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Military Strategies for Sustainment of Nutrition and Immune Function in the Field

Committee on Military Nutrition Research

Food and Nutrition Board

Institute of Medicine

NATIONAL ACADEMY PRESS
Washington, D.C.
1999



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--> Military Strategies for Sustainment of Nutrition and Immune Function in the Field Committee on Military Nutrition Research Food and Nutrition Board Institute of Medicine NATIONAL ACADEMY PRESS Washington, D.C. 1999

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--> NATIONAL ACADEMY PRESS 2101 Constitution Avenue, N.W. Washington, DC 20418 NOTICE: The project that is the subject of this report was approved by the Governing Board of the National Research Council, whose members are drawn from the councils of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine. The members of the committee responsible for the report were chosen for their special competences and with regard for appropriate balance. The Institute of Medicine was established in 1970 by the National Academy of Sciences to enlist distinguished members of the appropriate professions in the examination of policy matters pertaining to the health of the public. In this, the Institute acts under both the Academy’s 1863 congressional charter responsibility to be an adviser to the federal government and its own initiative in identifying issues of medical care, research, and education. Dr. Kenneth I. Shine is president of the Institute of Medicine. This report was produced under grant DAMD17-94-J-4046 between the National Academy of Sciences and the U.S. Army Medical Research and Materiel Command. The views, opinions, and/or findings contained in chapters in Parts II through VI that are authored by U.S. Army personnel are those of the authors and should not be construed as official Department of the Army positions, policies, or decisions, unless so designated by other official documentation. Human subjects who participated in studies described in those chapters gave their free and informed voluntary consent. Investigators adhered to U.S. Army regulation 70-25 and United States Army Medical Research and Materiel Command regulation 70-25 on use of volunteers in research. Citations of commercial organizations and trade names in this report do not constitute an official Department of the Army endorsement or approval of the products or services of these organizations. The chapters are approved for public release; distribution is unlimited. Library of Congress Catalog Card No. 98-89702 International Standard Book Number 0-309-06345-0 Additional copies of this report are available from: National Academy Press, 2101 Constitution Avenue, N.W., Lock Box 285, Washington, D.C. 20055 Call (800) 624-6242 or (202) 334-3313 (in the Washington metropolitan area), or visit the NAP's online bookstore at http://www.nap.edu. Copyright 1999 by the National Academy of Sciences. All rights reserved. Printed in the United States of America The serpent has been a symbol of long life, healing, and knowledge among almost all cultures and religions since the beginning of recorded history. The image adopted as a logotype by the Institute of Medicine is based on a relief carving from ancient Greece, now held by the Staatliche Museen in Berlin. Cover: Resting monocyte/macrophage being activated to produce proinflammatory cytokines which form complexes with receptor binding proteins. Adapted from Figure 1-2.

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--> COMMITTEE ON MILITARY NUTRITION RESEARCH ROBERT O. NESHEIM (Chair, through June 30, 1998), Salinas, California JOHN E. VANDERVEEN (Chair), Office of Plant and Dairy Foods and Beverages, Food and Drug Administration, Washington, D.C. LAWRENCE E. ARMSTRONG, Departments of Physiology and Neurobiology, and Exercise Science, University of Connecticut, Storrs, Connecticut WILLIAM R. BEISEL, Department of Molecular Microbiology and Immunology, The Johns Hopkins University School of Hygiene and Public Health, Baltimore, Maryland GAIL E. BUTTERFIELD, Nutrition Studies, Palo Alto Veterans Affairs Health Care System and Program in Human Biology, Stanford University, Palo Alto, California WANDA L. CHENOWETH (from September 18, 1996), Department of Food Science and Human Nutrition, Michigan State University, East Lansing JOHN D. FERNSTROM, Department of Psychiatry, Pharmacology, and Neuroscience, University of Pittsburgh School of Medicine, Pennsylvania G. RICHARD JANSEN (through August 31, 1997), Department of Food Science and Human Nutrition, Colorado State University, Fort Collins ROBIN B. KANAREK, Department of Psychology, Tufts University, Boston, Massachusetts ORVILLE A. LEVANDER, Nutrient Requirements and Functions Laboratory, U.S. Department of Agriculture Beltsville Human Nutrition Research Center, Beltsville, Maryland ESTHER M. STERNBERG, Neuroendocrinology and Behavior Section, National Institute of Mental Health, Bethesda, Maryland DOUGLAS W. WILMORE, Department of Surgery, Brigham and Women's Hospital, Boston, Massachusetts Food and Nutrition Board Liaison JOHANNA T. DWYER, Frances Stern Nutrition Center, New England Medical Center Hospital and Departments of Medicine and Community Health, Tufts Medical School and School of Nutrition Science and Policy, Boston, Massachusetts U.S. Army Grant Officer Representative LTC KARL E. FRIEDL, Military Operational Medicine Program, U.S. Army Medical Research and Materiel Command, Fort Detrick, Frederick, Maryland

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--> Staff REBECCA B. COSTELLO (through May 22, 1998), Study Director MARY I. POOS (from May 23, 1998), Study Director SYDNE J. CARLSON-NEWBERRY, Program Officer MARIZA SILVA (from August 31, 1998), Project Assistant

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--> FOOD AND NUTRITION BOARD CUTBERTO GARZA (Chair), Division of Nutrition, Cornell University, Ithaca, New York JOHN W. ERDMAN, JR. (Vice Chair), Division of Nutritional Sciences, College of Agriculture, University of Illinois at Urbana-Champaign LINDSAY H. ALLEN, Department of Nutrition, University of California, Davis BENJAMIN CABALLERO, Center for Human Nutrition, The Johns Hopkins School of Hygiene and Public Health, Baltimore, Maryland FERGUS M. CLYDESDALE, Department of Food Science, University of Massachusetts, Amherst ROBERT J. COUSINS, Center for Nutritional Sciences, University of Florida, Gainesville JOHANNA T. DWYER, Frances Stern Nutrition Center, New England Medical Center Hospital and Departments of Medicine and Community Health, Tufts Medical School and School of Nutrition Science and Policy, Boston, Massachusetts SCOTT M. GRUNDY, Center for Human Nutrition, University of Texas Southwestern Medical Center at Dallas CHARLES H. HENNEKENS, Harvard Medical School and Brigham and Women's Hospital, Boston, Massachusetts SANFORD A. MILLER, Graduate School of Biomedical Sciences, University of Texas Health Science Center, San Antonio ROSS L. PRENTICE, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington A. CATHARINE ROSS, Department of Nutrition, Pennsylvania State University, University Park ROBERT E. SMITH, R. E. Smith Consulting, Inc., Newport, Vermont VIRGINIA A. STALLINGS, Division of Gastroenterology and Nutrition, The Children's Hospital of Philadelphia, Pennsylvania VERNON R. YOUNG, Laboratory of Human Nutrition, School of Science, Massachusetts Institute of Technology, Cambridge

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--> Ex-Officio Member STEVE L. TAYLOR, Department of Food Science and Technology and Food Processing Center, University of Nebraska, Lincoln Institute of Medicine Council Liaison BARBARA J. CULLITON, Nature Medicine, Washington, D.C. Staff ALLISON A. YATES, Director GAIL E. SPEARS, Administrative Assistant

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--> PREFACE This publication, Military Strategies for Sustainment of Nutrition and Immune Function in the Field, is the latest in a series of reports based on workshops sponsored by the Committee on Military Nutrition Research (CMNR) of the Food and Nutrition Board (FNB), Institute of Medicine, National Academy of Sciences. Other workshops or symposia have included such topics as food components to enhance performance; nutritional needs in hot, cold, and high-altitude environments; body composition and physical performance; nutrition and physical performance; cognitive testing methodology; and fluid replacement and heat stress. These workshops form part of the response that the CMNR provides to the Commander, U.S. Army Medical Research and Materiel Command (USAMRMC), regarding issues brought to the committee through the Military Nutrition Division (currently the Military Nutrition and Biochemical Division) of the U.S. Army Research Institute of Environmental Medicine (USARIEM) at Natick, Massachusetts.

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--> History of the Committee The CMNR was established in October 1982 following a request by the Assistant Surgeon General of the Army that the Board on Military Supplies of the National Academy of Sciences set up a special committee. The purpose of this committee was to advise the U.S. Department of Defense on the need for and conduct of nutrition research and related issues. The CMNR was transferred to the FNB in 1983. The CMNR's current tasks are to identify nutritional factors that may critically influence the physical and mental performance of military personnel under all environmental extremes, to identify deficiencies in the existing database, to recommend research that would remedy these deficiencies as well as approaches for studying the relationship of diet to physical and mental performance, and to review and advise on standards for military feeding systems. Within this context, the CMNR was asked to focus on nutrient requirements for performance during operational missions rather than requirements for military personnel in garrison (the latter were judged to be not significantly different from those of the civilian population). Although the membership of the committee has changed periodically, the disciplines represented consistently have included human nutrition, nutritional biochemistry, performance physiology, food science, and psychology. For issues that require broader expertise than exists within the committee, the CMNR has convened workshops or utilized consultants. The workshops provide additional state-of-the-art scientific information and informed opinion for the consideration of the committee. Committee Tasks and Procedures The request for this review of nutrition and immune function and its application to military operations originated with Army scientists from USARIEM and USAMRMC. In December 1995, a committee subgroup of the CMNR participated in a series of conference calls with USARIEM, USAMRMC, and other CMNR members to identify the key areas that should be reviewed and to solicit suggestions for names of scientists who were active in the research fields of interest. On May 20–21, 1996, the CMNR convened a workshop in response to a request from Army representatives to provide information on the impact of nutritional status on immune function. The purpose of the workshop was twofold: (1) to assess the current state of knowledge about immune function to

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--> ascertain how military stressors (including food deprivation) could impact unfavorably upon these functions and (2) to evaluate ongoing research efforts by USARIEM scientists to study immune status in special forces troops. Organization of the Report The CMNR's background summary, responses to questions, conclusions, and recommendations constitute Part I of this volume; Parts II through VI include papers contributed by speakers at the workshop. Part I has been reviewed anonymously by an outside group with expertise in the topic areas and experience in military issues. For the most part, the authored papers in Parts II through VI appear in the order in which they were presented at the workshop (see the workshop agenda in Appendix E). These chapters have undergone limited editorial changes, have not been reviewed by the outside group, and represent the views of the individual authors. Selected questions directed toward the speakers and the speakers' responses are included when they provide a flavor of the workshop discussion. An overview of the immune system and other host defense mechanisms is presented in Appendix A and a glossary of immunological terms is provided in Appendix B. The invited speakers also were requested to submit a brief list of selected background papers prior to the workshop. These recommended readings, relevant citations collected by CMNR staff prior to the workshop, and selected citations from each chapter are included in the selected bibliography (see Appendix H). Acknowledgments It is my pleasure as chairman of the CMNR to acknowledge the contributions of the FNB staff. Their involvement in the planning, organization, and publication of the proceedings of this workshop was essential in responding to the Army's request for this review. In particular, I wish to acknowledge the excellent efforts of Sydne J. Carlson-Newberry, staff officer for the CMNR. She successfully enlisted the participants and organized the proceedings in a timely manner. Rebecca B. Costello joined the FNB staff as project director for the CMNR in July 1996 and worked actively in organizing the summary and publication of the proceedings, and Mary I. Poos who brought the report to completion. I also wish to commend the workshop speakers for their excellent contributions in preparing papers and participating through their presentations and discussions at the workshop. Without their willing cooperation, this review and report could not have been accomplished.

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--> In addition, I wish to acknowledge the excellent editorial efforts and able assistance of technical editor Judy Grumstrup-Scott and research assistant Susan M. Knasiak-Raley, and project assistant Mariza Silva who also prepared the camera-ready copy for this report. The effort of Donna F. Allen, former senior project assistant to the CMNR, in coordinating the workshop arrangements is greatly appreciated. I express my deepest appreciation to the members of the CMNR who participated extensively during the workshop and in the discussions and preparation of summaries and recommendations in this report. I wish to commend William R. Beisel for his preparation of the overview of the immune system (see Appendix A). I want to thank former committee member Dick Jansen for his contributions and faithful services to the CMNR. I would also like to express appreciation to Gilbert A. Leveille, who rotated off the committee prior to its preparation of this report, for his many years of service. I continue to be stimulated by the committee's dedication and willing contribution of their time and expertise to the activities of the CMNR. I thank all of you for your continuing contributions to this program. This report has been reviewed by individuals chosen for their diverse perspectives and technical expertise, in accordance with procedures approved by the NRC's Report Review Committee. The purpose of this independent review is to provide candid and critical comments that will assisst the authors and the Institute of Medicine in making the published report as sound as possible and to ensure that the report meets institutional standards for objectivity, evidence, and responsiveness to the study charge. The review comments and draft manuscript remain confidential to protect the integrity of the deliberative process. The CMNR wishes to thank the following individuals for their participation in the review of this report: Kent L. Erickson, University of California, Davis; Arthur L. Hecker, Abbott Laboratories; Ronald B. Herberman, University of Pittsburg; John L. Ivy, University of Texas; Melvin M. Mathias, U.S. Department of Agriculture; Charles E. Putman, Duke University; David D. Schnakenberg (retired); Adria R. Sherman, Rutgers University; and Esther M. Sternberg, National Institute of Mental Health. While the individuals listed above have provided many constructive comments and suggestions, it must be emphasized that responsibility for the final content of this report rests entirely with the authoring committee and the IOM. ROBERT O. NESHEIM, CHAIR COMMITTEE ON MILITARY NUTRITION RESEARCH

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--> CONTENTS Preface   vii Executive Summary   1 I Committee Summary, Responses to Questions, Conclusions, and Recommendations     1   A Review of the Role of Nutrition in Immune Function   19 2   Committee Responses to Questions   99 3   Committee Conclusions and Recommendations   125 II Stage Setting: The Military Situation     4   Why Is the Army Interested in Nutrition and Immune Function? LTC Karl E. Friedl   139

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--> 5   Physiological and Immunological Impact of U.S. Army Special Operations Training: A Model for the Assessment of Nutritional Intervention Effects on Temporary Immunosuppression LTC Ronald L. Shippee   163 6   Immune Function Studies During the Ranger Training Course of the Norwegian Military Academy Pål Wiik   185 III Introduction to Immune Function     7   Nutrition and Immune Responses: What Do We Know? Ranjit Kumar Chandra   205 8   Cytokines and Nutritional Status: Possible Correlations and Investigations Jeffrey L. Rossio   221 IV Assessment     9   Methodological Issues in Assessment of Human Immune Function Susanna Cunningham-Rundles   235 10   Application of Whole-Blood Cultures to Field Study Measurements of Cellular Immune Functions In Vitro Tim R. Kramer   249 V Nutrition     11   Glutamine Douglas W. Wilmore   265 12   Vitamin A and Immune Function Richard D. Semba   279 13   Vitamin E, Vitamin C, and Immune Response: Recent Advances Laura C. Rall and Simin Nikbin Meydani   289 14   Fatty Acids and Immune Functions Darshan S. Kelley   305 15   Iron Metabolism, Microbial Virulence, and Host Defenses Gerald T. Keusch   317 16   Trace Minerals, Immune Function, and Viral Evolution Melinda A. Beck   337

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--> VI Health and Stress     17   Exercise, Infection, and Immunity: Practical Applications David C. Nieman   363 18   Neuroendocrine Consequences of Systemic Inflammation Seymour Reichlin   391 19   Inflammatory Stress and the Immune System Leonard P. Kapcala   409 20   Chronobiology of the Immune System Erhard Haus   437 21   Conclusions: Militarily Important Issues Identified in this Report William R. Beisel   497 Appendixes     A   Overview of the Immune System and Other Host Defense Mechanisms William R. Beisel   511 B   Glossary of Immunological Terms William R. Beisel   527 C   Overview of Immune Assessment Tests   537 D   Emerging Infections, Nutritional Status, and Immunity Presentation by Stephen S. Morse, Edited by William R. Beisel   543 E   Workshop Agenda   553 F   Biographical Sketches   559 G   Acronyms and Abbreviations   575 H   Nutrition and Immune Function: A Selected Bibliography   581 Index   657

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