CjigVXZji^XVah HZXdcYZY^i^dc 7g^VcAdX`lddY 00 Prelim 2/3/07 18:51 Page i Nutraceuticals 00 Prelim 2/3/07 18:51 Page ii 00 Prelim 2/3/07 18:51 Page iii Nutraceuticals A guide for healthcare professionals Second edition Brian Lockwood BPharm, PhD, MRPharmS Senior Lecturer in Pharmacy, School of Pharmacy and Pharmaceutical Sciences, University of Manchester, Manchester, UK London • Chicago 00 Prelim 2/3/07 18:51 Page iv Published by the Pharmaceutical Press An imprint of RPS Publishing 1 Lambeth High Street, London SE1 7JN, UK 100 South Atkinson Road, Suite 200, Grayslake, IL 60030–7820, USA © Pharmaceutical Press 2007 is a trade mark of RPS Publishing RPS Publishing is the publishing organisation of the Royal Pharmaceutical Society of Great Britain First edition published 2002 Second edition published 2007 Typeset by Type Study, Scarborough, North Yorkshire Printed in Great Britain by TJ International, Padstow, Cornwall ISBN 978 0 85369 659 9 All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, without the prior written permission of the copyright holder. The publisher makes no representation, express or implied, with regard to the accuracy of the information contained in this book and cannot accept any legal responsibility or liability for any errors or omissions that may be made. The right of Brian Lockwood to be identified as the author of this work has been asserted by him in accordance with sections 77 and 78 and subject to section 79(6) of the Copyright, Designs and Patents Act, 1988. A catalogue record for this book is available from the British Library 00 Prelim 2/3/07 18:51 Page v To my father Thomas George Lockwood MRPharmS (deceased) who retired from the register after 60 years, and died just before completion of the book. He had a great interest in scientific and literary knowledge, and worked prodigiously on both pharmaceutical and non-pharmaceutical matters for the good of others. 00 Prelim 2/3/07 18:51 Page vi 00 Prelim 2/3/07 18:51 Page vii Contents Preface xiii Acknowledgements xvi About the author xvii Abbreviations xviii 1 Introduction 1 Foods or medicines? The relationship between nutraceuticals, foods and medicines 1 The use of nutraceutical supplements – demographic trends 6 Safety 9 Scientific evidence 10 Market trends 12 Major nutraceuticals and their applications 15 Overview 15 References 15 2 Monographs – general and specific properties 19 Glucosamine 19 Chondroitin 20 Methylsulfonylmethane 21 Coenzyme Q10 22 Melatonin 23 Carnitine 24 Acetyl-L-carnitine 26 Octacosanol/policosanol 27 S-Adenosyl methionine 28 Polyunsaturated fatty acids 29 n-3 Fatty acids from fish oils 30 ␥-Linolenic acid 31 Flaxseed/␣-linolenic acid 32 Conjugated linoleic acid 33 Flax lignans 34 Pycnogenol 35 Resveratrol 37 00 Prelim 2/3/07 18:51 Page viii viii Contents Grape seed proanthocyanidin extract 38 Lycopene 39 Lutein 41 Zeaxanthin and astaxanthin 41 ␣-Lipoic acid 42 Dehydroepiandrosterone 43 Soy isoflavones 44 Tea 47 Creatine 52 References 53 3 Source, manufacture and analysis of major nutraceuticals 59 References 64 4 Metabolism, bioavailability and pharmacokinetics of nutraceuticals 69 Metabolism data 69 Bioavailability data 69 Pharmacokinetic data 75 References 79 5 Joint health 85 Prevalence of joint disease 85 Glucosamine and chondroitin 87 Methylsulfonylmethane 97 S-Adenosyl methionine 98 Fish oils 99 ␥-Linolenic acid 102 Cetylated fatty acids 104 Miscellaneous nutraceuticals 105 Conclusions 106 References 106 6 Cardiovascular health 111 Black and green tea 113 Soy 119 n-3 and n-6 Essential fatty acids 124 Flax lignans 130 Coenzyme Q10 131 Lycopene 133 Octacosanol/policosanol 136 Pycnogenol 138 Melatonin 140 00 Prelim 2/3/07 18:51 Page ix Contents ix Resveratrol 140 Grape seed proanthocyanidin extract 141 Lutein 143 Carnitine 143 Dehydroepiandrosterone 145 Conclusions 145 References 146 7 Eye health 155 Age-related macular degeneration 155 Lutein and zeaxanthin 156 Other eye conditions 161 Conclusions 164 References 165 8 Mental health 169 Acetyl-L-carnitine 170 Phosphatidylserine 173 Docosahexaenoic acid 174 Soy isoflavones 175 Other nutraceuticals 175 Treatments for depression 177 Conclusions 178 References 178 9 Sleep enhancement 183 Melatonin 183 Miscellaneous 188 References 188 10 Cancer prevention 191 Epidemiological evidence for soy 192 Tea 200 Lycopene 206 Flaxseed 211 n-3 Polyunsaturated fatty acids 212 Coenzyme Q10 214 Melatonin 215 Conjugated linoleic acid 218 Overall conclusions 220 References 220 00 Prelim 2/3/07 18:51 Page x x Contents 11 Nutraceuticals and bone health 229 Osteoporosis 231 Melatonin 233 L-Carnitine 235 Polyunsaturated fatty acids 237 Conjugated linoleic acid 239 Soy isoflavones 240 Conclusion 242 References 242 12 Respiratory health 247 Asthma 247 Other respiratory conditions 253 Other effects of nutraceuticals on respiratory conditions 254 Conclusion 254 References 255 13 Women’s health 259 Menopausal symptoms 259 Soy isoflavones 260 Cardiovascular disease 265 Cognitive function 266 Osteoporosis 267 Conclusion 273 References 274 14 Weight management 279 Obesity 279 Nutraceuticals 280 Conclusions 286 References 287 15 Skin health 291 Grape seed proanthocyanidin extract 291 Carotenoids 292 Polyunsaturated fatty acids 292 Tea 293 Soy isoflavones 293 Coenzyme Q10 294 Glucosamine 294 Melatonin 294 Activity of nutraceuticals on hair growth 294 References 295 00 Prelim 2/3/07 18:51 Page xi Contents xi 16 Oral health 297 Tea 297 Pycnogenol 299 Coenzyme Q10 299 References 299 17 Enhancement of sporting performance 301 Creatine 301 Carnitine 304 Acetyl-L-carnitine 305 Octacosanol 305 Conjugated linoleic acid 306 Other nutraceuticals 306 Conclusion 308 References 308 18 Animal health 311 Cardiovascular disease 311 Joint disease 316 Periodontal disease 320 Cognitive dysfunction 321 Cancer 322 Conclusions 323 References 324 19 Meta-analyses and systematic reviews of nutraceutical clinical trials 327 References 332 20 Synergism, beneficial interactions and combination products 339 Glycoaminoglycan supplementation in arthritis, liver injury and pain 340 Beneficial interactions between nutraceuticals and medicines 345 Combination products 348 Commercially available combinations 351 Conclusions 352 References 352 21 Minor nutraceuticals and their therapeutic aplications 359 Theanine 359 Cetyl myristoleate 363 00 Prelim 2/3/07 18:51 Page xii xii Contents Reduced form of nicotinamide adenine dinucleotide 364 Superoxide dismutase 364 Polyamines 365 Other candidates 365 References 366 22 Safety, adverse effects and interactions of nutraceuticals 369 Safety data 369 General adverse effects 369 Drug interactions 372 Carnitine and acetyl-L-carnitine 373 Soy isoflavones 374 Catechins 375 Melatonin 376 Glucosamine 377 Conclusions 378 References 379 23 Quality of nutraceuticals 383 Glucosamine and chondroitin products 384 Other nutraceuticals 386 Non-formulated products 388 Possible contaminants in nutraceuticals 390 Analytical issues 392 Other quality issues 393 Cost comparisons of different products 395 Conclusions 395 References 396 24 Conclusions 401 Future trends influencing consumers 401 Future trends facing manufacturers 404 Scientific community, regulatory authorities and consumer organisations 405 New horizons 407 Overall 407 References 408 Index 409 00 Prelim 2/3/07 18:51 Page xiii Preface This book was written in response to the obvious need for a scientifi- cally based text on the evidence for the use of nutraceuticals for the prevention and treatment of important disease states. The use of nutraceuticals is by now an established complementary therapy, with a few being used as if they were conventional pharmaceuticals, and a number of others being purchased and used by the general public as self- medication. Although nutraceuticals are constantly discussed in the media and freely available, comprehensive knowledge concerning their activities, mode of action and safety is not yet widely available. The main aim of this book was, therefore, to explore, discuss and possibly substantiate claims that a number of nutraceuticals can actually treat or prevent the underlying causes of disease. Consumers clearly hope that they will benefit from intake of these products either through long-term use or via a conscious decision to change lifestyle. That is why I have decided here, unlike a number of other books on the subject, to organise the information according to disease states. In addition, any evidence quoted should be of under- standable quality. The inclusion of directly attributable information sources was considered vital for this, producing a usable text for both patient, consumer and healthcare practitioners wanting to find further details by checking the original publications. Wherever possible, I have tried to focus on clinical and human research, although results from animal studies are included, particularly for the chapter on animal health, but also when there are major findings or there are insufficient human data. Previous books have either focused on the individual chemical entities and their applications, or consist of information in therapeutic areas which is not directly attributed to published data, hence not allowing easy access to original material. In contrast, this text aims to cover a wide range of nutraceuticals, specifically focusing on their use in specific therapeutic categories. Although the book was designed as a text to inform readers as to the claimed benefits of specific nutraceuticals in 00 Prelim 2/3/07 18:51