Present Knowledge in Nutrition: Basic Nutrition and Metabolism

Present Knowledge in Nutrition

Basic Nutrition and Metabolism

Eleventh Edition

Editors

Bernadette P. Marriott, PhD

Diane F. Birt, PhD

Virginia A. Stallings, MD, MS

Allison A. Yates, PhD, MSPH, RD

Table of Contents

Cover image

Title page

Copyright

Dedication

Editor Biographies

Contributors to Volume 1

Foreword

Preface

Acknowledgments

Section A. Macronutrients

Chapter 1. Energy metabolism

I. Introduction

II. Nutrient and Energy Metabolism

III. Components of Energy Expenditure

IV. Energy Requirement

V. Energy Requirement and Disease

Chapter 2. Protein and amino acids

I. Introduction

II. Nutrient Metabolism

III. Dietary Requirements

IV. Issues Related to Protein and Amino Acids in Human Health

Chapter 3. Carbohydrates

I. Introduction

II. Nutrient Metabolism

III. Role in Normal Cell and Organ Function

IV. Dietary Requirements

V. Issues Related to Carbohydrates in Human Health

Chapter 4. Lipids

I. Introduction

II. Nutrient Metabolism

III. Lipids—Normal Cell and Organ Function

IV. Dietary Requirements

V. Issues Related to Fat in Human Health

Section B. Vitamins

Chapter 5. Vitamin A and provitamin A carotenoids

I. Introduction

II. Vitamin A Metabolism

III. Role in Normal Cell and Organ Function

IV. Dietary Requirements

V. Issues Related to Vitamin A in Human Health

Chapter 6. Vitamin D

I. Introduction

II. Nutrient Metabolism

III. Dietary Requirements

IV. Issues Related to Vitamin D in Human Health

Chapter 7. Vitamin E

I. Introduction

II. Nutrient Metabolism

III. Role in Normal Cell and Organ Function

IV. Dietary Requirements

V. Issues related to vitamin E in human health

VI. Future Needs

Chapter 8. Vitamin K

I. Introduction

II. Nutrient Metabolism

III. Role in Normal Cell and Organ Function

IV. Dietary Requirements

V. Issues Related to Vitamin K in Human Health

Chapter 9. Vitamin C

I. Introduction

II. Nutrient Metabolism

III. Role in normal cell and organ function

IV. Dietary Requirements

V. Issues Related to Vitamin C in Human Health

Chapter 10. Thiamine

I. Introduction

II. Nutrient Metabolism

III. Role in Normal Cells and Organs

IV. Dietary Requirements

V. Issues Related to Thiamine in Human Health

Chapter 11. Riboflavin

I. Introduction

II. Nutrient Metabolism

III. Role in Normal Cell and Organ Function

IV. Dietary Requirements

V. Issues Related to Riboflavin in Human Health

Chapter 12. Niacin

I. Introduction

II. Nutrient Metabolism

III. Role in Normal Cell and Organ Function

IV. Dietary Requirements

V. Issues Related to Niacin in Human Health

Chapter 13. Vitamin B6

I. Introduction

II. Nutrient Metabolism

III. Role in Normal Cell and Organ Function

IV. Dietary Requirements

V. Issues Related to Vitamin B6 in Human Health

Chapter 14. Folate

I. Introduction

II. Nutrient Metabolism

III. Role in Normal Cell and Organ Function

IV. Dietary Requirements

V. Issues Related to Folate in Human Health

Chapter 15. Vitamin B12

I. Introduction

II. Nutrient Metabolism

III. Role in Normal Cell and Organ Function

IV. Dietary Requirements

V. Issues Related to Vitamin B12 in Human Health

Chapter 16. Pantothenic acid

I. Introduction

II. Nutrient Metabolism

III. Role in Normal Cell and Organ Function

IV. Dietary Requirements

Chapter 17. Biotin

I. Introduction

II. Nutrient Metabolism

III. Role in Normal Cell and Organ Function

IV. Dietary Requirements

V. Issues Related to Biotin in Human Health

Chapter 18. Choline

I. Introduction

II. Choline Metabolism

III. Role in normal cell and organ function

IV. Dietary Requirements for Choline

V. Issues Related to Choline in Human Health

Section C. Minerals

Chapter 19. Calcium

I. Introduction

II. Calcium Metabolism

III. Role in normal cell and organ function

IV. Calcium Requirements

V. Issues Related to Calcium in Human Health

Chapter 20. Phosphorus

I. Introduction

II. Phosphorus Metabolism

III. Role in normal cell and organ function

IV. Dietary Requirements

V. Issues related to phosphorus in human health

Chapter 21. Magnesium

I. Introduction

II. Nutrient Metabolism

III. Dietary Requirements

IV. Issues Related to Magnesium and Human Health

Chapter 22. Iron

I. Introduction

II. Iron Metabolism

III. Role in Normal Cell and Organ Function

IV. Dietary Requirements

V. Issues Related to Iron in Human Health

Chapter 23. Zinc

I. Introduction

II. Metabolism

III. Role in Normal Cell and Organ Function

IV. Dietary Recommendations

V. Issues Related to Zinc in Human Health

VI. Conclusion

Chapter 24. Copper

I. Introduction

II. Copper Metabolism

III. Copper: Role in Normal Cell and Organ Function

IV. Dietary Requirements

V. Issues Related to Copper in Human Health

VI. Concluding Remarks

Chapter 25. Iodine and the iodine deficiency disorders

I. Introduction

II. Nutrient Metabolism

III. Role in normal cell and organ function

IV. Dietary Requirements

V. Issues Related to Iodine in Human Health

Chapter 26. Selenium

I. Introduction

II. Nutrient Metabolism

III. Role in Normal Cell and Organ Function

IV. Dietary Requirements

V. Issues Related to Selenium in Human Health

Chapter 27. Chromium

I. Introduction

II. Nutrient Metabolism

III. Lack of a Role in Normal and Organ Function

IV. Dietary Requirements

V. Issues Related to Chromium in Human Health

Chapter 28. Sodium, chloride, and potassium

I. Introduction

II. Sodium

III. Chloride

IV. Potassium

V. Issues of concern with sodium, potassium, and chloride

Chapter 29. Manganese, molybdenum, boron, silicon, and other trace elements

I. General Introduction

II. Manganese Introduction

III. Manganese Metabolism

IV. Manganese Role in Normal Cell and Organ Function

V. Manganese Dietary Requirements

VI. Issues Related to Manganese in Human Health

VII. Molybdenum Introduction

VIII. Molybdenum Metabolism

IX. Molybdenum Role in Normal Cell and Organ Function

X. Molybdenum Dietary Requirements

XI. Issues Related to Molybdenum in Human Health

XII. Boron Introducton

XIII. Boron Metabolism

XIV. Role of boron in normal cell and organ function

XV. Boron Dietary Requirements

XVI. Issues related to boron in human health

XVII. Silicon introduction

XVIII. Silicon metabolism

XIX. Role of silicon in normal cell and organ function

XX. Silicon Dietary Requirements

XXI. Issues related to silicon in human health

XXII. Other trace elements introduction

XXIII. Nickel introduction

XXIV. Nickel metabolism

XXV. Beneficial effects of nickel in normal cell and organ function

XXVI. Nickel dietary requirements

XXVII. Vanadium introduction

XXVIII. Beneficial effects of vanadium in normal cell and organ function

XXIX. Vanadium Dietary Requirements

Section D. Other Dietary Components

Chapter 30. Water

I. Introduction

II. Water metabolism

III. Cell Function

IV. Dietary Requirements

V. Issues Related to Water in Human Health

Chapter 31. Fiber

I. Introduction

II. Fiber and Metabolism

III. Role in Normal Cell and Organ Function

IV. Dietary Requirements

V. Issues Related to Fiber in Human Health

Chapter 32. Carotenoids

I. Introduction

II. Nutrient Metabolism

III. Role in Normal Cells and Organ Functions

IV. Dietary Requirements

V. Issues related to carotenoids in human health

Chapter 33. Carnitine

I. Introduction

II. Nutrient Metabolism

III. Role in Normal Cell and Organ Function

IV. Dietary requirements

V. Issues Related to Carnitine in Human Health

Chapter 34. Dietary flavonoids

I. Introduction

II. Absorption, Metabolism, and Excretion—Quantitative and Mechanistic Aspects

III. Role in Cell and Organ Function and in Human Health

IV. Dietary recommendations

Chapter 35. Dietary supplements

I. Introduction

II. Dietary supplement use

III. Dietary Supplement Efficacy, Safety, and Quality

IV. Regulation, Oversight, and Assessment of Dietary Supplements in the United States

V. Sample Evaluations of Dietary Supplement Efficacy, Safety, and Quality

VI. Challenges and Opportunities for Dietary Supplement Research

VII. Sources of information on dietary supplements

VIII. Advice for Investigators and Health Care Providers

Section E. Cross Discipline Topics

Chapter 36. Systems biology and nutrition

I. Introduction and background

II. Current Status of the Field

III. Issues Related Specifically to Nutrition: The Growth of Computational Modeling

Chapter 37. The microbiome and health

I. Introduction

II. Key issues

III. Current Status of the Field

IV. Tools And Methods In Microbiome Research

V. Issues Specifically Related To Nutrition

Chapter 38. Nutrient regulation of the immune response

I. Introduction

II. Key Issues

III. Issues Specifically Related to Nutrition

Index

Contents of Volume 2

Copyright

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Notices

Knowledge and best practice in this field are constantly changing. As new research and experience broaden our understanding, changes in research methods, professional practices, or medical treatment may become necessary.

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Dedication

We dedicate this 11th edition of Present Knowledge in Nutrition to the members of the global nutrition community who continue to seek the best science, interpret that science for the better good of people worldwide, and persist in countering nonscientifically based nutrition information with evidence-based approaches to better human health. We also dedicate this edition to our own scientific mentors and colleagues who have persuaded and occasionally pushed us in the direction of the highest quality nutrition science—no matter the cost.

Editor Biographies

Bernadette P. Marriott, PhD

Bernadette P. Marriott holds the position of Professor Emerita and Nutrition Section Director Emerita, Departments of Medicine and Psychiatry, Medical University of South Carolina. Bernadette has over 35 years of experience in the fields of nutrition, psychology, and comparative medicine with expertise in diet, nutrition, and chronic disease. Dr. Marriott has worked in scientific and administration positions in the federal government, the National Academies, universities, and foundations. She was founding director of the Office of Dietary Supplements, NIH and Deputy Director, Food and Nutrition Board, NAS. Her research has focused on both human and animal nutrition and related behavioral studies (in humans: diet and health research and food labeling; in animals: nonhuman primate nutrition and behavioral ecology). She is currently leading or has recently led research projects funded by the Army, DoD, NSF, NIH, USDA, industry, and foundations. Bernadette Marriott has a BSc in biology/immunology from Bucknell University (1970), a PhD in psychology from the University of Aberdeen, Scotland (1976), and postgraduate training in trace mineral nutrition, comparative medicine, and advanced statistics. She has published extensively, is on a number of national committees and university scientific advisory boards, and is a frequent speaker on diet, dietary supplements, and health. She is currently a member of the Food and Nutrition Board, US National Academy of Sciences, and the American Society for Nutrition Committee on Advocacy and Science Policy. In 2016, Dr. Marriott was inducted as a Fellow of the American Society for Nutrition.

Diane F. Birt, PhD

Diane F. Birt is a Distinguished Professor in Food Science and Human Nutrition at Iowa State University. She has BS degrees in Home Economics and Chemistry from Whittier College (1971) and a PhD in Nutrition from Purdue University (1975). Her expertise is in diet and cancer prevention and plant components and health promotion. She was at the University of Nebraska Medical Center (1976–97) before becoming Chair of the Department of Food Science and Human Nutrition (1997–2004) at Iowa State University. Dietary prevention of cancer has been a long-standing interest in the Birt laboratory. More recent research has focused on the prevention of colon cancer by slowly digested maize starches using cell culture and animal models that reflect particular genetic changes that are important in human colon cancer development. She was on the Board of Scientific Counselors for the National Toxicology Program (US Department of Health) and the Food and Nutrition Board of the Institute of Medicine, US National Academy of Sciences. In 2015, Dr. Birt was inducted as a Fellow of the American Society for Nutrition, and in 2016, she was inducted as a member of the National Academy of Medicine.

Virginia A. Stallings, MD, MS

Virginia Stallings is a Professor of Pediatrics at the Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania and is the recipient of the Jean A. Cortner Endowed Chair in Pediatric Gastroenterology and Nutrition. She holds a BS in Nutrition and Food from Auburn University, MS in Nutrition and Biochemistry from Cornell University, and MD from the University of Alabama Birmingham. Her general pediatric residency was completed at the University of Virginia followed by a subspecialty fellowship in nutrition at the Hospital for Sick Children. Over her career at the Children's Hospital of Philadelphia, she contributed to clinical care, fellow and faculty training, and clinical and translational research in the abnormalities of growth, nutritional status, and health of children with chronic diseases and in those in good health. She has served on many National Academy of Sciences committees to advise on child health, nutrition, and federal nutrition programs and is a member of the National Academy of Medicine. The American Academy of Pediatrics and American Society for Nutrition have recognized her efforts with awards for science, mentoring, and service.

Allison A. Yates, PhD, MSPH, RD

Allison A. Yates holds Bachelor's and Master's degrees from the University of California at Los Angeles in public health and dietetics and a PhD from the University of California at Berkeley in nutrition, and is a registered dietitian having completed a dietetic internship at the VA Center in Los Angeles. She served on the faculties of the University of Texas Health Science Center in Houston, Emory University School of Medicine, and was the founding Dean of the College of Health and Human Sciences at the University of Southern Mississippi, where she led the development of the first accredited public health program in the state. Her research focused on human protein and energy requirements. In 1994, she was named Director of the Food and Nutrition Board of the Institute of Medicine of the US National Academy of Sciences, where, over a 10-year period, she led the expanded approach to establishing human requirements and recommendations for nutrients, termed Dietary Reference Intakes, for the United States and Canada. She then served as Director of the Beltsville Human Nutrition Research Center of the US Department of Agriculture, Agricultural Research Service (ARS), and served as Associate Director for the ARS Beltsville Area region, retiring from USDA in 2014, when she was also inducted as a fellow of the American Society for Nutrition. Since that time, she has led a volunteer effort to establish a framework for establishing reference values for bioactive components in foods.

Contributors to Volume 1

Peter J. Aggett, MSc, FRCPCH, FRCP, R.Nutr ,     Emeritus, University of Central LancashirePrestonUnited Kingdom

Rylee T. Ahnen, MS ,     University of MinnesotaSt. Paul, MNUnited States

Tolunay Beker Aydemir, PhD ,     Cornell UniversityIthaca, NYUnited States

Lynn B. Bailey, PhD ,     University of GeorgiaAthens, GAUnited States

Lucien Bettendorff, PhD ,     University of LiègeLiègeBelgium

William S. Blaner, PhD ,     Columbia UniversityNew York, NYUnited States

Peggy R. Borum, PhD ,     University of FloridaGainesville, FLUnited States

Richard S. Bruno, PhD, RD ,     The Ohio State UniversityColumbus, OHUnited States

Philip C. Calder, PhD, DPhil ,     University of SouthamptonSouthamptonUnited Kingdom

Marie A. Caudill, PhD, RD ,     Cornell UniversityIthaca, NYUnited States

Samuel N. Cheuvront, PhD, RD, FACSM ,     Sports Science Synergy, LLCFranklin, MAUnited States

Paul M. Coates, PhD ,     Office of Dietary Supplements, National Institutes of HealthBethesda, MDUnited States

James F. Collins, PhD ,     University of FloridaGainesville, FLUnited States

Rebecca B. Costello, PhD ,     National Institutes of HealthBethesda, MDUnited States

Vanessa R. da Silva, PhD, RDN ,     University of ArizonaTucson, AZUnited States

Alan Mark Diamond, PhD ,     University of Illinois ChicagoChicago, ILUnited States

Guylaine Ferland, PhD ,     University of MontrealMontreal, QuebecCanada

James C. Fleet, PhD ,     Purdue UniversityWest Lafayette, INUnited States

Naomi K. Fukagawa, MD, PhD ,     USDA, ARS Beltsville Human Nutrition Research CenterBeltsville, MDUnited States

Jesse F. Gregory III PhD ,     University of FloridaGainesville, FLUnited States

Orlando M. Gutiérrez, MD, MMSc ,     University of Alabama at BirminghamBirmingham, ALUnited States

Carol J. Haggans, MS, RD ,     Office of Dietary Supplements, National Institutes of HealthBethesda, MDUnited States

Lenny K. Hong, MS ,     University of Illinois ChicagoChicago, ILUnited States

Ian T. Johnson, BSc, PhD ,     Quadram Institute BioscienceNorwich, NorfolkUnited Kingdom

Carol S. Johnston, PhD, RD ,     Arizona State UniversityPhoenix, AZUnited States

Peter J.H. Jones, PhD ,     University of ManitobaWinnipeg, MBCanada

Robert W. Kenefick, PhD, FACSM ,     Entrinsic Health Solutions, Inc.Norwood, MAUnited States

James B. Kirkland, PhD ,     University of GuelphGuelph, ONCanada

Vanessa A. Leone, PhD ,     University of Wisconsin-MadisonMadison, WIUnited States

Alice H. Lichtenstein, DSc ,     Tufts UniversityMedford, MAUnited States

Mark Tomás Mc Auley, BSc, MSc, PhD ,     University of ChesterChesterUnited Kingdom

Donald B. McCormick, PhD ,     Emory UniversityAtlanta, GAUnited States

Alfred H. Merrill Jr. PhD ,     Georgia Institute of TechnologyAtlanta, GAUnited States

Joshua W. Miller, PhD ,     Rutgers UniversityNew Brunswick, NJUnited States

Scott J. Montain, PhD, FACSM ,     United States Army Research Institute of Environmental MedicineNatick, MAUnited States

Rachel Mottet, MS ,     University of MinnesotaSt. Paul, MNUnited States

Forrest H. Nielsen, PhD ,     USDA Grand ForksGrand Forks, NDUnited States

Morrine Omolo, MSc ,     University of MinnesotaSt. Paul, MNUnited States

William Todd Penberthy, PhD ,     Continuing Medical EducationWinter Park, FLUnited States

Joseph F. Pierre, PhD ,     University of Tennessee Health Science CenterMemphis, TNUnited States

Harry G. Preuss, MD, MACN, CNS ,     Georgetown University Medical CenterWashington, DCUnited States

A. Rosanoff, PhD ,     The Center for Magnesium Education & ResearchPähoa, HIUnited States

Robert B. Rucker, PhD ,     University of California DavisDavis, CAUnited States

Moon-Suhn Ryu, PhD ,     University of MinnesotaSt. Paul, MNUnited States

Mahrou Sadri, MS ,     University of Nebrasksa–LincolnLincoln, NEUnited States

Michael N. Sawka, PhD, FACSM ,     Georgia Institute of TechnologyAtlanta, GAUnited States

Sue A. Shapses, PhD, RDN ,     Rutgers University Department of MedicineNew Brunswick, NJUnited States

Joanne Slavin, PhD, RDN ,     University of MinnesotaSt. Paul, MNUnited States

Sally P. Stabler, MD ,     University of Colorado School of MedicineAurora, COUnited States

Paul R. Thomas, EdD, RDN ,     Office of Dietary Supplements, National Institutes of HealthBethesda, MDUnited States

Maret G. Traber, PhD ,     Oregon State UniversityCorvallis, ORUnited States

Isis Trujillo-Gonzalez, PhD ,     University of North Carolina at Chapel HillChapel Hill, NCUnited States

John B. Vincent, PhD ,     University of AlabamaTuscaloosa, ALUnited States

Johannes von Lintig, PhD ,     Case Western Reserve UniversityCleveland, OHUnited States

Connie M. Weaver, PhD ,     Weaver and Associates Consulting, LLCWest Lafayette, INUnited States

Allyson A. West, PhD, RD ,     Cornell UniversityIthaca, NYUnited States

Klaas R. Westerterp, PhD ,     Maastricht UniversityMaastrichtThe Netherlands

Gary Williamson, PhD, FRSC, RNutr ,     Monash UniversityMelbourne, VICAustralia

Parveen Yaqoob, Dphil ,     University of ReadingReadingUnited Kingdom

Yong-Ming Yu, MD, PhD ,     Shriners Hospital, HarvardBoston, MAUnited States

Steven H. Zeisel, MD, PhD ,     University of North Carolina at Chapel HillChapel Hill, NCUnited States

Janos Zempleni, PhD ,     University of Nebrasksa–LincolnLincoln, NEUnited States

Michael B. Zimmermann, MD ,     Swiss Federal Institute of Technology ZürichZürichSwitzerland

Foreword

Timely information regarding nutrition is critical to improving human health and well-being and safeguarding the environment. The mission of the International Life Sciences Institute (ILSI) is in part to provide such information, and we are pleased to present the 11th edition of Present Knowledge in Nutrition.

First published in 1953, Present Knowledge in Nutrition was launched with the goal of providing readers with the most comprehensive and current information covering the broad fields within the nutrition discipline. Reflecting the global relevance of nutrition, this edition's authors are from a variety of countries and reflect a who's who of nutritional science.

ILSI is a worldwide nonprofit organization that seeks to foster science for the public good and collaboration among scientists, all governed by ILSI's core principles of scientific integrity. With 16 entities worldwide, ILSI published 70 scientific articles globally in 2019 and hosted 152 workshops addressing nutrition, food safety, and sustainability. ILSI is a world leader in creating public–private partnerships that advance science for the betterment of public health and achieve positive, real-world impact.

We trust the two volumes of Present Knowledge in Nutrition will be valuable resources for researchers, health professionals, clinicians, educators, and advanced nutrition students. ILSI is proud of the contributions made by the authors and editors of this key reference, and we are excited to advance the discipline of nutrition with this publication.

Kerr Dow, ILSI Board of Trustees Co-Chair

Michael Doyle, ILSI Board of Trustees Co-Chair

Preface

As editors, we feel privileged to have been asked to edit the 11th edition of Present Knowledge in Nutrition. The 11th edition moves this major nutrition reference source beyond its 65-year history and into an explosion of exciting new methodologies and understandings of the role of diet and nutrition in human health and well-being. In a global survey conducted in 2017, Present Knowledge in Nutrition was identified as a key resource for the latest information in the nutrition field for nutrition and dietetic professionals and clinicians. Specifically, survey participants stated that Present Knowledge in Nutrition was the source to which they turned when seeking the latest information in an area of nutrition that was outside their main expertise. Further, Present Knowledge in Nutrition is valued as an academic text in advanced nutrition courses. Recognizing the important role of the periodic updates of Present Knowledge in Nutrition among scientists and practitioners, as editors we have sought to maintain the long-standing tradition of identifying content-thought leaders to provide the most comprehensive and latest information in their fields in the chapters represented in this edition.

The 11th edition of Present Knowledge in Nutrition is presented in two companion volumes: Volume 1: Basic Nutrition and Metabolism and Volume 2: Clinical and Applied Topics in Nutrition. Provision of two volumes enables the reader to more quickly identify the location of relevant materials and makes the printed copies of this 72-chapter edition more physically portable. This 11th edition includes full color illustrations and other color-enhanced features. At the end of each chapter, authors clearly have identified important research gaps and needs for future research. Volume 1 includes chapters that provide the latest scientific knowledge on requirements for specific nutrients and genomics and chapters that discuss important cross-disciplinary topics including systems biology, the microbiome, and the role of nutrition in regulation of immune function. Volume 2 provides the most recent information on life-stage nutrition, obesity, physical activity, and eating behavior; dietary guidance; and nutrition surveillance, as well as major topics in nutrition and disease processes and medical nutrition therapy.

In addition to print volumes, the 11th edition of Present Knowledge in Nutrition is available in electronic format through the website: https://pkn11.org/where-to-buy/. The electronic format provides broader access not only globally but also for educational use.

We believe the authors have done an outstanding job in presenting the latest information in their respective fields and hope this edition will continue the long tradition of being an essential resource broadly in the nutrition field.

Bernadette P. Marriott

Charleston, South Carolina

Diane F. Birt

Ames, Iowa

Virginia A. Stallings

Philadelphia, Pennsylvania

Allison A. Yates

Johnson City, Tennessee

Acknowledgments

Development of a book of this in-depth and highly scientifically current content represents a large commitment of time and effort by many people. First, we would like to thank the authors of the 72 chapters for their commitment to this two-volume reference work and most importantly their dedication to presenting the best information of the current status of the science in their respective fields. Second, this edition would not have come to fruition without the untiring work and guidance of Allison Worden and James Cameron of the International Life Sciences Institute. We appreciated very much the early guidance of two of the editors of the 10th edition, John Erdman and Steven Zeisel, as we were forming the 11th edition concept. Key to any endeavor of this size is the support of family, colleagues, and friends to whom we owe our gratitude for their forbearance during the many hours devoted to this work's development and production.

Section A

Macronutrients

Outline

Chapter 1. Energy metabolism

Chapter 2. Protein and amino acids

Chapter 3. Carbohydrates

Chapter 4. Lipids

Chapter 1: Energy metabolism

Klaas R. Westerterp, PhD     Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University Medical Centre, Maastricht, The Netherlands

Summary

Man covers energy expenditure by the oxidation of the nutrients carbohydrate, protein, fat, and sometimes alcohol. Energy expenditure is assessed with indirect calorimetry, measuring oxygen consumption and/or carbon dioxide production, and with direct calorimetry, measuring heat loss from nutrient oxidation. Energy expenditure is a function of (1) body composition determining resting energy expenditure (REE), (2) food intake determining the energy cost of food processing, and (3) body movement determining activity-induced energy expenditure (AEE). Energy expenditure, and thus energy requirement, is generally higher in larger individuals, e.g., overweight and obese subjects, through a higher REE. Subjects in negative energy balance show reduced energy expenditure, mainly through a reduction of AEE. Physical activity is rather a function than a determinant of energy balance. The main determinant of energy balance is energy intake.

Keywords

Body composition; Diet-induced energy expenditure; Doubly labeled water; Energy requirement; Indirect calorimetry; Physical activity level; Resting energy expenditure

I. Introduction

Man, as a heterotrophic organism, derives his energy by the oxidation of nutrients. The oxidation yields energy to synthesize ATP for energy metabolism and is finally mainly transformed into heat. Total energy expenditure (TEE) consists of three components: energy expenditure for the processing of food—diet-induced energy expenditure (DEE); energy expenditure for maintenance—resting energy expenditure (REE); and energy expenditure for physical activity—activity-induced energy expenditure (AEE).

The following sections describe the measurement of nutrient and energy metabolism, components of energy expenditure, energy requirement, and disease-related alterations in energy requirement.

II. Nutrient and Energy Metabolism

A. Nutrient Metabolism

Energy expenditure is covered by the oxidation of carbohydrate, protein, and fat—taken together, the macronutrients—and sometimes alcohol. Methods for the measurement of energy expenditure are based on oxygen consumption, carbon dioxide production, and heat production of the metabolized nutrients. As an example, oxidation of 1   mol of glucose requires 6   mol of oxygen and produces 6   mol of water, 6   mol of carbon dioxide, and 2.8   MJ heat. Carbohydrate, fat, and alcohol are usually completely oxidized to water and carbon dioxide, whereas in the oxidation of protein, the nitrogen component is excreted in the urine, mainly as urea.

Thus, the contribution of the three macronutrients, carbohydrate, protein, and fat, to energy metabolism is derived from the three parameters: oxygen consumption; carbon dioxide production; and urine nitrogen loss.

As an illustration, the formula of Brouwer calculates macronutrient oxidation based on the relationships of the three end products of metabolism (Box 1.1).

Energy of ingested macronutrients is not fully available to energy metabolism, since part of it is lost in urine and feces. The energy loss in urine is mainly a function of protein catabolism to excrete the nitrogen, as mentioned above. Fecal energy loss is mainly a function of the consumption of nondigestible fiber. Metabolizable energy, ingested energy minus energy loss in urine and feces, of the typical Western diet varies around 90% of gross dietary energy intake, the energy as measured with a bomb calorimeter. Surprisingly, energy loss in urine and feces is not affected by the amount of food consumed. ¹ , ²

Box 1.1

Brouwer formula for calculation of the contribution of carbohydrate, protein, and fat to energy metabolism as derived from the three parameters: oxygen consumption, carbon dioxide production, and urine nitrogen loss.

¹²

  –   0.390   P;

Protein oxidation (g/d)                           =   6.25   N;

  =   oxygen consumption (L/d), corrected for alcohol oxidation; P   =   protein oxidation (g/d); N   =   total nitrogen excreted in urine (g/d).

Food composition tables for the calculation of energy intake have traditionally used the Atwater factors to adjust for energy losses in urine and feces and thus convert gross nutrient intake to metabolizable energy intake. ³ The Atwater factors for carbohydrate, protein, fat, and alcohol are, respectively, 17, 17, 37, and 29   kJ (4, 4, 9, and 7   kcal)/g.

There is a hierarchy in nutrient metabolism after consumption, reflecting the storage capacity in the body. ⁴ Alcohol, as a toxin, is readily absorbed and is principally eliminated by metabolism in the liver. Since ethanol is not stored in the body, it must be oxidized. Thus, alcohol ingestion results in short-term reduction of oxidation of the other nutrients. Carbohydrate and protein intake cause an increase in their oxidation by autoregulation. The increase in their oxidation is governed by the relative small storage capacity of carbohydrate as glycogen and protein in the labile protein and amino acid pool. ⁴ Fat is at the bottom of the oxidation hierarchy. Alcohol, carbohydrate, and protein oxidation suppress fat oxidation. ⁵ Fat oxidation is a function of the presence or absence of the other energy-providing nutrients. Fat oxidation is mainly a function of energy balance in that when intake exceeds expenditure, excess energy is stored by storing ingested fat. When intake is lower than expenditure, mobilized body fat, which in general is abundantly available, makes up the difference.

Humans are discontinuous eaters and continuous metabolizers. Thus, part of the energy intake has to be stored before it is used. Within a day, intervals with a positive energy balance after a meal alternate with intervals with a negative energy balance, such as overnight. There is a marked diurnal pattern of nutrient metabolism, with a higher rate of carbohydrate oxidation after meals and a higher rate of fat oxidation during the night and in the early morning, before food consumption. ⁶ Energy intake usually balances energy expenditure over several days up to a week. Energy intake strongly correlates with energy expenditure on a weekly basis. ⁷ For example, military cadets did not show an increase in energy intake on days with higher energy expenditure; the matching energy intake came some days afterward. ⁷ Similarly, a change in fat intake does not immediately affect fat oxidation. It took 7   days before fat oxidation was raised sufficiently in young lean subjects to match fat intake, when diet composition was isoenergetically switched from low-fat to high-fat diet. ⁸

In conclusion, measuring oxygen consumption, carbon dioxide production, and urinary nitrogen loss allows assessment of energy and nutrient metabolism. Results are affected by energy balance, and thus, especially for the assessment of nutrient metabolism, measurements should cover at least a full 24   h cycle and possibly up to a week.

B. Energy Metabolism

Energy production for energy expenditure can be assessed by measuring heat loss from the oxidation of nutrients (direct calorimetry) or by measuring gas exchange in the oxidation of nutrients (indirect calorimetry). One of the first devices to measure energy expenditure was a direct calorimeter for small animals.

Direct calorimetry

As early as 1780, Lavoisier measured heat loss of a guinea pig by placing the animal in a wire cage surrounded by ice chunks. Energy expenditure was calculated from the amount of ice melted by the animal's body heat. Later, direct calorimetry systems, including human calorimeters, used airflow or water flow to measure heat exchange. ⁹

An airflow calorimeter consists of a temperature-insulated ventilated space—for instance, a room large enough to house a subject. The temperature change of air flowing through the room multiplied by its mass flow rate and specific heat gives the rate of heat loss from the subject. ⁹

Box 1.2

Equations to calculate total energy expenditure (TEE) from oxygen consumption, carbon dioxide production, and urinary nitrogen loss.

deV Weir production (L)   –   2.17 urinary nitrogen loss (g)

Brouwer production (L)   –   0.15 urinary nitrogen loss (g)

An example of a water flow calorimeter is a suit calorimeter. The subject is dressed in a close-fitting elastic undergarment, which carries a network of small plastic tubing over the entire body surface, except for the face, fingers, and soles of the feet. Water circulated through the tubing carries heat from the skin, which is measured as the product of the mass flow of water and the change in temperature across the suit. An insulating outside garment limits the exchange of heat with the environment. ¹⁰

Indirect calorimetry

Presently, state of the art is the assessment of energy expenditure with indirect calorimetry because body heat loss, when measured with direct calorimetry, does not include power output for external work during exercise. Body heat loss can be up to 25% lower than TEE during endurance exercise. ¹¹

In indirect calorimetry, energy expenditure is calculated from nutrient metabolism by measuring oxygen consumption, carbon dioxide production, and urinary nitrogen loss. Examples of equations that are used to calculate the relationships are the Weir equation and the Brouwer equation (Box 1.2).

Usually, for the calculation of energy expenditure, one does not measure urinary nitrogen loss, so the protein correction is neglected. It is difficult to measure urinary nitrogen loss, especially over intervals shorter than a day, and the resulting error is small. For a subject in energy balance consuming a regular diet containing 10%–15% of the energy from protein, the protein correction is smaller than 1% of energy expenditure. ¹² Thus, energy expenditure is usually assessed by measuring oxygen consumption and carbon dioxide production.

In a recent variant of indirect calorimetry, the doubly labeled water method, energy expenditure is primarily calculated from measured carbon dioxide production. ¹³ With this method, the energy equivalent of carbon dioxide used in the calculation of energy expenditure is based on an estimate of nutrient metabolism. The energy equivalent of carbon dioxide ranges between a lower value of 21.1   kJ/L for carbohydrate to a higher value of 27.8   kJ/L for fat. ¹² For an average diet of energy from carbohydrate (55%), protein (10%–15%), and fat (30%–35%), the energy equivalent of carbon dioxide is 23.6   kJ/L.

The doubly labeled water method is based on the observation that oxygen in respiratory carbon dioxide is in isotopic equilibrium with oxygen in body water. ¹⁴ After enriching body water with oxygen-18 ( ¹⁸O), a stable isotope of oxygen, ¹⁸O is lost as a function of normal water loss and carbon dioxide production. The ¹⁸O loss in water is measured by simultaneous enrichment of body water with hydrogen-2 ( ²H), a stable isotope of hydrogen, lost from the body in water only. Thus, after consumption of doubly labeled water ( ²H2 ¹⁸O), carbon dioxide production can be calculated from the difference in washout between the two isotopes.

C. Application

The optimal technique for the indirect measurement of nutrient metabolism utilizes a respiration chamber, allowing measurements of oxygen consumption, carbon dioxide production, and urinary nitrogen loss over a 24-h cycle. Most respiration chambers have a volume of 10–30   m³ and are equipped with a bed, toilet, washbasin, and communication facilities like television and Internet (Fig. 1.1). A measurement in a respiration chamber typically covers one or more days. The optimal observation interval for application of the doubly labeled water method is 1–3   weeks: 1   week for subjects with a high energy turnover and 3   weeks when energy turnover is low as in sedentary older individuals. ¹⁵

Figure 1.1 Respiration chamber used for indirect calorimetry of subjects to measure energy expenditure for one or more days.

Energy metabolism techniques utilizing indirect calorimetry for the measurement of human energy expenditure also include measurement with a mouthpiece or facemask, or with a ventilated hood. Mouthpiece or facemask and ventilated hood are used for the measurement of gas exchange over limited time intervals, lasting one or more hours.

max. A ventilated hood allows the measurement of REE and DEE. TEE can be measured in a respiration chamber or with doubly labeled water. TEE, as measured in a respiration chamber over 24   h, can be split in the three components: REE, DEE, and AEE, with an independent simultaneous measurement of body movement in the chamber. ¹⁶ In contrast, the doubly labeled water method allows assessment of TEE without constraining the behavior of a subject. ¹³

Indirect calorimetry systems for the measurement of energy expenditure require regular validation with a reference method. The standard option is a gas mixture of known composition to check the calibration of the gas analyzers and passing a known air volume through the system to check the flow detector. A more sophisticated method is burning methanol, which checks the gas analyzers and the flow detector simultaneously. ¹⁷ , ¹⁸ Alternatively, one or more healthy subjects can be measured, where the resulting energy expenditures should be comparable with the values derived from a prediction equation for the same subjects.

III. Components of Energy Expenditure

TEE is mainly a function of food intake, body composition, and physical activity. Food intake determines energy expenditure for the processing of food. Body composition determines energy expenditure for maintenance or REE, generally the largest component of TEE. Physical activity determines AEE, the most variable component of TEE, showing large differences within a day and between days. Here, determinants of energy expenditure are described with respect to mechanisms and effect size.

A. Diet-Induced Energy Expenditure

Energy expenditure for the processing of food or DEE is the energy expenditure for intestinal absorption of nutrients, the initial steps of their metabolism and the storage of the absorbed but not immediately oxidized nutrients. Other names for the same component of TEE are specific dynamic action, thermic effect of food, and diet-induced thermogenesis. It is measured as the increase in energy expenditure above REE after consumption of a meal and expressed as the increase in energy expenditure divided by the energy content of the meal consumed. Measuring energy expenditure after a typical single meal providing about 25% of estimated daily energy expenditure with 15% of the meal energy as protein showed that DEE lasts beyond 6   h. ¹⁹ Measuring energy expenditure over 24   h in a respiration chamber showed the level of energy expenditure, after adjustment for AEE and thus including only REE and DEE, did not return to REE before lunch (at 4   h after breakfast), or before dinner at 5   h after lunch (Fig. 1.2 ¹⁶ ). Overnight, REE was reached at 8   h after dinner. ¹⁶

Figure 1.2 The mean pattern of diet-induced energy expenditure (DEE) throughout the day, calculated by plotting the residual of the individual relationship between energy expenditure and physical activity in time, as measured over 30-min intervals from a 24-h observation in a respiration chamber (blue line   =   level of resting energy expenditure [REE]; arrows   =   meal times). 

Reproduced from Westerterp KR. Diet induced thermogenesis. Nutr Metab. 2004;1:5.

The main determinants of DEE are the amount of food consumed and food composition. Theoretical values for DEE, based on the amount of ATP required for the initial steps of their metabolism and storage, are 0%–3% for fat, 5%–10% for carbohydrate, and 20%–30% for protein. ²⁰ For a mixed diet with 30%–35% of energy from fat, 50%–55% from carbohydrate, and 10%–15% from protein, DEE is about 10% of the total amount of energy ingested. Thus, when a subject's energy intake meets the subject's energy requirement, DEE is 10% of TEE. In practice, reported DEE values are around 10% of energy intake with slightly higher values for diets higher in protein, as expected. ¹⁶

B. Resting Energy Expenditure

Maintenance metabolism or REE is defined as the daily rate of energy expenditure to maintain and preserve the integrity of vital functions. The measurement of REE must meet four conditions: the subject is awake; is measured in a thermoneutral environment to avoid heat production for the maintenance of body temperature; is fasted long enough to eliminate DEE; and is at rest to eliminate AEE. To meet measurement conditions, a subject usually stays overnight in the research facility where food intake and physical activity are controlled and REE is measured directly after waking up in the morning, 10–12   h after the last food intake and before getting physically active.

Figure 1.3 Resting energy expenditure (REE) plotted as a function of fat-free mass (FFM) with the linear regression line: REE (MJ/d)   =   0.097 FFM (kg)   +   1.61, R²   =   0.83 (green dots, women; red dots men). 

Data from Pannemans DL, Westerterp KR. Energy expenditure, physical activity and basal metabolic rate of elderly subjects. Br J Nutr 1995;73:571–581.

The major determinant of REE is body composition, i.e., fat-free body mass. Differences in REE between subjects are largely explained by differences in fat-free mass. REE in women is generally lower than REE in men because, for the same body weight, women generally have a lower fat-free mass. In a multivariate analysis with fat-free mass and gender, gender did not emerge as a significant contributor to the explained variation. ²¹

The regression of REE on fat-free mass has a significant and positive intercept (Fig. 1.3 ²² ). Thus, adjusting REE for differences in fat-free mass between subjects by dividing REE by the absolute fat-free mass value is not meaningful. Then, the smaller the fat-free mass, the higher the REE per kg fat-free mass.

When measurements of REE are not available, there are prediction equations for REE, based on an estimation of fat-free mass from subject sex, weight, height, and age. Examples are Harris–Benedict ²³ ; Food and Agricultural Organization (FAO) ²⁴ ; Owen ²⁵ , ²⁶ ; and Mifflin equations ²⁷ (Table 1.1). They all were derived in Caucasian subjects and thus are applicable for Caucasian subjects. The more an individual shares characteristics with the group of people from whom the equation was developed, the better the estimate. For example, the Mifflin equation was derived from a population with a larger number of obese subjects and thus is usually applied for overweight and obese subjects.

Ethnicities differing in body build affecting body composition require ethnicity-specific equations to accurately predict REE from subject sex, weight, height, and age.

Alternatively, there are equations predicting REE directly from fat-free mass such as the Cunningham equation. ²⁸ The Cunningham equation was based on data from eight studies, including more than 100 subjects each, women and men, lean and obese (Table 1.1). An exception, where even the Cunningham equation based on fat-free mass did not produce accurate estimates for REE, are elite athletes. Sjödin and colleagues measured REE values 16% higher in Olympic cross-country skiers than predicted from the weight-based FAO equation and 12% higher than in sedentary fat-free mass-matched control subjects. ²⁹

Table 1.1

a  Equation derived by combining the original data for women and men.

C. Activity-Induced Energy Expenditure

Energy expenditure for physical activity or AEE is the energy produced by skeletal muscle, mainly for body movement. It is calculated from TEE by adjustment for REE and DEE. Measurement of TEE for calculation of AEE in daily life, without interference with the behavior of a subject, is performed with the doubly labeled water method, which was first applied in humans in 1982. ³⁰

The physical activity level (PAL) can then be calculated from a measured or estimated REE value where PAL   =   TEE/REE. ²⁴ , ³¹ Alternatively, AEE can be calculated as 0.9 (TEE   −   REE), assuming DEE is a fixed fraction of 10% of the consumed energy, and energy intake meets TEE (thus no contribution from body fat as an energy source; see Section IV.A).

Figure 1.4 General model for the physical activity level (PAL), total energy expenditure (TEE) as a multiple of resting energy expenditure (REE), in relation to age (green   =   women; red line   =   men). 

Data from FAO/WHO/UNU. Human energy requirements. Joint FAO/WHO/UNU Expert Consultation. FAO Food and Nutrition Technical Report Series no. 1. Rome, 2004; Westerterp KR. Exercise, energy expenditure and energy balance, as measured with doubly labelled water. Proc Nutr Soc 2018;77:4–10.

Based on a compilation of doubly labeled water-measured TEE values over 20 years worldwide, the World Health Organization classified PAL values as 1.40–1.69 for a sedentary or light active lifestyle; 1.70–1.99 for active or moderately active lifestyles; and 2.00–2.40 for a vigorously active lifestyle. ³¹ Similarly, the US Institute of Medicine classified PAL values as 1.0–1.39 for a sedentary lifestyle; 1.4–1.59 for a low active lifestyle; 1.6–1.89 for an active lifestyle; and 1.9–2.49 for a very active lifestyle. ³² A PAL value of 1.4 is typical for one-year-olds, starting to move around by walking (Fig. 1.4 ³¹ , ³³ ). Subsequently, PAL increases to reach a mean adult level around 1.7, decreasing after reaching the age of 50   y in most subjects. At a PAL value of 1.7, AEE is about one-third of TEE, assuming DEE is 10% of TEE. Higher PAL values than 2.4 for a vigorously active lifestyle are observed in extremely active young adults, including athletes. However, in most studies with PAL values higher than 2.00–2.40, subjects were in a negative energy balance showing there is a limit to AEE for a sustainable lifestyle. ³⁴

IV. Energy Requirement

Energy requirement is a function of body composition, food intake, and physical activity as determinants of, respectively, REE, DEE, and AEE, the components of TEE. For healthy subjects in energy balance, energy requirement is based on measured or estimated REE and PAL. Thus, energy requirement for an average adult woman is 11   MJ (2630   kcal)/d and for an average adult man 13   MJ (3107   kcal)/d (Box 1.3). The difference in energy requirement between similar age women and men is mainly due to a difference in body composition, resulting in a lower REE for women. Women generally have lower fat-free mass than men, resulting in a lower energy requirement despite a similar PAL.

Box 1.3

Example: Energy requirement for an average adult woman and man with a typical PAL of 1.7 (active lifestyle).

Subject characteristics, average adult woman: age 25   y; height 1.70   m; body mass 65   kg.

Subject characteristics, average adult man: age 25   y; height 1.80   m; body mass 75   kg.

Resting energy expenditure (REE) is estimated with the Harris–Benedict equation (Table 1.1) and TEE estimated based on PAL   =   1.7:

Woman, REE   =   6.4   MJ (1530   kcal)/d; TEE (1.7   ×   6.4)   =   11   MJ (2630   kcal)/d

Man, REE   =   7.6   MJ (1816   kcal)/d; TEE (1.7   ×   7.6)   =   13   MJ (3107   kcal)/d

Figure 1.5 General model for total energy expenditure (TEE) as a function of body mass (green   =   women; red   =   men). 

Data from Westerterp KR. Exercise, energy expenditure and energy balance, as measured with doubly labelled water. Proc Nutr Soc 2018;77:4–10.

In addition to body composition, food intake, and physical activity, energy requirement is affected by adaptive thermogenesis and exercise economy.

A. Body Composition and Energy Requirement

Energy requirement increases with body mass. Energy expenditure and thus energy requirement is higher in overweight and obese than in lean subjects, an observation confirmed by doubly labeled water assessment of TEE in free-living subjects. ³⁵ The relationship between body mass and TEE is curvilinear (Fig. 1.5 ³³ ) and mainly reflects the higher REE in subjects with a larger body mass. ³⁶ Overweight and obese subjects are characterized by a larger, metabolically inert, fat mass as well as a larger metabolically active body mass.

A larger maintenance requirement for a larger body mass requires more energy from food, and thus DEE is higher in larger subjects as well. There has been the suggestion of a reduced DEE in obese subjects, explained by insulin resistance. ³⁷ However, a later review did not confirm DEE is reduced in obese subjects. ³⁸ Thus, a larger body mass implies a higher REE and DEE in overweight and obese, as well as lean individuals.

A larger body mass requires more energy to perform the same physical activities, especially weight-bearing activities. Doubly labeled water studies have shown that PAL is similar at different levels of body mass index, except the very highest. ³⁹ , ⁴⁰ Body mass index is defined as the weight (kg) of an individual divided by height (m)². Subjects with a body mass index higher than 40   kg/m², generally show a lower PAL. TEE increases with body mass as a function of fat-free mass and not as a function of total body mass ⁴¹ , ⁴² because AEE per kg body mass is negatively related to body fat percentage. ⁴² Thus, fatter subjects generally move less than lean subjects despite similar or higher measured AEE. ⁴³

B. Food Intake and Energy Requirement

Underfeeding

The Minnesota Experiment is a classical study conducted to determine the effect of food intake on energy expenditure. ⁴⁴ Famine in Europe during World War II was the impetus for a controlled experiment in America in 1944 to determine changes in energy balance induced by semistarvation. Thirty-two men, conscientious objectors to the war recruited from work camps in the United States, stayed in the laboratory for a total of 48   weeks. Following a 12-week baseline period, 24   weeks of semistarvation concluded with an additional 12   weeks of rehabilitation. During the study, subjects were assigned to specific maintenance tasks and outdoor activities. The diet in the baseline period was adjusted to body weight maintenance, providing an average of 14.6   MJ (3490   kcal)/d. In the semistarvation period, the diet was served in two meals per day at 8:30 and 17:00, providing an average of 6.6   MJ (1575   kcal)/d. The body weight of the subjects with an initial mean body mass index of 21.4   kg/m² decreased from a mean value of 69.4   –52.6   kg, resulting in a final mean body mass index of 16.3   kg/m². The weight loss decreased progressively and nearly reached a plateau toward the end of the semistarvation period ⁴⁴ (Fig. 1.6). Thus, the subjects adjusted energy expenditure to reach energy balance after 24   weeks at an average of 45% of what had been their ad libitum energy intake during the first 12   weeks. The main part of the 8.0   MJ (1912   kcal)/d adaptation of TEE stemmed from a reduction of AEE by 4.7   MJ (1123   kcal)/d, one-third of which resulted from the loss of weight making movement less energy demanding and the remaining two-thirds through reduction of body movement.

Figure 1.6 Mean daily energy intake (green dots) and mean body weight (red dots) of 32 men during 24 weeks of semistarvation. 

Data from Keys A, Brozeck J, Henschel A, et al., The Biology of Human Starvation, 1950, University of Minnesota Press, Minneapolis.

Reducing energy intake by 8   MJ (1912   kcal)/d would result in a reduction of DEE by 0.8   MJ (191   kcal)/d, 10% of the reduction of energy intake. The remaining 2.5   MJ (600   kcal)/d of the 8   MJ (1912   kcal)/d adaptation of TEE resulted from a reduction of REE, two-thirds of which came from a decrease in fat-free mass to be maintained and the remaining one-third from a lowering of tissue metabolism.

Together, the adaptation can be split into a passive component of about 4   MJ (950   kcal)/d (through the reduction of DEE due to lower food intake, a reduction of AEE due to moving less weight when physically active, and a reduction of REE due to having less fat-free mass to maintain), and an active component of 4   MJ (950   kcal)/d (through a reduction in physical activity and a reduction in tissue metabolism). Similar adaptations have been observed in overweight and obese subjects when subjected to an energy-restricted diet to lose weight. ⁴⁵ , ⁴⁶

Overfeeding

So far, overfeeding studies have not shown active adaptations of energy expenditure. Overfeeding only induces an increase in TEE through the increase of DEE due to a higher food intake and an increase of AEE due to moving more weight due to the resulting higher body weight when physically active and an increase of REE resulting from having more fat-free mass to maintain. ⁴⁷ There are no indications for an overfeeding-induced increase in physical activity or an increase in tissue metabolism. One study which doubled energy intake for 9 weeks induced a mean body weight increase of 17   kg, while showing the opposite for AEE, with a reduction of PAL from 1.87 (an active lifestyle) to 1.45 (a very sedentary activity level). ⁴⁸

C. Physical Activity and Energy Requirement

A typical study showing the effect of a change in PAL on energy expenditure is a report of an experiment training young adults for 44 weeks to run a half marathon competition. ⁴⁹ Before the training, subjects were not participating in any sports such as running or jogging and were not active in any other sport for more than 1   hour per week. Out of nearly 400 respondents, 16 women and 16 men were selected of comparable age (28–41   y) and normal body weight (reported body mass index 20–25   kg/m²). The training consisted of four training sessions per week, increasing the running time from 0 to 10–30   min, 20–60   min, and 30–90   min per session after 8, 20, and 40 weeks, respectively. Energy expenditure measurements included overnight REE in a respiration chamber and TEE over 2-week intervals with doubly labeled water, after 0, 8, 20, and 40 weeks of training. During the study, five women and four men withdrew from the study. All dropouts had an initial body mass index higher than the group mean, suggesting a higher body weight limited an ability to participate in weight-bearing activities like running. In those who completed the study, the training induced a change in PAL from an initial mean value below 1.7 for a sedentary or light active lifestyle to values around 2.0 for a vigorously active lifestyle ⁴⁹ (Fig. 1.7). PAL increased initially and subsequently leveled off despite a further doubling of the training volume. The initial increase in PAL was higher than the predicted cost of the training and could not be explained by a decrease in nontraining activity, indicating a low exercise economy. The subsequent increase in training volume without a further increase in PAL shows a training-induced increase in exercise economy in novice runners. At the group level, the training did not induce a change in body weight despite a 20%–30% increase in TEE, indicating a compensatory increase in energy intake. However, most subjects gained fat-free mass and lost fat mass. The loss in fat mass was positively related to initial fat mass, fatter individuals losing more than lean ones. Other studies have confirmed that exercise training results in a healthier body composition as reflected by a reduction of body fat, especially in overweight and obese subjects, with little or no long-term effect on body weight. ⁵⁰

Figure 1.7 Training distance (green line) and physical activity level (PAL, red dots), total energy expenditure (TEE) as a multiple of resting energy expenditure (REE), in subjects completing a 40-week preparation to run a half marathon. 

Data from Westerterp KR, Meijer GA, Janssen EM, et al., Long-term effect of physical activity on energy balance and body composition. Br J Nutr 1992;68:21–30.

D. Adaptive Thermogenesis

Adaptive thermogenesis is a change in energy expenditure beyond that which can be predicted by the change in body weight and/or body composition. Thus, as described above, there was an adaptive reduction in REE and AEE through a lowering of tissue metabolism and a reduction in body movement, respectively, during long-term semistarvation. ⁴⁴ So far, there is no evidence for a similar adaptive response to a positive energy balance, through an increase in energy expenditure. ⁴⁷ There is a biological defense against weight loss and little or no defense against weight gain. ⁵¹

Adaptive thermogenesis in response to energy restriction is one of the explanations for the limited success of attempts to lose weight in overweight and obese subjects. Studies suggest that a reduction in REE and in AEE occurs at as small a weight loss as >5% and >10%, respectively. ⁵² The rate of weight loss does not seem to affect the extent of adaptive thermogenesis. Adaptive thermogenesis was not different for obese subjects losing a similar amount of weight with a total fast, a very low energy diet proving 2.5   MJ (600   kcal)/d, or a low energy diet providing 5.2   MJ (1250   kcal)/d. ⁵³ Most studies applying intermittent energy restriction—dieting on some days of the week—show no difference in weight loss with continuous dieting either. ⁵⁴ So far, there is no dieting strategy to overcome energy restriction–induced adaptive thermogenesis.

The adaptive reduction in AEE in response to energy restriction was shown to recover when energy balance was reached during weight maintenance after weight loss. ⁴⁶ However, the adaptive reduction in REE in response to energy restriction did not recover during weight maintenance after weight loss. ⁴⁵ The