Ines Egli

Worldwide prevalence of anaemia, WHO Vitamin and Mineral Nutrition Information System, 1993-2005.

OBJECTIVE To provide current global and regional estimates of anaemia prevalence and number of persons affected in the total population and by population subgroup. SETTING AND DESIGN We used anaemia prevalence data from the WHO Vitamin and Mineral Nutrition Information System for 1993-2005 to generate anaemia prevalence estimates for countries with data representative at the national level or at the first administrative level that is below the national level. For countries without eligible data, we employed regression-based estimates, which used the UN Human Development Index (HDI) and other health indicators. We combined country estimates, weighted by their population, to estimate anaemia prevalence at the global level, by UN Regions and by category of human development. RESULTS Survey data covered 48.8 % of the global population, 76.1 % of preschool-aged children, 69.0 % of pregnant women and 73.5 % of non-pregnant women. The estimated global anaemia prevalence is 24.8 % (95 % CI 22.9, 26.7 %), affecting 1.62 billion people (95 % CI 1.50, 1.74 billion). Estimated anaemia prevalence is 47.4 % (95 % CI 45.7, 49.1 %) in preschool-aged children, 41.8 % (95 % CI 39.9, 43.8 %) in pregnant women and 30.2 % (95 % CI 28.7, 31.6 %) in non-pregnant women. In numbers, 293 million (95 % CI 282, 303 million) preschool-aged children, 56 million (95 % CI 54, 59 million) pregnant women and 468 million (95 % CI 446, 491 million) non-pregnant women are affected. CONCLUSION Anaemia affects one-quarter of the worlds population and is concentrated in preschool-aged children and women, making it a global public health problem. Data on relative contributions of causal factors are lacking, however, which makes it difficult to effectively address the problem.

Polyphenols and Phytic Acid Contribute to the Low Iron Bioavailability from Common Beans in Young Women

Low iron absorption from common beans might contribute to iron deficiency in countries where beans are a staple food. High levels of phytic acid (PA) and polyphenols (PP) inhibit iron absorption; however, the effect of bean PP on iron absorption in humans has not been demonstrated and, with respect to variety selection, the relative importance of PP and PA is unclear. To evaluate the influence of bean PP relative to PA on iron absorption in humans, 6 stable iron isotope absorption studies were conducted in women (16 or 17 per study). Bean PP (20, 50, and 200 mg) were added in studies 1-3 as red bean hulls to a bread meal. Studies 4- 6 investigated the influence on iron absorption of PP removal and dephytinization of whole red bean porridge and PP removal from dephytinized porridge. Iron absorption was lowered by 14% with 50 mg PP (P < 0.05) and by 45% with 200 mg PP (P < 0.001). The mean iron absorption from whole bean porridge was 2.5%. PP and PA removal increased absorption 2.6-fold (P < 0.001) and removal of PP from dephytinized porridge doubled absorption (P < 0.001). Between-study comparisons indicated that dephytinization did not increase iron absorption in the presence of PP, but in their absence, absorption increased 3.4-fold (P < 0.001). These data suggest that in countries where beans are a staple food, PP and PA concentrations should be considered when selecting bean varieties for human consumption. Lowering only one inhibitor will have a modest influence on iron absorption.

Optimization of a phytase-containing micronutrient powder with low amounts of highly bioavailable iron for in-home fortification of complementary foods.

BACKGROUND In-home fortification of complementary foods with micronutrient powders containing low amounts of iron may be potentially safer than powders containing high amounts of iron. However, low iron doses have little nutritional effect, unless iron absorption is high. OBJECTIVE The objective was to maximize iron absorption from a low-iron micronutrient powder for in-home fortification by testing combinations of iron as NaFeEDTA, ascorbic acid, and a microbial phytase active at gut pH. In addition, a recently proposed enhancer of iron absorption, L-alpha-glycerophosphocholine (GPC), was tested. DESIGN In 6 separate iron-absorption studies using a crossover design, women (n = 101) consumed whole-maize porridge fortified with 3 mg stable isotope-labeled FeSO4 or NaFeEDTA with different combinations of enhancers added to the meals at the time of consumption. Incorporation of iron isotopes into erythrocytes 14 d later was measured. RESULTS The addition of phytase when iron was present as either NaFeEDTA or FeSO4, with or without ascorbic acid, significantly increased iron absorption. The combined addition of phytase, ascorbic acid, and NaFeEDTA resulted in an absorption of 7.4%, compared with an absorption of 1.5% from FeSO4 without enhancers in the same meal (P < 0.001). The addition of ascorbic acid did not significantly increase iron absorption from NaFeEDTA, and the addition of calcium did not significantly inhibit iron absorption from NaFeEDTA in the presence of ascorbic acid. The addition of L-alpha-glycerophosphocholine did not significantly increase iron absorption. CONCLUSION Optimization of the micronutrient powder increased iron absorption from a highly inhibitory meal approximately 5-fold. This approach may allow for effective, untargeted in-home fortification of complementary foods with low amounts of highly bioavailable iron.

Afebrile Plasmodium falciparum parasitemia decreases absorption of fortification iron but does not affect systemic iron utilization: a double stable-isotope study in young Beninese women

BACKGROUND Iron deficiency anemia (IDA) affects many young women in sub-Saharan Africa. Its etiology is multifactorial, but the major cause is low dietary iron bioavailability exacerbated by parasitic infections such as malaria. OBJECTIVE We investigated whether asymptomatic Plasmodium falciparum parasitemia in Beninese women would impair absorption of dietary iron or utilization of circulating iron. DESIGN Iron absorption and utilization from an iron-fortified sorghum-based meal were estimated by using oral and intravenous isotope labels in 23 afebrile women with a positive malaria smear (asexual P. falciparum parasitemia; > 500 parasites/μL blood). The women were studied while infected, treated, and then restudied 10 d after treatment. Iron status, hepcidin, and inflammation indexes were measured before and after treatment. RESULTS Treatment reduced low-grade inflammation, as reflected by decreases in serum ferritin, C-reactive protein, interleukin-6, interleukin-8, and interleukin-10 (P < 0.05); this was accompanied by a reduction in median serum hepcidin of ≈ 50%, from 2.7 to 1.4 nmol/L (P < 0.005). Treatment decreased serum erythropoietin and growth differentiation factor 15 (P < 0.05). Clearance of parasitemia increased geometric mean dietary iron absorption (from 10.2% to 17.6%; P = 0.008) but did not affect systemic iron utilization (85.0% compared with 83.1%; NS). CONCLUSIONS Dietary iron absorption is reduced by ≈ 40% in asymptomatic P. falciparum parasitemia, likely because of low-grade inflammation and its modulation of circulating hepcidin. Because asymptomatic parasitemia has a protracted course and is very common in malarial areas, this effect may contribute to IDA and blunt the efficacy of iron supplementation and fortification programs. This trial was registered at clinicaltrials.gov as NCT01108939.

Stable iron isotope studies in Rwandese women indicate that the common bean has limited potential as a vehicle for iron biofortification.

Biofortification of plants is a new approach to combat iron deficiency. Common beans (Phaseolus vulgaris) can be bred with a higher iron concentration but are rich in iron absorption inhibitors, phytic acid (PA), and polyphenols (PP). To evaluate the potential of beans to combat iron deficiency, three iron absorption studies were carried out in 61 Rwandese women with low iron status. Studies 1 and 2 compared iron absorption from high and low PP beans, similar in PA and iron, fed as bean puree in a double meal design or with rice and potatoes as multiple meals. Study 3 compared iron absorption from high and normal iron beans with similar PP levels and a PA:iron molar ratio, fed with potatoes or rice in multiple meals. Iron absorption was measured as erythrocyte incorporation of stable iron isotopes. In study 1, iron absorption from the high PP bean (3.4%) was 27% lower (P < 0.01) than from low PP bean (4.7%), but when fed in multiple meals (study 2), there was no difference (7 and 7.4%, respectively; P > 0.05). In study 3, iron absorption from the high iron bean (3.8%) was 40% lower (P < 0.001) than from the normal iron bean (6.3%), resulting in equal amounts of iron absorbed. When beans were combined with other meal components in multiple meals, high PP concentration had no negative impact on iron absorption. However, the quantity of iron absorbed from composite meals with high iron beans was no higher than with normal iron beans, indicating that efficacious iron biofortification may be difficult to achieve in beans rich in PA and PP.

Total Iron Absorption by Young Women from Iron-Biofortified Pearl Millet Composite Meals Is Double That from Regular Millet Meals but Less Than That from Post-Harvest Iron-Fortified Millet Meals

Iron biofortification of pearl millet (Pennisetum glaucum) is a promising approach to combat iron deficiency (ID) in the millet-consuming communities of developing countries. To evaluate the potential of iron-biofortified millet to provide additional bioavailable iron compared with regular millet and post-harvest iron-fortified millet, an iron absorption study was conducted in 20 Beninese women with marginal iron status. Composite test meals consisting of millet paste based on regular-iron, iron-biofortified, or post-harvest iron-fortified pearl millet flour accompanied by a leafy vegetable sauce or an okra sauce were fed as multiple meals for 5 d. Iron absorption was measured as erythrocyte incorporation of stable iron isotopes. Fractional iron absorption from test meals based on regular-iron millet (7.5%) did not differ from iron-biofortified millet meals (7.5%; P = 1.0), resulting in a higher quantity of total iron absorbed from the meals based on iron-biofortified millet (1125 vs. 527 μg; P < 0.0001). Fractional iron absorption from post-harvest iron-fortified millet meals (10.4%) was higher than from regular-iron and iron-biofortified millet meals (P < 0.05 and P < 0.01, respectively), resulting in a higher quantity of total iron absorbed from the post-harvest iron-fortified millet meals (1500 μg; P < 0.0001 and P < 0.05, respectively). Results indicate that consumption of iron-biofortified millet would double the amount of iron absorbed and, although fractional absorption of iron from biofortification is less than that from fortification, iron-biofortified millet should be highly effective in combatting ID in millet-consuming populations.

Inulin modifies the bifidobacteria population, fecal lactate concentration, and fecal pH but does not influence iron absorption in women with low iron status

BACKGROUND Bioavailability of nonheme iron is influenced by the concentration of inhibitors and enhancers in the diet. The fructans inulin and oligofructose have been shown to improve iron absorption in animals through colonic uptake, but this has not been confirmed in humans. OBJECTIVE The aim of the intervention study was to evaluate the influence of inulin on iron absorption, bifidobacteria, total bacteria, short-chain fatty acids (SCFAs), and fecal pH in women with low iron status (plasma ferritin <25 μg/L). DESIGN The subjects (n = 32) consumed inulin or placebo 3 times/d (∼20 g/d) for 4 wk, separated by a 2-wk washout period. Iron absorption was measured after 3 wk of inulin and placebo consumption from a standard test meal by using stable-iron-isotope techniques. Fecal bacteria were measured by quantitative polymerase chain reaction, and fecal acids by HPLC. RESULTS Mean fractional iron absorption in the inulin (15.2%; 95% CI: 8.0%, 28.9%) and placebo (13.3%; 95% CI: 8.1%, 24.3%) periods did not differ significantly (P = 0.10). Inulin decreased fecal pH (P < 0.001) and increased fecal bifidobacteria (P < 0.001) and fecal lactate (P < 0.001) but had no effect on fecal SCFAs and total bacteria. Changes in lactate and acetate concentrations were positively correlated with changes in propionate (P < 0.001) and butyrate (P < 0.02) concentrations, respectively. Iron absorption correlated with fecal pH in the placebo period (P < 0.01) but not in the inulin period (P = 0.37). CONCLUSION Although inulin showed prebiotic activity, we were unable to show an increase in iron absorption in women with low iron status. This trial was registered at clinicaltrials.gov as NCT0148309.

Plasma hepcidin is a modest predictor of dietary iron bioavailability in humans, whereas oral iron loading, measured by stable-isotope appearance curves, increases plasma hepcidin

BACKGROUND Plasma hepcidin appears to be a major regulator of iron absorption and homeostasis, but there are few data in humans. OBJECTIVES With the use of iron stable isotopes, we aimed to determine whether circulating hepcidin predicts dietary iron bioavailability, to quantify the amount of absorbed iron after oral iron loading, and to measure the plasma hepcidin response. DESIGN In the first study, young women (n = 98) with an iron status varying from iron deficiency anemia to iron sufficiency (women with serum ferritin concentrations 25-40 microg/L were not included) were given stable isotope-labeled test meals (n = 196) containing ferrous sulfate, ferrous fumarate, or ferric pyrophosphate, after which plasma hepcidin and iron bioavailability were measured. In the second study, iron-sufficient men (n = 4) were given 3.8- and 60-mg oral doses of labeled ferrous sulfate. The stable isotope appearance curve was determined, and the plasma hepcidin response was measured over 6 h. RESULTS In study 1, plasma hepcidin and plasma ferritin were strongly correlated (r = 0.79, P < 0.001). Plasma hepcidin significantly, but modestly, predicted iron bioavailability from ferrous sulfate and ferrous fumarate (r = -0.51 and -0.46, respectively; P < 0.0001) but not from ferric pyrophosphate (r = -0.30, P = 0.056, respectively). In study 2, the 3.8-mg dose increased mean circulating absorbed iron to a peak of 0.42 micromol/L at 60 min but did not increase plasma hepcidin, The 60-mg dose increased mean circulating absorbed iron to a peak of 5.9 micromol/L at 120 min and produced an approximately 30% increase in mean plasma hepcidin at 6 h (P < 0.01). CONCLUSIONS Plasma hepcidin is only a modest predictor of dietary iron bioavailability in humans. Oral iron loading, measured by stable-isotope appearance curves, increases circulating hepcidin.

Phytic Acid Concentration Influences Iron Bioavailability from Biofortified Beans in Rwandese Women with Low Iron Status

BACKGROUND The common bean is a staple crop in many African and Latin American countries and is the focus of biofortification initiatives. Bean iron concentration has been doubled by selective plant breeding, but the additional iron is reported to be of low bioavailability, most likely due to high phytic acid (PA) concentrations. OBJECTIVE The present study evaluated the impact of PA on iron bioavailability from iron-biofortified beans. METHODS Iron absorption, based on erythrocyte incorporation of stable iron isotopes, was measured in 22 Rwandese women who consumed multiple, composite bean meals with potatoes or rice in a crossover design. Iron absorption from meals containing biofortified beans (8.8 mg Fe, 1320 mg PA/100 g) and control beans (5.4 mg Fe, 980 mg PA/100 g) was measured with beans containing either their native PA concentration or with beans that were ∼50% dephytinized or >95% dephytinized. RESULTS The iron concentration of the cooked composite meals with biofortified beans was 54% higher than in the same meals with control beans. With native PA concentrations, fractional iron absorption from the control bean meals was 9.2%, 30% higher than that from the biofortified bean meals (P < 0.001). The quantity of iron absorbed from the biofortified bean meals (406 μg) was 19% higher (P < 0.05) than that from the control bean meals. With ∼50% and >95% dephytinization, the quantity of iron absorbed from the biofortified bean meals increased to 599 and 746 μg, respectively, which was 37% (P < 0.005) and 51% (P < 0.0001) higher than from the control bean meals. CONCLUSIONS PA strongly decreases iron bioavailability from iron-biofortified beans, and a high PA concentration is an important impediment to the optimal effectiveness of bean iron biofortification. Plant breeders should focus on lowering the PA concentration of high-iron beans. This trial was registered at clinicaltrials.gov as NCT01521273.

Genetic Reduction of Phytate in Common Bean (Phaseolus vulgaris L.) Seeds Increases Iron Absorption in Young Women

Iron bioavailability from common beans is negatively influenced by phytic acid (PA) and polyphenols (PPs). Newly developed low-PA (lpa) beans with 90% less PA and variable PPs might improve iron bioavailability. The aim of this study was to evaluate the influence of lpa beans on iron bioavailability in women (n = 20). We compared iron absorption from 4 different beans using a paired, double meal, crossover design. Iron absorption was measured as erythrocyte incorporation of stable iron isotopes (Fe(57), Fe(58)) from 2 lpa bean lines, one high in PPs (means ± SDs; PA = 124 ± 10 mg/100 g; PPs = 462 ± 25 mg/100 g) and one low in PPs (PA = 70 ± 10 mg/100 g; PPs = 54 ± 2 mg/100 g). The other 2 beans used were their parents with a normal PA concentration, one high in PPs (PA = 1030 ± 30 mg/100 g; PPs = 676 ± 19 mg/100 g) and one low in PPs (PA = 1360 ± 10 mg/100 g; PPs = 58 ± 1 mg/100 g). Fractional iron absorption from the lpa bean high in PPs was 6.1% (95% CI: 2.6, 14.7), which was 60 and 130% higher compared with the parent high in PPs (P < 0.001) and low in PPs (P < 0.001), respectively. The total amount of iron absorbed per test meal from the lpa bean high in PPs (372 μg; 95% CI: 160, 890) was 60 and 163% higher compared with the parent high in PPs (P < 0.001) and low in PPs (P < 0.001), respectively. Fractional iron absorption from the lpa line low in PPs (4%; 95% CI: 1.8, 8.7) was 50% higher and the total amount of iron absorbed per test meal (261 μg; 95% CI: 120, 570) was 85% higher than iron from the parent low in PPs (P < 0.001). There was no difference between the lpa beans high or low in PPs or between the parents high or low in PPs. A 90% reduction in PA leads to an increase in bioavailable iron from beans, independent of the PP concentration. The lpa mutation could be a key tool for improving iron bioavailability from beans.