Vitamin B12 - Safety

Toxicity

No toxic or adverse effects have been associated with large intakes of vitamin B₁₂ from food or supplements in healthy people. Doses as high as 1 mg (1000 mcg) daily by mouth or 1 mg monthly by intramuscular (IM) injection have been used to treat pernicious anemia, without significant side effects. When high doses of vitamin B₁₂ are given orally only a small percentage can be absorbed, which may explain its low toxicity. Because of the low toxicity of vitamin B₁₂, no tolerable upper intake level (UL) was set by the Food and Nutrition Board in 1998 when the RDA was revised.

Drug interactions

A number of drugs reduce the absorption of vitamin B₁₂. Proton pump inhibitors (e.g., omeprazole and lansoprazole), used for therapy of Zollinger-Ellison syndrome and gastroesophageal reflux disease (GERD), markedly decrease stomach acid secretion required for the release of vitamin B₁₂ from food but not supplements. Long-term use of proton pump inhibitors has been found to decrease blood vitamin B₁₂ levels. However, vitamin B₁₂ deficiency does not generally develop until after at least three years of continuous therapy. Another class of gastric acid inhibitors known as H₂-receptor antagonists (e.g., Tagamet, Pepsid, Zantac), often used to treat peptic ulcer disease, has also been found to decrease the absorption of vitamin B₁₂ from food. Because inhibition of gastric acid secretion is not as prolonged as with proton pump inhibitors H₂-receptor antagonists have not been found to cause overt vitamin B₁₂ deficiency even after long-term use. Individuals taking drugs that inhibit gastric acid secretion should consider taking vitamin B₁₂ in the form of a supplement, because gastric acid is not required for its absorption. Other drugs found to inhibit the absorption of vitamin B₁₂ from food include cholestyramine (a bile acid-binding resin used in the treatment of high cholesterol), chloramphenicol, neomycin (antibiotics), and colchicine (anti-gout). Metformin, a medication for individuals with type 2 (non-insulin dependent) diabetes, decreases vitamin B₁₂ absorption by tying up free calcium required for absorption of the IF- B₁₂ complex. This effect is correctable by drinking milk or taking calcium carbonate tablets along with food or supplements. Previous reports that megadoses of vitamin C resulted in the destruction of vitamin B₁₂ have not been supported and may have been an artifact of the assay used to measure vitamin B₁₂ levels.

Nitrous oxide, a commonly used anesthetic inhibits both vitamin B₁₂ dependent enzymes and can produce many of the clinical features of vitamin B₁₂ deficiency, such as megaloblastic anemia or neuropathy. Because nitrous oxide is commonly used for surgery in the elderly, some experts feel vitamin B₁₂ deficiency should be ruled out prior to its use.

Large doses of folic acid given to an individual with an undiagnosed vitamin B₁₂ deficiency could correct megaloblastic anemia without correcting the underlying vitamin B₁₂ deficiency, leaving the individual at risk of developing irreversible neurologic damage. For this reason the Food and Nutrition Board of the Institute of Medicine advises that all adults limit their intake of folic acid (supplements and fortification) to 1000 mcg (1 mg) daily.

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