Dietary w3 and w6 Fatty Acids Biological Effects and Nutritional Essentiality NA TO ASI Series Advanced Science Institutes Series A series presenting the results of activities sponsored by the NA TO Science Committee, which aims at the dissemination of advanced scientific and technological knowledge, with a view to strengthening links between scientific communities. The series is published by an international board of publishers in conjunction with the NATO Scientific Affairs Division A Life Sciences Plenum Publishing Corporation B Physics New York and London C Mathematical Kluwer Academic Publishers and Physical Sciences Dordrecht, Boston, and London o Behavioral and Social Sciences E Applied Sciences F Computer and Systems Sciences Springer-Verlag G Ecological Sciences Berlin, Heidelberg, New York, London, H Cell Biology Paris, and Tokyo Recent Volumes in this Series Volume 166-Vascular Dynamics: Physiological Perspectives edited by N. Westerhof and D. R. Gross Volume 167-Human Apolipoprotein Mutants 2: From Gene Structure to Phenotypic Expression edited by C. R. Sirtori, G. Franceschini, H. B. Brewer, Jr., and G. Assmann Volume 168-Techniques and New Developments in Photosynthesis Research edited by J. Barber and R. Malkin Volume 169-EvolutionaryTinkering in Gene Expression edited by Marianne Grunberg-Manago, Brian F. C. Clark, and Hans G. Zachau Volume 170-ra8 Oncogenes edited by Demetrios Spandidos Volume 171-Dietary w3 and w6 Fatty Acids: Biological Effects and Nutritional Essentiality edited by Claudio Galli and Artemis P. Simopoulos Volume 172-Recent Trends in Regeneration Research edited by V. Kiortsis, S. Koussoulakos, and H. Wallace Series A: Life Sciences Dietary w3 and w6 Fatty Acids Biological Effects and Nutritional Essentiality Edited by Claudio Galli Institute of Pharmacological Sciences University of Milan Milan, Italy and Artemis P. Simopoulos ILSI Research Foundation Washington, D.C. Springer Science+Business Media, LLC Proceedings of a NATO Advanced Research Workshop on Dietary w3 and w6 Fatty Acids: Biological Effects and Nutritional Essentiality, held June 20-23, 1988, in Belgirate, Italy Library of Congress Cataloging in Publication Data NATO Advanced Research Workshop on Dietary [Omega] 3 and [Omega] 6 Fatty Acids: Biological Effects and Nutritional Essentiality (1988: Belgirate, Italy) Dietary [omega] 3 and [omega] 6 fatty acids. (NATO ASI series. Series A, Life sciences; v. 171) "Proceedings of a NATO Advanced Research Workshop on Dietary [Omega] 3 and [Omega] 6 Fatty Acids: Biological Effects and Nutritional Essentiality, held June 20-23,1988, Belgirate, Italy"-T.p. verso. "Published in cooperation with NATO Scientific Affairs Division." Includes bibliographies and index. 1. Omega-3 fatty acids-Physiological effect-Congresses. 2. Omega-6 fatty acids-Physiological effect-Congresses. 3. Unsaturated fatty acids in human nutrition-Congresses. I. Galli, Claudio. II. Simopoulos, Artemis P., 1933- III. North Atlantic Treaty Organization. Scientific Affairs Division. IV. Title. V. Series. [DNLM: 1. Dietary Fats, Unsaturated-congresses. 2. Fatty Acids, Un· saturated-congresses. 3. Fish Oils-congresses. QU 90 N2789d 1988] QP752.F35N38 1988 612.3/97 89-8583 ISBN 978-1-4757-2045-7 ISBN 978-1-4757-2043-3 (eBook) DOI 10.1007/978-1-4757-2043-3 © 1989 Springer Science+Business Media New York Originally published by Plenum Press, New York in 1989 Softcover reprint of the hardcover 1st edition 1989 All rights reserved No part of this book may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, microfilming, recording, or otherwise, without written permission from the Publisher PREFACE On June 24-26, 1985, a major International Conference on the Hea1th Effects of P01yunsaturated Fatty Acids in Seafoods was held in Washington, D.C. The conference had two objectives: (1) to review the research data on the health effects of polyunsaturated fatty acids in seafoods in terms of the impact of omega-3 fatty acids on eicosanoid formation, thrombosis and inflammation, and the role of docosahexaenoic acid in membrane function and metabolism, and (2) to develop a research agenda to determine the spectrum of the health effects of polyunsaturated fatty acids of seafood origin in the American diet. The 1985 conference established the fact that omega-3 fatty acids of marine origin - eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) - play important roles in prostaglandin metabolism, thrombosis and atherosc1erosis, immunology and inflammation, and membrane function. In response to the conference recommendations, the Congress of the United States provided special funding for the establishment of a "test materials 1aboratory" within the US Department of Commerce to produce under documented quality contr01 the types and quanti ties of omega-3 te~3t materials required by biomedica1 researchers. The forms of test materials to be produced include refined fish oil, polyunsaturated fatty acid enhanced triglycerides, concentrates of esters of fatty acids, purified omega-3 fatty acids, and omega-3 mono-, di- and tri~lyceride mixtures. The proceedings of the conference were published (1) and in response to the conference recommendations the National Institutes of Health (NIH) developed a program announcement that led to expansion of research on omega-3 fatty acids. This 1985 conference and other conferences held in 1986, 1987 (2) and 1988 (3,4) focused on the role of omega-3 fatty acids of marine origin. A NATO Advanced Research Workshop was also held in 1986 devoted to "Advanced Technologies and Their Nutritional Implications in the Production of Edible Fats" (5), in which selected aspects concernings the biological effects of highly unsaturated fatty acids of the omega-3 series were presented and discussed. Only slight attention was given to the role of omega-3 fatty acids from terrestrial sources such as alpha-linolenic acid and its metabolism to its longer chain derivatives and its relationship to omega-6 fatty acids, specifically lin01eic acid and arachidonic acid, and most important1y the question of the essentiality of omega-3 fatty acids. Research on these issues has expanded over the past 5 years and the role of omega-3 fatty v acids in growth and development has been progressing in parallel to the research on the role of omega-3 fatty acids in thrombosis, atheroscleroHis,. inflammation, cancer, autoimmune disorders and aging. The long chain members of the omega-3 fatty acid series EPA and DHA are found in relatively high concentrations in lipids from various tissues of marine animals, whereas in terrestrial animals, e.g. mammals, they appear to be concentrated in structural lipids of selected membranes, such as the retina and hte synaptic membranes of the centra] nervous system. In addition, in mammalian tissues mainly the very long chain members of the omega-3 series, DHA is present rather than the less unsaturated product EPA which is found in high concentrations in marine animals. It would thus appear that in terrestrial animals and especially in the highest species, very complex regulatory processes are at work favoring the accumulation of selected highly unsaturated omega-3 fatty acids in specific sites. Also, the endogenous metabolic conversion of the short chain precursor of dietary origin, alpha-linolenic acid, to the long chain highly unsaturated derivatives, rather than the intake of preformed products in the diet appears to be the major process for the utilization of omega-3 fatty acids. Alpha-linolenic acid is very rapidly converted to the long chain members of the omega-3 series, but the incorporation of the formed products into cell phospholipids depends to a large extent on the selectivity of acyl transferase reactions for different substrates, in addition to those of the chain elongating and desaturating enzymes. Finally the interactions of omega-6 and omega-3 fatty acids at various stages of their utilization (intake, desaturation and elongation, transport and uptake in cellular lipids) are certainly important feature::; in the overall fates of long chain polyunsaturated fatty acids of both series. Although the effects of the intake of omega-3 fatty acids on several physiological parameters show interesting applications for the dietary prevention of pathological states, it is felt that a more general and balanced evaluation of the biological roles of both omega-6 and omega-3 fatty acid series in different biological systems, of their relative distribution and stability in different food sources and of the comparative utilization of short chain precursors and long chain productE; of both series, is essential. It was therefore thought timely and most appropriate to hold a NATO Advanced Research Workshop on Dietary w3 and w6 Fatty Acids: Biological Effects and Nutritional Essentiality. The objectives of the workshop were to assess the comparative biological significance of omega-3 and omega-6 fatty acids in relation to the a) dietary availability, utilization and metabolism of different members of these fatty acid series; and b) roles of endogenous long chain members of the omega-3 (e.g. 20:5 and 22:6) and omega-6 (e.g. 20:3 and 20:4) series in different biological systems. vi These aspects were extensively analyzed and discussed at the workshop. The workshop consisted of review papers on various aspects of omega-3 fatty acids and on selected topics on utilization, metabolism and interaction between the fatty acids of the two-series omega-3 and omega-6. There were extensive discussions following each presentation and a special round table discussion on the essentiality of omega-3 fatty acids. Approximately 120 scientists from 15 countries participated. The program consisted of papers presented at plenary sessions and a poster session. There were seven sessions on the following topics: Dietary Sources of Omega-3 and Omega-6 Fatty Acids; Chemistry, Biosynthesis and Interactions of Omega-3 and Omega-6 Fatty Acids; The Role of Omega-3 and Omega-6 Fatty Acids in Development; Biological Effects of Omega-3 and Omega-6 Fatty Acids on Cell Activation Processes; two sessions on The Role of Omega-3 and Omega-6 Fatty Acids in Human Diseases; and a Round Table on the Essentiality of Omega-3 Fatty Acids. Thirthy-two papers and an equal number of posters were presented. The Executive Summary, at the end of the Proceedings, highlights the presentations, discussions, poster session papers and is followed by comprehensive "General Recommendations". We are indebted to the presenters at the workshop, and at the poster session for their excellent papers, and we are confident that the proceedings of this workshop will be an important milestone in the field. Many of the participants emphasized the importance of this workshop and recommended to hold such a workshop every 2 years in order to present new findings and exchange ideas and views in this very rapidly advancing field. Finally, we would like to express our gratitude to the program and workshop participants and the financial sponsors of the workshop, mainly NATO, the Division of Nutritional Sciences-ILSI Research Foundation and the Nutrition Foundation of Italy, and the following cosponsors: BSN, Canola Council, DNA Plant Technology Corporation, Hoffmann-La Roche, ILSI-Europe, Nestle', Procter & Gamble Company, Quaker-Chiari & Forti S.p.A., Ross Laboratories, Star S.p.A., u.s. Department of Commerce-National Marine Fisheries Service, and Warner-Lambert Company. As a last point in this preface, we would like to thank all those who contributed to the success of the workshop. Special thanks are addressed to Daniela Galli for all the burden of the local organization and of the preparation of this volume, to Brita Rolander-Chilo' for the administrative responsabilities, to Peggy Roberts for her help with the international liaisons, in addition to all the others who participated to the organization. Claudio Galli Artemis P. Simopoulos vH REFERENCES 1. A.P. Simopoulos, R.R. Kifer and R.E. Martins,eds., "Health Effects of Polyunsaturated Fatty Acids in Seafoods", Academic Press, Orlando, Fl (1986) 2. The American Oil Chemists' Society (AOCS) Short Course on Polyunsaturated Fatty Acids and Eicosanoids, held May 14-17, 1987 in Biloxi, Mississippi 3. Health Effects of Fish and Fish Oils: An International Conference held July 30-August 2, 1988 in st. John's, Newfoundland 4. The Fifth Acta medica Scandinavica Symposium on N-3 Fatty Acids in health and Disease held August 11-13, 1988 in Tr~mso, Norway 5. C. Galli and E.Fedeli, eds.,"Fat Production and Consumption - Technologies and Nutritional Implications", Plenum Press, New York (1987). viii CONTENTS Dietary sources of w3 and w6 fatty acids Early studies on the biosynthesis of polyunsaturated fatty acids ..................................................... . K. Bloch The food chain for n-6 and n-3 fatty acids with special reference to animal products ............................. 5 M.A. Crawford, W.Doyle, P.Drury, K.Ghebremeskel, L.Harbige, l.Leyton, G.Williams Some aspects of omega-3 fatty acids from di fferent foods ................................................. 21 l.L. Beare-Rogers Linoleic and linolenic acids intake ................................... 33 O. Adam Omega-3 fatty acids from vegetable oils ............................... 43 1 . E. Hunter Preparation of fish oil for dietary applications ...................... 57 H.l. Wille, P.Gonus Chemistry, Biosynthesis and Interactions of w3 and w6 fatty acids (N-3) and (N-6) fatty acid metabolism ................................. 69 H. Sprecher The effect of dietary fish oil supplementation and in vitro collagen stimulation on human platelet phospholipid fatty acid composition ............................. 81 H.M. Aukema, B.l.Holub In vitro studies on docosahexaenoic acid in human platelets ................................................. 91 M. Lagarde, M.Croset, M.Hajarine ix
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