Another nail in the coffin of a medical myth

Tradition has it that parenteral therapy is necessary to treat vitamin B-12 malabsorption. In recent years accumulating evidence has suggested the effectiveness of oral treatment. Much of the evidence has been in the form of case control and case series studies. This was the subject of a recent Cochrane review which found two RCTs of oral versus parenteral vitamin replacement, totaling 108 participants. 1000 to 2000 mcg of oral B-12 daily was found equal to a standard parenteral regimen.

Two recent narrative reviews of vitamin B-12 deficiency are linked here. [1] [2] They explain the physiologic rationale for oral replacement and highlight the only recently appreciated and most common cause of B-12 deficiency, known as food-cobalamin malabsorption syndrome. Now believed to be more common than classic pernicious anemia, food-cobalamin malabsorption syndrome is largely a disorder of the elderly. As explained in these reviews a common form of age related gastric atrophy results in deficient secretion of acid and pepsin, which are necessary to strip cobalamin from food protein. Patients with this common disorder can absorb B-12 from pills, but not food. Such patients have a normal Schilling’s test. The disorder is poorly understood, and some cases may be the result of longstanding H. pylori infection.

Food-cobalamin malabsorption is to be distinguished from classic pernicious anemia, an autoimmune disease characterized by antibodies to parietal cells and intrinsic factor. The effectiveness of oral B-12 replacement in such patients is less well understood, but apparently there is an alternate pathway of absorption which is independent of intrinsic factor. The absorptive mechanism is simple diffusion and requires a high concentration gradient, which is provided by the large daily oral doses of 1000-2000 mcg used in the studies.

As suggested in the Cochrane review this evidence, if put into widespread practice, could ease a substantial burden on health care resources. (The clinical effects may be more modest in those patients who derive substantial placebo effect from B-12 shots---anecdotal observation).

A few caveats:
1) The number of patients studied is small. The number with classic PA is smaller still.
2) The effective oral dose is high---1000 to 2000mcg daily.
3) Parenteral therapy has stood the test of time and may be preferable in patients with questionable compliance.
4) If oral treatment is elected the patient should be followed carefully in the short and long term for resolution of neurologic, hematologic and metabolic abnormalities including monitoring of the hemogram, reticulocyte response, homocysteine and methylmalonic acid levels.