The condition affects 5% of adults older than 60 years.1 Vitamin B12 (hereafter B12) is a cofactor for enzymes involved in DNA synthesis and is necessary for normal bone marrow and central nervous system function.2 Its absorption in the distal ileum requires intrinsic factor.

Common symptoms are fatigue and pallor, but features can also include cognitive deficits, subacute combined degeneration of the dorsal and lateral columns of the spinal cord and peripheral neuropathies. 2 Hematologic findings include macrocytic anemia, hypersegmented neutrophils on blood film and pancytopenia.2 Plasma concentrations of B12 should be assessed if macrocytosis is identified.

Marginal deficiency, defined by plasma concentrations of 148–221 pmol/L, is observed in 20% of patients older than 60 years and seldom leads to hematologic abnormalities.1 Testing for methylmalonic acid and homocysteine levels can be considered in patients with an equivocal plasma concentration of B12 and symptoms or signs compatible with deficiency.2

Common causes include autoimmune gastritis (which causes pernicious anemia), diets low in animal products, malabsorptive states (e.g., postgastrointestinal surgery), and medications, including metformin, proton pump inhibitors and histamine-2 receptor antagonists.2,3

Daily high-dose (≥ 1000 μg) oral B12 is as effective as intramuscular supplementation. 4 Concentrations of B12 can be monitored every 3–6 months while on treatment; hematologic abnormalities should resolve within weeks and neuropsychiatric symptoms within months.2 Urgent referral can be considered for patients with severe sequelae of deficiency (e.g., pancytopenia, neurologic deficits). If reversible causes are addressed, supplementation can be stopped once B12 concentrations normalize, whereas patients with irreversible causes often require lifelong treatment. Parenteral B12 is often prescribed without evidence of deficiency and fails to improve nonspecific complaints, including cognitive dysfunction and fatigue.5,6 This practice should be discouraged.

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Competing interests: Yulia Lin reports grants from Canadian Blood Services, consulting fees from Choosing Wisely Canada and participation on the data safety monitoring board of the RAPID trial. She is chair of the Ontario Transfusion Coordinators Network. No other competing interests were declared.

This article has been peer reviewed.

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