Introduction to Human Nutrition 2nd Edition ( PDFDrive )

Introduction to Human Nutrition Second Edition Edited on behalf of The Nutrition Society by Michael J Gibney Susan A Lanham-New Aedin Cassidy Hester H Vorster A John Wiley & Sons, Ltd., Publication



Introduction to Human Nutrition

The Nutrition Society Textbook Series Introduction to Human Nutrition Nutrition and Metabolism Introduction to Human Nutrition: a global perspective on Core concepts of nutrition food and nutrition Molecular nutrition The regulation of food intake Body composition Integration of metabolism 1: Energy Energy metabolism Integration of metabolism 2: Carbohydrates and lipids Nutrition and metabolism of proteins and amino acids Integration of metabolism 3: Protein and amino acids Digestion and metabolism of carbohydrates Phytochemicals Nutrition and metabolism of lipids Pregnancy and lactation Dietary reference standards Growth and aging The vitamins Gastrointestinal tract Minerals and trace elements Cardiovascular system Measuring food intake The skeletal system Food composition The immune and inflammatory systems Food and nutrition: policy and regulatory issues The sensory systems Nutrition research methodology Physical activity Food safety: a public health issue of growing importance Overnutrition Food and nutrition-related diseases: the global challenge Undernutrition The brain Public Health Nutrition Clinical Nutrition An overview of public health nutrition General principles of clinical nutrition Nutrition epidemiology Metabolic and nutritional assessment Food choice Overnutrition Assessment of nutritional status at individual and Undernutrition Metabolic disorders population level Eating disorders Assessment of physical activity Adverse reactions to foods Overnutrition Nutritional support Undernutrition Ethical and legal issues Eating disorders, dieting and food fads Gastrointestinal tract PHN strategies for nutrition: intervention at the level of The liver The pancreas individuals The kidney PHN strategies for nutrition: intervention at the Blood and bone marrow The lung ecological level Immune and inflammatory systems Food and nutrition guidelines Heart and blood vessels Fetal programming The skeleton Cardiovascular disease Traumatic diseases Cancer Infectious diseases Osteoporosis Malignant diseases Diabetes Pediatric nutrition Vitamin A deficiency Cystic fibrosis Iodine deficiency Clinical cases Iron deficiency Water and electrolytes Maternal and child health Breast feeding Adverse outcomes in pregnancy

Introduction to Human Nutrition Second Edition Edited on behalf of The Nutrition Society by Michael J Gibney Susan A Lanham-New Aedin Cassidy Hester H Vorster A John Wiley & Sons, Ltd., Publication

This edition first published 2009 First edition published 2002 © 2009, 2002 by The Nutrition Society Blackwell Publishing was acquired by John Wiley & Sons in February 2007. Blackwell’s publishing programme has been merged with Wiley’s global Scientific, Technical, and Medical business to form Wiley-Blackwell. Registered office John Wiley & Sons Ltd, The Atrium, Southern Gate, Chichester, West Sussex, PO19 8SQ, United Kingdom Editorial offices 9600 Garsington Road, Oxford, OX4 2DQ, United Kingdom 2121 State Avenue, Ames, Iowa 50014-8300, USA For details of our global editorial offices, for customer services and for information about how to apply for permission to reuse the copyright material in this book please see our website at www.wiley.com/wiley-blackwell. The right of the author to be identified as the author of this work has been asserted in accordance with the Copyright, Designs and Patents Act 1988. 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, electronic, mechanical, photocopying, recording or otherwise, except as permitted by the UK Copyright, Designs and Patents Act 1988, without the prior permission of the publisher. Wiley also publishes its books in a variety of electronic formats. Some content that appears in print may not be available in electronic books. Designations used by companies to distinguish their products are often claimed as trademarks. All brand names and product names used in this book are trade names, service marks, trademarks or registered trademarks of their respective owners. The publisher is not associated with any product or vendor mentioned in this book. This publication is designed to provide accurate and authoritative information in regard to the subject matter covered. It is sold on the understanding that the publisher is not engaged in rendering professional services. If professional advice or other expert assistance is required, the services of a competent professional should be sought. Library of Congress Cataloging-in-Publication Data Introduction to human nutrition / edited on behalf of the Nutrition Society by Michael J. Gibney . . . [et al.]. – 2nd ed. p. ; cm. – (The human nutrition textbook series) Includes bibliographical references and index. ISBN 978-1-4051-6807-6 (pbk. : alk. paper) 1. Nutrition. I. Gibney, Michael J. II. Nutrition Society (Great Britain) III. Series. [DNLM: 1. Nutrition Physiology 2. Food. QU 145 I623 2009] QP141.I665 2009 612.3–dc22 2008035123 A catalogue record for this book is available from the British Library. Set in 10 on 12 pt Minion by SNP Best-set Typesetter Ltd., Hong Kong Printed in Singapore by Fabulous Printers Pte Ltd 1 2009

Contents vii ix Contributors xi xii Series Foreword 1 12 Preface 31 49 Acknowledgments 74 86 1. Introduction to Human Nutrition: A Global Perspective on Food and Nutrition 122 HH Vorster 132 188 2. Body Composition 238 P Deurenberg 276 293 3. Energy Metabolism 305 A Astrup and A Tremblay 324 350 4. Nutrition and Metabolism of Proteins and Amino Acids 361 NK Fukagawa and Y-M Yu 5. Digestion and Metabolism of Carbohydrates J Mathers and TMS Wolever 6. Nutrition and Metabolism of Lipids BA Griffin and SC Cunnane 7. Dietary Reference Standards KM Younger 8. The Vitamins DA Bender 9. Minerals and Trace Elements JJ Strain and KD Cashman 10. Measuring Food Intake UE MacIntyre 11. Food Composition HC Schönfeldt and JM Holden 12. Food and Nutrition: Policy and Regulatory Issues MJ Gibney and A McKevitt 13. Nutrition Research Methodology JA Martínez and MA Martínez-González 14. Food Safety: A Public Health Issue of Growing Importance A Reilly, C Tlustos, J O’Connor, and L O’Connor 15. Food and Nutrition-Related Diseases: The Global Challenge HH Vorster and MJ Gibney Index



Contributors Professor Arne Astrup Dr Bruce A Griffin Head, Department of Human Nutrition, Reader in Nutritional Metabolism, Faculty of Life Sciences, Nutritional Sciences Division, University of Copenhagen, Faculty of Health and Medical Sciences, Copenhagen, Denmark University of Surrey, Guildford, UK Dr David A Bender Sub-Dean (Education), Joanne M Holden University College London Medical School, Nutrient Data Laboratory, London, UK Beltsville, Maryland, USA Professor Kevin D Cashman Department of Food and Nutritional Sciences, Una E MacIntyre University College Cork, Institute for Human Nutrition, Ireland University of Limpopo, Medunsa, Dr Stephen C Cunnane South Africa Departments of Medicine, Physiology and Dr Aideen McKevitt Biophysics and Research Center on Aging, School of Biomedical Sciences, Université de Sherbrooke University of Ulster, Canada Northern Ireland Professor Paul Deurenberg Professor J Alfredo Martínez Associate Professor in Nutrition, Intitute of Nutrition and Food Sciences, Department of Human Nutrition, University of Navarra, Wageningen University, Spain The Netherlands Visiting Professor, Professor Miguel A Martínez-González University Tor Vergata, Rome, Italy Department of Preventive Medicine and Public Nutrition Consultant, Singapore Health, Professor Naomi K Fukagawa University of Navarra, Department of Medicine, Spain University of Vermont, Burlington, Vermont, USA Professor John Mathers Human Nutrition Research Centre, Professor Michael J Gibney Institute for Ageing and Health Department of Clinical Medicine, University of Newcastle, UK Trinity College, Dublin, Ireland Dr Judith O’Connor Food Safety Authority of Ireland, Dublin, Ireland

viii Contributors Professor Hester H Vorster Director of the Centre of Excellence for Nutrition Dr Lisa O’Connor Faculty of Health Sciences, Food Safety Authority of Ireland, North-West University Dublin, Ireland Potchefstroom, South Africa Alan Reilly Dr Thomas MS Wolever Food Safety Authority of Ireland, Department of Nutritional Sciences, Dublin, Ireland Faculty of Medicine, University of Toronto, Professor Hettie C Schönfeldt Canada School of Agricultural and Food Science University of Pretoria, Dr Kate M Younger South Africa Lecturer in Human Nutrition, School of Biological Sciences, Professor JJ (Sean) Strain Dublin Institute of Technology, Professor of Human Nutrition, Ireland Northern Ireland Centre for Food and Health, University of Ulster, Dr Yong-Ming Yu Coleraine, Northern Ireland Department of Surgery, Massachusetts General Hospital and Shriners Burns Christina Tlustos Food Safety Authority of Ireland, Hospital, Dublin, Ireland Harvard Medical School, Boston, Massachusetts, USA Angelo Tremblay Preventive and Social Medicine, Laval University, Ste-Foy, Québec, Canada

Series Foreword The early decades of the twentieth century were a medium for the publication of primary research on period of intense research on constituents of food all aspects of human and animal nutrition by scien- essential for normal growth and development, and tists from around the world. Recognizing the needs of saw the discovery of most of the vitamins, minerals, students and their teachers for authoritative reviews amino acids and essential fatty acids. In 1941, a group on topical issues in nutrition, the Society began pub- of leading physiologists, biochemists and medical lishing Nutrition Research Reviews in 1988. In 1997, scientists recognized that the emerging discipline of we launched Public Health Nutrition, the first inter- nutrition needed its own learned society and the national journal dedicated to this important and Nutrition Society was established. Our mission was, growing area. All of these journals are available in and remains, “to advance the scientific study of nutri- electronic, as well as in the conventional paper form tion and its application to the maintenance of human and we are exploring new opportunities to exploit the and animal health”. The Nutrition Society is the largest web to make the outcomes of nutritional research learned society for nutrition in Europe and we have more quickly and more readily accessible. over 2000 members worldwide. You can find out more about the Society and how to become a member To protect the public and to enhance the career by visiting our website at www.nutsoc.org.uk prospects of nutritionists, the Nutrition Society is committed to ensuring that those who practice as The ongoing revolution in biology initiated by nutritionists are properly trained and qualified. This large-scale genome mapping and facilitated by the is recognized by placing the names of suitably quali- development of reliable, simple-to-use molecular fied individuals on our professional registers and biological tools makes this a very exciting time to be by the award of the qualifications Registered Public working in nutrition. We now have the opportunity Health Nutritionist (RPHNutr) and Registered Nutri- to obtain a much better understanding of how spe- tionist (RNutr). Graduates with appropriate degrees cific genes interact with nutritional intake and other but who do not yet have sufficient postgraduate expe- lifestyle factors to influence gene expression in indi- rience can join our Associate Nutritionist registers. vidual cells and tissues and, ultimately, affect our We undertake accreditation of university degree pro- health. Knowledge of the polymorphisms in key genes grams in public health nutrition and are developing carried by a patient will allow the prescription of accreditation processes for other nutrition degree more effective, and safe, dietary treatments. At the programs. population level, molecular epidemiology is opening up much more incisive approaches to understanding Just as in research, having the best possible tools is the role of particular dietary patterns in disease cau- an enormous advantage in teaching and learning. sation. This excitement is reflected in the several sci- This is the reasoning behind the initiative to launch entific meetings that the Nutrition Society, often in this series of human nutrition textbooks designed for collaboration with sister learned societies in Europe, use worldwide. This was achieved by successfully organizes each year. We provide travel grants and launching the first series in multiple languages includ- other assistance to encourage students and young ing Spanish, Portuguese and Greek. The Society is researchers to attend and participate in these deeply indebted to Professor Mike Gibney and his meetings. team of editors for their tireless work in the last 10 years to bring the first edition of this series of text- Throughout its history a primary objective of the books to its successful fruition worldwide. We look Society has been to encourage nutrition research and forward to this new edition under the stewardship of to disseminate the results of such research. Our first Dr Susan Lanham-New in equal measure. Read, learn journal, The Proceedings of the Nutrition Society, and enjoy. recorded, as it still does, the scientific presentations made to the Society. Shortly afterwards, The British Professor Ian McDonald Journal of Nutrition was established to provide a President of the Nutrition Society



Preface The Nutrition Society Textbook Series started ten The study of human nutrition needs a solid base in years ago as an ambitious project to provide under- the physiology and biochemistry of human metabo- graduate and graduate students with a comprehen- lism and that is the basis of the textbook Nutrition and sive suite of textbooks to meet their needs in terms Metabolism. The present textbook is designed to serve of reference material for their studies. By all accounts two needs. Firstly, many will use this book as an intro- the project has been successful and the Nutrition duction to human nutrition and go no further. Stu- Society Textbook Series have been adapted by all of dents in pharmacy, food science, agriculture and the the best academic nutrition units across the globe. like may take introductory modules to human nutri- The series has been translated into Spanish and tion and leave the subject there but be well informed in Portuguese. the area. Those who will go on to study human nutri- tion will find within this textbook an introduction to This second edition of Introduction to Human the many areas of diet and health that they will go on Nutrition is an update of the very basic foundations to study in greater depths using the remaining text- for the study of human nutrition. Although little has books in the Nutrition Society series. Besides the basic changed, all authors have made whatever updates are biology, students will be introduced to the concept of necessary and we have made some re-arrangements food policy and to the dual challenges to the global of some chapters. The study of human nutrition at food supply, both over and under nutrition. universities across the globe is rapidly expanding as the role of diet in health becomes more evident. As I write, I am handing over the leadership of Indeed, the sequencing of the human genome has the Nutrition Society Textbook Series to Dr Susan highlighted the narrower range of genes controlling Lanham-New at the University of Surrey who has human biology, emphasising the critically important agreed to take on this important task for the Society. role of the environment including diet in human I would like to thank all those with whom I have health. Moreover, we now recognize the important worked with on this project and to wish Sue and her role that diet plays in interacting with our genome new team all the very best. both in utero and in the immediate period of post natal development. Michael J Gibney The Nutrition Society Textbook Series Editors Outgoing Editor-in-Chief Incoming Editor-in-Chief Professor Michael J Gibney Susan A Lanham-New University College Dublin, Ireland University of Surrey, UK Assistant Editor Assistant Editor Julie Dowsett Jennifer Norton University College Dublin, Ireland The Nutrition Society, UK

Acknowledgments With grateful appreciation to all those who have time to make this edition possible. Very special thanks served on the International Scientific Committee and must go to Mike Gibney and Julie Dowsett, for their the Textbook Editors, without whom this task would effort and dedication in seeing this textbook of the be insurmountable and to all the authors who gave second edition through to publication.

1 Introduction to Human Nutrition: A Global Perspective on Food and Nutrition Hester H Vorster Key messages • The hundreds of millions of food- and nutrition-insecure people globally, the coexistence of undernutrition and overnutrition, and • Human nutrition is a complex, multifaceted scientific domain inappropriate nutritional behaviors are challenges that face the indicating how substances in foods provide essential nourish- nutritionist of today. ment for the maintenance of life. • Nutrition practice has a firm and well-developed research and • To understand, study, research, and practice nutrition, a holistic knowledge base. There are, however, many areas where more integrated approach from molecular to societal level is needed. information is needed to solve global, regional, communal and individual nutrition problems. • Optimal, balanced nutrition is a major determinant of health. It can be used to promote health and well-being, to prevent ill- • The development of ethical norms, standards, and values in health and to treat disease. nutrition research and practice is needed. • The study of the structure, chemical and physical characteristics, and physiological and biochemical effects of the more than 50 nutrients found in foods underpins the understanding of nutrition. 1.1 Orientation to human nutrition renaissance with the observation by scientists that intakes of certain foods, later called nutrients, and The major purpose of this series of four textbooks on eventually other substances not yet classified as nutri- nutrition is to guide the nutrition student through the ents, influence the function of the body, protect exciting journey of discovery of nutrition as a science. against disease, restore health, and determine people’s As apprentices in nutrition science and practice stu- response to changes in the environment. During dents will learn how to collect, systemize, and classify this period, nutrition was studied from a medical knowledge by reading, experimentation, observation, model or paradigm by defining the chemical struc- and reasoning. The road for this journey was mapped tures and characteristics of nutrients found in foods, out millennia ago. The knowledge that nutrition – their physiological functions, biochemical reactions what we choose to eat and drink – influences our and human requirements to prevent, first, deficiency health, well-being, and quality of life is as old as diseases and, later, also chronic noncommunicable human history. For millions of years the quest for diseases. food has helped to shape human development, the organization of society and history itself. It has influ- Since the late 1980s nutrition has experienced a enced wars, population growth, urban expansion, second renaissance with the growing perception that economic and political theory, religion, science, med- the knowledge gained did not equip mankind to solve icine, and technological development. the global problems of food insecurity and malnutri- tion. The emphasis shifted from the medical or path- It was only in the second half of the eighteenth ological paradigm to a more psychosocial, behavioral century that nutrition started to experience its first one in which nutrition is defined as a basic human © 2009 HH Vorster.

2 Introduction to Human Nutrition right, not only essential for human development but tual framework, illustrating the complex interactions also as an outcome of development. between internal or constitutional factors and exter- nal environmental factors which determine nutri- In this first, introductory text, the focus is on prin- tional status and health, is given in Figure 1.1. ciples and essentials of human nutrition, with the main purpose of helping the nutrition student to On a genetic level it is now accepted that nutrients develop a holistic and integrated understanding of dictate phenotypic expression of an individual’s gen- this complex, multifaceted scientific domain. otype by influencing the processes of transcription, translation, or post-translational reactions. In other 1.2 An integrated approach words, nutrients can directly influence genetic (DNA) expression, determining the type of RNA formed Human nutrition describes the processes whereby (transcription) and also the proteins synthesized cellular organelles, cells, tissues, organs, systems, and (translation). For example, glucose, a carbohydrate the body as a whole obtain and use necessary sub- macronutrient, increases transcription for the synthe- stances obtained from foods (nutrients) to maintain sis of glucokinase, the micronutrient iron increases structural and functional integrity. For an under- translation for the synthesis of ferritin, while vitamin standing of how humans obtain and utilize foods and K increases post-translational carboxylation of glu- nutrients from a molecular to a societal level, and of tamic acid residues for the synthesis of prothrombin. the factors determining and influencing these pro- Nutrients, therefore, influence the synthesis of struc- cesses, the study and practice of human nutrition tural and functional proteins, by influencing gene involve a spectrum of other basic and applied scien- expression within cells. tific disciplines. These include molecular biology, genetics, biochemistry, chemistry, physics, food Nutrients also act as substrates and cofactors in all science, microbiology, physiology, pathology, of the metabolic reactions in cells necessary for the immunology, psychology, sociology, political science, growth and maintenance of structure and function. anthropology, agriculture, pharmacology, communi- Cells take up nutrients (through complex mecha- cations, and economics. Nutrition departments are, nisms across cell membranes) from their immediate therefore, often found in Medical (Health) or Social environment, also known as the body’s internal envi- Science, or Pharmacy, or Agriculture Faculties at ronment. The composition of this environment is tertiary training institutions. The multidisciplinary carefully regulated to ensure optimal function and nature of the science of nutrition, lying in both survival of cells, a process known as homeostasis, the natural (biological) and social scientific fields, which gave birth to a systems approach in the study demands that students of nutrition should have a of nutrition. basic understanding of many branches of science and that they should be able to integrate different con- Nutrients and oxygen are provided to the internal cepts from these different disciplines. It implies that environment by the circulating blood, which also students should choose their accompanying subjects removes metabolic end-products and harmful sub- (electives) carefully and that they should read widely stances from this environment for excretion through in these different areas. the skin, the kidneys, and the large bowel. 1.3 A conceptional framework for The concerted function of different organs and the study of nutrition systems of the body ensures that nutrients and oxygen are extracted or taken up from the external environ- In the journey of discovery into nutrition science it ment and transferred to the blood for transport and will often be necessary to put new knowledge, or new delivery to the internal environment and cells. The applications of old knowledge, into the perspective digestive system, for example, is responsible for the of the holistic picture. For this, a conceptual frame- ingestion of food and beverages, the breakdown work of the multidisciplinary nature of nutrition (digestion and fermentation) of these for extraction science and practice may be of value. Such a concep- of nutrients, and the absorption of the nutrients into the circulation, while the respiratory system extracts oxygen from the air. These functions are coordinated and regulated by the endocrine and central nervous

Global Perspective on Food and Nutrition 3 Levels of human function Accompanying scientific disciplines (factors) of study Constitutional • Cell nucleus DNA RNA • Molecular biology, foods (Genetic level) • Cells: metabolism • Biochemistry, foods • Biochemistry, physiology, foods • Internal environment • Physiology, pathology, foods, pharmacology, etc. • Circulation • Psychology, pathology, foods, pharmacology, etc. • All organ systems, also • Central nervous system Nutritional status Health/ill-health External environment • Foods, agriculture, food systems, sociology, anthropology, economics, politics, policy, etc. • Food security/insecurity Figure 1.1 Conceptual framework • Household characteristics; care for a holistic, integrated understand- • Social circumstances ing of human nutrition. • Economic circumstances • Housing, sanitation, politics • Agriculture, health services (resources; ideologies) systems in response to the chemical and physical tions. A medical, natural science or biological model composition of the blood and internal environment, underpinned the study of the relationships between and to cellular needs. nutrition and health or ill-health. During the second renaissance, these aspects are not neglected, but The health or disease state of the different organs expanded to include the study of all other external and systems will determine the nutrient requirements environmental factors that determine what and how of the body as a whole. much food and nutrients are available on a global level. These studies are underpinned by social, behav- The central nervous system is also the site or “head- ioral, economic, agricultural, and political sciences. quarters” of the higher, mental functions related to The study of human nutrition therefore seeks to conscious or cognitive, spiritual, religious, and cul- understand the complexities of both social and bio- tural behaviors, which will determine, in response to logical factors on how individuals and populations the internal and external environments, what and maintain optimal function and health, how the how much will be eaten. What and how much is eaten quality, quantity and balance of the food supply are will further depend on what is available, influenced influenced, what happens to food after it is eaten, and by a host of factors determining food security. All of the way that diet affects health and well-being. This these factors, on an individual, household, commu- integrated approach has led to a better understanding nity, national, or international level, shape the exter- of the causes and consequences of malnutrition, and nal environment. of the relationship between nutrition and health. During the first renaissance of nutrition, emphasis was placed on the study of nutrients and their func-

4 Introduction to Human Nutrition 1.4 Relationship between nutrition nutrients. The study of nutrients, the ABC and and health numeric calculations of nutrition, will form a major part of the student’s nutrition journey, and should Figure 1.2 shows that individuals can be broadly cat- include: egorized into having optimal nutritional status or being undernourished, overnourished, or malnour- ● the chemical and physical structure and character- ished. The major causes and consequences of these istics of the nutrient nutritional states are indicated. It is important to realize that many other lifestyle and environmental ● the food sources of the nutrient, including food factors, in addition to nutrition, influence health and composition, the way in which foods are grown, well-being, but nutrition is a major, modifiable, and harvested, stored, processed and prepared, and the powerful factor in promoting health, preventing and effects of these on nutrient composition and nutri- treating disease, and improving quality of life. tional value 1.5 Nutrients: the basics ● the digestion, absorption, circulatory transport, and cellular uptake of the nutrient, as well as regu- People eat food, not nutrients; however, it is the com- lation of all these processes bination and amounts of nutrients in consumed foods that determine health. To read one must ● the metabolism of the nutrient, its functions, know the letters of the alphabet; to do sums one must storage, and excretion be able to count, add, subtract, multiply, and divide. To understand nutrition, one must know about ● physiological needs (demands or requirements) for the nutrient in health and disease, and during special circumstances (pregnancy, lactation, sport events), as well as individual variability ● interactions with other nutrients, nonnutrients (phytochemicals), antinutrients, and drugs Nutritional situation Health consequences, outcomes Optimum nutrition Health, well-being, normal development, Food-secure individuals with high quality of life adequate, balanced and prudent diets • Decreased physical and mental development • Compromised immune systems Undernutrition: hunger • Increased infectious diseases Food-insecure individuals living • Vicious circle of undernutrition, in poverty, ignorance, politically unstable environments, underdevelopment, poverty disrupted societies, war Obesity, metabolic syndrome, cardiovascular Overnutrition disease, type 2 diabetes mellitus, certain Overconsumption of food, cancers: chronic NCDs, often characterized especially macronutrients, plus: by overnutrition of macronutrients and • low physical activity undernutrition of micronutrients • smoking, stress, alcohol abuse Malnutrition Double burden of infectious diseases plus NCDs, Nutrition transition: Individuals often characterized by overnutrition of and communities previously macronutrients and undernutrition of food insecure → confronted with micronutrients abundance of palatable foods → some undernourished, others too many macronutrients and too few micronutrients Figure 1.2 Relationship between nutrition and health. NCD, noncommunicable disease.

Global Perspective on Food and Nutrition 5 ● the consequences of underconsumption and over- not sufficient to understand and address the global consumption of nutrients problem of malnutrition facing mankind today. This perception has resulted in the cultivation of social ● the therapeutic uses of the nutrient science disciplines to support knowledge from the ● factors influencing food and nutrition security and biological sciences to address global malnutrition. food safety. 1.6 Global malnutrition There are more than 50 known nutrients (includ- It is a major tragedy that millions of people currently ing amino acids and fatty acids) and many more live with hunger, and fear starvation. This is despite chemicals in food thought to influence human func- the fact that food security or “access for all at all times, tion and health (Box 1.1). Nutrients do not exist in to a sustainable supply of nutritionally adequate and isolation, except for water and others in some phar- safe food for normal physical and mental develop- maceutical preparations. In foods, in the gut during ment and healthy, productive lives” is a basic human digestion, fermentation and absorption, in the blood right embedded in the constitution of most develop- during transport, and in cells during metabolism, ing countries. It is also despite the fact that sufficient nutrients interact with each other. Therefore, a par- food is produced on a global level (see Box 1.2). Food ticular nutrient should not be studied in isolation, but integrated with other nutrients and seen in the context Box 1.2 of total body function. The study of nutrition also includes how to determine nutrient requirements to Food insecurity: when people live with hunger, and fear starvation. make recommendations for intakes and how nutri- Food security: access for all, at all times, to a sustainable, tional status is monitored by measuring intakes, anthropometry, body composition, biochemical affordable supply of nutritionally adequate and safe food for markers reflecting nutritional status, and the clinical normal physical and mental development and healthy, produc- signs of malnutrition. tive lives. This knowledge of nutrients and their functions will enable the nutritionist to advise individuals what and how much to eat. However, this knowledge is Box 1.1 Classes of nutrients for human nutrition Class/category Subclass/category Nutrient examples Carbohydrates (macronutrients) Monosaccharides Glucose, fructose, galactose Proteins (macronutrients) Disaccharides Sucrose, maltose, lactose Polysaccharides Starch and dietary fiber Plant and animal source proteins Amino acids (n = 20): aliphatic, aromatic, sulfur-containing, acidic, basic Fats and oils (lipids) Saturated fatty acids (macronutrients) Monounsaturated fatty acids Palmitic and stearic acid Polyunsaturated fatty acids (n-3, n-6, Oleic (cis) and elaidic (trans) fatty acids Minerals (micronutrients) Linoleic, α-linolenic, arachidonic, eicosapentaenoic, n-9) docosahexaenoic acid Minerals and electrolytes Trace elements Calcium, sodium, phosphate, potassium, iron, zinc, selenium, copper, manganese, molybdenum, fluoride, Vitamins (micronutrients) Fat soluble chromium Water soluble Retinol (A), calciferols (D), tocopherols (E), vitamin K Water Water Ascorbic acid (C), thiamine (B1), riboflavin (B2), niacin (B3), pyridoxine (B6), folate, cobalamin (B12) Water

6 Introduction to Human Nutrition insecurity is an obstacle to human rights, quality of date of 2015; the blueprint of these goals was agreed life, and human dignity. It was estimated that, during to by all the world’s countries and leading develop- the last decade of the twentieth century, 826 million ment institutions. people were undernourished: 792 million in develop- ing countries and 34 million in developed countries. A 2001 report from the FAO indicated that in In developing countries, more than 199 million chil- 1997–1999 there were 815 million undernourished dren under the age of 5 years suffer from acute or people in the world, of whom 777 million were in chronic protein and energy deficiencies. An estimated developing countries, 27 million in transitional coun- 3.5–5 billion people are iron deficient, 2.2 billion tries and 11 million in the industrialized countries. iodine deficient, and 140–250 million vitamin A defi- The annual decrease in undernourished people from cient. This has led to several global initiatives and the 1990–1992 period was 6 million. To reach the commitments, spearheaded by a number of United World Food Summit’s goal of halving the number of Nations organizations, to reduce global undernutri- undernourished in developing countries by 2015, it is tion, food insecurity, hunger, starvation, and micro- estimated that the annual decrease required is 22 nutrient deficiencies. Some progress has been made million. in reducing these numbers, but the problems are far from solved. Some of the initiatives are: Clearly, this is a huge challenge for food and nutri- tion scientists and practitioners. It would need a ● the 1990 United Nations Children’s (Emergency) holistic approach and understanding of the complex, Fund (UNICEF)-supported World Summit for interacting factors that contribute to malnutrition on Children, with a call to reduce severe and moderate different levels. These include immediate, intermedi- malnutrition among children under 5 years of age by ate, underlying, and basic causes: half the 1990 rate by the year 2000, including goals for the elimination of micronutrient malnutrition ● individual level or immediate causes: food and nutrient intake, physical activity, health status, social ● the 1992 World Health Organization/Food and structures, care, taboos, growth, personal choice Agriculture Organization (WHO/FAO) Interna- tional Conference on Nutrition that reinforced ● household level or intermediate causes: family size earlier goals and extended them to the elimination and composition, gender equity, rules of distribu- of death from famine tion of food within the household, income, avail- ability of food, access to food ● the 1996 FAO-supported World Food Summit during which 186 heads of state and governments ● national level or underlying causes: health, educa- pledged their political will and commitment to a tion, sanitation, agriculture and food security, plan of action to reduce the number of undernour- war, political instability, urbanization, population ished people to half their 1996 number by 2015 growth, distribution and conflicts, war, natural disasters, decreased resources ● the establishment in 1997 of the Food Insecurity and Vulnerability Information and Mapping System ● international level or basic causes: social, economic (FIVIMS) and their Interagency Working Group and political structures, trade agreements, popula- (IAWG), which consists of 26 international organi- tion size, population growth distribution, environ- zations and agencies with a shared commitment to mental degradation. reduce food insecurity and vulnerability and its multidimensional causes rooted in poverty; infor- To address these causes of undernutrition food- mation about these initiatives can be accessed at: insecure and hungry communities and individuals http://www.fao.org/ must be empowered to be their own agents of food security and livelihood development. Complicating ● Millennium Development Goals: the United Nations the task of fighting food insecurity and hunger are articulated eight goals,ranging from halving extreme natural disasters such as droughts, floods, cyclones poverty and hunger, halting the spread of the human and extreme temperatures, ongoing wars and regional immunodeficiency virus (HIV)/acquired immuno- conflicts, as well as the devastating impact of HIV and deficiency syndrome (AIDS) and providing univer- AIDS, especially in sub-Saharan Africa. sal primary education, to be reached by the target In many developing countries, indigenous people have changed their diets and physical activity patterns

Global Perspective on Food and Nutrition 7 to those followed in industrialized countries. Supple- be aware of the dynamics within particular mentary feeding programs in these countries communities responsible for nutritional problems. have often been associated with increasing trends These would include household food security, towards obesity, insulin resistance, and the emergence socioeconomic background, education levels, of chronic diseases of lifestyle in some segments of childcare practices, sanitation, water, energy these populations, while other segments are still sources, healthcare services, and other quality-of- undernourished. life indicators. The community nutritionist will design, implement, and monitor appropriate, com- The coexistence of undernutrition and overnutri- munity-participatory programs to address these tion, leading to a double burden of infectious and problems. chronic, noncommunicable diseases, and the multi- ● The public health or public nutritionist covers the factorial causes of malnutrition, call for innovative health and care practice areas but will also be con- approaches to tackle both undernutrition and overnu- cerned with food security (agricultural) and envi- trition in integrated nutrition and health-promoting ronmental issues on a public level. The public programs, focusing on optimal nutrition for all. health or public nutritionist will, for example, be responsible for nutrition surveillance, and the 1.7 Relationship between nutrition design, implementation, and monitoring of dietary science and practice guidelines that address relevant public health prob- lems. A background knowledge in economics, The journey through the scientific domain of nutri- agriculture, political science, and policy design is tion will, at a specialized stage, fork into different essential for the formulation and application of roads. These roads will lead to the different scopes or nutrition policy in a country. branches of nutrition science that are covered in the second, third, and fourth texts of this series. These Many developing countries will not have the capac- different branches of nutrition science could lead to ity or the financial resources to train and employ the training of nutrition specialists for specific prac- professionals for different specialties. However, future tice areas. specialized training and employment of different pro- fessionals could result in a capacity to address nutri- The main aim of nutrition professionals is to apply tional problems more effectively. nutrition principles to promote health and well- being, to prevent disease, and/or to restore health 1.8 Nutrition milestones: the development (treat disease) in individuals, families, communities of nutrition as a science and the population. To help individuals or groups of people to eat a balanced diet, in which food supply Ancient beliefs meets nutrient needs, involves application of nutri- tion principles from a very broad field to almost every Throughout human existence people have attributed facet of human life. It is therefore not surprising that special powers to certain foods and developed beliefs these different branches or specialties of nutrition and taboos regarding foods. These were often based have evolved and are developing. They include clini- on climatic, economic, political, or religious circum- cal nutrition, community nutrition, public health, stances and principles, but also on observations and public nutrition. It can be expected that there will regarding the relationship between the consumption be overlap in the practice areas of these specialties. of certain foods and health. ● The clinical nutritionist will counsel individuals Recorded examples are ancient Chinese and Indian from a biomedical–disease–behavioral paradigm to philosophers who advised on the use of warming and promote health, prevent disease, or treat disease. cooling foods and spices for certain conditions and The clinical nutritionist will mostly work within the for “uplifting the soul,” the Mosaic laws documented health service (facility-based settings such as hospi- in the Old Testament which distinguished between tals, clinics, private practice). clean and unclean foods, the fasting and halal prac- tices of Islam, and the Benedictine monks from ● The community nutritionist, with additional skills Salerno who preached the use of hot and moist versus from the psychosocial behavioral sciences, should

8 Introduction to Human Nutrition cold and dry foods for various purposes. Hippocrates, that beriberi in Japanese sailors could be prevented the father of modern medicine, who lived from 460 by supplementing their polished rice diets with wheat to about 377 bc, and later Moses Maimonides, who bread, and, eventually, the isolation of the responsible lived in the twelfth century, urged people to practice factor, thiamine or vitamin B1, by Funk in 1911. abstemiousness and a prudent lifestyle. They, and Others are the Nobel Prize-winning discovery by others, advised that, for a long and healthy life, one Minot and Murphy in 1926 that pernicious anemia is should avoid too much fat in the diet, eat more fruit, a nutritional disorder due to a lack of vitamin B12 in get ample sleep, and be physically active – advice that the diet, the description of kwashiorkor as a protein- is still incorporated in the modern, science-based deficiency state by Cecily Williams in 1935, and dietary guidelines of the twenty-first century! the discovery of resistant starch and importance of colonic fermentation for humans by nutritionists of Cultural beliefs the Dunn Clinical Nutrition Centre in the 1980s. The perception that food represents more than its The history of modern nutrition as practiced today constituent parts is still true. Eating together is an is an exciting one to read, and students are encour- accepted form of social interaction. It is a way in aged to spend some time on it. It is often character- which cultural habits and customs, social status, ized by heartbreaking courage and surprising insights. kinship, love, respect, sharing, and hospitality are An example of the former is the carefully documented expressed. Scientists and nutrition professionals clinical, metabolic, and pathological consequences of realize that, when formulating dietary guidelines for hunger and starvation by a group of Jewish doctors traditional living people, cultural beliefs and taboos in 1940 in the Warsaw ghetto: doctors who them- should be taken into account and incorporated. There selves were dying of hunger. An example of the latter are numerous examples of traditional food habits and is the studies by Price, an American dentist, who tried diets, often based on what was available. Today, with to identify the dietary factors responsible for good the world becoming a global village, cultures have dental and overall health in people living traditional learned from each other, and dietary patterns associ- lifestyles. He unwittingly used a fortigenic paradigm ated with good health, such as the Mediterranean in his research, examining the strengths and factors diet, are becoming popular among many cultures. that keep people healthy, long before the term was defined or its value recognized. The first renaissance: development of an evidence base At present, thousands of nutrition scientists examine many aspects of nutrition in laboratories The knowledge of the specific health effects of par- and field studies all over the world and publish in ticular diets, foods, and nutrients is now firmly based more than 100 international scientific nutrition jour- on the results of rigid scientific experimentation. nals. This means that nutrition science generates new Nutrition developed gradually as a science, but knowledge based on well-established research meth- advanced with rapid strides during the twentieth odologies. The many types of experiments, varying century. There are numerous meticulously recorded from molecular experimentation in the laboratory, examples of how initial (often ancient and primitive) through placebo-controlled, double-blinded clinical observations about diet and health relationships led interventions, to observational epidemiological sur- to the discovery, elucidation of function, isolation, veys, and experiments based on a health (fortigenic) and synthesis of the different nutrients. Perhaps the or a disease (pathogenic) paradigm, will be most often quoted example is James Lind’s descrip- addressed in this volume (Chapter 13). The peer- tion in 1772 of how citrus fruit could cure and prevent review process of published results has helped in the scurvy in seamen on long voyages. The anti-scurvy development of guidelines to judge how possible, factor (ascorbic acid or vitamin C) was only isolated probable, convincing, and applicable results from in 1921, characterized in 1932, and chemically syn- these studies are. New knowledge of nutrients, foods, thesized in 1933. Other examples of nutritional mile- and diet relationships with health and disease is, stones are the induction of beriberi in domestic fowl therefore, generated through a process in which many by Eijkman in 1897, the observation of Takaki in 1906 scientists examine different pieces of the puzzle all

Global Perspective on Food and Nutrition 9 over the world in controlled scientific experiments. different substances in plant foods, not yet classified Therefore, nutrition practice today has a firm research as nutrients, will also be examined. These substances base that enables nutritional professionals to practice are produced by plants for hormonal, attractant, and evidence-based nutrition. chemoprotective purposes, and there is evidence that many of them offer protection against a wide range The second renaissance: of human conditions. It is possible that new functions solving global malnutrition of known nutrients, and even new nutrients, may be discovered, described, and applied in the future. There is little doubt that improved nutrition has con- tributed to the improved health and survival times Clinical and community nutrition experienced by modern humans. However, global figures on the prevalence of both undernutrition and Today, the focus has moved from simple experiments overnutrition show that millions of people do not with clear-cut answers to studies in which sophisti- have enough to eat, while the millions who eat too cated statistics have to be used to dissect out the role much suffer from the consequences of obesity. It is of specific nutrients, foods, and diets in multifactorial tempting to equate this situation to the gap between diseases. Nutrition epidemiology is now established the poor and the rich or between developing and as the discipline in which these questions can be developed countries, but the situation is much more addressed. A number of pressing problems will have complex. Obesity, a consequence of overnutrition, is to be researched and the results applied, for example: now a public health problem not only in rich, devel- oped, food-secure countries but also in developing, ● the biological and sociological causes of childhood food-insecure countries, especially among women. obesity, which is emerging as a global public health Undernutrition, the major impediment to national problem development, is the biggest single contributor to childhood death rates, and to impaired physical ● the nutrient requirements of the elderly: in the year growth and mental development of children in both 2000, more than 800 million of the Earth’s inhabit- developing and developed countries. Moreover, a ants were older than 60 years; to ensure a high- combination of undernutrition and overnutrition quality life in the growing elderly population, much in the same communities, in single households, and more needs to be known about their nutrient even in the same individual is often reported. requirements Examples are obese mothers with undernourished children and obese women with certain micronutri- ● the relationships between nutrition and immune ent deficiencies. The perception that these global function and how improved nutrition can help to problems of malnutrition will be solved only in inno- defend against invading microorganisms; in the vative, multidisciplinary, and multisectorial ways has light of the increasing HIV/AIDS pandemic, more led to the second, very recent renaissance in nutrition information in this area is urgently needed research and practice. ● dietary recommendations: despite sufficient, con- 1.9 Future challenges for nutrition vincing evidence about the effects of nutrients and research and practice foods on health, nutritionists have generally not been very successful in motivating the public to Basic, molecular nutrition change their diets to more healthy ones. We need to know more about why people make certain food The tremendous development in recent years of choices in order to design culturally sensitive and molecular biology and the availability of sophisticated practical dietary guidelines that will impact posi- new techniques are opening up a field in which nutri- tively on dietary choices. The food-based dietary ent–gene interactions and dietary manipulation of guidelines that are now being developed in many genetic expression will receive increasing attention countries are a first step in this direction. (see Chapter 15). The effects of more than 12 000 Public health nutrition The single most important challenge facing mankind in the future is probably to provide adequate safe

10 Introduction to Human Nutrition food and clean water for all in an environmentally Functional foods: a new development safe way that will not compromise the ability of future generations to meet their needs. In addition to the Functional foods are new or novel foods, developed hundreds of millions not eating enough food to meet to have specific health benefits, in addition to their their needs for a healthy, active life, an additional 80 usual functions. Examples are spreads with added million people have to be fed each year. The challenge phytosterols, to lower serum low-density lipoprotein to feed mankind in the future calls for improved agri- cholesterol and the risk of coronary heart disease, and culture in drought-stricken areas such as sub-Saharan the development of starchy products with resistant Africa, the application of biotechnology in a respon- starch and lower glycemic indices, to help control sible way, interdisciplinary and intersectorial coop- blood glucose levels. The development and testing of eration of all involved, and a better distribution of the functional foods is an exciting new area. These foods food supply so that affordable food is accessible by may help to improve or restore nutritional status in all. The need for sustained economic growth in poor many people. However, much more should be known countries is evident. about suitable biomarkers to test their efficacy, vari- ability in human response to specific food products, Nutritionists have an important part to play in safety, consumer understanding, and how their ensuring food security for all, a basic human right, in health messages must be formulated, labeled, and the future. One of their main functions would be to communicated. educate and inform populations not to rely too heavily on animal products in their diet, the produc- Food safety tion of which places a much heavier burden on the environment than plant foods. A major challenge The continued provision of safe food, free from would be to convince political leaders and govern- microorganisms, toxins, and other hazardous sub- ments that addressing undernutrition (the major stances that cause disease, remains a huge challenge. obstacle in national development) in sustainable pro- Recent experiences with animals suffering from bovine grams should be the top priority in developing and spongiform encephalopathy (BSE or mad cow disease) poor communities. Another challenge is to develop or from foot-and-mouth disease, or birds infected models based on the dynamics within communities with the influenza A virus (bird flu), have shown how and, using a human rights approach, to alleviate quickly a national problem can become an interna- undernutrition without creating a problem of over- tional one because of global marketing of products. nutrition. There are examples where such models, The list of possible hazardous substances in foods incorporated into community development pro- emphasizes the need for continuous monitoring of grams, have been very successful (e.g., in Thailand). the food supply by health officials (Figure 1.3). Microbial contamination Bacteria and mold (fungi) producing toxins and aflatoxins Toxins cause “food poisoning” and aflatoxins are carcinogenic Natural toxins Agricultural residues Such as cyanide in cassava, solanine in potatoes; Pesticides such as DDT or hormones used to can be produced by abnormal circumstances, promote growth such as bovine somatotrophin could be enzyme inhibitors or antivitamins Environmental contamination Intentional additives Heavy metals and minerals Artificial sweeteners Criminal adulteration, industrial pollution Preservatives Substances from packaging materials Phytochemicals Changes during cooking and processing of foods Modified carbohydrates (for functional foods) Figure 1.3 Potential hazardous substances in food. DDT, dichloro-diphenyl-trichloroethane.

Global Perspective on Food and Nutrition 11 1.10 Perspectives on the future Box 1.3 Future challenges that require exceptional leadership Nutrition research and practice, although it has been • Basic molecular nutrition around for many years, is in its infancy as a basic and • Nutrient–gene interactions applied scientific discipline. The present and future • Role of phytochemicals in health nutrition student will take part in this very exciting • New nutrients? New functions? second renaissance of nutrition and see its matura- tion. However, to influence effectively the nutrition • Community and public health nutrition and health of individuals and populations, the nutri- • Childhood obesity tionist will have to forge links and partnerships with • Requirements of the elderly other health professionals and policy-makers, and • Dietary recommendations will have to develop lateral thinking processes. The • Nutrition of patients with human immunodeficiency virus/ magnitude and complexity of nutritional problems acquired immunodeficiency syndrome facing mankind today demand concerted multidisci- plinary and multisectorial efforts from all involved to • Public nutrition solve them. Therefore, the principal message to take • To feed mankind on a nutrition science journey is that teamwork is • Food security essential: one cannot travel this road on one’s own; partners from different disciplines are needed. • Functional foods Another essential need is the continuous develop- • To ensure that novel foods are effective and safe ment of leadership in nutrition. Leaders on every level of research and practice are necessary to respond to • Food safety the existing challenges of global malnutrition and to • Continuous monitoring face future challenges. • Partnerships with other disciplines The modern advances in molecular biology and • Leadership biotechnology on the one hand, and the persistence of global malnutrition on the other, increasingly The student in nutrition, at the beginning of this demand a re-evaluation of ethical norms, standards, journey of discovery of nutrition as a science, must and values for nutrition science and practice. Direc- make use of the many opportunities to develop lead- tion from responsible leaders is needed (Box 1.3). ership qualities. May this be a happy, fruitful, and There is an urgent need for ethical guidelines and a lifelong journey with many lessons that can be applied code of conduct for partnerships between food in the research and practice of nutrition to make a industries, UN agencies, governments, and academ- difference in the life of all. ics. These partnerships are necessary for addressing global malnutrition in sustainable programs. Further reading Websites http://whq.libdoc.who.int/trs/who_trs_916 http://www.who.int/nutrition/en http://www.ifpri.org http://fao.org/ag/agn/nutrition/profiles_en.stm

2 Body Composition Paul Deurenberg Key messages • Several direct, indirect, and doubly indirect techniques are avail- able to measure body composition, each with its own distinct • Body composition data are used to evaluate nutritional status, advantages and disadvantages. growth and development, water homeostasis, and specific disease states. • The choice of method will be influenced by the availability of instrumentation, invasiveness, and radiation danger to subjects, • Human body composition is studied at atomic, molecular, cellu- price, accuracy required, and application objectives. lar, tissue, and whole body levels. The levels are interrelated. • Interpretation and application of data from body composition • A “normal weight” human body consists of approximately 98% measurements should be carried out with care and should take oxygen, carbon, hydrogen, nitrogen, and calcium; of 60–70% into account the limitations of the method used, age, gender, water, 10–35% fat (depending on gender), 10–15% protein, and and ethnic group. 3–5% minerals. • The variation in body composition between individuals is large, mainly because of variations in fat mass. Variations in fat-free mass are smaller. 2.1 Introduction into the changes occurring during growth and devel- opment. They also form the basis for a number of Mankind has long been fascinated with the composi- methods now widely used to assess body composition tion of the human body. Centuries ago, the Greeks in vivo. dissected human cadavers to obtain an insight into the structure and build of the human body, and draw- Today, it is known that many diseases and disor- ings from the Middle Ages of gross muscle structures ders are related to abnormal body composition or to grace the walls of many famous art galleries. They are changes in body composition. The most common of prized not only for their artistic merit, but also for these conditions is obesity, in which the amount of what they reveal of the work of the dissectionists of body fat is excessively high, leading to abnormalities that era. With progress in the development of analyti- in lipid and carbohydrate metabolism, high blood cal chemical methods in the twentieth century, these pressure, and adult-onset diabetes. At the other end studies of body composition were applied to body of the nutritional spectrum, energy and protein mal- tissues, fetuses, and cadavers of newborns. Scientists nutrition results in a decrease in the amount of fat such as Mitchell, Widdowson, and Forbes performed and protein stores in the body, and many diseases are the most important work of chemical analyses in related to abnormalities in total body water or to the adult cadavers during the 1940s and 1950s. Today, distribution of body water across the intracellular and neutron activation analysis allows the chemical com- extracellular spaces. position of the human body to be studied in vivo. These early chemical analyses of the body gave insights Because of the high variability between subjects in chemical body composition, mainly due to the high variation in body fat stores, the concept of fat-free © 2009 P Deurenberg.

Body Composition 13 mass (FFM) was introduced at the end of the nine- Table 2.1 Body composition at the atomic level of a 70 kg reference teenth century. If body composition data are expressed man as a proportion of the FFM, data become much more consistent between individuals. For example, the Atomic element Amount (kg) Amount (% body weight) fraction of water in the FFM (0.73 ± 0.02) is very consistent across individuals, whereas the between- Oxygen 43 61 subject variation is two to three times higher if Carbon 16 23 expressed per kilogram of body weight. This high Hydrogen 7 10 variability in body components led to the definition Nitrogen 1.8 2.6 of a “reference man,” an imaginary person with a Calcium 1.0 1.4 given body composition. Phosphorus 0.6 0.8 Total 69.4 98.8 In this chapter a (global) description of the com- position of the healthy human body is given and dis- Box 2.1 cussed at the following levels: The water content in the body varies with age. In a fetus, the water ● atomic content slowly decreases from more than 90% after conception to ● molecular about 80% before delivery at about 7 months of gestation. A ● cellular newborn has about 70% body water, which is about 82% of the ● tissue fat-free mass. This value slowly decreases further to 72% of the ● whole body. fat-free mass until the body is chemically mature at age 15–18 years. In general, males have more body water (related to body Of the many methods available to measure body weight) than females, as their body fat content is lower. composition, a few are highlighted and a short description of each is given. For more detailed infor- still forms the basis for many in vivo techniques that mation, the books by Forbes (1987) and Heymsfield are used to assess body composition. et al. (2005) on human body composition are recom- mended for further reading. Molecular level 2.2 Five levels of body composition The chemical elements in the human body are bound in molecules and, in very global terms, the main com- Human body composition can be studied at the partments are water, lipids, proteins, minerals, and atomic, molecular, cellular, tissue, and whole body carbohydrates. The total amount of water in the body level. These five levels are related to each other. For is high and, depending on the body fat content, can example, information at the atomic level can be used, be as high as 60–70% of total body weight. Total body subject to certain assumptions, to provide informa- water can be divided into intracellular water and tion at the whole body level. extracellular water, and the ratio of the two is an important health parameter that is disturbed in many Atomic level diseases (Box 2.1). Many chemical elements (atoms) are found in the Lipids appear in the human body in different human body, but the six elements oxygen, carbon, forms. Essential structural lipids such as the phospho- hydrogen, nitrogen, calcium, and phosphorus are the lipids (cell membranes) and sphingomyelin (nervous most abundant and together account for more than system) form only a minor part of the total lipids in 98% of body weight (Table 2.1). Indeed, the 11 most the body. The nonessential lipids, mostly triglycerides common elements account for 99.5% of the atomic or triacylglycerol (fat), are the most abundant. They body composition. This information was initially are the energy store of the adult human body, insulate based on chemical analysis of carcasses, but today the against cold, protect vital organs such as the kidneys information can also be obtained by in vivo neutron against mechanical damage, and, to a certain extent, activation analysis (IVNAA). The classical chemical enhance the body’s appearance. In a “normal weight” cadaver analysis, as carried out mainly in the 1940s, healthy adult, the amount of body fat varies between 10% and 25% in men and between 15% and 35% in

14 Introduction to Human Nutrition Table 2.2 Body composition at the molecular level of a 70 kg refer- Table 2.3 Body composition at the tissue level of a 70 kg reference ence man man Component Amount (kg) Amount (% body weight) Tissue/organ Amount (kg) Amount (% body weight) Water 18 26 Muscle 28 40 Extracellular 24 34 Adipose tissue 15 21.4 Intracellular Blood 5.5 7.9 1.5 2.1 Bone 5 7.1 Lipid 12 17 Skin 2.6 Essential 10.1 14.4 Liver 1.8 3.7 Nonessential 5.3 Total 57.9 2.6 3.7 82.7 Protein 0.5 0.6 Mineral 69.8 99.4 Carbohydrate Total women. In severe obesity body fat can be as high as Tissue level 60–70% of body weight. Cells with equal functions form tissues, including Body protein varies between 10% and 15%. It is muscular, connective, epithelial, and nervous tissue. higher in males than in females, as males generally have Bones are connective tissue and consist mainly of more muscles. There is no protein storage in the body hydroxyapatite, [Ca3(PO4)2]3Ca(OH)2, bedded in a and, generally speaking, loss of protein coincides with protein matrix. A rather simple body composition a loss of functionality given the high protein content model at the tissue level would be: and high protein turnover rates in vital organs. Body weight = adipose tissue + skeletal muscle The amount of minerals in the body varies between + bone + organs + rest 3% and 5%, again dependent on body fat. Calcium and phosphorus are the two main minerals. They are Several of these components can now be measured found mainly in bones. Carbohydrates are found in with, for example, computed tomography (CT) or the body as glucose (blood sugar) and glycogen, a magnetic resonance imaging (MRI) for adipose tissue; polysaccharide in muscle and liver cells that serves as creatinine excretion or N-methyl-histidine excretion a short-term energy store. The amount of carbohy- in 24 h urine for skeletal muscle; dual-energy X-ray drates in the body rarely exceeds 500 g. Table 2.2 gives absorptiometry (DXA) for bones; and MRI or ultra- the body composition of the reference man at a sound for organs. Body composition at the tissue level molecular level. is given in Table 2.3. Cellular level Whole body level At the cellular level, body composition can be Body composition measurements at the whole body described in terms of body cell mass, extracellular level use simple body parameters to give an insight fluids, and extracellular solids. The body cell mass into body composition. Formulae, based on statistical includes the cells with all their contents, such as water, relationships that have been established in earlier proteins, and minerals. Extracellular fluid contains studies between body parameters (e.g., skinfold thick- about 95% water, which is plasma in the intravascular ness) and information on body composition (e.g., space and interstitial fluid in the extravascular space. body fat by density), also enable the assessment of Extracellular solids are mainly proteins (e.g., colla- body composition. Another example is the assess- gen) and minerals (bone minerals and soluble miner- ment of body water based on weight, height, age, and als in the extracellular fluid). Body composition at the gender. cellular level is not easy to measure, owing to its complex nature. As will be discussed later, the 40K 2.3 Relationships between different method can be used to assess body cell mass and some levels of body composition dilution techniques, for example bromide dilution, can be used to assess extracellular water. The five levels of body composition are interrelated. This means that information at one level can be trans-

Body Composition 15 Box 2.2 Table 2.4 Methods used to determine body composition Adipose tissue is made of adipocytes, which are cells that store Direct Indirect Doubly indirect triglycerides in the form of small fat droplets. Adipose tissue con- tains about 80% triglycerides and some 1–2% protein (enzymes), Carcass analyses Densitometry Weight/height indices and the remaining part is water plus electrolytes. During weight IVNAA Skinfolds/ultrasound loss adipose tissue decreases: the actual fat loss will be about 80% Deuterium oxide of the actual weight loss. dilution Circumferences/diameters Impedance lated to another level. This is important as it forms 40K counting the basis of many techniques used to determine body More-compartment Infrared interactance composition. In the context of this chapter, only a few Creatinine excretion examples are given. After determining the amount of models calcium in the body by, for example, IVNAA (atomic DXA level), the amount of bone can be calculated assuming CT/MRI scans that a certain amount of total body calcium is in the skeletal tissue. Determination of total body potassium IVNAA, in vivo neutron activation analysis; DXA, dual-energy X-ray (by 40K or IVNAA) enables the assessment of the body absorptiometry; CT, computed tomography; MRI, magnetic resonance cell mass, as most of the body potassium is known to imaging. be intracellular. Skinfold thickness measurements (total body level) enable the assessment of body fat ● In direct methods, the body component of interest (molecular level). Formulae used for these calcula- is determined directly without or with only minor tions are component based, property based, or some- assumptions. Examples are chemical carcass analy- times a combination. Component-based formulae ses and IVNAA for the atomic components. are based on fixed relationships between components. An example is the calculation of total body water ● In indirect techniques, the body component of from measured hydrogen: the chemical formula of interest is determined indirectly. Examples are the water determines the factor. Property-based formulae determination of body protein from body nitrogen, are based on established statistical relationships assuming a constant conversion factor of 6.25 from between variables. An example is the prediction of nitrogen to protein, and the determination of body body fat percentage (body composition parameter) cell mass using 40K. In both examples, assumptions from skinfold thickness (property) (Box 2.2). are used. These assumptions may not be valid in Property-based formulae tend to be population spe- the given situation or for the subject(s) under study cific, which limits the widespread application. and hence could lead to biased results. Most body composition techniques that are in ● Doubly indirect methods rely on a statistical rela- use today are based on assumptions, often derived tionship between easily measurable body para- from carcass analyses or experimentally derived from meter(s) and the body component of interest. observational studies. Violation of these assumptions Examples are the assessment of skeletal muscle mass leads to biased results, and some methods are more by creatinine excretion and the assessment of body prone to bias than others. In the following short fat from skin-fold thickness. Table 2.4 gives an over- description of different methodologies, the most view of the most common methods. important assumptions are highlighted. 2.5 Direct methods 2.4 Body composition techniques Carcass analysis Body composition techniques can be described in terms of direct, indirect, and doubly indirect The (chemical) analysis of carcasses is a time- methods. consuming exercise and requires very precise approaches to the task. The carcass has to be carefully dissected into the different tissues that are then exactly weighed, after which the chemical analyses have to be performed. To avoid errors it is important that no unaccounted water losses occur during the analytical work. As early as the nineteenth century, it was rec- ognized that the variation in chemical body composi- tion was reduced when results were expressed as a

16 Introduction to Human Nutrition fraction of the fat-free body. The data on the chemical example, from total body nitrogen total body protein composition of only a few human cadavers form the can be calculated as 6.25 times the total nitrogen, basis for the assumptions that are normally used in assuming that body protein consists of 16% nitrogen. indirect methods. These chemical analyses were per- The advantage of the method is that the chemical formed in five men and one woman. It was concluded body composition can be determined in vivo and can that, on the basis of FFM, the mean amounts of water, be compared with other, indirect, techniques. For protein, and minerals in the body are 72.6%, 20.5%, fundamental studies and for validation of existing and 6.9%, respectively. The variability in these figures techniques in special groups of subjects, for example is about 13% for protein and minerals and 4% for in different ethnic groups, elderly subjects, obese sub- water. Although one can question the quality of these jects, or in the diseased state, the methodology can be data as a basis for other methods (low number, high of great importance. The disadvantage of IVNAA is variation in age, variation in gender, some carcasses not only the price. The subject is irradiated, with the were not analyzed immediately after death), they radiation dose used depending on the number and form the basis for many indirect and doubly indirect kind of elements to be determined. It is relatively body composition methods. Chemical carcass analy- low for nitrogen (0.26 mSv) but high for calcium sis also revealed that the amount of potassium in the (2.5 mSv). FFM is fairly constant. This fact is used as the basis for the calculation of the amount of FFM or for body 2.6 Indirect methods cell mass from total body potassium, determined by 40K scanning. Densitometry In the 1980s, cadaver studies were performed again The densitometric method assumes that the body in the “Brussels study.” Unfortunately, only informa- consists of two components, a fat mass, in which all tion at a tissue level and not at atomic or molecular “chemical” fat is located, and the FFM, which consists level was collected. However, the need for cadaver of (fat-free) bones, muscles, water, and organs. studies has greatly diminished given that the same Chemically, the FFM consists of water, minerals, information can now be obtained in vivo by protein, and a small amount of carbohydrate, the last IVNAA. often being neglected. The density of the fat mass is 0.900 kg/l and, from carcass analysis data, the density In vivo neutron activation analysis of the FFM can be calculated as 1.100 kg/l, depending on the relative amount of minerals, protein, and IVNAA is a relatively new body composition tech- water in the FFM (Box 2.3). nique that allows the determination of specific chemi- cal elements in the body. The body is bombarded with The density of the total body depends on the ratio fast neutrons of known energy level. The neutrons of fat mass to FFM. Once the density of the body has can be captured by chemical elements (as part of mol- been determined, the percentage of fat in the body ecules) in the body, resulting in a transition state of (BF%) can be calculated by Siri’s formula (Box 2.4): higher energy for that element – energy that is finally emitted as gamma rays. For example, capture of BF% = (495/body density) − 450 neutrons by nitrogen results in the formation of the isotope 15N, which will emit the excess energy as Body density can be determined by several tech- gamma rays: niques, the oldest and perhaps most accurate being underwater weighing. Behnke first used the tech- 14N + 1n → 15N* + gamma rays nique, showing that excess body weight in American football players was not the result of excess fat but of where 14N is nitrogen with atomic mass 14, 15N is enlarged muscle mass. nitrogen with atomic mass 15, and 1n is a neutron. In underwater weighing, the weight of the subject With IVNAA, many elements in the body can be is first measured in air and then while totally immersed determined, including calcium, phosphorus, nitro- in water. The difference between weight in air and gen, oxygen, potassium, and chlorine. weight under water is the upwards force, which equals the weight of the displaced water (Archimedes’ law), The information obtained at the atomic level can be converted to more useful information. For

Body Composition 17 Box 2.3 The density of the fat-free mass (FFM) can be calculated if its com- position is known. In the calculation example below it is assumed that the FFM consists of 73.5% water, 19.6% protein, and 6.9% minerals with densities (at 37°C) of 0.993, 1.340, and 3.038 kg/l, respectively. In addition, it is assumed that the volumes of the separate com- partments can be added up to the total volume of the FFM (in fact, the compartments do not “mix”). Thus, the volume of the FFM equals the sum of the other compartments: FFMvolume = Watervolume + Mineralvolume + Proteinvolume As volume is weight/density, the equation can be written as: 100/DensityFFM = 73.5/0.993 + 6.9/3.038 + 19.6/1.340 From this, the density of the FFM can be calculated as 1.0999 kg/l. It is obvious that differences in composition of the FFM will result in a different density. Box 2.4 Siri’s formula can be derived assuming that the body consists of fat Figure 2.1 Underwater weighing. The subject is submerged com- mass (FM) and fat-free mass (FFM). If body weight is assumed to pletely and breathes via a respirometer (1) for simultaneous residual be 100% and body fat is x%, then FFM is 100 − x%. It is assumed lung volume measurement. Weight (W) (2) under water (uw) is that the volumes of these two compartments can be added up to recorded and density (D) is calculated as Dbody = Wair/(Wair − Wuw). total body volume. Then: Corrections are made for water temperature and lung volume: percent- age of fat in the body = 495/Dbody − 450. Bodyvolume = FMvolume + FFMvolume fat is assumed to be maximal 3% of BF%. This error As volume is weight/density, the equation can be written as: is mainly due to violation of the assumption that the density of the FFM equals 1.100 kg/l in the subject 100/body density = x/0.9 + (100 − x)/1.1 under study. It can be argued that in certain subjects or groups of subjects this assumption may be vio- From this, body fat percentage (BF%) can be calculated as: lated, as for example in young children and in preg- nant women. Use of Siri’s formula will then lead to BF% = 495/density − 450 biased conclusions. Some laboratories have attempted to use water displacement instead of underwater The general formula to calculate BF% from body density (Db) is: weighing, but the technique failed, mainly because of the difficulty in accurately reading the water level in BF% = 1 × ⎝⎜⎛ DFFM × DFM ⎞⎟⎠ − ⎛⎝⎜ DFM ⎟⎠⎞ the tank. Db DFFM − DFM DFFM − DFM An air-displacement method has been commer- In general, a lower density of the FFM than 1.1 kg/l will result in an cially available since 1995. This method measures overestimation of BF% if Siri’s formula is used. It is likely that the body volume after placing the subject in a small, air- density of the FFM is lower in elderly people, owing to bone tight chamber and increasing the pressure by adding mineral loss (osteoporosis). a known amount of air into the chamber. Boyle Gay- Lussac’s law enables the calculation of body volume. Densitometry (using Siri’s equation) overestimates body fat Corrections are made for temperature and humidity compared with a four-compartment model (see Figure 2.7). changes, and lung volume is assessed simultaneously. from which, after correction for the water tempera- ture (density), the displaced water volume (and thus the body volume) can be calculated. Corrections must be made for residual lung volume and air in the gut. Figure 2.1 shows an underwater weighing. The technique gives very reproducible results within about 1% of BF%. The absolute error in determined body

18 Introduction to Human Nutrition Research to date has generally shown good agreement Bias in body fat percentBox 2.5 between underwater weighing and air displacement. Air displacement is better accepted by the volunteers, A person with a body weight of 75 kg is given an exactly weighed but some experience difficulties because of the dose of 15 g deuterium oxide. This deuterium oxide is allowed to breathing pattern to be followed or because of be equally distributed in the body water compartment for about claustrophobia. 3–5 hours. Then, blood is taken and the deuterium concentration in the sample is determined. Assuming the plasma level to Dilution techniques be 370 mg/kg, the “deuterium space” can be calculated as 15 000/370 = 40.5 kg. As deuterium exchanges in the body with Carcass analyses revealed that the amount of water in hydroxyl groups from other molecules, the deuterium space has to the FFM is relatively constant at about 73%. Total be corrected for this nonaqueous dilution (4–5%). Thus, total body body water (TBW) can be determined by dilution water is 0.95 × 15 000/370 = 38.5 kg. Assuming a hydration of techniques. Dilution techniques are generally based the fat-free mass of 73%, the body fat percentage of this 75 kg on the equation: weight subject would be: 100 × [75 − (38.5/0.73)/75] = 29.7%. C1 × V1 = C2 × V2 = Constant Box 2.6 where C is the tracer (deuterium oxide, tritium, or 7 18O water) concentration and V is the volume. 6 5 When a subject is given a known amount of a tracer 4 (C1 × V1), which is known to be diluted in a given 3 body compartment, the volume of that body com- 2 partment can be calculated from the dose given and 1 the concentration of the tracer in that compartment 0 after equilibrium has been reached. Suitable tracers -1 for the determination of TBW are deuterium oxide, 70 71 72 73 74 75 tritium oxide, and 18O-labeled water. Other tracers can also be used, such as alcohol and urea, but they Percent water in FFM are less suitable because they are partly metabolized (alcohol) or because they are actively excreted from For the computation of body composition from dual-energy X-ray the body (urea) during the dilution period. After absorptiometry, especially body fat and lean tissue, several giving a subject the tracer and allowing around 3–5 assumptions are made, one of which is a constant hydration of the hours for equal distribution throughout the body, fat-free mass (FFM). The figure shows that the bias in calculated determination of the concentration of deuterium in body fat percentage depends on the hydration of the FFM. blood, saliva, or urine allows the calculation of TBW (Box 2.5). Reference is a four-compartment model. Alternatively, other tracers can be used, such as jects with a larger than 73% water content in the FFM tritium oxide and 18O-labeled water, and the tracer (pregnant women, morbid obese subjects, and patients can be given intravenously, which is advantageous with edema), the factor 0.73 will result in an overesti- when the subject has gastrointestinal disorders. The mation of the FFM. A three-compartment model of reproducibility of the method is 1–3%, depending on the body that contains fat mass, water, and dry FFM the tracer used and the analytical method chosen. has a lower bias than a two-compartment model. From TBW, the FFM, and hence fat mass, can be An overestimation of body fat by densitometry, for calculated, assuming that 73% of the FFM is water: example because of a relatively high amount of water in the FFM, will be counteracted by an underestima- BF% = 100 × (Weight − TBW/0.73)/Weight tion using the dilution method (see also Box 2.6). The precision for estimations of body fat is about The use of tracers that do not cross the cell mem- 3–4% of body weight. As with the densitometric brane enables the determination of extracellular method, this error is due to violations of the assump- tion used (i.e., that the relative amount of water in the FFM is constant and equals 73% of the FFM). In sub-

Body Composition 19 water (ECW). Commonly used tracers in this respect 3TBK:FFM are bromide salts or sodium-24. Intracellular water (ICW) cannot be determined directly and is calcu- Men lated as the difference between TBW and ECW. 2 Total body potassium Women Chemical carcass analysis has revealed that the amount of potassium in the fat-free body is relatively con- 1 stant, although the amount of potassium in 25 45 65 85 different tissues varies widely. The determination Age (years) of total body potassium (TBK) is relatively easy, owing to the natural occurrence of three potassium isotopes Figure 2.2 Difference in total body potassium (TBK) content of the (39K, 40K, and 41K), in constant relative amounts, of fat-free mass (FFM) between men and women and the relationship which 40K is radioactive (gamma emission). Counting with age. the emission of the gamma rays from the body reveals the amount of radioactive potassium, from which instrument’s software generates a two-dimensional TBK and hence FFM can be calculated. The chamber picture of the body or the body compartment under in which the subject is scanned has to be carefully study. The software can calculate several body com- shielded to avoid any background radiation (cosmic ponents: bone mineral content and bone mineral radiation). The scanning of the body for potassium density, lean mass, and adipose tissue fat mass. These lasts for 20–30 min and the reproducibility is 2–3%. calculations are possible for each of the body parts, e.g., for legs, trunk, spine, femur, and arms. However, Several authors have shown that the amount of the method cannot distinguish between subcutane- potassium in the FFM is different between males and ous adipose tissue and discrete adipose tissue sites females, is lower in obese subjects, and is probably such as perirenal adipose tissue. The reproducibility also age dependent. Thus, TBK is much more useful of DXA is very high, varying from about 0.5% for as a measure of body cell mass (BCM) than as a bone mineral density to about 2% for total body com- measure of FFM. However, this discrepancy can be position. The reproducibility for regional body com- used to calculate the “quality” of FFM, defined as the position is less. The method is quick and easy to ratio of cellular to extracellular components of FFM, perform and places very few demands on the subject. or operationally as BCM/FFM. Thus, when TBK is The radiation dose (0.02 mSv) is only a fraction of the used to assess BCM, and another method such as radiation dose of a normal chest radiograph, and hydrodensitometry or DXA is used to assess FFM hardly higher than the normal background. Apart independently, it can be shown that the quality of from repeated scanning, the radiation dose should FFM declines with age, along with the quantity (Figure not be a limiting factor in terms of volunteers being 2.2). When potassium values are used to calculate exposed to hazardous levels of radiation. A disadvan- intracellular water, BCM, or FFM, assuming constant tage of the method is that the attenuation of the X- amounts of potassium in these body components, the rays depends on the thickness of the tissue. Therefore, same errors can occur as with densitometry and dilu- correction for the body size has to be made. Compared tion techniques. with traditional methods, DXA scanning is easy and widely available which, in turn, leads to prediction Although the technique is easy to apply in patients, the high cost of the scanning instrumentation limits its use other than in research settings. Dual-energy X-ray absorptiometry During DXA (also known as DEXA), the body or part of the body is scanned with X-rays of two distinct levels of energy. The attenuation of the tissues for the two different levels of radiation depends on its chemi- cal composition and is detected by photocells. The

20 Introduction to Human Nutrition equations for body composition based on DXA. Figure 2.3 Dual-energy X-ray absorptiometer (DXA) scan using a However, as with other methods, DXA relies on HOLOGIC whole-body DXA (QDR-4500). Subcutaneous body fat, bone, certain assumptions (Box 2.6) and there are many and muscle are distinguished by different colors. publications showing that the error in body composi- tion measurements using DXA can be considerable (Figure 2.3). Moreover, identical machines, even using the same software versions, can give different results in scanning the same person. Multicompartment models Two-compartment models, consisting of fat mass and FFM, lack validity in many situations where the composition of the body is “abnormal.” Examples already mentioned are pregnancy, morbid obesity, and the elderly. A combination of techniques often results in more valid estimates, as is the case when, for example, body density and body water are com- bined. In this particular case, the body is divided into three compartments: Body weight = Fat mass + Body water + Dry fat-free mass In this three-compartment model the variation of the water content in the FFM is accounted for. There are fewer assumptions in this model, leading to more valid results. Modern techniques such as DXA enable the valid and precise measurement of bone mineral, from which total body mineral can be estimated. When the mineral content of the body is com- bined with body density and body water, a four- compartment model of the body is generated: Body weight = Fat mass + Water + Minerals + Protein In this model, most of the variation in the amounts of the chemical components is accounted for, result- ing in a very reliable body composition measure (Box 2.7). Four-compartment models can also be obtained using other techniques. For example, the measure- ment of calcium, phosphorus, and nitrogen with IVNAA in combination with TBW provides informa- tion for a model consisting of fat, minerals, protein, and water. In the literature, models based on six compartments are also described. However, they do not provide much additional information and the increased technical error negates the methodological advantage. More-compartment models enable the best possi- ble estimate of body composition for populations as

Body Composition 21 Box 2.7 FM FM M+P M FM P FFM TBW TBW The first bar represents a two-compartment model of body compo- Figure 2.4 Magnetic resonance imaging scan at the L4 level in an sition, in which the body is divided into fat mass and fat-free mass obese subject. The white areas in the image are adipose tissue. Sub- (FFM). In the second bar, the FFM is divided into water and a “dry” cutaneous adipose tissue and intra-abdominal adipose tissue are sepa- FFM, consisting of protein and mineral. The third bar shows a four- rated by the abdominal muscles. compartment model in which the body is divided into water, protein, mineral, and fat. The four-compartment model shown has amounts of tissues with different attenuation, for only minor assumptions and provides body composition data that example adipose tissue against nonadipose tissue. are very accurate. The CT technique was introduced for body composi- tion assessments in the 1980s and is now widely used, well as for individuals. Although some studies com- predominantly for measurements of body fat distri- paring body composition from four-compartment bution. Figure 2.4 shows a scan of the abdomen at the models show that mean values generally agree with level of the umbilicus, made by MRI, a technique that simpler approaches, there are also studies showing gives comparable information. The precision of the directional bias of two-compartment body composi- calculation of a tissue area or tissue volume from the tion models. For this reason, more-compartment same scan(s) is very accurate, with an error of about models should ideally be used as a reference (gold 1%. Partial volume effects (pixels that contain tissue standard). However, only a limited number of labo- with different attenuation) may influence the accu- ratories can perform all of the necessary measure- racy and reproducibility of the method. ments for the calculation of maximum compartment models. Moreover, the data are expensive to collect, A single CT scan provides only relative data, for and measurements are time-consuming and not very example in a scan of the abdomen the relative amount practical in clinical situations. of visceral adipose tissue to subcutaneous adipose tissue. Multiple CT scanning allows the calculation of Imaging techniques tissue volumes. From adipose tissue volumes (tissue level) and an assumed density and composition of the CT scanning enables the visualization of tissues in adipose tissue, the amount of fat mass (molecular cross-sectional slices of the body. The thickness of level) can be calculated. Multiplying tissue volumes those slices can vary, but is normally about 1 cm. with specific densities of these tissues (determined in During CT scanning a source of X-rays rotates per- vitro) allows a recalculation of the body weight, a pendicularly around the body or a body segment, necessary but not sufficient exercise for validation of while photodetectors, opposite to the source, register a whole body technique. Research in this area has the attenuation of the X-rays after they have passed shown that the CT technique allows the determina- through the body in the various directions. The infor- tion of total body composition, with an error of mation received by the photodetectors is used to gen- estimate for fat mass of 3–3.5 kg (compared with erate images. Software enables the calculation of the densitometry).

22 Introduction to Human Nutrition CT scanning is expensive and, because of the rela- Table 2.5 Classification of weight in adults according to body mass tively high level of radiation, the method is limited to index subjects for whom scanning is indicated on clinical grounds. An alternative method to CT scanning is Classification Body mass index (kg/m2) Risk of comorbidities MRI, which has the advantage that no ionizing radia- tion is involved. Underweight <18.5 Low Normal range 18.5–24.9 Average During MRI, the signals emitted when the body is Overweight >25.0 placed in a strong magnetic field are collected and, as Increased with CT scanning, the data are used to generate a Preobese 25.0–29.9 Moderate visual cross-sectional slice of the body in a certain Obese class I 30.0–34.9 Severe region. The determination of adipose tissue versus Obese class II 35.0–39.9 Very severe nonadipose tissue is based on the shorter relaxation Obese class III >40 time of adipose tissue than of other tissues that contain more protons or differ in resonance frequency. MRI Reproduced with permission of the World Health Organization. has the advantage over CT scanning that the subject is not exposed to ionizing radiation. However, the time tion specific). The Quetelet index or BMI is the most necessary to make an MRI image is relatively long widely used index today. Its correlation with body fat (minutes versus seconds using CT), which has impli- is high (depending on the age group r = 0.6–0.8) and cations for the quality of the image. Any movement of the correlation with body height is generally low. The the subject, even the movements of the intestinal tract World Health Organization (WHO) promotes the when making images in the abdominal region, will BMI as a crude indicator for weight judgment. In decrease the quality of the image. Table 2.5 the cut-off points for underweight, normal weight, overweight, and obesity according to the As with CT scanning, images can be combined to WHO are given. These cut-off values are based on the obtain information on total body composition. Infor- relation of BMI with mortality and with risk factors mation about organ size can be obtained with a high for disease as found in Caucasian populations. For accuracy. For example, MRI is used to study the con- non-Caucasian populations other cut-off values may tribution of various organs to the resting metabolic apply (WHO, 2004). rate of the total body. The cut-off values for BMI as in Table 2.5 cannot Both CT scanning and MRI are expensive, and be used in children. In younger children, weight com- therefore their use will remain limited to a few labo- pared with height is relatively low, and so is the BMI. ratories and for very specific situations. During growth, the increase in weight is larger than the increase in height and, consequently, the BMI 2.7 Doubly indirect methods increases with age during the pubertal phase of life. There are age-related BMI cut-off values for obesity Anthropometry for children. Weight/height indices The BMI can also be used as a predictor for the A weight/height index aims to correct body weight percentage of body fat. Several studies have been pub- for height. As a measure of body composition, for lished in which a good relationship between the BMI example body fat, a weight/height index should have and the amount of body fat (either as fat mass or as a high correlation with body fat, but also a low cor- body fat percentage) was demonstrated. The relation- relation with body height, otherwise in short people ship between BMI and body fat percentage is age and body fat would be systematically overestimated or gender dependent and is different among certain underestimated. ethnic groups (Box 2.8). When using such age- and gender-specific prediction equations, body fat per- In the literature, a number of weight/height indices centage can be predicted with an error of 3–5%. This have been proposed. Examples are the Quetelet index error is similar to the prediction error of other doubly or body mass index (BMI: weight/height2), the Broca indirect methods, for example skinfold thickness or index [weight/(height – 100)], and the Benn index total body bioelectrical impedance measurements. (weight/heightp, in which the exponent p is popula- The disadvantage of these prediction formulae is that they obviously cannot be used in certain subjects or

Body Composition 23 Box 2.8 Box 2.9 Recent studies have shown that the relationship between body From Table 2.6 it can be seen that for the same amount of subcu- mass index (BMI) and body fat percentage differs among ethnic taneous fat (identical skinfold thickness) women have more body groups. For example, compared with Caucasian populations some fat than men. This is because of the higher internal (organ) fat Asian populations have 3–5% more body fat for the same BMI, content in women. It can also be seen (in both females and males) age, and gender. These differences can be explained by differences that at equal skinfold thickness older people have more body fat: in body build or frame size, subjects with a smaller frame having with age the amount of internal fat increases. more body fat at the same BMI. These differences can have important consequences for the definition of obesity (based on BMI cut-off values) and the preva- lence of obesity in a population. In Indonesia, obesity has recently been redefined as BMI ≥ 27 kg/m2. At this BMI, Indonesians have a similar body fat to Caucasians with a BMI of 30 kg/m2. The lower- ing of the cut-off point for obesity from 30 to 27 kg/m2 increased the prevalence of obesity from less than 5% to over 10%. Recently an Expert Consultation of the World Health Organiza- tion (WHO) resulted in new guidelines to redefine “action points” in non-Caucasian populations. For this not only was the different relationship between BMI and body fat percentage important, but also the high levels of cardiovascular risk factors at low BMI values (WHO, 2004). groups of subjects such as pregnant women or body- Figure 2.5 Measurement of the biceps skinfold. builders. However, other predictive methods also have their limitations in these subjects. total body fat are skinfolds on the upper arm biceps (Figure 2.5) and triceps, under the scapula (subscapu- TBW can also be predicted from weight and height, lar) and above the iliac crest (suprailiac). The sum of and numerous prediction formulae have been pub- more skinfolds is normally used to reduce the error lished. The standard error of estimate of these equa- in measurement and to correct for possible differ- tions is, however, considerable. ences in subcutaneous body fat distribution between subjects within the same age and gender group. Skinfold thickness measurements Various prediction formulae for body fat from skin- fold thickness have been published. For children, in Body fat is located both internally and subcutane- whom the relationship between skinfold thickness ously. If one assumes a constant relationship between and body fat depends on biological age, separate for- subcutaneous fat and total body fat, then total body mulae must be used. fat can be estimated by measuring the amount of the subcutaneous adipose tissue. The amount of subcu- Measuring skinfolds adequately requires a trained taneous tissue can be estimated by measuring the and experienced observer, otherwise excessively large thickness of the subcutaneous fat layer at different errors in the assessment of the body fat can occur. A sites of the body using a skinfold caliper, infrared disadvantage of the method is that the subject has to interactance, or ultrasound measurements. In a given be partly undressed. This hampers the use of the age group, the relation between subcutaneous fat and method in epidemiological studies. In bed-ridden or total fat is indeed relatively constant. However, the seriously ill patients the measurement of the trunk relationship is different between males and females, females having relatively more internal fat (Box 2.9). Thus, it is possible by using age- and gender-specific prediction equations to assess the total amount of body fat by measuring skinfolds at different sites of the body. Skinfolds can be measured all over the body. The most often measured skinfolds for the assessment of

24 Introduction to Human Nutrition Table 2.6 Body fat percentage from the sum of four skinfolds (biceps, triceps, subscapular, suprailiac) in males and females of different agesa Skinfolds (mm) Age (Males) 40–49 ≥50 60–87 Age (Females) 40–49 ≥50 60–87 20 17–29 30–39 12 13 24 17–29 30–39 20 22 34 30 18 19 27 25 27 37 40 8 12 21 23 29 14 17 28 30 39 50 13 16 25 27 31 20 22 31 33 41 60 16 19 27 29 32 23 26 33 36 42 70 19 22 29 32 33 27 28 35 38 43 80 21 24 31 34 34 29 31 37 40 44 90 23 25 33 36 35 31 33 38 41 45 100 25 27 34 37 36 33 34 40 43 46 110 26 28 36 39 37 35 36 41 44 47 120 28 29 37 40 37 36 37 42 45 48 130 29 30 38 42 38 38 39 43 46 48 140 30 31 39 43 38 39 40 44 47 49 150 31 32 40 44 39 40 41 45 48 49 32 33 41 42 33 34 42 43 aBased on data from Durnin and Womersley (1974) for the age groups 17 to ≥50 and on Visser et al. (1994) for the elderly. skinfold thicknesses can be difficult. This can be over- gender, and level of body fatness. Given the possible come by measuring only the skinfold thickness at the error in densitometry (3%), this means that in extreme upper arm, for example the triceps. However, the cases body fat from skinfolds can be as much as 10– error can be large because the triceps does not neces- 15% off. sarily represent the total amount of subcutaneous fat. With advancing age, the triceps skinfold becomes less Other anthropometric variables representative of total body fat. Measurements of widths of skeletal diameters provide In elderly subjects, the correlation between skin- an indication of the amount of skeletal mass. There fold thickness and total body fat as measured by are formulae that allow the calculation of the skeletal densitometry is generally lower than in young and mass from body height, wrist diameter, and knee middle-aged adults. This is due to an increased diameter. The current reference data for ideal weight amount of internal fat in the elderly. Obese subjects in the USA use the elbow diameter to classify people are difficult to measure and the error is large even into three types of body build. when measured by trained observers. This is also the case in subjects with edema, in whom the thickness In elderly subjects, the measurement of stature can of the subcutaneous adipose tissue is easily overesti- be difficult owing to kyphosis and/or shrinkage of the mated. In patients with human immunodeficiency spinal vertebrae. Knee height can then be used to virus (HIV) lipodystrophy, peripheral subcutaneous predict the maximal stature during lifetime. Arm fat may be almost absent, while abdominal fat is span is also used for that purpose. However, one has increased. In this situation, skinfolds can be very mis- to realize that the current prediction formulae are leading as indicators of total body fat, and should be developed in younger populations, in which the rela- used only to assess regional fat. tionship between stature and surrogate measure- ments may be different. In addition, the prediction The calculation of the body fat percentage once the error (3–5 cm) is relatively high. Knee height can also skinfolds have been measured is very simple. For a be used by itself (without predicting total stature), given skinfold thickness, the amount of body fat can when comparing stature-adjusted body composition be read from a table (Table 2.6). between young and old people. The prediction error in body fat percentage is 3– Circumferences of the extremities or the trunk are 5% compared with densitometry, depending on age, used to obtain information on body composition.

Body Composition 25 From the mid-arm circumference, in combination skinfold thickness measurements have a better pre- with the triceps skinfold thickness, information on dictive value. muscle mass and fat mass of the upper arm can be obtained. Circumferences of the trunk at waist, hip, Internal abdominal body fat can also be assessed and upper thigh level are used as indicators of body with ultrasound. Studies have shown that ultrasound fat distribution. The WHO suggests an upper limit measurements provide a better method than anthro- waist-to-hip circumference ratio above 0.85 for pometry to assess internal abdominal fat depots. females and 1.00 for males for abdominal fat distribu- tion. Diameters can also be used to gain insights into Bioelectrical impedance body fat distribution. A high sagittal diameter com- pared with transverse diameter of the abdomen is In bioelectrical impedance, a small alternating current indicative of an enlarged amount of visceral fat. is applied to the body. It is assumed that the body However, it has to be kept in mind that the relation- consists of different components, of which water and ship between these anthropometric parameters of dissolved electrolytes are able to conduct the current. body fat distribution and the intra-abdominal fat Hence, body impedance is a measure of body water. determined by CT or MRI scan is generally low. The electrical resistance or impedance of an electro- Changes in internal fat detected by MRI are only lyte solution depends on several factors, of which the weakly associated with changes in these anthropo- most important are the amount of electrolytes (pure metric parameters of fat distribution. water does not conduct the current), the kind of electrolytes, and the temperature of the solution. If Infrared interactance currents of low frequency (<5 kHz) are used, body impedance is a measure of ECW, as a low-frequency The principle of infrared interactance is based on current cannot penetrate the cell membrane, which differences in absorbance and reflection of infrared acts, with its layers of protein, lipids, and proteins, as light in different tissues. When the absorbance an electrical capacitor. With increasing frequencies of near-infrared light (700–1100 nm) is measured the capacitor features of the cell membrane diminish at well-defined sites of the body, information on and gradually ICW also participates in the conduc- the thickness of the subcutaneous adipose tissue tance of the current, resulting in lower impedance layer can be obtained. In the prediction formulae values at higher frequencies. Hence, at higher fre- used, many other parameters are included, such as quencies, TBW is measured. TBW and ECW can be weight, height, age, and gender, and it has been argued predicted from impedance at high and low frequency, that the prediction of body fat depends more on respectively, using empirically derived prediction for- these parameters than on the measured infrared mulae. Other parameters are often taken into consid- interaction. eration, such as body weight, age, and gender. Ultrasound measurements Most prediction equations are based on statistical relationships between empirically measured im- Ultrasound measurements can also be used to study pedance index values (height2/impedance) and body several aspects of body composition. With ultrasound water values obtained by dilution techniques such as measurements, the thickness of the subcutaneous fat deuterium oxide dilution (for TBW) and bromide layer can be determined and total body fat can be dilution (for ECW). As body water in healthy subjects calculated. A good reflection signal depends heavily is an assumed fixed part (73%) of the FFM, bioelectri- on the absence of connective tissue between adipose cal impedance measurements can also be used for the tissue and muscle. The main difficulty in ultrasound prediction of the FFM and hence body fat percentage. measurements is the exact application of the ultra- For those prediction equations, the impedance index sound transducer perpendicular to the tissue without was related to measures of FFM, normally obtained any pressure. In the literature, several studies report by densitometry or by DXA. a good correlation between skinfold thicknesses mea- sured by calipers and those measured by ultrasound. Body impedance depends on the frequency of the The correlation of skinfolds with total body fat was current used and on body water distribution between higher than when using ultrasound, suggesting that the extracellular and intracellular space and between the different geometrical body compartments (legs, trunk, and arms). This calls for extreme caution in the

26 Introduction to Human Nutrition Box 2.10 Total body electrical conductivity The relative validity of impedance prediction formulae can be Total body electrical conductivity (TOBEC) was devel- demonstrated by a simple calculation example. A man, aged 35 oped in the 1970s. The principle of the method is that years, of height 170 cm, weight 75 kg, and measured impedance conductive material (body water and dissolved elec- (from foot to hand) 400 Ω, has a predicted fat-free mass (FFM) of trolytes) that is placed in an electromagnetic field will 64.7 kg according to Lukaski et al. (1986) and a predicted FFM of cause an inductive current, which is related to the 60.5 kg according to Segal et al. (1988). Both prediction formulae amount of conductive material. In practice, the subject were developed in US populations and were cross-validated. The lies on a stretcher, which enters the inner space of an instrument used was the same and the method of reference in both electric wire coil, through which a high-frequency studies was underwater weighing. current (2.5–5 MHz) passes. The measurement is very quick (it takes only seconds), painless, and without interpretation of calculated body composition values any risk to the subject. The reproducibility of a mea- in situations where body water distribution can be surement is within 2% and the error in the predicted disturbed, as is the case, for example, in dialysis FFM was found to be about 3 kg in a group of adult patients and in ascites. In general, prediction formulae subjects, which is similar to, for example, skinfold based on impedance values are strongly population thickness measurements or impedance measurements. specific, and age and gender are important contribu- The TOBEC method is especially suitable for mea- tors. Differences between populations and individuals surements in infants and young children, in whom are partly caused by differences in body build (e.g., bioelectrical impedance measurements are difficult or relatively long legs), which is not surprising, as the legs impossible to perform, owing to movement. The main contribute most to total body impedance relative to disadvantage of the method is the high price. other parts of the body (Box 2.10). Creatinine excretion and Currently available impedance analyzers vary in N-methyl-histidine excretion their electrical features and in their principles. Many companies have developed impedance analyzers In the muscle cell, creatine phosphate, necessary for for personal use, anticipating considerable interest the energy metabolism of the cell, degenerates to cre- among the public in determining their body fat per- atinine at a constant daily rate of about 2%. It is centage. There are instruments that measure imped- assumed that 1 g of excreted creatinine is equivalent ance from foot to foot while standing on a weighing to 18–22 kg of muscle mass. As the cell cannot recycle scale and provide not only body weight but also body creatinine, the kidneys excrete it. Since metabolized fat percentage. Other instruments measure imped- creatine phosphate is not the only source of urinary ance from hand to hand and allow the reading of creatinine (e.g., creatinine in ingested meat is also body fat percentage, using a built-in software program excreted immediately), the validity of the method is in which weight, height, age, and gender have to be dubious. A day-to-day coefficient of variation in the entered. Combinations of foot-to-foot and hand-to- excretion of creatinine of almost 20% is reported, hand impedance analyzers are also marketed. when the subject is “free living” and the urine is sampled over constant periods of 24 hours. The high As for all other impedance analyzers, the incorpo- variation is due to the ingestion of creatinine with rated formulae are population specific and have a nonvegetarian meals, differences in physical activity prediction error of 4–5%. This means that, apart levels, and variation in creatinine excretion within the from a systematic error (prediction formula is not phase of the menstrual cycle. After careful standard- valid), the value can be as much as 10% off in extreme ization, which includes a controlled diet, the day-to- cases. This kind of error is similar to the possible error day variability in excretion can be decreased to about in skinfold thickness measurements, and hence 5%. To obtain a reliable assessment of the creatinine impedance is no better than skinfold thickness mea- excretion, sampling of urine over multiple 24 hour surements. The advantage of impedance analyzers is periods is necessary. that there is no need to undress and measurements are less prone to observer bias. The excretion of 3-methylhistidine has also been proposed as a measure for muscle mass. FFM deter-

Body Composition 27 mined by densitometry correlates well with excreted the required accuracy. The use in epidemiological 3-methylhistidine. The chemical determination of studies is different than that in clinical situations or 3-methylhistidine is, however, more complicated in physiological research. Table 2.7 provides a “buyer’s than that of creatinine. A unique feature of 3- guide” to the several methods discussed in this methylhistidine is that it gives a measure of muscle chapter. It is difficult to generalize as to which method protein breakdown. Given the greater expense of should be used in a given study. Apart from the measuring 3-methylhistidine and the limited benefit factors mentioned in Table 2.7, availability plays for muscle mass estimates, it is probably best to use an important role. Some situations are discussed it primarily for turnover studies. below. The main disadvantages of creatinine and 3- For the description of body fatness of a large general methylhistidine excretion as measures for body com- population group, the calculation of the body fat per- position are the large variability in excretion, the centage from the BMI may be as good as or even necessity to follow a controlled (meat-free) diet for better than the more expensive information obtained several days before and during the urine collections, from bioelectrical impedance or the laborious mea- and the difficulties associated with collecting 24 hour surement of skinfold thicknesses. Whichever method urine samples. is to be used for the prediction of body fat percentage in the population, it is important to remember that Use and misuse of body composition data the formulae used should have been validated in the population under study. The fact that a formula is Information on the body composition of groups of cross-validated by the authors who published the subjects or individuals is important, as body compo- formula does not mean that the formula is valid in sition is an indicator of nutritional status and also another population. The use of the Durnin and provides information about acute water homeostasis. Womersley (1974) equations for estimating body fat Depending on what information is needed, several from the sum of four skinfolds may be correct if the methods are available. However, all have their advan- population is adult but younger than about 60 years. tages and limitations. The price of the method In older subjects, the amount of body fat is likely to (both the instrument and the required personnel), the be underestimated with these formulae. Therefore, eventual stress and danger (e.g., radiation) for the their use and thoughtless interpretation in the elderly subject, and the time necessary to obtain the informa- would lead to completely wrong conclusions about tion determine the choice of the method, as well as Table 2.7 Buyer’s guide to different methods used to determine body composition Method Accuracy Expenses Radiation Time Convenience for subject Carcass analysis +++ −− −− ++ ++ Neutron activation +++ −− ++ +/− Densitometry ++ + (−) + + Dilution method ++ +/− ++ ++ 40K method ++ − − ++ ++ DXA +++ +/− − − + More-compartment models +++ − −− ++ ++ CT scanning ++ − ++ + MRI scanning ++ − ++ + Anthropometry + +++ ++ ++ Infrared interactance + ++ +++ ++++ Bioelectrical impedance + + ++ ++ TOBEC + − − − Creatinine/N-methylhistidine excretion + + DXA, dual-energy X-ray absorptiometry; CT, computed tomography; MRI, magnetic resonance imaging; TOBEC, total body electrical conductivity. + + +, excellent; + +, very good; +, good; +/–, reasonable; –, bad; – –, very bad.

28 Introduction to Human Nutrition body composition in the elderly and changes in body among other factors, and there are no universally composition with age. For the same reason, the BMI valid prediction equations based on impedance. as an indicator of body fatness is only suitable when Choice of method to assess body composition in a corrections for age and gender are made; for example, population would also take into consideration within- a BMI of 25 kg/m2 at the age of 20 years reflects a and between-observer variability. Thus, impedance much lower percentage of body fat than at the age of may be better than skinfold thickness measurements 70 years. Body fat in females is always higher than in a study of 1000 people, where variability between body fat in males with the same BMI and age. Recent technicians is important. One may argue that, for studies have shown that the relationship between population studies, a slight overestimation or under- BMI and body fat percentage also differs among estimation of body fat is not important. However, if, ethnic groups. Figure 2.6 gives a good insight on how for example, obesity is defined as a certain amount of misleading a low BMI can be. The biodata also show body fat that is achieved at a certain distinct level of the differences in body build, which is at least part of BMI, even minor differences in body fat percentage the reason for the paradox. Prediction equations or in BMI will result in large differences in the preva- based on impedance are dependent on body build, lence of obesity. Age (years) Dutch Asian Height (cm) 21 22 Weight (kg) Relative sitting height 175.6 158.0 Wrist (cm) 77.2 43.9 Knee (cm) 0.53 0.55 Arm span (cm) 5.6 4.4 Waist (cm) 9.1 8.4 Hip (cm) BMI 177.0 157.5 BF (%) 82.0 62.2 87.0 104.0 17.6 25.0 29.6 31.1 Figure 2.6 The difference in the relationship between BMI and body fat percentage across populations is best demonstrated in this figure and the given biodata. Note that the two young women are the same age and their percentage body fat as determined by a chemical four- compartment model (bias free!) is the same. The Asian woman has relatively shorter legs and a more slender body build (determined as height/(sum of knee and wrist diameter). Relative leg length and “slenderness” are main determining factors in the BMI/percentage body fat relationship in addition to physical activity level.

Body Composition 29 20 Bias in body fat percentage (% body weight) 10 0 Elderly females Figure 2.7 Individual differences in mea- (72 years) sured body fat percentage compared with a –10 chemical four-compartment model in 20 Young females young and 20 elderly females using various (22 years) techniques. y-axis, BF% from four-compart- ment model minus: ᮀ, densitometry (Siri); ᭺, deuterium dilution; ᭝, DXA; +, three- compartment model (Siri); ᭿, skinfold thick- ness; ᭞, bioelectrical impedance. In physiological studies where, for example, report changes in impedance values instead of changes energy metabolism has to be corrected for body in predicted body composition. Another example is composition, a systematic bias in body composition the very low change in impedance after water removal results may lead to completely wrong conclusions. in patients with ascites. Despite the fact that a consid- When a body composition formula or method sys- erable amount of water is removed from the body, the tematically overestimates the FFM in obese subjects, change in total body impedance is low as the trunk a “normal” resting metabolic rate in obese subjects hardly contributes to total body impedance. would be underestimated after “correction” for dif- ferences in body composition (expressed as kJ/kg All methods have their limitations, doubly indirect FFM). This may lead to the conclusion that obese more than indirect methods. Figure 2.7 shows the subjects have lower metabolic rates, which might individual errors in body fat percentage from den- have caused their excess adipose tissue stores. This sitometry, DXA, deuterium dilution, a chemical argument does not even imply whether the FFM can three-compartment model, skinfold thicknesses, and be treated as one entity in different populations bioelectrical impedance in young and elderly women instead of different components such as the heart, compared with body fat percentage obtained from a liver, or muscles (Gallagher et al., 1998). These con- four-compartment model. It is obvious that errors siderations are important for comparative studies can be considerable, both at a group level and espe- between groups (e.g., obese versus nonobese, elderly cially at an individual level in the elderly. Many of versus young or middle-aged), but also for longitudi- these errors can be explained by the violation of nal studies (e.g., weight-loss studies). assumptions. This clearly shows that information on body composition must be used with an awareness of The use of bioelectrical impedance to predict the limitations of the techniques. changes in FFM, TBW, or body fat during weight loss is questionable. The difference in body water distri- 2.8 Perspectives on the future bution (anatomically as well as intracellular/extracel- lular) before and after weight loss may be considerable, Given the importance of body composition to evalu- leading to a different and systematic bias of the pre- ate nutritional status and to gain information on diction equation. In such a study it may be better to certain disease processes, it can be expected that more

30 Introduction to Human Nutrition easy-to-use methods and instrumentation will be ments on 481 men and women aged from 17 to 72 years. Br J developed and become available in the future. Nutr 1974; 32: 77–97. Application and interpretation of data from these Forbes GB. Human Body Composition. Springer, New York, 1987. methods should be used with an awareness of pos- Gallagher D, Belmonte D, Deurenberg P, Wang Z-M, Krasnow N, sible limitations, as mentioned above. There is a Pi-Sunyer FX, Heymsfield SB. Organ-tissue mass measurement growing perception that, because of differences in by MRI allows accurate in vivo modeling of REE and metabolic body build, frame size, and possibly also other vari- active tissue mass. Am J Physiol 1998: 275: E249–258. ables, there are differences in the relationship between Heymsfield SB, Lohman TG, Wang ZW, Going SB. Human BMI and body fat percentage among ethnic groups. Body Composition, 2nd edn. Human Kinetics, Champaign, IL, Some Aboriginal and Asian people have a higher fat 2005. percentage and therefore greater risk for several Lukaski HC, Bolonchuk WW, Hall CB, Siders WA. Validity of tet- chronic diseases at a given BMI than Caucasian popu- rapolar bioelectrical impedance method to assess human body lations. Conversely, Africans often have higher bone composition. J Appl Physiol 1986; 60: 1327–1332. density than Caucasians. Much more research is Segal KR, Van Loan M, Fitzgerald PI, Hodgdon JA, Van Itallie TB. needed to define the optimal BMI values that will Lean body mass estimation by bio-electrical impedance analysis: correlate with optimal health and the lowest risk of a four site cross-validation study. Am J Clin Nutr 1988; 47: disease for different populations. 7–14. Visser M, Heuvel van den E, Deurenberg P. Prediction equations Acknowledgment for the estimation of body composition in the elderly using anthropometric data. Br J Nutr 1994; 71: 823–833. This chapter has been revised and updated by Paul WHO Expert Consultation. Appropriate body-mass index for Deurenberg based on the original chapter by Paul Asian populations and its implications for policy and interven- Deurenberg and Ronenn Roubenoff. For more infor- tion strategies. Lancet 2004; 363: 157–163. mation on this topic visit www.nutritiontexts.com Further reading References Siri WE. Body composition from fluid spaces and density: analysis Durnin JVGA, Womersley J. Body fat assessed from total body of methods. In: Brozek J, Henschel A, eds. Techniques for density and its estimation from skinfold thickness: measure- Measuring Body Composition. National Academy of Sciences, Washington, DC, 1961: 223–244. Snijder WS, Cook MJ, Nasset ES, et al. Report of the Task Group on Reference Man. Pergamon Press, Oxford, 1984. Wang Z-M, Pierson RN, Heymsfield SB. The five-level model; a new approach to organise body composition rsearch. Am J Clin Nutr 1992; 56: 19–28. World Health Organization. Obesity: Preventing and Managing the Global Epidemic. WHO, Geneva, 1998.

3 Energy Metabolism Arne Astrup and Angelo Tremblay Key messages composition, and level of physical activity, consistent with long- term good health. This includes the energy needs for optimal • Energy balance in the body is the balance between how much growth and development in children, and the needs of pregnancy energy is consumed and how much is expended. Positive balance and lactation (deposition of tissue and secretion of milk). is when intake exceeds expenditure and is associated with • Body mass index (BMI) classifies weight relative to height squared increases in body energy stores (weight gain). During negative and is the most accepted and widely used crude index of obesity. balance, as in periods of starvation, body energy stores are A BMI of 18–24.9 kg/m2 is regarded as normal for adults, depleted. between 25 and 29.9 kg/m2 as overweight, and >30 kg/m2 as obese. • Energy intake corresponds to the energy content of macro- • Energy expenditure can be measured by direct methods (calor- nutrients in foods. Carbohydrate provides 16.8 kJ/g, protein also imetry) or indirect methods, in which oxygen consumption and 16.8 kJ/g, and fat 37.8 kJ/g. In addition, alcohol provides carbon dioxide production are used to calculate energy expendi- 29.4 kJ/g. ture. However, the modern gold standard is measurement by doubly labeled water, which is a noninvasive method used to • Total energy expenditure constitutes approximately two-thirds of measure total energy expenditure over periods of 7–14 days the energy expended by the body to maintain basic physiological while subjects are living in their usual environments. functions plus the thermic effect of a meal and energy expended • Hunger is the physiological need to eat and results in actions to during physical movement. The basic physiological functions attempt to obtain food for consumption. Appetite is a psychologi- include heart beat, muscle function, and respiration (resting or cal desire to eat and is related to the pleasant sensations that basal metabolic rate). The thermic effect of a meal is about 10% are often associated with food. Thus, hunger is more of an of the caloric value of the meal needed to digest, metabolize, intrinsic instinct, whereas appetite is often a learned response. and store ingested macronutrients. The energy expended during physical activity is energy expended when skeletal muscles are used for any type of physical movement. In infants and children, the cost of growth is added. • Energy requirement is the amount of food energy needed to balance energy expenditure in order to maintain body size, body 3.1 Introduction results in maintenance of body weight and body energy stores. This regulation of energy balance is Definition and conceptualization of achieved over the long term despite large fluctuations energy balance in both energy intake and energy expenditure within and between days. The accuracy and precision by The average adult human consumes close to 1 000 000 which the body maintains energy balance is high- calories (4000 MJ) per year. Despite this huge energy lighted by the fact that even a small error in the system intake, most healthy individuals are able to strike a can have detrimental consequences over time. If remarkable balance between how much energy is energy intake chronically exceeds energy expenditure consumed and how much energy is expended, thus by as little as 105 kJ/day, then, over time, a person resulting in a state of energy balance in the body. This will become substantially obese. The achievement of accurate balance between energy intake and energy energy balance is driven by the first law of thermo- expenditure is an example of homeostatic control and © 2009 A Astrup and A Tremblay.

32 Introduction to Human Nutrition dynamics, which states that energy can be neither energy cost of arousal. Because of the difficulty in destroyed nor created. This principle necessitates that achieving BMR under most measurement situations, when energy intake equals energy expenditure, body resting metabolic rate (RMR) is frequently measured energy stores must remain constant. This chapter using the same measurement conditions stated for explains how the body is able to achieve this state of BMR. Thus, the major difference between BMR and energy balance through control of energy intake and RMR is the slightly higher energy expended during energy expenditure. In addition, the various ways that RMR (~ 3%) owing to less subject arousal and non- body energy stores can be measured and some exam- fasting conditions. Because of this small difference, ples of conditions in which energy balance may be the terms basal and resting metabolic rate are often disrupted are summarized. Particular emphasis is used interchangeably. RMR occurs in a continual placed on obesity, which is the end-result of a positive process throughout the 24 hours of a day and remains energy balance and is now considered one of the relatively constant within individuals over time. In major nutritional disorders. the average adult human, RMR is approximately 4.2 kJ/min. Thus, basal or resting metabolic rate is the Components of energy balance largest component of energy expenditure and makes up about two-thirds of total energy expenditure. Energy intake Energy intake is defined as the caloric or energy In addition to RMR, there is an increase in energy content of food as provided by the major sources of expenditure in response to food intake. This increase dietary energy: carbohydrate (16.8 kJ/g), protein in metabolic rate after food consumption is often (16.8 kJ/g), fat (37.8 kJ/g), and alcohol (29.4 kJ/g). referred to as the thermic effect of a meal (or meal- induced thermogenesis) and is mainly the energy that Energy storage is expended to digest, metabolize, convert, and store The energy that is consumed in the form of food or ingested macronutrients, named obligatory thermo- drinks can either be stored in the body in the form of genesis. The measured thermic effect of a meal is fat (the major energy store), glycogen (short-term usually higher than the theoretical cost owing to a energy/carbohydrate reserves), or protein (rarely facultative component caused by an activation of used by the body for energy except in severe cases of the sympathoadrenal system, which increases energy starvation and other wasting conditions, as discussed expenditure through peripheral β-adrenoceptors. later in the chapter), or be used by the body to fuel The energy cost associated with meal ingestion is pri- energy-requiring events. marily influenced by the composition of the food that is consumed, and also is relatively stable within indi- Energy expenditure viduals over time. The thermic effect of a meal usually The energy that is consumed in the form of food is constitutes approximately 10% of the caloric content required by the body for metabolic, cellular, and of the meal that is consumed. The third source of mechanical work such as breathing, heart beat, and energy expenditure in the body is the increase in muscular work, all of which require energy and result metabolic rate that occurs during physical activity, in heat production. The body requires energy for a which includes exercise as well as all forms of physical variety of functions. The largest use of energy is activity. Thus, physical activity energy expenditure needed to fuel the basal metabolic rate (BMR), which (or the thermic effect of exercise) is the term fre- is the energy expended by the body to maintain basic quently used to describe the increase in metabolic rate physiological functions (e.g., heart beat, muscle con- that is caused by use of skeletal muscles for any type traction and function, respiration). BMR is the of physical movement. Physical activity energy expen- minimum level of energy expended by the body to diture is the most variable component of daily energy sustain life in the awake state. It can be measured after expenditure and can vary greatly within and between a 12 hour fast while the subject is resting physically individuals owing to the volitional and variable nature and mentally, and maintained in a thermoneutral, of physical activity patterns. quiet environment. The BMR is slightly elevated above the metabolic rate during sleep, because energy In addition to the three major components of expenditure increases above basal levels owing to the energy expenditure, there may be a requirement for energy for three other minor needs.

Energy Metabolism 33 ● The energy cost of growth occurs in growing indi- occur in very inactive individuals as well as in highly viduals, but is negligible except within the first few active individuals provided that adequate energy months of life. sources are available. It is also important to think of energy balance in terms of the major sources of ● Adaptive thermogenesis is heat production during energy, i.e., carbohydrate, protein, and fat. For exposure to reduced temperatures, and occurs in example, carbohydrate balance occurs when the body humans, e.g., during the initial months of life and balances the amount of carbohydrate ingested with during fever and other pathological conditions, but that expended for energy. also as a contributor to daily energy expenditure. 3.2 Energy intake ● Thermogenesis is increased by a number of agents in the environment, including in foods and bever- Sources of dietary energy ages. Nicotine in tobacco is the most important one, and heavy smokers may have a 10% higher As mentioned above, the sources of energy in the food energy expenditure than nonsmokers of similar we eat include the major macronutrients: protein, car- body size and composition and physical activity. bohydrate, and fat, as well as alcohol. Carbohydrate Caffeine and derivatives in coffee, tea, and choco- and protein provide 16.8 kJ of energy for each gram; late, capsaicin in hot chilies, and other substances alcohol provides 29.4 kJ/g, whereas fat is the most in foods and drinks may possess minor thermo- energy dense, providing 37.8 kJ/g. Note that 4.2 kJ is genic effects that affect energy expenditure. defined as the amount of heat that is required to raise the temperature of 1 liter of water by 1°C. The energy Energy balance content of food can be measured by bomb calori- Energy balance occurs when the energy content of metry, which involves combusting a known weight of food is matched by the total amount of energy that is food inside a sealed chamber and measuring the expended by the body. An example of energy balance amount of heat that is released during this process. would be the scenario cited at the outset of this Thus, 1 g of pure fat would release 37.8 kJ during its chapter in which, over a year, the average adult con- complete combustion, whereas 1 g of pure carbohy- sumes and expends 1 000 000 calories, resulting in no drate would release 16.8 kJ. Thus, if the gram quanti- net change in the energy content of the body. When ties of any type of food are known, the energy content energy intake exceeds energy expenditure, a state of can easily be calculated. For example, if a protein-rich positive energy balance occurs. Thus, positive energy nutrition snack contains 21 g of carbohydrate, 6 g of balance occurs when excessive overfeeding relative to fat, and 14 g of protein, then the total energy content energy needs occurs, and the body increases its overall is (21 × 16.8) + (6 × 37.8) + (14 × 16.8) = 814.8 kJ. The energy stores. Examples of positive energy balance macronutrient composition of food is typically include periods around major festivals when overeat- assessed in the percentage contribution of each mac- ing and inactivity generally prevail, and during preg- ronutrient to the total number of calories. If a food has nancy and lactation when the body purposefully a carbohydrate content of 21 g, which is 352.8 kJ, and increases its stores of energy. When energy intake is the total energy content is 820 kJ the proportion of lower than energy expenditure, a state of negative energy derived from carbohydrate is 43%; the fat energy balance occurs, for example during periods of content is 6 g, or 226.8 kJ, equivalent to 28% of the starvation. In this regard, evidence suggests that, energy; and the protein contributes 14 g, 235.2 kJ and under conditions of substantial energy imbalance, be 29% of the energy. it positive or negative, energy expenditure may reach a level that is beyond what could be predicted by body Regulation of food intake weight changes. This so-called “adaptive thermogen- esis” might contribute to the occurrence of resistance Appetite, hunger, and satiety to lose fat in the context of obesity treatment or the The quality and quantity of food that is consumed are achievement of a new body weight plateau following closely regulated by the body. Food intake is regulated overfeeding. It is important to note that energy by a number of factors involving complex inter- balance can occur regardless of the levels of energy actions among various hormones, neuroendocrine intake and expenditure; thus, energy balance can

34 Introduction to Human Nutrition factors, the central nervous system, and organ systems Sensory Cognitive Postabsorptive (e.g., brain and liver), and environmental and exter- nal factors. Postingestive Appetite is usually defined as a psychological desire Food Early Late to eat and is related to the pleasant sensations that are often associated with specific foods. Scientifically, Satiation Satiety appetite is used as a general term of overall sensations related to food intake. Figure 3.1 The satiety cascade by John Blundell (1987). The four categories of mechanisms are sensory, cognitive, postingestive, and Hunger is usually defined as the subjective feeling postabsorptive. The sensoric phase includes stimuli mediated via that determines when food consumption is initiated sensory fibers in the cranial nerves and relates to the palatability of and can be described as a nagging, irritating feeling the ingested meal including smell, taste, temperature, and texture. The that signifies food deprivation to a degree that the cognitive phase of the satiety cascade represents learned, known, and next eating episode should take place. assumed properties of the ingested food. In the postingestive phase the gastrointestinal tract is involved in a number of satiety signals both Satiety is considered as the state of inhibition over via chemo- and mechanoreceptors and appetite-regulating peptides eating that leads to the termination of a meal, and is from the gut and pancreas either entering circulation and acting related to the time interval until the next eating episode. directly in the CNS or signaling via the vagus nerve. Important satiety Thus, hunger and satiety are more intrinsic instincts, signals in the postabsorptive phase include circulating nutrients, whereas appetite is often a learned response. signals derived from differences in energy turnover, substrate oxida- tion, and neurohormonal factors. Reprinted from Blundell et al. The internal factors that regulate the overall feeling (1987), copyright 1987 with permission of Elsevier. of hunger and satiety include the central nervous system (primarily the hypothalamus and the vagus and drink in the stomach and intestine and the resul- nerve), the major digestive organs such as the stomach tant pressure that they exert may regulate food intake. and liver, and various hormones. In addition, envi- This effect is known as gastrointestinal distension. ronmental factors (e.g., meal pattern and composi- In addition, the stomach produces a hormone called tion, food availability, smell and sight of foods, cholecystokinin (CCK) in response to food intake, climate), emotional factors (e.g., stress), and some which may, in turn, regulate food intake. Furthermore, diseased states (e.g., anorexia, trauma, infection) may when subjects have fat or carbohydrate infused influence the feelings of both hunger and appetite. directly into the small intestine, they report feelings The factors that influence appetite include factors of satiety. This suggests that factors in the intestine external to the individual (e.g., climate, weather), regulate food intake. Indeed, receptors in the intes- specific appetite cravings, specific learned dislikes or tine have been identified that recognize the presence avoidance (e.g., alcohol), intrinsic properties of food of specific macronutrients; these receptors are linked (e.g., taste, palatability, texture), cultural practices or to the brain and therefore can communicate directly preferences, specific effects of some drugs and dis- with the central nervous system, resulting in regula- eases, and metabolic factors such as hormones and tion of energy balance. In addition, other gastrointes- neurotransmitters. Some of these factors are described tinal hormones, such as glucagon-like peptide-1 and in further detail below. -2 (GLPs), CCK, and glucose-dependent insulinotro- pic polypeptide (GIP) are likely to play a role in the The classic way to describe the complex appetite- mediation of gut events and brain perception of regulating system is the satiety cascade put forth by hunger and satiety. John Blundell. The satiety cascade describes four dis- tinctly different but overlapping categories of mecha- Central nervous system factors nisms involved in acute within-meal feeling of satiety The main contributory factor regulating food intake (referred to as satiation) and the inbetween-meal in the central nervous system is the hypothalamus. satiety (Figure 3.1). The hypothalamus is linked to specific parts of the Factors influencing food intake Digestive factors Several factors in the digestive system exert a short- term influence over food intake. The presence of food

Energy Metabolism 35 brain that are known to modify feeding behavior, gut- and pancreas-derived satiety signals CCK, peptide specifically the paraventricular nuclei and the nigro- YY (PYY), GLP-1, oxyntomodulin (OXM), and pan- striatal tract. These areas of the brain respond to creatic polypeptide (PP). Many of the peripheral various neurotransmitters as well as sympathetic satiety signals have receptors in the arcuate nucleus nervous system activity. In general, food intake will (ARC) of the hypothalamus, which plays an impor- decrease as sympathetic nervous system activity tant role in appetite regulation. The ARC contains increases, and vice versa. neuropeptide Y (NPY)- and agouti-related peptide (AgRP)-expressing neurons acting to stimulate food Circulating factors intake along with the adjacent pro-opiomelanocortin After consumption of a meal, food is broken down (POMC) and cocaine- and amphetamine-regulated into its basic components (i.e., carbohydrate is broken transcript (CART)-expressing neurons which inhibit down to glucose, protein to amino acids, and fats or feeding. Besides the ARC, the nucleus of the solitary triglycerides to glycerol and fatty acids) and the cir- tract (NTS) and the area postrema (AP) receive appe- culating levels of some of these breakdown products tite-regulating inputs from vagal afferents and circu- increase in the blood. Consequently, glucose, amino lating factors and are connected to the hypothalamic acids, glycerol, and fatty acids are further metabo- nuclei controlling food intake. lized, primarily in the liver, or used for immediate energy (e.g., in muscle or brain). There is evidence to External factors suggest that this resultant metabolism, especially in Various nonphysiological or external factors are also the liver, may in turn regulate food intake. After meal known to modify food intake, and these effects may consumption, the circulating levels of nutrients fall be mediated through the intrinsic factors described (within minutes for glucose, several hours for triglyc- above. Psychological factors such as depression may erides) and the feelings of hunger return. The link lead to either increased or decreased food intake, or from nutrient metabolism to central control of food changes in the consumption of specific types of foods. intake occurs through signals from the liver to the Environmental factors are also important, the most brain via the vagus nerve. Thus, circulating factors obvious being food availability. Even when food is provide a link between the digestive system and the available, some of the specific properties of foods central nervous system, which provides another make them more or less appealing, thereby modifying system for regulating food intake. food intake. Important physical characteristics of food include taste, texture, color, temperature, and Signals from the periphery presentation. Other cultural influences in the envi- Leptin is a hormone that is produced by fat cells ronment, such as time of day, social factors, peer and communicates with the central nervous system influence, and cultural preferences, can also play a through leptin receptors in the hypothalamus. Reduced role in influencing food intake. production of leptin, or lack of sensitivity of the hypo- thalamus to leptin, may regulate food intake and play 3.3 Energy expenditure a key role in the etiology of rare forms of obesity in humans. Leptin and the other peripheral hormones Concept of energy expenditure with a central effect on appetite are divided into two broad categories: (1) the so-called adiposity signals, The process of energy expenditure and the oxidation which are tonically active providing information on or combustion of food for energy in the body is anal- body fat stores to the CNS and (2) the satiety signals ogous to a woodstove that burns wood to release heat which are released in response to food intake and are in a controlled fashion. In this analogy, large chunks thought to be involved in short-term regulation of of wood are fed to the stove and the wood is gradually energy intake. Currently known adiposity signals are combusted in the presence of oxygen to release carbon insulin, leptin, and adiponectin, which are considered dioxide, water vapor, and heat. Similarly, in the body, as long-acting signals reducing energy intake. Among the food consumed is oxidized or combusted in the the satiety signals are the hunger hormone ghrelin, presence of oxygen to release carbon dioxide, water, which is secreted in the stomach, and the short-acting and heat. When ingested food is used for energy,