Impacts of  Vitamin B12 (Cobalamin) Status on Health and Disease Prevention

Prieto, Neuburger, Spingler & Zelder (2016) described vitamin B12, (also known as cobalamin) as a water-soluble vitamin involved in the metabolism of every cell of the human body. It is one of eight B vitamins. Yamada (2013) recognizes vitamin B12 as a cofactor in DNA synthesis, and in both fatty acid and amino acid metabolism. This particularly important in the normal functioning of the nervous system via its role in the synthesis of myelin, and in the maturation of developing red blood cells in the bone marrow (Greer, 2014).

Vitamin B12 exists in four near-identical chemical forms (vitamers): cyanocobalamin, hydroxocobalamin, adenosylcobalamin and methylcobalamin. Cyanocobalamin and hydroxocobalamin are used to prevent or treat vitamin deficiency; once absorbed they are converted into adenosylcobalamin and methylcobalamin, which are the forms that have physiological activity. All forms of vitamin B12 contain the biochemically rare element cobalt (chemical symbol Co) positioned in the center of a corrin ring. The only organisms to produce vitamin B12 are certain bacteria and archaea. Bacteria are found on plants that herbivores eat; they are taken into the animals’ digestive system, proliferate and form part of their permanent gut flora, producing vitamin B12 internally.

Omnivorous people obtain vitamin B12 from consuming animal-sourced foods, including meat, fish, fowl, milk and eggs. Grain-based foods can be fortified by having the vitamin added to them. Vitamin B12 supplements are available as single or multivitamin tablets. Since there are few non-animal sources of the vitamin, vegans are advised to consume a dietary supplement or fortified foods for B12 intake, or risk serious health consequences. Children in some regions of developing countries are at particular risk due to increased requirements during growth coupled with diets low in animal-sourced foods (Stabler, 2020).

Sources of Vitamin B12 for the Body

According to Stabler (2020), most omnivorous people in developed countries obtain enough vitamin B12 from consuming animal products including meat, fish, eggs, and milk. Absorption is promoted by intrinsic factor, a glycoprotein; deficiencies of intrinsic factor can lead to a vitamin deficient state despite adequate consumption, as can low postprandial stomach acid production, a common failing in the aged. Vegan sources in the common food supply are rare, hence the recommendations to consume a dietary supplement or fortified foods (Woo, Kwok & Celermajer, 2014).

The following are most notable sources of vitamin B12

Bacteria and Archaea

Vitamin B12 is produced in nature by certain bacteria, and archaea. It is synthesized by some bacteria in the gut flora in humans and other animals, but it has long been thought that humans cannot absorb this as it is made in the colon, downstream from the small intestine, where the absorption of most nutrients occurs. Ruminants, such as cows and sheep, are foregut fermenters, meaning that plant food undergoes microbial fermentation in the rumen before entering the true stomach (abomasum), and thus they are absorbing vitamin B12 produced by bacteria. Other mammalian species (examples: rabbits, pikas, beaver, guinea pigs) consume high-fibre plants which pass through the intestinal system and undergo bacterial fermentation in the cecum and large intestine. The first-passage of feces produced by this hindgut fermentation, called “cecotropes”, are re-ingested, a practice referred to as cecotrophy or coprophagy. Re-ingestion allows for absorption of nutrients made available by bacterial digestion, and also of vitamins and other nutrients synthesized by the gut bacteria, including vitamin B12. Non-ruminant, non-hindgut herbivores may have an enlarged forestomach and/or small intestine to provide a place for bacterial fermentation and B-vitamin production, including B12. For gut bacteria to produce vitamin B12 the animal must consume sufficient amounts of cobalt. Soil that is deficient in cobalt may result in B12 deficiency, and B12 injections or cobalt supplementation may be required for livestock (McDowell, 2008).

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Animal-derived Foods

Animals store vitamin B12 in the liver and muscles and some pass the vitamin into their eggs and milk; meat, liver, eggs and milk are therefore sources of the vitamin for other animals as well as humans. For humans, the bioavailability from eggs is less than 9%, compared to 40% to 60% from fish, fowl and meat. Insects are a source of B12 for animals (including other insects and humans). Food sources with a high concentration of vitamin B12 include liver and other organ meats from lamb, veal, beef, and turkey; shellfish and crab meat (Rooke, 2013).

Plants and Algae

Natural plant and algae sources of vitamin B12 include fermented plant foods such as tempeh and seaweed-derived foods such as nori and laver. Other types of algae are rich in vitamin B12, with some species, such as Porphyra yezoensis, containing as much cobalamin as liver. Methylcobalamin has been identified in Chlorella vulgaris. Since only bacteria and some archea possess the genes and enzymes necessary to synthesize vitamin B12, plant and algae sources all obtain the vitamin secondarily from symbiosis with various species of bacteria, or in the case of fermented plant foods, from bacterial fermentation. The Academy of Nutrition and Dietetics considers plant and algae sources “unreliable”, stating that vegans should turn to fortified foods and supplements instead (Melina, Craig & Levin, 2016).

Fortified Foods

Vegan advocacy organizations, among others, recommend that every vegan consume B12 from either fortified foods or supplements. Foods for which vitamin B12-fortified versions are available include breakfast cereals, plant-derived milk substitutes such as soy milk and oat milk, energy bars, and nutritional yeast. The fortification ingredient is cyanocobalamin. Microbial fermentation yields adenosylcobalamin, which is then converted to cyanocobalamin by addition of potassium cyanide or thiocyanate in the presence of sodium nitrite and heat (Martins, Barg, Warren & Jahn, 2002).

Supplements

Vitamin B12 is included in multivitamin pills; in some countries grain-based foods such as bread and pasta are fortified with B12. In most countries, non-prescription products can be purchased providing up to 5,000 µg each, and it is a common ingredient in energy drinks and energy shots, usually at many times the recommended dietary allowance of B12. The vitamin can also be a prescription product via injection or other means. Sublingual methylcobalamin, which contains no cyanide, is available in 5 mg tablets. The metabolic fate and biological distribution of methylcobalamin are expected to be similar to that of other sources of vitamin B12 in the diet. The amount of cyanide in cyanocobalamin is generally not a concern, even in the 1,000 µg dose, since the amount of cyanide there (20 µg in a 1,000 µg cyanocobalamin tablet) is less than the daily consumption of cyanide from food, and therefore cyanocobalamin is not considered a health risk (European Food Safety Authority (2008).

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Intramuscular or Intravenous Injection

Injection of hydroxocobalamin is often used if digestive absorption is impaired, but this course of action may not be necessary with high-dose oral supplements (such as 0.5–1.0 mg or more), because with large quantities of the vitamin taken orally, even the 1% to 5% of free crystalline B12 that is absorbed along the entire intestine by passive diffusion may be sufficient to provide a necessary amount. A person with cobalamin C disease (which results in combined methylmalonic aciduria and homocystinuria) may require treatment with intravenous or intramuscular hydroxocobalamin or transdermal B12, because oral cyanocobalamin is inadequate in the treatment of cobalamin C disease (Thauvin-Robinet, Roze, Couvreur, Horellou, Sedel, Grabli, Bruneteau, Tonneti, Masurel-Paulet, Perennou, Moreau, Giroud, de Baulny, Giraudier & Faivre, 2008).

Health Benefits of Vitamin B12

According to Fielding and Cassetty (2021), vitamin B12 plays a crucial role in the body’s formation of red blood cells and neurological functioning.  Below are some of the most remarkable benefits of vitamin B12:

Formation of Red Blood Cells

Red blood cells carry oxygen from the lungs to tissues throughout the body. They also carry carbon dioxide — a toxic by-product of cell functioning — from those tissues back to the lungs where it’s then expelled. Vitamin B12 participates in the production of red blood cells therefore If the rates of vitamin B12 are too poor, red blood cell output is impaired, inducing megaloblastic anemia. Megaloblastic anemia refers to anemia — a lack of red blood cells — specifically caused by lack of vitamin B12. It causes symptoms like fatigue, difficulty concentrating, clumsiness, and dry skin. While there are other reasons a person may develop anemia, such as excessive bleeding or low iron, maintaining healthy levels of vitamin B12 is one way to prevent it (Fielding & Cassetty, 2021).

Prevention of Dementia

Vitamin B12 helps to slow brain atrophy in the elderly. Brain atrophy means an overall shrinkage in brain volume and also a loss of neurons, which can cause diseases like Parkinson’s and Alzheimer’s making it difficult to function independently in society. Vitamin B12 is crucial for a well-functioning brain and nervous system. Its role in the brain is so important that research suggests vitamin B12 might play a role in preventing dementia (Fielding & Cassetty, 2021).

Improves Mood and Prevents Depression

Research has shown a connection between vitamin B12 deficiency and neuropsychiatric manifestations. These include depression, obsessive compulsive disorder (OCD), and mood swings. Vitamin B12 is required for serotonin development, which is a chemical that controls mood. This link has led researchers to encourage vitamin B12 supplements as part of treatment plans for those with depression (Fielding & Cassetty, 2021).

Prevents Birth Defects

People who are pregnant have a higher recommended dose of vitamin B12. That’s because the compound may help prevent severe birth defects like partial paralysis and an undeveloped skull.  Adequate amounts of vitamin B12 are important for a successful pregnancy. If someone with low levels of B12 becomes pregnant, they have a greater chance of giving birth to a child with neural tube defect. This class of birth defects includes anencephaly, a fatal condition where the baby’s brain and skull are severely underdeveloped. Along with maintaining proper vitamin B12 levels, taking folic acid before and after conception can decrease the chances of a baby having neural tube defects (Fielding & Cassetty, 2021).

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Supports Healthy Hair, Skin, and Nails

Maintaining healthy levels of vitamin B12 can also assist in hair, skin, and nail growth by providing oxygen to these tissues.  However, vitamin B12 levels are already adequate, consuming a supplement probably won’t boost your health in those regions.  People with vitamin B12 deficiency may suffer from vitiligo — a condition in which the skin has discolored patches, slower hair growth, or skin hyperpigmentation. In this case, adding vitamin B12 to their diet or taking a supplement may improve the condition (Fielding & Cassetty, 2021).

References

European Food Safety Authority (2008). “5′-deoxyadenosylcobalamin and methylcobalamin as sources for Vitamin B12 added as a nutritional substance in food supplements: Scientific opinion of the Scientific Panel on Food Additives and Nutrient Sources added to food”. EFSA Journal. 815 (10): 1-21. doi:10.2903/j.efsa.2008.815

Fielding, S. & Cassetty, S. (2021). 5 Science-backed benefits of vitamin B12 and how to get enough of it. Retrieved from https://www.insider.com/vitamin-b12-benefits on 7th May, 2021.

Greer, J.P. (2014). Wintrobe’s Clinical Hematology Thirteenth Edition. Philadelphia, PA: Wolters Kluwer/Lippincott Williams & Wilkins.  Chapter 36: Megaloblastic anemias: disorders of impaired DNA synthesis by Ralph Carmel

Prieto, T., Neuburger, M., Spingler, B. & Zelder, F. (2016). Inorganic Cyanide as Protecting Group in the Stereospecific Reconstitution of Vitamin B12 from an Artificial Green Secocorrinoid. Org. Lett. 18 (20): 5292–5295. Doi:10.1021/acs.orglett.6b02611.

Martins. J.H., Barg, H., Warren, M.J. & Jahn, D. (2002). “Microbial production of vitamin B12”. Appl Microbiol Biotechnol. 58 (3): 275–85. doi:10.1007/s00253-001-0902-7.

Melina, V., Craig, W. & Levin, S. (2016). “Position of the Academy of Nutrition and Dietetics: Vegetarian Diets”. J Acad Nutr Diet. 116 (12): 1970–80. doi:10.1016/j.jand.2016.09.025.

McDowell, L.R. (2008). Vitamins in Animal and Human Nutrition (2nd ed.). Hoboken: John Wiley & Sons. pp. 525, 539

Rooke, J. (2013). “Do carnivores need Vitamin B12 supplements?”. Baltimore Post Examiner

Stabler, S.P. (2020). “Vitamin B12″. In BP Marriott, DF Birt, VA Stallings, AA Yates (eds.). Present Knowledge in Nutrition, Eleventh Edition. London, United Kingdom: Academic Press (Elsevier). pp. 257–72.

Thauvin-Robinet, C., Roze, E., Couvreur, G., Horellou, M.H., Sedel, F., Grabli, D., Bruneteau, G., Tonneti, C., Masurel-Paulet, A., Perennou, D., Moreau, T., Giroud, M., de Baulny, H.O., Giraudier, S. & Faivre. L (June 2008). “The adolescent and adult form of cobalamin C disease: clinical and molecular spectrum”. Journal of Neurology, Neurosurgery, and Psychiatry. 79 (6): 725–28. doi:10.1136/jnnp.2007.133025

Woo, K.S., Kwok, T.C. & Celermajer, D.S. (2014). “Vegan diet, subnormal vitamin B-12 status and cardiovascular health”. Nutrients. 6 (8): 3259–73. doi:10.3390/nu6083259

Yamada, K. (2013). “Cobalt: Its Role in Health and Disease”. In Sigel A, Sigel H, Sigel RK (eds.). Interrelations between Essential Metal Ions and Human Diseases. Metal Ions in Life Sciences. 13. Springer. pp. 295–320. doi:10.1007/978-94-007-7500-8_9.

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