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.
Vitamin B-12 deficiency and depletion are common in wealthier countries, particularly among the elderly, and are most prevalent in poorer populations around the world. This prevalence was underestimated in the past for several reasons, including the erroneous belief that deficiency is unlikely except in strict vegetarians or patients with pernicious anemia, and that it usually takes 20 y for stores of the vitamin to become depleted. This article reviews the prevalence of deficiency and its underlying causes, which is relevant to assessing the potential benefits of fortifying flour with this vitamin.
DIAGNOSIS OF DEFICIENCY
A diagnosis of vitamin B-12 deficiency is usually made on the basis of serum or plasma vitamin B-12 concentration, with deficiency currently defined as a concentration < 148 pmol/L (200 pg/mL) and marginal status defined as a concentration of 148–221 pmol/L. The gold-standard indicator is elevated serum (or less commonly, urinary) methylmalonic acid (MMA). Recently, a cutoff of >210 nmol/L has been proposed, ie, the 95th percentile for vitamin B-12–replete participants with normal renal function in the National Health and Nutrition Examination Survey in the United States (1). The limitations of MMA as an indicator include the cost of analysis, the need for mass spectrometry, and, especially in developing countries, the possibility of concentrations being increased by bacterial overgrowth. Although vitamin B-12 deficiency is the major cause of elevated plasma total homocysteine (tHcy) in folate-replete populations such as in the US elderly after the folic acid fortification of flour (2), in other locations deficiencies of folate, riboflavin, and vitamin B-6 must be ruled out because these too will increase tHcy. However, if vitamin B-12 supplementation or fortification of a population group lowers tHcy, this can be used as an indicator of improved status (3). Megaloblastic anemia does not usually result from chronic, marginal depletion of the vitamin caused by low dietary intake (4) but occurs more commonly in pernicious anemia and severe vitamin B-12 deficiency (serum vitamin B-12 < 120–150 pmol/L).
PREVALENCE OF DEFICIENCY IN SURVEYS
Serum vitamin B-12 concentrations in the US population were reported in the National Health and Nutrition Examination Surveys from 1999 to 2002 (1, 5). The prevalence of deficiency (serum vitamin B-12 < 148 pmol/L) varied by age group and affected 3% of those aged 20–39 y, 4% of those aged 40–59 y, and 6% of persons aged 70 y. Deficiency was present in <1% of children and adolescents but was 3% in children aged <4 y (the youngest age group reported). Marginal depletion (serum vitamin B-12: 148–221 pmol/L) was more common and occurred in 14–16% of those aged 20–59 y and >20% of those >60 y. Plasma MMA concentrations were markedly higher after age 60 y. Of >1600 elderly (age 60 y) California Hispanics in the Sacramento Area Latino Study on Aging (SALSA), 6% had plasma vitamin B-12 in the range of deficiency and an additional 16% had marginal status, with evidence of further decline in plasma vitamin B-12 with age (6). The prevalence of vitamin B-12 deficiency (serum B-12 150 pmol/L) increased substantially after age 69 y in 3 UK surveys (combined n = 3511); it affected about 1 in 20 people aged 65–74 y and at least 1 in 10 of those aged 75 y (7, 8).
Across studies in Latin America, 40% of children and adults had deficient or marginal status (9), including a nationally representative sample of women and children in the 1999 Mexican National Nutrition Survey. The reported prevalence of deficient and marginal values is much higher in African and Asian countries, eg, 70% in Kenyan school children (10, 11), 80% in Indian preschoolers (12), and 70% in Indian adults (13).
LOW INTAKE AND RISK OF DEFICIENCY
The 2 main causes of vitamin B-12 deficiency are inadequate dietary intake and, in the elderly, malabsorption of the vitamin from food. Contrary to popular belief, not only strict vegetarians (vegans) are at high risk of vitamin B-12 deficiency, and there is strong evidence that status reflects usual intake across a wide range. In the United States and Canada, the Estimated Average Requirement is 0.7–2.0 µg/d across the life span, whereas the respective Recommended Dietary Allowance is 0.9–2.4 µg/d. The vitamin is present only in animal-source foods (ASFs) or fortified foods. In the large EPIC study in the United Kingdom, intakes increased progressively with ASF intake, averaging 0.4 µg for vegans, 2.6 µg for lactoovovegetarians, 5.0 µg for those who also consumed fish, and 7.2 µg for consumers of meat (omnivores) (14). Numerous other studies on smaller population groups confirmed that both vitamin B-12 intake and serum vitamin B-12 concentrations increase progressively from vegans to lactoovovegetarians, to those who consume fish or some meat, to omnivores (15–17).
ASF intake may be restricted for cultural or religious reasons and, by many people in the world, because of low income. Food and Agriculture Organization food balance sheets reveal that most of the world's population consumes <20% of their energy as ASFs, with many countries in Africa consuming <10%, compared with >20% in wealthier regions and 40% in the United States. Predictably, lower intakes are associated with a higher prevalence of deficient and marginal serum B-12 concentrations; strong correlations were found in all studies that measured both vitamin B-12 intake and serum vitamin B-12 (10–17).
Fortified foods, especially ready-to-eat cereals, and supplements can be important sources of vitamin B-12. In the US Framingham Offspring Study, 16% of those aged 26–83 y had serum vitamin B-12 <185 pmol/L and 9% had values <148 pmol/L (18). Mean intake of the vitamin was 9 µg/d. Intake from all sources was higher in persons with serum vitamin B-12 >185 pmol/L than in those with serum vitamin B-12 <148 pmol/L, including supplements (1.5 compared with 0.4 µg/d) and fortified cereals (0.6 compared with 0.3 µg/d). Overall, plasma vitamin B-12 increased by 45 pmol/L for each doubling of intake, with response to supplements and cereals similar to that produced by other foods. In nonconsumers of supplements, for each doubling of intake, plasma vitamin B-12 was increased by 24 pmol/L with fortified cereals, 39 pmol/L with dairy products, and only 12 pmol/L with meat, fish, and poultry. Thus, it is clear that animal-source or fortified foods affect serum vitamin B-12 across the usual range of daily intake.
Plasma vitamin B-12 concentrations plateaued at intakes >10 µg/d in the Framingham Offspring Study. This is consistent with earlier observations by Chanarin (19) who summarized studies that measured vitamin B-12 absorption from radioactively labeled aqueous solutions and foods. Although >70% of the vitamin is absorbed when intake is in the range of 0.1–0.5 µg, the ileal receptors for the vitamin B-12–intrinsic factor complex become saturated with higher intakes such that absorption falls to 50% of a 1-µg dose, 15% of a 10-µg dose, and 3% of a 25–50-µg dose (Figure 1). The maximum amount that can be absorbed from a 5–50-µg single dose is 1.5 µg. Above 25 µg, only 1% of a dose is absorbed, by passive diffusion, which explains why the relative increase in serum vitamin B-12 is related to the log of the dose. In healthy Danish women, serum vitamin B-12 and other vitamin B-12 status indicators appeared to plateau at an intake (from food + supplements) >6 µg/d (20), but in part this is expected because of the lower efficiency of absorption of the vitamin at higher intakes.
And of course I initially heard about it via Mercola: