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1 HERBAL SUPPLEMENTS Efficacy, Toxicity, Interactions with Western Drugs, and Effects on Clinical Laboratory Tests Edited by AMITAVA DASGUPTA CATHERINE A. HAMMETT-STABLER A JOHN WILEY & SONS, INC., PUBLICATION

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3 HERBAL SUPPLEMENTS

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5 HERBAL SUPPLEMENTS Efficacy, Toxicity, Interactions with Western Drugs, and Effects on Clinical Laboratory Tests Edited by AMITAVA DASGUPTA CATHERINE A. HAMMETT-STABLER A JOHN WILEY & SONS, INC., PUBLICATION

6 Copyright 2011 by John Wiley & Sons, Inc. All rights reserved Published by John Wiley & Sons, Inc., Hoboken, New Jersey Published simultaneously in Canada No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, scanning, or otherwise, except as permitted under Section 107 or 108 of the 1976 United States Copyright Act, without either the prior written permission of the Publisher, or authorization through payment of the appropriate per-copy fee to the Copyright Clearance Center, Inc., 222 Rosewood Drive, Danvers, MA 01923, (978) , fax (978) , or on the web at Requests to the Publisher for permission should be addressed to the Permissions Department, John Wiley & Sons, Inc., 111 River Street, Hoboken, NJ 07030, (201) , fax (201) , or online at Limit of Liability/Disclaimer of Warranty: While the publisher and author have used their best efforts in preparing this book, they make no representations or warranties with respect to the accuracy or completeness of the contents of this book and specifically disclaim any implied warranties of merchantability or fitness for a particular purpose. No warranty may be created or extended by sales representatives or written sales materials. The advice and strategies contained herein may not be suitable for your situation. You should consult with a professional where appropriate. Neither the publisher nor author shall be liable for any loss of profit or any other commercial damages, including but not limited to special, incidental, consequential, or other damages. For general information on our other products and services or for technical support, please contact our Customer Care Department within the United States at (800) , outside the United States at (317) or fax (317) Wiley also publishes its books in a variety of electronic formats. Some content that appears in print may not be available in electronic formats. For more information about Wiley products, visit our web site at Library of Congress Cataloging-in-Publication Data: Herbal supplements : efficacy, toxicity, interactions with western drugs and effects on clinical laboratory tests / edited by Amitava Dasgupta and Catherine A. Hammett-Stabler. p. ; cm. Includes bibliographical references and index. ISBN (cloth) 1. Herbs Toxicology. 2. Herbs Therapeutic use. 3. Drug-herb interactions. I. Dasgupta, Amitava, 1958 II. Hammett-Stabler, Catherine A., 1952 [DNLM: 1. Plants, Medicinal chemistry. 2. Plants, Medicinal toxicity. 3. Dietary Supplements toxicity. 4. Herb-Drug Interactions. 5. Pathology, Clinical methods. 6. Phytotherapy adverse effects. QV 766 H ] RA1250.H dc Printed in Singapore

7 We dedicate this book to Alice and Tom. v

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9 CONTENTS PREFACE CONTRIBUTORS xi xiii PART I INTRODUCTION AND OVERVIEW 1 1 Introduction to Complementary and Alternative Medicine 3 Catherine A. Hammett-Stabler 2 Relatively Safe Herbal Remedies 19 Angela M. Ferguson and Uttam Garg 3 Risk of Toxicity Associated with Unregulated Herbal Products 45 Steven W. Cotten PART II EFFECTS OF HERBAL REMEDIES ON SPECIFIC ORGAN SYSTEMS 73 4 Herbal Medicines with Immunomodulatory Effects 75 Jeffrey K. Actor 5 Kelp and Thyroid Function 125 Bruce Rosenzweig vii

10 viii CONTENTS 6 Herbal Remedies and the Patient with Chronic Kidney Disease 135 Mariana S. Markell 7 Abnormal Liver Function Tests Due to Hepatotoxic Herbs 155 Amitava Dasgupta and Catherine A. Hammett-Stabler 8 Homeopathic Medicine: Principle, Efficacy, and Toxicity 169 Amitava Dasgupta 9 Indian Ayurvedic Medicines: An Introduction 193 Amitava Dasgupta 10 Tradition and Perspectives of Greco-Arab and Islamic Herbal Medicine 209 Bashar Saad and Omar Said 11 Licorice and Laboratory Tests 255 Salvador F. Sena PART III DRUG INTERACTIONS Drug Interactions with St. John s Wort 275 Matthew D. Krasowski and John L. Blau 13 Drug Herb Interactions in Patients with HIV/AIDS 291 Natella Y. Rakhmanina and John N. van den Anker 14 Interactions between Fruit Juices and Drugs 305 Amitava Dasgupta 15 Drug Interactions with Ginkgo Biloba and Ginseng 321 Ashok Tholpady and Semyon A. Risin 16 Drug Interactions with Garlic and Ginger Supplements 333 Charbel Abou-Diwan and James Ritchie PART IV CONTAMINATION Heavy Metal Toxicity and Herbal Remedies 353 Christine L. H. Snozek and Loralie J. Langman 18 Adulteration of Herbal Remedies with Conventional Drugs: Role of the Clinical Laboratory 369 Uttam Garg and Angela M. Ferguson 19 Beyond Herbals: An Introduction to Poisonous Plants 387 Catherine A. Hammett-Stabler

11 CONTENTS ix PART V ANALYTICAL IMPLICATIONS Interferences of Herbal Remedies with Immunoassays for Therapeutic Drugs: Focus on Digoxin 407 Amitava Dasgupta 21 Role of the Clinical Laboratory in Detecting Plant Poisoning 425 Ronald W. McLawhon INDEX 443

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13 PREFACE Today, a significant percentage of Americans turn to complementary and alternative medicine (CAM) practices. These range from biological - based products, which include herbal remedies, supplements, and traditional medicines, to noninvasive modalities such as massage, acupuncture, meditation, and yoga. Although many alternative modalities such as massage, yoga, and meditation are safe and may also have efficacy, there are significant safety issues regarding the use of herbal supplements and many traditional medicines (e.g., Ayurvedic medicines). A number of herbal supplements have been found to cause organ-specific toxicity, while other herbal supplements are capable of interacting both pharmacodynamically and pharmacokinetically with many Western drugs. Contamination of some Asian herbal supplements and Indian Ayurvedic medicines with heavy metals and possibly with undisclosed Western drugs is a serious public health hazard. Numerous herbals have been used for many years as traditional medicines and many appear to be safe when used appropriately. Research has yet to show many to be as effective as pharmaceuticals, and this is an area in which considerable work is needed. We decided a book such as this was needed because of the cases of toxicity we have seen and the questions we each receive as clinical laboratory professionals. While we present both safe and unsafe herbal supplements, we emphasize the pharmacological interactions identified between Western drugs and herbal supplements and the effects of herbal supplements on clinical laboratory tests. Other books and reviews discuss some of these issues, but there are few that discuss the effects of herbal supplements on clinical laboratory tests despite the fact that these tests are often the first indicators of a problem, that is, toxicity or an unwanted drug herb interaction. xi

14 xii PREFACE This book is divided into five parts. The first part provides a general introduction to CAMs as well as an introduction to herbals considered safe versus those with a darker reputation. The second part provides more detailed information in an organ - or disease - based focus and delves into some of the traditional practices of which most allopathic professionals have limited knowledge. These are by no means intended to provide all that is known about these practices but to give a sound overview that one could use to engage patients and others in discussions about their use of such practices. Part III is dedicated to the key interactions between herbal supplements and various pharmaceutical drugs. Despite much play by the media several years ago, patients continue to mix herbals and pharmaceuticals without telling their allopathic providers. This often becomes the explanation of many unexpected drug reactions. Importantly, contamination of herbal supplements, especially those manufactured in various Asian countries, and Indian Ayurvedic medicines with heavy metals is a serious public safety issue. The metals found include, but are not limited to, lead, mercury, arsenic, and cadmium, and there are numerous case reports in the literature describing heavy metal toxicity following consuming such supplements. In addition, more than a few products have been found to contain significant amounts of pharmaceuticals. Part IV (Contamination) addresses these important points. Part V discusses various analytical techniques used in the investigation of herbal remedies. This book is dedicated to healthcare professionals who we hope will find it valuable in their practice of medicine. We thank our authors for taking time to conduct thorough literature reviews and we respect the opinions their work derived. We have tried to provide an unbiased, literature - based opinion on each herbal supplement. Most importantly, we thank our spouses for putting up with us during the time we worked on this project. Amitava Dasgupta Catherine A. Hammett-Stabler

15 CONTRIBUTORS Charbel Abou-Diwan, PhD, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA; Jeffrey K. Actor, PhD, Professor of Pathology and Laboratory Medicine, University of Texas Medical School at Houston, Houston, TX; John L. Blau, MD, Department of Pathology, University of Iowa Hospitals and Clinics, Iowa City, IA Steven W. Cotten, PhD, Division of Medicinal Chemistry and Natural Products, Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill; Amitava Dasgupta, PhD, Professor of Pathology and Laboratory Medicine, University of Texas Medical School at Houston, Houston, TX; Angela M. Ferguson, PhD, Assistant Professor of Pathology and Laboratory Medicine, Children s Mercy Hospitals and Clinics, University of Missouri - Kansas City School of Medicine; amferguson@cmh.edu Uttam Garg, PhD, Professor of Pathology and Laboratory Medicine, Children s Mercy Hospitals and Clinics, University of Missouri - Kansas City School of Medicine; ugarg@cmh.edu Catherine A. Hammett-Stabler, PhD, Professor of Pathology and Laboratory Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC; cstabler@unch.unc.edu xiii