The effect of a natural polyphenol supplement on iron absorption in adults with hereditary hemochromatosis.

OBJECTIVES: We developed a natural polyphenol supplement that strongly chelates iron in vitro and assessed its effect on non-heme iron absorption in patients with hereditary hemochromatosis (HH). METHODS: We performed in vitro iron digestion experiments to determine iron precipitation by 12 polyphenol-rich dietary sources, and formulated a polyphenol supplement (PPS) containing black tea powder, cocoa powder and grape juice extract. In a multi-center, single-blind, placebo-controlled cross-over study, we assessed the effect of the PPS on iron absorption from an extrinsically labelled test meal and test drink in patients (n = 14) with HH homozygous for the p.C282Y variant in the HFE gene. We measured fractional iron absorption (FIA) as stable iron isotope incorporation into erythrocytes. RESULTS: Black tea powder, cocoa powder and grape juice extract most effectively precipitated iron in vitro. A PPS mixture of these three extracts precipitated ~ 80% of iron when 2 g was added to a 500 g iron solution containing 20 µg Fe/g. In the iron absorption study, the PPS reduced FIA by ~ 40%: FIA from the meal consumed with the PPS was lower (3.01% (1.60, 5.64)) than with placebo (5.21% (3.92, 6.92)) (p = 0.026)), and FIA from the test drink with the PPS was lower (10.3% (7.29 14.6)) than with placebo (16.9% (12.8 22.2)) (p = 0.002). CONCLUSION: Our results indicate that when taken with meals, this natural PPS can decrease dietary iron absorption, and might thereby reduce body iron accumulation and the frequency of phlebotomy in patients with HH. TRIAL REGISTRY: clinicaltrials.gov (registration date: 9.6.2019, NCT03990181).

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. In nonanemic Taiwanese women (n=79, 44 TT variant, 35 CC variant), we administered standardized rice-based test meals containing 4 mg of labeled 57Fe or 58Fe as FeSO4 on alternate days. Fractional iron absorption was measured by erythrocyte incorporation of the tracers 14 days after administration. Compared to the CC variant, in the TT variant serum 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). Serum hepcidin did not differ between groups (P=0.862). Geometric mean (95% CI) fractional iron absorption, corrected to a serum ferritin of 15 µg/L, was 26.6% (24.0, 29.5) in the CC variant and 18.5% (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); 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 at www.clinicaltrials.gov as NCT03317873, and funded by the Kaohsiung Chang-Gung Memorial Hospital, Kaohsiung, Taiwan, (grant CMRPG8F0721) and ETH Zurich, Switzerland.

Effectiveness of zinc-fortified water on zinc intake, status and morbidity in Kenyan pre-school children: a randomised controlled trial.

OBJECTIVE: Zn deficiency and diarrhoea are prevalent and may coexist in children living in low-resource settings. Recently, a novel approach for delivering Zn via microbiologically treated, Zn-fortified water was shown to be effective in improving Zn status in West African schoolchildren. We assessed the effectiveness of Zn-fortified, microbiologically purified water delivered as a household intervention on Zn intake, status and morbidity in children aged 2-6 years from rural western Kenya. DESIGN: Randomised controlled trial. Intervention included households assigned to water treatment device with (ZFW) or without (FW) Zn delivery capability SETTING: Rural households in Kisumu, western Kenya. SUBJECTS: Children aged 2-6 years. RESULTS: The ZFW group had higher dietary Zn intake compared with the FW group. ZFW contributed 36 and 31 % of daily requirements for absorbable Zn in children aged 2-3 and 4-6 years, respectively, in the ZFW group. Consumption of Zn-fortified water resulted in lower prevalence of reported illness (risk ratio; 95 % CI) in the ZFW group compared with the FW group: for cold with runny nose (0·91; 0·83, 0·99; P=0·034) and abdominal pain (0·70; 0·56, 0·89; P=0·003) in the intention-to-treat analysis and for diarrhoea (0·72; 0·53, 0·96; P=0·025) in the per-protocol analysis. We did not detect an effect of treatment on plasma Zn concentration. CONCLUSIONS: Daily consumption of Zn-fortified, microbiologically treated water results in increased intake of absorbable dietary Zn and may help in preventing childhood infections in pre-school children in rural Africa.

Asymptomatic Helicobacter Pylori Infection in Preschool Children and Young Women Does Not Predict Iron Bioavailability from Iron-Fortified Foods.

Helicobacter pylori infection is common in low-income countries. It has been associated with iron deficiency and reduced efficacy of iron supplementation. Whether H. pylori infection affects iron absorption from fortified and biofortified foods is unclear. Our objective was to assess whether asymptomatic H. pylori infection predicts dietary iron bioavailability in women and children, two main target groups of iron fortification programs. We did a pooled analysis of studies in women of reproductive age and preschool children that were conducted in Benin, Senegal and Haiti using stable iron isotope tracers to measure erythrocyte iron incorporation. We used mixed models to assess whether asymptomatic H. pylori infection predicted fractional iron absorption from ferrous sulfate, ferrous fumarate or NaFeEDTA, controlling for age, hemoglobin, iron status (serum ferritin), inflammation (C-reactive protein), and test meal. The analysis included 213 iron bioavailability measurements from 80 women and 235 measurements from 90 children; 51.3% of women and 54.4% of children were seropositive for H. pylori. In both women and children, hemoglobin (Hb), serum ferritin (SF), and C-reactive protein (CRP) did not differ between the seropositive and seronegative groups. Geometric mean (95% CI) fractional iron absorption (%), adjusted for SF, was 8.97% (7.64, 10.54) and 6.06% (4.80, 7.67) in H. pylori positive and negative women (p = 0.274), and 9.02% (7.68, 10.59) and 7.44% (6.01, 9.20) in H. pylori positive and negative children (p = 0.479). Our data suggest asymptomatic H. pylori infection does not predict fractional iron absorption from iron fortificants given to preschool children or young women in low-income settings.

A heat-stable microparticle platform for oral micronutrient delivery.

Micronutrient deficiencies affect up to 2 billion people and are the leading cause of cognitive and physical disorders in the developing world. Food fortification is effective in treating micronutrient deficiencies; however, its global implementation has been limited by technical challenges in maintaining micronutrient stability during cooking and storage. We hypothesized that polymer-based encapsulation could address this and facilitate micronutrient absorption. We identified poly(butylmethacrylate-co-(2-dimethylaminoethyl)methacrylate-co-methylmethacrylate) (1:2:1) (BMC) as a material with proven safety, offering stability in boiling water, rapid dissolution in gastric acid, and the ability to encapsulate distinct micronutrients. We encapsulated 11 micronutrients (iron; iodine; zinc; and vitamins A, B2, niacin, biotin, folic acid, B12, C, and D) and co-encapsulated up to 4 micronutrients. Encapsulation improved micronutrient stability against heat, light, moisture, and oxidation. Rodent studies confirmed rapid micronutrient release in the stomach and intestinal absorption. Bioavailability of iron from microparticles, compared to free iron, was lower in an initial human study. An organotypic human intestinal model revealed that increased iron loading and decreased polymer content would improve absorption. Using process development approaches capable of kilogram-scale synthesis, we increased iron loading more than 30-fold. Scaled batches tested in a follow-up human study exhibited up to 89% relative iron bioavailability compared to free iron. Collectively, these studies describe a broad approach for clinical translation of a heat-stable ingestible micronutrient delivery platform with the potential to improve micronutrient deficiency in the developing world. These approaches could potentially be applied toward clinical translation of other materials, such as natural polymers, for encapsulation and oral delivery of micronutrients.