Oxidative Stress and Human Health Open Access

Abstract

The role of oxidative stress in disease causation has been the focus of research for several decades. Despite a considerable body of evidence from basic science and animal studies, observational studies and clinical trials evaluating the roles of pro- and anti-oxidant nutrients and other oxidative stress-related exposures yielded inconsistent results. We, and others, previously proposed an oxidative balance score (OBS) as a measure of combined pro- and anti-oxidant exposure status. Using this method, the individual oxidative stress-related exposures are combined such that higher OBS values reflect the relative predominance of anti-oxidant factors. The primary objective of this dissertation is to examine the association between OBS and human degenerative diseases and mortality.

In the first study, I used data from a large national prospective cohort study, Reasons for Geographic and Racial Differences in Stroke (REGARDS) to examine the association between OBS and all-cause and cause-specific mortality while exploring alternative methods of weighting the OBS components. Higher OBS was associated with reduced risk of all-cause, and particularly cancer mortality. Similar results were observed across all weighting methods. In the second study, I examined the association between OBS and incident stroke using the same methods of score weighting. I found that higher OBS had no significant effect on incident stroke or stroke mortality, irrespective of the weighting scheme. In the third study, I extended the previous analyses of questionnaire-based OBS and colorectal adenoma by assessing: 1) the association between plasma nutrient-based OBS and colorectal adenoma; 2) the association of OBS with biomarkers of oxidative stress (F2-isoprostanes [FIP] and fluorescent oxidation products [FOP]), and with biomarker of inflammation (C-reactive protein [CRP]); and 3) the association of each of the three biomarkers with adenoma. OBS was inversely associated with colorectal adenoma, plasma FIP, and serum CRP. However, there was significant positive association between higher OBS and elevated levels of FOP. All three biomarkers were directly related to adenoma risk.

This dissertation research has important implications for epidemiologic studies evaluating the roles of oxidative stress in chronic disease etiology by showing that OBS is associated with the risks of certain (but not all) age-related degenerative conditions.

Table of Contents

LIST OF FIGURES
LIST OF TABLES
CHAPTER 1. Introduction and Background...1

Introduction...1
Background...3

Overview of Oxidative Stress and Antioxidant Defense System...3
Individual Pro- oxidant Factors...7
Individual Anti-oxidant Factors...10
Consequences of Oxidative Damage...12
Oxidative Stress and Cancer...13
Oxidative Stress and Stroke...16
Oxidative Stress and Aging...17
Disappointing Results from Epidemiological Studies of Antioxidants...17
Oxidative Balance Score (OBS)...21

Research Plan...24

Objective, Specific Aims, and Study Hypotheses...24
Methods for Aims 1 and 2...25
Methods for Aim 3...31

Significance and Impact of the Study...34

CHAPTER 2. Oxidative Balance Score is Predictor of All-Cause, Cancer, and Non-cancer Mortality in the Reasons for Geographic and Racial Differences in Stroke Cohort...37

Abstract...38
Introduction...39
Materials and Methods...41
Results...48
Discussion...50
Tables and Figures...54

CHAPTER 3. Oxidative Balance Score to Risk of Stroke Incidence and Mortality in a Large Nationwide Cohort...62

Abstract...63
Introduction...64
Materials and Methods...66
Results...71
Discussion...73
Tables and Figures...77

CHAPTER 4. Oxidative Balance Score Colorectal Adenoma, and Markers of Oxidative Stress and Inflammation...85

Abstract...86
Introduction...87
Materials and Methods...90
Results...94
Discussion...96
Tables and Figures...102

CHAPTER 5. Discussion and Future Directions...112

Overview of Findings...112
Public Health Implications and Future Directions...114

REFERENCES...116

About this Dissertation

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School	Laney Graduate School
Department	Epidemiology
Degree	PhD
Submission	Dissertation
Language	English
Research Field	Health Sciences, Epidemiology
Keyword	Oxidative Balance Score Stroke Mortality Oxidative Stress
Committee Chair / Thesis Advisor	Goodman, Michael, Emory University
Committee Members	Bostick, Roberd M, Emory University McClellan, William, Emory University Flanders, W Dana, Emory University Judd, Suzanne, University of Alabama at Birmingham

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