Nutrition and Health Series Editors: Adrianne Bendich · Connie W. Bales Peter Weber Marc Birringer Jeff rey B. Blumberg Manfred Eggersdorfer Jan Frank Editors Vitamin E in Human Health Nutrition and Health Series Editors: Adrianne Bendich, PhD, FACN, FASN Wellington, FL, USA Connie W. Bales, PhD, RD Durham VA Medical Center Duke University School of Medicine Durham, NC, USA The Nutrition and Health series has an overriding mission in providing health professionals with texts that are considered essential since each is edited by the leading researchers in their respective fields. Each volume includes: 1) a synthesis of the state of the science, 2) timely, in-depth reviews, 3) extensive, up-to-date fully annotated reference lists, 4) a detailed index, 5) relevant tables and figures, 6) identification of paradigm shifts and consequences, 7) virtually no overlap of information between chapters, but targeted, inter- chapter referrals, 8) suggestions of areas for future research and 9) balanced, data driven answers to patient/health professionals questions which are based upon the totality of evidence rather than the findings of a single study. Nutrition and Health is a major resource of relevant, clinically based nutrition volumes for the professional that serve as a reliable source of data-driven reviews and practice guidelines. More information about this series at http://www.springer.com/series/7659 Peter Weber • Marc Birringer Jeffrey B. Blumberg Manfred Eggersdorfer • Jan Frank Editors Vitamin E in Human Health Editors Peter Weber Marc Birringer University of Hohenheim University of Applied Sciences Fulda Institute of Nutritional Sciences Nutritional, Food and Consumer Stuttgart Sciences Germany Fulda Germany Jeffrey B. Blumberg Friedman School of Nutrition Science Manfred Eggersdorfer and Policy, Jean Mayer USDA Human University Medical Center Groningen Nutrition Research Center on Aging Hanzeplain 1 Tufts University Groningen Boston, MA The Netherlands USA Jan Frank University of Hohenheim Institute of Nutritional Sciences Stuttgart Germany Nutrition and Health ISBN 978-3-030-05314-7 ISBN 978-3-030-05315-4 (eBook) https://doi.org/10.1007/978-3-030-05315-4 Library of Congress Control Number: 2019934811 © Springer Nature Switzerland AG 2019 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publisher, the authors, and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, express or implied, with respect to the material contained herein or for any errors or omissions that may have been made. The publisher remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. This Humana Press imprint is published by the registered company Springer Nature Switzerland AG The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland We dedicate this book to the diverse community of biochemical, molecular, clinical, and public health scientists exploring the many roles of vitamin E in human health. We especially appreciate the commitment shown by the many devoted scientists who have contributed directly to this book. Last but not the least, we are most grateful to the unending support of our families for the work we do in nutrition science to promote health and treat disease. Peter Weber, MD, PhD Marc Birringer, PhD Jeffrey B. Blumberg, PhD Manfred Eggersdorfer, PhD Jan Frank, PhD Foreword Progress in nutrition science is continuing at an ever more rapid pace. New data from experimental and preclinical studies are emerging at the same time as advanced designs in prospective cohorts, metabolic studies, and clinical trials are providing evidence that needs to be evaluated and translated into dietary guidelines for health promotion and disease prevention. This is no small challenge when nutrition research is criticized as based on confounded or inaccurate methods and scorned for changing recommendations to follow or avoid specific nutrients, foods, and dietary patterns. In fact, when properly evaluated, there is a great deal of concordance between conclusions drawn from multiple research approaches, while changes in the science and recom- mendation largely follow these advances. When there is a discordance between these results, for example, between observational studies and clini- cal trials, then we need to examine them more closely. By doing so, we often gain valuable insights and learn to ask new and more targeted questions. A book like this one provides an opportunity to bring together the disparate information collected from basic research and human studies to be consid- ered jointly in a broad context of applications from food science to public policy. The early reductionist approaches in nutrition research focused on the dis- covery of individual nutrients and their mechanisms in the prevention of cor- responding deficiency syndromes. However, much like more recent holistic approaches to tackling complex biological pathways and to addressing socio- cultural factors that underlie health outcomes, parallels exist for individual nutrients like vitamin E. Most micronutrients have pleiotropic effects on mul- tiple physiological systems, including the microbiome, and interact broadly with other dietary components as well as drugs and environmental toxins. We need to understand better how the various congeners of vitamin E and their metabolites affect the molecular and cellular functions and structures of the body that ultimately impact human health. These issues are urgent because the consumption of vitamin E from foods falls below recommended intakes in about 90 percent of populations around the globe. Together with other under-consumed micronutrients and healthy foods, we continue to be faced with the problem of “hidden hunger” where the effect of these chronic short- falls may not be immediately apparent but whose consequences can be long vii viii Foreword term and profound. After being studied for close to a century, we are far from knowing all that is relevant about vitamin E and other micronutrients. This volume brings together the history and the science of vitamin E and looks to its future in human health. Dariush Mozaffarian, MD, DrPH Friedman School of Nutrition Science and Policy Tufts University Boston, MA, USA Series Editor Page The great success of the Nutrition and Health Series is the result of the con- sistent overriding mission of providing health professionals with texts that are essential because each includes (1) a synthesis of the state of the science; (2) timely, in-depth reviews by the leading researchers and clinicians in their respective fields; (3) extensive, up-to-date, fully annotated reference lists; (4) a detailed index; (5) relevant tables and figures; (6) identification of paradigm shifts and the consequences; (7) virtually no overlap of information between chapters but targeted, interchapter referrals; (8) suggestions of areas for future research; and (9) balanced, data-driven answers to patient as well as health professional questions which are based upon the totality of evidence rather than the findings of any single study. The series volumes are not the outcome of a symposium. Rather, each edi- tor has the potential to examine a chosen area with a broad perspective, both in subject matter and in the choice of chapter authors. The international per- spective, especially with regard to public health initiatives, is emphasized where appropriate. The editors, whose trainings are both research- and practice- oriented, have the opportunity to develop a primary objective for their book, define the scope and focus, and then invite the leading authorities from around the world to be part of their initiative. The authors are encour- aged to provide an overview of the field, discuss their own research, and relate the research findings to potential human health consequences. Because each book is developed de novo, the chapters are coordinated so that the resulting volume imparts greater knowledge than the sum of the information contained in the individual chapters. Vitamin E in Human Health edited by Peter Weber, MD, PhD; Marc Birringer, PhD; Jeffrey B. Blumberg, PhD; Manfred Eggersdorfer, PhD, and Jan Frank, PhD, is a very welcome and timely addition to the Nutrition and Health Series and fully exemplifies the series’ goals. There has been a continuous stream of basic as well as clinical research over the last decade on the associations between oxidative stress and increased risk of cellular dam- age that provide increasing evidence of the critical antioxidant role of vitamin E. Moreover, the recent findings of non-antioxidant functions of the vitamin, including biological activities of metabolites as well as activation of enzymes and, of great significance, vitamin E-gene interactions, are reviewed in depth so that the reader is brought up-to-date on the many new findings at the cel- lular and intracellular levels. With regard to vitamin E, the major lipid-solu- ble antioxidant capable of reducing the adverse effects of oxidative stress, significant clinical research has been published on the importance of vitamin ix x Series Editor Page E in reducing the damage to the vessels and organs of the cardiovascular and cerebrovascular systems in aging populations as well as in the very youngest newborns. Of equal importance are the detailed studies of the critical role of vitamin E in tissues of the nervous and immune systems. Contemporary data on the vitamin E status in at-risk populations, especially in children and women of childbearing potential, are also of great importance; these studies alone warrant the development of this 31-chapter tome. Vitamin E, as an essential fat-soluble nutrient for humans and animal spe- cies, plays key roles in the retina and related brain tissues, lymphocytes, mac- rophages and other immune cells, red cells, sperm and ova, and basically every cell membrane in the body. As a former vitamin E researcher, and Roche colleague of Dr. Peter Weber, I am personally very pleased to note the thoughtful organization of this new volume. There are chapters that review data on the biology and biochemistry of the vitamin, its metabolism and metabolomics, and effects on gene regulation and the genetic defect that results in severe neurological and muscular defects associated with ataxia in isolated vitamin E deficiency; intakes and status in healthy individuals are included as well as an extensive section that is devoted to clinically relevant discussions of safety in healthy individuals as well as in patient populations. The volume is designed as an important resource for nutritionists and dieti- tians, research and public health scientists, diabetes specialists, ophthalmolo- gists, nephrologists, cardiologists, gastroenterologists, and related physicians and healthcare professionals who interact with clients, patients, and/or family members. The volume provides objective, relevant information for professors and lecturers, advanced undergraduates and graduates, researchers, and clini- cal investigators who require extensive, up-to-date literature reviews, instruc- tive tables and figures, and excellent references on all aspects of the importance of vitamin E in human health and disease. The editors of this volume are experts in their respective fields. Dr. Peter Weber, MD, PhD, is Adjunct Professor of Nutrition at the Institute of Nutritional Sciences at the University of Hohenheim, Germany. Dr. Weber received his PhD in Nutritional Sciences from the University of Bonn, Germany, and his MD degree from the University of Mainz, Germany. He then worked at the Research Institute of Child Nutrition in Dortmund, Germany, and then trained in Internal Medicine with a subspecialty in endo- crinology at the University of Mainz, Germany. Dr. Weber practiced medi- cine and clinical research for 10 years before joining the vitamins R&D area at Hoffmann-La Roche in New Jersey, USA, and following the purchase of the Vitamins Division by DSM, he continued to lead the research and devel- opment team human nutrition in various functions until his recent retirement. Dr. Weber has more than 70 peer-reviewed publications in the fields of iodine deficiency and goiter, thyroid diseases, metabolic syndrome, postprandial lipid metabolism, vitamin K, vitamin status of populations, and the role of vitamins and polyunsaturated fatty acids in human health. He is a Coeditor of several books on micronutrients and health. His scientific interests include the role of micronutrients in the prevention of chronic diseases, nutritional status in risk groups such as the elderly, and the emerging topic of nutrition security. Dr. Marc Birringer received his PhD in Chemistry from the University of Siegen (Germany). His postdoctoral research included investigations of the