B₁₂ deficiency: A look beyond pernicious anemia

Over the past 20 years, postsurgical malabsorption of B₁₂ has been on the decline, due in large part to the decreasing frequency of gastrectomy and surgical resection of the terminal small intestine.^1,2,5 There are, however, several disorders commonly seen in gastroenterology practice that may be associated with cobalamin malabsorption. These include deficiency in the exocrine function of the pancreas after chronic pancreatitis (usually alcoholic), lymphomas or tuberculosis (of the intestine), Crohn’s disease, Whipple’s disease, and occasionally celiac disease.^3,13

Rounding out the list of causes of B₁₂ deficiency is food-B₁₂ malabsorption, which is the leading cause of B₁₂ malabsorption—especially in elderly patients.^1-4 In our own studies in which we have followed more than 300 patients with a documented B₁₂ deficiency, food-B₁₂ malabsorption accounts for about 60% to 70% of the cases of B₁₂ deficiency in elderly patients, whereas pernicious anemia accounts for only 15% to 25%.^5,24 In our study of 172 hospitalized patients with B₁₂ deficiency (median age, 70), 53% had food-B₁₂ malabsorption.⁵

A form of malabsorption that’s tough to spot

Food-B₁₂ malabsorption is a syndrome characterized by the inability to release B₁₂ from food or intestinal transport proteins, particularly in the presence of hypochlorhydria, in which the absorption of “unbound” B₁₂ is normal. As various studies have shown,^4,5,24 this syndrome is defined by B₁₂ deficiency in the presence of sufficient food-B₁₂ intake and normal Schilling test results, which rules out pernicious anemia. In theory, indisputable evidence of food-B₁₂ malabsorption comes from using a modified Schilling test, which uses radioactive B₁₂ bound to animal proteins (eg, salmon, trout) and reveals malabsorption when the results of a standard Schilling test are normal.^1,5,24

Some authors have speculated about the significance of B₁₂ deficiency related to food-cobalamin malabsorption,¹ because many patients have only mild clinical or hematological features. Several of our patients, however, have had significant features classically associated with pernicious anemia, including polyneuropathy, confusion, dementia, medullar-combined sclerosis, anemia, and pancytopenia.⁵ Nevertheless, the partial nature of this form of malabsorption might produce a more slowly progressive depletion of B₁₂ than does the more complete malabsorption engendered by disruption of intrinsic factor–mediated absorption. The slower progression of depletion probably explains why mild, preclinical deficiency is associated with food-B₁₂ malabsorption more often than with pernicious anemia.^1,5

H pylori, antacid use should raise suspicions

Food-B₁₂ malabsorption is caused primarily by atrophic gastritis.⁵ More than 40% of patients older than 80 years have gastric atrophy that might (or might not) be related to H pylori infection.^3,25 Other factors that contribute to food-B₁₂ malabsorption in elderly people include:

• Chronic carriage of H pylori and intestinal microbial proliferation (in which case B₁₂ deficiency can be corrected by antibiotic treatment)^25,26
• Long-term ingestion of antacids, including H₂-receptor antagonists and proton-pump inhibitors,^27,28 particularly among patients with Zollinger-Ellison syndrome^29,30
• Long-term ingestion of biguanides (metformin)^31-33
• Chronic alcoholism
• Surgery or gastric reconstruction (eg, bypass surgery for obesity)
• Partial pancreatic exocrine failure^1,5
• Sjögren’s syndrome or systemic sclerosis³⁴

In our research involving 92 elderly patients (mean age: 76 years) with food-B₁₂ malabsorption,⁵ we found at least one of the associated conditions or agents listed at left in 60% of the patients. These conditions mainly included atrophic gastritis (H pylori infection) in 30% of the patients and long-term metformin or antacid intake in 20% of the elderly patients.

TABLE 2
French hospital findings support use of oral B₁₂ treatment^38-41,45