Why Vitamin B12 Deficiency Should be on your Radar Screen

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<strong>Vitamin</strong> <strong>B12</strong> <strong>Deficiency</strong> The first to conceptualize the natural history of a vitamin <strong>B12</strong> deficiency, Her<strong>be</strong>rt noted that vegetarians with dietary vitamin <strong>B12</strong> insufficiency progressed through four stages: serum depletion; cell depletion; biochemical deficiency (defined as elevated levels of Hcy and MMA); and, finally, the classic signs and symptoms of clinical deficiency, such as anemia (Table 2).(9, 15) Table 2. Typical Stages in the Development of a <strong>Vitamin</strong> <strong>B12</strong> <strong>Deficiency</strong>. Her<strong>be</strong>rt, 1994 Stage Manifestation Comment I II III IV Circulating serum <strong>B12</strong> levels depleted Cellular stores of <strong>B12</strong> are depleted Evidence of biochemical deficiency via increases in serum homocysteine and methylmalonic acid Clinical signs and symptoms apparent Patients are typically asymptomatic and can remain in this stage for several years. Patients can remain asymptomatic. This stage can also continue for several years. <strong>Vitamin</strong> <strong>B12</strong> is required for the conversion of these compounds. The spectrum of clinical manifestations is broad and the sequence of symptom development varies markedly. Although this model provides a useful perspective, untreated patients will not necessarily advance through the stages chronologically or linearly. Progression to a later stage is not inevitable, and some patients with evidence of an early stage deficiency might have normal laboratory values when retested.(11) Malabsorption of food-derived cobalamin <strong>be</strong>cause of decreased gastric acid production is a more likely reason for vitamin <strong>B12</strong> deficiency, while malabsorption of cobalamin <strong>be</strong>cause of lack of IF in pernicious anemia is a less prevalent cause.(3) 17
<strong>Vitamin</strong> <strong>B12</strong> <strong>Deficiency</strong> Prevalence of <strong>Vitamin</strong> <strong>B12</strong> <strong>Deficiency</strong> The true prevalence of vitamin <strong>B12</strong> deficiency tends to <strong>be</strong> underestimated for several reasons. The common misconception that most vitamin <strong>B12</strong> deficiencies are due to inadequate dietary intake might lead to overlooking important high-risk groups. Older adults who routinely consume meat and other animal proteins can still <strong>be</strong> vitamin <strong>B12</strong> deficient due to malabsorption. Clinical vitamin <strong>B12</strong> deficiencies are relatively rare. Most patients are far more likely to have mild, subclinical vitamin <strong>B12</strong> deficiency.(1) Most prevalence estimates are based solely on serum vitamin <strong>B12</strong> results. Confusion can arise <strong>be</strong>cause cobalamin values are measured in picomoles per liter (pmol/L) in some research studies, while clinical laboratories express values in picograms per milliliter (pg/mL) or nanograms per liter (ng/L). The most frequently reported threshold value is 200 pg/mL (148 pmol/L).(1, 16) Studies that have established higher cutpoints invariably have reported higher prevalence estimates. In the research literature, some investigators have used diagnostic algorithms that combine serum <strong>B12</strong> results with one or more additional laboratory findings, typically either serum Hcy or MMA.(1, 4, 17, 18) Depending on the approach used, the additional test findings have raised(4, 18, 19) or lowered(6, 19, 20) the observed prevalence of vitamin <strong>B12</strong> deficiency compared with findings based solely on serum vitamin B 12 levels. Unpublished data from the National Health and Nutrition Examination Survey (NHANES) 2001–2004 in Table 3 stratified by age have estimated that 1 (3.2%) of every 31 adults 51 years of age or older in the United States has a low vitamin <strong>B12</strong> serum level. Most of these people are ambulatory and do not have overt symptoms of vitamin <strong>B12</strong> deficiency. 18 Conversions ng/L = pg/mL pmol/L = pg/mL x 0.738 pg/mL = pmol/L ÷ 0.738 Keep in mind that ng/L has the same value as pg/mL but conversion to pmol/L requires multiplication of pg/mL by 0.738 (200 pg/mL x 0.738 = 148 pmol/L).
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Why Vitamin B12 Deficiency Should be on your Radar Screen

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