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SIGHT AND LIFE

Press

Edited by

Klaus Kraemer

Michael B. Zimmermann

Nutritional Anemia

Preface 1

Nutritional Anemia

SIGHT AND LIFE

Press

Edited by

Klaus Kraemer

SIGHT AND LIFE, Basel, Switzerland

Michael B. Zimmermann

Swiss Federal Institute of Technology, Zurich, Switzerland

Nutritional Anemia

SIGHT AND LIFE Mission Statement

SIGHT AND LIFE is a humanitarian initiative of DSM. It aims to ensure a sustainable and significant

improvement in human nutrition and health by encouraging partnerships with universities and intergov￾ernmental and governmental agencies, by generating and exchanging scientific information and by

forming networks.

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ISBN 3-906412-33-4

IV

For half a billion women in developing

regions worldwide, anemia is a life-long bur￾den, one which affects most of their infants

and young children as well. Controlling ane￾mia in these vulnerable groups could signifi￾cantly reduce maternal and infant morbidity.

It would also enhance intellectual and work

capacity, thereby improving family, commu￾nity and national socioeconomic development.

In May 2002, the General Assembly of

the United Nations reemphasized that control

of nutritional anemia should be one of the

global Development Goals to be achieved in

the early years of this new millennium. Despite

this, the global prevalence of anemia has

hardly declined in the past decade, although

considerable programmatic experience exists

and a vast amount of scientific data has been

compiled on iron metabolism. Much is still

unknown, however, and many new issues

continue to emerge from the ongoing research,

both basic and programmatic. The reasons for

this lack of improvement include the multi￾factorial etiology of anemia, underfunding and

poor program implementation, often designed

on the assumption that the sole cause of

anemia is iron deficiency.

It is increasingly clear that effective con￾trol of anemia requires integrated solutions

that are tailored to the particular needs and

opportunities in each country. Components of

such an approach include food fortification,

micronutrient supplementation of vulnerable

groups (particularly children and women of

childbearing age), education, and dietary

diversification, as well as control of diseases

such as malaria, worm infections, and other

chronic endemic infections. While each of

these can help reduce the burden of anemia,

none is capable of doing the job on its own.

The chapters of this book offer an account

of the information that was presented and

comprehensively discussed at a workshop on

Nutritional Anemia in Barcelona, Spain, on

September 27, 2006, in which all the contribu￾tors to this volume themselves took part. This

event was co-organized by the editors of this

volume. We sought the timely publication of

this book in order to provide the latest update

on the complex causes and consequences of

nutritional anemia, and the effectiveness of

current control strategies. The field of anemia

is clearly of great interest to scientists, policy

makers and program mangers. We hope this

volume will help point the way forward in con￾trolling this major global health problem. The

introductory chapters in this book give an

overview of the global burden of anemia

prevalence, the economic implications and

functional consequences, and the significance

of these factors for policy makers. Subsequent

chapters provide basic scientific information

on iron metabolism and interactions with

macronutrients and micronutrients as well as

the role of infections in fostering anemia.

Other chapters address the information needs

of program managers, detailing programmatic

approaches and outlining the safety and techni￾cal aspects of interventions.

We are particularly grateful to the authors,

who are all leading scholars from UN agencies

and the wider academic world, for their excel￾lent contributions. A special acknowledgement

is also due to all reviewers whose valuable

comments have helped to improve the quality

of the chapters. We would like to give a very

Preface 1

PREFACE

special thanks to the SIGHT AND LIFE team,

Svenia Sayer-Ruehmann and Anne-Catherine

Frey, for assisting with the workshop as well as

for all their technical support in finalizing this

book. Svenia devoted much of her time and

energies to corresponding with the authors to

ensure that our tight timeline was met. We

would also like to express our deep apprecia￾tion to Jane Badham for her invaluable assis￾tance with the editing of the chapters. Lastly,

we wish to thank SIGHT AND LIFE and DSM,

in particular its President and incoming CEO,

Feike Sijbesma, for his continuing support of

our work and the publication of this book.

Klaus Kraemer

Michael B. Zimmermann

VI Preface

Every year hunger and undernutrition claim

more than 10 million lives – more than the deaths

from AIDS, malaria and tuberculosis combined.

Many of these people are affected by “hidden

hunger,” a lack of essential vitamins and miner￾als, known as micronutrient deficiencies, which

do not necessarily result in the swollen bellies and

stick-like limbs many associate with serious mal￾nutrition.

The effects of poor nutrition are not always

easy to spot. Undernourished children are less

likely to attend school, more likely to have learn￾ing difficulties, are more susceptible to disease.

They are more likely to die young. Undernour￾ished adults are less capable of providing suffi￾cient food and other necessities for their families.

Their immune systems may be compromised.

Their productivity and income is invariably

lower.

Poor nutrition impacts the health and devel￾opment of individuals. It also retards the eco￾nomic and social development of nations. For

instance, it is estimated that anemia alone causes

US $50 billion in gross domestic product losses

annually.1 Reducing the number of hungry and

malnourished people translates into a better qual￾ity of life for individuals, as well as narrowing

national disparities in health, education, and

wealth.

Infants, young children and women of child￾bearing age are those at greatest risk of nutritional

anemia. This condition, which claims one million

lives each year, is associated with increased child

and maternal mortality, stillbirths, low-birth￾weight and premature babies. It is one of the

world's leading causes of disability and can cause

mild mental retardation and decreased work per￾formance.

Caused predominantly by iron-deficiency,

anemia is inextricably linked with people's nutri￾tional status and hunger. In 2000, the United

Nations Sub-Committee on Nutrition reported

that 43% of people in developing countries cur￾rently suffer from anemia2. In spite of the signifi￾cant burden anemia places on health systems and

economies, it has often been overlooked by the

international and public health communities.

This book assembles some of the leading

research on health and nutrition. The evidence

clearly points to the benefits – and feasibility – of

reducing the prevalence of anemia and combating

undernutrition. This textbook also serves as a

guide for how government, international agen￾cies, and non-governmental organizations can

work together to decrease rates of nutritional ane￾mia worldwide. It reviews the most effective

ways of measuring and monitoring the prevalence

of nutritional anemia and the most successful pro￾gram designs for public health interventions.

International organizations, such as the World

Food Programme, depend on such research in

order to deliver the best possible assistance to

Preface 1

1 MacDonald B, Haddad L, Gross R, McLachlan M. A foundation for development.

Administrative Committee on Coordination/Subcommittee on Nutrition. Accessed July 24, 2005.

Available at: http://www.ifpri.org/pubs/books/intnut/intnut.pdf

2 ibid

FOREWORD

hungry and malnourished poor people. These are

the people who have least choice in their diet, and

who are at tremendous risk of anemia and other

micronutrient deficiencies. The World Food Pro￾gramme and its partners help to provide iron sup￾plements and fortified foods in developing coun￾tries around the world.

Iron fortification is one of the most cost￾effective interventions and nutrition education

programs have reduced the prevalence of anemia

among infants and young children by increasing

their consumption of fortified foods. Presently,

the World Food Programme is the world's largest

purchaser of vitamin- and mineral-fortified blended

foods.

Fortified foods alone are not enough. Suc￾cessful delivery of such interventions requires the

strengthening of health systems, increased aware￾ness, and financial investment. An integrated

approach – including better water and sanitation,

infectious disease control, nutrition education,

food security, and poverty-reduction programs –

is required.

Together with partners like DSM and SIGHT

AND LIFE, we can and must do more to reduce

micronutrient deficiencies such as nutritional

anemia. This textbook, which focuses on re￾ducing the prevalence of nutritional anemia, is

key to reducing overall hunger and malnutrition

rates. It is incumbent upon us to use this informa￾tion to combat nutritional anemia, improve the

nutritional status of those in developing countries,

and mitigate one of today's greatest public health

problems.

The health and well being of millions of

hungry women and children depends on it.

James T. Morris

Executive Director

World Food Programme

VIII Foreword

HAROLD ALDERMAN

Africa Region of the World Bank, Washington,

DC, USA; [email protected]

JANE BADHAM

JB Consultancy, Health Communication and

Strategy Consultants, Johannesburg, South

Africa; [email protected]

HANS-KONRAD BIESALSKI

Institute for Biological Chemistry and Nutrition

at the University of Hohenheim, Hohenheim,

Germany; [email protected]

MARTIN BLOEM

World Food Programme (WFP), Rome, Italy;

[email protected]

TOMMASO CAVALLI-SFORZA

Nutrition and Food Safety, WHO Regional Office

for the Western Pacific, Manila, Philippines;

[email protected]

MARY COGSWELL

Division of Nutrition and Physical Activity, Cen￾ters for Disease Control and Prevention, Atlanta;

USA

IAN DARNTON-HILL

Nutrition Section, UNICEF, New York, USA;

[email protected]

OMAR DARY

A2Z Project, Academy for Educational Develop￾ment, Washington, DC, USA; [email protected]

BRUNO DE BENOIST

World Health Organization (WHO), Geneva,

Switzerland; [email protected]

SASKIA DE PEE

World Food Programme (WFP), Rome, Italy;

[email protected]

INES EGLI

Institute of Food Science and Nutrition, Swiss

Federal Institute of Technology (ETH), Zurich,

Switzerland; [email protected]

JÜRGEN ERHARDT

University of Indonesia, SEAMEO-TROPMED,

Jakarta, Indonesia; [email protected]

ALISON D. GERNAND

Bloomberg School of Public Health, Johns Hopkins

University, Baltimore, USA; [email protected]

GARY R. GLEASON

Friedman School of Nutrition Science and Policy,

Tufts University, Boston, USA;

[email protected]

EVA HERTRAMPF DÍAZ

Institute of Nutrition and Food Technology

(INTA), University of Chile, Santiago, Chile;

[email protected]

SUSAN HORTON

Wilfrid Laurier University, Waterloo, Canada;

[email protected]

RICHARD HURRELL

Institute of Food Science and Nutrition, Swiss

Federal Institute of Technology (ETH), Zurich,

Switzerland; [email protected]

ALAN JACKSON

Institute of Human Nutrition, University of

Southampton, Southampton, UK; [email protected]

AFAF KAMAL-ELDIN

Department of Food Science, Swedish University

of Agricultural Sciences, Uppsala, Sweden;

[email protected]

KLAUS KRAEMER

SIGHT AND LIFE, Basel, Switzerland; klaus.

[email protected]

Preface IX

CONTRIBUTORS

SEAN LYNCH

Eastern Virginia Medical School, Norfolk, USA;

[email protected]

M.G. VENKATESH MANNAR

The Micronutrient Initiative, Ottawa, Canada;

[email protected]

ERIN MCLEAN

World Health Organization (WHO), Geneva,

Switzerland; [email protected]

REGINA MOENCH-PFANNER

Global Alliance for Improved Nutrition (GAIN),

Geneva, Switzerland; rmoenchpfanner@gain￾geneva.org

CHRISTINE A. NORTHROP-CLEWES

Northern Ireland Centre for Food and Health, Univer￾sity of Ulster, Coleraine, UK; [email protected]

MANUEL OLIVARES

Institute of Nutrition and Food Technology

(INTA), University of Chile, Santiago, Chile;

[email protected]

NEAL PARAGAS

Institute of Human Nutrition, Columbia Univer￾sity, New York, USA; [email protected]

KLAUS SCHÜMANN

Technical University of Munich, Freising, Ger￾many; [email protected]

JOHN M. SCOTT

School of Biochemistry & Immunology, Trinity

College Dublin, Dublin, Ireland; [email protected]

NEVIN SCRIMSHAW

International Nutrition Foundation, Boston, USA;

[email protected]

RICHARD SEMBA

School of Medicine, Johns Hopkins University,

Baltimore, USA; [email protected]

NOEL SOLOMONS

Center for Studies of Sensory Impairment, Aging

and Metabolism (CeSSIAM), Guatemala City,

Guatemala; [email protected]

ALFRED SOMMER

Bloomberg School of Public Health, Johns

Hopkins University, Baltimore, USA;

[email protected]

ELISABETH STOECKLIN

R & D Human Nutrition and Health, DSM Nutri￾tional Products Ltd, Kaiseraugst, Switzerland;

[email protected]

BRIAN THOMPSON

Food and Agriculture Organization (FAO), Rome,

Italy; [email protected]

DAVID THURNHAM

Northern Ireland Centre for Food and Health,

University of Ulster, Coleraine, UK;

[email protected]

MELODY C. TONDEUR

Division of Gastroenterology, Hepatology and

Nutrition, Hospital for Sick Children, Toronto,

Canada, [email protected]

MARET G. TRABER

Linus Pauling Institute & Department of Nutrition

and Exercise Sciences, Oregon State University,

Corvallis, USA; [email protected]

RICARDO UAUY

Institute of Nutrition and Food Technology

(INTA), University of Chile, Santiago, Chile;

[email protected]

KEITH P. WEST

Bloomberg School of Public Health, Johns Hopkins

University, Baltimore, USA; [email protected]

DANIEL WOJDYLA

Escuela de Estadistica, Universidad Nacional de

Rosario, Argentina

MICHAEL ZIMMERMANN

Laboratory for Human Nutrition, Swiss Federal

Institute of Technology (ETH), Zurich, Switzer￾land; [email protected]

STANLEY ZLOTKIN

Departments of Paediatrics and Nutritional Scien￾ces and Public Health Sciences, University of

Toronto, Canada; [email protected]

X Contributors

Preface V

Foreword VII

Contributors IX

Contents XI

CHAPTER 1 Worldwide prevalence of anemia in preschool aged children,

pregnant women and non-pregnant women of reproductive age

Erin McLean, Ines Egli, Mary Cogswell, Bruno de Benoist

and Daniel Wojdyla 1

CHAPTER 2 The case for urgent action to address nutritional anemia

M.G. Venkatesh Mannar 13

CHAPTER 3 The economics of addressing nutritional anemia

Harold Alderman and Susan Horton 19

CHAPTER 4 Diagnosis of nutritional anemia – laboratory assessment of iron status

Hans-Konrad Biesalski and Jürgen G. Erhardt 37

CHAPTER 5 An overview of the functional significance of iron deficiency

Gary Gleason and Nevin S. Scrimshaw 45

CHAPTER 6 Iron metabolism

Sean Lynch 59

CHAPTER 7 Optimizing the bioavailability of iron compounds for food fortification

Richard Hurrell and Ines Egli 77

CHAPTER 8 Copper and zinc interactions in anemia: a public health perspective

Manuel Olivares and Eva Hertrampf and Ricardo Uauy 99

CHAPTER 9 Nutritional anemia: B-vitamins

John M. Scott 111

CHAPTER 10 Vitamin A in nutritional anemia

Keith P. West, Jr., Alison D. Gernand and Alfred Sommer 133

Preface XI

CONTENTS

CHAPTER 11 Oxidative stress and vitamin E in anemia

Maret G. Traber and Afaf Kamal-Eldin 155

CHAPTER 12 Selenium

Richard D. Semba 189

CHAPTER 13 Interactions between iron and vitamin A, riboflavin, copper,

and zinc in the etiology of anemia

Michael B. Zimmermann 199

CHAPTER 14 Anemia in severe undernutrition (malnutrition)

Alan A. Jackson 215

CHAPTER 15 Infection and the etiology of anemia

David I. Thurnham and Christine A. Northrop-Clewes 231

CHAPTER 16 Making programs for controlling anemia more successful

Saskia de Pee, Martin W. Bloem, Regina Moench-Pfanner

and Richard D. Semba 257

CHAPTER 17 Successful approaches: Sprinkles

Stanley H. Zlotkin and Melody Tondeur 269

CHAPTER 18 Safety of interventions to reduce nutritional anemias

Klaus Schümann and Noel W. Solomons 285

CHAPTER 19 The importance and limitations of food fortification for the

management of nutritional anemias

Omar Dary 315

CHAPTER 20 Food-based approaches for combating iron deficiency

Brian Thompson 337

CHAPTER 21 Global perspectives: accelerating progress on preventing

and controlling nutritional anemia

Ian Darnton-Hill, Neal Paragas and Tommaso Cavalli-Sforza 359

CHAPTER 22 Conclusions and research agenda

Klaus Kraemer, Elisabeth Stoecklin and Jane Badham 383

Index 389

XII Contributors

1

Worldwide prevalence of anemia in pre￾school aged children, pregnant women and

non-pregnant women of reproductive age*

1Department of Nutrition for Health and Development, World Health Organization,

Geneva, Switzerland

2Division of Nutrition and Physical Activity, Centers for Disease Control and Prevention,

Atlanta, USA

3Human Nutrition Laboratory, Swiss Federal Institute of Technology, Zurich, Switzerland

4Escuela de Estadistica, Universidad Nacional de Rosario, Rosario, Argentina

Contact: [email protected]

* Two of the authors are staff member of the World health Organization. They alone are responsible for the views expressed in

this publication and they do not necessarily represent the decisions, policy or views of the World Health Organization. Moreover

the findings and conclusions in this report are those of the authors and do not necessarily represent the views of CDC.

and Mary Cogswell2

Erin McLean1 Ines Egli3

Bruno de Benoist1 Daniel Wojdyla4

ERIN MCLEAN

Erin obtained her PhD in Nutrition from the

University of California, Davis, USA. She is cur￾rently working as a Technical Officer for the

Micronutrient Program in the Department of

Nutrition for Health and Development at the World

Health Organization in Geneva, Switzerland. Erin’s

primary work is with the Micronutrient Deficiency

Information System, developing regional and global

prevalence estimates for anemia.

MARY COGSWELL

Mary obtained her PhD. in nutritional epidemiol￾ogy from Johns Hopkins University, School of

Hygiene and Public Health, Baltimore, USA. She

is currently an epidemiologist with the Division

of Nutrition and Physical Activity, Centers for

Disease Control and Prevention. Mary collabo￾rates with and provides consultation to state

health departments, universities, international

organizations, and other constituents on nutrition

assessment, surveillance, and evaluation of pro￾grams. She has over 50 publications in peer￾reviewed journals and has won awards for her

research on perinatal nutrition and on the assess￾ment and prevention of iron deficiency.

INES EGLI

Ines has a PhD in Nutrition from the Swiss Federal

Institute of Technology (ETH), Zurich, Switzerland.

She is currently a senior scientist and lecturer at the

Human Nutrition Laboratory at ETH where she

supervises research projects on mineral bioavailabil￾ity and infant nutrition, and leads a postgraduate

course in Nutrition and Health. She has also worked

in the Nutrition Department of the World Health

Organization in the area of micronutrient deficien￾cies with a special focus on iron, iodine, and vitamin

A.

DANIEL WOJDYLA

Daniel has an MSc in Biostatistics from the

University of North Carolina, Chapel Hill, USA. He

is currently Adjunct Professor in the School of

Statistics of the National University of Rosario,

Rosario, Argentina and is also a statistician at the

Rosario Center for Perinatal Studies (CREP), where

he is in charge of statistical analyses for clinical tri￾als and epidemiologic studies on reproductive

health.

BRUNO DE BENOIST

Bruno is a paediatrician. He obtained his MD from

the University of Paris, France, and an MSc in

Nutrition from the London School of Hygiene and

Tropical Medicine, UK. He is currently Coordinator

of the Micronutrient Unit at the World Health

Organization, Geneva, Switzerland. His special inte￾rest is micronutrient disorders and their relation to

public health and food fortification.

2 E. McLean, M. Cogswell, I. Egli, D. Wojdyla and B. de Benoist