B12 Deficiency


The true prevalence of vitamin B12 deficiency tends to be underestimated for several reasons. The common misconception that most vitamin B12 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 be vitamin B12 deficient due to food-cobalamin malabsorption (FCM). FCM occurs when vitamin B12 bound to proteins in foods cannot be cleaved and released.[9] Any process that interferes with gastric acid production can lead to this impairment.[8],[9] Atrophic gastritis, with resulting hypochlorhydia, is a major cause, especially in the elderly.[8],[10] In addition, the use of gastric acid suppression medications such as proton pump inhibitors (PPIs) and histamine 2 receptor antagonists (H2RA’s) for two or more years identifies as a population at higher risk of B12 deficiency (as a result of food-bound Cbl malabsorption), independent of additional risk factors.[10],[11]

The traditional cut-off point to define clinical vitamin B12 deficiency is 200 pg/ml (148 pmol/L).[12] However, there is evidence that the sensitivity of this clinical cutoff is poor and that many individuals with what was previously labeled low-normal status have clinical symptoms.[12] Carmel describes vitamin B12 deficiency in two states: Clinical and Subclinical.

Clinical deficiency manifests with hematologic or neurologic signs and symptoms, serum cobalamin levels <200 pg/mL (148 pmol/L), and levels for homocysteine and methylmalonic acid (MMA) that are usually elevated.

Subclinical deficiency includes absent signs and symptoms, although some patients might have subtle changes on neurologic examination; low to low-normal serum cobalamin levels (200–350 pg/mL); and at least one metabolic abnormality (elevated homocysteine or elevated methylmalonic acid), usually mild.[13]

Epidemiological studies show a prevalence of cobalamin deficiency of around 20% (between 5% and 60%, depending on the definition of cobalamin deficiency used in the study) in the general population of industrialized countries.[14] In the Framingham Offspring study, the prevalence of vitamin B12 concentrations was estimated with three descriptive cutoffs for 2,999 subjects between the ages of 26-89.[12]

  1. Serum B12 <200 pg/ml (148 pmol/L)—the current clinical cutoff.
  2. Serum B12 >200 pg/ml and <250 pg/ml (185 pmol/L)—an intermediate cutoff.
  3. Serum B12 >250 pg/ml and <350 pg/ml (258 pmol/L)—a point where individuals still may be at risk of deficiency).

Thirty-nine percent (39%) of subjects had plasma vitamin B12 concentrations <350 pg/ml, 17% had concentrations <250 pg/ml, and 9% had concentrations <200 pg/ml, with little difference between the age groups.[12]

Other countries, such as Japan, have significantly higher recommended levels of B12 than the United States. In Japan, minimum recommended blood levels of B12 are >500 pg/ml (370 pmol/L) a limit associated with psychological and behavioral manifestations, such as cognitive decline, dementia and memory loss,[15] and a level more than twice the current clinical cutoff level in the United States.