Efficacy and Safety of Fortification and Supplementation with Vitamin B 12 : Biochemical and Physiological Effects

Abstract

Long known as an uncommon but serious medical disorder requiring medical management, vitamin B₁₂ 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 B₁₂ levels, few of whom are deficient. The spread of folic acid fortification has also introduced concerns about folate's potentially adverse neurologic consequences in persons with undetected vitamin B₁₂ deficiency. Fortification with vitamin B₁₂ may prove more complicated than fortification with folic acid, however, because the bioavailability of vitamin B₁₂ is limited. Bioavailability for those who need the vitamin B₁₂ the most is especially poor, because they often have malabsorption affecting either classical intrinsic factor-mediated absorption or food-vitamin B₁₂ absorption. Moreover, new evidence shows that many elderly persons respond poorly to daily oral doses under 500 μg (1 μg = 0.74 nmol), even if they do not have classical malabsorption, which suggests that proposed fortification with 1 to 10 μg may be ineffective. Those least in need of vitamin B₁₂ 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 B₁₂ 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 B₁₂, such as vegetarians, nursing mothers, and the elderly.