16 intrauterine programming of ncd 24 olson memori... - DSM

VOL. 25 (2) | 2011Sight and Life16 INTRAUTERINE PROGRAMMING OF NCD24 OLSON MEMORIAL LECTURE – CARIG WORKSHOP 201132 THE LINK BETWEEN NUTRITION, DISEASE AND PROSPERITY38 VITAMIN D AND INFLAMMATION

Contents04 EditorialCongress Reports08 The “Sight and Life in My Life” Essay Competition14 Special Feature: NCDs – Silent Killers16 Intrauterine Programmingof Non-Communicable Disease:Role of Maternal Micronutrients24 2011 James A Olson Memorial Lecture –CARIG Workshop at Experimental Biology 2011:Isotope Dilution Assessment of Vitamin A Status32 The Link Between Nutrition, Disease and Prosperity:Preventing Non-Communicable Diseases AmongWomen and Children by Tackling Malnutrition38 Plasma 25-Hydroxy-Cholecalciferol (Vitamin D)is Depressed by Inflammation: Implications andParallels with Other Micronutrients48 Opinion 1: Vitamin D Status and Tuberculosis49 Opinion 2: The D-Cline may be Dueto Drug-SXR Interaction62 The Carotenoids Research Interaction Group(CARIG) Conference, Washington, DC, 8 April 201164 Tackling Iron Deficiency and Anemia in Infantsand Young Children in Malaria-Endemic AreasField Reports70 Report from ThikaProgress at the Macheo Children’s Centre73 Report from NairobiProgrammatic Qualitative Research: A New Initiativeto Build Capacity for Nutrition Programming Withinthe DSM-WFP PartnershipObituaries76 RememberingMichael C Latham (1928 –2011)80 RememberingPhilip Musgrove (1941 –2011)82 News52 Systematic Data Analysis in Qualitative HealthResearch: Building Credible and Clear Findings58 Sight and Life InterviewFeike Sijbesma: A Vision of Life96 Publications102 Imprint103 Disclaimer

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4As I write of the risk of doing nothing, Sight andLife is devastated by the tragedy unfolding in theHorn of Africa – a humanitarian crisis on a scale wehave never seen before. There is daily loss of lifeand untold long-term effects as children are starvedof both calories and vital nutrients, leaving themstunted forever if they survive.Sight and Life and DSM have responded by donatingto the World Food Programme ready-to-usefood to feed a significant number of children untilthe end of the year. We urge all our readers to takeaction and to make a difference. At times like thisdonations to the World Food Programme are urgentlyrequired and ensure the immediate pro-vision of ready-to-use foods for those in dire need.Visit www.wfp.org and let us as the world’s nutritioncommunity show our support for those doingsomething to save the lives of thousands.Urgentneed !

WelcomeThe risk of doing nothing …As Sight and Life commemorates 25 years of service to scienceand humanity, it is appropriate that we ask ourselves if our existencehas made at least some difference to the way in whichmicronutrient malnutrition is addressed or has helped ensurethat this issue receives greater attention within the ever noisierglobal public health and nutrition space.For us the answer is yes. We believe we have made a contribution.Now we would like to reflect more closely on the specificsand magnitude of this contribution, a question which is more difficultto answer and quantify. Over the years, we have gatheredmany letters from grateful beneficiaries, in addition to numerouscase studies on how Sight and Life’s direct contribution to vitaminA supplementation and, more recently, the way in which ithas addressed multiple micronutrient deficiencies has improvedlives; and on how our partnerships, capacity building initiativesand sponsorship of individuals to attend meetings and programshave given people an opportunity for personal and professionaldevelopment that they would never otherwise have had. We arecertainly “building bridges for better nutrition,” as our by-linestates. Yet the very word “building” implies and was carefullyselected to mean that the process is still happening − it is ongoing,and needed now more than ever. We only need to look at thecurrent global nutrition statistics, and the real concern aboutreaching the Millennium Development Goal (MDG) targets thatare linked to nutrition, to know that we still have a long wayto go before we can truly say that we have done our work andachieved our mission of “ensuring a sustainable and significantimprovement in human nutrition, health and well-being.” Thechallenges are enormous and frequently the obstacles seem insurmountable.We have to actSo, what is the risk that those involved, from all sectors of society,do nothing? The dictionary has a number of definitions forrisk, but the one that strikes me as being relevant to the field ofhumanitarian work is to “act in such a way as to bring about thepossibility of an unpleasant or unwelcome event.” Add to thatthe definition of nothing, “not anything; no single thing,” andit becomes clear that if we, the global public health nutritioncommunity, do nothing, we must ask ourselves if this will resultin an unpleasant or unwelcome event? I am sure that most of uswould agree that inaction would have negative consequences.The prevalence of malnutrition in all its forms would increase,the quality of life of millions of individuals would decrease, andthe negative impact on the growth of economies would continue.Thus, indeed, we have to act – defined as “the process of doing”;however, it is perhaps time to act and do differently.“The world we’ve made, as a result ofthe level of thinking we have donethus far, creates problems we cannotsolve at the same level of thinking”Albert EinsteinIn the words of Albert Einstein, “the world we’ve made, asa result of the level of thinking we have done thus far, createsproblems we cannot solve at the same level of thinking.” In otherwords, “insanity is when you keep doing the same things expectingdifferent results.” However, challenging the way in which wehave done things can be uncomfortable. It means we need tobe prepared to shift, to move out of our comfort zone or even toconsider that what we have done has not yielded the results wehad hoped for.The need for political willIn her thought-provoking book Dead Aid, Dumbisa Moyo challengesthe aid culture and writes, “Has more than US$1 trillionin development assistance over the last several decades made⇢

6EDITORIALAfrican people better off? No … Aid has helped make the poorpoorer, and growth slower.” She follows the aid culture fromthe 1960s, which she defines as the decade of industrialization,through the 1970s (“the shift to poverty”), to the 1980s (“thelost age of development”) and the 1990s (“a question of governance”),and into the 2000s, which she refers to as “the riseof glamour aid.” Moyo ascertains that we need to abandon ourobsession with aid and, instead, focus on proven financial solutionsand models – which, she says, should not be on a one-sizefits-allbasis. Above all, she states that what is needed, but whatis lacking, is political will.We can and must advocate for the political will componentand are grateful that the Scaling Up Nutrition (SUN) movementrecognizes, in the words of Special Representative on Food Securityand Nutrition to the UN Secretary General, David Nabarro,that the main investors in SUN are national governments themselves.However, those of us involved in humanitarian work alsoneed to look at how we have done things in the past and reassessand be open to change! We cannot simply be do-gooders– which, as the dictionary states, is a disparaging term for awell-intentioned, naive idealist who supports philanthropic orhumanitarian causes or reforms.Research and programs at scale in parallelThe challenge we face going forward, however, is the need tobalance the evidence, which is critical to forming and growingknowledge, and to continue monitoring, evaluating and fine tuningthe policies that guide public health nutrition, with turningthe evidence into scaled-up programs at the community levelwhere there is a real urgency for delivery. The dilemma is to decidewhether more research is still needed to sharpen our knowledgeof what to do and how to do it, or whether we should turnimmediately to the scaling up of interventions at a country levelto achieve the MDGs. Perhaps this is a case of ensuring that bothresearch and programs at scale run in parallel and both receiveadequate attention and funding. If we neglect one for the other,we could find in future that we have missed an important pieceof the puzzle.We also need to tread carefully between the triumphalism– the attitude or belief that a particular doctrine, religion, culture,or social system is superior to and should triumph overall others – necessary for advocacy, and the realism relative tothe potential risks and benefits and nutrition programming’slimitations. The time has come to break down the silos in whichwe have traditionally functioned and to build meaningful partnershipsacross multiple cross-cutting disciplines: the need fordirect nutrition interventions, together with nutrition sensitiveinvestments. Ultimately, none of our individual actions directlyresult in reaching the goal of the improved nutritional status ofthe world’s population. It is the compounded effects of all ouractions that lead to a world where this goal becomes possible.We cannot “do nothing”In a world where so many families still live in poverty, wheresome billion people go to bed hungry each night, and hundredsof millions of children will never reach their full potential becauseof micronutrient deficiencies and inadequate care, doingnothing is not an option. We must not become paralyzed by theenormity of the challenges we face. What is so insidious aboutthe absence of action is that no single decision to delay ever appearsmonumental at the time. Because the cost of inaction takestime to be fully revealed, it does not necessarily impact the worldtoday, but may well severely affect the world of tomorrow.By and large, policy makers are risk averse, which perpetuatesthe cycle of inaction: They would rather do nothing todaythan run the greater risk of taking the wrong decision. This confersan ethical dimension on the risk of doing nothing, but thisis a discussion on its own. Ultimately, I strongly believe that, despitethe risk involved, doing something outweighs doing nothing– but I also believe that it is time to reassess what we do andhow we do it …With best regards,“And the day came when the riskit took to remain tight inthe bud became greater than the riskit took to blossom”Anais Nin

The Sight and Life editorial board are pleased to announcethe incorporation into Sight and Life Magazineof Nutriview, the newsletter previously published bythe DSM Nutrition Improvement Program (NIP). Thisfollows in the footsteps of the very successful incorporationof the Xerophthalmia Club Bulletin into Sightand Life Magazine in the year 2000 under the editorshipof late Secretary General Dr Martin Frigg.Nutriviewjoins …7… Sightand Life …Nutriview and Sight and Life have already overlapped extensively,particularly as Sight and Life’s focus shifted fromvitamin A alone to covering all micronutrients and nutritionin general. Indeed, both publications address similarstakeholders and have followed similar objectives for sometime. Such objectives include contributing towards a betterunderstanding of the importance of micronutrients forgood health; encouraging efforts aimed at improving humannutrition; and communicating relevant aspects of nutritionresearch to show how the public and private sectorscan interact to improve human health.We are also pleased that Nutriview editor AnthonyBowley, who has headed the newsletter for the past18 years, will continue to contribute his perspectiveson nutrition research developments around the worldto Sight and Life Magazine.Given the close overlap between both organs, themerger is a welcome next step in the development ofSight and Life, as well as a logical progression in theorganization’s 25 th anniversary year.… Magazine.

8THE “SIGHT AND LIFE IN MY LIFE” ESSAY COMPETITIONThe“Sight and Lifein My Life”Essay CompetitionThe Sight and Life in My Life essay competition was set up withthe goal of finding out how Sight and Life has influenced its readersover the years, as part of the organization’s 25 th anniversary.In the final issue for 2010, therefore, we asked our readers to submitstories to us by mid-March 2011. Entrants were asked to addresstheir personal experiences, provide an assessment of the relevantcommunity’s experience, and give a definition of Sight and Life.We received many fascinating stories, as well as some beautifulphotographs and original artwork, from many countries, from Ghana toSri Lanka, and our Sight and Life team of judges in Basel, Switzerlandwas delighted with every entry. As promised, we are sharing the winningentries with you in this issue. However, we will also share highlightsof other entries with you in the next issue of our magazine.A heartfelt thank you again to everyone who entered the competition,for the time you spent on your wonderful entries and, last but not least,the great work you do in your communities.With warmest wishes.The Sight and Life Team

SIGHT AND LIFE | VOL. 25 (2) | 2011THE “SIGHT AND LIFE IN MY LIFE” ESSAY COMPETITION9Abubakar BulakoSight and Life in MyLifeI am a refugee who lives in Kenya, and have spent manyyears in Kakuma refugee camp. I was forced to leave my landand my country and had to flee to Burundi, Rwanda, Uganda,and Kenya after the outbreak of civil war. I have been separatedfrom my family since 2003, which was the beginningof my long and unending journey as a refugee. I am inKakuma refugee camp. This camp is located in the Turkanadistrict of the northwestern region of Kenya, 120 km fromLodwar district headquarters and 95 km from Lokichoggio oand the Kenya-Sudan border.Life in the semi-arid desert environment of Kakuma israther challenging. The area has always been full of problems:dust storms, high temperatures, poisonous spiders, snakesand scorpions, outbreaks of malaria and cholera andother hardships.“Life in a refugee campis life without hope”The camp is a small city of thatched-roof huts,tents andmud abodes. Living in here is like living in a prison. Life in arefugee camp is life without hope; it’s about living like a blindperson, who only knows where he or she comes from, butdoes not know where he or she is heading. This was my wayof life in Kakuma camp. Living in a camp is not an easy task,nor is life easy withoutemployment or any means to generateincome. I did find itdifficult to survive the day, and mostlyrelied on the limited food supplies distributed twice a monthby the World Food Programme (WFP).However, being in the camp taught me more about life.I decided to volunteer and start helping others; first of all,I worked for the Lutheran World Services (LWF) as a foodclerk at the distribution centers. Secondly, I joined the InternationalRescue Committee (IRC) which deals with healthissuesin the camp – after being trained as a nurse aid andnutritionist. After that, I was retrained by the Jesuit RefugeeServices (JRS) as a counselor, inspired by the situation peopleare living in. Many people commit suicide and this is whatpushed me to become a community counselor …Abubakar BulakoAs my aim is to help people who cannot do things on theirown, I did not stop there. I continued to help the most vulnerable,in a different field. As the camp was also full of differenttypes of violence, I was also trained as an ambassador forwomen in Gender Based Violence. The camp is multiculturaland there usedto be conflicts. In this instance, I also decidedto do “Peace and Reconciliation” in order to become a peacekeeperin the community. All of these projects were to the endof assistingmy people who cannot do things on their own.“In Kakuma refugee camp,the most challenging issue is food”In Kakuma refugee camp, the most challenging issue isfood. It’s what I call the source of everything – if people don’tget food, this can lead to disease and fighting, among manyother things. This is why I decided to join WFP. After beingselected by the community to represent them on the FoodAdvisory Committee (FAC), my work involved attending meetingson the food basket and food pipeline situation, and thedistribution plan through working with WFP.⇢

10THE “SIGHT AND LIFE IN MY LIFE” ESSAY COMPETITIONI started to have Sight and Life in my life. That is to say,I hope one day to develop my own non-profit entity to attemptto help solve some of the issues of poverty in Africa,I started seeing ahead, because it was through WFP meetingsthat I met different WFP donors and held discussions and alsoby providing people with the skills to reduce poverty in theirinteractions with them. Everything was about food-related dcountries.issues. The beginning of my new journey also started when I I would like toacknowledge the efforts of the Sight andfirst met the new WFP donor – DSM. We held a meeting with Life teamfor their charity, stimulation, love and support,Madam Milka when she first visited the camp in 2008. Shewhich has given me success in my life. Thank you very muchtold us about a new micronutrient product called MixMe.and may God bless you all.She also told us that she was working hand in hand with Sightand Life, DSM’s humanitarian initiative. That was the first Ihad ever heard about this; later on, we met the DSM team andCorrespondence: Abubakar Bulako, Catholic University ofSight and Life when they visited the camp.Eastern Africa, Department of Social Science, Faculty of Arts andLater, I had the opportunity to meet Dr Klaus Kraemer, the Social Sciences, PO BOX 863-00600, Nairobi, KenyaDirector. This was a special day and something I had neverE-mail: aboubadiobg@yahoo.frexperienced as a refugee, or indeed since I had started volunteeringas an FAC. Working with WFP and Sight and Life onMixMe at Kakuma was a great opportunity. ty. I was able“I entered the competition because, after reading Sight andto take part in every activity and every survey in the camp;LifeMagazine, I felt that I had something to be proud about.I had the chance to transform myself and overcome my own I wanted to share this with people who might have lost hopelimitations. I also developed the skills to help my people andin their lives.”unfortunate Rwandese and Burundians who did not knowabout MixMe, as well as other refugees fromother countries.Abubakar BulakoNairobi, Kenya“Thanks to Sight and Life,I got the chance to see far andto regain hope”Thanks to Sight and Life, I got the chance to see far and toregain hope. It has helped me find myself again, re-think andalso restore my dreams. Sight and Life gave me the chanceto go back to school. As I write, I am in Nairobi, the Kenyancapital – a place that I could not have imagined visiting asa refugee. But I am here now, pursuing my degree in Arts &Social Sciences at the Catholic University of Eastern Africa.In my life, Sight and Life is more than everything to me. It hasrebuilt my life and has given it sight. Today, I am a personwho can speak out and to whom people listen, who can shareideas and change other people. I will become a social scientisttomorrow and all of this is thanks to Sight and Life. I am sograteful to you. It is my hope and belief that this companionshipwill remain for many years to come, not only for me butalso for those who are in greater need than me. With yourhelp, I know who I am. I promise to work hard and do more tohelp those who cannot help themselves. Assisting and helpingwill be my personal battle, so that I can help the vulnerablewithout expecting any rewards in return.“I“ I would like to sendmythanks to all the teammembers who selectedme. I don’t know how toca express myfeelingsbecause I am so happyand feel as if I am flyingwithout wings!”

SIGHT AND LIFE | VOL. 25 (2) | 2011THE “SIGHT AND LIFE IN MY LIFE” ESSAY COMPETITION11Prince AbugriSight and Life in My Life:A Life-Changing gEncounterI first learned about Sight and Life in August 2009, when Ijoined Presbyterian Primary Health Care (PPHC) – Bolgatanga,Ghana after school. I completed my University for Develop-elopmentStudies (UDS) in Ghana and now have a bachelor ofscience in Community Nutrition.One day, I was at the office and came across an old magazinewith the inscription Sight and Life, and began to lookthrough it. It was a 2008 edition and I was so happy aboutthe wealth of information it contained. I fell in love with themagazine; it led me to its website, where I learned more aboutthe organization and its work on improving the health of themasses. There, I came across a “call for proposals”, askingorganizations to submit proposals for the funding ofnutrition programs in their communities.I told my immediate boss, who was a senior nutritionist,tionist,about the proposal and he said we should give it a try. Afterreading through the procedures and requirements, we sentour application to Sight and Life for consideration. Althoughwe were not selected for the maximum mum $15,000 grant, wewere asked if we would like to receive materials on nutritionand other equipment on a periodic basis. Our answer wasa resounding yes; since then, we have received hard and softcopies of relevant information on that equips us for betterhealth h delivery in the nutrition ion department.“We receive e relevantinformation to equip us forbetter health deliveryin the nutrition department”Prince AbugriUntil recently, PPHC did not have a comprehensivenutrition module for children and adolescents, especiallythose in school. This was because we did not have muchinformation to deal with on improving their nutritionalstatus. tus. I am, however, grateful to Sight and Life because I wasput in charge of developing a module for school children onnutrition,which I was able to do with the help of the booksandother materials we received from you. I also developeda small book called Youth Nutrition, to enable me undertakea programknown as “School Health”, which educates youngpeoplein our catchment areas – the northern and upper eastregions of Ghana. It teaches better ways to improve theirnutrition and health status, and educates them on how theycan help their illiterate parents and siblings at home.This program has received the necessary support fromthe school authorities and from the students themselves.They have sent appreciative messages to me, thanking me forhelping them learn how to improve their nutritional status,and their general health status. I have also been given thegreen light from the office to continue with the program in2011 at various schools, thanks to the wealth of informationI have received.⇢

12 THE “SIGHT AND LIFE IN MY LIFE” ESSAY COMPETITIONPersonally, I have improved my level of knowledge in the “Thank youfor selecting me to be the joint winner of thisfield of nutrition and I have had a lot of project topics from prestigious award. ard. I feel sohonored to have won an awardone of the CDs you gave me. This will help me as I prepare tofrom such agreat organization. This is a wonderful momentpursue my master’s degree in September. It has enabled me for me, because it is the first time I have won an award fromto present a research proposal to the University of Ghana for an international ional organization such as Sight and Life.consideration for a master’s program in public health. I presenteda project proposal on how to improve the nutritionalI did not know what prize I was going to win. I joined the com-“I didnot enter for the sake of winning an award, becausestatus of pregnant women and lactating mothers in ruralpetition to let the world know that there is a group of peopleareas. I have had most of my references and other informationout there in an organization that is changing the lives of manyfrom the materials I receive from you, and will hopefully be in around the world, and that it is good to be associated withschool in September.them in order to help improve the health standards of peopleI am also very grateful to you because, during our proposalsubmission, we came across a document on how towrite proposals. The title was Tips for Proposal Writing whichwas prepared by Muzi Na, a graduate student from JohnsHopkins School of Public Health. We printed it outand havesince been using it as a guide to write proposals osals to variousorganizations, churches and other partners to fund ournutritionaland other health programs. I am happy to inform youthat these materials are more important to us than money.Weare receiving favorable responses from our partners, as wellas a lot of help from our partners from Switzerland (theparish of Horn) and others from the Netherlands. Your materialshave also helped me in my work during reporting, afterconducting various programs or projects such as schoolhealth, and other reports for PPHC.Thank you for all the relevant information I receivefrom you. The Bible says, “For lack of knowledge my peopleperish.” Thank God that I have knowledge relating to my fieldof work. Continue with the good work you are doing, for youimpact many more lives than you can imagine. Thank you.in vulnerable communities. This group is Sight and Life.”Prince AbugriBolgatanga, Ghana““I also wanted to let thestaff of Sight and Lifeknow that they are doinggreat work and thatI appreciate preci everythingu they are doing”Correspondence: Abugri Prince, Presbyterian PrimaryHealth Care (PPHC), PO BOX 42, Bolgatanga, GhanaE-mail: princekebo@yahoo.com

14NCDs–Silent Killersle “Non-Communicable Diseases (NCDs) are the leading causes of death globally,killing more people each year than all other causes combined. Despite theirrapid growth and inequitable distribution, much of the human and socialimpact caused each year by NCD-related death could be averted through wellunderstood,cost-effective and feasible interventions.” WHO 2010infant and young child overweight trends from 1990 to 2015 (by world bank income group)Percentage of population2015105High-incomeUpper-middle-incomeLower-middle-incomeLow-income01990 1995 2000 2005 2010 2015associations between poverty, non-communicable diseases and millenium development goalsGlobalizationUrbanizationPopulation ageingIncreased exposure to risk factors> Tobacco use and exposure> Poor nutrition> Physical inactivity> Alcohol misuse> Decreased access to health care> Air pollutionSocial and economicdeterminants of health> Poverty> Trade agreements> Agriculture and transportation policies> Capital flows> Activities of multinational companiesNCDs> Heart disease> Stroke> Cancer> Diabetes> Chronic respiratory diseaseLimited ability to reachDevelopment Goals> MDG 1: Poverty reduction> MDG 4: Reduce child mortality> MDG 5: Improve maternal health> MDG 6: Combat HIV/AIDS,malaria, and tuberculosisHealth effects> Premature deaths & disabilityHousehold effects> Low productivity> High household costsHealth care effects> Limited access to effective andequitable health-care servicesMacroeconomic effects> Losses in economic growthLoss of household income from> High health-care costs> Poor physical status& premature death> Agriculture andtransportation policies> Unhealthy behaviours

15prevalence of overweight* males | ages 20 +*bmi≥ 25kg/m2percentage of overweightDeath rate per 1000 adults aged 15 – 69 years

16 INTRAUTERINE PROGRAMMING OF NCDIntrauterine Programmingof Non-Communicable Disease:Role of MaternalMicronutrientsUrmila S Deshmukh,Himangi G Lubree,Chittaranjan S YajnikKamalnayan Bajaj Diabetology Research Centre,King Edward Memorial Hospitaland Research Centre,Pune, IndiaIntroductionTwo thirds of all deaths in the world are due to non-communicablediseases (NCDs), and 80% of NCD deaths occur in low- andmiddle-income countries. 1 Cardiovascular diseases, obesity andtype 2 diabetes (T2D) are the major contributors to the globalburden of NCDs. Studies in the life course evolution of thesechronic diseases have highlighted an etiological role for factorswhich govern intrauterine and post-natal growth. Research inthis field could offer a novel solution to the “primordial” preventionof conditions which are the most prominent killers intoday’s world.These novel ideas arose from a series of studies by DavidBarker and his colleagues in the UK. They proposed that intrauterineundernutrition initiated a number of adaptations in thefetus which increased disease susceptibility in later life, especiallywhen post-natal nutrition tended to be “excessive”. 2 A developingfetus has the ability to grow in different ways dependingon the surrounding (intrauterine) environment; this abilityis called the “plasticity”. 3 An unfavorable environment restrictsthe ability of the fetus to grow “wildly” and causes a permanentstructural or functional change, known as “programming”. 4 Indiais the world’s capital of low birth weight (LBW) babies, while atthe same time it is evolving into one of the economic powers ofthe world. It was clear that research in India would shed importantlight on these new and exciting ideas.Fetal nutrition, growth, birth size and programmingThe original ideas in this field were based on birth weight, forwhich there is a large database. However, it was clear from thebeginning that birth size was only a proxy for factors which affectfetal growth. These include genetic factors, maternal size,and intrauterine environment. Birth weight is not a sensitive indicatorof intrauterine nutrition, nor is it specific for nutrition. 5Animal experiments show that a brief nutritional disturbancein early pregnancy permanently alters fetal physiology withoutany effect on birth size. 6 Thus, birth weight studies helped focusattention on intrauterine life as an important determinantof future health, but the excitement will focus on defining theenvironmental factors which are the “true exposures” in this association.This is where the current research is being directed.Possible mechanisms of programmingFetal growth and development are influenced by an interactionbetween genetic factors and the intrauterine environment. Thiswas beautifully shown with reference to the interaction betweenthe glucokinase gene and maternal hyperglycemia. 7 The birthsize of the newborn is influenced not only by inheritance of thegene, but also by maternal glycemia.Fetal programming can be manifested in various ways. Itmight affect size, body composition, systems, organs and cells.It also affects physiology, sometimes without affecting size.Changes include altered setting of different enzyme systemsand resetting of the endocrine axes. Endocrine mechanisms aremajor contributors to programming. Insulin-IGF (insulin-likegrowth factor) and the hypothalamic-pituitary-adrenal axis havebeen shown to be prominently affected. 6It is increasingly being appreciated that epigenetic changesare at the center of programming. These changes may be mediatedby methylation of DNA, acetylation of histones and throughthe role of micro RNAs, all of which modify gene expression. 8,9

SIGHT AND LIFE | VOL. 25 (2) | 2011 17“Epigenetic changes areat the center of programming”

18 INTRAUTERINE PROGRAMMING OF NCDfigure 1: Thin-Fat Indian Baby. A schematic diagram to compare the body composition of Indian and white Caucasian babies.5, 21Indian babies were ≈ 800 g lighter, muscle thin but more adipose compared to the white babies.white caucasian, 3500 gindian, 2700 gFatMuscleVisceraOtherFatMuscleVisceraOtherThe role of DNA methylation in influencing the phenotype of agrowing fetus has been well demonstrated in animal models.Feeding pregnant Agouti mice with a methylating cocktail (vitaminB₁₂ + folate + betaine + choline) changes the coat colorand reduces obesity, despite inheritance of the mutation. 10 Thechange in phenotype is linked to methylation in the promoterregion of the Agouti gene, which silences it.Evidence from Pune studiesResearch at the Diabetes Unit, King Edward Memorial Hospital,Pune has made important contributions to programming research.Our original observation was that diabetes occurred inIndians at a much lower body mass index (BMI), as compared toEuropeans, and that this could in part be due to their higher centralobesity and higher body fat percent, or adiposity. 11 This ledto the “thin-fat” Indian concept. Many suggested that this was“genetically” determined, but we have not found any major differencesin genetic associations of T2D in Indians compared toEuropeans. 12 In 1991, we joined David Barker and Caroline Fallin their “fetal origins” research. The first collaborative research(Pune Children Study) confirmed that low birth weight was associatedwith insulin resistance as early as four years of age, 13 andthat children who were born small but grew big in childhood hadthe highest level of risk factors for diabetes and cardiovasculardisease. 14 We realized that intrauterine undernutrition could bean important contributor to the risk of adult disease. At the sametime, we knew that fetal overnutrition (as in maternal diabetes)also increases the risk of obesity and diabetes in the child. 15 Thestage was set to investigate the factors influencing fetal growthand programming. This was the birth of the Pune Maternal NutritionStudy (PMNS).The PMNS was established between 1993 and 1996 in six villagesnear Pune, to investigate the influence of maternal bodysize and nutrition during pregnancy on fetal growth and itsfuture metabolic risks. 16 We also investigated the fathers’ contributions.Over 800 pregnancies were studied. Children werevisited every six months for anthropometric measurements, andparents and children were investigated every six years for a detailedassessment of body composition, cardio-metabolic riskfactors and neurocognitive development.Predictors of fetal growth and birth sizeFetal growth and size are influenced by genes, parental bodysize, maternal nutrition and the mother’s metabolic and vascularcompetence during pregnancy. Our measurements were guidedby McCance’s writings of over 50 years ago: “The size attainedin utero depends on the services which the mother is able to provide;these are mainly food and accommodation.” 17 We assessedmaternal nutrition via anthropometric measurements, nutrientintake and physical activity, and by measurement of circulatingnutrient levels.Maternal body size, body compositionand weight gain during pregnancyThe average mother in the PMNS was 21 years old, weighed42 kg (BMI 18.1 kg/m²), and ate ≈1,700 kcal and 45 g proteinsper day during pregnancy. The newborns weighed on average2,700 g with a ponderal index (PI) of 24.1 kg/cm³; 28% wereLBW (< 2,500 g). 18Babies of heavier mothers were larger in all aspects, and babiesof taller mothers were longer. Maternal fat measurementsinfluenced the baby’s weight and skin folds. It is interesting that

SIGHT AND LIFE | VOL. 25 (2) | 2011 INTRAUTERINE PROGRAMMING OF NCD 1919paternal size predominantly influenced skeletal measurements,while the baby’s adiposity was predominantly determined bymaternal factors. Short and fat mothers gave birth to the mostadipose babies, suggesting an intergenerational influence ofmaternal early life “growth retardation” and the mother’s subsequentweight gain on body composition of the growing fetus. 17One more interesting finding was that babies born to multiparouswomen had higher skin folds and a higher abdominal circumferencethan those born to primiparous women. 19“A gain in maternal tissue during earlyweeks is an important determinant offetal growth”Maternal weight gain during the first 18 weeks influenced allneo-natal measurements, indicating that a gain in maternaltissue during early weeks is an important determinant of fetalgrowth. Placental volume measurement at 18 weeks’ gestationwas also an independent determinant of fetal growth, highlightingthe role for this important organ. 20The “thin-fat” Indian babyWe compared the birth measurements of Indian babies withthose of white Caucasian babies born in Southampton, UK. Indianbabies were lighter (2.7 vs. 3.5 kg, z score -1.74), shorter (47.3vs. 50.2 cm, z score -1.01) and thinner (PI 24.5 vs. 28.2 kg/cm³,z score -1.62), but their sub-scapular skin fold measurementswere relatively well preserved (4.2 vs. 4.6 mm, z score -0.53). Atany sub-scapular skin fold thickness, Indian babies had a lowerPI than that of the white Caucasian babies. 21In a subsequent study, we used whole body MRI to calculatebody fat and its regional distribution in neonates. Compared tothe larger white Caucasian babies, the Indian babies had similarwhole body adipose tissue content (“thin-fat”) and significantlyhigher absolute adiposity in all three abdominal compartments,viz internal (visceral), deep subcutaneous and superficial subcutaneous.Non-abdominal superficial subcutaneous adipose tissuewas, however, lower. 22 Thus, Indian babies are more adiposeand have a fat distribution that is suggestive of a higher risk ofdiabetes, as compared to white Caucasian babies.(Figures 1 and 2)figure 2: Thin-Fat Indian Baby. Anthropometry and MRI comparison of Indian and white Caucasian babies. Despite their anthropometricsmallness, Indian babies had a higher amount of fat in subcutaneous and visceral abdominal compartments. White Caucasian babiesare used as reference, and z scores for Indian babies are plotted. 22 This figure is not to scale. The figure highlights relative adiposity ofIndian newborns.3.002.00Mean z score (95% CI)1.000.00–1.00–2.00Anthropometry Abdominal Non-AbdominalWeightHead circumferenceLengthInternal-abdominalDeep subcutaneous abdominalSuperficial subcutaneous abdominalInternal non-abdominalDeep subcutaneous non-abdominalSuperficial subcutaneous non-abdominalTotal adipose tissue

20 INTRAUTERINE PROGRAMMING OF NCDMaternal nutrition during pregnancyIn the PMNS, we measured maternal macronutrient and micronutrientnutrition, with special attention to one-carbon (1-C,methyl) metabolism, which is crucial for cell growth, differentiationand development. Maternal energy and protein intake wasnot associated with birth size; fat intake was weakly associated.On the other hand, the intake of micronutrient-rich foods (greenleafy vegetables, milk and fruits) had a substantial effect on fetalgrowth. Maternal erythrocyte folate concentrations and vitaminC concentrations predicted larger neonatal size; vitamin B₁₂ wasnot predictive. 16 Maternal plasma homocysteine concentrationspredicted smaller birth weight. 23 Our results suggested an importantrole for micronutrients, especially for maternal 1-C metabolismin fetal growth and its body composition. (Figure 3)“The intake of micronutrient-richfoods had a substantial effect onfetal growth”figure 3: Maternal size and nutrition influence baby’ssize and body composition. Maternal head circumference(a surrogate for early life growth and nutrition) is relatedto neonatal size, her height is related to neonatal lengthand muscle, and fat to neonatal fat. Maternal dietary andcirculating micronutrients (folate and vitamin C) influenceneonatal size, circulating glucose and triglycerides are16, 24predominantly related to neonatal fat.MaternalsizeHeadHeightMuscleFatBabyʼs size &body compos.HeadLengthMuscleFatAbdomenWeightMaternalnutritionMicronutrients(nutritional& circulating)TriglyceridesGlucoseAdipocytes – more than a bag of fat:the role of adipocytokinesIt is remarkable that the human newborn has the highest bodyfat percentage (≈15%) of all mammals, including pigs (≈2%) andsea lions (≈5%). 25 The significance of this fact is yet to be established,but it suggests that neonatal adipose tissue must havea significant role in survival. Until recently, adipose tissue wasconsidered only to be a storehouse for triglycerides, to provideenergy and mechanical and thermal insulation. We now knowthat it is the biggest “endocrine organ” in the body. The amountand distribution of adipose tissue influence a wide variety ofphysiological functions and also predispose to a variety of clinicaldisorders. Adipocytes secrete a number of molecules called“adipocytokines”. These influence food intake and energy metabolism,the insulin sensitivity of tissues, vascular reactivity, bloodclotting mechanisms and, importantly, regulate “innate inflammation”.A growing number of adipocytokines are being discoveredand ascribed crucial physiological roles. 26 This representsa novel link between diet, physical activity and susceptibility toa number of non-communicable disorders.We studied one such adipocytokine, leptin, in newborn Indianand white Caucasian babies. Cord leptin concentrations(median: 6.2 ng/mL, Pune; 6.4 ng/mL, London) were comparablein the two groups, but higher in Indian babies when adjusted forthe difference in birth weight. 27 Thus, the excess adiposity of theIndian babies was reflected in functional disturbances indicativeof an increased risk of diabetes and related disorders.Recently, there has been interest in other adipocytokineswhich influence insulin resistance and, therefore, the risk of diabetes.These include adiponectin and retinol-binding protein 4(RBP4). Adiponectin has the highest circulating concentration ofall the adipocytokines and influences insulin resistance, inflammationand other cardiovascular risk factors. 28 Low adiponectinis an important risk factor for diabetes. RBP4 transports circulatingretinol and is synthesized in liver and adipose tissue. Itreduces insulin sensitivity and affects glucose metabolism. 29There is scant information on adiponectin and RBP4 concentrationsin cord blood.We measured adiponectin and RBP4 concentrations in storedcord blood samples, and investigated their associations withmaternal size, nutrition and metabolic parameters and newbornsize. Adiponectin and RBP4 concentrations in cord blood werelower compared to the published data on western newborns.Maternal calorie, fat and protein intake and the mother’s bodysize were not related to cord adiponectin and RBP4 concentrations.Both adipocytokines were positively associated with thebaby’s body composition (adiponectin with neonatal length, andRBP4 with sum of skin folds). Cord RBP4 was positively associatedwith maternal intake of vitamin A rich foods, suggestingthat maternal vitamin A status may influence fetal adipocytefunctioning. Longitudinal follow-up of these associations is ex-

SIGHT AND LIFE | VOL. 25 (2) | 2011 INTRAUTERINE PROGRAMMING OF NCD 2121pected to reveal the long-term effects of maternal nutrition onadipocyte functioning in offspring.Follow-up of the PMNS childrenThe Developmental Origins of Health and Disease (DOHaD) theorysuggests that structural and functional changes in the fetusconsequent upon maternal nutritional, metabolic and other influencespersist in later life. There are not many human studieslinking maternal nutrients with offspring body composition andrisk factors for NCD. Design of the PMNS allows us to follow upthe children and study the effects of fetal programming.We found that a child’s adiposity (DXA) and insulin resistance,the two major risk factors for future diabetes, were significantlyrelated to maternal micronutrient nutrition, especially those nutrientswhich regulate 1-C metabolism. Maternal folate concentrationswere directly related to the adiposity of the child at sixyears of age, and also to insulin resistance. On the other hand,low maternal vitamin B₁₂ status predicted higher insulin resistance.The most insulin resistant children were born to motherswho had the lowest vitamin B₁₂ but highest folate status. 30In addition, we found that maternal vitamin B₁₂ and folatepredicted a child’s neurocognitive function, suggesting that the1-C metabolism of the mother also programs the child’s braindevelopment and function. 31“Our research suggests that animbalance in vitamin B₁₂ and folatenutrition and consequent disturbancesin maternal 1-C metabolismmay contribute to the epidemic ofadiposity and T2D in India”influences the growth of a fetus and its future health and susceptibilityto disease. This will be a step forward in the “primordialprevention” of diabetes and other NCDs.“Future research should target theoption of intervening in the youngto influence the intergenerationaltransmission of health”SummaryRecent developments in the field of DOHaD have thrown an interestinglight on the life-course evolution of many of the chronicNCDs. It is becoming increasingly obvious that a substantial proportionof adult health is programmed in utero. The health ofyoung girls in a community is of paramount importance and is amajor influence on the health of the next generation. Maternalmicronutrient nutrition contributes to the fetal programmingof NCDs. Current ideas on preventing NCDs in the middle-agedand the elderly via difficult-to-perform lifestyle adjustments arevery ineffective models. Future research should target the morepromising option of intervening in the young to influence theintergenerational transmission of health. Balanced micronutrientnutrition of young mothers may be the key.AcknowledgementsWe are funded by the Wellcome Trust (London, UK); the NestléFoundation (Lausanne, Switzerland); The International AtomicEnergy Agency (Vienna, Austria); the Department of Biotechnology(DBT), Government of India (New Delhi, India); and Sightand Life, Basel, Switzerland. Thanks are due to colleagues, collaborators,field workers, and parents and children who participatedin the studies mentioned in this article.In the PMNS, two-thirds of mothers had low vitamin B₁₂ (10 μmol/L). Folate deficiency was rare. 29 Thisnutrient pattern is at least partly ascribable to vegetarian foodhabits and partly to the prescription of folic acid by obstetricians.Our research suggests that an imbalance in vitamin B₁₂and folate nutrition and consequent disturbances in maternal1-C metabolism may contribute to the epidemic of adiposity andT2D in India.Folate and vitamin B₁₂ are the major methyl donors in diet,and methylation of DNA is one of the major mechanisms of regulationof gene expression (epigenetics). Methylation silences thegenes and affects the phenotype. It will be important to studyhow an improvement in the maternal nutrition of these nutrientsCorrespondence: Prof. Chittaranjan S Yajnik, Diabetes Unit,6th floor, Banoo Coyaji Building, KEM Hospital, Rasta Peth, Pune411011, Maharashtra, India E-mail: diabetes@vsnl.com⇢

22 INTRAUTERINE PROGRAMMING OF NCDReferences01. The Global Status Report on Non-communicable Diseases 2010.World Health Organization. http://whqlibdoc.who.int/publications/2011⁄9789240686458_eng.pdf.(Accessed on 4 May 2011).02. Hales CN, Barker DJP. Type 2 (non-insulin dependent)diabetes mellitus: the thrifty phenotype hypothesis. Diabetologia1992;35:595–601.03. Bateson P, Barker D, Clutton-Brock T et al. Developmental plasticityand human health. Nature 2004;430:419-21.04. Lucas A. Programming by early nutrition in man. In: Bock GR,Whelan J, editors. The childhood environment and adult disease.CIBA Foundation Symposium 156. Chichester: Wiley; 1991.pp 38–55.05. Yajnik CS. Obesity epidemic in India: Intrauterine origin? Proc NutrSoc. 2004;63:387-396.06. Harding JE. The nutritional basis of the fetal origins of adult disease.Int J Epidemiol. 2001;30:15-23.07. Hattersley AT, Tooke JE. The fetal insulin hypothesis: an alternativeexplanation of the association of low birth weight with diabetes andvascular disease. Lancet 1999;353:1789-92.08. Demerath EW, Cameron N, Gillman MW et al. Telomeres andtelomerase in the fetal origins of cardiovascular disease: a review.Hum Biol 2004;76:127-46.09. Burdge GC, Lillycrop KA, Jackson AA. Nutrition in early life, andrisk of cancer and metabolic disease: alternative endings in anepigenetic tale? Br J Nutr 2009;101:619-30.10. Waterland RA, Jirtle RL. Transposable elements: targets for earlynutritional effects on epigenetic gene regulation. Mol Cell Biol2003;23:5293-300.11. Yajnik CS. The insulin resistance epidemic in India: fetal origins,later lifestyle, or both? Nutr Rev 2001;59:1-9.12. Chauhan G, Spurgeon CJ, Tabassum R et al. Impact of commonvariants of PPARG, KCNJ11, TCF7L2, SLC30A8, HHEX, CDKN2A,IGF2BP2, and CDKAL1 on the risk of type 2 diabetes in 5,164Indians. Diabetes 2010;59:2068-74.13. Yajnik CS, Fall CH, Vaidya U et al. Fetal growth and glucose andinsulin metabolism in four-year-old Indian children. Diabetic Med1995;12:330-6.14. Bavdekar A, Yajnik CS, Fall CH et al. Insulin resistance syndrome in8-year-old Indian children: small at birth, big at 8 years, or both?Diabetes 1999;48:2422-9.15. Dabelea D, Hanson RL, Lindsay RS. Intrauterine exposure to diabetesconveys risks for type 2 diabetes and obesity: a study of discordantsibships. Diabetes. 2000;49:2208-11.16. Rao S, Yajnik CS, Kanade A et al. Intake of micronutrient-rich foodsin rural Indian mothers is associated with the size of their babies atbirth: Pune Maternal Nutrition Study. J Nutr 2001;131:1217-1224.17. McCance RA. Food, growth, and time. Lancet 1962;2:621-6.18. Fall CHD, Yajnik CS, Rao S et al. The effects of maternal bodycomposition before pregnancy on fetal growth; The Pune MaternalNutrition Study. In: Fetal programming Influences on Developmentand Disease in Later life. Shaughn O'Brien PM, Wheeler T, Barker JPeds RCOG, London, 1999, Chapter 21, p231-245.19. Joshi NP, Kulkarni SR, Yajnik CS et al. Increasing maternal paritypredicts neonatal adiposity: Pune Maternal Nutrition Study.Am J Obstet Gynecol 2005;193:783-9.20. Kinare AS, Natekar AS, Chinchwadkar MC et al. Low midpregnancyplacental volume in rural Indian women: A cause for low birthweight? Am J Obstet Gynecol 2000;182:443-8.21. Yajnik CS, Fall CHD, Coyaji KJ et al. Neonatal anthropometry:the thin-fat Indian baby: The Pune Maternal Nutrition Study.Int J Obes 2003;26:173-80.22. Modi N, Thomas EL, Uthaya SN et al. Whole body magnetic resonanceimaging of healthy newborn infants demonstrates increasedcentral adiposity in Asian Indians. Pediatr Res 2009;65:584-7.23. Yajnik CS, Deshpande SS, Panchanadikar AV et al. Maternal totalhomocysteine concentration and neonatal size in India.Asia Pac J Clin Nutr. 2005;14:179-81.24. Yajnik CS. The lifecycle effects of nutrition and body size on adultadiposity, diabetes and cardiovascular disease. Obesity Reviews2002;3:217-224.25. Kuzawa CW. Adipose tissue in human infancy and childhood: anevolutionary perspective. Am J Phys Anthropol. 1998;27:177-209.26. Antuna-Puente B, Feve B, Fellahi S et al. Adipokines: the missinglink between insulin resistance and obesity. Diabetes Metab2008;34:2-11.27. Yajnik CS, Lubree HG, Rege SS et al. Adiposity and hyperinsulinemiain Indians are present at birth. J Clin Endocrinol Metab2002;87:5575-80.28. Whitehead JP, Richards AA, Hickman IJ et al. Adiponectin-akey adipokine in the metabolic syndrome.Diabetes Obes Metab.2006;8:264-80.29. Yang Q, Graham TE, Mody N et al. Serum retinol binding protein4 contributes to insulin resistance in obesity and type 2 diabetes.Nature 2005;436:356-362.30. Yajnik CS, Deshpande SS, Jackson AA et al. Vitamin B12 andfolate concentrations during pregnancy and insulin resistance inthe offspring: The Pune Maternal Nutrition Study. Diabetologia2008;51:29-38.31. Bhate V, Deshpande S, Bhat D et al. Vitamin B12 status of pregnantIndian women and cognitive function in their 9-year-old children.Food Nutr Bull. 2008;29:249-54.

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24 OLSON MEMORIAL LECTURE – CARIG WORKSHOP 2011James A Olson Memorial Lecture –CARIG Workshop at Experimental Biology 2011:Isotope Dilution Assessmentof Vitamin A StatusHarold C FurrUniversity of Wisconsin, Department of NutritionalSciences, Madison, Wisconsin 53706 USAMethods for estimation of vitamin A statusVitamin A deficiency is still a major public health problem inmany parts of the world. The clinical, social, and economic consequencesof vitamin A deficiency are well known, and will notbe discussed here. But this problem creates a need for appropriatemethods for estimating human vitamin A status. Hencea number of methods exist for assessing vitamin A status, eachof which is useful in only certain ranges of vitamin A status.(Figure 1) However, it is worth keeping in mind that, wheneverthere are so many different methods for doing something, notone of those methods is fully satisfactory – each of these methodshas disadvantages.It is generally accepted (and numerous studies have agreed)that most of the body’s vitamin A is in the liver, especially inthe well-nourished subject (animal or human). 1 Therefore determiningvitamin A concentration in the liver is unequivocally thebest method of assessing vitamin A status. From considerationsof the estimated length of time for protection from vitamin Adeficiency, liver concentration at which plasma RBP is saturatedwith retinol and catabolism of vitamin A, Olson 2 defined vitaminA status in terms of liver vitamin A concentration, and suggestedthat liver vitamin A >0.07 μmol/g (20 μg/g) is adequate,0.035 to 0.07 μmol/g (10 to 20 μg/g) is considered marginal,and

SIGHT AND LIFE | VOL. 25 (2) | 201125“Determining vitamin A concentrationin the liver is unequivocallythe best method of assessingvitamin A status”Dr Harold C Furr

26 OLSON MEMORIAL LECTURE – CARIG WORKSHOP 2011figure 1: The relationship of vitamin A status indicators to liver reserves of vitamin A. (CIC, conjunctival impression cytology; RAG,retinoyl β-glucuronide; RBP:TTR, retinol binding protein to transthyretin molar ratio; RDR, relative dose response; MRDR, modifiedrelative dose response.) From Tanumihardjo. 47indicator deficient sub-clinical adequate sub-toxic toxicxerophthalmianight blindnessdark adaptometrycicserum retinolrag-hydrolysisrbp:ttrbreast milk retinolrdrmrdrisotope dilutionliver sampleRadioactive tracers use ³H or ¹⁴C incorporated into the vitamin Amolecule. Each has been used in animal models and in early humanstudies and usually employs liquid scintillation counting forquantitation. Accelerator mass spectrometry allows the use ofminute amounts of ¹⁴C which pose no discernable risk to humansubjects, 5 but is expensive to implement. Non-radioactive tracersuse ²H or ¹³C labels and mass spectrometry to determine theratio of labeled to non-labeled vitamin A. 6-8 Quadrupole massspectrometers have been used to measure ²H retinol; they arerelatively inexpensive and rugged instruments, but do not haveas much sensitivity as other techniques. Isotope-ratio combustionmass spectrometers provide high sensitivity for measuring¹³C/¹²C ratios, 6 thus allowing lower doses of tracer; but samplepreparation is more demanding.Tracee: The molecule of interest (vitamin A) which is to be quantitated.Concentrations of vitamin A in plasma and liver can bemeasured by conventional techniques (HPLC or fluorescence).Mixing (“equilibration”): In early writings on isotope dilutionas a means of quantitating vitamin A pools, it was assumed that“In the well-nourished individual,some 80 to 90% of total bodyvitamin A is in the liver”the tracer would completely equilibrate with the tracee, and thata certain period of time would be necessary for equilibration.However, kinetic considerations show that true equilibration oftracer with tracee can occur only if there is no dietary input ofvitamin A after the administration of the tracer, and this is usuallynot realistic in practice. Dietary input of vitamin A continuouslydilutes the tracer, as both tracer and tracee are catabolizedand lost.Pools (compartments): Vitamin A in the body (animal or human)is present in a number of discrete compartments, distinguishableby tissue and even by cell type. It is difficult to distinguishall the compartments by kinetic models, however. In the wellnourishedindividual, some 80 to 90% of total body vitamin A isin the liver, so the usual validation of isotope dilution estimatesis by comparison with the vitamin A content of the liver.Introduction of isotope dilution forestimating vitamin A statusThe first publication on the use of isotope dilution to assess vitaminA status was by Rietz et al 9 at Hoffmann-La Roche, describingthe use of radioactive vitamin A to estimate vitamin A storesin rats. Subsequent publications 10,11 expanded on the initialexperiments, and a paper by Bausch and Rietz 12 summarizeda number of experiments, using both radioactive and stableisotope-labeled tracers, in both humans and animals. Good correlationwas obtained with direct analysis of vitamin A in liver inthe animal studies; in the human studies, a single subject, there

SIGHT AND LIFE | VOL. 25 (2) | 2011 OLSON MEMORIAL LECTURE – CARIG WORKSHOP 2011 2727figure 2: Simple dilution calculation, for one unit of traceradded to a tracee pool of varying size. Note that the tracer/tracee ratio gives highest precision at low tracee poolsize (most important for detecting deficient and marginalvitamin A status).Tracer/tracee ratio0.0120.010.0080.0060.0040.002The first study in human subjects to directly compare measuredliver vitamin A content with the predictions of isotope dilutionwas performed in the laboratory of Prof James Olson at IowaState University. 16,17 Robert Bergen synthesized the labeled vitaminA; Andrew Clifford and Daniel Jones performed the massspectrometric analyses of D/H ratio at the University of California;Olivier Amedee-Manesme, a visiting pediatrician fromFrance, was the liaison with the local hospital where the studywas performed; and Dale Anderson was a surgeon in the localhospital in Ames, Iowa, who obtained the liver biopsies. Weused a rather substantial oral dose of ²H-vitamin A, 45 mg foreach subject, to ensure that there would be sufficient tracer labelto measure with confidence. When we had the resulting data inhand, I spent weeks trying to make sense of them; they did notfit the Bausch and Rietz equation well. One Friday afternoon, DrOlson and I discussed the problem; he offered to take the datahome over the weekend. On Monday morning, he came in withthe “Olson equation”, which provided a good fit for almost all thedata: (Figure 3)00 2000 4000 6000 8000 10.000TraceeTotal liver reserves = F * dose * [S * a * [(H:D) - 1]]wherewas good agreement with total vitamin A as estimated by theuse of both radioactive and stable isotope labels.Their equation contained an “experimental factor” (“0.5" inthe equations) for loss of tracer, attributed to inefficiency of absorptionor catabolic loss; this experimental factor was not examinedfor dependence on time nor on vitamin A status, but wastaken to be a constant for either radioactive or stable isotopetracer studies: 12For radioactive tracer:0.5 * test dose (dpm)Vitamin A liver stores =Specific activity of vitamin Ain plasmaF is a factor to express efficiency of storage (taken to be 0.5from the work of Rietz)H:D is the isotope ratio of non-deuterated (tracee) todeuterated (tracer) retinol in plasmaS is the ratio of specific activity of retinol in plasma tothat in liver (taken as 0.65 from rat studies)a = e- kt is the fraction of absorbed tracer dose remainingin liver at time t after dosing, using the estimated rate ofcatabolism of vitamin A obtained by Sauberlich et al 18(k = (ln 2) / 140 days = 0.00495 per d); this was assumedto be constant, independent of the size of vitamin A stores.For stable isotope tracer, the vitamin A liver stores werecalculated by use of the ratio of tracer-to-tracee in plasmaretinol (as determined by mass spectrometry); theircalculation included a correction (“+ 1”) for the mass oftracer dose administered.For stable isotope tracer:Vitamin A liver stores =0.5* test dose* [(H-retinol/D-retinol) + 1]⇢ A similar relationship was observed in rat studies byHuque 13,14 and by Cullum et al. 15⇢ This relationship was subsequently corroborated byHaskell et al 19 in Bangladeshi subjects; a linear relationshipbetween measured liver vitamin A content and total bodyvitamin A stores as calculated by the Olson equation wasfound. Haskell et al found the ratio of plasma to liverspecific activities to be 0.80, and they estimated meanrecovery of tracer in liver to be 0.378; multiplied togetherin the Olson equation, the product of these factors is 0.30,which was statistically not different from the product ofF x S (0.5 x 0.65 = 0.325) used originally by Olson.

28 OLSON MEMORIAL LECTURE – CARIG WORKSHOP 2011Cord plasma retinol [μmol/l]figure 3: Relationship between calculated and measuredamounts of vitamin A (μmol /g wet weight) in the livers of 11generally healthy human adults. The solid line is the line ofidentity (1:1 correspondence). From Furr et al. 161.21.00.80.60.40.200 0.1 0.2 0.3 0.4 0.5 0.6Measured liver vitamin A [μmol/g]“The first study in human subjectsto directly compare measuredliver vitamin A content with thepredictions of isotope dilution wasperformed in the laboratory ofProf James Olson”Applications of isotope dilution assessmentRibaya-Mercado et al 20 showed that the isotope dilution techniquecould indeed detect changes in total body stores of vitaminA in elderly subjects in Guatemala. Haskell et al 21 foundthat the isotope dilution technique could detect changes in totalvitamin A body stores in male adult subjects in Bangladesh,subsequent to long-term consumption of different amounts ofvitamin A. These two studies provided early corroboration of thetechnique. The improvement in vitamin A status in Nicaraguanschoolchildren after a sugar fortification program was evaluatedby Ribaya-Mercado et al. 22The kinetics of an oral dose of tracer vitamin A was examinedin preschool children in Peru. 23 There was also an apparent correlationbetween serum tracer/tracee ratio at three days afterdosing with the total body stores, as estimated from the ratio atlonger times of mixing.Conversion of carotenoids to vitamin Aand estimates of bioequivalencyTang et al 24,25 were the first to use isotope dilution to demonstratethat carotenoids from green and yellow vegetables canmaintain liver vitamin A stores, from a study in Chinese children.Lin et al 26 used double-label techniques (tracer retinol labeledwith ²H₆, and ²H₆-β-carotene which yielded ²H₃-retinol on cleavage)to verify that the extent of conversion of β-carotene to vitaminA is quite variable among human subjects, a finding corroboratedby Wang et al. 27 Ribaya-Mercado et al 28 subsequentlyfound that the extent of conversion of provitamin A-carotenoidsto vitamin A varies inversely with vitamin A stores as determinedby isotope-dilution, but is independent of serum retinolconcentration. Tang et al 29 used the double-label approach toshow that β-carotene can be cleaved to vitamin A in tissues afterabsorption. And Ribaya-Mercado et al 30 showed an increase invitamin A pools in Filipino children after dietary consumption ofcarotene-rich foods.Haskell et al 31 determined the bioequivalence of β-carotenefrom sweet potato (13:1) and Indian spinach (10:1), comparedwith that from isolated β-carotene in capsules (6:1). You et al 32did not estimate vitamin A status, but did use labeled retinolto estimate the intestinal absorption and conversion of an oraldose of carotenoids from red palm oil. Wang et al 33 measureda conversion factor of 4.5 for spirulina β-carotene in Chineseadults. The vitamin A equivalency of labeled β-carotene in capsuleswas determined to be approximately 3.36, whether administeredin an oil matrix or a vegetable diet, but the absorptionefficiency of β-carotene was much greater from the oil than fromthe vegetables. 34Estimation of human dietary requirements of vitamin AThe dietary intake of vitamin A (preformed plus provitamin A-carotenoids) was correlated with vitamin A stores by Ribaya-Mercado et al 35 in an elderly Filipino population. They calculatedthat a daily intake of 400 μg RAE for women, or 500 μgRAE for men, is sufficient to maintain adequate vitamin A stores.(This may be compared with estimates of 567 μg RAE for women,707 μg RAE for men, calculated by Olson from other considerations).36 Recently, Haskell et al 37 used isotope-dilution estimatesof vitamin A pool size to calculate an estimated averagerequirement of approximately 350 μg RAE per day to maintain aliver pool of 0.047 μmol/g for Bangladeshi men of small stature;maintaining a higher vitamin A pool would, of course, requirea greater intake. Clearly, this approach is useful for estimatingRecommended Dietary Intakes for vitamin A.

SIGHT AND LIFE | VOL. 25 (2) | 2011 OLSON MEMORIAL LECTURE – CARIG WORKSHOP 2011 2929Alternative isotope dilution calculationsA practical problem with the Olson equation is the impliedneed for a lengthy mixing period between administration oftracer and collection of a blood sample for determination ofisotope ratio. From the human studies by Bausch and Rietz 12and Sauberlich et al, 18 it was concluded that 21 days were necessaryfor complete mixing. However, tracer:tracee ratios atthree and six days after dosing were shown by Ribaya-Mercadoet al to correlate well to those at 21 days. 20 Three-day predictiveequations were determined by Tang et al, 38 Haskell et al 23and Ribaya-Mercado et al. 39 Although these equations differ inform, happily they give similar results.Duncan et al 40 developed empirical two-component exponentialregression equations to correlate rat liver vitamin Astores with plasma isotope dilution data for 4, 4.4, 5 and 5.4days for rats given tracer intravenously. Similarly, Adams andGreen 41 developed empirical biexponential regression equationsto correlate rat liver vitamin A stores with plasma isotopedilution data at 3 days, 4, 4.4, 5, 5.4, and 6 days after oral administrationof tracer dose. An extension of this approach forapplication to humans has been developed (Duca and Green,personal communication).Further research needs for application of isotopedilution to assess human vitamin A statusThe kinetics of vitamin A metabolism in children has been examinedin only one study, among 12–24 month children. 23 Sofar, the Olson equation as determined for adults has been usedwithout verification. Although such studies pose ethical concerns,further data on vitamin A metabolism in young humansare essential for developing suitable prediction equations to allowthe extension of this technique to children.Further development of short-term prediction equations willfacilitate the use of the isotope-dilution procedure. Mathematicalmodels of human vitamin A kinetics show promise for thedevelopment of general prediction equations which are applicableto a wide range of sampling times (Green MH and Furr HC,unpublished work).“Further data on vitamin Ametabolism in young humans areessential for developing suitableprediction equations to allowthe extension of this techniqueto children”ReviewsAmong the generally available reviews of isotope dilution for assessmentof vitamin A status are those of Wasantwisut, 42 Tanumihardjoet al, 43 Furr et al, 44 Haskell et al 45 and Furr et al. 46AcknowledgmentsThe author happily acknowledges the support of Prof JamesOlson in helping understand and implement the application ofisotope dilution for assessment of human vitamin A status, andis also grateful for collaborations with many colleagues.Correspondence: Harold C Furr, 115 West Rainbow Drive,Bridgewater, VA 22812-1735 USA E-mail: hfurr581@yahoo.comReferences01. Moore T. Vitamin A. Amsterdam: Elsevier, 1957.02. Olson JA. New approaches to methods for the assessment of nutritionalstatus of the individual. Am J Clin Nutr 1982;35:1166-1168.03. Burri BJ, Jacob RA. Vitamin A analogs as tests for liver vitamin Astatus in the rat. Am J Clin Nutr 1988; 47:458-462.04. Tanumihardjo SA, Furr HC, Erdman JW Jr et al. Use of the modifiedrelative dose response (MRDR) assay in rats and its applicationto humans for the measurement of vitamin A status. Eur J ClinNutr 1990;44:219-224.05. Fonseca de Moura F, Burri BJ, Clifford AJ. Accelerator massspectrometry in the study of vitamins and mineral metabolism inhumans. In: Zempleni J, Rucker RB, McCormick D B, Suttie JW, eds.Handbook of Vitamins. Boca Raton FL: CRC Press,2007: pp545-557.06. Tanumihardjo SA.Vitamin A status assessment in rats with 13C4-retinyl acetate and gas chromatography/combustion/isotope ratiomass spectrometry. J Nutr 2000;130:2844-2849.07. van Lieshout M. Bioavailability and bioefficacy of β-carotenemeasured using 13C-labeled β-carotene and retinol: studies inIndonesian children. Wageningen, Netherlands: WageningenUniversity, 2001.08. Aklamati EK, Mulenga M, Dueker SR et al. Accelerator mass spectrometrycan be used to assess vitamin A metabolism quantitativelyin boys in a community setting. J Nutr 2010;140:1588-1594.09. Rietz P, Vuilleumier JP, Weber F et al. Determination of thevitamin A bodypool of rats by an isotopic dilution method.Experientia 1973;29:168-170.⇢

30 OLSON MEMORIAL LECTURE – CARIG WORKSHOP 201110. Rietz P, Wiss O, Weber F. Metabolism of vitamin A and thedetermination of vitamin A status. Vitamins and Hormones1974;32:237-249.11. Hughes DR, Rietz P, Vetter W et al. A method for the estimation ofthe vitamin A status of rats. Int J Vit Nutr Res 1976;46:231-234.12. Bausch J, Rietz P. Method for the assessment of vitamin A liverstores. Acta Vitaminol Enzymol 1977;31:99-112.13. Huque T. Assessment of vitamin A status by an isotope dilutionmethod. Int J Vit Nutr Res. 1981;31:119-123.14. Huque T. A simplified isotope dilution procedure for theassessment of vitamin A status in rats. Int J Vitam Nutr Res.1983;53:123-129.15. Cullum ME, Zile MH, Veysey SW. Analysis of retinol and dideuteratedretinol in rat plasma by gas chromatography combined massspectrometry. Int J Vitam Nutr Res. 1984;54:11-16.16. Furr HC, Amedee-Manesme O, Clifford AJ et al. Vitamin A concentrationsin liver determined by isotope dilution assay withtetradeuterated vitamin A and by biopsy in generally healthyadult humans. Am J Clin Nutr 1989;49:713-716.17. Olson JA. Correcting for vitamin A turnover in isotope-dilutionstudies [letter]. Am J Clin Nutr 1999;69:576-577.18. Sauberlich HE, Hodges RE, Wallace DL et al. Vitamin A metabolismand requirements in the human studied with the use oflabeled retinol. Vitamins and Hormones 1974;32:251-275.19. Haskell MJ, Handelman GJ, Peerson JM et al. Assessment ofvitamin A status by the deuterated-retinol-dilution technique andcomparison with hepatic vitamin A concentration in Bangladeshisurgical patients. Am J Clin Nutr. 1997;66:67-74.20. Ribaya-Mercado JD, Mazariegos M, Tang G et al. Assessment oftotal body stores of vitamin A in Guatemalan elderly by the deuterated-retinol-dilutionmethod. Am J Clin Nutr 1999;69:278-284.21. Haskell MJ, Mazumder RN, Peerson JM et al. Use of the deuteratedretinol dilution technique to assess total body vitamin A stores ofadult volunteers consuming different amounts of vitamin A.Am J Clin Nutr 1999;70:874-880.22. Ribaya-Mercado JD, Solomons NW, Medrano Y et al. Use of thedeuterated-retinol-dilution technique to monitor the vitamin Astatus of Nicaraguan schoolchildren 1 y after initiation of theNicaraguan national program of sugar fortification with vitamin A.Am J Clin Nutr 2004;80:1291-1298.23. Haskell MJ, Lembcke JL, Salazar M et al. Population-based plasmakinetics of an oral dose of [2H4]retinyl acetate among preschoolaged,Peruvian children. Am J Clin Nutr 2003;77:681-686.24. Tang, G, Gu X, Hu S et al. Green and yellow vegetables canmaintain body stores of vitamin A in Chinese children. Am J ClinNutr 1999;70:1069-1076.25. Tang G, Qin J, Hu S et al. Protection of vitamin A status in Chinesechildren by a dietary intervention with vegetables. Food Nutr Bull2000;21:161-164.26. Lin Y, Dueker SR, Burri BJ et al. Variability of the conversion ofβ-carotene to vitamin A in women measured by using a doubletracerstudy design. Am J Clin Nutr 2000;71:1545-1554.27. Wang Z, Yin S, Zhao X et al. β-Carotene-vitamin A equivalence inChinese adults assessed by an isotope dilution technique.Br J Nutr 2004;91:121-131.28. Ribaya-Mercado JD, Solon FS, Solon MA et al. Bioconversionof plant carotenoids to vitamin A in Filipino school-agedchildren varies inversely with vitamin A status. Am J Clin Nutr2000;72:455-465.29. Tang G, Qin J, Dolnikowski GG, Russell RM. Short-term (intestinal)and long-term (postintestinal) conversion of β-carotene to retinolin adults as assessed by a stable-isotope reference method. Am JClin Nutr 2003;78:259-266.30. Ribaya-Mercado JD, Maramag CC, Tengco LW et al. Carotenerichplant foods ingested with minimal dietary fat enhance thetotal-body vitamin A pool size in Filipino schoolchildren as assessedby stable-isotope-dilution methodology. Am J Clin Nutr2007;85:1041-1049.31. Haskell MJ, Jamil KM, Hassan F et al. Daily consumption of Indianspinach (Basella alba) or sweet potatoes has a positive impact ontotal body vitamin A stores of Bangladeshi men. Am J Clin Nutr2004;80:705-714.32. You CS, Parker RS, Swanson JE. Bioavailability and vitamin Avalue of carotenes from red palm oil assessed by an extrinsicisotope reference method. Asia.Pac J Clin Nutr 2002;11 (Suppl7):S438-S442.33. Wang J, Wang Y, Wang Z et al. Vitamin A equivalence of spirulinaβ-carotene in Chinese adults as assessed by using a stable-isotopereference method. Am J Clin Nutr 2008;87:1730-1737.34. Loo-Bouwman CA, West CE, van Breemen RB et al. Vitamin Aequivalency of β-carotene in healthy adults: limitation of theextrinsic dual-isotope dilution technique to measure matrix effect.Br J Nutr 2009;101:1837-1845.35. Ribaya-Mercado JD, Solon FS, Fermin LS et al. Dietary vitaminA intakes of Filipino elders with adequate or low liver vitaminA concentrations as assessed by the deuterated-retinol-dilutionmethod: implications for dietary requirements. Am J Clin Nutr2004;79:633-64136. Olson JA. Recommended dietary intakes (RDI) of vitamin A inhumans. Am J Clin Nutr 1987;45:704-716.37. Haskell MJ, Jamil KM, Peerson JM et al. The paired deuterated retinoldilution technique can be used to estimate the daily vitamin aintake required to maintain a targeted whole body vitamin a poolsize in men. J Nutr 2011;141:428-432.38. Tang G, Qin J, Hao LY et al. Use of a short-term isotope-dilutionmethod for determining the vitamin A status of children.Am J Clin Nutr 2002;76:413-418.

SIGHT AND LIFE | VOL. 25 (2) | 2011 OLSON MEMORIAL LECTURE – CARIG WORKSHOP 2011 313139. Ribaya-Mercado JD, Solon FS, Dallal GE et al. Quantitativeassessment of total body stores of vitamin A in adults with theuse of a 3-d deuterated-retinol-dilution procedure. Am J ClinNutr 2003;77:694-69940. Duncan TE, Green JB, Green MH. Liver vitamin A levels in ratsare predicted by a modified isotope dilution technique. J Nutr1993;123:933-939.41. Adams WR, Green MH. Prediction of liver vitamin A in rats by anoral isotope dilution technique. J Nutr 1994;124:1265-1270.42. Wasantwisut E. Application of isotope dilution technique in vitaminA nutrition. Food Nutr Bull 2002;23:103-106.43. Tanumihardjo S, Nestel P, Furr H et al. Appropriate uses of vitaminA tracer (stable isotope) methodology. Washington DC: ILSIHuman Nutrition Institute, 2004.44. Furr HC, Green MH, Haskell M et al. Stable isotope dilutiontechniques for assessing vitamin A status and bioefficacy ofprovitamin A carotenoids in humans. Public Health Nutr2005;8:596-607.45. Haskell MJ, Ribaya-Mercado JD, Furr H et al. Handbook onvitamin A tracer dilution methods to assess status and evaluateintervention programs. Washington, DC: Harvest Plus TechnicalMonograph 5, 2005.46. Furr HC, Green MH, Green JB et al. HarvestPlus Technical MonographSeries. Handbook on vitamin A tracer dilution methodsto assess status and evaluate intervention programs. Part 3:mathematical modeling of stable isotope data to estimate vitaminA stores and other parameters of vitamin A metabolism. Vienna:International Atomic Energy Agency, 2006.47. Tanumihardjo SA. Assessing vitamin A status: past, present andfuture. J Nutr 2004;134:290S-293S.Order now !DSM’s new color poster“A Practical Guide to Vitaminsin Nutrition” examines thefull range of fat- and water-solublevitamins, their roles andmain sources. You can ordercopies of this poster by emailingcelia.gies@dsm.com

32 THE LINK BETWEEN NUTRITION, DISEASE AND PROSPERITYThe Link Between Nutrition, Diseaseand Prosperity:PreventingNon-Communicable DiseasesAmong Women and Childrenby Tackling MalnutritionJane Badham, Klaus KraemerSight and Life, Basel, SwitzerlandWe face a harsh health reality in the developing world. Nutritionaldeficiencies, predominantly in the form of micronutrient malnutrition,increase the susceptibility to communicable diseasesand non-communicable diseases (NCDs) such as heart disease,diabetes and cancer. Many economically developing regions arenow suffering a double burden of obesity, diabetes and otherrelated NCDs, on top of nutritional deficiencies and infectiousdiseases.These all have a significant and negative impact on the livesof individuals that flows over to affect communities and ultimatelyharms national economies. Low- and middle-income countriesare at the center of both longstanding and new public healthchallenges. Much is now being spoken about nutritional deficienciesin the context of undernutrition; while important, we alsoneed to focus attention on addressing the NCDs that will causeover three quarters of all deaths in 2030 and will pose additionalchallenges for already stretched health care budgets. A key linkbetween undernutrition and NCDs is micronutrients (vitaminsand minerals), which yet again mostly affects the world’s poorwomen and children – further increasing the disparities betweenthe affluent and the poor. The fact remains that women make uplittle over half of the world’s population, but they account for60% of the world’s hungry. They also produce between 60 and80% of the food in most developing countries, where they haveless access to land and credit than men do.The powerful consequences of nutrition transitionHuman diet and nutritional status have undergone a numberof major shifts over the last three centuries. The concept of thenutrition transition can be defined as a stepwise sequence ofcharacteristic changes in dietary patterns and nutrient intakesassociated with societal, economic and cultural changes duringthe demographic transition of populations. It focuses on shifts indiet, especially its structure and overall composition, is reflectedin outcomes such as changes in body stature and body composition,and is paralleled by major changes in health status. A clearexample is how changes in European and American diets havecaused fluctuations in the average height of men and womenthroughout time.Now, more than ever, we need to not only understand the dietaryand health changes taking place and their consequences,but we also need to define and implement program and policychanges that will positively improve the total nutritional andhealth status of people in developing economies.The prevalence of overweight and obesity exceeded that ofundernutrition in the majority of 37 developing countries studiedas far back as 2005. Recent trends show the rising prevalencehas spread and the incidence of obesity has further acceleratednot only amongst adults but also adolescents and even childrenin the emerging middle class. It is not obesity alone but also diabetes,hypertension, dyslipidemia and arthrosclerosis that appearto be on the increase. The reality is that four out of five NCDdeaths are in low- and middle-income countries. (Figure 1) Thisindicates a negative nutrition transition that has serious implicationsfor physical and mental development and performance.

SIGHT AND LIFE | VOL. 25 (2) | 201133“Nutrition has to bethe basis of judging nationaldevelopment”The double burden of malnutrition occurs in a single family,as seen with this mother and child in Micronesia.

34 THE LINK BETWEEN NUTRITION, DISEASE AND PROSPERITYfigure 1: Projected deaths by cause for high-, middle- and low-income countries35Middle-income30Low-incomeIntentional injuriesOther unintentional injuries25Road traffic accidentsOther non-communicable diseases20CancersDeaths (millions)1510High-incomeCardiovascular diseaseMaternal, perinatal and nutritional conditionsOther infectious diseasesHIV, TB and malaria50200420152030200420152030200420152030“Research shows that stunting attwo years of age is possibly the bestpredictor of human capital”Disease susceptibility determinedin first 1,000 days of our livesSome 20 years ago, Dr David Barker’s ground-breaking researchshowed that low birth weight babies had a greater lifetime riskfor coronary heart disease. Subsequently numerous studies haveextended the association to an increased risk of hypertension,stroke and type 2 diabetes. This phenomenon is now recognizedas the “Barker Hypothesis” or “Fetal Origins Hypothesis.” Thetheory proposes that coronary heart disease, and the diseasesrelated to it, originates through responses to undernutrition duringfetal life and infancy. These responses permanently changethe body’s structure, physiology and metabolism.Recent findings have shown that a woman’s body compositionand diet at the time of conception and during pregnancyhave important effects on the subsequent health of her offspring.Malnourished mothers often give birth to underweight babieswho are 20% more likely to die before the age of five; around17 million babies are born underweight every year. The risk oflater chronic disease is further increased if a baby has not onlya low weight at birth but also a low weight gain after birth, resultingin the child being underweight or stunted at the age oftwo. In addition, rapid post-natal weight gain – especially duringchildhood and adolescence – further increases the risk oflater NCDs. Research shows that stunting (low height-for-age) attwo years of age is possibly the best predictor of human capitaland that undernutrition is associated with lower human cognitionand lower lifetime income potential. The damage sufferedin early life leads to permanent impairment, and may also affectfuture generations. Its prevention can bring about importanthealth, educational and economic benefits.In 2008 the Lancet issued a five-part series on nutrition thatreviewed the evidence for the impact of undernutrition on infantand child mortality and its almost irreversible long term effectson health and on cognitive and physical development. Optimalnutrition is now recognized as being especially critical in thefirst 1,000 days – from conception (in fact from even beforepregnancy) to two years of age. Thus this research adds an importantdimension to maternal and child health by spotlightingthe critical role nutrition plays in health and development.NCDs and the Millennium Development GoalsSome believe that human development initiatives, such as theMillennium Development Goals (MDGs), will not fulfill theirgoals until they include strong international and country actionsagainst NCDs, especially in low- and middle-income countries. Arecent WHO publication on health and the MDGs has recognizedthis and noted that there is scope for them being consideredwithin Goal 6 (Combat HIV/AIDS, malaria and other diseases).It is now well documented that antiretroviral therapy itself in-

SIGHT AND LIFE | VOL. 25 (2) | 2011 THE LINK BETWEEN NUTRITION, DISEASE AND PROSPERITY 3535creases the risk of cardiovascular complications, thus havinga direct impact on NCDs. In addition, health more broadly, includingNCD prevention, contributes to poverty reduction andso anti-NCD strategies could also be part of Goal 1 (Eradicateextreme poverty and hunger). The MDGs have to address the notionof human development having quality of life, not only theextension of life, as a central value.A recent Lancet paper on NCDs highlights that there are tworeasons why the poorest are the most likely to develop and dieprematurely from NCDs. First, they have less access to comprehensivehealth services and secondly, they live in environmentswhere policies to tackle NCDs are either non-existent or inadequate.Furthermore, they are more likely to be exposed to risksincluding a poor nutritional status. Thus it cannot be neglectedthat NCDs can also be causal in poverty. (Figure 2)Addressing NCDs among women and childrenGovernments and development and donor agencies need to beproactive with regard to NCDs. The approach needs complex,multifaceted, and intersectoral interventions based on long timeperiods to tackle the wide range of social determinants of health;a decisive move in this direction is a prerequisite for the reductionof poverty and health inequities.The conditions in which women and children are born, growup, live and work have a major impact on their health. Thusthe Global Strategy for Women’s and Children’s Health states:“Efforts to improve health must be closely linked to those intendedto tackle poverty and malnutrition, improve access to education,ensure gender equity and empowerment, tackle major diseases,and improve access to safe drinking water, adequate sanitationand a clean, safe environment. Integrating the care of womenand children with other services is an efficient and cost-effectiveroute to success.” The reality is that, despite the billions of dollarsgiven and spent on aid and development each year, we simplydo not allocate enough resources to solve all of the world’sbiggest problems. It thus becomes necessary to direct additionalresources where they can achieve the most good.Nutrition’s role in human health and developmentOver and above food security (sufficient food to provide the requiredenergy), nutrition security (the nutritional quality of thefood and care) is thus not only the cornerstone to preventing undernutritionbut also contributes to reducing and, in many cases,preventing NCDs. Nutrition has to be the basis of judging nationaldevelopment. Without good nutrition, neither nutritionaldeficiencies nor NCDs can be controlled. The 2008 CopenhagenConsensus saw the world’s most distinguished economists compareways to spend US$75 billion on more than 30 interventionsaimed at addressing the world’s top 10 biggest challenges. Theirbasis was costs versus benefits, analyzing interventions that withrelatively small amounts of money could generate significant returnsin terms of health, prosperity, and community advantages.Among these interventions, five in the top 10 featured nutritionprograms, supplementation and fortification with micronutrients.figure 2: Inter-relation between poverty, chronic disease, and developmentKey risk factors influencing the onsetand course of chronic diseases> Tobacco use and exposure> Poor nutrition> Physical inactivity> Alcohol misuse> Indoor air pollution> Decreased access to health care servicesPovertyand socialdeterminantsof healthChronicdiseasesChronic diseases and their riskfactors limit the abilityto reach development goalsMillennium Development Goals> Poverty reduction (MDG 1)> Reduce child mortality (MDG 4)> Improve maternal health (MDG 5)> Combat HIV/AIDS, malaria, andtuberculosis (MDG 6)Effect of chronic diseases and their riskfactors on individuals and families> Low productivity> Increased risk of disabilities> High household expenditures,which include health care> Increased risk of premature death

36 THE LINK BETWEEN NUTRITION, DISEASE AND PROSPERITYFor example, every US$1 spent on vitamin A supplements wascalculated to achieve more than US$17 of benefits in health andlong-term prosperity. In the words of the Scaling Up Nutrition(SUN) Framework: “Undernutrition is one of the world’s most seriousbut least addressed health problems.” Nutrition is often anafterthought in terms of development priorities and has largelybeen neglected.Preventing NCD through adequate nutritionThe Lancet series also demonstrated that there are proven andhighly cost-effective interventions that could address the problemand save millions of lives. Supplementation, fortified staples,the promotion of exclusive breastfeeding for the first sixmonths and appropriate complementary foods after six monthsof age, together with continued breastfeeding, are some of theinterventions available to help break the cycle of malnutritionthat will also see a reduction in NCDs in the future. Just oneexample of such an effective intervention are the research findingsthat show that supplementation of pregnant women withjust one recommended daily allowance (RDA) of multiple micronutrientsnot only improves the health status of the motherbut also increases birth weight and substantially reduces therates of low birth weight and small-for-gestational-age births inchildren. This has a potentially important impact on reducingchronic disease in later life amongst these children.Saving lives, improving futuresThe Global Strategy for Women’s and Children’s Health statesthat addressing undernutrition in pregnant women and childrenleads to an increase of up to 10% in an individual’s lifetime earningsand an estimated 2–3% growth in the economic wealth ofdeveloping countries. This is as a result of the fact that womenare the sole breadwinners in one out of three households aroundthe world, so improving their nutrition is crucial. The SUN roadmap identifies investments that have been shown to work if implementedin the context of nutrition-focused development policies.Comprehensive and integrated actions at the country levelare what will ultimately lead to real change. The SUN Road Mapis expected, if fully implemented, to avert the deaths of one millionchildren per year; mitigate against disease and reduce theburden on healthcare systems; increase school attendance andeducational attainment; and improve economic prosperity andthe ability of all citizens to realize their full potential.Failure to respond is now a political, rather than a technicalissue. We need political will and resource commitment to turnknowledge and talk into action. Action that will save lives nowand into the future.Correspondence: Klaus Kraemer, Sight and Life, PO Box 2116,4002 Basel, Switzerland E-mail: info@sightandlife.orgThis article originally appeared in The Commonwealth HealthMinisters Update 2011Resources:> For details on the work of Sight and Life visit:www.sightandlife.org> For details on the Copenhagen Consensus 2008 visit:www.copenhagenconsensus.com/Home.aspx> For details on the 1000 Day movement visit:www.thousanddays.org> For the Scaling Up Nutrition (SUN) documents search onwww.unscn.org> For the Lancet series on Chronic Disease:The Lancet, Volume 376, Issue 9753, 13 November 2010

Buildingbridgesfor betternutrition.37

38 VITAMIN D AND INFLAMMATIONPlasma 25-Hydroxy-Cholecalciferol (Vitamin D)is Depressed by Inflammation:Implications and Parallelswith Other MicronutrientsDavid I ThurnhamNorthern Ireland Centre for Diet and Health,University of Ulster, Coleraine, BT52 1SA, UKIt was recently shown that serum concentrations of 25-hydroxycholecalciferol(25-hydroxyvitamin D; 25(OH)D) fell by more than40% within 24 hours of elective joint replacement surgery andwere still 20% lower than pre-operative values three months afterthe operation. 1 Quantification of serum 25(OH)D concentrationshas provided us with a measure of vitamin D status for more than40 years. The pioneering work of David Frazer, Eric Lawson, EganKodicek, Michael Holick and Hector DeLuca in the 1970s identified25-hydroxyvitamin D and 1,25-dihydroxyvitamin D; they showedus that 25(OH)D and 1,25 dihydroxy-cholecalciferol (1,25(OH)₂D)were the two major metabolites of vitamin D in our blood controllingcalcium and phosphate metabolism. Subsequent workshowed that the plasma concentration of 25(OH)D was an accurateindication of vitamin D stores, whether obtained from ultravioletirradiation or dietary intake over long periods. 2Since that time, vitamin D has been found to be an importantmodulator of immune function with anti-inflammatory and antiproliferativeproperties. In recent years, low concentrations of serum25(OH)D, ie poor vitamin D status, have been associated withan increased risk of a number of chronic diseases, including cancer,diabetes, rheumatoid arthritis, cardiovascular disease andmortality. 3 However, the rapid and long-lasting effect of traumaon circulating 25(OH)D concentrations 1 should make us pause toconsider whether the low concentrations of serum 25(OH)D associatedwith chronic disease are a metabolic consequence of thosediseases and not a true reflection of vitamin D status.Endogenous vitamin D synthesisEndogenous vitamin D synthesis is summarized in Figure 1. Theaction of sunlight on human skin converts 7-dehydrocholesterolinto cholecalciferol, otherwise known as vitamin D₃. The knowl-Key messages> Arthroplasty (joint replacement) surgery in otherwisehealthy adults induced a 40% depression in plasma concentrationsof 25-hydroxy-cholecalciferol (25(OH)D).> 25(OH)D is the principal vitamin D metabolite in the bloodand reflects both vitamin D ingestion and synthesis in thebody under the influence of sunlight irradiation; it is usuallythe best measure of vitamin D status.> Vitamin D binding protein (12%) and free 25(OH)D (40%)concentrations were also depressed by the surgery; the responseof the vitamin D metabolites was very similar to thatof vitamin A.> 1,25-dihydroxy-cholecalciferol (1,25(OH)₂D) is the primeregulator of calcium metabolism.> 1,25(OH)₂D is also an extremely important regulator of innateimmune function with anti-inflammatory activity.> As part of innate immunity, inflammation-activatedimmune cells take up 25(OH)D and synthesize 1,25(OH)₂D,which up-regulates IL-10 production and the synthesis of theanti-microbial peptide cathelicidin, and depresses TNFαproduction.> We do not know what the function of the depressedplasma 25(OH)D concentration is, but rapid changes associatedwith the acute phase response are usually protectivefor the host.

SIGHT AND LIFE | VOL. 25 (2) | 2011 VITAMIN D AND INFLAMMATION 3939> I speculate that the surgery also activated many componentsof the immune system.> Therefore, the fall in plasma 25(OH)D concentrations may beassociated with a rapid uptake of 25-OHD by immune cells,priming innate immune defences in the body.> I speculate that the 25(OH)D results obtained followingsurgery may also be obtained following any infection orinflammatory trauma.> Therefore, the many epidemiological studies showing low25(OH)D concentrations associated with chronic diseasesmay be a consequence of those diseases and not the cause.> A worrying feature of the surgical study was the persistentdepression in plasma 25(OH)D concentration by 20-25% for3 months following surgery.> We also do not know what implications these results havefor children’s vitamin D status, especially where they may beexposed to frequent infections.edge that sunlight could provide vitamin D was first shown byHarriett Chick after World War I, when she demonstrated thatrickets in children could be cured by irradiation with ultra-violetlight. Cholecalciferol is fat-soluble and stores of this compoundare found in adipose tissue. These stores of vitamin D are in equilibriumwith plasma 25(OH)D concentration, which is producedin the liver when cholecalciferol undergoes hydroxylation of carbon-25.(Figure 1) Plasma 25(OH)D has a half-life of approximatelythree weeks and this is longer than all other vitamin D metabolites.2 Further metabolism of 25(OH)D is mostly determinedby calcium metabolism. A fall in plasma calcium concentrationsstimulates the formation of another hydroxylase enzyme in thekidney, which converts 25(OH)D to 1,25(OH)₂D. 1,25(OH)₂D controlsa number of metabolic process that raise plasma calciumconcentrations, either by increasing calcium absorption and/orreleasing calcium from bone. However, the 1α-hydroxylase enzymeand vitamin D receptor is also found in many immune andother cells throughout the body 4 so 1,25(OH)₂D has other, nonclassical,functions. These important functions necessitate amuch tighter control over plasma 1,25(OH)₂D than 25(OH)D concentrationsand the half-life is only four hours. 2 Concentrationsin plasma of 25(OH)D and 1,25(OH)₂D differ almost 1000-fold(nmol/L and pmol/L).Interpretation of plasma25-hydroxy-cholecalciferol concentrationsIn my previous commentary on vitamin D, 5 a major concern wasthe reproducibility of plasma 25(OH)D measurements, interassayvariation and appropriate cut-offs to assess those at riskof vitamin D deficiency. The methodological issues were understudy at that time by the UK Food Standards Agency; the subsequentreport indicates the most reliable methods. The reportalso points out the newly available Reference Material from theNational Institutes of Standards and Technology, which shouldimprove inter-laboratory comparisons. 6 Newer studies willtherefore be better able to assure accuracy; however, the problemof interpretation may, if anything, have worsened if plasmaconcentrations of 25(OH)D are influenced by inflammation. 1 Appropriatecut-offs to assess the risk of vitamin D deficiency arestill not resolved. Deficiency is generally regarded as 50, >80 7 oreven >150 8 nmol/L.In terms of functional vitamin D concentration, some workersconsider it is best to assess the free (ie unbound) concentration inplasma, 9 although this is probably not necessary in most clinicalsettings. 2 Most plasma 25(OH)D circulates bound to vitamin D-binding protein (VDBP; 80 – 90%) and most of the remainder isbound to albumin (10 –20%). Very little 25(OH)D remains free,ie biologically active in plasma (0.02–0.05%). 10,11 VDBP alsobinds to 1,25(OH)₂D but the relative affinity is 10-fold less thanfor 25(OH)D, so the proportion of free plasma 1,25(OH)₂D concentrationsis 10-fold higher compared with 25(OH)D (0.2–0.6%).The concentration of VDBP in plasma is 20-fold higher than thetotal amount of vitamin D metabolites and the physiological consequenceof the large molar excess of circulating VDBP is unclear.Only 5% of the total VDBP capacity is usually occupied by vitaminD compounds; the physiological consequence is thereforethat all circulating vitamin D compounds are protein bound andwill have limited access to target cells. Thus, concentrations offree rather than total forms of 25(OH)D and 1,25(OH)₂D may providea better assessment of functional vitamin D status. 12“Workers suggest that the molarratio of 25(OH)D:VDBP or free 25(OH)Dmay be more useful indices of biologicalactivity in the plasma than thetotal 25(OH)D concentration alone”The influence of variations in the concentration of VDBPon the availability of the free vitamin D metabolites was clearlyshown in a comparative study of patients with idiopathic

40 VITAMIN D AND INFLAMMATIONfigure 1: Endogenous vitamin D synthesisin skinin liverHOin kidneyHO7-dehydrocholesterolcholecalciferol (vitamin D₃)HO25-hydroxy-cholecalciferol(25-hydroxy vitamin D₃)HOOHActive Form1,25-dihydroxy-cholecalciferol(1,25-hydroxy vitamin D₃)OHOHosteoporosis and matched controls. 12 There was no differencebetween the groups in plasma 25(OH)D concentrations butplasma VDBP concentrations were significantly higher in the patientswith the result that unbound concentrations of 25(OH)Dand 1,25(OH)₂D were significantly lower in the patients with osteoporosis(Table 1). The converse can also be true, since plasmaVDBP concentration can decrease with cellular damage andtissue loss 10 and this would have the effect of increasing vitaminD accessibility to tissues. Thus, workers suggest that themolar ratio of 25(OH)D:VDBP or free 25(OH)D may be more usefulindices of biological activity in the plasma than the total25(OH)D concentration alone. 1,12Influence of elective joint-replacement surgery on plasmaDBP and “free” 25(OH)D concentrationsThe study of Reid et al provided an opportunity to examine theinfluence of an altered inflammatory state on vitamin D statuswithout the complication of accompanying disease. 1 In fact,similar observations to those of Reid et al were first reportedby Louw et al 13 almost 20 years ago. Louw et al showed that atransient depression in plasma 25(OH)D concentrations of ~16%followed uncomplicated orthopedic surgery in 25 volunteers ofboth sexes. The fall in 25(OH)D was accompanied by similar rapidfalls in plasma retinol, retinol-binding protein (RBP), leukocytevitamin C, α-tocopherol, total lipid, albumin and pyridoxal-5-phosphate over the first three days post-operatively. In almost allcases, concentrations had normalized by day 6, when C-reactiveprotein had also almost returned to normal. The authors pointedout that the nutritional status of the group prior to surgery wasgood and no patient fasted more than 12 hours post-operatively.The authors also monitored hydration and concluded that thepatients had a normal fluid intake; this made hemodilution veryunlikely. The authors concluded that the self-correcting nature ofthe decreased values in the study argued against the low valuesrepresenting true nutritional status.In contrast to the study by Louw et al, Reid and colleaguesfocused their efforts entirely on vitamin D. They measured theeffects of inflammation on plasma 25(OH)D, 25(OH)D:VDBP ratioand free 25(OH)D concentrations in the immediate post-operativeperiod. The depression in concentrations was large (~40%)(Table 2) but consistent with the previously observed effects ofinflammation on plasma retinol, 13,14 ferritin 15 and many othernutrients. 16 Not only concentrations of 25(OH)D were depressed,but also the 25(OH)D:VDBP ratio and free 25(OH)D. Furthermore,in blood samples taken at three months, the three markers ofvitamin D status were no different to those observed in the samplescollected on day 5 post-operatively, but CRP concentrationshad returned to the pre-operative value.Thus, the behavior of the 25(OH)D concentrations in the surgicalstudies of Louw (South Africa) and Reid and colleagues

SIGHT AND LIFE | VOL. 25 (2) | 2011 VITAMIN D AND INFLAMMATION 4141(Scotland) was similar, 1,13 except that in the more recent studybaseline 25(OH)D values were not restored by Day 5. Mean plasma25(OH)D values remained approximately 25% lower than preoperativevalues at day 5 and were still depressed by this amountat three months post-op. It is probable that the depression of25(OH)D concentrations at three months may have been due tothe nature of the surgery. For patients undergoing replacement ofa knee joint, it is conceivable that mobility remained a problem,whereas the CRP response of the subjects in the South Africanstudy suggested that the severity of the surgery was less. Furthermore,the latitude of the surgical unit in Scotland (55ºN) andthe high rainfall in that area will not have helped the patients toobtain much useful solar radiation throughout much of the year.Reid and colleagues considered what might have contributedto the loss of 25(OH)D from the blood. The possibility that thefall in the binding protein and albumin concentrations may havecontributed to the loss of 25(OH)D was considered, but the fallin protein concentrations was only ~20% while 25(OH)D concentrationsfell by 40%. However, it is interesting to compare thebehavior of 25(OH)D with that of plasma retinol, about whichmore is known. (Table 3) Early changes in epithelial permeabiltable1: Influence of idiopathic osteoporosis on “free” vitamin D metabolitesVitamin D metabolite Osteoporosis n=56Mean ± SDControls n=114Mean ± SDP

42table 3: Factors influencing vitamins D and Ain serum in health and diseaseFactors of interestVitamin DVitamin APredominant form in serum25-hydroxy-cholecalciferol (25(OH)D) ²RetinolTransported byGc-globulin or vitamin D binding protein(VDBP, 80–90%); albumin (10–20%)¹²1:1:1 molar association with retinolbindingprotein and transthyretin (95%);retinol:RBP (~4.5%)Unbound vitamin in serum0.02 – 0.5%

SIGHT AND LIFE | VOL. 25 (2) | 2011 VITAMIN D AND INFLAMMATION 4343indicated a considerable inflammatory response. This inflammationwill have also increased the activity of macrophages in bodytissues and the uptake of 25(OH)D by stimulated macrophagescan be considerable. 24“Innate immunity is the body’sfirst line of defenseagainst microbial attack”Innate immunity is the body’s first line of defense againstmicrobial attack. 25(OH)D taken up by stimulated macrophagesand epithelial cells is rapidly converted to 1,25(OH)₂D, whichinduces production of cathelicidin, a potent anti-microbial peptide.4 Innate immunity is also especially important in protectingthe gut, and vitamin D modulates anti-inflammatory Treg cellsand interleukin-10 production. 25 Experimental work has shownthat 1,25(OH)₂D inhibits the development of inflammatory boweldisease in IL-10, knock-out (KO) mice and that vitamin D-receptor-KOmice were hypersensitive to exogenous injections ofbacterial lipo-polysaccharide (LPS), 26 while others have shownthat if such mice are infected with Salmonella there is greaterbacterial burden and mortality than in wild-type mice. 27 Furtherresearch is needed, however, to determine to what extent an upregulationof macrophage activity could explain the changes inplasma 25(OH)D concentrations.It was interesting that the reduction in free 25(OH)D concentrationsslightly increased plasma calcium during the postoperativeperiod, but did not disturb parathyroid hormone (PTH)concentrations. PTH would normally be sensitive to changes inplasma calcium, so the absence of any movement was a reflectionof the minimal changes in calcium as a result of the inflammation.Alterations in fluid balance could also explain theconcentration changes in vitamin D, but the authors assured thereader that any fluids given were to maintain fluid balance andnot expand volumes. Furthermore, they were given over severalhours and therefore would have equilibrated with the entire extravascularfluid volume of ~14 L in an adult. This large volumewould not have significantly altered during the post-operativeperiod and would not, therefore, explain the 40% decrease in25(OH)D concentration.There was no association between plasma 25(OH)D and CRPconcentrations. 1 This is not surprising, since we have observedsimilar effects with other nutrients influenced by inflammation.No doubt there would be a close correlation between 25(OH)Dand CRP if multiple samples were taken over the first 24 hourspost-operatively. However, CRP concentrations will start to fallas soon as the clinical symptoms of the trauma recede. In contrast,25(OH)D concentrations and biomarkers such as retinol,ferritin and many other nutrients remain affected by the inflammationinto the convalescent period. 28 The rise in CRP, as withthe fall in 25(OH)D concentrations, is a product of the inflammatoryresponse but these probably have independent functions.That is, the changes are induced for different reasons as indicatedby CRP starting to fall on Day 4, while the concentration of25(OH)D remained unaltered.“Vitamin D is important for innateimmunity and rapid changes invitamin D metabolites in the plasmaare likely to be part of the innateimmune response”The potential benefit of large changes in 25(OH)DWhat the potential benefit of the large changes in 25(OH)D concentrationsbrought about by trauma is for the patient, is an interestingquestion. The data suggest that not only did total25(OH)D concentrations fall but there were also similar largereductions in the biologically active “free” 25(OH)D. It has to beremembered, however, that the concentration of 25(OH)D inplasma is 1,000-fold higher than 1,25(OH)₂D in plasma 9 and theauthors did not measure this important vitamin D metabolite inthe patients. Furthermore, a fall in the concentration of the VDBPmay have the effect of increasing the concentration of “free”table 4: Free (unbound) concentrations of 25-hydroxy-cholecalciferol (25(OH)D) in maternal and cord serumVitamin D binding-protein mg/L 25(OH)D μg/L Free 25(OH)D ng/LMothers n =30 574 14 0.34Infants n =30 268 8 0.44 #Data shown are means taken from Bouillon et al. 29# Free 25(OH)D concentrations were significantly higher in cord than maternal serum.

44 VITAMIN D AND INFLAMMATION1,25(OH)₂D in target tissues. An example of a low concentrationof VDBP increasing the relative amount of “free” 25(OH)D wasobserved in a study of the VDBP in maternal and cord serum. 29Table 4 shows lower 25(OH)D and VDBP concentrations in thecord compared with maternal blood, although these were associatedwith a substantially higher concentration of “free”25(OH)D.Free 25(OH)D did not increase in the study by Reid, but wedo not know what effect the low VDBP concentrations had on1,25(OH)₂D concentrations in the tissues. Alterations in the1,25(OH)₂D concentration would modify the immune and antiinflammatoryfunctions of vitamin D in spite of, or in partnershipwith, the fall in total 25(OH)D. As discussed above, vitaminD is important for innate immunity and the rapid changes invitamin D metabolites in the plasma are likely to be part of theinnate immune response. However, caution should be used beforespeculating on changes in free vitamin D metabolites. Suchmolecules are small and easily lost in the urine, 9 even though nosignificant changes were reported in glomerular filtration in thestudy of Reid et al. 1The reason for the depression in plasma 25(OH)D concentrationsassociated with inflammation is currently not known.We have suggested above that a fall in VDBP may increase theconcentration of “free” 1,25(OH)₂D in target tissues, but this hasnot yet been shown and more research is needed. Most early featuresin the acute phase response are generally regarded as beneficialactivities to protect the host metabolism from the causeor consequences of infection or trauma. Likewise, comparativeevidence with several other micronutrients similarly affectedby inflammation would suggest that the depression in plasma25(OH)D concentrations may be associated with a protectivefunction, but this remains to be elucidated.Can the effects of acute inflammation on 25(OH)Dbe extrapolated to chronic inflammation?Reid et al argue that it would not be reasonable to extrapolatethe data from their study to the relation between the systemicinflammatory response and plasma 25(OH)D concentrations inchronic disease. They argue that changes in CRP in chronic inflammatoryconditions are likely to be of a lesser magnitude thanthose seen after arthroplasty. 1 However, the changes in 25(OH)Dwere not correlated with CRP in their study and the concentrationsof 25(OH)D remained depressed when CRP was alreadyfalling. That is, we cannot assume that a lesser increase in CRPwould necessarily not be associated with a fall in 25(OH)D concentrations.Earlier work with plasma retinol showed that acuteinflammation was associated with a 40–50% fall in concentration.13,14,30 Where the cause of the fall in retinol was acute stressand recovery was quick, retinol concentrations tended to returnto the pre-existing conditions. However, we have shown in apparentlyhealthy persons living in the community that plasmaretinol can be depressed by 32% (95% CI,12-55%) in personshaving both a moderately raised CRP (>5mg/L) and a raisedchronic acute phase protein, namely α₁-acid glycoprotein (AGP;>1g/L). 31 These are the conditions associated with early convalescence.16 Inflammation is a universal response to trauma. Inthe initial inflammatory response, the body does not distinguishbetween knee arthroplasty and severe pneumonia or any othersevere illness. It responds to the magnitude of the pro-inflammatorycytokine stimulus. It is therefore quite probable that theinitial depression in 25(OH)D is a universal response to inflammation;however, the magnitude and duration of that responsewill vary in relation to the severity of the stimulus.“It is quite probable that the initialdepression in 25(OH)D is a universalresponse to inflammation; however,the magnitude and durationof that response will vary in relationto the severity of the stimulus”The measurement of plasma 25(OH)D concentrations to providean assessment of vitamin D status is widely used and lowconcentrations of 25(OH)D have been shown to be associatedwith a number of chronic diseases, including cancer, diabetes,rheumatoid arthritis, cardiovascular disease and mortality. 3,5,32In fact, other workers may have suspected that sickness predisposedto vitamin D deficiency. Lee and colleagues in Australiareported a high prevalence of hypovitaminosis D in 1,100 patientsadmitted to the intensive care unit and supplementationwith either calcium or vitamin D or both before admission wasnot protective. 33 The authors accepted that limited exposure tosunlight during chronic illness was probably an important factorcausing low 25(OH)D concentrations, but also did not rule outaltered parathyroid metabolism. Acute and chronic disease isaccompanied by an activated acute phase response; thus, theobservation of Reid and colleagues could well suggest that thelow concentrations of 25(OH)D accompanying chronic diseaseare both a product of disease and poor vitamin D status.In considering any chronic disease, it is always very likelythat people with the poorest health will be the ones at risk ofleast exposure to sunlight. Hence, observations that people withthe lowest 25(OH)D concentrations have the greatest risk of cardiovasculardisease (CVD) or diabetes, etc are not surprisingand do not necessarily point to any direct effect of inflammationon vitamin D status. However, there is evidence of inflam-

SIGHT AND LIFE | VOL. 25 (2) | 2011 VITAMIN D AND INFLAMMATION 4545matory activity in people who subsequently develop cancer orcardiovascular disease, five or more years before the diseaseis clinically evident. In the British Regional Heart Study, bloodwas taken from 7,735 healthy middle-aged men and there were660 deaths during an average follow-up period of 9.2 years.The authors reported that low plasma albumin concentrations(a negative acute phase protein) was the principle factor associatedwith mortality from cardiovascular disease and cancer,even when deaths in the first five years were excluded. 34 Similardata was obtained in the Multiple Risk Factor Intervention Trial,when low albumin was associated with cardiovascular deaths6 –10.5 years after the serum was measured. 35 Similar resultswere also obtained from the National Health and Nutrition ExaminationSurvey Epidemiologic Follow-up Study, although theywere expressed differently. In subjects followed up for a medianof 15 years, high albumin (>45 g/L) was associated with a lowerrisk of death from all causes and CVD.The use of albumin versus CRPThese days, the use of albumin to indicate inflammation hasbeen replaced by CRP but, nevertheless, all three studies pointto evidence of inflammation being present in people who wereapparently healthy at the time the blood was taken, but wedo not know how or whether that inflammation will have influencedplasma 25(OH)D concentrations. However, in a veryrecent study of vitamin D and mortality risk in the general population,albumin (positively) and CRP (negatively) were bothcorrelated with plasma 25(OH)D concentrations. 3 In addition,there is another group of subjects who displayed evidence ofmild inflammation as raised CRP concentrations 36,37 and havebeen reported to have poor vitamin D status. 38 Brot and colleagues38 listed a number of studies that showed smokers hadpoor vitamin D status and concluded that the effects of smokingon vitamin D metabolism was not likely to be explainedby other confounding lifestyle variables. Five hundred and tenhealthy peri-menopausal women, of whom 50% were smokers,were found to have similar dietary intakes. If anything, the smokerssunbathed more often than the non-smokers, but serum25(OH)D levels in the smokers were 10% less than in the nonsmokers.There was a significant negative association betweensmoking and serum concentrations of 25(OH)D and 1,25(OH)₂D.Unfortunately, Brot and colleagues did not include indices ofinflammation in their investigations, but it would be importantto measure both acute and chronic markers of inflammation asCRP alone only measures acute inflammation.In fact, a study to examine the possibility that serum 25(OH) Dconcentrations were correlated with CRP or other biomarkers ofsub-clinical vascular injury was reported by Michos and colleagues.39 The authors were investigating whether serum25(OH) D was causally linked to subclinical vascular disease.Serum CRP levels are associated with cardiovascular risk; therefore,the authors speculated that 25(OH)D and CRP would be correlated.They found no correlation between 25(OH)D and CRP orany other marker of vascular disease and concluded that there isno causal relationship between 25(OH)D and CVD risk or, if thereis, it may be mediated through mechanisms other than subclinicalvascular disease severity. However, if low 25(OH)D concentrationsare a product of inflammation with a protective functionin the inflammatory cascade, the concentrations of 25(OH)D seenin a cross-sectional study will be both a product of that clinicalcondition, the pre-sickness concentration of 25(OH)D and thelength of time being ill. We should not necessarily expect to seeany relationship with markers of vascular disease as there aretoo many variables potentially influencing the 25(OH)D concentrationand this will be a general feature of many diseases.“If the depression of plasma 25(OH)Dis a general response to inflammation,what are the consequencesfor vitamin D status in children?”A final point to consider is that, if the effects on plasma25(OH)D are a general response to inflammation, what are theconsequences for vitamin D status in children? The acute depressionin plasma 25(OH)D did not appear to affect concentrationsof PTH in the adults, but would this be the same in thegrowing child? The continued depression in plasma 25(OH)Dconcentrations in the Scottish study is also a point of concern. Itis important to determine if the depression was due to mobilityand environmental factors directly influencing the patients orto something more insidious associated with the inflammation.These points cannot be answered without further studies.Harmful effects of low plasma 25(OH)D concentrationsAlthough I have argued that the fall in plasma 25(OH)D concentrationsassociated with acute inflammation may be a physiologicalresponse by the body to increase “free” plasma 1,25(OH)₂D andbenefit or modulate immune function, it is possible that the concentrationof 25(OH)D may be too low at the outset to produceany benefit from the response. Plasma 25(OH)D concentrationsin critically ill patients admitted to an intensive care unit in Sydney,Australia were found to be inversely correlated with theirdisease severity as assessed by the Simplified Acute PhysiologyScore (SAPS; high scores indicating severe organ dysfunction).Plasma 25(OH)D and age were the only two independent predictorsof SAPS (β=-0.59, P

46 VITAMIN D AND INFLAMMATIONwere 41 (22) nmol/L with 38%

SIGHT AND LIFE | VOL. 25 (2) | 2011 VITAMIN D AND INFLAMMATION 4747production and a decrease in circulating transferrin receptors incancer patients. Eur J Clin Invest 1998; 28:520-527.16. Thurnham DI, Mburu ASW, Mwaniki DL et al. Using plasma acutephaseprotein concentrations to interpret nutritional biomarkersin apparently healthy HIV-1-seropositive Kenyan adults. Brit J Nutr2008; 100:174-182.17. Fleck A, Raines G, Hawker F et al. Increased vascular permeability:a major cause of hypoalbuminaemia in disease and injuries. Lancet1985; i:781-783.18. Baumann H, Gauldie J. The acute phase response. Immunol Today1994; 15:74-80.19. Stephensen CB, Alvarez JO, Kohatsu J et al. Vitamin A is excreted inthe urine during acute infection. Am J Clin Nutr 1994; 60:388-392.20. Rosales FJ, Ritter SJ, Zolfaghari R et al. Effects of acute inflammationon plasma retinol, retinol-binding protein, and its messengerRNA in the liver and kidneys of vitamin A sufficient rats. J Lipid Res1996; 37:962-971.20. Haddad JG. Plasma vitamin D-binding protein (Gc-globulin): Multipletasks. J Steroid Biochem Mol Biol 1995; 53:579-582.20. Binder R, Kress A, Kan G et al. Neutrophil priming by cytokines andvitamin D binding protein (Gc-globulin): impact on C5ª-mediatedchemotaxis, degranulation and respiratory burst. Mol Immunol1999; 36:885-892.20. Sato KA, Gray RW, Lemann JJr. Urinary excretion of 25-hydroxyvitaminD in health and the nephrotic syndrome. J Lab Clin Med 1982;99:325-330.20. Reichel H, Koeffler HP, Bishop JE et al. 25-Hydroxyvitamin D3metabolism by lipopolysaccharide-stimulated normal human macrophages.J Clin Endocrinol Metab 1987; 64:1-9.20. Castellani ML, Shaik-Dasthagirisaheb YB, Tripodi D et al. Interrelationshipbetween vitamins and cytokines in immunity. J Biol RegulHomeost Agents 2010; 24:385-390.20. Froicu M, Cantorna MT. Vitamin D and the vitamin D receptor arecritical for control of the innate immune response to colonic injury.BMC Immunol 2007; 8:Mar 30.20. Wu S, Liao AP, Xia Y et al. Vitamin D receptor negatively regulatesbacterial-stimulated NF-kappaB activity in intestine. Am J Pathol2010; 177:686-697.20. Thurnham DI, Mburu ASW, Mwaniki DL et al. Micronutrients inchildhood and the influence of subclinical inflammation. Proc NutrSoc 2005; 64:502-509.20. Bouillon R, van Baelen H, De Moor P. 25-hydroxyvitamin D and itsbinding protein in maternal and cord serum. Clin Endocrinol Metab1977; 45:679-684.30. Mitra AK, Alvarez JO, Wahed MA et al. Predictors of serum retinol inchildren with shigellosis. Am J Clin Nutr 1998; 68:1088-1094.30. Thurnham DI, McCabe GP, Northrop-Clewes CA et al. Effect of subclinicalinfection on plasma retinol concentrations and assessmentof prevalence of vitamin A deficiency: meta-analysis. Lancet 2003;362:2052-2058.30. Zittermann A, Schleithoff S, Frisch S et al. Circulating calcitriolconcentrations and total mortality. Clin Chem 2009; 55:1163-1170.30. Lee P, Eisman JA, Center JR. Vitamin D deficiency in critically illpatients. N Engl J Med 2009; 360:1912-1914.30. Phillips A, Shaper AG, Whincup PH. Association between serumalbumin and mortality from cardiovascular disease, cancer andother causes. Lancet 1989; ii:1434-1436.30. Kuller LH, Eichner JE, Orchard TJ et al. The relation between serumalbumin levels and risk of coronary heart disease in the MultipleRisk Factor Intervention Trial. Am J Epidemiol 1991; 134:1266-1277.30. Das I. Raised C-reactive protein levels in serum from smokers. ClinChim Acta 1985; 153:9-13.30. Ohsawa M, Okayama A, Nakamura M et al. CRP levels are elevatedin smokers but unrelated to the number of cigarettes and aredecreased by long-term smoking cessation in male smokers.Prev Med 2005; 41:651-656.30. Brot C, Jorgensen NR, Sorensen OH. The influence of smoking onvitamin D status and calcium metabolism. Eur J Clin Nutr 1999;53:920-926.30. Michos ED, Streeten EA, Ryan KA et al. Serum 25-hydroxyvitamind levels are not associated with subclinical vascular disease orC-reactive protein in the old order amish. Calcif Tissue Int 2009;84:195-202.40. Hussey GD, Klein M. A randomized, controlled trial of vitamin A inchildren with severe measles. New Engl J Med 1990; 323:160-164.41. Barclay AJG, Foster A, Sommer A. Vitamin A supplements andmortality related to measles: a randomised clinical trial. B M J 1987;294:294-296.42. Schleithoff S, Zittermann A, Tenderrich G et al. Vitamin Dsupplementation improves cytokine profiles in patients withcongestive heart failure: a double-blind, randomized, placebocontrolledtrial. Am J Clin Nutr 2006; 83:754-759.43. Thraikill KM, Jo CH, Cockrell GE et al. Enhanced excretion ofvitamin D binding protein in type 1 diabetes: a role in vitamin Ddeficiency? J Clin Endocrinol Metab 2011; 96:142-149.44. Mitra AK, Alvarez JO, Stephensen CB. Increased urinary retinol lossin children with severe infections. Lancet 1998; 351:1033-1034.45. Bikle DD, Gee E, Halloran B et al. Assessment of the free fractionof 25-hydroxyvitamin D in serum and its regulation by albuminand the vitamin D-binding protein. Clin Endocrinol Metab 1986;63:954-959.46. Lemire JM, Archer DC, Beck L et al. Immunosuppressive actions of1,25-dihydroxyvitamin D3: preferential inhibition of Th1 functions.J Nutr 1995; 125:1704S-1708S.47. Stephensen CB, Rasooly R, Jiang X et al. Vitamin A enhances invitro Th2 development via retinoid X receptor pathway. J Immunol2002; 168:4495-4503.48. Glasziou PP, Mackerras DEM. Vitamin A supplementation ininfectious diseases: a meta-analysis. B M J 1993; 306:366-370.

48 OPINION 1Opinion 1: Vitamin D Status and TuberculosisHenrik FriisDepartment of Human Nutrition, Faculty of LifeSciences, University of Copenhagen, DenmarkResearch in vitamin D has increased dramatically, mainly dueto the discovery that vitamin D is important not just for bonehealth, but also for a range of body functions, and in terms ofthe risk of chronic and infectious diseases. While some of theresearch is basic science, much is based on observational epidemiology,linking low serum concentrations of 25-hydroxyvitaminD (25(OH)D) to various diseases. Since the validity of mostmarkers of micronutrient status is affected by an acute phaseresponse, the review of the validity of 25(OH)D by Dr Thurnhamin this issue is timely.The main source of vitamin D is sunlight, yet deficiencyseems to be a problem in Asia and Africa, and even in equatorialcountries. 1 The burden of infectious diseases is high in lowincome populations, even among apparently healthy individuals.If, indeed, an acute phase response reduces 25(OH)D independentof vitamin D status, this will lead to an overestimation of theprevalence of deficiency, and probably confound the estimatesof association between 25(OH)D and the various outcomes.Vitamin D and tuberculosisAn area of research that illustrates the implications of poor validityof 25(OH)D in the presence of an acute phase responseis the role of vitamin D for the risk of pulmonary tuberculosis(TB). It is biologically plausible that vitamin D – given its importancefor the immune system – is a determinant of TB. 2 However,most research has been based on case-control studies, inwhich 25(OH)D is determined, as a measure of vitamin D status,in new cases with TB and in controls. Since TB patients have ahuge acute phase response, any negative effect on 25(OH)D will,hence, either lead to overestimation of a true or create a falsenegative association.Not surprisingly, a review of seven studies found that low25(OH)D was associated with the risk of TB. 3 The authors rightlyconclude that there is a need for prospective studies, but arguethat, given the evidence for the role of vitamin D in immunity,the association is likely to be due to an effect of vitamin D deficiencyon risk of TB. But what is the evidence for the opposite?Well, other protein-bound vitamins are affected during the acutephase response, since most proteins behave as negative acutephase proteins. And, as Dr Thurnham points out, not only therecent paper by Reid 4 but also an older study 5 suggest that theacute phase response affects the validity of 25(OH)D as a vitaminD marker. However, several other studies failed to demonstratesuch an effect. 1,6 Yet the absence of evidence is not evidenceof absence, and the issue should have been much betterresearched.So, what is the way forward? Intervention trials are importantbut expensive, and research funding is scarce. Thus, observationalstudies are needed to justify and prioritize trials, andto guide the design. There is a need for a better understandingof vitamin D metabolism, better markers of vitamin D status, andways to adjust for the acute phase response, as has been suggestedfor other nutrients. 7,8 Finally, when vitamin D trials areconducted, this provides an opportunity to study the effects onvarious metabolites that should not be missed.Correspondence: Henrik Friis, Department of Human Nutrition,University of Copenhagen, Rolighedsvej 30, 1958 Frederiksberg C,Denmark E-mail: hfr@life.ku.dk“Observational studiesare needed to justifyand prioritize trials, andto guide the design”References01. Friis H, Range N, Pedersen ML et al. Hypovitaminosis D is commonamong pulmonary tuberculosis patients in Tanzania but is not explainedby the acute phase response. J Nutr 2008;138:2474-2480.02. Liu PT, Stenger S, Tang DH et al. Cutting edge: vitamin D-mediatedhuman antimicrobial activity against Mycobacterium tuberculosisis dependent on the induction of cathelicidin. J Immunol2007;179:2060-2063.

SIGHT AND LIFE | VOL. 25 (2) | 2011 OPINION 1 / 2 494903. Nnoaham KE, Clarke A. Low serum vitamin D levels andtuberculosis: a systematic review and meta-analysis.Int J Epidemiol 2008;37:113-119.04. Reid D, Toole BJ, Knox S et al. The relation between acute changesin the systemic inflammatory response and plasma 25-hydroxyvitaminD concentrations after elective knee arthroplasty.Am J Clin Nutr 2011;93:1006-1011.05. Louw JA, Werbeck A, Louw ME et al. Blood vitamin concentrationsduring the acute-phase response. Crit Care Med 1992;20:934-941.06. Newens K, Filteau S, Tomkins A. Plasma 25-hydroxy-vitamin D doesnot vary over the course of a malarial infection. Trans R Soc TropMed Hyg 2006;100:41-44.07. Thurnham DI, Mburu ASW, Mwaniki DL et al. Using plasmaacute-phase protein concentrations to interpret nutritionalbiomarkers in apparently healthy HIV-1-seropositive Kenyan adults.Br J Nutr 2008;100:174-182.08. Friis H, Range N, Braendgaard Kristensen C et al. Acute-phaseresponse and iron status markers among pulmonary tuberculosispatients: a cross-sectional study in Mwanza, Tanzania.Br J Nutr 2009;102:310-317.Opinion 2: The D-Cline may be Dueto Drug-SXR InteractionMichael F HolickDepartment of Medicine, Section of Endocrinology,Nutrition, and Diabetes, Vitamin D, Skin and BoneResearch Laboratory, Boston University MedicalCenter, Boston, MA, USAThe dramatic 40% decline in serum 25-hydroxy-vitamin D(25(OH)D) levels recently reported by Reid et al 1 within 24 hoursof elective joint replacement surgery has important short- andlong-term consequences, especially during post-operative healingafter surgery. It has been suggested that this 40% decline is,in part, due to the uptake of 25(OH)D by the inflammatory cells.It has been known for more than 100 years that vitamin D deficiencywas associated with increased risk for upper respiratorytract infections, and that sun exposure was effective in helpingto treat patients with tuberculosis. 2The connection between vitamin D and the immune systemis nicely documented by Dr Thurnham. Activated macrophagesafter ingesting an infective agent like a tuberculous bacteriumimmediately begin preparation for its destruction by increasingtranscriptional activity to produce 1,25-dihydroxy-vitamin D(1,25 (OH)₂D), and to enhance its responsiveness to this hormoneby increasing the number of vitamin D receptors (VDR). 3 Once1,25 (OH)₂D is bound to the VDR and retinoic acid X receptor,this complex interacts with the gene that produces the defensenprotein, cathelicidin, which in turn binds to the tubercle, resultingin its demise. Therefore, one explanation for the observationof the marked decrease in circulating levels of 25(OH)D can beattributable to this mechanism.“Another mechanismcould also have adramatic influence onvitamin D statusduring and after surgicalintervention”The role of steroid and xenobiotic receptor (SXR)However, what is not appreciated is another mechanism thatcould also have a dramatic influence on vitamin D status duringand after surgical intervention. The steroid and xenobioticreceptor (SXR) is responsible for destroying foreign substancesthat enter the body. It accomplishes this by increasing theexpression of cytochrome P450 enzymes such as CYP 3A4 andCYP 2C8. It is believed that the association of taking a wide⇢

50 OPINION 2variety of medications, including antiseizure medications, glucocorticoidsand some antibiotics, such as rifampicin, with increasedrisk for developing vitamin D deficiency osteomalaciais due to enhancing the destruction of 25(OH)D and 1,25(OH)₂D.These drugs activate SXR, which enhances the expression of theCYP 3A4 enzyme in the liver and small intestine that hydroxylatesboth 25(OH)D and 1,25(OH)₂D on carbons 23 and 24, leadingto the formation of water soluble inactive metabolites. 4Thus, another explanation for the observation that is oftenoverlooked is that the variety of medications that these patientsreceived prior to, during and after surgery may have activatedthe SXR-CYP3A4 pathway, causing increased catabolism of25(OH)D which, in turn, resulted in the dramatic decrease in theserum 25(OH)D levels that persisted for several months after thesurgery. The message is clear; the serum 25(OH)D is a true reflectionof vitamin D status. These patients should receive vitamin Dbefore any surgical intervention and should then be maintainedon an adequate amount of vitamin D for at least three monthsafter surgery. You can treat vitamin D deficiency with 50,000 IUof vitamin D₂ or vitamin D₃ (the equivalent to taking 6,000 IUof vitamin D a day). To prevent the recurrence of vitamin Ddeficiency, patients can receive 50,000 IU of vitamin D₂ or vitaminD₃ once every two weeks (the equivalent to taking 3,000 IUof vitamin D a day). This is an effective method for treating andpreventing vitamin D deficiency under most circumstances. 5Correspondence: Michael F. Holick, Boston University School ofMedicine, 85 East Newton Street, M-1013, Boston MA 02118, USA.E-mail: mfholick@bu.eduSources of supportThis work was supported in part by the UV Foundation.References01. Reid D, Toole BJ, Knox S et al. The relations between acutechanges in the systematic inflammatory response and plasma25-hydroxyvitamin D concentrations after elective kneearthroplasty. Am J Clin Nut. 2011.02. Holick MF. Resurrection of vitamin D deficiency and rickets.J Clin Invest 2006; 116:2062-207203. Liu PT, Stenger, S, Li, H et al. Toll-like receptor triggering of avitamin D-mediated human antimicrobial response. Sciencexpress2006;3:1770-1773.04. Zhou C, Assem M, Tay JC et al. Steroid and Xenobiotic Receptorand Vitamin D Receptor Crosstalk Mediates CYP24 Expression andDrug-induced Osteomalacia. J Clin Invest 2006;116:1703-12.05. Pietras SM, Obayan BK, Cai MH et al. Vitamin D2 treatment forvitamin D deficiency and insufficiency for up to 6 years. Arch InternMed 2009;169:1806-8.Erratum: Diversification from Agricultureto Nutritionally and Environmentally PromotiveHorticulture in a Dry-Land AreaIn the article Diversification from Agriculture to Nutritionally and EnvironmentallyPromotive Horticulture in a Dry-Land Area in Sight and Life Magazine 25 (1) | 2011,the technical support of N Venaktesham was not acknowledged. We would like totake this opportunity to acknowledge Mr Venaktesham’s technical support withthis project, and apologize for any confusion this error may have caused.

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52 SYSTEMATIC DATA ANALYSIS IN QUALITATIVE HEALTH RESEARCHSystematic Data Analysisin Qualitative Health Research:Building Credibleand Clear FindingsStephen Kodish, Joel GittelsohnJohns Hopkins Bloomberg School of Public Health,Department of International Health, Social &Behavioral Interventions Program & Center forHuman Nutrition, Baltimore, MD, USAOverviewTextual data sets can be intimidating to public health researchersand practitioners who are unfamiliar with qualitative research.The amount of textual data collected from in-depth interviews(IDI), focus group discussions (FGD), and direct observations –three common methods in qualitative research – can be extensiveand can prove challenging to systematically analyze. 1This article outlines one primary approach to qualitativedata analysis (QDA) in health research and discusses the analysisprocess and interpretation, leading to the development of acredible product. It also briefly describes how computer softwarecan assist in both the analysis and display of findingsthrough data graphs, tables, and conceptual models.A dynamic aspect of qualitative inquiry is the variety of approachesthat one can take. The disparate approaches include,but are not limited to, phenomenology, ethnography, or groundedtheory, 2 each of which might utilize a different analytic approachto data. 3 Although there is no one-size-fits-all approach to dataanalysis in qualitative health research, commonalities acrossmethodological approaches do exist and can be represented byan illustrative schemata (Figure 1) developed by Creswell. 3Analysis starts at the bottom of the figure (i.e., during datacollection) and proceeds upward through various stages untila written account is developed that presents the findings.The spiral image highlights the non-linear, iterative nature ofQDA and offers both procedures and examples throughout eachstage of the process, from initial data management to representationof findings. The remainder of this paper will highlightthe three procedural stages at the top of Creswell’s spiral:“Reading, Memoing”, “Describing, Classifying, Interpreting”, and“Representing, Visualizing”.Reading, memoingAn important analytic strategy in QDA is memo writing, or “memoing”,which assists a researcher in making a conceptual bridgefrom raw textual data to abstractions used to explain the phenomenaof interest. 4 It is the process of writing down thoughtsand questions in relation to the text in which the researcher isimmersed. Writing memos is often an intermediate step betweendata collection and coding and, as Charmaz 5 explains, the processof memoing helps to, “catch your thoughts, capture thecomparisons and connections you make, and crystallize questionsand directions you want to pursue.”Describing, classifying, interpretingAfter textual data have been collected, read, and reviewed, aresearcher may begin coding the data in order to reduce theminto meaningful segments for interpretation. Any kind of textualdata can be coded, including memos, field notes, or direct observationnotes. This article focuses on in-depth interview andfocus group discussion data due to their popularity as methodsin the field. Coding is a process of identifying themes – that is,analytic categories – in text and is one of the key elements inQDA. 6,7 Codes, identifiers of themes in the coding process, arethe building blocks for theory or model building and the foundationon which project findings most often rest. 8 One mightdevelop 100 codes for a data set or perhaps just 10. For easeof interpretation and clarity, however, Creswell recommendsutilizing no more than 25–30 categories of information regardlessof the size of the database. 3 Coding can be inductive ordeductive. 9Inductive codingAn inductive coding approach is commonly utilized in an early,exploratory stage of a research project, when the researcher has

SIGHT AND LIFE | VOL. 25 (2) | 2011 SYSTEMATIC DATA ANALYSIS IN QUALITATIVE HEALTH RESEARCH 5353figure 1: Data analysis spiralProceduresaccountExamplesRepresenting,VisualizingMatrix, Trees,PropositionsDescribing,Classifying,InterpretingContext,Categories,ComparisonsReading,MemoingReflecting,Writing Notes,Across QuestionsDataManagingSource: Creswell 3datacollection(text, images)Files, Units,Organizingnot formulated hypotheses, and is based on few (if any) preconceivednotions of the final results. Plans for additional datacollection are frequently the outcome of early coding with thisexploratory approach.Consider, for instance, a qualitative acceptability study of aspecialized food commodity, such as a lipid-based nutrient supplement(LNS), perhaps Nutributter (Nutriset SAS, Malaunay,France). LNS containing energy, protein, essential fatty acids,and micronutrients have been developed to overcome nutrientshortfalls in existing diets of young children 6–24 months. 10 AlthoughNutributter has been accepted by target populationsin some settings, 11 a researcher examining acceptability in anew setting using a qualitative approach might analyze initialqualitative data using open coding; that is, he or she exploresthe textual data line-by-line for conceptualization of “emergent”themes related to beneficiary perceptions of the unfamiliar commodity.3,5 Themes from the data might emerge that are unexpectedto the researcher, for example, unique cultural characteristicsthat directly relate to acceptability. In such a scenario,analysis using inductive coding would be concurrent with datacollection to shape future stages of the research project. Newquestions could be asked or additional methods added based onthose emergent themes.figure 2: Visual representation of the theoryof planned behaviorAttitudeSubjectiveNormsPerceivedBehavioralControlIntentionBehaviorSource: Adapted from 12Deductive codingDeductive coding is oriented towards confirming or testing theinvestigator’s preconceived terms and relationships. It is oftenbased on a researcher’s a prior 4 (a Latin term that refers to priorknowledge about a population) hypotheses and might utilize“prefigured” codes derived from a theoretical model or existingliterature on the topic of interest. 12,13 Using pre-determinedcodes is popular in the health sciences – a field that utilizesmany models to explain health-seeking behavior.As an example, consider the Theory of Planned Behavior (TPB)(Figure 2), which seeks to explain why people perform certainactions 14,15 – for example adhering to daily consumption of Nutributter.A researcher deductively analyzing a textual data setwould apply codes based on the TPB in relation to the majorconstructs of the theory: perceived behavioral control (PBC),

54 SYSTEMATIC DATA ANALYSIS IN QUALITATIVE HEALTH RESEARCHtable 1: Excerpt of a codebook developed for inductive QDA of data collected at Kakuma Refugee Camp, Kenya.Mnemonic or numeric “Brief” Code Full Description of Code When to use/not to use the code2.0 Life in Kakuma Refugee experiences residing in KRC Use this family of codes when the CL or MNP beneficiarydiscusses his or her life as a refugee at KRC.2.1 Hardship Hardships faced while living in Kakuma, related tosecurity, violence, tribalism, etcUse this code for the array of hardships refugeesdiscuss at KRC unrelated to illness experiences.Illness is mentioned a lot but use 2.2.2.2 Illness Illness experiences of the individual or of his or herfamily and/or communityUse this umbrella code for any health-relatedexperience related to life in KRC. It can be relatedto anemia or another illness. Codes 2.2.1 and 2.2.2will be used to distinguish between the typesof illness discussed.2.2.1 Ill. Anemia Experiences with anemia or malnutrition, specifically Use this code for health-related experiences, inparticular those related to anemia and/ormalnutrition. Also, “lack of blood” should be includedin this code as it’s referring to anemia.Source: Adapted from one of the authors’ projectsattitude (ATT), subjective norm (SN), and intention (INT). Whileexamining texts, he or she would specifically look for themes inrelation to those constructs and, perhaps, ignore other topics unrelatedto the theory. Creswell suggests, however, that researcherswho employ this approach to analysis be open to additionalcodes emerging during the analytic process, because using thistable 2: Advantages and disadvantages of using computer software.AdvantagesDisadvantages1. Provides an organized storage file 1. Requires the researcher to learnsystem, especially large data sets how to use the software program,which can be very time consuming2. Helps a researcher locate textual 2. Better programs may bematerial quicklycost prohibitive3. Creates visually informative3. Distances the researcherschemata to illustrate findingsfrom the data4. Provides time-saving functions 4. Makes analysis as a team(eg, quickly can determinechallenging due to logistics behindfrequencies of codes)sharing files5. Allows for coding of not only text, 5. Nascent compared tobut also images and video files quantitative software programs –can be frustrating to work withContent adapted from 3,8 and the authors’ experiencestype of coding scheme may limit the analysis to the “prefigured”codes rather than open up the codes to reflect the views of participantsfrom an emic perspective 3 and, consequently, may limitfindings.Using a codebookIn both deductive and inductive coding, researchers usually developa codebook to assist with the process. The standardizedstructure of a codebook provides a stable frame for the analysisof textual data and can help to establish more stability and guidancewhen coding. 8 Put simply, a codebook is a reference toolthat tells a researcher when to apply what code to a chunk oftext in a transcript. Both the codes themselves and their respectivedefinitional parameters should be included in a codebook.(Table 1) In general, during inductive analysis a researcherdevelops the codebook as part of the coding process, whereasduring deductive analysis the researcher develops the codebookbefore the textual analysis.Representing, visualizingFollowing memoing and coding, researchers present what wasfound during analysis, often in the form of a table, matrix, orchart. A visual representation of findings can be helpful for summarizingand highlighting key findings. For example, a simple2 x 2 table that compares individuals by gender or ethnic groupin terms of one of the themes or categories in the study might beuseful and informative. 6 In public health research, conceptual

SIGHT AND LIFE | VOL. 25 (2) | 2011 SYSTEMATIC DATA ANALYSIS IN QUALITATIVE HEALTH RESEARCH 5555models are commonly used to illustrate relationships betweenthemes, with the purpose of showing how different factors relateto a health-seeking behavior or outcome. Figure 3 is offered asan example. 16 When choosing the most appropriate display offindings, one should consider not only what visual representationmost clearly and completely answers the research question(s),but also the audience for whom the graphics are intended.Using computer softwareComputer software programs are available to help with theanalysis and presentation of textual data. Such programs helpa researcher code and retrieve text, create data matrices, andbuild models of how the themes in a data set are associatedwith each other. 9 As the process used for textual analysis is thesame for hand coding or using a computer, this type of softwaremay be most useful while working with large data sets(eg, more than 500 pages of text 3 ) and an unnecessary burdenwhile working with those smaller. (Table 2) Two popular commercialprograms available include NVivo (Nvivo (Version 9.0).[Computer Software]. Victoria, AU: QSR International Pty Ltd)and Atlas.ti (Atlas.ti (Version 6.1) [Computer Software]. Berlin:Scientific Software Development), both of which can only beused with Windows-based operating systems.Credibility of qualitative research findingsComputer software can help with coding, but it cannot help ensurehigh-quality data or findings. Strategies exist to enhancethe quality in qualitative research, some during data collectionand others during analysis. Creswell points to eight majorstrategies that can be utilized to help ensure the “trustworthiness”of a study and recommends that at least two be used inany given qualitative study. (Table 3) 3 Member checking, peerdebriefing, and investigator triangulation, described in Table 3,are particularly useful tools for enhancing the credibility ofqualitative findings.ConclusionsCreswell’s data analysis spiral offers a good representation ofthe dynamic process that QDA should undergo. It highlights aniterative and systematic approach to data analysis that can helpto ensure credible findings. 17 However, just as is the case whileanalyzing a quantitative data set, one’s findings are only as goodfigure 3: Conceptual model illustrating findings from a diabetes prevention studyParents havediabetesHave carsExerciseEat healthyReturn to traditionallifestyles or focuson healingMay not beable to avoid ifboth parentshave itways to avoidWatch toomuch TV,play videogamesEating toomuch sugaror sweetsThe food weeat nowadays,the wrongkinds of foodDon't exercise,inactivecausesDiabetesAmputation,kidney failure,loss of weight,heart attackways totreatPillsNeedleTraditionalmedicineExerciseDietDeathSource: Adapted from 13

56 SYSTEMATIC DATA ANALYSIS IN QUALITATIVE HEALTH RESEARCHtable 3: Qualitative data validation procedures.Validation ProcedureExplanation1. Prolonged engagement in the field Building trust with participants, learning the culture, and checking for misinformation that stemsfrom distortions introduced by the research team2. Triangulation Making use of multiple and different sources, methods, investigators, and theories for data corroboration3. Peer review An external check of the research process4. Searching for negative cases Refinement of a working hypothesis by an active search for disconfirming evidence5. Clarifying researcher bias Critically reflecting on what the researcher, him or herself, brings to the research project(eg, past experiences, prejudices, etc)6. Member checking Soliciting participants’ views of the credibility of the findings and interpretations during analysis7. Providing a thick description Enables the reader to determine which characteristics, if any, of a program can be transferredto other settings through a detailed description of participants and setting8. External audits When an external consultant examines both the process and product for accuracySource: Adapted from 3as the data that have been collected. Methodological rigor duringdata collection can help make analysis easier and findingsmore credible.Correspondence: Stephen Kodish, MS, Social & BehavioralInterventions Program, Department of International Health,The Johns Hopkins Bloomberg School of Public Health, 615 N.Wolfe St., Baltimore, MD 21205-2130, USAEmail: skodish@jhsph.eduReferences01. Kodish S, Gittelsohn J. Report from the field: Exploringbarriers to micronutrient powder uptake at Kakuma refugee camp.Sight and Life 2010;3:61-63.02. Crotty M. The foundations of social science: meaning andperspective in the research process. Thousand Oaks:Sage Publications, 1998.03. Creswell JW. Qualitative inquiry and research design:choosing among five approaches. 2nd ed. Thousand Oaks:Sage Publications, 2007.04. Birks M, Chapman Y, Francis K. Memoing in qualitativeresearch: probing data and processes. J Res Nurs 2008;13:68-75.05. Charmaz K. Constructing grounded theory: a practicalguide through qualitative analysis. Thousand Oaks:Sage Publications, 2006.06. Miles MB, Huberman AM. Qualitative data analysis. 2nd ed.Thousand Oaks: Sage Publications, 1994.07. Strauss A, Corbin J. Basics of qualitative research: groundedtheory procedures and techniques. Newbury Park: SagePublications, 1990.08. MacQueen KM, McLellan E, Kay K et al. Codebook development forteam-based qualitative analysis. Cult Anthro Meth 1999;10:31-36.09. Bernard, HR. Research methods in anthropology: qualitative andquantitative approaches. 4th ed. Oxford: AltaMira Press, 2006.10. Hess SY, Bado L, Aaron GJ et al. Acceptability of zinc-fortified,lipid-based nutrient supplements (LNS) prepared for the youngchildren in Burkina Faso. Mat Ch Nutr 2010;1-11.11. Adu-Afarquah S, Lartey A, Brown KH et al. Home fortificationof complementary foods with micronutrient supplements is wellaccepted and has positive effects on infant iron status in Ghana.Am J Cl Nutr 2008;87:929-938.12. Crabtree BF, Miller WL. Doing qualitative research. Newbury Park:Sage Publications, 1992.13. Marshall C, Rossman GB. Designing qualitative research. 4th ed.Thousand Oaks: Sage Publications, 2006.14. Ajzen I. Action to control: from cognition to behavior. In: Kuhi J,Beckmann J. eds. From intentions to actions: A theory of plannedbehavior. Heidelberg: Springer, 1985.15. Ajzen I, Madden TJ. Prediction of goal-directed behavior: attitudes,intentions, and perceived behavioral control. J Exp Soc Psych1986;22:453-474.16. Ho LS, Gittelsohn J, Harris SB et al. Development of an integrateddiabetes development program with First Nations in Canada.Hlth Prom Intl 2006;21:88-97.17. Lincoln Y, Guba E. Naturalistic inquiry. New York: Sage, 1985.

Promotingpartnershipsand capacitybuilding.

58 FEIKE SIJBESMA: A VISION OF LIFEFeike SijbesmaA Vision of LifeFeike Sijbesmais the CEO and Chairman of the Managing Boardof Royal DSM NV. He talks about his work at DSM, aswell as his involvement in Sight and Life andin initiatives such as the United Nations World FoodProgramme (WFP).Sight and Life magazine (SAL): DSM has been the sponsor ofSight and Life since 2003. What does this relationship mean toDSM?Feike Sijbesma (FS): It fits completely with DSM’s activities andcompetences in the nutrition field, but also with our responsibilitytowards the world, and so with our values.SAL: DSM entered into a partnership with the WFP in 2007. Whatis the significance of this?FS: I have difficulties with the word “celebrate”. There isn’t muchto celebrate here. We need to conclude that we and the UN andseveral others have already been committed for a long time toaddressing this huge problem. Apparently we aren’t there yet! Inthe last couple of years, the number of people going to bed hungryevery evening has been fluctuating. On top of that another circa2 billion are suffering from so-called hidden hunger (sufficientcarbohydrate intake in combination with a shortage of micronutritients).It should be our concern to reduce that number significantly.DSM’s help has already seen millions of people get abetter diet. If more people from the private sector were to becomeinvolved, with a good deal of help from the public sector,we could improve the situation. Food security remains an importanttopic and we are absolutely not yet done with this.SAL: You have said of DSM that “We cannot be successful, nor canwe call ourselves successful, in a society that fails.” How have DSMemployees responded to this statement?FS: We wanted to further leverage our knowledge and competencesin the nutrition field, even beyond what we have builtwith Sight and Life. We believe we can contribute to makingfood healthier, so that people can grow up healthy and developtheir full potential without developing diseases and abnormalities.Micronutrient deficiencies, if occurring over a longer period,or during infancy and childhood, can have very harmful effectsfor an entire lifetime. We can be of help here! This is why wemake available to the United Nations World Food Programmeour know-how, technologies, expertise, patents, and so on, allto be used by them for free, to the benefit of people who cannottake care of themselves. Besides that, we are involved in developingnew products and product concepts which work for theUN programs (such as MixMe – micronutrient powder sachets,corn/soy-blends, vitamin-enriched NutriRice, datebars, and soforth). Our people are actively involved in all of this. And, finally,we also provide monetary help.SAL: WFP is celebrating the 50 th anniversary of its foundation thisyear, while Sight and Life is celebrating its 25 th anniversary, yetthe scourge of hunger is growing steadily worse. What can be doneto reverse this terrible trend?FS: We live in a global village, so to speak. And as in your ownfamily: if your direct surroundings aren’t OK, you can’t be OK.The world is no different! All the people in DSM are fully behindthe collaboration with the WFP. When the 2008 crisis occurredand we needed to make cost savings, many employees of DSMagreed not to cut any costs on the WFP … and we did not. Wecannot let down people who are hungry. We are continuing ourefforts. For example, around 25 DSM volunteers a year – includingmyself, in Bangladesh and Ethiopia – go into the field, get theexperience for themselves and return and tell stories internally.Many thousands of DSM people are completely energized by thework we do here.SAL: You have traveled extensively in connection with DSM’spartnership with the WFP. What are your most memorable impressions?FS: In both Bangladesh and Ethiopia, I was overwhelmed bythe poverty and the food need. What I found very hopeful wasvisiting the school feeding programs. At school they are learningsomething, which is very important because they can thendevelop their country better than their parents were able to. InEthiopia, I saw the Food for Work program, whereby farmers get

SIGHT AND LIFE | VOL. 25 (2) | 201159“We live in a global village,so to speak. And as in your ownfamily: if your direct surroundingsaren’t OK, you can’t be OK.”Feike Sijbesma, the CEO and Chairman ofthe Managing Board of Royal DSM NV.

60 FEIKE SIJBESMA: A VISION OF LIFEthree years’ free food if they develop the land in the right wayand so have better farm yields thereafter! That’s great.the people of this planet and of the planet itself. I think that wemake important contributions here, which is great.SAL: In 2010 you received the Humanitarian Award of the UnitedNations Association of New York. What did it mean to you?FS: I see this award as being given to everyone in DSM and asrecognition for the effort we all make. Every DSM employee ishelping to change the lives of 200 other people via our partnershipwith WFP. DSM is a big company but, in the relativesetting of the world, we are small – so this shows what companiescan do.SAL: DSM recently launched a new brand with the strap-line BrightScience. Brighter Living. Why did the company decide to rebranditself this year, and what does this strap-line mean?SAL: What do you enjoy most about your work?FS: I’m running a business, a company: and I like doing businessvery much, but at the same time I’m doing something broaderin life, which is a combination I enjoy very much. It’s not onlyabout growing the profits and share price. We perhaps did notinherit this planet in an excellent state from our parents, I agree:we (though not all) live well, but at the same time have the responsibilityto improve it in such a way that our children cancontinue to build on it, too. It’s a kind of stewardship, which Ireally enjoy.SAL: What are your interests outside work?FS: Over the last 10 to 20 years, we have been transforming ourcompany from a bespoke chemical company into a Life Sciencesand Materials Sciences company. This is DSM’s second big transformation– the first one, of course, was from being a coal-miningto a chemicals company. Our divestment process is finished, andnow we wish to grow the company. We are a company that isbased on science and technology. We have Bright Science, makingproducts to make the quality of life better in this world: abrighter living! I think the new strap-line really catches what thecompany does and stands for.SAL: Sight and Life also rebranded itself this year. What is thesignificance of this new style of presentation?FS: Sight and Life started by providing vitamin A to ward off malnutrition-relatedblindness to the displaced populations affectedby the Ethiopian Civil War in the mid-1980s. Over the years, ithas broadened its perspective to cover all kinds of health andnutrition issues. This new style reflects that broadening. It positionsitself as being a little bit more modern, but with a scientificbasis that is still very strong. It reflects the impact it makes onpeople’s Brighter Living.SAL: Besides your responsibilities towards DSM and your supportfor the DSM-WFP partnership, you are a member of various otherinfluential bodies. How do you cope with the stress that must beassociated with so much responsibility?FS: Sometimes there’s a bit of pressure, but it’s also a gift. Nothingis nicer than working for a company, doing business, providingshareholder value, making a profit and, at the same time,taking care that the company, business and all the employeeshave a higher purpose in life and contribute to the well-being ofFS: I am a (not so good) golf player, but while the children areyoung, I am devoting all my time to my wife, my children and myfamily. I do some exercise at least three times a week to keepmyself fit.SAL: Do you have a hero, or someone who you specially admire?FS: There are several people whom I admire for several aspects:journalists, governmental leaders and business leaders. But noone in particular is “my hero”. A book that caught my attentionrecently was something by Parag Khanna, a young US-Indianmanagement guru. He wrote a book entitled How to Run the World,in which he comes to the conclusion that the world’s problemsare so complicated that they can only be solved by governments,businesses and NGOs working together. What we do in the frameworkof the World Economic Forum in Davos, and in the UN withWFP, fits fully into that. I support this philosophy.SAL: Is there anything else that you would like our readers to know?FS: Sight and Life and WFP would not have been possible withoutthe support of our shareholders, customers, scientists, universitycollaborators, NGOs, and all our employees in DSM whogive much in this respect and, of course, to the benefit of societyat large. I would like to thank everyone who contributes to that.Interview by Jonathan Steffen

Sharingknowledgefor improvednutrition.

62ewsThe Carotenoids ResearchInteraction Group (CARIG)ConferenceWashington, DC, 8 April 2011Noel W SolomonsCenter for Studies of Sensory Impairment, Aging andMetabolism (CeSSIAM), Guatemala City, GuatemalaThe 2011 Carotenoids Research Interaction Group (CARIG) Conferencewas held as part of Experimental Biology in the WashingtonConvention Center, Washington, DC, on 8 April 2011. Themeeting was chaired by Sherry Tanumihardjo and co-chairedby Mario Ferruzzi, with some 70 professionals and students inattendance. The central theme of this year’s conference wasCarotenoids in Human Nutrition, focusing on diverse, recent researchinvolving human subjects.A pioneer in the fieldAs has been the custom since 2002, the conference began withthe James Allen Olson Memorial Perspectives on CarotenoidsLecture, this year delivered by Dr Harold Furr on the topic “Isotopedilution assessment of vitamin A status.” This was a fieldthat he pioneered with James Olson, elaborating the first comprehensivemethodology and mathematical calculation for determiningthe total body vitamin A pool using isotopic tracers ofthe vitamin A. This was also a precursor to the introduction ofisotope-labeled carotenoids into human experimentation. Theentire lecture is presented as a feature article elsewhere in thisissue of Sight and Life (see pp 24 – 31).The remainder of the program picked up on the theme of humansurveillance, experimentation or both. Georg Lietz, of NewcastleUniversity in the UK, spoke on the topic of “Physiological consequencesof single nucleotide polymorphisms in the β-carotene15,15’-monoxygenase gene.” The next two presentations camefrom researchers at the University of Wisconsin at Madison.First, Julie Mares spoke on “Lutein and eye health” and ponderedwhether factors affecting uptake of the intact xanthophylls fromthe intestine could explain the inconsistency in the epidemiologicaldata. This was followed by a presentation from Sara Arscott,a collaborator with Phillipe Simon and Sherry Tanumihardjoat Wisconsin, who presented “Colorful carrots: Basic nutritionand functions food.” The final presentation on the program wasgiven by Shellen Goltz of Purdue University on the topic: “Mealtriacylglycerol profiles modulates carotenoid postprandial absorptionin humans.”The CARIG-VARIG ReceptionAt the end of the day, interested students and professionalsgathered in the Renaissance Hotel for the traditional CarotenoidsResearch Interaction Group – Vitamin A Research InteractionGroup (CARIG-VARIG) Reception. Graduate students withfree papers on carotenoid and retinoid research programmed atExperimental Biology 2011 displayed posters to be judged in theannual contest.This year, the outstanding poster prizes were awarded tofour posters. These included: 1. “A daily dosing regimen ofα-retinol supports growth in rats despite its inability to bind toretinol-binding protein” by Napaporn Riabroy of the Universityof Wisconsin, whose advisor is Sherry Tanumihardjo; 2. “Some

SIGHT AND LIFE | VOL. 25 (2) | 2011 THE CAROTENOIDS RESEARCH INTERACTION GROUP CONFERENCE 6363John W Erdman Jr and Amy C Elsen,University of Illinois at Urbana-Champaign, USAα-apocarotenoids function as antagonists of retinoic acid receptorsby directly competing at the ligand site” by AbdulkarimEroglu of the Ohio State University, with Earl Harrison as hismentor; 3. “Laboratory-scale production of tomato carotenoidsusing bioengineered Escherichia coli” by Chi-Hua (Peter) Lu; and4. “CMO-II KO mice display altered lipid metabolism comparedto CMO-I KO and wild-type mice” by Amy Elsen, both of the Universityof Illinois and the laboratory of John Erdman.Next year’s CARIG-related eventswill be held in San Diego, Californiaat Experimental Biology 2012Correspondence:Noel W Solomons , CeSSIAM, 17ª Avenida 16–80, Zona 11,Guatemala City, Guatemala E-mail: cessiam@guate.net.gt

64ewsTackling Iron DeficiencyTACKLING IRON DEFICIENCY AND ANEMIA IN INFANTS AND YOUNG CHILDREN IN MALARIAand Anemia in Infants andYoung Children inMalaria-Endemic AreasKimberly B HardingMicronutrient Initiative, Ottawa, ON, CanadaPatrick E DuffyNational Institutes of Health Laboratory of MalariaImmunology and Vaccinology, Bethesda, USACaitlin Crowley Center for Studiesof Sensory Impairment, Aging and Metabolism,Guatemala City, GuatemalaKathryn G Dewey Department of Nutrition,University of California, Davis, USAAndrew M Prentice London School of Hygieneand Tropical Medicine, London, UKRebecca J Stoltzfus Division of Nutritional Sciences,Cornell University, Ithaca, USAAngus G ScrimgeourMilitary Nutrition Division, USARIEM, Natick, USALynnette M NeufeldMicronutrient Initiative, Ottawa, ON, CanadaThis article briefly summarizes a symposium entitled"Tackling Iron Deficiency and Anemia in Infants andYoung Children in Malaria-Endemic Areas: Moving fromControversy towards Guidance for Safe, Effective andFeasible Policies and Programs," presented at the annualmeeting of the American Society for Nutrition,Experimental Biology, in Washington DC, 9–13 April 2011.Each subsection includes a précis of the original titleand presentation by the respective author.Iron deficiency and control: A call to action and consensusKB HardingFollowing the publication of results from the Pemba trial, whichshowed an increased risk of hospitalization and mortality afteriron supplementation among iron-replete children in a malariaendemicsetting, 1 the World Health Organization (WHO) recommendedthat iron supplementation for young children living inmalaria-endemic areas be targeted to only those who are irondeficientand/or occur in the presence of effective mechanismsto control malaria and other infectious disease. 2,3 There hassince been much debate in the nutrition research communityover how best to address iron deficiency (ID) and anemia inthis context. Some question the feasibility of screening for IDin resource-poor areas which hold the majority of the ID andmalaria burdens. 4“Millions of children in malaria-endemicareas are at risk of anemia, irondeficiency and their consequences”

SIGHT AND LIFE | VOL. 25 (2) | 2011TACKLING IRON DEFICIENCY AND ANEMIA IN INFANTS AND YOUNG CHILDREN IN MALARIA65Five years have passed since the initial WHO response to thePemba trial and, although there are some advances in the understandingof the biology, much debate and little agreement existsamong nutrition experts on the way forward. 4-8 Meanwhile, millionsof children in malaria-endemic areas are at risk of anemia,ID and their consequences, and program developers and policymakers are left with little guidance on how to address theseproblems in their countries. The scientific community plays acritical role in developing policy guidance, and country programdevelopers look to this group to provide advice that is practical,feasible and based on the best available evidence, even whenthat evidence is not yet perfect. The incomplete understandingof risks and benefits of iron supplementation in malarial areaspresents a great challenge to this community.Researchers as well as agencies such as the MicronutrientInitiative have increasingly received requests for country guidanceon iron programming in malaria-affected areas. On a relativelysmall scale, iron programs using micronutrient powdersor lipid-based nutrient supplements are being implemented, forexample in Kenya. 9,10 WHO recommended the same precautionsbe taken with these home fortification products as with iron supplementsbecause, although the former approach may be saferdue to the food base, safety had not been demonstrated. 3Although forums on this important issue have been organizedat recent international meetings, few have addressed programmaticallyrelevant issues that can assist policy makers tomake decisions that maximize the potential benefits and minimizethe potential harm of programs that provide young childrenwith iron. A recent symposium at the American Society forNutrition annual meeting had the objective of exploring optionsfor addressing infant and young child ID and anemia in malariaendemic areas, now, with safe, effective and feasible interventions.This article presents an overview of the proceedings.The global malaria situation:implications for iron deficiency control strategiesPE Duffytable 1: Levels of malaria endemicity (or transmission intensity).Level of endemicityHypoendemic (low) 75%Malaria transmission levels range from low, or hypoendemic, tovery high, or holoendemic (Table 1). 11 The absolute rate of severemalaria is quite stable over a wide range of transmissionintensities, ie lower transmission rates do not necessarily meanlower rates of progressing to severe disease or death. 12 Althoughmajor progress has been made in reducing the disease burdenworldwide, malaria remains a major cause of death and claimedan estimated 780,000 lives in 2009. 13 The majority of malarialdeaths, approximately 90%, occur in Africa. Populations affectedby malaria are also likely affected by anemia and ID, bothbecause malaria is a major cause of anemia and because allthese conditions share many underlying and basic causes. It istherefore not surprising that the region with the highest prevalenceof anemia among children is Africa, where approximatelytwo-thirds of preschool-age children are anemic. 14“The region with the highestprevalence of anemia among childrenis Africa”There is evidence to suggest that ID may protect againstmalaria and death, 15 and that provision of iron may lead to increasedrisk of malaria and death. 1 In general, however, studiesthat show no increased risk of malaria with iron supplementationhave occurred in the context of intense malaria surveillanceand treatment. 1,16,17 With regard to the relationship betweeniron, ID and malaria, there are three important points to consider:1) iron (status or supplementary iron consumption) mayexacerbate malaria, for example by enhancing parasite growthin the liver; 2) both ID and malaria are causes of anemia, makingdisentangling causal pathways extremely difficult; and 3) thereare several other amendable factors that can modify the potentialeffect of iron status or supplementation on malaria risk,including immune status, malaria surveillance and control, andmalaria transmission intensity.Targeted provision of iron:the evolution of a practical screening optionC CrowleyTargeting may present the safest option for iron delivery, butthere are many theoretical and practical issues to be resolvedbefore effective screening prior to provision of iron can be rolledout in the field. Key theoretical considerations include the selectionof indicators (for anemia, iron status or both) and the inherenttradeoffs (eg sensitivity and specificity of the indicators).Ideally, screening should include both iron and anemia status;given the evidence of increased risk of harm, specificity (ie correctlyidentifying and excluding those who are not anemic, not

66 TACKLING IRON DEFICIENCY AND ANEMIA IN INFANTS AND YOUNG CHILDREN IN MALARIAfigure 1: Non-invasive devices used to measure hemoglobin levels in a Guatemalan field setting.The Haemospect® (indicated with the checkmark) showed the most promising sensitivity and specificity profile.iron-deficient or both) should be prioritized in malarial areas.Practical limitations include the application of screening testsin the field in resource-poor settings, and the inherent invasivenessof blood tests.Experience in Guatemala with four applications of three noninvasive(eg body-surface probe photometry or spectrometry) devicesfrom two manufactures to measure hemoglobin levels hasbeen informative. The major advantage of all these approachesis that they do not require the extraction of even capillary bloodsamples, improving the chances of universal acceptability infield settings and eliminating the risks of drawing blood. Of thefour applications illustrated in Figure 1, three required cumbersomefinger-clip sensors, and none of these achieved the requisitediagnostic accuracy. Only the Haemospect® (MBR OpticalSystems, Germany), as applied directly to the skin with a penlikeprobe, showed a promising sensitivity and specificity profile,although sensitivity was compromised at lower cut-off pointsfor anemia.Improvements to current non-invasive methods shouldinclude: 1) the improvement of diagnostic discrimination atlower cut-off points (particularly important for children andpregnant women); 2) the development of more robust and fieldfriendlydevices; and 3) the adaptation of applications to andtesting in children under three years of age, ie those most susceptibleto severe malaria. Currently, non-invasive instrumentsto assess iron status are not available, although efforts are underway to develop this technology using zinc protoporphyrinas an indicator.Universal iron provision throughhome fortification of complementary foodsKG DeweySince the Pemba trial, a more comprehensive approach to improvingnutrition in infants and young children has been recommendedas a programmatic priority, for example focusingefforts on improved complementary feeding as a whole, insteadof iron supplementation alone. Typical complementary foods invulnerable populations, however, are low in many micronutrients,including iron. A number of options to improve iron contentand bioavailability of complementary foods have been explored.These include home fortification products (eg micronutrientpowders or lipid-based nutrient supplements), fortified complementaryfoods, and traditional food processing techniques toenhance iron absorption.

SIGHT AND LIFE | VOL. 25 (2) | 2011 TACKLING IRON DEFICIENCY AND ANEMIA IN INFANTS AND YOUNG CHILDREN IN MALARIA 6767“Part of the complexity ofestimating the risk associated withthe provision of iron through differentproducts is our lack of understandingof the mechanisms underlyingadverse effects”Part of the complexity of estimating the risk associated withthe provision of iron through different products is our lack ofunderstanding of the mechanisms underlying adverse effects.There are currently two dominant hypotheses. 18 The first is thata large bolus of iron triggers a spike in plasma non-transferrinboundiron (NTBI). NTBI may induce cell damage via reactiveoxygen radicals, and the entry of NTBI into the liver may also facilitatethe penetration of hepatocytes by malaria sporozoites.A second hypothesis is that iron stimulates the growth of entericpathogenic organisms, which may impair the innate immuneresponse of the gastrointestinal tract and lead to bacterial invasionthrough the gut into the systemic circulation, causing bacteremiaand septicemia. Iron may influence morbidity by either,both, or perhaps neither of these routes.Home fortification may be the most promising alternative tosupplementation for the universal provision of iron. It is likelyto be safer than supplements given with food, and adequateamounts of iron can be provided, regardless of the amountof complementary foods consumed. A review of findings, forthe purpose of this symposium, from five home fortificationstudies in malarial areas (some not yet published) showed noincreased risk of adverse effects. 19-23 Most of these studies,however, had relatively small sample sizes, so adverse eventscannot be adequately assessed. There is also a lack of informationon the potential modifying effect of initial iron statuson treatment effects. Although the evidence to date suggestshome fortification with iron in malarial areas is safe, more researchis needed.However, it is very challenging, if not impossible, to obtainconclusive evidence on the safety of home fortification inmalaria endemic areas. Adverse events associated with ironconsumption are likely only to be seen where infectious diseasecontrol is lacking, yet it would be unethical in this typeof setting to conduct studies without providing any services tomonitor and treat infectious disease, including malaria. A hugesample size would be required to rule out a modest increase insevere adverse effects. For the moment, the safest option is todeliver home fortificants within the context of comprehensivemalaria control strategies.Research gapsAM PrenticeThe review of the literature related to malaria, screening for IDand anemia and the potential of home fortification and otheralternatives for universal delivery of iron to children, for thepurpose of the symposium, has highlighted a number of importantresearch gaps. Some promising developments in field-levelscreening have been demonstrated, particularly for the noninvasiveassessment of hemoglobin concentration, but these arestill not diagnostically specific for ID. Alternative indicators ofID and anemia have not been explored. For example, hepcidin,the principal regulator of iron homeostasis, could be assessedto indicate need for additional iron; this would require creativeand innovative research and development.The biggest challenge relates to our lack of a clear understandingof the role of iron and ID in infection. Such interactionshave been reported in the literature for decades 24 and somehave hypothesized that ID is a phenotypic adaptation to reducerisks among those chronically exposed to infectious disease. 25At this time, we do not have real evidence to support the hypothesesof the mechanisms underlying iron-malaria interactions. Tofully understand the complex relationship between iron statusand malaria, we should carefully review the malaria parasite lifecycleand how interactions with iron may vary by developmentalstage; we must also carefully review all results from the Pembaand other trials, exploring tendencies across the duration of theintervention and the implications that these may have for theunderlying mechanism(s) of effect.Some new research may also stimulate further discussionsrelated to mechanisms. For example, results from a recentPhD thesis found an increased risk of malaria infection in irondeficientchildren consuming a multi-micronutrient supplementwith no increased risk among those iron-replete at baseline. 26Findings from this study cannot be compared directly with thePemba results because of different interventions and indicatorsof iron status. This does, however, highlight that multiple contextualfactors may influence the associations between micronutrientinterventions and adverse outcomes and the risks ofaltering policy based on single study findings.⇢

68 TACKLING IRON DEFICIENCY AND ANEMIA IN INFANTS AND YOUNG CHILDREN IN MALARIAfigure 2: Regions of special concernIron deficiencyMalariaProgrammatic strategiesRJ StoltzfusPolicy makers often operate with incomplete information, incompleteresearch and competing priorities and timelines. 27 Weknow that providing iron supplements to some children undersome circumstances can increase the risk of severe morbidity,but keeping children iron-deficient as an intervention to decreasemalaria risk is unacceptable. The adverse effects of ID forlong-term child development are well known. 28Inadequate healthcareThe trials addressing the safety of home fortification reviewedin this symposium are somewhat reassuring, but they were notpowered to detect group differences in rare adverse events. Thetypes of studies that would provide definitive answers aboutsafety can no longer be conducted for obvious ethical reasons.Particular attention should be paid to the careful and thoughtfuldesign of research and programs in this context, where access tohealthcare is also limited. (Figure 2)Further research is needed to elucidate the mechanisms behindthe interactions between iron status, supplementary ironand morbidity, and is vital to advance our thinking about safeand effective programs. Following the revised WHO recommendation,the US National Institutes of Health, with funding fromthe Bill and Melinda Gates Foundation, promoted research to explorethe mechanisms responsible for the adverse impact of ironsupplementation. They have formed a technical working groupand have funded a number of research projects relevant to thischallenge.box 1: Programmatic strategies for addressing irondeficiency and anemia among infants and young childrenin malaria-endemic areas.> Adopt a lifecycle, preventative approach to policy andprogram design that avoids provision of relatively high dosesof oral iron to infants and young children> Target iron interventions to those who are most iron-deficientand likely to benefit (targeting can occur at the individualand/or group level)> Coordinate closely with malaria control programs“Viable alternatives existto address ID and three programmaticstrategies to identify them shouldbe adopted”We know little about the biological mechanisms underlying therelationship between iron and malaria, and about which childrenunder what circumstances are most at risk. Despite this uncertainty,viable alternatives exist to address ID and three programmaticstrategies to identify them should be adopted. (Box 1)First, programs should adopt a lifecycle, preventative approach;ID and its consequences begin before infants reach six monthsof age. Ensuring adequate maternal iron status before and duringpregnancy and delayed umbilical cord clamping can promoteadequate reserves for this period. Home fortification and otheralternatives to traditional iron supplements can avoid exposingchildren, as of six months of age, to relatively high doses of oraliron. Second, interventions should be targeted to those childrenwho are most iron-deficient and, therefore, most likely to benefit.Although individual indicators of iron status require furtherdevelopment, multiple level targeting (group and/or individual)could be developed. Finally, nutrition programs should coordinateclosely with malaria control programs. This could also beconsidered a form of targeting, to children least likely to sufferadverse effects, and interventions do exist with unprecedentedcoverage and success.Stopping all iron interventions in malaria-endemic areas is apolicy option, but would leave many children at risk of the adverseeffects of deficiency in those regions. Thoughtful and creative appliedresearch to resolve mechanistic and operational programmaticissues must continue hand in hand with moving forwardwith programmatic strategies. Finally, in the face of uncertainties,deliberations with local stakeholders are essential and willyield a variety of reasonable options for moving forward.

SIGHT AND LIFE | VOL. 25 (2) | 2011 TACKLING IRON DEFICIENCY AND ANEMIA IN INFANTS AND YOUNG CHILDREN IN MALARIA 6969Correspondence: Kimberly Harding, Micronutrient Initiative,180 Elgin Street Suite 1000, Ottawa, ON, K2P 2K3, CanadaE-mail: kharding@miconutrient.orgAcknowledgements: Support for the symposium was providedby the American Society for Nutrition and the US Army MilitaryInfectious Disease Research Program. The authors are grateful toDr Noel Solomons for comments on the draft paper.References01. Sazawal S, Black RE, Ramsan M et al. Effects of routine prophylacticsupplementation with iron and folic acid on admission to hospitaland mortality in preschool children in a high malaria transmissionsetting: community-based, randomised, placebo-controlled trial.Lancet 2006;367:133-43.02. WHO. Iron supplementation of young children in regions wheremalaria transmission is intense and infectious disease highlyprevalent. WHO Statement. 2006. Internet: http://www.who.int/child_adolescent_health/documents/iron_statement/en/index.html(accessed 28 June 2011).03. WHO Secretariat on behalf of the participants to the consultation.Conclusions and recommendations of the WHO Consultation onprevention and control of iron deficiency in infants and youngchildren in malaria-endemic areas. Food Nutr Bull 2007;28:S621-7.04. Stoltzfus R. Commentary: Cochrane Review on oral iron supplementationfor preventing or treating anaemia among children inmalaria-endemic areas. Int J Epidemiol. 2010;39:34-5.05. Suchdev PS, Leeds IL, McFarland DA et al. Is it time to changeguidelines for iron supplementation in malarial areas?J Nutr 2010;140:875-6.06. Ojukwu JU, Okebe JU, Yahav D et al. Oral iron supplementation forpreventing or treating anaemia among children in malaria-endemicareas. Cochrane Database Syst Rev 2009; CD006589.07. Verhoef H, Veenemans J. Safety of iron-fortified foods in malariaendemicareas. Am J Clin Nutr 2009;89:1949-50.08. Roth DE, Black RE, Ojukwu JU et al. Commentary on oral iron supplementationfor preventing or treating anaemia among childrenin malaria-endemic areas with a response from the review authors.Evid Based Child Health 2010;5:1186-8.09. WFP, DSM, UNHCR. Micronutrient powder (MixMe) use inKakuma refugee camp in Kenya. Health 2009;1(3):1-4. Internet:http://www.nutritionimprovement.com/pdf/kenya_briefing.pdf(accessed 29 June 2011).10. Suchdev PS, Ruth L, Obure A et al. Monitoring the marketing,distribution, and use of Sprinkles micronutrient powders in ruralwestern Kenya. Food Nutr Bull 2010;31:S168-78.11. Hay SI, Smith DL, Snow RW. Measuring malaria endemicity fromintense to interrupted transmission. Lancet 2008;8:369-78.12. Snow RW, Marsh K. New insights into the epidemiology of malariarelevant for disease control. Br Med Bull 1998;54:293-30913. WHO. World Malaria Report 2010. Geneva: WHO Press, 2010.14. WHO, CDC. Worldwide prevalence of anaemia 1993–2005: WHOglobal database on anaemia. Geneva: WHO Press, 2008.15. Kabyemela ER, Fried M, Kurtis JD et al. Decreased susceptibility toplasmodium falciparum infection in pregnant women with irondeficiency. J Infect Dis 2008;198:163-6.16. Verhoef H, West CE, Nzyuko SM et al. Intermittent administration ofiron and sulfadoxine-pyrimethamine to control anaemia in Kenyanchildren: a randomised controlled trial. Lancet 2002;360:908-14.17. Mebrahtu T, Stoltzfus RJ, Chwaya HM et al. Low-dose daily ironsupplementation for 12 months does not increase the prevalence ofmalarial infection or density of parasites in young Zanzibarichildren. J Nutr 2004;134:3037-41.18. Hurrell R. Iron and malaria: absorption, efficacy and safety. Int JVitam Nutr Res 2010;80:279-92.19. Adu-Afarwuah S, Lartey A, Brown KH et al. Randomized comparisonof 3 types of micronutrient supplements for home fortificationof complementary foods in Ghana: effects on growth and motordevelopment. Am J Clin Nutr 2007;86:412-20.20. Smuts CM, Dhansay MA, Faber M et al. Efficacy of multiple micronutrientsupplementation for improving anemia, micronutrient status,and growth in South African infants. J Nutr 2005;135:653S-9S.21. Sharieff W, Bhutta Z, Schauer C et al. Micronutrients (includingzinc) reduce diarrhoea in children: The Pakistan SprinklesDiarrhoea Study. Arch Dis Child 2006;91:573-9.22. Suchdev PS, Jung C, Sharma A et al. Sprinkles use not associatedwith morbidity among young children in western Kenya:the Nyando Integrated Child Health and Education Project (NICHE).2009 Micronutrient Forum, Beijing, China. Abstract.23. Zlotkin S, Newton S, Aimone AM. Impact of iron fortification onmalaria incidence in Ghanaian children. FASEB J 2011;25:227.624. Murray MJ, Murray AB, Murray MB et al. The adverse effect of ironrepletion on the course of certain infections. Br Med J 1978;2:1113-5.25. Denic S, Agarwal MM. Nutritional iron deficiency: an evolutionaryperspective. Nutr 2007;23:603-14.26. Veenemans J. Effect of preventive supplementation with zinc andother micronutrients on malaria and diarrhoeal morbidity in Africanchildren [PhD Dissertation]. Netherlands: Wageningen; 201127. Snider DE, Holtgrave DR, Duñet DO. Decision analysis. In: HaddixAC, Teutsch SM, Shaffer et al. eds. Prevention effectiveness:a guide to decision analysis and economic evaluation. Oxford:Oxford University Press, 1996:27-46.28. Lozoff B. Iron deficiency and child development. Food Nutr Bull2007;28:S560-71.

70Reportfrom ThikaProgress at the Macheo Children’s CentreVanessa M OddoTufts University, Boston, MA USAEditor’s note: Vanessa Oddo worked at Macheo Children’sCentre between March 25 and April 9 on behalf of theTufts University and Sight and Life Internship ProgramThika is a low-income, urban town located approximately 40miles northeast of Nairobi, Kenya. Nearly 50% of households inThika District are impoverished and HIV/AIDS affects nearly34% of the population. As a result of infectious disease, undernutritionand poverty, it includes a large orphan population.Macheo Children’s Centre recognizes the disproportionateburden of disease and poverty in Thika and seeks to meet theneeds of its community. Founded in 2005, Macheo is a nongovernmentalorganization whose vision is to “provide thechildren of today with a brighter future.” It runs several childcenteredprojects, with core activities centered around a children’shome and an education program.“Macheo Children’s Centrerecognizes the disproportionateburden of disease and povertyin Thika and seeks to meetthe needs of its community”Child eating porridge at Thika school.Activities and outreachCurrently, Macheo operates a children’s home for 56 orphanchildren where they are provided with regular meals, access toeducation, and housing. At the children’s home, Macheo is activewith infrastructure development. The children have recentlytransitioned into family-style housing where there is a mix ofgender and ages. The office space and number of staff is expanding,and security is being improved.In 2006, Macheo launched an education program in publicprimary schools in Thika. Its primary objective is that all childrenin this impoverished region obtain at least a basic level

SIGHT AND LIFE | VOL. 25 (2) | 2011REPORT FROM THIKA71The porridge provided by Thika school is a valuable source of nutrition for pupils.

72 REPORT FROM THIKAGirls at Thika school going to receive their lunchtime meal.of education by 2015, in line with the second Millennium DevelopmentGoal. Macheo sought to meet this objective with afood-based strategy, whereby primary schools are provided withone meal per day. For orphans and the most vulnerable children,the lunchtime meal is supplemented with porridge. The educationprogram now operates in 18 primary schools and feeds over11,000 students.Program progressMacheo continues to cultivate its core programs while fosteringnew programmatic activities. These include investing resourcesin income-generating, social business and family empowermentprojects in Thika. Macheo will soon be accepting HIV positivechildren into the children’s home setting. They will be doing athorough medical history and will work with the district hospitalto ensure that the children are getting the necessary care. Thenutritional status of the children is also a consideration. Duringthe field visit, anthropometric measurements were used as indicatorsof their nutritional status. Age, height and weight wereused to calculate their BMI-for-age z-score, which were thencompared with WHO standards. While many of the children livingat Macheo were malnourished upon arrival, only three childrenat Macheo had a BMI z-scores at or below negative two. Asa result of the field visit, Macheo is closely monitoring the weightand individual meal plans of all newly admitted children.The next steps for Macheo include improved data collectionpractices and program evaluation. Perhaps most notably, it continuesto seek input from its community to identify gaps in socialservices and health-care and then strives to address those needs.Its strong relationship with the community lends itself to longtermsustainability and success.Correspondence: Vanessa Oddo, Tufts University School ofMedicine, 145 Harrison Avenue Boston, MA 02111, USAE-mail: vanessa.oddo@tufts.eduFor more information on the Macheo Children’s Centreplease contact: Simon Wachieni, Program Manager at MacheoChildren’s Centre operations.macheo@gmail.com

SIGHT AND LIFE | VOL. 25 (2) | 2011 REPORT FROM NAIROBI 7373Reportfrom NairobiProgrammatic Qualitative Research:A New Initiative to Build Capacity for NutritionProgramming Within the DSM-WFP PartnershipStephen Kodish, Joel GittelsohnJohns Hopkins Bloomberg School of Public Health,Baltimore, United StatesAs part of the continuing efforts by Sight and Life to build capacityin nutrition program implementation within the DSM-WFPpartnership, a qualitative research workshop for the introductionof specialized food commodities was held in Nairobi, Kenyafrom 21–25 March 2011. The workshop was implemented incollaboration with Johns Hopkins Bloomberg School of PublicHealth (JHSPH).The World Food Programme (WFP) is increasingly using innovativecommodities such as micronutrient powders (MNP)and lipid-based nutrient supplements (LNS) to improve the nutritionalstatus of vulnerable groups such as women and children.These products are new to most populations, as well as toWFP staff. Hence, the carefully designed, culturally appropriateintroduction of the product to the target population is critical forsuccessful program implementation and to achieve anticipated“Participants gainedtheoretical and practical skills,including the introduction ofqualitative methods in the contextof the RAP manual and an emphasison qualitative data managementand interpretive data analysis innutrition programming”benefits. Qualitative research knowledge and skills for exploringcontextual factors such as traditional medical systems and localhealth-seeking behaviours of the target population are instrumentalin program design and implementation. Most WFP staffhave limited knowledge of how to elicit these types of informationusing qualitative data collection techniques.Qualitative research theory, methods and analysisThe workshop was supported by Sight and Life and facilitatedby Dr Joel Gittelsohn, a professor at JHSPH in the Center for HumanNutrition, and his doctoral advisee Stephen Kodish. Theparticipants comprised WFP international and local nutritionstaff from headquarters, country and regional offices in Africaand Asia, as well as UNHCR staff, and Sight and Life staff. Theworkshop taught participants qualitative research theory, methods,and analysis, both in seminar format and experientially inthe field. One day of the workshop was dedicated to data collectionin Thika, a poor slum area roughly 50 kilometers outside ofNairobi, to practice some of the skills learned. One participantcommented, “The field visit was a very good training on the useof the methodology presented.”Rapid assessment proceduresA key component of the workshop featured the testing and refinementof a Rapid Assessment Procedures (RAP) manual, whichmay be utilized in future DSM-WFP nutrition programming toassist with the culturally appropriate introduction of specialized⇢

74 REPORT FROM NAIROBIfood commodities. The RAP is a tool that aims to quickly gain sufficientunderstanding of a cultural setting from the community’sperspective, in order to make key decisions regarding the designand implementation of effective nutrition programming, using amixed methods approach. Because various data collection methods,such as in-depth interviews, focus group discussions, anddirect observations, are critical to systematic, qualitative workusing the RAP manual, WFP staff were introduced to these methodsand given opportunities to practice both in the classroomand the field. The sentiment after the qualitative training waspositive; one participant reflected that the RAP manual was a“very good method that fits well with the work of WFP.”“I would really like such workshopsto be conducted at least twiceannually to better prepare WFP staffto introduce new products”Overall, the workshop was a successful capacity-building experience.Participants gained both theoretical and practical skills,including not only an introduction to qualitative methods in thecontext of the RAP manual, but also an emphasis on qualitativedata management and interpretive data analysis in nutritionprogramming. As one attendee noted, “I would really like suchworkshops to be conducted at least twice annually to better prepareWFP staff to introduce new products.” Plans are being madeto continue with similar workshops on different continents.Correspondence: Stephen Kodish, MS, Social & BehavioralInterventions Program, Department of International Health,The Johns Hopkins Bloomberg School of Public Health, 615 N.Wolfe St., Baltimore, MD 21205-2130, USAEmail: skodish@jhsph.eduAvailable soon !The new “Manual on Vitamin ADeficiency Disorders (VADD)” bySight and Life Press

Growingthe evidencebase formicronutrients.

76REMEMBERING MICHAEL C LATHAMRememberingMichael C Latham(1928–2011)William GrimesThe New York Times, 13 April 2011 (abridged)Professor Michael C Latham, an expert on international nutritionand tropical health who waged a long campaign againstthe use of infant formula and for the practice of breastfeedingin developing countries, died on 1 April 2011 in Boston atthe age of 82.Michael Latham was born on 6 May 1928, in Kilosa, Tanganyika(now Tanzania). After earning a medical degree from TrinityCollege, Dublin, in 1952, he worked in hospitals in Britainand the United States before returning to Tanganyika to practicemedicine in rural areas. During intermittent leaves, he earneda diploma in tropical public health from the London School ofHygiene and Tropical Medicine in 1958.After leaving Tanzania in 1964, he taught nutrition at Harvard,where he received a degree in public health in 1965. In1968 he was recruited by Cornell as a Professor of InternationalNutrition. He turned the university’s small Program in InternationalNutrition into one of the world’s largest training centersfor nutritionists, many of whom went on to work in internationalagencies and public health departments around the world. Hisresearch led to improved programs on infant nutrition, the controlof parasitic diseases in humans, and the supply of micronutrientsto poor populations.Dr Latham often did consulting work in Africa, Asia andSouth America for organizations such as the World Health Organization,the United Nations Food and Agriculture Organization,UNICEF and the World Bank. He was the author of twoimportant books on international nutrition, Human Nutritionin Tropical Africa (1965) and Human Nutrition in the DevelopingWorld (1997), as well as a family memoir, Kilimanjaro Tales: TheSaga of a Medical Family in Africa (1995).ton Post eloquently covered his life. What we thought would bebetter is a reflection on the man and his impact on our lives.My first contact with Michael was in the highlands of PapuaNew Guinea, in the late 1970s. He, together with the late ProfessorJohn Waterlow, took the time to write and help me in mywork in nutrition, and to encourage me to pursue nutrition at thegraduate level. Michael’s generosity, wisdom, grace and intelligenceexisted long before that time, and were born of his familyand a life that began in Tanganyika.“One of Michael’s greatest qualitieswas his ability to listen”One of Michael’s greatest qualities was his ability to listen.He engaged you when so many would speak at you. He had thisquality of being able to empathize and being willing to speak onbehalf of those who could not speak. So many prominent peoplein our work often have forgotten to listen. Their cause dominatesas they do. Michael consistently humbled himself to the topicand the audience.He was not without controversy. Michael was critical ofthe role of the food and pharmaceutical industry, and was achampion for sensible solutions to malnutrition. His tirelessefforts remind me of the words of William Blake in Auguries ofInnocence:“To see a world in a grain of sand,And a heaven in a wild flower,Hold infinity in the palm of your hand,And eternity in an hour.”Recollections by Bruce CogillFormer Chief of Nutrition, USAID, Washington DC, USAWhen asked to write about Michael Latham’s recent passing, Idid not want to recall him as a chronology of significant eventsthat amounts to a life lived. No doubt, he had a singular, impressivelife. The obituaries in the New York Times and the Washing-⇢

SIGHT AND LIFE | VOL. 25 (2) | 201177“Michael consistentlyserved the international healthand nutrition community,often exceeding expectations,for close to six decades”Michael C Latham (1928 – 2011)

78 REMEMBERING MICHAEL C LATHAMMichael consistently served the international health and nutritioncommunity, often exceeding expectations, for close to sixdecades. In his capacity as physician, public health worker,nutritionist, author and academic, Michael contributed to theachievement of the many ambitious goals in technical fields,policy, programs, information sharing and capacity building inthe USA and internationally. He was one of the pioneers in movinga global public health agenda to one that embraces publichealth nutrition; nowhere is this needed more than in low- andmiddle-income countries where malnutrition continues to affectmillions of women and children. Michael established a technicaland policy foundation that continues to serve us well as we facea future of challenges embodied by financial uncertainty, climatechange, diminishing natural resources and insecurity.Lives saved and enrichedFor countless people throughout the world, his life, his work andhis passion lives on. Not only have lives been saved as a result ofhis work, but also all of our lives have been enriched by his graceand kindness. His love of and dedication to his family, place, studentsand mission was a constant part of his life.One of the last times we spoke was about the promise of anew US President. Michael’s enthusiasm and optimism for anotherWashington politician was truly impressive. He was someonewho had witnessed 10 administrations and was willing tostand on the threshold of another, embracing much needed hope.Here was a son of Africa, sharing dreams with another son ofAfrica. There is an Afghan proverb that states: “There is a pathto the top of even the highest mountain.” Michael C Latham tookthat path and I am grateful that he touched us on the way.Recollections from Victoria QuinnSenior Vice President, Programs, Helen Keller International,New York, USAThe nutrition community across the world has lost a good friendand colleague in Professor Michael Latham. I learned aboutMichael’s death the day it happened, whilst in Dakar this pastApril, working on my laptop looking out the window across thewater and waves. Unexpectedly, an e-mail with this stunninglysad news arrived in my inbox, just like that. In a millisecond, Iwas trying to process what it truly meant, as it seemed so surreal.I spent some time reconstructing the last time I saw Michael,which was in Bangkok at the 2009 International Congress ofNutrition – where he was in full fighting form, energetically challengingthe room of people to think beyond the typically safeboundaries.We can all admire, and thank, Michael for pushing us to questionthe accepted “norm” and strive to do better as nutritionalprofessionals. Michael was never complacent, and may haveshaken some of our community up in recent years with his thinking.But, when all is said and done, we must thank Michael formaking us think, reflect, reassess and do things better to improvethe nutrition and social conditions of those most in need.I can say with all sincerity that I owe my attending Cornell’s Programin International Nutrition to the lure of Michael and hiswork. I will never forget the first department party I went to athis and Lani’s house in Danby, over 30 years ago in 1979, whichwas bursting with people and music from many different countries,along with many other interesting offerings. It remainsfirmly imprinted on my memory forever.On a personal level, Michael’s support to me was especiallykind, as he provided handwritten letters of reference that heposted from his research station in Kwale, Kenya. It was a miraclethat they all arrived safely in my mailbox in Ithaca NY. In sucha way, Michael provided unflagging support to “his” students.He always had the time to talk, and took care of the next generationof nutrition professionals. In time, we all became membersof his huge extended family across the globe. Michael was agracious and warm-hearted man, and I am honored to have hadhim as my friend, professor and colleague.Recollections by Peter HeywoodHonorary Professor of International Health at the Universityof Sydney, AustraliaI arrived at Savage Hall in the spring of 1969 with the aimof studying International Nutrition and was soon sitting inMichael’s office for the first of many meetings over the courseof the next five years. I have many abiding memories of Michael,of which three illustrate the man and his concerns. At that time,the Biafra war was an important concern to many – especially toMichael. Eventually, he was involved in assessing the health andnutrition situation of the region and reporting to senior leadersin the USA. Given Michael’s deep commitment to Africa, this wasobviously of great importance to him and he devoted much timeand effort to it, something that made a great impression on meat the time.My second memory is much more personal. With Michael’s encouragement,I had run for election to the newly created CornellSenate. In the second year of the Senate, I was elected Chairmanof the Senate Executive Committee, a position which demanded alot of time. Several days after my election, I received a note fromMichael asking that I come to see him to discuss my courses forthe next semester. At the meeting, I presented a full course loadfor his approval. In a very “Michael” sort of way, he suggestedthat a full course load and discharging my Senate responsibilitiesrequired more time than I had available. After considerable discussion,he suggested that I halve the course load to make surethat I had enough time for the Senate. In many ways, this singlemeeting characterizes Michael for me – he believed in commitmentto a cause and that required engaging with the world. At

SIGHT AND LIFE | VOLUME 1 /2011 REMEMBERING MICHAEL C LATHAM 7979that time, the Senate embodied the response of the whole Cornellcommunity to the extraordinary events of the Spring of 1969, andif my participation in the Executive Committee required rearrangingmy academic program for that period, he would, as my supervisor,encourage me to do so.Passionate commitment to nutritionMy third memory is about Colombia, where Michael was, at thetime, a major collaborator in a large study of the effect of malnutritionon the behavioral development of children. With strongsupport from Michael, I was lucky enough to do my Master’sfieldwork as part of that project. This illustrated his passionatecommitment to understanding and alleviating the broader developmentaleffects of malnutrition.For me, these three memories illustrate the essence of Michael– his great concern for people and the need to engage with theworld in pursuit of a better life for all; his consistent and enthusiasticencouragement to students; and the sweeping breadth ofhis view about the scope and importance of nutrition.I remember him very fondly and benefited greatly from hisguidance and friendship.Correspondence: Bruce Cogill, E-mail: bcogill@gmail.com“We must thank Michaelfor making us think,reflect, reassess and dothings better to improvethe nutrition and socialconditions of thosemost in need”

80 REMEMBERING PHILIP MUSGROVERememberingPhilip Musgrove(1941–2011)Abridged from article by Chris Fleming,Health Affairs blog, March 22, 2011Health Affairs journal Deputy Editor Philip A Musgrove, 70, aneconomist and leading expert in global health, and a cherishedcolleague, died in a tragic boating accident at Iguazu Falls inArgentina on March 21, 2011.“Words can’t express our shock and grief at the loss of Phil,”said Health Affairs editor-in-chief Susan Dentzer. “His expertisein the economics of global health and development was profound.He was a generous and caring colleague, who always hada moment to help anyone on our team grapple with any economicor statistical issue. We were all the beneficiaries of histalents, wisdom, and friendship, and will miss him utterly.”Health Affairs’ executive editor, Don Metz, added, “Phil’spassing is a terrible loss to his family, the journal, and the healthpolicy community. Phil had deep knowledge of many subjects,but what I’ll remember most is his generous nature and his deepcommitment to improving the lives of others through his work asan economist and editor.”Phil, who lived in Rockville, MD, USA, joined Health Affairsin 2005 as a deputy editor in charge of global health coverage.From 2002 to 2005, he worked as an editor at the Fogarty InternationalCenter of the National Institutes of Health on the DiseaseControl Priorities Project. Prior to that, he was a principaleconomist at the World Bank, from which he retired in 2002. Hewas especially expert in health systems in Latin America, servingfrom 1990 – 92 in the bank’s Technical Department, LatinAmerica and Caribbean Region, and in 1992 – 93 on its WorldDevelopment Report. From early 1996 to mid-1998 he workedin its Resident Mission in Brasilia, Brazil. In 1999 – 2001 he wasseconded by the Bank to the World Health Organization, wherehe worked as editor on the World Health Report 2000 – HealthSystems: Improving Performance.From 1982 to 1990 Musgrove was Advisor in Health Economicsat the Pan American Health Organization (PAHO). Beforejoining PAHO, he was a consultant to the World Bank’s LivingStandards Measurement Study, and before that, from 1966 – 68and again from 1971 – 80, technical coordinator in the ECIELProgram of Joint Studies of Latin American Economic Integrationand a member of the staff of the Brookings Institution. In1977 – 78, he was a Research Associate with Resources for theFuture. He taught full time (as visiting professor) at the Universityof Florida, and part time at Johns Hopkins University’sSchool of Advanced International Studies, George WashingtonUniversity, and American University.Phil also lectured at numerous Latin American universitiesand research institutions. His many publications range from ConsumerBehavior in Latin America; The General Theory of Gerrymanderingto Public and Private Roles in Health: Theory and FinancingPatterns, in addition to more than 50 articles in economics andhealth journals and chapters in 20 books. He also edited andco-authored numerous publications.Phil received a PhD in economics from Massachusetts Instituteof Technology in 1974, following studies at Haverford College(BA, mathematics, 1962) and Princeton University (MPA,public affairs, 1964).“Phil had deep knowledge of manysubjects, but what I’ll remember mostis his generous nature and hisdeep commitment to improving thelives of others through his work as aneconomist and editor”

SIGHT AND LIFE | VOL. 25 (2) | 201181“Phil’s passing is a terribleloss to his family,the journal, and the healthpolicy community”Philip C Musgrove (1941 – 2011)

82 WHAT'S NEW010amineThis was the headline of the on-line edition of The EastThe worst affected country appears to be Somalia, whereAfrican on 10 July 2011. The picture was, once again, one that estimates are that 2.85 million people (a third of the population)are now in humanitarian crisis and in need of urgentwe have come to know – a desperately thin woman cradlingan even more desperately thin and lifeless-looking child. The assistance. This is an increase of 42.5% on the figure givenimages of famine always stir up emotions of shock and horror,as did the warning from the USAID-funded Famine Early estimates that around US$ 477 million is needed to addresssome six months ago. The World Food Programme (WFP)Warning Systems Network (Fews Net), which describedhunger needs in the region through to the end of the year.this famine as one of the world’s most severe food security Currently, it has a 40% shortfall in funding, with aboutemergencies. As drought, high food and fuel prices and conflicttake their toll, the lives of at least 10 million peopleUS$ 190 million still needed.in the Horn of Africa are threatened. There will be a growingneed for special fortified food products to help protect You can visit www.wfp.org or become a Facebook friend of thechildren against malnutrition.WFP to keep up to date with the latest developments.0United Nations Standing Committee on NutritionN) Quarterly Newsletter:02n Information in Crisis Situations (NICS)02of 2011: Tragedy Looms in the HornJust before the new crisis hit, the UNSCN Newsletter on NutritionInformation in Crisis Situations (available at www.unscn. and nutrition security situation is in already challengedThe information highlights just how fragile the global foodorg) was released. This quarterly publication provides updates regions and countries – and how quickly it can change. Thison the current situation and who is being affected in crisis is a must read for anyone working in Africa, Asia and thesituations across Africa (the most vulnerable continent), Asia Caribbean; you can also join the UNSCN e-group on Nutritionand the Caribbean, as well as giving information on public and Climate Change.nutrition and mortality rates. It notes that Africa’s majoreconomic sectors are particularly at risk of climate change andthat the existing developmental challenges are exacerbating Did you know?its vulnerability. In Asia, future climate change is likely toAccording to the global assessment report on Disaster Riskaffect agriculture, increase the risk of hunger, and increase the Reduction, the number of reported natural disasters hasscarcity of water, with enhanced climate variability and more more than doubled in the last decade, from approximatelyrapid melting of glaciers. In the Caribbean, Haiti has the highestvulnerability index to cyclones and is particularly sensitive Disaster Reduction 2009).200 to over 400 a year (UN International Strategy forto the adverse effects associated with climate change.

SIGHT AND LIFE | VOL. 25 (2) | 2011WHAT'S NEW83030ing Improved Nutrition –03s Food Aid Quality Review Reportproducts; exploring ways to reduce phytates and researchnew packaging to support more effective targeting andshelf life.2. Upgrade the vitamin and mineral mixes that are used, anddiversify approaches to addressing micronutrient needs,such as developing micronutrient powders and other pointof-usefortification options.3. Develop or adopt non-cereal-based (eg lipid-based) productsfor the management of nutritional deficiencies offeringvarying quantities and types of nutrients for differentprogrammatic contexts.4. Provide clearer programming guidance to enable implementersto match products to specific consumption andnutrition goals; address specific issues such as HIV/AIDSand home preparation of new products; and invest morein behavior change communication and programming thatsupports global infant and young child feeding principles.5. Establish an inter-agency committee to oversee all governmentinterests in the food aid agenda.For almost two centuries, the United States has been deliveringfood aid to vulnerable people in dire need. However, 6. Enhance processes along the product value chain. Thisfood aid is now at a crossroads. USAID recently undertook a acknowledges the need for effective interaction with thereview of both the formulations and specifications of food aid private sector to bring industry best practice to bear onproducts, together with the nature of programming and the food aid supply, food safety and quality assurance, and theprocesses from procurement through to delivery, as part of an need for public-private partnerships to promote producteffort to improve their quality as priorities and needs evolve. innovations.The report found that, although remarkable achievements 7. Strengthen the evidence base for innovations in products,have been made in terms of impact in often challengingprogramming approaches, and institutional processes.emergency settings, there is scope for improvement along theentire food aid chain. One lesson that everyone now accepts All of these recommendations should be taken to heart notis that the needs of food aid beneficiaries are not homogeneous;there is no one food product that can meet every kind of ing in providing not only food aid but also nutrition interven-only by USAID, but by any organization or government work-programming goal, nor is there one programming approach tions, especially as scaling up nutrition interventions is beingthat fits all needs. A salient point that nutritionists often encouraged towards the single goal of increasing food andforget is that “Combinations of foods are always more appropriateto the needs of beneficiaries than are combinations of hunger.nutrition security around the world and finally conqueringnutrients in a single food.”The report includes a number of valuable decisiontrees in the annexure and highlights seven specificrecommendations:1. Improve the formulation of existing Fortified Blended Food(FBF) products. This includes improving sources of proteinby adding whey protein; the development of new forms ofYou can visit http://www.usaid.gov/press/releases/2011/DeliveringImprovedNutrition.pdfto download the full report.

84 WHAT'S NEW0404G povertyCountdown – 2011 Report Availableand child mortality. The world is still on track toreach the poverty reduction target. In fact, by 2015 it isexpected that the global poverty rate will have fallen below15%, which is well under the 23% target. Moreover, targetedinterventions have succeeded in reducing child mortality,with nearly 12,000 fewer children dying each day. Successfulimmunization-against-measles programs are leading the wayand represent one quarter of the decline in mortality fromall causes among children under the age of five.Sadly, nutrition lags behind. Despite some decreases,underweight remains a major problem, especially in SouthernAsia. Children living in rural areas of developing regions aretwice as likely to be underweight as their urban counterparts.The report lists four factors that still play a key role in underweight:the lack of quality food; suboptimal feeding practices;repeated attacks of infectious diseases; and pervasiveundernutrition. The nutrition lag is recognized, and the reportstates: “Nutrition must be given higher priority in nationalIt seems that, in the foreword to the MDG 2011 report, the annualmantra of UN Secretary-General Ban Ki-moon is that, de-simple, cost-effective measures delivered at key stages of thedevelopment if the MDGs are to be achieved. A number ofspite the progress that has been made, we still have a long way life cycle, particularly from conception to two years after birth,to go. This year, the report highlights how much still has to could greatly reduce undernutrition.” This is in direct supportbe done in terms of empowering women and girls; promoting of the Scaling Up Nutrition (SUN) and 1,000 Days movements,and should spur the nutrition community not only tosustainable development; and protecting the most vulnerablefrom the devastating effects of multiple crises, whether conflicts,natural disasters or volatility in prices of food and energy. involved in the scaling up of the interventions that are knowncontinue to raise its voice but also, more importantly, to getBan Ki-moon states, “Progress tends to bypass those who are to have the greatest impact: improved maternal nutrition andlowest on the economic ladder or are otherwise disadvantaged care; breastfeeding within one hour of birth; exclusive breastfeedingfor the first six months of life; and timely, adequate,because of their sex, age, disability or ethnicity.”safe, and appropriate complementary feeding and micronutrientintake between six and 24 months of age.The good news centers around the fact that:> Many of the poorest countries have made the greatestIt is concerning to note that the proportion of people instrides in education, with sub-Saharan Africa being the the developing world who went hungry in 2005 – 2007region with the best record of improvement.remained stable, at 16%, despite significant reductions in> Investments in preventing and treating HIV, TB and malaria extreme poverty. This makes it unlikely that we will meet theare yielding results. New HIV infections are declininghunger reduction target in many regions of the developingsteadily (again led by sub-Saharan Africa) and worldwide world. The disconnect between poverty reduction and thedeaths attributed to TB have fallen by more than one third persistence of hunger has brought renewed attention to thesince 1990 and those caused by malaria have beenmechanisms governing access to food in the developingreduced by 20%.world, and will undoubtedly be one of the main focuses of> Every region has made progress in improving access to attention in the coming year.clean drinking water.There is also good news when it comes to the MDGs thatresonate most directly within the nutrition community –You can visit http://www.un.org/millenniumgoals/11_MDG%20Report_EN.pdf to download the full report.

SIGHT AND LIFE | VOL. 25 (2) | 2011WHAT'S NEW85Did you know?At the close of the World Health Assembly (WHA) 2011in May, 16 countries announced new commitments to dramaticallyreduce maternal, newborn and child mortality,as part of the Global Strategy for Women’s and Children’sHealth. New commitments were announced by Burundi,Chad, the Central African Republic, Comoros, Guinea,Kyrgyzstan, the Lao People’s Democratic Republic,Madagascar, Mongolia, Myanmar, Papua New Guinea,Sao Tome and Principe, Senegal, Tajikistan, Togoand Vietnam.050ging Agriculture for Improving Nutrition– IFPRI February 201105althtime together to find ways for all of us to do even more: moreto improve agricultural productivity, more to connect farmersto markets, more to increase access to nutritious crops andhealth-care, and more to support the women who are growingfood and caring for children around the world.”Although the challenges ahead for each sector are enormous,individually and jointly, the gains to be made in facingthem, creatively addressing them and ensuring ongoinginteraction, far outweigh the risks. Just as direct nutritioninterventions are the key to addressing global nutrition andhealth problems, in the long term the best way to conquermalnutrition is to also promote a nutrition sensitive growthstrategy. Such a strategy could, among other factors, increasedemand for and access to nutritious foods all along the valuechain; mitigate the health and nutrition risks associated withagriculture; breed more nutritious varieties of the staple foodcrops that are consumed by poor people; and promote thediversification of agriculture into nutritious and high valueNew Delhi, India saw some 1,000 delegates from across the products, such as dairy, the products of horticulture, and fish.agriculture, nutrition and health world in 65 countries come The words of Dr David Nabarro, Special Representative oftogether at a two-day forum. The forum was designed to the UN Secretary-General on Food Security and Nutrition andencourage thinking through interactions between agriculture, the Chair of the SUN movement, were sobering, and shouldnutrition and health, and to consider ways to exploit them to drive us to do things differently: “We’ve got nearly a billionimprove human nutrition and health. The meeting allowed for hungry people now, and we’ve got to prepare for feedingnetworking, brainstorming and collaboration across sectors, 9 billion by 2050 …”and also offered opportunities for a number of additionalside meetings.What makes this event exciting is that we are seeing the For more informationbeginning of the breaking down of the silos in which theIFPRI have made available the complete video coverage,three sectors have traditionally worked, and where they have conference papers and briefs, and slide presentations of theonly rarely worked together to reach their common goal of meeting at http://2020conference.ifpri.infoimproving human well-being. In her broadcast speech, USSecretary of State Hilary Clinton said, “I urge you to use your

86 WHAT'S NEWDid you know?In 2007, one third of the world’s workers wereemployed in agriculture; however, despite the size of itsworkforce, agricultural production accounts for less than5% of the gross world product (an aggregate ofall gross domestic products).060at the Bigger Picture – DFID Paperfor Cash Transfers06videnceWhile the evidence base for cash transfers is better than formany other policy areas, it is also uneven and less is knownabout some instruments (public works) and outcomes in certainregions (such as sub-Saharan Africa). The good news isthat there is convincing evidence from a number of countriesthat cash transfers can reduce inequality and the depth orseverity of poverty. In Brazil, for example, a combination ofcash transfer programs accounted for 28% of the total fall inthe Gini index (a summary measure of inequality) between1995 and 2004. There is also robust evidence that cashtransfers have leveraged sizeable gains in access to health andeducation services, as measured by increases in school enrolment(particularly for girls) and the use of health services(particularly preventative health, and health monitoring forchildren and pregnant women). They also have a proven rolein terms of supporting specific vulnerable groups, such aspeople living with HIV and AIDS, or orphans and vulnerablechildren. Effects are typically larger in lower income countriesCash transfers have become a talking point. Can they offer with lower baseline levels.a possible strategy that benefits food and nutrition security All this points in the right direction, yet transfers have hadamongst the poorest and most vulnerable? The UK Departmentfor International Development (DFID) has released tion. Cash transfers can help the poor overcome demand-sideless success in improving final outcomes in health or educa-a comprehensive paper that looks at the multiple forms of (cost) barriers to schooling or healthcare, but they cannotthe impact of cash transfers, based on the current global resolve supply-side problems with service delivery (eg teacherexperience.performance, or the training of public health professionals).The concept was pioneered in Latin America and isCash transfers therefore need to be complemented by strategiesto improve service quality. Nutrition may be an exception:increasingly gaining popularity as an instrument for socialprotection, where resources are transferred directly to poor Households receiving transfers spend more on food, resultingin significant gains in children’s weight and height inpeople rather than through the state, in order to reducepoverty and increase resilience. These “transfers” may take several countries. Where the main recipients are women, asthe form of cash transfers, in kind transfers (eg food), vouchers,or free or subsidized access to goods or services (egto increase their role in household spending decisions andin Mexico’s Oportunidades, cash transfers have often helpedexemption from health service user fees).promote more balanced gender relations. Cash transfers can

SIGHT AND LIFE | VOL. 25 (2) | 2011WHAT'S NEW87tion status of young children, by increasing breastfeedingrates and improving complementary feeding.The guide is based on the latest scientific evidence,lessons learned, reviews and best practices, and presentsthe “hows” of programming at all levels. It also pulls togetherall the important documents and guidelines that have beenissued on the topic. Sections include advocacy, partnershipsand coordination; situation assessment; developing a nationaland comprehensive IYCF policy and strategies; costing strategies;prioritizing interventions and mobilizing resources. Itclearly defines the regulatory actions required, together withbroader health service requirements, community level actionsand specific needs in special circumstances, such as HIV andemergencies. A highlight of the document is the excellentannexure, which details the resources, tools and useful websitesavailable.The conclusion is clear. Success in increasing optimalinfant and young child feeding practices is based on commitmentto implementing comprehensive, evidence-based,Given the significant focus on the importance of the first1,000 Days in reaching the MDGs, UNICEF recently launched at-scale programming, tailored to the local context. So, fora timely document, entitled “Infant and Young Child Feeding(IYCF) Programming Guide.” Evidence is growing that new guide is without doubt the most comprehensive singlethose who are committed to an evidence-based approach, thesupports improved feeding practices for infants and young reference on IYCF programming to date. The good news is thatchildren as a key component of child survival, growth and UNICEF intends periodically to review and update the guide,development programs. In the Executive Summary, UNICEF in the hope that this resource will remain the seminal referencewhen planning programs or interventions at anotes that: “The importance of breastfeeding as the preventiveintervention with potentially the single largest impact on time when IYCF is clearly under the spotlight.reducing child mortality has been highlighted. In addition,of the available nutrition interventions, improvement ofcomplementary feeding has been shown to be most effective The document is not yet on the UNICEF website,to improve child growth, and thereby, together with maternal but is available for downloading at:nutrition interventions, to contribute to reducing stunting.” http://oneresponse.info/GlobalClusters/Nutrition/This document has therefore been prepared in response to publicdocuments/Final%20IYCF%20prog%20guide%20requests from countries to assist with designing appropriate May%2026%202011.pdfstrategies to accelerate progress towards improving the nutrisupportgirls’ education and their access to health-care andother basic social services.As with any intervention, there are numerous factors thatinfluence the success or failure of a cash transfer system. Thus,long term sustainability, monitoring and evaluation, togetherwith ascertaining if they offer value for money, is crucial.For more information on DFIDThe full paper is available through the DFID website,www.dfid.gov.uk070F Launches InfantChild Feeding Resource07ung

88 WHAT'S NEWMaternal, Infant and Young Child Nutrition(MIYCN) Working Group Paper: Using the Code ofMarketing of Breast-Milk Substitutes to Guideketing of Complementary Foods to ProtectFeeding Practices08Infant08With infant and young child nutrition under the globalspotlight, this working paper by a sub-group of the “Maternal,Infant and Young Child Nutrition Working Group of the 10Year Strategy to Reduce Vitamin and Mineral Deficiencies” isimportant. The WHO Global Strategy on IYCF recognizes thatthe complementary feeding period is critical, and that infantsare particularly vulnerable during this transition period. Italso recognizes the need for “adequate complementary foodsthat provide sufficient energy, protein and micronutrients tomeet a growing child’s nutritional needs.”Consequently, and in line with the 1,000 Days windowof opportunity and call for partnership – bringing togethergovernments, the private sector and civil society organizationsto promote targeted action and investment to improvenutrition for mothers and children during this crucial time –commercialized complementary foods and supplements havegained attention and investment. The working group felt thatsome guidance was needed, even if it was preliminary andincomplete, in order to determine how the International Codeof Marketing of Breast-milk Substitutes applies to the marketingof commercialized complementary foods and supplementsto ensure that optimal breastfeeding practices are protectedand promoted. The document is extensive and practical(giving do’s and don’ts and best practice advice). It is valuableat a time when no official guidance is available to privatesector companies which are already moving ahead to developand market complementary foods and supplements.A copy of the working paper is included as a supplementto this edition of Sight and Life magazine; it is also availableelectronically from the GAIN website – www.gainhealth.org –under Reports and Publications, a subsection of Mediaand Resources.It is important to note that, subsequent to the developmentof this working paper, the World Health Assembly(WHA) passed Resolution 63.23 in May 2010. This urgesmember states “To end inappropriate promotion of food forinfants and young children and to ensure that nutrition andhealth claims shall not be permitted for foods for infantsand young children, except where specifically provided for,in relevant Codex Alimentarius standards or national legislation.”This means that the issue of the prohibition of nutritionand health claims has not been dealt with in the paperbut it is hoped that the WHO will give guidance as to whatconstitutes “appropriate” and “inappropriate” marketing ofcomplementary foods and supplements at the WHA meetingin May 2012.You can visit http://www.gainhealth.org/sites/default/files/working%20paper%203LR_with_insert.pdfto download the full report.

SIGHT AND LIFE | VOL. 25 (2) | 2011WHAT'S NEW890Fat in the Crucial 1,000 DAYS: Ensuring Adequacyntial Dietary Fats for Mothers and YoungLow- and Middle-Income Countries09n in09asA one-day meeting hosted by the International Union ofthe research shows that the conversion of ALA to DHA isNutritional Sciences (IUNS), The Home Fortification Technical poor and certain micronutrients are important. Turning the scienceinto programs, interventions which resulted in improvedAdvisory Group, GAIN and Unilever was held in Washington DCin early April. Speakers from Bolivia, Ghana, Malawi, Mexico, n-3 intake (including the fortification of products for consumptionby pregnant women or infants and young children) haveSouth Africa, India, Europe and the US addressed the importanceof essential polyunsaturated fatty acids (PUFAs), nutrientsthat are often neglected, for optimal growth, enhancedbeen successful.immunity and neurobehavioral development.Some examples include:Optimal omega-3 (n-3) PUFA intake is associated with reductionsin prematurity; improvements in gestational age; birth shown to have a high acceptance among infants and young> Lipid-based nutrient supplements (LNS), which have beenweight; birth length; and, in some groups, enhanced post-natal children as well as their caregivers and positive growth outcomeshave been observed in children consuming LNS;growth and development. The n-3 fatty acid supplementation oflactating mothers of preterm infants improves infant neurodevelopmentalperformance, as does supplementation of infant sociated with increases in birth length and placental weight> LNS given to pregnant women in Burkina Faso has been as-formula with docosahexaenoic acid, n-3 (DHA) and arachidonic in malnourished women;acid, n-6 (ARA) for sub-groups of preterm infants. The impact > Supplemental DHA given to lactating women increasedof DHA and ARA on the neurodevelopment of full term infants breast-milk DHA concentration and, subsequently, intake byhas been less studied, particularly in developing countries.infants;Although few studies have assessed PUFA intake and its > Fortified full-fat soy flour developed by the China Center forstatus in developing countries, the available data suggest that Disease Control and Prevention and DSM has had positivemany women and children are at risk of insufficient intake. impacts on anemia, growth and IQ.Both n-3 and n-6 fatty acids are important, and adequateintakes of both these classes of fatty acids need to be ensured. The meeting also looked at the role that can be played by agriculturein increasing the availability of n-3 PUFA; how healthEven when total fat intakes are adequate, intake of essentialPUFA α-linolenic acid (ALA, n-3) and linoleic acid (LA, n-3) programs need to encourage an increased intake; and whatand, particularly, of long-chain polyunsaturated fatty acids the private sector can do to develop new products, improve(LC-PUFA) derived from ALA, eicosapentaenoic acid (EPA, n-3) shelf life, expand the distribution of products containing n-3and DHA may be inadequate in some populations. In particular, PUFA and use their marketing expertise in developing behaviorthis may be an issue for n-3 PUFA intakes, given the fact that change communications that address not only the needs butcommonly consumed vegetable oils are good sources of n-6 also the wants of consumer beneficiaries.PUFA in many developing and emerging countries. However, There is no doubt that the role of essential PUFAs has beenin situations where total fat intake is low, interventions should neglected and needs more consideration as new innovationsaim to increase the intake of both n-6 and n-3 PUFA in a ratio come to the fore, in order to address the spectrum of nutrientof 5 to 15. Food availability and intake data in many developingcountries suggest that diets are often limited in n-3 PUFA.deficiencies impacting on low- and middle-income countries.Increasing intake is possible through foods that are rich inn-3 PUFA: animal products (especially fatty saltwater fish,Did you know? The 1,000 Days movement has abreast milk and eggs), soy, canola oil, some nuts/seeds (chiawebsite, www.thousanddays.org, where you can signseeds, walnuts and soy beans) and pastes and spreads madeup to receive updates on activities and events.with soy oil or full fat soy flour. It is important to note thatsupplementation with ALA alone is unlikely to be the solution,

90 WHAT'S NEW101the Momentum – Stakeholders UniteSupport of Scaling-Up Nutrition (SUN)10nueAt the 1,000 Days to Change a Life event, which was organizedby the US and Irish governments in September 2010, CEO General for Food Security and Nutrition; and a conversationDavid Nabarro, Special Representative of the UN SecretaryofConcern Worldwide Tom Arnold and President of Bread for style session between David Beckmann and Robert B Zoellick,the World David Beckmann committed to a follow-up meeting President of the World Bank. In addition, Hillary Rodhamin June 2011.Clinton, US Secretary of State; Andrew Mitchell, UK SecretaryOver 150 government officials (including 35 from developingcountries), donors, and representatives from civil society, Co-Chair of the Bill & Melinda Gates Foundation,of State for International Development; and Melinda French,academia and the private sector who are dedicated to ending prepared video addresses for the meeting.child and maternal undernutrition took part in a meeting in The morning session included a moderated panel discussionfeaturing representatives from partner nations and civilWashington DC on 13 June 2011. This unique gathering of keystakeholders and drivers of the SUN movement made a united society groups. The afternoon session consisted of four concurrentworking groups. These focused on advocacy and com-call for action, and conveyed the urgency and passion for sustainedcommitment to scaling up nutrition efforts. This served munications; capacity-building; implementation of SUN at aas a voice for civil society’s efforts to maintain and build on country level; and linkages with other sectors, such as health,the political momentum behind 1,000 Days, and to ensure agriculture and education. The working groups were a centralaction going forward. It is expected that a Civil Society Statementendorsing its commitment to SUN will soon be released. for participants to share their experiences and convey theirand fundamental part of the meeting since they set aside timeThe high level of international and developed countryperspectives on a variety of issues as SUN progresses.commitment to SUN and 1,000 Days was clearly illustratedthrough the active participation of the keynote speakers,including Maria Otero, US Under Secretary of State for Democracyand Global Affairs; Kevin Farrell, Irish Hunger Envoy;All presentations from the meeting are available atwww.bread.org/meetingMore information you can find onQuestions and answers s on SUN http//www.scalingupnutrition.orgAs the SUN movement continues to grow and gain momentum,the six Task Teams under the Transition Team led byDr David Nabarro, as the UN Secretary-General’s Special Advisoron Food Security and Nutrition, are hard at work ensuringnot only that the SUN shines, but also that it shines brightlyaround the world and leads to scaled-up actions and interventionsin countries that change the lives of the poorest andmost vulnerable.What is Scaling Up Nutrition?Scaling Up Nutrition (SUN) is a global movement to improvematernal and child nutrition during the critical window ofopportunity between pregnancy and age two. SUN is not anew institution, initiative or financial mechanism. Instead,the movement brings organizations across sectors togetherto support national plans to scale up nutrition, by helping toensure that financial and technical resources are accessible,coordinated, predictable and ready to go to scale. The SUNmovement focuses on promoting the implementation ofevidenced-based nutrition interventions, as well as integratingnutrition goals into broader efforts in critical sectors suchas health, social protection, development and agriculture.Who are the main investors in SUN?The main investors in SUN are national governments themselves.Successful, sustainable efforts to improve nutrition

SIGHT AND LIFE | VOL. 25 (2) | 2011WHAT'S NEW91must be anchored at a national level, with national level officialsowning and leading tailored efforts to address malnutrition.The SUN movement is built through the engagementof nations that are affected by undernutrition. At the centerof the movement is national level leadership that coordinatesboth national and international efforts, with the SUN movementcommitted to aligning financial and technical supportwith these country plans.What are the SUN Framework and Roadmap?The foundation for the SUN movement is the SUN Framework,which outlines core priorities, elements and actions necessaryto address malnutrition. The SUN Framework is not aprescriptive plan; rather, it is a foundational structure fromwhich national plans can be built and tailored. The SUN Roadmapserves to move the Framework into action, providing theprinciples and direction for increased support for countriesas they scale up nutrition efforts across a range of sectors.The SUN Roadmap encourages a coherent approach amongstnational leaders and stakeholders to promoting coordinatedactions and increasing the effectiveness of efforts.Who supports SUN?SUN is a global movement that brings together broad constituenciesof stakeholders in a partnership with shared vision,goals and the priority of initiating action to address malnutrition.The movement’s strategic direction is currently providedby a Transition Team of cross-sector, multi-partner leadersfrom developing and developed countries, CSOs, NGOs, thebusiness sector, academia and the United Nations System.A Transition Team, informed by an interim CountryPartner Reference Group of focal points from countries scalingup nutrition, along with a UN Reference Group, provides thetechnical expertise and tools to support efforts at a nationallevel. The Transition Team is organized into six task forces,each focusing on specific key elements of SUN in order toestablish a foundation for the movement by mobilizing thesupport of relevant stakeholders, developing useful resourcesand ensuring SUN sustainability. The task forces are workingto develop in-country capabilities; strengthen the engagementof civil society, development partners and the privatesector; monitor progress; and support effective communicationsand advocacy activities.2011 Commonwealth Health Ministers Meeting:Sight and Life Co-Hosts Round Table onting Non-Communicable Diseases inand Young People11en11The theme for the 2011 Commonwealth Health Ministersmeeting in Geneva in May was “NCDs – A priority for the Commonwealth.”It is well recognized that the developing worldfaces a harsh reality where nutritional deficiencies, mainlyin the form of micronutrient deficiency, are now also beingassociated with increased vulnerability to non-communicablediseases (NCD) such as heart disease, diabetes and cancerlater in life. This has led to many economically developingregions suffering from a double burden of disease. Togetherwith the Commonwealth Health Professions Alliance,Sight and Life co-hosted a half-day meeting on the day beforethe Commonwealth Health Ministers Meeting. In the firstsession, the meeting looked at healthy living and NCDs,including topics such as the role of physical activity, tobaccoand alcohol use and dental health, while the second sessionfocused on the role of nutrition.The nutrition session opened with an address byDr Anna Lartey, Associate Professor in the Department ofNutrition and Food Science at the University of Ghana⇢

92 WHAT'S NEWand President Elect of the IUNS, who spoke on “Early nutritionand adult non-communicable diseases: A vital link thatmust be broken.” She articulately introduced the conceptof early nutritional influences on NCDs and the 1,000 Dayswindow of opportunity. Dr Jee Huyn Rah of Sight and Lifepresented a paper jointly developed with Dr Parul Christian ofJohns Hopkins Bloomberg School of Public Health on “Linkingmicronutrient deficiencies of mother and child to long-termhealth consequences.” This highlighted the importance ofaddressing maternal health in the context of the ultimatepossibility of preventing NCDs in their children. Drs Sonia andJeff Sachs gave a joint presentation, via video link, onthe need for a holistic, lifecycle approach to addressing chronicdiseases, based on the Millennium Villages experience.The meeting clearly highlighted to delegates from around theworld the need to ensure that nutrition, especially inearly life, is considered central when examining thestrategies to prevent NCDs.Did you know?The Commonwealth is a voluntary association of54 countries that support each other and work togethertowards shared goals in democracy and development.The world’s largest and smallest, richest and poorestcountries make up the Commonwealth. Membercountries span six continents and oceans, from Africa(19) to Asia (8), the Americas (2), the Caribbean (12),Europe (3) and the South Pacific (10). The Commonwealthis home to two billion of the world’s citizens.1World Health Organization launches electronic12of Evidence for Nutrition Actions (eLENA)12ugust 2011Women and children are particularly important targets fornutrition interventions, as more than a third of child deathshave been attributed to maternal and child undernutrition.Effective and safe interventions aimed at addressing maternaland child undernutrition and survival need to be scaled-up inmany countries.Under the leadership of Dr Francesco Branca, Director ofthe Department of Nutrition for Health and Development, incollaboration with internal departments in the World HealthOrganization (WHO) with a vested interest in nutrition, nutritionguidelines are being developed and updated to helpmember states and partners in their efforts to make informeddecisions on the appropriate nutrition actions to improvenutrition of their population and achieve the MillenniumDevelopment Goals (MDGs) – in particular, the eradication ofpoverty and hunger (MDG 1), the reduction of child mortality(MDG 4) and the improvement of maternal health (MDG 5).Nutrition-related guidelines and recommendationsThe WHO electronic Library of Nutrition Actions (eLENA)aims to compile and display WHO guidelines and recommendationsrelated to nutrition, along with complementarydocuments such as Cochrane systematic reviews and otherevidence that informed the guidelines, biological and behavioralrationales, invited commentaries on recent systematicreviews and their applicability prepared by public healthexperts, and additional resources produced by member statesand global partners. The eLENA will, therefore, serve asan easily accessible web-based tool for policy makers, healthworkers, international organizations, bilateral agencies,non-governmental organizations, academicians and otherinterested actors to access the most up-to-date WHO guidanceon nutrition, as well as the information that has led tothe development of these recommendations.The content of potential nutrition interventions profiledwithin eLENA includes not only the most current WHO nutritionguidelines, but also the scientific evidence on whichthe guidelines were developed and based. This includes linksto the Cochrane Library through a collaboration agreementwith John Wiley and Sons Inc. The Cochrane Library is acollection of databases that contain high-quality, independentevidence to inform healthcare decisionmaking. Cochrane Reviews represent the highest level ofevidence on which to base clinical treatment decisions.

SIGHT AND LIFE | VOL. 25 (2) | 2011WHAT'S NEW93The six WHO languagesTranslation into the six official WHO languages (Arabic,Chinese, English, French, Russian and Spanish) will also beginin 2012, to facilitate the use of the information containedwithin eLENA and reach the maximum number of potentialusers. Access to information on the implementation of nutritionactions, allowing programmers and project managers tocontribute and retrieve information about different deliveryoptions, is also in the planning stages as a complementaryweb tool. This feature will be implemented in 2013.Former President John Agyekum Kufuor of Ghana andformer President Luiz Inácio Lula da Silva of Brazil are therecipients of the 2011 World Food Prize. Both men are beinghonored for implementing highly successful national policiesto improve food security, as well as for serving as leadersin the international discussion on hunger alleviation. Theawards will be handed over at the 2011 Borlaug Dialogue inDes Moines, Iowa on 13 October 2011.Advocate for improved agricultureFormer President Kufuor has been a vocal supporter of antihungerinitiatives both within his home country of Ghana andinternationally. Although 60% of Ghana’s population wasinvolved in agriculture when President Kufuor entered office,many rural Ghanaians were food insecure, and Ghana washeavily dependent on imports to meet the domestic demandfor food. During former President Kufuor’s two terms in office,the policies that his administration enacted helped to reducehunger levels from approximately 34% of the populationto 9%, making Ghana the first sub-Saharan African nation toachieve MDG 1.Former President Kufuor implemented a nationwideschool feeding program, and helped pass a number of policiesto modernize the Ghanaian agricultural sector; create incentivesfor the private sector to invest in agriculture; providesubsidized inputs, such as pesticides and fertilizers; andensure that farmers received higher returns for their crops.These initiatives boosted agricultural yields in Ghanaand greatly improved domestic food security. As ChaireLENAis now available on the WHO web site:http://www.who.int/elenaThis project receives financial support from MicronutrientInitiative, the International Micronutrient MalnutritionPrevention and Control Program at the Centers for DiseaseControl and Prevention (CDC), the Government of Luxembourg,and The Bill and Melinda Gates Foundation. Technicalsupport is being received from international experts,partners and collaborators.1The World Food Prize 2011:n – One from Africa and One from– are Honored13merica13person of the African Union and Global Ambassador againstHunger for the UN World Food Programme, former PresidentKufuor advocated for long-term agricultural investments andchild nutrition initiatives on an international level.Defender of the right to foodFormer President Lula made food security a priority in hisadministration by enacting a series of laws and policies thatensured that all Brazilians had access to sufficient, nutritiousfood. When President Lula was elected in 2002, nearly halfof all Brazilians lived in extreme poverty. Just five years afterhis term began, Brazil announced that they had achievedMDG 1 and had successfully halved the number of hungrythrough the right-to-food approach.The central program of former President Lula’s campaignagainst malnutrition was Fome Zero (Zero Hunger), an initiativethat sought to reduce hunger levels through a varietyof programs, such as subsidized produce markets; low-costrestaurants that served subsidized meals; and conditionalcash transfers for families that vaccinated their childrenand sent them to school. The government also expanded theschool lunch program; created incentives for companies to⇢

94 WHAT'S NEWprovide meals for low-income employees; and re-formed theNational Council of Food and Nutritional Security (CONSEA).CONSEA is an advisory body that monitors hunger and malnutrition,and reports its findings to the President and the Braziliangovernment. Brazil is also one of several countries to havelegally established the right to food for all of its citizens.Did you know?Blog 4 Global Health http://blog4globalhealth.wordpress.com/is an interactive blog from the Global HealthCouncil’s Policy, Research and Advocacy team. It coversblogs on 19 different health topics, including climatechange, maternal and child health and HIV/AIDS.This news is taken from“The Hunger and Undernutrition Blog” at http://www.hungerundernutrition.org/blog/,which aims to promote an informeddialogue, serve as a resource for those in the field, and empowerpeople at all levels to do what they can to make undernutritionandnutrition-related deaths and diseases things of the past.14Nominations:The Second Rainer Gross PrizeInnovations in Nutrition and Health14ntAt a point in global nutrition where innovative thinking and The first ever award of this biannual prize went to Aaron Lechtigof Peru and Angela Cespedes of Panama at the II WCPHNinnovation is a vital component of addressing the pressingproblems of food and nutrition security, the recognition of the in Oporto in September 2010.merits of those who generate innovative ideas and projectsin nutrition and health in developing countries is to beapplauded. The Rainer Gross Prize of the Hildegard Grunow Detailed information on both rules and instructions forFoundation is awarded for accomplishment in international applications for the award can be found atnutrition, in the spirit and memory of Dr Rainer Gross,http://www.hgrunowfoundation.org/rainer-gross-awardformer director of the Division of Nutrition of UNICEF.The awardee will be selected from applicants whodescribe the merits of their recent work (within the last fiveyears) making needy communities at nutritional risk andfellow professionals aware of problems that were previouslyunrecognized, while beginning to open pathways to theirpractical solution. The award includes US$2,500 in cash, atrip to the World Public Health Nutrition Congress for a lectureand awards ceremony, and the publication of their talk asa brief communication in the Food and Nutrition Bulletin.

SIGHT AND LIFE | VOL. 25 (2) | 2011WHAT'S NEW9515nd Life Co-Organizes UkrainianWorkshop15ritionProud participants with their training certificates at the Ukrainian Malnutrition WorkshopUkraine has 55 orphanages for 7,000 disabled children andadolescents aged 4 to 35 years which come under the umbrellaof the Ministry of Social Affairs. In level 3 – 4 orphanages forchildren with moderate and severe disabilities, a number ofchildren suffer from severe malnutrition. Ukraine also lacksknowledge and expertise in the field of malnutrition.The first ever workshop on malnutrition took place in Kyiv(Kiev) on 22 – 24 March, entitled “Malnutrition in children withdisabilities in level 3 – 4 internats: clinical signs and symptoms,treatment and prevention” and “Paediatric Nutrition Update.”Distinguished speakersJointly organized by the Ministry of Social Affairs of Ukraine,Sight and Life and the National Assembly of the Disabled ofUkraine and co-sponsored by the Early Nutrition Academy, theworkshop was attended by 32 representatives, including doctorsand nurses from 25 regions of Ukraine who work in level3 – 4 orphanages for children with disabilities.Following a welcome speech by Ihor Lushnikov, the DeputyMinister of Labor and Social Affairs of Ukraine, it featured inputfrom a range of distinguished speakers. These included HansBiesalski, director of the Institute of Organic Chemistry andNutrition, Stuttgart, Germany; Berthold Koletzko, directorof the Children’s Hospital, Munich, Germany; neurologist andpediatrician Tetyana Mishchuk, from the Children’s RehabilitationCenter Dzherelo, Lviv, Ukraine; Roksolana Tymiak-Lonchyna, founder of the “Starving for Color” foundation;Vassyl Lonchyna, director, Surgery and Intensive Care Unit,John H Stroger Hospital of Cook County, Chicago, USA; MarkFishbein, pediatric gastroenterologist at the Children’s MemorialHospital, Chicago, USA; Klaus Kraemer of Sight and Life,Basel, Switzerland; and Lesya Kalandyak, physiotherapist,the Children’s Rehabilitation Center Dzherelo, Lviv, Ukraine.

96Editor’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 fromus, nor do we have any privileged access to them.From One to Many:Scaling Up HealthPrograms in Low IncomeCountriestake-home message from the book is that concomitance ofcommunity acceptability, stake of local and national governments,and buy-in of local politicians and private entities areall key ingredients for success in community interventions.The case studies are a reminder of the importance of effectiveengagement of stakeholders to maximize their comparativeadvantage and to locally tailor community interventions.One of the most glaring differences between the commercialand social worlds is the constrained ability of the latter, inrelative terms, to go to scale. Markets, supply chains, andincentives enable consumer goods, many of them non-criticalfor human existence, to be supplied and “demanded” even inthe remotest parts of the world. In the same environment, theinfrastructure, resources, and will to mount thenecessary scale-up of proven and often life-saving technologiesand health interventions are often lacking.Scale-up is, therefore, a central question to most healthinterventions and is the focus of Richard Cash and colleagues’excellent From One to Many. The book, a consolidated outputof a conference on the subject hosted by the developmentorganization BRAC in Bangladesh, identifies scale-up in horizontalterms − expanding coverage of existing interventions.BRAC and Bangladesh were a perfect setting for the discourse.With its motto of “small is beautiful but big is necessary”and its operations spanning about 40,000 schools, 7 millionmicrofinance borrowers, and responsibility for the rolloutof national public health programs, BRAC is the epitomeof what the non-state sector can achieve in terms of outreachcapability.The book has done an impressive job of using casestudies to draw attention to strategies and factors commonto successfully scaled-up programs. The importance ofsystems, institutions, and organizations with strong deliverycapabilities has been reiterated throughout. A powerful policyReviewed bySania Nishtar, The Lancet, Volume 377, Issue 9770,19 March 2011 [abridged]For more information, please visitwww.uplbooks.com.bd/

SIGHT AND LIFE | VOL. 25 (2) | 2011PUBLICATIONS97Nutrition, EpigeneticMechanismsand Human DiseaseAs nutrition research is shifting its focus from epidemiologyand physiology to the effects of nutrients at a molecular level,a uniquely tailored diet that corresponds to the demands ofour genetic signature is emerging as an indispensable need.Nutritional genomics uses high-throughput genomic toolsto unravel the influence of micro- and macronutrients aspotent dietary signals regulating metabolic pathways. Nutrigenomicscan unmask how susceptible genotypes are predisposedto diet-related diseases. In the last decade, extensiveresearch on nutrigenomics has unveiled numerous epigeneticmechanisms that are influenced by our dietary signature, andare capable of modifying an individual’s susceptibility to dietrelateddisorders. The primary objective of this volume is toillustrate how nutrition can influence epigenetic inheritanceand the mechanisms that underlie modification of the metabolicimprint of an individual. This enriched understandingof nutrigenomics can then be applied to master a tailored dietthat can alleviate imprinted metabolic syndromes. Specifically,the focus of the book is on three key areas: discussionof the basics of nutrigenomics; epigenetic regulation types ofnutrition influencing the genetic imprinting; and the role ofnutrition in modulating an individual’s predispositionto cancer.The aim of nutrigenomics is to develop dietary interventionstrategies to alleviate diet-related diseases and restorethe body’s normal metabolic homeostasis. Epigenetic mechanismssuch as DNA methylation and transposing insertionhave been shown to play at the nexus between nutrition andthe genetic signature of an individual. Chromatin remodelingacross the genome, mediated via epigenetic mechanisms andtransient nutritional stimuli, can wield persistent changeson the genomic profile that are likely to be passed on to subsequentgenerations. Genomic imprinting refers to a uniquetype of epigenetic regulation, whereby differential modificationof the parental alleles at certain genetic loci in theparental germlines (imprinting control regions) takes placedepending on whether the allele is passed on to the offspringthrough the male or female gamete.For more information, please visitwww.crcpress.comwww.taylorandfrancis.com

98 PUBLICATIONSThe Fight forthe Right to Food:Lessons LearnedOver one billion people are gravely, permanently undernourishedbut, according to the 2008 report on world food insecurityby the Food and Agriculture Organization of the UnitedNations (FAO), world agriculture, in its present state, couldnourish 12 billion people. At the beginning of my mandate asUN Special Rapporteur on the Right to Food, I identified sevenmajor problems which directly affect or prevent the realizationof the right to food: (a) problems linked to developmentsin world trade; (b) external debt servicing and its impact onfood security; (c) developments in biotechnology and theirimpact on access to food; (d) wars and their destructiveimpact on food security; (e) corruption; (f) access to land andcredit; and (g) discrimination against women and its impacton food security.“More people than ever beforesuffer from grave, permanentundernourishment”especially in developing countries that have been requiredto liberalize agriculture to a much greater extent than developedcountries. Only the normative approach can graduallyeliminate hunger and permanent malnutrition in the world.The human right to food has to be implemented by all states,by all intergovernmental organizations and by all non-stateactors, including multinational corporations.Jean Ziegler, Vice President of the UN Human Rights CouncilAdvisory Committee, Former UN Special Rapporteur on the Rightto Food [abridged]For more information, please visitwww.palgrave.comToday, one of the key obstacles to the realization of the rightto food is the schizophrenia in the United Nations system andin states’ policies, which on the one hand support the promotionof the right to food, yet at the same time act to undermineit. The first aspect of this schizophrenia is the existence ofprofound internal contradictions within the internationalcommunity. The second aspect is that many states are not atall coherent as far as their own practices are concerned. Widedisparities in economic power mean that powerful statesnegotiate trade rules that are neither free nor fair. Such rulesseverely affect small farmers and threaten food security,

SIGHT AND LIFE | VOL. 25 (1) | 2011 PUBLICATIONS 99DRI Dietary ReferenceIntakes for Calcium andVitamin DCalcium and vitamin D are essential nutrients long knownfor their role in bone health. Over the last 10 years, the publichas heard conflicting messages about their other benefits– especially those of vitamin D – and also about how muchcalcium and vitamin D they need to be healthy. To helpclarify this, the US and Canadian governments asked the USInstitute of Medicine (IOM) to assess current data on healthoutcomes associated with calcium and vitamin D. A committeeof experts reviewed the evidence and updated the nutrientreference values, or Dietary Reference Intakes (DRIs), used bygovernment agencies and health professionals.The committee provided an exhaustive review of studieson potential health outcomes and found that the evidencesupported a role for these nutrients in bone health, but not inother health conditions.Health effects of vitamin D and calcium intakeThe new reference values are based on much more informationand higher quality studies than were originally available.This thorough review found that the health benefits beyondbone health were not sufficient to be considered for the DRIs.However, a strong body of evidence from rigorous testingsubstantiates the importance of vitamin D and calcium inpromoting bone growth and maintenance.The science indicates that, for example, on average500 milligrams of calcium per day meets the requirements ofchildren aged one through three, while on average 800 milligramsdaily is appropriate for those aged four through eight.Meanwhile, women aged 19 through 50 and men up to 71require on average 800 milligrams daily. Determining intakelevels for vitamin D is somewhat more complicated.Vitamin D levels in the body may come from not only the diet,but also from synthesis in the skin through sunlight exposure.Therefore, the committee assumed minimal sun exposurewhen establishing the DRIs for vitamin D, and determinedthat North Americans need on average 600 InternationalUnits (IUs) of vitamin D per day (up from 200 IU from theprevious DRIs), while people aged 71 and older may requireas much as 800 IU per day.For more information, please visitwww.iom.edu/vitamind

100 PUBLICATIONSDevelopmentand Application ofBiomarkersFirst introduced to biomedical research in 1980, the termbiomarker has taken on a life of its own in recent years andhas come to mean a number of things. In biomedical science,biomarker has evolved to most commonly mean a characteristicthat can be used as either a diagnostic or a prognostic, butmost significantly as a screening indicator for pathologies thattend to be somewhat silent prior to overt clinical display.Applying scientific rigor, as well as a disciplined approachto nomenclature, Roger L Lundblad’s Development andApplication of Biomarkers rationalizes the current enthusiasmfor biomarkers with the use of well-established clinicallaboratory analytes in clinical medicine. Highly respected forhis work as both a classical protein scientist and a pioneerin proteomics, Dr Lundblad catalogs various biomarkersrecognized in clinical medicine and, where possible, matchesthe expectations for advances in screening technologies withthe realities of statistical analysis. More specifically, thisimportant reference work details an extensive list of biomarkersfor various stages of a number of cancer types, includingovarian, pancreatic, prostate, and breast cancer. It also looksat how proteomics is used for the discovery and validation ofbiomarkers, and explores the use of microarray technology,ultra-high performance liquid chromatography, and computationalbioinformatics’ approaches for the discovery and useof biomarkers. In addition, it examines the use of cells andcell fragments as more complex biomarkers, and organizes ahost of significant biomarkers and essential research by typeand use in a series of readily accessible tables.Throughout this volume, Dr Lundblad encourages the considerationof biomarkers more as a concept than as laboratoryanalytes, emphasizing the relationship between the discoveryof a biomarker and the biology underlying its production.Ultimately, it is a thorough understanding of the underlyingbiology that will lead to the development of assays thatare robust and reproducible, as well as clinically significant.For more information, please visitwww.crcpress.com

Advocatingbetter nutritionfor brighterfutures.

102 IMPRINTImprintSight and Life MagazineLayout and graphics:Sight and LifeIncorporating theS1 Studio for Graphic Design,Dr Klaus KraemerXerophthalmia Club BulletinAugsburgDirectorand the Nutriview NewsletterPO Box 2116Printer: Burger Druck,4002 Basel, SwitzerlandPublisher: Sight and LifeWaldkirchPhone: +41 (0) 61 815 8756Carbon-neutral productionEditor: Klaus KraemerFax: +41 (0) 61 815 8190Editorial team:Language services:Email: info@sightandlife.orgJee Rah, Anne-Catherine Frey,transparent, Berlinwww.sightandlife.orgSvenia Sayer-Ruehmann,Jane BadhamOpinions, compilationsISBN 978-3-906412-65-8and figures contained inCommunication consultancythe signed articles doand text writing:not necessarily representThe Corporate Storythe point of view ofSight and Life and aresolely the responsibilityof the authors.Photo creditscover: Mike BloemPhotographypage 17: Mike BloemPhotographypage 66: C Crowleypage 70, 71, 72:Vanessa M Oddopage 77: Cornell Universitypage 81: Musgrove Estate

SIGHT AND LIFE | VOL. 25 (2) | 2011DISCLAIMER 103DisclaimerYou are free to share,including to copy, distributeand transmit the work toremix;adapt the work; andmake commercial use of thework, under the followingconditions. You must attributethe work in the mannerspecified by the authoror licensor (but not in anyway that suggests that theyendorse you or your useof the work).“Attribute this work” meansthat the page you camefrom contained embeddedlicensing metadata, includinghow the creator wishes tobe attributed for re-use. Youcan use the HTML here to citethe work. Doing so will alsoinclude metadata on yourpage, so that others can findthe original work as well.WaiverThis is based on theunderstanding that any ofthe above conditions canbe waived if you obtainpermission from the copyrightholder.Public domainWhere the work or any of itselements are in the publicdomain under the applicablelaw, that status is in no wayaffected by the license.Other rightsIn no way are any of thefollowing rights affected bythe license: your fair dealingor fair use rights, or otherapplicable copyright exceptionsand limitations; theauthor’s moral rights; andthe rights other persons mayhave either in the workitself or in how the work isused, such as publicity orprivacy rights.NoticeFor any reuse or distribution,you must make clear toothers the license termsof this work. The best wayto do this is with a linkto this web page:http://creativecommons.org/licenses/?lang=en

Buildingbridgesfor betternutrition.