Presents recent research on metabolism and the health effects of polyphenols
Consumer interest in the health benefits of many phenolic compounds found in plant foods and derivatives has grown considerably in recent years, giving rise to an increased demand for functional foods. Although preclinical and observational studies have promoted the protective properties of polyphenols for a range of chronic diseases, evidence has shown that most dietary polyphenols have little bioavailability. Once ingested, most of them are metabolized by either the intestinal enzymes or by the gut microbiota and then undergo extensive phase-II metabolism reaching significant concentrations of conjugated metabolites. They remain in the systemic circulation and target systemic tissues where trigger biological effects. The polyphenol-derived metabolites produced in humans are dependent upon the composition of the gut microbiota and the subject genetics. Thus all the metabolites do not show the same biological activity in different individuals. To fully understand the health effects of polyphenols, further clinical investigations are required.
Dietary Polyphenols describes the latest findings on the polyphenol metabolism and reviews the current evidence on their health effects and that of their bioavailable metabolites. Emphasizing the importance of interindividual variability and the critical role of gut microbiota, this authoritative volume features contributions from recognized experts in the field, exploring specific families of extractable and non-extractable phenolic compounds that exhibit potential health effects. Topics include structural diversity of polyphenols and distribution in foods, bioavailability and bioaccessibility of phenolics, metabolism, and gastrointestinal absorption of various metabolites and their health effects. This comprehensive volume:
- Discusses the bioavailability, bioaccessibility, pharmacokinetics studies, and microbial metabolism of different groups of phenolic compounds
- Examines the interaction between polyphenols and gut microbiota
- Describes analytical methods for identifying and quantifying polyphenols in foods and biological samples
- Reviews recent epidemiological and clinical intervention studies showing protective effects of polyphenols
Dietary Polyphenols: Metabolism and Health Effects is an important resource for scientists working in the area of dietary polyphenols and health effects, microbiota, and their interaction with other nutritional compounds, and for health professionals, nutritionists, dieticians, and clinical researchers with interest in the role of polyphenols in the prevention and treatment of chronic diseases.
Table of Contents
List of Contributors xv
1 Structural Diversity of Polyphenols and Distribution in Foods 1
Antonio González-Sarrías, Francisco A. Tomás-Barberán, and Rocío García-Villalba
1.1 Introduction 1
1.2 Classification and Chemistry of Polyphenols 2
1.2.1 Flavonoids 2
1.2.2 Nonflavonoids 7
1.3 Dietary Intake and Food Sources of Polyphenols 10
1.3.1 Flavonoids 11
1.3.2 Nonflavonoids 14
1.4 Databases Used to Assess Dietary Exposure to Polyphenols 16
1.5 Bioavailability, Metabolism, and Bioactivity of Dietary Polyphenols 17
Acknowledgments 20
References 20
2 Nonextractable Polyphenols: A Relevant Group with Health Effects 31
Yuridia Martínez-Meza, Rosalía Reynoso-Camacho, and Jara Pérez-Jiménez
2.1 Introduction: The Concept of Nonextractable Polyphenols (NEPP) 31
2.2 Contribution of NEPP to Total Polyphenol Content and Intake 33
2.2.1 Strategies for the Extraction and Analysis of NEPP 34
2.2.2 NEPP Content in Common Foods 38
2.2.3 Estimation of NEPP Intake in Different Populations 40
2.3 Metabolic Fate of NEPP: A Key Process for Their Health Effects 42
2.3.1 Current Evidence of the Metabolic Transformation of NEPP 42
2.3.2 Specific Features of the Metabolic Fate of NEPP 46
2.4 How NEPP may Exhibit Health Effects 48
2.4.1 Antioxidant Effects 48
2.4.2 Microbiota Modulation 51
2.4.3 Biological Activities of Microbial Metabolites 53
2.4.4 Synergy with Dietary Fiber 58
2.5 Studies on the Health Effects of NEPP 60
2.5.1 Local vs Systemic Effects 60
2.5.2 Effects on Gastrointestinal Health 62
2.5.3 Effects on Cardiometabolic Health 64
2.6 Perspectives 66
References 68
3 Analytical Strategies for Determining Polyphenols in Foods and Biological Samples 85
Lucía Olmo-García, Romina P. Monasterio, Aadil Bajoub, and Alegría Carrasco-Pancorbo
3.1 Introduction: Importance of the Determination of Polyphenols 85
3.2 Most Widely Used Extraction Systems and New Trends 89
3.3 Determination of the Phenolic Compounds in Foods 92
3.3.1 Classic Methods For Polyphenols Determination: Spectrophotometric Assays 92
3.3.2 Evolution of the Traditional Methods to Characterize the Polyphenolic Fraction of Foods: Chromatographic and Electrophoretic Separation and Subsequent Detection 94
3.3.3 Other Analytical Strategies 106
3.4 Some Considerations Regarding the Determination of Polyphenols in Biological Samples 107
3.5 Conclusions and Future Directions 111
Acknowledgments 116
References 116
4 Hydroxycinnamates 129
Iziar A. Ludwig, Laura Rubió, Alba Macià, and Maria P. Romero
4.1 Introduction 129
4.2 Metabolism of Hydroxycinnamates and Metabolic Pathways 130
4.2.1 Absorption in the Upper Gastrointestinal Tract 135
4.2.2 Absorption in the Lower Gastrointestinal Tract 136
4.3 Bioaccessibility and Bioavailability of Hydroxycinnamates: Influence of Food Matrix, Processing, Dose, and Interindividual Differences 138
4.3.1 Bioavailability of Hydroxycinnamates in Fruits, Vegetables, and Beverages 139
4.3.2 Bioavailability in Cereal-Based Products 144
4.4 Biological Activity of Hydroxycinnamates and Their Derivatives 148
References 153
5 Flavonols and Flavones 163
Cláudia Nunes dos Santos, Regina Menezes, Diogo Carregosa, Katerina Valentova, Alexandre Foito, Gordon McDougall, and Derek Stewart
5.1 Introduction 163
5.2 Uptake and Metabolism of Flavonols and Flavones 167
5.2.1 Flavonols or 3-Hydroxyflavones (Quercetin, Kaempferol, Myricetin) 167
5.2.2 Flavones (Luteolin, Apigenin) 170
5.3 Microbiota Formation of Low Molecular Weight Phenolic, Common Colonic Metabolites 173
5.3.1 Flavonols (Quercetin, Kaempferol, Myricetin) 173
5.3.2 Flavones (Luteolin, Apigenin) 175
5.4 Health Effects of Flavonol and Flavone Metabolites 177
5.4.1 Flavonols or 3-Hydroxyflavones 177
5.4.2 Flavones (Luteolin, Apigenin) 181
5.4.3 Flavonols, Flavones and Their Low Molecular Weight Colonic Metabolites in Health 184
5.5 Conclusions and Future Perspectives 185
Acknowledgments 186
References 186
6 Isoflavones 199
Cara L. Frankenfeld
6.1 Uptake and Metabolism of Isoflavones 199
6.1.1 Gut Microbial Metabolism 199
6.1.2 Pharmacokinetic Studies 201
6.2 Biological Mechanisms of Isoflavones 203
6.2.1 Hormonal 203
6.2.2 Antioxidant 204
6.2.3 Antiinflammatory 205
6.3 Physiological and Health Effects of Isoflavones 205
6.3.1 Bone 206
6.3.2 Cancer 208
6.3.3 Reproductive Hormones 212
6.3.4 Cardiovascular Disease, Blood Triglycerides and Cholesterol, and Inflammatory Markers 213
6.3.5 Diabetes, Insulin Resistance, and Blood Glucose and Insulin 216
6.3.6 Obesity 217
6.3.7 Menopausal Symptoms 218
6.3.8 Neurological Outcomes 218
6.4 Physiological and Health Effects of Isoflavone Metabolites and Metabotypes 219
6.5 Summary of Isoflavone Intake and Health 221
References 221
7 Dietary Anthocyanins 245
Iva Fernandes, Hélder Oliveira, Cláudia Marques, Ana Faria, Conceição Calhau, Nuno Mateus, and Victor de Freitas 7.1 Absorption and Metabolism of Anthocyanins 245
7.1.1 Oral Cavity Absorption 248
7.1.2 Gastric Absorption 251
7.1.3 Intestinal Absorption 254
7.1.4 Microbial Metabolism 255
7.2 Pharmacokinetics of Anthocyanins 258
7.3 Factors Affecting Anthocyanin Bioavailability 259
7.4 Biological Activity of Anthocyanin Metabolites 262
7.4.1 Phase II Metabolites 265
7.5 Conclusion 272
References 272
8 Flavan-3-ols: Catechins and Proanthocyanidins 283
Claudia Favari, Pedro Mena, Claudio Curti, Daniele Del Rio, and Donato Angelino
8.1 Introduction: Chemistry and Main Dietary Sources 283
8.2 Bioavailability of Flavan-3-ols 288
8.2.1 Absorption and Metabolism: Native and Colonic Phase II Metabolites 289
8.2.2 Pharmacokinetics and Urinary Excretion of Circulating Metabolites: Interindividual Differences 293
8.3 Health Benefits of Flavan-3-ols and Their Derived Circulating Metabolites 298
8.3.1 Cognitive 299
8.3.2 Inflammation and Cardiometabolic Diseases 302
8.3.3 Urinary Tract Infections 305
8.4 Conclusions and Future Perspectives 307
References 308
9 Ellagitannins and Their Gut Microbiota-Derived Metabolites: Urolithins 319
Rocío García-Villalba, Juan A. Giménez-Bastida, María A. Ávila-Gálvez, Francisco A. Tomás-Barberán, Juan C. Espín, and Antonio González-Sarrías
9.1 Chemistry and Sources of Ellagitannins and Ellagic Acid 319
9.2 Bioavailability of Ellagitannins and Ellagic Acid 323
9.3 The Microbial Metabolism of Ellagitannins and Ellagic Acid: Urolithins 324
9.3.1 Urolithin Production and Bioavailability 324
9.3.2 Tissue Distribution of Urolithins after Consumption of Ellagitannins 328
9.3.3 Interaction of ETs and Urolithins with the Gut Microbiota 329
9.3.4 Interindividual Variability: Metabotypes 331
9.3.5 Analysis of Urolithins 332
9.4 Significance of Ellagitannins, Ellagic Acid, and Urolithins for Human Health 335
9.4.1 Antioxidant Effects 336
9.4.2 Antiinflammatory Properties 338
9.4.3 Anticarcinogenic Effects 340
9.4.4 Neuroprotective Effects 343
9.4.5 Estrogenic Modulation 344
9.4.6 Urolithins, Clinical Trials, and Interindividual Variability-Health Relationship 345
9.5 Conclusion 347
Acknowledgments 348
References 348
10 Lignans 365
Knud E. Bach Knudsen, Natalja Nørskov, Anne K. Bolvig, Mette Skou Hedemann, and Helle Nygaard Lærke
10.1 Introduction 365
10.2 Lignans in Foods 368
10.3 Metabolism of Lignans 373
10.3.1 Kinetics of Absorption of Plant Lignans 376
10.3.2 Conversion of Plant Lignans to Enterolignans 382
10.4 Blood Levels of Lignans after Dietary Intervention 387
10.5 Bioactivity of Plant Lignans and Enterolignans 393
10.6 Conclusions and Future Perspectives 394
Acknowledgments 395
References 395
11 Stilbenes: Beneficial Effects of Resveratrol Metabolites in Obesity, Dyslipidemia, Insulin Resistance, and Inflammation 407
Itziar Eseberri, Iñaki Milton-Laskibar, Alfredo Fernández-Quintela, Saioa Gómez-Zorita, and María P. Portillo
11.1 Introduction: Occurrence and Intake 407
11.2 Absorption, Metabolism, and Excretion of Resveratrol 408
11.3 Biological Effects of Resveratrol Metabolites 412
11.3.1 In vitro Studies 413
11.3.2 In vivo Studies 428
11.4 Conclusion 429
Acknowledgments 429
References 430
12 Flavanones 439
Gema Pereira-Caro, Colin D. Kay, Michael N. Clifford, and Alan Crozier
12.1 Introduction 439
12.2 Flavanones and Their Occurrence 441
12.3 Absorption of Flavanone Metabolites in the Proximal and Distal Gastrointestinal Tract 443
12.4 Formation of 3-(3′-Hydroxy-4′-Methoxyphenyl) Hydracrylic Acid 454
12.5 Factors Affecting the Bioavailability of Flavanones 457
12.5.1 Impact of Physical Activity 457
12.5.2 Matrix Effects 458
12.5.3 Probiotics 459
12.5.4 Inter- and Intraindividual Variability 460
12.5.5 Other Effects 462
12.6 Analysis of Flavanone Metabolites and Catabolites 462
12.7 Biomarkers and Metabolomics 465
12.8 Protective Effects 467
12.8.1 Cardiovascular Disease 468
12.8.2 Diabetic and Metabolic Syndrome 471
12.8.3 Cancer 472
12.8.4 Cognition and Neuroprotection 473
12.8.5 Bones 474
12.8.6 Liver 474
12.8.7 Immunomodulation and Antiinflammatory Activity 474
12.8.8 Gastric Function and the Microbiome 475
12.8.9 Modulation of the Microbiota and Biological Activity of Microbial Metabolites 475
References 479
13 Understanding Polyphenols’ Health Effects Through the Gut Microbiota 497
Maria V. Selma, Francisco A. Tomás-Barberán, Maria Romo-Vaquero, Adrian Cortés-Martín, and Juan C. Espín
13.1 Microbial Metabolism of Dietary Polyphenols 497
13.2 Bacteria Responsible for Dietary Polyphenols Transformations and Health Implications 507
13.3 Modulation of Gut Microbiota by Dietary Polyphenols 516
Acknowledgments 519
References 519
Index 533
