The success of
folic acid fortification has generated consideration of similar fortification with
cobalamin for its own sake but more so to mitigate possible neurologic risks from increased
folate intake by
cobalamin-deficient persons. However, the
folate model itself, the success of which was predicted by successful clinical trials and the known favorable facts of high
folic acid bioavailability and the infrequency of
folate malabsorption, may not apply to
cobalamin fortification.
Cobalamin bioavailability is more restricted than
folic acid and is unfortunately poorest in persons deficient in
cobalamin. Moreover, clinical trials to demonstrate actual health benefits of relevant oral doses have not yet been done in persons with mild subclinical deficiency, who are the only practical targets of
cobalamin fortification because >94% of persons with clinically overt
cobalamin deficiency have severe malabsorption and therefore cannot respond to normal fortification doses. However, it is only in the severely malabsorptive disorders, such as
pernicious anemia, not subclinical deficiency, that neurologic deterioration following
folic acid therapy has been described to date. It is still unknown whether mild deficiency states, which usually arise from normal absorption or only food-bound
cobalamin malabsorption, have real health consequences or how often they progress to overt clinical
cobalamin deficiency. Reports of cognitive or other risks in the common subclinical deficiency state, although worrisome, have been inconsistent. Moreover, their observational nature proved neither causative connections nor documented health benefits. Extensive work, especially randomized clinical trials, must be done before mandatory dietary intervention on a national scale can be justified.