Mandatory fortification of the food supply with cobalamin: an idea whose time has not yet come

Abstract

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.Mandatory fortifications of food have had important successes but are never steps to be taken lightly. Typically, such steps were taken when a nutrient deficiency was widespread and had serious health consequences (not just biochemical changes) and the nutrient's properties readily permitted its assimilation by the population of interest without posing health risks to the nondeficient population. Mandatory fortification with cobalamin (Cbl) is now being contemplated for various reasons. Many of the reasons are related to the folic acid fortification that occurred in the late 1990s in the United States and elsewhere. Therefore, folic acid fortification will be discussed briefly before focusing on the two critical questions, the answers to which should determine whether fortification with Cbl will improve the public's health.Correspondence to: Ralph Carmel, rac9001@nyp.org.

Laboratory Evaluation for Vitamin B12 Deficiency: The Case for Cascade Testing

“…8,25,26 From a cost-effective public health standpoint, some might advocate widespread oral vitamin B 12 supplementation without laboratory testing to provide insurance against subclinical B 12 deficiency. 27 Although the general public and commercial health food suppliers have a seemingly insatiable appetite for "fountain of youth" dietary supplements, it seems premature to recommend mandatory fortification of the food supply without well-conducted, randomized clinical trials. Several patients in the current study were given vitamin B 12 injections solely at their request, and sometimes for psychological benefit; patient education would seem more appropriate.…”

Contribution of food sources to the vitamin B12 status of South Indian children from a birth cohort recruited in the city of Mysore

“…If subclinical cobalamin deficiency is shown to be an important problem, other affordable approaches will need to be found to improve vitamin B 12 intakes in India, especially among vegetarians. These may include food fortification (16) . Maternal B 12 status B 12 concentrations in our children showed a strong positive association with maternal concentrations during pregnancy.…”

“…Severe B 12 deficiency, as seen in pernicious anaemia, is characterised by megaloblastic anaemia and/or neurological dysfunction. However, subclinical cobalamin deficiency, currently defined as asymptomatic, mild metabolic abnormalities, may be of greater public health importance (16) . Recent research has related low B 12 status with an increased risk of adiposity and gestational diabetes in India (17) .…”

Haematological implications of folate food fortification

“…Regardless of the uncertainties about the amount of B 12 to be added, Carmel [19] has argued that clinical trials to demonstrate actual health benefits of relevant oral doses have not been done in persons with subclinical B 12 deficiency, who are the only practical targets of B 12 fortification, because more than 94% of persons with clinically overt B 12 deficiency have severe malabsorption. It is only in the severely malabsorptive disorders such as PA, not subclinical deficiency, that neurological deterioration following folic acid therapy has been described.…”