NUTRITION AND DRUG INTERRELATIONS THE NUTRITION FOUNDATION A Monograph Series HORACE L. SIPPLE AND KRISTEN W. MCNUTT, EDS. : Sugars in Nutrition, 1974 ROBERT E. OLSON, ED.: Protein-Calorie Malnutrition, 1975 ANANDA S. PRASAD, ED. : Trace Elements in Human Health and Disease, Volume I, Zinc and Copper, 1976; Volume II, Essential and Toxic Elements, 1976 MORLEY R. KARE AND OWEN MALLER, EDS. : The Chemical Senses and Nutri tion, 1977 JOHN N. HATHCOCK AND JULIUS COON, EDS.: Nutrition and Drug Inter relations, 1978 NUTRITION AND DRUG INTERRELATIONS Edited by John N. Hathcock Department of Food and Nutrition Iowa State University Ames, Iowa Julius Coon Department of Pharmacology Thomas Jefferson University Philadelphia, Pennsylvania ACADEMIC PRESS New York San Francisco London 1978 A Subsidiary of Harcourt Brace Jovanovich, Publishers COPYRIGHT © 1978, BY ACADEMIC PRESS, INC. ALL RIGHTS RESERVED. NO PART OF THIS PUBLICATION MAY BE REPRODUCED OR TRANSMITTED IN ANY FORM OR BY ANY MEANS, ELECTRONIC OR MECHANICAL, INCLUDING PHOTOCOPY, RECORDING, OR ANY INFORMATION STORAGE AND RETRIEVAL SYSTEM, WITHOUT PERMISSION IN WRITING FROM THE PUBLISHER. ACADEMIC PRESS, INC. Ill Fifth Avenue, New York, New York 10003 United Kingdom Edition published by ACADEMIC PRESS, INC. (LONDON) LTD. 24/28 Oval Road, London NW1 7DX Library of Congress Cataloging in Publication Data International Symposium on Nutrition and Drug Inter relations, Iowa State University, 1976. Nutrition and drug interrelations. (Nutritional Foundation monograph series) "Based on papers presented at the International Symposium on Nutrition and Drug Interrelations held at Iowa State University, August 4-6,1976." Includes bibliographies and index. 1. Drugs—Physiological effect—Congresses. 2. Nutrition—Congresses. 3. Diet therapy—Congresses. 4. Medicated feeds—Congresses. I. Hathcock, John N. II. Coon, Julius. III. Title. IV. Series: Nutrition Foundation, New York.Nutrition Foundation monograph series. RM300.I56 1976 615\73 77-82413 ISBN 0-12-332550-1 PRINTED IN THE UNITED STATES OF AMERICA Contents List of Contributors xiii Foreword xvii Preface xix 1 The Agile Role of Food: Some Historical Reflections JAMES HARVEY YOUNG I. Food as Patriotism 1 II. The Vast Variety of Food Image and Role 3 III. The American Version of Food Folklore 8 IV. The New Nutrition and Its Manipulation 10 V. The Vitamin Amendments of 1976 13 References 16 SECTION I / DRUG EFFECTS ON NUTRIENT INTAKE, FUNCTION, AND REQUIREMENT 2 Appetite Regulation and Its Modulation by Drugs ANN C. SULLIVAN AND LORRAINE CHENG I. Introduction 21 II. Regulation of Feeding Behavior 22 III. Disorders of Appetite Regulation 39 IV. Drugs Affecting Food Intake 42 V. Summary and Research Needs 64 References 65 3 Drugs and Water-Soluble Vitamin Absorption CHARLES H. HALSTED I. Introduction: Principles of Intestinal Absorption 83 II. Water-Soluble Vitamin Absorption and Drug Inhibition 86 ν vi Contents III. Discussion: Research Needs 105 References 107 4 Drug Effects on Fat-Soluble Vitamin Absorption JAMES A. BARROWMAN I. Introduction 113 II. Physiology of Digestion, Absorption, and Transport of Fat-Soluble Vitamins 114 III. Drugs Affecting Fat-Soluble Vitamin Absorption 117 IV. Miscellaneous Effects of Drugs on Fat-Soluble Vitamin Absorption 125 V. Research Needs 126 VI. Conclusion 126 References 126 5 Drugs and Environmental Chemicals in Relation to Vitamin Needs MYRON BRIN I. Introduction 131 II. Human Findings in Marginal Deficiency States 132 III. Some Drug-Vitamin Interrelations 137 IV. Implications of Marginal Deficiency on Human Performance 139 V. Preventive/Corrective Proposals to Attain Nutritional Adequacy 143 VI. Summary 146 References 147 6 Effects of Oral Contraceptives on Nutrient Utilization DAVID P. ROSE I. Introduction 151 II. Effects of Oral Contraceptives on Amino Acid and Protein Metabolism 153 III. Vitamin Requirements and Utilization 164 IV. Metals 179 V. Conclusions and Future Research 180 References 182 7 Nutritional Impact of Intestinal Drug-Microbe Interactions R. A. PRINS I. Introduction and Definitions 189 II. The Role of the Intestinal Microflora in Host Nutrition 190 III. Transformations of Foreign Compounds by Intestinal Microorganisms 193 IV. The Nutritional Consequences of Drug-Microbe Interactions in the Intestines of Monogastric Animals 200 Contents vii V. The Influence of Anutrients, Foreign Compounds, and Drugs on the Fermentation in the Forestomachs of Polygastric Animals 204 VI. Research Needs 237 References 238 8 Interactions of Drugs and Intestinal Mucosal Endoplasmic Reticulum RAJENDRA S. CHHABRA AND J. MICHAEL TREDGER I. Introduction 253 II. Distribution of Drug-Metabolizing Enzymes in the Intestine .. 254 III. Biochemical Properties of Some Intestinal Microsomal Drug-Metabolizing Enzymes 255 IV. Factors Affecting Intestinal Drug Metabolism 258 V. Conclusions and Research Needs 272 References 274 9 Drug Effects on Gastric Mucosa KEVIN J. IVEY I. Pathogenesis 280 II. Drug Treatment of Gastric Mucosal Damage 288 III. Research Needs 292 References 295 SECTION II / NUTRITIONAL EFFECTS ON DRUG METABOLISM AND ACTION 10 Nutrients in Drug Detoxication Reactions R. T. WILLIAMS I. Introduction 303 II. The Metabolic Reactions of Drugs 304 III. Nutrients Required in Phase I Reactions 305 IV. Nutrients in Phase II Reactions or Conjugations 309 V. General Mechanism of Conjugation and Nutrients Required . 310 VI. Conclusion 316 References 317 11 Diet-Drug Interactions and Incompatibilities DAPHNE A. ROE I. Introduction 319 II. Influence of Food and Other Dietary Constituents on Drug Absorption 320 III. Vitamin Intakes and Drug Responses 325 viii Contents IV. Drug-Induced Malnutrition 327 V. Systemic Reactions Induced by Drug-Food Incompatibilities 331 VI. Adverse Effects of Food Constituents on Nutrient Availability 333 VII. Nutrient-Nutrient Incompatibilities 337 VIII. Summary and Conclusions 338 IX. Research Needs 339 References 340 12 Ascorbic Acid and Drug Metabolism V. G. ZANNONI, P. H. SATO, AND L. E. RIKANS I. Introduction 347 II. In Vivo Effects of Ascorbic Acid 350 III. Specificity Studies 353 IV. In Vivo Reversal of Drug Metabolism and Cytochrome Ρ-450 Turnover in Deficient Guinea Pigs 357 V. Drug-Cytochrome P-450 Binding and K Studies 361 m VI. Lipid Peroxidation and Phosphatidylcholine in Normal and Deficient Animals 362 VII. Comparative Physicochemical Properties of Cytochrome P-450 in Normal and Ascorbic Acid-Deficient Microsomes 365 VIII. Research Needs 368 References 369 13 Dietary Minerals and Drug Metabolism GEORGE C. BECKING I. Introduction 371 II. Essential Minerals 374 III. Nonessential Minerals 394 IV. Conclusion and Research Needs 394 References 395 14 Drug Metabolism and Infantile Undernutrition FERNANDO MONCKEBERG, MARIA BRAVO, AND ONOFRE GONZALEZ I. Introduction 399 II. Antipyretic Drug Metabolism 400 III. Metabolism of Antibiotics 404 IV. Summary and Conclusions 404 References 406 15 Effects of Dietary Protein on Drug Metabolism T. COLIN CAMPBELL I. Introduction 409 II. Effect of Protein Deficiency on Mixed-Function Oxidase Enzyme System 414 III. Conclusions 420 References 421 Contents IX 16 Effect of Amino Acid Intake on Ethanol Toxicity CHARLES O. WARD AND MICHAEL A. DORATO I. Introduction 423 II. Ethanol Absorption and Metabolism 424 III. Acute and Chronic Toxicity of Ethanol 426 IV. Methods of Determining Ethanol Toxicity 435 V. Role of Acetaldehyde in Alcohol Toxicity 438 VI. Summary 440 References 441 17 Nutritional Effects on Drug-Protein Binding ARTHUR A. SPECTOR AND JOHN E. FLETCHER I. Introduction 447 II. Binding to Plasma Albumin 450 III. Free Fatty Acids 452 IV. Effects of Free Fatty Acids on Drug Binding to Plasma Albumin 457 V. Mechanism of Fatty Acid-Induced Albumin Binding Changes 462 VI. Summary and Conclusions 467 VII. Research Needs 468 References 469 18 Lipids in Drug Detoxication ADELBERT E. WADE, WILLIAM P. NORRED, AND JENET S. EVANS I. Introduction 475 II. Function of Lipoprotein in the Drug-Metabolizing Enzyme System 476 III. Effect of Dietary Lipid on Composition of Hepatic Endoplasmic Reticulum 477 IV. Role of Dietary Lipid in Hepatic Microsomal Drug Metabolism 478 V. Role of Dietary Lipid on Component Enzymes of Drug-Metabolizing System 484 VI. Effect of Dietary Lipid on Substrate Interaction with Cytochrome P-450 486 VII. Effect of Dietary Lipid on Intestinal Mixed-Function Oxidase Activity 487 VIII. Effect of Dietary Lipid on the Induction of Hepatic Drug Metabolizing Enzymes 487 References 500 19 Dietary Effects on Carcinogenicity of Drugs and Related Compounds ADRIANNE E. ROGERS I. Introduction 505 II. Review 506