[B.sub.12] deficiency: a look beyond pernicious anemia: food-[B.sub.12] malabsorption—not pernicious anemia—is the leading cause of [B.sub.12] malabsorption. It's also very subtle

Journal of Family Practice, July, 2007 by Emmanuel Andres, Laure Federici, Stephan Affenberger, Josep Vidal-Alaball, Noureddine Henoun Loikili, Jacques Zimmer, Georges Kaltenbach

Practice recommendations

* Mild, preclinical [B.sub.12] deficiency is associated with food-[B.sub.12] malabsorption more often than with pernicious anemia. (C)

* The classic treatment for [B.sub.12] deficiency--particularly when the cause is not a dietary deficiency--is 100 to 1000 mcg per month of cyanocobalamin, IM. (B)

* Oral crystalline cyanocobalamin is an effective treatment for food[B.sub.12] malabsorption, though it's effectiveness in the long term has not been demonstrated. (B)

If an image of an elderly patient with pernicious anemia is the first thing that comes to mind when you think of [B.sub.12] deficiency, take note: That image could obfuscate a more common case of [B.sub.12] deficiency--one caused by food-[B.sub.12] malabsorption.

Food-[B.sub.12] malabsorption, characterized by the inability to release [B.sub.12] from food or its binding proteins, is actually the leading cause of [B.sub.12] malabsorption, especially in elderly patients. (1-4) And unlike pernicious anemia, it's more likely to be associated with mild, preclinical [B.sub.12] deficiency. (1,5)

Spotting this form of [B.sub.12] deficiency requires that you focus on its nuances, such as its link to Helicobacter pylori infection and long-term antacid and biguanide use. It also requires that you consider not only a patient's serum [B.sub.12] levels, but his homocysteine and methylmalonic acid levels, since they are considered more sensitive indicators of cobalamin deficiency. (6) Keying in on these indicators early will ensure prompt treatment, which typically includes intramuscular injections of the vitamin, but which could revolve around a more convenient option: oral [B.sub.12].

A common problem that comes in many shades

[B.sub.12] deficiency is common in elderly patients (7) and its incidence increases with age. (7,8) The Framingham study revealed a prevalence of 12% among elderly people living in the community. (8) Other studies focusing on those who are in institutions or who are sick and malnourished, have suggested a higher prevalence of 30% to 40%. (3,9)

The clinical manifestations of [B.sub.12] deficiency are highly polymorphic and of varying severity ranging from milder conditions such as the common sensory neuropathy and isolated anomalies of macrocytosis and hypersegmentation of neutrophils, to severe disorders, including combined sclerosis of the spinal cord, hemolytic anemia and even pancytopenia (TABLE 1). (1,5,6,10-13)

[B.sub.12] deficiency is often unrecognized or not investigated because the clinical manifestations can be very subtle. In fact, one of its manifestations--mild memory loss--can mimic the early stages of dementia. (14)

Further muddying the waters is the fact that [B.sub.12] deficiency appears to be more common among patients who have a variety of chronic neurologic conditions such as stroke, Parkinson's disease, dementia, Alzheimer's disease, and depression--although it is unclear if these are causal relationships. (1,15) In our own studies in which we administered [B.sub.12] to patients with dementia, we did not observe any improvement. (2,5) Other studies have had similar results. (16,17)

[B.sub.12] deficiency is typically defined in terms of the serum concentration of [B.sub.12], as well as the concentration of homocysteine and methyl malonic acid--2 components of the cobalamin metabolic pathway. A deficiency exists if the patient's blood work reveals the following: (2,18)

* Serum [B.sub.12] levels <150 pmol/L and either total serum homocysteine levels >13 pmol/L or methylmalonic acid levels >0.4 pmol/L (in the absence of renal failure and folate and vitamin [B.sub.6] deficiencies).

* Low serum holotranscobalamin levels <35 pmol/L.

The "classic" cause is not the most common

The principal causes of [B.sub.12] deficiency include pernicious anemia, dietary deficiency, postsurgical malabsorption, and food-[B.sub.12] malabsorption. Of note is the fact that there is typically a 5- to 10-year delay between the onset of [B.sub.12] deficiency and the development of clinical illness, in part because of hepatic stores of cobalamin (>1.5 mg). (1,19)

In elderly patients, [B.sub.12] deficiency is classically caused by pernicious anemia, (3,7) the principal characteristics of which have been reported in detail in several reviews. (20-22) The one thing, of course, that bears repeating is that this form of anemia is associated with a lack of intrinsic factor, which facilitates the absorption of [B.sub.12].

[B.sub.12] deficiency caused by dietary deficiency is more rare. Dietary causes of deficiency are limited to elderly people who are already malnourished, such as those living in institutions (they may consume inadequate amounts of foods containing vitamin [B.sub.12]) and strict vegetarians. (1,19) (A typical Western diet contributes 3-30 mcg of [B.sub.12] per day towards the recommended dietary allowance set by the Food and Nutrition Board of the Institute of Medicine (US) of 2.4 mcg/day for adults and 2.6 to 2.8 mcg/day during pregnancy. (23))

Over the past 20 years, postsurgical malabsorption of [B.sub.12] 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)