The Vitamins Fourth Edition ELSEVIER science & technology books Companion Web Site: http://www.elsevierdirect.com/companions/ 9780123819802 The Vitamins: Fundamental Aspects in Nutrition and Health Gerald F. Combs, Jr. Resources: · All figures from the book available as both Power Point slides and .jpeg files ACADEMIC PRESS The Vitamins Fourth Edition Gerald F. Combs, Jr Professor Emeritus Cornell University Ithaca, NY AMSTERDAM • BOSTON • HEIDELBERG • LONDON • NEW YORK • OXFORD • PARIS SAN DIEGO • SAN FRANCISCO • SINGAPORE • SYDNEY • TOKYO Academic Press is an imprint of Elsevier Academic Press is an imprint of Elsevier 32 Jamestown Road, London NW1 7BY, UK 225 Wyman Street, Waltham, MA 02451, USA 525 B Street, Suite 1800, San Diego, CA 92101-4495, USA First edition 1990 Second edition 1998 Third edition 2008 Fourth edition 2012 Copyright © 2012 Elsevier Inc. 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Because of rapid advances in the medical sciences, in particular, independent verification of diagnoses and drug dosages should be made British Library Cataloguing-in-Publication Data A catalogue record for this book is available from the British Library Library of Congress Cataloging-in-Publication Data A catalog record for this book is available from the Library of Congress ISBN: 978-0-12-381980-2 For information on all Academic Press publications visit our website at elsevierdirect.com Typeset by MPS Limited, Chennai, India www.macmillansolutions.com Printed and bound in United States of America 12 13 14 15 16 10 9 8 7 6 5 4 3 2 1 to Barbara and Sylvia Thispageintentionallyleftblank Contents Preface xvii The Lines Converge 15 Preface to the Third Edition xix Funk’s Theory 15 Preface to the Second Edition xxi Impact of the New Concept 15 Preface to the First Edition xxiii Elucidation of the Vitamines 17 How to Use This Book xxv 6. Elucidation of the Vitamins 17 New Animal Model Reveals New Part I Vitamin: “C” 17 Fat-Soluble A: Actually Two Factors 18 Perspectives on the Vitamins in Vitamin A Prevents Rickets? 18 Nutrition New Vitamin: “D” 19 β-Carotene, a Provitamin 19 1. What is a Vitamin? 3 Vitamin A Linked to Vision 19 The Nature of Vitamin D 19 1. Thinking About Vitamins 3 Multiple Identities of Water-Soluble B 20 2. Vitamin: A Revolutionary Concept 4 Vitamin B : A Complex of Several 2 Everyday Word or Revolutionary Factors 20 Idea? 4 Components of the Vitamin B 2 Vitamin or Vitamine? 4 Complex 20 3. An Operating Definition of a Vitamin 4 Vitamin B Complex Yields Riboflavin 20 Some Caveats 4 2 Vitamin B Complex Yields Niacin 21 4. The Recognized Vitamins 6 2 Impact of an Animal Model for Pellagra 22 B Complex Yields Pyridoxine 22 2. Discovery of the Vitamins 7 2 B Complex Yields Pantothenic Acid 22 2 1. The Emergence of Nutrition as a Science 8 A Fat-Soluble, Anti-Sterility Factor: 2. The Process of Discovery in Nutritional Vitamin E 23 Science 8 Antihemorrhagic Factor: Vitamin K 23 Empiricism and Experiment 8 Bios Yields Biotin 24 3. The Empirical Phase of Vitamin Discovery 8 Anti-Anemia Factors 25 Diseases Linked to Diet 9 Antipernicious Anemia Factor 26 Ideas Prevalent by 1900 11 Vitamin B12 Isolated 27 Limitations of Empiricism 12 Vitamins Discovered in Only 4. The Experimental Phase of Vitamin Five Decades 27 Discovery 12 7. Vitamin Terminology 27 Requirements of Nutrition Research 12 8. Other Factors Sometimes Called Vitamins 29 Major Forces in the Emergence of 9. The Modern History of the Vitamins 29 Nutritional Science 13 Recommended Reading 30 An Animal Model for Beriberi 13 Antiberiberi Factor Is Announced 14 3. Properties of Vitamins 33 5. The Vitamine Theory 14 Defined Diets Revealed Needs for 1. Chemical and Physical Properties of the Accessory Factors 14 Vitamins 34 Two Lines of Inquiry 14 Classifying the Vitamins According Two Lines of Inquiry Leading to the to Their Solubilities 34 Discovery of the Vitamins 15 Vitamin Nomenclature 40 vii viii Contents 2. Vitamin A 40 17. Metabolism of the Vitamins 65 Vitamin A Nomenclature 41 Some Vitamins Have Limited Chemistry of Vitamin A 41 Biosynthesis 65 Vitamin A Biopotency 42 Most Vitamins Require Metabolic 3. Vitamin D 42 Activation 66 Vitamin D Nomenclature 43 Vitamin Binding to Proteins 66 Vitamin D Chemistry 43 Vitamin Excretion 66 Vitamin D Biopotency 44 18. Metabolic Functions of the Vitamins 69 4. Vitamin E 45 Vitamins Serve Five Basic Functions 69 Vitamin E Nomenclature 45 Recommended Reading 70 Vitamin E Chemistry 45 Vitamin E Biopotency 46 4. Vitamin Deficiency 71 5. Vitamin K 46 1. The Concept of Vitamin Deficiency 72 Vitamin K Nomenclature 46 What Is Meant by the Term Vitamin Vitamin K Chemistry 47 Deficiency? 72 Vitamin K Biopotency 47 Vitamin Deficiencies Involve Cascades 6. Vitamin C 47 of Progressive Changes 72 Vitamin C Nomenclature 48 Stages of Vitamin Deficiency 73 Vitamin C Chemistry 48 2. Clinical Manifestations of Vitamin Vitamin C Biopotency 49 Deficiencies 73 7. Thiamin 49 Many Organ Systems Can Be Affected Thiamin Nomenclature 49 by Vitamin Deficiencies 73 Thiamin Chemistry 49 3. Vitamin Deficiency Diseases: 8. Riboflavin 50 Manifestations of Biochemical Lesions 73 Riboflavin Nomenclature 50 Relationships Between Biochemical Riboflavin Chemistry 50 Lesions and Clinical Diseases of 9. Niacin 51 Vitamin Deficiencies 73 Niacin Nomenclature 51 4. The Many Causes of Vitamin Deficiencies 76 Niacin Chemistry 51 Primary and Secondary Causes of 10. Vitamin B 52 6 Vitamin Deficiencies 76 Vitamin B Nomenclature 52 6 Causes of Vitamin Deficiencies Vitamin B Chemistry 52 6 in Humans 76 11. Biotin 53 Causes of Vitamin Deficiencies Biotin Nomenclature 53 in Animals 79 Biotin Chemistry 53 Intervention is Most Effective in Early 12. Pantothenic Acid 53 Stages of Vitamin Deficiency 79 Pantothenic Acid Nomenclature 53 Recommended Reading 90 Pantothenic Acid Chemistry 54 13. Folate 54 Folate Nomenclature 54 Part II Folate Chemistry 55 Considering the Individual Vitamins 14. Vitamin B 55 12 Vitamin B Nomenclature 56 12 5. Vitamin A 93 Vitamin B Chemistry 56 12 15. General Properties of the Vitamins 57 1. The Significance of Vitamin A 94 Multiple Forms of Vitamins 57 2. Sources of Vitamin A 94 Vitamin Stability 57 Dietary Sources of Vitamin A 94 Vitamin Analysis 59 Expressing the Vitamin A Activities 16. Physiological Utilization of the Vitamins 59 in Foods 95 Vitamin Bioavailability 59 Foods Rich in Vitamin A 96 Vitamin Absorption 59 3. Absorption of Vitamin A 97 Vitamin Transport 64 Absorption of Retinoids 97 Tissue Distribution of the Vitamins 65 Absorption of Carotenoids 97 Contents ix Carotenoid Metabolism Linked to Case 2 135 Absorption 97 Case 3 136 Mucosal Metabolism of Retinol 99 Case Questions and Exercises 136 4. Transport of Vitamin A 100 Recommended Reading 137 Retinyl Esters Conveyed by Chylomicra in Lymph 100 6. Vitamin D 139 Transport of Carotenoids 100 1. The Significance of Vitamin D 140 Impact of Abetalipoproteinemia 100 2. Sources of Vitamin D 141 Vitamin A Uptake by the Liver 101 Distribution in Foods 141 Retinol Transported Protein-Bound Biosynthesis of Vitamin D 142 in the Plasma 101 3 Bioactive Vitamin D Analogs 145 Other Vitamin A-Binding Proteins 3. Enteric Absorption of Vitamin D 145 Involved in Vitamin A Transport 103 Micelle-Dependent Passive Cellular Uptake of Retinol 104 Diffusion 145 Transport Roles of Vitamin A-Binding 4. Transport of Vitamin D 146 Proteins 105 Transfer from Chylomicra to Retinol Recycling 106 Plasma 146 Plasma Retinol Homeostasis 106 Tissue Distribution 147 Vitamin A in the Eye 106 5. Metabolism of Vitamin D 147 Milk Retinol 107 Metabolic Activation 147 5. Metabolism of Vitamin A 107 Catabolism 149 Metabolic Fates of Retinol 107 Regulation of Vitamin D Metabolism 149 Role of Retinoid-Binding Proteins in 6. Metabolic Functions of Vitamin D 150 Modulating Vitamin A Metabolism 109 Vitamin D as a Steroid Hormone 150 Excretion of Vitamin A 110 3 1,25-(OH) -D as the Metabolically 6. Metabolic Functions of Vitamin A 110 2 3 Active Form 151 Vitamin A in Vision 110 Pathways of Vitamin D Function 151 Systemic Functions of Vitamin A 112 Roles of Vitamin D in Calcium and Vitamin A Regulation of Gene Phosphorus Metabolism 155 Transcription 112 Vitamin D Functions in Non-Calcified A Coenzyme Role for Vitamin A? 115 Tissues 161 Vitamin A in Embryogenesis 115 7. Vitamin D in Health and Disease 163 Vitamin A in Reproduction 116 Autoimmune Diseases 163 Vitamin A in Bone Metabolism 116 Risk of Falling 167 Vitamin A in Hematopoiesis 117 Cardiovascular Health 167 7. Vitamin A in Health and Disease 118 Anticarcinogenesis 167 Immune Function 118 Healthful Vitamin D Status 170 Skin Health 122 8. Vitamin D Deficiency 171 Obesity 122 Causes of Vitamin D Deficiency 171 Drug Metabolism 123 Signs of Vitamin D Deficiency 172 Antioxidant Protection 123 Vitamin D Deficiency in Humans 172 Cardiovascular Health 124 Vitamin D Deficiency in Animals 174 Anticarcinogenesis 124 9. Vitamin D Toxicity 175 8. Vitamin A Deficiency 126 10. Case Studies 176 Detection of Vitamin A Deficiency 129 Instructions 176 Treatment of Vitamin A Deficiency 131 Case 1 177 9. Vitamin A Toxicity 132 Case 2 177 Embryotoxic Potential of High Levels Case Questions and Exercises 178 of Vitamin A 133 Recommended Reading 178 Carotenoid Toxicity 134 10. Case Studies 135 7. Vitamin E 181 Instructions 135 Case 1 135 1. The Significance of Vitamin E 182
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