Vitamin C Volume III Author C. Alan B. Clemetson Professor Tulane University School of Medicine New Orleans, Louisiana Boca Raton London New York CRC Press, Inc. CRC Press is an imprint of the Taylor &B Forcanac isR Garotuop,n a,n Finlfoorrmiada b usiness First published 1989 by CRC Press Taylor & Francis Group 6000 Broken Sound Parkway NW, Suite 300 Boca Raton, FL 33487-2742 Reissued 2018 by CRC Press © 1989 by CRC Press, Inc. CRC Press is an imprint of Taylor & Francis Group, an Informa business No claim to original U.S. Government works This book contains information obtained from authentic and highly regarded sources. Reasonable efforts have been made to publish reliable data and information, but the author and publisher cannot assume responsibility for the validity of all materials or the consequences of their use. 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CCC is a not-for-profit organization that provides licenses and registration for a variety of users. For organizations that have been granted a photocopy license by the CCC, a separate system of payment has been arranged. Trademark Notice: Product or corporate names may be trademarks or registered trademarks, and are used only for identification and explanation without intent to infringe. Library of Congress Cataloging-in-Publication Data Clemetson, C. Alan B. Vitamin C / C Alan B. Clemetson. p. cm. Includes bibliographies and index. ISBN 0-8493-4841-2 (v. 1) ISBN 0-8493-4842-0 (v. 2) ISBN 0-8493-4843-9 (v. 3) 1. Vitamin C deficiency. 2.Vitamin C--Metabolism. I. Title. RC627.S36C53 1989 616.3’9--dc19 88-14735 A Library of Congress record exists under LC control number: 88014735 Publisher’s Note The publisher has gone to great lengths to ensure the quality of this reprint but points out that some imperfections in the original copies may be apparent. Disclaimer The publisher has made every effort to trace copyright holders and welcomes correspondence from those they have been unable to contact. ISBN 13: 978-1-315-89848-3 (hbk) ISBN 13: 978-1-351-07758-3 (ebk) Visit the Taylor & Francis Web site at http://www.taylorandfrancis.com and the CRC Press Web site at http://www.crcpress.com FOREWORD While frank scurvy is rare nowadays, subclinical vitamin C deficiency is common and is now known to be associated with elevated blood histamine levels, which rapidly return to normal when ascorbic acid is administered. Epidemiological and experimental evidence suggests that our common metabolic defect, the inability to synthesize ascorbic acid from simple sugars, may be largely responsible for the development of subendothelial hemorrhage, thrombosis, atheroma, and degenerative vascular disease. This book is more concerned with factors affecting ascorbic acid metabolism, such as aging, smoking, infection, trauma, surgery, hormone administration, heavy metals, pregnancy, hemolysis, ionizing radiation, aspirin, alcohol, and other drugs which cause a disturbance of ascorbic acid metabolism and may thereby lead to vascular disease, than it is with simple dietary deficiency of ascorbic acid. The clinical, pathological, and chemical changes observed in ascorbic acid deficiency are discussed in detail; several diseases and disorders associated with abnormalities of ascorbic acid metabolism are described. Possible toxic effects resulting from the oxidation of ascorbic acid are noted, and reasons for the use of D-catechin or other chelating fiber to prevent or minimize the release of ascorbate free radical are detailed. PREFACE About 60 years ago, and before the isolation of ascorbic acid, Mme. L. Randoin (1923)* found the number of research studies on the antiscorbutic vitamin so great as to make it impossible for her to review them all. "Jm maintenant a parler de,s recherches de toute Now I must speak of all kinds of studies of the naturefmtes sur lefacteur antiscorbutlque. La tache antiscorbutic factor. It IS a thankless task because est bien ingrate, car /e nombre de ces recherches the number of research studies is so great that 1t IS est si grand qu'il m'est eVldemment zmposszble de clearly impossible to review them all; moreover, by les passer toutes en revue et, au surplus, elles pre- failure of agreement, they present such gaps that It sentent, par defaut de convergence, de telles la- is truly difficult to present a consistent thesis. cunes, qu' zl est vraiment difficile d' en donner une idee d'ensemble." Today, the profusion of the literature on this subject is even more overwhelming. It is growing so fast that it is impossible to do justice to all the work that had been done in this field. Moreover, having written 57 chapters in 36 months, it is inevitable that the chapters written first will not be as up-to-date as those written last. Undoubtedly, some important works have been omitted, either because they have escaped my notice or because they were written in a language that I cannot read. Any workers whose contributions have been omitted must accept my assurance that it was not by intent. It is hoped that this book presents a consistent thesis and that its main message is clear. It does not so much concern the amount of vitamin C in the diet, as it does the factors affecting ascorbic acid metabolism, the diseases that may result from abnormalities of ascorbic acid metabolism, and some suggestions as to what we may be able to do to prevent them. Although the title of this book is Vitamin C, it could equally well have been entitled Vitamin C. Heavy Metals, and Chelating Fiber. C. Alan B. Clemetson, M.D. Pineville, Louisiana February, 1987 THE AUTHOR C. Alan B. Clemetson, M.D., was born in England. He attended the King's School, Canterbury, Magdalen College, Oxford, and Oxford University School of Medicine, grad- uating as a physician (B.M., B.Ch.) in 1948. He is an obstetrician and gynecologist, with fellowships in British, Canadian, and American colleges (F.R.C.O.G., F.R.C.S.C., and F.A.C.O.G.), but he has devoted most of his life to research and has published papers on many diverse subjects. His career has included academic positions at London University, the University of Sas- katchewan, the University of California at San Francisco, the State University of New York, and at Tulane University in Louisiana, where he is currently Professor at the School of Medicine. He has challenged many conventional ideas and believes that, "certainty of knowledge is the antithesis of progress." Thus, every statement in this book is backed by reference to experiments and observations in the literature; contrary findings are cited, weighed, and given due credence. VITAMIN C Volume I Vitamin C Deficiency Classical Scurvy: A Historical Review Chronic Subclinical Ascorbic Acid Deficiency Factors Affecting the Economy of Ascorbic Acid Inadequate Ascorbic Acid Intake Smoking Aging Sex Menstrual Cycle, Estrus Cycle, Ovulation Infection Trauma, Surgery, and Bums Heavy Metals, Water Supplies: Copper, Iron, Manganese, Mercury, and Cobalt Bioflavonoids Dietary Protein Hormone Administration: Birth Control Pills Pregnancy Hemolysis Stress and the Pituitary-Adrenal System Lack of Sleep Time of Day Season Achlorhydria Ionizing Radiation Aspirin and Salicylates Alcohol Other Factors Affecting Ascorbic Acid Needs Volume II Clinical and Pathological Findings in Ascorbic Acid Deficiency Vascular Changes Diabetes Mellitus Anemia Defective Wound Healing Bone Changes Joint Lesions Dental and Periodontal Changes Atherosclerosis Mental Depression Amyloid Venous Thrombosis Decreased Resistance to Infection Liver, Bile, and Gallstones Volume III Chemical Changes Associated with Vitamin C Deficiency Histamine Metabolism Proline and Lysine Metabolism Carbohydrate Metabolism Folic Acid Metabolism Cholesterol Metabolism Tyrosine and Phenylalanine Metabolism Tryptophan Metabolism Adrenal Corticoid Metabolism Uric Acid Clearance Clinical Conditions Associated with Disorders of Ascorbic Acid Metabolism Rheumatic Fever Menorrhagia Wound Dehiscence Habitual Abortion Abruptio Placentae Prematurity and Premature Rupture of the Fetal Membranes Megaloblastic Anemia of Infancy, Pregnancy, and Steatorrhea Gastrointestinal Ulcers and Hemorrhage Ocular Lesions Cerebral Hemorrhage and Thrombosis Coronary Thrombosis and Myocardial Infarction TABLE OF CONTENTS CHEMICAL CHANGES ASSOCIATED WITH VITAMIN C DEFICIENCY Chapter I Histamine Metabolism ................................................................. . I. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . I II. Guinea Pigs ....................................................................... I III. Humans ........................................................................... 3 A. Pregnancy ................................................................. 4 B. Age ........................................................................ 4 C. Sex ........................................................................ 5 D. Subsequent Work .......................................................... 5 IV. Implications ...................................................................... II References ............................................................................... II Chapter 2 Proline and Lysine Metabolism ........................................................ 15 References ............................................................................... 29 Chapter 3 Carbohydrate Metabolism ............................................................. 33 References ............................................................................... 39 Chapter 4 Folic Acid Metabolism ................................................................. 43 References ............................................................................... 47 Chapter 5 Cholesterol Metabolism ................................................................ 49 I. Guinea Pig Studies ............................................................... 49 II. Other Animals ................................................................... 59 III. Human Studies ................................................................... 60 IV. Summary ........................................................................ 70 V. Conclusions ...................................................................... 70 References ............................................................................... 70 Chapter 6 Tyrosine and Phenylalanine Metabolism .............................................. 75 I. Introduction ...................................................................... 75 II. Hydroxyphenyluria ............................................................... 75 III. Dopa, Dopamine, Norepinephrine, and Epinephrine ............................. 84 IV. Tyrosine Oxidation to Dopa and Melanin ........................................ 87 V. Tyrosine Iodination and Conversion to Thyroxine ............................... 88 VI. Conclusions Concerning Clinical Relevance ..................................... 88 References ............................................................................... 89 Chapter 7 Tryptophan Metabolism ............................................................... 93 References ............................................................................... 99 Chapter 8 Adrenal Corticoid Metabolism ....................................................... 10 1 I. Introduction ..................................................................... 101 II. Human Observations ............................................................ 101 III. Guinea Pigs ..................................................................... 102 IV. Rats ............................................................................. 10 8 V. In Vitro Studies ................................................................. 108 References .............................................................................. 109 Chapter 9 Uric Acid Clearance .................................................................. 113 References .............................................................................. 114 CLINICAL CONDITIONS ASSOCIATED WITH DISORDERS OF ASCORBIC ACID METABOLISM Chapter 10 Rheumatic Fever ...................................................................... 117 I. Experimental Production in the Guinea Pig ..................................... 117 A. Controls ................................................................. 117 B. Infection ................................................................. 117 C. Scurvy ................................................................... 117 D. Combined Scurvy and Infection ......................................... 118 E. Scurvy and Exotoxin .................................................... 119 II. Rheumatic Purpura .............................................................. 120 III. Epidemiology of Rheumatic Fever .............................................. 121 IV. Ascorbate Status in Rheumatic Fever ........................................... 121 A. Urinary Excretion Tests ................................................. 122 B. Blood Values ............................................................ 123 V. Ascorbic Acid Supplements in Rheumatic Fever. ............................... 124 VI. Use of Ascorbic Acid in Prophylaxis Against Rheumatic Fever ................ 125 VII. Other Prophylactic and Therapeutic Measures .................................. 125 VIII. The Hyperimmune Response .................................................... 127 IX. The Effect of Cortisone on Ascorbic Acid Metabolism in Rheumatic Fever ........................................................................... 127 X. Conclusions ..................................................................... 127 XI. Future Research ................................................................. 130 References .............................................................................. 130 Chapter 11 Menorrhagia ........................................................................... 133 References .............................................................................. 143 Chapter 12 Wound Dehiscence .................................................................... 145 References .............................................................................. 150 Chapter 13 Habitual Abortion ..................................................................... 151 References .............................................................................. 158
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