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Functional Foods, Nutraceuticals, and Degenerative Disease Prevention
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Functional Foods, Nutraceuticals and Degenerative Disease Prevention is a compilation of different segments of functional foods and nutraceuticals focusing on their mechanism of action in the human body leading to disease prevention. Numerous chapters deal with different functional foods in terms of their efficacy, highlighting the mechanism of action of their ingredients. The book focuses on the biochemistry and molecular biology of the disease prevention process rather than simply compiling the benefits of functional foods and nutraceuticals. Aimed primarily at an audience comprised of researchers, industry professionals, food scientists, medical professionals and graduate level students, Functional Foods, Nutraceuticals and Degenerative Disease Prevention offers a mechanism-based interpretation for the effect of nutraceuticals within the human body. Ultimately, the discussion of the biological effects of a variety of functional foods will provide a wholesome approach to the maintenance of health through judicious choice of functional foods.
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Table of Contents

Contributors xv Preface xvii About the Editors xix 1 Functional Foods, Nutraceuticals, and Disease Prevention: A Window to the Future of Health Promotion 3 Gopinadhan Paliyath and Kalidas Shetty 1.1 Chronic Degenerative Diseases in Modern Society: Implications on Life Quality, Productivity, Economic Burden 3 1.1.1 Diet and lifestyle changes: the missing foods 3 1.1.2 Social and economic burden of chronic degenerative diseases 4 1.2 Health Regulatory Properties of Foods: Prevention Is Better Than Cure 5 1.2.1 Fruit and vegetable consumption and disease prevention 6 References 8 2 Functional Foods and Nutraceuticals 11 Chung-Ja C. Jackson and Gopinadhan Paliyath 2.1 Introduction 11 2.2 Definition of Functional Foods and Nutraceuticals 12 2.2.1 Effects of functional foods and nutraceuticals on major chronic diseases 16 2.3 Sources and Biological Effects of Functional Foods and Nutraceuticals in Nature 19 2.3.1 Flaxseed (Linum usitatissimum) 20 2.3.2 Phytoestrogens 21 2.3.3 Tomatoes 21 2.3.4 Garlic (Allium sativum) 21 2.3.5 Cruciferous vegetables 22 2.3.6 Citrus fruits 22 2.3.7 Cranberry 23 2.3.8 Tea 23 2.3.9 Wine and grapes 24 2.3.10 Chocolate 24 2.3.11 Fish 25 2.3.12 Dairy products 25 2.3.13 Carbohydrates 26 2.3.14 Meat 26 2.3.15 Vitamins 26 2.3.16 Minerals 27 2.4 Functional Foods and Nutraceuticals: Health Claims and Benefits 27 2.4.1 Oats 27 2.4.2 Psyllium 27 2.4.3 Soybeans 28 2.4.4 Phytosterols 29 2.4.5 Fiber 29 2.4.6 D-Tagatose 29 2.5 Qualifi ed Health Claims 29 2.5.1 Selenium and cancer 29 2.5.2 Antioxidant vitamins and cancer 30 2.5.3 Nuts (e.g., walnuts) and heart disease 30 2.5.4 Omega-3 fatty acids and CHD 30 2.5.5 Phosphatidylserine/Phosphatidylcholine and cognitive dysfunction and dementia 30 2.5.6 Folic acid and neural tube birth defects 30 2.6 Functional Foods and Nutraceuticals: Safety Issues 30 2.6.1 Echinacea 31 2.6.2 Ephedra (also called ma huang, herbal ecstasy, or mahuanggen ) 31 2.6.3 Feverfew 31 2.6.4 Garlic 31 2.6.5 Ginger 32 2.6.6 Gingko biloba 32 2.6.7 Ginseng 32 2.6.8 Kava kava products 32 2.6.9 St. John s Wort 32 2.7 Regulation of Functional Foods and Nutraceuticals 33 2.8 Public Education and Dietary Guidance 35 2.9 Concluding Remarks 36 References 37 3 Nutritional Genomics: Fundamental Role of Diet in Chronic Disease Prevention and Control 45 Amy J. Tucker, Branden Deschambault, and Marica Bakovic 3.1 Introduction 45 3.2 Nutrigenetics 46 3.2.1 Gene polymorphisms 46 3.2.2 Single nucleotide polymorphisms (SNPs) 47 3.2.3 Nonsynonymous single nucleotide polymorphisms (nsSNPs) 47 3.2.4 Regulatory single nucleotide polymorphisms (rSNPs) 48 3.2.5 Splice site single nucleotide polymorphisms (ssSNPs) 48 3.2.6 Trans-Acting rSNPs 48 3.3 Complexities of chronic disease research in nutrigenetics 49 3.4 Chronic Disease and Rare SNPs 50 3.4.1 Copy number variants 50 3.5 CVD and Nutrigenetics 51 3.6 Nutrigenetics and Cancer 51 3.7 Summary of Nutrigenetic Research Potential 51 3.8 Nutriepigenetics 52 3.8.1 Role of the epigenome 52 3.8.2 Cause of epimutations 52 3.9 Epimutations in Chronic Disease 53 3.9.1 Epimutations and macronutrients/micronutrients 53 3.9.2 Epimutations and phytochemicals 54 3.10 Summary of Epigenetic Research Potential 54 3.11 Nutrigenomics 54 3.11.1 Genomic impact of diet 55 3.11.2 Carbohydrates and gene interactions 55 3.12.3 Cholesterol and gene interactions 56 3.11.4 FAs, lipids, and gene interactions 58 3.11.5 Lipids and APOE 59 3.11.6 Diet and APOE 60 3.11.7 Lipids and hepatic lipase (HL) 60 3.11.8 Diet and LIPC 61 3.11.9 Interaction between APOE and HL 61 3.12 Vitamin A and Gene Interactions 61 3.12.1 Dual roles of vitamin A 62 3.13 Vitamin E and Nutrigenomics 62 3.13.1 Vitamin E and atherosclerosis 62 3.13.2 Vitamin E and cholesterol biosynthesis 63 3.14 Vitamin D and Gene Interactions 63 3.14.1 Vitamin D and breast cancer 63 3.14.2 Vitamin D and FAs 64 3.15 Phytoestrogens and Gene Interactions 64 3.15.1 Phytoestrogens and breast cancer 64 3.15.2 Phytoestrogens and lipid, glucose metabolism 64 3.16 Phytosterols and Gene Interactions 65 3.16.1 Phytosterols and cholesterol metabolism 65 3.16.2 Phytosterols and cancer 65 3.17 Polyphenols and Gene Interactions 65 3.17.1 Polyphenols and CVD 65 3.17.2 Polyphenols and cancer 66 3.18 Nutrigenomics Summary: Advantages, Limitations, Future 66 3.19 Conclusions 67 References 67 4 Nutraceuticals and Antioxidant Function 75 Denise Young, Rong Tsao, and Yoshinori Mine 4.1 Introduction 75 4.2 Oxidative Stress and ROS 75 4.2.1 Endogenous sources of ROS 76 4.2.2 Exogenous sources of ROS 77 4.3 Antioxidants and Antioxidative Defense Systems 77 4.3.1 Endogenous antioxidants and antioxidative defenses 77 4.3.2 Dietary antioxidants 79 4.4 Phytochemicals 79 4.4.1 Polyphenols 80 4.4.2 Amides 85 4.4.3 Carotenoids 86 4.4.4 Mechanism of antioxidant action 87 4.5 Antioxidant Amino Acids, Peptides, and Proteins 90 4.6 Mechanism of Action of Antioxidant and Antioxidative Stress Amino Acids, Peptides, and Proteins 91 4.6.1 Amino acids 91 4.6.2 Peptides and proteins 91 4.7 Production of Antioxidant Peptides 95 4.8 Recent Advances in Analytical Techniques for Measuring Antioxidant Capacity and Oxidative Damage 96 4.8.1 Chemical antioxidant capacity assay 96 4.8.2 Cell-based antioxidant assays 99 4.9 Health Benefi ts of Nutraceutical Antioxidants 101 4.9.1 Evidence of antioxidant efficacy in disease states 101 4.9.2 Failure of antioxidants to demonstrate efficacy 102 4.10 Conclusion 102 References 103 5 Composition and Chemistry of Functional Foods and Nutraceuticals: Infl uence on Bioaccessibility and Bioavailability 113 Jissy K. Jacob and Gopinadhan Paliyath 5.1 Introduction 113 5.2 Polyphenols as Antioxidants 115 5.2.1 Free radicals and endogenous antioxidant defense mechanisms 115 5.2.2 Diet and exogenous antioxidants (flavonoids) 115 5.2.3 Antioxidant properties of flavonoids 117 5.3 Antioxidant Activity of Anthocyanins 118 5.4 Anthocyanin Biosynthesis and Localization 119 5.5 Bioaccessibility and Bioavailability of Polyphenols 121 5.6 Microstructural Characteristics of Grape Juice 122 5.7 Physicochemical Properties of the Dialyzed Juice Fraction 123 5.8 Ultrastructural Analysis of Juice Fractions 124 5.9 Composition of Juice Fractions 126 5.10 Antioxidant Activity of Juice Fractions 129 5.11 Metabolism and Bioavailability of Flavonoids 132 5.12 Dietary Polyphenols and Prevention of Diseases 135 5.12.1 Polyphenols and cardiovascular diseases 135 5.12.2 Polyphenols and cancer 136 5.13 Increasing Health Benefi cial Properties of Juices 137 References 139 6 Cruciferous Vegetable-Derived Isothiocyanates and Cancer Prevention 147 Ravi P. Sahu and Sanjay K. Srivastava 6.1 Introduction 147 6.2 Metabolism of Xenobiotics 149 6.3 ITCs and Inhibition of Cancer 150 6.3.1 Pancreatic cancer 150 6.3.2 Brain cancer 152 6.3.3 Prostate cancer 152 6.3.4 Lung cancer 154 6.3.5 Breast cancer 155 6.3.6 Colon cancer 156 6.3.7 Hepatic cancer 156 6.3.8 Bladder cancer 157 6.3.9 Multiple myeloma (MM) 158 6.3.10 Head and neck squamous cancer 159 6.3.11 Ovarian cancer 159 6.3.12 Skin cancer 160 Acknowledgments 161 References 161 7 The Disease-Preventive Potential of Some Popular and Underutilized Seeds 171 Rajeev Bhat 7.1 Introduction 171 7.2 Oil Seeds and Their Therapeutic Potential 172 7.2.1 Nigella seeds (Nigella sativa L.) 172 7.2.2 Sunfl ower seed (Helianthus annuus L.) 172 7.2.3 Groundnut seed (Arachis hypogea L.) 183 7.2.4 Sesame seeds (Sesamum indicum L.) 184 7.2.5 Oilseed rape (Brassica napus L.) 184 7.2.6 Saffl ower (Carthamus tinctorius L.) 184 7.2.7 Linseed (Linum usitatissimum L.) 185 7.3 Spice Seeds as Medicine 185 7.3.1 Coriander seeds (Coriandrum satium L.) 185 7.3.2 Caraway (Cumin carvi L.) 186 7.3.3 Pepper seeds (Piper nigrum L.) 186 7.3.4 Cumin seeds (Cuminum cyminum L.) 186 7.3.5 Fenugreek seeds (Trigonella foenum-graecum L.) 187 7.4 Legumes and Medicinal Use 187 7.4.1 Soybeans (Glycine max (L.) Merrill) 187 7.4.2 Mucuna pruriens L. 188 7.4.3 Tamarind seeds (Tamaridus indica L.) 188 7.5 Underutilized Seeds 189 7.5.1 Perilla (Perilla frutescens [Hassk.]) 189 7.5.2 Hunteria umbellata ([K. Schum] Hallier f.) 189 7.5.3 Microula sikkimensis (Hemsl.) 189 7.5.4 Chinese chive seeds (Allium tuberosum Rottl.) 190 7.5.5 Grape seeds (Vitis vinifera L.) 190 7.5.6 Pumpkin seeds (Cucurbita sp.) 191 7.5.7 Horse chestnut seeds (Aesculus hippocastanum L.) 192 7.6 Future Outlook 192 References 193 8 Effects of Carotenoids and Retinoids on Immune-Mediated Chronic Inflammation in Infl ammatory Bowel Disease 213 Hua Zhang, Ming Fan, and Gopinadhan Paliyath 8.1 Introduction 213 8.2 Carotenoids 213 8.3 IBDs 214 8.4 Phytochemicals and Downregulation of IBD 215 8.4.1 Antioxidative capacity of carotenoids to reduce oxidative stress generated from inflammation 215 8.4.2 Immune-modulating activity of carotenoids 216 8.5 Effects of Carotenoids on Immune Genetic Mechanism of IBD 221 8.5.1 Potential role of retinoid receptors in attenuation of inflammatory diseases 222 8.5.2 Modulation of inflammatory responses through activation of nuclear receptors containing RXR heterodimers 223 8.6 Effects of Retinoids and Carotenoids on the Oxidative Stress Signaling Pathway 226 References 229 9 Ruminant Trans Fat as Potential Nutraceutical Components to Prevent Cancer and Cardiovascular Disease 235 Ye Wang, Catherine J. Field, and Spencer D. Proctor 9.1 Introduction 235 9.2 c9,t11-CLA Isomer and Health Implications 237 9.2.1 CLA modulates carcinogenesis 237 9.3 Mechanisms of CLA Action on Cancer 245 9.4 CLA Modulates CHD Risk Factors 245 9.5 Mechanisms of CLA Action on CHD 246 9.6 Vaccenic Acid 252 9.6.1 VA modulates carcinogenesis 253 9.6.2 VA modulates CVD risk factors 253 9.7 Dairy Fat Enriched with VA and CLA 254 9.7.1 Enriched dairy fat modulates carcinogenesis 254 9.7.2 Enriched dairy fat modulates CVD risk factors 255 9.8 Discussion 255 References 256 10 Nanotechnology for Cerebral Delivery of Nutraceuticals for the Treatment of Neurodegenerative Diseases 263 Jasjeet Kaur Sahni, Sihem Doggui, Le Dao, and Charles Ramassamy 10.1 Introduction 263 10.2 Oxidative Stress in Mild Cognitive Impairment (MCI) and AD 264 10.3 Efficacy of Selected Components of Nutraceutical Compounds in the Amyloid Cascade and in the Prevention of AD 266 10.4 Targeted NPs for Delivery of Bioactives Compounds from Foods for the Treatment of AD 272 10.4.1 Catechins coupled with NPs 272 10.4.2 NPs targeted with ApoE containing curcumin 273 10.4.3 Resveratrol-loaded NPs protect againt Ass-induced toxicity 275 10.5 Conclusion 275 References 275 11 Cancer Prevention by Polyphenols: Influence on Signal Transduction and Gene Expression 285 Fatima Hakimuddin and Gopinadhan Paliyath 11.1 Introduction 285 11.2 Genetic Mechanisms of Carcinogenesis 285 11.3 Biochemical Mechanisms of Carcinogenesis 287 11.3.1 Pathways and signals involved in neoplastic cell transformation and carcinogenesis 287 11.3.2 Extracellular signal transduction 288 11.3.3 Intracellular signal transduction 289 11.4 Signaling Pathways in Breast Cancer 291 11.4.1 Calcium homeostasis and signaling 292 11.4.2 Role of calcium in regulating cell proliferation and cell cycle 293 11.4.3 Regulation of the cell cycle by calmodulin 293 11.4.4 Calcium signaling and cell death 293 11.4.5 Mitochondria, calcium signaling, and apoptosis 294 11.5 Cancer Prevention and Therapy 294 11.5.1 Targeted therapies 294 11.5.2 Phytochemicals and cancer prevention 296 11.6 Grapes and Red Wine as a Dietary Source of Polyphenols 298 11.6.1 Health benefi ts of red wine 298 11.6.2 Modulation of signaling pathways by fl avonoids 306 11.7 Genetic Approach: Identifi cation of Flavonoid Mediated Molecular Targets 308 11.8 Estrogen Metabolism, Breast Cancer, and Flavonoids 311 11.9 Polyphenols and Estrogen Signaling 312 References 313 12 Potato Herb Synergies as Food Designs for Hyperglycemia and Hypertension Management 325 Fahad Saleem, Ali Hussein Eid, and Kalidas Shetty 12.1 Introduction 325 12.2 Phenolic-Enriched Chilean Potato and Select Species of Apiaceae and Lamiaceae Families in Diet 327 12.3 Combination of Potato with Seeds and/or Herbs for Hypertension and Hyperglycemia Management 331 12.3.1 Chilean potato (Solanum tuberosum ssp. tubersocum L.) 331 12.3.2 Apiaceae family 333 12.3.3 Lamiaceae family 335 12.4 Conclusions: Combining the Chilean Potato with Seeds and Herbs from the Apiaceae and Lamiaceae Families 336 References 338 13 Fermentation-Based Processing of Food Botanicals for Mobilization of Phenolic Phytochemicals for Type 2 Diabetes Management 341 Chandrakant Ankolekar and Kalidas Shetty 13.1 Introduction 341 13.2 Diabetes: The Rising Burden 342 13.3 Fermentation and Health: A Historical Perspective 342 13.4 Fermentation: Adding Value 343 13.4.1 Preservation of food through acid/alcohol formation 343 13.4.2 Enrichment of food substrates through formation of micro and macro nutrients 344 13.4.3 Flavor, aroma, and texture development 344 13.4.4 Detoxification of substrates during fermentation 345 13.5 Phenolic Antioxidants and Diabetes Management 345 13.6 Microbial Aerobic Growth and Fermentation and Its Anti-Diabetes Potential by Phenolic and Antioxidant Mobilization 346 13.6.1 Solid State Growth (SSG) 346 13.6.2 Liquid state (submerged) fermentation 347 13.7 Fruit Juice Fermentation for Healthy Food Ingredients for Management of Type 2 Diabetes 348 13.7.1 Apple juice fermentation 348 13.7.2 Pear juice fermentation 349 13.7.3 Cherry juice fermentation 349 13.8 Summary 350 References 351 14 Postharvest Strategies to Enhance Bioactive Ingredients for Type 2 Diabetes Management and Heart Health 357 Dipayan Sarkar and Kalidas Shetty 14.1 Introduction 357 14.2 Changing Dietary Patterns: A Historical Perspective 357 14.3 Noncommunicable Chronic Diseases: Era of New Global Epidemics 358 14.4 Healthy Diet: Prevention Is Better Than Cure 360 14.4.1 Fruits and vegetables: from garden of eden to modern horticulture 360 14.5 Bioactive Ingredients 361 14.6 Dietary Polyphenols: Impact on Human Health 362 14.6.1 Role of polyphenols in glucose metabolism 362 14.6.2 Polyphenols and cardiovascular disease 364 14.7 Phenolic Biosynthesis: Biological Mechanism to Improve Dietary Polyphenols in Plant Models 365 14.8 Postharvest Strategies to Improve Bioactive Ingredients in Fruits and Vegetables 367 14.8.1 Temperature 367 14.8.2 Light and oxygen 368 14.8.3 Chemical treatment and natural compounds 368 14.9 Phenolic-Linked Antioxidant Activity During Postharvest Stages in Fruits and Relevance for Type 2 Diabetes 369 14.10 Future Direction of Research: When Functional Food and Diet Become Panacea 370 14.10.1 Stage 1: physiology and growth during germination to maturity 370 14.10.2 Stage 2: postharvest management 371 14.10.3 Stage 3: food processing 371 14.10.4 Stage 4: biotechnological tools 372 14.10.5 Stage 5: in vitro studies 372 14.10.6 Stage 6: animal, clinical, and epidemiological studies 372 14.10.7 Stage 7: marketing, awareness, and education 373 14.11 Conclusions 373 References 373 15 Enhancing Functional Food Ingredients in Fruits and Vegetables 381 Shaila Wadud and Gopinadhan Paliyath 15.1 Introduction 381 15.2 Strategies for Nutritional Enhancement 382 15.3 Improving the Mineral Content of Plant Foods 383 15.3.1 Iron and zinc 384 15.4 Improving the Antioxidants Content of Plant Foods 385 15.4.1 Lycopene and ss-carotene 385 15.4.2 Vitamin E 387 15.4.3 Flavonoids 387 15.5 Improving the Amino Acid Content of Proteins of Plant Foods 389 15.6 Improving the Fatty Acid Composition of Plant Seed Oil 390 15.7 Influence of Processing and Storage in the Nutritive Value of Plant Foods 391 15.7.1 Processing of plant oils 391 15.7.2 Processing of fruits and vegetables 391 References 392 Index 395

About the Author

Dr Gopinadhan Paliyath is Professor in the Department ofPlant Agriculture, University of Guelph, Guelph, Ontario, Canada Dr Marica Bakovic is Professor in the Department of HumanHealth & Nutritional Science, University of Guelph, Guelph,Ontario, Canada Dr Kalidas Shetty is Professor in the Department of FoodScience, University of Massachusetts, Amherst, MA, USA

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