Vitamin B12 deficiency: Risk factors and approach to prevention

Risk factor	Preferred approach to prevention
Insufficient dietary intake: Vegan or strict vegetarian diet Pregnancy or lactating with limited intake of animal protein Neonate breastfed by mother with vitamin B12 deficiency	Provide oral vitamin B12 supplementation: 2.4 mcg daily (adult RDA) or more is sufficient for most patients 2.6 mcg daily for pregnancy 2.8 mcg daily for breastfeeding Ensure that breastfeeding mothers are vitamin B12 replete
Inability to release vitamin B12 from food proteins (reversible causes): Untreated chronic Helicobacter pylori infection Chronic anti-acid therapy: Antacids Proton pump inhibitors Histamine receptor 2 blockers Chronic excess alcohol use	Treat H. pylori infection Review need for chronic anti-acid therapy Reduce alcohol use Monitoring or supplementation may be appropriate for individuals who cannot reverse the underlying cause
Gastric/bariatric surgery*	Provide routine supplementation with either: Oral vitamin B12 (350 to 1000 mcg daily) or IM (or deep subcutaneous) vitamin B12 1000 mcg per month (cyanocobalamin) or 1000 mcg every two to three months (hydroxocobalamin)
Inability to absorb vitamin B12-intrinsic factor complex: Metformin use^¶ Pancreatic insufficiency Small intestinal bacterial overgrowth Small intestinal inflammation Small intestinal surgery Fish tapeworm infection	Treat reversible infections (bacterial overgrowth, tapeworm) or inflammation Monitor vitamin B12 levels (once a year is reasonable, test at any time if symptoms occur) Some patients may reasonably choose to take a supplement rather than undergo monitoring
Inactivation of vitamin B12 and inhibition of cofactor function: Nitrous oxide^¶ (inhalation anesthetic or recreational use)	Avoid nitrous oxide in susceptible individuals Perioperative monitoring of the CBC; maintain a low threshold to evaluate any abnormalities Maintain a low threshold for measuring vitamin B12 levels when evaluating neurologic or neuropsychiatric symptoms Sometimes these individuals have normal vitamin B12 levels but the vitamin is dysfunctional, and testing of MMA is required

This table lists risk factors for which prevention and/or monitoring are appropriate; it does not address treatment once vitamin B12 deficiency is diagnosed. A comprehensive discussion of the causes of vitamin B12 deficiency (including pernicious anemia, heritable/genetic disorders, and others) and their treatment is presented in UpToDate. All individuals with vitamin B12 deficiency should have the cause determined, because some causes such as pernicious anemia carry additional risks and require additional monitoring or testing, some causes are reversible with treatment, and some causes require lifelong supplementation.

For conditions with a variable risk of causing vitamin B12 deficiency, monitoring vitamin B12 levels is often preferred, but some individuals may reasonably choose supplementation.
For established vitamin B12 deficiency, correction of the deficiency followed by routine supplementation is suggested.

CBC: complete blood count; IM: intramuscular; MMA: methylmalonic acid; RDA: recommended dietary allowance.

* May also be associated with decreased or absent intrinsic factor.

¶ The mechanism of metformin-induced vitamin B12 deficiency involves decreased intestinal calcium. The mechanism of nitrous oxide is inactivation of functional vitamin B12.

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Vitamin B12 deficiency: Risk factors and approach to prevention