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Large-scale food fortification (LSFF) can increase dietary micronutrient intake and improve micronutrient status. Here we used food balance sheet data from the Food and Agriculture Organization of the United Nations to estimate current country-specific prevalences of inadequate zinc intake. We assessed the potential effects of improving existing LSFF programmes for cereal grains or implementing new programmes in 40 countries where zinc deficiency is a potential public health problem. Accounting for LSFF programmes as currently implemented, 15% of the global population (1.13 billion individuals) is estimated to have inadequate zinc intake. In countries where zinc deficiency is a potential public health problem, the implementation of high-quality mandatory LSFF programmes that include zinc as a fortificant would substantially increase the availability of zinc in the national food supply, reducing the estimated prevalence of inadequate zinc intake by up to 50% globally. Investments in strong LSFF programmes could have a substantial impact on population zinc status., (© 2024. The Author(s).)

Purpose: Public health interventions to address stunting and wasting should be evaluated for possibly contributing to obesity risk. The present study tested the hypothesis that small-quantity lipid-based nutrient supplements (SQ-LNS) might increase fat deposition, and that additional zinc provided via SQ-LNS or in the form of dispersible tablets would increase fat-free mass (FFM) accretion., Methods: Using a two-stage, cluster-randomized trial design, 34 communities were randomly assigned to the intervention cohort (IC) or non-intervention cohort (NIC), and family compounds within the IC were randomly assigned to receive different amounts of zinc (0, 5 or 10 mg zinc) incorporated in SQ-LNS or 5 mg zinc in the form of dispersible tablets along with treatment for diarrhea, malaria and fever. Body composition was assessed in a subset of IC (n = 201) and NIC (n = 74) children at 9 and 18 months using the deuterium dilution method. A mixed linear model was used to examine average change in FFM and % fat mass (%FM) among intervention groups and by cohort., Results: Children in the IC had significantly greater change in FFM (Mean (95% Confidence Interval)) (1.57 (1.49, 1.64) kg) compared to the NIC (1.35 (1.23, 1.46) kg; p = 0.005). There were no significant differences in the change in %FM between the NIC and IC or among the intervention groups., Conclusion: SQ-LNS, along with morbidity treatment increased weight gain and FFM in young children from 9 to 18 months of age without increasing FM deposition. Additional zinc supplementation did not affect changes in FFM or %FM., Trial Registration: The study was registered as a clinical trial with the US National Institute of Health ( www., Clinicaltrials: gov ; NCT00944281)., (© 2022. The Author(s).)

Safe upper levels (UL) of zinc intake for children were established based on either (1) limited data from just one study among children or (2) extrapolations from studies in adults. Resulting ULs are less than amounts of zinc consumed by children in many studies that reported benefits of zinc interventions, and usual dietary zinc intakes often exceed the UL, with no apparent adverse effects. Therefore, existing ULs may be too low. We conducted a systematic bibliographic review of studies among preadolescent children, in which (1) additional zinc was provided vs. no additional zinc provided, and (2) the effect of zinc on serum or plasma copper, ceruloplasmin, ferritin, transferrin receptor, lipids, or hemoglobin or erythrocyte super-oxide dismutase were assessed. We extracted data from 44 relevant studies with 141 comparisons. Meta-analyses found no significant overall effect of providing additional zinc, except for a significant negative effect on ferritin ( p = 0.001), albeit not consistent in relation to the zinc dose. Interpretation is complicated by the significant heterogeneity of results and uncertainties regarding the physiological and clinical significance of outcomes. Current zinc ULs should be reassessed and potentially revised using data now available for preadolescent children and considering challenges regarding interpretation of results.

Nutrient reference values (NRVs) for zinc set by several expert groups differ widely and may affect the predicted prevalence of inadequate zinc intake. We examined this possibility using NRVs published by four different authorities and nationally representative dietary intake data collected among children aged 12-59 months and women in Cameroon. Usual zinc intake was estimated from 24 h recall data using the National Cancer Institute method. Prevalences of total zinc intake below the dietary requirement and of "absorbable zinc intake" below the physiological requirement were estimated using NRVs published by the World Health Organization (WHO), US Institute of Medicine (IOM), International Zinc Nutrition Consultative Group (IZiNCG), and European Food Safety Authority (EFSA). The prevalence of inadequate zinc intake ranged from 10% (IZiNCG-physiological requirement, 95% CI 7-13%) to 81% (EFSA-physiological requirement, 95% CI 78-84%) among children and 9% (WHO-physiological requirement, 95% CI 8-11.0%) to 94% (IOM-physiological requirement, 95% CI 92-95%) among women These differences in the prevalence of inadequate intake translated into sizeable differences in the predicted benefit and cost-effectiveness of zinc fortification programs. Depending on the NRVs applied, assessments differ regarding the need for and design of zinc fortification programs. Efforts are needed to harmonize NRVs for zinc.

Seventeen per cent of the world's population is estimated to be at risk of inadequate zinc intake, which could in part be addressed by zinc fortification of widely consumed foods. We conducted a review of efficacy and effectiveness studies to ascertain the effect of zinc fortification [postharvest fortification of an industrially produced food or beverage; alone or with multiple micronutrients (MMN)] on a range of health outcomes. Previous reviews have required that the effect of zinc be isolated; because zinc is always cofortified with MMN in existing fortification programs, we did not impose this condition. Outcomes assessed were zinc-related biomarkers (plasma or serum, hair or urine zinc concentrations, comet assay, plasma fatty acid concentrations, and the proportion of and total zinc absorbed in the intestine from the diet), child anthropometry, morbidity, mortality, cognition, plasma or serum iron and copper concentrations, and for observational studies, a change in consumption of the food vehicle. Fifty-nine studies were included in the review; 54 in meta-analyses, totaling 73 comparisons. Zinc fortification with and without MMN increased plasma zinc concentrations (efficacy, n = 27: 4.68 μg/dL; 95% CI: 2.62-6.75; effectiveness, n = 13: 6.28 μg/dL; 95% CI: 5.03-7.77 μg/dL) and reduced the prevalence of zinc deficiency (efficacy, n = 11: OR: 0.76, 95% CI: 0.60-0.96; effectiveness, n = 10: OR: 0.45, 95% CI: 0.31-0.64). There were statistically significant increases in child weight (efficacy, n = 11: 0.43 kg, 95% CI: 0.11-0.75 kg), improvements in short-term auditory memory (efficacy, n = 3: 0.32 point, 95% CI: 0.13-0.50 point), and decreased incidence of diarrhea (efficacy, n = 3: RR: 0.79, 95% CI: 0.68-0.92) and fever (efficacy, n = 2: RR: 0.85, 95% CI: 0.74-0.97). However, these effects cannot be solely attributed to zinc. Our review found that zinc fortification with or without MMN reduced the prevalence of zinc deficiency and may provide health and functional benefits, including a reduced incidence of diarrhea., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Adequate zinc nutrition is important for child growth, neurodevelopment, immune function, and normal pregnancy outcomes. Seventeen percent of the global population is estimated to be at risk for inadequate zinc intake. However, zinc is not included in the fortification standards of several low- and middle-income countries with mandatory fortification programs, despite data suggesting a zinc deficiency public health problem. To guide policy decisions, we investigated the factors enabling and impeding the inclusion of zinc as a fortificant by conducting in-depth interviews with 17 key informants from 10 countries. Findings revealed the decision to include zinc was influenced by guidance from international development partners and enabled by the assessment of zinc deficiency, mandatory regional food fortification standards which included zinc, the World Health Organization (WHO) guidelines for zinc fortification, and the low cost of zinc compound commonly used. Barriers included the absence of zinc from regional fortification standards, limited available data on the efficacy and effectiveness of zinc fortification, and the absence of national objectives related to the prevention of zinc deficiency. To promote zinc fortification there is a need to put the prevention of zinc deficiency higher on the international nutrition agenda and to promote large-scale food fortification as a key deficiency mitigation strategy.

Plasma zinc concentrations (PZC) have been shown to significantly increase during zinc supplementation. This study investigated the effects of daily preventive zinc supplementation on hair and nail zinc concentrations compared with a control group. In a randomized controlled trial, 6- to 23-month-old children (n = 3407) in Lao PDR were randomly assigned to one of four groups and followed for ~ 36 weeks: daily preventive zinc dispersible tablet (7 mg/d; PZ), daily micronutrient powder (10 mg zinc/d; MNP), therapeutic zinc supplements for diarrhea treatment (20 mg/d for 10 days; TZ), or daily placebo powder (Control). Plasma, hair, and nail zinc concentrations were assessed in a sub-sample of participants (n = 457) at baseline and endline. At baseline, 75% of children had low PZC (< 65 μg/dL). At endline, geometric mean (95% CI) PZC were greater in the PZ and MNP groups compared with the TZ and control groups (P < 0.01), but hair zinc concentrations did not differ among groups (P = 0.99). Nail zinc concentrations were marginally higher in the PZ (115.8 (111.6, 119.9) μg/g) and the MNP (117.8 (113.3, 122.3) μg/g) groups than in the TZ group (110.4 (106.0, 114.8) μg/g; P = 0.055) at endline. This study does not support the use of hair zinc as a biomarker of zinc exposure in young children. However, it provides some evidence that zinc concentrations in nails may respond to supplemental zinc interventions and supports the need for collecting additional data on this emerging biomarker.

Background: Zinc deficiency impairs immune function and is common among children in South-East Asia., Objectives: The effect of zinc supplementation on immune function in young Laotian children was investigated., Methods: Children (n = 512) aged 6-23 mo received daily preventive zinc tablets (PZ; 7 mg Zn/d), daily multiple micronutrient powder (MNP; 10 mg Zn/d, 6 mg Fe/d, plus 13 other micronutrients), therapeutic dispersible zinc tablets only in association with diarrhea episodes (TZ; 20 mg Zn/d for 10 d after an episode), or daily placebo powder (control). These interventions continued for 9 mo. Cytokine production from whole blood cultures, the concentrations of T-cell populations, and a complete blood count with differential leukocyte count were measured at baseline and endline. Endline means were compared via ANCOVA, controlling for the baseline value of the outcome, child age and sex, district, month of enrollment, and baseline zinc status (below, or above or equal to, the median plasma zinc concentration)., Results: T-cell cytokines (IL-2, IFN-γ, IL-13, IL-17), LPS-stimulated cytokines (IL-1β, IL-6, TNF-α, and IL-10), and T-cell concentrations at endline did not differ between intervention groups, nor was there an interaction with baseline zinc status. However, mean ± SE endline lymphocyte concentrations were significantly lower in the PZ than in the control group (5018 ± 158 compared with 5640 ± 160 cells/μL, P = 0.032). Interactions with baseline zinc status were seen for eosinophils (Pixn = 0.0036), basophils (Pixn = 0.023), and monocytes (P = 0.086) but a significant subgroup difference was seen only for eosinophils, where concentrations were significantly lower in the PZ than in the control group among children with baseline plasma zinc concentrations below the overall median (524 ± 44 compared with 600 ± 41 cells/μL, P = 0.012)., Conclusions: Zinc supplementation of rural Laotian children had no effect on cytokines or T-cell concentrations, although zinc supplementation affected lymphocyte and eosinophil concentrations. These cell subsets may be useful as indicators of response to zinc supplementation.This trial was registered at clinicaltrials.gov as NCT02428647., (Published by Oxford University Press on behalf of the American Society for Nutrition 2020.)

Background: Diarrhea and respiratory tract infections are leading causes of childhood morbidity and mortality. This individually randomized, double-blind placebo-controlled trial was designed to evaluate the effects of different zinc supplementation regimens on the incidence and duration of diarrhea and acute lower (ALRI) and upper (AURI) respiratory tract infections among rural Laotian children. The study included 3407 children, 6-23 months at enrollment., Methods: Children were randomized to one of four study groups: therapeutic zinc supplements for diarrhea treatment (20 mg/d for 10 days with each episode; TZ), daily preventive zinc tablets (7 mg/d; PZ), daily multiple micronutrient powder (10 mg/d zinc, 6 mg/d iron and 13 other micronutrients; MNP), or daily placebo powder for 9 months. Incidence and duration of diarrhea (≥3 liquid stools/24 hours), ALRI (persistent cough with wheezing, stridor or chest in-drawing) and AURI (purulent nasal discharge with cough) were assessed by parental report during weekly home visits and analyzed using negative binomial models., Results: Baseline mean age was 14.2 ± 5.1 months, and 71% had low plasma zinc (<65 μg/dL). Overall diarrhea incidence (0.61 ± 0.01 episodes/100 days at risk) and duration (2.12 ± 0.03 days/episode) did not differ by study group. Age modified the impact of the interventions on diarrhea incidence ( P  = 0.06) and duration ( P  = 0.01). In children >18 months, TZ reduced diarrhea incidence by 24% vs MNP ( P  = 0.035), and 36% vs Control ( P  = 0.004), but there was no difference with PZ. This patterned remained when analyses were restricted to diarrhea episode occurring after the first treatment with TZ. Also, in children >18 months, TZ reduced diarrhea duration by 15% vs PZ ( P  = 0.03), and 16% vs Control ( P  = 0.03), but there was no difference with MNP. There were no overall effects of study group on incidence of ALRI (overall mean 0.005 ± 0.001 episodes/100 days, P  = 0.14) or AURI (overall mean 0.09 ± 0.01 episodes/100 days, P  = 0.72)., Conclusions: There was no overall impact of TZ, PZ or MNP on diarrhea, ALRI and AURI. However, in children >18 months, TZ significantly reduced both the duration of diarrhea episodes and the incidence of future diarrhea episodes compared with placebo., Trial Registration: ClinicalTrials.gov: NCT02428647., Competing Interests: Conflicts of interest: KHB and the spouse of SYH worked for the Bill & Melinda Gates Foundation, which provided part of the financial support. The sponsors had no involvement in the study implementation, data analyses or manuscript writing. All authors have completed the ICMJE uniform disclosure form (available upon request from the corresponding author) and declare no further conflicts of interest., (Copyright © 2020 by the Journal of Global Health. All rights reserved.)

Background: The accurate estimation of zinc deficiency at the population level is important, as it guides the design, targeting, and evaluation of nutrition interventions. Plasma or serum zinc concentration (PZC) is recommended to estimate zinc nutritional status; however, concentrations may decrease in the presence of inflammation., Objectives: We aimed to assess the relation between PZC and inflammation in preschool children (PSC; 6-59 mo) and nonpregnant women of reproductive age (WRA; 15-49 y), and to compare different inflammation adjustment approaches, if adjustment is warranted., Methods: Cross-sectional data from 13 nationally representative surveys (18,859 PSC, 22,695 WRA) from the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project were analyzed. Correlation and decile analyses were conducted, and the following 3 adjustment methods were compared if a consistent negative association between PZC and C-reactive protein (CRP) or α-1-acid glycoprotein (AGP) was observed: 1) exclude individuals with CRP > 5 mg/L or AGP > 1 g/L; 2) apply arithmetic correction factors; and 3) use the BRINDA regression correction (RC) approach., Results: In 6 of 12 PSC surveys, the estimated prevalence of zinc deficiency increased with increasing CRP deciles, and to a lesser extent, with increasing AGP deciles. In WRA, the association of PZC with CRP and AGP was weak and inconsistent. In the 6 PSC surveys in which adjustment methods were compared, application of RC reduced the estimated prevalence of zinc deficiency by a median of 11 (range: 4-18) percentage points, compared with the unadjusted prevalence., Conclusions: Relations between PZC and inflammatory markers were inconsistent, suggesting that correlation and decile analyses should be conducted before applying any inflammation adjustments. In populations of PSC that exhibit a significant negative association between PZC and CRP or AGP, application of the RC approach is supported. At this time, there is insufficient evidence to warrant inflammation adjustment in WRA., (Copyright © The Author(s) 2020.)

Background: Dietary phytate inhibits zinc absorption from composite meals in adults., Objective: The objective of this study was to investigate the effect of adding exogenous phytase to a small-quantity lipid-based nutrient supplement (SQ-LNS) on zinc absorption among young children., Methods: In a double-blind randomized controlled trial, intraindividual differences in fractional and total absorption of zinc (FAZ and TAZ, respectively) from a millet-based porridge containing SQ-LNS with and without phytase were measured in 30 asymptomatic children 18-23 mo of age in the Kiang West district of The Gambia. Using a crossover design, children received for 1 d each porridge test meals with 20 g SQ-LNS containing 8 mg zinc and either 1) exogenous phytase or 2) no exogenous phytase. The test meals were provided on consecutive days in randomized order. FAZ was measured using a triple stable isotope tracer ratio technique with Zn-67 and Zn-70 as oral tracers and Zn-68 as the intravenous tracer., Results: Twenty-six participants completed the study. The prevalence of stunting and wasting were 20% and 13%, respectively; no children had low plasma zinc concentrations (<65 μg/dL). Total mean ± SD dietary zinc intake from the test meals was 7.3 ± 2.2 mg (phytate:zinc molar ratio = 3.1 ± 0.3, not accounting for phytase activity). Mean FAZ increased from 8.6% ± 1.3% to 16.0% ± 1.3% when exogenous phytase was added to the SQ-LNS product (P < 0.001). Mean TAZ from test meals containing SQ-LNS with phytase was more than double that from test meals containing SQ-LNS without phytase (1.1 ± 0.1 mg and 0.5 ± 0.1 mg, respectively; P < 0.001)., Conclusions: The addition of exogenous phytase to SQ-LNS increased both FAZ and TAZ. These results suggest that phytate reduction may be an important strategy to increase zinc absorption among young children. This trial was registered at clinicaltrials.gov as NCT02668133., (Copyright © American Society for Nutrition 2019.)

Background: Cross-sectional (CS) surveys indicate that individuals with acute inflammation have higher plasma ferritin (pF), and lower retinol-binding protein (RBP) and zinc (pZn) concentrations than those without. In populations with a high burden of infection, correction factors (CFs) or regression corrections (RCs) are applied to biomarkers to estimate the prevalence of micronutrient (MN) deficiencies adjusted for inflammation. This assumes that individuals with and without inflammation have the same nutritional status, which may not be the case., Objectives: The aim of this study was to investigate relations between short-term, longitudinal within-individual changes in acute phase proteins (C-reactive protein [CRP], α-1-acid glycoprotein [AGP]) and biomarkers of MN status (pF, soluble transferrin receptor [sTfR], RBP, and pZn), and compare them to CS differences., Methods: Two blood samples were obtained 21 d apart from 451 asymptomatic Burkinabé children aged 6-23 mo. To calculate CFs, inflammation was defined as CRP >5 mg/L or AGP >1 g/L, or both. The RC approach adjusted MN biomarkers to a presumably healthy reference point within the study population (10th percentile CRP or AGP concentration). CS CFs and RCs were estimated from a naive regression model, treating observations from the same children as independent. Longitudinal CFs and RCs, to estimate effects of within-individual changes in CRP and/or AGP, were estimated from general linear models, accounting for repeated measures., Results: In CS models, geometric mean pF and sTfR concentrations were 8-340% greater, and RBP and pZn 2-18% lower, in children with inflammation than those without. Except for sTfR, biomarker concentrations differed in the same direction and by similar magnitude within individuals whose inflammation status changed during the observation period. Although geometric mean MN concentrations differed significantly when adjusted with CS compared with longitudinal models, the estimated prevalence of MN deficiencies in CS and longitudinally adjusted models was similar., Conclusions: The CF and RC approaches to adjust MN biomarkers for inflammation between individuals in CS surveys are valid approaches for data collection and programmatic decisions in comparable populations. This study was registered at clinicaltrials.gov as NCT00944853., (Copyright © American Society for Nutrition 2019.)

Objectives: To evaluate the optimal zinc supplementation strategy for improving growth and hematologic and micronutrient status in young Laotian children., Study Design: In total, 3407 children aged 6-23 months were randomized to receive either daily preventive zinc tablets (7 mg/d), high-zinc, low-iron micronutrient powder (10 mg/d zinc, 6 mg/d iron, and 13 other micronutrients), therapeutic zinc supplementation for diarrhea (20 mg/d for 10 days per episode), or daily placebo powder; all were followed for ~9 months. Anthropometry, hemoglobin, zinc, and iron status were assessed at baseline and endline. Analyses were by intention-to-treat, using linear and modified Poisson regression., Results: At baseline, mean (±SD) age was 14.2 ± 5.1 months and stunting and anemia prevalence were 37.9% and 55.6%, respectively. At endline, zinc deficiency in the preventive zinc (50.7%) and micronutrient powder (59.1%) groups were significantly lower than in the therapeutic zinc (79.2%) and control groups (78.6%; P < .001), with no impact on stunting (37.1%-41.3% across the groups, P = .37). The micronutrient powder reduced iron deficiency by 44%-55% compared with other groups (P < .001), with no overall impact on anemia (P = .14). Micronutrient powder tended to reduce anemia by 11%-16% among children who were anemic at baseline (P = .06)., Conclusions: Despite improving zinc status, preventive zinc and micronutrient powder had no impact on growth. The micronutrient powder improved iron status and tended to reduce anemia among the subset of previously anemic children., Trial Registration: ClinicalTrials.govNCT02428647., (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Few data are available on the effectiveness of large-scale food fortification programs. Objective: We assessed the impact of mandatory wheat flour fortification on micronutrient status in Yaoundé and Douala, Cameroon. Methods: We conducted representative surveys 2 y before and 1 y after the introduction of fortified wheat flour. In each survey, 10 households were selected within each of the same 30 clusters ( n = ∼300 households). Indicators of inflammation, malaria, anemia, and micronutrient status [plasma ferritin, soluble transferrin receptor (sTfR), zinc, folate, and vitamin B-12] were assessed among women aged 15-49 y and children 12-59 mo of age. Results: Wheat flour was consumed in the past 7 d by ≥90% of participants. Postfortification, mean total iron and zinc concentrations of flour samples were 46.2 and 73.6 mg/kg (target added amounts were 60 and 95 mg/kg, respectively). Maternal anemia prevalence was significantly lower postfortification (46.7% compared with 39.1%; adjusted P = 0.01), but mean hemoglobin concentrations and child anemia prevalence did not differ. For both women and children postfortification, mean plasma concentrations were greater for ferritin and lower for sTfR after adjustments for potential confounders. Mean plasma zinc concentrations were greater postfortification and the prevalence of low plasma zinc concentration in women after fortification (21%) was lower than before fortification (39%, P < 0.001); likewise in children, the prevalence postfortification (28%) was lower than prefortification (47%, P < 0.001). Mean plasma total folate concentrations were ∼250% greater postfortification among women (47 compared with 15 nmol/L) and children (56 compared with 20 nmol/L), and the prevalence of low plasma folate values was <1% after fortification in both population subgroups. In a nonrepresentative subset of plasma samples, folic acid was detected in 77% of women (73% of those fasting) and 93% of children. Mean plasma and breast-milk vitamin B-12 concentrations were >50% greater postfortification. Conclusion: Although the pre-post survey design limits causal inference, iron, zinc, folate, and vitamin B-12 status increased among women and children in urban Cameroon after mandatory wheat flour fortification., Competing Interests: Author disclosures: LHA, SS-F, DH, DWK, M-MG, LAH, AF, and RAS, no conflicts of interest. RE-S, MN, AON, AT, and KHB received research funding from Sight and Life for the current study. RE-S received conference travel support from Sight and Life for an unrelated project.

Background: We assessed the effects of providing a package of interventions including small-quantity lipid-based nutrient supplements (SQ-LNS) containing 0, 5 or 10 mg zinc and illness treatment to Burkinabe children from 9 to 18 months of age, on biomarkers of zinc, iron and vitamin A status at 18 months and compared with a non-intervention cohort (NIC)., Methods: Using a two-stage cluster randomized trial design, communities were randomly assigned to the intervention cohort (IC) or NIC, and extended family compounds within the IC were randomly assigned to different treatment groups. IC children (n = 2435) were provided with 20 g SQ-LNS/d containing 0, 5 or 10 mg zinc, 6 mg of iron and 400 μg of vitamin A along with malaria and diarrhea treatment. NIC children (n = 785) did not receive the intervention package. At 9 and 18 months, hemoglobin (Hb), zinc, iron and vitamin A status were assessed in a sub-group (n = 404). Plasma concentrations of zinc (pZC), ferritin (pF), soluble transferrin receptor (sTfR) and retinol-binding protein (RBP) were adjusted for inflammation., Results: At baseline, 35% of children had low adjusted pZC (<65 μg/dL), 93% were anemic (Hb <110 g/L), 25% had low adjusted pF (<12 μg/L), 90% had high adjusted sTfR (>8.3 mg/L) and 47% had low adjusted RBP (<0.94 μmol/L), with no group-wise differences. Compared with the NIC, at 18 months IC children had significantly lower anemia prevalence (74 vs. 92%, p = 0.001) and lower iron deficiency prevalence (13% vs. 32% low adjusted pF and 41% vs. 71% high adjusted sTfR, p < 0.001), but no difference in pZC. Mean adjusted RBP was greater at 18 months in IC vs. NIC (0.94 μmol/L vs. 0.86 μmol/L, p = 0.015), but the prevalence of low RBP remained high in both cohorts. Within the IC, different amounts of zinc had no effect on the prevalence of low pZC or indicators of vitamin A deficiency, whereas children who received SQ-LNS with 10 mg zinc had a significantly lower mean pF at 18 months compared to children who received SQ-LNS with 5 mg zinc (p = 0.034)., Conclusions: SQ-LNS regardless of zinc amount and source provided along with illness treatment improved indicators of iron and vitamin A status, but not pZC., Trial Registration: NCT00944281 (July 21, 2009).

Background: The WHO and UNICEF recommend therapeutic zinc supplementation (TZS) for the treatment of diarrhea. In zinc-deficient populations, preventive zinc supplementation might provide greater benefits for reducing diarrhea and malaria incidence and increasing growth and plasma zinc (pZn) concentration. If effective, intermittent preventive zinc supplementation (IPZS) would cost less than daily preventive zinc supplementation (DPZS)., Objective: We assessed the effects of IPZS, DPZS, and TZS in children on the primary outcomes of diarrhea incidence, malaria incidence, growth, and pZn concentration compared with nonsupplemented control groups., Methods: Rural Burkinabe children (n = 7641; 6-30 mo old) in 36 clusters were randomly assigned to 1 of 5 treatment groups for 16, 32, or 48 wk: 1) IPZS (10 mg Zn/d for 10 d every 16 wk); 2) DPZS (7 mg Zn/d); 3) TZS (20 mg Zn/d for 10 d for diarrhea); 4) morbidity surveillance control (MSC); or 5) nonintervention control (NIC). Supplemented groups remained masked until completion of primary analyses with mixed models., Results: At baseline, stunting (28.6%) and low pZn concentration (<65 μg/dL; 43.5%) were common. After 48 wk, mean ± SE pZn increased more (P = 0.008) in the DPZS group (3.9 ± 1.3 μg/dL) than in the TZS (-0.5 ± 1.2 μg/dL) and NIC (-1.2 ± 0.9 μg/dL) groups. All supplemented groups had a moderately lower incidence of reported diarrhea (0.48-0.49 compared with 0.57 episodes/100 d, P = 0.001) and reported fever (1.1-1.2 compared with 1.5 episodes/100d, P < 0.001) and gained slightly less length (3.15-3.20 compared with 3.36 cm/16 wk, P < 0.001) than the MSC group, but did not differ from each other. Prevalence of diarrhea and incidences of confirmed fever and malaria were not different across study groups., Conclusions: The preventive and TZS groups had reduced diarrhea incidence, but it is uncertain whether this resulted from a functional response to zinc or reporting bias. The comparison should be re-examined in populations known to respond to zinc supplementation. This trial was registered at www.clinicaltrials.gov as NCT00944359., (© 2016 American Society for Nutrition.)

Objective: Preventive zinc supplementation in the form of tablets or syrup reduces the incidence of diarrhoea and acute lower respiratory tract infections (RTI), but its effect on malaria is inconsistent. When zinc is administered with other micronutrients or foods, its effect is also uncertain. We assessed the effects of different amounts and sources of zinc on the frequency of diarrhoea, malaria, fever and RTI in young children., Design, Setting and Populations: This community-based, double-blind, placebo-controlled, cluster-randomised trial of 2435 children 9 months of age was carried out between April 2010 and July 2012 in rural southwestern Burkina Faso., Interventions: Participants were randomly assigned at the concession level to receive daily 1 of 4 interventions for 9 months: (1) 20 g small-quantity lipid-based nutrient supplement (SQ-LNS) without zinc and placebo tablet, (2) 20 g SQ-LNS with 5 mg zinc and placebo tablet, (3) 20 g SQ-LNS with 10 mg zinc and placebo tablet or (4) 20 g SQ-LNS without zinc and 5 mg zinc tablet. Participants were visited weekly in their homes for morbidity surveillance for 9 months, and those with uncomplicated diarrhoea and malaria received treatment from the study field workers in the community., Main Outcomes: Incidence and longitudinal prevalence of diarrhoea, malaria, fever, and lower and upper RTI by intervention group., Results: The incidence of diarrhoea, malaria and fever was 1.10 (±1.03 SD), 0.61 (±0.66 SD) and 1.49 (±1.12 SD) episodes per 100 child-days at risk, respectively, and did not differ by intervention group (p=0.589, p=0.856 and p=0.830, respectively). The longitudinal prevalence of acute lower RTI (0.1%; 95% IC 0.1-0.2%) and of upper RTI (7.8%; 95% IC 7.1-8.4%) did not differ among groups (p=0.234 and p=0.501, respectively)., Conclusions: Inclusion of 5 or 10 mg zinc in SQ-LNS and provision of 5 mg zinc dispersible tablet along with SQ-LNS had no impact on the incidence of diarrhoea, malaria and fever or the longitudinal prevalence of RTI compared with SQ-LNS without zinc in this population., Trial Registration Number: NCT00944281., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Unlabelled: Small-quantity lipid-based nutrient supplements (SQ-LNS) are promising home fortification products, but the optimal zinc level needed to improve growth and reduce morbidity is uncertain. We aimed to assess the impact of providing SQ-LNS with varied amounts of zinc, along with illness treatment, on zinc-related outcomes compared with standard care. In a placebo-controlled, cluster-randomized trial, 34 communities were stratified to intervention (IC) or non-intervention cohorts (NIC). 2435 eligible IC children were randomly assigned to one of four groups:1) SQ-LNS without zinc, placebo tablet; 2) SQ-LNS containing 5mg zinc, placebo tablet; 3) SQ-LNS containing 10mg zinc, placebo tablet; or 4) SQ-LNS without zinc and 5mg zinc tablet from 9–18 months of age. During weekly morbidity surveillance, oral rehydration salts were provided for reported diarrhea and antimalarial therapy for confirmed malaria. Children in NIC (n = 785) did not receive SQ-LNS, tablets, illness surveillance or treatment. At 9 and 18 months, length, weight and hemoglobin were measured in all children. Reported adherence was 97 ± 6% for SQ-LNS and tablets. Mean baseline hemoglobin was 89 ± 15g/L. At 18 months, change in hemoglobin was greater in IC than NIC (+8 vs -1g/L, p<0.0001), but 79.1% of IC were still anemic (vs. 91.1% in NIC). Final plasma zinc concentration did not differ by group. During the 9-month observation period, the incidence of diarrhea was 1.10 ± 1.03 and of malaria 0.54 ± 0.50 episodes per 100 child-days, and did not differ by group. Length at 18 months was significantly greater in IC compared to NIC (77.7 ± 3.0 vs. 76.9 ± 3.4 cm; p<0.001) and stunting prevalence was significantly lower in IC (29.3%) than NIC (39.3%; p<0.0001), but did not differ by intervention group within IC. Wasting prevalence was also significantly lower in IC (8.7%) than in NIC (13.5%; p = 0.0003). Providing SQ-LNS daily with or without zinc, along with malaria and diarrhea treatment, significantly increased growth and reduced stunting, wasting and anemia prevalence in young children., Trial Registration: ClinicalTrials.gov NCT00944281.

Background: Biomarkers of iron [plasma ferritin (pF)], vitamin A [retinol binding protein (RBP)], and zinc status [plasma zinc (pZn)] are affected by the acute phase response, independent of micronutrient status., Objective: The objective of these analyses was to assess how asymptomatic malaria infection affects the interpretation of these biomarkers after adjustment for elevated acute phase proteins (APPs)., Methods: Soluble transferrin receptor (sTfR), pF, RBP, and pZn concentrations were measured among 451 asymptomatic children aged 6-23 mo in Burkina Faso and adjusted for elevated APP (C-reactive protein ≥5 mg/L and/or α-1-acid-glycoprotein ≥1 g/L) based on a 4-group categorical model. Plasma histidine-rich protein II (HRP2) concentrations ≥0.75 μg/L were considered indicative of current or recent malaria parasitemia., Results: Of the children in the study, 57.4% had at least 1 elevated APP, and 48.5% had elevated HRP2. After adjusting for APP, children with elevated HRP2 had higher pF (23.5 ± 1.5 μg/L vs. 11.1 ± 0.8 μg/L; P < 0.001) and lower RBP (0.79 ± 0.01 μmol/L vs. 0.92 ± 0.01 μmol/L; P < 0.001) than those without, but there were no differences in pZn among those with and without elevated HRP2 (64.9 ± 12.7 μg/dL vs. 64.9 ± 11.1 μg/dL; P = 0.98). Children with elevated HRP2 had higher sTfR than those without (17.6 ± 0.5 mg/L vs. 12.3 ± 0.4 mg/L; P < 0.0001). After adjusting for HRP2, along with APP, the estimated prevalence of iron deficiency (pF < 12 μg/L) increased from 38.7% to 50.6% and vitamin A deficiency (RBP < 0.84 μmol/L) decreased from 33.4% to 27.7%., Conclusions: Asymptomatic malaria is associated with indicators of micronutrient status, even after adjusting for APP. Adjusting indicators of iron and vitamin A status based only on APP may inaccurately estimate the prevalence of micronutrient deficiencies in settings with a high prevalence of malaria and inflammation. This trial was registered at clinicaltrials.gov as NCT00944853., (© 2014 American Society for Nutrition.)

Plasma zinc concentration (PZC) is a recommended biomarker to assess zinc status and the risk of zinc deficiency in populations. However, the relation between PZC and clinical signs of zinc deficiency remains uncertain. These analyses were conducted to evaluate the relation between PZC and clinical signs of zinc deficiency and to determine a cutoff for PZC below which individuals would have an increased likelihood of having clinical signs associated with zinc deficiency. Electronic bibliographic searches were conducted of literature indexed in PubMed, Embase, CINAHL Plus, and EBSCO and related to experimental zinc depletion studies in adults and case reports in children and adults (ages <1 mo-43 y) with acrodermatitis enteropathica (AE). Data extracted included demographic characteristics, PZCs, and the presence or absence of clinical signs likely associated with zinc deficiency (e.g., dermatitis, diarrhea). Mean PZC was significantly lower among adults consuming severely zinc-restricted diets (<1 mg Zn/d) who developed clinical signs compared with those who remained asymptomatic (36.0 ± 16.8 vs. 67.9 ± 13.3 μg/dL, P < 0.034). Likewise, patients with AE had a lower mean PZC when symptomatic compared with post-treatment PZC when they were asymptomatic (38.2 ± 20.7 vs. 102 ± 34.7 μg/dL, P < 0.01). Among individuals with restricted dietary zinc intake, PZC predicted clinical signs with 82% sensitivity and 92% specificity when using a cutoff of 50 μg/dL. Among individuals with AE, PZC predicted clinical signs with 80% sensitivity and 89% specificity when applying a cutoff of 50 μg/dL. These analyses demonstrate a clear relation between PZC and the presence of clinical signs associated with zinc deficiency among presumably healthy individuals undergoing periods of dietary zinc restriction, as well as in individuals with AE, further validating the usefulness of PZC as a biomarker of severe zinc deficiency., (© 2014 American Society for Nutrition.)

Information is needed on breast milk zinc concentration and amount of zinc transferred to the infant in relation to the time since birth for both appropriate-for-gestational-age (AGA) and small-for-gestational-age (SGA) infants. Breast milk zinc concentration and total milk volume were measured among mothers of AGA and SGA infants, using deuterium oxide "dose-to-mother" tracer technique and plasma zinc concentrations of mothers and infants. Forty-six mother-infant pairs (20 AGA and 26 SGA infants) were recruited from a low-income community in Bangladesh. Each mother-infant pair was studied 3 times: at 4, 12, and 24 wk postpartum. During each round, 2-wk studies of breast milk transfer were performed, using deuterium oxide dose-to-mother tracer technique. Breast milk samples were collected on days 1 and 5 of each round to determine milk zinc concentration. Mean ± SD birth weight and length were 3.02 ± 0.2 kg and 0.482 ± 0.012 m, respectively, for AGA and 2.34 ± 0.20 kg and 0.462 ± 0.011 m, respectively, for SGA infants, and both variables were different between groups (birth weight, P < 0.001; length, P < 0.001). Breast milk intake increased gradually with time postpartum in both groups. Breast milk zinc concentration decreased with increasing infant age (P < 0.001) but did not differ for mothers of AGA and SGA infants. Breast milk zinc transfer decreased significantly with age in both groups (P < 0.001) but did not differ by birth-weight category. Breast milk zinc concentration among Bangladeshi mothers and patterns of change at 24 wk were similar to those of wealthier countries, and there was no relation between infant birth-weight category and milk zinc concentration or transfer. This trial was registered at www.clinicaltrials.gov as NCT01728766.

Before initiating a mass zinc fortification program, this study assessed the prevalence of and risk factors for low zinc status among Cameroonian women and children. In a nationally representative survey, we randomly selected 30 clusters in each of 3 strata (North, South, and Yaoundé/Douala) and 10 households per cluster, each with a woman aged 15-49 y and a child aged 12-59 mo (n = 1002 households). Twenty-four-hour dietary recalls (with duplicates in a subset) and anthropometric measurements were conducted, and non-fasting blood was collected to measure plasma zinc concentration (PZC) and markers of inflammation. PZC was adjusted for methodologic factors (time of collection and processing, and presence of inflammation). The prevalence of stunting was 33% (32% South; 46% North; 13% Yaoundé/Douala). Among women, 82% had low adjusted PZC (<50 μg/dL for pregnant women; <66 μg/dL for others; 79% South, 89% North, 76% Yaoundé/Douala). Among children, 83% had low adjusted PZC (<65 μg/dL; 80% South, 92% North, 74% Yaoundé/Douala). Risk factors for low PZC among women and children and for low height-for-age Z-score among children were similar and included residence in the North region and rural areas and households with low socioeconomic status. Using estimated average requirement values from the International Zinc Nutrition Consultative Group (IZiNCG), 29 and 41% of women had inadequate zinc intakes, assuming moderate and low bioavailability, respectively, but only 8% of children had inadequate zinc intake. Depending on the estimated physiologic zinc requirement applied, 17% (IZiNCG) and 92% (Institute of Medicine) of women had inadequate absorbable zinc intakes. Total zinc intakes were greatest in the North region, possibly because of different dietary patterns in this area. Zinc deficiency is a public health problem among women and children in Cameroon, although PZC and dietary zinc yield different estimates of the prevalence of deficiency. Large-scale programs to improve zinc nutrition, including food fortification, are needed.

Objectives: Subclinical environmental enteropathy is associated with malabsorption of fats, carbohydrates, and vitamins A, B12, and folate; however, little information is available on mineral absorption. We therefore investigated the relation between intestinal mucosal function (measured by the lactulose:mannitol permeability test and plasma citrulline concentration), and zinc (Zn) absorption, as estimated by the change in plasma Zn concentration (PZC) following short-term Zn or placebo supplementation., Methods: We conducted a randomized, partially masked, placebo-controlled trial among 282 apparently healthy children 6 to 23 months of age in Burkina Faso. After completing baseline intestinal function tests, participants received either 5 mg Zn, as zinc sulfate, or placebo, daily for 21 days., Results: At baseline, mean ± standard deviation PZC was 62.9 ± 11.9 μg/dL; median (interquartile range) urinary lactulose:mannitol (L:M) recovery ratio and plasma citrulline concentrations were 0.04 (0.03-0.07) and 11.4 (9.0-15.6) μmol/L, respectively. Change in PZC was significantly greater in the Zn-supplemented versus placebo group (15.6 ± 13.3 vs 0.02 ± 10.9 μg/dL; P < 0.0001), and was negatively associated with initial urinary L:M recovery ratio (-1.1 μg/dL per 50% increase in urinary L:M recovery ratio; P = 0.014); this latter relation did not differ between supplementation groups (P = 0.26). Baseline plasma citrulline concentration was not associated with change in PZC., Conclusions: Although altered intestinal permeability may reduce dietary Zn absorption, it likely does not undermine the efficacy of Zn supplementation, given the large increases in PZC following short-term Zn supplementation observed in this study, even among those with increased urinary L:M recovery ratios.

Background: Zinc supplementation of young children in lower-income countries reduces morbidity from diarrhea and pneumonia and all-cause mortality, but the most cost-effective approach for distributing zinc supplements is unknown., Objective: To examine the potential impact of four possible strategies for delivering zinc supplements on disease prevention and deaths averted among children 6 to 59 months of age in sub-Saharan Africa., Methods: We analyzed different zinc supplementation strategies to assess their likely impact on morbidity and mortality of preschool children in sub-Saharan Africa and to estimate their possible costs., Results: Preventive zinc supplementation reduces diarrhea incidence by 27% among children 12 to 59 months of age, pneumonia incidence by 21% among children 6 to 59 months of age, and all-cause mortality by 18% among children 12 to 59 months of age. The likely average total program costs of zinc supplementation programs were estimated from the outlays of existing service delivery platforms, such as child health days, community-based nutrition programs, and clinic-based treatment of diarrhea, assuming different levels of coverage and target age ranges of children., Conclusions: We found that the average total costs per life saved ranged from approximately US$462 to US$3,111, and the most cost-effective interventions were weekly or intermittent preventive zinc supplementation, because of the possibility of high coverage and fewer supplements required. Empirical data from zinc supplementation programs will be needed to confirm these estimates.

Information is needed on zinc absorption from grain cultivars having higher zinc content. Total absorbed zinc (TAZ) from mixed diets containing high-zinc rice (HZnR), conventional rice (CR), or CR plus zinc fortificant (CR+Zn) was measured. Forty-two nonmalnourished preschool-aged children were enrolled in 1 of 2 groups. Using a crossover design, children in group A (n = 22) received for 1 d each a mixed diet containing 150 g CR or HZnR. Children in group B (n = 20) received HZnR on 1 d and CR+Zn on the other day. Fractional zinc absorption (FZA) was measured during each dietary period by using a dual-isotope tracer ratio technique; TAZ was calculated as the product of zinc intake [total dietary zinc (TDZ)] and FZA. TDZ was 3.83, 4.83, and 6.03 mg/d when the children were fed the CR, HZnR, and CR+Zn-containing diets, respectively. Mean FZA from the CR diet was greater than from the HZnR diet (25.1 vs. 20.1%, P < 0.001), and the mean FZA from the CR+Zn diet (18.8%) was less than from both the CR diet (P < 0.001) and the HZnR diet (P = 0.014). The mean TAZ was 0.96 ± 0.16, 0.97 ± 0.18, and 1.13 ± 0.20 mg/d from the CR, HZnR and CR +Zn diets, respectively. TAZ was not different for the CR and HZnR diets (P = 0.99) but was significantly greater from the CR+Zn diet compared with the other 2 diets (P < 0.001). Rice cultivars with higher zinc and/or lower phytate content are needed to increase TAZ by young children consuming this amount of rice.

Objective: To assess zinc absorption from dispersible tablets by investigating the effects of short-term zinc supplementation, provided either as zinc (Zn) sulfate dispersible tablets or solution, on changes in plasma Zn concentration in young children., Study Design: We conducted a randomized, partially-masked, placebo-controlled trial in 451 children 6 to 23 months of age in Burkina Faso, randomly assigned to receive a dispersible tablet containing 5 mg Zn, a Zn solution containing 5 mg Zn/5 mL, or a placebo solution, daily for 3 weeks. The main outcome measure was change in plasma zinc concentration after supplementation compared with baseline., Results: The mean plus or minus SD change in plasma Zn concentration (μg/dL) was significantly greater in both Zn supplemented groups (tablets: 16.9±13.1μg/dL, liquid: 16.6±14.2 μg/dL), compared with the placebo group (0.2±10.9 μg/dL; P<.001, ANOVA). In both Zn supplemented groups, but not in the placebo group, change in plasma Zn concentration was progressively less with increasing age in months (-0.79 μg/dL/mo and -1.15 μg/dL/mo, respectively; P<.001); this effect did not differ in the Zn supplemented groups (P=.18)., Conclusions: Short-term supplementation results in a large increase in plasma Zn concentration, regardless of whether the additional Zn is provided as a dispersible tablet or solution., (Copyright © 2012 Mosby, Inc. All rights reserved.)

Background: The prevalence of inadequate zinc intake in a population can be estimated by comparing the zinc content of the food supply with the population's theoretical requirement for zinc. However, assumptions regarding the nutrient composition of foods, zinc requirements, and zinc absorption may affect prevalence estimates. These analyses were conducted to: (1) evaluate the effect of varying methodological assumptions on country-specific estimates of the prevalence of dietary zinc inadequacy and (2) generate a model considered to provide the best estimates., Methodology and Principal Findings: National food balance data were obtained from the Food and Agriculture Organization of the United Nations. Zinc and phytate contents of these foods were estimated from three nutrient composition databases. Zinc absorption was predicted using a mathematical model (Miller equation). Theoretical mean daily per capita physiological and dietary requirements for zinc were calculated using recommendations from the Food and Nutrition Board of the Institute of Medicine and the International Zinc Nutrition Consultative Group. The estimated global prevalence of inadequate zinc intake varied between 12-66%, depending on which methodological assumptions were applied. However, country-specific rank order of the estimated prevalence of inadequate intake was conserved across all models (r = 0.57-0.99, P<0.01). A "best-estimate" model, comprised of zinc and phytate data from a composite nutrient database and IZiNCG physiological requirements for absorbed zinc, estimated the global prevalence of inadequate zinc intake to be 17.3%., Conclusions and Significance: Given the multiple sources of uncertainty in this method, caution must be taken in the interpretation of the estimated prevalence figures. However, the results of all models indicate that inadequate zinc intake may be fairly common globally. Inferences regarding the relative likelihood of zinc deficiency as a public health problem in different countries can be drawn based on the country-specific rank order of estimated prevalence of inadequate zinc intake.

Background: Adequate zinc nutrition is essential for adequate growth, immunocompetence and neurobehavioral development, but limited information on population zinc status hinders the expansion of interventions to control zinc deficiency. The present analyses were conducted to: (1) estimate the country-specific prevalence of inadequate zinc intake; and (2) investigate relationships between country-specific estimated prevalence of dietary zinc inadequacy and dietary patterns and stunting prevalence., Methodology and Principal Findings: National food balance sheet data were obtained from the Food and Agriculture Organization of the United Nations. Country-specific estimated prevalence of inadequate zinc intake were calculated based on the estimated absorbable zinc content of the national food supply, International Zinc Nutrition Consultative Group estimated physiological requirements for absorbed zinc, and demographic data obtained from United Nations estimates. Stunting data were obtained from a recent systematic analysis based on World Health Organization growth standards. An estimated 17.3% of the world's population is at risk of inadequate zinc intake. Country-specific estimated prevalence of inadequate zinc intake was negatively correlated with the total energy and zinc contents of the national food supply and the percent of zinc obtained from animal source foods, and positively correlated with the phytate: zinc molar ratio of the food supply. The estimated prevalence of inadequate zinc intake was correlated with the prevalence of stunting (low height-for-age) in children under five years of age (r = 0.48, P<0.001)., Conclusions and Significance: These results, which indicate that inadequate dietary zinc intake may be fairly common, particularly in Sub-Saharan Africa and South Asia, allow inter-country comparisons regarding the relative likelihood of zinc deficiency as a public health problem. Data from these analyses should be used to determine the need for direct biochemical and dietary assessments of population zinc status, as part of nationally representative nutritional surveys targeting countries estimated to be at high risk.

Micronutrient deficiencies are a public health concern among young children in low-income countries, and novel strategies are needed to improve the nutritional status of children at risk. One promising approach is the use of lipid-based nutrient supplements (LNS), which can be added to complementary food at the time of consumption. The optimal amount of zinc to include in LNS is uncertain, and concerns have been expressed about possible adverse effects of zinc on sensory characteristics of LNS. We conducted a series of acceptability studies of LNS containing either 0 or 10 mg of zinc per daily 20 g LNS dose among Burkinabe children 9-15 months old and their mothers. These acceptability studies included observations of children's consumption, maternal and child sensory reaction to the products using a 5-unit hedonic scale, a triangle test for detection of differences and a review of maternal reports of their child-feeding experiences during a 2-week home-feeding trial. The LNS products were well appreciated by the mothers and children during the sensory trials and the 2-week home-feeding trial. The addition of 10 mg zinc to LNS did not affect the consumed proportion of the offered porridge-LNS-mixture (P = 0.43). Results of the triangle test with mothers confirmed that there was no detectable difference between products containing 0 or 10 mg zinc per 20 g LNS dose. Most importantly, interviews and focus groups following the 2-week home-feeding trial indicated good acceptability of the products by mothers and their children., (© 2010 Blackwell Publishing Ltd.)

The responsiveness of plasma zinc concentration to zinc fortification is uncertain. Our objective in this study was to determine whether plasma zinc concentration changes in response to consuming zinc-fortified foods or liquid zinc supplements. We conducted a 4-wk double-blind, randomized trial among 132 healthy Senegalese men ≥ 18 y. Participants received 1 of 4 interventions: 1) (control) 200 g/d of wheat bread fortified with iron and folic acid, but not zinc, and a liquid multivitamin supplement without zinc between meals; 2) (zinc supplement) the same bread and the same multivitamin supplement with 15 mg zinc as ZnSO(4) added; 3) (moderate zinc fortification) the same bread cofortified with 7.5 mg zinc as ZnO and the same multivitamin supplement without zinc; or 4) (high zinc fortification) the same bread cofortified with 15 mg zinc as ZnO and the same multivitamin supplement without zinc. Fasting blood samples were collected twice at baseline and at d 15 and 29 of the intervention. There was no significant interaction between group and study day (P = 0.11). However, at d 15, the mean change in plasma zinc concentration in the zinc-supplemented group was greater than in the placebo and fortification groups ( 0.72 μmol/L vs. -0.09 to 0.03 μmol/L; P = 0.05). At d 29 there were no significant group-wise differences. Across all time points, the zinc-supplemented group was the only group where plasma zinc concentration increased from baseline (P = 0.006). These results suggest that plasma zinc concentration may not be a sufficiently sensitive indicator to evaluate short-term responses to zinc fortification.

Background: Simple, low-cost methods are needed to evaluate the effect of zinc-fortification programs. Plasma zinc concentration is a useful biomarker of zinc intake from supplementation, but responses to zinc fortification are inconsistent., Objective: The objective was to compare the change in plasma zinc concentrations in young children who received zinc from either a liquid supplement or a zinc-fortified complementary food., Design: A double-blind intervention trial was conducted in 137 young Senegalese children aged 9-17 mo who were randomly assigned to receive one of the following treatments for 15 d: 1) 30 g dry weight of an iron-fortified cereal porridge and a liquid multivitamin supplement without zinc (control group), 2) the same porridge and multivitamin supplement with 6 mg Zn added to the supplement dose (ZnSuppl group), or 3) the same porridge with added zinc to provide 6 mg Zn per 25 g dry weight of porridge and multivitamin without zinc (ZnFort group)., Results: Mean (±SD) plasma zinc concentration (μg/dL) increased by 4.7 ± 1.6 (P = 0.004) in the ZnSuppl group, which was significantly greater (P = 0.009) than the mean change in the control group (-1.0 ± 1.6; P = 0.51) and in the ZnFort group (-1.8 ± 1.7; P = 0.29). The latter 2 groups did not differ from each other (P = 0.99)., Conclusions: Plasma zinc concentration increased in children who received daily zinc supplementation for 15 d but not in those who received a zinc-fortified complementary food containing a similar amount of zinc. Additional longer-term studies are needed to assess the effect of zinc-fortification programs on zinc-related functional outcomes and the usefulness of plasma zinc as a biomarker of program effect. This trial was registered at www.clinicaltrials.gov as study NCT0094398.

Dietary phytic acid is a major causative factor for low Zn bioavailability in many cereal- and legume-based diets. The bioavailability of Zn in seed of low phytic acid (lpa) variants of maize ( Zea mays L.), rice ( Oryza sativa L.), and barley ( Hordeum vulgare L.) was evaluated using a suckling rat pup model. Suckling rat pups (14 days old, n = 6-8/treatment) were fasted for 6 h and intubated with (65)Zn-radiolabeled suspensions prepared using seed produced by either wild-type (normal phytic acid) or lpa genotypes of each cereal. Test solutions were radiolabeled overnight (all genotypes) or immediately prior to intubation (barley genotypes). Pups were killed 6 h postintubation and tissues removed and counted in a gamma counter. Zn absorption was low from wild-type genotypes of maize (21, 33%) and rice (26%), and phytic acid reduction resulted in significantly higher Zn absorption, 47-52 and 35-52%, respectively. Zn absorption from wild-type barley incubated overnight was high (86-91%), and phytate reduction did not improve Zn absorption (84-90%), which is likely due to endogenous phytase activity. When the wild-type barley solutions were prepared immediately before intubation, Zn absorption was significantly lower (63, 78%) than from the lpa cultivars (92, 96%). Variation in seed or flour phenolic acid levels did not affect Zn absorption. Differences in seed Zn levels did not substantially affect Zn absorption. Thus, when phytic acid is abundant in a diet, it has a larger effect on Zn absorption than the level of Zn. Therefore, reducing the phytic acid content of staple cereal grains may contribute to enhancing Zn nutrition of populations consuming these staple foods.

To assist with the evaluation of zinc (Zn) intervention programs, information is needed on the magnitude and velocity of response of plasma Zn concentration following changes in Zn intake. Our objective in this study was to measure plasma Zn concentration of healthy adult men before and after initiation and discontinuation of 1 of 2 dosages of Zn supplements or placebo. We conducted a randomized, double-blind, placebo-controlled trial in 58 apparently healthy males aged 19-54 y. Participants received 1 of 3 liquid supplements daily for 21 d: 10 or 20 mg Zn/d, as Zn sulfate, or placebo. Fasting plasma Zn concentrations were measured on 14 occasions before, during, and after supplementation. Data were analyzed using mixed-model ANCOVA. The plasma Zn concentration was related to day of study (P < 0.0001) and study group (P < 0.0001). Controlling for baseline concentrations, plasma Zn concentrations were consistently elevated above baseline by d 5 among individuals in both of the Zn-supplemented groups compared with those receiving placebo supplements, regardless of their initial plasma Zn concentration. There were no significant group-wise differences between those who received either 10 or 20 mg/d Zn. Plasma Zn concentrations of supplemented individuals declined following withdrawal of supplementation and within 2 wk no longer differed from those of the placebo group. Change in the plasma Zn concentration is a useful indicator to monitor compliance with, and possibly effectiveness of, Zn supplementation programs. To ensure accurate interpretation of the results, samples should be collected while the intervention is still in progress.

Rural Bangladeshi populations have a high risk of zinc deficiency due to their consumption of a predominantly rice-based diet with few animal-source foods. Breeding rice for higher zinc content would offer a sustainable approach to increase the population's zinc intakes. The objectives of the study were to quantify usual rice and zinc intakes in young children and their adult female primary caregivers and to simulate the potential impact of zinc-biofortified rice on their zinc intakes. We measured dietary intake in a representative sample of 480 children (ages 24-48 mo) and their female caregivers residing in 2 rural districts of northern Bangladesh. Dietary intakes were estimated by 12-h weighed records and 12-h recall in homes on 2 nonconsecutive days. Serum zinc concentrations were determined in a subsample of children. The median (25th, 75th percentile) rice intakes of children and female caregivers were 134 (99, 172) and 420 (365, 476) g raw weight/d, respectively. The median zinc intakes were 2.5 (2.1, 2.9) and 5.4 (4.8, 6.1) mg/d in children and women, respectively. Twenty-four percent of children had low serum zinc concentrations ( < 9.9 micromol/L) after adjusting for elevated acute phase proteins. Rice was the main source of zinc intake, providing 49 and 69% of dietary zinc to children and women, respectively. The prevalence of inadequate zinc intakes was high in both the children (22%) and women (73-100%). Simulated increases in rice zinc content to levels currently achievable through selective breeding decreased the estimated prevalence of inadequacy to 9% in children and 20-85% in women, depending on the assumptions used to estimate absorption. Rural Bangladeshi children and women have inadequate intakes of zinc. Zinc biofortification of rice has the potential to markedly improve the zinc adequacy of their diets.

Background: Zinc fortification is recommended as an appropriate strategy to enhance population zinc status, but guidelines are needed on the appropriate types and levels of zinc fortification of cereal flours for mass fortification programs., Objective: To review available information on the scientific rationale, efficacy, and effectiveness of zinc fortification programs, and to develop guidelines on appropriate levels of fortification of cereal flours, based on simulations of the amount of zinc absorbed under different dietary conditions and information on possible adverse effects., Methods: Systematic review of scientific literature and application of an existing prediction equation to estimate zinc absorption., Results: Previously completed research demonstrates that zinc intake and absorption are increased when zinc-fortified foods are consumed, but little information is, as yet, available on the biologic impact of large-scale fortification programs. Studies suggest that there are no disadvantages of the recommended ranges of zinc fortification with regard to the sensory properties of zinc-fortified foods, and most research indicates that there are no adverse effects of zinc fortification on the utilization of other minerals., Conclusions: Zinc fortification of cereal flour is a safe and appropriate strategy for enhancing the zinc status of population subgroups who consume adequate amounts of fortified cereal flour, although additional information is needed to confirm the efficacy and effectiveness of large-scale zinc fortification programs to control zinc deficiency. The appropriate level of fortification depends on the population subgroup, their usual amount of flour intake, the degree of milling and fermentation that is practiced, and the usual intakes of zinc and phytate from other food sources. Fortification recommendations are presented for different dietary scenarios.

Background: Zinc plays an important role in antioxidant defense and the maintenance of cellular DNA integrity. However, no experimental human studies have been performed to examine the role of zinc status on DNA damage., Objective: We evaluated the effects of dietary zinc depletion and repletion on DNA strand breaks, oxidative stress, and antioxidant defenses in healthy men., Design: Nine healthy men with reported mean daily zinc intakes >11 mg/d were recruited. Subjects completed 3 consecutive dietary periods: baseline (days 1 to 13; 11 mg Zn/d), zinc depletion (days 14 to 55; 0.6 mg Zn/d for 1 wk and 4 mg Zn/d for 5 wk), and zinc repletion (days 56 to 83; 11 mg Zn/d for 4 wk with 20 mg supplemental Zn for first 7 d). Blood samples were collected on days 1, 13, 35, 55, and 83. DNA damage in peripheral blood cells, plasma oxidative stress, and antioxidant defense biomarkers were assessed., Results: Dietary zinc depletion (6 wk) was associated with increased DNA strand breaks in peripheral blood cells (day 13 compared with day 55; P < 0.05), changes that were ameliorated by zinc repletion (day 55 compared with day 83; P < 0.05). Plasma zinc concentrations were negatively correlated with DNA strand breaks (r = -0.60, P = 0.006) during the zinc-depletion period. Plasma alpha- and gamma-tocopherol concentrations, plasma total antioxidant capacity, and erythrocyte superoxide dismutase activity did not change significantly, and plasma F(2)-isoprostanes were unaffected by dietary period., Conclusions: Changes in dietary zinc intake affected DNA single-strand breaks. Zinc appears to be a critical factor for maintaining DNA integrity in humans.

This paper summarizes the results of the foregoing reviews of the impact of different intervention strategies designed to enhance zinc nutrition, including supplementation, fortification, and dietary diversification or modification. Current evidence indicates a beneficial impact of such interventions on zinc status and zinc-related functional outcomes. Preventive zinc supplementation reduces the incidence of diarrhea and acute lower respiratory tract infection among young children, decreases mortality of children over 12 months of age, and increases growth velocity. Therapeutic zinc supplementation during episodes of diarrhea reduces the duration and severity of illness. Zinc fortification increases zinc intake and total absorbed zinc, and recent studies are beginning to confirm a positive impact of zinc fortification on indicators of population zinc status. To assist with the development of zinc intervention programs, more information is needed on the prevalence of zinc deficiency in different countries, and rigorous evaluations of the effectiveness of large-scale zinc intervention programs should be planned. Recommended steps for scaling up zinc intervention programs, with or without other micronutrients, are described. In summary, there is now clear evidence of the benefit of selected interventions to reduce the risk of zinc deficiency, and a global commitment is urgently needed to conduct systematic assessments of population zinc status and to develop interventions to control zinc deficiency in the context of existing public health and nutrition programs.

Zinc deficiency increases the risk and severity of a variety of infections, restricts physical growth, and affects specific outcomes of pregnancy. Global recognition of the importance of zinc nutrition in public health has expanded dramatically in recent years, and more experience has accumulated on the design and implementation of zinc intervention programs. Therefore, the Steering Committee of the International Zinc Nutrition Consultative Group (IZiNCG) completed a second IZiNCG technical document that reexamines the latest information on the intervention strategies that have been developed to enhance zinc nutrition and control zinc deficiency. In particular, the document reviews the current evidence regarding preventive zinc supplementation and the role of zinc as adjunctive therapy for selected infections, zinc fortification, and dietary diversification or modification strategies, including the promotion and protection of breastfeeding and biofortification. The purposes of this introductory paper are to summarize new guidelines on the assessment of population zinc status, as recommended by the World Health Organization (WHO), the United Nations Children's Fund (UNICEF), the International Atomic Energy Agency (IAEA), and IZiNCG, and to provide an overview on several new advances in zinc metabolism. The following papers will then review the intervention strategies individually.

Objective: To make the best use of limited resources for supporting health-related research to reduce child mortality, it is necessary to apply a suitable method to rank competing research options. The Child Health and Nutrition Research Initiative (CHNRI) developed a new methodology for setting health research priorities. To broaden experience with this priority-setting technique, we applied the method to rank possible research priorities concerning the control of Zn deficiency. Although Zn deficiency is not generally recognized as a direct cause of child mortality, recent research indicates that it predisposes children to an increased incidence and severity of several of the major direct causes of morbidity and mortality., Design: Leading experts in the field of Zn research in child health were identified and invited to participate in a technical working group (TWG) to establish research priorities. The individuals were chosen to represent a wide range of expertise in Zn nutrition. The seven TWG members submitted a total of ninety research options, which were then consolidated into a final list of thirty-one research options categorized by the type of resulting intervention., Results: The identified priorities were dominated by research investment options targeting Zn supplementation, and were followed by research on Zn fortification, general aspects of Zn nutrition, dietary modification and other new interventions., Conclusions: In general, research options that aim to improve the efficiency of an already existing intervention strategy received higher priority scores. Challenges identified during the implementation of the methodology and suggestions to modify the priority-setting procedures are discussed.

Food fortification is increasingly recognized as an effective approach to improve a population's micronutrient status. The present report provides a critical review of the scientific evidence currently available on the impact of zinc fortification on zinc nutrition. The available studies clearly show that zinc fortification can increase dietary zinc intake and total daily zinc absorption. Most absorption studies also indicate that adding zinc to food does not adversely affect the absorption of other minerals, such as iron. Despite the positive effect of zinc fortification on total zinc absorption, only a few studies have found positive impacts of zinc fortification on serum zinc concentrations or functional indicators of zinc status. The reasons for these inconsistent results are uncertain but may relate to the choice of food vehicles, the age group and zinc status of the study populations, or particular aspects of the study design. Thus, additional research is needed to determine the impact of zinc fortification, with or without other micronutrients, in populations at risk for zinc deficiency. Because of the benefits of increasing intake in populations at high risk for zinc deficiency, the documented increase in total zinc absorption that occurs following zinc fortification, the absence of any adverse effects, and the relatively low cost of adding zinc, public health planners should consider including zinc in mass and targeted fortification programs in such populations. Because of the limited available information on program impact, it will be important to evaluate the outcomes of such programs.

Breastmilk is the only dietary source of zinc for exclusively breastfed young infants, and it remains a potentially important source of zinc for older infants and young children who continue breastfeeding beyond early infancy. Therefore, we examined available information on breastmilk zinc concentration and total milk consumption to develop estimates of the amount of zinc transferred in breastmilk to children of different ages. Breastmilk zinc concentration declines rapidly during the first few months postpartum and more slowly thereafter. Breastmilk supplies all of the theoretical zinc needs for at least the first several months of life, although the period during which breastmilk alone remains sufficient is uncertain. Breastmilk continues to provide more than half of children's estimated zinc requirements after the introduction of complementary foods, even into the second year of life. Public health programs to promote and support breastfeeding should be included among the strategies to ensure adequate zinc status of young children.

Zinc supplementation trials carried out among children have produced variable results, depending on the specific outcomes considered and the initial characteristics of the children who were enrolled. We completed a series of meta-analyses to examine the impact of preventive zinc supplementation on morbidity; mortality; physical growth; biochemical indicators of zinc, iron, and copper status; and indicators of behavioral development, along with possible modifying effects of the intervention results. Zinc supplementation reduced the incidence of diarrhea by approximately 20%, but the impact was limited to studies that enrolled children with a mean initial age greater than 12 months. Among the subset of studies that enrolled children with mean initial age greater than 12 months, the relative risk of diarrhea was reduced by 27%. Zinc supplementation reduced the incidence of acute lower respiratory tract infections by approximately 15%. Zinc supplementation yielded inconsistent impacts on malaria incidence, and too few trials are currently available to allow definitive conclusions to be drawn. Zinc supplementation had a marginal 6% impact on overall child mortality, but there was an 18% reduction in deaths among zinc-supplemented children older than 12 months of age. Zinc supplementation increased linear growth and weight gain by a small, but highly significant, amount. The interventions yielded a consistent, moderately large increase in mean serum zinc concentrations, and they had no significant adverse effects on indicators of iron and copper status. There were no significant effects on children's behavioral development, although the number of available studies is relatively small. The available evidence supports the need for intervention programs to enhance zinc status to reduce child morbidity and mortality and to enhance child growth. Possible strategies for delivering preventive zinc supplements are discussed.

The role of zinc deficiency as an important cause of morbidity and impaired linear growth has prompted the need to identify indicators of population zinc status. Three indicators have been recommended - prevalence of zinc intakes below the estimated average requirement (EAR), percentage with low serum zinc concentrations, and percentage of children aged < 5 years who are stunted. This review outlines steps to estimate the prevalence of inadequate intakes, and confirm their validity based on the EARs set by International Zinc Nutrition Collaborative Group. Next, the appropriateness of serum zinc as a biochemical marker for population zinc status is confirmed by a summary of: (a) the response of serum zinc concentrations to zinc intakes; (b) usefulness of serum zinc concentrations to predict functional responses to zinc interventions; (c) relationship between initial serum zinc and change in serum zinc in response to interventions. Height- or length-for-age was chosen as the best functional outcome after considering the responses of growth, infectious diseases (diarrhoea, pneumonia), and developmental outcomes in zinc supplementation trials and correlation studies. The potential of other zinc biomarkers such as zinc concentrations in hair, cells, zinc-metalloenzymes, and zinc-binding proteins, such as metallothionein, is also discussed. Molecular techniques employing reverse transcriptase (RT)-polymerase chain reaction to measure mRNA in metallothionein and ZIP1 transporter hold promise, as do kinetic markers such as exchangeable zinc pools (EZP) and plasma zinc turnover rates. More research is needed to establish the validity, specificity, sensitivity, and feasibility of these new biomarkers, especially in community-settings.

Background: No studies have examined the independent effects of current and longer-term dietary zinc intakes on zinc absorption., Objective: We determined the effects of current compared with longer-term zinc intake on fractional zinc absorption (FZA)., Design: We studied 9 men whose usual zinc intakes were >11 mg/d. FZA was measured at baseline, depletion (0.6 mg Zn/d for 1 wk and 4 mg Zn/d for 5 wk), and repletion (11 mg Zn/d for 4 wk with 20 mg supplemental Zn/d for first 7 d). During 2 successive days after each dietary period, subjects consumed either adequate-zinc meals (11 mg Zn/d) with a zinc stable isotope tracer for 1 d, followed by low-zinc meals (4 mg Zn/d) with zinc tracer, or vice versa. Five days after oral dosing, a zinc tracer was infused intravenously. FZA was measured with the use of a modified double isotope tracer ratio method with urine samples collected on days 5-7 and 10-12 of absorption studies., Results: Plasma and urinary zinc did not vary by dietary period. Mean FZA was greater from low-zinc meals than from adequate-zinc meals (60.9% +/- 13.8% compared with 36.1% +/- 8.9%; P < 0.0001), whereas mean total absorbed zinc was greater from adequate-zinc meals than from low-zinc meals (3.60 +/- 0.91 compared with 2.48 +/- 0.56; P < 0.0001), regardless of the longer-term dietary period., Conclusions: FZA was inversely related to current zinc intake, but there was no detectable effect of longer-term dietary zinc. If longer- term zinc intake does modify FZA, such changes are smaller than those caused by current zinc intake, or they occur only after more severe zinc depletion.

Background: Multiple studies have shown the benefits of zinc supplementation among young children in high-risk populations. However, the optimal dose and safe upper level of zinc have not been determined., Objectives: The objectives of this study were to measure the effects of different doses of supplemental zinc on the plasma zinc concentration, morbidity, and growth of young children; to detect any adverse effects of 10 mg supplemental Zn on markers of copper or iron status; and to determine whether any adverse effects are alleviated by providing copper with zinc., Design: This randomized, double-masked, community-based intervention trial was conducted in 631 Ecuadorian children who were 12-30 mo old at baseline and who had initial length-for-age z scores <-1.3. Children received 1 of 5 daily supplements for 6 mo: 3, 7, or 10 mg Zn as zinc sulfate, 10 mg Zn + 0.5 mg Cu as copper sulfate, or placebo., Results: The change in plasma zinc concentration from baseline was positively related to the zinc dose (P < 0.001). Zinc supplementation, including doses as low as 3 mg/d, reduced the incidence of diarrhea by 21-42% (P < 0.01). There were no other significant group-wise differences., Conclusions: Zinc supplementation with a dose as low as 3 mg/d increased plasma zinc concentrations and reduced diarrhea incidence in the study population. There were no observed adverse effects of 10 mg Zn/d on indicators of copper or iron status. The current tolerable upper level of zinc recommended by the Institute of Medicine should be reassessed for young children.

The exact mechanism whereby zinc influences growth is unknown, although it has been postulated that zinc may stimulate appetite and energy intake or enhance fat-free mass (FFM) accrual directly. We compared energy intake, reported appetite, and body composition of 6- to 8-mo-old Peruvian children with initial length-for-age Z-score (LAZ) < -0.5 SD who were randomly assigned to receive daily for 6 mo: 1) 3 mg/d zinc in a liquid supplement; 2) 3 mg/d zinc in a fortified porridge; or 3) no extra zinc in either the supplement or porridge. There were no group-wise differences in changes in dietary energy intakes or body composition or in the prevalence of reported poor appetite. However, among children with an initial LAZ less than the median (-1.1 SD), those who received zinc as a liquid supplement had a 0.41 kg greater increase in FFM than those who did not receive zinc (P < 0.05). We concluded that daily provision of 3 mg of supplemental zinc did not affect energy intake or reported appetite. Among children with initial mild-to-moderate stunting, those who received the zinc supplement had a greater increase in FFM than those who did not receive additional zinc. It is possible that the growth-restricted children were more likely to be zinc deficient and that FFM accrual may be an early growth response to supplemental zinc. Zinc supplements may be more efficacious than the same dose of zinc provided in fortified food; therefore, further research is needed on the optimal level of zinc fortification that will result in improved health outcomes in populations with high rates of zinc deficiency.

Background: Leptin, ghrelin, and insulin are hormonal regulators of energy balance and, therefore, may be related to growth during infancy. Zinc is essential for growth, and its growth effects may be mediated through these hormones., Objective: We examined the effects of supplemental zinc on plasma leptin, ghrelin, and insulin concentrations among young children at risk of zinc deficiency and examined the relations between these hormones and physical growth., Design: Children (n = 142) aged 6-8 mo were randomly assigned to receive 3 mg Zn/d as a supplement, in a fortified food, or as a placebo for 6 mo. Relations between hormones and anthropometric z scores, body composition, and growth rates were examined at baseline and 3 and 6 mo after the start of the intervention., Results: No treatment group-related differences were found in plasma leptin, ghrelin, or glucose concentrations or in anthropometric z scores at 3 or 6 mo after the start of the zinc intervention. Neither plasma leptin nor ghrelin concentrations at baseline or 3 mo were predictive of subsequent changes in growth. However, changes in weight-for-age z scores over the two 3-mo time intervals were positively associated with subsequent leptin concentrations and inversely associated with subsequent plasma ghrelin concentrations., Conclusions: Supplemental zinc did not affect the children's growth, anthropometric indexes, or plasma hormone concentrations in this study population. Our results suggest that plasma leptin and ghrelin concentrations in later infancy are a consequence of previous weight changes rather than predictors of short-term growth.

Assessing the prevalence and severity of zinc deficiency in populations is critical to determine the need for and appropriate targeting of zinc intervention programs and to assess their effectiveness for improving the health and well-being of high-risk populations. However, there is very little information on the zinc status of populations worldwide due to the lack of consensus on appropriate biochemical indicators of zinc status. The objective of this review was to evaluate the use of serum zinc concentration as an indicator of population zinc status. We have reviewed the response of serum zinc concentration to dietary zinc restriction and zinc supplementation. In addition, we completed pooled analyses of nine zinc intervention trials in young children to assess the relations between serum zinc concentration of individuals before treatment and their responses to zinc supplementation. Also, in updated combined analyses of previously published data, we investigated the relation between the mean initial serum zinc concentration of a study population and their mean growth responses to zinc supplementation in randomized intervention trials among children. The results from depletion/repletion studies indicate that serum zinc concentrations respond appreciably to severe dietary zinc restriction, although there is considerable interindividual variation in these responses. There is also clear evidence that both individual and population mean serum zinc concentrations increase consistently during zinc supplementation, regardless of the initial level of serum zinc concentration. By contrast, an individual's serum zinc concentration does not reliably predict that person's response to zinc supplementation. Serum zinc concentration can be considered a useful biomarker of a population's risk of zinc deficiency and response to zinc interventions, although it may not be a reliable indicator of individual zinc status.

Zinc fortification is considered a potentially useful strategy for the control of zinc deficiency, but the success of such intervention programs depends on the population's access to and consumption of zinc-fortified foods and adequate absorption of zinc from these foods. The latter issue has been assessed by a variety of studies that applied zinc isotopic tracers to assess zinc uptake from zinc-fortified foods. These studies show that the additional zinc provided by zinc fortification decreases fractional absorption of zinc, but increases total zinc absorption from these foods. Available studies show no significant difference in zinc absorption from foods fortified with either zinc oxide or zinc sulfate, which are the two cheapest chemical forms of zinc that are generally recognized as safe for human consumption. It appears that high-phytate meals depress zinc absorption from zinc-fortified foods, although total zinc absorption from such foods is still likely to be greater than if the foods were not fortified with zinc. With the possible exception of Na2EDTA, putative enhancers of zinc absorption do not seem to confer major benefits for zinc absorption from zinc-fortified foods. There is little information on the effect of fortification with other micronutrients on zinc absorption from co-fortified foods, and zinc fortification does not seem to suppress iron absorption from iron-fortified foods in most studies.

Background: Zinc supplementation decreases morbidity from infections and increases growth of stunted children, but there is little information on functional responses to zinc delivered in fortified foods., Objective: The aim was to examine the effects of zinc fortification on the growth, morbidity from infections, and plasma zinc concentrations of young children., Design: We compared the physical growth, morbidity, and micronutrient status of 6-8-mo-old Peruvian children with initial length-for-age z score (LAZ) < -0.50 who were randomly assigned to receive one of the following treatments daily for 6 mo: 1) 30 g dry weight of an iron-fortified cereal porridge and a separate dose of an aqueous multivitamin (MV) supplement between meals (control group), 2) the same porridge and MV with 3 mg Zn added to the supplement dose (ZnSuppl group), or 3) the porridge with added zinc (150 mg/kg dry weight) and MV without zinc (ZnFort group)., Results: The children consumed a mean of 22-26 g dry porridge/d and 96% of the possible MV doses. After adjustment for small baseline differences in socioeconomic status and morbidity, no significant differences in weight or length increments were observed between the groups, even among the subset with an initial LAZ < -1.5, and no significant differences in the rates of common illnesses were observed. Mean plasma zinc concentrations decreased in the control group (-3.9 microg/dL), increased in the ZnSuppl group (4.3 microg/dL), and did not change significantly in the ZnFort group (-1.5 microg/dL; P < 0.001 for group-wise comparison)., Conclusions: Provision of additional zinc, either in an aqueous supplement or a fortified porridge, did not significantly affect the children's physical growth or morbidity from infections, possibly because they were not sufficiently growth-restricted or zinc-deficient initially or because the level of zinc intake or absorption was inadequate. Additional studies of the functional effect of zinc-fortified foods are needed in populations that are known to respond to zinc supplements.