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

Abstract

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.

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

“…Cellular zinc levels are highly buffered, and hence zinc depletion and restitution at a clinical level in this cohort may not have substantially altered intracellular zinc metabolism and function for cells involved in immune responses [ 27 ]. Our results are in line with a trial of preventive zinc supplementation in Laotian children, which likewise did not detect an effect from zinc on T cell cytokines, LPS-stimulated cytokines and T cell concentrations [ 28 ]. Previous data from in vitro treatment of cell lines with high or low zinc concentrations, from experimental animal models with markedly zinc-depleted or loaded diets or from humans receiving experimentally controlled zinc depletion diets may not apply to this more complex population of children with a variety of dietary and infectious exposures.…”

Plasma and Nail Zinc Concentrations, But Not Hair Zinc, Respond Positively to Two Different Forms of Preventive Zinc Supplementation in Young Laotian Children: a Randomized Controlled Trial

“…The main trial was designed to compare two forms of daily preventive zinc supplementation (7-mg/d zinc as zinc sulfate, provided as a dispersible tablet or 10-mg/d zinc as zinc gluconate, provided in a multiple micronutrient powder) versus therapeutic zinc supplementation (20-mg/d zinc as zinc sulfate, provided for 10 days in relation to an episode of diarrhea) or placebo on young children's physical growth and risk of infection over the 36-week intervention period. Detailed descriptions of the overall study design, as well as the effect of the interventions on the primary outcomes (i.e., physical growth, diarrhea incidence, hemoglobin and micronutrient status, and innate and adaptive immune response) have been reported previously [11][12][13][14]. The current analyses address secondary outcomes of the trial.…”

Serum Trace Element Levels and Their Correlation with Picky Eating Behavior, Development, and Physical Activity in Early Childhood

“…In addition, although the impact of picky eating on the growth and weight status of children is still controversial [ 22 , 23 , 54 , 62 ], this study found that children with picky eating behaviors had lower zinc levels and were significantly associated with a high prevalence of zinc deficiency. In addition to improving immunity [ 63 , 64 ] and reducing the duration and severity of diarrhea in children [ 65 , 66 ], recent clinical trials have shown that zinc supplementation can improve children’s development and physical activity. A randomized clinical trial of 251 infants by Colombo et al showed that zinc supplementation has a positive effect on of sensorimotor development [ 67 ].…”