Efficacy and safety of fortification and supplementation of vitamin B12:: Biochemical and physiological effects

Long known as an uncommon but serious medical disorder requiring medical management, vitamin B-12 deficiency is now seen to be common worldwide, but it is in a quite different form than traditionally envisioned. Most of the newly recognized deficiency is subclinical in nature, its health impact and natural history are uncertain, and its prevalence has been greatly inflated by also including persons with low-normal vitamin B-12 levels, few of whom are deficient. The spread of folic acid fortification has also introduced concerns about folate potentially adverse neurologic consequences in persons with undetected vitamin B-12 deficiency. Fortification with vitamin B-12 may prove more complicated than fortification with folic acid, however, because the bioavailability of vitamin B-12 is limited. Bioavailability for those who need the vitamin B-12 the most is especially poor, because they often have malabsorption affecting either classical intrinsic factor-mediated absorption or food-vitamin B-12 absorption. Moreover, new evidence shows that many elderly persons respond poorly to daily oral doses under 500 mu g (1 mu g = 0. 74 nmol), even if they do not have classical malabsorption, which suggests that proposed fortification with 1 to 10 mu g may be ineffective. Those least in need of vitamin B-12 usually have normal absorption and are thus at greatest risk for whatever unknown adverse effects of high-dose fortification might emerge, such as the effects of excess accumulation of cyanocobalamin. Studies are needed to define the still unproven health benefits of vitamin B-12 fortification, the optimal levels of fortification, the stability of such fortification, interactions with other nutrients, and any possible adverse effects on healthy persons. The answers will permit formulation of appropriately informed decisions about mandatory fortification or (because fortification may prove a poor choice) about targeted supplementation in subpopulations with special needs for additional vitamin B-12 such as vegetarians, nursing mothers, and the elderly.