Fractional Iron Absorption Research Articles

Kinetics of iron absorption from ferrous fumarate with and without galacto-oligosaccharides determined from stable isotope appearance curves in women

ABSTRACTBackgroundPrebiotic galacto-oligosaccharides (GOS) are novel enhancers of iron absorption from ferrous fumarate (FeFum). However, the mechanism(s) of this effect, and whether it occurs in the proximal or distal gut, are uncertain.ObjectivesWe studied: 1) in vitro, the effect of GOS on iron solubility and dialyzability from FeFum; 2) in volunteers, the absorption kinetics of FeFum given with and without GOS using stable isotope appearance curves (SIAC).MethodsWe measured iron solubility at various pH and dialyzability from FeFum with and without GOS. In crossover design, iron-depleted women [n = 11; median serum ferritin (SF) 15.2; IQR: 12.6–21.2 µg/L] received 2 14-mg iron doses as labeled (57Fe,58Fe) FeFum 14 d apart with and without 15 g GOS in randomly assigned order. Multiple blood samples were collected over a time period of 24 h and 14 d later to determine SIAC and fractional iron absorption (FIA), respectively. SIAC data were fitted using nonlinear mixed effects modeling to a 1-compartment model with first-order absorption, and AUC and time of peak serum isotope concentration (tmax) were calculated.ResultsIron dialyzability was 75% higher with GOS (P < 0.001) and iron solubility was more than doubled at pH 4 and 6 with GOS [both P < 0.001]. Mean ± SD AUC (5830.9 ± 4717.3 μg/min with GOS, 4454.0 ± 3260.7 μg/min for control), and median (IQR) FIA (20.3% (8.6%–38.7%) with GOS, and 15.6% (10.6%–24.8% f)or control) were not different with compared to without GOS (P = 0.064; P = 0.080). Mean ±SD tmax was not altered with GOS (3.08 ± 0.47 h with GOS; 2.80 ±0.50 h for control; P = 0.096). Iron bioavailability significantly increased with decreasing SF and this effect was significantly enhanced by GOS (P = 0.037, interaction of GOS with SF).ConclusionsGOS increases iron solubility from FeFum at physiological pH characteristic of the proximal duodenum. The absorption kinetics in vivo are consistent with effects on iron absorption in the proximal, rather than distal, parts of the gut. There was no overall effect of GOS on FIA in vivo, but the interaction of GOS and SF on FIA might benefit iron-deficient women, an effect potentially mediated by the higher solubility shown in vitro. This study was registered at clinicaltrials.gov as NCT03996421.

Iron Bioavailability from Infant Cereals Containing Whole Grains and Pulses: A Stable Isotope Study in Malawian Children

BackgroundCompared with infant cereals based on refined grains, an infant cereal containing whole grains (WGs) and pulses with adequate amounts of ascorbic acid to protect against absorption inhibitors could be a healthier source of well-absorbed iron. However, iron absorption from such cereals is uncertain. ObjectiveWe measured iron bioavailability from ferrous fumarate (Fefum) added to commercial infant cereals containing 1) refined wheat flour (reference meal), 2) WG wheat and lentil flour (WG-wheat-lentil), 3) WG wheat and chickpea flour (WG-wheat-chickpeas), and 4) WG oat flour (WG-oat) and from ferrous bisglycinate (FeBG) added to the same oat-based cereal (WG-oat-FeBG). MethodsIn a prospective, single-blinded randomized crossover study, 6- to 14-mo-old Malawian children (n = 30) consumed 25-g servings of all 5 test meals containing 2.25 mg stable isotope-labeled iron and 13.5 mg ascorbic acid. Fractional iron absorption (FIA) was assessed by erythrocyte incorporation of isotopes after 14 d. Comparisons were made using linear mixed models. ResultsSeventy percent of the children were anemic and 67% were iron deficient. Geometric mean FIA percentages (–SD, +SD) from the cereals were as follows: 1) refined wheat, 12.1 (4.8, 30.6); 2) WG-wheat-lentil, 15.8 (6.6, 37.6); 3) WG-wheat-chickpeas, 12.8 (5.5, 29.8); and 4) WG-oat, 9.2 (3.9, 21.5) and 7.4 (2.9, 18.9) from WG-oat-FeBG. Meal predicted FIA (P ≤ 0.001), whereas in pairwise comparisons, only WG-oat-FeBG was significantly different compared with the refined wheat meal (P = 0.02). In addition, FIAs from WG-wheat-lentil and WG-wheat-chickpeas were significantly higher than from WG-oat (P = 0.002 and P = 0.04, respectively) and WG-oat-FeBG (P < 0.001 and P = 0.004, respectively). ConclusionIn Malawian children, when given with ascorbic acid at a molar ratio of 2:1, iron bioavailability from Fefum-fortified infant cereals containing WG wheat and pulses is ≈13−15%, whereas that from FeBG- and Fefum-fortified infant cereals based on WG oats is ≈7−9%.

Comparative Effects between Oral Lactoferrin and Ferrous Sulfate Supplementation on Iron-Deficiency Anemia: A Comprehensive Review and Meta-Analysis of Clinical Trials.

Ferrous sulfate is a commonly used iron supplement for the correction of iron-deficiency anemia but with frequent gastrointestinal side effects. Milk-derived iron-binding glycoprotein lactoferrin possesses well gastrointestinal tolerance and fewer side effects caused by the intake of high-dose iron. However, the underlying mechanism of the iron-enhancing effect of lactoferrin remains unclear. In addition, the comparative efficacies between lactoferrin and ferrous sulfate are also remained to be determined. We conducted a systematic review and meta-analysis on published intervention studies to investigate how lactoferrin modulate iron metabolism and evaluate the comparative effects between lactoferrin and ferrous sulfate supplementation on iron absorption, iron storage, erythropoiesis and inflammation. Lactoferrin supplementation had better effects on serum iron (WMD: 41.44 ug/dL; p < 0.00001), ferritin (WMD: 13.60 ng/mL; p = 0.003) and hemoglobin concentration (11.80 g/dL; p < 0.00001), but a reducing effect on fractional iron absorption (WMD: −2.08%; p = 0.02) and IL-6 levels (WMD: −45.59 pg/mL; p < 0.00001) compared with ferrous sulfate. In conclusion, this study supports lactoferrin as a superior supplement to ferrous sulfate regarding the improvement in serum iron parameters and hemoglobin levels. Considering the weak influence of lactoferrin on iron absorption, the anti-inflammation effect of lactoferrin may be the potential mechanism to explain its efficacy on iron status and erythropoiesis.

A test to measure oral iron absorption and glucose tolerance simultaneously in 18 to 55 year old premenopausal women

Several methods are available to measure iron absorption (IA). The oral iron absorption test (OIAT) measures IA based on a change in serum iron (ΔSeFe) concentration after an oral iron dose. The objective of this study was to validate the OIAT by comparing it to the reference method of fractional iron absorption (FIA) using red blood cell incorporation of stable iron isotopes from a labeled iron dose. A second objective was to assess whether the OIAT could be done simultaneously with an oral glucose tolerance test (OGTT), since iron deficiency and glucose intolerance may coexist, especially among overweight individuals with low-grade inflammation. In this prospective experimental study, 116 women were enrolled and IA was measured using two different approaches 1) FIA from a labeled test meal containing 6mg of 57Fe and 2) the OIAT assessing ΔSeFe at 2h after the intake of 100mg oral iron, done simultaneously with an OGTT. Markers of iron status, glycaemia and inflammation, and serum hepcidin, were measured. Prevalence of anemia and iron deficiency (defined as low serum ferritin) were 21% and 14%, respectively. ΔSeFe during the OIAT-OGTT was positively associated with FIA (r=0.578, p<0.001). ΔSeFe was not significantly correlated with markers of glucose and insulin metabolism during the OIAT-OGTT. The combined OIAT and OGTT method described here correlates well with FIA measured by stable iron isotopes, and could provide information on both IA and glucose tolerance in a single 2-h test, decreasing the burden on patients. clinicaltrials.gov (NCT03642223).

Tea Consumption Reduces Iron Bioavailability from NaFeEDTA in Nonanemic Women and Women with Iron Deficiency Anemia: Stable Iron Isotope Studies in Morocco

BackgroundAvailable data suggest that polyphenols from tea can inhibit iron absorption from ferric sodium EDTA (NaFeEDTA), but previous studies were done in small groups of mostly nonanemic adults. Morocco recently introduced national wheat flour fortification with NaFeEDTA, but tea is the national beverage and is consumed with most meals. ObjectivesOur objective was to quantify bioavailability of iron from NaFeEDTA when added to a wheat flour–based meal in both nonanemic women and women with iron deficiency anemia (IDA), when consumed with and without traditional Moroccan green tea. MethodsWe recruited 2 groups of healthy Moroccan women (n = 46): women with IDA (n = 25; hemoglobin <12 g/dL, serum ferritin <15 μg/L) and nonanemic women (n = 21). Each group received in random order 2 standardized test meals containing 6 mg Fe as isotopically labeled NaFeEDTA and either 300 mL of tea or water. Fractional iron absorption (FIA) was measured by the erythrocyte incorporation of stable iron isotopes after 14 d. We performed linear mixed-model analysis and post hoc sample t tests to assess the effects of group and tea on FIA. ResultsThe polyphenol content of the tea serving was 492 mg. Tea consumption reduced iron absorption from NaFeEDTA by >85% in both IDA and nonanemic women. There were group (P < 0.001) and tea (P < 0.001) effects on FIA, but no group by tea interaction (P = 0.312). Median (IQR) FIA (%) in women with IDA from test meals consumed without and with tea was 36.7 (24.2–39.8) and 4.1 (2.8–6.1), respectively (P < 0.001). Median (IQR) FIA (%) in nonanemic women from test meals consumed without and with tea was 16.7 (9.2–24.2) and 1.4 (0.8–2.9), respectively (P < 0.001). ConclusionsFIA from wheat flour–based meals without and with tea was ∼2-fold higher in women with IDA than in nonanemic women. Providing fortificant iron as NaFeEDTA cannot overcome the inhibition of tea polyphenols on iron absorption, even in IDA, where iron absorption is strongly upregulated. This trial was registered at www.clinicaltrials.gov as NCT02175888.

Measuring Dietary Iron Absorption From Edible Tenebrio molitor and Assessing the Effect of Chitin on Iron Bioavailability: A Stable Iron Isotope Study in Young Women

Abstract Objectives Iron deficiency is estimated to affect up to 1.5–2 billion people worldwide. Edible insects can be a rich source of iron and may have a smaller environmental food print than other animal source foods. Mealworm (Tenebrio molitor) larvae are recognized as an edible insect, but iron bioavailability in humans has not been investigated. Chitin, a major component of insect biomass, is a known iron binder. Our primary objective was to measure fractional iron absorption (FIA) from T.molitor with and without chitin in young women. Secondly, we aimed to assess the effect of the presence of mealworm biomass on iron absorption from iron present in low-phytate maize porridge. Methods Non-anemic females (18–45 years, body weight &amp;lt; 65 kg) were recruited and FIA was measured as erythrocyte incorporation of stable isotopes tracers in red blood cells 14 days after test meal administration. Using a randomized cross over design, three different meals were administered to each subject, consisting of A) a low phytate refined maize porridge with 54FeSO4; B) intrinsically labelled (57Fe) T.molitor with native chitin and extrinsic 58FeSO4; C) intrinsically labelled (57Fe) T.molitor with reduced chitin and extrinsic 58FeSO4. Results Median serum ferritin concentration in the participating subjects (n = 21) was 22.7 µg/L. Iron content in T.molitor larvae was FIA from meals B (58Fe, 5.28%) and C (58Fe, 4.55%) in which mealworm biomass was given in combination with maize porridge did not significantly differ to FIA from maize porridge fed alone (5.84%). In case of intrinsic labelling, FIA from meals B (57Fe, 4.11%) and C (57Fe, 4.03%) were significantly lower compared to maize meal A (P &amp;lt; 0.001). Conclusions FIA from T.molitor was similar to low-phytate containing maize. Presence of mealworm biomass did not enhance or inhibit the FIA of iron present in the maize meal. Furthermore, a chitin reduction process did not show any discernible effect on FIA. T.molitor larvae could be a viable source of iron in the human diet, but iron absorption may be similar to plant-based foods. The study was registered at clinicaltrials.gov as NCT04510831. Funding Sources Coop Research Program, World Food System Center, ETH Zurich, Switzerland.

Kinetics of Iron Absorption From Ferrous Fumarate With Galacto-oligosaccharides Measured by Stable-isotope Appearance Curves in Iron Depleted Women in Switzerland

ObjectivesPrebiotic galacto-oligosaccharides (GOS) have shown promising results in enhancing the absorption of oral supplemental iron in form of ferrous fumarate (FeFum) in iron depleted adults. The mechanism behind this effect is unknown. We aimed to assess the absorption profile of FeFum given with and without GOS using stable isotope appearance curves (SIACs). MethodsWe conducted a controlled, single-center, prospective cross-over trial in iron depleted women between Sept and Nov 2019 at the Laboratory of Human Nutrition, ETH Zurich, Switzerland. All women (n = 11; median SF = 15.2 μg/L) received two supplemental iron doses of 14 mg in form of FeFum containing 6 mg of isotopic tracers (57Fe or 58Fe). The supplemental iron doses were administered in random order on d 1 and 15 after an overnight fast. The supplement combinations were: 1) 57FeFum + 300 ml water; and 2) 58FeFum + 15 g GOS + 300 ml water. Eleven blood samples were collected up to 24 h after administration of the iron supplements to determine serum iron appearance. Fractional iron absorption (FIA) of the isotopic tracers was calculated in whole blood collected 14 days after administration of each of the supplemental iron doses on the basis of the shift in iron isotope ratios according to the principle of isotope dilution. ResultsThere was a trend towards increased FIA and total absolute AUC of the SIAC from FeFum given with 15 g GOS compared to without (P = 0.064; P = 0.080 respectively). Estimated timepoints of the peak serum isotope concentration were not different (P = 0.096). Relative SF and relative bioavailability correlated significantly (P = 0.037). In subjects with a lower SF the increase in bioavailability of iron when given with GOS was more pronounced compared to participants with higher SF. ConclusionsAdding 15 g GOS to FeFum did not result in a different absorption profile compared to without GOS. The enhancing effect of GOS seems to depend on iron status, even though overall the improvement of iron absorption when given with 15 g GOS did not reach significance, probably due to the small sample size. Since women with a low iron status can benefit the most from an increase in iron bioavailability, the use of GOS for the improvement of iron bioavailability from FeFum in women with very low iron stores is promising. Funding SourcesInnosuisse, Swiss Innovation Agency, in collaboration with Antistress AG - Burgerstein Vitamine.

Consumption of a Single Dose of Prebiotic Galacto-Oligosaccharides Does Not Enhance Iron Absorption from Micronutrient Powders in Kenyan Infants: A Stable Iron Isotope Study

BackgroundLong-term feeding of prebiotic galacto-oligosaccharides (GOS) increases iron absorption in African infants, but the underlying mechanism and how long GOS need to be fed to infants to achieve an increase in absorption is uncertain. ObjectivesIn Kenyan infants, we tested whether the addition of GOS to a single test meal would affect iron absorption from a micronutrient powder (MNP) containing ferrous sulfate (FeSO4) and another MNP containing ferrous fumarate (FeFum) and sodium iron ethylenediaminetetraacetate (NaFeEDTA). MethodsIn a randomized-entry, prospective crossover study, iron deficient (87%) and anemic (70%) Kenyan infants (n = 23; mean ± SD age, 9.9 ± 2.1 months) consumed 4 stable iron isotope–labeled maize porridge meals fortified with MNPs containing 5 mg iron as FeFum + NaFeEDTA, or FeSO4, either without or with 7.5 g GOS. The primary outcome, fractional iron absorption (FIA), was assessed by erythrocyte incorporation of isotopic labels. Data were analyzed using a 2-way repeated-measures ANOVA. ResultsThere was no significant interaction between GOS and the iron compounds on FIA, and the addition of GOS did not have a significant effect on FIA. There was a statistically significant difference in FIA between the meals fortified with FeSO4 and with FeFum + NaFeEDTA (P < 0.001).Given with GOS, FIA from FeSO4 was 40% higher than from FeFum + NaFeEDTA (P < 0.001); given without GOS, it was 51% higher (P < 0.01). ConclusionsThe addition of GOS to a single iron-fortified maize porridge test meal in Kenyan infants did not significantly increase iron absorption, suggesting long-term feeding of GOS may be needed to enhance iron absorption at this age. This study was registered at clinicaltrials.gov as NCT02666417.

Investigation of Iron and Zinc Concentrations in Human Milk in Correlation to Maternal Factors: An Observational Pilot Study in Poland.

The aim of this study was to evaluate iron and zinc concentrations in the mature human milk (HM) and to investigate the relationship between these concentrations and maternal factors. HM samples were collected between 4–6 weeks postpartum from 32 healthy, exclusively breastfeeding mothers. The assessment of dietary intake during breastfeeding was based on a food frequency questionnaire and three-day dietary records. Nutritional status of participants was assessed with body mass index and body composition analysis, measured with bioelectrical impedance. HM intake was assessed with infants’ weighting, whereas iron and zinc contents in HM were determined by inductively coupled plasma mass spectrometer. The median intake of HM was 492.5 mL (466–528.5) and the concentrations of HM iron and zinc were 0.33 mg/L (0.26–0.46) and 2.12 mg/L (1.97–2.45), respectively. Maternal total zinc and iron intake (diet + supplementation) was positively correlated with their concentrations in HM. Consumption frequency of meat, vegetables and legumes was revealed to be a significant factor influencing zinc concentration in HM. Regarding iron, it was the consumption frequency of meat, fish and seafood, vegetables and legumes, nuts and seeds. The intake of iron from HM was low, and after assuming a mean fractional iron absorption, it was only 0.038 mg/d. Our results show that maternal diet influences iron and zinc content in HM, suggesting that adequate intake of food rich in investigated minerals may be a positive factor for their concentrations in HM.

Iron Absorption is Greater from Apo-Lactoferrin and is Similar Between Holo-Lactoferrin and Ferrous Sulfate: Stable Iron Isotope Studies in Kenyan Infants

Whether lactoferrin (Lf) binds iron to facilitate its absorption or to sequester iron from potential enteropathogens remains uncertain. Bovine Lf is added to many infant formulas, but previous studies in infants reported that Lf had no effect on or inhibited iron absorption. The effects of the apo (iron-free) or the holo (iron-loaded) forms of Lf on iron absorption are unclear. Our objective was to compare iron absorption from a maize-based porridge containing: 1) labeled ferrous sulfate (FeSO4) alone; 2) labeled FeSO4 given with bovine apo-Lf; and 3) intrinsically labeled bovine holo-Lf. In a crossover study, we measured iron absorption in Kenyan infants (n=25; mean±SD age 4.2±0.9 months; mean±SD hemoglobin 109±11g/L) from maize-based test meals containing: 1) 1.5mg of iron as 54Fe-labeled FeSO4; 2) 1.42mg of iron as 58Fe-labeled FeSO4, given with 1.41g apo-Lf (containing 0.08mg iron); and 3) 1.41g holo-Lf carrying 1.5mg iron as 57Fe. The iron saturation levels of apo- and holo-Lf were 0.56% and 47.26%, respectively primary outcome was fractional iron absorption (FIA), assessed by erythrocyte incorporation of isotopic labels. The FIA from the meal containing apo-Lf+FeSO4 (geometric mean, 9.8%; -SD and +SD, 5.4% and 17.5%) was higher than from the meals containing FeSO4 (geometric mean, 6.3%; -SD and +SD, 3.2% and 12.6%; P=0.002) or holo-Lf (geometric mean, 5.0%; -SD and +SD, 2.8% and 8.9%; P <0.0001). There was no significant difference in FIA when comparing the meals containing holo-Lf versus FeSO4 alone (P=0.24). The amount of iron absorbed from holo-Lf was comparable to that of FeSO4, and the addition of apo-Lf to a test meal containing FeSO4 significantly increased (+56%) iron absorption. These findings suggest that Lf facilitates iron absorption in young infants. Because Lf binds iron with high affinity, it could be a safe way to provide iron to infants in low-income countries, where iron fortificants can adversely affect the gut microbiome and cause diarrhea. This study was registered at clinicaltrials.gov as NCT03617575.

Iron Absorption from Iron-Biofortified Sweetpotato Is Higher Than Regular Sweetpotato in Malawian Women while Iron Absorption from Regular and Iron-Biofortified Potatoes Is High in Peruvian Women

ABSTRACTBackgroundSweetpotato and potato are fast-maturing staple crops and widely consumed in low- and middle-income countries. Conventional breeding to biofortify these crops with iron could improve iron intakes. To our knowledge, iron absorption from sweetpotato and potato has not been assessed.ObjectiveThe aim was to assess iron absorption from regular and iron-biofortified orange-fleshed sweetpotato in Malawi and yellow-fleshed potato and iron-biofortified purple-fleshed potato in Peru.MethodsWe conducted 2 randomized, multiple-meal studies in generally healthy, iron-depleted women of reproductive age. Malawian women (n = 24) received 400 g regular or biofortified sweetpotato test meals and Peruvian women (n = 35) received 500 g regular or biofortified potato test meals. Women consumed the meals at breakfast for 2 wk and were then crossed over to the other variety. We labeled the test meals with 57Fe or 58Fe and measured cumulative erythrocyte incorporation of the labels 14 d after completion of each test-meal sequence to calculate iron absorption. Iron absorption was compared by paired-sample t tests.ResultsThe regular and biofortified orange-fleshed sweetpotato test meals contained 0.55 and 0.97 mg Fe/100 g. Geometric mean (95% CI) fractional iron absorption (FIA) was 5.82% (3.79%, 8.95%) and 6.02% (4.51%, 8.05%), respectively (P = 0.81), resulting in 1.9-fold higher total iron absorption (TIA) from biofortified sweetpotato (P < 0.001). The regular and biofortified potato test meals contained 0.33 and 0.69 mg Fe/100 g. FIA was 28.4% (23.5%, 34.2%) from the regular yellow-fleshed and 13.3% (10.6%, 16.6%) from the biofortified purple-fleshed potato meals, respectively (P < 0.001), resulting in no significant difference in TIA (P = 0.88).ConclusionsFIA from regular yellow-fleshed potato was remarkably high, at 28%. Iron absorbed from both potato test meals covered 33% of the daily absorbed iron requirement for women of reproductive age, while the biofortified orange-fleshed sweetpotato test meal covered 18% of this requirement. High polyphenol concentrations were likely the major inhibitors of iron absorption. These trials were registered at www.clinicaltrials.gov as NCT03840031 (Malawi) and NCT04216030 (Peru).

Compared to Normal-Weight Pregnant Women, Overweight Pregnant Women Fail to Upregulate Iron Absorption in the Third Trimester Despite Iron Deficiency and Their Infants Are Born with Lower Body Iron Stores

Introduction: Overweight/obesity (OWOB) causes low-grade systemic inflammation which induces hepcidin and a reduces fractional iron absorption (FIA) even when iron stores are low. Pregnancy increases iron needs because of the expansion of maternal blood volume and fetal needs. It is unclear whether and/or to what extent OWOB during pregnancy influences FIA, iron supply of the fetus and risk of iron deficiency in mother and newborn. In this study, we (1) determined the impact of maternal OWOB on FIA in pregnancy and on the transfer of iron to the fetus and newborn iron status; (2) confirmed the relationship between BMI, hepcidin, serum ferritin (SF) and inflammatory markers. Methods: In this prospective experimental multi-center case-control study (normal-weight (NW) n=40; OWOB n=37) we administered labeled [57Fe]- or [58Fe]-FeSO4 to women during the 2nd and 3rd trimester of pregnancy. We measured FIA by determining erythrocyte incorporation of iron stable isotopes 14 days after administration. From pregnancy week (PW) 12 until PW 36, iron-, inflammation and hepcidin were monitored. Iron transfer to the fetus was determined isotopically as the concentration of circulating iron in the infant aged three days. We assessed iron status in infants born to NW (n=29) and OWOB (n=31) at age three days, three months and six months. Results: Subject characteristics in PW 12 for the NW/OWOB were: mean (±SD) age: 29±6/ 30±6 years, median (IQR) pre-pregnancy BMI: 21.6 (20.3-23.7)/ 31.6 (28.4-35.9) kg/m2 (p&amp;lt;0.001), mean (±SD) hemoglobin: 12.3±1.1/ 12.4±0.9 g/dL, median (IQR) SF: 27.7 (17.3-48.2)/ 30.6 (16.6-64.4) µg/L and median (IQR) interleukin-6: 1.41 (1.03-1.95)/ 2.37 (1.91-3.85) pg/ml (p&amp;lt;0.001). Independent sample t-test showed no difference in FIA between NW and OWOB in the 2nd trimester with median FIA (IQR) 12.3 (7.2-20.6) and 10.1 (6.9-17.2) % (p=0.788). Despite the OWOB had ≈30% lower body iron stores (BIS) and comparable hepcidin concentrations to the NW in the 3rd trimester, FIA was significantly higher in the NW compared to the OWOB with median FIA (IQR) 22.3 (10.6-33.8) and 12.7 (10.4-18.1) % (p=0.042). In the NW, FIA was upregulated by 80% in the 3rd trimester compared to the 2nd trimester, whereas in the OWOB FIA, it was only upregulated by 25%. Linear mixed effect model analysis (LMM) showed a significant group-effects on weight, IL-6 and CRP throughout pregnancy (all p&amp;lt;0.05), but surprisingly no group-effect on hepcidin. In multiple regression analysis, the main predictor of hepcidin throughout pregnancy was BIS, not inflammation. Iron transfer to the newborn was non-significantly higher in the NW compared to the OWOB with mean (±SD) circulating iron in the newborn at age three days 136.6 ± 42.7 and 126.3 ± 32.4 mg. LMM on infant BIS and on infant serum transferrin receptor (sTfR) over the first six months showed significant group (p=0.024, p=0.046) and time-effects (both p&amp;lt;0.001) with lower BIS and higher sTfR in infants born to OWOB. Median (IQR) BIS at age six months were 7.7 (6.3-8.8) and 6.6 (4.6-9.2) mg/kg bodyweight in infants born to NW and OWOB. Conclusion: In normal pregnancy, FIA increases over time to support increased iron needs of mother and fetus. Our data show a dramatically reduced increase in FIA in OWOB pregnant women in the 3rd trimester, despite low BIS and low hepcidin, and this results in less iron transfer to the fetus. Future molecular studies are needed to clarify the mechanism of reduced FIA and fetal iron transfer in OWOB. To our knowledge, this is the first study assessing the impact of maternal OWOB on infant iron status at multiple time points over the first six months. Our findings strongly argue for careful monitoring of iron status in OWOB pregnancy and for defining a more effective iron supplementation regimen for this population group. Prevalence of anemia in pregnancy and infancy is high, especially in low and middle income countries and is often associated with severe health consequences. If iron status of OWOB pregnant women and their infants could be improved by optimizing iron supplementation guidelines for OWOB, this could have major benefits. Disclosures No relevant conflicts of interest to declare.

Refining Treatment Strategies for Iron Deficient Athletes.

Iron deficiency (ID) is a prevailing nutritional concern amongst the athletic population due to the increased iron demands of this group. Athletes' ability to replenish taxed iron stores is challenging due to the low bioavailability of dietary sources, and the interaction between exercise and hepcidin, the primary iron-regulatory hormone. To date, copious research has explored the link between exercise and iron regulation, with a more recent focus on optimising iron treatment applications. Currently, oral iron supplementation is typically the first avenue of iron replacement therapy beyond nutritional intervention, for treatment of ID athletes. However, many athletes encounter associated gastrointestinal side-effects which can deter them from fulfilling a full-term oral iron treatment plan, generally resulting in sub-optimal treatment efficacy. Consequently, various strategies (e.g. dosage, composition, timing) of oral iron supplementation have been investigated with the goal of increasing fractional iron absorption, reducing gastric irritation, and ultimately improving the efficacy of oral iron therapy. This review explores the various treatment strategies pertinent to athletes and concludes a contemporary strategy of oral iron therapy entailing morning supplementation, ideally within the 30min following morning exercise, and in athletes experiencing gut sensitivity, consumed on alternate days or at lower doses.

The TMPRSS6 variant (SNP rs855791) affects iron metabolism and oral iron absorption - a stable iron isotope study in Taiwanese women.

Genome wide studies have associated TMPRSS6 rs855791 (2321 C>T) with iron status and hepcidin. It is unclear whether this polymorphism affects iron absorption. We administered standardized ricebased test meals containing 4 mg of labeled 57Fe or 58Fe as FeSO4 on alternate days in non-anemic Taiwanese women (n=79, 44 TT variant, 35 CC variant). Fractional iron absorption was measured by erythrocyte incorporation of the tracers 14 days after administration. Compared to the CC variant, iron and transferrin saturation were lower (P=0.001; P<0.001, respectively) and serum hepcidin/transferrin saturation and serum hepcidin/serum iron ratios were higher (P=0.042; P=0.088, respectively) in the TT variant. Serum hepcidin did not differ between the groups (P=0.862). Geometric mean (95% Confidence Interval [CI]) fractional iron absorption, corrected to a serum ferritin of 15 μg/L, was 26.6% (95% CI: 24.0-29.5) in the CC variant and 18.5% (95% CI: 16.2-21.1) in the TT variant (P=0.002). Overall, predictors of iron absorption were: serum ferritin (P<0.001); genetic variant (P=0.032); and hepcidin (P<0.001). In the models by variant, in the CC variant the model explained 67-71% of variability in absorption and serum ferritin was the only significant predictor (P<0.001); while in the TT variant, the model explained only 35-43% of variability, and hemoglobin (P=0.032), soluble transferrin receptor (P=0.004) and hepcidin (P<0.001) were significant predictors. Women with the TMPRSS6 rs855791 (2321 C>T) polymorphism show altered iron homeostasis which affects oral iron absorption and may increase their risk for iron deficiency. The trial was registered as clinicaltrials gov. Identifier: NCT03317873, and funded by the Kaohsiung Chang-Gung Memorial Hospital, Kaohsiung, Taiwan, (grant CMRPG8F0721) and ETH Zurich, Switzerland.

Addition of Whole Wheat Flour During Injera Fermentation Degrades Phytic Acid and Triples Iron Absorption from Fortified Tef in Young Women

Iron deficiency is a major public health concern in Ethiopia, where the traditional diet is based on tef injera. Iron absorption from injera is low due to its high phytic acid (PA) content. We investigated ways to increase iron absorption from FeSO4-fortified tef injera in normal-weight healthy women (aged 21-29 y). Study A (n=22) investigated the influence on fractional iron absorption (FIA) from FeSO4-fortified injera of 1) replacing 10% tef flour with whole wheat flour (a source of wheat phytase), or 2) adding an isolated phytase from Aspergillus niger. Study B (n=18) investigated the influence on FIA of replacing FeSO4 in tef injera with different amounts of NaFeEDTA. In both studies, the iron fortificants were labeled with stable isotopes and FIA was calculated from erythrocyte incorporation of stable iron isotopes 14 d after administration. In study A, the median (IQR) FIA from the 100% tef injera meal was 1.5% (0.7-2.8%). This increased significantly (P<0.05) to 5.3% (2.4-7.1%) on addition of 10% whole wheat flour, and to 3.6% (1.6-6.2%) on addition of A. niger phytase. PA content of the 3 meals was 0.62, 0.20, and 0.02g/meal, respectively. In study B, the median (IQR) FIA from the 100% tef injera meal was 3.3% (1.1-4.4%) and did not change significantly (P>0.05) on replacing 50% or 75% of FeSO4 with NaFeEDTA. FIA from tef injera by young women was very low. NaFeEDTA was ineffective at increasing iron absorption, presumably due to the relatively low EDTA:Fe molar ratios. Phytate degradation, however, greatly increased during tef fermentation on addition of native or isolated phytases. Replacing 10% tef with whole wheat flour during injera fermentation tripled FIA in young women and should be considered as a potential strategy to improve iron status in Ethiopia.

The effect of iron dosing schedules on plasma hepcidin and iron absorption in Kenyan infants

In adults, oral iron doses increase plasma hepcidin (PHep) for 24 h, but not for 48 h, and there is a circadian increase in PHep over the day. Because high PHep decreases fractional iron absorption (FIA), alternate day iron dosing in the morning may be preferable to consecutive day dosing. Whether these effects occur in infants is uncertain. Using stable iron isotopes in Kenyan infants, we compared FIA from morning and afternoon doses and from consecutive, alternate (every second day) and every third day iron doses. In prospective studies, we measured and compared FIA and the PHep response from 1) meals fortified with a 12-mg iron micronutrient powder given in the morning or afternoon (n=22); 2) the same given on consecutive or alternate days (n=21); and 3) a 12-mg iron supplement given on alternate days or every third day (n=24). In total, 65.7% of infants were anemic. In study 1, PHep did not differ between morning and afternoon (P=0.072), and geometric mean FIA[-SD, +SD](%) did not differ between the morning and afternoon doses [15.9 (8.9, 28.6) and 16.1 (8.7, 29.8), P=0.877]. In study 2, PHep was increased 24 h after oral iron (P=0.014), and mean FIA [±SD](%) from the baseline dose [23.3 (10.9)] was greater than that from the consecutive day dose (at 24 h) [20.1 (10.4); P=0.042] but did not differ from the alternate day dose (at 48 h) [20.9 (13.4); P=0.145]. In study 3, PHep was not increased 48 and 72 h after oral iron (P=0.384), and the geometric mean FIA[-SD, +SD](%) from doses given at baseline, alternate days, and every third day did not differ [12.7 (7.3, 21.9), 13.8 (7.8, 24.2), and 14.8 (8.8, 24.8), respectively; P=0.080]. In Kenyan infants given 12 mg oral iron, morning and afternoon doses are comparably absorbed, dosing on consecutive days increases PHep and modestly decreases iron absorption compared with alternate day dosing, and dosing on alternate days or every third day does not increase PHep or decrease absorption. This trial was registered at clinicaltrials.gov as NCT02989311 and NCT03617575.

Acute Consumption of Prebiotic Galacto-Oligosaccharides Increases Iron Absorption from Ferrous Fumarate, but not from Ferrous Sulfate and Ferric Pyrophosphate: Stable Iron Isotope Studies in Iron-Depleted Young Women

Although acute consumption of high doses of prebiotic galacto-oligosaccharides (GOS) increases fractional iron absorption (FIA) from ferrous fumarate (FeFum), it is uncertain if low doses of GOS have this effect. Furthermore, whether GOS improve iron absorption from other commonly used iron compounds and whether ascorbic acid (AA) enhances the effect of GOS on iron absorption from FeFum is unclear. In iron-depleted women [serum ferritin (SF) <30μg/L], we assessed: 1) whether the acute enhancing effect of GOS on FeFum is dose dependent; 2) if GOS would affect FIA from ferrous sulfate (FeSO4) or ferric pyrophosphate (FePP); and 3) if AA and GOS given together enhance FIA from FeFum to a greater extent compared with GOS alone. We recruited 46 women (mean age 22.0 y, mean BMI 21.3kg/m2, median SF 17.1μg/L), and measured FIA from 14mg iron labeled with stable isotopes in the following conditions: 1) FIA from FeFum given with 3.5g, 7g GOS, and without GOS; 2) FIA from FeSO4 and FePP given with and without 15g GOS; and 3) FIA from FeFum given with 7g GOS with and without 93mg AA. FIA was measured as erythrocyte incorporation of stable isotopes after 14 d. Comparisons were made using paired samples t-test or Wilcoxon rank sum test where appropriate. Giving 7g of GOS significantly increased FIA from FeFum (+26%; P=0.039), whereas 3.5g GOS did not (P=0.130). GOS did not significantly increase FIA from FeSO4 (P=0.998) or FePP (P=0.059). FIA from FeFum given with GOS and AA was significantly higher compared with FeFum given with GOS alone (+30%; P <0.001). In iron-depleted women, GOS does not increase FIA from FeSO4 or FePP, but it increases FIA from FeFum. Thus, a combination of FeFum and GOS may be a well-absorbed formula for iron supplements. The study was registered at clinicaltrials.gov as NCT03762148.

Iron Absorption from Bouillon Fortified with Iron-Enriched Aspergillus oryzae Is Higher Than That Fortified with Ferric Pyrophosphate in Young Women

ABSTRACTBackgroundBouillon cubes are a potential vehicle for iron fortification. They are currently fortified with ferric pyrophosphate (FePP), which is known to be poorly absorbed. The objective of this study was to assess the iron absorption of Aspergillus oryzae grown in FePP (ASP-p) and compare it with FePP and ferrous sulfate (FeSO4)–fortified bouillon cubes.MethodsIn 2 single-blinded, crossover studies, healthy women with serum ferritin concentrations <40 μg/L were randomly assigned to consume a rice-vegetable meal with iron-fortified chicken bouillon. Subjects in study I (n = 17, 18–26 y) consumed iron from both iron sources as 57FePP and 58ASP-p (intrinsically labeled with 58FePP) with a meal containing 4.2 mg of total iron provided for 3 d. Study II (n = 18, 18–29 y) was similar except that subjects consumed 57FeSO4 and 58ASP-p. Whole-blood stable isotope enrichment after 14 d was used to measure fractional iron absorption. Hemoglobin, hematocrit, serum ferritin, hepcidin, and serum C-reactive protein were analyzed at baseline and at 14 d. A t test was used to compare the mean differences in fractional absorptions within each study and baseline characteristics between studies.ResultsGeometric mean (95% CI) fractional iron absorption of FePP [0.94% (0.63%, 1.40%)] was lower than ASP-p [2.20% (1.47%, 3.30%)] (P < 0.0001) in study I. In study II, ASP-p fractional absorption [2.98% (2.03%, 4.38%)] was lower than that of FeSO4 [9.88% (6.70%, 14.59%)] (P < 0.0001). Both ferritin (r = −0.41, P = 0.014) and hepcidin (r = −0.42, P = 0.01) concentrations were inversely correlated with ASP-p iron absorption. Fractional absorption of ASP-p was also positively correlated with FePP (r = 0.92, P < 0.0001) and FeSO4 (r = 0.52, P < 0.02) absorption.ConclusionsASP-p–fortified bouillon provided 2.3-fold higher absorbable iron than the currently used FePP. Bouillon fortified with ASP-p may contribute sufficient bioavailable iron to meet the daily iron requirements in young women only if consumed with other iron-fortified staple foods. This trial was registered at clinicaltrials.gov as NCT03586245.

Polyphenol-rich tea decreases iron absorption from fortified wheat bread in Senegalese mother-child pairs and bioavailability of ferrous fumarate is sharply lower in children.

Fractional iron absorption (FAFe) from ferrous fumarate (FeFum) and ferrous sulfate (FeSO4) in adults is generally comparable. While FeFum is commonly used to fortify infant foods, FAFe from FeFum in young children and infants may be decreased compared with FeSO4 and this effect has not been assessed in inhibitory vs noninhibitory meals. Previous studies also reported FAFe to be strongly correlated in mother-child pairs. Our objective was to measure FAFe from fortified bread labeled with 58FeSO4 and 57FeFum in mother-child pairs with and without a commonly consumed herbal tea of Combretum micranthum (Tisane Kinkéliba, TK). Senegalese mother-child pairs (n = 17) were randomly assigned to receive, in a 2 × 2 factorial design, fortified bread with 58FeSO4 or 57FeFum consumed with TK or water. FAFe was assessed by measuring erythrocyte incorporation of stable iron-isotopes 14 days after administration. In children, relative bioavailability (RBV) from FeFum was 51 and 64% compared with FeSO4 when served with TK or water (both, P < 0.05). In mothers, the presence of TK decreased FAFe by 56% (P < 0.05) and 50% (P = 0.077) and in children by 65 and 72% (both, P < 0.0001), in the meals with 58FeSO4 and 57FeFum, respectively. After adjustment for plasma ferritin, there was a positive correlation between FAFe in mothers and children (r = 0.4142, P = 0.001). In Senegalese women and children, herbal tea decreased FAFe from a wheat-based meal. The RBV of FeFum was low in children but not in their mothers. FAFe was modestly correlated in mother-child pairs, possibly due to shared genetic, epigenetic or environmental background.

Maternal iron absorption and iron transfer to the fetus during pregnancy in normal- weight and overweight/obese women

AbstractOverweight/obesity (owob) causes low-grad systemic inflammation and thereby an up-regulation of hepcidin and a reduction in fractional iron absorption (FIA) even with low iron stores. Pregnancy increases iron needs because of the expansion of maternal blood volume and fetal needs. It is unclear to what extent owob pregnancy influences FIA, iron supply of the fetus and risk of iron deficiency. Therefore, the main aim of this study was to determine the effect of maternal owob on iron absorption during pregnancy and on the iron transfer to the fetus. Secondary objectives were to investigate the development of hepcidin, plasma ferritin and inflammatory markers over the course of pregnancy dependent on weight status. In this multicenter case-control study we included 44 normal weight (nw) and 36 owob women around pregnancy week (PW) 12. We administered 57Fe or 58Fe labeled FeSO4 to women during the 2nd and 3rd trimester of pregnancy. We measured FIA determining erythrocyte incorporation of iron stable isotopes 14 days after administration. From PW 12 until PW 36 iron-, inflammation and hepcidin were monitored. Iron transfer to the fetus was determined as iron stable isotope concentration in cord blood. Sample analysis is currently ongoing, all results will be available in October. Subject characteristics in PW 12 for the nw (n = 26) and owob (n = 10) were: mean BMI: 21.4 ± 2.2 and 36.7 ± 6.8 kg/m2, mean hemoglobin: 12.4 ± 1.2 and 12.4 ± 0.9 g/dL and median plasma ferritin: 41.3 (29.6–83.6) and 61.6 (24.3–119.0) μg/L. Preliminary results indicate FIA increased by 2.4 fold in the nw and by 1.3 fold in the owob women between the 2nd and the 3rd trimester of pregnancy. Iron stores decreased in both groups over the course of pregnancy. Hepcidin was still significantly higher in the owob women in the 3rd trimester. Inflammation tended to be higher in owob women throughout pregnancy. Iron isotopes were highly detectable in cord blood. The 58Fe:57Fe-ratio determined in cord blood corresponded to the 58Fe:57Fe-ratio determined in the mother in the 3rd trimester. Thus, in owob women, the increase in FIA throughout pregnancy to support iron needs of mother and fetus is blunted compared to nw women. This is consistent with elevated hepcidin in the 3rd trimester and higher inflammation throughout pregnancy. Thus, even though iron demands are strongly increased, owob may prohibit an adequate iron supply to the expecting mother and the fetus due to persistent subclinical inflammation.