Por Que Fortificar Con Vitamina B12

Is it time for vitamin B-12 fortification? What are the questions?1–4
Ralph Green
ABSTRACT Since the introduction of folic acid fortification of flour 10 y ago, an initiative to consider fortifying flour with vitamin B-12 has gained momentum in the United States. The impetus for this move stems from several considerations, including some evidence that a proportion of neural tube defect pregnanciesmay be the result of vitamin B-12 rather than folate deficiency. However, no interventional trials have taken place to show the efficacy of vitamin B-12 supplementation or fortification in the primary prevention or recurrence of neural tube defect pregnancies, as was the case with folic acid. Other reasons put forward for the institution of vitamin B-12 fortification include the high prevalence ofvitamin B-12 deficiency in certain demographic groups, including the elderly and the young in some countries. Much of this deficiency, however, is subclinical and not associated with manifest morbidity. Moreover, individuals affected by the most severe cases of vitamin B-12 deficiency that are associated with morbidity would not benefit from the concentrations of vitamin B-12 fortification that arepractical or that are being considered, because such individuals suffer from malabsorption of vitamin B-12 rather than from an inadequacy of intake of the vitamin. In addition to the well-recognized complications of vitamin B12 deficiency, such as macrocytic anemia and neurological complications affecting sensory and motor function, more subtle effects have also been described, including osteopenia,neurocognitive impairment, and increased vascular disease risk associated with elevated homocysteine. This analysis focuses on the research questions that are pertinent to the consideration of whether or not to introduce mandatory vitamin B-12 fortification in the United States. Am J Clin Nutr 2009;89(suppl):712S–6S.

INTRODUCTION

Mandatory fortification of flour with folic acid was introduced firstin the United States and then in Canada ’10 y ago to reduce the incidence of neural tube defect pregnancies. This public health measure has clearly been efficacious on the basis of estimates of a 20–50% reduction of neural tube defect pregnancies and births (1, 2). Other possible consequences of folic acid fortification are now emerging, some of which are potentially beneficial and others perhapsundesirable. The folate status of the entire US population has shifted. Folate deficiency has been almost completely eradicated, and the entire distribution of serum and red blood cell folate concentrations has shifted to states of sufficiency and even excess (3–5). Homocysteine concentrations have been lowered and the prevalence of hyperhomocysteinemia, a risk factor for vascular

disease, has beenmarkedly reduced (6). In the folic acid fortification era, vitamin B-12 deficiency has emerged as the most common modifiable risk factor for hyperhomocysteinemia (7). Some data suggest that a decline in stroke mortality in the United States and Canada coincides with the introduction of folic acid fortification in those countries (8). On the other hand, reduced natural killer cell cytotoxicity, whichis important in the host innate immune response to infection and malignancy, is decreased in association with elevated concentrations of unmetabolized folic acid, which occurs with the long-term consumption of folic-acid-fortified foods and supplements (9). Recent observations report an association between the introduction of folic acid fortification and an observed increased incidence of colonicneoplasia (10, 11). Folate may also play a beneficial role in cancer because it is required for a critical DNA repair pathway involving DNA synthesis and repair (12). This apparently paradoxical effect may relate to the timing of folate administration in relation to the stage of the cancer (13). The role of folic acid or folate intake as a risk factor in several cancers remains unsettled at this...