In considering the vitamin B-12 fortification of flour, it is important to know who is at risk of vitamin B-12 deficiency and whether those individuals would benefit from flour fortification. This article reviews current knowledge of the prevalence and causes of vitamin B-12 deficiency and considers whether fortification would improve the status of deficient subgroups of the population. In large surveys in the United States and the United Kingdom, ≈6% of those aged ≥60 y are vitamin B-12 deficient (plasma vitamin B-12 < 148 pmol/L), with the prevalence of deficiency increasing with age. Closer to 20% have marginal status (plasma vitamin B-12: 148–221 pmol/L) in later life. In developing countries, deficiency is much more common, starting in early life and persisting across the life span. Inadequate intake, due to low consumption of animal-source foods, is the main cause of low serum vitamin B-12 in younger adults and likely the main cause in poor populations worldwide; in most studies, serum vitamin B-12 concentration is correlated with intake of this vitamin. In older persons, food-bound cobalamin malabsorption becomes the predominant cause of deficiency, at least in part due to gastric atrophy, but it is likely that most elderly can absorb the vitamin from fortified food. Fortification of flour with vitamin B-12 is likely to improve the status of most persons with low stores of this vitamin. However, intervention studies are still needed to assess efficacy and functional benefits of increasing intake of the amounts likely to be consumed in flour, including in elderly persons with varying degrees of gastric atrophy.

This review describes current knowledge of the main causes of vitamin B₁₂and folate deficiency. The most common explanations for poor vitamin B₁₂status are a low dietary intake of the vitamin (i.e., a low intake of animal-source foods) and malabsorption. Although it has long been known that strict vegetarians (vegans) are at risk for vitamin B₁₂deficiency, evidence now indicates that low intakes of animal-source foods, such as occur in some lacto-ovo vegetarians and many less-industrialized countries, cause vitamin B₁₂depletion. Malabsorption of the vitamin is most commonly observed as food-bound cobalamin malabsorption due to gastric atrophy in the elderly, and probably as a result of Helicobacter pylori infection. There is growing evidence that gene polymorphisms in transcobalamins affect plasma vitamin B₁₂concentrations. The primary cause of folate deficiency is low intake of sources rich in the vitamin, such as legumes and green leafy vegetables, and the consumption of these foods may explain why folate status can be adequate in relatively poor populations. Other situations in which the risk of folate deficiency increases include lactation and alcoholism.

Infants should be exclusively breastfed for the first 6 mo of life. However, maternal deficiency of some micronutrients, conveniently classified as G

Two core nutrient intake reference values (NRVs) are required for assessing the adequacy and safety of nutrient intakes for population groups: the average requirement (AR) and the tolerable upper level of intake (UL). Applications of such assessments include providing advice to improve intakes, formulating complementary foods, estimating the amounts of nutrients to be added to fortified foods and monitoring changes in intake, and product labeling at the global, national, or regional level. However, there is a lack of unity across country-level organizations in the methodological approach used to derive NRVs, and ARs and ULs are lacking in many compilations, thus limiting the ability to assess nutrient intakes for their population groups. Because physiological requirements vary little across populations globally, and setting reference values requires determining an acceptable level of uncertainty, it is feasible to adapt current recommendations from different sources to harmonize these core reference values. The objective of this review is to demonstrate an approach for harmonizing the NRVs for ARs (here termed "H-ARs") and ULs ("H-ULs") that can be applied on a global scale to assessing intakes across populations. The approach incorporates the framework and terminology recommended by reports from the United Nations University, the National Academies of Sciences, Engineering, and Medicine (NASEM), the Institute of Medicine (IOM), and the European Food Safety Authority (EFSA). After reviewing available alternatives, the proposed harmonized values were selected from standards set by EFSA (for Europe) and the IOM (for the United States and Canada), giving priority to those published most recently. Justifications for the proposed values are presented, along with discussion of their limitations. Ideally, these methods should be further reviewed by an international group of experts. Meanwhile, the H-ARs and H-ULs suggested in this review can be used to assess intakes of populations for many applications in global and regional contexts.

Deficiencies of multiple micronutrients (MMN) usually coexist in developing countries, but supplements have usually provided only 1 or 2 micronutrien

Vitamin B-12 is a cofactor for 2 enzymes. In the cytoplasm, methionine synthase requires vitamin B-12 in the form of methylcobalamin and catalyzes the conversio