Estimating the Global Prevalence of Inadequate Zinc Intake from National Food Balance Sheets: Effects of Methodological Assumptions

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

Eff ect of increased concentrations of atmospheric carbon dioxide on the global threat of zinc defi ciency: a modelling study

Background Increasing concentrations of atmospheric carbon dioxide (CO2) lower the content of zinc and other nutrients in important food crops. Zinc defi ciency is currently responsible for large burdens of disease globally, and the populations who are at highest risk of zinc defi ciency also receive most of their dietary zinc from crops. By modelling dietary intake of bioavailable zinc for the populations of 188 countries under both an ambient CO2 and elevated CO2 scenario, we sought to estimate the eff ect of anthropogenic CO2 emissions on the global risk of zinc defi ciency. Methods We estimated per capita per day bioavailable intake of zinc for the populations of 188 countries at ambient CO2 concentrations (375–384 ppm) using food balance sheet data for 2003–07 from the Food and Agriculture Organization. We then used previously published data from free air CO2 enrichment and open-top chamber experiments to model zinc intake at elevated CO2 concentrations (550 ppm, which is the concentration expected by 2050). Estimates developed by the International Zinc Nutrition Consultative Group were used for country-specifi c theoretical mean daily per-capita physiological requirements for zinc. Finally, we used these data on zinc bioavailability and population-weighted estimated average zinc requirements to estimate the risk of inadequate zinc intake among the populations of the diff erent nations under the two scenarios (ambient and elevated CO2). The diff erence between the population at risk at elevated and ambient CO2 concentrations (ie, population at new risk of zinc defi ciency) was our measure of impact. Findings The total number of people estimated to be placed at new risk of zinc defi ciency by 2050 was 138 million (95% CI 120–156). The people likely to be most aff ected live in Africa and South Asia, with nearly 48 million (32–63) residing in India alone. Global maps of increased risk show signifi cant heterogeneity. Interpretation Our results indicate that one heretofore unquantifi ed human health eff ect associated with anthropogenic CO2 emissions will be a signifi cant increase in the human population at risk of zinc defi ciency. Our country-specifi c fi ndings can be used to help guide interventions aimed at reducing this vulnerability

Effects of Daily Zinc, Daily Multiple Micronutrient Powder, or Therapeutic Zinc Supplementation for Diarrhea Prevention on Physical Growth, Anemia, and Micronutrient Status in Rural Laotian Children: A Randomized Controlled Trial.

ObjectivesTo evaluate the optimal zinc supplementation strategy for improving growth and hematologic and micronutrient status in young Laotian children.Study designIn 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.ResultsAt 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 &lt; .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 &lt; .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).ConclusionsDespite 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 registrationClinicalTrials.govNCT02428647

Daily Preventive Zinc Supplementation Decreases Lymphocyte and Eosinophil Concentrations in Rural Laotian Children from Communities with a High Prevalence of Zinc Deficiency: Results of a Randomized Controlled Trial.

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

Exogenous Phytase Added to Lipid Based Nutrient Supplements Increases Fractional and Total Absorption of Zinc Among Young Gambian Children: A Randomized Controlled Trial (OR07-01-19).

Objectives: Dietary phytate inhibits zinc absorption from composite meals in adults. The objective of this study was to investigate the efficacy 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, intra-individual differences in fractional and total absorption of zinc (FAZ and TAZ, respectively) from SQ-LNS with and without phytase were measured in 30 asymptomatic 18-23 month old children in the Kiang West district of The Gambia. Using a cross-over design, children received for one day each test meals of a millet-based porridge with 20 g SQ-LNS containing 8 mg zinc and either: 1) exogenous phytase (∼500 phytase units (FTU)) or 2) no exogenous phytase. The test meals were provided on consecutive days in randomized order. FAZ was measured using a dual-stable isotope tracer ratio technique with 67 Zn and 70 Zn as oral tracers, randomized independently of SQ-LNS product, and 68 Zn as the intravenous tracer. TAZ was calculated as the product of total dietary zinc (TDZ) intake from test meals (i.e., porridge, SQ-LNS and stable isotope) and FAZ. FAZ and TAZ were compared for meals with and without phytase using mixed-models ANOVA with product, study day, and oral isotope allocation as fixed effects and individual child as a random effect. Results: Twenty-six participants completed the study. The prevalence of stunting, underweight and wasting were 20%, 30% and 13%, respectively; no children had low plasma zinc concentrations (< 65 μg/dL). TDZ and phytate intakes from the test meals were 7.2 ± 2.2 mg and 182.9 ± 64.7 mg, respectively (phytate: zinc molar ratio = 2.4 ± 0.2). Mean FAZ increased from 8.6 ± 1.3% to 16.0 ± 1.3% when exogenous phytase was added to the SQ-LNS product (P = 0.0002). Mean TAZ from porridge test meals containing SQ-LNS with phytase was more than double that from test meals containing SQ-LNS without phytase (1.12 ± 0.07 mg and 0.52 ± 0.07 mg, respectively; P < 0.0001). Conclusions: The addition of exogenous phytase to a meal of millet-based porridge with SQ-LNS improved both FAZ and TAZ. These results suggest that phytate reduction may be an important strategy to improve zinc absorption among young children. Funding Sources: Nutriset, SAS

Daily supplementation of a multiple micronutrient powder improves folate but not thiamine, riboflavin, or vitamin B ₁₂ status among young Laotian children:a randomized controlled trial

PURPOSE: To assess the effects of intervention with a daily multiple micronutrient powder (MNP) on thiamine, riboflavin, folate, and B(12) status among young Laotian children. METHODS: Children (n = 1704) aged 6–23 mo, participating in a double-blind placebo-controlled randomized trial were individually randomized to receive daily either MNP (containing 0.5 mg of thiamine, 0.5 mg riboflavin, 150 μg folic acid, and 0.9 μg vitamin B(12) along with 11 other micronutrients) or placebo and followed for ~ 36 weeks. In a randomly selected sub-sample of 260 children, erythrocyte thiamine diphosphate (eThDP), plasma folate and B(12) concentrations, and erythrocyte glutathione reductase activation coefficient (EGRac; riboflavin biomarker) were assessed at baseline and endline. RESULTS: There was no treatment effect on endline eThDP concentrations (110.6 ± 8.9 nmol/L in MNP vs. 109.4 ± 8.9 nmol/L in placebo group; p = 0.924), EGRac (1.46 ± 0.3 vs. 1.49 ± 0.3; p = 0.184) and B(12) concentrations (523.3 ± 24.6 pmol/L vs. 515.9 ± 24.8 pmol/L; p = 0.678). Likewise, the prevalence of thiamine, riboflavin, and B(12) deficiencies did not differ significantly between the two groups. However, endline folate concentration was significantly higher in the MNP compared to the placebo group (28.2 ± 0.8 nmol/L vs 19.9 ± 0.8 nmol/L, respectively; p < 0.001), and correspondingly, the prevalence of folate deficiency was significantly lower in the MNP group (1.6% vs 17.4%; p = 0.015). CONCLUSIONS: Compared to a placebo, daily MNP for 9 months increased only folate but not thiamine, riboflavin, or B(12) status in young Laotian children. TRIAL REGISTRATION: The trial was registered at www.clinicaltrials.gov (NCT02428647) on April 29 2015

Assessment of Dietary Intake and Nutrient Gaps, and Development of Food-Based Recommendations, among Pregnant and Lactating Women in Zinder, Niger: An Optifood Linear Programming Analysis.

Pregnant and lactating women in rural Niger are at high risk for inadequate intakes of multiple micronutrients. Thus, 24 h dietary recalls were conducted and analyzed for dietary intakes in this population (n = 202). Using linear programming analyses, micronutrient gaps in women's diets were identified, food-based recommendations (FBR) to improve dietary micronutrient adequacy were developed, and various supplementation strategies were modelled. Energy intakes were below estimated requirements, and, for most micronutrients, >50% of women were at risk of inadequate intakes. Linear programming analyses indicated it would be difficult to select a diet that achieved recommended dietary allowances for all but three (vitamin B₆, iron and zinc) of 11 modeled micronutrients. Consumption of one additional meal per day, and adherence to the selected FBR (daily consumption of dark green leafy vegetables, fermented milk, millet, pulses, and vitamin A fortified oil), would result in a low percentage of women at risk of inadequate intakes for eight modeled micronutrients (vitamin A, riboflavin, thiamin, B6, folate, iron, zinc, and calcium). Because the promotion of realistic FBRs likely will not ensure that a low percentage of women are at risk of inadequate intakes for all modeled micronutrients, multiple micronutrient supplementation or provision of nutrient-dense foods should be prioritized

The cost-effectiveness of small-quantity lipid-based nutrient supplements for prevention of child death and malnutrition and promotion of healthy development: modeling results for Uganda

Abstract Objective: Recent meta-analyses demonstrate that small-quantity lipid-based nutrient supplements (SQ-LNS) for young children significantly reduce child mortality, stunting, wasting, anemia and adverse developmental outcomes. Cost considerations should inform policy decisions. We developed a modeling framework to estimate the cost and cost-effectiveness of SQ-LNS and apply the framework in the context of rural Uganda. Design: We adapted costs from a costing study of micronutrient powder (MNP) in Uganda, and based effectiveness estimates on recent meta-analyses and Uganda-specific estimates of baseline mortality and the prevalence of stunting, wasting, anemia, and developmental disability. Setting: Rural Uganda. Participants: Not applicable. Results: Providing SQ-LNS daily to all children in rural Uganda (>1 million) for 12 months (from 6-18 months of age) via the existing Village Health Team system would cost ∼$52 per child (2020 US dollars), or ∼$58.7 million annually. Annually, SQ-LNS could avert an average of >242,000 disability adjusted life years (DALYs) as a result of preventing 3,689 deaths, >160,000 cases of moderate or severe anemia, and ∼6,000 cases of developmental disability. The estimated cost per DALY averted is $242. Conclusions: In this context, SQ-LNS may be more cost-effective than other options such as MNP or the provision of complementary food, although the total cost for a program including all age-eligible children would be high. Strategies to reduce costs, such as targeting to the most vulnerable populations and the elimination of taxes on SQ-LNS, may enhance financial feasibility