Table of Contents
What is vitamin B12?
Vitamin B12 is a water-soluble vitamin and also a unique vitamin made only by microorganisms; animals and humans take it from animal foods or supplements, not directly from plants. It is also known as the “anti-pernicious anemia vitamin” because its discovery solved the fatal anemia now known as pernicious anemia.
Structure and forms
- Chemically, vitamin B12 is the most complex vitamin, built around a corrin ring that holds a single cobalt atom at its center.
- The ring is formed by four small nitrogen‑containing units (pyrrole rings) linked together, and different chemical groups attached to cobalt give rise to forms like cyanocobalamin, hydroxocobalamin, methylcobalamin, and adenosylcobalamin.
- Inside the body, the two active coenzyme forms are methylcobalamin and 5′‑deoxyadenosylcobalamin, which perform the body’s main metabolic functions.
Vitamin B12 biosynthesis:
Only bacteria and archaea can synthesize vitamin B12, which then enters the food chain through animal tissues and fermented products. In humans, B12 is absorbed in excess of daily requirements and mainly stored in the liver as adenosylcobalamin, and total body stores (around a few milligrams) are usually enough to last several years, which is why deficiency often develops slowly.
Absorption and transport: step‑by‑step
Vitamin B12 absorption is a multistep process, and problems at any step can cause deficiency.
- In the stomach, gastric acid and enzymes free B12 from food proteins, and it first binds to salivary/gastric binding proteins (R‑proteins).
- In the duodenum, pancreatic enzymes release B12 again so that it can attach to intrinsic factor (IF), a glycoprotein produced by parietal cells of the stomach.
- The IF‑B12 complex then travels to the terminal ileum, where it binds to specific receptors on the mucosal cells; this uptake step depends on calcium.
- After entry into enterocytes, B12 is transferred to carrier proteins called transcobalamins: TC II delivers B12 to tissues, while TC I serves mainly as a circulating storage pool.
Because of this complex mechanism, conditions like autoimmune loss of intrinsic factor, gastric surgery, pancreatic insufficiency, or ileal disease can all reduce absorption and increase the risk of vitamin B12 deficiency.
Key biochemical functions of vitamin B12 in metabolism
In humans, vitamin B12 is required mainly for two critical reactions.
- Methylcobalamin acts as a cofactor for methionine synthase, which converts homocysteine to methionine and regenerates tetrahydrofolate; this reaction links B12 with folate and is vital for DNA synthesis and methylation reactions in rapidly dividing cells.
- Adenosylcobalamin serves as the cofactor for methylmalonyl‑CoA mutase, converting methylmalonyl‑CoA to succinyl‑CoA during the breakdown of odd‑chain fatty acids and certain amino acids, helping normal energy metabolism and maintaining the integrity of myelin lipids.
When B12 is lacking, homocysteine and methylmalonic acid accumulate, contributing to vascular risk and to demyelination in the nervous system.
Vitamin B12 deficiency:
Important causes often tested in exams and searched online include:
- Autoimmune destruction of gastric parietal cells (pernicious anemia), leading to intrinsic factor deficiency and poor B12 absorption.
- Total or partial gastrectomy, bariatric surgery, or chronic atrophic gastritis all of which reduce intrinsic factor and gastric acid.
- Hereditary malabsorption syndromes affecting intrinsic factor or ileal receptors.
- Long‑term strict vegetarian or vegan diets without fortified foods or supplements, especially in low‑income settings.
- Chronic pancreatic disease, ileal disease/resection, or prolonged use of certain drugs (e.g., metformin, proton pump inhibitors)
Symptoms and disorders associated with Vitamin B12
- Hematologic: megaloblastic (macrocytic) anemia with low hemoglobin, reduced red cell count, and sometimes leukopenia and thrombocytopenia; patients complain of fatigue, pallor, and dyspnea.
- Neurologic: progressive degeneration and demyelination of the posterior and lateral columns of the spinal cord and peripheral nerves, causing numbness and tingling in hands and feet, loss of vibration and position sense, unsteady gait, weakness, memory problems, and, in advanced stages, confusion or psychosis
Treatment and recommended intake:
Most expert bodies recommend around 2–2.5 micrograms (µg) of vitamin B12 per day for healthy adults. Children need roughly 0.5–1.5 µg/day, depending on age, and the requirement increases in pregnancy and breastfeeding, where an intake near 3 µg/day (or more, in some guidelines) is advised to support maternal and fetal needs.
Dietary sources
Natural vitamin B12 is found almost exclusively in animal‑based foods. Good sources of vitamin B12 include:
- Organ meats such as liver and kidney
- Meat (red meat, mutton, poultry), fish, and shellfish
- Eggs and dairy products like milk, curd/yoghurt, and cheese
Fermented dairy products may contain slightly more B12 than plain milk because lactic acid bacteria can synthesize small amounts during fermentation. For vegans and strict vegetarians, reliable intake usually requires fortified foods (such as fortified plant milks, breakfast cereals, or nutritional yeast) or vitamin B12 supplements.
References and resources :
- https://www.tandfonline.com/doi/full/10.1080/10408363.2021.1885339
- https://pmc.ncbi.nlm.nih.gov/articles/PMC5282855/
- https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/vitamin-b12
- https://en.wikipedia.org/wiki/Vitamin_B12_deficiency
- https://www.aafp.org/pubs/afp/issues/2017/0915/p384.html
- https://www.chm.bris.ac.uk/motm/vitaminb12/structure.html
- https://chem.libretexts.org/Bookshelves/Biological_Chemistry/Supplemental_Modules_(Biological_Chemistry)/Vitamins_Cofactors_and_Coenzymes/Vitamin_B:_Cobalamin
- https://pmc.ncbi.nlm.nih.gov/articles/PMC4999627/
- https://pubmed.ncbi.nlm.nih.gov/35337622/
- https://veganhealth.org/vitamin-b12/vitamin-b12-absorption/
- https://nutritionalassessment.org/b12/
- https://www.ncbi.nlm.nih.gov/books/NBK534419/
- https://www.news-medical.net/health/Foods-High-in-Vitamin-B12-and-Their-Health-Benefits.aspx
- https://www.bbc.co.uk/food/articles/vitamin_b12
