The Effect of Zinc Supplementation on Biomarkers of Zinc, Iron, and Copper Status in School Children in Guatemala Open Access

Abstract

The Effect of Zinc Supplementation on Biomarkers of Zinc, Iron, and Copper Status in School Children in Guatemala

by
Vinh Quang Bui

Preventive zinc supplementation is beneficial for children with high risk of zinc deficiency, but its adverse effect on biomarkers of iron and copper status is still a great concern.

A randomized controlled trial of zinc supplementation was conducted in five public schools in a low-income urban area in Guatemala City from January to October 2006. Eligible children aged 6-11 years were randomly allocated to receive daily chewable tablets of 10 mg zinc oxide or placebo for six months. All the children concurrently received fortified milk (daily 200 ml of whole milk, containing 1.6 mg zinc and 1.1 mg iron). Participants (n= 720) had high risk of zinc deficiency (21.6% low serum zinc and 39.4% low dietary zinc intakes). At baseline, serum ferritin and copper concentrations correlated with serum C-reactive protein concentration (p <0.001), but serum zinc and zinc-related biomarkers did not (p >0.05). Serum ferritin and copper concentrations were associated with high CRP levels, starting from the CRP >0.5 mg/L level (p<0.001). Among zinc biomarkers (i.e., serum zinc, ALP, and albumin), only serum zinc concentration was associated with dietary zinc intakes both before and after 6-month interventions (p ≤0.06). All significant associations and agreements were weak (r ≤0.21, kappa ≤0.12). At six-month follow-up, compared to placebo, zinc supplementation induced higher serum zinc concentration and ALP activity (p ≤0.03), but had no effect on iron or copper biomarkers (p >0.05). In the placebo group, fortified milk program improved serum zinc concentration and ALP activity (p <0.0001), but decreased serum ferritin and copper concentrations (p<0.0001).

Overall, serum CRP was associated with serum ferritin and copper, but not with serum zinc. Serum zinc concentration was consistently associated with dietary zinc intakes. Daily zinc supplementation increased zinc status but did not induce changes in iron and copper status. The fortified milk improved zinc biomarkers but decreased iron and copper biomarkers. This is the first study that observed a positive association between serum CRP and copper concentrations. The study confirms the beneficial impact of zinc supplementation on zinc status and its safety on iron and copper status.

Table of Contents

TABLES OF CONTENTS

ACKNOWLEDGEMENTS...i
TABLE OF CONTENTS...iii
LIST OF ABBREVIATIONS AND ACRONYMS...v
LIST OF TABLES...vi
LIST OF FIGURES...vii
CHAPTER 1: INTRODUCTION...1
CHAPTER 2: LITERATURE REVIEW...6

2.1. Overview of Zinc Nutrition...6
2.2. Measurements of Zinc, Iron, and Copper Status...24
2.3. Measurement Errors of Nutrition-Related Variables...44
2.4. The Effect of Inflammation on Nutrition-Related Biomarkers...53
2.5. Pairwise Interactions among Zinc, Iron, and Copper...68
2.6. The Effect of Zinc Supplementation on Biomarkers...75
2.7. Health and Nutritional Status of Children in Guatemala...82

CHAPTER 3: METHODS...89

3.1. Research Objectives...89
3.2. Study Design...89
3.3. Study Setting and Participants...90
3.4. Randomization and Blinding...91
3.5. Interventions...92
3.6. Unanticipated and Concurring Intervention...92
3.7. Data Collection Procedures and Study Variables...93
3.8. Definition of Variables...97
3.9. Sample Size...98
3.10. Statistical Methods...100

CHAPTER 4: MEASUREMENTS OF SERUM FERRITIN AND COPPER, BUT NOT ZINC, ARE INFLUENCED BY C-REACTIVE PROTEIN LEVELS IN GUATEMALAN SCHOOL CHILDREN...107

Abstract...110
Introduction...112
Methods...113
Results...117
Discussion...119
Cited References...124
Tables and Figures...127

CHAPTER 5: DIETARY ZINC INTAKE IS CONSISTENTLY ASSOCIATED WITH SERUM ZINC CONCENTRATION IN CROSS-SECTIONAL ANALYSES IN HEALTHY GUATEMALAN SCHOOL CHILDREN...133

Abstract...136
Introduction...137

Methods...138
Results...142
Discussion...143
Cited References...148
Tables and Figures...151

CHAPTER 6: THE EFFECT OF ZINC SUPPLEMENTATION ON BIOMARKERS OF ZINC, IRON, AND COPPER STATUS IN SCHOOL CHILDREN: A RANDOMIZED CONTROLLED TRIAL IN GUATEMALA...156

Abstract...159
Introduction...160
Methods...161
Results...167
Discussion...169
Cited References...176
Tables and Figures...179

CHAPTER 7: SUMMARY AND CONCLUSION...185

7.1. Keys Findings and Potential Significance....186
7.2. Strengths and Limitations of the Current Study...191
7.3. Future studies...194
7.4. Implications of the Study Findings...195
7.5. Conclusion...195

LITERATURE CITED (CHAPTER I-III, AND VII)...197
APPENDICES...217

Appendix 1: Form for Summary of Admission and Group Assignment...217
Appendix 2: Form for Socio-Economic Information...218
Appendix 3: Form for Food Frequency Questionnaire...220

About this Dissertation

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School	Laney Graduate School
Department	Biological and Biomedical Sciences
Degree	PhD
Submission	Dissertation
Language	English
Research Field	Health Sciences, Nutrition
Keyword	zinc alkaline phosphatase inflammation copper biomarkers ferritin dietary zinc intake C-reactive protein zinc supplementation trace nutrients
Committee Chair / Thesis Advisor	Martorell, Reynaldo, Emory University
Committee Members	Stein, Aryeh D, Emory University Flores-Ayala, Rafael C., Ramakrishnan, Usha, Emory University DiGirolamo, Ann, Emory University

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