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The Effects of Whole-Diet Interactions on Vascular Health and Inflammatory and Fatty Acid Status

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The Effects of Whole-Diet Interactions on Vascular Health and Inflammatory and Fatty Acid Status The effects of whole-diet interactions on vascular health and inflammatory and fatty acid status. Colette O’Neill BSc. (HONS) Submitted to the Norwich Medical School, University of East Anglia in fulfilment of the requirements for the degree of Doctor of Philosophy, August 2015 Project supervisors: Prof. Anne Marie Minihane Prof. Aedín Cassidy Dr. Amy Jennings 1 Table of Contents Table of Contents ..................................................................................................................... 2 Table of tables .......................................................................................................................... 8 Table of figures ...................................................................................................................... 10 Abbreviations ......................................................................................................................... 12 Declaration ............................................................................................................................. 15 Acknowledgements ................................................................................................................ 15 Abstract .................................................................................................................................. 17 1 Literature Review ........................................................................................................... 20 1.1 Ageing .................................................................................................................... 20 1.1.1 The definition and process of ageing ............................................................. 20 1.1.2 The demographics of ageing .......................................................................... 21 1.1.3 Compression of morbidity ............................................................................. 21 1.2 Cardiovascular Disease (CVD) ................................................................................ 22 1.2.1 Definitions, risk factors and prevalence......................................................... 22 1.2.2 The pathology of atherosclerosis ................................................................... 24 1.3 Endothelial dysfunction and CVD risk .................................................................... 25 1.3.1 Endothelial dysfunction ................................................................................. 25 1.3.2 Nitric Oxide .................................................................................................... 25 1.3.3 Endothelins .................................................................................................... 25 1.3.4 Clinical measures ........................................................................................... 26 1.3.5 Dietary manipulation of endothelial dysfunction .......................................... 27 1.4 Arterial Stiffness and CVD risk ............................................................................... 28 1.4.1 Arterial Stiffness ............................................................................................. 28 1.4.2 Clinical measures ........................................................................................... 28 1.4.3 Dietary manipulation of arterial stiffness ...................................................... 29 1.5 Inflammation and CVD risk .................................................................................... 29 1.5.1 The role of inflammation in atherosclerosis .................................................. 29 1.5.2 C-reactive protein as a biomarker for inflammation ..................................... 30 1.6 n-3 fatty acid status and cardiovascular health ..................................................... 31 1.6.1 Sources, benefits, recommendations and consumption ............................... 31 1.6.2 n-3 fatty acids and CVD risk ........................................................................... 32 1.6.3 Regulation of LC-PUFA status in vivo ............................................................. 35 1.7 Impact of common gene variants on LC-PUFA status ............................................ 36 1.7.1 FADS polymorphisms and the utilisation of haplotypes ................................ 36 2 1.7.2 The relationship between the FADS genotype, fatty acid status and CVD .... 37 1.7.3 The relationship between FADS genotype and diet ...................................... 38 1.8 Dietary compounds which may potentially influence fatty acid status; polyphenols ........................................................................................................................ 39 1.8.1 Background .................................................................................................... 39 1.8.2 Polyphenols .................................................................................................... 40 1.8.3 Flavonoids ...................................................................................................... 40 1.9 Dietary patterns and the use of diet scores ........................................................... 42 1.9.1 Whole-diet interactions and cardiovascular health ....................................... 42 1.9.2 The use of diet scores .................................................................................... 44 1.10 Summary, hypothesis and objectives .................................................................... 46 1.10.1 Summary ........................................................................................................ 46 2 The effect of select dietary compounds on blood and tissue levels of fatty acids in ageing humans and animals ................................................................................................... 51 2.1 Introduction ........................................................................................................... 51 2.2 Methods and study designs ................................................................................... 53 2.2.1 Fatty acid analysis of blood and tissue samples ............................................ 53 2.2.2 Animal champagne and alcohol intervention (Study 1) ................................ 55 2.2.3 Animal flavonoid and blueberry intervention (Study 2) ................................ 56 2.2.4 Human anthocyanin intervention (Study 3) .................................................. 56 2.2.5 Statistical Analysis .......................................................................................... 57 2.3 Results .................................................................................................................... 57 2.3.1 Animal champagne and alcohol intervention (Study 1) ................................ 57 2.3.2 Animal flavonoid and blueberry intervention (Study 2) ................................ 59 2.3.3 Human anthocyanin intervention (Study 3) .................................................. 64 2.4 Discussion ............................................................................................................... 66 2.4.1 Animal champagne and alcohol intervention (Study 1) ................................ 66 2.4.2 Animal flavonoid and blueberry intervention (Study 2) ................................ 67 2.4.3 Human anthocyanin intervention (Study 3) .................................................. 69 2.5 Additional Investigations at UEA and Conclusion .................................................. 70 3 NU-AGE Study Design; Investigating the impact of a year-long whole-diet intervention on vascular function ............................................................................................................... 73 3.1 Introduction ........................................................................................................... 73 3.2 Study Population .................................................................................................... 75 3.3 Clinical measures of vascular function ................................................................... 76 3.3.1 Introduction ................................................................................................... 76 3 3.3.2 Resting period and blood pressure measurements ....................................... 76 3.3.3 Pulse Wave Velocity (PWV) ............................................................................ 77 3.3.4 Cardio-Ankle Vascular Index (CAVI) and Ankle-Brachial Index (ABI) ............. 78 3.3.5 EndoPAT ......................................................................................................... 80 3.4 Sample Size – vascular function measurements .................................................... 80 3.5 Recruitment ........................................................................................................... 81 3.6 Pre-Study Health Screening ................................................................................... 81 3.7 Randomisation ....................................................................................................... 82 3.8 Dietary Intervention ............................................................................................... 82 3.8.1 NU-AGE nutrient guidelines ........................................................................... 82 3.8.2 NU-AGE food based dietary goals .................................................................. 83 3.8.3 Dietary intake assessment
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