen to cells and remove carbon dioxide. A deficiency in B12 results in elevated methylmalonyl-CoA levels. Methylmalonyl-CoA is then converted to methylmalonic acid, which is a good indicator for measuring B12 deficiency through blood and urine.

Methylcobalamin is formed when cobalamin acquires a methyl group from 5-methyltetrahydrofolate (folate obtained from food) in the methionine synthase pathway. Methylcobalamin is then required as a cofactor for the subsequent enzymatic activity. In the cytoplasm, the enzyme catalyzes the conversion of homocysteine (an intermediate in methionine metabolism) to the amino acid methionine 12. The methyl group of methylcobalamin is transferred to homocysteine, thereby reducing homocysteine levels. Methionine is needed for the formation of S-adenosylmethionine (SAM), which is essential for the synthesis of DNA, RNA, hormones, proteins, and lipids 13. As mentioned earlier, methionine synthase also catalyzes the conversion of 5-methyltetrahydrofolate (also known as 5-methyl-THF) to tetrahydrofolate (also known as THF), which is required for DNA synthesis. Therefore, vitamin B12 is also involved in cell structure, growth, and division. Insufficient cobalamin can lead to vitamin B12 deficiency anemia.

Vitamin B12 is also necessary for fatty acid synthesis in the myelin sheath 14. Myelin is a biomembrane that protects nerve cells.

Preventive Effects

To prevent megaloblastic anemia (a type of anemia characterized by very large red blood cells), vitamin B12 is needed. This form of anemia affects mood, among other things, causing people to become tired and sluggish 15. Together with folate and vitamin B6, vitamin B12 ultimately contributes to the control of homocysteine levels 16. Elevated homocysteine concentrations (also an indicator of B12 deficiency) in the body are associated with a range of mental and physical disorders 17. Therefore, B12 is needed to maintain low homocysteine levels.

Scientists in a summary of a study involving 10,601 patients from 2015 also observe a correlation between Vitamin B12 and prevention of colorectal cancer, particularly in population groups with high Vitamin B12 intake 18 19.

Vitamin B12 is produced by the body and excreted unused.

The colon bacteria produce larger amounts of Vitamin B12. However, this can only be absorbed in the lower part of the small intestine. Anatomically, the small intestine is located before the colon. As a result, we excrete the self-produced Vitamin B12 unused. 20. For this reason, Vitamin B12 needs to be supplemented at regular intervals.

According to some scientists, cobalamin is also produced by bacteria in the mouth, throat, esophagus, and tonsils once cobalt is present. 21 22. Whether (sufficient) production actually occurs in these areas is not clear. 23. Therefore, it should not be speculated upon, as improved oral hygiene kills many bacteria anyway.

Absorption

Non-plant-based vitamin B12 in food is bound to proteins. This binding is dissolved in the stomach with the help of enzymes and acids (pepsin and hydrochloric acid) 24. Subsequently, it is bound to an R-protein (also called haptocorrin or transcobalamin I), which is secreted by the salivary glands and the gastric mucosa. In the small intestine, the B12-R-protein complex is dissolved again by digestive enzymes (trypsin). The released B12 binds to the substance Intrinsic Factor (second carrier protein; secreted in the stomach) and is absorbed through the receptors of the small intestine in the presence of calcium 25. In the plasma, B12 is bound to transcobalamin I and II. Transcobalamin I transports excess B12 to the liver. Transcobalamin II delivers B12 to cell membranes and organs where it is stored. Vitamin B12 is then stored as transcobalamin III.

The absorption rate of bound cobalamin decreases significantly when the capacity of the small intestinal bacteria for the complex of B12 and intrinsic factor is exceeded. The capacity ranges from 1 to 2.5 µg per meal. 26 27 28.

Unbound vitamin B12 (e.g., in dietary supplements) is absorbed in small amounts through passive diffusion in the digestive tract (oral mucosa and intestinal mucosa). 29. Through passive diffusion, a portion of the water-soluble cobalamin reaches the membranes to equalize the existing concentration gradient. The cobalamin moves from an area of high concentration to an area of low concentration. This route is particularly important for individuals lacking intrinsic factor or intestinal receptors due to intestinal diseases (see vitamin B12 deficiency). Additionally, unbound vitamin B12 can be absorbed sublingually (under the tongue) 30.

When taking an oral dose of 1 µg of Vitamin B12, ideally 56% (0.56 µg) is absorbed 31. If the dosage is increased to 1,000 µg (common dosage in supplements like lozenges), approximately 13 µg is absorbed, which corresponds to an absorption rate of only 1.3% (see table below) 32:

The following table shows the absorption rates of Vitamin B12 after injection according to 33: