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研究生:米莉安
研究生(外文):Miriam Adoyo Muga
論文名稱:飲食型態與心血管疾病危險因子:人體與動物研究
論文名稱(外文):Dietary patterns and cardiovascular disease risk factors: human and animal studies
指導教授:趙振瑞趙振瑞引用關係
指導教授(外文):Jane C-J Chao
學位類別:博士
校院名稱:臺北醫學大學
系所名稱:保健營養學研究所
學門:醫藥衛生學門
學類:營養學類
論文種類:學術論文
論文出版年:2016
畢業學年度:104
語文別:英文
論文頁數:224
中文關鍵詞:飲食型心血管疾病危險因子
外文關鍵詞:Dietary patternsA prioriA posterioriCardiovascular diseaseCVD biomarkersBody mass indexUnderweightOverweightObesityHypercholesterolemiaSpirulinaFish oilOxidative stressInflammation
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Background and Aim: Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide. CVD is often caused by sedentary lifestyles and Western dietary habits which are positively associated with elevated plasma lipid levels and a state of sub-acute chronic inflammation. An effective way to diminish the risk of CVD is to reduce causative risk factors such as lifestyle and dietary habits. Dietary habits including the use of dietary supplements have been the focus in the management of cardiovascular disease, and there is sufficient evidence that certain types of dietary habits or dietary supplements have positive or negative effects on CVD health, since people consume foods with complex combination of nutrients. While assessing overall dietary intake may show greater associations with health outcomes, diet supplementation with therapeutic components may also be an effective alternative to decrease CVD. On the one hand, not many studies have been conducted in a free-eating middle-age and elderly Taiwanese population. In addition, studies on dietary patterns have either used a-priori or a-posteriori methods to derive dietary patterns of a population, hence limited literature on the use of both methods in the same population. On the other hand, while a number of dietary supplements have been associated with a reduction of primary cardiovascular risk factors, such as fish oil and spirulina, these supplements have only been evaluated individually on the primary risk factors of CVD, and there are no evidences that directly link their combined effect in preventing diet-induced hypercholesterolemia. In light of this, this study therefore, will determine the association between dietary patterns and cardiovascular risk factors in middle-aged and elderly population in Taiwan, using both a-priori and a-posteriori methods to derive the dietary patterns. And also, determine the effects of single treatment with fish oil and spirulina or in combination (Fish oil and spirulina) on lipid profiles, inflammation, and antioxidant status in hamsters fed a hypercholesterolemic diet.

Methods: We created three dietary patterns: 1) a priori using an “a priori diet quality score” that was based on hypothesized healthfulness of foods (a priori dietary pattern), 2) An empirical derived dietary pattern that reflected a high intake of fruits and vegetables (Vegi-fruits dietary pattern) and 3) An empirical derived dietary pattern that reflected a high intake of meat and processed foods (meat-processed dietary pattern). The dietary patterns were divided into quintiles of consumption and assessed continuously. While general linear regression was used to assess associations between dietary patterns and the CVD biomarkers: lipids (Total cholesterol, triacylglycerols, LDL cholesterol, HDL cholesterol), inflammatory marker (CRP), and fasting glucose, logistic regression was used to assess the associations between dietary patterns and weight status. In addition in determining the effect of fish oil and spirulina, the hamsters were divided into 7 groups: control, high cholesterol (HF), fish oil (post FO), spirulina (post SP), and a combination of fish oil and spirulina (post SF, pre-SF, and HF+SF) groups. The HF and HF+SF groups were given a high cholesterol diet for 8 weeks. The post FO, post SP, and post SF groups were given a high cholesterol diet for 4 weeks and then the treatment for 4 weeks. The pre-SF group was given the combined treatment for 4 weeks and then a high cholesterol diet for 4 weeks. At the end of the experiment period, lipids, lipid peroxidation, antioxidant status in plasma and inflammation biomakers were determined.

Results and Conclusions: Generally, dietary patterns rich in fruits and vegetables had a negative association with CVD risk factors while patterns high in meat and processed foods had a positive association with CVD risk factors. This suggests that vegetables and fruits are beneficial in the management of CVD risk factors. While single treatments with fish oil and spirulina inhibited oxidative stress and inflammation, fish oil alone increased plasma lipids. However, only a combination of fish oil and spirulina (post SF) inhibited oxidative stress and regulated inflammation. Hence it may be beneficial for diet induced hypercholesterolemia.


Table of contents

Dedication i
Acknowledgements ii
Foreword iii
Abstract iv
Table of contents vii
List of tables xvi
List of figures xviii
List of abbreviations xix
Chapter 1: Introduction 2
1.1 Background 2
1.2 Motivation 3
1.3 Statement of the problem 4
1.4 Significance of the study 6
1.5 General objective 9
1.5.1 Specific objectives 10
1.5.1.1 Study one objective 10
1.5.1.2 Study two objective 10
1.5.1.3 Study three objective 10
Chapter 2: Literature Review 12
2.1 Introduction 12
2.2 Diet and CVD risk factors 13
2.2.1 The effect of diet on cardiovascular disease risk factors 13
2.2.1.1 Diet and blood lipids 13
2.2.1.2 Diet and blood glucose level 14
2.2.1.3 Diet and blood pressure 16
2.2.1.4 Diet, inflammation and CVD 17
2.3 Fish oil, spirulina and CVD risk factors 19
2.3.1 Fish oil 19
2.3.2 Effects of fish oil 20
2.3.2.1 Fish oil, lipid peroxidation and antioxidants 20
2.3.2.2 Fish oil, plasma lipids and hypercholesterolemia 22
2.3.2.3 Fish oil and inflammation 23
2.3.3 Spirulina 25
2.3.4 Effects of spirulina 27
2.3.4.1 Spirulina, lipid peroxidation and antioxidant 27
2.3.4.2 Spirulina, plasma lipids and hypercholesterolemia 28
2.3.4.3 Spirulina and anti-inflammation effects 28
2.3.5 Comparison of the effects of fish oil and spirulina 30
2.4 Mechanism of disease: atherosclerosis and CVD 32
Chapter 3: Human Study One 36
3.1 Abstract 37
3.2 Introduction 39
3.3 Materials and Methods 41
3.3.1 Conceptual framework 41
3.3.1.1 Framework of human study one 41
3.3.2 Study population and sources of data 42
3.3.3 Cardiovascular risk factors 44
3.3.4 Dietary assessment 45
3.3.5 A priori (Taiwanese) dietary pattern 46
3.3.6 A posteriori dietary patterns 47
3.3.7 Other independent variables 47
3.3.8 Statistical analysis 48
3.3.9 Principal component analysis 49
3.4 Results 51
3.4.1 Dietary patterns 51
3.4.2 Participant characteristics 55
3.4.3 Relationship between dietary patterns and CVD risk factors 62
3.5 Discussion 70
3.5.1 Strengths, limitations and future study 73
3.5.2 Conclusions 75
Chapter 4: Human Study Two 77
4.1 Abstract 78
4.2 Introduction 80
4.3 Methods 82
4.3.1 Conceptual framework 82
4.3.1.1 Framework in study two (human study) 82
4.3.2 Data source and subjects 83
4.3.3 Ethical considerations 83
4.3.4 Variables 84
4.3.4.1 Outcome variable: Body mass index and weight status 84
4.3.4.2 Key independent variable: Dietary assessment and patterns 84
4.3.4.3 Other covariates 85
4.3.5 Statistical analysis 86
4.4 Results 87
4.5 Discussion 100
4.5.1 Strengths and limitations 102
4.5.2 Conclusion 103
Chapter 5: Animal Study 105
5.1 Abstract 106
5.2 Background 108
5.3 Methods 111
5.3.1 Conceptual framework 111
5.3.1.1 Framework in study three (animal study) 111
5.3.2 Experimental hamsters 112
5.3.3 Diets and treatments 114
5.3.4 Measurements of plasma lipids 117
5.3.5 Aortic cholesterol levels 117
5.3.6 Hepatic lipid peroxidation 118
5.3.7 Liver glutathione (GSH) level and glutathione peroxidase (GSHPx) activity 119
5.3.8 Liver superoxide dismutase (SOD) activity 119
5.3.9 Aortic TNF-α, IL-1β, and IL-10 levels 120
5.3.10 Statistical analysis 120
5.4 Results 121
5.4.1 General characteristics of the hamsters 121
5.4.2 Effect of treatments on plasma and aortic lipids 125
5.4.3 Effect of treatments on hepatic lipid peroxidation and antioxidant status 129
5.4.4 Effect of treatments on aortic inflammation 132
5.5 Discussion 134
5.5.1 Conclusions 139
Chapter 6: Summary 141
6.1 Significant findings 141
6.1.1 Human study one 141
6.1.2 Human study two 142
6.1.3 Animal study 142
6.2 Policy and future research implication 144
References 146
Appendices 182
Appendix A: Taipei Medical University-Joint Institutional Review Board (TMU-JIRB) ethical approval certificate 183
Appendix B: Characteristics of subjects across quintiles (Q) of an a priori-defined dietary pattern 184
Appendix C: Characteristics of subjects across quintiles (Q) of the vegi-fruits dietary pattern 187
Appendix D: Characteristics of subjects across quintiles (Q) of an a meat-processed foods dietary pattern 190
Appendix E: Correlation analysis of CVD biomarkers 193
Appendix F: Correlation coefficients of demographic, lifestyle and health characteristics and biomarkers of CVD 194
Appendix G: Animal model and maintenance 196
Appendix H: Experimental diet 197
Appendix I: Composition of fish oil 202
Appendix J: Composition of spirulina 203
Appendix K: Details of the measurements in the animal study 204
Appendix L: Results of the pilot animal study 218
Appendix M: Results of other CVD risk factors 223
Appendix N: Affidavit of approval of animal use protocol, Taipei Medical University 224

List of tables

Table 2 1 Summary of the effects of fish oil and spirulina 31
Table 3 1 Principal component analysis scores for the 22 food groups of the major dietary patterns.* 53
Table 3 2 Characteristics of the subjects across quintiles (Q) of dietary pattern scores (n = 62,965)a. 56
Table 3 3 Unadjusted linear regression coefficients (95% confidence interval) for respondents’ characteristics and cardiovascular disease risk factors among the adults aged 40 years and above in Taiwan. 60
Table 3 4 Multivariable linear regression coefficients (95% confidence interval) for the association between dietary patterns and cardiovascular disease risk factors among the adults aged 40 years and above in Taiwan. 63
Table 3 5 Comparison of the regression coefficients (95% confidence interval) for the association between dietary patterns and cardiovascular disease risk factors among the adults aged 40 years and above in Taiwan.a 69
Table 4 1 Characteristics of the Taiwanese middle-aged and elderly adults ( 40 years) across weight status 88
Table 4 2 Crude odds ratios of dietary patterns and characteristics according to weight status of the subjects aged ≥ 40 years in Taiwan 92
Table 4 3 Adjusted odds ratios (95% confidence interval) of the association between dietary patterns and weight status by sex among the subjects aged ≥ 40 years in Taiwan 97
Table 5 1 Compositions of the standard and hypercholesterolemic diets 115
Table 5 2 Body, liver, and aorta weights of hamsters in different groups 123
Table 5 3 Treatment effects on plasma and aortic lipids in the hamsters 127
Table 5 4 Treatment effects on aortic cytokine concentrations 133

List of figures

Figure 2 1 Chemical structure of C-phycocyanin (Romay et al., 2003). 26
Figure 3 1 Conceptual framework of the association between dietary patterns and cardiovascular disease risk factors 41
Figure 3 2 Sampling flow chart and sample size. The sampling flow chart for the association between dietary patterns and cardiovascular disease risk factors among the adults aged  40 years in Taiwan 43
Figure 4 1 Conceptual framework of the association between dietary patterns, gender and weight status 82
Figure 5 1 Conceptual framework of the effect of diet on hypercholesterolemic hamsters 111
Figure 5 2 Main study flow diagram 113
Figure 5 3 Effect of fish oil, spirulina, and their combination on lipid peroxidation expressed as thiobarbituric acid reactive substances (TBARS) in liver. 130
Figure 5 4 Effect of fish oil, spirulina, and their combination on (A) GSH concentration, (B) GSHPx, and (C) SOD activities in liver. 131

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