Assessing the role of inflammation on serum folate, red blood cell folate, vitamin B-12, vitamin D, and zinc in adolescents and school-age children Restricted; Files Only

Zeiler, Madeleine (Spring 2023)

Permanent URL: https://etd.library.emory.edu/concern/etds/wm117q351?locale=en%255D
Published

Abstract

Objectives: Knowledge gaps remain on the role of inflammation on micronutrient biomarker concentrations among school age children (SAC) and adolescents (ADL). Children and WRA are particularly vulnerable, with at least half of PSC and around two-thirds of non-pregnant WRA experiencing a micronutrient deficiency in some form.1 Associations between concentrations of inflammation biomarkers C-reactive protein (CRP) and α1-acid glycoprotein (AGP) and serum folate (SFO), red blood cell folate (RBC folate), vitamin B-12, vitamin D, and zinc were examined.

Methods: This study analyzed cross-sectional data from nutrition surveys in multiple countries from 2006-2016 in SAC and ADL. Survey eligibility criteria were as follows: inclusion of either SAC (5-9 years) or ADL (10-19 years), AGP or CRP and ≥ 1 micronutrient of interest, and n > 100. Micronutrient deficiencies were defined as SFO < 10 nmol/L, RBC folate < 340 nmol/L, vitamin B-12 < 150 pmol/L, vitamin D < 25 nmol/L, and zinc < 57 µg/dL – 74 µg/dL depending on specified conditions. Inflammation was defined as AGP > 1 g/L and CRP > 5 mg/L. Prevalence estimates were adjusted for complex survey design, and associations were assessed by rank correlation coefficient.

Results: Correlations between AGP or CRP and SFO, RBC folate, vitamin B-12, vitamin D, and zinc were weak, with no clear pattern of association. Of the 50 observations recorded 11 were statistically significant (p < 0.05). 10 of these were negative: 3 between SFO and CRP (r = -0.08 to -0.06); 2 between vitamin B-12 and CRP (r = -0.18 to -0.09); 1 between vitamin D and CRP (r = -0.06); 1 between zinc and AGP (r = -0.18); and 3 between zinc and CRP (r = -0.19 to -0.06). 1, vitamin B-12 and CRP (r = 0.10 to 0.13), was statistically significant and positive. Decile plots showed no clear pattern across biomarkers.

Conclusions: Due to weak and inconsistent correlations between the inflammation biomarkers and micronutrient biomarkers, there is no rationale to adjust for inflammation when estimating population prevalence SFO, RBC folate, vitamin B-12, vitamin D or zinc deficiencies in SAC or ADL.

Table of Contents

CHAPTER 1: INTRODUCTION 1

Introduction and Rationale 1

Problem Statement 2

Purpose Statement 2

Research Question 3

Significance Statement 3

Definition of Terms 3

CHAPTER 2: LITERATURE REVIEW 6

Micronutrient Overview 6

Folate 6

Vitamin B-12 8

Vitamin D 10

Zinc 12

Deficiency Cutoffs 15

Inflammation Overview 15

α1-Acid glycoprotein (AGP) 16

C-reactive protein (CRP) 17

Laboratory Analysis 18

The Public Health Implications of Micronutrient Deficiency 21

Past/Related Findings 22

The Case for Adjusting for Inflammation 24

Bidirectional Associations of Inflammation and Micronutrients 26

Biological Plausibility for B Vitamins (SFO, RBC folate, and Vitamin B-12) 26

Biological Plausibility for Vitamin D 27

Biological Plausibility for Zinc 28

Methods of Inflammation Adjustment 28

Potential Confounders 30

CHAPTER 3: MANUSCRIPT 33

Introduction 34

Methods 37

Study Design and Data Sources 37

Lab Methods 37

Statistical Methods 38

Results 39

Primary Analysis 39

Sensitivity Analysis 42

Discussion 45

CHAPTER 4: DISCUSSION 48

Overview 48

Biological Rationale 49

Next Steps 50

Suggested Cutoffs 50

Clinical Trial Design 51

Study Strengths 52

Study Limitations 52

Conclusions 53

SUPPLEMENTARY MATERIALS 56

Table 1: Prevalence of deficiency for each country included in the analysis for PSC and non-pregnant women* 56

Table 2: Prevalence of people with deficiencies in one more of three core micronutrients from 2003-2019* 57

Figure 1: Study Inclusion and Exclusion Criteria 58

Table 3: Age, AGP, and CRP status in adolescents and school-age children 59

Table 4: Serum folate, RBC folate, vitamin B-12, vitamin D, and zinc status in adolescents and school-age children 60

Table 5: Rank correlation coefficient between serum folate, red blood cell folate, vitamin B-12, vitamin D, and zinc and AGP or CRP in adolescents and school-age children 61

Figure 3: Estimated geometric means of (A) serum folate by AGP, (B) serum folate by CRP, (C) vitamin B12 by AGP, (D) vitamin B12 by CRP, (E) RBC folate by AGP and (F) RBC folate by CRP in school-age children by sex and age group 62

Figure 4: Estimated geometric means of (A) serum folate by AGP, (B) serum folate by CRP, (C) vitamin B12 by AGP, (D) vitamin B12 by CRP, (E) RBC folate by AGP and (F) RBC folate by CRP in school-age children by sex and age group. AGP, α1-Acid glycoprotein; CRP, C-reactive protein 63

Table 6: Age, AGP, and CRP status in school-age children by age 64

Table 7: Serum folate, RBC folate, vitamin B-12, vitamin D, and zinc status in school-age children by age group 65

Table 8: Rank correlation coefficient between serum folate, red blood cell folate, vitamin B-12, vitamin D, and zinc and AGP or CRP in school-age children by age group 66

Figure 5: Estimated geometric means of (A) serum folate by AGP, (B) serum folate by CRP, (C) vitamin B12 by AGP, (D) vitamin B12 by CRP, (E) RBC folate by AGP and (F) RBC folate by CRP in school-age children by sex and age group. AGP, α1-Acid glycoprotein; CRP, C-reactive protein 67

Figure 6: Estimated geometric means of (A) vitamin D by AGP, (B) vitamin D by CRP, (C) zinc by AGP, (D) zinc by CRP in school-age children by age group and sex. AGP, α1-Acid glycoprotein; CRP, C-reactive protein 68

Table 9: Data Sources and Availability 69

Table 10: Suggested lower* cutoffs for the assessment of serum zinc** 72

Table 11: Laboratory methods by biomarker and age group 72

Table 12: When to apply the BRINDA inflammation adjustment method and by AGP and/or CRP 72

REFERENCES 73

 

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