Risk Factors for Vitamin B12 Deficiency
“The clinical indications (for cobalamin deficiency) are of prime importance since routine screening tests, such as the blood count, are not always abnormal. The same criteria apply to both sexes and to all age groups, including preterm infants and children.” Amos, 1994
In the United States, most cases of vitamin B12 deficiency are due to malabsorption.
Patient characteristics that increase the likelihood of a vitamin B12 deficiency can be divided broadly into demographic and behavioral characteristics that increase the risk of inadequate dietary intake (malnutrition) and physiologic factors that increase the risk of malabsorption. Some factors, such as advanced age, might increase the risk of both malnutrition and malabsorption. In the United States, most cases of vitamin B12 deficiency are due to malabsorption rather than inadequate intake. We will review the more obvious demographic and behavioral “red flags” of aging and strict vegetarianism and vegan diets and then summarize the less readily apparent but more common physiologic factors that can affect absorption.
Demographic and Behavioral Risk Factors
The risk of developing a vitamin B12 deficiency increases with age.1, 6,16,21-23 The elderly, defined as individuals 65 years of age or older, are more likely to develop a vitamin B12 deficiency because they are at risk for both malabsorption and malnutrition. The frail elderly, especially, might have dietary insufficiency for a number of reasons, including cognitive dysfunction, social isolation, mobility limitations, and poverty.
In contrast to the importance of age, other demographic characteristics, including sex, race, and ethnicity, are not so important for predicting vitamin B12 deficiency. While several studies have found that mild cobalamin deficiency is most common in elderly White men and least common in Black or African-American and Asian-American women, 2,3,16,24 the differences are not sufficient to support sex- or race-specific nutrient recommendations. 10
A patient characteristic that should always raise the index of suspicion is long-term adherence to a strict vegetarian or vegan diet,10,16,25,26 because vegan diets exclude all forms of animal protein, including eggs and dairy products. Thoughtfully planned vegetarian diets that include eggs, milk, and yogurt can provide adequate amounts of vitamin B12. Short-term adherence to strict vegetarian and vegan diets might not cause a problem because of the large amount of vitamin B12 typically stored in the liver. However, it is prudent to advise all vegetarian and vegan patients, particularly if they are elderly or anticipating a pregnancy, to consume synthetic cobalamin daily, either by taking a supplement containing vitamin B12 or eating a serving of vitamin B12–fortified grain products.10 The requirement for vitamin B12 increases for pregnant and lactating women.10 To review the vitamin B12 content of a variety of vegetarian and vegan foods, see http://www.nal.usda.gov/fnic/foodcomp/search/.
Malabsorption is the physiologic cause of vitamin B12 deficiency and can result from a number of conditions. Frequently mentioned are pernicious anemia; 7, 24 atrophic gastritis;3,10,27 gastric surgery (e.g., ileal resection and gastrectomy);11,16,28 presence of a cobalamin-utilizing fish tapeworm such as Diphyllobothrium latum;2,29 and other concurrent diseases such as Crohn disease, HIV infection,30,32 celiac sprue,33,34 and bacterial overgrowth in the small intestine.35 Rare cases have been attributed anesthetic nitrous oxide exposure.2,36
Among the elderly, atrophic gastritis and pernicious anemia are the main causes of malabsorption. Atrophic gastritis often develops as people age. With resulting hypochlorhydria and achlorhydria, the body does not produce enough pepsin and hydrochloric acid to release from protein the food-bound vitamin B12. In pernicious anemia, missing IF needed to attach B12 in the small intestine impairs the uptake of vitamin B12. Undiagnosed and untreated pernicious anemia affects 1%–2% of the elderly population. 24
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