The development of a novel ferric phytate compound for iron fortification of bouillons (part I)

In a series of two studies, we report the development (this study) and evaluation (part II) of a novel ferric phytate compound designed as a condiment iron fortificant. Condiments are used as iron fortification vehicles to reduce the prevalence\ua0 of iron deficiency. The challenge for iron fortificants in e.g. a bouillon matrix is to avoid undesired sensory effects and to ensure a reasonable cost. We added phytic acid to chelate iron, and hydrolysed protein to counteract the inhibiting effect of phytic acid on iron bioaccessibility. We characterised four novel ferric phytate compounds, destabilised by hydrolysed plant protein or amino acids. Colour stability of fortified bouillons with ferric phytate compounds was superior to bouillons fortified with ferrous sulfate. The iron-phytate-hydrolysed corn protein compound (Fe-PAHCP) resulted in highest cellular ferritin induction in Caco-2 cells, in both vegetable (36.1 \ub1 13.40 ng/mg protein) and chicken (73.9 \ub1 19.93 ng/mg protein) bouillon matrices as observed in the human Caco-2/ HepG2 cell model. Iron uptake (as estimated by ferritin production) from the Fe-PA-HCP compound was about 55% (chicken bouillon) and 66% (vegetable bouillon) of the iron uptake from ferrous sulfate. Based on this study, the Fe-PA-HCP compound was chosen for further evaluation (part II)

The Impact of Consuming Zinc-Biofortified Wheat Flour on Haematological Indices of Zinc and Iron Status in Adolescent Girls in Rural Pakistan: A Cluster-Randomised, Double-Blind, Controlled Effectiveness Trial

Biofortification of wheat is potentially a sustainable strategy to improve zinc intake; however, evidence of its effectiveness is needed. A household-based, double-blind, cluster-randomized controlled trial (RCT) was conducted in rural Pakistan. The primary objective was to examine the effects of consuming zinc-biofortified wheat flour on the zinc status of adolescent girls aged 10–16 years (n = 517). Households received either zinc-biofortified flour or control flour for 25 weeks; blood samples and 24-h dietary recalls were collected for mineral status and zinc intake assessment. Plasma concentrations of zinc (PZC), selenium and copper were measured via inductively coupled plasma mass spectrometry and serum ferritin (SF), transferrin receptor, alpha 1-acid glycoprotein and C-reactive protein by immunoassay. Consumption of the zinc-biofortified flour resulted in a moderate increase in intakes of zinc (1.5 mg/day) and iron (1.2 mg/day). This had no significant effect on PZC (control 641.6 ± 95.3 µg/L vs. intervention 643.8 ± 106.2 µg/L; p = 0.455), however there was an overall reduction in the rate of storage iron deficiency (SF < 15 µg/L; control 11.8% vs. 1.0% intervention). Consumption of zinc-biofortified flour increased zinc intake (21%) but was not associated with an increase in PZC. Establishing a sensitive biomarker of zinc status is an ongoing priority

Food fortification programmes and zinc deficiency

The complex realities of most countries grappling with zinc deficiency pose challenges to the implementation of highly compliant, mandatory, large-scale food fortification programmes

School Feeding to Improve Cognitive Performance in Disadvantaged Children: A 3-Arm Parallel Controlled Trial in Northwest Pakistan

Malnutrition is associated with reduced learning aptitude and growth during childhood. We examined the impact of providing two school lunch variants, a standard school meal (school feeding, n = 70), or the standard meal with additional micronutrients (school feeding + micronutrient powder (MNP), n = 70), in children attending two schools in northwest Pakistan. A third local government school, where no lunch was provided (no school feeding, n = 70), served as the control. The primary outcome, cognitive function, was assessed using the Raven’s Coloured Progressive Matrices (RCPM) test, alongside haemoglobin, at three-time points: T1 (baseline, before the initiation of the school lunch programme), T2 and T3 (5 and 12 months, respectively, after the introduction of the school lunch). Data were analysed using linear mixed-effects models to contrast between trial groups, the changes from T1 to T2 and T3. Adjusted for T1 and other co-variates, improvements in the RCPM scores were significantly greater in the school feeding group at T2 (b = 1.61, (95% CI = 0.71–2.52), t = 3.52, p = 0.001) and T3 (b = 1.28, (95% CI = 0.22–2.35), t = 2.38, p = 0.019) compared with no school feeding. In addition, at T2 (b = 1.63, (95% CI = −0.10–3.37), t = 1.86, p = 0.065), there were no significant differences between school feeding + MNP and no school feeding groups. However, improvements in the RCPM scores were significantly greater in the school feeding + MNP group at T3 (b = 2.35, (95% CI = 0.51–4.20), t = 2.53, p = 0.013) compared with no school feeding. The findings indicate an improvement in cognitive performance in children who received a school meal with and without MNP, over a 12-month period. Currently there is no operational school feeding programme at the national or provincial level in Pakistan. Our findings, therefore, highlight the need for school feeding programmes to improve learning opportunities for children from underprivileged communities

Impact of consuming zinc-biofortified wheat flour on the growth and morbidity status of children aged 1–5 years: a cluster-randomised, double-blind, controlled trial

Wheat biofortification through conventional breeding and/or agronomic methods to increase zinc content may be a promising strategy for addressing zinc deficiency (Reference Gupta, Brazier and Lowe1). However, evidence on the effectiveness of zinc biofortification interventions on health outcomes are lacking. The aim of the present study was to assess the effectiveness of consuming zinc-biofortified wheat flour (Zincol-2016) on growth and zinc-related morbidity among children (aged 1–5 years), living in a rural community in northwest Pakistan. Households (N = 486) with at least one adolescent girl aged 10–16 years and one child aged 1–5 years (N = 517) near Peshawar were recruited to a double-blind, cluster-randomised controlled trial (BiZiFED2 RCT)(Reference Lowe, Zaman and Moran2,Reference Gupta, Zaman and Fatima3) . During phase 1 of the trial (November 2019 to September 2020), households were provided with locally procured flour from standard wheat varieties (control) to establish a baseline. During phase 2 (September 2020 to March 2021), households received either zinc-biofortified flour or control flour. Anthropometric measurements were collected at the beginning, middle and end of phase 2(Reference Lowe, Zaman and Moran2). Data pertaining to incidence and duration of respiratory tract infection (RTI) and diarrhea in the preceding two weeks were collected fortnightly. Analysis was performed using linear mixed models for continuous variables adjusted for baseline, and Pearson's chi-square test for categorical variables. No significant effect of the intervention was observed on linear growth (height: control 2.3 ± 1.32 cm vs intervention 2.2 ± 1.41 cm; height-for-age Z scores: control -0.21 ± 0.35 vs intervention -0.21 ± 0.38) and weight gain (control 1.7 ± 1.16 kgs vs intervention 1.5 ± 0.98 kgs; weight-for-age Z scores: control 0.39 ± 0.60 vs intervention 0.29 ± 0.54). Caregiver-reported incidence of RTIs were not significantly different for the two study arms between the baseline and midpoint, but towards the end of the trial a lower incidence of RTIs was reported in the intervention arm compared to the control arm (week 26: control 34.7% vs intervention 17.6%, p = 0.036). However, when the longitudinal prevalence of RTI (cumulative days of sickness as a percentage of total days of observations) was considered, no treatment effects were observed (mid-point: control 16.5% [95% CI: 14.1, 18.9] vs intervention 14.8% [95% CI:12.5, 17.2]; endline: control 14.0% [95% CI: 11.5, 16.4] vs intervention 12.2% [95% CI: 9.9, 14.5]). No intervention effects were reported either on the incidence of diarrhea or its longitudinal prevalence (mid-point: control 4.7% [95% CI: 3.2, 6.1] vs intervention 4.9% [95% CI: 3.5, 6.2]; endline: control 3.2% [95% CI: 2.1, 4.3] vs intervention 2.9% [95% CI: 1.6, 4.2]). Provision of zinc-biofortified wheat flour for 25 weeks did not have a significant effect on growth or morbidity status of children. Longer term interventions are warranted to monitor changes in functional outcomes in response to the ongoing national scale-up of the release of zinc-biofortified wheat varieties

Impact of consuming zinc-biofortified wheat flour on the growth and morbidity status of adolescent girls: a cluster randomised, double blind, controlled trial

Despite the known detrimental consequences of zinc deficiency and recognized benefits of supplementation in reducing morbidity and improving growth(1) , programmatic zinc supplementation is not feasible(2) thus other sustainable methods such as biofortification of staple crops to increase zinc intakes on a population scale needs to be explored. The aim of this study was to determine the effect�iveness of consuming zinc-biofortified wheat flour (Zincol-2016) on zinc-related morbidity and growth among adolescent girls, living in a rural, marginalized community in northwest Pakistan where the prevalence of zinc deficiency is high. Households (N = 486) with at least one adolescent girl aged 10–16 years (N = 517) near Peshawar, Pakistan were recruited to a double blind, cluster randomized controlled trial (BiZiFED2 RCT). During phase 1 of the trial (November 2019 to September 2020), households were provided with locally procured flour from standard wheat varieties (control) to establish a baseline. During phase 2 (September 2020 to March 2021), households received either zinc-biofortified flour or control flour. Anthropometric measurements and 24-hour dietary recalls were collected at the beginning, middle and end of the trial(3) . Data pertaining to incidence and duration of respiratory tract infection (RTI) in the preceding two weeks were collected fortnightly. Analysis was performed using linear mixed models for continuous vari�ables and Pearson’s chi-square test for categorical variables. Consumption of biofortified flour contributed to a moderate increase in estimated zinc (1.5 mg/day) and iron (1.2 mg per/day) intake. No significant effect of the intervention was observed on linear growth (height: control 150.6 ±8.5 cms vs intervention 148.7±8.5 cms; height for age Z scores: control -0.73±1.1 vs intervention -0.92 ±1.0) and weight (control 45.5 ±9.7 kgs vs intervention 43.4 ±10.1 kgs). Self-reported incidence of RTIs were not significantly different for the two study arms between the baseline and midpoint, but towards the end of the trial a lower incidence of RTIs was reported in the intervention arm compared to the control arm (week 22: control 19.3% vs. intervention 11.5%, p = 0.037; week 26: control 14.5% vs. intervention 6.1%, p = 0.014). However, when the longitudinal prevalence of RTI (cumulative days of sickness as a percentage of total days of observations) was considered with baseline adjustments, no treatment effects were observed (mid- point: control 10.6% [95% CI: 8.6, 12.7] vs intervention 6.3% [95% CI: 4.9, 7.7]; endline: control 8.1% [95% CI: 6.4, 9.8] vs intervention 9.9% [95% CI: 8.0, 11.9]). A moderate (21%) increase in dietary zinc through the consumption of zinc-biofortified flour for 25 weeks did not have a significant effect on growth or morbidity status of adolescent girls. Longer term interventions are warranted to monitor changes in functional outcomes in response to the ongoing national scale-up of the release of zinc- biofortified wheat varietie

Methods of assessment of zinc status in humans: an updated review and meta-analysis

Background: The assessment of zinc status is difficult, but vitally important for the identification of zinc deficiency and evaluation of interventions to improve zinc status. Objective: The purpose of this systematic review (SR) and meta-analysis was to update the previously published SR of biomarkers of zinc status, conducted by the European Micronutrient Recommendations Aligned (EURRECA) network in 2009, to answer the question: which putative measures (biomarkers) of zinc status appropriately reflect a change in zinc intake over a period of at least two weeks. Methods: A structured search strategy was used to identify articles published between January 2007 and September 2022 from MEDLINE (OVID), Embase (OVID), Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials (CENTRAL). Relevant articles were identified using previously defined eligibility criteria. Data were extracted and combined with data from the previous SR. A random-effect model was used to calculate pooled mean differences using STATA. The risk of bias and the certainty of evidence for all outcomes were assessed. Results: Additional data on 7 of the 32 previously reported biomarkers were identified, along with data on an additional 40 putative biomarkers from studies published since 2007. Pooled data analysis confirmed that in healthy participants, both plasma/serum zinc concentration, and urinary zinc excretion responded to changes in zinc intake [plasma/serum: mean effect, (95% CI), controlled studies: 2.17 µmol/L (1.73, 2.61), p<0.005, I2 =97.8; before and after studies: 2.87 µmol/L (2.45, 3.30), p <0.005, I2=98.1%; urine zinc: 0.39 mmol/mol creatinine (0.17, 0.62), p<0.005, I2= 81.2; 3.09 µmol/d (0.16, 6.02), p=0.039, I2= 94.3]. Conclusions: The updated analyses support the conclusion that plasma/serum and urinary zinc respond to changes in zinc intake in studies of healthy participants. Several additional putative biomarkers were identified, but more studies are needed to assess the sensitivity and reliability