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Zinc Supplementation and Fortification: The Unfinished Agenda

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A special issue of Nutrients (ISSN 2072-6643). This special issue belongs to the section "Micronutrients and Human Health".

Deadline for manuscript submissions: closed (20 February 2022) | Viewed by 30603

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Special Issue Editors

Prof. Dr. Robert E. Black

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Guest Editor

Department of International Health, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe Street, Baltimore, MD 21205, USA
Interests: child health; diarrhea; zinc; child growth; undernutrition; global health

Dr. Christine McDonald

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Guest Editor

1. Department of Pediatrics, UCSF School of Medicine; MLK Building, 5700 Martin Luther King Jr. Way, Oakland, CA 94609, USA
2. Department of Nutrition, University of California, Davis, CA 95616, USA
Interests: zinc; micronutrients; undernutrition; maternal and child health; child growth; environmental enteric dysfunction

Special Issue Information

Dear Colleagues,

An estimated 17% of the global population is at risk of inadequate zinc intake, making zinc deficiency one of the most prevalent micronutrient deficiencies worldwide. Young children and pregnant women in resource-limited settings are particularly vulnerable to zinc deficiency given cultural and socioeconomic factors that may make it challenging to consume a diet sufficiently high in bioavailable zinc to meet their nutrient requirements. An estimated 116,000 child deaths are attributable to zinc deficiency each year.

While zinc supplementation can be an effective strategy for improving the zinc status of nutritionally vulnerable populations, there are several outstanding questions regarding the optimal dose and form of zinc supplementation along with challenges related to delivery and sustainability. Similarly, while research has demonstrated the efficacy of zinc fortification in improving zinc status, zinc is often overlooked in national fortification policies.

This special issue of Nutrients will highlight the results of recent research that has aimed to fill gaps in the current evidence base around zinc supplementation and fortification as strategies to reduce the global burden of zinc deficiency. It will encompass findings from the laboratory to the policy arena, and will highlight priority actions that are needed to address the unfinished agenda.

Prof. Dr. Robert E. Black
Dr. Christine McDonald
Guest Editors

Manuscript Submission Information

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

Zinc
Essential minerals
Micronutrients
Supplementation
Fortification
Child health
Child growth

Published Papers (10 papers)

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Research

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12 pages, 789 KiB

Open AccessArticle

Effects of Different Doses, Forms, and Frequencies of Zinc Supplementation on Biomarkers of Iron and Zinc Status among Young Children in Dhaka, Bangladesh

by M. Munirul Islam, Robert E. Black, Nancy F. Krebs, Jamie Westcott, Julie M. Long, Kazi M. Islam, Janet M. Peerson, Rahvia Alam Sthity, Afsana Mim Khandaker, Mehedi Hasan, Shams El Arifeen, Tahmeed Ahmed, Janet C. King and Christine M. McDonald

Nutrients 2022, 14(24), 5334; https://0-doi-org.brum.beds.ac.uk/10.3390/nu14245334 - 15 Dec 2022

Cited by 2 | Viewed by 2149

Abstract

Young children in resource-constrained settings are susceptible to zinc deficiency and its deleterious health effects. The objective of this secondary analysis was to evaluate the effects of the following six interventions on biomarkers of iron and zinc status among a subgroup of young children in Dhaka, Bangladesh, who participated in the Zinc in Powders Trial (ZiPT): (1) standard micronutrient powders (MNPs) containing 4.1 mg zinc and 10 mg iron, daily; (2) high-zinc (10 mg) and low-iron (6 mg) (HiZn LoFe) MNP, daily; (3) HiZn (10 mg) and LoFe (6 mg)/HiZn (10 mg) and no-iron MNPs on alternating days; (4) dispersible zinc tablet (10 mg), daily; (5) dispersible zinc tablet (10 mg), daily for 2 weeks at enrollment and at 12 weeks; (6) placebo powder, daily. At the end of the 24 week intervention period, children in the daily dispersible zinc tablet group exhibited a mean serum zinc concentration (SZC) of 92.5 μg/dL, which was significantly higher than all other groups except the HiZn LoFe MNP alternating group (81.3 μg/dL). MNPs containing 10 mg and 6 mg of iron had a similar impact on biomarkers of iron status, with no evidence of an adverse interaction with zinc. Full article

(This article belongs to the Special Issue Zinc Supplementation and Fortification: The Unfinished Agenda)

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11 pages, 310 KiB

Open AccessArticle

Consumption of Micronutrient Powder, Syrup or Fortified Food Significantly Improves Zinc and Iron Status in Young Mexican Children: A Cluster Randomized Trial

by Armando García-Guerra, Juan A. Rivera, Lynnette M. Neufeld, Amado D. Quezada-Sánchez, Clara Dominguez Islas, Ana Cecilia Fernández-Gaxiola and Anabelle Bonvecchio Arenas

Nutrients 2022, 14(11), 2231; https://0-doi-org.brum.beds.ac.uk/10.3390/nu14112231 - 27 May 2022

Cited by 2 | Viewed by 2059

Abstract

The objective of this study was to compare the effect of three micronutrient products on biomarkers of iron and zinc status of Mexican children 6–12 months of age. As part of research to improve the impact of a national program, 54 communities were randomly assigned to receive: (1) fortified food (FF), provided by the program at the time, or (2) micronutrient powders (MNP) or (3) syrup. Each product contained 10 mg each of zinc and iron, plus other micronutrients. Children consumed the product 6 days/week for four months. Primary outcomes were changes in serum zinc, ferritin, soluble transferrin receptor, hemoglobin concentrations, and their deficiencies. Zinc concentration increased significantly from baseline to follow-up in all groups, with the largest change in the syrup group (geometric mean difference: +4.4 µmol/L; 95%CI: 3.2, 5.5), followed by MNP (+2.9 µmol/L; 95%CI: 2.1, 3.6) and FF (+0.9 µmol/L; 95%CI: 0.3, 1.6). There was a significant increase in hemoglobin concentration (+5.5 g/L; 2.5, 8.4) and a significant reduction in anemia prevalence (44.2% to 26.8%, p < 0.01) only in the MNP group. Compliance differed significantly among groups (MNP vs. FF, p = 0.04; MNP vs. syrup, p = 0.04), but may not fully explain the greater improvement in zinc and iron status in the syrup and MNP groups. The food matrix may influence nutrient utilization from supplements. Full article

(This article belongs to the Special Issue Zinc Supplementation and Fortification: The Unfinished Agenda)

13 pages, 272 KiB

Open AccessArticle

Barriers to and Enablers of the Inclusion of Micronutrient Biomarkers in National Surveys and Surveillance Systems in Low- and Middle-Income Countries

by Mari S. Manger, Kenneth H. Brown, Saskia J. M. Osendarp, Reed A. Atkin and Christine M. McDonald

Nutrients 2022, 14(10), 2009; https://0-doi-org.brum.beds.ac.uk/10.3390/nu14102009 - 10 May 2022

Cited by 3 | Viewed by 1885

Abstract

Including biomarkers of micronutrient status in existing or planned national surveys or surveillance systems is a critical step in improving capacity to promote, design, monitor, and evaluate micronutrient policies and programs. We aimed to identify the barriers to and enablers of the inclusion of micronutrient biomarker assessment in national surveys and surveillance systems, to identify the main challenges faced during the survey process, and to review experiences using existing platforms for micronutrient surveys. We conducted a series of key informant interviews with in-country and external representatives from six countries where national-level data on micronutrient status were collected in the past 5 years: Cambodia, Pakistan, Malawi, Uganda, Ghana, and Uzbekistan. Micronutrients associated with specific public health programs were always prioritized for inclusion in the survey. If funding, time, and/or logistics allowed, other considered micronutrients were also included. The most important and frequently reported barrier to inclusion of a more comprehensive panel of micronutrient biomarkers was inadequate funding to cover the laboratory analysis cost for all micronutrients considered at the planning stage. Government support and commitment was stressed as the most important enabling factor by all key informants. Advocacy for funding for micronutrient status assessment is needed. Full article

(This article belongs to the Special Issue Zinc Supplementation and Fortification: The Unfinished Agenda)

29 pages, 1526 KiB

Open AccessFeature PaperArticle

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

by Swarnim Gupta, Mukhtiar Zaman, Sadia Fatima, Babar Shahzad, Anna K. M. Brazier, Victoria H. Moran, Martin R. Broadley, Munir H. Zia, Elizabeth H. Bailey, Lolita Wilson, Iqbal M. Khan, Jonathan K. Sinclair and Nicola M. Lowe

Nutrients 2022, 14(8), 1657; https://0-doi-org.brum.beds.ac.uk/10.3390/nu14081657 - 15 Apr 2022

Cited by 10 | Viewed by 4410

Abstract

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. Full article

(This article belongs to the Special Issue Zinc Supplementation and Fortification: The Unfinished Agenda)

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21 pages, 1910 KiB

Open AccessArticle

Applying Zinc Nutrient Reference Values as Proposed by Different Authorities Results in Large Differences in the Estimated Prevalence of Inadequate Zinc Intake by Young Children and Women and in Cameroon

by Demewoz Haile, Kenneth H. Brown, Christine M. McDonald, Hanqi Luo, Michael Jarvis, Ismael Teta, Alex Ndjebayi, Guintang Assiene Jules Martial, Stephen A. Vosti and Reina Engle-Stone

Nutrients 2022, 14(4), 883; https://0-doi-org.brum.beds.ac.uk/10.3390/nu14040883 - 19 Feb 2022

Cited by 3 | Viewed by 2579

Abstract

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. Full article

(This article belongs to the Special Issue Zinc Supplementation and Fortification: The Unfinished Agenda)

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12 pages, 874 KiB

Open AccessArticle

Community Perceptions of Zinc Biofortified Flour during an Intervention Study in Pakistan

by Usman Mahboob, Marena Ceballos-Rasgado, Victoria Hall Moran, Edward J. M. Joy, Heather Ohly, Mukhtiar Zaman and Nicola M. Lowe

Nutrients 2022, 14(4), 817; https://0-doi-org.brum.beds.ac.uk/10.3390/nu14040817 - 15 Feb 2022

Cited by 3 | Viewed by 3914

Abstract

Zinc-biofortified flour may be a cost-effective approach to improve zinc status of populations in low-resource settings. The success of biofortification programmes is subject to acceptability and uptake by consumers. This study explored community leaders’ and community members’ (n = 72) experiences and attitudes towards the flour provided during a cluster randomised controlled trial of zinc biofortified wheat in rural Pakistan (BiZiFED2). Focus group discussions (n = 12) were conducted and thematic analysis applied using an inductive, semantic, contextualist approach. Five themes were identified: (1) Contribution to food security; (2) Better sensory and baking properties than local flour; (3) Perceived health benefits; (4) Willingness to pay for the flour; and (5) Importance of trusted promoters/suppliers. Although the participants were blind to whether they had received control or biofortified flour, referred to collectively as “study flour”, the results indicated that the study flour performed well in terms of its taste and bread making qualities, with no adverse reports from participants in either arm of the BIZIFED2 RCT. Participants suggested that they would buy the biofortified wheat if this was available at a fair price due to perceived health benefits, reporting positive sensory characteristics and cooking attributes when compared to the flour available in the local markets. Overall, there was a positive reception of the programme and flour among the participants, and members of the community hoped for its continuation and expansion. Full article

(This article belongs to the Special Issue Zinc Supplementation and Fortification: The Unfinished Agenda)

9 pages, 794 KiB

Open AccessArticle

Exchangeable Zinc Pool Size Reflects Form of Zinc Supplementation in Young Children and Is Not Associated with Markers of Inflammation

by Julie M. Long, Afsana Mim Khandaker, Rahvia Alam Sthity, Jamie E. Westcott, Andrei Matveev, Robert E. Black, Janet C. King, Kazi Munisul Islam, Shams El Arifeen, Tahmeed Ahmed, M. Munirul Islam, Christine M. McDonald and Nancy F. Krebs

Nutrients 2022, 14(3), 481; https://0-doi-org.brum.beds.ac.uk/10.3390/nu14030481 - 22 Jan 2022

Cited by 3 | Viewed by 2738

Abstract

A sensitive and reliable biomarker of zinc status has yet to be identified, but observational research suggests that the exchangeable zinc pool (EZP) size may be a possible biomarker. This randomized, placebo-controlled trial aimed to compare the change in EZP size from baseline to endline in 174 children who were preventatively supplemented with 10 mg of zinc as part of a multiple micronutrient power (MNP) or as a standalone dispersible tablet for 24 weeks versus a placebo powder. The effects of systemic inflammation on EZP size were also evaluated. Zinc stable isotopes were administered intravenously to children at baseline and endline, and the EZP was measured by the urine extrapolation method. A total of 156 children completed the study with the zinc dispersible tablet group having the greatest increase in EZP (14.1 mg) over 24 weeks when compared with the MNP group (6.8 mg) (p < 0.01) or placebo group (2.0 mg) (p < 0.001). Median EZP size was not different between children with normal or elevated serum inflammatory markers. EZP size was responsive to longitudinal zinc supplementation and reflected the expected difference in bioavailability for two forms of supplementation. The apparent absence of an effect of inflammation on EZP size may offer an advantage for use as a biomarker for group comparisons between different interventions. Full article

(This article belongs to the Special Issue Zinc Supplementation and Fortification: The Unfinished Agenda)

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11 pages, 5567 KiB

Open AccessArticle

Zinc Supplementation with or without Additional Micronutrients Does Not Affect Peripheral Blood Gene Expression or Serum Cytokine Level in Bangladeshi Children

by Thomas Hayman, Peter Hickey, Daniela Amann-Zalcenstein, Cavan Bennett, Ricardo Ataide, Rahvia Alam Sthity, Afsana Mim Khandaker, Kazi Munisul Islam, Katharina Stracke, Nawaf Yassi, Rosie Watson, Julie Long, Jamie Westcott, Nancy F. Krebs, Janet C. King, Robert E. Black, Md. Munirul Islam, Christine M. McDonald and Sant-Rayn Pasricha

Nutrients 2021, 13(10), 3516; https://0-doi-org.brum.beds.ac.uk/10.3390/nu13103516 - 07 Oct 2021

Cited by 2 | Viewed by 2904

Abstract

Preventive zinc supplementation provided as a stand-alone dispersible tablet, or via home fortification as multiple micronutrient powders (MNPs), has been considered a potential strategy to prevent zinc deficiency and improve health (including immune) outcomes among children in low- and middle-income countries. However, the impact of zinc supplementation on immune profiles has not been well characterized. We sought to define the effect of zinc supplementation on peripheral blood gene expression and cytokine levels among young children in Dhaka, Bangladesh. In a sub-study of a large randomized, controlled, community-based efficacy trial where children 9–11 months of age received one of the following interventions on a daily basis for 24 weeks: (1) MNPs containing 10 mg of zinc; (2) dispersible tablet containing 10 mg zinc; or (3) placebo powder, we used RNA sequencing to profile the peripheral blood gene expression, as well as highly sensitive multiplex assays to detect cytokine profiles. We profiled samples from 100 children enrolled in the parent trial (zinc MNPs 28, zinc tablets 39, placebo 33). We did not detect an effect from either zinc intervention on differential peripheral blood gene expression at the end of the intervention, or an effect from the intervention on changes in gene expression from baseline. We also did not detect an effect from either intervention on cytokine concentrations. Exploratory analysis did not identify an association between undernutrition (defined as stunting, underweight or wasting) and peripheral blood gene expression. Zinc interventions in children did not produce a gene expression or cytokine signature in the peripheral blood. However, this study demonstrates a proof of principle that sensitive multi-omic techniques can be applied to samples collected in field studies. Full article

(This article belongs to the Special Issue Zinc Supplementation and Fortification: The Unfinished Agenda)

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14 pages, 438 KiB

Open AccessArticle

Enablers and Barriers of Zinc Fortification; Experience from 10 Low- and Middle-Income Countries with Mandatory Large-Scale Food Fortification

by Ann Tarini, Mari S. Manger, Kenneth H. Brown, Mduduzi N. N. Mbuya, Laura A. Rowe, Frederick Grant, Robert E. Black and Christine M. McDonald

Nutrients 2021, 13(6), 2051; https://0-doi-org.brum.beds.ac.uk/10.3390/nu13062051 - 15 Jun 2021

Cited by 3 | Viewed by 3563

Abstract

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. Full article

(This article belongs to the Special Issue Zinc Supplementation and Fortification: The Unfinished Agenda)

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Review

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18 pages, 2089 KiB

Open AccessReview

Reconsidering the Tolerable Upper Levels of Zinc Intake among Infants and Young Children: A Systematic Review of the Available Evidence

by Sara Wuehler, Daniel Lopez de Romaña, Demewoz Haile, Christine M. McDonald and Kenneth H. Brown

Nutrients 2022, 14(9), 1938; https://0-doi-org.brum.beds.ac.uk/10.3390/nu14091938 - 05 May 2022

Cited by 6 | Viewed by 2664

Abstract

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. Full article

(This article belongs to the Special Issue Zinc Supplementation and Fortification: The Unfinished Agenda)

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