Methods of Assessment of Zinc Status in Humans: An Updated Review and Meta-analysis.

CONTEXT: The assessment of zinc status is difficult but essential 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 of at least 2 weeks? DATA SOURCES: 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 EXTRACTION: Data were extracted and combined with data from the previous SR. DATA ANALYSIS: A random-effects model was used to calculate pooled mean differences using STATA (StataCorp). The risk of bias and the certainty of evidence for all outcomes were assessed. 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 < .005, I2 = 97.8; before-and-after studies: 2.87 µmol/L [2.45, 3.30]; P < .005, I2 = 98.1%; urine zinc: 0.39 mmol/mol creatinine [0.17, 0.62]; P < .005, I2 = 81.2; 3.09 µmol/day [0.16, 6.02]; P = .039, I2 = 94.3). CONCLUSION: 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. SYSTEMATIC REVIEW REGISTRATION: PROSPERO no. CRD42020219843.

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.

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.

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  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-PA-HCP) resulted in highest cellular ferritin induction in Caco-2 cells, in both vegetable (36.1 ± 13.40 ng/mg protein) and chicken (73.9 ± 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).

Maternal anemia and underweight as determinants of pregnancy outcomes: cohort study in eastern rural Maharashtra, India.

OBJECTIVES: To study the trend in the prevalence of anaemia and low BMI among pregnant women from Eastern Maharashtra and evaluate if low BMI and anaemia affect pregnancy outcomes. DESIGN: Prospective observational cohort study. SETTING: Catchment areas of 20 rural primary health centres in four eastern districts of Maharashtra State, India. PARTICIPANTS: 72 750 women from the Nagpur site of Maternal and Newborn Health Registry of NIH's Global Network, enrolled from 2009 to 2016. MAIN OUTCOME MEASURES: Mode of delivery, pregnancy related complications at delivery, stillbirths, neonatal deaths and low birth weight (LBW) in babies. RESULTS: Over 90% of the women included in the study were anaemic and over a third were underweight (BMI <18 kg/m2) and with both conditions. Mild anaemia at any time during delivery significantly increased the risk (Risk ratio; 95% confidence interval (RR;(95% CI)) of stillbirth (1.3 (1.1-1.6)), neonatal deaths (1.3 (1-1.6)) and LBW babies (1.1 (1-1.2)). The risks became even more significant and increased further with moderate/severe anaemia any time during pregnancy for stillbirth (1.4 (1.2-1.8)), neonatal deaths (1.7 (1.3-2.1)) and LBW babies (1.3 (1.2-1.4)).,. Underweight at anytime during pregnancy increased the risk of neonatal deaths (1.1 (1-1.3)) and LBW babies (1.2;(1.2-1.3)).The risk of having stillbirths (1.5;(1.2-1.8)), neonatal deaths (1.7;(1.3-2.3)) and LBW babies (1.5;(1.4-1.6)) was highest when - the anaemia and underweight co-existed in the included women. Obesity/overweight during pregnancy increased the risk of maternal complications at delivery (1.6;(1.5-1.7)) and of caesarean section (1.5;(1.4-1.6)) and reduced the risk of LBW babies 0.8 (0.8-0.9)). CONCLUSION: Maternal anaemia is associated with enhanced risk of stillbirth, neonatal deaths and LBW. The risks increased if anaemia and underweight were present simultaneously. TRIAL REGISTRATION NUMBER: NCT01073475.