16 THE IMPORTANCE OF VITAMIN A

30 THE FEASIBILITY OF DELIVERING VITAMIN A TO NEWBORNS

38 FROM AGRICULTURE TO HORTICULTURE IN A DRY-LAND AREA

44 IRON FORTIFICATION – NEW REVELATIONS?

VOL.

25

(1) |

201

1

Sight and Life

SIGH

T AN

D LI

FE | V

OL.

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06 Editorial

10 Sight and Life Statement

13 The “Sight and Life in My Life” Essay Competition

14 Special Feature: Food prices on the rise again

16 The Importance of Vitamin A for the Development

and Function of Lungs in Newborns

30 Testing the Feasibility of Delivering Vitamin A

to Newborns in Nepal and Bangladesh

38 Diversification from Agriculture to Nutritionally

and Environmentally Promotive Horticulture in

a Dry-Land Area

44 Iron Fortification – New Revelations?

55 Opinion 1: Comments on “Iron Fortification –

New Revelations?”

56 Opinion 2: Venturing into the Jungle of Multiple

Interactions between Iron, Modulating Influences,

and Human Health

58 Sight and Life Interview A Day in the Life of

Johann C Jerling

Congress Reports

62 Fourth Africa Nutritional Epidemiology Conference

(ANEC 4) Nutrition and Food Security: Successes

and Emerging Challenges

64 Report from the First Global Conference

on Biofortification

67 New Developments in Carotenoids Research

Conference at Tufts University, Boston, USA,

11–12 March 2011

Field Reports

72 Report from Gogounou

Blessings at the I-Domarou Health Center

74 Report from Kathmandu

A Project Report on Training of Adolescent Girls

for Prevention and Control of Iron Deficiency Anemia

2009/10

77 Report from Lemba

Centre de Lutte Contre la Malnutrition de Lemba

78 Report from Ratanakkiri

School Health Watch

80 News

96 Letter to the Editor

98 Publications

103 Imprint

Contents

⇢

“Our work is more vital today than ever before”

4

5

6

It would be impossible to imagine the modern world without

brands. From airlines to computers, from fruit drinks to clothes,

from football teams to hair shampoo, our choices are infor-

med by brands. There are many definitions of the word ‘brand’.

David Ogilvy, famous advertising copywriter and founder of the

influential advertising agency Ogilvy and Mather, defined it thus:

“The intangible sum of a product’s attributes: its name, pack-

aging and price, its history, its reputation, and the way it’s

advertised.”

The rebrand of Sight and Life coincides with the rebrand

of DSM – the first for forty years. The new DSM brand pro-

mises Bright Science. Brighter Living. At Sight and Life we

strive in our own way to make continually evolving scienti-

fic insights available to the ultimate benefit of the poorest

and most disadvantaged populations of the world.

What is a brand ?

Two newbrands !

⇢

Welcomeconcurrent multiple micronutrient deficiencies on the other. In

2007, marking our 21st anniversary, I wrote in our Annual Report

that we still faced the problem of two billion people worldwide

being affected by hidden hunger. Further, I noted that it was un-

acceptable that approximately one third of all children under five

years of age worldwide were stunted and almost 50% anemic,

while at the same time some 155 million school-age children

were overweight or obese. These problems cannot be addressed

by concentrating on vitamin A alone. Hence the widening of our

focus to comprise the entire range of micronutrients.

Our new logo

This expanded focus is expressed by our new logo, which sym-

bolizes the multiplicity of micronutrients essential for a healthy

life. Whereas our original logo was based on the letter A and

the human eye, clearly linking vitamin A with eye health, this

new one puts Sight and Life at the nexus of better nutrition and

health. Whether this means growing the evidence, sharing infor-

mation, advocating, promoting partnerships, or capacity build-

ing in the micronutrient arena, the message is clear: Sight and Life’s mission is to build bridges for better nutrition focusing on

life, using a multiplicity of approaches and interacting with a

wide range of stakeholders.

We hope that you too will like the new logo and also enjoy the

new look and feel of the magazine. Our intention was to create

a publication that retained the scientific rigor for which our or-

ganization has always been known while presenting the content

in a more accessible and compelling manner. The Sight and Lifeteam welcomes your feedback – please let us know what you

think, as the magazine is produced not for us but for you, the

reader.

A new look – an unchanging commitment

This year, 2011, sees the 25th anniversary of Sight and Life. We

celebrate this significant milestone in our history with the launch

of a new Sight and Life brand – one that illustrates our move from

a focus on vitamin A and sight to the vital role played by multiple

micronutrients in promoting health and preventing hidden hun-

ger. This is the first issue of our magazine to reflect our new look

and feel. As we celebrate 25 years of service in the field of micro-

nutrients, we look back to where we have come from and look

forward to where we need to go. For despite our achievements in

the first quarter-century of our existence, our work in the world

is more vital today than ever before.

The founding of Sight and LifeThe Sight and Life Task Force, as it was originally known, com-

menced operations on 1 April 1986. Its objective was to help

combat xerophthalmia – the eye disease caused by vitamin A

deficiency from which approximately ten million young children

in developing countries suffered at the time. The 1986 Sight and Life Annual Report estimated that every year, one million of these

children lost their eyesight. Of these, it noted that two-thirds

died after a short period.

A direct response to requests from the World Health Organi-

zation, the creation of Sight and Life was part of a much wider

approach to tackling vitamin A deficiency, which had been iden-

tified by the 37th World Health Conference as one of the five main

nutritional problems in the world. The initial activities of Sight and Life included the provision of scientific and technical sup-

port, free distribution of vitamin A capsules for emergency situ-

ations, and financial support for selected research programs.

Over the past 25 years, our focus has broadened to encompass

the entire spectrum of micronutrients, reflecting advances in sci-

ence on the one hand and the increasingly recognized burden of

“Our work is more vital today

than ever before”

EDITORIAL8

is written not only against the backdrop of the current political

upheavals in the Arab world but also in the light of the appall-

ing scenes following the earthquake and tsunami in Japan that

have claimed thousands of lives and left the country battling for

survival in the face of a nuclear disaster whose possible conse-

quences can barely be imagined. Already we are hearing reports

of food and water that has been contaminated by radioactivity.

At a moment in the history of our organization that calls for

celebration, and for honoring the efforts of everyone who has

helped to make Sight and Life what it is today, the task before

us is greater than ever. Born in response to the famine created

by the war in Ethiopia in the mid-1980s, and initially focused on

the prevention of xerophthalmia caused by vitamin A deficiency,

Sight and Life now works across the entire spectrum of micronu-

trients, creating the bridges that link scientific research, policy-

making and programs on the ground. We have more opportuni-

ties to influence the world than ever before. We also have more

challenges. Our commitment in the face of those challenges is as

strong as ever. The spirit of the 1986 Sight and Life Task Force

lives on in today’s organization, and we are proud to carry it

forward with us into the next quarter-century.

Yours sincerely,

Our history between two covers

While April 2011 is the quarter-centenary of the founding of

Sight and Life, we will be officially celebrating our birthday in

October of this year, to tie in with World Food Day, which is cel-

ebrated every year around the world on 16 October, and which I

would like to see renamed World Food and Nutrition Day to rec-

ognize that food does not automatically mean nutrition provid-

ing all the required micronutrients. Our jubilee celebrations will

be accompanied by the launch of a book recounting our 25-year

history in the context of the global fight against malnutrition. It

tells the story of the founding of Sight and Life, of our changing

focus over the course of time, and of our enduring commitment

to combating malnutrition worldwide. Watch this space for more

news of the book launch!

As I mentioned in my opening remarks, our commitment to

combating global micronutrient malnutrition is more necessary

than ever before. I am writing this editorial against the backdrop

of extensive political unrest in the Arab world. Tunisia, Algeria,

Syria, the Yemen and Egypt have witnessed unprecedented up-

risings against long-established governments; Libya is in a state

of civil war as we prepare to go to press. While the reasons for

these revolts are multi-faceted and vary in their detail from coun-

try to country, there can be no doubt that the rising cost of food

is one of the main drivers. The populations of North Africa have

to dedicate 35 to 50% of their income to food (contrast this with

the USA, for instance, where the figure is 7%). From 2010 to 2011,

the cost of wheat rose by 73%, that of maize by 88%.

While these figures are already shocking, the future promises

to bring even more challenges. Global consumption of cereals

in 2010 amounted to two billion tons. This figure will double

by 2050 in the light of unprecedented population growth. And

while the world’s population is growing, the resources available

to feed it are shrinking: the rising sea levels associated with cli-

mate change are likely to eliminate vast swathes of land in the

course of time, especially in the world’s poorest countries that

cannot afford costly flood defenses. At the same time, urbaniza-

tion continues inexorably: in China alone, half a million hectares

of arable land disappear each year as a result of that country’s

spectacularly developing infrastructure.

In 2008 this publication predicted that micronutrient mal-

nutrition would result from the rising price of food. The issue

in question was written against the background of the 2008 cy-

clone that hit Burma and the earthquake that devastated areas

of China in the late spring of the same year. The present editorial

“We are committed to combating

malnutrition worldwide”

“The task before us is greater

than ever”

9

… Sight and Life …

… got its name.

The story: how …

“Roche had decided to make a formal commitment

to the battle against vitamin A deficiency, building

on the ad hoc interventions it had already been sup-

porting for a number of years,” recollects Professor

Al Sommer, Dean Emeritus, Johns Hopkins Bloom-

berg School of Public Health.

“One day John told me that Roche had decided to

sponsor a new organization called Sight or Life –

the implication being that if you couldn’t see, you

weren’t living. I felt, however, that this sent too neg-

ative a message, and that it might be construed as

offensive by people who were blind and lived very

full lives. I therefore suggested calling the new or-

ganization Sight and Life, because vitamin A is im-

portant for sight specifically but also for life in ge-

neral. This little change gave the Task Force a very

positive name, and one which was intimately asso-

ciated with vitamin A.”

“Dr John Gmünder would drop by from time to time to

discuss this undertaking and seek advice as to where

Roche should be focusing its efforts. We at Bloomberg

were aware at the time that vitamin A had a huge

influence on physical and mental well-being. The link

had not yet been proven, however, and the rest of the

world seemed reluctant to accept the theory.

10 SIGHT AND LIFE STATEMENT

Multiple micronutrient powders (MNPs) are packaged in single

or multi-dose sachets. These sachets contain micronutrients

in powdered form, and can be added to foods prepared in the

household just before consumption. Usually, one dose of MNP

provides the fu ll unit of recommended nutrient intake (RNI) of

vitamins and minerals.

In 2007, the use of MNPs, particularly in emergency condi-

tions, was endorsed by the World Health Organization (WHO),

the World Food Programme (WFP) and the United Nations

Children’s Fund (UNICEF) as an eff ective way of improving the

micronutrient status of nutritionally vulnerable sections of the

population, such as children under fi ve years of age and preg-

nant and lactating women.1

The risk of untargeted iron supplementation

Based on results fr om a study conducted in Zanzibar2 and other

bodies of evidence,3,4 it was concluded that untargeted iron sup-

plementation may increase child morbidity and mortality fr om

malaria in the absence of monitoring and treatment programs.

A sub-study analysis suggested that adverse events occurred

in supplemented children who had not been iron-defi cient. The

WHO Consultation on Prevention and Control of Iron Defi ciency

in Infants and Young Children in Malaria Endemic Areas5 con-

cluded that the safety of home fortifi cation, as practiced at that

time, is uncertain, whereas food fortifi cation programs are still

regarded as safe. In the above-mentioned study in Zanzibar, the

negative impact on iron-replete children was demonstrated at

levels of 12 mg Fe (as FeSO₄ supplement) per day. The bioavail-

ability of FeSO₄ fr om a supplement is considerably higher than

bioavailability fr om fortifi ed food, where the amount of avail-

able iron depends on the food matrix. The children who showed

adverse eff ects during iron supplementation had therefore been

exposed to high doses of absorbed and unabsorbed iron.

As a result, the micronutrient powder mix for malaria endemic

areas designed by DSM contains a signifi cantly lower dose of

iron (2.5 mg, as NaFeEDTA) in combination with a known en-

hancer of iron absorption (ascorbic acid). This iron dose is close

to or even lower than amounts provided in food fortifi cation pro-

grams, and is not comparable to the bolus doses administered

in iron supplementation programs. A consequence of the lower

iron dose contained in the MNP sachets is the need to ensure

that the amount of (bioavailable) iron delivered is high enough

to the cover the needs of the individual.

Currently the compound used is NaFeEDTA, which belongs to

a group of iron compounds with a high relative bioavailability

compared to ferrous sulphate (FeSO₄). The main advantage of

NaFeEDTA is better bioavailability in the presence of iron ab-

sorption inhibitors such as phytic acid and tannins, whereas the

bioavailability of FeSO₄ is heavily dependent on the presence or

absence of such inhibitors. In particular, home-fortifi cation is

linked to the consumption of the local diet or local complemen-

tary foods, where starchy staples with a signifi cant amount of

iron absorption inhibitors are consumed. In addition, according

to the latest recommendations for fl our fortifi cation,6 NaFeEDTA

is the recommended compound for fl ours with high levels of

phytates (e.g. maize fl our).

Possible explanations for the Zanzibar results

Two possible explanations for the results seen in Zanzibar have

been proposed: the formation of non-transferrin-bound iron

(NTBI) in plasma, and the stimulation of pathogen growth in the

gastrointestinal tract (due to the amount of unabsorbed iron).

It has been proposed that administration of bolus doses of iron

can result in large amounts of unabsorbed iron, which enters

and passes through the intestine. Recently published results7

indicate that unabsorbed iron fr om fortifi ed foods modifi es the

Sight and LifeStatementLow Dose Iron Multi ple Micronutr ient Powder: Rati onale for Use in Malaria Endemic Areas

SIGHT AND LIFE | VOL. 25 (1) | 2011 11

“The main advantage of NaFeEDTA is bett er bioavailability in the presence of iron absorpti on inhibitors.”

12 SIGHT AND LIFE STATEMENT

colonic microflora in African children to create a potentially

more pathogenic profile. If this is confirmed, it could help to ex-

plain the reported adverse effects of iron supplementation and

bolus doses of iron.

The other potential mechanism discussed is the formation

of non-transferrin-bound iron (NTBI). Recently presented data

on the formation of NTBI8 after administration of iron in women

with low iron status (NTBI formation monitored over eight hours),

showed that the highest NTBI concentrations were produced by

a 60 mg dose without food, followed by 60 mg and 6 mg with

food. These first data indicate that iron administered with food

and through fortification (rather than supplementation) resulted

in lower NTBI formation.

In conclusion, based on current knowledge, the two-step ap-

proach of optimizing the MNP formulation for malaria endemic ar-

eas is expected to be safer than typically used iron doses (12.5mg).

The reduction of the iron dose to levels closer to the amount of iron

provided in food fortification helps to reduce the amount of unab-

sorbed iron in the intestine. Meanwhile, using a highly bioavail-

able iron compound in combination with iron absorption enhanc-

ers is crucial to supplying the individual with the iron needed.

References

01. WHO/WFP/UNICEF Joint Statement. Preventing and controlling

micronutrient deficiencies in populations affected by an emergency.

Multiple vitamin and mineral supplements for pregnant and

lactating women, and for children aged 6 to 59 months. WHO,2007.

02. Sazawal, S, Black R, Ramsan M et al. Effects of routine prophylactic

supplementation with iron and folic acid on admission to hospital

and mortality in preschool children in a high malaria transmission

setting: community-based, randomized, placebo-controlled trial.

Lancet 2006;367(9505):133–43

03. Oppenheimer SJ. Iron and its relation to immunity and infectious

disease. J Nutr 2001;131(2S-2):616S-633S; discussion 633S–635S.

04. Ojukwu J, Okebe J, Yahav D et al. Oral iron supplementation for

preventing or treating anemia among children in malaria-endemic

areas. Cochrane Database Syst Rev 2009;(3): CD006589.

05. WHO. Conclusions and recommendations of the WHO

Consultation on prevention and control of iron deficiency in infants

and young children in malaria-endemic areas. Food Nutr Bull

2007;28:S621–S7

06. Hurrell, R, Ranum P, de Pee S et al. Revised recommendations for

iron fortification of wheat flour and an evaluation of the expected

impact of current national wheat flour fortification programs.

Food Nutr Bull 2010;31(1 Suppl):S7–21

07. Zimmermann, M, Chassard C, Rohner F et al. The effects of iron for-

tification on the gut microbiota in African children: a randomized

controlled trial in Côte d'Ivoire. Am J Clin Nutr 2010;92:1406–15.

08. Egli I, Brittenham G, Zeder C et al. The influence of supplemen-

tation and fortification iron doses on the formation of plasma-non-

transferrin-bound iron. (UC Davis) Conference on Bioavailability,

Asilomar, CA, September 26–30, 2010 (only abstract available)

“The two-step approach of optimizing

the MNP formulation for malaria

endemic areas is expected to be safer

than typically used iron doses”

13SIGHT AND LIFE | VOL. 25 (1) | 2011

The“Sight and Lifein My Life” Essay Competition

In the last issue of the magazine, we launched the Sight and Life in

My Life Essay Competition. Its aim was to fi nd out how Sight and Life has

played a part in readers lives, as part of the organization’s 25th

anniversary.

¶

The closing date for the competition was 15 March 2011 and we have

received many wonderful stories. We have been delighted with the

entries we have received and are looking forward to sharing these with

you in future issues. We are now in the process of reading and judging

the entries and will be contacting the winners and those who sent us

highly commended entries later this summer.

¶

We have received entries from many countries, from Nigeria to Sri

Lanka. Many fascinating photographs and even some original artwork

has come our way, such as the picture here by Dr Narendra Kumar,

which is the cover of her booklet that helps children and families in

India.

¶

We would like to say a very heartfelt thank you to all you who entered

the competition. We appreciate the time you have spent on writing your

entries and would also like to thank you for all the amazing good work

you do in your communities.

With warmest wishes

The Sight and Life Team

16

Introduction

Vitamin A is essential for the growth and development of cells

and tissues. In its active form, retinoic acid (RA), it controls reg-

ular diff erentiation as a ligand for retinoic acid receptors (RAR,

RXR).1,2 Vitamin A plays a substantial role in the respiratory

epithelium and the lung. In the presence of moderate vitamin A

defi ciency the incidence of diseases of the respiratory tract is

considerably increased. Repeated respiratory infections can be

infl uenced therapeutically by moderate vitamin A supplementa-

tion.3,4,5 Besides its importance for lung fu nction, vitamin A is

also responsible for the development of many tissues and cells,

as well as for embryonic lung development. Recent studies have

demonstrated that this occurs by various expressions of retin-

oid receptors, as well as by time-dependent changes of the vita-

min A concentration in the tissue. Where maternal vitamin A is

defi cient fetal lung maturation might be seriously impaired, with

consequences for postnatal fu nction.

The infl uence of vitamin A on the maturation

and diff erentiation of the lung

Vitamin A and its major active metabolite RA have a profound

infl uence on the alveolar development, maintenance and fu nc-

tion of the lung. Type II alveolar cells synthesize and secrete

surfactant.6 RA is able to stop – dependent on its concentra-

tion 7 – the expression of the surfactant-protein A (SP-A) in hu-

man fetal lung explants. Insulin, TGF- and high concentrations

of glucocorticoids can also down-regulate the expression of SP-

A-mRNA,8 but lower concentrations of glucocorticoids stimulate

the expression of these genes.9 In contrast, the expression of

SP-A-mRNA is increased by hyperoxia in rats 10 and by dexam-

ethasone in human fetal lung explants.7

Type PGE₂ prostaglandins are able to increase surfactant

synthesis. Under the infl uence of EGF (epidermal growth factor)

the formation of prostaglandin rises, especially that of PGE₂. On

the other hand, the expression of the EGF receptor is increased

by RA. EGF increases proliferation of the lung tissues, leading

to an amplifi ed formation of surfactant phospholipids.11 RA and

EGF both lead to an increase (40%, 80%) in the secretion of

PGE₂ in fetal lung cells of the rat in vitro.12 The combination of

RA and EGF, however, leads to a more than a six-fold increase

in the secretion of PGE₂. Consequently, RA can interfere in lung

development due to its modulating eff ect on the expression of

EGF and the subsequent PGE₂-induced surfactant formation.

Suffi cient and continuous availability of vitamin A (either on the

blood pathway or fr om local storage sites) is pivotal, especially

Hans Konrad Biesalski

University of Hohenheim,

Stuttgart, Germany

THE IMPORTANCE OF VITAMIN A

The Importance of Vitamin Afor the Developmentand Funct ion of Lungs in Newborns

SummarySummary

Vitamin A is essential for growth and development, in

particular for the adequate maturation of the lung in late

embryogenesis. If the developing embryo is not supplied with

suffi cient amounts of vitamin A delivered from the mother, em-

bryonic lung retinyl ester stores remain low. As a consequence,

the sources for retinol and subsequently the active metabolite

retinoic acid, important for gene expression in the lung, are not

suffi ciently available during the time of lung maturation.

Low vitamin A stores in the lung impair the expression of sur-

factant proteins, alveoli formation and the development of the

respiratory epithelium. Newborns with low vitamin A stores

are at risk for respiratory diseases such as bronchopulmonary

dysplasia and frequent infections in early childhood.

17SIGHT AND LIFE | VOL. 25 (1) | 2011

“Repeated resp iratory infect ions can be infl uenced therapeuti cally by moderate vitamin A supplementati on.”

18 THE IMPORTANCE OF VITAMIN A

for the timely regulation of lung development and the related

formation of the active metabolite RA. During embryonic devel-

opment, RA regulates cell proliferation and diff erentiation, and

regular morphogenesis. In the postnatal period, RA is important

for lung growth, alveolarization, and elastin formation.13, 14

Vitamin A kinetics during fetal lung development

Local extrahepatic stores are present in fi broblast-like cells close

to the alveolar cells, in type II cells and in the respiratory epi-

thelium retinyl esters. The importance of these retinyl esters as

an acute reserve during the development of the lung becomes

apparent during the late phase of gestation and the beginning

of lung maturation. During this period, rapid emptying of the

retinyl ester stores in the lung of rat embryos occurs.15 This de-

pletion is the result of increased RA demand in the lung devel-

opment process, because RA is instantly needed for the process

of cellular diff erentiation and metabolic work. Indeed, RA is im-

portant for the formation of alveoli, and may rescue failed al-

veolar formation.16,17 The eff ect of an adequate amount of RA on

alveolar formation which starts prior to birth and lasts up to the

age of eight years or even longer has recently been documented.

Checkley and co-workers18 reported that children of mothers

fr om a region with vitamin A defi ciency who were supplemented

during pregnancy and for six months aft er pregnancy with 7 mg

preformed vitamin A (7 mg retinol equivalents, RE) as a single

oral supplement once a week had signifi cantly better lung fu nc-

tion at nine to 11 years old than those of mothers receiving either

a placebo or 42 mg -carotene (7 mg RE).

Vitamin A kinetics during lung development

The fact that the -carotene group had no benefi t regarding

lung fu nction may be due to either poor absorption, a lower

cleavage rate or polymorphism of the -carotene monooxyge-

nase (BCMO), as discussed recently.19,20 Administration of pre-

formed vitamin A will contribute to a more suffi cient supply of

the lung. The eff ect of vitamin A on later lung fu nction might

be a consequence of adequate alveolar formation during fetal

lung development and during early childhood. However, if there

was no fu rther supplementation six months aft er delivery in the

vitamin A defi cient area, how might improvements of the lung

fu nction 10 years later be explained? One explanation might be

the suffi cient repletion of vitamin A storing cells in the lung of

the off spring, which may serve as storage sites for a longer time

period. Retinyl ester stores have been described in lipid-laden

fibroblasts21 and in the bronchiolar epithelium.22 These lipid

interstitial cells deliver RA, which induces alveolus formation.23

In the alveolus, the lipid-laden fi broblast is a major contributor

to the formation of the extracellular matrix.24 Following hydroly-

sis of retinyl esters to form retinol, retinol is oxidized via alcohol

dehydrogenase (ADH) followed by irreversible oxidation to retin-

oic acid. All steps are tightly controlled via intracellular binding

proteins. Retinol bound to the cytoplasmic retinol binding pro-

tein (holo-CRBP) is protected fr om degradation and delivered to

the lecithin: retinol acyltransferase (LRAT) for esterifi cation.25

Cytoplasmic retinoid binding proteins form a substrate-control-

led network, which at least controls the delivery of RA to the

nuclear-related metabolic enzymes (LRAT, ADH) via a feedback

mechanism.26,27 This feedback network might explain why a

“The combinati on of RA and EGF leads

to more than a six-fold increase of the

secreti on of PGE₂”

“Vitamin A supplementati on before,

during and aft er pregnancy improved

lung fu nct ion in off sp ring”

figure 1: Decline of retinyl palmitate concentration

and in-crease of retinol in embryonic rat lungs prior to and

shortly aft er birth (Geevarghese and Chytil)15

Gestational age (days)

Ret

inyl

pal

mit

ate

(μg/

g w

eigh

t)

0

12

10

11

8

6

7

9

4

5

2

1

3

18 19 20 21 22

Birth

Gestational age (days)

1,50

1,75

2,50

2,25

2,00

18 19 20 21 22

Ret

ino

l (μ

g/g

wei

ght)

Birth

19SIGHT AND LIFE | VOL. 25 (1) | 2011 19THE IMPORTANCE OF VITAMIN A

release fr om the liver; but also infl uence, as recently described,15

the metabolization of the vitamin A esters stored in the lung. Fol-

lowing administration of dexamethasone, even without steroid

application, a signifi cant reduction of retinyl esters in the ma-

turing lung can be detected, as well as a moderate increase in

retinol, the hydrolysis product of retinyl esters. This observation

may explain therapeutic successes with steroids, as well as their

failures in cases of poor retinyl ester stores, during the therapy

of lung distress syndrome of premature infants.

Vitamin A binding proteins

A fu rther component involved in the hydrolysis and formation of

retinyl esters is the concentration of CRBP.35 A high apo-CRBP

concentration increases the activity of the retinyl ester hydro-

lase, which subsequently results in an increase in retinol and,

as a consequence, an increase in holo-CRBP. Liganded CRBP

is responsible for the delivery of retinol to LRAT for esterifi ca-

tion.36 Indeed, lipid-laden pulmonary interstitial fi broblasts de-

rived fr om perinatal rat lungs show a high CRBP concentration,

which declines following the formation of retinol and, fi nally,

retinoic acid during the early postnatal period. 37 (Figure 2)

Where the supply of Vitamin A is insuffi cient, inadequate ret-

inyl ester stores due to a shortage in the supply to the fetal lung

during late pregnancy mean that glucocorticoids and apo-CRBP

cannot act to regulate vitamin A metabolism in the lung cells.

Consequences of marginal defi ciency

Masuyama and co-workers38 demonstrated that a marginal vi-

tamin A defi ciency, which is not necessarily detected via low

plasma retinol due to homoeostatic control, may have an impor-

tant impact on late lung development. (Figure 3)

They also documented an additional aspect: Retinyl ester in-

creased rapidly to a peak on day 17 of gestation and decreased

to a minimum on day 21 of gestation. These data show that there

combination of RA and retinyl palmitate, given orally on post-

natal days 5–7, signifi cantly increases lung retinyl esters in neo-

natal rats compared to RA and vitamin A alone.28 RA increases

esterifi cation of retinol and blocks hydrolysis of retinyl palmi-

tate to avoid RA overload of the cells. Liver vitamin A stores, as

well as plasma levels of retinol and retinol binding protein (RBP),

are relatively low at birth.29-32 Consequently, suffi cient prenatal

pulmonary retinyl ester stores and their metabolization to RA in

the lung are the critical component regulating fetal lung matura-

tion, including alveolarization and postnatal fu nction.

Three days prior to delivery, the retinyl ester stores of rat

fetal lungs decline and the retinol concentration increases.15

(Figure 1)

Retinol is metabolized to RA, which serves as a ligand for the

nuclear receptors, which control the gene expression of various

proteins responsible for late lung development and maturation.

Impact of steroids on lung development

Prenatal lung development is also infl uenced by glucocorticoids.

Steroid hormones have a similar eff ect on lung development to

vitamin A, and the two factors complement each other. This is not

surprising, however, as the receptors for steroids and retinoids

belong to the same multireceptor complex. The mode of action

of glucocorticoids exists not only on the level of gene expression,

but seems also to have an impact during a much earlier phase of

vitamin release. The application of dexamethasone leads to an

increase in the maternal and fetal retinol binding protein, lead-

ing to an improvement of the vitamin A supply by channeling out

via the normal hepatic pathway. This increase in the vitamin A

concentration in the systemic circulation clearly diminishes the

morbidity and mortality attributable to bronchopulmonary dys-

plasia 33,34 in the case of babies born prematurely.

Dexamethasone and glucocorticoids not only lead to an im-

provement of the total vitamin A supply through a change of the

figure 2: Time dependent pattern of pre- and postnatal CRBP and CRABP in rats. CRABP increases during the fi rst days of life

as a sign of increased formation of RA. (Ong and Chytil, 1976)69

nm

ol

CR

BP

/g l

un

g (

)

nm

ol

CR

AB

P/g

lu

ng

(

)

0 0

0.2 0.2

0.1 0.1

–3

Age, days

Adult–1 0 1 3 5 10 12 15 21

AlveoliSaccules Septation Thinning

20 THE IMPORTANCE OF VITAMIN A

might be a very small window during which the retinyl esters are

stored in the lung shortly before they are needed. If, in the case

of early delivery, the stores are not adequately fi lled, this might

have serious consequences for lung maturation. Retinoic acid

receptor (RAR) and RAR mRNA were detected in all samples

obtained fr om perinatal and adult rat lung, but only a trace of

RAR mRNA was detected in the fetuses on days 15, 17 and 19

of gestation and in adults. Aft er a maternal retinol defi ciency of

28 days, fetal body and lung weights were signifi cantly lower

than those of the controls; concentrations of retinyl palmitate

and phosphatidylcholine (PC) in the lung aft er a maternal reti-

nol defi ciency over 14, 21, or 28 days were signifi cantly lower

than those of controls. Expression of RAR mRNA in the group

with 28-day retinol defi ciency was lower than in controls. That

of RAR mRNA was increased and that of RAR mRNA was not

infl uenced by retinol defi ciency. In the developing mouse em-

bryo, RAR expression is spatially and temporally restricted in

various tissues, suggesting a role for RAR in morphogenesis.39

RAR is both a strong target for RA and also highly activated by

treatment with exogenous RA.40 The rate of choline incorpora-

tion into PC in fetal lung explants was signifi cantly higher in the

group treated with RA than in the controls. RA enhanced the

eff ect of epidermal growth factor on choline incorporation and

prevented that of dexamethasone. Taken together, marginal de-

fi ciency results in the altered expression of nuclear receptors of

vitamin A, with impaired maturation as a consequence.

The infl uence of vitamin A supply for the post-natal

development of the lung in preterm infants

An adequate vitamin A intake during pregnancy is of great im-

portance for the formation of retinyl ester stores in the develop-

ing lung. These stores are the basis for RA formation during lung

maturation and postnatal fu nction, with long-term benefi ts as

above.18 However, in the case of early delivery or very low birth

weight, an insuffi cient vitamin A supply during pregnancy might

have serious consequences.

A disease observed recurrently in connection with vitamin A

supply is bronchopulmonary dysplasia (BPD). The pathogenesis

of BPD certainly depends on a multitude of factors. Some of the

observed morphological changes are strongly reminiscent of

vitamin A defi ciency in humans and animals. Of particular note

is the focal loss of ciliated cells with keratinizing metaplasia and

necrosis of the bronchial mucosa, as well as an increase in mu-

cous secreting cells.41

Focal keratinizing metaplasia, such as may occur aft er vita-

min A defi ciency, especially strengthens the assumption of an

impairment of diff erentiation on the level of gene expression.

Since vitamin A regulates the expression of diff erent cytokerat-

ins and therefore infl uences terminal diff erentiation, it seems

obvious to assume the existence of common mechanisms. Con-

sequently, premature neonates are dependent on a suffi cient

supply of vitamin A to ensure adequate lung maturation. The

earlier a child is born before its due date, the lower its serum

retinol levels.31

Retinol serum levels in neonates

It was shown repeatedly that serum retinol level and RBP level

depends on birth weight and is signifi cantly lower in premature

infants with low birth weight, compared to similar-aged neo-

nates with higher birth weight.30 In addition, mothers fr om low

income groups had lower levels of serum vitamin A and a higher

incidence of prematurity.42 Signifi cantly lower retinol levels can

be found in the liver of premature infants, in comparison to neo-

nates.43 Plasma values lower than 0.70 μmol/L are not rare in

this case, and they should be taken as an indicator of a relative

vitamin A defi cit.

Very low plasma vitamin A levels can be found recurrently

in premature infants compared to term neonates.44,45 This can,

among other things, be attributed to the relative immaturity of

the liver for the synthesis of retinol binding proteins. The neonate

is almost exclusively dependent on the mother for its supply: this

includes the lung retinyl esters which are either directly absorbed

by the cells (fr om chylomicrons) or by esterifi cation of retinol

aft er uptake into the cells. These lung retinyl ester stores can only

be suffi ciently fi lled if the mother guarantees an appropriate vita-

min A supply, especially during late pregnancy.

Reduced plasma levels during the fi rst developmental months

figure 3: Pattern of retinyl ester concentration in

the pre- and post-natal rat lung (Masuyuma et al., 1997).38

The data show the 10-fold concentration of retinyl esters

in the fetal lung, compared to the adult lung of the rat.

The rapid decline prior to birth documents the

importance of retinyl ester hydrolysis to form retinol

and subsequently retinoic acid. The latter controls

lung maturation.

Adult

0

6

5

4

3

2

1

15 17 19 21 1 3 5 7

Ret

inyl

pal

mit

ate

(μg/

g w

eigh

t)

Birth

Prenatal Postnatal

21SIGHT AND LIFE | VOL. 25 (1) | 2011 21THE IMPORTANCE OF VITAMIN A

Marginal vitamin A defi ciency in developed countries

Even in developed countries with a wide variety of food contain-

ing preformed vitamin A, low plasma levels (<1.4 μmol/L) occur

and result in low umbilical cord blood levels.50 The study inves-

tigated 23 women with short birth intervals (defi ned as a second

delivery within 24 months) and six women with twins. (Figure

4 and 5)

According to Godel,51 a normal range of vitamin A in cord

blood should be between 0.7 and 2.3 μmol/L. There is no clear

consensus on the cut-off concentration for “vitamin A defi ciency”

in cord blood. Levels below 0.35 and 0.7 μmol/L are discussed.51

Taking 0.35 μmol/L as the cut-off level, 31.4% of newborns in the

study by Schulz and co-workers50 showed levels below the cut-

off . Twins showed the lowest levels.

have a considerable infl uence on the total development of in-

fants, as well as on their susceptibility to infections. In the case

of reduced retinol plasma levels, repeated infections are more

oft en described,3,46 and are counted among the main compli-

cations of a poor vitamin A supply in developing countries. In

addition, the serum vitamin A level during infectious diseases,

particularly of the respiratory tract, continues to drop.47,48 This

can be explained on the one hand by an increased metabolic

demand, and on the other hand by renal elimination of retinol

and of RBP during the process of acute infections.49 If the retinyl

ester stores of the lung are low at delivery, these storage sites are

replenished with diffi culty, and as a consequence lung fu nction

may be impaired.

figure 4: Correlation of maternal retinol or -carotene in plasma with cord plasma and colostrum. Dotted lines show the area of sus-

pected defi ciency according to Godel et al. 51 Dotted lines defi ne the lower level of physiological retinol in plasma. (Schulz et al., 2007)50

Maternal plasma retinol [μmol/L]

0

8

6

4

2

12

10

0.5 1.0 1.5 2.0 2.5 3.00.0

Co

lost

rum

ret

ino

l [μ

mo

l/L]

r = 0.4623 / p = 0.0152

Maternal plasma -carotene [μmol/L]

0

2

1

3

1 2 3 40.0

Co

lost

rum

-c

aro

ten

e [μ

mo

l/L]

r = 0.8023 / p <0.0001

Maternal plasma retinol [μmol/L]

0.0

0.5

1.0

1.5

0.5 1.0 1.5 2.0 2.5 3.00.0

Co

rd p

lasm

a re

tin

ol

[μm

ol/

L]

r = 0.4573 / p = 0.0058

Co

rd p

lasm

a -c

aro

ten

e [μ

mo

l/L]

Maternal plasma -carotene [μmol/L]

0.0

0.1

0.2

0.3

1 2 3 40

r = 0.8366 / p < 0.0001

22 THE IMPORTANCE OF VITAMIN A

Despite low plasma retinol levels, most of the women had high

-carotene levels (80% >0.5 μmol/L). However, the high levels

of -carotene in plasma may be taken as a sign of low conver-

sion to vitamin A due to the recently described BCMO polymor-

phism.20 As a consequence, these women are at risk of low vi-

tamin A supply due to a very low intake of preformed vitamin A.

This results in very low levels of retinol in blood and breast milk

for the newborn.

There is limited data linking the intake of vitamin A during

pregnancy to cord blood levels and fetal development. Shah and

co-workers demonstrated a strong relationship between low

socio-economic status, low cord blood and low body weight of

the newborn.44

If there is evidence that the vitamin A status of the mother is

poor, a parenteral supply (intramuscular application) is recom-

mended. The impact on the general health of the child including

lung fu nction is controversial, however.

Prevention and therapy

In view of the importance of vitamin A, as above, the question

arises as to possible therapeutic interventions – especially for

imminent premature deliveries, but also for premature infants

and, in cases of poor maternal vitamin A status, for prevention of

potential diseases and /or immaturities of the lung. Where there

is a risk of prematurity, vitamin A might be delivered antenatally,

regardless of maternal vitamin A status, to ensure suffi cient fetal

lung retinyl ester stores. Based on US Dietary Reference Intake

recommendations, daily vitamin A supplementation during any

part of the fertile period should be limited to 3,000 IU. How-

ever, a moderate dosage and a short period of supply might not

be suffi cient to replete lung retinyl ester stores in cases of poor

maternal vitamin A status. Higher doses during the last term

of pregnancy might be more eff ective and pose no risk of tera-

togenicity, but this has not been proven to date.

One solution could be the intravenous administration of vi-

tamin A. However, with the infu sion systems used so far it ap-

pears that vitamin A is almost completely absorbed by the poly-

ethylene tubes and is damaged by light.6 One way of improving

availability consists of coating the infu sion systems with foil to

avoid fu rther loss of the vitamin due to light. Since such solu-

tions are no longer available on the market and new parenteral

vitamin A preparations are not yet available, the importance of

supplying the mother with vitamin A before delivery needs to

be highlighted. Parenteral administration of retinyl margari-

nate (an unphysiological fatty acid ester of retinol) resulted in a

rapid increase of retinyl margarinate and fu rther retinyl esters

(as a result of hydrolysis and re-esterifi cation) in several tissues,

including the lung, in vitamin A depleted rats.52 The results of

this study clearly document that retinyl esters can be taken up

into diff erent tissues circumventing the liver and the control of

delivery via retinol-RBP. At present there are no data regarding

the risk of parenteral vitamin A supply in pregnant women with

a high risk of preterm labor (e.g. those on bed rest). However,

because teratogenic eff ects occur during the fi rst term, adminis-

figure 5: Retinol and -carotene in maternal plasma, cord blood and colostrum in women who delivered twins (n=6) (A)

or women with short birth intervals (n=24) (B). (Schulz et al., 2007) 50

B

Maternalplasma

Cordplasma

Colostrum0.0

0.5

2.0

1.5

1.0

2.5

-car

ote

ne

[μm

ol/

L]

A

Maternalplasma

Cordplasma

Colostrum0.0

2.5

5.0

7.5***

*Ret

ino

l [μ

mo

l/L]

*p <0.05, ***p < 0.001

23SIGHT AND LIFE | VOL. 25 (1) | 2011 23THE IMPORTANCE OF VITAMIN A

level after delivery poorly reflects the supply of the lung with

vitamin A before delivery. It should be borne in mind that this

study confirmed that relative vitamin A deficiency is character-

istic of premature infants, in particular. Thus, attention should

be directed to their supply of vitamin A. On the other hand, the

vitamin A supply of the premature infant appears to be either

insufficient to ensure adequate concentrations in the lung or the

availability of the vitamin to the corresponding cells of the lung

is not guaranteed.

All trials delivered vitamin A in doses of <50,000 IU to the

child. The data clearly documented that a late supply in high

doses might not work due to the reasons set out above (imma-

turity of RBP synthesis in the liver, distribution problems and,

finally, low accumulation of retinyl esters in the lung). Ambala-

vanan and co-workers 56 evaluated three different intramuscular

dosage regimens in extremely low birth weight infants (5,000 IU

three times per week for four weeks, 10,000 IU three times per

week and 15,000 IU once per week. They used a water-soluble

formulation of vitamin A (Aquasol A) based on polysorbate mi-

celles. As a result, the authors stated, “Compared with the stan-

dard regimen, once per week dosing worsened, and higher doses

did not reduce, vitamin A deficiency. Therefore the standard

regimen is recommended.” However, this conclusion does not

consider the metabolism of vitamin A in early newborns and the

importance of retinyl esters in the lung. Indeed, they could show

that the outcome in the once-per-week group with a high dosage

of vitamin A was better, even if not significantly so. A high dose

tration during the second or third term might be without any risk,

and vitamin A could be administered to pregnant women with a

high risk of preterm labor.

Vitamin A supply and lung disease

The results of two randomized double-blind controlled stud-

ies53,54 of premature infants show that supplementation with

vitamin A in a study54 led to a considerable reduction (55%) in

the risk of being affected by chronic lung disease of prematurity.

In a third study,55 12 premature infants received vitamin A intra-

venously for a period of 28 days (400 IU/d) and during later de-

velopment vitamin A was also administered orally (1,500 IU/d).

During supplementation the initially reduced plasma and RBP

values rose significantly. The latter is an indication of an actual

vitamin A deficiency of premature infants, because an increase in

retinol-RBP is only observed if a vitamin A deficiency really exists

(the principle of the relative dose response test).

A direct effect of plasma concentration on the development

of chronic lung disease of prematurity could not be determined.

The author has come to the logical conclusion that the plasma

“The significance of supplying the

mother with vitamin A before delivery

needs to be highlighted”

figure 6: Model of VA metabolism in neonatal rat lung (Wu and Ross, 2010)68

RE

RA, 12 h

VA

ROH RAPolarmetabolites

Cyp26B1LRAT

B

RE

RA, 6 h

VA

ROH RAPolarmetabolites

Cyp26B1LRAT

Stra6

AThe two panels represent the observed and proposed pathways of

retinoid uptake, esterification, and oxidative metabolism in the

lungs of neonates treated with RA for 6 h (A) and 12 h (B). Changes

in gene expression represent the effects of the acidic retinoids, with

and without VA, while retinol uptake and retinyl ester formation re-

present the treatments that included VA.

A When RA is administered to neonatal rats with a supplement

of VA, RA up-regulates the expression of LRAT and CYP26B1 to the

same extent at 6 h, with the flow of retinol to RE formation or to

polar metabolites kept in balance. More dietary retinol is taken up

by lung tissue due to up-regulation of STRA6 and elevated plasma

retinol at 6 h.

B At 12 h, RA is metabolized by CYP26B1. Although the biological

activity of RA has declined, the pathway is still balanced as STRA6,

LRAT, and CYP26B1 have all returned to basal levels.

24 THE IMPORTANCE OF VITAMIN A

leads to higher plasma concentrations of retinyl palmitate and,

subsequently, to higher uptake of the retinyl esters into tissues.

However, the fact that more cases of retinopathy and necrotiz-

ing colitis occurred in the once-per-week dose group, compared

with the 10,000 IU three times per week group, may be the con-

sequence of the solubilzer polysorbate. Hale and co-workers57

evaluated the eff ect of the solubilizer (polysorbate 80) in neo-

natal pigs. The authors speculate that “rapid intravenous injec-

tion of vitamin E emulsions produces massive accumulation in

phagocytic cells of the spleen and to a lesser extent liver and

lung, possibly leading to increased susceptibility to sepsis and/

or abnormal pulmonary fu nction.” The intravenously supplied

vitamin E (E-Ferol) led to deaths in 38 cases in 1984 in the US

and was consequently stopped. Because a mixture of polysor-

bate 80 and polysorbate 20 is used as a carrier in E-Ferol, these

components were also tested and were found to be responsible

for the suppression, especially the polysorbate 80.

Improving lung retinyl ester stores

Ross and co-workers documented a way to improve vitamin A

supply to the lung via administration of preformed vitamin A

(VA) and RA (VARA) in a ratio of 10:1.58 Based on their data, Ross

and co-workers created a model of how and why retinyl ester

stores are formed following delivery of preformed vitamin A plus

RA. RA induces CYP26 and LRAT to save the cell fr om high and

potentially toxic concentrations.59 As a consequence, the sup-

plied preformed vitamin A entering the cell via the Stra6 recep-

tor is stored as retinyl esters and the RA is detoxifi ed; 6 h later,

normal RA and ROH levels document the homoeostatic control

of the cell. (Figure 6)

Ross and co-workers’ data also demonstrate that an isolated

supply with RA might exert a short-term eff ect on lung matu-

ration, but that, in the long term, the surplus of RA is detoxi-

fi ed and, consequently, without effi cacy. In fu rther experiments,

James and co-workers showed that the synergistic eff ect of VARA

on lung retinyl ester content was blunted in mice exposed to

hyperoxia.60 Regardless of the mechanism by which RA exert

their eff ects, a suffi cient content of retinyl esters or an increase

following the VARA application is essential for this benefi t. The

combination of VA and RA has the therapeutic potential of re-

ducing BPD to a greater extent than VA or RA supplementation

alone. (Figure 7)

This data also clearly demonstrates that the usual approach

to supply the lung of the newborn with vitamin A (intramuscu-

larly) might be not very successfu l and explains the moderate

and sometimes confl icting results. The proposed mechanism

also shows that delivery of RA alone might be counterproductive,

and might lead to an up-regulation of the detoxify ing enzymes

(CYP26) and, in parallel, to an increased expression of CRABP,

which may reduce RA action. The intramuscular supply in ex-

tremely low birth weight infants with vitamin A might be also of

limited success, if it is not ensured that the liver can transport

Age: 0.0001

Treatment: 0.0001

Age*Trt: 0.003

a > b > c > d, p < 0.003

Control

Vitamin A alone

VARA

P4

a(45.7)

b(5.5)

c,d(1.6)

b(6.8)

c(2.8)

d(1.0)

0

0.2

0.4

2.6

2.4

2.2

2.0

1.8

1.6

1.4

1.2

1.0

0.8

0.6

Log

₁₀R

E +

reti

no

l, n

mo

l/g

lun

g

P8

A

figure 7a: Schematic model of retinyl ester storage in the neonatal rat lung following VARA67

A Lung RE on postnatal (P) days 4 and 8 in newborn rats treated

with VARA, vitamin A or oil. Newborn rats (n = 7/group) were treated

on days 1, 2 and 3 with oil (control), vitamin A alone, or VARA, and

lung RE was determined on P4 (n = 4/group) and P8 (n = 3/group).

Data are the mean SD and were analyzed by 2-way ANOVA aft er

log ₁₀ transformation (as illustrated), and the least squares means

test. Values shown in parentheses are the anti-logs of the log ₁₀ means.

(Adapted fr om Ross and Ambavalanan, 2007)67

B Lung and liver retinyl ester in 8-day-old rats treated with oil

(control), VARA, dexamethasone (Dex), or Dex and VARA. (1) A Lung

RE + retinol concentration. (2) B Liver RE + retinol concentration.

(3) C Plasma total retinol. For each treatment, n = 3 pools/group

were analyzed by HPLC; each pool contained equal portions of tissue

fr om 2 identically treated neonates. The results were analyzed by

two-way ANOVA; diff erent letters above groups indicate signifi cant

diff erences by the least squares means test. (Adapted fr om Ross and

Ambalavanan, 2007)67

25SIGHT AND LIFE | VOL. 25 (1) | 2011 25THE IMPORTANCE OF VITAMIN A

retinol bound to RBP to the lung. Nevertheless, if an increase in

circulating retinyl esters following parenteral application occurs,

the retinyl esters are directly delivered to the cells.52

From recent data in two cases of completely impaired RBP

synthesis due to a mutation61 it can be concluded that retinyl

esters delivered to cells and tissues can serve as major vitamin A

source.

Inhalation of vitamin A

An alternative solution could be inhaled vitamin A. With this,

the lung is directly targeted and retinyl esters administered by

inhalation can be absorbed into the cells and metabolized in a

controlled way, as shown in various animal studies.62 In addi-

tion, the inhalative approach results in an increase of vitamin A

in plasma and tissues of rats.63 We reported successful vitamin A

supplementation by inhalation of retinyl palmitate in a placebo-

controlled pilot study in 25 pre-school children (two to five years

of age) in the rural district of Gondar, Ethiopia.64 Pre-school chil-

dren (n = 161) were randomly selected from 220 households. Out

of this cohort, 25 children were randomly assigned to each of two

treatment groups: One received retinyl palmitate by inhalation

of two puffs of an aerosol containing 1 mg (3,000 IU) per deliv-

ery to give a total of 2 mg (6,000 IU); and the other received an

aerosol without retinyl palmitate. Both treatments were admin-

istered every two weeks for three months. Serum retinol and RBP

concentrations in the group treated with vitamin A were 0.68

(SD 0.31) μmol/L and 59.4 (SD 24.2) mg/L before and 1.43 (SD

0.46) μmol/L (P<0.01) and 97.3 (SD 31.2) mg/L (P<0.05) three

months after supplementation with retinyl palmitate, suggesting

that this novel method of delivery of retinyl palmitate by inhala-

tion is effective in improving vitamin A status. (Figure 8)

Unfortunately, we were not able to follow the development of

the children to elucidate whether this approach might contribute

to a lower incidence of respiratory tract infections or mortality.

However, in patients with chronic obstructive pulmonary disease

(COPD), the inhalation of vitamin A improved metaplastic and

dysplastic morphological changes.65 Nevertheless inhalation of

vitamin A results in an immediate delivery of retinyl esters to

the lung, independent from hepatic control, and contributes to

an improvement of the vitamin A status independent from in-

testinal absorption. The latter is impaired in cases of diarrhea

and parasitical infections, or delivery of vitamin A without fat.

Very recently, vitamin A was described as being systemically

bioavailable after intratracheal administration with surfactant

in an animal model of newborn piglets.66 This administration

was associated with hepatic uptake of vitamin A, but lung vita-

min A was not determined.

We found that administration of vitamin A in the form of an

aerosol is an effective, safe and routinely manageable method to

elevate vitamin A and RBP levels. Consequently, this procedure

figure 7b:

B

VARA: 0.0001

Dex: NS

VARA*Dex: NS

a > b, p < 0.0001

0

2

4

18

20

16

14

12

10

8

6

Control VARA Dex VARA + Dex

a

b b

a1

Lun

g R

E +

reti

no

l, n

mo

l/g

VARA: 0.0001

Dex: NS

VARA*Dex: NS

a > b > c, p < 0.01

0

50

100

400

350

300

250

200

150

VARA Dex VARA + Dex

a

c b

a2

Control

Live

r R

E +

reti

no

l, n

mo

L/g

VARA: 0.0027

Dex: NS

VARA*Dex: NS

a > b, p < 0.05

0

0.5

2.5

2.0

1.5

1.0

VARA Dex VARA + Dex

a

bb

a

3

Pla

sma

tota

l ret

ino

l, μ

mo

l/L

Control

26 THE IMPORTANCE OF VITAMIN A

may serve as an alternative method for vitamin A therapy during

chronic or acute episodes of malnutrition, malabsorption or in

the case of insuffi cient compliance with other therapies, and it

might be usefu l in treating respiratory diseases associated with

vitamin A defi ciency.

It should be investigated to what extent the “topical” appli-

cation of retinyl esters on the respiratory epithelium, especially

in those with chronic lung disease of prematurity, can contribute

to the replenishment of lung stores and thus lead to an improved

clinical outcome.

Conclusion

The results cited show that retinyl esters in respiratory epithe-

lium and in alveolar cells form a pool of vitamin A, which can be

used physiologically by the tissue. The formation of retinol and,

subsequently, retinoic acid fr om retinyl esters is strictly control-

led. So far, unphysiological formation of retinoic acid and subse-

quent toxicity do not seem possible. Retinyl esters, however, are

biochemically inert with respect to gene expression or vitamin A

activity as long as they are not hydrolyzed. Consequently, inhala-

tive application, especially in cases of insuffi cient lung develop-

ment, could represent a true alternative. Oral administration is

hardly successfu l because of poor RBP synthesis by the liver, and

a parenteral solution is currently not available.

To ensure suffi cient ante- and postnatal lung maturation, a

continuous adequate supply of vitamin A is important before

and during pregnancy. The vicious cycle of poor vitamin A status

in pregnancy and the consequently poor status of the newborn

and the consequences for fu rther development including adult-

hood and pregnancy needs to be interrupted. If no fortifi ed food

with preformed vitamin A is available, -carotene sources either

fr om green leafy vegetables and fr uit or biofortifi ed food (e.g.

maize, sweet potatoes) represent an alternative to improve the

vitamin A supply. In cases of an “emergency” approach, supple-

ments with high doses either before pregnancy or in the fi nal

term may be usefu l, but data are inconsistent. A fu ture approach

which might help to overcome poor vitamin A status with im-

paired lung fu nction is the inhalation of retinyl esters.

Despite confl icting results fr om intervention studies, due to

diff erent study protocols and dosages, there can be no doubt that

the adequate vitamin A statuses of mother and newborn have a

great impact on outcome and, in particular, the lung fu nction of

the newborn and the mortality and morbidity of both mother and

child. It is therefore of great importance to harmonize diff erent

supplementation protocols to develop usefu l and eff ective re-

commendations for vitamin A delivery at the diff erent stages of

pregnancy, as well as the antenatal and postnatal periods.

“Delivery of reti nyl palmitate by

inhalati on is eff ect ive in improving

vitamin A st atu s”

figure 8: Retinol and RBP in plasma before and aft er inhalation of retinyl palmitate (Biesalski et al., 1999)64

Inhalation of vitamin A improves vitamin A status in Ethiopian children with severe fat malabsorption

Whole population (n =161)

Study group (n =25)

Placebo group (n =25)

Pre-inhalation

0

2

1

Ret

ino

l [μ

mo

l/L]

Post-inhalation

Normal range Retinol

Study group

Placebo group

Pre-inh.

0

2

1

RB

P [

μm

ol/

L]Post-inhalation

Normal range RBP

⇢

27SIGHT AND LIFE | VOL. 25 (1) | 2011 27THE IMPORTANCE OF VITAMIN A

coincides with lung prenatal morphological maturation. Biochem

Biophys Res Commun 1994; 200:529–535.

16. Massaro D, Massaro GD. Toward therapeutic pulmonary alveolar

regeneration in humans. Proc Am Thorac Soc.3: 709-712 2006

17. Massaro D, Massaro GD. Lung development, lung function, and

retinoids. N Engl J Med. 2010; 362(19):1829-31 (8):709-12

18. Checkley W, West KP Jr, Wise RA et al. Maternal vitamin A

supplementation and lung function in offspring. N Engl J Med.

2010;362:1784–94

19. Grune T, Lietz G, Palou A et al. Beta-carotene is an important

vitamin A source for humans. J Nutr. 2010 Dec;140(12):

2268S–2285S.

20. Leung WC, Hessel S, Méplan C et al. Two common single

nucleotide polymorphisms in the gene encoding beta-carotene

15,15'-monoxygenase alter beta-carotene metabolism in female

volunteers. FASEB J. 2009;23(4):1041–5

21. Shenai JP., Chytil F. Vitamin A stores in the lungs during perinatal

development in the rat. Biol. Neonate. 1990; 57: 126–132

22. Biesalski HK. Separation of retinyl esters and their geometric

isomers by isocratic adsorption high-performance liquid

chromatography. Methods Enzymol. 1990;189:181–9.

23. Dirami G, Massaro GD, Clerch LB et al. Lung retinol storing cells

synthesize and secrete retinoic acid, an inducer of alveolus forma-

tion. Am J Physiol Lung Cell Mol Physiol. 2004;286(2):L249–56

24. Isakson BE, Lubman RL, Seedorf GJ et al. Modulation of pulmonary

alveolar type II cell phenotype and communication by extracellular

matrix and KGF. Am.J.Cell.Physiol. 2001; 281: C1291–C1299

25. Gottesman ME, Quadro L, Blaner WS. Studies of vitamin A meta-

bolism in mouse model systems. Bioessays 2001; 23: 409–419

26. Blomhoff R, Green RH, Berg T et al. Transport and storage of vita-

min A. Science 1990; 250:399–404

27. Theodosiou M., Laudet V, Schubert M. From Carrot to clinic:

an overview of the retinoic acid signaling pathway. Cell Mol Life Sci.

2010; 67:1423–1445

28. Ross AC, Ambalavanan N. Retinoic acid combined with vitamin

A synergizes to increase retinyl ester storage in the lungs of

newborn and dexamethasone-treated neonatal rats. Neonatology.

2007;92:26–32.

29. Ambalavanan N, Tyson JE, Kennedy KA et al. National Institute of

Child Health and Human Development Neonatal Research Network.

Vitamin A supplementation for extremely low birth weight infants:

outcome at 18 to 22 months. Pediatrics. 2005;115:249–54.

Correspondence: Hans-Konrad Biesalski, University of

Hohenheim, Institute 140, Fruwirthstrasse 12, 70593 Stuttgart,

Germany E-mail: biesal@uni-hohenheim.de

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41. Stofft E, Biesalski HK, Zschaebitz A et al. Morphological changes

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(retinol) concentrations and association with respiratory disease in

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serum retinol of children in a community-based study in northern

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childhood diarrhoea, respiratory infection and in maternal and

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49. Pinnock CB, Douglas RM, Badcock NR. Vitamin a status in children

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30

Background

Infants are born with small livers and total body stores of vi-

tamin A (VA).1–5 Exclusively breastfed infants depend on ade-

quate breastfeeding and good health to build body stores.6

However, low breast milk vitamin A, inadequate breast milk in-

take concentration,5–8 poor complementary food quality9 and/or

fr equent infection10 can all reduce an infant’s ability to achieve

normal vitamin A status.

A promising new intervention

Newborn vitamin A supplementation (NVAS) is a promising new

intervention that involves supplementing infants shortly aft er

birth with a single, large oral dose of vitamin A (50,000 IU)

(Figure 1). The intervention was tested in three fi eld trials in

southern Asia (Indonesia, India, and Bangladesh), each of which

reported signifi cant reductions of ≥ 15% in infant mortality in

the fi rst six months of life.11–13 When combined, the results

suggest that infant mortality can be reduced by approximately

20% in southern Asia by giving newborns a single, oral dose of

vitamin A.14 Given previous evidence of safety with respect to

short- or long-term side eff ects,15–20 newborn vitamin A supple-

mentation appears to be a low-cost approach to reducing infant

mortality in South and Southeast Asia.

In Afr ica, however, this intervention had no benefi cial eff ect

on early infant survival in an urban setting in Zimbabwe,21 and

a peri-urban setting in Guinea Bissau.22,23 All three Afr ican stud-

ies (two in Guinea Bissau) were done in populations with little,

if any, vitamin A defi ciency. Mortality in the Zimbabwean study

was very low.21 In one study in Guinea Bissau, investigators

reduced mortality by excluding the highest risk infants (those

with low birth weight) and giving fr ee care and drugs to sick

infants.22

A 2008 WHO Technical Consultation on Neonatal Vitamin A

Supplementation Research Priorities24 made the following

Rolf DW Klemm

Center for Human Nutrition, Bloomberg, School of

Public Health, Johns Hopkins University and A2Z:

The USAID Micronutrient and Child Blindness Project

Raj Kumar Pokharel, R P Bichha

Ministry of Health and Population, Nepal

Makhduma Nargis

Revitalization of Community Health Care

Initiative/Community Clinic, Ministry of Health and

Family Welfare, Bangladesh

Zeba Mahmud

Micronutrient Initiative, Bangladesh

Lesley Oot

A2Z: The USAID Micronutrient and Child Blindness

Project, AED, Washington, DC, USA

Pankaj Mehta, Naveen Paudyal UNICEF, Nepal

Jaganath Sharma NFHP II/USAID, Nepal

M R Maharjan, Neera Sharma

Micronutrient Initiative, Nepal

Mahbubur Rashid The JiVitA Project,

Gaidbandha, Bangladesh

THE FEASIBILITY OF DELIVERING VITAMIN A TO NEWBORNS

Test ing the Feasibility of Delivering Vitamin A to Newborns in Nepal and Bangladesh

figure 1: Female community health volunteer (FCHV)

dosing newborn with vitamin A in Nepal

31SIGHT AND LIFE | VOL. 25 (1) | 2011

“Insuffi cient evidence exist s to recommend a global policy of supplementi ng newborns with vitamin A.”

32 THE FEASIBILITY OF DELIVERING VITAMIN A TO NEWBORNS

recommendation: “Operational research on how to reach most

babies in developing countries within two days of birth should

be conducted in general, not necessarily in the context of neona-

tal vitamin A supplementation.” The consultation also reviewed

a systematic review of neonatal vitamin A trials.25 It concluded

that insufficient evidence existed to recommend a global policy

of supplementing newborns with vitamin A until further efficacy

trials in appropriate populations are conducted in Africa and

Asia. WHO is currently supporting additional efficacy studies in

Africa (Tanzania and Ghana) and South Asia (India), as well as

studies investigating potential biological mechanisms through

which NVAS may decrease the risk of early infant mortality.

Program implications

Adequate and effective NVAS will require innovative but feasible

programs in South Asian settings, where often >80% of infants

are born at home. For example, newborn dosing might require

identifying and engaging neighborhood “watch” networks to

detect births and rapidly dose infants, or using cell phones to

contact health workers at the time of birth. The capsule would

need to be widely available, perhaps through both the private

and public sectors. It could be included as a new component in

“safe birthing kits” for women to use themselves (obtained dur-

ing antenatal care or purchased in local shops), provided at the

time of home-delivery by nurse midwives or trained traditional

birth attendants or, lastly, at clinic- or hospital-based obstetric

care and delivery programs. Newborn VA delivery could be com-

bined with other emerging and effective neonatal care services,

such as cord cleaning with chlorahexadine wipes26 and newborn

care intervention packages.27 It could provide an opportunity

to establish birth dates and set the timing for an infant’s “six-

month” VA-dosing visit – an idea that is currently gaining inter-

est. Alternatively, in contexts where a high proportion of women

attend antenatal clinics, women could be given the supplement

and instructed on its use and administration, and then give it

directly to their newborn shortly after birth.

NVAS feasibility activities purpose

In both Nepal and Bangladesh, NVAS feasibility activities were

to identify, develop, and evaluate feasible models for delivering

NVAS integrated within existing ante- and postnatal interven-

tions at a scalable level within existing delivery platforms and

government health services.

Nepal

Background. Nepal is on track to meet its Millennium Develop-

ment Goal (MDG)-4 to reduce under-five mortality by two-thirds;

however, the government is finding ways to make further reduc-

tions by seeking efficacious interventions that reduce neonatal

and early infant deaths. The Child Health Division, Department

of Health Services of the Nepal Ministry of Health and Popula-

tion formulated a policy to pilot first, and piloted NVAS in 2009

in four districts (Figure 2), in partnership with the USAID-fund-

ed Nepal Family Health Program-II (NFHP-II), UNICEF, and the

Micronutrient Initiative (MI).

Delivery models. Considering that ~80% of births in Nepal

occur in the home, the extensive network of female commu-

nity health volunteers (FCHVs), and the government’s efforts

to intensify and improve access to Antenatal Care services,

Nepal selected two distribution models for feasibility testing:

1. The “FCHV Dosing” model, using postnatal home visits by

female community health volunteers to administer vitamin A

directly to newborns in two districts (Banke and Nawalparasi)

(Figure 3); and

2. The “Mother / Family Member Dosing” model, in which moth-

ers who attend an antenatal clinic at a health facility (HF), or are

visited at home by the FCHV after the eighth month of pregnancy,

are counseled about NVAS and given a supplement which they

give directly to their newborn, also in two districts (Sindhuli and

Tanahu) (Figure 4).

Monitoring and evaluation. NVAS implementation is being

monitored through the routine government health manage-

ment and information system. To record information on NVAS

receipt, the existing Iron Intensification Register, a record used

to track iron and folic acid tablet receipt among pregnant and

postpartum mothers, was modified. Data from this record are

compiled and sent monthly to the district and national levels.

In addition, three to four external monitors per district provide

Figure 2: Map of NVAS pilot districts in Nepal

Far-Western Region

Mid-Western Region

Western Region

Central Region

Eastern Region

India

NVAS pilot districts

0 20 60 100 Kilometers

FCHV dosing model

Mother dosing model

Banke

Nawalparasi

Tanahu

Sindhuli

⇢

33SIGHT AND LIFE | VOL. 25 (1) | 2011 33THE FEASIBILITY OF DELIVERING VITAMIN A TO NEWBORNS

special technical support visits, and interview health workers

and mothers whose babies have received the VA. In addition, the

effectiveness of the intervention is being evaluated using two

population-based cross-sectional surveys at baseline (Septem-

ber 2009) and end-line (February 2011).

Preliminary findings. Through the initial nine months of im-

plementation in the four pilot districts, >18,000 newborns have

been supplemented. Preliminary findings suggest that 62% of

newborns are reached in the female community health volunteer

(FCHV) and community health worker dosing model, and only

45% in the mother/family member dosing model.

Interesting preliminary observations from

monitoring surveys include:

> High NVAS coverage in districts where institutional deliveries

are high, and where other community-based services target-

ing newborns have been well established (e.g. in Banke).

> Low ANC attendance, especially the last visit at eight months’

gestation, appears to lead to low NVAS coverage.

> In the “Mother/Family Member Dosing” model, ~11% of moth-

ers are reluctant to dose their newborns. Instead, they wait

for the community health worker (i.e. the FCHV) to visit and

dose the newborn.

> Fewer than one percent of mothers and about one percent of

health workers reported a bulging fontanel in dosed infants.

All cases were transitory and recovered without treatment.

Bangladesh

Background. The Ministry of Health and Family Welfare (Mo-

HFW) in Bangladesh has extensive experience in considering

research findings, establishing a permissive policy, piloting

models to test implementation feasibility, and scaling up inter-

ventions. In December 2009, the Government of Bangladesh ap-

proved pilot feasibility testing activities for NVAS in three dis-

tricts (Tangail, Pirojpur and Nilphamari), and six sub-districts

divided between the Directorate General of Family Planning and

Revitalization of Community Health Care Initiative/Community

Clinic, Bangladesh (Figure 5).

Delivery models. In Bangladesh >80% of births occur in the

home, <18 % of deliveries are attended by a professional health

worker, and only 20 % of women receive a postpartum visit.28

To identify potentially feasible delivery platforms for NVAS, a

figure 3: FCHV Dosing Model

FCHV notified at birth by

family

FCHV doses newborn

with vitamin A and

records

FHCV visits newborn’s

home within 48 hours

of birth

Newborn dosed with

vitamin A within 48 hours

of birth

Antenatal contact

with pregnant women

Iron distribution by FCHV

Delivery at health

institution

Postnatal visit by FCHV to

confirm if dosed at HF

figure 4: Mother Dosing Model

NVAS dispensing

to pregnant women

at 8 months of

pregnancy by HF

staff or FCHV

Confirmation

of newborn dosing

and dosing if missed

and recording

FCHV visit

within

48 hours of

delivery

NVAS dosing within

48 hours of delivery

by mothers/family

members

Newborn

dosed with

vitamin A

Antenatal contact

with pregnant

women

ANC visit

HF

Outreach

clinic

Iron

distribution

by FCHV and

counseling

NVAS

Delivery at

health

institution

figure 6: NVAS design workshop participants

in Bangladesh

34 THE FEASIBILITY OF DELIVERING VITAMIN A TO NEWBORNS

design workshop, including national, district and sub-district

level health and family planning managers, was held in October

2010 (Figure 6) and proposed two delivery platforms:

1. The “Mother / Family Member Dosing” model in Bangladesh

uses two cadres of community health workers: The “Female Wel-

fare Assistant” (FWA) and the “Health Assistant” (HA), who in-

tegrates NVAS into routine home-based pregnancy surveillance

and home- or clinic-based antenatal (ANC) visits (Figure 7). In

addition to key ANC services and messages, pregnant women

receive an individually packaged dose of vitamin A (50,000 IU),

and are instructed about why, when, and how to administer the

dose to their newborns, and how to manage potential side ef-

fects. This information is accompanied by a counseling card

and a “Health Worker Contact Card” that includes the name,

cell phone number, and address of the local health worker. The

potential advantage of this model is that the VA supplement is

in the home at the time of delivery, and does not require the

notifi cation of or waiting for the arrival of a health worker to

administer the dose.

2. The “Health Worker Dosing” model also uses FWAs and HAs;

however, the mother or a family member must contact the health

worker at the time of birth and the health worker must visit the

mother and her newborn to directly administer the vitamin A

(Figure 8). To facilitate birth notifi cation, health workers inform

pregnant mothers about the importance of early birth notifi ca-

tion so that the baby can obtain newborn vitamin A and other

essential newborn services. In this model, a “Health Worker

Contact Card” is also provided to promote prompt and direct

communication with the health worker.

Monitoring and evaluation. Monitoring the pilot activities

involves a two-pronged strategy consisting of (1) routine data

collection within the MoHFW system; and (2) special monitor-

ing interviews and observations conducted by locally hired

“extenders” to assess how well NVAS is being integrated into

existing ANC and postpartum visits, and to assess community

acceptability (Figure 9). Two cross-sectional surveys in each

program upazila, or region, at baseline and at six months aft er

implementation (i.e. end-line), will be conducted among recent-

ly delivered mothers to assess coverage and timeliness of the

delivery of newborn vitamin A. In addition, community health

workers (CHW) will be surveyed at baseline and end-line to

assess knowledge, attitudes, and practices about integrating

NVAS into existing services.

Conclusions

Both Nepal and Bangladesh have made important strides in bridg-

ing the research-to-program gap by examining scientifi c evidence

and its relevance within each country’s context, establishing

policies that permit feasibility testing of this new intervention,

and closely monitoring and evaluating NVAS implementation

before formulating a policy for national scale-up. From prelimi-

nary data, implementation challenges facing NVAS are similar to

those faced by other interventions that target pregnant women

and newborns. These include identify ing and reaching a high

proportion of pregnant women and their newborns in a timely

manner, overcoming geographic, travel and time constraints

figure 5: Map of districts in Bangladesh where

NVAS is being piloted

PirojpurSadar and Nesarabad upazilas

TangailJaldhaka and Dimla upazilas

NilphamariJaldhaka and Dimla upazilas

0 25 50 Kilometers

India

(West

Bengal)

India

(Assam)

India

(Tripura)

Myanmar

(Burma)

35SIGHT AND LIFE | VOL. 25 (1) | 2011 35THE FEASIBILITY OF DELIVERING VITAMIN A TO NEWBORNS

figure 7: Mother/Family Dosing Model

figure 8: Health Worker Dosing Model

Pregnancy

Birth

Postpartum (0–2 days after birth)

Contact Points Actions

> Postnatal home visit by FWA

or HA

FWA or HA confirms newborn

dosing and doses baby if missed

Phone call Actions

Mother or family members gives NVAS to

newborn within 2 days of birth

Contact Points Actions

> Home-based pregnancy

identification/registration

> Home-based ANC visit

> Satellite-clinic ANC visit

> FWC-based ANC

Antenatal contact with pregnant women

Pregnant women given NVAS and instructed

on why, what, when, how and who will give NVAS

(integrated into usual ANC services/counseling)

Phone call

Birth

Actions

Family member contacts health worker by

mobile phone or drops card at clinicBaby is born,

please come!

Postpartum (0–2 days after birth)

Contact Points Actions

> Postnatal home visit by FWA

or HA

Health worker directly doses newborn

Pregnancy

Contact Points Actions

> Home-based pregnancy

identification/registration

> Home-based ANC visit

> Satellite-clinic ANC visit

> FWC-based ANC

Antenatal contact with pregnant women

Pregnant women given NVAS and instructed

on why, what, when, how and who will give NVAS

(integrated into usual ANC services/counseling)

36 THE FEASIBILITY OF DELIVERING VITAMIN A TO NEWBORNS

07. Rice AL, Stoltzfus RJ, de Francisco A et al. Low breast milk vitamin A

concentration refl ects an increased risk of low liver vitamin A stores

in women. Adv Exp Med Biol 2000;478:375–6.

08. Stoltzfus RJ, Humphrey JH. Vitamin A and the nursing mother-

infant dyad: evidence for intervention. Adv Exp Med Biol

2002;503:39–47.

09. Kimmons JE, Dewey KG, Haque E et al. Low nutrient intakes

among infants in rural Bangladesh are attributable to low intake

and micronutrient density of complementary foods. J Nutr 2005

Mar;135(3):444–51.

10. Mitra AK, Wahed MA, Chowdhury AK et al. Urinary retinol excre-

tion in children with acute watery diarrhoea. J Health Popul Nutr

2002;20(1):12–7.

11. Humphrey JH, Agoestina T, Wu L et al. Impact of neonatal vitamin

A supplementation on infant morbidity and mortality. J Pediatr

1996;128:489–96.

12. Rahmathullah L, Tielsch JM, Thulasiraj RD et al. Impact of

supplementing newborn infants with vitamin A on early infant

mortality: community based randomized trial in southern India.

BMJ 2003;327:254.

13. Klemm RD, Labrique A, Christian P et al. Newborn vitamin A supple-

mentation reduced infant mortality in rural Bangladesh. Pediatrics,

2008:122;E242–E250

14. West KP, Jr. Newborn vitamin A dosing: Policy implications for Asia

and Africa. Micronutrient Forum Abstracts, Istanbul, Turkey, 16–18

April 2007.

15. Agoestina T, Humphrey JH, Taylor GA et al. Safety of one 52-μmol

(50,000 IU) oral dose of vitamin A administered to neonates. Bull

World Health Organ. 1994;72(6):859–68.

16. Humphrey JH, Agoestina T, Juliana A et al. Neonatal vitamin A

supplementation: Eff ect on development and growth at 3 y of age.

Am J Clin Nutr 1998;68(1):109–17.

17. Baqui AH, de Francisco A, Arifeen SE et al. Bulging fontanelle aft er

supplementation with 25,000 IU of vitamin A in infancy using

in reaching a health facility or a home, and tracking pregnant

women who travel to their parental home to give birth. Lessons

learned fr om these pilot activities will provide usefu l insights

on how to introduce and integrate this new intervention within

existing health systems and delivery platforms in South Asia.

Correspondence: Rolf DW Klemm, A2Z: The USAID

Micronutrient and Child Blindness Project, AED, 1825 Connecticut

Avenue, NW, Washington, DC 20009, USA

E-mail: rklemm@jhsph.edu

References

01. Dahro M, Gunning D, Olson JA. Variations in liver concentrations

of iron and vitamin A as a function of age in young American

children dying of the sudden infant death syndrome as well as of

other causes. Int J Vitam Nutr Res 1983;53

02. Gebre-Medhin M, Vahlquist A. Vitamin A nutrition in the human

fetus. A comparison of Sweden and Ethiopia. Acta Paediatr Scand

1984;73:333–40.

03. Montreewasuwat N, Olson JA. Serum and liver concentrations

of vitamin A in Thai fetuses as a function of gestational age.

Am J Clin Nutr 1979 Mar;32(3):601–6.

04. Shah RS, Raalakshmi R, Bhatt RV et al. Liver stores of vitamin A

in human fetuses in relation to gestational age, fetal size and

maternal nutritional status. Br J Nutr 1987;58:181–9

05. West KP, Jr. Public health impact of preventing vitamin A

defi ciency in the fi rst six months of life. In: Delange FM, West KP Jr,

eds. Micronutrient Defi ciencies in the First Months of Life. Vevey,

Switzerland: Karger; 2003;103–28.

06. Haskell MJ, Brown KH. Maternal vitamin A nutriture and the

vitamin A content of human milk. J Mammary Gland Biol

Neoplasia 1999;4(3):243–57

figure 9: Monitoring and evaluation of NVAS pilot activities in Bangladesh

Formative research, advocacy, planning,

training, communications, logistics

District Level Programm (CC, FP)

Upazila 1

NBVAS-Mother/Family Member Model

Upazila 2

NBVAS-CHW Model

Dec

. ‘10

Jan

. ‘11

Feb

. ‘11

Mar

ch ‘1

1

Ap

ril

‘11

May

‘11

Jun

e ‘1

1

July

‘11

NBVAS Implementation

Baseline Endline

Performance Monitoring

Routine (through MoHFW) and special monitoring

conducted by externally hired “extenders”

Recently

delivered

women and

community

health

workers

Recently delivered

women and

community health

workers

37SIGHT AND LIFE | VOL. 25 (1) | 2011 37THE FEASIBILITY OF DELIVERING VITAMIN A TO NEWBORNS

23. WHO 2009 http://www.who.int/nutrition/publications/micronutri-

ents/vitamin_a_deficieny/NVAS_report.pdf

24. Gogia S, Sachdev HS. Neonatal vitamin A supplementation for

prevention of mortality and morbidity in infancy: systematic review

of randomised controlled trials. BMJ. 2009 Mar 27;338:b919

25. Tielsch JM, Darmstadt GL, Mullany LC et al. Impact of newborn

skin-cleansing with chlorhexidine on neonatal mortality in south-

ern Nepal: a community-based, cluster-randomized trial. Pediatrics.

2007 Feb;119(2):e330–40.

26. Baqui AH, El-Arifeen S, Darmstadt GL et al. Projahnmo Study Group.

Effect of community-based newborn-care intervention package

implemented through two service-delivery strategies in Sylhet

district Bangladesh: a cluster-randomised controlled trial. Lancet.

2008;371(9628):1936-44.

27. National Institute of Population Research and Training (NIPORT),

Mitra and Associates, and Macro International. 2009. Bangladesh

Demographic and Health Survey 2007. Dhaka, Bangladesh and

Calverton, Maryland, USA: National Institute of Population Research

and Training, Mitra and Associates, and Macro International.

immunization contacts. Acta Paediatr 1995;84(8):863–6.

18. Iliff et al. Nutr Res 1999;19:437.

19. West KP Jr, Khatry SK, LeClerq SC et al. Tolerance of young infants to

a single, large dose of vitamin A: a randomized community trial in

Nepal. Bull World Health Organ 1992;70(6):733–9.

20. WHO/CHD. Randomized trial to assess benefits and safety of

vitamin A supplementation linked to immunization in early infancy.

WHO/CHD immunization-linked vitamin A supplementation study

group. Lancet 1998;352:1257–63.

1 Malaba LC, Iliff PJ, Nathoo KH et al. Effect of post-partum maternal

or neonatal vitamin A supplementation on infant mortality among

infants born to HIV-negative mothers in Zimbabwe. Am J Clin Nutr

2005;81:454–60.

21. Benn CS, Diness BR, Roth A et al. Randomized trial of the effect on

mortality of 50,000 IU vitamin A given with BCG vaccine to infants

in Guinea-Bissau, West-Africa. BMJ 2008; 336:1416–20.

22. Benn CS, Fisker AB, Napirna BM et al. Vitamin A supplementation

and BCG vaccination at birth in low birthweight neonates: two by

two factorial randomised controlled trial. BMJ. 2010;340:c1101.

Available soon !

The new “Manual on Vitamin A

Deficiency Disorders (VADD)” by

Sight and Life Press

38

nutrient-rich varieties of vegetable and fr uit were distributed

among the farmers identifi ed. Drumstick, papaya, curry leaves

(Murraya Koenigii) and creeper spinach (Basilla alba) seedlings

were raised by village women in backyard nurseries and then

purchased fr om them, providing them with some income.

Organic fertilizers, such as vermi compost, and botanical

pesticides, such as neem kernel and chili garlic decoction, were

promoted. Once every two months, experts were invited as fac-

ulty and centralized training programs were conducted on the

campus of the Dangoria Charitable Trust (DCT) in the village

of Narsapur. Hands-on training was also given via village-level

meetings and visits to individual farms. In addition to horticul-

ture, and the use of organic methods of farming, education in nu-

trition, health and environment formed an important part of the

training. Focused group discussions (FGD) and slide and sound

shows were organized in the evenings. School education was

also an important part of creating awareness.

Impact assessment was carried out by making a record of

diverted land, crops grown and their survival, the adoption of

organic methods of farming etc. A rough estimate of vegetables

sold and consumed at home was obtained by visiting households

every month and making enquiries.

Baseline and end-line surveys on Knowledge, Attitude, and

Practice (KAP) were carried out in four villages, representing three

mandals, using a pretested questionnaire to test know-ledge on

green methods of farming and nutrition. A diet survey using a

semi-quantitative method was held to examine the impact on

consumption of protective foods such as vegetables, pulses and

animal products. This method involves obtaining information on

the fr equency of consumption of diff erent foods by the family

during a typical week (when there are no guests, festivities, or

Introduction

Cereal pulse-based Indian diets are qualitatively poor in vitamins

and minerals due to inadequate consumption of vegetables and

fr uits – the major source of micronutrients in vegetarian diets.1

Homestead gardens have been reported to improve access to

and consumption of vegetables.2, 3, 4 Homestead food production

also helps with household food security.2, 5

This study has attempted partial diversifi cation fr om the wa-

ter-intensive cropping pattern (rice and sugar cane) to horticul-

ture using green methods of farming in a dry-land area to improve

household access to vegetables and environment security.

Subjects and methods

The study was conducted in 15 villages fr om 4 mandals (popula-

tion 24,000), of the Medak district of the South Indian state of

Andhra Pradesh. The project was explained in village-level meet-

ings; 222 farmers who had land (marginal or small) and were

willing to partially diversify fr om rice and sugar cane to horti-

culture (mixed orchards, vegetable gardens), and adopt green

methods of farming, were identifi ed. Seeds/seedlings of micro-

Mahtab S Bamji, PVVS Murty

Dangoria Charitable Trust, Hyderabad, India

M Vishnuvardhan Rao

National Institute of Nutrition, Hyderabad, India

G Satyanarayana

ANGR Agriculture University, Hyderabad, India

FROM AGRICULTURE TO HORTICULTURE IN A DRY-LAND AREA

Diversifi cati on fr om Agricultu re to Nutr iti onally and Environmentally Promoti ve Horti cultu re in a Dry-Land Area

3939SIGHT AND LIFE | VOL. 25 (1) | 2011 FROM AGRICULTURE TO HORTICULTURE IN A DRY-LAND AREA

fasting), the daily quantity cooked and the number of household

members above the age of one year (capita).

Based on this information, an estimate of mean quantity in

grams of diff erent foods consumed per capita per day was ob-

tained. During the end-line survey, intake per consumption unit

(CU),1 in addition to per capita intake, was also ascertained by

obtaining additional information on the sex, age, physiological

status and activity of diff erent members of the family (data not

reported). However, the diff erence between per capita and per

CU values was negligible. This method of diet survey can be ap-

plied in rural households where diets and menus are routine.

The initial survey in the four selected villages included all

farmers who had agreed to participate in the project. All of the

farmers who actually participated (stakeholders) were also in-

cluded in the end-line survey (experimental group). This covered

82% of the initial cohort. Some farmers who initially accepted

then dropped out, but some who were initially unwilling joined

later on. To allow for the impact of time, in the end-line survey

50 farming households fr om the same villages who had not par-

ticipated in land diversion were also interviewed (control group).

However, even the control group farmers were allowed to partici-

pate in the training programs conducted in the villages. Due to

material and human resource constraints, the KAP survey could

not be carried out in all 15 villages. In addition, more than 50%

of the farmers who joined the project were fr om the four selected

villages. The two interviewers were trained and spoke the local

language fl uently.

Mixed orchards in India contribute to home food production

and boost vegetable consumption

“Monthly inquires suggest ed sales

of 25–50% of the vegetables

grown, with the rest being consumed

at home”

40 FROM AGRICULTURE TO HORTICULTURE IN A DRY-LAND AREA

table 1: Knowledge of nutrition. Values are % of respondents. No prompting. Multiple answers.

Good health 70.4 *** 95.3 80.0 **

Gives energy 40.0 *** 76.6 64.0 **

Gives strength 32.8 *** 55.5 54.0

Protects against diseases 3.2 *** 63.8 24.0 *** ***

For living 5.6 *** 49.6 40.0 ***

For hunger 12.8 19.5 28.0 *

Any other 0.8 3.3 4.0

Cereals 63.2 *** 98.4 100.0 ***

Roti (dry pancakes fr om cereals

and millets)

49.6 *** 71.1 60.0

Pulses 23.2 *** 95.9 66.0 *** ***

Vegetables 36.0 *** 98.4 70.0 *** ***

Fruits 38.4 *** 62.2 42.0 *

Green leafy vegetables 42.4 *** 81.1 38.0 ***

Milk 19.2 *** 77.3 56.0 ** ***

Eggs 13.6 *** 66.4 36.0 *** ***

Meat/fi sh etc 19.2 39.8 32.0

Good health 64.0 *** 85.9 76.0

Gives energy 51.2 57.0 62.0

Gives strength 47.2 45.7 55.1

Protects against diseases 5.6 *** 69.6 22.0 *** ***

Improves eyesight 4.0 *** 58.0 52.0

Protects against anemia 0 75.8 34.0 *** ***

Makes teeth and bones stronger 0 37.6 16.0 **

For taste 0 39.1 52.0

Any other 0.8 3.1 2.0

Description Initial

March / April 2007

End-line Experimental

March / April 2010

End-line Control

March / April 2010

Number of respondents 125 128 50

Why do we eat food?Why do we eat food?

What are the components of a balanced diet ?What are the components of a balanced diet ?

What are the fu nctions of fr uits and vegetables ?What are the fu nctions of fr uits and vegetables ?

The Two Proportion Z test was used to see the diff erences in proportions between two groups

* * P<0.05, ** ** P0.01, *** *** P<0.001 compared to end- line experimental

* * P< 0.05, ** ** P<0.01, *** *** P<0.001 compared to initial

⇢

41SIGHT AND LIFE | VOL. 25 (1) | 2011 41FROM AGRICULTURE TO HORTICULTURE IN A DRY-LAND AREA

Statistical methods

The statistical tests used to test signifi cance are given as foot-

notes under each table.

Results

A total of 222 farmers diverted 62.1 acres of land to horticulture.

Monthly inquiries suggested sales of 25–50% of the vegetables

grown, with the rest being consumed at home. The impact of

the project on participating farmers was marked in terms of

knowledge of nutrition (fu nctions of foods and components of

balanced diet, particularly protective foods) (Table 1). Respons-

es suggest the contact eff ect of education. Thus, in the end-line

survey, the knowledge of even the control group was better than

it had been in the initial survey. Knowledge and the adoption

of green farming methods also improved. Acceptance of botani-

cal pesticides and vermi compost was good. Microbial products

were introduced, but were not accepted due to lack of access to

reliable material.

On average, the families consumed vegetables and pulses

three times a week (Table 2). In the end-line survey, families

in the experimental group tended to report higher consumption

of vegetables (52.3 g) compared to the control group (37.4 g),

but not compared to the initial survey (57.7 g). Consumption of

green leafy vegetables (GLV) tended to be higher in the end-line

survey, compared to the initial survey. Pulse (dal) consumption

took place two to three times a week, but only in quantities of

about 20 g. Milk was consumed daily, mostly in tea. Milk con-

sumption tended to be lower in the end-line than the initial

survey – perhaps due to a price rise over the three-year period.

Animal products such as meat (mutton, chicken, and fi sh) and

eggs were consumed once or twice a week, in small amounts.

Consumption of animal products tended to be higher in the end-

line than the initial survey.

Over 95% of families in both surveys mentioned that they ob-

tained their requirement of rice fr om their own farms or fr om the

same village. In addition, in the end-line survey 90% of farmers

mentioned that they obtained rice and pulses fr om the Public

Distribution System (PDS) of the government, as compared to

10% in the initial survey. For other food grains, such as wheat,

maize, sorghum, fi nger millet, pulses and vegetables and fr uits,

table 2: Food consumption: Weekly fr equency and quantity consumed per capita per day.

Vegetables: fr equency 3.85 ± 1.04 c 3.4± 0.631a 3.1 ± 0.340 b

g /capita /day 57.7± 31.11 ac 52.3 ± 21.7 a 37.1 ± 10.34 b

GLV: fr equency-mean 2.2 ± 0.72 2.9 ± 0.750 2.5 ± 0.614

g /capita /day 36.0 ± 20.08 c 51.6 ± 24.3 a 57.1 ± 24.4 ab

Pulses: fr equency-mean 2.63 ± 1.08 2.8 ± 0.741 2.7± 0.519

g /capita /day 20.4 ± 13.03 19.0 ± 8.62 17.9 ± 5.52

Milk: fr equency-mean 6.76 ± 1.30 6.94 ± 0.621 7.0 ± 0.000

g /capita /day 95.8 ± 138.68 c 71.3 ± 46.75 a 47.7 ± 18.78 b

Eggs: fr equency-mean 1.3 ± 0.87a 2.0 ± 1.458 b 1.9 ± 0.274 bc

number / capita / day 0.15 ± 0.1199 a 0.41 ± 1.16 b 0.3 ± 0.079 b

Meat: fr equency-mean 1.02 ± 0.297a 1.35 ± 0.685 b 1.64 ± 0.485 c

g /capita /day 18.49 ± 8.745 a 27.8±44.62 b 27.3± 9.36 bc

Description Initial

March / April 2007

End-line Experimental

March / April 2010

End-line Control

March / April 2010

Number of respondents 125 128 50

FoodFood

Means with diff erent superscripts a, b, c are signifi cantly diff erent at P<0.05 using one way analysis of variance with post hoc LSD method.

Where necessary, the data was log-transformed and subjected to ANOVA to stabilize the variations in the groups.

42 FROM AGRICULTURE TO HORTICULTURE IN A DRY-LAND AREA

over 50% of families depended on sources outside the village

for their household requirements. In both the surveys, over 90%

of families mentioned that they ate all of the above food grains,

except maize, which a third of the families did not eat despite

cultivating it.

Discussion

Diets were poor with regard to foods such as pulses, vegetables

and animal products. The marked reduction in the mean con-

sumption of vegetables in the control group in the end-line sur-

vey, as compared to the initial survey, demonstrates the adverse

impact of the price rise. The experimental group seems to have

been shielded against this effect, stressing the need to promote

the homestead production of protective foods. An almost 44%

increase in the consumption of GLV in the end-line, as compared

to the initial survey, suggests the positive impact of nutrition

education. The increase, which occurred even in the control

group, is not surprising; growing GLV is easy and all of these

were included in the community education efforts. Despite the

fact that vegetable consumption was far below the recommended

level, all of the farmers mentioned that they sold 25–50% of the

vegetables grown. For poor households, economic compulsions

outweigh nutritional wisdom. Village-level security for rice was

better than that for other foods which had to be procured from

outside sources. The fact that most families consumed cereals

and millets other than rice suggests a healthy traditional prac-

tice of consuming mixed-grain diets. This needs to be nurtured,

particularly since, in recent years, the preference for millets has

declined due to easy access to rice and wheat.

In earlier studies6,7 aimed at promoting home gardens to com-

bat vitamin A deficiency in the Medak district, it was observed

that home gardening alone may not be adequate to prevent vi-

tamin A deficiency. Other methods, including the promotion of

animal husbandry and poultry, would be needed to complement

this food-based approach. In the authors’ experience, diversi-

fication to horticulture from other crops requires considerable

advocacy and persuasion, since farmers with marginal and small

land-holdings hesitate to diversify from traditional crops. On the

other hand, acceptance of back-yard poultry was good (unpub-

lished).

In conclusion

Homestead gardening can have a positive impact on the con-

sumption of horticultural produce, but this by itself will not meet

the daily requirements in a small-farm-holding family where in-

come is a priority. Poverty alleviation measures are needed to

improve household food security.

Acknowledgements

The authors are grateful to the Department of Biotechnology,

Government of India for financial support; the Dangoria Chari-

table Trust for logistical support, and Dr T Vishnumurthy and Sri

Narsimha Reddy for training in horticulture.

Correspondence: Mahtab S Bamji, Dangoria Charitable Trust

DCT), 1-7-1074, Musheerabad, Hyderabad 500020, India

E-mail: msbamji@gmail.com

References

01. National Nutrition Monitoring Bureau. Diet and nutrition status

of population and prevalence of hypertension among adults in

rural areas. Technical Report No. 24, National Institute of Nutrition,

Hyderabad, India, Indian Council of Medical Research, 2006.

02. Talkukdar A, Haselow NJ, Osel AK et al. Homestead food production

model contributes to improved household food security and nutri-

tion status of young children and women in poor populations. Field

Actions Science Reports (online), Special Issue 1: Urban Agriculture,

online since 17 February 2010, accessed 13 June 2010. http//

factsreports.revues.org/index404.html.

03. Rahman FMM, Mortuza MGG, Rahman MT et al. Food security

through homestead vegetable production in the smallholder agri-

cultural improvement project (SAIP) area. J Bangladesh Agril Univ

2008;6:261–69.

04. Iannoti L, Cunningham K, Ruel M. Improving diet quality and

micronutrient nutrition. Homestead food production in Bangladesh.

IFPRI discussion paper 00928, prepared for the project on Millions

Fed: Proven Successes in Agriculture Development, November

2009;1–44. www.IFPRI.org/millions fed

05. Ndaeyo NU. Assessing the contributions of homestead farming to

food security in a developing economy: A case study of Southern

Nigeria. J Agri Soc Sci 2007;3:11–16

06. Vijayraghavan K, Nayak UM, Bamji MS et al. Home gardening for

combating vitamin A deficiency in rural India. Food and Nutrition

Bulletin 1997;18:337-343.

07. Murty PVVS, Lakshmi KV, Bamji MS. Impact of home gardening

and nutrition education in a district of rural India. Readers’ Forum.

Bulletin of the World Health Organization 1999;77:784.

“For poor households, economic

compulsions outweigh nutritional

wisdom”

Building bridges for better nutrition.

44

Key messages

> Iron defi ciency anemia is a worldwide problem

> Fortifying fl our with iron is an eff ective way to address the

problem if iron defi ciency is the underlying cause

> Electrolytic or elemental iron is commonly used as a

fortifi cant in cereal fl ours

> Only 2–3% of these forms of iron are absorbed,

so most ends up in the colon

> Ivorian children received an extra ~9 mg electrolytic

iron/d for 6 months

> Children who received the supplemental iron had a

higher proportion of Enterobacteria and fewer Lactobacilli

spp in their feces

> Excess iron may accelerate the growth of Enterobacteria

at the expense of Lactobacilli spp.

> Iron supplementation is also associated with increased

colonic infl ammation

> Cause of infl ammation is not known

The results of the recent randomized controlled trial (RCT) in

Pemba,1 where there was more severe child morbidity and mor-

tality in the group receiving supplements of iron and folic acid,

brought to a halt the unsupervised use of iron supplements to

remove iron defi ciency anemia – especially in malaria-endemic

areas.2 However, there is uncertainty whether the adverse ef-

fects of the supplements were due to interactions between iron

and malaria, iron and enteric infections, impaired eff ectiveness

of anti-malarial treatment due to the folate, a combination of

all three, or some other explanation. In this issue of Sight and Life, I will discuss the issue of iron and its apparent eff ects on

enteric bacteria, following a recent article in which the authors

described the impact of poorly bioavailable fortifi cation iron

on the profi le of the gut microbiota of Afr ican children.3 In this

study, the additional iron appeared to increase the proportion of

pathogenic bacteria and act as a biomarker of infl ammation in

the feces. Nevertheless, there was no evidence of any increase

in systemic infection in the children receiving the iron. To try to

understand the meaning of the observations, I will also describe

some results fr om two other papers where the authors exam-

ined individual sub-strains of commensal Clostridium bacteria

and showed that they had both individual and collective eff ects

on immune cells within the lining of the gut, and can have both

pro- and anti-infl ammatory eff ects in diff erent circumstances.4,5

Such results indicate that quantitation of the major bacterial

strains within the microbiota may, in fact, tell us very little about

David Thurnham

Northern Ireland Centre for Food and Health,

University of Ulster, Coleraine, United Kingdom

IRON FORTIFICATION – NEW REVELATIONS?

IronForti fi cati on

– New Revelati ons?

4545IRON FORTIFICATION – NEW REVELATIONS?SIGHT AND LIFE | VOL. 25 (1) | 2011

the physiological eff ects of the microbiota on the host. To under-

stand the interaction of iron and the microbiota, the source of

the infl ammation and /or the bacteria involved must be charac-

terized fi rst.

Introduction

Defi ciencies of iron, vitamin A, iodine and other micronutrients

aff ect at least one third of the world’s population, the majority

of whom live in developing countries. Public health nutritionists

are acutely aware that iron defi ciency is the most prevalent, and

it is estimated that just over 2 billion people are anemic due to

nutritional and non-nutritional causes.6,7 Reports that iron sup-

plementation of iron-defi cient individuals can improve cognitive

fu nction, school performance, and work capacity,8,9 and that se-

vere anemia increases the risk of maternal and child mortality,10

have provided a strong rationale for iron interventions.

Unfortunately, there are health risks associated with iron. It

has been known for more than 40 years that it is dangerous to

give iron supplements to sick, malnourished children;11 acciden-

tal overdose of iron-containing products is a leading cause of

fatal poisonings in healthy children under six years;12 diets rich

in iron have been linked to a higher risk of colon cancer;13,14 and

iron supplements, even at nutritional levels, produce a number

of unpleasant side eff ects such as diarrhea, nausea, and vomit-

ing. But the main problem taxing the minds of the regulatory

authorities is how to combat the huge problem of iron-defi ciency

anemia in the developing world, following the publication of the

“Pemba” study1 that found routine treatments of iron and folic

acid given to pre-school children were associated with higher

risks of severe illness and death than in the control groups.

Currently, iron supplementation programs have come to a halt

around the world, potentially putting millions of children at risk

of the adverse impacts of iron-defi ciency anemia.2

Food fortifi cation with iron can be an eff ective strategy to

control iron defi ciency anemia,15 and the foodstuff s most oft en

used for mass fortifi cation are cereal fl ours. Worldwide, the most

commonly used fortifi cants for fl ours are elemental iron powders

such as hydrogen-reduced iron or electrolytic iron, despite their

low bioavailability, which can oft en be as low as <2–3%.16 Low

absorption of iron fortifi cants results in >90% of unabsorbed

iron passing unabsorbed into the colon.3 Iron is able to undergo

reduction and oxidation, making it important in many physio-

logical processes. This inherent redox property of iron, however,

also renders it toxic when it is present in excess. Iron-mediated

generation of reactive oxygen species via the Fenton reaction,

if uncontrolled, may lead to cell damage as a result of lipid per-

oxidation, oxidation of DNA, and protein damage.13 Most iron

in the blood and tissues of the body is tightly bound to various

proteins to control its reactivity, but there is no similar system

for sequestration of dietary iron in the gut lumen. Instead, the

human gut is packed with resident bacteria, collectively known

as the microbiota, and the multiple strains vigorously compete

for unabsorbed iron, which they need in order to grow.17 Growth

of some pathogenic species of bacteria, however, (e.g. Salmo-

nella or Shigella) was associated with increased virulence and

colonization.18 Animal experiments have shown that increasing

dietary iron increased the incidence of diarrhea, and increased

the proportion of pathogenic bacteria within gut lumen.19 Mind-

fu l of the uncertainty about what caused the higher risks of se-

vere illness and mortality in the iron/folate group in Pemba, the

WHO consultation that followed cautioned about whether the

risks associated with iron supplementation were specifi c to ma-

laria or applied to other infections, including sepsis and enteric

bacteria.20

Iron fortifi cation

The best way to prevent micronutrient malnutrition is to ensure

consumption of a balanced diet that is adequate in every nutri-

ent. Unfortunately, this is far fr om being achievable everywhere,

since it requires universal access to adequate food and appro-

priate dietary habits. From this standpoint, food fortifi cation has

the dual advantage of being able to deliver nutrients to large

segments of the population without requiring radical changes in

food consumption patterns. In fact, fortifi cation has been used

“Iron-defi ciency anemia is a

huge problem in the third world”

> There was no increase in systemic infl ammation in

the children

> Endogenous species of bacteria can stimulate CD4+

lymphocytes to produce T helper (Th)17 or Treg cells in the

intestinal wall

> Th17 cells are potentially pro-infl ammatory and Treg cells are

anti-infl ammatory

> Iron may stimulate (as yet unknown species of) Enterobacteria

to increase pro-infl ammatory immune cells in the gut wall

> Infl ammatory eff ects of supplemental iron may be reduced

by using less but more bioavailable forms of iron and phytase

to release intrinsic iron from phytate.

46 IRON FORTIFICATION – NEW REVELATIONS?

for about 80 years in industrialized countries as a means of

restoring micronutrients, in particular some of the B vitamins,

lost by food processing, and has been a major contributory fac-

tor in the eradication of diseases associated with defi ciencies in

these vitamins.7

The study to investigate the eff ects of iron on gut bacteria

was carried out in Côte d’Ivoire. The study was nested within a

larger intervention trial that tested the interactions of the inter-

mittent treatment of malaria (IPT), anthelmintic treatment and

iron fortifi cation,21 and was a six-month, randomized, double-

blind, controlled trial, enrolling 591 six to 14 year old school

children.

The interventions were: (1) iron-fortifi ed biscuits providing

an additional 20 mg iron/d as electrolytic iron (A-131, Dr Paul

Lohmann GmbH, Emmerthal, Germany) 4 times/wk; (2) intermit-

tent treatment of malaria with sulfadoxine-pyrimethamine at 0

and 3 months; (3) anthelmintic treatment at 0 and 3 months;

and (4) a placebo of unfortifi ed biscuits in several combinations.

The prevalence of anemia (hemoglobin ≥80 g/L and ≤115 g/L),

iron defi ciency, malaria parasitemia, and helminth infection was

70.4, 9.3, 57.7, and 54.8%, respectively. The usual wet season

is fr om March to November and the fi eld studies were carried

out fr om November 2006 to July 2007. The biochemical results

for the microbiota sub-groups (taken fr om treatments 1 and 4,

above) were no diff erent to those of the whole groups, except for

small, unimportant diff erences in ferritin.

The results for hemoglobin and anemia are shown in Table 1.

Estimated daily mean intakes of iron ranged fr om 12.2 to 14.5 mg

for the boys and girls, and the authors estimated that the ad-

ditional iron fr om the biscuits amounted to 8.8 ± 1.2 (SD) mg

fortifi cant iron/day. Alternatively expressed, the iron interven-

tion increased the overall dietary intake ~60–70%. The data in

Table 1 show that more than 70% of the children in the study

were anemic at baseline and the prevalence increased to more

than 90% at six months. If the anemia was, in fact, due to iron

defi ciency, you would expect the combined dietary and fortifi -

cant iron to have reduced the level of anemia, unless, of course,

the anemia was due to the high exposure to infection, and other

causes (e.g. vitamin A defi ciency). Table 2 shows the concentra-

tions of the two acute phase proteins C-reactive protein (CRP)

and ₁-acid glycoprotein (AGP) in the Afr ican children. The au-

thors calculated fr om these fi gures that 16–19% of the children

had systemic infl ammation. However, if these were apparently

healthy children, the cut-off s used by the authors were high

(CRP 10 mg/L and AGP 1.2 g/L). In my opinion, and those of

table 1: Anemia and hemoglobin concentration (mean ± SD) in children in Côte d’Ivoire at baseline

and following 6 months of iron supplementation ¹,²

table 2: Concentrations of C-reactive protein (CRP) and 1-acid glycoprotein (AGP) (median and range) in Ivorian children

at baseline and following 6 months iron supplementation ¹

Control Group (n=70)

Control Group

Iron Group (n=69)

Iron Group

¹ Anemia defi ned as hemoglobin >80 g/L and <115 g/L

² Iron supplement was 20 mg electrolytic iron per day per child, 4 times per week

¹ For details of iron supplement see Table 1

Baseline 6 months Baseline 6 months

Hemoglobin g/L 110.7 ± 10.5 107.1 ± 10.5 110.8 ± 9.4 106.6 ± 9.7

Anemia % 75.4 88.4 71.4 87.1

Baseline 6 months Baseline 6 months

CRP mg/L 2.7 (0.2 – 47.5) 2.1 (0.2 – 86.3) 2.0 (0.2 – 68.7) 1.7 (0.2 – 49.8)

AGP g/L 1.0 (0.4 – 2.6) 0.8 (0.4 – 1.5) 1.0 (0.2 – 1.8) 0.9 (0.3 – 2.1)

47SIGHT AND LIFE | VOL. 25 (1) | 2011 47IRON FORTIFICATION – NEW REVELATIONS?

bacterial species; and (4) detect bacterial gut pathogens. Base-

line and six-month samples from the same volunteer were al-

ways run together where gel electrophoresis was involved, for

accurate comparisons.

Influence of the fortification iron on the gut microbiota

The authors investigated whole bacterial diversity by using two

universal primers for the polymerase chain reaction that at-

tached to variable regions 2 and 3 on the bacterial 16S ribos-

omal RNA genes, in conjunction with temperature gradient elec-

trophoresis of the resultant products. These qualitative results

suggested that there was no difference between baseline and six

months in the absolute number of bands revealed in the electro-

phoretic gels, i.e., the number of bacterial types or groups in the

fecal samples. However, when the consistency (or comparabil-

ity) in band behavior between baseline and six months was com-

pared, consistency in band behavior was significantly greater in

the control than the iron-treated group. That is, band distances

differed by only 15 ± 7.5% in the controls, whereas bands dif-

fered by 32.3 ± 12.5% (Dice coefficient analysis, P <0,0001) in

the iron-treated group, indicating that bacterial diversity was

much greater after iron supplementation.3,24

The authors also carried out similar experiments to the above,

but used primers that specifically targeted Lactobacillus species.

They noted that, in the iron group, the microbiotic profile at six

months strongly differed from that at baseline for each volunteer,

but the responses were variable and no specific band pattern

could be related to iron fortification.

In addition to looking at diversity, the authors also used quan-

titative real-time PCR, using a universal primer pair to obtain the

total bacterial count and specific primers to measure Bacteroides,

Enterobacteria, Bifidobacteria and Lactobacillus spp (Table 3).

The mean log numbers of bacteria per g feces for all 60 chil-

dren at baseline are shown in Figure 1. During the intervention,

there were no significant changes in the total numbers of bac-

teria (log numbers, control 11.29 ± 0.67 and 11.28 ± 0.81; iron

group 11.62 ± 0.70 and 11.78 ± 0.59) but in the iron group there

was a significant increase in Enterobacter spp and a decrease in

Lactobacilli spp (Figure 2). The population of enterobacteria in-

cludes many of the enteric pathogens and 26.6% of the children

had positive fecal samples for Shigella spp and enteroinvasive

E. coli and/or Salmonella spp at baseline, although the counts

of these pathogenic species were generally low, namely ≤10³/g

feces. This number is small, when one report suggested that 10¹⁴

bacteria reside in the large intestine alone.25 Salmonella was the

predominant bacterial pathogen in the fecal sample occurring in

~79 % of the positive samples and, after six months, more chil-

dren were positive for Salmonella in the iron group (23%) than

in the controls (16.6%), but this difference was not significant.

Furthermore, there were no significant correlations between any

my colleagues,22,23 the cut-offs should be lower (CRP 5 mg/L;

AGP 1.0 g/L), which would suggest that more like 40% of the

children had systemic inflammation on the basis of AGP alone.

Furthermore, the underestimates of inflammation will also have

produced underestimates of iron deficiency, which were derived

on the basis of serum ferritin concentrations. However, there

was no significant difference in these inflammation biomarkers

between the two groups at baseline or after intervention, so the

underestimate in systemic inflammation is unlikely to have af-

fected any difference in iron deficiency between the groups.

Detection and quantitation of gut microbiota

The main aim of the Ivorian sub-study was to determine what

effect, if any, the additional iron in the fortified biscuits had on

the gut microbiota. Thirty children were randomly selected from

groups 1 and 4 (see above). None of the children had unusual

dietary habits or had received antibiotics in the three months

before the baseline survey. During the survey, the number of

days of antibiotics did not differ between the two groups. No

child was given antibiotics in the three weeks before the six-

month sample. In the mornings at school, fecal samples were

collected into pre-labeled beakers with lids and stored for the

rest of the morning in an ice chest, and then aliquots were frozen

at -30° C until analysis. Total bacterial DNA was extracted from

200 mg fecal samples (Fast DNA SPIN kit, MP Biomedicals, Ill-

kirch, France) and DNA was measured at 260 nm, before storing

the samples at -24° C until further analysis.

The polymerase chain reaction (PCR) was used to quantify

the total bacterial content and individual species in the fecal

DNA sample. In the PCR, short nucleotide sequences (= prim-

ers), originally obtained from the 16S ribosomal ribonucleic acid

(rRNA) sub-units of specific bacteria, attach to complementary

DNA sequences in the fecal DNA sample, together with a DNA

polymerase enzyme. 16S rRNA gene primers are used, as they

contain many highly conserved primer binding sites and, in ad-

dition, hyper-variable regions that can provide species-specific

signature sequences useful for bacterial identification. The DNA

polymerase enzymatically assembles new DNA strands from

each primer using deoxy-nucleotide triphosphates, the building

blocks from which the new DNA strand is synthesized. As the

PCR progresses, the DNA generated attaches to more primer and

is itself used as a template for replication. This sets in motion

a chain reaction in which the DNA template is identified or tar-

geted by the primer and exponentially amplified. The pro-cess is

precisely temperature regulated and timed to enable the prod-

ucts to be quantitatively related to the starting amount of fecal

DNA.

Several types of PCR were used on the fecal DNA at baseline

and six months, to (1) investigate the whole bacterial diversity;

(2) identify the species of Lactobacillus; (3) quantify the major

48 IRON FORTIFICATION – NEW REVELATIONS?

of the bacterial counts or changes in the fecal bacteria and base-

line serum ferritin, transferrin receptors or zinc protoporphyrin

concentrations.

Gut infl ammation in the Ivorian children

The authors measured fecal concentrations of the infl ammatory

protein, calprotectin. Calprotectin is a calcium-binding protein

that is found in all body fl uids, in proportion to the level of in-

fl ammation present. Calprotectin is derived predominantly fr om

neutrophils and, to a lesser extent, fr om monocytes and reac-

tive macrophages. The presence of calprotectin in the feces is

directly proportional to neutrophil migration towards the in-

testinal tract.26 Fecal calprotectin is remarkably stable and a

usefu l marker of gastrointestinal infl ammation.27,28 Infl amma-

tion in the bowel implies a loss of barrier fu nction and a loss

of tolerance against luminal and self antigens, and both these

phenomena cause the recruitment of leukocytes in the intesti-

nal wall.28 Activated leukocytes infi ltrating into the intestinal

mucosa are detected in the feces due to epithelial shedding in

the intestinal lumen. The most important leukocyte population

in the mucosal wall is polymorphonuclear neutrophils; hence,

there is an increase in fecal calprotectin when there is intesti-

nal infl ammation. Several studies have shown that a cut-off of

30 mg/L had 100% sensitivity and 94% specifi city for screening

irritable bowel syndrome, but the calprotectin threshold predic-

tive of systemic infl ammation (CRP >6 mg/L) was 284 mg/L.28

Thus, infl ammation in the bowel will not necessarily be detected

systemically until intestinal infl ammation is severe.

Fecal calprotectin concentrations in the Ivorian children

who received additional iron for six months were signifi cantly

A genus of gram negative bacillus bacteria; motile and non motile forms; non-endospore forming;

anaerobes but some are aerotolerant; cell wall oft en confers pathogenicity by containing lipopolysaccaride

(LPS); some opportunistic infections caused by infection of the peritoneal cavity and appendicitis; most

substantial portion of the human mammalian gastrointestinal fl ora (~30%); bulk may benefi t host by

excluding potential pathogens; will metabolize simple sugars but mainly polysaccharides; important role

in metabolizing complex molecules to simple ones; resistant to a wide variety of antibiotics.

Example Bacteroides fr agilis (causes most opportunistic peritoneal infections)

Gram negative; motile; facultative anaerobes; rod shaped; several strains pathogenic but usual route of

infection is opportunistic; most infections in immune-compromised hospital patients fr equently targeting

the urinary and respiratory tracts.

Examples include Escherichia coli, Salmonella spp, Shigella spp

Gram positive; non-motile; branched shape; anaerobic; aid digestion; may lower the risk of allergy; some

species used as probiotics; before 1960 species referred to as Lactobacillus bifi dus; optimal growth at more

acid pH which may discourage growth of gram negative organisms

Gram positive; facultative anaerobes; aerotolerant and high tolerance to hydrogen peroxide; produce

lactic acid which lowers pH and discourages growth of some pathogenic bacteria; as many as 125 species

identifi ed; many species do not require iron for growth; potential therapeutic properties – anti-infl amma-

tory, anti-neoplastic; potential probiotic activity; used for production of many foods e.g. cheese, yogurt,

sauerkraut, beer, pickles etc; convert lactose and other sugars to lactic acid.

table 3: Some characteristics of the main bacteria species in the microbiota (99% anaerobes)

Bacteroides

Enterobacteria

Bifi dobacteria

Lactobacilli

49SIGHT AND LIFE | VOL. 25 (1) | 2011 49IRON FORTIFICATION – NEW REVELATIONS?

ginal intestinal inflammation. Furthermore, the authors found a

correlation between the changes in calprotectin and the changes

in numbers of enterobacteria (r = 0.32, P <0.05).3 However, there

was no increase in systemic inflammation (Table 2), confirm-

ing the mild nature of the intestinal inflammation and/or that

the duration of increased iron intake might not have been long

enough.

Bacterial composition of the microbiota

in the Ivorian children

The authors reported that the composition of the gut microbiota

was markedly different at baseline from that reported in Euro-

pean populations. The colonic microflora is generally viewed as

being adult-like after the age of two years, and once the major

bacterial groups in the feces become established they remain

relatively constant over time.30 Total bacterial counts per g feces

in the Ivorian children (10¹¹.⁵, Figure 1) were similar to those

of European children (10¹⁰.⁹), adults (10¹¹) or elderly persons

(10¹⁰.⁴) but there were some big differences in the composi-

tion.30,31 Bacteroides spp were the major group in both Ivorian

and European feces but in the Ivorian children, there were 100

million (10⁸) enterobacteria/g feces, whereas in young Euro-

pean adults there were <1 million (<10⁶)/g feces. In the case of

bifidobacteria, the situation was reversed; Ivorian children had

25 million compared with 1,600 million/g feces respectively.

In the case of lactobacilli, the numbers were very similar: around

3–5 million bacteria cells/g feces (Table 5).

In addition to there being more enterobacteria in the gut of

the Ivorian children than Western persons at baseline, supple-

mentation with iron for three months increased the proportion

increased (Figure 4). The authors used a more sensitive assay

than that described above, in which the median calprotectin con-

centrations in healthy persons was 25 μg/g29 or below a cut-off of

50 μg/g.26 Hence, the calprotectin concentration in the children

who received iron, viz. 75 μg/g feces, indicated evidence of mar-

figure 1: Profile of fecal bacteria in Ivorian children

before iron supplementation

log

nu

mb

er b

acte

ria

/ g f

eces

0

12

10

8

6

4

2

Total counts

Bacteroides

Enterobacteria

Bifidobacteria

Lactobacilli

Columns are means of the log number of gene copies of cell numbers

of bacteria indicated by real-time polymerase chain reaction (PCR)

on baseline fecal DNA samples from Ivorian children (n = 59). All counts

were significantly different from each other (one factor ANOVA with post

hoc ‘t’ tests; P < 0.02). Modified from reference 3

figure 2: Influence of iron supplement on profiles of fecal bacteria

Control 0

Control 6

Iron 0

Iron 6

Columns are log mean bacteria counts per g feces obtained

by real-time polymerase chain reaction (PCR) at baseline and

after 6 months supplementation with or without iron. Groups

compared by 2-factor ANOVA or for lactobacilli by ANCOVA be-

cause groups were dissimilar at baseline. Values significantly

different (*, P < 0.01). Modified from reference 3

0

12

10

8

6

4

2log

nu

mb

er b

acte

ria

/ g f

eces

Bacteroides Enterobacter Bifidobacter Lactobacilli

**

50 IRON FORTIFICATION – NEW REVELATIONS?

of enterobacteria by a fu rther 100 million (log numbers 7.8 to

8.3 bacteria/g feces) while reducing the proportion of lactoba-

cilli (Figure 2). If these changes in enterobacteria and lactoba-

cilli are expressed as percentages of the total number of bacteria

in the microbiota, there is a four-fold increase in enterobacteria

fr om 0.01 to 0.039%, while there is a fourfold fall in the propor-

tion of lactobacilli fr om 0.004% to 0.001%. There was also a

fall in bifi dobacteria, but this was not signifi cant.

Reasons why iron favored the growth of

enterobacteria over lactobacilli

Iron is a nutrient which is essential for the growth of most bac-

teria, but not in the case of most Lactobacilli spp (Table 3). Most

enteric gram-negative pathogens, including Salmonella spp,

E.coli and Shigella spp,18 take up iron-siderophore complexes

by specifi c outer membrane receptors and display increased

virulence in situations of increased iron availability.32 It is also

interesting to note that fecal lactoferrin is as good an indicator

of gut infl ammation as calprotectin.33 Lactoferrin is a powerfu l

iron-binding protein that is particularly eff ective under acid con-

ditions and is derived fr om the polymorphonuclear neutrophils

that are drawn into the gut lining at the onset of infl ammation.

Whether the neutrophil lactoferrin depresses pathogen growth

at the mucosal lining is not known, but bacterial growth in the

microbiota will be limited by iron availability, and the additional

iron provided by the supplement may have provided a growth

advantage for the enterobacteria, which enabled them to in-

crease cell numbers at the expense of the lactobacilli and pos-

sibly the bifi dobacteria.

The potential hazards of iron loading are well recognized.34

Not only do we have the results of the recent study in Pemba1

but it has previously been noted that iron given to patients with

quiescent tuberculosis appeared to reactivate the disease.35 In

addition, Murray and colleagues noted that, in areas of hyper-

endemic Plasmodium falciparum, patients with clinical iron

defi ciency enjoyed an attenuated incidence and severity of ma-

laria but when such subjects were fed an iron-replete diet, many

exhibited a recrudescence of malaria36 and when iron-defi cient

Maasai pastoralists were treated with iron, there was an increase

in amebiasis in the iron group.37

The signifi cant correlation between the increase in entero-

bacteria and fecal calprotectin concentrations (r = 0.32, P <0.05)

suggests that the increased infl ammation in the Ivorian chil-

dren was a consequence of increased enterobacterial growth

stimulated by the supplemental iron. According to the authors,

other factors which are known to raise fecal calprotectin such

as gastroenteritis, fecal blood, non-steroidal anti-infl ammatory

drug use and helminth infection were unlikely to be relevant in

these children.3 However, it was known that 27% of the chil-

dren had Shigella spp, enteroinvasive E.coli or Salmonella spp at

baseline, and that more children were positive for Salmonella

spp in the iron group than the controls at six months. We are

not told whether these specifi c-pathogen-infected children were

the ones with the highest calprotectin concentrations, so we

have to assume that infl ammation was proportionally increased

in response to the entire enterobacterial load. It is known that

gut bacteria interact with mucosal cells lining the intestinal wall,

and signals are transmitted into the lamina propria which illicit

immune responses (Figure 4).4 These will be discussed below.

Interactions between the microbiota and

the mucosal cells lining the gut wall

Research suggests that the relationship between gut fl ora and

the digestive tract in the healthy person is not merely commen-

sal (a non-harmfu l coexistence), but rather a symbiotic relation-

ship. Microorganisms perform a host of usefu l fu nctions, such as

fermenting unused energy substrates, metabolizing food toxins,

preventing growth of harmfu l, pathogenic bacteria, regulating

the development of the gut, producing vitamins for the host

(such as biotin and vitamin K), and many other fu nctions. In par-

ticular, the composition of the intestinal microbiota is particu-

¹ Data shown are mean (SE) log number of bacteria/g feces

table 4: Total numbers of bacteria in control and iron group

aft er 6 months iron supplementation ¹

Control Group Iron Group

Baseline 11.29 (0.67) 11.62 (0.94)

6 Months 11.28 (0.81) 11.78 (0.59)

table 5: Comparison of main bacterial groups in feces of Ivorian

children and young European adults

Young European adultsIvorian children

Data for Ivorian children fr om reference33 and for European adults

fr om reference3030

Log number

bacteria/g feces

Log number

bacteria/g feces

Bacteroides 10 9.2

Enterobacteria 8 5.9

Bifi dobacteria 7.5 9.2

Lactobacilli 6.5 6.7

Bacterial

group

⇢

51SIGHT AND LIFE | VOL. 25 (1) | 2011 51IRON FORTIFICATION – NEW REVELATIONS?

larly important in the maturation and function of the immune

system and in influencing the immune fitness of the individual.4

The large number of bacteria ensures the stability of the compo-

sition, as all bacteria are constantly competing with one another

for nutrients with which to grow and multiply. In these circum-

stances, it is difficult to demonstrate individual effects of specific

bacteria on immune cells.

To determine the effects of individual bacteria on mucosal

immunity, bacterial composition of the microbiota has to be

altered. Two recent papers have investigated the effects of

Clostridium-related bacteria on immune cells in the tissues lin-

ing the gut. In the first of these, the composition of commensal

bacteria in the mouse was changed by introducing a Clostridium-

related, gram-positive, segmented filamentous bacteria (SFB).

SFB attached itself to mucosal cells and shifted immune status

by increasing production of T helper (Th)17 cells in the lamina

propria layer of the intestinal lining. Th17 cells are one of the

subsets of T helper cells that are formed from CD4+ T cells on ac-

tivation and expansion.38 Colonization of healthy mice with SFB

caused no observable immune pathology but, in conditions that

favor chronic inflammation, the presence of SFB promoted in-

flammation.4,25 The increased production of Th17 cells increased

production of pro-inflammatory effector cytokines interleukin

(IL)-17 and IL-22, which stimulated the mucosal epithelial cells

to produce antimicrobial peptide to augment the host’s ability

to fight intestinal pathogens.4 However, the generation of the

potentially harmful cytokine IL-17 may increase the risk of au-

toimmune inflammation in susceptible hosts,4,25 illustrating the

importance of a large number of bacteria to prevent the over-

induction of one particular immune cell.

Clostridium bacteria are a large component of mammalian

microbiota and, very recently, another group of workers demon-

strated that indigenous species of Clostridium bacteria promote

anti-inflammatory immune responses by expanding and activat-

ing regulatory T (Treg) cells.5,25 We normally associate Clostrid-

ium bacteria with the pathogenic species that cause food-poi-

soning, tetanus and botulism, but there are ~100 species, and

two clusters, IV and XIVa (C. leptum and C. coccoides resp.) have

been implicated in the maintenance of mucosal homeostasis

and the prevention of inflammatory bowel disease (IBD). This

makes the report particularly interesting, since IBD is a common

0

80

70

10

20

30

40

50

60

Feca

l C

alp

rote

ctin

μg/

g fe

ces

Control 0

Control 6

Iron 0

Iron 6

Calprotectin concentrations were measured by immunoassay and ex-

pressed as μg/g feces. Median calprotectin level in healthy subjects

was described as 26 μg/g.29 Concentration in the children who received

additional iron increased significantly (*, ANOVA with post hoc t-tests,

P <0.01)

Figure shows different signals (arrows) from different components of the

microbiota in the lumen of the gut regulating different branches of the mu-

cosal T cell response in the lamina propria. Modified from reference 4

figure 4: Regulation of immune homeostasis

Gut Lumen

Mucosal liningto gut wall

Lamina propriatreg

treg

treg

th 17

th 2

th 1

figure 3: Profile of fecal bacteria in Ivorian children

before iron supplementation

treg

treg treg

treg

th 17

52 IRON FORTIFICATION – NEW REVELATIONS?

disease which was reported in 2004 to affect 1.4 million people

in the United States, and 2.2 million in Europe.39

Treg cells are also derived from CD4+T cells. Their importance

lies in their ability to suppress the immune responses of other

cells – that is, to keep the immune responses in check. The au-

thors showed that the increase in Treg in response to oral inocu-

lation with Clostridia (spp) during the early life of convention-

ally reared mice promoted anti-inflammatory immune responses

and were more resistant to experimental models of allergy and

experimental colitis – the murine equivalent of IBD. The paper

is a fascinating piece of investigative murine microbiology but,

unfortunately, there is not space to discuss it in detail. Inter-

estingly, the ability to stimulate Tregs was not blocked by SFB

bacteria or Lactobacilli. A cocktail of 45 strains of Clostridia was

more effective in raising Treg production than three strains indi-

cating, possibly, that a number of stimuli is necessary for a full

response.5 Clostridium species appear to be specialized in their

ability to promote Treg cell accumulation in the colon.25 Adher-

ence to the intestinal epithelium did not appear to be necessary,

as in the case of SFB bacteria, possibly because Clostridia spp

promoted the release of the transforming growth factor- that

stimulated CD4+T cell differentiation.25 The effects of these bac-

teria on T-cell development give us a clear indication that, po-

tentially, many fecal bacteria may have an important influence

on immune defenses in the gut and on the systemic health of the

host. We currently have little idea of the specific role of iron in

this “orchestra.”

Concluding remarks

Three papers have been discussed in this report, which describes

interactions between diet, the microbiota and the immune sys-

tem. The paper by the Zimmermann group illustrates that an

increase in a poorly available form of iron was associated with

alterations in the colonic microbiota and evidence of inflamma-

tion in the intestinal lining.3 The two other papers illustrate that

specific, or groups of, gram-positive bacteria can have stimu-

latory effects on the immune system and promote potentially

inflammatory4 and anti-inflammatory5 immune responses. The

iron supplementation study identified an increase in the gram-

negative, enterobacterial fecal fraction as being positively as-

sociated with calprotectin, a biomarker of inflammation. There

were also increases in several species of pathogenic bacteria in

this group and some were identified in several of the children. In

addition, there was a reduction in the gram-positive Lactobacil-

lus group of bacteria.

Host protection against bacterial pathogenicity is partly af-

forded by the large number of commensal bacteria in the micro-

biota, many of which will occupy important niches within the

intestinal lining and so prevent occupancy by incoming patho-

genic strains.40 Dietary requirements will also determine which

bacteria can propagate themselves at the expense of others. Iron

is an important regulator of bacterial growth and pathogenicity.

Supplemental iron may well have been responsible for the four-

fold increase in the numbers of enterobacteria and the associ-

ated inflammation. The particular bacterial species and mecha-

nism causing the inflammation are not known, but the marked

effects that SFB bacteria and Clostridia spp can have on T-cell

regulation indicate the type of mechanism that may have been

involved. As the authors suggest, minimizing the inflammatory

effects of supplemental iron may be possible with a lower dose

of more bioavailable iron to promote iron uptake and reduce the

amount available to the microbiota.

In the last issue of Sight and Life, Barbara Troesch, from the

same group, reported on the successful use of low-dose iron

from NaFeEDTA, in combination with ascorbic acid and phytase,

to increase body iron stores and reduce iron and zinc deficiency

in South African school children.41 It should also be remembered

that the study in Côte d’Ivoire was intended to show the poten-

tial effects of food fortified with iron. In fact, the iron load was

18.2 mg/day, given in a biscuit four days/week. The equivalent

daily dose of fortified iron would have been 8.8 mg iron/day, but

this amount may not have had the same microbiological or in-

flammatory effects as the higher dose. Currently, the selection of

the type and quantity of vitamins and minerals to add to flour,

either as a voluntary standard or a mandatory requirement, lies

with national decision-makers in each country. As a result, the

choice of compounds as well as quantities should be viewed in

the context of each country’s situation. Recommended amounts

of electrolytic iron are only given where the daily consumption

of flour is >150 g (60 ppm) or >300 g (40 ppm) for low extraction

flour or 20 and 15 ppm resp. for those amounts of high extraction

flour.42 Three hundred grams of flour containing 40 ppm Fe is

equivalent to a daily intake of 18 mg iron, i.e. comparable to the

amount used in the Ivorian children. Thus, the effects of the iron

supplement reported by Zimmermann and colleagues3 are appli-

cable to those countries where flour is fortified with electrolytic

iron, and there is a high consumption of wheat flour.

Correspondence: David I Thurnham, 46 High Street,

Little Wilbraham, Cambridge CB21 5JY, United Kingdom

E-mail: di.thurnham@ulster.ac.uk

⇢

53SIGHT AND LIFE | VOL. 25 (1) | 2011 53IRON FORTIFICATION – NEW REVELATIONS?

19. Lee SH, Shine P, Choi J et al. Effects of dietary iron levels on growth

performance, hematological status, liver mineral concentration,

fecal microflora, and diarrhea incidence in weanling pigs. Biol Trace

Element Res 2008;126:S57-S68.

20. World Health Organisation. Conclusions and recommendations of

the WHO consultation on prevention and control of iron deficiency

in infants and young children in malaria-endemic areas. Food Nutr

Bull 2007;28:S621-S627.

21. Rohner F, Zimmermann MB, Amon RJ et al. In a randomized

controlled trial of iron fortification, anthelmintic treatment, and

intermittent preventive treatment of malaria for anemia control in

Ivorian children, only anthelmintic treatment shows modest

benefit. J Nutr 2010;140:635-641.

22. Thurnham DI, McCabe GP, Northrop-Clewes CA et al. Effect of

subclinical infection on plasma retinol concentrations and assess-

ment of prevalence of vitamin A deficiency: meta-analysis. Lancet

2003;362:2052-2058.

23. Thurnham DI, McCabe LD, Haldar S et al. Adjusting plasma ferritin

concentrations to remove the effects of subclinical inflammation in

the assessment of iron deficiency: a meta-analysis. Am J Clin Nutr

2010; 92:546-555.

24. Monira S, Alam NH, Suau A et al. Time course of bacterial diversity

in stool samples of malnourished children with cholera receiving

treatment. J Pediatr Gastroenterol Nutr 2009;48:571-578.

25. Barnes MJ, Powrie F. The gut's Clostridium cocktail. Science

2011;331:289-291.

26. Gisbert JP, McNicholl AG. Questions and answers on the role of

faecal calprotectin as a biological marker in inflammatory bowel

disease. Dig Liver Dis 2009;41:56-66.

27. Fagerberg UL, Lööf L, Merzoug RD et al. Fecal calprotectin levels in

healthy children studied with an improved assay. J Pediatr Gastroen-

terol Nutr 2003;37:472468.

28. Angriman I, Scarpa M, D'Incà R et al. Enzymes in feces: useful mark-

ers of chronic inflammatory bowel disease. Clin Chim Acta 2007;

381:63-68.

29. Tøn H, Brandsnes, Dale S et al. Improved assay for fecal calprotectin.

Clin Chim Acta 2000; 292:41-54.

30. Hopkins MJ, Sharp R, Macfarlane GT. Age and disease related

changes in intestinal bacterial populations assessed by cell culture,

16S rRNA abundance, and community cellular fatty acid profiles.

Gut 2001;48:198-205.

References

01. Sazawal S, Black RE, Ramsan M et al. Effects of routine prophylactic

supplementation with iron and folic acid on admission to hospital

and mortality in preschool children in a high malaria transmission

setting: community-based, randomised, placebo-controlled trial.

Lancet 2006;367:133-143.

02. Suchdev PS, Leeds IL, McFarland DA et al. Is it time to change the

guidelines for iron supplementation in malarial areas?

J Nutr 2010;140:875-876.

03. Zimmermann MB, Chassard C, Rohner F et al. The effects of iron

fortification on the gut microbiota in African children: a randomized

controlled trial in Cote d'Ivoire. Am J Clin Nutr 2010;92:1406-1415.

04. Ivanov II, Littman DR. Segmented filamentous bacteria take the

stage. Mucosal Immunol 2010;3:209-212.

05. Atarashi K, Tanoue T, Shima T et al. Induction of Colonic

Regulatory T Cells by Indigenous Clostridium Species. Science

2011;331:337-341.

06. World Health Organization. Iron deficiency anaemia: assessment,

prevention and control. A guide for programme managers. WHO/

NHD/01.3. 2001. Geneva, World Health Organisation.

07. Guidelines on food fortification with micronutrients. Geneva: World

Health Organisation & Food and Agricultural Organisation; 2006.

08. Haas JD, Brownlie T4. Iron deficiency and reduced work capacity:

a critical review of the research to determine a causal relationship.

J Nutr 2001;131:676S-690S.

09. Pollitt E. The developmental and probabilistic nature of the func-

tional consequences of iron-deficiency anemia in children. J Nutr

2001;131:669S-675S.

10. Stoltzfus RJ. Iron-deficiency anemia: reexamining the nature and

magnitude of the public health problem. Summary: implications for

research and programs. J Nutr 2001;131:697S-700S.

11. McFarlane H, Reddy S, Adcock KJ et al. Immunity, transferrin and

survival in kwashiorkor. B M J 1970;4:268-270.

12. United States Food and Drug Administration. US FDA Backgrounder.

Preventing iron poisoning in children. 62 FR 2217. 1997.

13. Chua AC, Klopcic B, Lawrance IC et al. Iron: an emerging factor in

colorectal carcinogenesis. World J Gastroenterol 2010;16:663-672.

14. Bastide NM, Pierre FH, Corpet D. Heme iron from meat and risk of

colorectal cancer: a meta-analysis and a review of the mechanisms

involved. Cancer Prev Res (Phila) 2011; Jan 5 ahead of print.

15. Baltussen R, Knai C, Sharan M. Iron fortification and iron supple-

mentation are cost-effective interventions to reduce iron deficiency

in four subregions of the world. J Nutr 2004; 134:2678-2684.

16. Zimmermann MB, Hurrell RF. Nutritional iron deficiency. Lancet

2007; 370:511-520.

17. Andrews SC, Robinson AK, Rodríguez-Quiñones F. Bacterial iron

homeostasis. FEMS Microbiol Rev 2003;27:215-237.

18. Naikare H, Palyada K, Panciera R et al. Major role for FeoB

in Campylobacter jejuni iron acquisition, gut colonization and

intracellular survival. Infect Immun 2006; 74:5433-5444.

54 IRON FORTIFICATION – NEW REVELATIONS?

31. Singhal A, Macfarlane G, Macfarlane S et al. Dietary nucleotides and

fecal microbiota in formula-fed infants: a randomized controlled

trial. Am J Clin Nutr 2008;87:1785-1792.

32. Bullen J, Griffiths E, Rogers H et al. Sepsis: the critical role of iron.

Microbes Infect 2000;2:409-415.

33. Gisbert JP, McNicholl AG, Gomollon F. Questions and answers on

the role of fecal lactoferrin as a biological marker in inflammatory

bowel disease. Inflamm Bowel Dis 2009;15:1746-1754.

34. Weinberg ED. The hazards of iron loading. Metallomics

2010;2:732-740.

35. Weinberg GA, Boelaert JR, Weinberg ED. Iron and HIV infection. In:

Friis H, editor. Micronutrients and HIV infection. 2002. 135-157.

36. Murray MJ, Murray NJ, Murray AB et al. Refeeding malaria and hy-

perferremia. Lancet 1977;i:653.

37. Murray MJ, Murray A, Murray CJ. The salutary effect of milk on amoe-

biasis and its reversal by iron. B M J 1980;2:1151-1152.

38. Korn T, Bettelli E, Oukka M et al. IL-17 and Th17 Cells. Ann Rev

Immunol 2009; 27:485-517.

39. Loftus EV Jr. Clinical epidemiology of inflammatory bowel disease:

Incidence, prevalence, and environmental influences. Gastroenter-

ology. 2004 May;126(6):1504-17. Gastroenterol 2004;126:1504-1517.

40. Borriello SP, Barclay FE. Protection of hamsters against Clostridium

difficile ileocaecitis by prior colonisation with non-pathogenic

strains. J Med Microbiol 1985; 19:339-350.

41. Troesch B. Optimized micronutrient powder containing low levels of

highly bioavailable iron and zinc together with EDTA, phytase and

ascorbic acid improves the nutritional status of children. Sight and

Life 2010;3:9–11.

42. WHO, FAO, UNICEF et al. Recommendations on Wheat and Maize

Flour Fortification Meeting Report: Interim Consensus Statement.

WHO/NMH/NHD/MNM/09.1. 2009. Geneva, WHO (http://www.who.

int/nutrition/publications/micronutrients/wheat_maize_fort.pdf,

accessed February 2011).

Erratum: Optimized Micronutrient Powder

In the article Optimized Micronutrient

Powder in Sight and Life Magazine 3/2010, the figures in Table 2 were

incorrect. The table to the right has the

correct figures. We apologize for any

confusion this error may have caused.

table 2: Composition of the micronutrient powder used

in the intervention study

Nutrient Pro serving Pro kg premix

Vitamin A (RAE) 400 μg 80 mg

Vitamin D 5 μg 1 mg

Vitamin E (TE) 5 mg 1 g

Thiamine 0.5 mg 100 mg

Riboflavin 0.5 mg 100 mg

Pyridoxine 0.5 mg 100 mg

Folic Acid 90 μg 18 mg

Niacin 6 mg 1.2 g

Pantothenic acid 2 mg 400 mg

Vitamin B12 0.9 μg 180 μg

Vitamin C 60 mg 12 g

Iron (as NaFeEDTA) 2.5 mg 500 mg

Calcium 200 mg 40 g

Copper 0.34 mg 68 mg

Iodine 30 μg 6 mg

Selenium 17 μg 3.4 mg

Zinc 2.5 mg 500 mg

Phytase 190 FTU 38,000 FTU

Carrier Ad 5g ad 1000g

55SIGHT AND LIFE | VOL. 25 (1) | 2011 55OPINION 1

I have always been struck by the fact that it is easily accepted,

by science and medical communities, that just a few cells of a

pathogen like E. coli 0157 can exert destructive eff ects, yet the

impact of a larger number of probiotic microbes gets written

off , more oft en than not. The science of metabonomics recently

entered the gut microbiology arena and off ers a similar “revolu-

tion” in our understanding of the impact of gut microbes to that

generated by molecular-based assessments of composition in

the last decade.1

On that note, David cites an extensive study which led to the

contentious decisions on iron supplementation. High through-

put and accurate PCR-based technologies were used to assess

the gut microbiota in Ivorian populations.2 These were seen to

diff er markedly fr om European profi les, although parallel stud-

ies were clearly not feasible and diff ering techniques may have

been used. That aside, it seemed that the Ivorians harbored

higher levels of enterobacteria and lesser populations of Gram

positive bacteria said to be benefi cial (bifi dobacteria). The iron

use was said to fortify the enterobacteria, and that led to health

issues. It is worth noting that these are facultative, rather than

strict, anaerobes whose enhanced growth rates are likely able

to allow better scavenging of iron. I was also struck by the de-

tection of salmonellae and shigellae. These are clear pathogens

which oft en only exist in a transient manner. In European trials

they are hardly ever reported unless in association with a food

safety outbreak. Perhaps this is the key to the health diffi culties

seen, and maybe those few probiotics that boost bifi dobacteria

and consequently decrease pathogens are worth trying.3 Micro-

biota modulation through probiotics or prebiotics is popular in

Europe, North America and Asia, but it seems to me that the

Ivorian children studied here could be major benefactors of a

harmless intervention.

David also gives us an example of how fu nctional microbial

assessments are needed rather than just compositional. The

clostridia were seen to exert varying eff ects upon infl ammation

The decision to withdraw iron supplementation in certain mala-

ria-aff ected areas was the subject of David Thurnham’s objective

assessment of recent science fi ndings. David has outlined some

of the thinking behind this decision and input his own evidence-

based views.

As with so many current nutritional concepts, the drift of at-

tention has been drawn to the gut microbiota. This is not surpris-

ing, given the vast numbers of bacteria that use the human ali-

mentary tract as their home and their concomitant major impact

upon metabolism. I especially like David’s conclusion that it is

not enough nowadays to simply measure predominant gut fl ora

components without an assessment of the fu nctional or physi-

ological impact. Perhaps some bacteria not present in large

numbers can exert a major impact upon health. In this context,

Opinion 1: Comments on “Iron Forti fi cati on – New Revelati ons?”

Glenn Gibson

Department of Food and Nutritional Sciences,

University of Reading, United Kingdom

“It is not enough nowadays to simply measure predominant gut fl ora components without an assessment of the fu nct ional or physiological impact ”

⇢

56 OPINION 1 / 2

Opinion 2: Venturing into the Jungle of Multiple Interactions between Iron, Modulating Infl uences, and Human Health

Klaus Schuemann

Technische Universität München, Zentralinstitut

fü r Ernährung und Lebenswissenschaft en, Germany

Over the last 10 years it has become a truism that iron is a dou-

ble-edged sword. It is essential for bacteria, parasites and host

organisms, but can also cause oxidative damage. Dr Thurnham’s

contribution is on the crest of present day eff orts to widen the

scope fr om such direct iron eff ects to the increasing number of

mutual interactions and cross-talks, such as those between iron,

the composition of intestinal fl ora, and the well-being of the

host. We congratulate Sight and Life on recognizing this new

trend and inviting this article.

We must stay aware, however, that the subject under discus-

sion here is only the tip of an iceberg which might be termed

“modulation of health-related iron eff ects.” Some examples

may illustrate how complex the scene has become. Extracellu-

lar bacteria, indeed, merrily hijack each other’s iron-fi shing si-

derophores by imitating the siderophore-receptors of competing

species. The host organism does the same in trying to recuper-

ate part of its iron. Playing this game more or less successfu lly

modulates the expansion of, for example, pathogenic germs and

thus the prevalence of corresponding disease. Some bacteria

even hijack entire heme molecules to an extent permitting them

to abolish endogenous heme biosynthesis.1

Another major player in the multidimensional contest for

iron supplies is the host’s homeostatic regulation of iron-ab-

sorption and distribution kinetics.2 In the Pemba trial,3 iron-

defi cient children profi ted fr om iron supplementation, while

iron-adequate children suff ered fr om more severe clinical ma-

laria courses. This may seem paradoxical at fi rst glance, as the

absorption of potentially harmfu l iron increases iron defi ciency.

However, iron drainage to hematopoiesis seems to be increased

to an even higher extent in terms of iron defi ciency, so that less

iron circulates with the plasma.

By contrast, iron concentration in the gut lumen is not home-

ostatically regulated. It depends on iron ingestion and induces

oxidative stress, the extent of which is modulated by dietary

antioxidants. The results of this interaction can be determined

in the stool.4 Correspondingly, low dietary iron content reduced

the extent of Crohn-like intestinal bowel disease in a murine

model.5 This concurred with increases in endoplasmic reticulum

(ER) stress in the ileal mucosa such as the impaired regulation

References

01. Martin FP, Sprenger N, Montoliu I et al. Dietary modulation of gut

functional ecology studied by fecal metabonomics. J Proteome Res

2010; 9:5284–5295

02. Zimmermann MB, Chassard C, Rohner F et al. The eff ects of iron

fortifi cation on the gut microbiota in African children: a randomized

controlled trial in Cote d’Ivoire. Am J ClinNutr 2010; 92:1406–1415.

03. Saulnier DM, KolidaS, Gibson GR. Microbiology of the human intes-

tinal tract and approaches for its dietary modulation. Curr Pharm

Design 2009;15:1403–1444.

04. Rowan FE, Docherty NG, Coff ey JC et al. Sulphate-reducing bacteria

and hydrogen sulphide in the aetiology of ulcerative colitis. Br J

Surg 2009;96:151–158.

depending upon species type and experimental conditions. Not-

ing David’s cited implications of some clostridia with IBD, this

story could have an added twist. Research has shown elevated

levels of microbially generated sulphides in the fecal stream of

ulcerative colitis (UC) suff erers (one of two major types of IBD).4

Above a certain level, sulphides are destructive to colonocyte

fu nction, resulting in typical infl ammatory patterns of UC. They

are also volatile, and can be rendered innocuous by binding to

metals – such as iron!

Correspondence: Glenn Gibson, Department of Food and

Nutritional Sciences, University of Reading, Whiteknights, PO Box

217, Reading, Berkshire, RG6 6AH, United Kingdom

E-mail: g.r.gibson@reading.ac.uk

57SIGHT AND LIFE | VOL. 25 (1) | 2011 57OPINION 2

of protein folding. Injecting the missing dietary iron quantities

parenterally did not re-induce ileal Crohn symptoms, showing

that the underlying pathology depends on luminal iron concentra-

tions. Iron also mutually interacts with immunological responses

in multiple ways, as illustrated in Crohn’s disease in a correspond-

ing comment.6 All these events illustrate that the role of iron in the

underlying pathology is extensively modulated by a considerable

number of interfering processes.

With the wide application of powerful genetic and biochemi-

cal tools, the number of examples of such interactions is likely

to expand exponentially in the near future. Their clinical implica-

tions will serve to judge the relevance of such novel modulating

effects. Some of these may be academic in nature, but others

may yield ground-breaking new therapeutic principles or im-

pulses for public health and nutrition. We hope that Sight and Life will continue to report on such developments.

Correspondence: Klaus Schuemann, Zentralinstitut für

Ernährung und Lebensmittelwissenschaft, Technische Universität

München,Gregor-Mendelstr 2, D-85350 Freising-Weihenstephan,

Germany E-mail: kschuemann@schuemann-muc.de

References

01. Nairz M, Schroll A, Sonnweber T et al. The struggle for iron – a metal

at the host-pathogen interface. Cell Microbiol 2010;12:1691–702.

02. Hentze MW, Muckenthaler MU, Galy B et al. Two to tango: regulation

of mammalian iron metabolism. Cell 2010;142:24–38.

03. Sazawal S, Black RE, Ramsan M et al. Effects of routine prophylactic

supplementation with iron and folic acid on admission to hospital

and mortality in preschool children in a high malaria transmission

setting: community-based, randomised, placebo-controlled trial.

Lancet 2006;367:133–43.

04. Orozco M, Solomons NW, Schümann K et al. Antioxidant-rich oral

supplements attenuate the effects of oral iron on in situ oxidation

susceptibility of human feces. J Nutr 2010;149:1105–10.

05. Werner T, Wagner SJ, Martinez I et al. Depletion of dietary iron

prevents Crohn’s disease-like ileitis affecting epithelial stress

repression and the gut microbial ecology. Gut 2010, on line,

10.1136/gut.2010.216929. February 2011.

06. Weiss G. Iron in the inflamed gut: another pro-inflammatory hit?

Gut 2010, on line, 10.1136/gut 2010 229047. February 2011.

⇢

58

research program in nutrigenetics that is fairly new and together

they form the basis of our molecular work. We also do research

in the area of micronutrients and cognition; in body composition,

both overweight and underweight; and we have a research pro-

gram on nutrition transition, which is an overriding theme that

we have. As with most parts of the developing world, in South

Afr ica nutrition transition already has a huge impact on the

health systems of our and other countries. We also have a very

strong research program in fatty acids and lipids, which is linked

to cognition, micronutrient status, and under- and over-nutri-

tion. Another theme is best described as nutrition in exercise

and sport. This is fairly new and we are investigating the possi-

bility of a postgraduate specialization degree in this area.

We try to develop track records in all of these areas. I really

believe in teamwork. I don’t believe that, as academics, we can

do everything well – I’m a big fan of getting strong teams together

and pooling the expertise that is necessary to do the job and do

it well. We develop trans-disciplinary research teams around im-

portant health themes and steer clear fr om developing research

areas focused on individual capabilities. Sometimes you are a

team member, sometimes you are a leader; it all depends on

where you are at.

SAL: Is there such a thing as a “normal” day for you?

JJ: Not at all! Every once in a while, I wish I could have a day

where I could say, “Now it’s fi nished,” but that’s not the case in

my role. I work long hours, and every day is a mixture of all sorts

of things. Some are administrative, others might be research-

related, but a lot of them are people-related. People come to me

Sight and Life (SAL): Johann, what does your work as the Direc-

tor of TReNDS involve?

Johann Jerling (JJ): I became the director fairly recently, on

January 1, 2011. I see my role as developing and leading a team,

which in this case is a team of nutrition scientists. In general,

as a group, we spend 40 percent of our time on undergraduate

student training, 40 percent on research, and 20 percent on the

implementation of expertise.

SAL: What do you do in the course of a working day, and what

impact does it make?

JJ: I aim to create an environment where team members excel

at what they do. I also believe that we should really enjoy what

we do, which is something that is sometimes neglected in our

world. I aim to create an environment where people enjoy what

they are doing. I try to achieve this on diff erent levels; the fi rst

thing is to listen to what people have to say, and to try and solve

problems. I have access to resources, so I try to use these wisely.

If you can throw money at a problem, that’s fi ne, but very oft en

it’s about supporting someone, creating energy, and then, some-

times, putting a little bit of fu n into it, so we don’t take ourselves

too seriously!

We are a group of about 18 academic staff members, as well

as about 30 graduates and postgraduates, who form a central

part of our research eff ort. We carry out research in various

fi elds at a level ranging fr om molecular to societal. The fi rst is

in the area of diet and hemostasis, or blood clotting. We have a

Johann C Jerling (PhD)

is the Director of TReNDS – Centre of Excellence for

Nutrition at North-West University (Potchefstroom

Campus), South Afr ica. He talks about his work at

TReNDS, as well as his involvement in initiatives such

as the Afr ican Nutrition Leadership Program (ANLP).

A DAY IN THE LIFE OF JOHANN C JERLING

Sight and LifeInterviewA Day in the Life of Johann C Jerling

59SIGHT AND LIFE | VOL. 25 (1) | 2011

“Although it’s something that I haven’t done for three or four years, I really enjoy fl y fi sh ing, as it takes my mind off everything.”

A stunning sunset – taken by a team member of the

Afr ican Nutrition Leadership Program (ANLP)

60 A DAY IN THE LIFE OF JOHANN C JERLING

for advice and a chat, so I do spend a lot of my time on this. If the

team is doing well, I’m happy and think I’ve done my bit.

SAL: What do you look forward to in your working day, and what

do you fi nd challenging?

JJ: Seeing people grow gives me a huge amount of satisfaction.

I enjoy solving problems, and seeing the end result of solving

a problem. I also greatly enjoy discovering new things, which

might be really complex … or really simple. Overall, I really en-

joy the enthusiasm in the group. We have some more senior re-

searchers, plus a fairly large batch of 30-somethings, who are

fu n to work with, as they are all developing careers, and are en-

ergetic, adaptable and eager to try to do things in a new way. It

really adds to the feeling of the whole job being worthwhile.

SAL: Which aspect of your work is most important to you?

JJ: The activity I fi nd most rewarding is the leadership devel-

opment program that I am director of – the Afr ican Nutrition

Leadership Program, or ANLP. Every year about 120 candidates

apply fr om all over Afr ica. Thirty get selected and join a 10-day

leadership development course. To me, this is the single most

worthwhile thing that I have done in my whole life. It’s a lot of

really hard work, but the rewards that I get in many ways are

just fantastic. It’s great to see how people discover things about

themselves that they never knew before, how they change in en-

vironments where they are challenged in all sorts of ways. It’s

also wonderfu l to see how we can get 30 people together fr om

17 diff erent countries for 10 days, and discover how irrelevant

the diff erences between nations become. I can see how strongly

religious Christians and devout Muslims can work together, de-

spite the fact that we have seen confl ict along religious lines in

many Afr ican countries. Above all, it’s great to see how people

develop and progress in their careers, and as part of this Afr ica-

wide network. I fi nd it really satisfy ing.

SAL: What does Sight and Life mean to you in the context of the

global fi ght against malnutrition?

JJ: Maybe six years ago, if I heard someone talk about Sight and Life, I would have thought about vitamin A. Now, however, I think

it is about people who create awareness, stir, and build capacity.

For me, the whole transition that has been undergone by Sight and Life, at least in my lifetime, has built that enthusiasm. This

is an organization that gets all sorts of things done. Although I

do not believe that there is one single organization that will ever

win the battle against malnutrition, Sight and Life plays a really

important role in the whole movement. I have great respect for

it because it actually delivers.

As for the magazine, it contains articles, inspiring stories, and

news, and its content is strikingly diff erent fr om what many

other organizations do. I also appreciate that it is not simply

so focused that it’s only interested in its own small area, per-

haps because it is positioned to be fairly broadly interested in

malnutrition. I get the impression that it’s an organization that’s

genuinely interested in solving issues.

SAL: How do you switch off fr om work? Do you have interests

outside your professional existence?

JJ: Although it’s something that I haven’t done for three or four

years, I really enjoy fl y fi shing, as it takes my mind off every-

thing. I also enjoy mountain biking and photography. I’m prob-

ably something of an undercover artist! I can’t do it very well, but

I do have the urge to create… I love putting together slide shows,

manipulating photographs and video editing.

SAL: Thank you, Johann, and good luck with everything you do.

JJ: Thank you.

Interview by Susie Lunt

Johann Jerling and the ANLP team, fr om left to right:

Violet Mugalavai, Marlien Pieters, Victor Owino, Nyagosya Range,

Namukolo Covic, Johann Jerling, Mercy Achu, Charles Mokoena,

Olympia Keino, Chrissie Thakwalakwa.

Growing the evidence base for micronutrients.

news62

security, food availability, food access, food use, food safety,

food quality, and food utilization.

The evidence of the impact of food on health and human pro-

ductivity is well established in infants and young children, and

scientifi c data shows the impact of malnutrition on infant and

young children’s growth. Given the complexity of food security,

nutritionists, food scientists and healthcare workers must work

together to fi ght malnutrition in developing countries.

Maff o Tazoho Ghislain

University of Dschang, Cameroon

Last year, courtesy of Sight and Life, I attended the Fourth Afr ica

Nutritional Epidemiology Conference (ANEC 4) on Nutrition and

Food Security: Successes and Emerging Challenges. The fi ve-day

event took place fr om October 4 – 8, 2010 in Nairobi, Kenya and

provided me with an excellent opportunity to share, learn and

network.

Adequate nutrition is key to health

and general well-being

In recent decades, nutritional science has clearly demonstrated

the importance of nutrition for health and general well-being.

Adequate nutrition means when people have access to, and con-

sume enough, food which their body is then able to absorb to

meet all its nutritional requirements. It is a combination of food

Nutr iti on and Food Security : Successes and Emerging Challenges

Fourth Afr ica Nutr iti onal Epidemiology Conference (ANEC 4)

Maff o Tazoho Gislain in fr ont of his poster at the Fourth Afr ica

Nutritional Epidemiology Conference (ANEC), held in Nairobi,

Kenya in October 2010

“ANEC 4 was an important

opportunity for researchers to discuss

the best strategy for overcoming

malnutrition in Afr ica

and other developing regions”

63SIGHT AND LIFE | VOL. 25 (1) | 2011 63FOURTH AFRICA NUTRITIONAL EPIDEMIOLOGY CONFERENCE (ANEC 4)

The Fourth Africa Nutritional Epidemiology Conference was

therefore an important opportunity for researchers to discuss

the best strategy to overcome malnutrition and promote food

security in Africa and other developing regions.

As a young researcher, attending this outstanding scientific

event was an important opportunity for me to present the latest

findings from our research group in the area of nutrition and

food security. It was also an opportunity for me to learn how

others are contributing to this field in their own countries, and

to be updated on what is happening in the field of nutrition on a

global scale.

The discussion around the theme and sub-theme of this

conference was to be instrumental in helping me improve my

knowledge of food security, and equipping me in better orient-

ing my efforts to contribute to the fight against malnutrition as

an inevitable cause of disease.

Participation with fascinating insights

On Day 1, after registration, I took part in a sponsored preconfer-

ence symposium entitled “Iron interventions in malarious areas:

where are we now?” This was followed by the opening ceremony,

during which the chair and the co-chair of the local organizing

committee presented their welcome message and a summary of

the co-organizer of the conference, the Africa Nutrition Society

(ANS).

The following day, I participated in several plenary sessions,

including the parallel oral session “Climate change, food secu-

rity and nutrition”. This was followed by a Nestlé symposium and

a poster session, during which I presented my research work on

“Effect of folere juice (dried calyx of Hisbiscus sabdariffa L) on

some biochemical parameters in humans”. The results showed

hemoglobin increased significantly (P=0.021), suggesting a po-

tentially positive effect of folere juice consumption in increas-

ing hemoglobin concentration. Serum iron, however, decreased

(P=0.042), suggesting the utilization of iron in the synthesis of

hemoglobin.

The third and fourth days brought much, in the form of ses-

sions on “Maternal and child heath and nutrition”, “School

health and nutrition”, “Nutrition, immunity and communicable

diseases in developing countries”, “Current management strat-

egies for nutritional disorders”, and “Nutrition, immunity and

communicable diseases in developing countries”. There were

also fascinating symposia from Unilever and World Vision.

Finally, on Day 5, after a couple of plenary sessions focus-

ing on “Nutrition in emergency situations” and “ANS capacity

building for nutrition in Africa”, I enjoyed the closing ceremony

during which the Nairobi declaration was read.

The week was not all work. A number of social events were

organized, including a gala dinner at the Nyama Chioma Ranch,

during which traditional African music was played, and a safari

Njema lunch.

A valuable visit with future implications

Overall, the Fourth Africa Nutritional Epidemiology Conference

enabled me to meet and talk with leading scientists and experts

in nutrition, as well as other students working in my field of re-

search. I also made many new contacts whom I plan to stay in

touch with as I continue my studies – in particular Ngozi Nnam

of the University of Nigeria Nsukka, who is working on the same

biological material as me.

Such contacts, and the knowledge I gained will be translated

to other researchers in my institutions for the scientific develop-

ment of our young university in Cameroon.

Correspondence: Mr Ghislain Maffo Tazoho, University of

Dschang Department of Biochemistry, Dschang, Cameroon

E-mail: maghis2006@yahoo.fr

“Attending this outstanding scientific

event was an opportunity to learn and

be updated on what is happening in

the field of nutrition on a global scale”

“My research work showed

the effects of folere juice in humans:

increasing hemoglobin

but decreasing serum iron”

64 THE FIRST GLOBAL CONFERENCE ON BIOFORTIFICATION

The First Global Conference on Biofortifi cation was the fi rst in a

series of potentially three biofortifi cation-focused conferences

over the next few years. HarvestPlus convened the conference to

bring together the many organizations and individuals conduct-

ing biofortifi cation research over the past decade.

The conference took place in Washington, DC on November

9–11, 2010, attended by 300 scientists, researchers,

practitioners, decision-makers, and students. Its main

objectives were to:

> determine the current state of biofortifi cation, taking

stock of research, global investment, and experience in bio-

fortifi cation;

> raise the visibility of biofortifi cation as a promising agricul-

tural intervention for public health; and

> chart the fu ture for biofortifi cation, identify ing synergies

and gaps in knowledge and how to forge partnerships and

collaborations.

Spanning two and half days, it featured a keynote address and

panel discussion each morning and technical symposia in the

aft ernoons. The gala dinner, on the fi rst evening, included bio-

fortifi ed maize on the menu and a keynote address by David

Nabarro, Special Representative on Food Security and Nutrition

to United Nations Secretary-General Ban Ki-moon. The dinner

also featured a letter fr om Senator George McGovern of the US, a

strong supporter of hunger and nutrition issues for the past four

decades, who has shown interest in biofortifi cation. He wrote,

“Biofortifi cation, and its potential benefi ts to those who are mal-

nourished, clearly should have a prominent place in our research,

in our advocacy, and in our global development goals.”

Summary of keynote speakers

The conference opened with a keynote address by Ambassador

William Garvelink, US Government Deputy Coordinator for De-

velopment at the Feed the Future Initiative, who focused his

Report fr om the First Global Conference on Bioforti fi cati on

Hannah Guedenet

HarvestPlus, Washington, USA

“Biofortifi cation, and its potential

benefi ts to those who are

malnourished, clearly should have

a prominent place in our research,

in our advocacy, and in our global

development goals”Ambassador William J Garvelink, US Government Deputy

Coordinator for Development, Feed the Future: Global Hunger

and Food Security Initiative, opens the First Global Confer-

ence on Biofortifi cation, Washington DC, USA

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65SIGHT AND LIFE | VOL. 25 (1) | 2011 65THE FIRST GLOBAL CONFERENCE ON BIOFORTIFICATION

remarks on the need to build momentum around linking agri-

culture and nutrition to address food insecurity. While funding

for agricultural interventions has been on the decline in recent

decades, Ambassador Garvelink reiterated the US Government’s

recent commitment to increasing funding for agricultural and

nutrition interventions, and to continuing the advancement of

biofortified crops.

Dr Howarth Bouis, Director of HarvestPlus, presented an

overview of biofortification progress. He identified five

major challenges:

1. Identifying optimal delivery strategies for getting

biofortified foods to people;

2. Ensuring and measuring the public health impact

of biofortification;

3. Developing a better understanding of how foods

impact human nutrition;

4. Getting the agricultural sector to prioritize improving

nutrition; and

5. Getting the nutrition community to prioritize agriculture

in order to improve nutrition.

Figure 1 shows a proposed framework for establishing bioforti-

fication as a sustainable solution for micronutrient malnutrition.

Conference participants were encouraged to provide their feed-

back on the framework through an online forum:

http://biofortconf.ifpri.info/

Nicholas Kristof, Pulitzer Prize-winning columnist for the New

York Times, delivered day two’s keynote address. He encour-

aged participants to think about ways to raise the visibility of

micronutrient malnutrition in the media, by doing a better job

of “selling their story” and building emotional connections to

the issues.

Navyn Salem from Edesia Global Nutrition Solutions deliv-

ered the keynote address on day three. She focused on the link

between the private and public sectors, given Edesia’s work on

delivering ready-to-use therapeutic foods for the treatment of

acute malnutrition. Her comments provided potential strategies

“Biofortification must use multiple

disciplines and channels to promote

and disseminate crops”

on how biofortification must use multiple disciplines and chan-

nels to promote and disseminate crops.

Commissioned papers and moderated panel discussions

Two papers had been commissioned for the conference. The first,

From HarvestPlus to harvest driven: How to realize the elusive po-

tential of agriculture for nutrition? by Lawrence Haddad of the

UK’s Institute of Development Studies, focused on how agricul-

ture can be used, more effectively, to improve nutrition.

He answered three questions: 1) What are the pathways

between agriculture and nutrition? 2) Is the potential being re-

alized? and 3) What can be done to increase the realization of

this potential? After presenting his paper, Roger Beachy of the

USDA, Shenggen Fan of the International Food Policy Research

figure 1: Broad categories for investments to establish

biofortification as a sustainable strategy

Midstream

Breeding

& Nutrition

Research (2)

Downstream

”Pilot“

Delivery (3)

Measure

Impact (4)

Internat.

& Regional

Advocacy (7)

Ownership

by AG

Decision

Makers (5b)

Ownership

by Nutrition/

Public Health

Decision

Makers (6b)

Upstream

Research (1)

Increase

Breeding

Effectiveness

and Capacity

(5a)

Increase Bio-

availability

and Efficacy

Evidence

(6a)

$ $

$

66 THE FIRST GLOBAL CONFERENCE ON BIOFORTIFICATION

table 1: The aft ernoon symposia presented fi ndings on:

> Progress, challenges, and the way forward in nutrition research

on biofortifi ed crops: vitamin A

> Progress, challenges, and the way forward in nutrition research

on biofortifi ed crops: iron and zinc

> Progress, challenges, and the way forward in breeding and gene

development for vitamin A: taking stock, gaps, and solutions

> Progress, challenges, and the way forward in breeding and gene

development for iron and zinc: taking stock, gaps, and solutions

> Delivering vitamin A crops: a visible nutrient

> Delivering iron and zinc crops: an invisible nutrient

> Biofortifi cation for the developed world: progress with

antioxidants and other nutrients

> Biofortifi cation through agronomic practices

> Breeding for bioavailability

> Building public trust in transgenic biofortifi ed crops: a dialogue

> Climate change and the nutritional quality of foods

> Orange-fl eshed sweet potato is making a diff erence

> Weaving biofortifi cation into the global development agenda

> What about protein?

Institute, Iain MacGillivray of the Canadian International Devel-

opment Agency, and Ruth Oniang’o of the Afr ican Journal of Food,

Agriculture, Nutrition, and Development discussed his fi ndings

and took questions fr om the audience.

Keith West of the Johns Hopkins Bloomberg School of Public

Health presented the second commissioned paper, Biofortifi ca-

tion as a complementary approach to controlling micronutrient

defi ciencies in the developing world. This discussed how biofor-

tifi cation fi ts into already existing nutritional strategies of di-

etary diversifi cation, food fortifi cation, and supplementation.

Panelists included Shawn Baker of Helen Keller International,

Mahabub Hossain of the Bangladesh Rural Advancement Com-

mittee, MG Venkatesh Mannar of Micronutrient Initiative, and

Meera Shekar of the World Bank.

On the fi nal day, Dr Bouis summarized the conference key-

notes, panel discussions, and symposia, looking back at the

fr amework proposed on day one (Figure 1). A panel discus-

sion followed, including Pamela Anderson of the International

Potato Center, Arun Joshi of the International Wheat and Maize

Improvement Center, Denis Kyetere of the National Agriculture

Research Organisation – Uganda, and Francisco Reifschneider of

Embrapa (Brazil). Panelists discussed ideas for moving biofor-

tifi cation forward. The conference concluded with a strong call

to action by moderator Roger Thurow of the Chicago Council on

Global Aff airs.

The aft ernoon symposia (Table 1), featuring the work of 50

scientists and researchers, focused on the technical aspects of

breeding, nutrition, and delivery of biofortifi ed crops. It also fo-

cused on biofortifi cation through agronomic practices, building

trust around transgenic biofortifi ed crops, and climate change’s

role in diminishing the nutritional quality of foods.

Highlights included a session on a recent project that dis-

seminated orange-fl eshed sweet potato to 24,000 households

in Uganda and Mozambique. By researchers fr om HarvestPlus

and the International Food Policy Research Institute, this also

presented strategies used by the project to promote new sweet

potato varieties.

All videos, presentations, and papers fr om the conference

can be downloaded at: http://biofortconf.ifpri.info.

http://www.fl ickr.com/photos/48533839@N05/sets/

Correspondence: Hannah Guedenet, HarvestPlus, c/o IFPRI,

2033 K Street, NW Washington, DC 20006-1002, USA

E-mail: HarvestPlus@cgiar.org

New York Times columnist Nicholas Kristof during his keynote

address on the second day of the First Global Conference on

Biofortifi cation, Washington DC, USA.

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67SIGHT AND LIFE | VOL. 25 (1) | 2011 67NEW DEVELOPMENTS IN CAROTENOIDS RESEARCH

New Developments in Carotenoids Research Conference at Tuft s University, Boston, USA, 11–12 March 2011

more instances of unnecessary death and blindness every year.

-carotene is an important, but insuffi cient source of vitamin A

among poor populations, which accounts for the widespread

nature of vitamin A defi ciency. It has only recently become ap-

parent that the bioconversion of traditional dietary sources of

-carotene to vitamin A is much less effi cient than previously

supposed. The other major carotenoids, particularly lycopene,

lutein and zeaxanthin, have been found to have important

Introduction

With its copious research and development (R&D) activities and

passion for innovation, DSM is an authority on nutrition science,

supporting multiple activities dedicated to the fi eld of nutrition.

The company regularly brings together scientists fr om academia

and industry, as well as experts fr om health authorities, to com-

municate and advocate for the role of micronutrients in human

health. In March 2011, an international group of leading research-

ers in the growing fi eld of carotenoids met at Tuft s University,

Boston, USA, for an information-packed, two-day conference on

“New Developments in Carotenoids Research.” Jointly organized

by Tuft s University and DSM, and presented by The Jean Mayer

USDA Human Nutrition Research Center on Aging (HNRCA), the

conference featured keynotes fr om global experts on the role

of -carotene, lycopene, lutein and zeaxanthin, as well as vita-

min A in human health. The about 150 participants experienced

a high-level conference where the “Who’s Who” in carotenoid

and vitamin A science shared latest research fi ndings.

DSM is continuing to support carotenoid science events with

the “Macular Carotenoids & AMD” conference in Cambridge,

UK (www.macularcarotenoids.org) and the “16th International

Symposium on Carotenoids” in Krakow, Poland (www.caroten-

oid.pl).

Summary of selected key lectures

In his keynote lecture, Alfr ed Sommer (Johns Hopkins Univer-

sity, USA) gave a global clinical overview on vitamin A and car-

otenoids. The clinical importance of vitamin A as an essential

nutrient has become increasingly clear. Adequate vitamin A is

required for normal organogenesis, immune competence, tis-

sue diff erentiation and the visual cycle. Defi ciency, widespread

throughout the developing world, is responsible for a million or

Peter Engel

DSM Nutritional Products on behalf of Sight and Life,

Basel, Switzerland

“The use of systematic reviews will

be essential to provide harmonization

and transparency in the process of

developing intake recommendations”

Co-Chair, Dr Simin Meydani welcoming

everyone to HNRCA

68 NEW DEVELOPMENTS IN CAROTENOIDS RESEARCH

chronically insuffi cient in meeting needs imposed by life stage,

infection and other metabolic stresses. Preventing such defi -

ciency can be achieved through an adequate diet of preformed

(e.g., liver, dairy products, egg, etc) and provitamin A carotenoid

food sources (e.g., dark green leaves, yellow-orange fr uits and

vegetables). Dietary -carotene is the most important precursor

of vitamin A and has the potential to fi ll dietary vitamin A gaps.

The challenge in attaining nutritional adequacy for vitamin A

and -carotene was discussed by Marjorie J Haskell (University

of California, USA). The bioavailability and vitamin A equiva-

lency of -carotene fr om foods is highly variable and can be af-

fected by food and diet-related factors (such as the food matrix,

food processing techniques) and also by characteristics of the

target population, such as vitamin A status, other nutrient de-

fi ciencies, gut integrity and genetic polymorphisms associated

with -carotene metabolism. Thus, the variability in estimates

of vitamin A equivalency is high across studies, as is the varia-

bility in vitamin A equivalency ratios between individuals within

studies. Hans Konrad Biesalski (University of Hohenheim, Ger-

many) emphasized that consensus among experts in the fi eld of

carotenoids holds that -carotene is a safe source of vitamin A biologic properties, including antioxidant and photo-protective

activity. In observational studies, high intake of these has been

linked with the reduced risk of a number of chronic diseases.

Focusing on the role of -carotene as a safe source for vi-

tamin A, Robert M Russell (National Institutes of Health, USA)

gave perspectives on vitamin A and carotenes with regard to

defi ning their dietary requirements. In 2001, the old ratio of 6:1

-carotene to vitamin A equivalence (1 retinol equivalent = 6 μg

of -carotene) was jettisoned in the US for a new ratio of 12:1,

based on new and reproducible stable isotope data. However,

there is great variation of the bioconversion equivalence, de-

pending on the food being tested (e.g., for green leafy vegetables

>20:1 and for carrots ~15:1). In addition, there is new evidence

that foods with a simple, digestible matrix have an equivalence

that is much better than 12:1. The tolerable upper level for vita-

min A is set at 3,000 μg per day in the US and EU, based upon

liver toxicity and teratogenicity among women of reproductive

age. In the UK, it is recommended that people not consume

more than 1,500 μg per day. The US and EU panels concluded

that there was not enough data on which to base a tolerable

upper level for -carotene. However, in the UK an upper level

for -carotene was set at 7 mg per day. In fu ture, the use of

systematic reviews will be essential to provide harmonization

and transparency in the process of developing intake recommen-

dations.

Nutritional relevance and challenges

Keith P West (Johns Hopkins Bloomberg School of Public Health,

USA) outlined the nutritional relevance of -carotene as provi-

tamin A. Vitamin A defi ciency can arise when dietary intake is

“Retinoids infl uence, and in some

cases appear to be principal drivers

of, immune cell diff erentiation that, in

turn, aff ects a number of processes”

Listening intently fr om left to right Yoav Sharoni, Adrian Wyss,

Georg Lietz, Johannes von Lintig, Catherine Ross

Roundtable discussion fr om left to right: Rob Russell, Helmut Sies,

Cathy Ross, Johannes von Lintig, Marjorie Haskell, Al Sommer

69SIGHT AND LIFE | VOL. 25 (1) | 2011 69NEW DEVELOPMENTS IN CAROTENOIDS RESEARCH

intake, and that the provitamin A function of -carotene is es-

sential to achieve vitamin A intake recommendations in both

developed and developing countries.

Summarizing the results of epidemiological and human sup-

plementation studies with -carotene in chronic disease pre-

vention, Susan T Mayne (Yale Schools of Public Health and Medi-

cine, USA) concluded that intervening in populations with low

-carotene status in order to improve it may be a more prom-

ising approach than intervening in populations with adequate

status in order to raise it to a “supra” adequate status. However,

this more personalized approach to nutrient-based intervention

is critically dependent on the availability of biological markers

of status – in this case, carotenoid status. Recent advances in

the development of promising new methods for rapidly and non-

invasively assessing carotenoid status suggest that it is increas-

ingly feasible to identify the persons most likely to benefit from

carotenoid interventions, allowing for future intervention trials

with a greater likelihood of demonstrating beneficial effects than

seen to date.

Landmark findings

Francine Grodstein (Harvard Medical School, USA) reported on

clinical studies evaluating the effect of antioxidant -carotene

supplements on cognitive decline in older persons. Most notably,

in the Physicians’ Health Study II 6,000 older men were rand-

omized to 50 mg of -carotene supplementation on alternate

days, ranging from one to up to 18 years. For participants with

long-term supplementation, cognitive function was significantly

better compared to long-term placebo. Other research in this

area has been inconsistent with these landmark findings. The

explanation for these discrepant findings is not clear, although it

is possible that some combination of the appropriate dose and

-carotene

Lutein

Zeaxanthin

Lycopene

is a safe source of vitamin A. Its pro-vitamin A function is a crucial contribution to the required total

vitamin A intake in both developed and developing countries. Vitamin A is essential for normal growth and

development, the immune system, vision and other functions in the human body. The intake of preformed

vitamin A from animal products is not sufficient in major parts of the population all over the world, including

Europe, the US and Asia. Recent studies suggest that suboptimal levels of vitamin A and -carotene, even

levels well above those causing clinical defi ciency syndromes, can be a contributing risk factor in chronic

diseases. An appropriate intake of -carotene in diets, forti fied foods and/or dietary supplements could

safely compensate for the lack of vitamin A.

is a natural pigment and potent antioxidant present in the macula of the eye and in the skin. It acts as a

filter, shielding against the damaging near-to-UV blue light of the sun. Higher dietary intake of foods rich in

lutein and zeaxanthin is being discussed for its potentially positive, preventive effects on macular degenera-

tion and cataracts, as well as improved visual performance. Based on a wealth of scienti fic literature, lutein

is considered an eye health nutrient, supporting healthy eyes and vision as people age.

is, in addition to lutein, the only other major carotenoid specifically located in the macula of the eye.

Zeaxanthin, found in the retina, also protects the eye from damage caused by the near-to-UV blue light of the

sun. Higher dietary intake of foods rich in lutein and zeaxanthin has been associated with a reduced risk of

macular degeneration and cataracts.

is one of the strongest antioxidants among the carotenoids. Scientifi c evidence suggests that lycopene helps

protect cells against oxidative damage, and it is discussed and researched in the scienti fic community for its

benefi ts to cardiovascular health.

expert key messages

70 NEW DEVELOPMENTS IN CAROTENOIDS RESEARCH

duration of -carotene exposure is necessary for brain health.

Future research needs to better consider these questions of dose

and duration.

Study results showing -carotene- and lycopene-rich diet or

supplementation to provide protection against skin damage from

sunlight were presented by Helmut Sies (Heinrich Heine Univer-

sity, Germany). Although photoprotection through individual

carotenoid intake is considerably lower than that achieved us-

ing topical sunscreens, optimal supply of antioxidant micronu-

trients to the skin increases basal dermal defense against UV

irradiation, supports longer-term protection and contributes to

the maintenance of skin health and appearance.

In a second keynote lecture, A Catharine Ross (Pennsylvania

State University, USA) comprehensively outlined the effects of

vitamin A and retinoic acid on the immune system. Retinoids

influence, and in some cases appear to be principal drivers of,

immune cell differentiation that, in turn, affects a number of

processes. Vitamin A’s active metabolite all-trans-retinoic acid

seems to exert effects on the immune system by heightening

antibody responses through promotion of antibody production,

regulating T-cell differentiation, and programming precursor

T cells for innate immunity. In addition, the retinoic acid induc-

ible gene-1 is a major factor in the response to viral infections

and other stimuli.

The lycopene effect

Xiang-Dong Wang (Tufts University, USA) discussed the impor-

tance of lycopene for human health. A high intake of tomatoes

and tomato products have been found to reduce the risk of cer-

tain chronic diseases in many epidemiological studies, yielding

evidence that lycopene (a major carotenoid in tomatoes) is a

micronutrient with important health benefits, such as chronic

disease prevention (e.g., various types of cancer). Whether the

effect of lycopene on various cellular functions and signaling

pathways is a result of the direct actions of intact lycopene or

its derivatives remains unknown. Steven K Clinton (Ohio State

University, USA) noted that epidemiologic studies suggest lyco-

pene as a way to reduce risk or slow the progression of prostate

cancer. Human studies focus upon the distribution of lycopene

to the human prostate and the potential impact upon biomarkers

related to prostate cancer progression.

Paul S Bernstein (University of Utah, USA) elucidated the role

of macular pigment carotenoids. Abundant epidemiological evi-

dence suggests that the macular pigment carotenoids lutein and

zeaxanthin play key roles in the prevention and treatment of age-

related macular degeneration (AMD), a leading cause of irrevers-

ible visual loss in the elderly in the developing world. Evidence

that lutein and zeaxanthin also seem to improve visual perform-

ance in healthy subjects was highlighted by B Randy Hammond

(University of Georgia, USA). Finally, Elizabeth J Johnson (Tufts

University, USA) reviewed these carotenoids’ effects on cogni-

tive performance in older adults: Cognitive decline in the elderly

is a significant public health issue. Oxidative stress and inflam-

mation are believed to be involved in the pathogenesis of cog-

nitive decline. Epidemiological studies suggest that intake of

dietary carotenoids may be of benefit in maintaining cognitive

health. Given their role as antioxidants and anti-inflammatory

agents, lutein and zeaxanthin may play a role in the prevention

or delay of cognitive decline. Among all of the carotenoids, only

these two cross the blood-retina barrier to form macular pig-

ment in the eye.

Correspondence: Peter Engel, Scientific Communications,

Human Nutrition and Health, DSM Nutritional Products Ltd,

PO Box 2676, 4002 Basel, Switzerland

E-mail: peter.engel@dsm.com

Promoting partnerships and capacity building.

72

Philippe Bani Mora

Domarou Health Centre, Gogounou, Benin

One of the Millennium Development Goals is to reduce the child

mortality rate via people’s access to primary healthcare. With

this in mind, in April 2010 the I-Domarou health care center was

established in Gogounou, thanks to fi nancial support fr om our

faithfu l partner Sight and Life. The center’s fame quickly spread

and it soon set consultation records for the whole community.

I-Domarou, which means blessings in the local language, is

competitive in terms of its quality of care, aff ordability and hos-

pitality. Providing a fu ll range of care, it is run by three people,

including a senior public health technician/nutritionist, who

also acts as center manager; a social assistant; and a caregiver

trained at the center.

Curative work

I-Domarou is an integrated health center and its activities are

patient-driven. Cases include childhood illnesses, nutritional

diseases, and many others, including skin infections, cuts, in-

juries and defi ciencies in micronutrients. The center initially

treated 328 cases in April 2010; however, numbers have risen

and a grand total of 2,927 patients were seen over a period of

six months. At a community level, the center received 150 pa-

tients whose parents did not even have one fr anc to support their

children – most of whom were seriously ill. It also received four

orphans and assisted with their medical care. In addition, it has

seen 10 cases of night blindness.

Nutritional, preventative and educational work

Nutritional recovery is made on the basis of a “food square” con-

sisting of a source of cereal (starch or tuber); a source of protein

(vegetable or animal); a source of mineral complexes and vita-

Report fr om GogounouBlessings at the I-Domarou Health Center

Philippe Bani Mora, manager of the Domarou Health Centre,

Gogounou, Benin, established in 2010 with the fi nancial support

of Sight and Life

73SIGHT AND LIFE | VOL. 25 (1) | 2011 73REPORT FROM GOGOUNOU

In future, the center might grow to include a laboratory. However,

the need for maternity facilities is also evident and mother and

child protection is in great demand. Prenatal consultation and

pregnancy monitoring could be carried out in liaison with the

area hospital. We need to increase staff with qualified personnel

and to obtain a means of transport to enable us to raise aware-

ness in Fula camps and settlements far from the town center and

ensure the transportation of medication from the central vendor

to our remote workstation 175 km away.

Correspondence: Philippe Bani Mora,Domarou Health Centre, Gogounou Alibori Department, Benin

E-mail: banimorap@yahoo.fr

mins (dried Moringa leaves); and an energy supplement (sugar

or oil). The center is in contact with Niger’s Office of Pharmaceu-

tical Products, which provides it with chocolate products rich in

vitamins and minerals. It also carries out minor surgery, such as

suturing wounds, draining abscesses and applying bandaging.

We raise awareness about various topics, from the impor-

tance of exclusive breastfeeding, best weaning practices, food

supplements and vaccinations to the need to monitor children

for a healthy infancy. The center also distributes vitamin A to

vulnerable groups and home visits are arranged.

Progress and prospects

Since its inception, we have made good progress in a number

of areas, ranging from collaboration with the state structure to

cooperation with the commune’s elected officials. We have sub-

mitted an application to the town hall for more land, to enable

the future expansion of the center, including the construction

of a clinic.

“An integrated health center with patient-driven activities”

74 REPORT FROM KATHMANDU

Report fr om Kathmandu

The continuation of a previous project

supported by Sight and Life

This is the fi nal report on the training of adolescent girls work-

ing in the mining and stone quarrying industries in rural hilly

areas of eastern Nepal, in the prevention and control of ane-

mia. This activity was implemented in diff erent locations within

Kavrepalanchok district to create awareness among mine and

quarry workers. In order to do so and bring taught subjects to

life, adolescent girls fr om diff erent locations were fi rst trained to

identify people with iron defi ciency anemia (IDA), provide nutri-

tion education, and change behavior in terms of utilizing existing

health care service centers early on. Aft er training, during their

leisure time these adolescent girls were involved in identify ing

IDA among pregnant women, nursing mothers and adolescent

girls, in order to achieve the stated objectives for the period

of 10 months to compare the results of IDA prevalence among

these high-risk populations. This project is part of a continua-

tion of a previous project supported by Sight and Life.

Project rationale

IDA is the most common nutritional problem in Nepal and has

profound economic and social consequences. Many activities

have been implemented by diff erent organizations to combat

this. However, some groups or pockets of the population have

signifi cant problems and still need to be reached with special

packages.

> Although mine and stone quarry workers live in communities

that are comparatively similar, it has been found that they are

not aware of the problem and do not utilize available health

care facilities. More attention needs to be paid to them to re-

duce the existing burden of IDA.

> As the government does not have a program to reach these

groups, there is a strong need for regular outreach health care

activities. One-off activities do not help reduce the present

problem.

> Mine and quarry owners need to support regular health

check-ups, and the provision of nutritious food, especially for

pregnant and nursing mothers. Currently, whenever someone

wants a check-up, he or she loses pay. Leave facilities should

therefore be provided when health check-ups are required.

> Specifi c target groups require extra eff orts and therefore need

special attention.

Utpal Chalise

Youth Volunteer Group,

Kathmandu, Nepal

A Project Report on Training of Adolescent Girls for Prevention and Control of Iron Defi ciency Anemia 2009/10

Adolescent girls who are employed in the mines and stone

quarries of rural eastern Nepal are being trained to identify

people with anemia

⇢

75SIGHT AND LIFE | VOL. 25 (1) | 2011 75REPORT FROM KATHMANDU

Overall objective

To create awareness of the consequences of micronutrient defi -

ciencies, with a special focus on iron defi ciency anemia among

pregnant and lactating mothers and adolescent girls of repro-

ductive age working as mine and stone quarry workers.

Specifi c objectives

> Organize one batch of peer educator training for 25 adoles-

cent girls at diff erent mining and stone quarrying work sites.

> Identify , keep records of and treat pregnant women, lactating

mothers, and adolescent girls of reproductive age with IDA.

> Raise awareness of the need for and importance of iron sup-

plementation for pregnant women, lactating mothers, and

adolescent girls of reproductive age.

> Raise awareness among pregnant women of the importance of

iron supplementation during pregnancy.

> Motivate pregnant women to take iron-coated tablets regu-

larly during pregnancy.

> Create awareness among pregnant women, lactating mothers,

and adolescent girls of reproductive age about the importance

of daily, suffi cient consumption of foods containing vitamin A

and iron and the importance of vitamin C rich food to increase

dietary iron absorption.

The activity was implemented at 10 diff erent locations in Kavre-

palanchok district, 46 km fr om central Kathmandu, the Nepalese

capital. The majority of people in the project areas are fr om spe-

cial ethnic, marginalized, socio-economically poor and under-

privileged groups. Three hundred and twenty-four families, or

2,231 people, were covered of whom 1,530 were mine and stone

quarry workers and the remaining 701 fr om a village near the

work site.

Achievement

Two meetings were conducted with those in charge of health

posts, female community health volunteers (FCHVs), social

workers, and NGO representatives in program areas.

Two general health check-up camps were held at the begin-

ning and end of the 10-month period for all quarry and mine

workers’ family members and people fr om the community, with

a special focus on pregnant women, lactating mothers, and ado-

lescent girls. Health check-up camps to detect IDA among the

target groups were organized at the work place at 10 sites to

make them accessible and save workers’ time, so that they could

return to work quickly.

The heart of the program was to identify and train adoles-

cent girls fr om among the quarry and mine workers and develop

them as motivators to early identify people with IDA and re-

fer them to nearby health care units for treatment, followed by

nutritional education. The prevalence of IDA is summarized in

Tables 1 and 2.

Nutrition education

Aft er the selection process, three-day nutrition orientation train-

ing was organized. It focused on the magnitude of the problem,

the target group, nutrition defi ciency disorders, early identifi ca-

tion of problems, selection and preparation of foods, timely use

of available health care units, etc.

Health check-ups are held at the beginning and end of

a 10-month period for all quarry- and mine-workers’ family

members and people fr om the community

table 1: IDA in the fi rst health check camp

Description No. examined IDA detected %

Pregnant women 64 27 42.2

Nursing mothers 52 17 32.7

Adolescent girls 80 24 30.0

table 2: IDA in the second health check camp

Description No. examined IDA detected %

Pregnant women 57 11 19.3

Nursing mothers 48 9 18.8

Adolescent girls 86 16 18.6

76 REPORT FROM KATHMANDU

Records of existing health care units have shown that those

adolescent girls, pregnant women, and nursing mothers referred

and detected as having IDA have been found to have visited the

health units. Pregnant women and nursing mothers have been

found to have adopted preventive measures as suggested, and

improved the practice of planning and consuming iron-rich

foods. Vitamin A capsules were distributed at all 10 sites, and

100 percent of children aged 6 – 59 months received vitamin A

capsules. This was mainly thanks to the trained adolescent girls,

aided by female community health volunteers who visited each

house. However, the majority of the target groups did not utilize

the health care units as expected, despite regular motivation by

trained persons. This was mainly for fear of losing their daily

wages. Making the service accessible and providing regular mo-

tivation by family members can help reduce the problem of IDA

in such target populations.

Correspondence: Uptal Chalise, Youth Volunteer Group,

c/o GPO Box 1144 Kathmandu, Banepa, Kavrepalanchok, Nepal

E-mail: vg87@hotmail.com

Each trainee was provided with a kit bag containing a record

book to record details of people with nutritional anemia and vi-

tamin defi ciency disorders, nutrition posters, iron tablets, and

referral slips. As a preventive measure for the whole target popu-

lation, nutrition education was delivered with the help of picto-

rial printed materials.

Trained adolescent girls took responsibility in their respec-

tive workplaces and health educators delivered nutrition educa-

tion to a group every two months. Due consideration was given

to the importance of micronutrient supplements for safe delivery,

safe motherhood, prevention and control of childhood blindness,

and mortality. Nursing mothers were encouraged to breastfeed

their children up to at least two years of age, and to feed children

food rich in iron and vitamin A fr om six months.

“IDA is the most common nutr iti onal problem in Nepal”

Pregnant women and nursing mothers are identifi ed to visit

health care units and adopt preventive measures

77SIGHT AND LIFE | VOL. 25 (1) | 2011 77

Strategies for proper diagnosis

We were then in a position to diagnose and treat. Two strategies

were used to ensure proper diagnosis: door-to-door visits and

diagnosis at community sites. Several diagnostic materials were

used (anthropometric kit) and we diagnosed 342 cases of mal-

nutrition. Once diagnosed, three courses of action were taken.

The challenges

Numerous problems were encountered, including diffi culties in

accessing people, solid meals given to parents of sick children

being consumed by the whole family, seasonal food out of stock,

untimely power cuts, lack of transport, rental diffi culties and in-

suffi cient fu nds.

Despite this, the center achieved most of its goals, with fi ve

staff trained, four sites created, 36 visits undertaken and 342

children diagnosed and treated. All this was assisted in part by

the US $6,600 that was received fr om Sight and Life.

Correspondence: Georges Nicks Tsimba, BP 111 Boma, Bas-Congo E-mail: georgesnickst@yahoo.fr

Anne-Catherine Frey Sight and Life, Basel, Switzerland

E-mail: Anne-Cath.Frey@sightandlife.org

REPORT FROM LEMBA

Report fr om LembaCentr e de Lutt e Contr e la Malnutr iti on de Lemba

The Centre de Lutte Contre la Malnutrition de Lemba (Center for

the Fight Against Malnutrition in Lemba) is located on avenue

Mambu N°20, in the settlement of Kinsundi-Lemba, Bas-Congo

province. It is 40 km fr om the port town of Boma in the south

west of the Democratic Republic of Congo and 540 km fr om

Kinshasa. The settlement of Kinsundi-Lemba is home to 21,935

inhabitants including 3,729 children aged up to 59 months. The

majority of the population farms, while the remainder is made

up of traders, teachers, craft smen and the unemployed.

The creation of the center began on September 11, 2009 on

the initiative of Georges Nicks Tsimba, senior ophthalmologist

and nutritionist at the NGO Foyer d’Encadrement pour le Dével-

oppement FED-ASBL. He had the excellent idea to set up a health

facility to combat malnutrition and its eff ects on vulnerable peo-

ple (children and others).

A year of action

From September 11, 2009 to September 11, 2010 there was an

extensive program of activities.

The training of community liaison staff was the fi rst task to

be carried out, since it enabled us to gain the facilities to raise

people’s awareness about malnutrition, micronutrients and nu-

tritional anemia. We trained fi ve community liaison staff : three

men and two women.

Taking into account the diffi cult access to the most remote

villages, we then created three diagnostic sites. Each of these

has a representative to deal with cases of malnutrition.

A need to raise awareness followed and was addressed by

making use of the community liaison staff as well as posters,

radio and word of mouth.

Anne-Catherine Frey

Sight and Life, Switzerland

Georges Nicks Tsimba

Boma, Bas-Congo

Dietary treatment: First, we needed food. Since our center is

located in a farming area, we carried out a survey to fi nd out which

foodstuff s are most commonly consumed and how, as well as the

methods of producing them. From the results, we determined the

best foodstuff s to be consumed. A parallel study was conducted

to identify the components and nutritional values of each foodstuff ,

with most having been processed into fl our, juice or pulp. These

were mixed to increase the nutritional strength, then packaged and

stored. Treatment depended on the degree of malnutrition.

Medical treatment: Consisting of vitamin A, folic acid, Vermox,

Amoxicillin, and eye and dental products.

Preventative treatment: Including nutritional education

about exclusive breastfeeding, feeding a sick child, food hygiene,

culinary principles and personal hygiene, and teaching

mothers about vegetable growing.

78 REPORT FROM RATANAKKIRI

Report fr om Ratanakkiri School Health Watch

Janie Rose Ilustre,

Pen Sarouen and Kim Chhay Sotheavy

Voluntary Service Overseas,

Cambodia

The School Health Watch government-initiated project provides

health and nutrition guardianship in schools, and aims to target

the prevention, treatment and control of health and nutrition

problems among school children.

The province of Ratanakkiri, in northeast Cambodia, clearly

illustrates a higher prevalence in malnutrition, in comparison

with the data of malnutrition for the entire country (see Table 1).

It is for this reason that the School Health Watch project was

initiated.

The problems of undernutrition remain particularly severe in

countries recovering fr om recent wars and civil unrest, where

improvements in economic conditions tend to benefi t the ad-

vantaged groups and result in widespread inequalities. Also, in

Cambodia, aft er the tragedy of losing millions of children, wom-

en and men in the “killing fi elds”, the lack of people to attend

the physical and overall wellness of the children aggravated the

situation, and the country is still engaged in mobilizing resourc-

es to rebuild and strengthen its society.

School Health Watch was conceptualized in order to assess the

health and nutrition status of school children and provide in-

terventions for prevention and control by building the capac-

ity of teachers and parents, and strengthening its linkages. The

project’s aim is to improve the quality of health and nutritional

status of primary school children through early and proper diag-

nosis, treatment and prevention interventions in schools.

Ground-breaking changes

Aft er the implementation of the project, a Health and Nutrition

Manual was developed to serve as reference material and na-

tional trainers fr om the School Health Department were identi-

fi ed as core trainers for possible expansion in fu ture.

A total of 70 primary school teachers fr om fi ve diff erent

schools were trained in health and nutrition skills and the know-

ledge to implement the project eff ectively. In addition, each

school received water fi lters, fi rst aid kits, hygiene sets, weigh-

ing scales, and height boards.

Anthropometric data on 1,572 primary school children were

recorded. The results revealed that 23.2% were severely under-

weight; 62.8% were moderately underweight; and 14% were

mildly underweight. Two hundred and fi ft y malnourished chil-

dren were therefore identifi ed to receive 15-day supplemental

feeding, and among them 176 showed signifi cant improvement

(70.4%). Furthermore, the parents of these children attended a

nutrition orientation workshop to ensure continued rehabilita-

tion at home. The Ministry of Education, Youth and Sport recti-

fi ed the School Health Policy Guidelines that were developed to

ensure the sustainability and adaptability of the project among

interested partners and stakeholders. To date, the project has

become a successfu l benchmark for other partners. Belgium’s

Handicapped International supported a rolling-out of the project

in two of their targeted provinces in Takeo and Battambang,

Cambodia, and the World Food Programme has shown an inter-

est, with initial discussions taking place.

Correspondence: Janie Rose Ilustre, Pen Sarouen and Kim Chhay Sotheavy, Voluntary Service Overseas, Cambodia,

School Health Department, Ministry of Education, Youth and

Sports, Cambodia E-mail: jrilustre@hotmail.com

table 1: Cambodian Demographic and Health Survey (CDHS)

(children 6–59 months old)

Anthropometrics Cambodia Ratanakirri

Stunted 37% 54%

Underweight 36% 52%

Wasting 7% 8%

2005; National Institute of Public Health and

National Institute of Statistics.

79SIGHT AND LIFE | VOL. 25 (1) | 2011 79REPORT FROM RATANAKKIRI

“The project has become a successfu l bench mark for other partners”

Cambodia is engaged in mobilizing resources to strengthen and rebuild its society,

including the health and nutritional status of its schoolchildren

80

nd Life01 Special Research Grant 2010 Awardedl For 2011 Grant01

0 N Keeps on Rising02

The theme for the 2010 Sight and Life Special Research Grant

was “Assessing vitamin A dietary intake and status in devel-

oping countries where fortifi ed foods are commercially avail-

able.” Seventeen applications were received and two groups

of researchers were selected. The fi rst grant was awarded to

the South African Medical Research Council (MRC), under

the aegis of lead researcher Dr Mieke Faber. The research will

determine the vitamin A intake and status of a representative

sample of randomly selected South African children aged

two to fi ve years and their caregivers in each of fi ve diverse

geographical sites. The second grant was awarded to the

University of California, Davis, and Helen Keller International,

Cameroon, with the lead researcher being Dr Kenneth Brown.

The theme of the research is “Vitamin A fortifi cation

The nutrition world is abuzz with activity as, now that both

the Framework and the Road Map have been developed, the

Scaling Up Nutrition (SUN) process moves from its talk phase

to its action phase. The SUN concept has been reinforced

by political interest in nutrition among leaders of national

governments and development partners alike – some 14 coun-

tries have already been enlisted as “Early Risers”. However,

there is still much work to be done. In 2011, the focus

will be on translating the Road Map into actions with a view

to helping countries aff ected by malnutrition to achieve long-

term reduction in undernutrition, realize the fi rst Millennium

Development Goal, and start demonstrating this impact

within three years.

The ongoing development of SUN is being led by a Transi-

tion Team and six inter-linked Task Forces, while the overall

of refi ned cooking oil in Cameroon: Optimization of fortifi ca-

tion levels using dietary intake data and use of biological

indicators of vitamin A status for program impact evaluation.”

We look forward to sharing the results from both research

programs.

The 2011 Special Grant theme will be “Examining the

optimal formulation of micronutrient powders and the eff ect

of their use on anemia, micronutrient status, and physical

growth in malaria endemic settings.”

For details on the theme and how to apply, visit

www.sightandlife.org

Speakers fr om the 1,000 Days conference join Mr Shah,

USAID administrator

81SIGHT AND LIFE | VOL. 25 (1) | 2011 WHAT'S NEW

process is chaired by Dr David Nabarro the Special Representa-

tive of the UN Secretary General for Food Security and Nutrition.

The three principles

guiding the SUN movement are:

1. Efforts are led from countries and external support

processes must add value to this country-led action and

must be demand-driven;

2. Ongoing initiatives to improve nutrition should be linked

together for greater coherence, efficiency, and impact

wherever possible; and

3. A combination of networks and movements are needed to

enable a range of stakeholders to work together and

contribute to lasting results.

The Transition Team is made up of and working closely

with individuals from the UN’s Standing Committee on Nutri-

tion (SCN) and a wide range of organizations that includes

the FAO, UNICEF, WHO, WFP and the World Bank, the REACH

initiative, the African and European Unions, other regional

bodies, civil society, farmers’ organizations, the research com-

munity, private companies, development partners and phil-

anthropic foundations. The Transition Team is focusing on

arrangements through which national authorities can request,

and then access, support for actions to Scale Up Nutrition.

The team has begun to consider how best to ensure that sup-

port is responsive to country needs and requests, coordinated,

of high technical quality and effective.

Four outcomes are being pursued

by the Transition Team:

1. Rapid increase in support for “Early Riser” countries that

seek immediate help with their efforts to Scale Up Nutrition

through encouraging links between the national authorities

that want to get going now and those development partners

that are ready to help them. This support will take stock

of existing efforts and implementation gaps and will

facilitate the development (or strengthening) of national

multi-stakeholder nutrition platforms.

2. Ensure the development of long-term systems that provide

support to Scaling Up Nutrition in all countries affected

by undernutrition. These systems will enable national

authorities to better connect and engage with key nutrition

stakeholders from both civil society and the private sector,

in ways that are effective, credible and accountable.

3. Foster the SUN Movement with effective advocacy and lead-

ership. A durable multi-audience advocacy campaign will

be built that encourages the emergence of effective

and self-sustaining nutrition leadership at community,

national, regional and global levels. The accomplishments

of the SUN movement throughout its first three years and

beyond will be documented and communicated, in close

coordination with the 1,000 Days movement.

4. Agreement on transparent and accountable institutional

arrangements for the SUN effort, once the Transition Team

has completed its work. This will require analysis of need-

ed features, organizational arrangements, and available

options. It is intended that countries will be engaged as full

partners and that key stakeholders wishing to contribute

to country-led SUN actions will be able to do so. This work

is being taken forward in conjunction with efforts to

reform the SCN.

Each of the six Task Forces is responsible

for the development of more detailed aspects of

giving SUN life and cover:

> Task Force A: Country capability development. This

focuses on developing and strengthening country capabilities

for Scaling Up Nutrition. It includes the provision of support

to multi-stakeholder platforms, the development of manage-

ment systems and increased access to knowledge, standards

and harmonized policies.

> Task Force B: Communication for Scaling Up Nutrition. This

is responsible for communications and advocacy for Scaling

Up Nutrition, with the 1,000 Days movement at its core. The

Task Force also encourages the emergence of “Nutrition Lead-

ers” at community, national, regional and global levels.

> Task Force C: Civil society participation. The focus is on ways

to ensure inclusive civil society participation in the SUN

process, at local, country, regional and global levels, ensuring

the rights and well-being of those at risk of malnutrition and

promoting the accountability of decision makers.

> Task Force D: Engagement of development partners. De-

veloping ways in which development partners, including

bilateral agencies, development banks and philanthropic or-

ganizations, can be fully engaged in a coordinated response

and the effort to Scale Up Nutrition and can take

a leading role in work with national governments.

> Task Force E: Engagement of the business community. Work-

ing on ways in which the business community can be better

engaged in the effort to Scale Up Nutrition at all levels in

ways that have the potential to be sustainable,

and explore market-based responses at a national level.

> Task Force F: Monitoring and reporting on in-country

progress. This focuses on multi-country and multi-stakehold-

er action to monitor and report on progress on Scaling Up

Nutrition at country level; working with authorities

and with the other Task Forces identifying the need for more

effective approaches that could be the subject of

in-depth analysis.

82 WHAT'S NEW

Each Task Force is fi nalizing its specifi c terms of reference

as well as an action plan and many are doing this at the same

time as beginning to deliver on specifi c projects.

Sight and Life is represented on Task Force B by Jane Badham.

We will ensure that we give regular updates on the various

SUN activities, as its aim is to be transparent and include as

many stakeholders as possible.

SUN is currently consolidating and building stakeholder

alliances and aligning donor commitments with country-led

plans for improving nutrition. In a recent article by David

Pelletier et al, published in Health Policy and Planning

(2011;1–13) and entitled “Nutrition agenda setting, policy

formulation and implementation: lessons from the Main-

streaming Nutrition Initiative”, the authors highlight the real-

ity that we face. While undernutrition is the single largest con-

tributor to the global burden of disease and can be addressed

through a number of highly effi cacious interventions, in

general it has not received commensurate attention in policy

agendas at global and national levels. Implementing these

effi cacious interventions at a national scale has also proven

diffi cult. This is an important fact that has to be considered

and overcome as SUN rolls out at a country level.

Key messages include:

> Strengthening the full spectrum of policy activities

is necessary if large-scale and sustained reductions in

undernutrition are to be achieved.

> Within this policy spectrum, high priority should be given

to strengthening strategic capacities because these are

fundamental to advancing commitment building, agenda

Sight and Life and the non-profi t organization Vitamin Angels,

whose mission is to mobilize and deploy private sector re-

sources to advance availability, access and use of vitamin A

by newborns, infants and children most in need, have recent-

ly signed a Memorandum of Understanding. The partnership

will work together to build on their individual strengths to

foster local ownership of the problem of vitamin A defi ciency

in India, and catalyze a locally sustainable supply and distri-

bution system in India.

Fift y-one percent of the 190 million children under fi ve

who suff er from moderate and severe vitamin A defi ciency

live in India, making addressing vitamin A defi ciency in

India a critical component of the global challenge to eliminate

micronutrient defi ciencies. While the Government of India

fully supports initiatives for vitamin A supplementation and

a large proportion of infants, children and lactating women

receive supplementation, there remains a signifi cant portion

of the population that has yet to be reached.

“Through this partnership, Sight and Life’s advocacy and

technical expertise and Vitamin Angels’ successful implemen-

tation of universal vitamin A supplementation projects aim

to reach millions of those in India who have to date not

setting, policy formulation, capacity building for operations,

and all other aspects of a long-term nutrition agenda at

country level.

> These conclusions are especially relevant for major global

initiatives currently under development that seek to ad-

dress nutrition through country-led processes and conver-

gence between multiple organizations.

> The extensive investments in documenting the effi cacy of

nutrition interventions are unlikely to produce sustainable

reductions in undernutrition unless or until these weak-

nesses in the policy spectrum are better understood and

addressed.

SUN and the 1,000 Days movement are the start of a

larger movement that hopes to address these real global

nutrition issues by focusing attention, aligning and increasing

resources, and building partnerships. The SUN must shine

if nutrition is to take its rightful place and deliver to alleviate

the suff ering caused by undernutrition among millions of

people around the world – especially pregnant women and

children under two years of age.

Coming soon will be a SUN website

watch for the link fr om www.sightandlife.org

nd Life03 and Vitamin Angelser Improving Lives in India03

⇢

83SIGHT AND LIFE | VOL. 25 (1) | 2011 WHAT'S NEW

UNICEF Workshop on Scaling Up the Use of Micronutrient Powders to Improve the Quality

lementary Foods for Young Children04America and the Caribbean04

In June 2011, UNICEF and the US Centers for Disease Control

and Prevention (CDC) co-hosted a four-day workshop in

Mexico to discuss the role of micronutrient powders (MNPs)

in improving the quality of complementary feeding in Latin

America and the Caribbean and to support countries in their

plans to introduce and scale up MNP programs. Extensive

research shows that MNPs are safe, effi cacious, acceptable,

easy to use and do not alter the taste or appearance of food.

MNPs are particularly useful to improve the quality of comple-

mentary foods prepared at home. Based on current evidence,

MNPs can easily and cost-eff ectively be administered under

programmatic conditions and implemented at scale. Success-

ful public health scale-up of MNPs does require that they are

integrated within Infant and Young Child Nutrition (IYCN)

had access to life-saving vitamin A,” says Dr Klaus Kraemer,

Director of Sight and Life. In signing this Memorandum of Understanding, both part-

ners hope to engage other international and Indian for-profi t,

not-for-profi t and government entities. The aim is to mobilize

support and participate in this initiative, in order to harness

innovative public-private partnerships to sustainably tackle

the vitamin A defi ciency epidemic in India and improve the

lives of millions of infants, children and women.

For more information on Vitamin Angels go to

www.vitaminangels.org

and Early Child Development (ECD) programs. Under these

conditions, MNPs have the potential not only to improve the

micronutrient content of complementary food and decrease

the burden of anemia, but also to improve complementary

feeding and care practices of young children that will, in turn,

lead to better growth and development outcomes for young

children.

Many countries in Latin America and the Caribbean (LAC)

are poised to scale up the use of MNPs as part of integrated

IYCN and ECD strategies. Furthermore, a unique aspect of the

Latin American experience is the use of MNPs as part of an in-

tegrated package of services included under social protection

schemes such as Conditional Cash Transfer (CCT) programs to

reduce social inequities.

The comprehensive workshop covered relevant topics,

including the current status of MNP interventions in Latin

America and the Caribbean; the evidence base for MNPs;

relevant recommendations regarding MNPs; MNPs in national

policies; MNPs integrated in nutrition strategies; the design of

MNP interventions; MNPs and other interventions to improve

micro-nutrient intake; choice of MNP formulation; target

Peruvian children are among those to be impacted

by plans to scale up MNPs

84 WHAT'S NEW

In an excellent on-line article (www.slate.com/id/2281097⁄)

originally from Project Syndicate, Copenhagen Consensus

Centre Director Bjørn Lomborg writes: “Micronutrient defi -

ciency is known as ‘hidden hunger’. This is a fi tting descrip-

tion, because it is one of the global challenges that we hear

relatively little about in the developed world. It draws scant

media attention or celebrity fi repower, which are oft en crucial

to attracting charitable donations to a cause. But there is a

larger point here: Billions of dollars are given and spent on

aid and development by individuals and companies each year.

Despite this generosity, we simply do not allocate enough re-

sources to solve all of the world’s biggest problems. In a world

fraught with competing claims on human solidarity, we have

a moral obligation to direct additional resources to where

they can achieve the most good. And that is as true of our

own small-scale charitable donations as it is of governments’

or philanthropists’ aid budgets. In 2008, the Copenhagen

Consensus Center asked a group of the world’s top economists

to identify the ‘investments’ that could best help the planet.

The experts – including fi ve Nobel laureates – compared ways

to spend US$75 billion on more than 30 interventions aimed

at reducing malnutrition, broadening educational opportunity,

slowing global warming, cutting air pollution, preventing

confl ict, fi ghting disease, improving access to water and

sanitation, lowering trade and immigration barriers, thwart-

ing terrorism, and promoting gender equality. Guided by their

consideration of each option’s costs and benefi ts, and setting

aside matters such as media attention, the experts identifi ed

the best investments: those for which relatively tiny amounts

of money could generate signifi cant returns in terms of health,

prosperity, and community advantages. These included:

increased immunization coverage, initiatives to reduce school

dropout rates, community-based nutrition promotion, and

micronutrient supplementation.”

The article goes on to ask: “How could US$ 10 best be spent?

Should we, say, buy carbon off sets, or donate to a charity

providing micronutrient supplements? By putting all benefi ts

to individuals, communities, and countries in monetary terms,

we can compare the two options. Expert researchers for

the Copenhagen Consensus found that carbon off sets are a

relatively ineff ective way of reining in global warming and

reducing its eff ects – US$ 10 would avoid about US$ 3 of

damage from climate change. By contrast, US$10 spent on

vitamin A supplements would achieve more than US$ 170

of benefi ts in health and long-term prosperity. One lesson we

can draw is that while global warming may exacerbate

problems like malnutrition, communities bolstered by ad-

equate nutrition will generally be less vulnerable to climate-

based threats. Overall, we can typically best help through

direct interventions, including micronutrient supplements,

fortifi cation, biofortifi cation, and nutritional promotion.”

groups; distribution channels; MNPs in acute emergencies;

schedules of administration; communication; supply and

procurement; and monitoring and evaluation. The workshop

concluded by looking at the challenges and areas for follow

up. Information exchange and support mechanisms were

discussed and a number of suggestions were made including

inter-country exchange of information through information

circulars, websites, inter-country exchange visits, tailored

country support and documentation of best practices and les-

sons learned through ad hoc consultation.

The workshop was attended by participants representing

15 countries in LAC, who had the opportunity to engage in and

discuss the current status of MNP activities in their respec-

tive countries and improve the design of these interventions.

Countries exchanged experiences in a way that contributed

to strengthening their program design, which in turn had the

potential to substantially contribute to the body of evidence

on the eff ectiveness of MNPs in programmatic settings.

5555550000 st Dollar05ll Ever Spend05

27th UNAIDS Programme Coordinating iscusses Food and Nutrition Security in06gramming06

⇢

85SIGHT AND LIFE | VOL. 25 (1) | 2011 WHAT'S NEW

“Food and nutrition security and HIV: how to ensure food and

nutrition security are integral parts of HIV programming” was

the theme of the 27th meeting of the UNAIDS Programme Co-

ordinating Board meeting held in Geneva in December 2010.

The day was organized by representatives of the three UNAIDS

constituencies and included a range of expert speakers, as

well as speakers with experience of working in countries and

programs. It aimed to provide a stimulating opportunity for

dialog, exchange, and learning, in order to identify pragmatic

policy and programmatic strategies to ensure that food and

nutrition become integral parts of HIV programming – sup-

porting prevention, treatment care and support measures.

Experience and evidence are mounting that an eff ective re-

sponse to the HIV/AIDS epidemic, including the achievement

of universal access to prevention, treatment, care and support,

requires issues of food and nutrition security to be addressed.

Adequate nutrition is crucial for good health outcomes in

general and a strong immune system in particular. For HIV

and frequent co-infection tuberculosis (TB), as with any other

infection, good nutrition is critical to keeping the immune

system strong. Good nutrition can impact the pace of either

disease, but will not eliminate the infection. Good nutrition is

not only a critical adjunct of any treatment regimen, but

is also important at all stages of the disease.

Before the initiation of treatment, good nutrition is critical in

order to maximize the chances of slowing down disease pro-

gression. At around the start of antiretroviral therapy (ART),

nutritional support is necessary to minimize side eff ects and

metabolic challenges, thereby improving adherence. In low

resource settings, HIV and frequent co-infection TB oft en

strike where malnutrition is already prevalent and compound

it. Additionally, malnutrition is associated with high mortality

in the early months of treatment. The faster the achievement

of nutritional recovery through a combination of ART or

TB treatment and nutritional support, the better the chances

of reducing early mortality.

People living with HIV (PLHIV) are at high risk of weight

loss and wasting, which may compound existing malnutrition.

Symptomatic HIV-positive children, for example, have calorie

needs that are 50–100% greater than those of HIV-negative

children. However, young children oft en struggle to consume

the amount of calories required, especially when they do

not have access to energy dense foods.

Although advances in ART have enabled many people to

lead relatively normal lives and have signifi cantly reduced

HIV-related mortality and morbidity, fewer than half of the

people living with HIV had access to treatment in 2010. While

supply-side issues are part of the reason for this, many fail

to seek treatment or show poor adherence. The reasons

behind the lack of uptake and adherence are not always well

understood, but evidence suggests that food insecurity and

the cost of transport may be partially responsible. For those

who have access to treatment, weight loss or malnutrition

may aff ect the effi cacy of ART.

Michel Sidibé, Executive Director UNAIDS

(photo: by courtesy of UNAIDS)

86 WHAT'S NEW

Food and nutrition security is also an essential element of ef-

fective care and support in HIV-aff ected households and com-

munities. In low-income countries, HIV contributes to food

insecurity and malnutrition and has consequences for entire

communities and societies, with the potential to signifi cantly

slow down economic development. Livelihoods are disrupted

as PLHIV lose the ability to work, which exacerbates food in-

security, and they and their families are oft en excluded from

informal safety nets because of the stigma associated with

the disease.

Food insecurity frequently places people, especially wom-

en and girls, in situations that make them more vulnerable

to transmission. It can lead to behaviors that have negative

consequences, such as selling assets, removing children from

school, migrating and engaging in transactional sex. These

behaviors exact a substantial price in the long term, including

increased exposure to HIV. Mitigating food insecurity can,

therefore, contribute to a reduction in the risk of transmission.

All these elements highlight the importance of appropriate

policy and programs to ensure the integration of food and

nutrition in HIV and co-infection program design and imple-

mentation, with reference to the related reality that eff ective

food and nutrition security programming must also be

HIV-sensitive.

All aspects of UNAIDS work are directed by the following guiding principles:

> aligned to national stakeholders’ priorities;

> based on the meaningful and measurable involvement of

civil society, especially people living with HIV and

populations most at risk of HIV infection;

> based on human rights and gender equality;

> based on the best available scientifi c evidence and

technical knowledge;

> promoting comprehensive responses to AIDS that integrate

prevention, treatment, care and support; and

> based on the principle of non-discrimination.

To access the UNAIDS Strategy 2011-2015, go to

www.unaids.org/en/strategygoalsby2015/

Economic growth, which many assume has a natural positive

impact on nutritional status through increased incomes and

food expenditures, has not translated into improved nutrition

in a number of developing countries. Considering this discon-

nect, IFPRI has released an important paper entitled “The

nexus between agriculture and nutrition – Do growth patterns

and conditional factors matter?” This seeks to provide an

overview of the complex and dynamic relationship between

nutrition and growth, examine how diff erent growth

patterns lead to diff erent nutritional outcomes, and identify

the factors that infl uence the magnitude of this relationship.

It aims to off er researchers insights on areas for future re-

search and analysis and to provide policymakers with

knowledge regarding potential development strategies and

investment policies that will increase the likelihood of

positive nutritional outcomes.

As globally we try to break down the individual silos that

nutrition and agriculture have built and functioned within,

and in light of the growth of the Scaling Up Nutrition (SUN)

movement, this paper is important. It will hopefully lead to

many meaningful discussions and, more importantly, agricul-

tural growth that leads not only to increased production and

reduced poverty, but also to improved nutrition.

The paper can be accessed at www.ifpri.org/publication/

nexus-between-agriculture-and-nutrition-0

International Food Policy Research Institute – Making the Link between Agriculture07trition07

ure of Food and Farming: Challenges08ices for Global Sustainability0887SIGHT AND LIFE | VOL. 25 (1) | 2011 WHAT'S NEW

The report is comprehensive and covers

fi ve specifi c challenges:

1. Balancing future demand and supply sustainably, and

ensuring that food is aff ordable;

2. Ensuring adequate stability in food supplies, and protecting

the most vulnerable from any volatility that does occur;

3. Achieving global access to food, and an end to hunger;

4. Managing the contribution of the food system to the

mitigation of climate change; and

5. Maintaining biodiversity and ecosystem services while

feeding the world. The report emphasizes the need to build

in greater resilience to future food price shocks, highlights

the vulnerability of the global food system and is a must-

read for anyone interested in the food system.

The fu ll report and executive summary can be found at

www.bis.gov.uk/foresight/our-work/projects/current-projects/

global-food-and-farming-fu tures/reports-and-publicationsThe UK Government Offi ce for Science recently published

the Foresight Project Global Food and Farming Futures report,

which provides an overview of the evidence and discusses

the challenges and choices for policy makers pertaining to all

aspects of the global food system. The impetus for the devel-

opment of the document was the question of how to balance

the competing pressures and demands on the global food

system. The project brought together evidence and expertise

from a wide range of disciplines across the natural and social

sciences to assess what might enable or inhibit future change.

88 WHAT'S NEW

Global food prices rose to a fresh high in February 2011 –

the eighth consecutive month of rising prices. Averaging

236 points, prices were up 2.2% from January and were the

highest since January 1990, the inception date of the index.

With the exception of sugar, the prices of all other

commodity groups monitored registered gains in February,

with dairy products and cereals climbing the most. The

Food and Agriculture Organization of the United Nations

(FAO) index measures monthly price changes for a food bas-

ket composed of dairy, meat and sugar, cereals and oilseeds.

With the current global unrest and recent natural

disasters, it is unclear where prices will go in 2011. This is

cause for real concern, especially given that the last crisis

pushed 100 million additional people into hunger and, in ad-

dition, that rising food prices have the greatest impact on poor

countries, where food and energy are people’s major

spending focus.

To monitor the index, visit

www.fao.org/worldfoodsituation/wfs-home/foodpricesindex/en/

0 rices 09Rise Yet Again …in …09

The Hungrier the Louder

Rat

es o

f ce

real

sel

f-su

ffic

ien

cy (

in %

)

Weighting of food in calculation of inflation (in %)

Source: Challenges, March 3,2011

0

10 20 30 40 50 60

250

200

150

100

50

South Africa Turkey

Tunisia

Morocco

Albania

Egypt

GeorgiaArmenia

JordanAlgeria

Russia

Kazakhstan

Ukraine

Belarus

Israel

TunisiaThe government announced a rise of

6 % of the food prices in 2010, which bears

little relation to the reality experienced by

the population

MoroccoThe country lays out an agricultural

system which makes it a little less fragile

than its neighbors’

AlgeriaNational production covers only

14% of annual cereal requirements

EgyptFood price rises make up 55% of

overall increases - a burden for families

on modest incomes

89SIGHT AND LIFE | VOL. 25 (1) | 2011 WHAT'S NEW

With nutrition gaining more visibility at all levels inter-

nationally, regionally and nationally, the USAID Nutrition

Update 2010 is an important resource. The 36-page document

provides information on nutritional status, anemia status,

breastfeeding, the introduction of solid, semi-solid or soft

foods, minimum dietary diversity, minimum meal frequency,

minimum acceptable diet, women’s dietary diversity, and

micronutrient supplementation among pregnant and postpar-

tum women and infant and young children (less than

fi ve years).

With the exception of reported data on Guatemala (which

comes from the 2008-09 Encuesta Nacional de Salud Materno

Infantil (ENSMI), a Regional Health Survey), the study

summarizes data from the results of Demographic and Health

Surveys (DHS) providing population level estimates of key

nutrition indicators and carried out between 2003 and 2009

in 35 countries in Sub-Saharan Africa, South/Southeast Asia,

Latin America, and the Caribbean. The majority of these

countries are among those identifi ed in the 2008 Lancet

Series on Maternal and Child Nutrition as having the greatest

burden of undernutrition. All the data presented in this docu-

ment were re-run for comparative purposes and thus some

numbers in the report might not be an exact match with the

DHS fi nal country reports.

The English document is available at

www.measuredhs.com/pubs/pdf/NUT4/NUT4.pdf

Launches Valuable Resources:10n Update 2010 10

90 WHAT'S NEW

WHO Launch a Set of Recommendations on rketing of Food and Non-Alcoholic Beverages12dren12

According to the WHO, non-communicable diseases

(NCDs) represent a leading threat to human health and socio-

economic development. Eighty percent of NCD deaths occur

in low- and middle income countries. And, while deaths

from NCDs primarily occur in adulthood, the risks associated

with an unhealthy diet begin in childhood and build up

throughout life.

“The already heavy burden caused by NCDs, along with the

fact that the majority of these deaths are premature and

could be averted, provide a strong public health and policy

imperative to act,” states Dr Ala Alwan, the Assistant Director-

General Non-communicable Diseases and Mental Health of

the WHO, in the foreword to a new WHO publication entitled

“Set of recommendations on the marketing of food and non-

alcoholic beverages to children.”

A2Z: The USAID Micronutrient and Child Blindness

Project consolidates, builds, and expands on USAID’s long-

term investment in micronutrients, child survival, and nutri-

tion. Food fortifi cation is viewed by A2Z as an important strat-

egy in achieving its goal and focus countries have included

Bangladesh, Cambodia, the ECSA region, India, Nepal,

Philippines, Tanzania, Uganda and the West Bank. A2Z have

provided technical assistance to the Palestinian Authority in

order to increase the provision of essential micronutrients

in the Palestinian diet, thereby reducing the risk of micronu-

trient defi ciencies in the West Bank.

In line with this, it recently released fi ve publicationsfocused on the West Bank:

> Determining the Dietary Patterns and Biochemical

Markers among Women and Children in Hebron

and Gaza City

> The Demand for Locally Manufactured

Complementary Food Products among Palestinian

Caregivers

> Manual of Methods for Determining Micronutrients

in Fortifi ed Foods

> Inspection Manual for Monitoring Salt and

Flour Fortifi cation

> Analysis of Inspection Results from Salt and

Wheat Flour Samples

All fi ve publications are available at

http://a2zproject.org/node/89

A2Z: The USAID Micronutrient and Child Blindness Project Releases Five New Publications

ed to Support Food Fortifi cation Eff orts 11West Bank11

91SIGHT AND LIFE | VOL. 25 (1) | 2011 WHAT'S NEW

This review by Aamer Imdat and coworkers includes 43

randomized trials representing 215,633 children and shows

that giving vitamin A capsules to children aged six months

to fi ve years can reduce death and some diseases. The results

of 17 of the studies have been summarized and indicate that

vitamin A reduces the overall risk of death by 24%. Death due

to measles, respiratory infections or meningitis was not spe-

cifi cally reduced, but vitamin A could reduce new occurrences

of diarrhea and measles. When people took very large doses

of vitamin A, they were more likely to vomit within two days.

In the author’s opinion, given the evidence that vitamin

A supplementation (VAS) causes a considerable reduction

in child mortality, further placebo-controlled trials of VAS

in children between six months and fi ve years of age are not

required. There is, however, a need for further studies that

compare diff erent doses and delivery mechanisms (for exam-

ple, fortifi cation). In addition, as the eff ects of VAS on relevant

pathogens and disease pathways are not well understood,

these could be further researched, together with the elucida-

tion of the relationship (if any) between vitamin A and growth.

The reviewers also give implications for practice, given

that national and regional programs of VAS are in place

in over 70 countries worldwide and may be among the most

cost-eff ective public health interventions. As more than

190 million children are vitamin A defi cient around the

globe, a reduction in their risk of mortality by 24% could save

almost 1 million lives a year. These interventions respond

to an immediate need for adequate nutrition; however, they

are not ideal long-term solutions to the underlying problem.

Fortifi cation, food distribution programs and horticultural

Considering that it is estimated that in 2010 more than

42 million children under the age of fi ve years were over-

weight or obese, of whom nearly 35 million were living

in developing countries, these recommendations are timely.

Their purpose is to guide eff orts by UN Member States in

designing new and/or strengthening existing policies on

food marketing communications to children.

The recommendations can be accessed in a number of

languages fr om www.who.int/dietphysicalactivity/publications/

recsmarketing/en/

developments may provide more permanent relief.

Furthermore, if vitamin A reduces mortality by preventing

measles, widespread vaccination will reduce the relative

contribution of vitamin A supplementation. Until such long-

term solutions are in place, supplementation should continue.

The researchers also recommend that, as access to vitamin A

increases, it will be important to continue to identify at-risk

groups and deliver supplements to them. They strongly rec-

ommend vitamin A supplementation to children under fi ve in

areas at risk of VAD. The exact nature of how these programs

should be structured and administered – the dose, frequency,

and duration of intervention – is less certain. The researchers

also suggest that VAS for pregnant and lactating mothers and

other eff orts to promote the delivery of vitamin A (such as

increased rates and duration of breastfeeding) may require

further attention.

Finally, it is worth noting that two additional Cochrane

reviews recently investigated the eff ects of vitamin A during

the neonatal period (infants aged one to six months) and will

be available shortly.

For the fu ll review, go to

http://onlinelibrary.wiley.com/o/cochrane/clsysrev/articles

CD008524/fr ame.html

A Cochrane Review of Vitamin ASupplementation for Preventing Morbidity and

y in Children from Six Months13Years13

92 WHAT'S NEW

ns New York Academy 15nces’ Nutrition Council15

The Cochrane Collaboration was recently accepted as a

Non-Governmental Organization in Official Relations with the

World Health Organization (WHO). In formalizing the relation-

ship with the WHO, the Collaboration has been awarded a

seat as an observer at the World Health Assembly, allowing

the Cochrane Collaboration to provide input on WHO health

resolutions and formalizing the communications between

the two bodies.

The partnership will allow the Cochrane Collaboration to

significantly influence the way research evidence is created

and used by the WHO, by improving the collection of reliable

health information and promoting intersectoral collaboration

and high-quality research to produce the necessary evidence

to ensure policies in all sectors contribute to improving

health and health equity.

Current plans for continued partnership between the

Cochrane Collaboration and the World Health Organization

include the development of the WHO e-Library of Evidence

for Nutrition Actions (eLENA). Cochrane contributors have

identified relevant Cochrane Reviews and are updating or

conducting new Cochrane Reviews in response to the WHO’s

priorities. This process will facilitate the development of

sound, evidence-informed guidelines on nutrition issues

relevant to WHO Member States and other partners.

For more information on the Cochrane Collaboration, visit

www.cochrane.org

DSM, of which Sight and Life is the humanitarian initiative,

officially joined the Leadership Council of the New York Acad-

emy of Sciences’ Global Nutrition Science Research Initiative

during the Academy’s gala dinner. DSM is the only food ingre-

dient company to be among the more than 20 organizations

coming from government, academia and the non-profit and

private sectors that comprise the Council.

This landmark move will bring together the best scientific

research and development competences available on nutri-

tion to address global hidden hunger in rich and poor coun-

tries alike. In collaboration with the World Health Organiza-

tion, this initiative will shape the global nutrition science

research agenda and facilitate a multi-sector action plan. The

objective is for this body of research to be used to help donor

countries, development organizations, and governments

to design and implement more effective nutrition programs.

“I am excited and honored to be part of such an ambitious and

one-of-a-kind initiative and [to have] the opportunity to work

with such a prestigious group of experts,” commented

444444444ne Collaboration Joins 14ld Health Assembly14

From left to right: Manfred Eggersdorfer, Michael Burney,

Jim Hamilton, Bruce Cogill, Grace Xu, Hugh Welsh, Jim Elliott

and Jon Peters

93SIGHT AND LIFE | VOL. 25 (1) | 2011 WHAT'S NEW

CeSSIAM – Center for Studies of y Impairment, Aging and Metabolism16tes 25 Years16

CeSSIAM began in Guatemala as a non-profi t organization

dedicated to nutrition research and education and has as its

mission the improvement of human health and well-being in

underprivileged societies through better nutrition. It works

in partnership with the Hildegard-Grunow-Foundation for

Nutrition Research (HGF) and the Nevin Scrimshaw Interna-

tional Nutrition Foundation (INF). The current Executive and

Scientifi c Director is Dr Noel Solomons, who was awarded the

National Science and Technology Medal for 2010 in recogni-

tion of his scientifi c research in the area of nutrition, and its

signifi cant contribution to health in Guatemala. His research

has also had a signifi cant impact on child nutrition policies at

both national and international levels. Sight and Life has had

a long relationship with CeSSIAM and presented Dr Solomons

with a certifi cate to mark its 25th Anniversary at a celebration

at the World Public Health Nutrition Congress in Porto in

October 2010.

To fi nd out more about CeSSIAM, visit

www.hgrunowfoundation.org/cessiam

Manfred Eggersdorfer, Senior Vice President Nutrition

Science & Advocacy, DSM Nutritional Products. “The design

and implementation of successful nutrition programs requires

serious research and I hope that our work can help scientists,

governments and organizations around the world tackle one

of the most serious global health problems which, until re-

cently, has been underappreciated and oft en misunderstood.”

Klaus Kraemer presents Noel Solomons with a certifi cate

that commemorates his long-standing commitment to fi ghting

micronutrient defi ciencies

94

tional Year of Chemistry:18C Molecule on Swiss Stamp182011 having been declared by the United Nations to be

“International Year of Chemistry”, the Swiss Post has released

a special issue stamp that features a vitamin C molecule.

Synthetic vitamin C was fi rst developed by Tadeus Reichstein

in 1933 at the Swiss Federal Institute of Technology (ETH)

Zurich.

mala’s Medal of Science and Technology17ded to CeSSIAM’s Dr Noel Solomons17At their fourth regular meeting in 2010, the National Council

of Science and Technology of Guatemala (CONCYT) reviewed

the proposals for the 2010 competition for the award of the

Medal of Science and Technology, or “Medalla de la Ciencia

y Tecnología.” The medal is the highest annual recognition at

a national level for a scientist who has made a transcending

social impact.

The Guatemalan Academy of Medical, Physical and Natural

Sciences submitted a proposal for the award to go to Dr Noel

W Solomons of the Center for Studies of Sensory Impairment,

Aging and Metabolism (CeSSIAM). As a result, CONCYT deci-

ded to name Dr Solomons as the winner of this award, on the

basis of his contribution to nutrition research in Guatemala.

The medal was presented at a ceremony held in conjunc-

tion with the Congress by Dr Rafael Espada, Vice President of

the Republic of Guatemala.

WHAT'S NEW

Noel Solomons is awarded the Medal of Science

and Technology by the National Council of Science and

Technology of Guatemala

Swiss Post is commemorating the International Year

of Chemistry with a special issue stamp showing a vitamin C

molecule

Advocating better nutrition for brighter futures.

96

Comments on the Comparison of the Eff ects of Organic and Conventional Food on Health in Sight And Life 2/2010

Tsige-Yohannes Habte, Michael Krawinkel

University of Giessen, Germany

“The major health concern about

conventi onal food is its contamina-

ti on with agroch emicals”

We read the article on Organic vs Conventional Food1 in Sight And Life Magazine 2/2010 with interest. It states that the nutri-

tional quality of organic food is not diff erent fr om conventional

food, and that there is no evidence of any diff erence that might

have an impact on health. At a certain point, the argument veers

to the subject of epidemiological studies that show that a diet

high in fr uit and vegetables reduces mortality fr om cardiovascu-

lar diseases, but there is scant evidence on the eff ects of cancer.

We have no reservations about the health advantages of recom-

mended levels of fr uits and vegetables. However, the compari-

son of conventional and organic food impact on health appears

to require fu rther revision.

What is conventional food?

We understand the term “conventional food” to mean the food-

stuff s that are produced by intensive agricultural systems where

considerably improved technology, particularly in the form of

agrochemicals, is applied to enhance productivity. However, a

marked level of uncertainty about health risk still attaches to

this sort of conventional food.

When conventional food is compared with organic food, nu-

trient composition is not a major concern with regard to health

risks. Indeed, varying foodstuff s are diff erent in terms of their

composition, which is why diverse sources of nutrients are used

to balance a healthy diet. No foodstuff is complete on its own,

and diversity and complementarities are the order of nutrition.

The major health concern about conventional food is its

contamination with agrochemicals, particularly those related to

pesticides, hormones and antibiotics. A large number of studies

reveal that people consuming a conventional diet are more ex-

posed to pesticide residues than those who consume an organic

diet; some examples are cited below.

Recent studies in the US show that children fed organic diets

had signifi cantly lower exposure to organophosphorus pesticide

than children with primarily conventional diets. The median

total methyl metabolite concentration in their urine was about

six times higher for those children on a conventional diet than it

was for children on organic diets (0.7 vs 0.03 μmol/L; P=0003),

and mean concentration diff ered by a factor of nine (0.34 vs

0.04 μmol/L).2 At present, the pesticides that are most commonly

and widely used are organophosphate pesticides. They are nor-

mally eliminated fr om the body aft er three to six days, and the

detection of this compound indicates continuing exposure.

Assessments conducted on more than 90,000 samples of

20 major crops, grown organically or conventionally, indicated

that the fr equencies of residue detection and residue levels were

considerably higher in conventional than in organic foods. Con-

ventional food contained pesticide residues in more than 75%

of the cases.3 Not all of the organic foods were, however, totally

fr ee fr om pesticide residue. They were also adulterated, but to

a markedly lesser extent and fr equency than conventional food.

Most of the residues in organic foods are explained as the una-

voidable results of environmental contamination by post-pesti-

cide use, or drift (sprays blown in fr om adjacent, non-organic

farms).

97SIGHT AND LIFE | VOL. 25 (1) | 2011 LETTERS TO THE EDITOR

Pesticide exposure around the world

Human beings can be exposed to pesticides in a variety of ways,

at different dose levels, and for varying periods of time. In the

developed world, the problem of acute pesticide poisoning has

largely been controlled; major health problems arise from expo-

sure to low levels of pesticide residues in food over a long pe-

riod of time. In developing countries, however, the main health

problem arising from pesticides is that due to acute poisoning.

A minimum of 25 million agricultural workers in developing

countries suffer an episode of pesticide poisoning each year.4

It has become evident in the last few years that acute pesticide

poisoning is mainly the concern of the developing world, which

lacks appropriate protection and management mechanisms due

to low levels of awareness and inadequate infrastructures.

Exposure to pesticides can potentially affect human health.

Controlled studies on animals indicate substantial toxicologi-

cal evidence showing that repeated low-level exposure to orga-

nophosphate pesticides affects neural development and growth

in developing animals. Some of these studies indicate the im-

pairment of maze performance, locomotion and balance in neo-

nates exposed in the uterus and early in postnatal life. Possible

mechanisms leading to these effects include inhibition of brain

acetylcholinesterase, down-regulation of muscarinic receptors,

decreased brain DNA synthesis, and reduced brain weight. It is

also possible that exposure to organophosphate pesticides re-

lates to respiratory diseases in children through improper regu-

lation of the autonomic nervous system.5

Studies of the effects of pesticide exposure on children’s

health have been limited to birth defects. Several case-control

studies have associated parental exposure to pesticides or pes-

ticide use in the home with childhood brain tumors, leukemia,

lymphomas, and testicular cancer.6,7

A small number of ecological studies have examined whether

the low-level chronic exposure of children to pesticides can lead

to adverse health consequences. A study in Mexico found that

children of four to five years of age living in an agricultural valley

with presumably higher pesticide exposure had deficits when

tested for stamina, coordination, and recall, as compared to chil-

dren living in the foothills where there was mainly ranching.8

Advantages of organic food over conventional food

In general it can be said that, despite the paucity of information

concerning the potential health effects in children of chronic, low-

level exposure to pesticides, substantial evidence from rodents

and limited information from adult humans shows that chronic,

low-level exposure to pesticides may affect neurological functions,

neurodevelopment, and growth. The preference for organic food

over conventional food appears advantageous in view of the low-

er exposure to insecticide residues and minimizing health risks.

Correspondence: Michael Krawinkel,Institute of Human Nutrition, University of Giessen,

Wilhelmstrasse 20, 35392 Giessen, Germany

E-mail: michael.krawinkel@ernaehrung.uni-giessen.de

References

01. Thurnham DI. Should Organically Produced Foods be Healthier

than Conventionally Grown Foods? Sight and Life Magazine

2010;2:30–38.

02. Curl CL, Fenske RA, Elgethun K. Organophosphorus Pesticide

Exposure of Urban and Suburban Preschool Children with Organic

and Conventional Diets. Environmental Health Perspectives

2003;111:377–382.

03. Baker BP, Benbrook CM, Groth E et al. Pesticide residues in conven-

tional, IPM-grown and organic foods: Insights from three US data

sets. Food Additives and Contaminants 2002; 19:427–446.

04. Jeyaratnam J. Acute Pesticide Poisoning: A Major Global Health

Problem. World Health Statistics Quarterly 1990:43:139–144.

05. Eskenazi B, Bradman A, Castorina R. Exposure of Children to

Organophosphate Pesticides and Their Potential Adverse Effects.

Environmental Health Perspectives 1999;107:409–419.

06. Blair A, Zahm SH, Pearce NE et al. Clues to cancer etiology from

studies of farmers. Scand J Work Environ Health 1990;18:209–215.

07. Buckley JD, Robison LL, Swotinsky R et al. Occupational exposure

of parents of children with acute nonlymphocytic leukaemia: a

report from the Children’s Cancer Study Group. Cancer Research

1989;49:4030–4037.

08. Guillette EA, Meza MM, Aquilar MG et al. An anthropological

approach to the evaluation of preschool children exposed to pesti-

cides in Mexico. Environ Health Perspect 1998;106:347–353. “Chronic, low-level exposure

to pesticides may affect neurological

functions, neurodevelopment,

and growth”

98

More than a decade has passed since the fi rst edition of

Folate in Health and Disease was published. During this time,

there have been thousands of new research studies related to

folate and its link to disease and birth defect risk, thus pro-

viding the impetus for an updated interpretation of this large

body of scientifi c evidence. The public health implications

of these new fi ndings are enormous; therefore, the second

edition bridges basic science with clinical medicine and

public health.

The fi rst chapters provide background knowledge related

to folate chemistry, metabolism, bioavailability, and the infl u-

ence of genetic polymorphisms. Folate’s role in reproduction

and birth defect prevention is then reviewed, followed by a

separate chapter in which epidemiological evidence linking

specifi c birth defects and folate status is evaluated. Chronic

disease is covered in a similar manner to that of birth defects.

The interrelationships between folate and other nutrients

required for normal one-carbon metabolism are then covered

in several chapters, and the biochemical and clinical rami-

fi cations of alterations in status are highlighted. The inter-

action between folate and vitamin B₁₂ is addressed from a

biochemical and public health perspective. The complexities

of diagnosis and treatment of a clinical folate defi ciency are

discussed, followed by a related chapter on the eff ect of

alcohol on folate and methionine metabolism. Choline is

covered in a separate chapter.

Dietary intake recommendations for select countries world-

wide are compared with an overview of the approaches used

by the Institute of Medicine’s committee to estimate the

Dietary Reference Intakes. Changes in folate status over time

within the US population are a focus of this chapter, with

attention given to the infl uence of folic acid fortifi cation and

supplement use on folate status. Estimated dietary folate in-

takes for the US population and specifi c population subgroups

are presented.

For more information, please visit

http://www.routledge.com/books/details/9781420071245/

Folate in Health and Disease 2nd Edition

Editor’s note: Sight and Life reviews recent publications which

may be of particular interest to our readers. However, no publi-

cations other than Sight and Life publications are available fr om

us, nor do we have any privileged access to them.

99SIGHT AND LIFE | VOL. 25 (1) | 2011 PUBLICATIONS

Because carotenoids are widely consumed and their con-

sumption is a modifi able health behavior (via diets or supple-

ments), health benefi ts for chronic disease prevention, if real,

could be very signifi cant for public health.

This book spans the breadth of ongoing work by research-

ers around the world, ranging from basic studies to advanced

applied biomedical research. As in many fi elds of research,

new tools and techniques for measuring carotenoids in vari-

ous systems are critical to support research progress. Several

chapters discuss new methodologies to measure carotenoids,

carotenoid metabolites/radicals, or carotenoids in vivo in

complex biological systems, especially in the human eye. Oth-

er chapters describe the oxygenase enzymes that are essential

components of carotenoid metabolism to active metabolites.

How carotenoids behave

Carotenoids are highly lipophilic: an active area of research

concerns how carotenoids interact with and aff ect membrane

systems. Also, the lipid solubility of these compounds has

important implications for carotenoid intestinal absorption:

models such as the Caco-2 cell model are being used to con-

duct detailed studies of carotenoid absorption / competition

for absorption. The lipid solubility of these carotenoids also

leads to the aggregation of carotenoids. Carotenoids aggregate

both in natural and artifi cial systems, with implications for

carotenoid excited states. This in turn has implications for a

new indication for carotenoids, namely, serving as potential

materials for harnessing solar energy.

In summary, the amazing breadth and depth of research

in carotenoids are reasons why it draws investigators to this

fascinating fi eld of research. The research spans the con-

tinuum from detailed studies of the roles of photoprotective

carotenoids in plants to the potential application in the pre-

vention of disease in humans. This is translational research

at its best and I commend the editor, Dr John Landrum, for

assembling such an interesting and informative collection of

current research.

Reviewed by

Susan T Mayne Yale University School of Medicine

For more information, please visit

http://www.routledge.com/books/details/9781420052305/

Carotenoids A Colorful andTimely Research Field

100 PUBLICATIONS

Omega-3Fatty Acids and the DHA Principle

The physical and chemical properties of the omega-3

fatty acid DHA (docosahexaenoic acid) enable it to facilitate

biochemical processes in the membrane. This eff ect has

numerous benefi ts, including those involved in the growth

of bacteria, rapid energy generation, human vision, brain im-

pulse, and photosynthesis, to name but a few. However DHA

also carries risks that can lead to cellular death and disease.

Omega-3 Fatty Acids and the DHA Principle explores the

roles of omega-3 fatty acids in cellular membranes, ranging

from human neurons and swimming sperm to deep sea

bacteria, and develops a principle by which to assess their

benefi ts and risks.

The DHA Principle states that the blending of lipids to

form cellular membranes is evolutionarily honed to maximize

benefi t while minimizing risk, and that a complex blending

code involving conformational dynamics, energy stress,

energy yield, and chemical stability underlies all cellular

membranes.

Understanding the code

This book lays the groundwork to understanding this code.

It examines the evolution of DHA and the membrane, and

explores the general properties of omega-3s and other

membrane lipids. It then focuses on cellular biology before

shift ing to a practical discussion on applications. The

authors discuss the DHA Principle as applied to petroleum

degradation, winemaking, global warming, molecular farming,

aging, neuro-degenerative diseases, and the prevention of

colon cancer.

A refl ection on the increased public interest to have

emerged over the years, this volume uses an integrative

approach to explain the complex roles of omega-3s in

the membrane. Incorporating principles from chemistry,

cellular biology, evolution, and ecology, this work gives

researchers in a variety of fi elds the building blocks to

stimulate further study.

For more information, please visit

http://www.routledge.com/books/details/9781439812990/

101SIGHT AND LIFE | VOL. 25 (1) | 2011 PUBLICATIONS

TALC (Teaching Aids at Low Cost) is a unique charity provid-

ing and developing educational material which promotes

the health of children and advanced medical knowledge and

teaching in the UK and throughout the world.

The organization was founded in 1965 by David Morley

when he was lecturer at the Institute of Child Health, in re-

sponse to many requests from overseas students for teaching

equipment to use in their own countries.

TALC believes good health provision should be available

to all – especially those in the poorest communities in Africa,

Asia, and Latin America – and has been working for over

40 years to achieve this. They currently supply over 10,000

health workers with health materials, ranging from text books

and videos to CDs and weight charts.

Below is a list of nutrition books, CD-ROMs and accessories

available from TALC, as recommended by Ann Burgess

and Marko Kerac (* indicates the book is available in other

languages besides English).

> Community Nutrition: a handbook for health and develop-

ment workers; 2009 Burgess, Bijlsma & Ismael; £5.50.

> Infant and Young Child Feeding – model chapter for

textbooks for medical students and allied health

professionals; 2009 WHO; £1.30.

> Caring for Severely Malnourished Children; 2003

Ashworth & Burgess; £4.10 (also available at the same price

as a PDF download).

> Sight And Life Manual on Vitamin A Defi ciency Disorders

(VADD); (2nd ed 2001) Sight And Life; £1 (*French, Spanish).

> The Politics of Breastfeeding (3rd edition);

2009 Palmer; £7.70.

> Protein-Energy Malnutrition; 2006 Waterlow; £7.50.

> Hospital Care for Children – Guidelines for the

Management of Common Illnesses with Limited

Resources; 2005 WHO; £4.50 (*French, Russian).

> ABC of Nutrition (4th edition); 2003 BookPower; £6.00.

> Nutrition for Developing Countries (2nd edition);

1993 Savage King & Burgess; £12.00.

> Community Nutrition CD-ROM; TALC 2006. Free to health

professionals who have limited access to the internet,

Community Nutrition is a new CD-ROM

containing hundreds of nutrition resources including

manuals, training courses, academic papers, briefs,

practical guidelines, pictures, presentations, and a video.

> Topics in International Health – Nutrition CD-ROM;

2000 Wellcome Trust; £5.00. Twelve interactive tutorials

that provide an illustrated introduction to the causes,

epidemiology, treatment, and prevention of malnutrition

in developing countries.

> e-TALC Health Development CD-ROMs. The e-TALC project

provides a reliable and regular source of free health

information, aimed at healthcare workers in developing

countries who have no or limited access to the internet.

Small colored insertion tape (MUAC); 115mm; £0.25.

> Hemoglobin color scale; £24.00. A simple device

for estimating hemoglobin, for use when laboratory

hemoglobinometry is not available.

TALC is based in the UK. To order any of these items, visit

http://www.talcuk.org/index.htm or e-mail info@talcuk.org or call

+44 (0)1727 853869. Prices do not include postage

If you know of any other recent, good value nutrition-

related books that TALC might add to its catalogue, please

let them know.

Nutr iti on Books Available fr om TALC Valuable for Nutrition Practitioners and Trainers

Sharing knowledge for improved nutrition.

ImprintSight and Life Magazine

Incorporating the

Xerophthalmia Club Bulletin

Publisher: Sight and LifeEditor: Klaus Kraemer

Editorial team:

Jee Rah, Anne-Catherine Frey,

Svenia Sayer-Ruehmann,

Jane Badham

Communication consultancy

and text writing:

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Layout and graphics:

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Opinions, compilations

and figures contained in

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the point of view of

Sight and Life and are

solely the responsibility

of the authors.

Photo credits

cover: Mike Bloem

Photography

page 4,5: Mike Bloem

Photography

page 11,17: Mike Bloem

Photography

page 64,66:

Neil Palmer (CIAT)

page 85: UNAIDS

Sight and LifeDr Klaus Kraemer

Director

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Phone: +41 (0) 61 815 8756

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Building bridges for better nutrition.