Biomarkers in Nutrition (Biomarkers in Disease: Methods, Discoveries and Applications)

Preface Contents About the Editors Contributors Part I: Circulating and Body Fluid Biomarkers 1 Advanced Glycation End Products as Biomarkers in Nutrition Introduction AGEs: Definition and Historical Background AGEs Sources and Formation Bioactivity of AGEs and Impact of dAGEs on Health Accumulation in Tissues and Organs Mechanisms Underlying the Pathogenetic Pathways of AGEs Biological Effects of dAGEs Implication of dAGEs in Aging and Pathological Conditions Premature Aging and Age-Related Diseases Metabolic Syndrome Diabetes and Diabetic Complications Cardiovascular Diseases Neurodegenerative Diseases Renal Disease Oral Diseases Strategies to Reduce AGEs Load The Effects of Nutritional Intervention on Health Outcomes Physical Exercise Pharmacological Agents The Role of AGEs as Biomarkers in Nutrition Applications to Prognosis Controlling/Reducing the Amount of dAGEs Intake Could Help to Improve Health Applications to Other Diseases or Conditions Diagnostic Approaches Based on Measurement of AGEs Levels in the Biofluids Mini-Dictionary of Terms Key Facts of Advanced Glycation End Products (AGEs) Key Facts of Impact of Dietary Advanced Glycation End Products (dAGEs) on Health Summary Points References 2 Trimethylamine N-Oxide (TMAO) as a Biomarker Introduction TMAO Metabolism: The Role of the Diet and the Microbiome Dietary Sources TMA-Producing Bacteria TMAO Metabolism: From Absorption to Excretion TMAO and Diseases TMAO Detection TMAO and Cardiovascular Diseases TMAO and Chronic Kidney Diseases TMAO and Metabolic Diseases TMAO and Other Diseases TMAO as a Potential Therapeutic Target: From Nutrition Interventions to Gut Microbiota Modulations TMAO as a Biomarker: Potentiality and Limits Potentialities Limits and Pitfalls Conclusions Applications to Prognosis and Other Diseases or Conditions Mini-Dictionary of Terms Key Facts of Trimethylamine N-Oxide (TMAO) as a Biomarker: Features and Applications Summary Points References 3 The Redox State of Serum Albumin as a Potential Protein Nutrition Biomarker Introduction Biological Roles of Serum Albumin Albumin Synthesis and Breakdown Redox State of Serum Albumin Analytical Chemistry for the Redox State of Serum Albumin Association Between the Redox State of Serum Albumin and Pathological Conditions Association Between the Redox State of Serum Albumin and Physiological Conditions Redox State of Serum Albumin as a Potential Protein Nutrition Biomarker Application of the Redox State of Serum Albumin to Prognosis of Protein Nutritional Status in Humans Conclusions Mini-dictionary of Terms Key Facts of the Redox State of Serum Albumin Summary Points References 4 Branched Short-Chain Fatty Acids as Biological Indicators of Microbiota Health and Links with Anthropometry Introduction Microbial BCFA Biosynthesis Methods for BCFA Analysis Gas Chromatography Liquid Chromatography Nuclear Magnetic Resonance and Capillary Electrophoresis Branched-Chain Fatty Acids in the Context of Nutrition Dietary Interventions Related with Changes in BCFA and Anthropometric Factors Possible Implications of Branched-Chain Fatty Acids in Host Health BCFA in the Healthy Microbiota Changes in the Profile of BCFA Associated with Disease Potential Applications to Prognosis and Other Diseases or Conditions Mini-Dictionary of Terms Key Facts of Gut Microbiota Summary Points References 5 Plasma Nitrate and Nitrite as Biological Indicators of Health and Disease in Nutritional Studies Introduction Definition of Nitrates Sources of Dietary Nitrates in Nutritional Studies Foods Containing Nitrate Nitrate as a Food Additive in Processed Meats Nitrate as a Dietary Supplement Nitrate and Nitrite Salts Beets and Beetroot Juice Red Spinach Nitrates and Nitrites in Nutritional Studies Half-Life of Nitrate and NO Nitrate and Nitrite as a Biomarker Importance of NO Concentration Indirect Physiological Biomarkers of NO Exposure NO and its Metabolites in Diseases and Pathological States Laboratory Assessment of Nitrate and Nitrite Nitrate as a Biomarker to Determine Potential Health Benefits of Nitrate Increased NO Improved Blood Flow: Response to Hypoxia Reduction in Blood Pressure General Cardioprotection Improved Cognition Mitigation of Erectile Dysfunction Improvement in Aerobic Exercise Performance Improved Glycemia: Diabetes and Insulin Resistance Directions for Future Research on Nitrates Related to Health Conclusion Applications to Prognosis of Other Diseases or Conditions Mini-Dictionary of Terms Key Facts of Nitrates Summary Points References 6 Blood and Urinary Flavonoids Introduction Chemical Composition and Bioactivity Food Sources, Intake, and Metabolism Measurement of Exposure Sample Preparation Separation and Detection Techniques Liquid Chromatography and Mass Spectrometry Gas Chromatography and Mass Spectrometry Capillary Electrophoresis Electrokinetic Chromatography Nuclear Magnetic Resonance Time-Resolved Fluorescence Immunoassay Applications of Flavonoid Biomarkers Assessment of the Effect on Disease Risk Dietary Assessment Mini-Dictionary of Terms Key Facts of the Flavonoid Exposure Assessment and Their Use as Biomarkers Summary Points References 7 Uric Acid as a Biomarker in Nutritional Metabolism Introduction Uric Acid Metabolism Inflammation and Uric Acid Metabolism Uric Acid Metabolism and Metabolic Disorders Nutritional Approach to Hyperuricemia Uric Acid and Diabetes Conclusion Applications to Prognosis and Other Diseases or Conditions Mini-Dictionary of Terms Key Facts of Uric Acid Summary Points References 8 Ceramides as Dietary Biomarkers Introduction Following the Metabolic Pathway of Ceramides Ceramides: Metabolic Messengers Driving Cardiovascular Diseases (CVDs) Diet-Induced Responses to Ceramide Concentrations Conclusions Applications to Prognosis Applications to Other Diseases or Conditions Mini-dictionary of Terms Key Facts of Ceramides Summary Points References Part II: Micronutrients and Minerals 9 Urinary Arsenic as a Biomarker: Speciation Analysis for the Assessment of Dietary Exposure Introduction Arsenic Species in the Environment and Biota HPLC-ICP-MS for Speciation Analysis of As Urinary As Species as a Biomarker of Exposure Urinary iAs Speciation Analysis in Environmental Epidemiology Quantitative Relationship Between Urinary As Speciation and Dietary Intake Problem in Using Urinary As Speciation as a Biomarker of Exposure Urinary As Speciation as a Biomarker of Susceptibility Concluding Remarks Applications to Other Diseases or Conditions Mini-Dictionary of Terms Key Facts of Urinary Arsenic as a Biomarker: Speciation Analysis for the Assessment of Dietary Exposure Key Facts of Urine As Species as a Biomarker of Exposure Key Facts of Urinary As Speciation Analytical Method Summary Points References 10 Use of Histology in Nutrition Introduction Arsenic Epidemiology of Arsenic Mechanism of Arsenic Toxicity Use of Histology in Identifying the Hallmarks of Arsenic Toxicity Liver Kidney Brain Lungs Heart Testis Ovary Approaches to Combat Arsenic Toxicity Chelation Therapy Use of Nutritional Supplements as Antioxidants Zinc Histological Studies on the Ameliorating Effect of Zinc on Arsenic Toxicity Applications of Histology in Other Diseases Mini-Dictionary of Terms Key Facts About Arsenic Toxicity Summary Points References 11 Measures of Iron Metabolism and Applications to Dietary Patterns Introduction Overview of Iron Metabolism and Iron Disorder Disease Iron Distribution Hepcidin-Ferroportin Axis and Iron Disorder Disease Iron Requirement Recommended Daily Allowances Iron Bioavailability in Foods Types of Iron Sources in Food Factors That Affect Dietary Iron Absorption Iron Enhancers MFP Factors Organic Acids (Vitamin C, Citric Acids, Malic Acids) and Gastric Acids Alcohol Copper ß-Carotene and Vitamin A Body Iron Stores Iron Inhibitors Phytate and Oxalate Polyphenols: Tea and Coffee Polyphenols: Quercetin Proteins from Plants, Eggs, and Milk (Calcium) Sugar Dietary Approaches for Iron Disorder Dietary Approaches for Absolute Iron Deficiency and Iron Deficiency Anemia Dietary Approaches for Functional Iron Deficiency and Anemia of Inflammation Dietary Approaches for Hereditary Iron Disorders Diagnosis of Iron Disorder Diseases Absolute Iron Deficiency and Iron Deficiency Anemia Functional Iron Deficiency and Anemia of Inflammation Hereditary Iron Disorder Diseases Hemochromatosis β-Thalassemia Conclusion Applications to Prognosis Mini-Dictionary of Terms Key Facts of Anemia of Inflammation Summary Points References 12 Glycolate as a Biological Marker of B Vitamins Introduction Glycolate Intestinal Absorption of GA Cellular Uptake of GA GA Excretion GA Metabolism Glyoxylate Detoxification Glycolate Oxidase (GO) Vitamin B2 and GA Metabolism Agxt1 Vitamin B6 and GA Metabolism Factors Influencing GA Metabolism Markers in VB2 and VB6 Deficiency and Applications to Prognosis Applications to Prognosis Applications to Other Diseases or Conditions Mini-Dictionary Key Facts of Xylitol Metabolism Summary Points References 13 Assays for Carotenoids: Linking Breastmilk and Maternal Intakes Introduction Carotenoid´s Absorption and Transport Carotenoid Transport into the Breastmilk Breastmilk Composition Breastmilk Carotenoids Carotenoid Intake During Lactation Assays for Carotenoids: Methodological Implications Breastmilk Sample Collection Breastmilk Sample Handling and Storage Breastmilk Analysis Nutritional Assessment Data Collection Carotenoid Database Applications to Prognosis, Other Diseases, or Conditions Mini-Dictionary of Terms Key Facts of Carotenoids in the Breastmilk Summary Points References Part III: Diets and Macronutrients 14 The Dietary Diversity Score Introduction The Diet Diversity Score as Diet Quality Indicator Diet Diversity Score in Relation to Diet Quality Dietary Diversity and Nutrient Adequacy Seasonality and the Dietary Diversity Score Calculation of the Dietary Diversity Score The Dietary Diversity Score and NCDs The Dietary Diversity Score and Anthropometric Measurements Applications to Prognosis, Other Diseases, or Conditions Conclusion Summary Points Key Facts of DDS Mini-dictionary of Terms References 15 Dietary Phytochemical Index as a Biomarker in Nutritional Studies: Features and Applications Introduction Sources and Types of Phytochemicals Definition and Utility of ``Phytochemical Index´´ Application of Dietary Phytochemical Index as a Biomarker for Non-communicable Diseases (Fig. 3) Phytochemical Index, Obesity, and Metabolic Disorders Phytochemical Index and Cardiovascular Diseases Phytochemical Index and Cancer Phytochemical Index and Neurological Disorders Limitations of DPI and Concluding Remarks Mini-dictionary of Terms Key Points of Dietary Phytochemical Index (DPI) Summary Points References 16 Mediterranean Diet Adherence and Serum Markers of Lipids Introduction Serum Lipid Profile Association of Serum Lipid Profile with Human Health Influence of Lipid Profile by Environmental Factors, Such as Nutritional Attitudes Association of Dietary Nutrients (Fats, Carbohydrates, Proteins, Fibers, and Antioxidants) with Serum Lipid Profile Fats Saturated Fatty Acids Polyunsaturated Fatty Acids Monounsaturated Fatty Acids Dietary Cholesterol Carbohydrates Proteins Fibers Antioxidants The Mediterranean Diet and Serum Markers of Lipids Definition and Main Characteristics of the Mediterranean Diet Interaction of the Mediterranean Diet Adherence with Various Biomarkers (Including Lipid Markers) and Consequently Health Outc... Summary of Research Findings About the Effect of the Mediterranean Diet on Serum Lipid Profile and Health Lyon Diet Heart Study HALE Study ATTICA Study Medi-RIVAGE Study Randomized Controlled Trials Comparative Study BioCycle Study Crossover Design Studies Cross-Sectional Study PREDIMED Sub-study Retrospective Observational Study Functional Foods of the Mediterranean Diet with a Beneficial Effect on Serum Markers of Lipids Further Analyze the Significance of Specific Mediterranean Foods with Functional Value in Regulating the Serum Lipid Profile Olive Oil Fruits and Vegetables Pomegranate Raisins Wild Greens Aromatic Plants and Essential Oils Fish and Fish Oil Nuts and Walnuts Mushrooms Dairy Products Herb Drinks (Green Tea, Et Cetera) Red Wine Application to Prognosis, Other Diseases, or Conditions Applications to Prognosis Applications to Other Diseases or Conditions Mini-dictionary of Terms Key Facts Key Facts of Dyslipidemia Summary Points References 17 Fecal Volatile Organic Compounds Introduction The Origins of Fecal Volatile Organic Compounds Analysis of VOCs Chemical Classification of VOCs Specific Dietary Components and Their Effect on VOC Profiles Dietary Patterns and VOC Profiles VOCs from Other Sources Applications and Further Study Conclusion Application to Other Diseases Mini-Dictionary of Terms Key Facts of Volatile Organic Compounds Summary Points References 18 Calprotectin as a Biological Indicator in Nutrition Introduction Main Mechanisms of Calprotectin Action (Table 1 and Fig. 1) Fecal Calprotectin as a Marker of Inflammation In the Intestine In Chronic Low-Grade Inflammatory Disease Obesity-Driven Insulin Resistance (Table 2) Type 2 Diabetes-Driven Insulin Resistance Calprotectin and Macrovascular/Cardiovascular Disease Calprotectin and Microvascular Disease Therapeutic Opportunities Effects of Lifestyle and Diet on Levels of Calprotectin Future Prospects in the Potential Impact of Calprotectin Modulation Conclusions Mini-Dictionary of Terms Key Facts of Calprotectin as a Biological Indicator in Nutrition: Insulin Resistance and Beyond Summary Points References 19 Omega-6 Fatty Acids Introduction Omega-6 Fatty Acids as Biomarkers for Dietary Intake Omega-6 Fatty Acids as Biomarkers for Cardiovascular Disease Omega-6 Fatty Acids as Biomarkers for Diabetes Omega-6 Fatty Acids as Biomarkers for Asthma Omega-6 Fatty Acids as Biomarkers for Autoimmune Disease Omega-6 Fatty Acids as Biomarkers for Cancer Limitations on the Application of Omega-6 Biomarkers Mini-Dictionary of Terms Summary Points References 20 Fatty Acid Profile of Red Blood Cells as Markers in Dietary Regimes and Beyond Introduction Lipids in Nutrition Evaluating Fatty Acids in Tissues and the Impact of PUFA The Importance of Omega-6 and Omega-3 Fatty Acids as Biomarker of Intakes from Nutrition Omics Technologies and Membrane Lipidomics The Information Provided by ``Omics´´ Technologies Lipidomics and Membrane Lipidomics The Development of RBC Fatty Acids as Biomarkers The Importance of Sampling Procedure, Analytical Recognition, and Evaluation of Biological Significance The Choice of Red Blood Cell Membrane and Comparison with Other Blood Compartments The Proof of the RBC/Lipoprotein Fatty Acid Exchange Applications to Prognosis, Other Diseases, or Conditions Application of C-16 Monounsaturated Fatty Acids in Cancer Diagnostics Applications to Other Diseases or Conditions Membrane Lipidomics Applied to Overweight and Obese Cohorts Mini-Dictionary of Terms Key Facts of Fatty Acids as Biomarkers in Nutrition Key Facts of Membrane Fatty Acids Key Facts of Fatty Acid Analysis Key Facts of Membrane Fatty Acids Used in Prevention Summary Points References 21 Assessing Pyruvate Carboxylase Flux as a Mechanistic Biological Marker in Fasting Introduction PC Flux During Fasting Direct Assessment of PC: Gene Expression, Protein Level, and Colorimetric Assays Metabolomics Approach: Isotopomer Analysis In Vivo Assessment of PC Activity Using 13C MR Spectroscopy Complication with Other Pathological Conditions Mini-dictionary of Terms Key Facts of Pyruvate Carboxylase Summary Points References 22 Biological Markers of Plant Phenolic Compounds Intake Introduction Classification and Structure of Major Dietary PC Phenolic Acids Flavonoids Tannins Stilbenes Lignans Coumarins Curcuminoids Biotransformation of PC During Digestive Process Anthocyanins and Other Flavonoids Hydrolyzable Tannins Flavan-3-Ols Isoflavones Phenolic Acids Lignans Kinetics of PC After Dietary Intake Absorption Distribution Metabolization Excretion Methods Used for Estimation of Dietary Intake of PC Dietary Assessment Methods Biomarkers Plasma Urine Analytical Techniques Used to Identify and Quantify PC Biomarkers Conclusion Applications to Other Diseases or Conditions Mini-Dictionary of Terms Key Facts Key Facts of PC Digestion and Metabolism Key Factors of Biomarkers of PC Intake Summary Points References Part IV: Genetic, Molecular, and Cellular Variables 23 Blood Gene Expression of Zinc Transporters as Biological Indicators of Zinc Nutrition Introduction Zinc Metabolism and Homeostasis Zinc Transporters Zinc Transporters mRNA as Biomarkers of Zinc Status Applications to Diseases Diabetes Cardiovascular Disease Alzheimer´s Disease Mini-Dictionary of Terms Key Facts of Zinc Transporters in Diabetes Key Facts of Zinc Transporters in Cardiovascular Disease Key Facts of Zinc Transporters in Alzheimer´s Disease Summary Points References 24 Circulating MicroRNA (miRNA)s as Biological Markers and Links with Obesity and Obesity-Related Morbid Conditions Introduction An Overview of White Adipose Tissue miRNAs: Small RNAs Playing a Central Role in Gene Expression Control Biogenesis of miRNAs and Mechanisms of Action miRNAs Detection miRNAs Target Prediction The Role of miRNAs Across Tissues in the Context of Obesity Circulating miRNAs in Obesity and Obesity-Related Comorbidities Applications to Prognosis, Other Diseases, or Conditions Mini-Dictionary of Terms Summary Points References 25 Plasma MicroRNA (miRNA)s as Novel Markers of Nonalcoholic Fatty Liver Disease Introduction MiRNA Biogenesis MiRNA-Dependent Epigenetic Reprogramming in NAFLD Hepatic Lipid Metabolism Hepatic Carbohydrate Metabolism Stress-Activated Pathways MiRNAs That Regulate NAFLD Progression Applications to Prognosis, Other Diseases or Conditions Conclusion Key Facts Mini-Dictionary of Terms Summary Points References 26 Telomere Length Introduction Section 1. Telomere Length: Measurements Terminal Restriction Fragments (TRF) Quantitative PCR Methods Quantitative FISH STELA Methods Single Telomere Absolute-Length Rapid (STAR) Main Remarks Section 2. Telomere Length: Links with Anthropometry in Lifestyle Intervention Inflammation and Oxidative Stress Linked to Obesity and TL Lifestyle Factors for Obesity Development Dietary Treatment Promoting Physical Activity Behavioral Therapy Lifestyle Intervention Studies TL as a Biomarker in Lifestyle Intervention Applications to Prognosis or Applications to Other Diseases or Conditions Mini-Dictionary of Terms Key Facts of TL Measurement Key Facts of Obesity Key Facts of Lifestyle Intervention Summary Points References 27 GWAS and GWAIS for Identifying Connections Between Genetics, Nutrition, and Health: The Example of Omega-3 and Plasma Trigl... Introduction Overview of Precision Nutrition The Interplay Between Nutrition and Genetics What´s a GWAS? What´s a GWAIS? Example: Using the GWAS Approach for Determining Gene-Diet Associations Related to TG and Omega-3 Fatty Acids Variability in Plasma TG Response to Omega-3 Fatty Acids Fine Mapping of GWAS Signals Validation of Nutri-GRS and Contribution of EPA Versus DHA to TG Change Importance of Understanding Biological Plausibility Conclusion Other Applications of GWAS and GWAIS for Precision Nutrition Mini-Dictionary of Terms Key Facts of GWAS and GWAIS for Nutritional Genomics and Precision Nutrition Summary Points References 28 The Alpha-Klotho Gene as an Anti-ageing Biomarker: Measures and Applications to the Effects of Nutrition Introduction Plausible Mechanisms of the Effect of Nutrition on S-Klotho Levels Effect of Nutrition in Klotho: Evidence from Preclinical Models Dietary Energy Dietary Macronutrients Micronutrients Effect of Nutrition in Klotho: Human Studies Observational Evidence Intervention Studies Future Investigations into S-Klotho Fasting Strategies Dietary Compounds Dietary Patterns Conclusion Applications to Prognosis, Other Diseases, or Conditions Mini-Dictionary of Terms Key Facts of Klotho Summary Points References Part V: Functional and Physiological Variables and Platforms 29 BMI as a Biomarker in Patients´ Nutritional Assessment Introduction BMI as a Biomarker of Nutritional Status BMI as a Biomarker of Malnutrition Overweight and Obesity BMI as a Biomarker of Fat Distribution and Body Composition BMI Applications to Other Diseases or Conditions BMI Applications to Prognosis Further Study Conclusions Key Facts of BMI as a Biomarker in Patients´ Nutritional Assessment Mini-Dictionary of Terms Summary Points References 30 Three-Dimensional Ultrasound for Sensitive Assessment of the Effects of Nutritional Therapy on Carotid Atherosclerosis Introduction Quantitative Assessment of Treatment Effect Based on 3D Carotid US Images Plaque Texture Analysis Plaque Segmentation and Texture Extraction Dimensionality Reduction and Biomarker Generation Physical Understanding of the Biomarker Vessel-Wall-Plus-Plaque Thickness (VWT) Analysis Generation of 2D VWT Map Quantitative Assessment Based on Discussion and Future Perspectives Applications to Other Anti-atherosclerotic Treatments/Interventions and Image Modalities Mini-Dictionary of Terms Key Facts of 3D Carotid Ultrasound Biomarkers Summary Points References 31 NMR Metabolomics for Marker Discovery of Metabolic Syndrome Introduction Carbohydrate Dysfunction Glucose Lactate Uric Acid BCAAs and AAAs Glutamine and Glutamate Citrate Propionylcarnitine Dyslipidemia Fatty Acids Choline Lipoproteins Ketone Bodies Inflammation N-Acetylglycoproteins Lysophospholipids Oxidative Stress Uric Acid and Allantoin 8-OHdG and Pseudouridine One-Carbon Metabolism Intermediates: GSH/GSSG Ratio, Glycine, and Serine Gut Microbiota Dysbiosis Lactate Acetate Succinate TMA, TMAO, and DMA Anxiety, Psychological Stress, and Related Disorders Lipids GlycA Glutamine Glucose Applications to Prognosis, Other Diseases, or Conditions Funding Mini-Dictionary of Terms Key Facts of Metabolic Syndrome Key Facts of NMR Metabolomics Summary Points References 32 Central and Peripheral Biomarkers for the Study of Appetite Regulation in Humans Introduction Central and Peripheral Appetite Regulation in Humans Biomarkers for the Study of Central Appetite Regulation in Humans Biochemical Biomarkers of Central Appetite Regulation Image Methods to Study Central Appetite Regulation Behavioral Measures of Central Appetite Regulation Biomarkers for the Study of Peripheral Appetite Regulation in Humans Peripheral Signals that Regulate Appetite Metabolomics and Central Appetite Regulation Fatty Acids and Their Derivatives as Biomarkers of Appetite Regulation Amino Acids as Biomarkers of Appetite Regulation Glucose and Other Carbohydrates as Biomarkers of Appetite Regulation Other Metabolites Proposed as Biomarkers of Appetite Regulation Conclusion and Future Directions Applications to Prognosis, Other Diseases, or Conditions Mini-Dictionary of Terms Key Facts of Appetite Regulation Summary Points Reference 33 Growth Reference Charts as Biological Indicators of Nutrition Introduction Biological Indicators of Nutrition Growth Reference Charts Types of Growth Reference Charts Z-score (SD Score) Percentiles Percent of Median Head Circumference as a Biological Indicator Construction of Growth Charts for HC: Different Methods Assessment of Nutritional Status Using the HC Applications to Prognosis Mini-Dictionary of Terms Key Facts of Human Growth Key Facts of Growth Reference Charts Key Facts of Measuring HC Summary Points References Part VI: Biomarkers in Specific Conditions or Scenarios 34 Biomarkers of Malnutrition in Cirrhosis Introduction Mechanisms of Malnutrition in Cirrhosis Reduced Oral Intake Increased Metabolic Demand Malabsorption Clinical Assessment Nutritional Questionnaires Energy Expenditure Laboratory Evaluation Plasma Proteins Albumin Prealbumin Transferrin Retinol-Binding Protein-4 Branched-Chained Amino Acids Adipokines Leptin Adiponectin Resistin Plasma Ghrelin Micronutrients Fat-Soluble Vitamins (Vitamins A, D, E, and K) Water-Soluble Vitamins Minerals Emerging Biomarkers Metabolomics Proteomics Ancillary Tests Anthropometric Tests Radiologic Assessment Conclusion Applications to Prognosis Mini-dictionary of Terms Key Facts Key Facts of Malnutrition in Cirrhosis Key Facts of Biomarkers of Malnutrition in Cirrhosis Summary Points References 35 Inflammatory Biomarkers in Nutrition Introduction Biomarkers of Inflammation Nutrients and Inflammation Food and Inflammation Dietary Patterns and Inflammation Conclusion Applications to Prognosis and Other Diseases or Conditions Applications to Prognosis Applications to Other Diseases or Conditions Key Facts of Cytokines Summary Points References 36 YKL-40 as an Inflammatory Biomarker in Nutrition Introduction General Characteristics of YKL-40 The Effects of YKL-40 on Signaling Pathways Related to Nutrition and Metabolism The Role of YKL-40 in Obesity and Diabetes YKL-40´s Relationship with Diet and Vitamins YKL-40 in Cancers Relationship Between YKL-40 and Cardiovascular Diseases Applications to Prognosis and Other Diseases or Conditions Conclusion Mini-dictionary of Terms Key Facts of YKL-40 References 37 The Dietary Inflammatory Index Introduction The DII Score Calculation The DII Score and Diseases DII Score and Cardiovascular Diseases The DII Score and Cancer Applications to Prognosis, Other Diseases, or Conditions Conclusion Summary Point Mini-dictionary of Terms Key Facts of DII References 38 Thiol-Disulfide Homeostasis as an Oxidative Stress Indicator Introduction Features of Kits Used in Thiol-Disulfide Homeostasis Measurement Analytical Recovery Linearity Lower Detection Limit Analytical Sensitivity Interference Precision Storage Thiol(-SH)-Disulfide(-S-S-) Homeostasis Test Profile Principle of the Assay Application Parameters of the Assays Free Radicals and Nutrition Oxidative Stress and Nutrition Antioxidant Nutrition Priorities Healthy and Natural Nutrition Dietary Preferences and Oxidative Stress Applications to Prognosis and Other Diseases or Conditions Applications to Prognosis Applications to Other Diseases or Conditions Key Facts of Thiol-Disulfide Homeostasis as an Oxidative Stress Indicator: Applications to Nutrition Summary Points References 39 Oxidative Stress Biomarkers in Exercise Introduction Oxidative Stress and Redox Oxidative Stress in Exercise Applications to Prognosis Intake of Supplements in Exercise/Physical Activation and Redox Nutritional Oxidative Stress Biomarkers in Exercise Protein Carbonyl Groups Oxidized Low-Density Lipoprotein Thiol-Disulfide Homeostasis Oxidative Stress Caused by Exercise and Vitamin Diet Vitamins C and E Vitamin A Vitamins B6 and B9 Mini-dictionary of Terms Key Facts of Oxidative Stress in Exercise and Nutrition Summary Points References 40 Biological Indicators of Oxidative Stress [Malondialdehyde, Catalase, Glutathione Peroxidase, and Superoxide Dismutase] and... Introduction Catalase (CAT) Characterization and Historical Basis Determination Methods Importance and Applications to Prognosis, Other Diseases, or Conditions Glutathione Peroxidase (GPx) Characterization and Historical Basis Determination Methods Importance and Applications to Prognosis, Other Diseases, or Conditions Superoxide Dismutase (SOD) Enzyme Characterization and Historical Basis Determination Methods Importance and Applications to Prognosis, Other Diseases, or Conditions Malondialdehyde (MDA) Characterization and Historical Basis Determination Methods Importance and Applications to Prognosis, Other Diseases, or Conditions Mini-Dictionary of Terms Key Facts of Oxidative Stress in Chronic Noncommunicable Diseases Summary Points References 41 The Oxidative Balance Score as a New Nutritional Scoring System Introduction Oxidative Balance Score The Effects of Antioxidants Involved in the OBS on Development of the Non-communicable Diseases Oxidative Balance Score, Cardiovascular Diseases, and Their Related Risk Factors Oxidative Balance Score and Cancers Oxidative Balance Score and Mortality Oxidative Balance Score, Inflammatory Biomarkers, and Related Diseases Conclusion Applications to Other Diseases or Conditions Mini-dictionary of Terms Key Facts of Oxidative Balance Score Summary Point References 42 Urinary Gluten Immunogenic Peptides as a Biomarker in Celiac Patients Introduction Current Methods for Assessing Gluten-Free Diet Adherence Development of a Method for the Detection of Gluten Immunogenic Peptides in Human Specimens Process to Consolidate the Detection of Immunogenic Peptides as a Biomarker in Patients with Celiac Disease Applicability Mini-dictionary of Terms Key Facts of Urinary Gluten Immunogenic Peptides as Biomarkers in Celiac Patients Key Facts of GIP Determination in Human Specimens Summary Points References 43 Citrulline as a Marker of Villous Abnormality and Implications for Diet and Nutrition Introduction Citrulline: Biochemical Characteristic, Synthesis, and Functions Synthesis of Citrulline from Glutamine in Enterocytes Utilization of Citrulline in Different Tissues Synthesis of Arginine from Citrulline Nitric Oxide Synthesis from Arginine and Citrulline Urea Cycle Normative Concentration of Citrulline in the Plasma Causes for High and Low Plasma Citrulline Levels Diagnostic and Therapeutic Value of Citrulline Blood Levels of Citrulline for the Assessment of Enterocyte Mass/Enteropathy Plasma Citrulline as a Marker of Enteropathic or Reduction in the Absorptive Surface Cyclical Changes in the Level of Plasma Citrulline in a Model of Enteropathy Citrulline and Mucositis Citrulline and HIV Enteropathy Citrulline and Intestinal Transplantation Rejection Citrulline in Patients with Necrotizing Enterocolitis Levels of Citrulline as a Marker of Intestinal Function: A Meta-analysis Therapeutic Role of Citrulline Muscles Cardiovascular Diseases Erectile Dysfunction Antidepressant Effects Ageing and Sarcopenia Mini-Dictionary of Terms Key Fact Preface Contents About the Editors Contributors Part I: Circulating and Body Fluid Biomarkers 1 Advanced Glycation End Products as Biomarkers in Nutrition Introduction AGEs: Definition and Historical Background AGEs Sources and Formation Bioactivity of AGEs and Impact of dAGEs on Health Accumulation in Tissues and Organs Mechanisms Underlying the Pathogenetic Pathways of AGEs Biological Effects of dAGEs Implication of dAGEs in Aging and Pathological Conditions Premature Aging and Age-Related Diseases Metabolic Syndrome Diabetes and Diabetic Complications Cardiovascular Diseases Neurodegenerative Diseases Renal Disease Oral Diseases Strategies to Reduce AGEs Load The Effects of Nutritional Intervention on Health Outcomes Physical Exercise Pharmacological Agents The Role of AGEs as Biomarkers in Nutrition Applications to Prognosis Controlling/Reducing the Amount of dAGEs Intake Could Help to Improve Health Applications to Other Diseases or Conditions Diagnostic Approaches Based on Measurement of AGEs Levels in the Biofluids Mini-Dictionary of Terms Key Facts of Advanced Glycation End Products (AGEs) Key Facts of Impact of Dietary Advanced Glycation End Products (dAGEs) on Health Summary Points References 2 Trimethylamine N-Oxide (TMAO) as a Biomarker Introduction TMAO Metabolism: The Role of the Diet and the Microbiome Dietary Sources TMA-Producing Bacteria TMAO Metabolism: From Absorption to Excretion TMAO and Diseases TMAO Detection TMAO and Cardiovascular Diseases TMAO and Chronic Kidney Diseases TMAO and Metabolic Diseases TMAO and Other Diseases TMAO as a Potential Therapeutic Target: From Nutrition Interventions to Gut Microbiota Modulations TMAO as a Biomarker: Potentiality and Limits Potentialities Limits and Pitfalls Conclusions Applications to Prognosis and Other Diseases or Conditions Mini-Dictionary of Terms Key Facts of Trimethylamine N-Oxide (TMAO) as a Biomarker: Features and Applications Summary Points References 3 The Redox State of Serum Albumin as a Potential Protein Nutrition Biomarker Introduction Biological Roles of Serum Albumin Albumin Synthesis and Breakdown Redox State of Serum Albumin Analytical Chemistry for the Redox State of Serum Albumin Association Between the Redox State of Serum Albumin and Pathological Conditions Association Between the Redox State of Serum Albumin and Physiological Conditions Redox State of Serum Albumin as a Potential Protein Nutrition Biomarker Application of the Redox State of Serum Albumin to Prognosis of Protein Nutritional Status in Humans Conclusions Mini-dictionary of Terms Key Facts of the Redox State of Serum Albumin Summary Points References 4 Branched Short-Chain Fatty Acids as Biological Indicators of Microbiota Health and Links with Anthropometry Introduction Microbial BCFA Biosynthesis Methods for BCFA Analysis Gas Chromatography Liquid Chromatography Nuclear Magnetic Resonance and Capillary Electrophoresis Branched-Chain Fatty Acids in the Context of Nutrition Dietary Interventions Related with Changes in BCFA and Anthropometric Factors Possible Implications of Branched-Chain Fatty Acids in Host Health BCFA in the Healthy Microbiota Changes in the Profile of BCFA Associated with Disease Potential Applications to Prognosis and Other Diseases or Conditions Mini-Dictionary of Terms Key Facts of Gut Microbiota Summary Points References 5 Plasma Nitrate and Nitrite as Biological Indicators of Health and Disease in Nutritional Studies Introduction Definition of Nitrates Sources of Dietary Nitrates in Nutritional Studies Foods Containing Nitrate Nitrate as a Food Additive in Processed Meats Nitrate as a Dietary Supplement Nitrate and Nitrite Salts Beets and Beetroot Juice Red Spinach Nitrates and Nitrites in Nutritional Studies Half-Life of Nitrate and NO Nitrate and Nitrite as a Biomarker Importance of NO Concentration Indirect Physiological Biomarkers of NO Exposure NO and its Metabolites in Diseases and Pathological States Laboratory Assessment of Nitrate and Nitrite Nitrate as a Biomarker to Determine Potential Health Benefits of Nitrate Increased NO Improved Blood Flow: Response to Hypoxia Reduction in Blood Pressure General Cardioprotection Improved Cognition Mitigation of Erectile Dysfunction Improvement in Aerobic Exercise Performance Improved Glycemia: Diabetes and Insulin Resistance Directions for Future Research on Nitrates Related to Health Conclusion Applications to Prognosis of Other Diseases or Conditions Mini-Dictionary of Terms Key Facts of Nitrates Summary Points References 6 Blood and Urinary Flavonoids Introduction Chemical Composition and Bioactivity Food Sources, Intake, and Metabolism Measurement of Exposure Sample Preparation Separation and Detection Techniques Liquid Chromatography and Mass Spectrometry Gas Chromatography and Mass Spectrometry Capillary Electrophoresis Electrokinetic Chromatography Nuclear Magnetic Resonance Time-Resolved Fluorescence Immunoassay Applications of Flavonoid Biomarkers Assessment of the Effect on Disease Risk Dietary Assessment Mini-Dictionary of Terms Key Facts of the Flavonoid Exposure Assessment and Their Use as Biomarkers Summary Points References 7 Uric Acid as a Biomarker in Nutritional Metabolism Introduction Uric Acid Metabolism Inflammation and Uric Acid Metabolism Uric Acid Metabolism and Metabolic Disorders Nutritional Approach to Hyperuricemia Uric Acid and Diabetes Conclusion Applications to Prognosis and Other Diseases or Conditions Mini-Dictionary of Terms Key Facts of Uric Acid Summary Points References 8 Ceramides as Dietary Biomarkers Introduction Following the Metabolic Pathway of Ceramides Ceramides: Metabolic Messengers Driving Cardiovascular Diseases (CVDs) Diet-Induced Responses to Ceramide Concentrations Conclusions Applications to Prognosis Applications to Other Diseases or Conditions Mini-dictionary of Terms Key Facts of Ceramides Summary Points References Part II: Micronutrients and Minerals 9 Urinary Arsenic as a Biomarker: Speciation Analysis for the Assessment of Dietary Exposure Introduction Arsenic Species in the Environment and Biota HPLC-ICP-MS for Speciation Analysis of As Urinary As Species as a Biomarker of Exposure Urinary iAs Speciation Analysis in Environmental Epidemiology Quantitative Relationship Between Urinary As Speciation and Dietary Intake Problem in Using Urinary As Speciation as a Biomarker of Exposure Urinary As Speciation as a Biomarker of Susceptibility Concluding Remarks Applications to Other Diseases or Conditions Mini-Dictionary of Terms Key Facts of Urinary Arsenic as a Biomarker: Speciation Analysis for the Assessment of Dietary Exposure Key Facts of Urine As Species as a Biomarker of Exposure Key Facts of Urinary As Speciation Analytical Method Summary Points References 10 Use of Histology in Nutrition Introduction Arsenic Epidemiology of Arsenic Mechanism of Arsenic Toxicity Use of Histology in Identifying the Hallmarks of Arsenic Toxicity Liver Kidney Brain Lungs Heart Testis Ovary Approaches to Combat Arsenic Toxicity Chelation Therapy Use of Nutritional Supplements as Antioxidants Zinc Histological Studies on the Ameliorating Effect of Zinc on Arsenic Toxicity Applications of Histology in Other Diseases Mini-Dictionary of Terms Key Facts About Arsenic Toxicity Summary Points References 11 Measures of Iron Metabolism and Applications to Dietary Patterns Introduction Overview of Iron Metabolism and Iron Disorder Disease Iron Distribution Hepcidin-Ferroportin Axis and Iron Disorder Disease Iron Requirement Recommended Daily Allowances Iron Bioavailability in Foods Types of Iron Sources in Food Factors That Affect Dietary Iron Absorption Iron Enhancers MFP Factors Organic Acids (Vitamin C, Citric Acids, Malic Acids) and Gastric Acids Alcohol Copper ß-Carotene and Vitamin A Body Iron Stores Iron Inhibitors Phytate and Oxalate Polyphenols: Tea and Coffee Polyphenols: Quercetin Proteins from Plants, Eggs, and Milk (Calcium) Sugar Dietary Approaches for Iron Disorder Dietary Approaches for Absolute Iron Deficiency and Iron Deficiency Anemia Dietary Approaches for Functional Iron Deficiency and Anemia of Inflammation Dietary Approaches for Hereditary Iron Disorders Diagnosis of Iron Disorder Diseases Absolute Iron Deficiency and Iron Deficiency Anemia Functional Iron Deficiency and Anemia of Inflammation Hereditary Iron Disorder Diseases Hemochromatosis β-Thalassemia Conclusion Applications to Prognosis Mini-Dictionary of Terms Key Facts of Anemia of Inflammation Summary Points References 12 Glycolate as a Biological Marker of B Vitamins Introduction Glycolate Intestinal Absorption of GA Cellular Uptake of GA GA Excretion GA Metabolism Glyoxylate Detoxification Glycolate Oxidase (GO) Vitamin B2 and GA Metabolism Agxt1 Vitamin B6 and GA Metabolism Factors Influencing GA Metabolism Markers in VB2 and VB6 Deficiency and Applications to Prognosis Applications to Prognosis Applications to Other Diseases or Conditions Mini-Dictionary Key Facts of Xylitol Metabolism Summary Points References 13 Assays for Carotenoids: Linking Breastmilk and Maternal Intakes Introduction Carotenoid ́s Absorption and Transport Carotenoid Transport into the Breastmilk Breastmilk Composition Breastmilk Carotenoids Carotenoid Intake During Lactation Assays for Carotenoids: Methodological Implications Breastmilk Sample Collection Breastmilk Sample Handling and Storage Breastmilk Analysis Nutritional Assessment Data Collection Carotenoid Database Applications to Prognosis, Other Diseases, or Conditions Mini-Dictionary of Terms Key Facts of Carotenoids in the Breastmilk Summary Points References Part III: Diets and Macronutrients 14 The Dietary Diversity Score Introduction The Diet Diversity Score as Diet Quality Indicator Diet Diversity Score in Relation to Diet Quality Dietary Diversity and Nutrient Adequacy Seasonality and the Dietary Diversity Score Calculation of the Dietary Diversity Score The Dietary Diversity Score and NCDs The Dietary Diversity Score and Anthropometric Measurements Applications to Prognosis, Other Diseases, or Conditions Conclusion Summary Points Key Facts of DDS Mini-dictionary of Terms References 15 Dietary Phytochemical Index as a Biomarker in Nutritional Studies: Features and Applications Introduction Sources and Types of Phytochemicals Definition and Utility of ``Phytochemical Index ́ ́ Application of Dietary Phytochemical Index as a Biomarker for Non-communicable Diseases (Fig. 3) Phytochemical Index, Obesity, and Metabolic Disorders Phytochemical Index and Cardiovascular Diseases Phytochemical Index and Cancer Phytochemical Index and Neurological Disorders Limitations of DPI and Concluding Remarks Mini-dictionary of Terms Key Points of Dietary Phytochemical Index (DPI) Summary Points References 16 Mediterranean Diet Adherence and Serum Markers of Lipids Introduction Serum Lipid Profile Association of Serum Lipid Profile with Human Health Influence of Lipid Profile by Environmental Factors, Such as Nutritional Attitudes Association of Dietary Nutrients (Fats, Carbohydrates, Proteins, Fibers, and Antioxidants) with Serum Lipid Profile Fats Saturated Fatty Acids Polyunsaturated Fatty Acids Monounsaturated Fatty Acids Dietary Cholesterol Carbohydrates Proteins Fibers Antioxidants The Mediterranean Diet and Serum Markers of Lipids Definition and Main Characteristics of the Mediterranean Diet Interaction of the Mediterranean Diet Adherence with Various Biomarkers (Including Lipid Markers) and Consequently Health Outc... Summary of Research Findings About the Effect of the Mediterranean Diet on Serum Lipid Profile and Health Lyon Diet Heart Study HALE Study ATTICA Study Medi-RIVAGE Study Randomized Controlled Trials Comparative Study BioCycle Study Crossover Design Studies Cross-Sectional Study PREDIMED Sub-study Retrospective Observational Study Functional Foods of the Mediterranean Diet with a Beneficial Effect on Serum Markers of Lipids Further Analyze the Significance of Specific Mediterranean Foods with Functional Value in Regulating the Serum Lipid Profile Olive Oil Fruits and Vegetables Pomegranate Raisins Wild Greens Aromatic Plants and Essential Oils Fish and Fish Oil Nuts and Walnuts Mushrooms Dairy Products Herb Drinks (Green Tea, Et Cetera) Red Wine Application to Prognosis, Other Diseases, or Conditions Applications to Prognosis Applications to Other Diseases or Conditions Mini-dictionary of Terms Key Facts Key Facts of Dyslipidemia Summary Points References 17 Fecal Volatile Organic Compounds Introduction The Origins of Fecal Volatile Organic Compounds Analysis of VOCs Chemical Classification of VOCs Specific Dietary Components and Their Effect on VOC Profiles Dietary Patterns and VOC Profiles VOCs from Other Sources Applications and Further Study Conclusion Application to Other Diseases Mini-Dictionary of Terms Key Facts of Volatile Organic Compounds Summary Points References 18 Calprotectin as a Biological Indicator in Nutrition Introduction Main Mechanisms of Calprotectin Action (Table 1 and Fig. 1) Fecal Calprotectin as a Marker of Inflammation In the Intestine In Chronic Low-Grade Inflammatory Disease Obesity-Driven Insulin Resistance (Table 2) Type 2 Diabetes-Driven Insulin Resistance Calprotectin and Macrovascular/Cardiovascular Disease Calprotectin and Microvascular Disease Therapeutic Opportunities Effects of Lifestyle and Diet on Levels of Calprotectin Future Prospects in the Potential Impact of Calprotectin Modulation Conclusions Mini-Dictionary of Terms Key Facts of Calprotectin as a Biological Indicator in Nutrition: Insulin Resistance and Beyond Summary Points References 19 Omega-6 Fatty Acids Introduction Omega-6 Fatty Acids as Biomarkers for Dietary Intake Omega-6 Fatty Acids as Biomarkers for Cardiovascular Disease Omega-6 Fatty Acids as Biomarkers for Diabetes Omega-6 Fatty Acids as Biomarkers for Asthma Omega-6 Fatty Acids as Biomarkers for Autoimmune Disease Omega-6 Fatty Acids as Biomarkers for Cancer Limitations on the Application of Omega-6 Biomarkers Mini-Dictionary of Terms Summary Points References 20 Fatty Acid Profile of Red Blood Cells as Markers in Dietary Regimes and Beyond Introduction Lipids in Nutrition Evaluating Fatty Acids in Tissues and the Impact of PUFA The Importance of Omega-6 and Omega-3 Fatty Acids as Biomarker of Intakes from Nutrition Omics Technologies and Membrane Lipidomics The Information Provided by ``Omics ́ ́ Technologies Lipidomics and Membrane Lipidomics The Development of RBC Fatty Acids as Biomarkers The Importance of Sampling Procedure, Analytical Recognition, and Evaluation of Biological Significance The Choice of Red Blood Cell Membrane and Comparison with Other Blood Compartments The Proof of the RBC/Lipoprotein Fatty Acid Exchange Applications to Prognosis, Other Diseases, or Conditions Application of C-16 Monounsaturated Fatty Acids in Cancer Diagnostics Applications to Other Diseases or Conditions Membrane Lipidomics Applied to Overweight and Obese Cohorts Mini-Dictionary of Terms Key Facts of Fatty Acids as Biomarkers in Nutrition Key Facts of Membrane Fatty Acids Key Facts of Fatty Acid Analysis Key Facts of Membrane Fatty Acids Used in Prevention Summary Points References 21 Assessing Pyruvate Carboxylase Flux as a Mechanistic Biological Marker in Fasting Introduction PC Flux During Fasting Direct Assessment of PC: Gene Expression, Protein Level, and Colorimetric Assays Metabolomics Approach: Isotopomer Analysis In Vivo Assessment of PC Activity Using 13C MR Spectroscopy Complication with Other Pathological Conditions Mini-dictionary of Terms Key Facts of Pyruvate Carboxylase Summary Points References 22 Biological Markers of Plant Phenolic Compounds Intake Introduction Classification and Structure of Major Dietary PC Phenolic Acids Flavonoids Tannins Stilbenes Lignans Coumarins Curcuminoids Biotransformation of PC During Digestive Process Anthocyanins and Other Flavonoids Hydrolyzable Tannins Flavan-3-Ols Isoflavones Phenolic Acids Lignans Kinetics of PC After Dietary Intake Absorption Distribution Metabolization Excretion Methods Used for Estimation of Dietary Intake of PC Dietary Assessment Methods Biomarkers Plasma Urine Analytical Techniques Used to Identify and Quantify PC Biomarkers Conclusion Applications to Other Diseases or Conditions Mini-Dictionary of Terms Key Facts Key Facts of PC Digestion and Metabolism Key Factors of Biomarkers of PC Intake Summary Points References Part IV: Genetic, Molecular, and Cellular Variables 23 Blood Gene Expression of Zinc Transporters as Biological Indicators of Zinc Nutrition Introduction Zinc Metabolism and Homeostasis Zinc Transporters Zinc Transporters mRNA as Biomarkers of Zinc Status Applications to Diseases Diabetes Cardiovascular Disease Alzheimer ́s Disease Mini-Dictionary of Terms Key Facts of Zinc Transporters in Diabetes Key Facts of Zinc Transporters in Cardiovascular Disease Key Facts of Zinc Transporters in Alzheimer ́s Disease Summary Points References 24 Circulating MicroRNA (miRNA)s as Biological Markers and Links with Obesity and Obesity-Related Morbid Conditions Introduction An Overview of White Adipose Tissue miRNAs: Small RNAs Playing a Central Role in Gene Expression Control Biogenesis of miRNAs and Mechanisms of Action miRNAs Detection miRNAs Target Prediction The Role of miRNAs Across Tissues in the Context of Obesity Circulating miRNAs in Obesity and Obesity-Related Comorbidities Applications to Prognosis, Other Diseases, or Conditions Mini-Dictionary of Terms Summary Points References 25 Plasma MicroRNA (miRNA)s as Novel Markers of Nonalcoholic Fatty Liver Disease Introduction MiRNA Biogenesis MiRNA-Dependent Epigenetic Reprogramming in NAFLD Hepatic Lipid Metabolism Hepatic Carbohydrate Metabolism Stress-Activated Pathways MiRNAs That Regulate NAFLD Progression Applications to Prognosis, Other Diseases or Conditions Conclusion Key Facts Mini-Dictionary of Terms Summary Points References 26 Telomere Length Introduction Section 1. Telomere Length: Measurements Terminal Restriction Fragments (TRF) Quantitative PCR Methods Quantitative FISH STELA Methods Single Telomere Absolute-Length Rapid (STAR) Main Remarks Section 2. Telomere Length: Links with Anthropometry in Lifestyle Intervention Inflammation and Oxidative Stress Linked to Obesity and TL Lifestyle Factors for Obesity Development Dietary Treatment Promoting Physical Activity Behavioral Therapy Lifestyle Intervention Studies TL as a Biomarker in Lifestyle Intervention Applications to Prognosis or Applications to Other Diseases or Conditions Mini-Dictionary of Terms Key Facts of TL Measurement Key Facts of Obesity Key Facts of Lifestyle Intervention Summary Points References 27 GWAS and GWAIS for Identifying Connections Between Genetics, Nutrition, and Health: The Example of Omega-3 and Plasma Trigl... Introduction Overview of Precision Nutrition The Interplay Between Nutrition and Genetics What ́s a GWAS? What ́s a GWAIS? Example: Using the GWAS Approach for Determining Gene-Diet Associations Related to TG and Omega-3 Fatty Acids Variability in Plasma TG Response to Omega-3 Fatty Acids Fine Mapping of GWAS Signals Validation of Nutri-GRS and Contribution of EPA Versus DHA to TG Change Importance of Understanding Biological Plausibility Conclusion Other Applications of GWAS and GWAIS for Precision Nutrition Mini-Dictionary of Terms Key Facts of GWAS and GWAIS for Nutritional Genomics and Precision Nutrition Summary Points References 28 The Alpha-Klotho Gene as an Anti-ageing Biomarker: Measures and Applications to the Effects of Nutrition Introduction Plausible Mechanisms of the Effect of Nutrition on S-Klotho Levels Effect of Nutrition in Klotho: Evidence from Preclinical Models Dietary Energy Dietary Macronutrients Micronutrients Effect of Nutrition in Klotho: Human Studies Observational Evidence Intervention Studies Future Investigations into S-Klotho Fasting Strategies Dietary Compounds Dietary Patterns Conclusion Applications to Prognosis, Other Diseases, or Conditions Mini-Dictionary of Terms Key Facts of Klotho Summary Points References Part V: Functional and Physiological Variables and Platforms 29 BMI as a Biomarker in Patients ́ Nutritional Assessment Introduction BMI as a Biomarker of Nutritional Status BMI as a Biomarker of Malnutrition Overweight and Obesity BMI as a Biomarker of Fat Distribution and Body Composition BMI Applications to Other Diseases or Conditions BMI Applications to Prognosis Further Study Conclusions Key Facts of BMI as a Biomarker in Patients ́ Nutritional Assessment Mini-Dictionary of Terms Summary Points References 30 Three-Dimensional Ultrasound for Sensitive Assessment of the Effects of Nutritional Therapy on Carotid Atherosclerosis Introduction Quantitative Assessment of Treatment Effect Based on 3D Carotid US Images Plaque Texture Analysis Plaque Segmentation and Texture Extraction Dimensionality Reduction and Biomarker Generation Physical Understanding of the Biomarker Vessel-Wall-Plus-Plaque Thickness (VWT) Analysis Generation of 2D VWT Map Quantitative Assessment Based on Discussion and Future Perspectives Applications to Other Anti-atherosclerotic Treatments/Interventions and Image Modalities Mini-Dictionary of Terms Key Facts of 3D Carotid Ultrasound Biomarkers Summary Points References 31 NMR Metabolomics for Marker Discovery of Metabolic Syndrome Introduction Carbohydrate Dysfunction Glucose Lactate Uric Acid BCAAs and AAAs Glutamine and Glutamate Citrate Propionylcarnitine Dyslipidemia Fatty Acids Choline Lipoproteins Ketone Bodies Inflammation N-Acetylglycoproteins Lysophospholipids Oxidative Stress Uric Acid and Allantoin 8-OHdG and Pseudouridine One-Carbon Metabolism Intermediates: GSH/GSSG Ratio, Glycine, and Serine Gut Microbiota Dysbiosis Lactate Acetate Succinate TMA, TMAO, and DMA Anxiety, Psychological Stress, and Related Disorders Lipids GlycA Glutamine Glucose Applications to Prognosis, Other Diseases, or Conditions Funding Mini-Dictionary of Terms Key Facts of Metabolic Syndrome Key Facts of NMR Metabolomics Summary Points References 32 Central and Peripheral Biomarkers for the Study of Appetite Regulation in Humans Introduction Central and Peripheral Appetite Regulation in Humans Biomarkers for the Study of Central Appetite Regulation in Humans Biochemical Biomarkers of Central Appetite Regulation Image Methods to Study Central Appetite Regulation Behavioral Measures of Central Appetite Regulation Biomarkers for the Study of Peripheral Appetite Regulation in Humans Peripheral Signals that Regulate Appetite Metabolomics and Central Appetite Regulation Fatty Acids and Their Derivatives as Biomarkers of Appetite Regulation Amino Acids as Biomarkers of Appetite Regulation Glucose and Other Carbohydrates as Biomarkers of Appetite Regulation Other Metabolites Proposed as Biomarkers of Appetite Regulation Conclusion and Future Directions Applications to Prognosis, Other Diseases, or Conditions Mini-Dictionary of Terms Key Facts of Appetite Regulation Summary Points Reference 33 Growth Reference Charts as Biological Indicators of Nutrition Introduction Biological Indicators of Nutrition Growth Reference Charts Types of Growth Reference Charts Z-score (SD Score) Percentiles Percent of Median Head Circumference as a Biological Indicator Construction of Growth Charts for HC: Different Methods Assessment of Nutritional Status Using the HC Applications to Prognosis Mini-Dictionary of Terms Key Facts of Human Growth Key Facts of Growth Reference Charts Key Facts of Measuring HC Summary Points References Part VI: Biomarkers in Specific Conditions or Scenarios 34 Biomarkers of Malnutrition in Cirrhosis Introduction Mechanisms of Malnutrition in Cirrhosis Reduced Oral Intake Increased Metabolic Demand Malabsorption Clinical Assessment Nutritional Questionnaires Energy Expenditure Laboratory Evaluation Plasma Proteins Albumin Prealbumin Transferrin Retinol-Binding Protein-4 Branched-Chained Amino Acids Adipokines Leptin Adiponectin Resistin Plasma Ghrelin Micronutrients Fat-Soluble Vitamins (Vitamins A, D, E, and K) Water-Soluble Vitamins Minerals Emerging Biomarkers Metabolomics Proteomics Ancillary Tests Anthropometric Tests Radiologic Assessment Conclusion Applications to Prognosis Mini-dictionary of Terms Key Facts Key Facts of Malnutrition in Cirrhosis Key Facts of Biomarkers of Malnutrition in Cirrhosis Summary Points References 35 Inflammatory Biomarkers in Nutrition Introduction Biomarkers of Inflammation Nutrients and Inflammation Food and Inflammation Dietary Patterns and Inflammation Conclusion Applications to Prognosis and Other Diseases or Conditions Applications to Prognosis Applications to Other Diseases or Conditions Key Facts of Cytokines Summary Points References 36 YKL-40 as an Inflammatory Biomarker in Nutrition Introduction General Characteristics of YKL-40 The Effects of YKL-40 on Signaling Pathways Related to Nutrition and Metabolism The Role of YKL-40 in Obesity and Diabetes YKL-40 ́s Relationship with Diet and Vitamins YKL-40 in Cancers Relationship Between YKL-40 and Cardiovascular Diseases Applications to Prognosis and Other Diseases or Conditions Conclusion Mini-dictionary of Terms Key Facts of YKL-40 References 37 The Dietary Inflammatory Index Introduction The DII Score Calculation The DII Score and Diseases DII Score and Cardiovascular Diseases The DII Score and Cancer Applications to Prognosis, Other Diseases, or Conditions Conclusion Summary Point Mini-dictionary of Terms Key Facts of DII References 38 Thiol-Disulfide Homeostasis as an Oxidative Stress Indicator Introduction Features of Kits Used in Thiol-Disulfide Homeostasis Measurement Analytical Recovery Linearity Lower Detection Limit Analytical Sensitivity Interference Precision Storage Thiol(-SH)-Disulfide(-S-S-) Homeostasis Test Profile Principle of the Assay Application Parameters of the Assays Free Radicals and Nutrition Oxidative Stress and Nutrition Antioxidant Nutrition Priorities Healthy and Natural Nutrition Dietary Preferences and Oxidative Stress Applications to Prognosis and Other Diseases or Conditions Applications to Prognosis Applications to Other Diseases or Conditions Key Facts of Thiol-Disulfide Homeostasis as an Oxidative Stress Indicator: Applications to Nutrition Summary Points References 39 Oxidative Stress Biomarkers in Exercise Introduction Oxidative Stress and Redox Oxidative Stress in Exercise Applications to Prognosis Intake of Supplements in Exercise/Physical Activation and Redox Nutritional Oxidative Stress Biomarkers in Exercise Protein Carbonyl Groups Oxidized Low-Density Lipoprotein Thiol-Disulfide Homeostasis Oxidative Stress Caused by Exercise and Vitamin Diet Vitamins C and E Vitamin A Vitamins B6 and B9 Mini-dictionary of Terms Key Facts of Oxidative Stress in Exercise and Nutrition Summary Points References 40 Biological Indicators of Oxidative Stress [Malondialdehyde, Catalase, Glutathione Peroxidase, and Superoxide Dismutase] and... Introduction Catalase (CAT) Characterization and Historical Basis Determination Methods Importance and Applications to Prognosis, Other Diseases, or Conditions Glutathione Peroxidase (GPx) Characterization and Historical Basis Determination Methods Importance and Applications to Prognosis, Other Diseases, or Conditions Superoxide Dismutase (SOD) Enzyme Characterization and Historical Basis Determination Methods Importance and Applications to Prognosis, Other Diseases, or Conditions Malondialdehyde (MDA) Characterization and Historical Basis Determination Methods Importance and Applications to Prognosis, Other Diseases, or Conditions Mini-Dictionary of Terms Key Facts of Oxidative Stress in Chronic Noncommunicable Diseases Summary Points References 41 The Oxidative Balance Score as a New Nutritional Scoring System Introduction Oxidative Balance Score The Effects of Antioxidants Involved in the OBS on Development of the Non-communicable Diseases Oxidative Balance Score, Cardiovascular Diseases, and Their Related Risk Factors Oxidative Balance Score and Cancers Oxidative Balance Score and Mortality Oxidative Balance Score, Inflammatory Biomarkers, and Related Diseases Conclusion Applications to Other Diseases or Conditions Mini-dictionary of Terms Key Facts of Oxidative Balance Score Summary Point References 42 Urinary Gluten Immunogenic Peptides as a Biomarker in Celiac Patients Introduction Current Methods for Assessing Gluten-Free Diet Adherence Development of a Method for the Detection of Gluten Immunogenic Peptides in Human Specimens Process to Consolidate the Detection of Immunogenic Peptides as a Biomarker in Patients with Celiac Disease Applicability Mini-dictionary of Terms Key Facts of Urinary Gluten Immunogenic Peptides as Biomarkers in Celiac Patients Key Facts of GIP Determination in Human Specimens Summary Points References 43 Citrulline as a Marker of Villous Abnormality and Implications for Diet and Nutrition Introduction Citrulline: Biochemical Characteristic, Synthesis, and Functions Synthesis of Citrulline from Glutamine in Enterocytes Utilization of Citrulline in Different Tissues Synthesis of Arginine from Citrulline Nitric Oxide Synthesis from Arginine and Citrulline Urea Cycle Normative Concentration of Citrulline in the Plasma Causes for High and Low Plasma Citrulline Levels Diagnostic and Therapeutic Value of Citrulline Blood Levels of Citrulline for the Assessment of Enterocyte Mass/Enteropathy Plasma Citrulline as a Marker of Enteropathic or Reduction in the Absorptive Surface Cyclical Changes in the Level of Plasma Citrulline in a Model of Enteropathy Citrulline and Mucositis Citrulline and HIV Enteropathy Citrulline and Intestinal Transplantation Rejection Citrulline in Patients with Necrotizing Enterocolitis Levels of Citrulline as a Marker of Intestinal Function: A Meta-analysis Therapeutic Role of Citrulline Muscles Cardiovascular Diseases Erectile Dysfunction Antidepressant Effects Ageing and Sarcopenia Mini-Dictionary of Te