Dictionary of Nutraceuticals and Functional Foods

FUNCTIONAL FOODS AND NUTRACEUTICALS SERIESSeries Editor G.Mazza, Ph.D. Senior Research Scientist and Head Food Research Program Pacific Agri-Food Research Centre Agriculture and Agri-Food Canada Summerland, British Columbia Functional Foods: Biochemical and Processing Aspects Volume 1 Edited by G.Mazza, Ph.D. Herbs, Botanicals, and Teas Edited by G.Mazza, Ph.D. and B.D.Oomah, Ph.D. Functional Foods: Biochemical and Processing Aspects Volume 2 Edited by John Shi, Ph.D., G.Mazza, Ph.D., and Marc Le Maguer, Ph.D. Methods of Analysis for Functional Foods and Nutraceuticals Edited by W.Jeffrey Hurst, Ph.D. Handbook of Functional Dairy Products Edited by Collete Short and John OBrien Handbook of Fermented Functional Foods Edited by Edward R.Farnworth, Ph.D. Handbook of Functional Lipids Edited by Casimir C.Akoh, Ph.D. Dictionary of Nutraceuticals and Functional Foods N.A.Michael Eskin, Ph.D. and Snait Tamir, Ph.D.

Dictionary of Nutraceuticals and Functional FoodsN.A.Michael Eskin Snait Tamir

Boca Raton London New York A CRC title, part of the Taylor & Francis imprint, a member of the Taylor & Francis Croup, the academic division of T&F Informa plc.

Published in 2006 by CRC Press Taylor & Francis Group 6000 Broken Sound Parkway NW, Suite 300 Boca Raton, FL 334872742 2006 by Taylor & Francis Group, LLC CRC Press is an imprint of Taylor & Francis Group This edition published in the Taylor & Francis e-Library, 2006. To purchase your own copy of this or any of Taylor & Francis or Routledges collection of thousands of eBooks please go to http://www.ebookstore.tandf.co.uk/. No claim to original U.S. Government works ISBN 0-203-48685-4 Master e-book ISBN

ISBN 0-203-61273-6 (OEB Format) International Standard Book Number-10:0-8493-1572-7 (Print Edition) (Hardcover) International Standard Book Number-13:978-0-8493-1572-5 (Print Edition) (Hardcover) Library of Congress Card Number 2005050698 This book contains information obtained from authentic and highly regarded sources. Reprinted material is quoted with permission, and sources are indicated. A wide variety of references are listed. Reasonable efforts have been made to publish reliable data and information, but the author and the publisher cannot assume responsibility for the validity of all materials or for the consequences of their use. No part of this book may be reprinted, reproduced, transmitted, or utilized in any form by any electronic, mechanical, or other means, now known or hereafter invented, including photocopying, microfilming, and recording, or in any information storage or retrieval system, without written permission from the publishers. For permission to photocopy or use material electronically from this work, please access www.copyright.com (http://www.copyright.com/) or contact the Copyright Clearance Center, Inc. (CCC) 222 Rosewood Drive, Danvers, MA 01923, 9787508400. 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 Eskin, N.A.M. (Neason Akivah Michael) Dictionary of nutraceuticals and functional foods/by N.A.Michael Eskin and Tamir Snait. p. cm. (Functional foods and nutraceuticals series; no. 8) Includes bibliographical references. ISBN13:978-0-8493-1572-5 (acid-free paper) ISBN-10:0-8493-1572-7 (acid-free paper) 1. Functional foodsDictionaries. 2. Dietary supplementsDictionaries. I. Snait, Tamir. II. Title. III. Functional foods & nutraceuticals series; no. 8. QP144.F85E85 2005 613.203dc22 2005050698

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DedicationThis book is dedicated to a wonderful wife Nella Eskin and a wonderful daughter Orr Tamir

PrefaceThe current emphasis in preventative medicine encourages healthy lifestyles such as a balanced diet and exercise. In recent years a balanced diet has focused on ensuring functional foods are part of our diet. Functional foods are similar in appearance to conventional foods, but in addition to providing basic nutritional components, have physiological benefits that can reduce the risk of chronic diseases. The bioactive components responsible for the health benefits of functional foods are referred to as nutraceuticals. The past decade has witnessed a dramatic expansion in research activities worldwide to identify new functional foods and nutraceuticals. The latter will hopefully enhance the health and wellbeing of an aging population. Research on functional foods and nutraceuticals is scattered throughout the scientific literature with only a very few journals devoted specifically to nutraceuticals. We have attempted to bring together, in a concise and informative manner, some of the literature published on 480 functional foods and nutraceuticals. This dictionary, which is more of a mini-encyclopedia, provides the reader with useful information on the nature of the bioactives in functional foods and their reported efficacy in cell cultures, animal studies, and, in some cases, human clinical trials. In addition to providing the structures of some of the bioactives or nutraceuticals, data showing their efficacy are also included. The information is presented alphabetically with some areas more extensively researched in the literature than others. We hope this book will prove a useful resource for researchers, teachers, as well as those working in the functional food and nutraceutical industry by providing reliable and accurate information based solely on peer-reviewed literature. The authors acknowledge the professional help afforded by the staff of Taylor & Francis as well as the assistance of Marie Speare, reference librarian at the University of Manitoba. The authors are particularly appreciative of the support given by their respective families and academic institutions in preparing this unique volume. N.A.Michael Eskin S.Tamir

The AuthorsMichael Eskin, PH.D., was born and educated in Birmingham, England. He completed his B.Sc. Hons. degree in biochemistry and Ph.D. in physiological chemistry at Birmingham University where he conducted research on toxicology focusing on mercapturic acid formation. After teaching at the Borough Polytechnic (now Southbank University) in London, England for several years he joined the Department of Human Nutritional Sciences (formerly the Department of Foods and Nutrition) at the University of Manitoba in Winnipeg, Canada where he served a term as vice-chair and chair. He is currently an associate dean of the Faculty of Human Ecology Professor Eskin holds several patents and has published 15 chapters and 100 scientific papers related to edible oils, methodology and mustard gum. He has authored and edited 8 books including Biochemistry of Foods which was translated into German, Japanese and Malay. He is currently working on a third edition of this book. Dr. Eskin also coedited Methods to Assess the Stability of Oils and Fat-Containing Foods, published by the American Oil Chemists Society, and more recently Food Shelf Life Stability, published by CRC Press and translated into Portuguese. Professor Eskin was the recipient of a number of awards including the 2001 W.J.Eva Award for outstanding contributions to research and service by the Canadian Institute of Food Science and Technology. He was recently honored by the Natural Sciences and Engineering Research Council of Canada (NSERC) for holding an NSERC grant for more than 25 years. Dr. Eskin is a Fellow of the Canadian Institute of Food Science and Technology and the Institute of Food Science and Technology in the UK. In 2004, he was inducted a Fellow of the American Oil Chemists Society at their Annual Meeting in Cincinnati for outstanding contributions to the society and to oilseed research. He is an associate editor of the Journal of the American Oil Chemists Society as well as sits on the editorial boards of Food Chemistry (UK), Journal of Food Lipids (USA), Indian Journal of Food Science and Technology and served a term on the board of Food Hydrocolloids (USA). He also sits on the advisory board of INFORM, the technical publication of the American Oil Chemists Society. Snait Tamir, Ph.D., is professor of biochemistry and nutrition sciences, and head of the Department of Nutrition Sciences at Tel Hai Acadmeic College, Israel. In 1985 Dr. Tamir received her B.Sc. (cum laude), and in 1991 she received her Ph.D. (supervised by Prof. Yehudith Birk) in biochemistry and human nutrition from the Hebrew University of Jerusalem, Israel. In 1986 she completed her internship at Ichilov Medical Center in Tel Aviv, Israel and became a registered dietician. She conducted her postdoctoral study on Nitric Oxide in DNA Damage and Repair at the Division of Toxicology at the Massachusetts Institute of Technology, Cambridge, USA, with Professor Steven Tannenbaum, from 19921995.

In 1989, she studied, under the supervision of Professor T.Finlay, Medical Research Center, New York University, research techniques in breast cancer cells as part of a joint research project with Professor Yehudith Birk, the Hebrew University of Jerusalem. In 1985 she was awarded The Deans Scholarship at the Faculty of Agriculture Food and Environmental Sciences, The Hebrew University of Jerusalem. In 1987 she was awarded the Annual Distinction Award by the Womens Academic Association in Israel. She was also awarded the Rothschild Fellowship for the academic years 1992/3 by the Rothschild Foundation, Yad Hanadiv, Jerusalem, Israel, and the Guastella Fellowship for the academic years 1997/2000 by the Rashi Foundation, Jerusalem, Israel. Dr. Tamir joined the academic staff at the Tel Hai Academic College in 1997 as a senior lecturer in the Department of Biotechnology and Environmental Sciences, in which she participated in the design, establishment, and management of the academic curriculum. Since 1999 she has served as head of the Nutrition Science Department and was head of the Biotechnology and Environmental Sciences Department in the years 20012002. In 1999 Dr. Tamir joined the research group in the Laboratory of Natural Medicinal Compounds, Galilee Technological Center (MIGAL), which deals with the development of natural therapeutic compounds, mainly the isolation, characterization, and synthesis of new compounds, in collaboration with various leading academic institutes in Israel. Dr. Tamir has published about 40 papers and book chapters. Her current research interest is the therapeutic actions of natural compounds such as phytoestrogens, antioxidants, whitening agents and psoriasis inhibitors. Based on the structure-activities relationship studies she aims to design the optimal anti-atherogenic compounds, hormone replacement agents, melanin biosynthesis inhibitors, and to develop new biological agents for psoriasis.

AAcacia gumAcacia gums, or gum arable, are Acacia-tree exudates that are highly branched galactan polymers with galactose or arabinose side chains terminated by rhamnose or glucuronic acid. It cannot be digested in the small intestine but behaves as a prebiotic by enhancing the growth of the probiotic bifidobacteria (Wyatt et al., 1986; Crociani et al., 1994). Michel and coworkers (1998) confirmed the similarity between two acacia gums and a prebiotic fructooligosaccharide with respect to their ability to decrease Clostridium sp. levels in human intestinal microbiota, as well as increase Lactobacillus sp. counts. However, the fructooligosaccharide preparation induced higher levels of Lactobacillu sp. The overall effect was attributed to increased production of short-chain fatty acids. Hosobuchi et al. (1999) demonstrated the efficacy of supplementing diets with acacia gum, pectin, and guar gum for controlling hypercholesterolemia. A significant reduction was observed for both total and LDL cholesterol in 50 adults after four weeks on the supplemented diet. Arabic gum was shown by Rehman et al. (2001) to scavenge nitric oxide. The decrease in the production of nitric oxide by arabic gum was later shown by Gamal eladin et al. (2003) to protect against acetaminophen-induced hepatoxicity in mice. This reduction in oxidative stress (nitric-oxide production) was similar to the protection by arabic gum against gentamycin-induced nephrotoxicity reported previously by Al-Majed et al. (2002). ReferencesAl-Majed, A., Mostafa, A.M., Al-Rikabi, A.C., and Al-Shabanah, O.A., Protective effects of oral arabic gum administration in gentamycin-induced nephrotoxicity, Pharmacol. Res., 47:4456 451, 2002. Crociani, F., Alessandrini, A., Mucci, M.M., and Biavati, B., Degradation of complex carbohydrates by Bifidobacterium spp., Int. J. Food Microbiol., 24:199210, 1994. Gamal el-adin, A.M., Mostafa, A.M., Al-Shabanah, O.A., Al-Bekairi, A.M., and Nagi, M.N., Protective effect of arabic gum against acetaminophen-induced hepatoxicity in mice, Pharmacol. Res., 48:631635, 2003. Hosobuchi, C., Lapa Rutanassee, B.S., Bassin, S.L. and Wong, N.D., Efficacy of acacia, pectin, and guar gum-based fiber supplementation in the control of hypercholesterolemia, Nutr. Res. 19:643649, 1999.

Michel, C., Kravtchenko, T.P., David, A., Gueneau, S., Kozlowski, F., and Cherbut, C., In vitro prebiotic effects of acacia gums onto the human intestinal microbiota depends on both botanical and environmental pH, Anaerobe, 4:257266, 1998. Rehman, K., Wingertzahn, M.A., Harper, R.G., and Wapnir, R.A., Proabsorptive action of gum arabic: Regulation of nitric oxide metabolism in basolateral potassium channel of the small intestine, Gastroenterol. Nutr., 35:429533, 2001. Wyatt, G.M., Bayliss, C.E., and Holcroft, J.D., A change in human faecal flora in response to inclusion of gum arabic in the diet, Br. J. Nutr., 55:261266, 1986.

Acetyl-L-carnitinesee also Carnitine Acetyl-L-carnitine, an acetyl ester of carnitine, functions as a carrier of long-chain fatty acids into the mitochondria for -oxidation. It also contributes to oxidative phosphorylation by the acetyl group forming acetyl-CoA, which enhances the supply of energy substrates to the Krebbs cycle (Dolezal and Tucek, 1981). During normal oxidative metabolism, the continuous production of reactive-oxygen metabolites (ROM) is extremely reactive, causing extensive mitochondrial DNA, cellular, and tissue damage over time. Such changes are associated with many chronic diseases, such as atherosclerosis, arthritis, autoimmune diseases, cancers, heart disease, and cerebrovascular accidents, as well as aging. Seidman and coworkers (2000) examined the ability of two mitochondrial metabolites, including acetyl-L-carnitine, to enhance mitochondrial function and reverse age-related processes in experimental rats. Acetyl-Lcarnitine was found to delay the decline in mito-

Acetyl-L-carnitine. (From Bias et al., Mitochon-drion. 4:163168, 2004. With permission.) chondrial function by reducing age-associated deterioration in auditory sensitivity and improving cochlear function. Kopke and colleagues (2002) also found that acetyl-Lcarnitine reduced noise-induced hearing loss in animals due to cochlear injury from oxidative stress. Turpeinen et al. (2000) showed acetyl-L-carnitine prevented loss of myocardial sympathetic nervous function in patients with diabetes. Kaur and coworkers (2001) demonstrated new antiaging effects of acetyl-L-carnitine by its ability to enhance glutathione S-transferase and multiple-unit activity and reduce lipid peroxidation and lipofuscin levels in the brain regions of aged rats. Biagiotti and Cavallini (2001) reported acetyl-L-carnitine was a far more effective and safer alternative to tamoxifen in the

treatment of Peyronies disease. A recent study by Mazzio et al. (2003) showed acetyl-Lcarnitine prevented neurological damage in mouse brain neuroblastoma cells by 1methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP+), a cogent Parkinson-causing agent. This beneficial effect may be due to its ability to sustain neuronal energy supplies in the absence of oxygen or when there is a malfunction of mitochondrial oxygen utilization, typical of Parkinsons disease. Recent studies by Loots et al. (2004) suggested acetyl-Lcarnitine may prevent MPTP+ toxicity by denying cation access to the inner mitochondrial membrane, thereby attenuating its ability to produce radical-oxygen species via the electron-transport chain. These results suggest acetyl-L-carnitine may have potential in the therapeutic treatment of Parkinsons disease. Tomassini et al. (2003) found that acetyl-L-carnitine was well-tolerated as an alternative to the drug amantadine for the treatment of fatigue in multiple-sclerosis patients. A recent review by Ilias et al. (2004) pointed to the potential of acetyl-Lcarnitine for treating complications associated with HIV infection and antiretroviral therapy. However, the data obtained so far were based on small, uncontrolled clinical trials and require further investigation. ReferencesBiagiotti, G. and Cavallini, G., Acetyl-L-carnitine vs tamoxifen in the oral treatment of Peyronies disease: a preliminary report, B. J. U. Int., 88(1):6367, 2001. Dolezal, V. and Tucek, S., Utilization of citrate, acetylcarnitine and carnitine palmityltransferase in the transport of fatty acyl groups across mitochondrial membranes, J. Neurochem., 36:1323 1330, 1981. Ilias, I., Manoli, I., Blackman, M.R., Gold, P.W., and Alesci, S., L-Carnitine and acetyl-L-carnitine in the treatment of complications associated with HIV infection and antiretroviral therapy, Mitochondrion. 4:163168, 2004. Kaur, J., Sharma, D., and Singh, R., Acetyl-L-carnitine enhances Na(+), K(+)-ATP-ase glutathioneS-transferase and multiple unit activity and reduces lipid peroxidation and lipofuscin concentration in aged rat brain regions, Neurosci. Lett., 301:14, 2001. Kopke, R.D., Coleman, J.K., Liu, J., Campbell, K.C., and Riffenburgh, R.H., Candidates thesis: Enhanc-ing intrinsic cochlear stress defenses to reduce noise-induced hearing loss, Laryngoscope, 112(9): 15151532, 2002. Loots, D.T., Mienie, L.J., Bergh, J.J., and Van der-Schyf, C.J., Acetyl-L-carnitine prevents total body hydroxyl free radical and uric acid production induced by 1-methyl-4-phenyl-1,2,3,6tetrahydropyridine (MPTP) in the rat, Life Sci., 75:12431253, 2004. Mazzio, E., Yoon, K.J., and Soliman, K.F.A., Acetyl-L-carnitine protection against 1-methyl-4phenylpyridinium toxicity in neuroblastoma cells, Biochem. Pharmacol., 66:297306, 2003. Seidman, M.D., Khan, M.J., Bai, U., Shirwany, N., and Quirk, W.S., Biologic activity of mitochondrial metabolites on aging and age-related hearing loss, Am. J. Otol., 21(2): 161167, 2000.

SCHEME A.1 Structures of acridone alkaloids tested for inhibition of TPAinduced EBV-EA activation. (From Itoigawa et al., Cancer Lett., 193:133 138, 2003. With permission.)Tomassini, V., Pozzilli, C., Onesti, E., Pasqualetti, P., Marinelli, F., Pisani, A., and Fieschi, C., Comparison of the effects of acetyl-L-carnitine and amantadine for the treatment of fatigue in multiple sclerosis: Results of a pilot, randomised, double-blind, crossover study, J. Neurol. Sci., 218:103108, 2004. Turpeinen, A.K., Kuikka, J.T., Vanninen, E., Yang, J., and Uusitupa, M.I., Long-term effect of acetyl-L-carnitine on myocardial 1231-MIBG uptake in patients with diabetes, Clin. Auton. Res., 10(1): 1316, 2000.

Acridone alkaloidsAcridone alkaloids have been isolated from a number of plant sources, including citrus plants (family Rutacea). Some of them have been shown to exhibit cytotoxic, antiviral, and antimalarial properties (Kawaii et al., 1999; Yamamoto et al., 1989; Queener et al., 1991). A screening test showed that acri-done alkaloids from citrus plants exhibited the most potent inhibition of 12-O-tetrade-canoylphorbol-13-acetate (TPA)-induced EpsteinBarr virus early antigen (EBV-EA) activation (Takemura et al., 1995). Further studies by Itoigawa and coworkers (2003) isolated 17 acridone alkaloids from Rutaceous plants. Their structures are shown in Scheme A.1. Of these, the prenylated acridones were found to be the most potent cancer protective agents when tested in a short-term, in vitro assay of 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced Epstein-Barr virus early antigen (EBVEA) activation in Raji cells. The prenylated acridone alkaloids included glycocitrinII (6), O-methylglycocirine-II (7), severifoline (12), and ataphyllinine (13). The importance of the prenyl group was confirmed with the synthetic diprenylated acridone, 1,3-dihydroxy-10-methyl-2,4-diprenylacridone (18). Using an in vivo, two-stage mouse skin carcinogenesis model, it reduced the percentage of tumor-bearing mice to 73 percent after 10 weeks (Figure A.1), and the number of papillomas by approximately 48 percent

after 20 weeks (Figure A.1B), compared to the nonprenylated acridones, 1,3-dihydroxy10-methylacridone (1) and glycofilinine (5). ReferencesItoigawa, M., Ito, C., Wu, T-S., Enjo, F., Tokuda, H., Nishino, H., and Furukawa, H., Cancer chemopreventive activity of acridone alkaloids on Epstein-Barr virus activation and two-stage mouse skin carcinogenesis, Cancer Lett., 193:133138, 2003. Kawaii, S., Tomono, Y., Katase, E., Ogawa, K., Yano, M., Takemura, Y., Ju-ichi, M., Ito, C., and Furukawa H., The antiproliferative effect of acridone alkaloids on several cancer cell lines, J. Nat. Prod., 62:587589, 1999.

FIGURE A.1 Inhibitory effects of acridone alkaloids on DMBA-TPA mouse skin carcinogenesis. Tumor formation in all mice was initiated with DMBA (dimethylbenz[] anthracene) (390 nmol) and promoted with TPA (1.7 nmol) twice weekly, starting one week after initiation, (a) Percentage of mice with papillomas. (b) Average number of papillomas per mouse: , control TPA alone; o, TPA+85 nmol of 1,3-dihydroxy-10-methyl-2.4diprenylacridone (18); , TPA+85 nmol of 1,3-dihydroxy-10methylacridone (1); , TPA+85 nmol of glycofolinine (5). After 20 weeks of

promotion, a difference in the number of papillomas per mouse between the groups treated with acridones and the control was evident (p