Vitamin B12


Vitamin B12 has the largest and most complex chemical structure of all the vitamins. It is unique among vitamins in that it contains a metal ion, cobalt. For this reason, cobalamin is the term used to refer to compounds having vitamin B12 activity. Methylcobalamin and 5-deoxyadenosylcobalamin are the forms of vitamin B12 used in the human body. The form of cobalamin used in most nutritional supplements and fortified foods, cyanocobalamin, is readily converted to 5-deoxyadenosylcobalamin and methylcobalamin in the body.

  • Vitamin B12 or cobalamin plays essential roles in folate metabolism and the synthesis of the citric acid cycle intermediate, succinyl-CoA.
  • Vitamin B12 deficiency is commonly associated with chronic stomach inflammation, which may contribute to an autoimmune vitamin B12 malabsorption syndrome called pernicious anemia and to a food-bound vitamin B12 malabsorption syndrome. Impairment of vitamin B12 absorption can cause megaloblastic anemia and neurologic disorders in deficient subjects.
  • Normal function of the digestive system required for food-bound vitamin B12 absorption is commonly impaired in individuals over 60 years of age, placing them at risk for vitamin B12 deficiency.
  • Vitamin B12 and folate are important for homocysteine metabolism. Elevated homocysteine levels in blood are a risk factor for cardiovascular disease (CVD). Although B vitamin supplementation has been proven effective in controlling homocysteine levels, current data from intervention trials have not shown that lowering homocysteine levels decreases CVD risk.
  • The preservation of DNA integrity is dependent on folate and vitamin B12 availability. Poor vitamin B12 status has been linked to increased risk of breast cancer in some, but not all, observational studies. There is a need to evaluate whether supplemental vitamin B12, along with folic acid, could help reduce breast cancer incidence.
  • Low maternal vitamin B12 status has been associated with an increased risk of neural tube defects (NTD), but it is not known whether vitamin B12 supplementation could help reduce the risk of NTD.
  • Vitamin B12 is essential for the preservation of the myelin sheath around neurons and for the synthesis of neurotransmitters. While hyperhomocysteinemia may increase the risk of cognitive impairment, it is not clear whether vitamin B12 deficiency contributes to the risk of dementia in the elderly. Although B-vitamin supplementation lowers homocysteine levels in older subjects, the long-term benefit is not yet known.
  • Both depression and osteoporosis have been linked to diminished vitamin B12 status and high homocysteine levels.
  • Products of animal origin constitute the primary source of vitamin B12. Older individuals and vegans are advised to use vitamin B12-fortified foods and supplements to meet their needs.
  • The long-term use of certain medications, such as inhibitors of stomach acid secretion, can adversely affect vitamin B12 absorption.

B12 Deficiency Symptoms

Manifestations of vitamin B12 deficiency may include macrocytic anemia, neurological disorders, psychiatric symptoms (including memory loss, depression, confusion, delirium, and paranoia), glossitis, hyperpigmentation of the skin, orthostatic hypotension, and impaired capacity of leukocytes to kill bacteria. Severe vitamin B12 deficiency can result in malabsorption of vitamin B12 and other nutrients secondary to intestinal damage, which is reversible with vitamin B12 therapy. The neurological manifestations of vitamin B12 deficiency may become irreversible if not treated promptly.

Drug interactions

  • Acid-suppressive therapy: Histamine-2 (H2) blockers and proton pump inhibitors have been reported to inhibit the absorption of vitamin B12 from food, but not the absorption of crystalline vitamin B12 from supplements. This difference is because vitamin B12 in food is mainly protein-bound, and an acid environment is required for proteolytic enzymes in the stomach to release the vitamin from protein. In a case report, megaloblastic anemia secondary to vitamin B12 deficiency developed in a man who had taken omeprazole for 4 years.
  • The prevalence of vitamin B12 deficiency was significantly higher by 75% among aspirin users than among nonusers, after adjustment for potential confounding variables. It is not known whether this association is causal. However, aspirin use might promote the development of vitamin B12 deficiency by damaging the gastric mucosa, thereby decreasing the secretion of intrinsic factors or hydrochloric acid.
  • In guinea pigs, administration of colchicine decreased vitamin B12 absorption as a result of a decrease in the number of vitamin B12-intrinsic factor receptors in the intestinal mucosa. It would be prudent to give a vitamin B12 supplement to patients receiving long-term treatment with colchicine.
  • Contraceptives, oral: Use of oral contraceptives may lead to a deficiency or a suboptimal serum level of vitamin B12.
  • Intramuscular administration of vitamin B12 (methylcobalamin) protected against the development of gentamicin-induced ototoxicity in guinea pigs.
  • Studies in animals suggest that glucocorticoids may interfere with vitamin B12 metabolism; this effect may be counteracted by vitamin B12 supplementation.
  • Metformin has been reported to inhibit the absorption of vitamin B12 in a dose-dependent manner. Discontinuation of the drug corrected vitamin B12 malabsorption in only about 50% of cases. In a case report, a diabetic woman developed vitamin B12-responsive megaloblastic anemia after 8 years of metformin treatment.
  • Vitamin B12 in the form of hydroxocobalamin may decrease the adverse effects of nitroprusside.
  • Nitrous oxide: Nitrous oxide oxidized vitamin B12 in vitro and interfered with the function of vitamin B12 in vivo. Administration of nitrous oxide to vitamin B12-deficient patients can precipitate significant neurological dysfunction. Because of the high cost of screening for vitamin B12 deficiency, it has been recommended that vitamin B12 be given perioperatively to all patients who are going to receive nitrous oxide, except perhaps patients receiving it for a very short period of time.
  • Potassium citrate and potassium chloride: Treatment of humans with potassium citrate or potassium chloride resulted in a modest decrease in vitamin B12 absorption. Decreased vitamin B12 absorption appeared to be due to drug-induced acidification of the ileal contents. Treatment of heart patients with potassium chloride for 6–24 months was not associated with decreased serum vitamin B12 levels. However, since it may take longer than 5 years to deplete vitamin B12 stores, one cannot rule out the possibility that a longer duration of treatment would result in vitamin B12 deficiency.

Dosage and administration

  • Patients with pernicious anemia are typically given 1,000 μg of vitamin B12 intramuscularly daily or weekly for a short period, followed by maintenance injections once a month. Since hydroxocobalamin is better retained in the body than cyanocobalamin, the use of hydroxocobalamin may allow for less frequent maintenance injections (such as every 2–3 months).
  • Pernicious anemia can also be treated effectively with oral vitamin B12, as long as large doses are used (such as 1,000 μg/day) and the patient complies with the treatment.
  • Gauge: The gauge refers to the thickness of the needle. A higher gauge number indicates a thinner needle. For Vitamin B12 injections, a gauge between 22 and 25 is commonly used.
  • Length: The length of the needle determines how deep the injection will go. For intramuscular injections, a needle length of 1 to 1.5 inches is typically recommended.

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