SIGHT AND LIFEMagazine Issue No 2/2009

Face-changer at 2nd Micronutrient Forum, Beijing

2nd International Meeting of the Micronutrient Forum – Micronutrients,Health and Development: Evidence-Based Programs

The 2nd International Meeting of the Micronutrient Forum, held in Beijing, China, fromMay 12–15, 2009, brought together delegates from more than 90 countries, includingcountry-level program implementers and their partners, multi-laterals, donors,researchers, and representatives of the private sector. Read from the Forum on pages25, 34 and 57

Carotenoids, Retinoids andMetabolic Syndrome

Good Start in Life Program in Peru

Filling the Gaps in Maraland

Iodized Salt Use in Pakistan

Micronutrient Forum: Executive Summary

Micronutrient Forum: Concluding Remarks

CARIG Conference

UGAN Conference

A Day in the Life

Selenium

News

Letters to the Editor

Publications

ContentsSIGHT AND LIFE

Correspondents

William S Blaner Martin BloemGeorge BrittonIan Darnton-HillOmar DaryFrances R DavidsonJohn W Erdman JrPhilip Harvey

Richard F HurrellRolf DW KlemmDonald S McLarenRegina Moench-PfannerChristine Northrop-ClewesNoel W SolomonsFlorentino S SolonAlfred Sommer

David I ThurnhamAndrew TomkinsEmorn WasantwisutKeith P West JrYu XiaodongChittaranjan SYajnikMichael B Zimmermann

2

Contents

Editorial 4

Carotenoids, their Retinoid and Non-Retinoid Metabolites and the Metabolic Syndrome 6

Nutritional Impact of the Good Start in Life Program (Buen Inicio) in Peru 16

Filling the Gaps in Maraland 20

Iodized Salt Use in Pakistan 23

Micronutrients, Health and 25Development: Evidence-Based Programs2nd Micronutrient Forum

Leaving the Chrysalis Behind 342nd Micronutrient Forum

Annual CARIG Conference 37

Carotenoids, their Retinoid and Non-Retinoid Metabolites and the MetabolicSyndromeThis article provides a brief overview of recentresearch on potential linkages between vitamin Aand carotenoid nutrition, and metabolism and com-ponent diseases of the metabolic syndrome. 6

Nutritional Impact of the Good Start inLife Program (Buen Inicio) in PeruExternal evaluation of the program reported adecreased prevalence of stunting, anemia and vita-min A deficiency in children less than three yearsof age in the Andean highlands and the Amazonforest. 16

Magazine Issue 2/2009Contents

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Selenium – Some Notes on ImmuneFunction and Recent Cancer TrialsThe photo is from Keshan in China where the first case of selenium deficiency was identified.The article describes the role of selenium inimmune function and implications for cancer prevention. 49

Uganda Action for Nutrition Society(UGAN) Conference 40

Too Much – Too Little 42Wageningen Nutritional Sciences Forum

A Day in the Life of Marc Van Ameringen 45

Selenium – Some Notes on ImmuneFunction and Recent Cancer Trials 49

NewsMicronutrient Forum Provides NewPlatform for Public Private Partner shipsand the Development of SustainableSolutions Fighting Hidden Hunger 57

Nutritional Education Should Be on the Table 58

Ukraine Government and NGOsCommitted to Fighting Malnutrition 60

Letters to the Editor 61

Publications 65

Micronutrients, Health and Develop -ment: Evidence-Based ProgramsThe 2nd International Meeting of the MicronutrientForum took place in Beijing in May and was an excellent opportunity for knowledge sharingamong scientists, programmers and policy -makers. 25

SIGHT AND LIFE Editorial

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Nutrition Security as a Cornerstone of Recovery,Renewal and Resilience

Inflationary food prices, a global economic downturn,and climate change – this confluence of ills is worsen-ing the plight of the world’s most vulnerable populations, and exacerbating long-term inequities infood and health. The immediate as well as long-termeffects of these crises are compromising the diet andhealth of up to 80% of the population in most develop-ing countries, and places at risk the future health andintellectual abilities of an estimated 250 million infantsand unborn children (-9–24 months of age).

We have clear evidence that high food prices have adirect impact on household consumption in developingcountries. As a strategy to cope with higher costs (andreduced incomes due to localized economic declines),most households reduce the diversity and nutritionalquality of their diet by including fewer animal-sourcefoods, fruits, processed foods, and vegetables to main-tain portions of staple foods, such as rice. Eventually,the quantity of food consumed is also reduced as theirfood stocks and purchasing power decline without animprovement of their income or a reduction of foodprices. Poor households that already spend 50–80% oftotal expenditure on food are hit hardest. The impact ofmacronutrient malnutrition from reduced quantities offood consumed is dramatically visible, often havingreached a severity that draws attention to seriouslyacute conditions too inhumane for us to ignore.

However, the impact of micronutrient malnutrition –which invisibly lurks in far more people within anacutely distressed or chronically deprived population –from reduced quality of food consumed may be felt fordecades. Of particular concern is the negative impact ofvitamin and mineral deficiencies on young child devel-opment, given that the period from conception until 24 months of age irreversibly shapes a person’s healthand intellectual ability. Left unaddressed, micronutri-ent-deficient children may grow up unable to reachtheir full intellectual, physical and economic potential –a lost generation that will be the legacy of inaction orineffective action today.

The Second Meeting of the MicronutrientForum in Beijing thispast May underscoresthe fact that we haveaccumulated a wealthof knowledge and ex perience from decades of researchand programs to chart the most effective courses ofaction to address the global nutrition crisis, based onrigorous evidence of what works. The processes origi-nating in Innocenti, Italy, are taking us further towardsmarter ways of managing the complex web of know-ledge and know-how needed to better coordinateefforts, and lead to efficiencies of action and cost. Akeystone of this smarter strategy in tackling global mal-nutrition is the renewed emphasis on public-privatepartnerships during this Micronutrient Forum, whichwitnessed a breakthrough in the history of the Forumand its progenitors as prominent leaders of industrycommitted to the shared goals of working toward aworld without hunger, hidden and otherwise.1

The mindshare on nutrition did not end there as the fol-lowing month of July saw the leaders of the Group ofEight (G8) leading economies convene at the group’slatest Summit in the earthquake-ravaged town ofL’Aquila in Italy. The world has indeed been (some-times violently) shaken by the interlocked crises of highfood prices, economic decline, and climate change inrecent years, which made L’Aquila a fitting metaphorand setting for these key global decision makers to dis-cuss measures for addressing these and related issues.They issued a joint statement2 recognizing the prob-lems and needs relating to ensuring global food securi-ty, and pledging additional billions to this cause –based, in no small measure, on the advocacy of USPresident Barack Obama. While many of our col-leagues in the development and humanitarian fielddecry the ambiguity of the pledges, which have all toooften been left unhonored, and are impatient (as Prof.Al Sommer rightly encourages in his remarks at theMicronutrient Forum, p34) to see these leaders put theirmoney where their mouths are, it is perhaps useful tosee this as a step – albeit a small one – in the rightdirection, given the recognition afforded to “nutrition,”which appears five times in the text of the G8 foodsecurity statement (six, if you count “malnutrition”).

Welcome

SIGHT AND LIFE Magazine 2009;2:4–5

Magazine Issue 1/2009Editorial

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Also in July 2009, the U.S. National Academy ofSciences’ Institute of Medicine (IOM) convened athree-day workshop, Mitigating the NutritionalImpacts of the Global Food Price Crisis3, exploring theimplications of the global food price increases and eco-nomic crisis on nutrition and health. The discussionfocused on key topics, including nutrition surveillance,responses to the crises on individual country and glob-al levels, US policies relevant to the crises, and actionsto mitigate the current crises as well as prevent futurecrises. International participants included eminentspeakers from the Chicago Initiative on GlobalAgricultural Development, World Bank, UN TaskForce on Global Food Security Crisis, EmoryUniversity, Roadmap to End Global Hunger, CornellUniversity, IFPRI, and the University of Chile andLondon School of Hygiene and Tropical Medicine.

Several of the individuals from the above-mentionedinstitutions are also featuring in an upcoming supple-ment to the Journal of Nutrition, sponsored by SIGHTAND LIFE, on the impact of the interlocked crises onnutrition. This supplement further underscores thestrength of institutional partnerships across the public,private and nonprofit/academic sectors, allowing thekey messages on the problems of and solutions to hid-den hunger to be voiced consistently and compellinglyacross communicators and target audiences. At theheart of these messages is the insight that investmentsin nutrition are among the most cost-effective develop-ment actions because of the very high benefit-to-costratios; these not only benefit the individual, they alsosupport the sustainable growth of nations because theyprotect health, prevent disability, boost economic pro-ductivity and save lives.

Moving forward, let’s keep up the momentum by echo-ing the call for Nutrition Security to be a cornerstoneof efforts for Recovery (from the multiple crises),Renewal (of commitments by all stakeholders to assistthe most vulnerable among us), and Resilience (of ourclosely-integrated food, energy, social, economic, eco-logical, and related systems).

This edition of the Magazine also features an executivesummary of the Micronutrient Forum (p25) as well asProf. Sommer’s aforementioned concluding remarks.The full report will be released as a supplement toSIGHT AND LIFE Magazine, Issue 3/2009. Thisyear’s James A Olson Memorial Perspectives onCarotenoids Lecture was given by William Blaner dur-ing the annual CARIG Conference in New Orleans,providing an overview on the potential role ofcarotenoids and retinoids in metabolic syndrome (p6).We would also like to draw your attention to the nutri-tional impact of the Good Start in Life Program in Peru(p16), and an article on selenium and its immune sys-tem and anti-cancer properties (p49).

With best regards

1 Private Sector Declaration for download at

http://www.sightandlife.org/images/stories/pageimages/content/News/bei-

jing%20joint%20declaration.pdf2 Available for download at

http://www.g8italia2009.it/static/G8_Allegato/LAquila_Joint_Statement_

on_Global_Food_Security[1],0.pdf3 Catch the webcast highlights from this workshop at

http://globalhealth.kff.org/Multimedia/2009/July/14/gh071409video.aspx

SIGHT AND LIFE James A Olson Memorial Lecture

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Introduction

The diseases that compose themetabolic syndrome are now amajor public health concern in thedeveloped world. The metabolicsyndrome is a complex of risk fac-tors linked to excessive bodyweight and obesity, that when pres-ent, increases one’s risk for bothcardiovascular disease and type IIdiabetes mellitus (T2DM) as wellas other health complications.1

These risk factors include abdomi-nal obesity, atherogenic dyslipi-demia, hypertension, insulin resist-ance, inflammation, and prothrom-botic states. The populations ofmany developing countries areexperiencing increasing incidenceof the metabolic syndrome.2 Thisincreased prevalence of the meta-bolic syndrome in developing coun-tries has been attributed to in-creased urbanization, nutrition transi-tion, reduced physical activity, andaggressive community nutritionintervention programs for under-nourished children.2 The molecularevents that underlie the pathogene-sis associated with the metabolic

syndrome are now the subject of anextensive research effort aimed atdeveloping therapeutic interven-tions to combat this growing publichealth concern. Some of thisresearch effort is focused on estab-

lishing linkages between vitamin Aand carotenoid nutrition and metab-olism and the component diseasesof the metabolic syndrome. Thisarticle will provide a brief overviewof this research.

Carotenoids, their Retinoid and Non-Retinoid Metabolites and theMetabolic SyndromeJames A Olson Memorial Perspectives on CarotenoidsLecture 2009

Jian Zhang Yang and William S Blaner Department of Medicine, Columbia University, New York, USA

Correspondence: Jian Zhang Yang, Department of Medicine, Collegeof Physicians and Surgeons, Columbia University, 650 W. 168th St.,New York, NY 10032, USAEmail: jzy2103@columbia.edu

SIGHT AND LIFE Magazine 2009;2:6–15

Figure 1: Scheme for the metabolism and actions of retinoids with-in the body. It has long been believed that all retinoidactions within the body, aside from those involved invision, involve regulation of retinoic acid-responsive geneexpression through the RARs and RXRs. However, agrowing body of published evidence now suggests thatretinol, retinal and retinoic acid have other importantphysiological actions in the body.

DIETDIET

RetinylEsters

Retinol Retinal Retinoic Acid

β-CaroteneDIETELIMINATION

OxidizedRetinoids

Storage inlipid droplets

Transported in bloodbound to retinol-binding protein (RBP)

CMO1

11-Cis-retinal is the chromophore forrhodopsin and is required for vision

All-trans- and 9-cis-retinoic acid aretranscriptionally active retinoids that respectively act through the 3 retinoic acid respectors (RARs) and 3 retinoid X receptors (RXRs).

> 500 genes regulated by retinoic acid

?

.

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Within the modern biomedical research literature, vita-min A and its metabolites are now referred to collec-tively as retinoids. Retinoids have been consistentlylinked to conditions associated with the metabolic syn-drome. Because many developing countries are cur-rently administrating vitamin A supplementation pro-grams, it is important to tease out the role of retinoidsand retinoid-related parameters in the pathophysiologyof the metabolic syndrome. Retinoids are essentialmicronutrients that must be obtained from the diet.3

There are two sources of retinoids in the diet. The firstis proretinoid (provitamin A) carotenoids, obtainedfrom dark green and colorful fruits and vegetables, andthe second is preformed retinoid, from animal productssuch as meat and dairy. Retinoids are involved in manyphysiological functions, including the maintenance ofnormal reproduction, immunity, growth, and cellularproliferation and differentiation. The active retinoidforms, all-trans- and 9-cis-retinoic acid, act as nuclearligands that activate gene transcription by binding totwo families of ligand-dependent transcription factors,the retinoic acid receptors (RARs) and the retinoid Xreceptors (RXRs). Figure 1 provides an overview ofretinoid metabolism and actions within the body. Sincemembers of the RXR family serve as partners in form-ing heterodimers with the vitamin D receptor, the thy-roid hormone receptors, the peroxisomal proliferatoractivator receptors (PPARs), and other ligand depend-

ent transcription factors, retinoids regulate a broad-spectrum of hormonally responsive genes.

Carotenoids are found abundantly in nature and may ormay not possess proretinoid activity.4 Some caro -tenoids, such as b-carotene, the primary precursor forretinoid, can be cleaved centrally to form two mole-cules of retinal, which can be subsequently reduced toretinol and then esterified for storage, or oxidized toretinoic acid in tissues requiring retinoid action (seeFigure 1). As depicted in Figure 2, carotenoids canalso undergo eccentric cleavage, giving rise to a num-ber of different apo-carotenals, which, like retinal, canundergo oxidation to apo-carotenoic acids or reductionto apo-carotenols. Though carotenoid cleavage occursprimarily in the intestinal mucosa, the liver and otherorgans can also cleave carotenoids after they have beentaken up from the diet along with other dietary fat inchylomicrons. Both central and eccentric carotenoidcleavage products have been proposed in the recent lit-erature to be associated with obesity, dyslipidemia andimpaired insulin responsiveness.

Retinoid intake influences blood triglyceride con-centrations as well as tissue triglyceride concentra-tions and metabolism

Retinoids have long been used as drugs in clinicalmedicine to treat skin diseases. Clinical experiencewith retinoids suggests that they influence fat (triglyc-eride) metabolism and insulin responsiveness.Specifically, 13-cis-retinoic acid, commonly known asAccutane or isotretinoin, has well-recognized sideeffects that include elevated serum triglyceride,5-7

cholesterol,5,7 and glycerol concentrations6 andinsulin resistance,5,6 in both human populations andanimal models. These effects are proposed to arisethrough Accutane-derived impaired clearance oftriglyceride-rich lipoproteins from the blood.7 Itshould be noted that 13-cis-retinoic acid is a naturallyoccurring retinoid that is found in all humans and inother species. The expression of apolipoprotein C-III,a gene involved in lipoprotein metabolism, and oneassociated with dyslipidemia, is reported to beincreased after Accutane administration.6 Oral admin-istration of all-trans-retinoic acid has a similar effecton serum triglyceride concentrations.8 Rodent studiesindicate that retinoids mediate these effects on serumlipid levels through RAR-activated genetic transcrip-tion, since rats given bolus doses of RAR agonists dis-played dose-dependent increases in serum triglyc-erides, which were not observed in rats given RXRagonists.9

Figure 2: Proretinoid and non-proretinoid caro -tenoids can be cleaved eccentricallythrough the actions of the eccentriccleavage enzyme CMO2 to apo-carote-nals, which can be subsequently oxi-dized to apo-carotenoic acid metabo-lites or reduced to apo-carotenol met -abolites. It has been proposed in the lit-erature that apo-carotenal metabolitesmay, like retinoic acid, possess activityfor regulating gene transcription.65Thus, it is possible that some of theactions of carotenoids in the body maybe accounted for by the actions of theapo-carotenoid metabolites.

PRORETINOID OR NON-PRORETINOID CAROTENOIDS

Transcriptionallyactive metabolites?

CMO2

Apo-carotenals

Apo-carotenoic acidmetabolites

Apo-carotenolmetabolites

SIGHT AND LIFE James A Olson Memorial Lecture

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Human population studies haveestablished associations betweendietary retinoid and carotenoidintake and the development of non-alcoholic fatty liver disease(NAFLD). In a case-control studyinvolving 138 adults, low dietaryintake of retinoids in subjects withNAFLD was one of only two differ-ing features between control sub-jects and those with NAFLD (Table 1).10 In a cross-sectionalstudy of 91 children, a trend wasobserved between inadequate serumretinoid levels and risk of NAFLDdevelopment, as determined byultrasound.11 Another study of 145obese adults reported that subjectswith NAFLD had significantlylower serum b-caro tene levels thansubjects not experiencing NAFLDand that there was a significant pos-itive association between the pres-ence of insulin resistance andretinol and b-carotene inadequacyin their subjects.12

The basic research literature, how-ever, still lacks consensus as to therole of retinoids in fatty liver devel-opment. Rodents fed a retinoid-deficient diet were reported by one

research group to display decreasedexpression of genes involved inhepatic fatty acid oxidation andincreased hepatic triglyceride accu-mulation13, but opposite findings –specifically, increased expressionof genes involved in hepatic fattyacid oxidation and decreased hepat-ic fatty acid synthesis – have beenreported by other groups.14,15

Moreover, administration of anagonist of RXR-mediated geneexpression resulted in an increasein the size and number of fatdroplets in the liver, along withincreased liver mass in geneticallydiabetic mice.16

Retinol-binding protein (RBP)may influence insulin responsiveness

Insulin resistance is one of themajor risk factors implicated in themetabolic syndrome. The serumtransport protein for retinol,retinol-binding protein (RBP, alsocalled RBP4 in the diabetes litera-ture), has become the focus ofmuch research interest. This isbecause RBP has been proposed tobe a determinant for insulin resist-

ance. Kahn and colleagues were thefirst to report a relationship be -tween RBP and insulin resistancebased on a variety of studies carriedout in both humans and mice.17,18

The studies carried out by theseinvestigators suggest that RBP syn-thesized specifically in adipose tis-sue causes insulin resistance inmuscle and liver. Moreover, asillustrated in Figure 3, these inves-tigators showed that weight gainand obesity increases expression ofRBP in adipocytes, elevates serumRBP levels, and increases insulinresistance.17,18 Based on theirresearch findings, Kahn and col-leagues proposed that RBP is anadipokine secreted from adiposetissue that mediates insulin resist-ance in peripheral tissues. The liter-ature focused on proving or dis-proving this theory is controversial,but is expanding rapidly. A numberof research groups have shown ele-vations in serum RBP in differenthuman cohorts and in mouse mod-els experiencing insulin resistanceand type 2 diabetes17–20; however,other groups have not observed thisassociation21–23. Results of a 3-yearlongitudinal study showed that sub-

Table 1: Vitamin A intake in non-alcoholic fatty liver disease (NAFLD) patients and control subjectsgrouped according to the number of associated features (criteria) of the metabolic syndrome.1

Criteria0–1 2 ≥ 3

Control NAFLD Control NAFLD Control NAFLDSubjects Patients Subjects Patients Subjects Patients(N = 30) (N = 23) (N = 25) (N = 21) (N = 19) (N = 20)

Dietaryvitamin A, µg 711 ± 109 348 ± 342,3 554 ± 59 262 ± 313,4 546 ± 52 232 ± 253,4,5

1The features or “criteria” considered as components of the metabolic syndrome are: hypertension (systolic and diastolic blood pressure ≥ 130/85 mm Hg or

taking antihypertensive therapy); hypertriglyceridemia (fasting plasma triacylglycerol ≥ 150 mg/dL or taking lipid-lowering therapy); low plasma high den-

sity lipoprotein (HDL) cholesterol (HDL < 40 mg/dL in men and < 50 mg/dL in women); impaired glucose regulation (impaired fasting glycemia: fasting

plasma glucose ≥ 100 mg/dL but < 126 mg/dL (5.6–7.0 mmol/L) or impaired glucose tolerance: plasma glucose ≥ 140 mg/dL after 2 hours on oral-glucose-

tolerance test); abdominal obesity (waist circumference > 102 cm in men and > 88 cm in women). 2 Significantly different from control subjects matched for the number of criteria, P < 0.01.3 Significantly different from all control subjects, P < 0.05.4 Significantly different from NAFLD patients meeting 0–1 criteria, P < 0.05.5 Significantly different from NAFLD patients meeting 2 criteria, P < 0.05.

Adapted from Muso et al.10

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jects who developed insulin resist-ance over the 3-year study perioddid not experience increases inserum RBP levels.24 In contrast,weight reduction arising from exer-cise, gastric bypass surgery, orcaloric restriction was reported tobe effective in reducing serum RBPlevels and improved insulin respon-siveness.18,22,23 Lifestyle modifica-tion and appetite suppressant-induced visceral fat loss, but nottotal or abdominal subcutaneous fatloss, was reported to decreaseserum RBP concentrations in non-diabetic adults.25 Similarly, admin-istration of fenofibrate and rosigli-tazone, drugs used for the treatmentof insulin resistance, along withcinnamaldehyde, berberine, andcyanidin 3-glucoside – agentsclaimed to have insulin sensitizingeffects – downregulated RBP inwhite adipose tissue26,27 anddecreased serum RBP concentra-tions17,26–28 in insulin-resistanthumans and rodents.

Other investigators have investigat-ed RBP-related parameters that

might account for the associationbetween RBP and insulin resist-ance. Insulin resistance is thoughtto be heritable29 and, because ofthis, many research groups haveexamined associations betweengenetic variants in the RBP geneand insulin responsiveness in case-control studies of diabetic patients.Four single nucleotide polymor-phisms (SNP) in the RBP genehave been associated with in-creased risk of diabetes in aMongolian population30; a haplo-type of 3 RBP SNPs was foundmore frequently in diabetic patientsin a Chinese population31; a haplo-type of 6 RBP SNPs was associatedwith increased risk of insulin resist-ance in a Caucasian population liv-ing in Germany32; and a RBP pro-moter polymorphism was associat-ed with increased risk of type 2 dia-betes in a Dutch population. Agenetic study in twins shows a 63%heritability for plasma RBP levelsand that genetic effects on serumRBP levels decrease with age,while environmental effects be-come increasingly important.20

These studies only focus on RBPexpression, so it is unclear whetherit is solely RBP expression or theretinol-RBP complex that isresponsible for the associationbetween RBP and insulin resist-ance. Two independent groupsexamined the molar ratio of serumretinol to RBP in the circulation asa possible explanation for theRBP/insulin resistance associationand showed that the molar ratio ofserum retinol to RBP is a betterpredictor of insulin resistance than serum RBP concentrationsalone.33,34 But another study, oneinvolving overweight subjects withor without diabetes, reported thatthe holo-RBP to apo-RBP ratio inthe overweight subjects was thesame as that of the lean subjectsand also as that previously reportedfor healthy subjects.35 Still anotherstudy showed positive associationsbetween serum retinol and im-paired glucose tolerance in humansubjects.36 There has also beenresearch interest focused on otherfactors that may account for whyserum RBP levels may be elevated

Figure 3: Relationship of serum RBP (RBP4) levels with body-mass index (Panel A) and fasting plas-ma insulin levels (Panel B) in five lean, seven obese non-diabetic, and nine obese diabetic sub-jects. In Panel A, the 95% confidence interval for the Spearman correlation coefficient of 0.64was 0.30 to 0.84. In Panel B, the 95% confidence interval for the Spearman correlation coef-ficient of 0.72 was 0.41 to 0.88. All blood samples were drawn after an overnight fast. To con-vert values for insulin to picomoles per liter, multiply by 7.175. Taken from Graham et al.18

0

65

60

55

50

45

40

35

30

25

20

RB

P4 (µ

g/m

L)

0 22 27 32 37 42

Body-Mass Index

A BR = 0.64P = 0.001

0

65

60

55

50

45

40

35

30

25

20

RB

P4 (µ

g/m

L)

0 20 40 60

Insulin (µU/mL)

R = 0.72P < 0.001

Lean subjects Obese nondiabeticsubjects

Obese diabeticsubjects

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in insulin resistant patients. RBP ispresent in the circulation bound totransthyretin, a larger molecularweight protein that prevents renalfiltration of RBP. Several researchgroups investigated serum trans-thyretin levels and kidney functionin insulin resistant humans andmice, and observed elevatedtransthyretin levels and impairedkidney function in insulin-resistantpatients.37,38 Based on their find-ings, these investigators speculatedthat the elevated serum RBP levelsfound in diabetic subjects are theresult of impaired renal RBP clear-ance.

The published research regardingthe possible role of RBP and/orretinol in the development ofinsulin resistance does not allow foran unequivocal conclusion to bereached.

Retinoic acid and retinal influ-ence adipose tissue formationand triglyceride accumulation

Fat-storing adipocytes are formed(differentiate) from adipose tissueprecursor cells that do not containfat. Adipogenesis first involvesproliferation of preadipocytes,which then differentiate into ma- ture adipocytes. Retinoids areknown to have many effects on adipose accumulation, primarilythrough their actions on adipo-cyte differentiation and metabo-lism.39–50 Studies employing pre -adipo cytes in culture reveal thatretinoic acid has a time-dependenteffect in the process of adipogene-sis, where high-dose retinoic acid,acting through its nuclear receptorRAR, initially inhibits the tran-scriptional activity of PPARg,C/EBPa and C/EBPb, proteinswhose actions are essential for ini-tiation of preadipocyte differentia-tion to adipocytes.39–41 This inhibi-tion can be reversed by the removalof retinoic acid.44 Interestingly,

when preadipocytes are treatedwith retinoic acid 48 hours afterbeing exposed to differentiationconditions, retinoic acid is nolonger effective in inhibitingadipocyte differentiation.39,41 How -ever, these findings should be inter-preted cautiously, since the studiesthat report a negative effect ofretinoic acid on adipogenesis haveinvolved administration of “supra-physiological” doses of retinoicacid. In fact, studies which involvedthe administration of low concen-trations of retinoic acid topreadipocytes in culture reportedthat retinoic acid acted as a potentadipogenic hormone that is criticalfor adipocyte differentiation.42,43

Ziouzenkova et al. reported a simi-lar effect of retinal, a retinoidessential for vision, but previouslythought to be inactive outside of theeye, on inhibiting adipocyte differ-entiation, even at the later stages ofthe differentiation process, whenretinoic acid is no longer able toinhibit adipogenesis.42 These inves-tigators also reported that alcoholdehydrogenase-1, an en zyme thatconverts retinol to retinal, is highlyexpressed in pre adipo cytes, where-as retinal dehydrogenase-1, anenzyme that oxidizes retinal toretinoic acid, is highly expressed in

differentiated adipocytes. Thisobservation suggests a temporalregulation of retinal synthesis andoxidation in fat. Moreover, leanmice were reported to have higherlevels of alcohol dehydrogenase-1in fat, compared to obese mice.Mice that genetically lack retinaloxidizing activity resist diet-induced obesity and insulin resist-ance and maintain smalleradipocyte size.

Studies of mature adipocytes showa role for retinoids in maintainingnormal adipocyte function. Re -tinoic acid treatment is reported todecrease adipocyte triacylglycerolcontent and increase oxidativemetabolism in adipoctyes.45 Whilewhite adipose tissue primarilystores fat as an energy reserve,brown adipose tissue regulates thedissipation of energy as heat forthermogenesis through the actionof uncoupling proteins found in thistissue. Published studies haveshown that retinoic acid adminis-tration to rodents increases expres-sion of uncoupling proteins andremodels white adipose tissue sothat it acquires properties thatresemble those of brown adiposetissue.46–48 Retinoic acid treatmentalso decreases expression of leptin,

Vegetable garden in India

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an adipose-derived satiety signalimportant in regulating food intake;conversely, administration of aretinol-deficient diet to miceincreased leptin and decreaseduncoupling protein expression.46,48

Retinoid effects on leptin expres-sion may be part of a feedback con-trol in the body’s regulation of itsenergy stores. Retinoid-deficiencyin mice and inadequacy in humanpopulations also seems to be relat-ed to increased adiposity.48-50 Reti -noids have important and variedroles in adipose tissue differentia-tion and maintenance. Since dietsrich in fat historically containedgreater concentrations of retinoidscompared to vegetarian diets,where the primary source ofretinoids is from b-carotene con-version, poor retinoid status may bean indicator of the body’s need toconserve energy in the form of fat,while good or high retinoid statuscan serve as an indicator of abun-dance. Unfortunately, in the mod-ern world, many foods high in fatare no longer abundant in micronu-trient content, and re tinoid-deficiency may further exacerbateadiposity.48–51

b-Carotene and its metabolitesmay influence fat metabolismand development of the metabol-ic syndrome

Several reports in the literatureindicate that serum levels of b-carotene are inversely associatedwith risk factors in the metabolicsyndrome in humans.52–56 Onestudy involving over 8,000American adults found that serumb-carotene concentrations wereinversely associated with the num-ber of metabolic syndrome diag-nostic criteria present in the study’ssubjects.52 Fasting serum glucoseand insulin concentrations werealso inversely associated withserum b-carotene levels in anAustralian population, where mean

serum carotenoid concentrationsdecreased with declining glucosetolerance.53 Low serum levels of b-carotene were observed to beassociated with indices of over-weight and obesity in studies of Australian and American children and Swedish and Frenchadults.54–57 Collectively, these stud-ies suggest that increases in b-carotene intake may be beneficialfor the prevention of risk factorsimplicated in the metabolic syn-

drome. However, an interventionstudy involving administration ofb-carotene containing antioxidantsupplements carried out over a 7-year period and involving 5,220French adults detected no differ-ence between the intervention andplacebo groups with regards totheir risk of the metabolic syn-drome determined at the termina-tion of the study and their develop-ment of the metabolic syndromeduring the years of supplemena-tion.57 Another supplementationtrial also found no associationbetween b-carotene intake and riskof diabetes (Figure 4).58 Thus, the

results of the epidemiological stud-ies do not agree with those obtainedfrom the supplementation trials.Perhaps some of this discrepancymay reflect individual variations inhuman efficiency to convert b-caro tene to retinal, given thatsome of the epidemiological stud-ies also reported relationshipsbetween serum retinol status andindices of the metabolic syn -drome.52,59

Carotenoid-15,15’-monooxygenase(CMO1) is the sole enzyme thatcleaves b-carotene into two mole-cules of retinal. Three CMO1 SNPshave been identified in the humanCMO1 gene, with the two commonSNPs having estimated allele fre-quencies of 24% and 42% inCaucasian populations.60,61 Plas matriglyceride concentrations werenot found to be different betweenindividuals harboring or not har-boring these SNPs.60 A patient witha rare CMO1 SNP that results in a~90% loss of function in CMO1was found to have high serum lev-els of b-carotene and mild hypovit-

Figure 4: Cumulative incidence of type 2 diabetes by randomizedantioxidant intervention: active b-carotene compared withplacebo in the Women’s Antioxidant CardiovascularStudy. Adapted from Czernichow et al.58

0

0.2

0.18

0.16

0.14

0.12

0.1

0.08

0.06

0.04

0.02Cum

ulat

ive

inci

denc

e of

type

2 d

iabe

tes

0 2 4 6 8 10

Years of follow-upNo. at riskβ-Carotene active group 3284 3178 2822 2661 1316Placebo group 3290 3178 3018 2667 1366

β-CarotenePlacebo

Log rank P = 0.70

0

0.2

0.18

0.16

0.14

0.12

0.1

0.08

0.06

0.04

0.02Cum

ulat

ive

inci

denc

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type

2 d

iabe

tes

0 2 4 6 8 10

Years of follow-upNo. at riskβ-Carotene active group 3284 3178 2822 2661 1316Placebo group 3290 3178 3018 2667 1366

β-CarotenePlacebo

Log rank P = 0.70

SIGHT AND LIFE James A Olson Memorial Lecture

12

aminosis A, but no other apparentphenotype.61 Inter estingly, a studyby Hessel et al. reported that micewith genetic CMO1 deficiencydeveloped fatty livers independentof serum retinol levels.62 Thesemice were reported to have elevatedlevels of total liver lipids andtriglycerides, and serum free fattyacids, compared to normal mice.On a high fat diet, CMO1-deficientmice gained more weight and accu-mulated larger and morelipid droplets in their liv-ers, as well as showingincreased serum choles-terol ester and free fattyacid levels. CMO1-defi-cient mice also showedaltered expression ofgenes involved in fattyacid metabolism in theliver and adipose tissue.Maintenance of CMO1-deficient mice on high-fat diets by anothergroup also resulted insignificant increases inbody weights of CMO1-deficient mice, com-pared to normal mice,along with elevatedserum triglyceride con-centrations, but no differ-ences in serum choles-terol, hepatic lipids, or hepatic cho-lesterol concentrations between thetwo genotypes.63 The findings fromstudies with mice are inconsistentwith human data which shows aninverse association between serumb-carotene levels and fat accumula-tion in the liver, as determined byultrasonography.64

As depicted in Figure 2, aside fromcentral cleavage of b-carotene byCMO1, b-carotene can also becleaved asymmetrically by caro tene-9’,10’-oxygenase (CMO2) to pro-duce apo-carotenals.65 Some ofthese eccentric cleavage productsmay act to regulate metabolism orother processes within the body.

b-apo-14’-carotenal (apo14), one ofthe products produced by CMO2action on b-carotene, has beenshown to inhibit adipogenesis ofpreadipocytes, specifically throughits inhibition of PPARg and RXRtarget gene expression, even in thepresence of a PPARg agonist.65

Apo14 was also effective in inhibit-ing expression of adiponectin, anadipose tissue secreted hormonethat is proposed to be inversely cor-

related with development of themetabolic syndrome.65,66 Thus,apo14 may be an important signalthat regulates the body’s fat stores.Based on this evidence, the apo-carotenals and/or their metabolitesmay mediate carotenoid effects onfat metabolism, insulin responsive-ness and other factors associatedwith the metabolic syndrome.

On the whole, the literature regard-ing b-carotene and its metabolitesand their effects on fat metabolismand the development of the meta-bolic syndrome is inconclusive. Itis clear that more research needs tobe done before a role of b-caroteneand/or its metabolites in either the

prevention or the causation of themetabolic syndrome can be estab-lished.

Summary

The considerable published evi-dence that suggests linkages be - t ween dietary carotenoids, theirretinoid metabolites, and eccentriccleavage products of carotenoids,and the diseases that collectively

compose the metabolic syndrome isvery intriguing, but inconclusive.The literature suggests a causal rolefor retinoic acid in the developmentof elevated blood triglyceride lev-els. Though RBP is consistentlylinked to parameters associatedwith insulin resistance, it is notclear whether these linkages aredirect and causal in disease preven-tion or disease development, orindirect markers of disease. Bothretinoic acid and retinal appear tohave temporal and concentration-dependent effects on both adipoge-nesis and the maintenance of nor-mal adipose tissue. b-caroteneinsufficiency has been inverselyassociated with risk factors in the

Vegetable market

Magazine Issue 2/2009James A Olson Memorial Lecture

13

metabolic syndrome in manyhuman studies, but administrationof b-carotene-containing supple-ments has not been shown to beprotective against the developmentof the metabolic syndrome in clini-cal trials. Collectively, the litera-ture suggests that carotenoids,through both their retinoid and non-retinoid metabolites, may haveroles in the metabolic syndrome.The effects of carotenoids on ener-gy metabolism seem to be influ-enced by genetic and environmen-tal factors, and by the amounts ofthese compounds present in specif-ic tissues in the body. These possi-bilities will only be understoodthrough future basic and clinicalresearch that conclusively shifts theweight of the scientific evidencetowards one possibility or the other.Thus, before scientific proof ofrelationships between retinoids andcarotenoids and the metabolic syn-drome is established, guidelines forretinoid and/or carotenoid supple-ment intake may need to be recon-sidered, especially in re tinoid-sufficient populations.

Acknowledgements

The authors gratefully acknowl-edge the financial support theyreceive from grants R01DK068437 (Postprandial VitaminA) and R01 DK079221 (Vitamin AStorage) from the United StatesPublic Health Service, NationalInstitutes of Health.

References

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2. Misra A, Khurana L. Obesity and themetabolic syndrome in developing

countries. J Clin Endocrinol Metab2008;93(11 Suppl 1):S9–30.

3. Ross AC. Vitamin A and Retinoids. In:Shils ME, Olson JA, Shike M, RossAC, eds. Modern Nutrition in Healthand Disease. 10th ed. LippincottWilliams and Wilkins; 2006:351–375.

4. Bendich A, Olson JA. Biologicalactions of carotenoids. FASEB J1989;3(8):1927–32.

5. Heliövaara M, Remitz A, Reitamo S et al. 13-cis-Retinoic acid therapyinduces insulin resistance, regulatesinflammatory para meters, and paradox-ically increases serum adiponectin con-centration. Meta bolism 2007;56(6):786–91.

6. Sedova L, Seda O, Krenova D et al.Isotretinoin and fenofibrate induce adi-posity with distinct effect on metabolicprofile in a rat model of the insulinresistance syndrome. Int J Obes RelatMetab Disord 2004;28(5):719–25.

7. De Marchi M, Maranhão R, BrandizziL et al. Effects of isotretinoin on themetabolism of triglyceride-rich lipo -proteins and on the lipid profile inpatients with acne. Arch Dermatol Res2006;297(9):403–8.

8. Cisneros F, Gough B, Patton R et al.Serum levels of albumin, triglycerides,total protein and glucose in rats arealtered after oral treatment with lowdoses of 13-cis-retinoic acid or all-trans-retinoic acid. J Appl Toxi col2005;25(6):470–8.

9. Standeven A, Beard R, Johnson A et al.Retinoid-induced hypertriglyceridemiain rats is mediated by retinoic acidreceptors. Fundam Appl Toxicol1996;33(2):264–71.

10. Musso G, Gambino R, De Michieli F etal. Nitrosative stress predicts the pres-ence and severity of nonalcoholic fattyliver at different stages of the develop-ment of insulin resistance and metabol-ic syndrome: possible role of vitamin Aintake. Am J Clin Nutr 2007;86(3):661-71.

11. Suano de Souza F, Silverio Amancio O,Saccardo Sarni R et al. Non-alcoholicfatty liver disease in overweight chil-dren and its relationship with retinolserum levels. Int J Vitam Nutr Res2008;78(1):27–32.

12. Villaça Chaves G, Pereira S, Saboya Cet al. Non-alcoholic fatty liver diseaseand its relationship with the nutritionalstatus of vitamin A in individuals withclass III obesity. Obes Surg 2008;18(4):378–85.

13. Kang H, Bhimidi G, Odom D et al.Altered lipid catabolism in the vitamin

A deficient liver. Mol Cell Endocrinol2007;271(1-2):18–27.

14. Oliveros L, Domeniconi M, Vega V etal. Vitamin A deficiency modifies lipidmetabolism in rat liver. Br J Nutr2007;97(2):263–72.

15. McClintick J, Crabb D, Tian H et al.Global effects of vitamin A deficiencyon gene expression in rat liver: evi-dence for hypoandrogenism. J NutrBiochem 2006;17(5):345–55.

16. Lenhard J, Lancaster M, Paulik M et al.The RXR agonist LG100268 causeshepatomegaly, improves glycaemiccontrol and decreases cardiovascularrisk and cachexia in diabetic mice suf-fering from pancreatic b-cell dysfunc-tion. Diabetologia 1999;42(5):545–54.

17. Yang Q, Graham T, Mody N et al.Serum retinol binding protein 4 con-tributes to insulin resistance in obesityand type 2 diabetes. Nature 2005;436(7049):356–62.

18. Graham T, Yang Q, Blüher M et al.Retinol-binding protein 4 and insulinresistance in lean, obese, and diabeticsubjects. N Engl J Med 2006;354(24):2552–63.

19. Xu M, Li X, Wang J et al. Retinol-bind-ing protein 4 is associated withimpaired glucose regulation andmicroalbuminuria in a Chinese popula-tion. Dia betologia 2009. (Epub aheadof Publi cation)

20. Ribel-Madsen R, Friedrichsen M, Vaag A et al. Retinol-binding protein 4in twins: regulatory mechanisms andimpact of circulating and tissue expres-sion levels on insulin secretion andaction. Diabetes 2009;58(1):54–60.

21. Lewis J, Shand B, Elder P et al. Plasmaretinol-binding protein is unlikely to bea useful marker of insulin resistance.Diabetes Res Clin Pract 2008;80(1):e13–5.

22. Gómez-Ambrosi J, Rodríguez A,Catalán V et al. Serum retinol-bindingprotein 4 is not increased in obesity orobesity-associated type 2 diabetes mel-litus, but is reduced after relevantreductions in body fat following gastricbypass. Clin Endocrinol (Oxf) 2008;69(2):208–15.

23. Vitkova M, Klimcakova E, KovacikovaM, et al. Plasma levels and adipose tis-sue messenger ribonucleic acid expres-sion of retinol-binding protein 4 arereduced during calorie restriction inobese subjects but are not related todiet-induced changes in insulin sensi-tivity. J Clin Endocrinol Metab 2007;92(6):2330–5.

SIGHT AND LIFE James A Olson Memorial Lecture

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24. Lewis J, Shand B, Frampton C et al.Plasma retinol-binding protein is not amarker of insulin resistance in over-weight subjects: a three year longitudi-nal study. Clin Biochem 2008; 41(13):1034–8.

25. Lee J, Lee H, Shim J et al. Abdominalvisceral fat reduction is associated withfavorable changes of serum retinolbinding protein-4 in nondiabetic sub-jects. Endocr J 2008; 55(5):811–8.

26. Sasaki R, Nishimura N, Hoshino H etal. Cyanidin 3-glucoside ameliorateshyperglycemia and insulin sensitivitydue to downregulation of retinol bind-ing protein 4 expression in diabeticmice. Biochem Pharmacol 2007;74(11):1619–27.

27. Wu H, Wei L, Bao Y et al. Fenofibratereduces serum retinol-binding protein-4by suppressing its expression in adiposetissue. Am J Physiol Endocrinol Metab2009;296(4):E628–34.

28. Zhang W, Xu Y, Guo F et al. Anti-dia-betic effects of cinnamaldehyde andberberine and their impacts on retinol-binding protein 4 expression in ratswith type 2 diabetes mellitus. Chin MedJ (Engl) 2008;121(21):2124–8.

29. Bergman R, Zaccaro D, Watanabe R etal. Minimal model-based insulin sensi-tivity has greater heritability and a dif-ferent genetic basis than homeostasismodel assessment or fasting insulin.Diabetes 2003;52(8):2168–74.

30. Munkhtulga L, Nakayama K, Utsumi Net al. Identification of a regulatory SNPin the retinol binding protein 4 geneassociated with type 2 diabetes inMongolia. Hum Genet 2007;120(6):879–88.

31. Hu C, Jia W, Zhang R et al. Effect ofRBP4 gene variants on circulatingRBP4 concentration and type 2 dia-betes in a Chinese population. DiabetMed 2008;25(1):11–8.

32. Kovacs P, Geyer M, Berndt J et al.Effects of genetic variation in thehuman retinol binding protein-4 gene(RBP4) on insulin resistance and fatdepot-specific mRNA expression.Diabetes 2007;56(12):3095–100.

33. Mills J, Furr H, Tanumihardjo S.Retinol to retinol-binding protein(RBP) is low in obese adults due to ele-vated apo-RBP. Exp Biol Med (May - wood) 2008;233(10):1255–61.

34. Erikstrup C, Mortensen O, Nielsen A etal. RBP-to-retinol ratio, but not totalRBP, is elevated in patients with type 2diabetes. Diabetes Obes Metab 2009;11(3):204–12.

35. Frey S, Spranger J, Henze A et al.Factors that influence retinol-binding

protein 4-transthyretin interaction arenot altered in overweight subjects andoverweight subjects with type 2 dia-betes mellitus. Metabolism 2009.(Epub)

36. Tavridou A, Unwin N, Laker M et al.Serum concentrations of vitamins Aand E in impaired glucose tolerance.Clin Chim Acta 1997; 266(2):129–40.

37. Mody N, Graham T, Tsuji Y et al.Decreased clearance of serum retinol-binding protein and elevated levels oftransthyretin in insulin-resistant ob/obmice. Am J Physiol Endo crinol Metab2008;294(4):E785–93.

38. Henze A, Frey S, Raila J et al. Evidencethat kidney function but not type 2 diabetesdetermines retinol-binding protein 4 serumlevels. Diabetes 2008; 57(12):3323–6.

39. Xue J, Schwarz E, Chawla A et al.Distinct stages in adipogenesis revealedby retinoid inhibition of differentiationafter induction of PPARgamma. MolCell Biol. 1996;16(4):1567–75.

40. Schwarz E, Reginato M, Shao D et al.Retinoic acid blocks adipogenesis byinhibiting C/EBPb-mediated transcrip-tion. Mol Cell Biol 1997;17(3):1552–61.

41. Kuri-Harcuch W. Differentiation of3T3-F442A cells into adipocytes isinhibited by retinoic acid. Differen -tiation 1982;23(2):164–9.

42. Safonova I, Darimont C, Amri E et al.Retinoids are positive effectors of adi-pose cell differentiation. Mol CellEndocrinol 1994;104(2):201–11.

43. Bost F, Caron L, Marchetti I et al.Retinoic acid activation of the ERKpathway is required for embryonic stemcell commitment into the adipocyte lineage. Biochem J 2002;361(Pt 3):621–7.

44. Ziouzenkova O, Orasanu G, Sharlach Met al. Retinaldehyde represses adipoge-nesis and diet-induced obesity. NatMed 2007;13(6):695–702.

45. Mercader J, Madsen L, Felipe F et al.All-trans retinoic acid increases oxida-tive metabolism in mature adipocytes.Cell Physiol Biochem. 2007;20(6):1061–72.

46. Kumar M, Scarpace P. Differentialeffects of retinoic acid on uncouplingprotein-1 and leptin gene expression. JEndocrinol 1998;157(2):237–43.

47. Mercader J, Ribot J, Murano I et al.Remodeling of white adipose tissueafter retinoic acid administration inmice. Endocrinology 2006;147(11):5325–32.

48. Bonet M, Oliver J, Picó C et al.Opposite effects of feeding a vitaminA-deficient diet and retinoic acid treat-

ment on brown adipose tissue uncou-pling protein 1 (UCP1), UCP2 and lep-tin expression. J Endocrinol 2000;166(3):511–7.

49. Ribot J, Felipe F, Bonet M et al.Changes of adiposity in response tovitamin A status correlate with changesof PPAR gamma 2 expression. ObesRes 2001;9(8):500–9.

50. Vaughan L, Benyshek D, Martin J. Foodacquisition habits, nutrient intakes, andanthropometric data of Havasupaiadults. J Am Diet Assoc 1997;97(11):1275–82.

51. Tanumihardjo S, Anderson C, Kaufer-Horwitz M et al. Poverty, obesity, andmalnutrition: an international perspec-tive recognizing the paradox. J Am DietAssoc. 2007;107(11):1966–72.

52. Ford E, Mokdad A, Giles W et al. Themetabolic syndrome and antioxidantconcentrations: findings from the ThirdNational Health and Nutrition Exam-ination Survey. Diabetes 2003; 52(9):2346–52.

53. Coyne T, Ibiebele T, Baade P et al.Diabetes mellitus and serum caro -tenoids: findings of a population-basedstudy in Queensland, Australia. Am JClin Nutr 2005;82(3):685–93.

54. Burrows T, Warren J, Colyvas K et al.Validation of overweight children's fruitand vegetable intake using plasmacarotenoids. Obesity (Silver Spring)2009;17(1):162–8.

55. Strauss R. Comparison of serum con-centrations of alpha-tocopherol and b-carotene in a cross-sectional sampleof obese and nonobese children(NHANES III). National Health andNutrition Examination Survey. J Pediatr1999;134(2):160–5.

56. Wallström P, Wirfält E, Lahmann P etal. Serum concentrations of b-caroteneand alpha-tocopherol are associatedwith diet, smoking, and general andcentral adiposity. Am J Clin Nutr2001;73(4):777–85.

57. Czernichow S, Vergnaud A, Galan P etal. Effects of long-term antioxidantsupplementation and association ofserum antioxidant concentrations withrisk of metabolic syndrome in adults.Am J Clin Nutr 2009. (Epub)

58. Song Y, Cook N, Albert C et al. Effectsof vitamins C and E and b-carotene onthe risk of type 2 diabetes in women athigh risk of cardiovascular disease: arandomized controlled trial. Am J ClinNutr 2009;90(2):429–37.

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59. Hickenbottom S, Follett J, Lin Y et al.Variability in conversion of b-caroteneto vitamin A in men as measured byusing a double-tracer study design. AmJ Clin Nutr 2002; 75(5):900–7.

60. Leung W, Hessel S, Méplan C et al. Twocommon single nucleotide polymor-phisms in the gene encoding b-carotene 15,15'-monoxygenase alterb-carotene metabolism in female vol-unteers. FASEB J 2009;23(4):1041–53.

61. Lindqvist A, Sharvill J, Sharvill D et al.Loss-of-function mutation in caro -tenoid 15,15'-monooxygenase identi-fied in a patient with hypercarotenemia

and hypovitaminosis A. J Nutr 2007;137(11):2346–50.

62. Hessel S, Eichinger A, Isken A et al.CMO1 deficiency abolishes vitamin Aproduction from b-carotene and alterslipid metabolism in mice. J Biol Chem2007;282(46):33553–61.

63. Lindshield B, King J, Wyss A et al.Lycopene biodistribution is alteredin 15,15'-carotenoid monooxygenaseknock out mice. J Nutr. 2008;138(12):2367–71.

64. Park S, Lee H, Lee D et al. Asso cia tionsof non alcoholic fatty liver with themetabolic syndrome and serum caro-

tenoids. J Prev Med Public Health2008;41(1):39–44.

65. Ziouzenkova O, Orasanu G, Sukhova Get al. Asymmetric cleavage of b-carotene yields a transcriptionalrepressor of retinoid X receptor andperoxisome proliferator-activated re -ceptor responses. Mol Endocrinol2007;21(1): 77–88.

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SIGHT AND LIFE Good Start in Life Program

16

Introduction

The prevalence of chronic malnu-trition, iron deficiency anemia(IDA), and vitamin A deficiency(VAD) in Peru continue to beamong the highest in SouthAmerica1 and there is little scaled-up experience on interventions toreduce stunting and micronutrientdeficiencies countrywide2. Thisarticle reports on the external eval-uation of the Good Start in Life

Initiative Program, implemented inPeru with the support of the United Nations Children’s Fund(UNICEF) and funding from theUnited States Agency for Inter -national De velop ment (USAID).The aim of the program was tocombat chronic malnutrition inchildren under three years of agefrom rural poor populations of theAndean highlands and the Amazonforest.3,4

Methods

The study design was quasi-experi-mental study, with the baseline sur-vey conducted in April–November2000 and the endline survey inOctober–December 2004. Surveysamples were representative andthere were no control groups due toethical considerations.

Starting in 1999 with capacitystrengthening of counselor wo men,rural health promoters, and com-munity leaders, the programfocused on two main elements: 1) the preventive intervention innutrition, hygiene, health and earlystimulation, and 2) participatoryprocesses and the mobilization ofhuman, economic and organiza-tional resources. The main interfacewas with the health sector and, fre-quently, one NGO was in charge ofimplementing the intervention.

All educational activities were per-formed by the health promoters andthe community counselors duringthe daily home visits and the daily

Nutritional Impact of the Good Startin Life Program (Buen Inicio) in PeruDecreased Prevalence of Stunting, Anemia andVitamin A Deficiency in Children Less than ThreeYears of Age, from the Poorest Indigenous Populationsin the Andean Highlands and the Amazon Forest

Aarón Lechtig,1 Guido Cornale,2 María Elena Ugaz2 and Lena Arias21Agencia Internacional de Seguridad Alimentaria (AISA), Lima,Peru; 2UNICEF Lima, Peru.

Correspondence: Aarón Lechtig, Malecón Lurín J2- 27, Cieneguilla, Lima 40, PeruEmail: alechtig1@yahoo.com

SIGHT AND LIFE Magazine 2009;2:16–19

Impressions from a field trip in Peru

Magazine Issue 2/2009Good Start in Life Program

17

community meetings organized for growth monitoringand early stimulation. The educational messages wererepeated through communal radio and word-of-mouth.4

Key components of the intervention included commu-nity-level promotion and monitoring of child growthand development with parents’ participation; promo-tion of support and consideration for pregnant and lac-tating mothers; twice-yearly vitamin A supplementa-tion of the infants and children under three years of agein combination with immunization; iron supplementa-tion for pregnant and lactating women (with and with-out iron deficiency anemia, IDA) and children underthree years of age using ferrous sulfate pills or syrup;prenatal controls, including monthly control of weightgain during pregnancy; and nutrition and hygiene edu-cation for mothers.

Results and discussion

The results from the Good Start in Life Program arepresented in Tables 1–3 and Figure 1. Among chil-dren under three years of age, the results show a highprevalence of stunting (54.1%) and anemia (76.0%);moderate prevalence of VAD (30.5%) and lowweight- for-age (21.9%). Acute malnutrition was 1.5% and only 16.8% had urinary iodine excretion lev-els below 100 µg/L.

A high prevalence of retardation in mental and psy-chomotor development was suspected due to the lackof systematic early stimulation, and high prevalence ofIDA and stunting.5 The program was carried out in a

Figure 1: Nutritional impact of the Good Start inLife Program: Decrease in the preva-lence of stunting, anemia and vitamin Adeficiency in children under three yearsof age from the poorest indigenouspopulations in the Andean high -lands and the Amazon forest, Peru,2000–2004. In parenthesis number of cases. Total populationcovered: 223 communities with approxi-mately 1 million inhabitants. The three compar-isons between 2000 and 2004 were significant(t-test: P < 0.01, two tails).

0

80

70

60

50

40

30

20

10

20002004

Stunting Anemia Vitamin A deficiency

(1206)

(877)

(1402)

(520)

(381)

(479)

Perc

ent

Table 1: Anthropometry: comparison between baseline and endline surveys. In vertical order: Prevalence in %; in parenthesis, number of cases and Z-score.

The same 19 communities which were surveyed in 2000 and 2004

Height-for-age Weight-for-age Weight-for-height(Chronic malnutrition) (Acute malnutrition)Baseline Endline Baseline Endline Baseline Endline53.5 37.3** 23.2 21,7 1,4 1.8 (508) (327) (508) (327) (508) (327)-2.01 -1.71** -1.29 -1.30 0.00 -0.16

t-Test between baseline and endline: ** p < 0.01; two tails.

Total sample

Height-for-age Weight-for-age Weight-for-height(Chronic malnutrition) (Acute malnutrition)Baseline Endline Baseline Endline Baseline Endline54.1 36.9** 23.7 20.3 1.8 1.5 (1206) (877) (1206) (877) (1206) (877) -2.04 -1.68** -1.28 -1.21 0.04 -0.14**

By age groups (total sample)

By number of inhabitants per community within the subsam-ple of the same 19 communities surveyed in the baseline and inthe endline.

Sex Baseline % Endline %Male 54.3 41.0**

(589) (458)Female 54.0 32.5**

(617) (419)

from 434 health facilities, severallocal NGOs, 23 local radio stations,and the leaders of 223 poor com-munities.

Immunization coverage was regu-larly above 80%. The coverage ofpolio vaccination was 84.4%,measles vaccination 82.3%, andtuber culosis 92.5% (N = 147 chil-dren, 2004).

The percentage of parents showingthe updated carnet and those whoreceived information on the growthand development of their childrenwas 75.6% and 79.3%, respective-ly; the proportion of communitymembers supporting child care was81.4%; and the proportion of chil-dren who received early stimula-tion 5–7 times a week was 52.5%(N = 927, 2004).

Stunting decreased from 54.1 to36.9%, anemia decreased from76.0 to 52.3%, and VAD decreasedfrom 30.5 to 5.3% (t-test: p < 0.01in each case, two tails). The annualcost per child actually covered bythe program was US$116.50.3

Was there a program impact?

The degree of causality between theprogram and the improvement ofnutritional indicators was indi-cated by 1) a very consistent statis-tical association; 2) presence of atime response; 3) results were in theexpected direction; 4) similarresults were not observed inregions not intervened; 5) therewere no changes in the nationalprevalence of stunting or anemia;6) reductions in prevalence werenot due to age, sex, region or topopulation size; 7) no confoundingfactor explained the decreases inthe three indicators; 8) the data andthe analyses were coherent; and 9)similar results were obtained whenthe variables were used either incontinuous or categorical formats.

SIGHT AND LIFE Good Start in Life Program

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context of chronic malnutrition, poverty, social exclusion, and ineffectivefood assistance programs.4,6,7

Program progress, coverage and impact

In 2004, the program covered 75,000 children, 35,000 mothers and 1 mil-lion inhabitants. The main participating partners were the health direc-torates of Cusco, Apurímac, Loreto, Cajamarca and Aya cucho; personnel

Table 2: Prevalence of chronic malnutrition by sex and age groupsand by number of inhabitants per community within thesubsample of the same 19 communities surveyed in thebaseline and in the endline.Percentages. In parenthesis, number of cases.

Age (months) Baseline % Endline %0–5 16.6 8.2**

(163) (85)6–1 37.6 22.9**

(234) (179)12–23 67.3 47.6**

(453) (313)24–35 65.4 42.1**

(355) (299)Total 54.1 36.9**

(1205) (876)

Number of inhabitants Baseline % Endline %per communityMore than 60 41.0 30.9*

(205) (152)60 or less 62.0 42.9**

(303) (175)

By sex (total sample)

t-Test between baseline and enline: *P < 0.05; **P < 0.01.Analysis of variance was performed to explain prevalence of chronic malnutrition:Significant predictor variables (P < 0.01); child age, region, sex, inhabitants perpopulation unit and type of survey (baseline and endline).

Magazine Issue 2/2009Good Start in Life Program

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Table 3: Reduction of the prevalence of anemia and vitamin A deficiency by region among childrenunder three years of age. Percentages and, in parenthesis, number of cases.

Anemia (%) Vitamin A deficiency A (%)Hemoglobin < 110 g/L Serum retinol < 20 µg/L

REGION Baseline Endline Baseline EndlineCusco 85.6 (353) 72.4** (112) 33.0 (109) 6.2** (128)Cajamarca 88.3 (332) 50.7** (24) 29.9 (87) 4.5** (24)Apurímac 75.1 (401) 62.0** (178) 29.6 (95) 2.4** (170)Loreto 55.1 (316) 24.1** (163) 28.6 (90) 8.0** (157)Total 76.0 (1402) 52.3** (520) 30.4 (381) 5.3** (479)

No side effects were detected and itwas thus concluded that the pro-gram as a whole produced theobserved decrease in stunting, ane-mia and VAD.

The net additional annual cost perinhabitant was US$7.07 during thefirst year of implementation andUS$3.69 during the subsequentyears. The annual cost per childprogrammed and actually coveredwas US$116.50. If applied to coverthe entire poor population in Peru,estimated at 15.12 million, the totalcost would be US$106.9 millionduring the first year of implementa-tion and US$55.8 million duringeach subsequent year.

For comparison, the country spendsmore than US$200 million per yearin food assistance programs, whichhad no detectable impact on nutri-tion, poverty prevalence or preva-lence of food insecurity at thehousehold level.

The cost/benefit ratios wereUS$1.64 per decrease of one per-centage point in the prevalence ofchronic malnutrition in childrenunder three years of age, per inhab-itant, during the first year of imple-mentation, and US$0.86 duringeach of the subsequent years. A 15-year period would be required todecrease the current national level

of stunting from 24.5% to less than10%. There would be an annualincrease of US$1.15 in the GNPper US$ invested during this 15-year period. This is equivalent to areturn of 115% per year in the GNP,starting in the 16th year.

Conclusions

This program was implementedbased on a common conceptualframework. Participation was keyand strengthened capacities at com-munity level. With a focus on chil-dren under three years of age andpregnant and lactating women, andincluding daily intensive earlystimulation of children, it wasadaptable to different realities. Theprogram had a significant impacton stunting, anemia and VADreduction, and the costs and thebenefits of the investment wereknown and feasible. Furthermore,it strengthened compliance withwomen’s and children’s rights.

Local governments and communi-ties can be successful in decreasingthe prevalence of stunting, anemiaand VAD by applying multicausalprograms like this one. Adaptationsof this program may be useful atnational level in Peru and in othersimilar countries. However, it isimportant to the success of such aprogram to ensure the essential par-

ticipatory processes in implement-ing the package of activities.7

References

1. Gross R, Gross U, Lechtig A, López deRomaña D. Introduction. We know muchabout what to do but little about how todo it: Experiences with a weekly multi-micronutrient supplementation cam - paign. Food Nutr Bull 2006;27(4):(S)111–4.

2. Lechtig Aarón. Evaluación externa delPrograma Buen Inicio en la Vida. Lima,Peru: UNICEF, 2007.

3. United Nations Children’s Fund. TheNutrition Strategy. New York: UNICEF,1990.

4. Gross R, Lechtig A, López de RomañaD. Baseline evaluation of nutritional sta-tus and government feeding programs inChiclayo, Peru. Food Nutr Bull 2006;27(4):(S)115–21.

5. Lechtig A, Shrimpton R. Maternal nutri-tion: what relevance for childrens’ sur-vival and development? In: KretchmerN, Quilligan EJ, Johnson JD, eds.Prenatal and perinatal biology and medi-cine. Chur, Switzerland: HarwoodAcademic Publishers, 1997:93–160.

6. Becker R., Lechtig A. Increasing pover-ty and infant mortality in the northeast ofBrazil. Letter to the Editor. J Trop Ped1987;33:58–9.

7. Ministerio de Promoción de la Mujer ydel Desarrollo Humano, Peru. XICumbre Iberoamericana de Jefes deEstado y de Gobierno. III ConferenciaIberoamericana de Ministras y Ministrosy Altos responsables de Infancia yAdolescencia. Fondo Editorial delCongreso del Perú. Lima 29-30 deOctubre 2001. Texto Base de consenso.Aaron Lechtig y Ana María DíazRangel. 99 pp.

t-Test between baseline and enline: **P < 0.01, two tails.

SIGHT AND LIFE Filling the Gaps

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Background

Maraland is a tribal region separat-ed into east and west by the inter-national border between India andMyanmar. The area is naturallyremote, with poor infrastructure onboth sides. Under Myanmar’s mili-tary government, economic andsocial welfare in East Maraland isalmost totally dependant on theMara Self-Help Movement pro-moted by the Evangelical Churchof East Maraland and supported bythe Mara Evangelical Church in

West Maraland (on the Indianside).1

Food insecurity and famine havebeen reported regularly in EastMara. In 2007, the Mara Self-HelpGroup failed to obtain UNDPassistance due to governmentalrestrictions.2 Thus, the East MaraSelf-Help Group turned to NGOsfor help. German KNH-Kinder -nothilfe Duisburg immediatelyresponded and granted acutefamine relief and further supportfor the Mara Self-Help Movement.

Besides regular basic food sup plies, the KNH-supportednutritional supplement powderNutrimix, fortified in Kerala,South India, was introduced forchildren.3

In 2008, a survey was carried outby German Doctors Committee forDeveloping Countries to assess thenutritional status of defined riskgroups in order to evaluate the effi-ciency of current support anddefine features for further struc-tured assistance. The intention andfuture perspective is to fill the gapbetween a society highly motivatedfor self-im provement on the onehand and the political difficultiesin obtaining UNDP assistance onthe other.

Methods

Underfive children and their moth-ers are the most vulnerable and at-risk groups in situations of foodinsecurity and hunger.4 As a propercluster sampling methodology5

could not be undertaken due totravel restrictions to tribal areas inMyanmar, the survey was carriedout from two border villages 2–5

Filling the Gaps NGO-Approved Self-Help in Tribal East Maraland,Myanmar

Katja Maschuw1, Tobias Vogt1, Sathish Samuel2, Guido Falkenberg2,Mai Ki3, Shi Khaw3, Lisa Sous11German Doctors for Developing Countries, Frankfurt, Germany; 2KNH-Kindernothilfe, Duisburg, Germany; 3HUB East Mara Self-Help Movement

Correspondence: Katja Maschuw, German Doctors for Developing Countries, Offenbacher Landstrasse 224, 60599 Frankfurt, GermanyEmail: katja.maschuw@gmx.de

SIGHT AND LIFE Magazine 2009;2:20–22

Poor housing conditions

Magazine Issue 2/2009Filling the Gaps

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days walking distance from most ofthe East Mara villages. Hence, onlythose who were strong enough tomake the effort were screened.Sub sequently, our results are biasedtoward the strongest among theweak.

Screening criteria for malnutritionwere weight-for-height Z-score foracute and height-for-age Z-scorefor chronic malnutrition in under-five children.6 In mothers, bodymass index and sex-specific mid-upper arm circumference (MUAC)were used to define underweightand chronic energy deficiency mal-nutrition.7 The average number of

pregnancies; prevalence of deaths,births, and miscarriages; and dura-tion of breastfeeding were recordedsince iron deficiency is known to bean independent risk factor for pre-maturity and fetal growth.8 Hemo -globin (Hb) was measured by Hb-photometry in both mothers andchildren as an indicator of micronu-trient deficiency.9 In children,prevalence of acute respiratory tractinfections10 and diarrhea11 wereadditionally recorded along withclinical signs of vitamin A, D andB-complex deficiencies, such asBitot’s Spots, rickets, angular stom-atitis, and retardation.12

Since 18 out of 52 underfive chil-dren did not receive the Nutrimixsupplement due to mothers’ con-cerns about altered digestion, theeffect of Nutrimix could be assessedby an analysis of weight and Hbusing two-tailed Student's t-test.

Results

In total, 52 children and 54 moth-ers were screened. In children, theprevalence of malnutrition was84.6%, including 44.2% severeacute malnutrition, 13.5% acutemalnutrition, 46% severe chronic malnutrition, 17.3% chronic mal-nutrition, and 36.5% overlaps.Acute respiratory tract infections(38.5%), diarrhea (32.7%), andanemia (100%) were the only obvi-ous signs of micro nutrient defi-ciency.

In mothers, the prevalence ofunderweight was 57.4%. Amongthem, 3.7% showed severe, 16.7%moderate and 37% mild under-weight. The prevalence of chronicenergy deficiency malnutritionwas 1.9%. The prevalence of ane-mia reached 100% (Table 1).Mean duration of breastfeedingwas 41.8 months (range 31–50months). The prevalence of deaths,births, and miscarriages was 10%,with 3.5 pregnancies on average(range 1–10).

Although the average weight ofchildren obtaining regular nutri-tional supplementation with Nutri -mix was higher (9.15 kg versus8.62 kg), the difference was notsignificant (p = 0.45). Hemoglobinlevels were likewise higher in sup-plemented children (8.0 mg/dLversus 7.78 mg/dL) but not signifi-cantly (p = 0.42).

Conclusion for further support

Our data indicate food and nutri-tion insecurity and hunger in tribal

Table 1: Malnutrition and micronutrient deficiencies in underfivechildren and their mothers in Mara.

Children < 5 years of age Total (N = 52)Severe acute malnutrition 23 (44.2%)Acute malnutrition 7 (13.5%)Severe chronic malnutrition 24 (46.2%)Chronic malnutrition 9 (17.3%)Overlaps 19 (36.5%)No signs of malnutrition 8 (15.4%)Hb (g/dL) 7.9 (range 6.5–9.5 )Diarrhea 17 (32.7%)ARI 20 (38.5%)

Mothers Total (N = 54)Severe underweight 2 (3.7%)Moderate underweight 9 (16.7 %)Mild underweight 20 (37%)Chronic energy deficiency 1 (1.9%)Hb (g/dL) 8 (range 7–9.5)

Cut-off levels for childrenSevere acute malnutrition: Weight-for-height Z-score < -3Acute malnutrition: Weight-for-height-Z-score < -2Severe chronic malnutrition: Height-for-age Z-score < -3Chronic malnutrition: Height-for-age Z-score < -2Diarrhea: > 3 loose stools/24 hoursARI: Fever and cough or breathing problems during

the preceding 14 days

Cut-off levels for mothersMild underweight: BMI 17–18.49 kg/m2

Moderate underweight: BMI 16–16.99 kg/m2

Severe underweight: BMI < 16 kg/m2

Chronic energy deficiency: MUAC < 22 cm

SIGHT AND LIFE Filling the Gaps

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East Maraland even after one year of basic nutritionalsupport from NGOs. Con sidering the one-sided analy-sis, which includes only those who were strongenough to take a 2–5-day walk, the situation isassumed to be worse for the average East Mara moth-er and child. Basic nutritional support and nutritionalsupplementation for children could at least keep thetribe alive since there are no comparable data beforefamine relief. The lack of any health care besides nat-urally limited traditional healing, the lack of vaccina-tion, the presence of endemic malaria tropica, andpoor housing and infrastructure further aggravate thesituation.

Based on these findings, a more differentiated form ofsupport focusing on nutrition, improvement ofmicronutrient supplementation and public health isnecessary. Through cooperation with a Mara hospitalfor primary health care in Indian West Maraland,structured health-worker training was provided for sixhealth worker during the past months. Dispensariesare about to be installed in two West Mara border vil-lages; from these, malaria treatment, mosquito nets,iron and vitamin supplementation, and dewormingtreatment and vaccination will be provided by trainedhealth worker in East Mara villages.

Pregnancy is monitored and supported by deworming,and vitamin, iodine and iron supplementation. Kitchengardening is promoted for every family to prevent vita-min deficiencies. Awareness camps for public health,focusing on topics such as nutrition, hygiene andmalaria, traditional birth attendance, and the use andeffects of Nutrimix, are organized for the community.

The Mara project is an example that NGO-approvedself-help is possible in remote tribal areas where peo-ple are aware of their problems, and motivated andcreative enough to achieve their own solutions.

References

1. http://wwwmaraland.net/content/view/692/9.2. http://wwwmaraland.net/content/view/674/9.3. http://wwwmaraland.net/content/view/712/9.4. UNICEF, The silent emergency, www.unicef.org/socw98/.5. Nutrition Survey. Recommendations for Somalia. Nairobi,1999, 4–13.

6. WHO Expert Committee on Physical Status: Physical Status:The use and interpretation of anthropometry. World HealthOrganization Technical Report Series, 1995; 854.

7. Salama RP, Collins S. An ongoing omission; adolescent andadult malnutrition famine situation. ENN Filed Exchange,2000;18(5).

8. McGregor MW. Maternal Anemia as a risk factor for prematu-rity and perinatal mortality. Scot Med J 963;8: 134–140.

9. Cohen AR, Seidl-Friedman J. HemoCue system for hemoglo-bin measurement and evaluation in anemic and nonanemicchildren. Am J Clin Pathol 1988;90(3):302–305.

10. Cunha AL. Relationship between acute respiratory infectionand malnutrition in children under 5 years of age. ActaPaediatr 2000;89(5):608–9.

11. Black RE, Brown KH, Becker S. Malnutrition is a determin-ing factor in diarrheal duration, but not incidence, amongyoung children in a longitudinal study in rural Bangladesh.Am J Clin Nutr 1984;8:134–140.

12. Rao NP, Sastry JG. Monitoring nutrient intakes in India.Indian J Pediatr 1987;54(4):495–501.

Severe acute malnutrition

Poor infrastructure

Magazine Issue 2/2009Iodized Salt Use in Pakistan

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Introduction

Iodine deficiency disorders (IDD) are a major publichealth issue in Pakistan. Prevention measures have ledto a dramatic improvement in the quality of life andproductivity. Reduction of IDD would contribute sig-nificantly to the attainment of the MillenniumDevelopment Goals.

The Department of Paediatrics and Child Health, AgaKhan University and UNICEF Sindh jointly conducteda cross-sectional household survey targeting threeareas in Sindh Province to assess the extent of iodinedeficiency in underfive children and women of repro-ductive age (WRA), and their current knowledge, atti-

tudes and practices regarding IDD and iodized salt.Lessons learned from this survey will inform iodizedsalt social marketing projects in Pakistan.

Methods

The community-based, cross-sectional survey was car-ried out during January–February 2007 in three areasof the province of Sindh, namely the rural Matiari andKhairpur Districts, and the urban slum area of BilalColony, Karachi. Probability proportionate to size(PPS) sampling was used to select the primary sam-pling units and a systematic sampling strategy wasused for the selection of eligible households having atleast one child between 0–59 months of age.

A knowledge, attitudes and practice (KAP) question-naire was administered among WRA in the householdsto assess household-level information regarding theuse of iodized salt and its rural-urban variation. Saltused in the households was analyzed using a rapid testkit to provide estimates of the iodine content in eachselected household. The test kit provided a semi-quan-titative estimate of iodine concentration at five levels:0, 15, 25, 50, and 75 ppm. Urinary iodine excretiontests were used among the underfive children andWRA to estimate the prevalence of IDD, using the cri-teria recommended by WHO/UNICEF/ICCIDD in2001.

A total of 485 households participated in the study,providing information on salt consumption, purchas-ing habits, salt use, awareness of iodine and iodizedsalt, and media habits. Among these households, 540

Iodized Salt UseAssessment of Iodine Deficiency among UnderfiveChildren and Women of Reproductive Age in Sindh Province, Pakistan

Imtiaz Hussain, Gul Nawaz Khan, Sajid Bashir Soofi,Zulfiqar A BhuttaAga Khan University, Department of Pediatrics and Child Health,Karachi, Pakistan

Correspondence: Imtiaz Hussain, Aga Khan University, Department of Pediatrics and Child Health, PO Box 3500, Karachi, PakistanEmail: imtiaz.hussain@aku.edu

Goiter of a child reflecting iodine deficiency

SIGHT AND LIFE Magazine 2009;2:23–24

SIGHT AND LIFE Iodized Salt Use in Pakistan

children aged 0–5 years and 520 WRA were assessedfor iodine deficiency. The average respondent age was32 years, an average 7.3 family members shared theirfood (ate meals together), and 1.8 family memberswere WRA, aged 15–49 years.

Key findings

The results show that most respondents were familiarwith iodine (29.7%) and iodized salt (73.8%), and thatiodized salt was available in nearby markets (50.1%).Surprisingly, location-wise, the level of orientation oniodine differed from 16% (urban) to 45% (rural) in ourstudy areas. This may be due to the active involvementand routine visits of the lady health workers (LHW) inthese areas. Both rural Matiari and Khairpur have ahigh coverage of LHWs, as described in the NationalLady Health Workers Program.

About 39% of the respondents reported using iodizedsalt in their households but observation by the enumer-ators found that only 21% of households had iodizedsalt at the time of the interview. The results variedaccording to location, ranging from 57% to 19% inurban and rural areas, respectively, for reported use,and 30.2% to 11.2% in urban and rural areas, respec-tively, for observed use. Similar findings on reporteduse of iodized salt were found for Sindh Province in anevaluation survey of the IDD prevention and controlprogram 2000–2001. Unfortunately, the content ofiodine in the iodized salt was found to be very low,with only 8.4% iodized salt containing adequateamounts of iodine (i.e. iodine content > 15 ppm).Another alarming and disappointing finding was thatcrystal salt was being mislabeled and marketed asiodized salt.

Urinary iodine concentration is the most reliable indi-cator of IDD. WHO/UNICEF/ICCIDD have also re-commended that no iodine deficiency be indicated in apopulation when median urinary iodine (UI) excretionlevel is 10 µg/dL, or more than 50% of the urine sam-ples have UI levels of ≥10 µg/dL (WHO/UNICEF/ICCIDD, 1994). The results of urinary iodine analysisof WRA and underfive children found 34% and 22%,respectively, to be iodine deficient (< 4.9 µg/dL);14.6% and 12.2%, respectively, severely iodine defi-cient (< 2.0 µg/dL); and 19.2% and 9.7%, respectively,moderately deficient (2.0–4.9 µg/dL). A high preva-lence (52%) of iodine deficiency was found amongchildren in rural areas and among WRA in urban areas.

High acceptability, knowledge and wide availability ofnon-iodized crystal salt and lack of knowledge regard-ing the presence of iodine in salt and its relationship toIDD were the major factors highlighted from this sur-vey as the cause of low use of iodized salt in bothurban and rural communities.

Iodized salt

Manual on Vitamin ADeficiency Disorders (VADD)

available soon

Magazine Issue 2/2009Micronutrient Forum: Executive Summary

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The 2nd International Meeting of the MicronutrientForum, held in Beijing, China, from May 12–15, 2009,brought together 670 delegates from more than 70countries, including country-level program imple-menters and their partners, multi-laterals, donors,researchers, and representatives of the private sector.Delegates were welcomed by the Chair of the Micro-nutrient Forum Steering Committee, Dr Alfred Sommer,as well as representatives of the Chinese and USGovernments, and the major United Nations agencies.

The four-day Beijing Meeting wasguided by an expert consultation –referred to, hereafter, as theInnocenti Process – convened in2008 at the UNICEF InnocentiResearch Center in Florence, Italy.Participants at that meeting were inconsensus that the micronutrientcommunity has sufficient scientificknowledge and evidence to moveforward. At the same time, we arechallenged by how to translate sci-ence into effective interventionsand deliver those interventions atscale. Implementers, partners,donors and program-oriented aca-demics involved in the InnocentiProcess were charged with identify-

ing which interventions work at scale and documentinggaps in both evidence and programmatic experiences.This process shaped an agenda for Beijing, whereinvited speakers addressed the state of the art and rec-ommendations for each of the major program areasand deficiency-control strategies. This was supple-mented by case studies of lessons learned and a tech-nical update on emerging research in the field ofmicronutrients.

Micronutrients, Health andDevelopment: Evidence-BasedProgramsThe 2nd International Meeting of the MicronutrientForum, 12–15 May 2009, Beijing, China

Amanda C Palmer, Christine P StewartJohns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, USA

Correspondence: Johns Hopkins Bloomberg School of Public Health,615 North Wolfe Street, W42041, Baltimore, MD 21205–2179, USAEmail: Amanda C Palmer, acpalmer@jhsph.edu Email: Christine P Stewart, cpstewar@jhsph.edu

The Olympic Stadium of Beijing, also called the Bird’s Nest

SIGHT AND LIFE Magazine 2009;2:25–33

Status of micronutrient deficien-cies in China

Leading academics and representa-tives from the host country openedthe plenary sessions by describingthe current state of micronutrientnutrition, as well as deficiency-control efforts. With the rapiddevelopment of China’s economyover the past 20 years, the countryhas achieved significant gains innutrition. However, micronutrientdeficiencies have proven moreintractable. Iron deficiency andanemia are a continued risk toreproductive-aged women and chil-dren of all ages. Poor maternalfolate status in early pregnancy isalso a major concern, with the inci-dence of neural tube defects(NTDs) as high as 100 per 10,000births in some parts of the country.

China has adopted multiple strate-gies to prevent the consequencesof micronutrient deficiencies. Itssuccess with salt iodization is per-haps most widely cited. As of2008, 97% of counties haveachieved universal salt iodization(USI), exceeding programmaticgoals. Furthermore, iron-fortifiedsoy sauce now reaches nearly 60million people in targeted pro -vinces. The government is active-ly pursuing a combination ofsocial marketing and partnershipwith the private sector to improvethe distribution system, therebyincreasing national coverage withthis fortified product.

Two strategies have been piloted toaddress the high incidence ofNTDs. As of 2005, national cover-age with folic acid supplementationstood at 41% among pregnantwomen, with only 11% consumingsupplements during the critical pre-pregnancy period. Coverage waseven lower in high risk areas,where up to 50% of women wereaffected by folate deficiency.

Efforts to increase coverage andcompliance have been somewhateffective, but remain challenged bythe fact that few women begin totake supplements before a pregnan-cy is recognized. Flour fortificationwith multiple micronutrients maybe a more appropriate strategy.Pilot research reported universalacceptance of fortified flour in tar-geted areas, as well as a dramatic83% reduction in the incidence ofNTDs.

Vitamin A supplementation pro-grams for children aged 6–59months

Vitamin A deficiency (VAD) is theprimary cause of preventable child-hood blindness and a major con-tributor to severe morbidity andmortality. According to revised

WHO estimates released at thismeeting, approximately 190 mil-lion preschool-aged children(33.3%) and 19.1 million pregnantwomen (15.3%) worldwide areaffected (serum/plasma retinol < 0.70 µmol/L). Yet, large-scalevitamin A supplementation (VAS)programs implemented over thepast decade have achieved remark-able success in preventing the con-sequences of deficiency.

Supplementation has also served asa platform for other child survivalinterventions. Semi-annual ChildHealth Days have become regularevents organized by countries todeliver vitamin A as part of an inte-grated package of preventive serv-ices. These events have enabledprograms in some of the leastdeveloped countries to sustaintwice-yearly coverage in excess of80%. Challenges remain to test andimplement delivery strategies capa-ble of reaching the remaining10–20% of children. A major tran-sition is also underway as govern-ments begin to assume a greaterproportion of program costs.

In response to the success of sup-plementation programs and selectachievements with vitamin A-forti-fied foods, program managers and

policy-makers are beginning toraise important questions regardingprogram impact. Dr Amy Rice, ofSocial Sectors DevelopmentStrategies, Inc., addressed the chal-lenges of detecting an impact ofVAS programs on child mortality(TU21). She stressed that the pro-gram impact pathway is not alwaysstraightforward. Even in countrieswith regular high coverage, thedesired impact is unlikely to be

SIGHT AND LIFE Micronutrient Forum: Executive Summary

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A plenary session

Magazine Issue 2/2009Micronutrient Forum: Executive Summary

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achieved until the remaining hard-to-reach children – often those atgreatest risk of VAD – are consis-tently supplemented. Suitable datato answer this complex question areoften lacking as well.

A subsequent presentation by MsAmanda Palmer, from JohnsHopkins University, reviewed theimpact of high-potency supple-ments on serum retinol concentra-tions. Experimental and observa-tional data from multiple settingsclearly illustrate a temporary right-shift in the population serum retinoldistribution, followed by a return tobaseline levels within roughly twomonths (TU3). Serum retinol istherefore not an informative im-pact indicator for vitamin A supple-mentation. Regardless, a large bodyof research attests to the child sur-vival benefit of VAS programs.Given coverage in the range of80–90% and dosing on a four to sixmonth schedule, large-scale pro-grams can presume a similarimpact.

Rather than investing in mortalityor serum retinol assessments, pro-gram managers and partners wereurged to focus on coverage.Improved coverage monitoring andthe more constructive use of thesedata to guide activities are criticalto program performance. Thisinformation can also serve as aproxy for program impact.Although VAD continues to be aproblem, the sustained commit-ment and growing governmentownership of semi-annual ChildHealth Days or other strategies canprotect large proportions of at-riskchildren, even in the poorest partsof the world.

Iodine and universal salt iodization

Universal salt iodization (USI) pro-grams received considerable atten-

tion during the Innocenti Process,both in terms of their success incontrolling iodine deficiency disor-ders and also as a source of lessonslearned that may prove useful for other mass fortification pro-grams. Reviewing data on urinaryiodine concentrations and coveragewith iodized salt, Dr MichaelZimmerman of the Swiss FederalInstitute of Technology reportedthat populations in the Europeanand Eastern Mediterranean regionsremain at highest risk of deficien-cy, although much work remains inboth Southern Asia and Africa.

Case studies from countries imple-menting USI programs were pre-sented in plenary and poster ses-sions, highlighting innovativemethods to increase USI coverage.In Senegal, for example, targetedefforts to improve the capacity ofsmall-scale salt producers andrevolving funding to cover the costof the fortificant have significantlyimproved coverage (TU6). At thesame time, presentations under-scored the need for continued mon-itoring. Mandatory salt iodizationin Denmark has increased iodineintakes across the country, but mayalso have increased the prevalenceof hypothyroidism in some areas(TU4). Excess iodine intake wasalso identified by urinary iodinemonitoring in Uganda (TU5).While salt samples indicate compli-ance with current fortification lev-els (W12), it is now clear that initialregion-wide assumptions regardingsalt intake and fortificant levelswere incorrect.

Continual monitoring and feedbackis necessary to ensure that the pop-ulation is adequately protectedfrom deficiency while not exposedto excess doses. In locations whereiodized salt is regionally distrib-uted, collaboration between coun-tries in the region will be needed toharmonize legislation and iodiza-

tion standards. Addressing thechallenge of deficiency in remotepopulations with poor access is alsocritical. Some success in this areawas reported from Tibet (TU14),where more than 95% of reproduc-tive-aged women and children lessthan two years of age are now beingreached with iodized oil capsules.

Maternal iron-folic acid supplementation programs

There is substantial evidenceregarding the consequences of ane-mia during pregnancy. Presen -tations at this meeting providedfurther support for antenatal ironand folic acid (IFA) supplementa-tion, showing a reduced risk ofpreterm delivery and associatedlow birth weight (F3), as well asbenefits to early neonatal survival(W7, F3) and survival throughoutchildhood (W2). Yet, national sur-veys continue to report consider-able gaps between other maternalsurvival interventions, such asantenatal care attendance, and coverage with IFA supplements.Participants at the InnocentiMeeting also stressed the need forwell-documented programmaticsuccesses.

Dr Tina Sanghvi, from the Aca -demy for Educational Develop ment

Prof. Junshi Chen, ChineseCenter for Disease Control andPrevention, Beijing

(AED), highlighted two such programs. Nicaragua andThailand have achieved impressive gains in anemiacontrol. Both country programs placed special empha-sis on assuring the availability of IFA capsules. Theyalso committed to improving the links between fixedhealth services and front-line community workers, i.e.,those charged with counseling women and monitoringcompliance.

Additional programmatic successes were highlightedby delegates from Nepal and India. Nepal’s programsimilarly relied on the strength of its FemaleCommunity Health Volunteers to register pregnantwomen and ensure their monthly supply of IFA supple-ments (W6). Volunteers conducted weekly home visitsto monitor compliance. They were aided by school-

children, who assisted in registering newly pregnantwomen. A dramatic reduction in anemia prevalence –from 75% to 42% – has been attributed to this pro-gram, which now exceeds 85% coverage. In India, sev-eral states have adopted multi-pronged approaches toaddress anemia among adolescent girls (W8, W72-74,W77, W79). To date, school-based efforts have beenmost effective, likely as a result of better supervisionand associated higher compliance. Maintaining a time-ly and adequate supply of IFA supplements remains achallenge in both countries.

Dr Sean Lynch from the Eastern Virginia MedicalSchool concluded the plenary session by remindingdelegates of the question posed in its title: “MaternalIron-Folic Acid Supplementation: Great Policy, Failedor Forgotten Imple men tation?” He reviewed the strongevidence in support of supplementation or other inter-ventions to improve iron and folate status amongreproductive aged women. Yet, policies and programsrequire more effort. Dr Lynch underscored the need to

link IFA supplementation with related measures toimprove antenatal programs, as well as other anemiacontrol interventions such as deworming, malaria pro-phylaxis and delayed cord clamping.

Food fortification programs

The essential goal of food fortification is to add vita-mins or minerals to processed foods, either to restorenutrients lost during processing; to imitate the nutri-tional value of natural products or to add value toprocessed foods; or to incorporate nutrients that areabsent or present in low amounts in the diet. Saltiodization remains the most successful example ofmass fortification. Yet additional products show prom-ise in reducing the prevalence of iron deficiency ane-

mia and reducing the inci-dence of NTDs.

Efficacy trials from Indiaprovided additional evi-dence and technical guid-ance for iron fortification.Fortification of wheat flourwith NaFeEDTA dramati-cally reduced the prevalenceof iron deficiency and ane-mia among school childrenover an eight month period(W10). Sensory testsrevealed NaFeEDTA to bean ideal iron compound for use with wheat flour.

Findings were also released on the efficacy ofmicronized ground ferric pyrophosphate (MGFePP)and encapsulated ferrous fumarate (EFF) as fortifi-cants for dual-fortified salt (W11). Both compoundsimproved iron stores and reduced anemia among chil-dren aged 5–15 years. However, issues of stability,bioavailability and sensory changes underline the needfor programs to carefully review their choice of ironfortificants and salt production standards within thelocal context.

Fortification of flour and maize meal with folic acid inSouth Africa has reduced the incidence of NTDs by42% since its implementation (W9). This program hasalso faced several challenges. Non-compliance was amajor challenge across all manufacturers, primarilyrelated to quality control concerns with the premix.Based on their experience, presenters recommendedthat future programs engage the country’s Bureau ofStandards in compliance monitoring from the outset.In South Africa, this required a corrective amendment

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Dr Werner Schultink, UNICEF; Prof. Junshi Chen, China CDC; Dr Alfred Sommer, Johns Hopkins University

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to the original fortification mandate. Experience alsosuggested the need for ongoing assessment and refine-ment of communication messages, including greateremphasis on the health benefits of foods bearing theprogram’s fortification logo.

Overall, the success of mass fortification programsmay be attributed to a number of factors, including1) providing adequate additional intake of bioavailablemicronutrients, 2) garnering political support, 3) part-nering with the food industry, 4) implementing legisla-tion, standards, and regulations, and 5) monitoring andevaluation. As Dr Omar Dary, of AED, reminded dele-gates, the principles and scientific evidence for fortifi-cation are universal and well-accepted. However, theremaining challenges and their solutions must beaddressed at the local level.

Micronutrient powders and spreads

Considerable progress has been achieved over the pastdecade in developing micronutrient powders (MNPs)and ready-to-use supplementary or complementaryfoods. The Innocenti consensus statement called atten-tion to the efficacy of these interventions in reducingmicronutrient deficiencies among target populations.Yet, as new products for both health services and con-sumers, there are a number of lessons to be learnedregarding appropriate formulations, distribution strate-gies, marketing and acceptability, many of which wereaddressed in plenary sessions and poster presentations.

With strong links to women in the community andexisting counseling services on diverse topics, theLady Health Worker program could provide an idealplatform for delivering MNPs to young children inPakistan (TH2). Results of an initial evaluationdemonstrated the feasibility and effectiveness of thisstrategy. Remaining barriers can be largely overcomewith training and communication to reinforce the benefits of MNPs and optimal feeding practices,including food hygiene. Although prevalence waseffectively reduced, ~30% of children remained ane-mic at follow-up, suggesting a need to revisit dosingor to consider additional actions in this setting.

In Kenya’s Nyanza Province, MNPs were integratedinto an existing social marketing program and sold byprivate vendors. Introduction of MNPs in this malariaendemic setting also decreased anemia (TH41), withno measurable increase in morbidity or hospitalization(TH42). As in Pakistan, instruction on the proper useand possible changes in stool color or frequency werecritical to adherence and utilization of MNPs (TH33).

Presenters also highlighted the importance of processmonitoring in guiding strategic implementation (TH3).For instance, vendor feedback on the distance and lim-ited time for wholesale purchases was addressed byopening an additional wholesale site. Overall, Kenya’sexperience illustrates the effectiveness of social mar-keting for MNP delivery, even among the rural poor.

MNPs were also explored as a potential replacementfor an energy-dense drink, Nutrivida, currently provid-ed to pregnant women enrolled in Mexico’s Opor -tunidades program. Comparing Nutrivida with eithermultiple micronutrient (MMN) tablets or MNPs,researchers found no differences in weight gain but astrong preference for tablets among participants.Although the hypothesized impact on weight gain wasnot observed, transition from Nutrivida to MMN intablet form was recommended for future beneficiaries.Not only was this more consistent with public healthmessages in a country affected by the double burden ofunder- and over-nutrition, but it was more convenientfor beneficiaries and less costly. Further analyses froma parallel child supplementation trial revealedimproved hemoglobin levels and a maternal preferencefor MNPs over the energy drink targeted to young children.

Zinc treatment for diarrhea management and control

Diarrheal disease remains the leading cause of deathamong infants and young children. In combinationwith low osmolarity oral rehydration salts, dispersiblezinc tablets are efficacious in treating diarrhea. Thereis also a growing body of evidence attesting to theintervention’s field effectiveness. Data from Indiashared at this meeting further demonstrated that deliv-ery of zinc through existing health care providers couldeffectively reduce diarrhea and prevent hospitali -zations among young children (TH8). However, majorobstacles remain in scaling up this intervention, mostnotably an absence of political commitment and ade-quate supplies.

The most widely recognized effort to roll out zinctreatment has been Bangladesh’s “Scaling Up Zinc forYoung Children” or “SUZY” project (TH5). The pri-mary focus of SUZY was to accelerate the productionof zinc at the local level. ‘Baby Zinc’ was released inNovember 2006 in conjunction with intensive trainingand Behavior Change Communication (BCC) efforts.However, a lack of demand has kept production atroughly 20% of estimated needs. In terms of coverage,the percentage of children treated with zinc increased

from 7% to 18% within six monthsof the product’s launch. Althoughthis is quite low, other countries lagwell behind Bangladesh in theircoverage and may gain from theSUZY experience.

In Nepal, strides have been made tointroduce zinc through private-sec-tor providers and pharmacies(TH6). Education and advocacycampaigns have strengthenedknowledge and awareness amongprivate-sector distributors, whothen pass this information on totheir patients. Tanzania was cited asanother example of promising zincscale up (TH7). Although there is agreat deal of trust in public sectorhealth providers, they have beenslow to adopt new treatment guide-lines. While continuing to strength-en public delivery mechanism, theprogram is also targeting drugwholesalers, accredited pharmaciesand rural duka la dawa outlets withlicenses to prescribe a limited rangeof drugs.

Evidence-based impact of pover-ty alleviation programs: maxi-mizing nutritional benefits

Poverty reduction strategies – con-ditional cash transfer (CCT) pro-grams, microcredit with education

(MCE), or agricultural interven-tions – have the potential to im -prove micronutrient status of at-risk populations. However, limiteddata attest to the nutritional effectsof these programs. There has beenlittle thought as to how these pro-grams may improve nutrition,which requires greater attention tothe potential impact pathways. DrMarie Ruel, of the InternationalFood Policy and Research Institute(IFPRI), recommended that nutri-tional objectives be stated explicitlyfrom the outset and incorporatedinto each phase of programming,from design through evaluation.

Data from the Oportunidades pro-gram in Mexico and similar CCTinterventions throughout LatinAmerica illustrate reductions inpoverty, increased food expendi-tures, improved dietary quality, andprogress in terms of women’sempowerment. Yet nutritionalimpacts have been more modest.MCE programs have not been aswell documented or rigorouslyevaluated. Several of these havecited improvements in infant andyoung child feeding practices,although the pathways by whichMCE programs affected thesechanges are unclear. Agriculturalinterventions have been imple-mented in a variety of settings.Data from increasingly thoroughevaluations suggest the potential toimprove vitamin A status, althoughevidence of impact on iron statusand growth has been weaker.

Plenary and poster presentationsshared field experiences from Asiaand Africa. For example, an evalua-tion of Helen Keller Inter -national’s homestead food produc-tion programs in Bangladesh,Cambodia, Nepal, and thePhilippines reported increasedaccess to micronutrient-rich foodsand improvements in dietary diver-sity (F11). Increases in agricultural

production were also associatedwith greater household income,women’s empowerment, and foodsecurity. Another innovative exam-ple was a keyhole gardening pro-gram in Lesotho, where partici-pants reported that they were ableto produce more food than theirfamily could consume and that theywere highly enthusiastic about theprogram (F12).

Biofortification

Conventional breeding techniques,genetic engineering or fertilizerwith trace elements have all beenemployed in efforts to improve thenutrient content of crops such assweet potatoes, rice, corn, andbeans. These “biofortified” staplefoods are a novel vehicle for deliv-ering nutrients in modest amountson a daily basis. They are largelytargeted to poor, rural areas thatdepend on subsistence farming,and aim to correct underlyingdietary inadequacies. Progress isbeing made with several crops.While carotenoid-rich sweet pota-toes are the only biofortified staplereleased to date, iron-biofortifiedbeans and Golden Rice are bothscheduled for roll out within thenext two years.

Initial studies have demonstratedthat the additional nutrients provid-ed by biofortified staple foods canimprove vitamin A, zinc, and ironstatus. Exciting results were pre-sented at this meeting that illustrat-ed the high bioavailability of provi-tamin A carotenoids from bioforti-fied Golden Rice (TH10) and bio-fortified maize (TH9). This re -search reveals that Golden Rice is,in fact, one of the most bioavailableplant sources of vitamin A. Both ofthese crops have the potential toprovide a significant proportion ofthe Recommended Dietary Allow-ance (RDA) to children in corn- orrice-consuming areas.

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Prof. Emorn Wasantwisut,Mahidol University, Thailand

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As biofortification is a relativelynew strategy, there are limited dataon effectiveness and large-scaleprogrammatic experiences. Les -sons are emerging from the careful-ly designed introduction of orange-fleshed sweet potato in Mozam -bique, introduced at the 1st Meetingof the Micronutrient Forum inIstanbul, Turkey, in 2007. Thisstrategy is currently being taken toscale, reaching more than 14,000households in Mozambique and anadditional 10,000 households inUganda (TH20, TH21). Furtherefforts to demonstrate efficacy andthe effectiveness of biofortificationin program settings will be a majorfocus in the next several years.

Moving beyond coverage: achieving sustainability

Although much attention has beenfocused on bringing programs toscale, Dr Michael Zeilinger, ofUSAID, asked delegates to ponderwhether that alone was the finishline. As VAS and USI achievehigher coverage in many countriesaround the world, are we near thepoint of declaring success andable to move on to the next inter-vention? Dr Zeilinger emphasizedthe need to integrate sustainabilityinto systems that have traditionally

focused only on coverage monitor-ing. He provided several illustra-tions of how potential threats tosustainability may be identified in aproactive manner. For instance,emphasis on a new intervention or areduction in training budgets mightbe identified as threats in the areaof capacity building.

Supply systems are a major area ofconcern across interventions. Thesewere addressed in two plenary pre-sentations. A review of micronutri-ent supply chains in several coun-tries revealed constraints at all lev-els, from forecasting throughinventory management (F6, F7).Decentralized micro-planning withcentralized procurement, as well asimprovements in stock and flowdata at all levels, were emphasizedas imperative. Although the chal-lenges to effective supply manage-ment are important, case studiesfrom two states in India and fromUganda demonstrated that consi-derable progress can be achievedeven over a short period of time.

Presentations under this theme alsohighlighted major successes in thetransition to government ownershipof VAS programs. In Tanzania, dis-trict-level self-assessments identi-fied planning and budgeting as

areas in need of strengthening (F5).A tool was developed through con-sultation with national and districtlevel stakeholders to streamline theplanning and budgeting process.Since its adoption, districts havebegun to assume a progressivelylarger proportion of costs whilemaintaining high coverage. Plan -ning tools have been similarlyeffective in Senegal, ensuring asmooth transition to local programownership with no breakdown inVAS coverage (F4).

A United Call to Action

Governments, non-governmentalorganizations, and private sectorcompanies working in collabora-tion will be needed to move micro -nutrient programming forward. Therelease of the 2009 global report onvitamin and mineral deficiencies,“Investing in the Future: A UnitedCall to Action on Vitamin andMineral Deficiencies”, was an -nounced during the Micro nu trientForum meeting. This effort servesas a catalyst for future cooperationand enables the micronutrient com-munity to speak with one voice.

Private sector strategies forreducing micronutrient malnu-trition

In a parallel statement, representa-tives from the private sector reas -serted their commitment to elimi-nating micronutrient malnutrition.These representatives confirmedthe private sector’s clear recogni-tion that those at the bottom of thepyramid represent a large potentialmarket, but they need help to reachthis segment of society. Many com-panies are incorporating socialcomponents into their vision andmission statements, not only out ofa sense of social responsibility, butalso to reflect the values of theiremployees, who wish to be en -gaged in work that provides a

Winners of the SIGHT AND LIFE Young Investigators Award.From left to right: Hossain Md Iqbal, Christine Stewart andSebayang Susy Katikana with Klaus Kraemer (second from right)

greater benefit. This is an area where companies can“do well by doing good.” Partnerships between indus-try, government, NGOs and local agencies to determineneeds, create demand, and conduct social marketing allrepresent potentially positive collaborative efforts. Theendeavors will require a foundation of mutual trust,shared interests, and cooperation to effectively meet theneeds of the poor and underserved populations aroundthe world.

SIGHT AND LIFE Young Investigators Award

Dr Klaus Kraemer, Secretary General of SIGHT ANDLIFE, launched the SIGHT AND LIFE YoungInvestigators Award, which will be presented on a bian-nual basis at the Micronutrient Forum meetings. Itspurpose is to recognize young researchers for undertak-ing micronutrient research that has scientific, policyand/or programmatic relevance and to facilitate interac-tions between young investigators, leading scientistsand researchers. Dr Christine Stewart from the JohnsHopkins Bloomberg School of Public Health receivedthe inaugural award for her presentation regarding theeffects of antenatal micronutrient supplementation ongrowth, body composition and early markers of cardio-vascular risk among children in rural Nepal.

New research findings

The 2nd Meeting of the Micro nutrient Forum also pro-vided an opportunity to share recent scientificadvances in micronutrient research. These includedwork in the evolving fields of genomics and pro-teomics, as well as further evidence as to the immedi-ate and long-term impacts of micronutrients on healthand development. The value of context and timing ofmicronutrient interventions was emphasized by manyof the presenters as critical to understanding impact.

In a series of presentations on nutrient metabolism,genomics and proteomics, speakers drew attention tothis exciting new field of research. Dr Georg Lietzdescribed how a mutation in one single nucleotidepolymorphism influenced the expression of the enzymeresponsible for the cleavage of b-carotene (F8). Thiscould explain some of the genetic variability in the con-version of b-carotene into retinol. Dr Keith West alsopresented exciting new research suggesting that thehuman plasma proteome may provide a reliable pictureof micronutrient status (F10). While only in the deve-lopment stage, the ultimate goal is to design a low cost,relatively portable, rapid, high-throughput platform,enabling micronutrient deficiency assessment in realtime.

As emphasized during several plenary sessions, contextmatters. Data presented previously had shown thatmaternal supplementation with vitamin A in Nepal, apopulation with high maternal mortality and endemicmaternal VAD, significantly reduced the risk of mater-nal mortality (TU49). However, in Bangladesh, wherematernal mortality is lower, and maternal vitamin Astatus better, there was no evidence of an impact. DrBetty Kirkwood, from the London School of Hygieneand Tropical Medicine, presented findings from a thirdtrial of this intervention – the ObaapaVitA Trial – con-ducted in the Bron Ahafo region of Ghana, wherematernal mortality and vitamin A status were similar tothat in the Bangladesh trial. Enrolling more than200,000 women over an eight year period, they foundno significant impacts on pregnancy-related mortality.Supplementation also failed to have an effect on non-pregnancy related mortality, all-cause female mortalityand pregnancy-associated morbidities. The combinedresults of these trials confirm that, while potentiallyimportant in high mortality, deficient settings, a globalpolicy for maternal VAS is unwarranted.

Throughout the life course, nutrient needs are continu-ally changing, reflecting varying requirements for thegrowth and development of organ systems, immuno-logic needs to fight infection, and energy and micronu-trient requirements to promote growth. The importanceof folate nutrition during the peri-conceptional periodhas been long recognized for its essential role in theprevention of NTDs. However, there have been recentadvances underscoring how exposure to micronutrientsduring critical periods of development may impacthealth outcomes in different ways, some having long-lasting effects.

Dr Michael Dibley, from the University of Sydney,drew attention to the varying effects of micronutrientsupplementation at different times during pregnancy(F3). Using data from a randomized control trial(RCT) conducted in China’s Xi’An Province, hereported that both IFA and MMN supplementationimproved birth weight and duration of gestation. IFAsupplementation also reduced neonatal mortality. Theimpacts on birth weight and neonatal survival weregreater when supplementation began early in gestation(≤12 wks) and attenuated or non-significant whensupplementation started later in pregnancy. Dr ParulChristian, of Johns Hopkins University, presentedadditional evidence from Nepal regarding antenatalIFA supplementation’s protective effect on mortality,in this case, continued through the school-age years(W2).

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Further alluding to the importanceof time and context, two presenta-tions by Dr Siddhartha Gogia andDr James Tielsh debated the impactof newborn VAS. Dr Gogia pre-sented the results from a recentlypublished systematic review of theliterature, combining data from sixtrials in Asia and Africa, on theeffects of neonatal dosing on mor-tality and morbidity through sixmonths of age (F1). This analysisrevealed no evidence of an all-causemortality effect (RR: 0.92; 95% CI0.75 to 1.12) and no evidence of areduction in cause-specific mortali-ty. Dr Tielsch offered an alternativeinterpretation, asserting that the pri-mary inclusion criteria should belimited to studies conducted in pop-ulation-based settings with highmortality, a high prevalence ofVAD, and little targeted treatmentof morbidity. Further more, the tim-ing of dosing is important.Newborn VAS appears to have agreater effect than supplementinginfants at later points during theneonatal period. He contended thatonly two studies – the trials fromIndia and Bangladesh – meet allthese criteria and that a systematicreview that includes studies notdirectly addressing this context andtiming is uninformative. Feedbackfrom several delegates failed toyield any consensus on the topic,

with the exception of a continuedcall for research into mechanismsthat may be influenced by a singlehigh dose of vitamin A.

Finally, researchers from JohnsHopkins University described find-ings from a recent follow-up studyof children originally enrolled orborn to participants in previousmicronutrient RCTs conducted inNepal. VAS among preschool-agedchildren had a lasting impact onhearing ability measured in youngadulthood, particularly among thosewho had suffered from ear infec-tions in early life (W5). Exposure toadequate vitamin A in utero andpost partum improved lung functionof children, measured 9–13 yearslater (W4). Follow-up of childrenborn during a multi-armed trial ofantenatal micronutrient supplemen-tation (W3) revealed modestimpacts on height and reduced armfat area (IFA + Zn), as well as areduced risk of kidney dysfunctionand metabolic syndrome (FAalone). Combined, these presenta-tions indicate that micronutrientsdelivered during critical periods oflife may have a permanent healthimpact. Until such relationships arebetter understood, we may be under-estimating the true cost-bene-fit ratios of micronutrient interven-tions.

Conclusion

Dr Alfred Sommer closed the meet-ing by reflecting on how far themicronutrient community has comesince the first International Vit-amin A Consultative Group (IVACG)meeting, 35 years ago. Today, wehave evidence attesting to the effi-cacy of various micronutrient inter-ventions, including innovative andexciting developments such ashome fortification, biofortificationand the roll-out of zinc for the treat-ment of diarrhea. We are approach-ing a time when dietary strategiesmay prove successful through thebiofortification of staple crops. TheMicronutrient Forum and its prede-cessors were overwhelmingly domi-nated by researchers. Yet, unlessthere are dramatic new insights, wenow have the knowledge and theevidence that we need to move for-ward. Programs will drive the agen-da. With this shift in focus, there arenew issues of concern: supply chainlogistics, management, social mar-keting, etc. These are areas in whichthe private sector excels. Going for-ward, broad-based coalitions will beessential to improving and sustain-ing micronutrient nutrition.

References

1. These codes identify the abstractsrelated to the presentations (oral andposter) given at the MicronutrientForum in Beijing. Abstracts can beviewed in the “Program Book.” Formore information refer to:

1. http://www.micronutrientforum.org/Mee ting2009/program.cfm

Beijing International Convention Center

IVACG, the earliest progenitor of the Micronutrient Forum (MF), wasbuilt by Martin Foreman, of the US Agency for International Development(USAID), to bring together clinical researchers, like myself, with nutri-tional scientists, policy makers and others who design and implement pro-grams, to pursue the possibility that vitamin A deficiency as a cause ofchildhood blindness might be much greater than the world recognized, andto conduct research that would establish its cause and design effectiveintervention programs. It proved, as we all now know, to be a major causeof pediatric blindness. But most ministers of health remained disinterest-ed, on the not-unreasonable grounds that they had committed their meagerresources to child survival strategies. For those who can remember that farback, there was GOBI1.

By 1992, multiple teams in multiple countries had conclusively demon-strated that improving vitamin A status dramatically reduced childhoodmortality. The ministers of health could prevent up to a million childrenfrom dying and going blind every year with one intervention; a “twofer”if ever there was one.

Instead of reveling in this commitment, discussions at IVACG remainedacrimonious for many years, riven with fruitless arguments over what con-stituted a natural solution to the problem. Most of the field trials hademployed periodic large-dose vitamin A, because it was the quickest andmost controlled way to determine whether improving vitamin A statusreally worked. If it could be scaled, it could dramatically impact the prob-lem. But supplementation was opposed by many nutritionists as an“unnatural” act, insisting, unhelpfully, that the real answer was to get peo-ple to grow and consume more green leafy vegetables. They eventually, ifgrudgingly, accepted twice-yearly supplementation but only if labeled a“short-term” measure, until changes in dietary habits solved the problem.

Twenty years later, we are still awaiting those effective dietary changes,while periodic dosing, driven by UNICEF, HKI, and others, and large-

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I can’t help but reflect on how farthis meeting, and our shared jour-ney to control micronutrient defi-ciency, has come since the firstInternational Vitamin A Consul -tative Group (IVACG) meetingnearly 35 years ago. It was not as ifthe world was ignorant aboutmicronutrients – iodine and ironhad long been on the agenda. Butthe world just didn’t care. Micro -nutrient deficiency did not providethe same public urgency, as say,H1N1 Flu. And I believe – at greatrisk to life and limb, given themake-up of this audience – thatnutritional scientists and policymakers were caught in a time-warpof orthodoxy.

Leaving the Chrysalis BehindChairman’s Concluding Remarks, 2nd MicronutrientForum, Beijing, May 15, 2009

Alfred Sommer Johns Hopkins Bloomberg School of Public Health, Baltimore, USA

Correspondence: Johns Hopkins Bloomberg School of Public Health,615 North Wolfe Street, W1041, Baltimore, MD 21205–2179, USAEmail: asommer@jhsph.edu

1GOBI stands for Growth monitoring, Oral rehydration, Breastfeeding, and Immuni zation – thefour cornerstone child survival interventions in developing countries.

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Prof. Alfred Sommer, JohnsHopkins Bloomberg School ofPublic Health

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ly funded by the Canadian andAmerican governments, has provedto be a remarkably effective andscalable strategy. As we heardfrom Werner Schultink, in the past10 years, UNICEF has supplied5.3 billion high-dose supplementsof vitamin A – and that does notcount vitamin A dosing with syrupin India. Extrapolating UNICEFestimates, even with current cover-age rates of only 70–80%, thelives of 3.5 million children haveprobably been saved in the past10 years alone.

I dwell on this because I was struck,at this meeting, by how far we’vecome from that original orthodoxy;by the range of innovativeapproaches to micronutrient defi-ciencies now being vigorously pur-sued. These include everythingfrom centralized fortificationschemes using multiple micronutri-ents, to “point of consumption” for-tification with micronutrient pow-ders in the home. We’ve heardabout wheat flour fortification,UltraRice and NutriRice. We’veheard about the pro-active andthoughtful rollout of zinc for hometreatment of diarrhea.

As Chairman Mao once pro-claimed, “Let a thousand flowersbloom.” They are blooming, andthose that prove most successfulneed to be aggressively pursued aswe sharpen the focus of our advo-cacy, investment, and momentum.

Oh yes, what about those naturaldietary solutions that had proved soproblematic? They might now beon the cusp of realization. Why?Because we are finally developingthe tools that the poor needed fromthe start. Traditional plant breedinghas provided a range of staplecrops, from corn to sweet potato,with 10–100 times the b-carotenecontent of their native strains, and,with a bioavailability five times

that of spinach, carrots and kang -kung.

What if the staple is rice? Do a little bioengineering. “Golden Rice 2” has nearly thirty timesthe b-carotene content of GoldenRice 1, while the original nativestrains have zero. And, like hybridcorn, Golden Rice has a foodmatrix that favors high bioconver-

sion. There’s a lot more to learnabout these fantastic new crops,such as their yield, or whether tradi-tional populations will consumethem. Golden Rice is, well, golden,not white. Nevertheless, for thefirst time, traditional populationsmay finally have the inexpensive,culturally appropriate food varietiesthey need to correct their nutrition-al deficiencies.

It is easy to become impatient tosolve the world’s micronutrientproblem – and we should be. But ittook nearly 20 years to begin tocome to grips with a single defi-ciency: vitamin A. Let's not bepatient; too many lives are in thebalance. But, as our host, Prof.Chen Junshi concluded at the startof this meeting, “Feel confident!But we still have a long way to go.”The discussions over the past four

days brought something else tomind. The MF must continue toevolve to meet changing chal-lenges. From the start, beginningwith IVACG, these meetings weremeant to bring clinical researcherstogether with policy makers andprogram managers. But, as therewasn’t much in the way of pro-grams to talk about, the “center ofgravity” sat with the clinical re -

searchers, who strove to documentthe extent and severity of the prob-lem. It now appears that the centerof gravity has begun to shift to theprogram side.

Innocenti 2006 reached a consen-sus on the physiological and clini-cal impacts of many specific defi-ciencies, and the health benefits ofinterventions. These formed thecore around which the first MF wasconstructed. Unless someone has ablindingly new insight – say, by dis-covering vitamin X – we now knowmost of what we need to knowabout the most immediate biologi-cal consequences of these micronu-trients to move forward. Newinsights, like the exciting light theNepal cohorts shed on the develop-mental origins of health and dis-ease, are important intellectualstimulants and a reminder that we

Show at the conference banquet

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must keep biologists at the table;there is always more they canteach us. And, as we saw demon-strated this morning, we need tobe thoughtful in fine-tuning policyconclusions, as for newborn dos-ing or reduction of maternal mor-tality, where the specific contextcan be a determinant.

Innocenti 2008 focused on pro-grams and was the core aroundwhich this MF was built. Its bot-tomline consensus statement isthat we don’t know nearly as muchas we could or should. TheInnocenti participants designed a template by whichwe can learn more as we go, though I must say, DavidPelletier’s carefully detailed and rationally constructedmodel reminded me of that old definition of an econo-mist: someone who claims “it may work in practice butit will never work in theory.” The many contextualcomplexities he urged us to consider left me exhaust-ed; it seems a miracle that any intervention program, aspresently constituted, actually works. Science is easy –implementation is tough! But as China’s salt iodizationprogram and Nepal’s vitamin A distribution programdemonstrate, enlightened leadership and political com-mitment can move mountains.

One last observation. Much of what we heard werevaliant attempts to create markets for new solutions,difficulties in managing supply chains, and problemsencountered in reaching remote villages. This, ofcourse, is what managers and the management sci-ences are all about, particularly those employed in theprivate sector. We need to recruit these experts to theMF. The marvelous dialogue on Thursday betweenleaders of multinational companies and those of us inacademia, the public sector, and civil society showedexactly why public-private partnerships have becomethe vogue. We must actively work to strengthen theserelationships, as the private sector’s declarationpledges them to do.

Make no mistake; the world now takes notice. For thoseof you who don’t yet know, Nicholas Christoff, thehighly regarded New York Times columnist presentlytravelling in Africa, extolled the virtues of “that simplevitamin A capsule” in his column yesterday.

It is now my distinct honor to thank our wonderfulhosts, the Local Organizing Committee. Quite literally,without the leadership of Prof. Chen Junshi, this meet-ing would never have taken place. The opening sympo-sium, highlighting the micronutrient status andattempts to combat deficiency in China, ranks as oneof the most insightful and thoughtful we have beenprivileged to hear. To top it off, Junshi then took us offto a fantastic reception, with great food, marvelousdancers, and a master “face-changer.”

Plans are already underway for the next MF. We havereceived, and gladly accepted, an offer from the PrimeMinister of Senegal to host the next meeting.

Meeting hall at Beijing International Conference Center

Blind musician in HouHai. The instrument iscalled Erhu (Chinese 2-string fiddle).

Magazine Issue 2/2009CARIG Conference

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The annual Carotenoid Research Interactive Group(CARIG) Conference was held in the Marriott Hotel inNew Orleans on Friday, April 17, 2009. The four-hourafternoon session was held a day before the officialinauguration of Experimental Biology 2009. This rep-resented the first year for CARIG in its new, formalstatus as a Research Interest Section (RIS) within theformal structure of the American Society of Nutrition(ASN). The Conference attracted upwards of 60 eagerand attentive professionals and trainees. The program,entitled Molecular Aspects of Carotenoid Metabolism,with a central theme surrounding the biology andfunction of the carotene monooxygenase (CMO) fam-ily of cleavage enzymes, was superbly crafted andmoderated by this year’s organizers, Lewis P Rubinand Sherry Tanumihardjo.

The emphasis of the presentation was on a diversity offunctions for CMO1 (the enzyme responsible for thecentral cleavage of carotenoid molecules) and CMO2(the enzyme responsible for the eccentric cleavage ofcarotenoids). The former enzyme was originallyknown as carotene 15,15’-dioxygenase, co-discoveredin 1965 by the late James Allen Olson. It was ever soappropriate, therefore, that the annual tribute withinthe CARIG meeting, the James A Olson MemorialPerspectives on Carotenoids Lecture, featured newfunctions for the old enzyme as its theme. In this ninthlecture in the series, Prof. William Blaner, ofColumbia University in New York, was the awardeeand speaker. The title of his address was “Carotenoids,their retinoid and non-retinoid metabolites and themetabolic syndrome.” In many ways, the prize lectureset the tone and direction for the rest of the meeting. Itfeatured insights derived from the creation of gene-deletion (‘knock-out’) experimental animals, a tech-nique that contributed in much of the conference’s

research. It also focused on participation of the enzymeproteins in metabolic functions not necessarily relatedto the oxidative cleavage of carotenoids. As the entirelecture is reproduced in full on page 6 in this issue, itwill not be treated in any further detail here.

Lewis P Rubin, from the University of South Florida inTampa, presented on the topic of “New functions ofCMO1 and CMO2 in cell regulation.” The first seriesof findings presented related to the confirming ofCMO2 in various tissues, including liver, in a patternof frequent variation among tissue sites, from the 10th

day of mouse fetal development until birth andbeyond. He then changed tack and presented someinteresting data from a prostate cancer cell model, inwhich it was shown that lycopene could induce CMO2expression in certain cell types. Lycopene dosing alsohad the effect of decreasing proliferation of cells withCMO2 over-expression. The speculation here is thatany role for lycopene in prostatic cancer may be by

Annual CARIG Conference Meets in New Orleans

Noel W SolomonsCenter for Studies of Sensory Impairment, Aging and Metabolism (CeSSIAM), Guatemala City, Guatemala

Correspondence: Noel W Solomons, CeSSIAM, 17 a Avenida 16–80, Zona 11, Guatemala City, GuatemalaEmail: cessiam@guate.net.gt

William Blaner, Columbia Univerity, New York

regulating this enzyme, rather thanproducing specific metabolites ofthe carotenoid. Further studies withpartial deletion (CMO2+/-) systemsin prostatic cancer cells, moreover,suggested a role for inflammation-related transcription factor involve-ment, under the influence ofCMO2. Linked to these observa-tions, the speaker speculated thatCMO2 may influence resistance orsusceptibility to prostatic malig-nancy by a mechanism totally inde-pendent of carotene cleavage.

Loredana Quadro, from RutgersUniversity in Brunswick, NewJersey, spoke next on “The role of b-carotene-15,15’-oxygenase(CMO1) during mammalian em -bryo genic development.” Thedirection of her research focusesultimately on how the fetus is nour-ished with respect to vitamin A, amechanism that is poorly under-stood in humans and other species.It is a critical point, given thedegree to which cell differentiationduring organ development inembryos and fetuses depends on aconsistent supply of retinoid acid(RA). In earlier research, it hadbeen established that vitamin Abound to retinol-binding protein(RBP) was the source of RA fordevelopment whereas retinyl esterson lipids provided the vitamin Areserves to the mouse fetus. She hasestablished that both CMO1 andCMO2 are expressed in the placen-ta, yolk sac and embryo of themouse. Basic ontological researchlocates CMO1 protein expressionto different tissues during thecourse of embryogenesis. Thenovel, leading-edge question towhich Dr Quadro brought new evi-dence was the degree to which sys-temic b-carotene contributes to thevitamin A economy of the fetus.Combining the full knock-out sys-tem for retinol-binding protein(RBP-/-) and the homologue for the15,15’ cleavage enzyme (CMO-/-)

as a double knock-out model inmouse dams, and with injections of b-carotene into the peritoneal cavi-ty of animals, the provitamin Asource was partially able to restorethe vitamin A status of the fetus.The fetal vitamin A nutrition wasimproved further with a partialknock-out in the cleavage enzyme,combined with the full RBP exclu-sion in an RBP-/-/CMO 1+/- - com-bination mouse. This is interpretedto demonstrate that b-carotene canindeed be a source of vitamin A,and hence RA for development inthe uterus, with both non-enzymat-ic and enzyme-mediated cleavageto provide the retinoids.

Nikki Ford, a doctoral candidate atthe University of Illinois atChampaign-Urbana, presented atalk entitled “Alterations in caro -tenoid bioaccumulation in micelacking the CMO1 or the CMO2carotenoid cleavage enzyme.” Ittook a different tack from the com-panion presentations insofar as itconcentrated almost exclusively onthe oxidative cleavage function,itself. This study took advantage offindings from mice with deletion ofeither the central-cleavage oreccentric-cleavage monooxyge-nase. One of its observations, foradult mice, coincides with that ofDr Quadro in her embryonic stud-ies: CMO1 and CMO2 are differen-tially expressed in different tissues.As herbivores, mice in nature relyon plant sources for all of their vita-min A, and have an efficient CMO1system. However, with sufficientpreformed vitamin A in their diet,they survive double deletion ofCMO1 without deficits or deficien-cy. This knock-out model can castlight on the role of CMO1 in themetabolism of a non-provitamin Acarotene, lycopene. Its biodistribu-tion in mouse tissues is altered inthe CMO1 knock-out, suggestingthat central cleavage plays somerole in its murine metabolism.

CMO2 knock-out animals alsohave alterations in lycopene distri-bution, suggesting it is subject toeccentric cleavage as well. Thebasic precursor carotenoids, phy -toene and phytofluene, however,are not affected in their distributionin the CMO2-deleted mousemodel. The Illinois laboratoryadvances the notion that CMO1 hasits primary cleavage function with b-carotene in creating vitamin A,whereas CMO2 is the principalcleavage enzyme for dietarylycopene.

Xiang-Dong Wang, Senior Sci-entist at the Human NutritionResearch Center on Aging, TuftsUniversity in Boston, closed the conference program with apresentation on “The mole -cular link between PPAR-g andlycopene metabolites: a double-edged sword.” He oriented the audi-ence to his topic by reviewing theputative biological actions oflycopene in biology (Box 1). Hethen set the parameters of a hepat-ic-damage model, which uses a car-cinogen (diethylnitrosamine, DEN)to produce fat accumulation in cells(steatosis), pre-malignant transfor-mation when injected into rats. Theeffects were exacerbated by a high-fat diet, but generally unaffected by

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Nikki Ford, University ofIllinois at Champaign-Urbana

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a high-alcohol exposure of the animals. When eitherpure lycopene or tomato extract (containing lycopeneand other phytochemicals) were added, the adverseeffects of the rats’ exposure of DEN were ameliorated.Dr Wang noted that, by eccentric cleavage oflycopene, a 21-carbon fragment (apo-10’-lycopenal)can be derived. Further degradation of this apo-lycopenal eventually produces a molecule of RA.More interesting, however, is the fact that the apo-lycopenal induces retinoic acid receptors in nuclearmembranes, thereby up-regulating RA-dependentpathways. Other actions for apo-10’-lycopenal and itsmetabolites were described from assorted experi-ments, including its intervention to ameliorate thehepatocytic abnormalities induced by DEN exposurein rats, as described above. This provides a feasibilityframework of a mechanism for lycopene’s impedingcarcinogenesis. Finally, returning to the alcohol-fedrat model, Dr Wang produced evidence for lycopenesupplementation to the rat effecting an increase (trans-activation) of the nuclear transcription factor, peroxi-some proliferators-activated receptor-g (PPARg). Thiscould explain the downstream consequences of dietaryexposure to lycopene, and provide a mechanistic basisfor a number of the actions imputed to this carotene inBox 1.

The CARIG/VARIG social reception was held onSaturday, the day after the CARIG conference and theevening following the ASN mini-symposium oncarotenoids. Along with the libations, snacks and con-versation, the event hosted the annual best-poster com-petition for graduate students and post-doctoral fel-lows. The US State of Illinois was favored in the judg-ing. One winner was Eunyoung Park, from the labora-

tory of Phyllis Bowen at the University of Illinois cam-pus in Chicago; her poster topic was “Tomato productadherence dynamics in African-American men at riskfor prostate cancer.” The other winner was Nancy JEngelmann from the University of Illinois campus inChampaign-Urbana; her poster was entitled “[13C]-carotenoid production from hp-1 tomato cell culturesfor human metabolic tracing.”

Finally, the CARIG community lamented the demiseof two of the more notable senior contributors tocarotenoid research: Prof. Norman Krinsky, of Boston,and Prof. Hans-Dieter Martin, of Düsseldorf. The first40 minutes of the session were devoted to a formaltribute to these departed leaders of the field. RobertRussell and Liz Johnson of Boston led the homage toNorman Krinsky with a slide presentation containingremembrances of his life, career and science. This wascomplemented by brief comments from the assembledattendees. Prof. Helmut Sies concluded the memorialsection with a brief slide presentation on the career ofProf. Martin.

This was a strong initiation of CARIG as a ResearchInterest Section (RIS) within the organizational struc-ture of the ASN. Enthusiastic attendance at theConference, as a pre-meeting satellite event, wasencouraging, showing that the scientific interest of thecarotene constituency is truly dedicated. The nextCARIG Conference will be held in Anaheim in April2010, in conjunction with Experimental Biology (EB).

Left to right: Monica Orozco, Klaus Schuemann,Liza Hernandez, Noel W Solomons, GabrielaMontenegro-Bethancourt at the CARIG/VARIGsocial reception

• Antioxidant

• Anti-inflammation

• Anti-angiogenesis

• Gap junction communication

• Immune modulation

• Induction of apoptosis

• Induction of cell differentiation

• Induction of Phase II enzymes modulation

• Inhibition of cell proliferation

• Inhibition of cholesterol synthesis

• Interaction with growth factors

Box 1: Putative actions of lycopene

As modified from presentation of X-D Wang

SIGHT AND LIFE Uganda Action for Nutrition Society

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Uganda Action for NutritionSociety (UGAN) was founded byprofessionals, mostly academicsand researchers within nutritionand allied fields, from the EastAfrican region (Tanzania, Kenyaand Uganda). The rationale for thesetup of the Nutrition CoalitionSocieties for Action in the EastAfrican region is to “work togetherfor better nutrition.” The UGANconference, held in Kampala, onFebruary 19–20, 2009, was the firstto be held in Uganda, and secondonly to the inaugural conferenceheld in Kenya.

A number of institutions sponsoredthe conference by supporting vari-

ous aspects of it, including fullysponsoring a number of youngscholars, whose posters and oralpresentations had been accepted,bearing the costs of hosting somesymposia and dinners, and waivingregistration fees for invited speak-ers. The sponsoring companieswere too many for singling out anyparticular one. The conference washosted by UGAN and received highaccolades from the relevant govern-ment ministries as well as goodmedia coverage. The opening cere-mony was attended by the FirstLady of the Republic of Uganda,Mrs Janet Museveni, who inciden-tally is the Patron of UGAN.

Conference focus

A whole-day pre-congress work-shop was held at the Department ofFood Science and Nutrition atMakerere University, Kampala, onFebruary 18. The workshop, whichwas packed full of lectures, discus-sions and practical sessions,focused on a variety of topics,including writing and publishingresearch, designing scientificposters, and preparing nutritioneducation tools.

The main conference was held atKampala’s prestigious MunyonyoCommonwealth Resort Hotel. Thetheme was Challenges, Successes& Opportunities to Improve Nu -trition. Over the two days of theconference, six sub-themes werecovered in parallel symposia:

• Rising food prices, livelihoodsand nutritional well-being• Maternal nutrition and infant andyoung child feeding• Biofortification• Nutrition and HIV• Micronutrient deficiencies • Food and nutritional assessment

Uganda Action for Nutrition Society(UGAN) ConferenceKampala, Uganda, February 19–20, 2009

Francis B Zotor1, Folake O Samuel21University of Greenwich, London, UK; 2University of Ibadan, Department of Nutrition, Ibadan, Nigeria

Correspondence: Folake O Samuel, University of Ibadan, Department of Nutrition, PO Box 22378, Ibadan, NigeriaEmail: samuelfolake@yahoo.co.uk

SIGHT AND LIFE Magazine 2009;2:40–41

Oral presentation of Francis Zotor

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The objective of the conference was to fulfill UGAN’smandate, namely increased lobbying and advocacy for bet-ter nutrition, improved networking channels and the forma-tion of strong partnerships, and information disseminationand knowledge sharing. The conference attracted over 300nutritional scientists from across 19 countries in and out-side of Africa.

The conference was strong on public health nutrition. Mostof the keynote speeches were on this theme. The postersand shorter oral presentations were more varied and cov-ered new foods and formulations to treat and manage vari-ous nutrition-related conditions. Food fortification wasgiven prominence and featured during both the plenary andoral presentation sessions. Aspects covered were specifi-cally in the areas of biotechnology, biodiversity, biofortifi-cation and general agriculture-related issues.

The conference gave some emphasis to food-basedapproaches to solving the nutrition and hunger challengesof the continent. Our observation, however, was that therewas little coverage on more preventive approaches. The

curative approachesto Africa’s nutrition-al challenges maycome at a time whenit is too late to halt orreverse some of thedamage caused bymany preventableconditions currentlybeing witnessed.

The authors of thisreport were support-ed by SIGHT ANDLIFE in their partici-

pation at the conference. Dr Francis Zotor served as chairof the plenary session on micronutrient deficiencies on thesecond day of the conference, during which two key paperswere presented by GAIN and FANTA-2. Both Dr Zotorand Dr Folake Samuel gave oral presentations during thesymposia sessions; the former on the “Application of thefood multimix concept in meeting the nutritional needs ofmalnourished children between the ages of 6–36 months atdifferent stages of rehabilitation” and the latter on“Assessing the prevalence of child undernutrition usingconventional indices and the composite index of anthropo-metric failure (CIAF).” Dr Samuel also submitted a posterpresentation that she co-authored with Wilna Oldewage-Theron on “Nutritional assessment of an elderly populationin a poor peri-urban area in South Africa.”

Where is the Food Basket?

By Mukundane B Albert

Read at the Uganda Nutrition Congress 2009:Challenges, Successes & Opportunities toImprove Nutrition

Planted among farmersMoving in cargo of transportersSinking in a turbulent lake of alcoholDefended and protected in a military campHospitalized by the nongovernmental organizationsWhere is the food basket?

Is it laid at the altarOr a ball kicked by sportsmenScrambled by the politicianCentered amidst mob justiceAccounted with financial statementsWhere is the food basket?

Is it established by public debatesInspected by the extension workersManaged in serious investmentsSearch-lighted by professionalsLaunched by the big honorablesWhere is the food basket?

Is it hidden in the journalists’ recordsOr in centers of higher learningMushrooming in business units of the global worldIn no-go areas of slums or urban regionsIn tribal granaries infested with weevilsWhere is the food basket?

Modern supermarket of modern manDecentralized units of common manIn fragmented blocks of investments inheritedlands of royal empiresMarginalized in hidden territoryWhere is the food basket?

Torn apart by the scavengersRebuilt by the visionary leadersMasterminded by the research unitsAdvertized by the sweet ingredients in itKept in viable projectsWhere is the food basket?

Designed by an artistAuthorized by the force of natureValued like a dollarMesmerized like in sleepProtected like the environmentWhere is the food basket?

Francis B Zotor and Folake O Samuel

SIGHT AND LIFE Wageningen Nutrition Sciences Forum

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Celebrating its 40 years of research and education,Wageningen University welcomed over 300 re-searchers, young investigators and professionals innutrition and health from European, American, andAfrican countries for the Nutritional Sciences Forum

held at Burger’s Zoo in Arnhem City on March 4–6,2009. The global theme of the forum, Too Much –Too Little, covered four main topic areas, namelyhuman nutrition, molecular nutrition, internationalnutrition, and nutritional epidemiology. Six oralcommunications and over fifty posters were present-ed by students and young investigators on these top-ics (see details in Box 1). Very important at thisforum were also the keynote addresses by differentspecialists in nutrition and related fields, and thegeneral forum discussion.

Keynote addresses

In summary, the speakers first described the overallfood and nutrition situations, the challenges of theresearch addressing nutritional problems, and thepublic and private responsibilities when making

decisions for intervention approaches. Two specifickeynote presentations, one addressing policies innutritional science and the second addressing theimportance of nutrient profiling in measuring thenutrient content of the diet at national level were alsopresented.

The overall food and nutrition situations

In summary, two food and nutrition situations haveoccurred: the Western situation and the non-Westernsituation. The former is characterized by an optimalintake of folate, B6, B12 and amino acids, and the sus-tainability of the global food supply, with the impor-tant production of dairy foods. But the greatest cur-rent problems are the massive intake of refined starchand sugar, and important questions relating to thedevelopment of dairy products are to know theireffective role and what is too much. In non-Westernsituations, while multiple micronutrients deficienciesare still public health issues, especially in resource-poor countries, the dietary pattern is more and morecontrolled by the global food companies, so thatintake of refined starch and sugar is increasing.

The challenges of research addressing nutritional issues

An important challenge in research addressing theissue of obesity in Western situations is energyunder-reporting in food intake assessment studies.The speakers suggested that nutrition must be inte-grated with genetics and nutrigenomics must movetoward the behavioral side of diet and health to bet-

Too Much – Too LittleThe Wageningen Nutritional Sciences Forum, Arnhem,March 4–6, 2009

Nadia Fanou FognyUniversity of Abomey Calavi, Department of Nutrition and Food Sciences, Cotonou, Benin

Correspondence: Nadia Fanou Fogny, University of Abomey Calavi,Department of Nutrition and Food Sciences, Faculty of Agronomic Sciences, 01 BP 1025 Cotonou, Benin.Email: nadia.fanou@gmail.com

SIGHT AND LIFE Magazine 2009;2:42–44

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ter understand the causes and thecontext of obesity. Furthermore, toincrease the accuracy of publisheddata, energy under-reporting mustbe an issue for every journal editor.In non-Western situations, researchshould give priority to the effect ofmultiple micronutrient supple-ments in meeting nutritional ade-quacy. The possible gains from newtechnology to ensure nutritionaladequacy through the advantagesand the challenges of genetic engi-neering, biofortification and nan-otechnology were also discussed.

Public and private responsibilitiesin preventing nutritional problems

The speakers suggested that, toprevent obesity as a public healthissue, interventions should be tar-geted (target persons would bethose susceptible to obesity), se -lective (focusing on a specificapproach), and participatory(involving the effective participa-tion of the targeted groups). In thekeynote talk addressing the non-Western situations, the public andprivate responsibilities when cho osing fortification as an inter -

ven tion approach to micro nutrientdeficiencies were discussed. Thespeaker discussed market-drivenfortification, mostly the responsi-bility of the food in dustries butwith governments setting regula-tory limits; mass fortification andtargeted fortification, which aremainly public responsibilities andtarget a combination of micronu-trient deficiencies of public healthsignificance. Finally, monitoringand eva luation are essential for aneffective food fortification appro -ach and the key challenge in foodfortification is to maintain theequilibrium between need andsafety.

Nutrient profiling

In this specific keynote address,the definition and importance ofthe nutrient profile (NP) wasdefined as the nutrient content ofindividual foods or diets. Twokey concepts can be derived fromthe NP: the NP for an overall(habitual) diet and the NP for abalanced diet (recommendeddaily allowance, daily recom-mended intake). The NP of indi-

vidual foods does not need tomatch that of a balanced diet butthe NP of individual foods caninfluence that of the overall diet.Nonetheless, nutrient profiling isa science-based concept andfoods should not be classified byNP alone, but must be consistentwith dietary guidelines.

From ‘little science’ to ‘big sci-ence’: a philosophical perspective

This keynote address reviewed theimportant periods in the nutrition-al sciences, from the ‘dark ages’(1960-1980), marked by a succes-sion of disasters and periods ofhunger, to the booming decades,with the development of systemscombining nutritional and biolog-ical approaches. Important chal-lenges remaining for researchteams at universities includedeveloping strong teamworkcrossing departmental boundaries,with clear guidelines for data own-ership, and fair access to creditand technology, with support bygood funding streams.

Forum discussion

A forum discussion has been start-ed based on the key points of thekeynote addresses. The threestatements discussed are presentedin Box 2, along with the discus-sions and conclusions.

Conclusions

The Wageningen NutritionalScience Forum was a great oppor-tunity to highlight the strengthsand the weaknesses of the nutri-tional sciences throughout the lastand present decades, not only forthe scientists of WageningenUniversity but also for profession-als in nutrition and health theworld over. Moreover, the bigchallenges in alleviating the bur-den of nutritional problems were

Box 1: Keynote addresses and speakers

• Too much: Nutrition in abundance by Prof. Mike J Gibney,University College of Dublin, Ireland• Too little: Nutrition inadequacy by Prof. Keith West, Johns HopkinsBloomberg School of Public Health, USA• Weight management: Public health target, by Prof. ShirikiKumanyika, University of Pennsylvania, USA• Healthy food and nutrition in Western situations by Prof. WalterWillett, Havard University, USA• Healthy food and nutrition in non-Western situations by Prof. EmornWasantwisut, Mahidol University, Thailand• Fortification, public and private responsibilities by Prof. Richard FHurrell, Swiss Federal Institute of Technology, Switzerland• Nutrient profiling by Prof. Sean J Strain, University of Ulster, UK• Nutritional adequacy: Possible gains from new technology by Prof.Michael B Zimmermann, Swiss Federal Institute of Technology,Switzerland and Wageningen University, The Netherlands• Nutrition: From ‘little science’ to ‘big science’ a philosophical perspective, by Prof. John C Mathers, Newcastle University, UK

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emphasized, along with possiblenew approaches that can be help-ful for research. The friendlyambience of the Forum was fur-ther brightened with interestingdemonstrations of advanced tech-nologies in food and nutrition, acomedy troupe performance onthe importance of teamwork infood and nutrition research, andtours around Burgers’ Zoo.

Reader Survey 2009 – A Success!

Since April, we have been evaluating our readers’ satisfaction and gathering a sample of opinions that willform the basis for upgrading the Magazine. Indeed, well over a thousand respondents have kindly taken thetime to fill in this survey and we are very grateful to all of you.

The online version of the survey has been particularly successful, capturing more than 70% of the responses,and tremendously facilitating our processing and analysis. We are equally grateful to our readers with limitedaccess to the Internet who made sure their responses reached us by post, sometimes even at their own expense.The names of online and hardcopy respondents were pooled for the lucky draw and a hundred readers havebeen randomly chosen to receive SIGHT AND LIFE goodies for their participation.

While we are still analyzing the full results and will report our findings in the next edition of the Magazine(Issue 3/2009), we are already aware of some positive feedback from the survey. Our intermediate analysisrevealed that 85% of our readers found the Magazine useful to their work and most of them were highly appre-ciative of the scientific and technical articles. Nonetheless,some aspects of the Magazine were not as well-rated and willbe our focus for futureimprovements.

We are truly grateful forthe warm words of appre-ciation and encourage-ment for SIGHT ANDLIFE and our Magazineincluded in many of theresponses. Your supportis always a source ofrenewed inspiration thatstrengthens our in serv-ing our community asbest as we can.

Box 2: Discussion statements and conclusions from the forum discussion

Statement 1: Food patterns are a useful concept for improving healthin Western but not non-Western situations. Conclusion: There should be no differences between concepts for oneor the other situation; food patterns are a useful concept for all situa-tions.

Statement 2: To reduce micronutrient deficiencies in non-Westernsituations, biofortification of staple foods is the preferable strategy.Conclusion: No strategy is more preferable than another – all strate-gies should be complementary.

Statement 3: Nutrient profiling will adversely affect populationhealth by increasing the risk of unfavorably high intake in subgroups.Conclusion: It is a public matter – consumers have to be careful aboutwhat they buy in supermarkets.

Magazine Issue 2/2009A Day in the Life

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SIGHT AND LIFE (SAL):Marc,what does your job entail and whatare your key responsibilities?

Marc Van Ameringen (MVA):I’m responsible to the Board ofGAIN, which represents key stake-holders and shareholders, for meet-ing our agreed performance targets,which include reaching a billionpeople and reducing key deficien-cies by certain percentages. Addi -tionally my role in GAIN includesensuring alliance partnerships areestablished that are needed to deliv-er programs at the country level. Aswell as mobilizing the financial andtechnical resources that we need toget the programs in place, I makesure that we’re delivering lastingresults.

SAL: It’s a very big responsibilityin a serious field. Do you enjoy yourjob?

MVA: On the whole yes. I thinkGAIN has made a huge amount ofprogress in the last 3–4 years, whichis rewarding. The pace of change isoften slower than we’d like to see as

programs have a high level of com-plexity and we can’t influence allthe factors that determine whetherprograms will be successful. At thesame time, the challenges inaddressing malnutrition are enor-mous and a lot of learning andadaptation is involved – whichmakes it exciting, from both a tech-nical and programmatic standpoint.

SAL: GAIN’s vision is a worldwithout malnutrition. Is this a feasi-ble objective? Can you imagine aworld in which malnutrition doesnot exist?

MVA: Yes. There are certainly theresources and technology out thereto end malnutrition. In the best casescenario there will still be someminimum level of under-nutritionand obesity in the world but it is fea-sible to dramatically reduce mostforms of malnutrition. The keyobstacle is changing peoples’ atti-tudes, especially at the level of keydecision-makers in all sectors, onthe importance of investing in pro-grams and partnerships that can sig-nificantly improve nutrition andhealth outcomes for the two billionpeople who are malnou rished.Unlike in the case of many vaccineswe’re not waiting for a new big dis-

covery; we already know enough todo something. I’ve spent 25 yearsmanaging programs in developingcountries and feel strongly that if wehave the right leadership and com-mitment, I don’t see why in 20–30years we should have anywhere nearthe same level of malnutrition wehave today.

SAL: Who are the key decision-makers and what do you have to doto try and gain their understandingand support for your activities?

MVA: They are the people in devel-oping countries who are leaders andcan influence national policy andresource allocations. They createthe advocacy needed across theministries of planning, economicaffairs, trade and industry, healthand standards. In the private sectoryou need people in key industries toalso play a leadership role, and insociety at large you need consumergroups and NGOs who also step up.They all need to be aligned on thesame theme and issues.

You also need the citizens to bemuch more engaged. Our surveysshow, especially in Africa and Asia,that food is one of the most impor-tant issues for families, yet this con-

A Day in the Life of Marc Van Ameringen

Marc Van Ameringen is the Director of the Global Alliance forImproved Nutrition (GAIN) which fights malnutrition by mobilizingpublic-private partnerships. Under his leadership, GAIN has become amajor partner of governments and business leaders, implementingnutrition programs in 27 countries. These are improving the lives ofclose to 200 million people with targets to reach 1 billion by 2010.

In the latest of our series A Day in the Life, Marc van Ameringen talkswith SIGHT AND LIFE about his work at GAIN and the challengeshe has faced.

Marc van Ameringen

SIGHT AND LIFE Magazine 2009;2:45–48

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cern has not translated into policy, especially wherenutrition is concerned.

Within OECD and DAC the people who are decidingpriorities on development assistance need to understandthat nutrition is a critical area of investment. Under-nutrition receives around USD 400 millions a year infunds where HIV/AIDS gets USD 3–4 billion eachyear. This lack of emphasis exists in not just the G8 butthe G20 as well.

SAL: What do you do to try and overcome it? Whatkinds of communications work?

MVA: GAIN has large-scale programs for 27 or socountries. These programs have big advocacy elementsand the communication is focused on raising awarenessof the importance of food fortification or micronutrientdeficiencies or malnutrition more generally. However,where we have supported large-scale public campaigns,we have seen quite low levels of return on these invest-ments. This has led us to rethink our approach and weare now supporting more targeted advocacy aroundspecific policy outcomes we are hoping to achieve.

As a result, GAIN has developed a new advocacy strat-egy where we will be making greater investments inthis area starting with 10 developing countries over thenext 4–5 years. We will be working closely withalliance partners and our funding partners who are sup-porting us in this area like the Gates Foundation andChildren’s Investment Fund Foundation.

SAL: You mentioned fortification. What are the keytrends in food fortification at the moment?

MVA: GAIN has become known as the major playersupporting large-scale food fortification initiatives. Forthe last 6 years we’ve been supporting these large pro-grams, which reach entire populations in a country –something which had never been done before. Wefound that national fortification alliances came togeth-er easily around GAIN grant opportunities. So onetrend is that there is a lot of interest and demand forthese large-scale national food-fortification interven-tions.

We’re seeing a lot more companies along the valuechain voluntarily committing to fortifying products andto tackling malnutrition. This includes at all sizes andtypes of businesses: local, regional and multinational.We at GAIN encourage this approach as well and try toensure that the products they deliver will have a nutri-tional impact especially on women and children.

Some donors are beginning to realize that everythingstarts with nutrition. The US and Canadian govern-ments have always understood this, but now someEuropean donors are starting to come on board. Thisgoes alongside a greater awareness of the value of nutri-tion among the multilateral agencies such as UNICEF,WHO, WFP and World Bank. Private foundations areincreasingly recognizing the importance of nutrition,and here the Gates Foundation is worth highlighting asthey have been supporting this area for the last 8 yearsand have been instrumental in getting nutrition on theradar screen of other key donors.

There is more research interest around micronutrients,and the Micronutrient Forum and USAID have played acritical role. People are looking at how quickly newresearch can make a difference and be applied in pro-grams.

SAL: A huge number of groups are involved. What’sthe key to getting all these different organizations towork together in an effective way?

MVA: Getting all these groups working together at aglobal level is very difficult to achieve but it’s also whyGAIN was created. From the outset we have focussedour efforts at the country level which is where we canhave the biggest impact. It’s about getting local buy-in,investment, resources and an effective environmentwhere the public and private sectors can co-operate.Before GAIN, nutrition was seen as a public issue: nowwe drive it as a public/private issue. So creating a plat-form for public, private and civil society sectors to worktogether is key, and being able to provide incentives,including funding for initiatives, is also important.

SAL: What made you move from the MicronutrientInitiative in 2005 to GAIN?

MVA: Before the Micronutrient Initiative I was withthe International Development Research Centre for 15years, nine of those in Africa, and then I worked for theG8 as their advisor on Africa for a year before joiningMI for a short period. I was asked in 2005 to restructureGAIN, which involved moving it to outside the UN sys-tem and reconstituting it as a Swiss foundation. Ialready had a reputation for being able to deliver devel-opment programs in complex environments from mywork in Africa and felt that I could apply my broaderknowledge of development to the challenges of nutri-tion. One of the things that I realized early on in the jobwas that 75% of the issues GAIN faces in reaching itstargets had little to do with nutrition. Getting programsgoing was more about making a large upfront invest-

Magazine Issue 2/2009A Day in the Life

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ment in countries building the enabling environment,it's about changing national development agendas, cre-ating incentives for parties to act, it’s about exploitingpartnerships, getting all the stakeholders to come to thetable, and it’s about showing results. I came in to reor-ganize the original GAIN model, which will take timeto roll out but can work, and when it does, is veryrewarding for me and my colleagues.

SAL:What do you enjoy most about your job, Marc?

MVA: The most interesting part is getting programsgoing and seeing their health impact, reaching millionsof people every day. GAIN is a leader in innovation; itwas even listed as one of the top 50 innovative compa-nies a few years back by Fast Company in the US, even

though we’re not a company. Although we’ve got manynutritionists at GAIN, we also have a real cross-sectionof experts, from investment bankers and supply chainmanagement as well as experts from the pharmaceuti-cal industry, to those who have come from NGOs, gov-ernments and the UN, all of which leads to newapproaches and a great deal of innovation. We’rerethinking the traditional approaches to addressing mal-nutrition and this is exciting.

SAL: If you could change one thing about your job,what would that be?

MVA: I wouldn’t do so much stakeholder manage-ment. There’s a huge amount of energy spent on it andit is crucial, otherwise programs won’t happen. But I’d

About Marc Van Ameringen

Marc Van Ameringen has been the Executive Directorof the Global Alliance for Improved Nutrition (GAIN)since 2005. Under his leadership, the Global Alliancefor Improved Nutrition has become a major partner ofgovernments and business leaders in 27 countries.Currently nutrition programs supported by GAINreach 200 million people and at scale will improve thelives of more than 600 million people, the target beingto reach 1 billion by 2010. Prior to joining GAIN, in2005, Mr Van Ameringen was Vice President of theCanadian-based Micronutrient Initiative, which focus-es primarily on delivering vitamin supplementationprograms around the world. Before this assignment, he

was Special Advisor to the G8 Summit, assisting theG8 in responding to the NEPAD initiative. From 1992to 2002, Mr Van Ameringen was a Director based inAfrica for the International Development ResearchCentre (IDRC), responsible for a number of largedonor programs across Africa. He played an importantrole in assisting South Africa and other countries inSouthern Africa in their reconstruction and develop-ment. Prior to moving to Africa, he held various seniorpositions in Canada for IDRC and other organizations.Mr Van Ameringen has served as a Board Member andTrustee of many different development organizationsand has published a number of books on developmentin Africa.

About the Global Alliance forImproved Nutrition (GAIN)

The Global Alliance for Improved Nutrition (GAIN) isa Swiss foundation whose vision is a world withoutmalnutrition. Created in 2002 at a special UN sessionon children, GAIN’s mission is to reduce malnutritionthrough food fortification and other strategies aimed atimproving the health and nutrition of populations atrisk.

GAIN is an alliance of governments, internationalorganizations, the private sector and society at large.The organization funds and advises national govern-ments, businesses and social organisations to worktogether to develop and distribute high-quality andaffordable fortified food products and complementaryfoods for low-income populations.

The GAIN Secretariat is a small team of professionalsand support staff who manage the day-to-day opera-tions of the foundation. GAIN is internally organizedin four main areas of activity:

• Nutrition Programs (National Food Fortification,Infant and Young Child Nutrition, Infection andNutrition and Infectious Diseases, Universal SaltIodization, the GAIN Premix Facility) • Performance Measurement & Research• Partnerships & Capacity Building• External Relations (which includes Communications& Advocacy)

GAIN is headquartered in Geneva, Switzerland, andhas Regional Offices in New Delhi, India; Beijing,China; Cairo, Egypt and Johannesburg, South Africa.

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prefer to be able to devote all my time to other aspectslinked to the delivery of programs.

SAL:What does SIGHT AND LIFE mean to you?

MVA: I read the magazine and it brings new evidenceand knowledge to bear on vitamin and mineral defi-ciencies. It’s good that it highlights different programsand successes. We also work closely with DSM, whichis one of the leading companies in our businessalliance. The magazine shows its commitment to phil-anthropic work. The publications are rigorous andthought-provoking; we need a lot more of this. SIGHTAND LIFE is seen as an impartial commentator.

SAL: What are your interests outside work? What doyou do in your free time?

MVA: Unfortunately my weakness is that I’ve worked60–70 hours a week to turn GAIN around, which hasn’t left much time for outside work. But this ischanging. I used to play ice hockey in my spare time buthad to abandon that when I moved to Geneva. Now Ispend time with my family, visiting the region and ski-ing. When I do get time off, I take advantage of thestunning countryside here, especially the Alps.

SAL: Is there anything else you’d like our readers toknow, Marc?

MVA:Yes: we need to bring the private sector into playmuch more to get real investment into this sector. It’snot just more money; it’s about getting industry to beresponsible and recognizing that being responsible isgood for business.

Interview by Jonathan Steffen

The Guidebook Nutritional Anemia isnow available in

English, French and Spanish

Magazine Issue 2/2009Selenium

49

Introduction

Over the last 10–15 years, selenium deficiency wasfound to increase viral pathogenicity by inducing permanent changes in the viral genome to increase itsvirulence, and selenium supplements appeared tolower the risk of certain important cancers. Theseobservations stimulated both fundamental and publichealth research on this important trace element. Morethan 35 proteins have been identified where seleniumis a constituent element but, for many of these, there isstill no known function. Furthermore, the persuasiveproperties of selenium compounds as cancer preven-tive agents in man have so far eluded identification.

Selenium is an essential nutrient that plays a catalyticrole at the center of some proteins. Many of these proteins have essential antioxidant functions with animportant role in immune defenses. Some are involvedin thyroid metabolism and in sperm motility and oth-ers may play a role in reducing the risk of some can-cers.1 Extremely low dietary intakes (< 19 µg/d) resultin severe disease, such as Keshan disease in humansand white muscle disease in domestic livestock. Lesssevere deficiencies can cause a variety of signs andsymptoms more closely related to reduced selenopro-tein activity2 and experimental studies suggested thatviral pathogenicity was increased by selenium defi-ciency.3 However, no evidence of deficiency is seen inpopulations with intakes of 40 µg/d.4 A dietary intakeof 50–55 µg/day will permit functional saturation andsupport the catalytic and immunological roles of sele-nium.5 Amounts in excess of a normal daily intakemay be necessary to protect against cancer and someevidence suggests that selenium metabolites in theexcretory pathway may be responsible for the latter.1

Hence, anti-cancer benefits may only be achieved with

selenium supplements that promote the synthesis andexcretion of specific selenium metabolites. However,selenium is toxic at high intakes and a maximal safeselenium intake of 450 µg/d from all sources for adultmales was recommended in the UK.5

Dietary selenium is found in both plant and animalfoods but wheat and meat (not fish) are probably themost important sources of selenium. Bioavailability of

Selenium – Some Notes on ImmuneFunction and Recent Cancer Trials

David I ThurnhamMRC Human Nutrition Research, Elsie Widdowson Laboratory, Cambridge, UK

Correspondence: David I Thurnham, 46 High Street, Little Wilbraham, Cambridge CB21 5JY, UKEmail: di.thurnham@ulster.ac.uk

Figure 1: Biologically important pathways inselenium metabolism.Selenium occurs naturally in selenoproteins ofplants and meats as amino acids selenomethion-ine (SeMet) or selenocysteine (SeCys), or asinorganic salts, such as sodium selenate(Na2SeO4). These forms are reduced or degrad-ed to hydrogen selenide (H2Se), which is a gen-eral precursor compound for the endogenoussynthesis of selenoproteins, e.g., the glutathioneperoxidase (GPX), deiodinases, thioredoxinreductases, etc. Excretion of selenium can occurafter methylation of hydrogen selenide. Someplants contain methylated forms of selenium(methylSeCys) that can enter directly into theexcretion pathway. Modified from Finley.1

Inorganic saltsof selenium e.g.,Na2SeO4

Food selenium,e.g. SeCys proteins

H2Se

SeCys proteins,e.g., GPXs

Excretion,i.e., urine, breath

Reduction

SeCys SeMet

MethylSeCys(some plants)

Syntheticmetabolism

Methylation

SIGHT AND LIFE Magazine 2009;2:49–56

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selenium in these foods is high.Fish is unusual in that the seleniumcontent is relatively high butbioavailability is reported to be low,especially when compared withwheat.1 Because dietary seleniummust undergo metabolic transfor-mation to biologically activemetabolites, measurements ofabsorption of selenium are unfortu-nately not sufficient to measurebioavailability as with zinc or iron.The chemical form of seleniumpartially determines its metabo-lism. Thus, ingested selenium hasthree potential fates; (1) it may bereduced or degraded to selenideand inserted into specific proteinsas selenocysteine (SeCys); (2) inthe form of selenomethionine(SeMet), it may be inserted intogeneral proteins as a substitute forthe amino acid, methionine (storeor reservoir?); or (3) it may bereduced to selenide, sequentiallymethylated and ultimately excretedfrom the body, mainly in urine(Figure 1). Because of the severalpossible paths dietary seleniummay take, the chemical form deter-mines the ease with which the sele-nium is stored, utilized or excretedand its bioavailability.

Metabolic roles of selenium

In general, selenoproteins serve asenzymes that catalyze redox reac-tions. Specific selenocysteine-con-taining selenoproteins with knownfunctions include two deiodinases,

several thioredoxin reductases,selenoprotein P, five glutathioneperoxidases and others.6 Seleniumis involved in thyroid hormonemetabolism through the deiodinas-es, in regenerating the antioxidantsystems through the thioredoxinreductases, and selenoprotein P

may serve as a transport protein forselenium as there were sharpdecreases in the brain and testis,and an increase in urinary seleniumin mice when the selenoprotein Pgene was deleted.6,7 Selenopro -tein P is only found in extracellularfluids and may provide redox pro-tection in the plasma. It has recent-ly been suggested that the concen-

tration of selenoprotein P in plasmamay be a better biomarker of wholebody selenium status that glu-tathione peroxidase.7

The glutathione peroxidase are par-ticularly important enzymes re -quired to remove oxidative end-

products, including hydrogen per-oxide and lipid hydroperoxides.The two main enzymes are GPX1and GPX2. GPX1 is abundant in thecytosol and in mitochondria, andprimarily removes hydrogen perox-ide, while GPX2 is abundant inlipid membranes and removes lipidhydroperoxides. An important by-product of oxidative metabolism in

Map of Keshan where the first case of selenium deficiency wasidentified.

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mitochondria is the free-radical superoxide and thiscan be converted to hydrogen peroxide through theactivity of superoxide dismutase (SOD) (Figure 2).Superoxide is one of a group of reactive oxygen inter-mediates (ROI) that are formed in tissues. Free radi-cals are highly reactive; they cause lipid peroxidation,disrupt cellular membranes and can potentially dam-age any organic cellular component, including DNA.Their destructive power can be used to advantage, forROI are part of our cell-mediated immune defensesand assist in the killing of invading bacteria and virus-es. However, in less traumatic situations, they need tobe deactivated and, in the case of superoxide, thewidely-distributed enzymes, SOD and GPX1, harm-lessly convert most superoxide through hydrogen per-oxide to water (Figure 2).

Selenium and immune function

Investigations into the etiology of Keshan disease(KD) lead to some important observations on the roleof antioxidant defenses in host tissues in controllingviral multiplication and preventing development ofviral pathogenicity.3 Conventionally, malnutrition isviewed as impairing the immune system and facilitat-ing increased pathogenesis in the malnourished hostwhen attacked by disease. Two workers, Beck andLevander, chose to study viral pathogenicity in experi-mental selenium deficiency as Chinese work suggest-ed there was viral component in KD. They observedgreater pathogenesis in the selenium-deficient host andfound that this was at least partly due to permanentchanges in the genomic structure of the virus.8,9 Thatis, their work suggested that a viral disease was notonly more severe in the presence of selenium deficien-

cy but that a malnourished host could potentially trans-mit a more severe disease to others.

KD is an endemic cardiomyopathy first described inChina in the 1930s. It is characterized by necroticlesions in heart muscle and was limited to persons withvery low selenium status living in regions of Chinawith selenium-poor soils. Women and children were athighest risk and selenium supplementation of popula-tions living in these areas appeared to prevent the dis-ease.10 However, not all individuals with low seleniumstatus develop KD and other factors were suspected.Eventually, Chinese scientists were able to isolateRNA enteroviruses from the blood and tissues of KDvictims. RNA enteroviruses are members of thePicornavirus family that includes viruses responsiblefor polio, foot and mouth disease, and the commoncold.3

Beck and Levander chose to study selenium deficien-cy using a mouse model and a coxsackievirus, which isa member of the same family of RNA enterovirusesand was known to cause inflammation and necroticdamage in heart muscle. They infected groups of sele-nium-deficient and selenium-adequate mice with twostrains of coxsackievirus, one benign and one virulent,and then assessed the damage produced in the heartmuscle of the mice after 10 days. The height of the barin Figure 3 indicates the extent of the damage andshowed that both strains of virus caused more damagein selenium-deficient mice.8 The workers also showedthat the viral load was greater at 3, 5, 7 and 10 dayspost-infection in the selenium-deficient mice but that,

Figure 2: Efficient removal of superoxide by super -oxide dismutase and glutathione peroxi-dase.The free radical superoxide is reduced by theenzyme superoxide dismutase to hydrogen per-oxide and oxygen. The hydrogen peroxide isthen further reduced by glutathione to water byglutathione peroxidase. Oxidized glutathione isconverted back to reduced glutathione by theenzyme glutathione reductase (not shown).

2O2•-+ 2H+ H2O2 + O2 Superoxide

Dismutase (SOD)Hydrogenperoxide

H2O2 + 2GSH GSSG + 2H2O GlutathionePeroxidase(GPX)Reduced

glutathioneOxidisedglutathione

Figure 3: Effect of selenium status on the devel-opment of myocarditis.Mice were fed selenium-deficient or -adequatediets for 4 weeks before infection with either abenign or a virulent strain of coxsackievirus.Heart pathology (myocarditis) was measuredafter 10 days. The heights of the bars indicatethe degree of damage, inflammation, and necro-sis in the heart muscle. Adapted from Beck.8

0

3.5

3

2.5

2

1.5

1

0.5

Inflammation

Virulent +Se Virulent -Se Benign +Se Benign -Se

Arb

itrar

y un

its

by day 14, the virus was cleared from the body. Therate of viral clearance was the same as for the seleni-um-adequate mice. That is, in the malnourished ani-mal, although the viral infection was worse than in theadequately nourished animal, the ability to clear thevirus was not altered.8

Investigations of the immune responses in the seleni-um-deficient mice found that B-cell functionsappeared to be unaltered but that cell-mediated immu-nity was impaired since T-cells were less able to proliferate on stimulation with specific antigens ormitogens, and the production of cytokines interferon-g(IFNg) and interleukin-2 (IL-2) were both impaired incomparison to selenium-adequate mice.8 The impair-ment in immune responses may explain why the viralmultiplication was increased by selenium deficiencybut the authors also found that viral pathogenicity wasincreased in the selenium-deficient mouse.

Further experiments were done in which selenium-deficient mice were once more exposed to the benigncoxsackievirus but, on this occasion, when the infec-tion was at its height (day 7), blood from the mice wastaken and re-inoculated into selenium-adequate mice.Previously, the benign virus in the selenium-adequateanimal caused no infection and no damage to theheart; on this occasion, the infection progressed andthere was inflammatory damage to the heart. Theseresults suggested that the viral genotype had beenaltered in the selenium-deficient mice and subsequentsequencing identified changes in six nucleotides. Allsix of the nucleotide changes have been found in othervirulent strains of the coxsackievirus and the experi-ments demonstrated for the first time that replicationof a normally benign virus in a selenium-deficient hostcan alter the genotype of the pathogen.8

Selenium deficiency per se is probably not the cause ofthe changes in genotype but rather an impairment inantioxidant defenses initiated by a lack of selenium.The authors also showed that similar changes in viralpathogenesis of the benign coxsackievirus were produced by vitamin E deficiency, and by vitamin Edeficiency plus polyunsaturated fatty acid excess tofurther aggravate the oxidant stress,11 by feedingexcess iron to mice before infection,3 or by usingGPX1-knockout mice.3 Interestingly, the immuneresponses of GPX1-knockout mice were opposite tothose of selenium-deficient mice. GPX1-knockoutmice displayed normal cell-mediated immunity to bothmitogen and antigen but there was a greatly reducedantibody response. These results may suggest that theimpairment in antioxidant defenses far outweighs any

alterations in immune defenses caused by seleniumdeficiency in stimulating the pathogenicity of thebenign coxsackievirus.

Figure 4 summarizes the results of these experiments.A disturbance in the antioxidant defenses of the hostpromoted genomic changes and increased virulence ina previously benign form of the coxsackievirus. Bothselenium, through the enzyme glutathione peroxidase,and vitamin E in lipid membranes are importantantioxidants, and deficiencies potentially increase oxidant stress. Iron is a known pro-oxidant but manymechanisms are in place to prevent iron-induced oxidation. To account for the effects of iron, theauthors suggested that viral replication takes place initially in the liver and, in mice with iron overload,

tissue damaged by viral replication may release theiron and increase oxidant stress with the same effect asan antioxidant deficiency. Lastly, polyunsaturatedfatty acids (PUFA) were used in conjunction with vita-min E deficiency by Beck and her colleagues. PUFAare easily oxidized and could increase oxidant stress,as suggested, but PUFA are also known to increasemembrane fluidity, influence eicosanoid production,and reduce lymphocyte proliferation and production ofIFNg and IL-2. That is, PUFA have a similar effect onimmune function as selenium deficiency so the precise

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Figure 4: Methods by which host malnutritionmay alter viral pathogenesis.The figure illustrates the potential importance ofmicronutrients that cause host malnutrition andcan influence antioxidant defenses through defi-ciency (e.g., selenium, vitamin E) or excess(iron, polyunsaturated fatty acids). Impairedantioxidant defenses increase oxidant stress andoxidant stress may be the main facilitator ofgenomic changes and increased viral virulence.Changes in immune defenses are more variablein response to different micronutrient abnormal-ities but they too will influence disease patho-genesis. Modified from Beck.8

HOST MALNUTRITION

Se deficiencyPUFA excess

Fe andPUFA excess

Se and Vitamin Edeficiency

Altered immunedefenses

Increasedoxidantstress

Impairedantioxidant

defenses

Altered viral genome

Increased susceptibility to viral pathogenesis

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role of PUFA in promoting genom-ic change is unclear.

Anti-cancer role of selenium

The well-established antioxidantproperties of selenium automati-cally implicate it in reducing therisk of some cancers. Low seleni-um status may impair antioxidantdefenses and increase the risk ofdamage to cell components in-cluding DNA. A long-standinghypothesis on the etiology ofsome cancers is that they are aresult of the failure to repair dam-age to nucleotides in DNA causedby ROI.12,13 Furthermore thepotency of supplemental seleniumwas exemplified by a meta-analy-sis of the combined data from anumber of studies comparing thesignificance of selenium, retinol,b-carotene and vitamin E in rela-tion to cancer risk. Among theseselenium emerged as the micronu-trient with the most consistentlyprotective effect.14 However, thesupplementation study reportedby Clark and colleagues was themost exciting study to beannounced, for it appeared that200 µg/d from selenized yeast(Se-yeast) was capable of reduc-ing overall cancer morbidity andmortality by almost 50%.15

The study reported by Clark et al.15

was a double-blind, randomized,placebo-controlled trial of involving1,312 patients (mostly men) whowere recruited initially because of ahistory of basal cell or squamouscell carcinoma of the skin. The con-trol group received the average dailyintake of selenium in the USA, i.e.~100 µg, and treatment was for amean of 4.5 years. Although therewas no significant effect of the treat-ment on the incidence of the non-melanomatous skin lesions, patientsreceiving the Se-yeast showed amuch lower prevalence of develop-ing or dying from lung, colon or

prostate cancer. Unfortunately how-ever the apparent benefits of the Se-yeast could only be considered assecondary effects as the trial wasoriginally set up to determine theeffect of selenium supplements onskin cancer. Therefore further trialswere needed.

One such trial has just been com-pleted (SELECT).16 The Seleniumand Vitamin E Cancer PreventionTrial was set up to determine theeffect of selenium and vitamin E onthe risk of prostate cancer. Men (N = 35,533) from 427 sites in theUSA, Canada and Puerto Ricowere randomly assigned to one offour groups to receive selenium,selenium plus vitamin E, vitamin Eand placebo in a double-blind fash-ion. The men were 50 years orolder and had normal prostate spe-cific antigen level (≤ 4 ng/mL). Thetrial was stopped when the medianoverall follow-up was 5.46 yearsbecause no significant differencesin any of the pre-specified cancerend-points had appeared.

In the SELECT trial the seleni -um treatment was 200 µg/day from L-seleno methionine and there wereno differences between the groupsreceiving selenium alone or seleni-um plus 400 IU/d of all rac-a-toco-pherol acetate. The vitamin E wasincluded as it too had appeared toprovide protection against prostatecancer in the ATBC study inFinland.17 However, the effect ofvitamin E in that study was also asecondary effect.

Hatfield and Gladyshev18 dis-cussed some of the possible reasonsfor the differences in the effects ofselenium in the two trials.15,16 Theypoint to early work that showed Se-yeast is a complex mixture of dif-ferent forms of selenium of whichonly ~20% is selenomethionine,19

the form of selenium used in theSELECT trial. Forms of seleniumpresent in Se-yeast include seleno -methionine (~20%), selenocystine,Se-methylselenocysteine and un -identified components representing40–50% of the total.19 Seleno -

Figure 5: Selenium and the inflammatory response.Figure shows a hepatocyte containing the transcription factor NF-kB inthe cytoplasm. NF-kB is normally inhibited but can be activated by anumber of factors of which monocyte cytokines and TNF-a areshown. Physiological concentrations of selenium inhibit the activationbut concentrations < 1.0 µmol/L are permissive. Upon activation, NF-kB translocates to the nucleus and binds to genes that stimulate rapidtranscription of cytokines, adhesion molecules, chemotactic factors,acute phase proteins etc. Information from Maehira et al.29

Cytokines from activatedmonocytes

TNF-α

[InhibitedNF-κB]

Active NF-κB

NF-κB DNA-binding domains

Nucleus

++

++

Hepatocyte

PhysiologicalSe concentration1–2 µmol/L

Low Seconcentration0.5–1 µmol/L

++ ++

--

methionine provides selenium forselenoprotein biosynthesis via thetranssulfuration pathway but it canalso be diverted into general pro-tein synthesis in place of methio-nine.18 Therefore the importance ofthe complex mixture present in Se-yeast cannot be underestimatedsince different chemical forms ofselenium have different anti-cancereffects in rat-cancer models and ithas to be remembered that the anti-cancer activity of selenium is anexpression of the specific chemicalcompounds and not that of the ele-ment per se.19,20

Anticancer – methylation hypothesis

There is some evidence to suggestthat one of the components of Se-yeast, namely Se-methylselenocys-teine, may have anti-cancer proper-ties.20 In vivo, work has demonstrat-ed the presence of an enzyme thatremoves the cysteine leaving amonomethylated metabolite of sele-nium. Using a simplified form ofthis compound (methylselenic acid)without the attached amino acid cys-teine, in vitro studies showed thatthe selenium metabolite inhibitedaccumulation, and induced celldeath in a mouse mammary hyper-plastic cell line. The authors suggestthat their work supported thehypothesis that the monomethylatedselenium metabolite is important forcancer prevention. In contrast,selenomethionine, the form used inthe SELECT trial, can be incorpo-rated into proteins as a substitute forthe amino acid methionine ormetabolized by conversion toselenocysteine through transsulfura-tion, and then to hydrogen selenidebefore it is methylated and excreted(Figure 1). The different fates of thetwo forms of selenium used in thetwo supplementation studies15,16

may account for the different effectson risk of prostate cancer.

Nutritional status and cancer prevention

Further evidence for the potentialimportance of Se-yeast as a cancer-preventive agent has emerged froma 15-year follow-up21 of the nutri-tion-intervention trials in Linxianin China between 1985 and 1991.22

Following the intervention, itemerged that significantly lowerrisks of total mortality and gastriccancer occurred in Chinese menand women who received a dailysupplement containing b-carotene(15 mg), vitamin E (30 mg) andselenium (50 µg from Se-yeast).The effect on mortality was mainlyattributable to gastric cancer wherethe reduction was first noted within1–2 years of the start of supplemen-tation and over the five yearsthere was 21% reduction in relativerisk of gastric cancer (95% CI0.64–0.99).22

Mortality results are now availableto 2001 and they show lower over-all and gastric mortality over the 15years for the b-carotene, vitamin Eand selenium-supplemented sub-jects.21 In addition, there was still a6% lower risk of total mortality in the supplemented subjects (HR =0.94, CI 0.88–1.00) for the period1996–2001 and hazard ratios wereless than 1.0 for most endpointsbut not significant.21 Further moreanalysis by age over the 15 yearfollow-up, showed that most of thebenefits of the supplement were inthose who were younger than 55 year at the time of recruitment.The differential effect of age sup-ports the suggestion that the nutri-tional supplement was only benefi-cial in those early in the course ofcarcinogenesis.

It has been suggested that the nutri-tional supplement reduced the riskof cancer in the Chinese becausenutritional status was poor in thatpart of China.21 Our own studies on

Chinese farmers in Linxian aged35–64 year at that time certainlyshowed that vitamin A, zinc andriboflavin status was low but therewas little evidence that vitamins Eor C were poor and mean serum b-carotene concentrations werealmost identical with those ofBritish people.23 It is unlikelytherefore that the supplementincreased the status of b-caroteneor vitamin E but later work showedthat mean concentrations of seleni-um in the Linxian people were onlyhalf those in the SELECT trial.24

These authors found also that therewas a significant inverse associa-tion between baseline seleniumconcentrations and incident eso ph -ageal and gastric cancers in theLinxian trial.

Thus the active ingredient in thesupplement may well have been theSe-yeast but the selenium status ofthe subjects was also important.One of the criticisms of theSELECT trial was that it recruitedmainly people whose selenium sta-tus was good and that it would havebeen better to have done the trial inEurope where serum selenium con-centrations were much poorer.18

Baseline serum selenium concen-trations in Linxian were ~74 µg/L(0.94 µmol/L)24 whereas theywere 135 and 113 µg/L (1.71, 1.43µmol/L resp.) in the SELECT16

and the National Prevention ofCancer15 trials, respectively. Thuspoor selenium status and the appro-priate selenium supplement may benecessary to demonstrate a cancer-protective effect.

Inflammation and serum selenium concentrations

Circulating selenium levels are lowin many diseases but this does notnecessarily imply that selenium isinvolved in the pathogenesis of thediseases. In many diseases, traceelements, such as zinc and iron or

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vitamins like vitamin A, C, or B6,fall as part of the acute phaseresponse.25,26 In the case of seleni-um, several reports suggest thatselenium is a negative acute phasereactant25,27,28 and that, in a seriesof intensive-care patients admittedfor various clinical conditions, cir-culating selenium concentrationswere, on average, 40–60% lowerthan in healthy individuals. Gallo -way and colleagues found that thefall in circulating selenium couldnot be explained by increased uri-nary excretion and suggested thatthe distribution of body seleniummay be changed during critical ill-ness.25 Experimental studies sup-ported this suggestion. Injection oflipopolysaccharide (LPS) in ratsproduced significant falls in seleni-um concentration in plasma(69.5%) and liver (81.6%) whileselenium content of muscle, kidney,lung, spleen, heart and thymuschanged very little (< 10%).27

The redistribution of selenium dur-ing illness may play a role in thepotentiation of the acute phaseresponse. Workers reported a recip-rocal relationship between lowserum selenium concentrations andelevated C-reactive protein (CRP)concentrations in various patholog-ical conditions.29 CRP is one of anumber of acute phase proteins(APP) that are produced by theliver in response to tissue injury.The pro-inflammatory cytokinesinterleukin-1 (IL-1), interleukin-6(IL-6) and tumor necrosis factor-a�(TNF-a) that are released at the siteof injury by macrophages and otherimmune cells, activate APP-geneexpression through nuclear factor(NF)-kB. NF-kB is critical for theinducible expression of many genesinvolved in the immune and inflam-matory responses (IL-1, IL-2, IL-2Ra, IL-6, IL-8, TNF-a, TNF-b,IFNb, GM-colony stimulating fac-tor, serum amyloid, a1-acid glyco-protein (AGP)).30 Using a human

cell line derived from a hepato-cellular carcinoma to mimichepatocytes exposed to TNF-aor medium from LPS-stimulatedmonocytes, Japanese workers in-vestigated the effects of seleniumconcentrations on induction of NF-kB. They found that activationof NF-kB in the system was maxi-mal at selenium concentrations of0.5–1.0 µmol/L, that is, half theserum concentration found inhealthy human subjects and verysimilar to those concentrationsfound in subjects with elevatedCRP.29 Thus, the reduction in liverselenium concentrations may wellassist the maximal expression ofthe immune and inflammatoryresponses by the liver (Figure 5).

Thus, selenium is important in theimmune response and is concen-trated in tissues associated with theimmune response, namely spleen,liver and the lymph nodes.2

Selenium is important in the up-regulation of T-cells and in promot-ing antibody synthesis by B-cells.However, the functions of seleniumare a consequence of the proteins inwhich it is incorporated. The redis-

tribution of selenium that occurs incritical illness25 may also be a fea-ture of illness at an earlier stage. Sothe low concentrations of serumselenium associated with cardio-vascular disease, HIV, asthma andothers2 may simply be a feature ofthe inflammatory response and rep-resent a redistribution of seleniumamong the different selenium-requiring proteins to tailor theinflammatory response to the spe-cific disease. Thus, great care hasto be taken in interpreting seleniumstatus from either circulating sele-nium concentrations or a selenoen-zyme activity when inflammationis present.

References

1. Finley JW. Bioavailability of seleniumfrom foods. Nutr Rev 2006; 64:146–51.

2. McKenzie RC, Rafferty SP, BeckettGJ. Selenium: an essential element forimmune function. Trends Immu nolToday 1998;19:342–5.

3. Beck MA, Levander OA. Dietaryoxidative stress and potentiation ofviral infection. Ann Rev Nutr 1998;18:93–116.

4. Robinson MF. 1988 McCollum awardlecture. The New Zealand selenium

experience. Am J Clin Nutr 1988;

Key Messages

• Selenium is an essential element for immune function. • Selenium is incorporated into proteins with several different functions but in many of these there is a redox involvement.

• These redox-active proteins are important in defending tissuesagainst oxidative stress.

• A reduction in circulating and liver selenium concentrations isinduced by the inflammatory response and is associated with an up-regulation of many immune and inflammatory responses.

• A deficiency of selenium impairs anti-viral defenses and increasesthe risk of viral mutagenesis.

• The redox-active selenoproteins may protect against cancer development and promote tissue repair.

• Some evidence suggests that excreted forms of selenium have specific anticancer properties but further work is needed to supportthis hypothesis in man.

• Cancer-preventive properties of selenized yeast may only be effec-tive in people with low selenium status.

48:521–34.5. Department of Health. Dietary Re -ference Values for Food Energy andNutrients for the United King dom.Report on Health and Social Subjects,No. 41. London: HMSO, 1991.

6. Behne D, Kyriakopulos A. Mamma -lian selenium-containing proteins.Ann Rev Nutr 2001;21:453–73.

7. Burk RF, Hill KE. Selenoprotein P:an extracellular protein with uniquephysical characteristics and a role inselenium homeostasis. Ann Rev Nutr2005;25:215–35.

8. Beck MA. Selenium and host de -fence towards viruses. Proc Nutr Soc1999;58:707–11.

9. Beck MA, Matthewes CC. Micro -nutrients and host resistance to viralinfection. Proc Nutr Soc 2000;59:581–5.

10. Chen X, Yang G, Chen J et al. Studieson the relations of selenium andKeshan disease. Biol Trace ElementRes 1980;2:91–107.

11. Beck MA, Kolbeck PC, Rohr LH etal. Vitamin E deficiency intensifiesthe myocardial injury of coxsack-ievirus B3 infection of mice. J Nutr1994; 124:345–58.

12. Ames B. Micronutrients prevent can-cer and delay aging. ToxicologyLetters 1998;102/103:5–18.

13. Thurnham DI. Anti-oxidant vitaminsand cancer prevention. J MicronutAnal 1990;7:279–99.

14. Comstock GW, Bush TL, HelzlsouerKJ. Serum retinol, beta-carotene,vitamin E, and selenium as related tosubsequent cancer of specific sites.Am J Epidemiol 1992;135:115–21.

15. Clark LC, Coombs GFJ, TurnbullBW et al. Effects of selenium supple-mentation for cancer prevention inpatients with carcinoma of the skin. A

randomized controlled trial. Nu -tritional Prevention of Cancer StudyGroup. J Am Med Assoc 1996;276:1957–63.

16. Lippman SM, Klein EA, GoodmanPJ et al. Effect of selenium and vita-min E on risk of prostate cancer andother cancers: the Selenium andVitamin E Cancer Prevention Trial(SELECT). J Am Med Assoc 2009;301:39–51.

17. Heinonen OP, Albanes D, Virtamo Jet al. Prostate cancer and supplemen-tation with a-tocopherol and b-caro-tene: incidence and mortality trial ina controlled trial. J Natl Cancer Inst1998;90:440–6.

18. Hatfield DL, Gladyshev VN. The out-come of selenium and vitamin E can-cer prevention trial (SELECT)reveals the need for better under-standing of selenium biology. MolInterv 2009;9:18–21.

19. Ip C. Lessons from basic research inselenium and cancer prevention. JNutr 1998;128:1845–54.

20. Ip C, Thompson HJ, Zhu Z, GantherHE. In vitro and in vivo studies ofmethylseleninic acid: evidence that amonomethylated selenium metaboliteis critical for cancer chemopreven-tion. Cancer Res 2000;60:2882–6.

21. Qiao YL, Dawsey SM, Kamangar Fet al. Total and cancer mortality aftersupplementation with vitamins andminerals: follow-up of the LinxianGeneral Population Nutrition Inter -vention Trial. J Natl Cancer Inst2009;101:507–18.

22. Blot WJ, Li J-Y, Taylor PR et al.Nutrition intervention trials inLinxian, China: supplementationwith specific vitamin/mineral combi-nations, cancer incidence, and dis-ease specific mortality in the general

population. J Natl Cancer Inst1993;85:1483–92.

23. Thurnham DI, Munoz N, Lu J-B et al.Nutritional and haematological statusof Chinese farmers: the influence of13.5 months treatment with ribo -flavin, retinol and zinc. Eur J ClinNutr 1988;42:647–60.

24. Mark SD, Qiao YL, Dawsey SM et al.Prospective study of serum seleniumlevels and incident esophageal andgastric cancers. J Natl Cancer Inst2000;92:1753–63.

25. Galloway P, McMillan DC, Sattar N.Effect of the inflammatory responseon trace element and vitamin status.Ann Clin Biochem 2000;37:289–97.

26. Thurnham DI, Mburu ASW, MwanikiDL et al. Using plasma acute-phaseprotein concentrations to interpretnutritional biomarkers in apparentlyhealthy HIV-1-seropositive Kenyanadults. Brit J Nutr 2008; 100:174–82.

27. Maehira F, Luyo GA, Miyagi I et al.Alterations of serum selenium con-centrations in the acute phase ofpathological conditions. Clin ChimActa 2002;316:137–46.

28. Manzanares W, Biestro A, Galusso Fet al. Serum selenium and glutathioneperoxidase-3 activity: biomarkers ofsystemic inflammation in the critical-ly ill? Intensive Care Med 2008;Nov26 ahead of print.

29. Maehira F, Miyagi I, Eguchi Y.Selenium regulates transcription fac-tor NF-kB activation during the acutephase reaction. Clin Chim Acta2003;334:163–71.

30. Kopp EB, Ghosh S. NF-kB and relproteins in innate immunity. AdvImmunol 1995;58:1–27.

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NewsMicronutrient Forum ProvidesNew Platform for Public PrivatePartner ships and theDevelopment of SustainableSolutions Fighting HiddenHunger

Around the world some two billion people sufferfrom micronutrient malnutrition (deficiencies ofvital vitamins and minerals), also known as hiddenhunger, which impacts on individuals’ growth anddevelopment and, ultimately, on economies andpoverty.

The 2nd International Meeting of the MicronutrientForum took place in Beijing, China, in May and wasan excellent opportunity for knowledge sharingamong scientists, programmers and policymakers

on the theme of ‘Micronutrients, Health, and Devel-opment – Evidence-Based Programs.’

The biennial conference focuses on the impact ofmicronutrient deficiencies, specifically of vitaminA, iron, folate iodine, and zinc, on public health anddevelopment. It serves as a platform for collabora-tion and the sharing of new research and operationalfindings for the scale-up of successful micronutrientinterventions. The Forum is a successor to previousinternational meetings that focused on singlemicronutrients and the related global problems.

DSM’s humanitarian initiative, SIGHT AND LIFE,was a key sponsor of the event, which was attendedby over 650 delegates from some 90 countries, whocame from academic and research institutions, inter-national agencies, food and ingredient industries,national ministries, educational institutions, NGOs,and clinical and community nutrition organizations.The SIGHT AND LIFE involvement included abooth that showcased videos and publications, andsponsored plenary sessions and satellite meetings.

SIGHT AND LIFE also inaugurated the YoungInvestigators Award at the Forum, aimed at recog-nizing young researchers for micronutrient researchthat has scientific, policy and/or programmatic rel-evance, and facilitating interactions between younginvestigators, leading scientists and researchers. Thefirst recipients of the award were Christine Stewart(USA), Hossain Md Iqbal (Bangladesh), andSebayang Susy Katikana (Australia/Indonesia). Inher award-winning lecture, Christine Stewart, fromJohns Hopkins University, reported on her work inrural Nepal, examining the impact of maternalmicronutrient supplementation on risk factors ofchronic diseases in the next generation.

One of SIGHT AND LIFE’s key contributions tothis year’s Micronutrient Forum was the organiza-tion of a panel discussion that brought togetherhigh-level representatives from PepsiCo, DSM,Unilever, Interflour Group, and Amway to discussthe role of the private sector in eradicating hiddenhunger and the question of how public-private part-nerships could efficiently deliver micronutrients tothose at the bottom of the pyramid. DSM was repre-sented on the panel by its member of the ManagingBoard, Stephan Tanda.

SIGHT AND LIFE also organized a well-attendedsatellite symposium that highlighted the partnershipbetween DSM and the United Nations World Food

SIGHT AND LIFE Magazine 2009;2:57–60

The SIGHT AND LIFE booth

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Programme (WFP) that seeks to create sociallyinnovative solutions through the use of micronutri-ent powder (MixMe™) to improve the nutritionalquality of food assistance to refugees and vulnera-ble populations supported by WFP.

Dr Klaus Kraemer, Secretary General of SIGHTAND LIFE, remarked, “This year’s Micro nutrientForum has shown that SIGHT AND LIFE’s leader-ship role in the micronutrient field goes beyond the

creation of awareness and advocacy, and successful-ly facilitates networks between the public and pri-vate sector.” This is critical, as the key take-awaymessage from the meeting is that success in eradi-cating hidden hunger will only be achieved throughcollaboration between cross-cutting groups andpublic-private partnerships that promote andadvance the development of accessible, affordableand innovative solutions toward eradicating vitaminand mineral deficiencies around the world.

Panelists from left to right: Stephan Tanda (DSM), Mehmood Khan (PepsiCo), Jane Badham (JBConsultancy), Venkatesh Mannar (Micronutrient Initiative), Saskia Osendarp (Unilever), Greg Harvey(Interflour Group), Jeff Dornoff (Amway)

Nutritional Education Should Beon the Table

Representatives from German political parties, media,science and industry debated the potential effects ofthe economic crisis on the productivity of the next gen-eration at the 2nd Dialogue on Nutrition and Politics onJune 17, 2009, held at the studios of German TV sta-tion ARD.

SIGHT AND LIFE organized the event and Dr KlausKraemer emphasized that experience gained in devel-oping countries shows “an inadequate supply ofmicronutrients impairs the mental and physical devel-opment of children and young people.” Prof. HansKonrad Biesalski, a medical nutritionist from the

University of Hohenheim, explained the link betweendietary imbalances and potential vitamin and mineraldeficiencies. Stephan Tanda, from DSM’s ManagingBoard, stated that experience in developing countrieshas shown socioeconomic status plays a crucial role in dietary imbalance – a statement backed by Gerd Häuser, from the organization BundesverbandDeutsche Tafel.

From the perspective of Ulrike Höfken, a member ofBündnis 90/Die Grünen and chairperson of theParliamentary Committee for Food, Agriculture andConsumer Protection, although the subject frequentlycomes up in political debates, it often falls victim toarguments about who holds the responsibility. Shecalled for “this Gordian Knot to be cut” for the good ofthe children. Uda Heller, from the Christlich Demo -

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kratische Union (CDU) and mem-ber of the Parliamentary Com -mittee for Food, Agriculture andConsumer Protection, emphasizedthe important role of nutrition edu-cation and the family in ensuringan adequate diet. Ms Heller alsomentioned positive approaches thathad been established in former EastGermany. There, school canteens,school gardens and communalmeals promoted the idea of healthyeating among the children.

Hans-Michael Goldmann, whospoke on the food policies of theFreiheitlich Demokratische Partei(FDP) parliamentary fraction, saidpoliticians have a leading role to

play. He considers courses in nutri-tion to be sensible since, in manyinstances, knowledge of foodpreparation has been lost. The rep-resentatives of all three partiesagreed that a sensible place to startwould be childcare facilities aschildren spend the greater part ofthe day in them. But otherapproaches are possible and thesubject should be broached “as un-bureaucratically as possible,” saidMr Goldmann.

All the participants agreed thatthere is a marked lack of knowl-edge about nutrients and nutritionin general among parents as well aschildren and young people. In addi-tion, there is too little knowledgeabout the nutrient needs of chil-dren. One possible solution for thiswould be to supervise children’snutrient intake from an early age. InProf. Biesalski’s opinion, thisshould be incorporated into theseries of nine standard medicalexaminations routinely undertakenby the child’s physician during itsearly years.

Although Ulrike Höfken had reser-vations about wide-ranging supple-

mentation with vitamins, Prof.Biesalski did not consider supple-ments within the dose range recom-mended for nutrient intake to beproblematic. Noting the GermanNational Study on Food Con -sumption (Nationale Verzehrs -studie) finding that the provision ofmicronutrients (such as vitamin D,folic acid, vitamin A, calcium andselenium) to large sections of thepopulation is a cause for concern,he explained that there have been

no cases of overdosing in the mod-erate dose range. Indeed, Prof.Biesalski found it shocking that theresults of the Study would havebeen even worse if people had notresorted to nutrient supplements. InMr Tanda’s opinion, fortifying foodcould contribute to nutrient intakeand improve health. In the USA,fortifying foods such as flour withfolic acid led to a reduction in therate of death from stroke andischemic heart disease by 31,000fatal strokes and 17,000 fatal heartattacks a year.

Over the course of this constructivediscussion, the key focus for themajority of the participants was

ensuring health by preventingpotential nutrient deficiencies. Butas Dr Kraemer summed up in hisclosing address, this can only beachieved if those concerned aregiven the appropriate information,“which requires concerted effortson the part of all societal groups.”

From left to right: Hans-Michael Goldmann (FDP), Uda Heller (CDU), Gaby Papenburg (SAT 1), UlrikeHöfken (Bündnis 90/Die Grünen), Stephan Tanda (DSM), Gerd Häuser (Bundesverband Deutsche Tafel),Prof. Hans-Konrad Biesalski (University of Hohenheim)

Ukraine Governmentand NGOsCommitted toFightingMalnutrition

During the roundtable on Improve-ment of Nutrition in Level 3–4Orphanages for Disabled Childrenin Ukraine, held on June 30, 2009,in Kiev, malnutrition issues in level3–4 orphanages for multiply dis-abled children were presented anddiscussed. The roundtable wasorganized by the National Assemblyof the Disabled of Ukraine, sup-

ported by the Socires Foundationfrom the Netherlands and heldin the context of the DutchGovernment’s Matra program.

The positive results of the therapeu-tic feeding program for disabledchildren in four different institu-tions, and international experiencein the prevention and treatment ofmalnutrition stimulated open dis-cussion on this issue. Dr KlausKraemer, Secretary General ofSIGHT AND LIFE presented onthis international experience in“Preventing Malnutrition,” encour-aging representatives from theMinistries of Health, Social Affairsand Education to cooperate withinternational organizations and

experts on these issues and toimprove knowledge on the malnu-trition issue in the Ukraine. InFebruary, Dr Kraemer visited alevel 3–4 orphanage for disabledchildren to observe the situationfirst-hand and commit SIGHTAND LIFE’s support for therapeuticfeeding in one of the orphanages.

Ukraine’s Deputy Minister of SocialAffairs, Sergij Bychkov, declaredthat the next important steps for theUkrainian Government will be tofinancially support therapeuticfeeding programs in orphanages fordisabled children, improve nutri-tion, increase the number of staffmembers, and invest in the educa-

tion of personnel and policy mak-ers. All participants of the round-table were committed to furthercooperation to achieve these chal-lenging goals.

Background

There are around 10 million chil-dren in the Ukraine, of whicharound 177,600 have disabilities.Approximately 60,000 of these chil-dren live in state-run institutions.Children with disabilities lack ade-quate services.

There are 23 level 3–4 orphanagesin the Ukraine, with an estimated5,000 multiply disabled childrenliving in them. They are the most

vulnerable of the already vulnerablegroup of disabled children becausethey need special care and highlyskilled and knowledgeable person-nel. Most of these institutions arelocated in remote locations, wherechildren live an isolated life.Caregivers and management do nothave special skills and knowledge inproviding adequate basic care formultiply disabled children and thenumber of staff members is lessthan needed. Due to this situationseverely disabled children spendmost of their time in their beds,without any rehabilitation services,and face severe problems such asmalnutrition.

This situation encouraged local,national and international NGOsworking in the Ukraine to combineefforts and create a network thatwould coordinate lobbying activi-ties aimed at improving the situa-tion of children with disabilities instate-run institutions. This cooper-ation dates back to the beginningof 2006, when individuals fromNGOs and churches started pilot-ing therapeutic feeding programs.This was the start of a process ofawareness-raising and looking forsupport from national and interna-tional NGOs, UN organizations inthe country, churches, privatecompanies, politicians and govern-mental bodies. Several meetings,conferences and roundtables wereheld over the course of three years,during which cooperation betweenthe government and civil societyon these issues was stimulated.

Communicated by:Oleksandra Kalandyak, Children’sRehabilitation Centre DzhereloLviv, UkraineEmail: gubka@lviv.farlep.netEric Bloemkolk, Socires/SOFTTulip, The NetherlandsEmail: e.bloemkolk@socires.nl

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Participants at the roundtable on malnutrition in Kiev

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Development Workers’ Training in Vitamin A inKathmandu, Nepal

Dear Sir,

Nepal suffers from widespread nutritional deficien-cies, reflected in the high rates of micronutrient malnu-trition in preschool and school children as well as ane-mia and night blindness in women of reproductive age.Although poverty and low levels of education may bethe basic causes, much can be done now to developmore appropriate nutritional practices and build astronger, healthier population for the future.

Providing methods to improve nutrition practices atcommunity and household levels is one of the chal-lenges. Nutrition must be meaningful and practical forfamilies to capture their interest and motivate them toaction. While much progress has been achieved, morestill needs to be done to combat vitamin A deficiency(VAD) in the country, with the support of developmentworkers at the community level. These developmentworkers from the various grassroots NGOs are theleaders and change agents in every community.

With support and guidance from SIGHT AND LIFE,the Rural Health Education Center (RHEC), a healthNGO in Nepal, trained 25 development workers in theearly detection and management of VAD xeroph-thalmia (VADX). The participants were from rural andsuburban communities in the northeastern area of

Kathmandu Valley, areas specifically chosen due totheir high prevalence of VADX. Training objectivesincluded mobilizing development workers to raiseawareness of VADX in their communities as well asspecific target groups, focusing particularly on preven-tion, early detection, and timely use of available healthcare services. Another objective was to identify chil-dren who did not receive a vitamin A capsule duringthe most recent mass distribution campaign and findout why.

Training participants included development workersfrom special ethnic groups, such as the Tamang,Gurung, Lama, Sherpas and other tribal populationsmostly inhabiting the hills surrounding KathmanduValley. These groups were selected due to the level ofdeprivation in their socioeconomic, education andhealth circumstances. The training took place overthree days, based on a curriculum developed in consul-tation with nutrition experts. Training modules coveredspecific topics and addressed the nutritional needs ofdifferent age groups. While major topics were deliv-ered through lectures, group discussions rounded offeach session to ensure participants were able to under-stand and apply the learning effectively among them-selves. At the end of the training, an evaluation wasperformed in the form of presentations on assignedtopics.

The training helped the participants to become fullyaware of the magnitude of the problem of VAD andinvited them to incorporate nutrition knowledge intheir daily lives. It is expected that the training willhelp the development workers in sharing knowledgeand raising awareness among the people in their com-munities on vitamin A and related issues.

Communicated by:Nirmal Dhungana, Rural Health Education Center(RHEC), Kathmandu, NepalEmail: rhec06@gmail.com

Letters to the Editor

Training on xerophthalmia prevention

SIGHT AND LIFE Magazine 2009;2:61–64

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Dear Sir,

For decades, Calcutta Rescue has been active in thefight against vitamin A deficiency in Kolkata, India.SIGHT AND LIFE’s contribution to this fight is ab-solutely essential and greatly appreciated by those dis-advantaged families that have benefited from it.Vitamin A supplementation is one of the pillars forimproving the health of malnourished children, and itscrucial role in facilitating proper mental and physicaldevelopment is gaining recognition in the medical lit-erature.

Calcutta Rescue works to deliver these supplements tochildren and adults who need them on the street and inthe slums of urban Kolkata, as well as in the larger ruralarea surrounding the city. Our Street Medicine programhas given 130 doses of vitamin A each week for the lastthree years. Approximately 30 of these doses are thefirst of five for children new to our services. Our TargetInitiated Program (TIP) delivers 130 doses of vita -min A in urban Kolkata and another 70 doses in areascovered by our rural TIP outreach program.

Many children in and around Kolkata are getting inad-equate amounts of vitamin A due to a combination of

financial constraints on the families, and infections –especially intestinal parasitic, bacterial, and amoebicinfections – which rob growing children of vitaminsand minerals essential for normal development.Vitamin A deficiency, in particular, has a strong asso-ciation with chronic intestinal parasites, which are verycommon among Kolkata’s urban poor. At our perma-nent clinics, and through our street medicine and TIPoutreach programs, Calcutta Rescue treats these infec-tions promptly and regularly deworms children with

albendazole in order to help prevent vitamin A defi-ciency. We follow up on those who fail to attend theclinics for their supplements, doing house visits toensure that all patients get the vitamins they need.

Despite these efforts, many children still need addi-tional nutritional supplements. That is where SIGHTAND LIFE comes into the picture. SIGHT ANDLIFE’s donations feed this process of improving nutri-tion, and ensuring the proper growth and developmentof some of India’s poorest residents. Research shows

that vitamin A deficiency is a majorcontributor to morbidity and mor-tality worldwide. Beyond stuntingchildren’s growth and making themmore susceptible to infection (theinfection-malnutrition cycle), vita-min A deficiency is also an impor-tant cause of blindness in children.Research also has shown that vita-min A supplements for children atrisk can significantly reduce thechances of damage to sight as wellas help them grow properly andthrive. The need for these supple-ments donated by SIGHT ANDLIFE is most apparent in childrenwho are already hindered by poorgrowth, disease, and malnutrition.

We try to ensure that these donations reach childrenwho are most in need.

We and our patients would like to thank SIGHT ANDLIFE for its generous contribution in the fight againstthe cycles of poverty, malnutrition, and hopelessness.

Communicated by:Jonathan Reisman, Calcutta Rescue, Kolkata, IndiaEmail: reisman.jonathan@gmail.com

The ambulance of the outreach project of Calcutta Rescue

Children from Kolkata

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Healthy Eyes Activity Book in Children’sSummer Personality Development Camp

Dear Sir,

SIGHT AND LIFE’s Healthy EyesActivity Book (HEAB) in theMarathi language has created inter-est in eye care among school chil-dren here. The book featured at the‘Summer Personality DevelopmentCamp’ organized by local NGORavikiran for schoolchildren inMay 2009 in Aurangabad City,Maharashtra, India.

The personality development campaims to help school children indeveloping organized patterns ofbehavior and attitude that enablethem to master formal skills, relatewith their peers, progress from freeto structured play governed byrules and requiring teamwork, andacquire basic intellectual skills.Activities include storytelling and games that chal-lenge mental and sensory abilities.

With the use of the HEAB, the children participated inactivities through which they learned the importantrole of healthy eyes and nutrition in their development.As ambassadors of our community and the future ofsociety, the schoolchildren can help to prevent blind-ness and nutritional deficiencies by learning aboutthese through the entertaining and informative experi-ences of this summer program.

Personality, in simple words, means distinctive per-sonal qualities that help one to establish one’s identity.A child’s personality develops in a very naturalprocess, which certainly can be improved by properguidance. We have found the HEAB to be a useful tool

for guiding behavior change in children that helpsthem develop personal qualities that identify withhealthy eyes.

Communicated by:Kailash Baviskar, Ophthalmic Officer, MaharashtraUniversity of Health Sciences, Regional CentreAurangabad, Maharashtra, IndiaEmail: kailashbaviskar@yahoo.co.in

School children from Aurangabad, Maharashtra, using the HEABduring summer personality development camp

Zambia National Food andNutrition Symposium, April28–30, 2009

Dear Sir,

Sharing nutrition knowledge is anintegral part of initiatives to pro-mote general health and nutrition.The nutrition fraternity in Zambiaheld a 3-day symposium on thetheme Food and Nutrition in the21st Century: Challenges forZambia, which way forward? onApril 28–30, 2009, in Lusaka.

Providing a forum for sharingexperiences, disseminating re -search information, critiquing cur-rent policies and programs, andcharting a way forward for improv-ing the food and nutrition situationin the country, the symposiumfocused on the following thematicareas:

• National Food and NutritionalPolicy, Monitoring and Research • Nutrition and Health • Nutrition Education andPromotion

• Food Security and Emergency• Food Science and Technology

The Symposium was held at theMulungushi International Con -ference Center in Lusaka. Parti -cipants included all stakeholdersand partners, including theMinistries of Health, Agriculture,Education, and Defense and HomeAffairs, local nutrition groups,United Nation Systems agencies inZambia, Care International, andDutch Church Aid. Over 160 peo-ple attended the program. Minister

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of Health Dr Kampembwa Simbao opened the pro-gram as the Guest of Honour, after which NutritionAssociation of Zambia Director Dr Drinah Nyirendadelivered the keynote address and vote of thanks.

The experience of the Malawian nutritional interven-tion was presented by Dr Mary Shawa, the Nutritionand HIV/AIDS Secretary under the Office of thePresident in Malawi. The nutrition situation improvedin Malawi through the involvement of the top leader-ship and it was further highlighted that, to date,Malawi’s nutrition fraternity receives good budgetaryallocations that make it easy to carry out nutritionactivities.

As participants deliberated on the symposium’s vari-ous thematic areas, it was highlighted that Zambia’sNational Food and Nutrition Policy has not beenaccessible to all stakeholders and, as such, no collabo-rations have been sustained between stakeholders onthese issues. Participants acknowledged that theNational Food and Nutrition Commission (NFNC) wascreated under the Ministry of Health by an act ofParliament to oversee nutrition and health activities.However, participants found it difficult to understandthe operations of the NFNC and members felt thatNFNC should have been given a wider sphere to oper-ate, hence making sure that all members of the nutri-tion fraternity are guided in the implementation ofactivities. It was further noted that this sector is receiv-ing low budgetary allocations and, as such, this makesit difficult to carry out interventions effectively andefficiently.

The Symposium produced recommendations on allthe above concerns to be presented to the Minister of

Health, Parliament and possibly the President. It wasfelt that, if this was done, nutrition activities wouldbe recognized and prioritized. The NFNC directorofficially closed the symposium on behalf of theMinister of Health and thanked all sponsors and par-ticipants.

This activity was well carried out. I felt like I was oneof the organizers as I freely gave out copies of theSIGHT AND LIFE Magazine. At some point, I askedthe organizers to provide me with a table in theexhibitors’ lounge, where I displayed the magazines –all copies of the Magazine were gone by the end of theday.

It was very important for me to attend the symposium,most especially coming from a Nutrition Group back-ground under the NFNC. It clearly showed me thatthere is still a lot to be done and that we need to broad-en our operations as a group, strengthen links withstakeholders, and find more partners for material andfinancial support since the nutrition fraternity at largein the country does not receive adequate funding. It isin this vein that I would like to thank SIGHT ANDLIFE for making it possible for me to be part of thisvery important agenda in the country, which will befelt even beyond our generation.

You are really partners in nutrition.

Communicated by: Halumba Munachonga, NdolaNutrition Group, Plot 1346, Nkana Road, P.O. Box71470, Ndola, ZambiaWebsite: www.geocities.com/ndolanutritiongroupEmail: ndolanutritiongroup@yahoo.com / hmunachonga@yahoo.com

School atmosphere in Zambia

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Global Prevalence of Vitamin A Deficiency inPopulations at Risk 1995–2005: WHO GlobalDatabase on Vitamin A Deficiency

WHO. Global Prevalance of Vitamin A Deficiency inPopulations at Risk 1995–2005: WHO GlobalDatabase on Vitamin A Deficiency. Geneva: WorldHealth Organization, 2009.

In 1987, the World Health Organization (WHO) esti-mated that vitamin A deficiency was endemic in 39countries based on the ocular manifestations of xeroph-thalmia or deficient serum (plasma) retinol concentra-tions (< 0.35 µmol/L). In 1995, WHO updated theseestimates and reported that vitamin A deficiency was ofpublic health significance in 60 countries, and was like-ly to be a problem in an additional 13 countries. Thecurrent estimates, detailed in this publication, reflectthe time period between 1995 and 2005, and indicatethat 45 and 122 countries have vitamin A deficiency of public health significance based on the pre-valence of night blindness and biochemical vitamin A deficiency (serum retinol concentration < 0.70 µmol/L), respectively, in preschool-age children.

As part of its mandate to provide information on thehealth status of the population at the global level, theDepartment of Nutrition for Health and Developmentunder the World Health Organization (WHO) initiatedthe Vitamin and Mineral Nutrition Information System(VMNIS) in 1991. The VMNIS includes three databas-es related to three micronutrient disorders of publichealth significance globally: iodine deficiency, irondeficiency and anemia, and vitamin A deficiency(VAD). The VMNIS aims to assess the status of thepopulation at the global level in order to increase theawareness of the public health community and policymakers, evaluate the impact of interventions and meas-ure progress towards international goals, compare databetween countries, track changes over time, andincrease the capacity of countries to manage health datarelated to micronutrients.

Global Prevalence of Vitamin A Deficiency inPopulations at Risk 1995–2005: WHO Global Databaseon Vitamin A Deficiency utilizes data from the WHOGlobal Database on Vitamin A Deficiency, which ispart of the VMNIS, developed by the Reduction ofMicronutrient Malnutrition Unit in the Department ofNutrition for Health and Development. The report pro-vides an overview of vitamin A deficiency; describesthe criteria used in interpreting the findings of the sur-veys and the methodology developed to generatenational, regional, and global estimates; and VADprevalence by country and WHO regions.

SIGHT AND LIFE, the Micronutrient Initiative, theGovernment of Luxembourg, the US Centers forDisease Control and Prevention provided financial sup-port for the database and the report.

To download the report, please visith t tp : / /whql ibdoc .who. in t /publ ica t ions /2009/9789241598019_eng.pdf

SIGHT AND LIFE Magazine 2009;2:65–67

PublicationsEditor’s note: SIGHT AND LIFE reviews recent publications whichmay be of particular interest to our readers. However, no publicationsother than SIGHT AND LIFE publications are available from us, nor dowe have any privileged access to them.

SIGHT AND LIFE Publications

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Investing in the Future: A United Call to Actionon Vitamin and Mineral Deficiencies

FFI, GAIN, MI, UNICEF, USAID & WHO. Investing inthe Future: A United Call to Action on Vitamin andMineral Deficiencies. Ottawa: FFI, GAIN, MI,UNICEF, USAID & WHO, 2009. Internet:http://www.unitedcalltoaction.org/documents/Investing_in_the_future.pdf (accessed July 24, 2009)

Around the world, billions of people live with vitaminand mineral deficiencies. Approximately one-third ofthe world’s underfive children are vitamin A-deficientand ill-equipped for survival, and iron deficiency ane-mia during pregnancy is associated with 115,000deaths each year, accounting for one-fifth of totalmaternal deaths. When whole populations suffer frommalnutrition, including a lack of critical vitamins andminerals, nations cannot fulfil their potential: Health-care costs rise, education efforts are thwarted, theworkforce is less capable and productive, and econom-ic activity is curtailed.

Encouragingly, national governments, donors, scienceand industry, working together, have made huge stridesin delivering cost-effective solutions to vulnerablepopulations. These successes, if further scaled-up,present opportunities to improve the lives of those whohave thus far not been reached.

Investing in the Future: A united Call to Action onVitamin and Mineral Deficiencies was officiallylaunched on May 12, 2009, at the 2nd InternationalMeeting of the Micronutrient Forum in Beijing, China,and represents an inter-agency call for more coordinat-ed efforts in this field. The report’s developmentincluded high-level participation from the FlourFortification Initiative (FFI), the Global Alliance forImproved Nutrition (GAIN), the MicronutrientInitiative (MI), the United Nations Children's Fund(UNICEF), the United States Agency for InternationalDevelopment (USAID), the World Bank, and theWorld Health Organization (WHO), and its develop-ment and production was financially supported by theGovernment of Canada through the CanadianInternational Development Agency (CIDA).

The causes of vitamin and mineral deficiencies aremultiple and interconnected. At the most basic level,the problem is related to diet, and it is made worse byinadequate health care and sanitation, disease, and alack of education in infant and childcare. Improvingthe diets of the world’s poor would resolve most vita-min and mineral deficiencies. However, it is a com-

plex and long-term undertaking, and requires sustain-able broad-based partnerships between the public, pri-vate and NGO sectors.

As the global financial crisis unfolds and availablefunds from all sources are shrinking, the need fordevelopment assistance is expanding at an alarmingpace. It is more important than ever that priority forinvestments goes to measures that yield the highestrates of return. Micronutrients are inexpensive com-modities and micronutrient initiatives can easily beintegrated into ongoing health services, or into existingmethods for food production.

The low cost of interventions and their high returns inimproved capacity have been endorsed by theCopenhagen Consensus panel of eight of the world’smost distinguished economists in 2008, which rankedthe provision of micronutrients as the world’s best investment for development. Achieving theMillennium Development Goals by 2015 will requirestrategic vision on the part of all those with resourcesto invest. Much is already understood about earlynutrition needs and what works. Commitment and dol-lars, supported by strong partnerships, will extend thereach of micronutrient interventions and leave no onebehind.

To download the report, please visit http://www.unitedcalltoaction.org.

Magazine Issue 2/2009Publications

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Recommendations on Wheat and Maize FlourFortification. Meeting Report: InterimConsensus Statement

WHO, FAO, UNICEF, GAIN, MI, & FFI.Recommendations on Wheat and MaizeFlour Fortification. Meeting Report: InterimConsensus Statement. Geneva, WorldHealth Organization, 2009. Internet:http://www.who.int/nutrition/publications/micronutrients/wheat_maize_fort.pdf (accessed July 24, 2009).

Leading public- and private-sector nutrition, pharma-ceutical and cereal scientists and milling experts fromaround the world gathered in Stone Mountain, GA,USA, on March 30–April 3, 2008, for the SecondTechnical Workshop on Wheat Flour Fortification:Practical Recommendations for National Application.The workshop, a follow up to the first technical work-shop in 2004, set out to provide guidance for countriesconsidering national wheat and/or maize flour fortifi-cation with iron, zinc, folic acid, vitamin B12 and vita-min A, and to develop guidelines on formulations ofpremix based on common ranges of flour consump-tion. A secondary aim was to agree on the best prac-tices guidelines for premix manufactures and millers.

This Interim Consensus Statement, which reflects theposition of the World Health Organization (WHO), theFood and Agriculture Organization of the UnitedNations (FAO), the United Nations Children’s Fund(UNICEF), the Global Alliance for Improved Nutrition(GAIN), the Micronutrient Initiative (MI) and theFlour Fortification Initiative (FFI), is based on the sci-entific reviews prepared for the 2008 workshop and isintended for a broad audience, including the foodindustry, and scientists and governments involved inthe design and implementation of flour fortificationprograms.

Wheat and maize flour fortification is a preventivefood-based approach to improve a population’smicronutrient status where vitamin and mineral defi-ciencies are public health problems, and should beconsidered when industrially produced flour is regular-ly and widely consumed in a country.

Wheat and maize flour fortification programs could beexpected to be most effective in achieving a publichealth impact if mandated at the national level.Worldwide, over 600 million metric tons of wheat andmaize flours are milled annually by commercial rollermills and consumed as noodles, breads, pasta, and

other flour products by people in many countries.Fortification of industrially processed wheat and maizeflour, when appropriately implemented, is an effective,simple, and inexpensive strategy for supplying vita-mins and minerals to the diets of large segments of theworld’s population.

To download the statement, please visithttp://www.who.int/nutrition/publications/micronutri-ents/wheat_maize_fortification/en/index.html.

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