Protective mechanisms of the Mediterranean diet on cardiovascular disease: a twin study Open Access

Abstract

The Mediterranean diet is cardioprotective, however underlying mechanisms are unknown. We examined the association between the Mediterranean diet and inflammation/oxidative stress, and between alpha-linolenic acid (ALA) and inflammation related to cellular response to interleukin-6 (IL-6), evaluating whether the associations persisted after further controlling for familial factors. We used data from raised-together middle-aged male twins, including monozygotic and dizygotic twins, in the Twins Heart Study (THS) at Emory University. Dietary data over the previous one year was collected with the Willett Food Frequency Questionnaire. We derived a diet score measuring adherence to the Mediterranean diet following a published algorithm. Mixed-effect regression analysis was used to partition the association into between- and within-twin pair differences. When examining within-pair effects, twins were matched for sociodemographic and familial factors. After adjusting for energy intake, other nutritional factors, known cardiovascular risk factors, and medication use, a one-unit increment in the diet score was associated with 5% lower interleukin-6 (IL-6) levels (P=0.008) and a 7% higher ratio of reduced (GSH) to oxidized glutathione (GSSG) (P=0.03), but not C-reactive protein (CRP) levels. A one-gram increment in habitual dietary ALA intake was associated with 11.4% lower levels of soluble IL-6 receptor (sIL-6R) (P=0.009). The association persisted within twin pairs: a one-unit within-pair absolute difference in the diet score was associated with 9.2% lower IL-6 levels (P <0.0001) and a 10% higher GSH/GSSG ratio (P=0.007); a one-gram within-pair absolute difference in dietary ALA intake was associated with 12.2% lower sIL-6R levels (P=0.005). In conclusion, the association between the Mediterranean diet and systemic inflammation/oxidative stress, and that between habitual dietary ALA intake and sIL-6R is not confounded by genetic and shared environmental factors. Decreased inflammation and /or oxidative stress are plausible mechanisms linking Mediterranean diet to reduced cardiovascular risk, and habitual dietary ALA may contribute to the cardioprotective properties of the Mediterranean diet.

Table of Contents

CHAPTER I INTRODUCTION CHAPTER II LITERATURE REVIEW I. Pathophysiology in inflammation, oxidative stress and atherosclerotic cardiovascular disease Biomarkers of low-grade systemic inflammation Biomarkers of oxidative stress Biomarkers of inflammation and oxidative stress in the epidemiological study II. The Mediterranean diet Quantitative methods to evaluate dietary patterns III. The Mediterranean diet and cardiovascular disease IV. Mechanisms of the cardioprotective properties of the Mediterranean diet The Mediterranean diet and low-grade systemic inflammation The Mediterranean diet and oxidative stress The Mediterranean diet, alpha-linolenic acid, cardiovascular disease, and inflammatory biomarkers of cellular response to interleukin-6 Genetic factors, cardiovascular disease, inflammation and oxidative stress Genetic factors, the Mediterranean diet, habitual dietary alpha-linolenic acid Other environmental factors References CHAPTER III ADHERENCE TO THE MEDITERRANEAN DIET IS INVERSELY ASSOCIATED WITH CIRCULATING INTERLEUKIN-6 AMONG MIDDLE-AGED MALES: A TWIN STUDY Abstract Introduction Methods Results Discussion Acknowledgments References CHAPTER IV ASSOCIATION BETWEEN ADHERENCE TO THE MEDITERRANEAN DIET AND OXIDATIVE STRESS Abstract Introduction Subjects and Methods Results Discussion Acknowledgments References CHAPTER V A HIGH HABITUAL DIETARY ALPHA-LINOLENIC ACID INTAKE IS ASSOCIATED WITH DECREASED SOLUBLE INTERLEUKIN-6 RECEPTOR LEVELS AMONG MALE TWINS Abstract Condensed Abstract Introduction Methods Results Discussion Acknowledgments References

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School	Laney Graduate School
Department	Biological and Biomedical Sciences
Degree	PhD
Submission	Dissertation
Language	English
Research Field	Health Sciences, Nutrition Health Sciences, Epidemiology
Keyword	Oxidative stress dizygotic twin alpha-linolenic acid monozygotic twin Inflammation Mediterranean diet
Committee Chair / Thesis Advisor	Vaccarino, Viola, Emory University
Committee Members	Jones, Dean P, Emory University Bostick, Roberd M, Emory University Ziegler, Thomas R, Emory University Manatunga, Amita, Emory University

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