SIGHT AND LIFE

Magazine Issue N o 3/2007

End of “Iron age”

WHO consultation: Control of iron deficiency in malaria

Golden Rice

School-based nutrition in Guatemala

Seasoning powders

Vitamin A research update

Behavior change research

Asian Congress of Nutrition

Inside SIGHT AND LIFE

Recent literature

Alumni in Community Eye Health

News

Letters to the editor

Publications Mosquito bite

Did the “iron age” end in Pemba? The dilemma of iron supplementation in malaria-endemic regions

Until 2006, micronutrient supplements in the order of recommended dietary allowance (RDA) dosages, including that for iron, were considered inherently safe. The RDA values for iron for children in this age bracket are based on estimates to cover the requirements for growth and metabolism and to replace iron losses. Please read further on page 6. SIGHT AND LIFE Contents

Hierarchization of school-based nutrition Did the “iron age” end in Pemba? 6 for Guatemalan schoolchildren 23

Contents

Welcome 4 Golden Rice and biofortification 16

Did the “iron age” end in Pemba? 6 Hierarchization of school-based nutrition for Guatemalan schoolchildren 23

Multiple micronutrient-fortified seasoning powders in preschool children in Chongqing suburb 28

Summary of the conclusions of the Recent advances in vitamin A WHO consultation 14 absorption and transport 32

Correspondents

Bruno de Benoist Philip Harvey Alfred Sommer William S. Blaner Richard F. Hurrell David I. Thurnham Martin Bloem Rolf D.W. Klemm Andrew Tomkins George Britton Donald S. McLaren Emorn Wasantwisut Ian Darnton-Hill Regina Moench-Pfanner Keith P. West Jr Omar Dary Christine Northrop-Clewes Yu Xiaodong Frances R. Davidson Noel W. Solomons Chittaranjan S. Yajnik John W. Erdman Jr Florentino S. Solon Michael B. Zimmermann

2 Contents Magazine Issue 3/2007

Multiple micronutrient-fortified seasoning Experiences of SIGHT AND LIFE Alumni in powders in preschool children in Chongqing Community Eye Health at the International suburb 28 Centre for Eye Health 63

Applying behavior change research Experiences of SIGHT AND LIFE to promote micronutrients 38 Alumni in Community Eye Health at the International Centre for 10th Asian Congress of Nutrition 43 Eye Health 63

Inside SIGHT AND LIFE 47 News 68

Recent literature 50 Letters to the editor 73

Publications 75

3 SIGHT AND LIFE Welcome

Welcome Biofuels or biofools ?

The tragic consequences of global warming, such as How “biofoolish” is the use floods, droughts and shortage of clean water, hit the of food crops for biofuel pro - poorest populations of the developing world the hard - duction instead of meeting est. The prognosis for the most vulnerable populations the ever-increasing demand is poor as the increased frequency and severity of these from global food needs? climate-related disasters stretches their resilience and Clearly, the possibility of choking the climate through adaptive capacity to the limits. But climate-related continuing reliance on fossil fuel-based energy humanitarian emergencies are not new, particularly in sources, or of poverty-striken masses starving as food parts of the world that are familiar as sites of major crops fill gas tanks instead of stomachs, are both unde - floods and food insecurity, such as sub-Saharan Africa, sirable outcomes. We all want a world which Nature Bangladesh, etc. defines as tolerable for all life on Earth; we also want to ensure that there is enough nutritious food to eradi - To put this into perspective, however, it must be stated cate global hunger and malnutrition. We have already that there is a clear link between increasing economic declared our commitment to achieving these outcomes growth and social development (as represented by per in the first and the seventh Millennium Development capita GDP, accompanied by improvements in health, Goals. Do we now really stand at a crossroads where such as increased life expectancy and child survival) we must choose one or the other? and increasing carbon dioxide and other greenhouse gas emissions resulting from increased energy con - A closer analysis of the issues reveals more complex sumption. Improved health and increased wealth in relationships between a whole host of factors relating large parts of the world, most markedly in Asia and to food production and use. Critics of biofuels warn Latin America, have literally been fueled by carbon- that large-scale fuel production could divert agricultur - intense operations. In short, development needs al production away from food crops, and result in energy. increased food prices as the increased demand for these commodities outstrip the available capacity to supply Given the centrality of energy needs to human devel - them. However, energy, agricultural and export policy, opment and well-being, one of the major global res- adverse weather, and greater numbers of people mov - ponses to mitigate climate change has been to seek ing out of poverty are also important factors. Recent alternative, low carbon-emitting sources of energy. Of disruptions caused by bad harvests have affected food all the options currently available (solar, wind, hydro, supply far more than the current demand resulting from nuclear, etc.), the candidate that appears most promis - biofuel production. Another significant factor is rising ing as the fastest way to reduce dependency on fossil wealth, particularly in the developing world: the rise of fuel-based energy sources is the class of crop-based per capita income in emerging markets is responsible renewable energy sources known collectively as bio- for as much as one-third of the current food-price infla - fuels. Yet, this potential solution has been fraught with tion. With increasing incomes, households can more controversy as current major sources of biofuels are regularly consume higher-value, micronutrient-rich also major staple food crops (the most controversial foods, such as meat and dairy products. In China, beef being corn, palm and soybean oil) and their use for consumption has risen by 26% since 2000, and pork – energy production could compete with food supply, an already popular meat – has risen by 19%. Even in particularly in poor countries that depend on imports – India, where much of the population is vegetarian, or aid donations – of these commodities. chicken consumption has almost doubled since 2000. Between these two most-populated countries, such per - centage increases represent millions of people.

4 Welcome Magazine Issue 3/2007

Rising demand for biofuels and high fuel prices are Connected to the topic of biofuels and climate change having a dramatic impact on millions of people relying are tropical diseases, such as malaria, which inspired on food aid. The overall cost of the World Food me to use the recent observation in Pemba, Zanzibar on Programme reaching a hungry person has gone up by iron supplementation in malaria-endemic areas as the 50% over the last five years. Biofuel critics also point cover story for this issue of the Magazine (see page 6 to the reduction in the quantity of food aid from the for a commentary and page 14 for a summary of the United States, the largest donor of food aid, to benefi - WHO recommendations). The dilemma of mitigating ciary countries, even as the needs continue to rise. iron deficiency anemia in these areas was also intense - However, reports have suggested that the proportion of ly discussed at the first meeting of the Micronutrient the food aid budget spent on overhead (i.e. shipping) Forum, which took place last April in Istanbul, Turkey. has also increased significantly as a result of rising fuel The theme was “Consequences and Control of prices, meaning less funds for actual food procurement Micronutrient Deficiencies,” and we are pleased to in addition to increased commodity prices. include a supplement on this meeting in this issue of the Magazine. The reporters, particularly Christine Nonetheless, the biofuel rush cannot escape all the crit - Northrop-Clewes and David Thurnham, did a wonder - icism leveled against it. In the near term, while farmers ful job of compiling the results of this high-profile in countries that account for a majority of the world’s meeting. biofuel crop production (i.e. USA, Brazil, Malaysia and Indonesia) will enjoy the promise of markedly Further topics in this issue of the Magazine include higher commodity prices and incomes, the urban and an update on recent developments in Golden Rice rural poor in food-importing countries will pay much (page 16), a study on multiple micronutrient-fortified higher prices for basic food staples and there will be school meals in China (page 28), and a report from a less grain available for humanitarian aid. recent conference organized by ILSI Asia Pacific on consumer behavior and nutrition (page 38). With undernutrition affecting over 800 million people (and hidden hunger affecting about 2 billion people) With best regards, worldwide and the demand for crop commodities expected to exceed supply in the near future, food security will depend as much on technological advances in increasing crop yields and production of micronutrient-rich food as it does on poverty allevia - tion and more equitable food distribution.

5 SIGHT AND LIFE End of iron age

Did the “iron age” end in Pemba?

Klaus Schümann Central Institute for Nutrition and Food Science, Technical University Munich, Freising-Weihenstephan Frank Christ Department of Anaesthesiology, University Hospital Grosshadern, Ludwig Maximilians University, Munich

Correspondence: Klaus Schümann, Central Institute for Nutrition and Food Science, Technical University Munich, Am Forum 5, 85350 Freising-Weihenstephan, Germany Email: [email protected]

The dilemma of iron supplementation in malaria-endemic regions

Until 2006, micronutrient supplements in the order of recommended dietary allowance (RDA) dosages, includ - ing that for iron, were considered inherently safe (1). The RDA values for iron for children in this age bracket are based on estimates to cover the requirements for growth and metabolism and to replace iron losses. The corresponding upper level (UL) for safe dietary intake in children is 40 mg Fe/d (2), based on side effects after oral intake in the form of supplements; this suggests a relatively broad margin of safety for iron in children. In this context, the WHO recommendation to supplement 12.5 mg Fe + 50 µg folic acid when the prevalence of ane - mia exceeded 40% in children 6–36 months of age (3) seemed safe and prudent. This continu- um of assumptions was severely disturbed when an excess number of hospital admissions and deaths occurred in malaria-exposed children during iron supplementation (4). Hemoglobin structure Iron is essential for the malaria pathogen, Plasmodium falciparum , and for its human hosts alike. During their intra-erythrocyte stages plasmodia cannot access the erythro - cytes’ ample heme iron content; for rapid reduplication they depend on adequate non- heme iron supply. As most malaria-endemic areas are located within the tropical iron- deficiency belt, iron supplementation pro - grams performed in these regions are likely to relieve iron-deficiency in the human popula - tion, but also in plasmodium parasites. As reviewed by Oppenheimer (5), two questions emerged regarding iron status and malaria out - comes: Data from a considerable number of Malaria transmission risk areas. studies were conflicting as to whether supple - From WHO-UNICEF World Malaria Report 2005 mental iron is more beneficial for the pathogen or the host, or whether low iron status is

6 End of iron age Magazine Issue 3/2007

protective against the ravages of malaria.

These questions prompted a large trial on the impact of low-dose, daily iron-folate supplementa- tion in infants and toddlers 6–36 months of age on the island of Pemba; this is a region with high malaria transmission rates in the Zanzibari island chain off the coast of Tanzania in East Africa. The carefully designed and well- conducted study compared the impact of routinely supplementing 12.5 mg Fe + 50 µg folic acid/d with or without 10 mg of Zn as compared to placebo in approx. 8000 subjects in each study arm. Mosquito bite The frequency of hospital admis - sion and the prevalence of deaths toporphyrin (with AGP-l/ ␣1-glyco- pital admissions and death of chil - in the course of malaria-attacks protein as inflammatory marker) dren seems to be as ethically unac - were chosen as end-points. The in a subgroup of approx. 1,500 ceptable as it would be to leave statistical power of this study infants in each study arm. More- iron-deficient children to their fate. exceeded the sum of all earlier over, plasmodia parasite density trials on the subject of the inter- and the prevalence of accompany - A parallel trial with a similar action of iron supplementation ing pneumonia and encephalitis design, intervention protocol, and with endemic malaria. Iron status events were registered during magnitude as the Pemba study was was assessed by determination of malaria attacks. Due to increased performed in Nepal (8). In this non- serum ferritin and erythrocyte pro - death rates and significantly higher malarial setting, no increased nor hospital admission rates in the decreased risk for hospital admis - two iron/folic acid-supplemented sion or death was associated with groups, the study was discontinued iron supplementation in infants. after 18 months in the two groups Therefore, the call to revise recom - supplemented with iron and folic mendations in preschool iron sup - acid (4). plementation programs, on the basis of these recent revelations (4, This finding on Pemba Island 8), is primarily restricted to ma- has put iron-supplementation pro- laria-endemic areas. Although the grams in malaria-endemic areas on Nepal trial found no reduced rates the horns of a dilemma: On the one of morbidity or death after iron hand, it has long been discussed supplementation as compared to that iron deficiency predisposes controls, the cited effects of infant infants to excessive infectious iron deficiency on morbidity and morbidity (6). Moreover, iron-de- impaired intellectual development ficiency anemia during the first mentioned above still militates 18 month of life is assumed to strongly in favor of IDA mitigation impair cognitive development irre - programs. versibly (7). All of this strongly argues for intervention programs to Iron-deficient and anemic infants combat iron deficiency anemia and toddlers coexist side by side (IDA) in early life. On the other with iron-sufficient peers in all Map of Pemba hand, a public intervention pro - locations, even where more than gram that risks an increase in hos - 40% of the population is anemic.

7 SIGHT AND LIFE End of iron age

Moreover, some of the endemic anemia in early life When the usual cereal gruels or paps are part of the will be attributable to causes other than iron deficien - weaning culture, liberation of the iron from the iron- cy. The Pemba findings (4) put into relief the poten - phytate complexes comes in as a potentially feasible tially problematic nature of one-size-fits-all solutions strategy to provide greater uptake of iron from tradi - in public health. Many valuable and positive lessons tional grain-based complementary foods (12). The can be derived from the Pemba saga and its aftermath. most basic approaches to phytate reduction involve First, the Data Safety Management Board of the study soaking or germination of the seeds (13). Specific was vigilant, and implemented measures to mitigate low-phytate varieties of grains, such as maize, have subjects’ risk in a timely and transparent manner. The been developed. A substantial increase in iron absorp - overseeing entities appropriately terminated the iron tion efficiency was seen from corn tortillas prepared supplementation arms of the study. from low-phytate maize (14). Fungal phytase prepara - tions, capable of digesting phytate in the dough or Considerations on the folic acid component even within the digestive tract have been developed (15). However, when considering children as young as It is worth bearing in mind that iron was not the only 6 months of age, any exposure to undenatured fungal common factor in the “iron treatment” groups; each allergens should be limited. daily supplement contained also 50 µg of folic acid. It has been suggested that simultaneous administration A final approach to improving iron delivery and to of folic acid may be deleterious, since anti-folate prevent or reverse IDA in infants in malarial areas metabolites are the basis of anti-malarial medications would be the application of oral iron supplements, but used to treat malaria attacks (9). Though this comment with specific precautions to mitigate the adverse con - deals with the safety of iron administration, it should sequences seen in the Pemba experience (4). These be understood that a comprehensive approach to mitigating strategies are detailed in the following malaria prevention requires other measures in parallel, section. such as insecticide-treated bed nets and malaria med - ication. Can the safety of supplemental iron administra - tion in malaria-regions be improved? How can the dilemma be tackled? In addition to the alternative approaches mentioned As observed in several commentaries (10, 11), iron is above it may be necessary to entertain the notion of a particular “problem nutrient” for complementary administering supplemental forms of iron to young foods fed in the weaning period. Some guidance is children in malarial areas. Are there approaches that available, though, to cut this can improve the safety? Two caveats “Gordian knot” of the supplement to the current practices can be iden - or no-supplement dilemma for tified. The first comes from an young children. Firstly, alter- analysis of a subgroup with hemato - native approaches to ease iron- logical evaluation in the Pemba trial. deficiency, other than routine, It showed that when a child in the daily iron supplementation, iron-intervention arms of the study should be considered. These was actually iron deficient, he or she include measures such as delayed benefited from iron supplementa - cord clamping during birth, tion; it improved iron and hemoglo - increasing food choice and food Iron and vitamin B drops bin status, while decreasing the num - security, providing iron-fortified ber of hospital admissions, concomi - complimentary foods and implementing hookworm tant infections, and fatalities related to malaria. Iron- treatment programs in endemic areas. Specifically replete children, in contrast, had an increased risk for within the domain of food choice is the recent notion such events. Thus, the dilemma might be resolved, if to rely more heavily on the heme iron of muscle and the iron status in all participants of a public health organ meat (11). It is suggested, from contemporary supplementation program and their response to iron hunter-gathers, that the evolutionary weaning food intervention could be monitored. All currently avail - was pre-masticated meat. This is rich in highly able options, however, have three drawbacks: 1) They bioavailable heme-iron. add considerable costs to IDA mitigation programs; 2) They have yet to be tested for their applicability in the field; and 3) They generally involve the sampling of

8 End of iron age Magazine Issue 3/2007

blood, with all that implies for discomfort to the child, be prohibitive. However, the costs of test chemicals acceptability to the families, and blood-borne in- for analysis of serum ferritin, transferrin receptor and fection hazard to the handlers and the environment. AGP can be reduced to approx. $1 US due to minitur - ization (22). In addition, cost for blood-sampling Assessment of anemia and iron status in a public devices, transport, laboratory equipment and staff health context come into prominence. The risk of blood-borne dis - eases, like HIV and hepatitis, should not be underesti - It is becoming more imperative to have methods, ac- mated, as single-use lancets and cannula may be used ceptable to the public and cost-efficient in nature, to repeatedly in developing country settings. Finally, screen populations to detect those individuals in since these tests require the extraction of blood, there whom iron treatment is indicated, in order to target are associated pain (albeit minimal), even with capil - therapy to the eligible and exclude exposure for those lary blood, and cultural taboos about blood handling; who do not need additional iron. The current options both of these consequences may induce widespread are to some extent both limited and problematic. rejection by the population, especially for application to such young children. Screening with capillary blood samples Inspection and questionnaire approaches There are obvious trade-offs between costs and accu - racy among the available options. The most accurate IDA-assessments by clinical inspection of sclera and assessment of IDA includes data on hemoglobin (16) pale skin, assisted by a questionnaire on risk factors of in combination with serum ferritin, transferrin recep - iron deficiency, may be put at the other end of the tor (TfR) plus C-reactive protein (CRP) (17), or AGP scale of cost, invasiveness, reliability, and precision. to control for inflammatory influences on serum fer - The questionnaire should contain questions to assess ritin. This “classic” set of variables can be determined dietary intake, socio-economic and educational status in approx. 30 µL serum from capillary blood samples of the family in analogy to earlier guidelines of the with satisfactory validity and precision (18–20). Center of Disease Control and Prevention (23) for the Although other biomarkers, such as transferrin satura - US, plus some more recent risk factors (e.g., tion, erythrocyte protoporphyrin, reticulocyte hemo - overweight) (24). Similar approaches are used in vet - globin content, or percentage of hypochromic red erinary health and require well-trained health workers blood cells (21) could be theoretically added, the basic (25). Their advantage is that they are inexpensive and package offers a very reliable assessment of iron and non-invasive; but their sensitivity and specificity are anemia status. Financing widespread screening could very limited.

Non-invasive assessment of hema - tological status

A first attempt to quantify hemoglo - bin concentration by non-invasive methods was based on back-scat - tered light from human tissues in vivo as determined by the Erlangen microlight-guide photometer (26). More recent technology has gained much precision. It uses orthogonal polarization spectrometry to pro - duce an image of the sublingual microcirculation at 548 nm, which permits hemoglobin measurement in the vessels in vivo . A probe the size of a pencil is connected to a portable processing unit and produces an image that is divided into vessel and Malaria cycle. From US CDC background regions. The optical density in a number of vessel seg -

9 SIGHT AND LIFE End of iron age

ments is used to determine hemoglobin concentration tions (33). NTBI was observed to increase after pulse (27). Estimation of the subjects’ systemic hemoglobin doses of readily available oral iron preparations (34) concentration was shown to be highly reproducible which are known to increase serum iron concentra - and closely correlated to conventionally determined tions rapidly but only for comparably short periods hemoglobin concentrations in venous blood samples (35). Thus, high concentration peaks of serum iron over a wide range of hemoglobin concentrations (28). and, thus, of NTBI should be avoidable, if iron Applicability in the field to assess the variability in a absorption were retarded. large number of subjects of different origin, however, has yet to be tested. As only about 50% of anemias in A potential problem of oral slow release preparations developing countries can be attributed to iron defi - for iron is that they may pass beyond the duodenum ciency (29–31), the presence (i.e., the location of the high - of iron deficiency needs to be est iron absorption rate) before established. This could be Non-invasive the iron is released from such done ex post facto by measur - galenic forms; this would ing the response of anemia to impair its bioavailability and 8 weeks of iron administra - screening methods reduce its biological impact. tion. This approach is non- Slow gastric delivery systems invasive and promises to com - may offer promise are an exception to this rule. bine high accuracy with easy These preparations float on the handling and low running costs beyond the expenses gastric juice and release their iron over an extended for the staff. Its applicability in the field, however, has period of time upstream of the duodenum. This type of yet to be tested. preparation increases iron absorption rates (36) and also avoids high peak concentrations of free iron in Slowing the rate of uptake of oral iron from the intestinal lumen, which significantly reduces supplemental forms intestinal side effects (37). At the same time the pro - tracted release attenuates peaks in circulating iron (BS Considerations to improve the safety of iron intake in Skikne, JD Cook, unpublished observations, 1991, malaria-endemic areas build on the observation that quoted by Simmons et al. (37)), which is likely to non-transferrin-bound iron (NTBI) activates the intra - reduce NTBI concentrations. This, in turn, could cellular adhesion molecules ICAM-1, VCAM-1 and reduce the prevalence of cerebral malaria manifesta - E-selectin in the vascular endothelium (32). These tions. Although this concept offers promise, its scien - changes, in turn, seem to ease the adhesion of P. fal - tific base is not yet very solid, as field experience is ciparum to the vascular endothelium and, thus, the lacking. According to this concept, offering iron (e.g., prevalence for example of cerebral malaria manifesta - via a gastric delivery system or with fortified food items over the whole day) should not increase the risk of severe ma- laria complications.

In this context, Sprinkles, Foodlets and iron-fortified spreads should be considered to be supplements, as they deliver the iron dosage for an entire day in a single dose. Several factors seem to influence the serum iron peak with these compounds. Among them would be the dose of iron, the iron status of the child, the matrix of the supplement, and the consistency of the meal. Presum- ably, the peak serum concentration reached after consumption of such ready-to-eat fortificants will deter - Anemia assessment by pallor staging mine whether they are harmful in a malarial setting or not.

10 End of iron age Magazine Issue 3/2007

Another alternative to avoid haz - tuberculosis (38). Moreover, the during the first 6 months can be ardous peak serum concentrations interim statement announced the obtained from breast milk.” How of iron would be to identify and use drafting of a detailed research such a recommendation would be oral iron complexes that are ab- agenda as one of the main charges operative in malarial areas falls sorbed as such. If such complexes of the Expert Consultancy Panel. into the large incognitos of malaria release their iron slowly after hav - Despite the need to develop evi - pathology and supplemental iron ing been absorbed, high peak con - dence to inform policy-makers on exposures. This theme is best centrations of free iron are avoid- oral iron supplementation, the viewed as a subject for research ed. Such approaches, however, degree to which research protocols prior to implementation. need more developmental work may be ethically challenged by the before they can be used in large- experience in Pemba cannot be Iron status screening scale interventions in young chil - overlooked. Finding a manner for dren. inquiry that is safe for the study Insistence on some sorting and populations may not be easy. selection of individuals for oral Commentary on the wisdom and Independent from this issue, we supplementation in malaria endem - limitations of the World Health touch on some gaps of knowledge ic areas heralds a new and safer – Organization below that relate to the WHO but more complex – era of iron Consultancy Statement and seem deficiency control. The putative Consultancy Statement to urge additional research. clinical diagnosis of severe anemia by pallor staging mentioned here The United Nations did not remain offers a low-cost, non-invasive idly on the sidelines in the face of approach with reasonable speci - public health and safety conse - ficity but poor sensitivity. We see quences of the Pemba experience. promise in improving the accept- In April 2006, the World Health ability and accessibility of screen - Organization and UNICEF issued ing methods by use of miniaturized an interim statement (38), an- approaches using capillary blood nouncing the convening of an (22), by non-invasive methods Expert Consultancy Panel, among (27), or by well-tested approaches others, to provide guidance regard - for IDA-assessments by clinical ing routing prophylactic supple - Mother with anemic child inspection, assisted by question - mentation of iron in the preschool naires on risk factors of iron de- age group. The group met in Lyon, Comprehensive and effective ficiency. A view on cost issues, on France; a summary of this Consult- healthcare the risk of blood-borne diseases, ancy has been released and is and on cultural acceptability seems reprinted in this issue of the Healthcare measures mean to paramount in all efforts to improve SIGHT AND LIFE Magazine insure the public’s health, and take IDA assessment. (page 14-15). The considerations on special relevance where holo- in this commentary provide theo- endemic malaria is established. Screening to avoid iron exposure retical and practical linkage to an Clearly, mosquito control and to the iron-replete has additional analysis of the lessons from the avoidance of the insect vector are merits in populations that may not Pemba trial (4). The WHO-spon - fundamental. Beyond such meas - suffer malaria endemicity. The evi - sored consultancies have offered ures, exclusive breastfeeding for dence is now convergent and virtu - sage and sound conclusions re- the first 6 months of life is expli- ally conclusive that iron-replete garding the proscription of routine citly recommended. Technically, children grow more poorly when iron supplementation in malaria- the administration of micronutrient exposed to oral iron supplementa - endemic settings. syrups, for example, is considered tion (41–43). This adds a strong a violation of exclusivity of breast - rationale to consider screening The WHO interim statement re- feeding (39). Recently, a sugges - before implementation of universal leased early in 2006 (38) is to be tion that there is a need for early supplementation for pre-school - praised for raising notes of caution iron supplementation in all infants children. Finally, we underscore with regard to universal, saturation has been made (40) based on the the need to move the proposed iron supplementation in settings consideration that “only about research agenda on routine univer - with a background of HIV and/or 50% of their iron requirements sal iron supplementation where

11 SIGHT AND LIFE End of iron age

“other infections” are prevalent. The pathogen biolo - Conclusion gy of plasmodia is not that distinct from other infec - tions with intracellular organisms, such as leprosy, Meanwhile, policy decisions and program operations tuberculosis or HIV, so that extension of the princi - that dismiss the warnings of the WHO Consultancy ples of the WHO Statement (38) and Summary (44) in Statement on blanket, routine oral iron supplementa - terms of selective coverage with iron supplementation tion imperil the health and lives of children living should now be seriously considered. within a background of chronic and recurrent malaria, in spite of good intentions. To maintain the first do no Home-fortification versus fortified foods as sources harm mandate for infant and toddler iron supplemen - of prophylactic iron tation we need to insure a better and safer way to deliver iron in this age group. Meanwhile, we should The Consultancy rightly claims lack of certainty re- seek creative ways to ensure that children absorb the garding the safety of oral iron when given with food. iron that is afforded by their diet and retain the iron They apply the theoretical con - they absorb. For those who sideration around potential still show obvious clinical adverse consequences of rapid Mosquito control signs of iron deficiency, a tar - uptake of iron into the circu- geted approach with supple - lation reviewed above. Supple- and avoidance of ments should be employed, mental iron in proven deficien - preferably with galenic com - cy is to be given with food, the insect vector positions that release as little rather than on an empty stom - free iron into the systemic ach. Extending this logic with - circulation as possible. In in the safety considerations for are fundamental the long run, screening for home fortification with iron iron deficiency by innovative (which is discouraged), and commercial food-fortifica - methods should be developed to reduce the exposure tion (which is encouraged), the admitted uncertainty to iron for those who have no need for additional takes center stage. Definitive research, rather than ten - amounts of the nutrients and to satisfy the requirement tative policy guidance, is the true priority in relation to of those who could benefit from repletion of their iron additional oral iron in the context of meals. reserves.

Proscription of folic acid supplementation and References fortification 1. Gross R. Micronutrient supplementation throughout the life cycle. The WHO Expert Consultancy Statement contains a New York: UNICEF, 2001. 2. Food and Nutrition Board, Institute of Medicine, Dietary recommendation for the total omission of folic acid Reference Intakes: Vitamin A, vitamin K, arsenic, boron, chromi - from multi-micronutrient preparations in malarial um, copper, iodide, iron, manganese, molybdenum, nickel, sili - areas, including in its traditional association with iron. con, vanadium and zinc. Washington DC: National Academy There is a prudent basis to omit folic acid exposure, Press, 2001. when anti-folate metabolism is the mainstay of anti- 3. Stoltzfus RJ, Dreyfuss ML. Guidelines for the use of iron supple - ments to prevent and treat iron deficiency anemia. Washington malaria therapy. However, the observation that DC: ILSI Press, 1998. the “widespread folate deficiency not known to be a 4. Sazawal S, Black RE, Ramsan M, et al. Effects of routine prophy - problem in infants and young children” should not be lactic supplementation with iron and folic acid on admission to given as a rationale to omit folic acid from preschool hospital and mortality in preschool children in a high malaria supplements. Folic acid should be seen as a compan - transmission setting: community-based, randomised, placebo- ion hematinic nutrient to iron. Presumably, in the controlled trial. Lancet 2006;367:133–43. 5. Oppenheimer SJ. Iron and its relation to immunity and infectious anticipation of a major reticulocytic response and disease. J Nutr 2001;131:616S–5S. rapid restoration of the red cell mass enabled by 6. McKay HM. Anemia in infancy: its prevalence and prevention. adequate iron supplementation, an additional presence Arch Dis Child 1928;3:117–47. of folates will be needed for the proliferative response 7. Lozoff B, Jimenez E, Hagen J, Mollen E, Wolf AW. Poorer in the bone marrow. behavioral and developmental outcome more than 10 years after treatment for iron deficiency in infancy. Pediatrics 2000;105:E51. 8. Tielsch JM, Khartry SK, Stoltzfus RJ, et al. Effects of routine pro - phylactic supplementation with iron and folic acid on preschool children mortality in southern Nepal: community-based, cluster- randomised, placebo-controlled trial. Lancet 2006;367:144–52.

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9. English M, Snow RW. Iron and folic acid supplementation and 28. Nadeau RG, Groner W. The role of a new non-invasive imaging malaria risk. Lancet 2006;367:90–1. technology in the diagnosis of anemia. J Nutr 2001; 131: 10. Brown KH, Dewey KG, Allen LH. Complementary feeding of 1610S–4S. young children in developing countries: A review of current sci - 29. Allen LH, Rosado JL, Casterline JE, et al. Lack of hemoglobin entific knowledge. Geneva, WHO/UNICEF, 1998. response to iron supplementation in anemic Mexican preschool - 11. Krebs NF, Westcott JE, Butler N, Robinson C, Bell M, ers with multiple micronutrient deficiencies. Am J Clin Nutr Hambidge KM. Meat as a first complementary food for breast - 2000;71:1485–94. fed infants: feasibility and impact on zinc intake and status. J 30. Straubli Asobayire F, Adou P, Davidsson L, Cook JD, Hurrell Pediatr Gastroenterol Nutr 2006;42:207–14. RF. Prevalence of iron deficiency with and without concurrent 12. Hurrell RF. Phytic acid degradation as a means of improving anemia in population groups with high prevalences of malaria iron absorption. Int J Vitam Nutr Res 2004;74:445–52. and other infections: a study in Côte d’Ivoire. Am J Clin Nutr 13. Gibson RS, Yeudall F, Drost N, Mtitimuni B, Cullinan T. 2001;74:776–82. Dietary interventions to prevent zinc deficiency. Am J Clin Nutr 31. Schümann K, Romero-Abal ME, Mäurer A, et al. Hematological 1998;68(2 Suppl):484S–7S. response to heme iron or ferrous sulphate mixed with refried 14. Mendoza C, Viteri FE, Lönnerdal B, Young KA, Raboy V, black beans in moderately anemic Guatemalan preschool chil - Brown KH. Effect of genetically modified, low-phytic acid dren. Pub Health Nutr 2005;8:572–81. maize on absorption of iron from tortillas. Am J Clin Nutr 32. Kartikasari AER, Georgiou NA, Visseren FLJ, van Kats-Renaud 1998;68:1123–7. H, Sweder van Asbeck B, Marx JJM. Endothelial activation and 15. Zhang H, Onning G, Oste R, Gramtkovski E, Hulthon L. induction of monocyte adhesion by nontransferrin-bound iron Improved iron bioavailability in an oat-based beverage: the com - present in human sera. FASEB J 2005;20:353–5. bined effect of citric acid addition, dephytinization, and iron sup - 33. Gray C, McCormick C, Turner G, Craig A. ICAM-1 can play a plementation. Eur J Nutr 2007 (Epub ahead of print). major role in mediating P. falciparum adhesion to endothelia 16. Muñoz M, Romero A, Gomez JF, Manteca A, Naveira E, under flow. Mol Biochem Parasitol 2003;28:187–93. Ramirez G. Utility of point-of-care measurement in the 34. Hutchinson C, Al-Ashgar W, Liu DY, Hider RC, Powell JJ, HemoCue-B haemoglobin for initial diagnosis of anaemia. Clin Geissler CA. Oral ferrous sulphate leads to a marked increase in Lab Haematol 2005;27:99–104. pro-oxidant nontransferrin-bound iron. Eur J Clin Invest 17. Fleming DJ, Jaques PF, Massaro JM, D’Agostino RB, Wilson 2004;34:782–4. PWF, Wood RJ. Aspirin intake and the use of ferritin as a meas - 35. Hoppe M, Hulten L, Hallberg L. The validation of using serum ure of iron status. Am J Clin Nutr 2001;74:219–26. iron increase to measure iron absorption in human subjects. Br J 18. Erhardt JG, Estes JE, Pfeiffer CM, Biesalski HK, Craft NE. Nutr 2004;92:485–8. Combined measurement of ferritin, soluble transferrin receptor, 36. Cook JD, Cavuiaga M, Kahn SG, Schalch W, Skikne BS. retinal binding protein, and C-reactive protein by an inexpen - Gastric delivery system for iron supplementation. Lancet sive, sensitive and simple sandwich enzyme-linked immunoab - 1990;335:1136–9. sorbed assay technique. J Nutr 2004;134:3127–32. 37. Simmons WK, Cook JD, Bingham KC, et al. Evaluation of a 19. Baynes RD. Refining the assessment of body iron status. Am J gastric delivery system for iron supplementation in pregnancy. Clin Nutr 1996;64:793–4. Am J Clin Nutr 1993;58:622–6. 20. Olivares M, Walter T, Cook JD, Hertrampf E, Pizarro F. 38. World Health Organization/UNICEF. Iron supplementation of Usefulness of serum transferrin receptor and serum ferritin in young children in regions where malaria is intense and infectious diagnosis of iron-deficiency in infancy. Am J Clin Nutr disease is highly prevalent. Joint statement. Geneva: WHO, 2000;72:1191–5. 2006. 21. Coyne D. Iron indices: what do they really mean? Kidney 39. World Health Organization. Indicators for assessing breastfeed - Internat 2006;69:54–8. ing practices. Report of an informal meeting in June 1991. 22. Biesalski HK, Erhardt J. Diagnosis of nutritional anemia – labo - Geneva: WHO, 1991. ratory assessment of iron status. In: Kraemer K, Zimmermann 40. Kraemer K, Stoecklin E, Badham J. Conclusions and research MB, eds. Nutritional Anemia. Basel: SIGHT AND LIFE Press, agenda. In: Badham J, Zimmermann MB, Kramer K, eds. The 2007:37–44. Guidebook: Nutritional Anemia. Basel: SIGHT AND LIFE 23. Center of Disease Control. Recommendations to prevent and Press, 2007:48–50. control iron deficiency in the United States. Morbid Mort 41. Idjradinata P, Watkins WE, Pollitt E. Adverse effect of iron sup - Weekly Rep 1998;47:1–29. plementation on weight gain of iron-replete young children. 24. Nead KG, Halterman JS, Kaczorowski JM, Auinger P, Lancet 1994;343:1252–4. Weitzman M. Overweight children and adolescents: a risk group 42. Majumdar I, Paul P, Talib VH, Ranga S. The effect of iron ther - for iron deficiency. Pediatrics 2004;114:104–8. apy on the growth of iron-replete and iron-deplete children. J 25. van Wyk JA, Bath GF, Groeneveld HT, Stenson MO, Malan FS. Trop Pediatr 2003;49:84–8. Extensive testing of the FAMACHA© system for accuracy of 43. Lonnerdal B, Lind T, Persson LA. Iron supplementation for iron clinical evaluation of anaemia caused by oxidative haemon - replete Indonesian infants impairs growth (abst). ESPHAGAN chosis. Proc. 5th Int. Sheep Veterinary Congress. Cape Town, Meeting, 2007. South Africa, 2001. 44. de Benoist B, Fontaine O. Summary of the Conclusions of the 26. Gross R, Gliwitzki M, Gross P, Frank K. Anaemia and haemo - WHO Consultation on prevention and control of iron deficiency globin status: A new concept and a new method of assessment. in infants and young children in malaria endemic areas. Lyon Food Nutr Bull 1996;17:27–36. France, 12–14 June 2006. SIGHT AND LIFE Magazine Issue 27. Nadeau RG, Groner W. Orthogonal polarization spectral imag - 3/2007; 14-15. ing: state of the art. In: Mesmer K, ed. Orthogonal Polarization Spectral Imaging. Basel: Karger, 2000:920.

13 SIGHT AND LIFE Control of iron deficiency in malaria

Summary of the conclusions of the WHO consultation Prevention and control of iron deficiency in infants and young children in malaria-endemic areas Lyon, France, 12–14 June 2006

Bruno de Benoist Department of Nutrition for Health and Development, WHO, Geneva Olivier Fontaine Department of Child and Adolescent Health, WHO, Geneva

Correspondence: Olivier Fontaine, Department of Child and Adolescent Health, WHO, Geneva Email: [email protected]

Iron deficiency anemia iron-folic acid with or without zinc, and those who received zinc alone or a placebo. The results from the is common in young study in Zanzibar, Tanzania (1) raised the issue of the safety of administering additional iron to infants and children young children in areas of malaria endemicity and its public health implications. and there is substantial evidence that iron deficiency has adverse effects on child health and development. WHO convened an expert Consultation to examine Therefore provision of additional iron to infants and this issue, in Lyon, France, 12–14 June 2006. The young children who are iron deficient should be a pub - objectives of the Consultation, which focused on lic health priority. infants and young children in malaria-endemic areas, were: 1) To review the scientific evidence on the safe - Two large trials, coordinated and supported by WHO, ty and efficacy of different ways of administering iron were conducted in Zanzibar, Tanzania, and in Nepal to to control iron deficiency and iron deficiency anemia; evaluate the impact of zinc and/or iron-folic acid sup - and 2) To provide guidance on the safest, most feasi - plementation on the mortality and severe morbidity of ble and effective ways of delivering additional iron to preschool children (1, 2). In Zanzibar, an area of control iron deficiency and anemia in such areas. stable, perennial and intense transmission of Plas- modium falciparum malaria, routine iron-folic acid The participants to the Consultation reached consensus supplements given with or without zinc resulted in an on several important issues related to providing addi - increased rate of severe adverse events in children tional iron to infants and young children in malaria- (morbidity and mortality). A concurrent substudy sug - endemic areas: gested that the adverse events occurred in supplement - ed children who were not iron deficient. In Nepal the • Strategies to control iron deficiency should be carried trial showed no difference in mortality or the incidence out in the context of comprehensive and effective of the common infections between children receiving health care, including the provision of insecticide-

14 Control of iron deficiency in malaria Magazine Issue 3/2007

reservations concerning the harmful effects of uni - Control of iron versal iron supplementation do not diminish the need for adequate iron therapy when iron deficiency is deficiency in the context diagnosed. • Because widespread folate deficiency is not known of comprehensive to be a problem in infants and young children, and supplemental folic acid may interfere with the effica - health care cy of antifolate antimalarial drug therapy, supple - mental folic acid or foods fortified with folic acid treated nets and vector control for the prevention of should not be given to infants and young children in malaria, and prompt recognition and treatment of areas where anti-folate anti-malarial drugs are used. malaria and its complications with effective anti - malarial and antibiotic drug therapy. They should • The potential pathophysiological mechanisms also include control of other prevalent parasitic dis - governing the relationships between iron metabolism eases and infections, and the promotion of exclusive and infection, and the risk of severe adverse events breastfeeding for the first six months of life followed after iron administration were also discussed, but it by consumption of nutrient dense and/or processed was felt that there are insufficient data to draw con- fortified complementary foods (3, 4). clusions that would justify changing public health programs. Further research on this topic is required. • Universal iron supplementation (i.e., use of medicinal iron as pills or References syrups) should not be implemented without the screening of individuals 1. Sazawal S, Black RE, Ramsan M, et al. for iron deficiency, because this Effects of routine prophylactic supple - mentation with iron and folic acid on mode of iron administration may admission to hospital and mortality in cause severe adverse events in iron- preschool children in a high malaria sufficient children. transmission setting: community- based, randomised, placebo-controlled • The safety of iron preparations trial. Lancet 2006;367:133–43. 2. Tielsch JM, Khatry S, Stoltzfus R, et administered through home fortifi - Anemic child al. Effects of routine prophylactic cation of complementary foods for supplementation with iron and folic infants and young children (i.e., powders, crushable acid on preschool child mortality tablets, and fat-based spreads) is uncertain in malar - in Southern Nepal: community-based, cluster-randomised, ia-endemic areas. Although there is reason to believe placebo-controlled trial. Lancet 2006;367:144–52. that those preparations may be safer than iron supple - 3. WHO, CDC. Assessing iron status of populations. Report of a joint World Health Organization/Centers for Disease Control ments, they cannot be recommended until this has and Prevention Technical Consultation on the Assessment of been demonstrated. Iron Status at the Population Level, Geneva, 6–8 April 2004. Geneva: WHO, 2005. • An option would be to administer additional iron to 4. WHO, UNICEF. Iron supplementation of young children in infants and young children as processed complemen - regions where malaria transmission is intense and infectious dis - ease highly prevalent. Joint Statement. Geneva: WHO, 2006 tary foods fortified with iron. Although the safety of their use in malaria-endemic areas has not been doc - umented, this is likely to avoid the potential adverse effects of a large bolus of iron taken in a single dose, since the iron would be consumed in smaller amounts throughout the day and therefore absorbed more slowly.

• Infants and young children who have malaria and are diagnosed with iron deficiency (3) or severe anemia, should be treated with antimalarial and where appro - priate antibiotic therapy as well as iron therapy, which should always be administered with food. The

15 SIGHT AND LIFE Golden Rice

Golden Rice and biofortification

Jorge E. Mayer Golden Rice Project, Campus Technologies Freiburg, Germany Email: [email protected]

Tackling micronutrient malnu - quarter of those children; a more countries, like Nepal or Ghana, are trition inclusive approach could save around $2 million per year (5); cov - many more (3). ering just 50% of India would Breeders have only recently gone require more than $100 million beyond increasing crop yields and Starchy staples, like rice, cassava, annually (2). As a result, globally, started paying attention to quality maize, and sorghum, are the main only 55% of the target population traits, among which micronutrient calorie sources in developing coun - has access to supplementation (6). content is of the utmost relevance tries, with good storability charac - Moreover, coverage fluctuates from for developing countries. Because teristics, but their micronutrient year to year due to the vagaries of of indirect cause-effect relation - content is generally low. A vast geopolitics and civil unrest (7). ships and the great variability of proportion of the population in nutritional status within popula - those countries cannot afford a bal - Biofortified crops with the geneti - tions, establishing the link between anced diet to cover their daily cally inbuilt capacity to produce or micronutrient malnutrition (MNM) micronutrient requirements. More- accumulate vitamins and minerals and various afflictions has been a over, people need regular access at higher concentrations offer a daunting statistical task (1). to vegetables, fruits and animal novel approach that does not attract sources to meet their daily micro- recurring costs and is capable of More recent population-wide sur - nutrient needs, but these are sea - reaching remote rural populations vey data on health and nutrition has sonal and perishable goods, and (1, 8-10) ( Table 1). Micronutrient- made it possible to identify MNM, often unaffordable or culturally dense crop plants can be obtained also known as ‘hidden hunger,’ as unacceptable. through conventional breeding or, one of the main culprits of a num - in the absence of genetic variability ber of syndromes. In Southeast Supplementation and industrial for - for the trait, by genetic engineering. Asia, the burden imposed by the tification programs are presently combined deficiencies of iron, zinc the best options to combat MNM. Nutritious mutants and vitamin A – common among The latter is well suited for urban low-income populations – leads to populations with access t o fortified Micronutrients are not always pres - a loss of disability-adjusted life foodstuffs, like vitamin A-fortified ent in the desired plant tissues. years (DALYs) comparable to that oils and margarine or iodinated salt. Sometimes, in nature, mutations caused by HIV/AIDS or tuberculo - Supplementation programs, on the lead to the activation of carotenoid sis, and is only second to respirato - other hand, suffer from the recurring biosynthesis in usually non-carote- ry infections, cardiovascular and costs. While the cost of vitamin A nogenic tissues, as was the case diarrhoeal diseases (2). Globally, capsules is only around 10 cents per with carrots (Daucus carota) , a around 5 million children under the unit, operational costs add another vegetable introduced from Afgha- age of five die every year as a direct 90 cents to every capsule (4). Five- nistan and which came initially in consequence of MNM. Supple- hundred million capsules are donat - various colours, except for orange. mentation with zinc and vitamin A ed and distributed every year around Carrots with purple-red antho - alone could save the lives of a the world! Recurring costs for small cyanins were first grown in the

16 Golden Rice Magazine Issue 3/2007

Middle and Far East, along with white, red, yellow, ing at the Swiss Federal Institute of Technology and green and black versions. An orange carrot mutant that University of Freiburg, respectively. Their ambitious accumulated up to 6 mg/g dry weight of ␤-carotene goal was to re-engineer the biosynthetic machinery of (provitamin A) in root tissues – the nature of the muta - the rice grain to produce and accumulate ␤-carotene, a tion is not yet understood – became popular in the pigment found in the green tissues of rice but not in the Netherlands in the 16th century because of its associa - grain. This ran into the scepticism of many experts, tion with the royal House of Orange. based on the knowledge that carotenogenic tissues not only possess active metabolic pathways, including the But large amounts of ␤-carotene are not necessarily presence of precursor molecules, but also deposition synonymous with high availability, as we know from mechanisms, such as carotenoid crystallization, forma - green leafy vegetables, where only 1 µg vitamin A tion of oil droplets, sequestration of carotenoids into turns up in our blood stream from 24 µg of ␤-carotene. membranes or protein-lipid complexes. The non- The bioavailability of ␤-carotene in raw carrots is lim - carotenogenic starchy endosperm of rice is very low in ited because it is deposited as crystals in the roots. lipids and apparently lacks the means for carotenoid Bioavailability can be raised by cooking and serving deposition. Nonetheless, the inventors relied on recent with some oil. The retention of carotenoids after heat advances in the fields of genetic transformation and treatment is very high and cooking generally increases the understanding of carotenoid biosynthesis to its bioavailability, as has been shown for orange- achieve their goal. fleshed sweet potato (11). Basically, Golden Rice technology succeeded because Another more recent example is an already commer - rice grains – though not carotenogenic – produce cially-available orange-coloured cauliflower (Brassica carotenoid precursor molecules and some of the oleracea var botrytis) . This semi-dominant mutation is enzymes responsible for further downstream process - due to the insertion of a retrotransposon into the so- ing. The addition of only two genes was sufficient to called Or allele (Or for orange) (12). The mutation render the pathway fully functional and consequently possibly interferes with the sequestration of capable of accumulating ␤-carotene in the seed carotenoids into chromoplasts. The principle can be endosperm (13). As it turns out, carotenoid production applied to other crops, as was shown by the generation can also be spurred in other plant species by increasing of transgenic yellow-fleshed potatoes expressing the the production of precursor molecules, filling in the Or gene (12). The downside of this approach thus far enzymatic gaps, or by blocking the synthesis of cata - is that, in homozygous plants, growth is stunted, prob - bolic enzymes downstream of the desired product. ably due to poorly understood pleiotropic effects. The clockwork orange The advent of Golden Rice Geranylgeranyl-diphosphate (GGDP) is a key biosyn - Golden Rice is a prime example of the metabolic engi - thetic intermediate of isoprenoids, a substance class neering of a nutrient-enhanced crop. The development that includes carotenoids. GGDP is the precursor of of the first Golden Rice prototype took a concerted several key compounds, including tocopherols (vita - seven-year effort, culminating in 1999, by the collabo - min E), tocotrienols, carotenoids, abscisic acid (a phy - rating groups of Ingo Potrykus and Peter Beyer, work - tohormone involved in regulatory processes, like bud and seed dormancy, and various stress responses), gibberellic acid Table 1: Advantages of biofortification (another phytohormone promoting growth and cell elongation), • One-off research investment with no maintenance costs chlorophyll, and other components • Seed-borne technology of the photosynthetic machinery. • Concept applicable to many crops The complexity of the meta- • Amenable to introgression into many varieties bolic turntable of GGDP was what • Utilizes the usual seed distribution channels fed the scepticism of many experts • Capable of reaching remote populations (Figure 1). • Sustainable and cost-effective • Compatible with ongoing fortification, supplementation and educa - Golden Rice technology relies on tion programs two transgenes ( Figure 2). The first codes for phytoene synthase

17 SIGHT AND LIFE Golden Rice

Pyruvate + Glyceraldehyde-3-phosphate DXS carotene desaturases: phytoene toes are vegetatively propagated 1-Deoxy-D-xylulose-5-phosphate desaturase (PDS), ␨-carotene desat - demand a Golden Rice -like ap- urase (ZDS) , and carotene iso - proach. High- ␤-carotene potatoes Dimethylallyl-diphosphate + 3 Isopentenyl-diphosphate GGPPS merase (CRTISO) (13,14). Due to have already been generated by Geranygeranyl-diphosphate PSY its multifunctionality and minimal either blocking the expression 15-15’-Phytoene co-factor requirements, CrtI was of ⑀-lycopene cyclase ( ⑀-LCY),

PDS Vitamin E chosen over the plant desaturases which diverts lycopene into the CRTI 9,9’-di-cis-␨-Carotene for the generation of Golden Rice . ␣-carotene and lutein branch of the ZDS pathway (15), or by the introduc - 7,9,9’,7’-tetra-cis-Lycopene CRTISO The predominance of ␤-carotene tion of a “mini-pathway” consisting All-trans-Lycopene ␤-LCY ␣-LCY, ␤-LCY, over ␣-carotene in Golden Rice is of three genes from Erwinia: phy - ␤-Carotene ␣-Carotene ␣-HYD ␣-HYD, ␤-HYD, aided by the fact that the lycopene toene synthase (CrtB) , phytoene Zeaxanthin Lutein isomer ratio leads preferentially to desaturase (CrtI) , and lycopene Figure 1: Carotenoid bio- ␤-carotene formation. Further pro - ␤-cyclase (CrtY) (16). In the latter, synthetic pathway and genetic cessing of ␤-carotene to hydrox- total carotenoid content increased intervention points in Golden ylated derivatives in rice grains 20-fold while ␤-carotene increased Rice. DXS, 1-deoxy-D-xylulose- occurs at a reduced rate, leading to 3600-fold, up to 47 µg/g dry 5-phosphate synthase; GGPPS, geranylgeranyl-diphosphate syn - greater ␤-carotene accumulation. weight. thase; PSY, phytoene synthase; CRTI, bacterial carotene desat - Spreading of a concept Indian mustard (Brassica juncea) , a urase; PDS, phytoene desaturase; popular source of cooking oil in ZDS, ␨-carotene desaturase; Most starchy crops lack adequate India, was transformed with bac- CRTISO, carotene cis-trans-iso - amounts of micronutrients. Potato, terial Psy and CrtI genes so as merase; LCY, lycopene cyclase; HYD, carotene hydroxylase. In for example, is one of the major to deliver highly bioavailable Golden Rice two transgenes have staple crops in the world, but in ␤-carotene to target populations. been introduced to reconstitute most cultivars, ␤-carotene is pres - This project is now awaiting an ex- the complete pathway, the other ent only in trace amounts. While ante socio-economic assessment necessary enzymes are present the yellow wild potato species before going ahead. Similarly, a and active in the rice grain. The two genes are Psy, from daffodil Solanum phureja may contain high Golden Maize (Zea mays) is being (Narcissus pseudonarcissus) in levels of carotenoids, only a small produced for Africa using the bac - GR1 or maize ( Zea mays ) in fraction consists of ␤-carotene. terial CrtB and CrtI genes. Lines GR2, and CrtI, from the soil bac - capable of meeting 50% of the esti - terium Erwinia uredovora . CRTI The complexity of introducing a mated average requirement (EAR) replaces PDS, ZDS and CRTISO. trait for ␤-carotene production by of vitamin A for children have Desaturation by CRTI proceeds via all-trans intermediates, as breeding and the fact that pota- already been generated. opposed to the plant enzymes

(Psy) from daffodil (Narcissus pseudonarcissus) or maize (Zea mays) , which utilizes GGDP to form colourless phytoene. The Figure 2: Gene construct used to generate Golden Rice. RB, T-DNA product of the second transgene is right border sequence; Glu, rice endosperm-specific glutelin promoter; carotene desaturase (CrtI) , from tpSSU, pea ribulose bis-phosphate carboxylase small subunit transit the bacterium Erwinia uredovora , peptide for chloroplast localization; nos, nopaline synthase terminator; which converts phytoene into the Psy, phytoene synthase gene from Narcissus pseudonarcissus (GR1) or fully conjugated ␤-carotene precur - Zea mays (GR2); Ubi1, maize polyubiquitin promoter; Pmi, phospho - mannose isomerase gene from E. coli for positive selection (GR2); LB, sor molecule lycopene. The T-DNA left border sequence. Carotenoid biosynthetic pathway and endogenous enzyme, ␤-lycopene genetic intervention points in Golden Rice. DXS, 1-deoxy-D-xylulose- cyclase (LCY), then leads to the 5-phosphate synthase; GGPPS, geranylgeranyl-diphosphate synthase; formation of ␤-carotene. The bac - PSY, phytoene synthase; CRTI, bacterial carotene desaturase; PDS, terial CrtI is a multifunctional phytoene desaturase; ZDS, ␨-carotene desaturase; CRTISO, carotene enzyme that replaces at least three cis-trans-isomerase; LCY, lycopene cyclase; HYD, carotene hydrox- ylase plant enzymes, namely the

18 Golden Rice Magazine Issue 3/2007

Within the Grand Challenges in folate deficiency leads to hundreds almost four-fold increase over the Global Health Initiative, the Bill & of thousands of babies being born prototype. Preliminary bioavailabil - Melinda Gates Foundation is fund - with neural tube defects, thus lead - ity trials suggest that GR1 could ing four biofortification projects, ing to spina bifida syndrome (23). possibly provide the Recommended led by the Queensland University Nutrient Intake (RNI) for children – of Technology for banana (Musa From proof of concept to a even more so if we factor in a spp) , Ohio State University for cas - product modest intake of vegetables and fish sava (Manihot esculenta) , the or other animal sources, as is usually Africa Biofortified Project for For Golden Rice to attain a positive the case in the rural diets of South- sorghum (Sorghum bicolor) , and impact on health, ␤-carotene must east Asian countries ( Figure 3). The the University of Freiburg for rice be present at a high enough concen - good results are not completely (Oryza sativa) . Within the frame of tration, taking into account its unexpected, since the rice grain rep - this project, genes are being added bioavailability. At 1.6 µg/g caro- resents a simple, highly digestible to Golden Rice to promote the tenoid, the first Golden Rice proto - food matrix, comparable to that of accumulation or bioavailability of type could have been regarded as a maize (25). iron, zinc, vitamin E, and high- dietary supplement but it was recog - quality protein in rice grains. The nized early on that, in the absence Complex biosynthetic pathways are other groups are pursuing similar of a more varied diet, an improved usually regulated by a rate-limiting goals, also incorporating genetic version would be required to cater step – in this case, phytoene pro - traits for biotic and abiotic stress for the needs of the target popula - duction by Psy . The comparison of resistance or tolerance. tions. Psy genes from different plant sources revealed that the maize and Similarly, efforts to increase iron The first improved version, GR1, rice genes were better than the daf - content and bioavailability in rice contained the same two genes as the fodil (used in the prototype ver - are well underway (17-20). More prototype, only that both genes were sion) and other homologues. This recently, re-engineering of the expressed exclusively in the grain finding led to the development of folate biosynthetic pathway in endosperm, rather than constitutive - GR2, which uses a maize Psy gene tomato was reported (21); this ly, to avoid potential interference (26) ( Figure 4). One GR2 line, approach has meanwhile been with photosynthesis in leaves (24). acceptable from the regulatory per - duplicated in rice (22). This could The amount of ␤-carotene obtained spective, contained 37 µg/g total be an important development, as with GR1 was 6 µg/g on average, an carotenoids, 80% of which was ␤-carotene, representing a 23-fold increase over the prototype. 250 Considering that the RNI of vita - 200 e k a

t min A for 1 –3 year-old children is n I t n

e 400 µg and based on a retinol i r

t 150 u

N equivalency ratio for ␤-carotene in d e d n e 100 Golden Rice of 6:1 (preliminary m m o

c results indicate that bioconversion e R

% 50 50% RNI values could be even better), half the RNI could be provided in 0 around 50 g of GR2. Children in 12481632 target countries eat 100 –200 g per µg/g ␤-carotene content from different GR lines day. Figure 3: Capacity of Golden Rice lines with varying carotene content to supply the recommended nutrient intake of vitamin A. The golden trait could, in principle, The values on the graph were calculated based on the following assump - be directly engineered into many tions: Recommended Nutrient Intake (WHO/FAO) for 1 –3 year-olds different rice varieties. However, (RNI) is 400 µg Retinol Equivalents (RE); a conservative bioconversion due to stringent regulatory require - of ␤-carotene into vitamin A for Golden Rice of 1:6; a low baseline of ments, the aim is to have only one 112 µg RE obtained from other foodstuffs, as observed for children regulatory clean event as the starter living in rural Bangladesh; retention of ␤-carotene after cooking 80%; and ingestion of 200 g of rice on a daily basis material for introgression in paral - lel breeding programs. The transfer

19 SIGHT AND LIFE Golden Rice

tively modest thus far ($2.4 million the parental varieties. The golden over nine years). Product develop - trait can be bred within two years ment, however, is time-consuming into any local variety by performing and requires substantial additional three to four conventional back - funding, which is normally not crosses with the help of molecular available for public sector projects. marker-assisted breeding. The local - The maturation of the Golden Rice ly-adapted golden varieties will technology was carried out within become the property of smallhold - the framework of a public-private ers, who will also be able to use part partnership, by the agribusiness of their harvest as seed for the next Syngenta, which then donated the growing season. Local trade and dis - improved products to the humanitar - tribution are desirable, and only ian project. export to high-income countries is not allowed under the terms of the Expenses increase even more dra - licence agreement. matically when it comes to biosafe - ty assessment, as required for The regulatory hurdle regulatory approval. Even then, however, the costs are well below Worldwide, there is plenty of good - the additive recurrent costs of will in the public and in the private supplementation programs. Further- sectors to exploit the potential of more, once a novel, biofortified green biotechnology for the benefit variety has been approved and hand - of the poor. However, without a Figure 4: Improvement of ed over to farmers, the system can realistic, science-based risk assess - Golden Rice over time . Top, develop its full potential. From this ment approach and funds for public control rice; middle, Golden Rice prototype; bottom, GR2 point on, the technology is built into research, the technology will not be each and every seed and does not able to develop its full potential. require additional investment. The often-times arbitrary use of the of the trait from selected transgenic precautionary principle stands in lines into locally adapted varieties Golden deal the way of scientific progress and is coming along in priority target product development, and thus the countries by conventional breeding From the onset, Golden Rice was population at large may not benefit techniques. conceived as a humanitarian project from this promising technology. to alleviate malnutrition in develop - Getting road-ready ing countries. Contrary to what Our plans for India and the many would expect, patenting of the Philippines are to hopefully release Moving Golden Rice from the lab - technology was key to accessing a locally-adapted Golden Rice vari - oratory to the field is a stony path, number of ancillary key technolo - eties within three to four years, which is being mastered under the gies used in the production of pending regulatory approval. Con- strategic guidance of the Huma- Golden Rice . The patent paved the sidering that Golden Rice could nitarian Board, a group of interna - way to the public-private partner - substantially help reduce morbidity tional experts from reputed institu - ship with Syngenta and provided and mortality in many developing tions, and in collaboration with a access to free humanitarian-use countries, it is difficult to under - network of national institutions licences to technologies from vari - stand why the project is not getting participating in the development ous sources. By providing freedom wider international support to fast- and distribution of locally adapted to operate to develop locally- track it through the regulatory varieties. To date, the Golden Rice adapted Golden Rice varieties, the process. Approval of a new trans - Network includes 16 national ins- arrangement opened the way to col - genic line might cost in the range of titutions in Bangladesh, China, laborations with public rice research $4 million to comply with all the India, Indonesia, Nepal, the Philip- institutions in developing countries. requirements of toxicology and pines, Viet Nam, and South Africa. allergenicity testing, biochemical Golden Rice does not preclude the equivalency analyses, environmen - Investment in the public sector to use of traditional varieties nor does tal effects, and other tests. Golden develop Golden Rice has been rela - it need more agricultural inputs than Rice has already undergone numer -

20 Golden Rice Magazine Issue 3/2007

ous greenhouse tests and two field More than 50% of under-five child 3. Jones G, Steketee RW, Black RE, trials carried out in Louisiana be- deaths in India and Bangladesh Bhutta ZA, Morris SS, and the cause, at the time, ta rget countries could be averted if Golden Rice Bellagio Child Survival Group. How many child deaths can we prevent had no biosafety regulations in place. were widely adopted (28-30). The this year? Lancet. 2003; 362:65-71. Also, the transgene products have recovery on investment for this 4. Neidecker-Gonzales O, Nestel P, been cleared by bioinformatic analy - intervention would be very fast and Bouis H. Estimating the global costs sis as not being potential allergens. maintenance costs minimal com - of vitamin A capsule supplementa - pared to present interventions tion: A review of the literature. Food and Nutrition Bulletin. 2007; 28:307- Socio-economic outlook (Table 2). Golden Rice and other 316. biofortified crops could substantial - 5. MOST, USAID Micronutrient Pro- Support for biofortification also ly help mitigate MNM worldwide, gram. Cost analysis of the national comes from a number of ex-ante thus contributing to the achieve- vitamin A supplementation programs socioeconomic impact studies on ment of the Millennium Develop- in Ghana, Nepal, and Zambia: A Golden Rice and other biofortified ment Goals in respect of health synthesis of three studies. Arlington, Virginia, USA; 2004. crops in selected target countries. A improvement and poverty allevia - 6. Allen LH. Ending hidden hunger: the recent World Bank report conclud - tion. Biofortification is compatible history of micronutrient deficiency ed that the potential welfare with tradition and has the potential control. Background analysis for improvement for Southeast Asian to generate a huge economic wind - the World Bank-UNICEF Nutrition countries derived from the adoption fall for countries presently affected Assessment Project. World Bank, Washington, D.C; 2000. of Golden Rice would be in the by micronutrient malnutrition. 7. Vijayaraghavan K. Control of micro- range of billions of dollars annually nutrient deficiencies in India: obsta - (27). This gain in terms of health cles and strategies. Nutr Rev. 2002; improvement of the population at References 60:S73-76. large and the economic benefit to 8. Graham RD, Welch RM, Bouis HE. the country could dwarf the nega - 1. Welch RM, Graham RD. Breeding for Addressing micronutrient malnutri - micronutrients in staple food crops tion through enhancing the nutrition - tive impact that the adoption of a al quality of staple foods: principles, transgenic technology could have from a human nutrition perspective. J Exp Bot. 2004; 55:353-364. perspectives and knowledge gaps. In: on trade, due to import bans 2. Stein AJ, Sachdev H, Qaim M. Can Sparks D, ed. Advances in Agro- imposed on transgenic commodi - genetic engineering for the poor pay nomy. Vol 70; 2001:77-142. ties. In most developing countries, off? An ex-ante evaluation of Golden 9. Nestel P, Bouis HE, Meenakshi JV, Rice in India. In: University of Pfeiffer W. Biofortification of staple the largest share of the rice produc - food crops. J Nutr. 2006; 136:1064- tion and most other crops is con - Hohenheim, ed. Research in Devel- opment Economics and Policy 5. Vol 1067. sumed locally anyway. 5; 2006. 10. White PJ, Broadley MR. Biofor- tifying crops with essential mineral elements. Trends Plant Sci. 2005; 10:586-593. Table 2: Disease burden of vitamin A deficiency in India and impact and 11. van Jaarsveld PJ, Faber M, Tanu- cost effectiveness of Golden Rice intervention (28). Even in a worst-case mihardjo SA, Nestel P, Lombard adoption scenario the cost per DALY saved with Golden Rice is well CJ, Benade AJ. Beta-carotene-rich below that of conventional supplementation. DALYs, Disability-Adjusted orange-fleshed sweet potato im- Life Years proves the vitamin A status of pri - mary school children assessed with Annual vitamin A deficiency disease burden the modified-relative-dose-response Annual DALY loss 2,328,000 test. American Journal of Clinical Lives lost 71,600 Nutrition. 2005; 81:1080-1087. 12. Lu S, Van Eck J, Zhou X, et al. The Potential impact of Golden Rice cauliflower Or gene encodes a DnaJ Lives saved 5,500 to 39,700 cysteine-rich domain-containing pro - DALYs saved annually 204,000 to 1,382,000 tein that mediates high levels of beta- (worst-case to best-case scenarios) (8.8 – 59.4 %) carotene accumulation. Plant Cell. 2006; 18:3594-3605. Cost effectiveness of intervention (cost per DALY saved) 13. Ye X, Al-Babili S, Klöti A, Zhang J, WHO benchmark $620 – $1,860 Lucca P, Beyer P, Potrykus I. World Bank benchmark $200 Engineering the provitamin A (beta- carotene) biosynthetic pathway into Conventional supplementation $134 to $599 (carotenoid-free) rice endosperm. Golden Rice (biofortification) $3 to $19 Science. 2000; 287:303-305.

21 SIGHT AND LIFE Golden Rice

14. Schaub P, Al-Babili S, Drake R, 21. Diaz de la Garza RI, Gregory JF, III, 28. Stein AJ, Sachdev HP, Qaim M. Beyer P. Why is Golden Rice golden Hanson AD. Folate biofortification Potential impact and cost-effective - (yellow) instead of red? Plant of tomato fruit. Proc Natl Acad Sci U ness of Golden Rice. Nat Biotechnol. Physiology. 2005; 138:441-450. S A. 2007; 104:4218-4222. 2006; 24:1200-1201. 15. Diretto G, Tavazza R, Welsch R, et 22. Storozhenko S, De Brouwer V, 29. Stein AJ, Sachdev H, Qaim M. al. Metabolic engineering of potato Volckaert M, et al. Folate fortifica - Genetic engineering for the poor: tuber carotenoids through tuber-spe - tion of rice by metabolic engineering. Golden Rice and public health in cific silencing of lycopene epsilon Nat Biotechnol. 2007. India. World Development. 2007; 36 cyclase. BMC Plant Biol. 2006; 6:13. 23. Honein MA, Paulozzi LJ, Mathews (1) (in press). 16. Diretto G, Al-Babili S, Tavazza R, TJ, Erickson JD, Wong LY. Impact 30. Zimmermann R, Qaim M. Potential Papacchioli V, Beyer P, Giuliano G. of folic acid fortification of the US health benefits of Golden Rice: A Metabolic engineering of potato food supply on the occurrence of Philippine case study. Food Policy. carotenoid content through tuber- neural tube defects. Jama. 2001; 2004; 29:147-168. specific overexpression of a bacterial 285:2981-2986. mini-pathway. PLoS ONE. 2007; 24. Al-Babili S, Beyer P. Golden 2:e350. Rice–five years on the road–five 17. Grusak MA, DellaPenna D. Improv- years to go? Trends Plant Sci. 2005; ing the nutrient composition of plants 10:565-573. to enhance human nutrition and 25. Howe JA, Tanumihardjo SA. Carot- health. Annu Rev Plant Physiol Plant enoid-biofortified maize maintains Mol Biol. 1999; 50:133-161. adequate vitamin a status in Mon- 18. Lucca P, Hurrell RF, Potrykus I. golian gerbils. J Nutr. 2006; 136: Genetic engineering approaches to 2562-2567. improve the bioavailability and the 26. Paine JA, Shipton CA, Chaggar S, et level of iron in rice grains. Theor al. Improving the nutritional value of Appl Genet. 2001; 102:392-397. Golden Rice through increased pro- 19. Gross J, Stein RJ, Fett-Neto AG, vitamin A content. Nature Bio- Palma J. Iron homoestasis related technology. 2005; 23:482-487. genes in rice. Genetics Molec. Biol. 27. Anderson K, Jackson LA, Pohl 2003; 26:477-497. Nielsen C. Genetically modified rice 20. Goto F, Yoshihara T, Shigemoto N, adoption: Implications for welfare Toki S, Takaiwa F. Iron fortification and poverty alleviation: Centre for of rice seed by the soybean ferritin International Economic Studies; gene. Nat Biotechnol. 1999; 17:282- 2004: Discussion Paper No 0413. 286.

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22 School-based nutrition in Guatemala Magazine Issue 3/2007

Hierarchization of school-based nutrition for Guatemalan schoolchildren J. De León Arana Universidad de San Carlos, Guatemala City, Guatemala F. Martinez Luzardo Instituto de Ciencias Superiores, Cuba

Correspondence: J. De León Arana, Universidad de San Carlos, Facultad Ciencias Quimicas y Farmacia, Guatemala City, Guatemala Email: [email protected]

Introduction been poorly targeted. Such pro - tions, but also facilitate the evalua - grams have therefore failed to tion of interventions after they In Guatemala, the strategy for improve and/or safeguard the have been carried out to ensure the school-based nutrition interven - nutrition and health of schoolchild - desired impact is achieved. To tions has not been modified since ren in Guatemala. develop these indices, the study 1954, nor has the real impact of included all primary school grades these programs been evaluated. The study reported here was aimed in an integral evaluation that Such interventions have never at developing two important in- assessed rates of anemia, access to been based on comprehensive data dices – the Gini index, used in con - sugar fortified with vitamin A, that include nutrition and health junction with the Lorenz curve, access to salt fortified with iodine, indicators, and access to fortified and a health inequity index microbiological quality of water, foods and drinking water of a high (INIQUIS) – aimed at assisting in rates of infection with parasites, quality in schools. Furthermore, the hierarchization of future and the health-promoting environ - lack of consideration of regional school-based nutrition interven - ment of schools. disparities and inequities means tions. These indices not only interventions were likely to have enable better planning of interven - We propose that the distribution of resources for school lunches has been disparate and inequitable because the principal indicator governing this has always been chronic malnutrition (indicated by height-for-age z-score). However, this approach is incorrect because it does not take into account acute malnutrition (indicated by weight- for-height z-score), which is con - centrated among a small percent - age of schoolchildren (no more than 20%) that varies according to gender, age group and geographic region. This is the principal con- tribution made by interpreting anthropometric information and various aspects of health within the framework of the indices. Eight regions of Guatemala

23 SIGHT AND LIFE School-based nutrition in Guatemala

Even in situations where malnu- Revista Panamericana de trition is observed, there are dis- Salud Pública (the Pan parities. These disparities become American Journal of Public inequitable when allocations are Health) dedicated its made without the aid of a technical May/June and December criterion to assess which region is issues completely to the worst affected. In the absence of factors that determine health such input, equal allocations are inequity and the measure- made, which favor regions that are ment of disparity in health less affected by malnutrition and respectively (2, 3). disfavor regions where it is a seri - ous problem. Past experience has shown that the allocation of funds In order to compile the data neces - in Guatemala has been made sary to fulfill our aims, we imple - according to political inter - mented a conglomerated sampling ests. It was only since 2000, procedure involving two stages: with the construction of First schools were selected; then poverty maps, and later the children were selected from each height census in 2001, that school. The data were subse- funds have been allocated quently classified according to the using poverty as a guideline. 8 regions into which Guatemala is But with time, it has also Weight measurement divided (1). been observed that this ap- proach does not match local realities either, because both the allocation The scientific novelty of this study of the funds and the limited evaluations of school-based nutritional pro - lies in the use of the Gini index in grams are done at the central level, thus leaving out of the process those conjunction with the Lorenz curve, who are truly aware of the needs – the communities themselves. and the inequity index. There are many examples of their use in the By using these indicators, which are simple to create, the local authority field of economics, however these – whether it be the municipality, the neighborhood committees or non- indicators have rarely been applied governmental organizations (NGOs) – will have very accessible informa - in the health field. Here, their tion with which it can meet demands at the local level, allocate appro- use has only been systematized priate funds, monitor processes, and evaluate the results of the school since 2002, when, for example, the lunch program. This would constitute the first undertaking of this kind in Guatemala.

Materials and methods

Population

The target population was established as 2,200,000 children attending classes during 2004 at one of the 15,226 primary schools in the Guate- malan public school system. Schoolchildren were of both sexes, aged between 5 and 14 years, in First to Sixth Grade, and attending morning or evening, urban or rural schools.

Sample

A sample size of 3,200 children was calculated by taking into account a non-response rate of approximately 10% among the selected children. The initial sample was thus 3,600 children. Methodological considera - tions are described in Table 1. Blood sampling

24 School-based nutrition in Guatemala Magazine Issue 3/2007

Table 1: Variables measured in this study

Variable measured Measurement scale (Dimension) Indicators Simple Variables Weight Ratio (weight in kg) Mean ± SD Height Ratio (height in cm) Mean ± SD Age Ratio (age in months) Mean ± SD Hematocrit Ratio (percentage of packed cells) Mean ± SD Intestinal parasites Nominal (presence/absence and type of parasite) Percent positive Ectoparasites Nominal (presence/absence) Percent positive Health promoting Nominal (‘positive’ if they comply Percentage of schools environment of schools with all items listed on the form, that comply ‘negative’ if otherwise) Vitamin A in sugar Ratio (µg/g of retinyl palmitate) Average standard deviation, then decreasing to a cut-off point of 10-20 µg/g to demonstrate adequate fortification (reported as a percentage) Iodine in salt Ratio (µg/g salt) Average standard deviation, then decreasing to a cut-off point of 60-120 ng/g salt to demonstrate if fortified or not (reported as a percentage) Microbiological quality Ratio (MPN of bacteria per mL) Compared with COGUANOR of water for human Standard 29001 for both consumption complying and non-complying schools (reported as a percentage) Composite Variables Gini index, Lorenz curve For boys older than Reported in area, with a value 10 years of age, BMI was of 0 indicating no disparity used; for boys younger than and a value of 1 indicating total 10 year of age, WHZ, HAZ disparity and WAZ were used Inequity indicator Created from: Groups above the cut-off (INIQUIS) 1. For children aged older than value of 0.5 are considered to 10 years: BMI, % anemia, be in a situation of % fortification with vitamin A, above-average inequity % salt iodization

2. For children aged 5-10 years: WHZ, HAZ and WAZ, % anemia, % fortification with vitamin A, % salt iodization

SD: standard deviation MPN: most probable number (method) from serial dilutions WHZ: weight-for-height z-score HAZ: height-for-age z-score WAZ: weight-for-age z-score BMI: body mass index (kg/m 2)

25 SIGHT AND LIFE School-based nutrition in Guatemala

The vertical axis of the graph in 1.0 1.0 Figure 1 represents the accumulated 0.9 0.9 number of cases in proportion to the 0.8 0.8 accumulated population (horizontal 0.7 0.7 axis), indicating that 50% of the

0.6 0.6 cases were found among 20% of the

0.5 0.5 population. This means that, across all the boys and girls in the sample, 0.4 0.4 the cases of acute malnutrition were 0.3 0.3 concentrated in less than 20% of the 0.2 0.2 group. 0.1 0.1

0.0. 0.0. The results from the inequity index,

0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 shown in Table 2 , were varied.

Figure 1: Lorenz curve for acute malnutrition (weight-for-height indi- For girls between 5 and 10 years of cator) among boys (left) and girls (right) from 5 to 10 years of age age, region 8, Petén, was shown to have the most unfavorable situation; Two data collection forms were used, as follows: a) A for boys of the same age group, region 4, the southeast form to record anthropometric data, and b) A form to (which includes Santa Rosa, Jalapa and Jutiapa), was evaluate the health-promoting environment of the shown as being most unfavorable. Of these areas, schools validated by the Institute of Nutrition for Jalapa and especially Jutiapa have often been reported Central America and Panama (INCAP) (4). as being the poorest districts in the country (5). While other municipalities may also be poor, residents in The form for recording anthropometric data was vali - several municipalities in Jalapa and Jutiapa survive on dated using the group mean method, which typically one Quetzal (approximately US$0.13) or less per day, bases the standardization process on 10 subjects. Each which easily meets globally-accepted definitions of subject was measured twice but the interviewer was extreme poverty. not allowed to see the results of the first measurement while taking the second one. The results of the initial Table 2: Inequity by age group and region measurement of the chil - dren were noted in the cor - Age Indicators Initial Regions with Region identified responding form and set group used indicator values >0.5 as the most aside until the second set of unfavorable measurements had been Girls W/H, H/A, H/A 1,2,4,5,6,8 8 made. 5 to 10 W/A, years % anemia, Results sugar and salt fortification Applying the Gini index, it Boys W/H, H/A, H/A 1,2,3,4,6,8 4 was observed that the 5 to 10 W/A, Lorenz curve only reported years % anemia, very obvious disparities along the weight-for-height sugar and salt indicator (acute malnutri - fortification tion) for children aged Girls BMI, % anemia, BMI 1,4,5,6,7 1 between 5 and 10 years, older sugar and salt with index values of 0.589 than fortification for girls and 0.583 for boys 10 years (shown in Figure 1 ). Boys BMI, % anemia, BMI 1,2,3,5,7 1 older than sugar and salt 10 years fortification

26 School-based nutrition in Guatemala Magazine Issue 3/2007

Clearly, the way in which re- cases were concentrated in a few regions. For both genders, 50% of these sources are currently administered cases were concentrated in 20% of the children studied. for school-based nutrition pro - grams does not adequately resolve The greatest inequities manifested in a very discrepant manner. Regions the nutritional problems of school - where the most inequities or unjustified disparities were observed dif - children in every region. fered according to sex and age group. For girls between 5 and 10 years of age, region 8, which corresponds to the district of Petén, displayed the Conclusions greatest inequity; for boys of the same age group, it was the southeast region (the districts of Jalapa, Jutiapa, and Santa Rosa). For both boys We analyzed anthropometric and and girls over 10 years of age, the greatest inequity was observed in health data among schoolchildren region 1, the Guatemala City metropolitan area. aged 5 to 14 years in 100 schools in Guatemala to develop indicators References for the prioritization of resources for school-based nutritional pro - 1. Scheaffer R, Mendenhall W, Ott L. Elementos de Muestreo. Grupo Editorial grams. When used simultaneously, Iberoamérica, México, p 232-240, 1995. 2. Casanueva E. et. al. Nutriología Médica. 2da. Ed. México. Editorial Médica we found that the Gini index and Panaméricana, S.A. de C.V., 2001. the inequity index are able to 3. Ministerio de Salud Pública y Asistencia Social. Encuesta de Salud Materno Infantil differentiate individual regions al- 2002 – ENSMI, 2002. ready known to be afflicted by 4. Martorell R. Results and implications of the INCAP follow-up study. J Nutr malnutrition and lack of a healthy 1995;S125:1127-38. school environment, and that de- 5. Programa Naciones Unidad Para el Desarrollo. Informe Desarrollo Humano, Guatemala, 2003. mand more urgent intervention.

Our results show that most of the schoolchildren did not suffer from acute malnutrition, although they did suffer from chronic malnutri - tion, which is indicated by a height that is lower than would be expect - ed for children of their age.

The greatest disparity in relation to acute malnutrition, as indicated by weight-for-height, was found among boys and girls between the ages of 5 and 10. Furthermore, a large percentage of the boys and Children receiving Albendazole medication girls studied who presented severe

Manual on Vitamin A Deficiency Disorders (VADD) available soon SIGHT AND LIFE Micronutrient powder

Multiple micronutrient-fortified seasoning powders in preschool children in Chongqing suburb

Chen Ke, Li Ting-Yu, Chen Li, Liu You-Xue, Qu Ping, Zhang Yi-Guan , Children’s Hospital, Chongqing University of Medical Science, Chongqing, China

Correspondence: Li Ting-Yu, Children’s Hospital, Chongqing University of Medical Science, Yuzhong District, Chongqing 400016, China Email: [email protected]

Introduction

Vulnerable populations in developing countries gener - ally suffer from multiple micronutrient deficiencies, among which deficiencies of iron, vitamin A, folic acid and iodine are the most commonly reported. Pre- school children are particularly likely to suffer from multiple, concurrent deficiencies, as these deficiences Drawing blood during trial process usually share the same causes. To address this prob - lem, governments have implemented programs to for - which met organoleptic acceptability, shelf life and tify food, provide supplements and transfer knowledge product stability requirements (3). However, the pro- aimed at increasing micronutrient intake – especially duct was not fortified with the full complement of vitamin A and iron. multiple micronutrients – such as vitamin B1, vita- min B2, niacin, folic acid, zinc and calcium – and its In developed countries, food fortification with multi - efficacy had not been tested in China. ple micronutrients has proven highly effective in re- ducing malnutrition (1). In China, several fortification Consequently, the Children’s Hospital of Chongqing methods have been developed but food products for- University of Medical Science in China conducted a tified with multiple micronutrients are currently not randomized controlled trial to investigate the efficacy available on the market (2). Furthermore, the fortifi- of a multiple-micronutrient-fortified seasoning pow - cation of hand-made food products, which are widely der, containing iron, zinc, calcium, vitamin B1, consumed in China, is plagued with problems, such as vitamin B2, niacin, folic acid, and vitamin A, on bio - the homogenization and stability of the nutrients, and chemical micronutrient indices of preschool children hygiene conditions in the production facilities. aged 2–6 years in Chongqing suburb. The purpose of the study was to establish a safe and effective fortified In 1995, a promising fortified product was developed food product for large-scale prevention of micronutri - in Thailand in the form of an instant noodle seasoning ent deficiencies in an at-risk population. powder fortified with iodine, vitamin A, and iron,

28 Micronutrient powder Magazine Issue 3/2007

140 baseline after intervention ) l / g

( 120 n i b o l

g 100 o m e h

f 80 o n o i t

a 60 r t n e c n

o 40 c n a i d

e 20 m

0 VA VAI MMN

Figure 1: Change of hemoglobin by treatment groups

Children putting seasoning pow- der into boiled water by them- 30 baseline after intervention selves (teacher was supervising) ) l / 25 g u ( maltodextrin as a filler was used; n i t i r

r 20 this was indistinguishable in color e f

f and packaging from the fortified o n o

i 15 powder, and had no unpalatable t a r t

n taste. Each serving of the fortified e c

n 10 seasoning powder provided 100% o c

n of the recommended nutrient intake a i d

e 5 (RNI) of the different nutrients. m Intervention subjects were assigned 0 VA VAI MMN to three groups: Group VA re- ceived seasoning powder that con - Figure 2: Change of ferritin by treatment groups tained 500 µg vitamin A; Group VAI received 500 µg vitamin A plus 12 mg iron; while Group Material and methods MMN (multiple micronutrients) provided 500 µg vitamin A, 12 µg Subjects and ethical approval iron, 0.7 mg thiamine, 0.7 mg riboflavin, 200 µg folic acid, 7 mg The supplementation program was performed in the Banan District of niacin, 12 mg zinc and 800 mg cal - Chongqing suburb from December 2005 to June 2006. Banan District is a cium. The study was designed as a middle-income suburb and had been the site of a previous child nutrition double-blinded randomized trial project supported by SIGHT AND LIFE. Over 300 preschool children and the three groups consumed the aged 2–6 years were recruited from three nurseries randomly chosen from fortified seasoning powder for six the region. Informed, written consent was obtained from parents and months. guardians who allowed their children to participate in the study. The research protocol was reviewed and approved by the institutional ethical Blood sampling and biochemical committee of the Children’s Hospital. assessment

Intervention At the start and end of the six- month trial, approximately 3 mL of For the study, researchers applied the seasoning powder, fortified with blood samples were collected by various combinations of micronutrients, to cooked porridge, bean milk, venepuncture from an antecubital soup or noodles. For the control, the same seasoning powder containing vein from each subject before

29 SIGHT AND LIFE Micronutrient powder

breakfast. Using the hemiglobincyanide method, 1 mL The age of the children (mean ± SD) was 4.0 ± 0.85 yr, was drawn into a container with heparin to measure and 50.1% were female. The total prevalence of ane - hemoglobin (Hb). The concentrations of serum ferritin mia was 23.5%, with the majority of those affected and serum retinol binding protein (RBP) were meas - (20.3%) having mild anemia. The proportions of ured by the method of enzyme-linked immunosorbent children suffering from vitamin A deficiency (VAD, and C-reactive protein (CRP) by particle-enhanced defined as serum retinol <0.7 µmol/L) and marginal immunoturbidimetry. Serum retinol concentration was VAD (defined as serum retinol 0.7–1.05 µmol/L) were determined by using high-performance liquid chro - 6.3% and 25.9%, respectively. Using a cut-off value matography (HPLC). of 12 µg/L for ferritin, 15.0% of these children were iron deficient. Differences in CRP among the groups Results were not apparent (data not shown).

At baseline, a total of 282 eligible preschool children After supplementation, the prevalence of anemia, were recruited for the study. The primary outcome – VAD and marginal VAD decreased to 10.2%, 0.9% micronutrient status indicated by biochemical analysis and 17.3%, respectively. The concentrations of Hb, and anthropometric indices – was obtained from the ferritin, retinol and RBP at baseline and after six 226 preschool children (61, 71 and 94 from groups months are shown in Figures 1–4 . The concentration VA, VAI and MMN, respectively) who participated of Hb increased significantly (P<0.0001) in all groups. until the study was completed. However, there were no significant differences in Hb (P>0.05) among the groups. The concentration of fer - ritin decreased significantly in all groups with the smallest decrease 2.0 baseline after intervention

) in group VA (P<0.05). After l / l o supplementation, the concentra - m u (

l 1.5 tions of serum retinol in group VAI o n i

t and MMN markedly increased e r f

o (P<0.01). RBP decreased sig- n o i

t 1.0 nificantly in group VA (P<0.01) a r t

n and increased in group MMN e c n

o (P<0.0001) while no change oc- c

f 0.5 o curred in group VAI (P>0.05). n a e m Discussion 0.0 VA VAI MMN Among all three groups, the con - centration of Hb was markedly Figure 3: Change of hemoglobin by treatment groups increased compared with the base - line level. However, the addition of

40 baseline after intervention iron to the fortified seasoning pow - der consumed by the the VAI and MMN groups had no additional 30 effect on Hb compared with the effect of the product fortified with vitamin A alone. This may be 20 associated with reasonably good iron status among the children at baseline, and the well-established 10 positive effects of vitamin A on

m hematopoesis (4). e d i a n

c 0.0

o Contradicting prior research (5, 6),

n VA VAI MMN c e

n the results of this study showed that t r a

t the three different fortification i Figuro e 4: Change of RBP by treatment groups n

o regimes decreased ferritin levels f R B P ( m g

30 / l ) Micronutrient powder Magazine Issue 3/2007

2. Liu ZH. http://scholar.ilib.cn/A-zgspjj200202002.html Manda- rin.(General situation on development of enhancing nutrition). http://scholar.ilib.cn/P-tgspjj.html China Food Additives 2002; 2:3–8. 3. Chavasit V, Tontisirin K. Triple fortification of instant noodles in Thailand. Food Nutr Bull 1998;19:164–16 . 4. West KP, Jr, Gernand AD, Sommer A. Vitamin A in nutritonal anemia. In: Kraemer K, Zimmermann MB, eds. Nutritional Anemia. Basel: SIGHT AND LIFE Press, 2007:133–53. 5. Graham JM, Haskell MJ, Pandey P, Shrestha RK, Brown KH, Allen LH. Supplementation with iron and riboflavin enhances dark adaptation response to vitamin A-fortified rice in iron-deficient, pregnant, night blind Nepali women. Am J Clin Nutr 2007;85: One of the trial sites: Dajiang Nursery 1375–84. 6. Makola D, Ash DM, Tatala SR, Latham MC, Ndossi G, Mehansho (an indicator of iron stores) after the six-month supple - H. A micronutrient-fortified beverage prevents iron deficiency, reduces anemia and improves the hemoglobin concentration of mentation period. This decrease is likely due to the for - pregnant Tanzanian women. J Nutr 2003;133:1339–46. tification with vitamin A of all the seasoning powder 7. Muslimatun S, Schmidt MK, Schultink W, et al. Weekly supple - consumed by the groups, suggesting the mobilization mentation with iron and vitamin A during pregnancy increases of iron for hematopoiesis (7). hemoglobin concentration but decreases serum ferritin concentra - tion in Indonesian pregnant women. J Nutr 2001;131:85–90. 8. Winichagoon P, McKenzie JE, Chavasit V, et al. A multimicronu - The results also indicate that adding other micronutri - trient-fortified seasoning powder enhances the hemoglobin, zinc, ents to food fortified with vitamin A had an additional and iodine status of primary school children in North East effect in improving serum retinol and RBP. As one Thailand: a randomized controlled trial of efficacy. J Nutr of the studies had reported (8), fortified seasoning 2006;136:1617–23. powder has several advantages as a supplementary vehicle. Firstly, it is packaged in a single-serving- sized sachet that can prevent an overdose and protects the contents from light, air and moisture. Secondly, seasoning powder can be used for many types of foods without the need for additional cooking before con - suming it, thus avoiding losses due to thermal instabil - ity and/or leaching. Lastly, it is an ideal vehicle to incoporate into pre-existing nursery lunch programs, which would help program planners avoid the need for costly social marketing campaigns.

The authors note that more studies on the effect of for - tified seasoning powder are needed, including assess - ments of anthropometric status.

Acknowledgements Children participating in field trial

We thank all the children and patients participating in the survey. We also thanks the health care workers in Banan Healthy Center for Women and Children of Chongqing, China, particularly Tian Weiming, Wang Wuli and Liu Guanjun, for their diligent assistance. This study was supported by a grant from SIGHT AND LIFE.

References

1. Mehansho H, Mellican RI, Hughes DL, Compton DB, Walter T. Multiple-micronutrient fortification technology development and evaluation: from lab to market. Food Nutr Bull 2003;24:111–9. Measurement of weight and height

31 SIGHT AND LIFE Vitamin A research update

Recent advances in vitamin A absorption and transport

Editor’s note: Nuttaporn Wongsiriroj received a travel grant from SIGHT AND LIFE to participate in the Micronutrient Forum in Turkey 2007

Nuttaporn Wongsiriroj Institute of Molecular Biology and Genetics, Mahidol University, Salaya, Nakhonpathom, Thailand William S. Blaner Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, USA

Correspondence: William S. Blaner, Department of Medicine, College of Physicians and Surgeons, Columbia University, 630 W. 168th St., New York, NY 10032, USA Email: [email protected]

Introduction acquired from the diet. There are min A is taken up by other organs, two forms of vitamin A available in including the eye and adipose tis - Vitamin A deficiency (VAD) re- the diet, preformed vitamin A and sue. Vitamin A stored in liver and mains a public health problem caus - provitamin A carotenoids. Pre- adipose tissue is mobilized and ing morbidity and mortality in formed vitamin A consists primari - delivered to target tissues for vita - infants throughout much of the ly of retinol and retinyl esters that min A action by retinol-binding world (1). To correct VAD, a large have been consumed in animal food protein (RBP or RBP4) (4, 5). dose of preformed vitamin A products. Provitamin A carotenoids (Although the older literature has (retinol) is administered (2). Al- such as ␤-carotene, ␣-carotene and referred consistently to this vita- though it has long been clear that ␤-cryptoxanthin are found in dark min A-binding protein as RBP, this approach is an effective one for green and yellow fruits and vegeta - investigators recently have started treating and preventing VAD, only bles (mangoes, papaya, carrots, to use a version of its genetic recently have the molecular pro- dark green leafy vegetables and red nomenclature, Rbp4 , to describe the cesses and factors responsible for palm oil are some rich dietary protein as RBP4.) facilitating vitamin A absorption in sources of provitamin A caroten- the intestine and transport in the cir - oids). The different dietary vita- Within tissues, retinol is converted culation begun to be understood min A forms are processed in the to its biologically active metabo - fully at the molecular level. This intestine (see Figure 1 and below lites. The active form of vitamin A review will focus on recent ad- for more details) to retinyl esters, needed to support vision is 11- cis - vances in our understanding of the and the retinyl esters are packaged retinaldehyde. All other actions of molecular processes and biochemi - along with other dietary lipids into vitamin A within the body are cal factors that are responsible for newly synthesized chylomicrons. thought to involve retinoic acid and the uptake of dietary vitamin A by These nascent chylomicrons are its effects on regulating gene the intestine and its transport in the secreted into the lymphatic system expression. All- trans -retinoic acid blood. for uptake into the general circula - can bind to each of the three tion and delivery to the liver and retinoic acid nuclear receptors Overview other tissues (3, 4). Approximately (RAR ␣, RAR ␤, and RAR ␥) and 75% of chylomicron (dietary) vita - each of three retinoic X receptors Humans as well as other animal min A is taken up by hepatocytes in (RXR ␣, RXR ␤, and RXR ␥), species have no capacity for de the liver, the major organ for vita - whereas 9- cis -retinoic acid binds novo vitamin A synthesis. All vita - min A storage in the body. The only the RXRs. After binding, these min A present in the body must be remainder of postprandial vita- nuclear receptors become activated

32 Vitamin A research update Magazine Issue 3/2007

and can then regulate (increase or needed to support reproduction, cell to retinol; 3) The conversion of decrease) gene expression in the proliferation and differentiation, and retinol to retinyl ester; and 4) nucleus of cells. Vitamin A has an immunity (5). Retinyl ester incorporation into important role in regulating the nascent chylomicrons for secretion actions of other hormone and nutri - Intestinal absorption of along with other dietary lipids into ent-dependent genes because the vitamin A the lymphatic system. These RXRs are able to form pro - processes are summarized in tei n–protein complexes with vita - The intestinal absorption of vita- Figure 1 . The proteins that are min D nuclear receptors (VDRs), min A can be thought of as occur - mentioned in this review that are thyroid hormone nuclear receptors ring in four stages. These are: 1) known to be involved in the intes - (TRs), and peroxisome proliferators- The processing of dietary vita- tinal absorption of vitamin A are activated nuclear receptors (PPARs). min A in the lumen of the intestine listed in Table 1. Through these interactions, vita- and uptake into the enterocyte min A and the RXRs can regulate a (also known as intestinal mucosa 1. Luminal processing and cellular broad spectrum of hormonally and cells); 2) The intracellular metabo - uptake nutrient-responsive genes that are lism of the different dietary forms The major sources of vitamin A present in the diet are retinol, ret- inyl ester and provitamin A carot-

Lumen Provitamin A Preformed vitamin A enoids. Retinol is absorbed as such ␤-carotene Retinol Retinyl ester from the intestinal lumen into the mucosal cells. Retinyl esters must SR-BI REH be hydrolyzed to retinol prior to

Retinol intestinal absorption either within ␤-carotene CRBP-II BCMO1 Retinol-CRBP-II the intestinal lumen by pancreatic Retinal reductase CRBP-II LRAT Enterocyte ARATs triacylglycerol lipase (PTL) or at Retinaldehyde-CRBP-II Retinyl ester surface of the enterocyte by brush Triglyceride ApoB Cholesterol MTP Chylomicrons border retinyl ester hydrolase (REH). At present, it is unclear Endothelium Lymph duct which enzyme is primarily respon - sible for this process. Another en- Figure 1: Vitamin A arrives from the diet in the intestinal lumen in two zyme long proposed to be impor - forms, provitamin A carotenoids (e.g., ␤-carotene) and preformed vita - tant for catalyzing luminal retinyl min A (retinol and retinyl esters). Provitamin A carotenoids; like ␤- ester hydrolysis, carboxyl ester carotene are absorbed both passively and via facilitated diffusion lipase (CEL), appears to not be involving the brush border membrane receptor SR-BI. Preformed vita - essentially involved in the intestin - min A arriving as retinyl ester from the diet must undergo hydrolysis al absorption of vitamin A. How- prior to its uptake into the enterocyte via the action of a retinyl ester ever, studies of CEL-deficient hydrolase (REH). Several luminal retinyl ester hydrolases and a brush border retinyl ester hydrolase have been proposed to have important mice indicated that this enzyme is roles in this process. Dietary vitamin A arriving as retinol is absorbed not needed to assure uptake of die- directly into the enterocyte. Upon entry of the retinol into the entero - tary vitamin A. Other enzymes cyte, it immediately binds to CRBP-II. Within the enterocyte, present in the lumen of the intes - ␤-carotene is acted upon by carotene cleavage enzyme (CCE) and con - tine or on the enterocyte surface verted to retinaldehyde, which then also binds CRBP-II. Retinaldehyde may also participate in the hydrol - bound to CRBP-II is subsequently reduced to retinol via the actions of ysis of dietary retinyl esters (6). a retinal (retinaldehyde) reductase. LRAT then catalyzes the esterifica - Enzyme assays in CEL-deficient tion of CRBP-II bound retinol to retinyl ester, which is incorporated into mice showed that PTL exhibits newly synthesized chylomicrons. Some retinyl ester is likely formed both pancreatic triacylglycerol from retinol through the actions of an acyl-CoA-dependent enzyme lipase activity and retinyl ester (ARAT) in a manner that becomes progressively more significant as the hydrolase activity, suggesting that amount of retinol being consumed in the diet or administered pharma - cologically increases. The assembly of newly synthesized chylomicrons PTL may be the main retinyl ester is dependent on the presence of apoB, MTP, and dietary triacylglycerols hydrolase in the intestinal lumen. and cholesterol However, a third unidentified ret- inyl ester hydrolase, neither CEL

33 SIGHT AND LIFE Vitamin A research update

Table 1: Proteins important for facilitating vitamin A absorption in the intestine

Pathway Protein(s) Role(s)

1. Cellular uptake into Retinyl ester hydrolases Hydrolyze retinyl ester arriving from the diet to the enterocyte (pancreatic triacylglycerol retinol hydrolase [PTL], brush border retinyl ester hydrolase)

Enterocyte receptor SR-BI is needed to facilitate intestinal scavenger receptor class B, carotenoid uptake across the enterocyte brush type I (SR-BI) border membrane

Unknown membrane receptors As yet to be identified transporters may facilitate provitamin A and preformed vitamin A uptake from the intestinal lumen into the enterocyte

2. Enterocyte metabo - Carotene cleavage enzyme Cleaves ␤-carotene symmetrically into two mol - lism of provitamin (BCMO1) ecules of retinaldehyde A carotenoids to vitamin A Retinaldehyde reductase Intestinal retinaldehyde reductase remains to be identified

Cellular retinol-binding protein, Binds retinol and retinaldehyde and serves as a type II (CRBP-II) substrate for esterification; is found only in the intestine in the adult

3. Retinol esterifica - Lecithin-retinol acyltransferase Primary enzyme responsible for retinyl ester for - tion within the (LRAT) mation in the intestine enterocyte Diacylglycerol acyltransferase 1 An enzyme that catalyzes triacylglycerol synthe - (DGAT-1) sis from diacylglycerol and fatty acyl-CoA. Able to catalyze retinyl esterification in a fatty acyl-CoA dependent manner. Acts in response to both physiologic and pharmacologic doses of retinol

Acyl-CoA:retinol acyltransferases Active under pharmacological (high dose) of (ARATs) retinol by unknown ARATs

4. Chylomicron Apolipoprotein B (apoB) ApoB48 is synthesized in the intestine and formation essential for chylomicron formation

Microsomal triacylglycerol Plays an important role in the transfer of lipid transfer protein (MTP) during lipoprotein assembly. Lack of this pro - tein (in abetalipoproteinemia patients) leads to an inability to produce chylomicrons and very low density lipoproteins, and impairs vitamin A uptake

34 Vitamin A research update Magazine Issue 3/2007

nor PTL, is present in the lumen (7). Regardless of the literature also suggests that an as yet to be identi - enzymatic origin, the free retinol formed from retinyl fied acyl-CoA:retinol acyltransferase (ARAT) activity ester hydrolysis appears to be taken up by the intestin - also may play a role in this process, especially when al mucosal cells by both passive diffusion and facili - very high doses of vitamin A are ingested (10). The tated diffusion. The proteins involved in facilitated molecular identity of this ARAT has long remained retinol uptake remain to be determined. elusive. Recently, three independent in vitro studies suggested that diacylglycerol acyltransferase, type 1 The uptake of provitamin A carotenoids by entero - (DGAT-1) is able to esterify retinol to retinyl ester in cytes has long been thought to occur via passive diffu - an acyl-CoA-dependent manner and thus able to act as sion, similar to other dietary lipids. However, recent an ARAT in vitro (11–13). DGAT-1 was originally studies suggest that some provitamin A carotenoid identified as an enzyme capable of triacylglycerol uptake may be mediated by a specific membrane biosynthesis from diacylglycerol and fatty acyl-CoA transporter (i.e., scavenger receptor class B, type I and is expressed in many tissues, including the intes - [SR-BI]) and possibly other enterocyte transporters. tine. This suggests that DGAT-1 may act physiologi - Studies of SR-BI-deficient mice indicated that SR-BI cally in the intestine to catalyze fatty acyl-CoA- can facilitate the absorption of ␤-carotene and may be dependent retinol esterification and may have a role in important for ␤-carotene absorption, at least in mice facilitating the processing of dietary vitamin A in the fed a high-fat diet (8). Once inside the enterocyte, intestine. provitamin A carotenoids can be cleaved centrally at the 15, 15’ bond to yield two molecules of retinalde - 4. Chylomicron formation and secretion into the lym - hyde by the actions of carotene cleavage enzyme. phatic system

2. Intracellular metabolism converging on retinol Upon retinol esterification, the resulting retinyl esters are incorporated into newly synthesized chylomi - Within the enterocyte, newly absorbed retinol or crons. Chylomicrons consist of triacylglycerols, phos - retinaldehyde formed through carotenoid cleavage is pholipids, cholesterol, retinol, retinyl esters and sever - bound to cellular retinol-binding protein, type II al specific apolipoproteins (apoB48, apoA-I, apoA-IV (CRBP-II). This protein is expressed solely in the small and apoCs). Chylomicron synthesis occurs within the intestine. CRBP-II plays a very important role in fa- enterocyte and requires apoB48. Additional proteins, cilitating vitamin A uptake in the intestine, since mice including microsomal triacylglycerol transfer protein lacking CRBP-II show an impaired capacity of (MTP), is required for chylomicron assembly (14). In vitamin A absorption especially when dietary vita- abetalipoproteinemia patients, intestinal chylomicron min A amounts are low, suggesting that CRBP-II has a and hepatic very low density lipoprotein (VLDL) syn - role in intestinal absorption but is not essentially need - thesis and secretion are absent due to a genetic defect ed for this process (9). Retinaldehyde bound to CRBP- of MTP. This results in the malabsorption of dietary II is subsequently reduced to retinol. Many enzymes fat and fat-soluble vitamins, including vitamin A. are able to catalyze this reaction, including short-chain These patients show an impaired ability to absorb and medium-chain alcohol dehydrogenases as well as vitamin A and develop retinal degeneration in spite of members of the aldo-keto reductase enzyme family. long-term vitamin A supplementation (15). Within Until now, no unique intestinal retinaldehyde reductase 6 to 10 hours after consumption of a meal containing has been identified as being responsible for catalyzing vitamin A, the dietary vitamin A is taken into the body conversion of retinaldehyde to retinol. The retinol as retinyl esters in chylomicrons for tissue uptake. formed through either retinaldehyde reduction or from However, small amounts of free retinol may also be retinyl ester hydrolysis (upon uptake of preformed vita - absorbed in chylomicrons or secreted into portal cir - min A) also binds CRBP-II where it serves as a good culation where it may bind intestinally synthesized substrate for reesterfication by the enzyme lecithin- high density lipoprotein (HDL) or possibly apo-RBP4 retinol acyltransferase (LRAT). that may be present in the circulation. Support for this possibility comes from the observation that 3. Retinol esterification abetalipoproteinemia patients absorb some dietary vitamin A (16). It has been postulated that these The literature suggests that CRBP-II facilitates retinyl patients absorb retinol on either intestinal HDL or ester formation from newly absorbed retinol and that apo-RBP4 present in the portal circulation. LRAT is the key enzyme involved in catalyzing retinyl ester synthesis in the small intestine. However,

35 SIGHT AND LIFE Vitamin A research update

Vitamin A transport in the in the circulation are summarized this is the case in humans as well circulation in Figure 2 . (22). Retinyl esters are normally secreted at low concentrations As mentioned above, after con - Retinol is transported in the blood (1–2% of those of retinol-RBP4) suming a vitamin A-rich meal, bound to RBP4 (17). RBP4 is pri - from the liver bound to newly syn - vitamin A can be present in the cir - marily synthesized and secreted thesized VLDL (3). The physiolog - culation at relatively high concen - from the liver, where the majority ic significance of VLDL retinyl trations as retinyl esters in chy - of the body’s vitamin A is stored ester has not been systematically lomicrons and chylomicron rem - (18, 19). However, RBP4 is also investigated but, invoking similari - nants. In addition, vitamin A is synthesized and secreted in lesser ties between VLDL and chylomi - present in the circulation in other amounts by adipose tissue (20). cron metabolism, it seems likely forms. The major form of vita- RBP4 forms a one-to-one protein- that retinyl ester contained within min A present in the fasting circu - protein complex with another VLDL is destined for uptake by lation is retinol bound to RBP4. blood protein, transthyretin (TTR), extrahepatic tissues. The circula - However, the fasting circulation and this prevents renal clearance of tion also contains low amounts also contains low amounts of the retinol-RBP4 by the glomeru - of retinol- ␤-glucuronides and retinoic acid bound to albumin, lus (21). In well-nourished humans retinoyl- ␤-glucuronides (amounts low amounts of retinyl esters and animal models, fasting blood similar to those of all- trans - and bound either to VLDL or low den - amounts of all- trans - and 13- cis - 13- cis -retinoic acid) that are fully sity lipoprotein (LDL), as well as retinoic acid bound to albumin are water soluble (3). The body may water soluble glucuronides of approximately 0.1–0.4% of those use these ␤-glucuronides of vita - retinol and retinoic acid. In addi - of retinol-RBP4 during fasting (3). min A to satisfy tissue vitamin A tion, provitamin A carotenoids Yet, this circulating retinoic acid needs, because they can be readily may be present in the circulation can contribute significantly to tis - hydrolyzed to retinol and retinoic bound to VLDL and LDL. The dif - sue pools of retinoic acid in well- acid (3); however, this hypothesis ferent forms of vitamin A present nourished animals and presumably has not been experimentally pro- ven. It is important to note that ␤-glucuronides of vitamin A meta- bolites are routinely eliminated Retinol-RBP4-TTR Retinyl-␤- Retinyl-␤- Retinoic acid bound glucuronides glucuronides to albumin from the body.

RBP4 and type 2 diabetes ADH or RALDH Retinol Retinal Retinoic acid RoIDH Until the recent publication of Retinyl esters in chylomicrons REH LRAT work by Kahn and colleagues (23), or their remnants the sole known physiologic action Retinyl esters BCMO1 of RBP4 was the mobilization of Retinyl esters in VLDL and LDL retinol from tissue stores. Kahn Transcriptional and colleagues reported data that Carotenoid acitivity Carotenoid in indicate RBP4 synthesized and VLDL and LDL secreted by adipocytes has an Target cell NUCLEUS important role in regulating sys - BLOOD CYTOPLASM temic insulin sensitivity and glu - cose homeostasis in humans, as well as in animal models (23). Figure 2: Vitamin A is present in the circulation in many forms. In the Serum RBP4 amounts were shown fasting circulation, retinol bound to RBP4 is the major vitamin A form to be significantly increased in sev - in the blood. Also present in the fasting circulation, albeit in much lower amounts than retinol-RBP4, are all- trans - and 13- cis -retinoic acids eral mouse models of obesity and bound to albumin, retinyl esters present in VLDL and LDL and ␤-glu - insulin resistance, thus suggesting curonides of both retinol and retinoic acid. In addition, provitamin A RBP4 is an adipocyte-derived sig - carotenoids are also present in VLDL and LDL and this provitamin A nal that can impair insulin sensitiv - carotenoid may be converted within tissues to vitamin A. The abbrevi - ity and hence modulate glucose ations given for enzymes catalyzing metabolic conversions are the same as in Figure 1 homeostasis. Studies in humans also support a role for RBP4 in the

36 Vitamin A research update Magazine Issue 3/2007

development of insulin resistance References and type 2 diabetes and provide a causal basis for known linkages 1. Sommer A, West KP Jr. Vitamin A deficiency: health, survival, and vision. New York between obesity, where RBP4 and Oxford: Oxford University Press, 1996. secretion would be elevated due to 2. WHO, UNICEF, IVACG Task Force: Vitamin A supplements. In: A guide to their use in the treatment and prevention of vitamin A deficiency and xerophthalmia. 2 nd an increase in adipocyte number, ed. Geneva: World Health Organization, 1997. and the development of type 2 dia - 3. Blaner WS, Olson JA. Retinol and retinoic acid metabolism. In: Sporn MB, Roberts betes (24) Human studies have AB, Goodman DS, eds. The retinoids: biology, chemistry and medicine. 2 nd ed. New shown statistically significant pos - York: Raven Press, 1994. itive correlations between serum 4. Harrison EH. Mechanisms of digestion and absorption of dietary vitamin A. Annu Rev Nutr 2005;25:87–103. RBP4 amounts and the magnitude 5. Wongsiriroj N, Wasantwisut E, Blaner WS. Vitamin A deficiency in children. In: of insulin resistance in obese pa- Glew R, Rosenthal M, eds. Clinical studies in medical biochemistry. 3 rd Ed. New tients experiencing impaired glu- York and Oxdord: Oxford University Press, 2006. cose tolerance and type 2 diabetes 6. Weng W, Li L, van Bennekum AM, et al. Intestinal absorption of dietary cholesteryl as well as in non-obese, non-dia - ester is decreased but retinyl ester absorption is normal in carboxyl ester lipase betic subjects with a strong family knockout mice. Biochemistry 1999;38:4143–9. 7. van Bennekum AM, Fisher EA, Blaner WS, Harrison EH. Hydrolysis of retinyl esters history of type 2 diabetes (24). by pancreatic triglyceride lipase. Biochemistry 2000;39:4900–6. These exciting findings provide a 8. van Bennekum AM, Werder M, Thuahnai ST, et al. Class B scavenger receptor-medi - new level of understanding of rela - ated intestinal absorption of dietary beta-carotene and cholesterol. Biochemistry tionships between vitamin A 2005;44:4517–25. transport and the development of 9. E X, Zhang L, Lu J, et al. Increased neonatal mortality in mice lacking cellular retinol- binding protein II. J Biol Chem 2002;277:36617–23. insulin resistance and raise the 10. Ong DE, Newcomer ME, Chytil F. Cellular retinoid-binding proteins. In: Sporn MB, possibility of a new therapeutic in- Roberts AB, Goodman DS, eds. The retinoids: biology, chemistry and medicine. 2 nd tervention to lower serum RBP4 ed. New York: Raven Press, 1994. concentrations as an anti-diabetic 11. O’Byrne SM, Wongsiriroj N, Libien J, et al. Retinoid absorption and storage is therapy. impaired in mice lacking lecithin: retinol acyltransferase (LRAT). J Biol Chem 2005;280:35647–57. 12. Yen CL, Monetti M, Burri BJ, Farese RV. A human skin multifunctional O-acyltrans - ferase that catalyzes the synthesis of acylglycerols, waxes, and retinyl esters. J Lipid Res 2005; 46:1502–11. 13. Orland MD, Anwar K, Cromley D, et al. Acyl coenzyme A dependent retinol esteri - fication by acyl coenzyme A: diacylglycerol acyltransferase 1. Biochim Biophys Acta 2005;1737:76–82. 14. Hussain MM, Fatma S, Pan X, Iqbal J. Intestinal lipoprotein assembly. Curr Opin Lipidol 2005;16:281–5. 15. Chowers I, Banin E, Merin S, Cooper M, Granot E. Long-term assessment of com - bined vitamin A and E treatment for the prevention of retinal degeneration in abetal - ipoproteinaemia and hypobetalipoproteinaemia patients. Eye 2001;15:525–30. 16. Berriot-Varoqueaux N, Aggerbeck LP, Samson-Bouma M. [Microsomal triglyceride transfer protein and abetalipoproteinemia.] Ann Endocrinol (Paris) 2000;61:125-9. 17. Kanai M, Raz A, Goodman DS. Retinol-binding protein: the transport protein for vita - min A in human plasma. J Clin Invest 1968;47:2025-44. 18. Blomhoff, R, Rasmussen M, Nilsson A, et al. Hepatic retinol metabolism. Distribution of retinoids, enzymes, and binding proteins in isolated rat liver cells. J Biol Chem 1985;260:13560–5. 19. Blaner WS, Hendriks HF, Brouwer A, et al. Retinoids, retinoid-binding proteins, and retinyl palmitate hydrolase distributions in different types of rat liver cells. J Lipid Res 1985;26: 1241–51. 20. Soprano DR, Blaner WS. Retinol-binding protein. In: Sporn MB, Roberts AB, Goodman DS, eds. The retinoids: biology, chemistry, and medicine. 2 nd Ed. New York: Raven Press, 1994. 21. Peterson PA. Studies on the interaction between prealbumin, retinol-binding protein, and vitamin A. J Biol Chem 1971;246: 44–9. 22. Kurlandsky SB, Gamble MV, Ramakrishnan R, Blaner WS. Plasma delivery of retinoic acid to tissues in the rat. J Biol Chem 1995;270: 17850–7. 23. Yang Q, Graham TE, Mody N, et al. Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes. Nature 2005; 436:356–62. 24. Graham TE, Yang Q, Blüher M, et al. Retinol-binding protein 4 and insulin resistance in lean, obese, and diabetic subjects. N Engl J Med 2006;354: 2552–63.

37 SIGHT AND LIFE Consumer research in micronutrients

Applying behavior change research to promote micronutrients

Dorothy Foote 3 Pickering Street #02-36, Nankin Row, China Square Central, Singapore 048660 Email: [email protected]

Introduction

What motivates people to change? Why do they choose the foods that they do? How can public health programs influence people to make healthy choices? These were some of the main questions addressed by scientists and nutrition practitioners at the Symposium on Understanding and Influencing Consumer Food Behaviors for Health, organized by the International Life Sciences Institute (ILSI) in Singapore on July 18–20, 2007. Consumer research aims to understand the various Many countries are now facing the double burden of factors that can predict food choices. This diagram is from the presentation, “Overview of consumer malnutrition: overnutrition and undernutrition coexist science and consumer food behavior” by Dr Adam within the same regions, cities, neighborhoods, and Drewnowski even households. The determinants of food security have been described as availability, accessibility and choice. However, poverty and increase the availabili - the relative contribution of these determinants varies across and within ty and accessibility of food among country settings (1). the poor, market research to under - stand the mind of the consumer, For middle to higher income segments of a population, most foods are and creative strategies to remove relatively available and accessible. Among these groups, influencing barriers and enable new behaviors consumer choices is the main challenge for public health communica - are all needed to ‘sell’ healthy tions. In this context, ‘healthier-choice’ products must compete with less products and healthy behaviors. healthy commercial alternatives on the traditional four P’s of marketing (product, price, placement and promotion). Among poorer segments of a The primary focus of the ILSI population, choices are more limited, based on the availability and acces - Symposium was behavior change sibility of products. as a means to address the rising levels of obesity and chronic dis - So although the relative contribution of choice as a determinant of food ease in the Asian region. However, behavior varies widely across the spectrum of development, it can be the theories and various approach - observed that in all contexts knowledge alone is not enough to change es that were described are also rel - practice. Eating is a complex behavior that is influenced by social, cul - evant for promoting micronutrients tural, economic, and psychological factors. Continuing efforts to reduce to address undernutrition. Case

38 Consumer research in micronutrients Magazine Issue 3/2007

studies from China, Indonesia, and Singapore demon - “Urbanization, a major global trend, has placed strated how programs are working to increase the severe constraints on the food distribution systems. availability and accessibility of micronutrients, and to The urban consumer is many stages away from the change consumer behaviors for healthier choices. sources of food production and the food supply. Foods and beverages delivered to city dwellers need to be Consumer science – know your audience nutritious, affordable, and safe. Another societal trend – the entry of women into the work force – has Dr. Adam Drewnowski, of the University of Washing- limited the amount of time traditionally given to the ton, g ave an overview of consumer science and con - purchasing and preparing of food. ‘Time Poverty’ is a sumer food behavior. The purpose of applying con - new social phenomenon”(2). sumer science and research methods is to understand the mind of the consumer – the ‘what, when, why, Marketing strategies – learning to listen where, and how often of eating.’ Understanding these factors opens the door to successful marketing. What In a market where many similar products compete for is the socioeconomic position of the target group? (I.e. the consumer’s choice, marketing strategies have had what cost can they afford?) What is the geographic to adapt quickly to rapidly changing consumer prefer - comparison of where people live and work, where ences. The methods and tools that modern marketers they eat, and what kinds of foods are available? (I.e. have developed to listen to consumers can also bene - markets, supermarkets, street vendors, fast-food, fit social marketing and nutrition promotion. etc.?) And importantly, what do they most like to eat? (I.e. what does the consumer think and feel about the Dr. Howard Moscowitz, of Moscowitz Jacobs Inc., taste of the food, the benefits, the concerns, and how described the method of Rule-Developing Experi- the food fits into their lifestyle, etc.?) All of these fac - mentation (RDE, www.mji-designlab.com), a method tors contribute to food choices and ultimately to for understanding the ‘mind’ of the consumer in an health outcomes. ongoing, disciplined, and archival fashion. RDE uses a rapid survey of respondents’ preferences (i.e. what The issue of food preference was explored in more product characteristics they like, or which messages detail in another presentation by Dr. Drewnowski, and visual elements on a poster or package design Biological, social, cultural, and psychological influ - appeal to them the most). The data on consumers’ ences on food choice. He described the concept of preferences, along with their basic sociodemographic ‘Time Poverty’ – a social phenomenon that plays an information, is then used to dissect the various prefer - increasingly important role in food choices: ence segments that exist within the population.

Theories of behavior change

The process by which people are led to adopt new severity) and the perceived effectiveness of the new behaviors has been described in various ways over the behavior to prevent or treat the illness. The individual years. Dr. John Foreyt, of Baylor University, gave an must be convinced that the new behavior is effective, overview of some of the most influential theories of and have confidence to perform the new behavior. behavior change. Social Cognitive Theory (3) describes behavior as a The Stages of Change model (1) describes six stages reciprocal interaction between a person and his/her of “readiness” that an individual can move through environment. Two central constructs of this theory toward adopting a new behavior. The stages are pre - include self efficacy, which is a person’s belief in their contemplation, contemplation, preparation, action, ability to change, and outcome expectation, which is maintenance, and relapse. By identifying where indi - the degree to which a person believes that a specific viduals – or the majority of the target population – are course of action will lead to an expected outcome. on this continuum, nutrition messages can be directed appropriately to help people move toward action and 1. Prochaska, J.O. & DiClemente, C.C. (1983). Stages and the maintenance of healthy behaviors, such as con - processes of self-change in smoking: Toward an integrative suming micronutrients. The case study from model of change. Journal of Consulting and Clinical Psychology, 51;3:390 –95. Singapore described in this article is an excellent 2. Becker, M. H., ed. (1974). The Health Belief Model and example of applying the Stages of Change model. Personal Health Behavior. Health Education Monographs, 2:324–473. The Health Belief Model (2) considers behavior 3. Bandura, A. (1986). Social foundations of thought and action: change as a function of the individual’s perceived vul - A social cognitive theory. Prentice-Hall, Englewood Cliffs, nerability to illness (perceived susceptibility and N.J.

39 SIGHT AND LIFE Consumer research in micronutrients

Researchers can then identify adopted food fortification as an cessible to the population. Another which combinations of elements important strategy for improving important step was engaging retail - are most attractive and motivating iron nutrition, and soy sauce was ers, including two major supermar - for each segment. This is a knowl - selected as one of the vehicles. In kets in China – Su Guo and Carre- edge-based approach that helps the first phase of the project four – to carry and promote the for - program planners learn how to (2003–2007), the fortified soy tified product. To reach poor rural motivate target groups to choose sauce reached over 50 million con - areas, one food company produces healthier products or behaviors. sumers in seven provinces, includ - and distributes 400 mL plastic ing about 33 million of the at-risk sachets of fortified soy sauce to The importance of this and similar population (women and children). local markets and retail outlets at a methods is to ensure that program Among this population, anemia reduced – hence more affordable – planners systematically listen to prevalence was reduced by 30%, cost for consumers. the reactions and preferences of the with 80% of people becoming target audience. Pre-testing mes - aware of the health benefits of To raise people’s awareness about sages and materials is an essential iron-fortified soy sauce. How did the health benefits of iron and cre - step in designing any health pro - the program achieve these results? ate demand for the fortified prod - motion program. uct, a broad social marketing cam - The Food Fortification Office paign was launched with simple Case studies of practical (FFO) of the China Center for Di- messages that iron is good for application sease Control and Prevention health, improves vitality, and is (CDC) takes a ‘two wheels run especially good for women. The Three case studies illustrated the simultaneously’ approach, meaning message of ‘vitality’ was targeted three main approaches to combat - that the CDC and soy sauce manu - to appeal to the desired health ing micronutrient malnutrition – facturers work together to move the effects of the working class popu - fortification, supplementation, and program forward. Other partners lation. dietary diversification. They elabo - include local governments, indus- rated the application of behavior try associations, inspection insti - The mass media campaign was change theories, consumer science, tutes, and mass media partners. launched via the press, television, and marketing principles for Importantly, the FFO established radio, internet, consultations and promoting micronutrients in large- 22 sentinel sites to monitor lectures, and a wide range of print scale public health programs. knowledge and use of the fortified media. Activities that were suitable product and bioeffective ness. to each local area were organized: Producing the fortified soy-sauce free anemia testing and health Marketing of iron fortified soy was just one step in making it ac- consultation in public areas raised sauce in China – Dr. Junsheng Huo, Chinese Centre for Disease Control and Prevention

The case study on iron-fortified soy sauce in China provided an ex- cellent example of a public health program working with industry and local markets to make a need - ed product available and accessible (i.e. affordable) to consumers while targeting messages that motivate consumers to choose the iron-fortified product over compet - ing products on the market.

Recognizing iron deficiency and iron deficiency anemia (IDA) as In China, iron-fortified soy sauce is promoted to “give vitality” and is sold at an affordable cost key public health problems, China

40 Consumer research in micronutrients Magazine Issue 3/2007

people’s awareness of their personal susceptibility to munity health center) How much? Free. For whom? anemia; village doctors, who are trusted sources of Blue capsules for children aged 6–11 months, red cap - health information, conducted training sessions in sule for children aged 12–59 months. The campaign their villages; information about the program was dis - media were colorful, festive, and simple. Print media seminated on buses and through television programs (posters, bumper stickers, banners, brochures, etc.) broadcast in the buses, as well as through the post, to and electronic media (radio and television spots) were reach people on their daily routes. distributed nationwide, and special community pro - motion events were organized around the campaign Program monitoring data from the sentinel sites months of February and August. revealed impressive success in the first years of the program. The general public in the program areas is During the same period (1999–2003), HKI, in collab - now more aware of iron deficiency and IDA. Speci- oration with the Government of Indonesia, conducted fically, they are more aware of the symptoms, and household-based surveys once every three months adverse health effects of anemia. They are more like - through the Nutrition and Health Surveillance System ly to take action if they know they are anemic, and the (NSS) among ~36,000 households (representing 70% majority of those taking action said that they would of Indonesia’s rural population and urban poor in the choose and use iron-fortified soy sauce to avoid ane - country’s four major cities). This made a population- mia. based evaluation of the social marketing campaign possible. NSS data showed increased knowledge Social marketing of vitamin A supplementation in about vitamin A supplementation in the target popula - Indonesia tion, and increased vitamin A capsule coverage in – Dorothy Foote, MPH, nutrition and health urban poor and rural areas – from 28% to 81% (urban consultant poor), and 41% to 77% (rural) among 6–11 month olds; and from 48% to 84% (urban Indonesia has a long and suc - poor), and 65% to 81% (rural) among cessful history in conducting 12–59 month olds. The MOH and research and programs to UNICEF ensured that vitamin A capsule combat vitamin A deficiency. supply (availability) during this period In the wake of the Asian was not a barrier to increased coverage. economic crisis, purchasing power and therefore access to This case study demonstrated that a well- micronutrient-rich foods de- designed and well-positioned social creased. The need to strength - The social marketing campaign marketing campaign can have a positive en the national vitamin A for vitamin A supplementation in impact on health behaviors. Reliable Indonesia conveyed the key mes - supplementation program for sages: What? Vitamin A capsule. monitoring systems are essential to children under five years of Why? Healthy eyes and strong documenting the reach and impact of age was recognized as urgent. body. How much? Free. When? such programs. Sustaining successful February and August. Where? vitamin A supplementation requires Helen Keller International Health Post or Health Center. resources not only for capsules (to (HKI) and the Indonesian For whom? Blue capsule for ensure supply), but also for social 6–11 month olds, red capsule for Ministry of Health (MOH) 12 –59 month olds marketing to create and sustain demand worked together from 1999– for this life-saving intervention. 2004 to implement an accel - erated national social marketing campaign to promote From knowledge to practice – application of con - twice-yearly vitamin A supplementation for children sumer research to promote fruit and vegetable aged 6–59 months. The promoted behavior was rela - consumption in Singapore tively simple – mothers had to take their children to – Dr Annie Ling, Singapore Health Promotion Board receive a free vitamin A capsule twice a year. In Singapore, the consumption of fruits and vegeta - To motivate mothers, it was essential for the cam - bles is on the rise following a widespread campaign paign to communicate the key information – What? across the city-state to promote the message: ‘2+2 a Vitamin A capsule. Why? For healthy eyes and strong Day’ (meaning the consumption of two fruits and two body. When? February and August. Where? At the vegetables daily). Dr Annie Ling of the Singapore Posyandu (integrated health post) or Puskesmas (com - Health Promotion Board reported on how consumer

41 SIGHT AND LIFE Consumer research in micronutrients

research was used to develop standing the complex factors the communication messages that influence consumer food and outreach strategies. choices. For all micronutrient program strategies, under - A cross-sectional study was standing what motivates the designed based on the ‘Stages choices of the target popula - of Change’ behavior change tion is essential. Another key model. The study investigated element for successful pro - the stages of readiness (pre- grams is to have monitoring contemplation, contempla - systems to evaluate program Outreach strategies for ‘2+2 a Day’ in tion, preparation, action, and Singapore promote fruits and vegetables in impact and provide ongoing maintenance) among Singa- places where people normally eat (hawker feedback about the appropri - porean adults to consume centers and food courts) ateness of interventions. adequate daily portions of fruits and vegetables. The findings and vegetables increased from 7.1% More detailed information from were used to identify which kinds to 31.8% from 2001 to 2004. the ILSI Symposium on Under- of messages and interventions NNS data from 1998 and 2004 standing and Influencing Con- would be most likely to move peo - also showed that the proportion sumer Food Behaviors for Health ple to the next stage of change in of Singaporean adults eating ‘2+2 can be obtained by email from: adopting and maintaining the a Day’ increased from 5.0% to [email protected]. behavior of consuming ‘2+2 a 14.0%. The program illustrates how Day.’ consumer-based, behavior change research can be integrated with pro - References People in the contemplation and fessional judgment and creativity to preparation stages, who represented successfully motivate consumers 1. Helen Keller International/Asia- 61.1% of Singaporean adults, were towards healthy choices. Pacific. Homestead Food Production – A Strategy to Prevent Malnutrition and selected as the primary target Poverty. Jakarta, Indonesia: Helen audience. This meant they were Conclusion Keller International, 2001. “intending to take action within the 2. Drewnowski, A (2007). Abstract of next six months” (contemplation) Across the various strategies to the presentation, Biological, Social, or “intending to take action within promote micronutrients (fortifica - Cultural, and Psychological Influences on Food Choice. ILSI Symposium on the next 30 days and had already tion, supplementation, dietary div- Understanding and Influencing Con- taken some behavioral steps ersification), and across different sumer Food Behaviors for Health, (preparation).” program settings, the relative influ - Singapore, 18–20 July 2007. ence of availability, accessibility, Intervention strategies were based and choice varies. A good under - on further research on where people standing of these determinants eat – National Nutrition Surveys through research and common (NNS) in Singapore in 1998 and sense about the context is essential 2004 showed that the frequency of to planning effective policies and eating at hawker centers increased programs. from 37.1% and 49.9% over the period. The ‘2+2 a Day’ Program While supplementation remains a therefore targeted outreach strate - key intervention for combating gies to these venues, deploying micronutrient malnutrition, food ‘Fruit Ladies’ at food courts, and fortification with micronutrients distributing labels at hawker stalls and other dietary interventions are encouraging consumers to “Ask for becoming an increasingly appro - More Vegetables” and “Have a priate intervention as globalization Serving of Fruit at Every Meal.” opens markets and shifts the struc - ture of where and how people An evaluation of the program access food. In this context, nutri - showed that knowledge of the rec - tion program planners will face ommended daily servings of fruits increasing challenges in under -

42 Asian Congress of Nutrition Magazine Issue 3/2007

10th Asian Congress of Nutrition Taipei, Taiwan, September 9–13, 2007

Noel W. Solomons Center for Studies of Sensory Impairment, Aging and Metabolism (CeSSIAM), 17a Avenida 16 –80, Zona 11, Guatemala City, Guatemala Email: [email protected]

The 10th Asian Congress of Nutrition (ACN) was literally held in the Dr Hisanori Kato’s presentation, shadow of the world’s tallest office building – the Taipei 101. The Taipei “Nutrigenomics: the cutting edge International Convention Center was the venue for the three-and-a-half- and the Asian perspective,” cov - day program of plenary lectures (5), dialogues (3), symposia (21), and ered the recent advances in and the workshops (6) at this quadrennial scientific event. Moreover, there was a remaining limitations of the analyt - permanent poster session throughout the event, nestled near the exhibition ical methods in proteomics and area. The attendance of 1,400 delegates from 30 nations made this the metabolomics. Dr Kato empha - largest gathering in the history of the ACN. sized that both the total diet and specific nutrients can influence the The local hosts were the Nutrition Society of Taiwan. On a related note, expression of genes, and postulated the Federation of Asian Nutrition Societies convened its regular meeting an eventual contribution of ge- and selected Singapore as the site for the 11th ACN in 2011. The Council nomics to individualized nutrition. of the International Union of Nutritional Sciences (IUNS) also held its Dr Nita Bhandari presented “The meeting in Taiwan to prepare for the 2009 International Congress of new growth standard of the 21st Nutrition in Bangkok; each of its members presented at least one invited century,” a perspective on the 2006 talk in a symposium and moderated a session of the ACN. World Health Organization (WHO)

Plenary program

The plenary program included hour-long talks by five renowned scientists from the USA, Chile, Japan, India and Australia, distributed between the first and last days’ morning sessions. Dr Walter C. Willett’s presen - tation, “Overview and perspectives in human nutri - tion,” centered on dietary patterns and their associa - tions with a reduced risk of chronic diseases. The Nurses’ Health Study found that alcohol intake increased the risk of breast cancer, but that this risk was eliminated by a high intake of folic acid and dietary folates. On the other hand, fruits and vegetables were found to reduce the risk of cardiovascular disease Banner at the entry of the conference centre (CVD), but had no influence on overall cancer risk.

Dr Ricardo Uauy’s presentation, “Tackling the burden of disease with a growth curves, which discussed the common agenda,” highlighted the persistence of nutrient deficiencies and data collection that was implement - their consequences on mortality, morbidity, and impaired function as well ed to cover the ethnic and geo - as demographic, epidemiological, and nutritional transitions. The key graphic spectrum of the planet. Dr message was that it is neither logical nor sufficient to address one or the Bhandari highlighted that all previ - other poles of the problem; rather, we should find ways to address both ous growth curves were references with a common agenda. to normative populations as they

43 SIGHT AND LIFE Asian Congress of Nutrition

existed, whereas the 2006 growth young investigators in the Asian curves represent a standard for region. The free papers on vitamin how growth should occur. and mineral nutrition were the fourth most abundant among the Dr Mark L. Wahlqvist ended the topics, representing 8.5% of all sequence with his discourse on posters. Interestingly, issues related “The new Nutrition science in to chronic disease, long-term func - practice.” The theoretical basis for tion, and health comprised the top nutrition science came out of the three free-paper topics, constituting 2003–2007 Task Force on Eco- over 50% of all programmed sub - Nutrition of the IUNS, suggesting missions. that nutritional science not only develops on the biomedical front, The traditional hallmark interests but also in the societal and environ - of SIGHT AND LIFE have always mental dimensions of nutrition. been micronutrients and micronu - Prof. Nevin S. Scrimshaw, Emer- The presentation illustrated the trient malnutrition. This was itus Institute Professor of the convergence of these dimensions recently updated to include the MIT, and President of the Inter- with concrete examples, such as the double-burden of nutrition and the national Nutrition Foundation issue of land use for food crops ver - extent to which vitamins and min - sus biofuels. erals play a role in either acute de- apple fruit.” In terms of assess- ficiencies or chronic diseases. For ments, the paper on “Estimation of Free-paper sessions economy of space, however, this dietary selenium intakes of Taiwan- report focuses primarily on the ese by a self-constructed food Over 490 free papers were listed in explicit reports and observations in selenium content database” was the ACN program. Several of the the area of micronutrient nutrition intriguing. There were many papers best in each category were present - in its classic context of require - on unique sources of pro-vitamin A ed orally within the symposia. A ments and deficiencies. carotenoids in Asian plants and total of 268 abstracts were present - algae, on the role of vitamins in the ed in the poster session. Table 1 In the vitamin and mineral nutrition regulation of gene transcription of provides a breakdown of the num - section, two posters that caught active proteins, and on toxic trace ber of posters on different topic people’s attention were “Biological elements such as aluminum and areas. The range of topics is illus - activities of banana peel” and “An arsenic. trative of the emerging research apple a day, with or without the priorities among students and skin: vitamin content in parts of Dialogue sessions

Table 1: Overview of topics and number of posters of the free papers A series of three debates between included in the 10th ACN program two speakers with divergent views on a central topic were part of the Topic area No of program. Within the context of posters Asian culture, which generally fav- Dietary bioactive compounds and functional foods 105 ors harmony over confrontation, Diet, nutrition and chronic disease 97 the debates were re-christened dia - Nutritional epidemiology 42 logues. Two of these sessions had Vitamin and mineral nutrition 40 specific relevance to micronutrient Energy nutrient metabolism 37 nutrition. Nutrition education 30 Diet, nutrition and immune function 28 Dialogue D2 had as its topic Nutrition through the life cycle 21 “National fortification policy.” Nutrition and food processing 19 Two observers, who were not na- Clinical nutrition 15 tive to Asia, provided their per - Community and public health 14 spectives on fortification programs Diet, nutrition and physical activity 12 at the national level in the region. Gastrointestinal function 8 Dr Noel W. Solomons, from Guatemala, framed his remarks

44 Asian Congress of Nutrition Magazine Issue 3/2007

under the title “Balanced advo- Table 2: Selected symposia of relevance to micronutrient nutrition at the cacy.” His counterpart, Dr Wahlq- 10th ACN vist, from Australia, chose the title “Policy in evolution.” A point of S3 Dietary pattern, health and total well-being contention was whether it was fea - S4 Agricultural food production sible or desirable for Asian popula - S5 Approaches to combat double burdens: micronutrient deficiencies tions to make major changes in and complex diseases their dietary patterns for the sake of S6 Nutrient-gene interactions consuming nutrients from nutrient- S7 Diet, nutrition and bone health dense foods. The former speaker S13 GMO foods favored fortification of staples or S17 Assessment and evaluation of diet in Asian region condiments, whereas the latter favored food-based approaches. Both speakers found common retention at equivalent levels of cal - The “Agricultural food production ground in the emerging promise of cium intake; studies show that and public health” (S4) symposium the bio-fortification of staple crops, black adolescents, particularly fe- included two topics of relevance to such as rice and wheat, to increase males, retain and deposit more cal - micronutrient nutrition. These their micronutrient content. cium in their bones than their white included the development of rice peers. Asian girls, whether living in varieties that improve human nutri - the US or in East Asia, are also tion and a global perspective of more efficient in the bony utiliza - plant-based health food from an tion of dietary calcium. The ful - agricultural point of view. crum issue remained whether the level of adequate intake recom- The “Approaches to combat double mended by the US Dietary Re- burdens: micronutrient deficiencies ference Intake is appropriate for and complex diseases” (S5) sym- ethnic groups other than North posium best embodied and exem- American Caucasians. plified the paradigm that SIGHT AND LIFE announced in Sep- Symposia program tember of 2006. The keynote address in this symposium by A total of 21 symposia were con - Dr Lindsay Allen, from the US, ducted during the morning and addressed the question, “To what Prof. Mark L. Wahlqvist of Australia afternoon sessions of the second extent can food-based approaches and third days of the Congress. improve micronutrient status?” Many of the symposium themes Dr Allen concluded that foods of Dialogue D3 was on the topic were outside our central area of in- animal origin could close some of “Current calcium recommenda - terest, with only seven being of the gap, but that fortification or bio- tions,” which initiated a discussion selected relevance to micronutri - fortification is needed for full on calcium intake in early life and ents. These are listed in Table 2 . micronutrient security. Case-study its implications for the accretion of discussions from Thailand, Viet- skeletal bone mass and mineraliza - The “Dietary pattern, health and nam, and Malaysia confirmed the tion throughout life. Dr Connie total well-being” (S3) symposium difficulty of achieving a nutrient- Weaver, from the US, led the dia - was remarkable in its explicit dense diet and, at the same time, logue with her chosen topic, exploration and promotion of the rise of overweight and chronic “Current calcium recommenda - “dietary quality.” This perspective diseases in each Southeast Asian tions in North America for children on healthful eating goes beyond state. and adolescents.” Dr Warren Tak just satisfying energy needs; it also Keung Lee, from the UK (formerly takes nutrient density, pattern of An international panel in the “Nu- from Hong Kong), addressed the foods, and beneficial constituents trient-gene interactions” (S6) sym - topic of “Calcium requirements for into consideration. The symposium posium explored the topic of Asian children and adolescents.” touched on ways to define and Nutrigenomics, which touched on The discussion focused on the real - measure dietary quality, and even modern analytical capacity in ity of ethnic discrepancies in bone assess it with biomarkers. genomic dissection, and the re-

45 SIGHT AND LIFE Asian Congress of Nutrition

sponse of organisms to nutrient availability and food forming partnerships or alliances between industry and consumption. The diverse interaction of energy- public sector entities. Dr Kennedy outlined four areas restricted diets, berries, folic acid, phytochemicals, and of contention that need to be addressed: 1) Lack of essential fatty acids with genetics and the genome mutual trust; 2) Advertising to children; 3) Academics were discussed. paid as consultants; and 4) Biases, transparency and conflict of interest. The “Diet, nutrition and bone health” (S7) symposium was led by a keynote address by Dr Weaver on the role Closing remarks of nutrition in optimizing peak bone mass. Other talks within the symposium looked at calcium-isoflavone The Asian region has two nations with over a billion interactions in bone metabolism and the resurgence of inhabitants each (China and India) and, overall, consti - the importance of vitamin D in bone health. tutes almost half of the world’s population. With Taiwan being the site of the 10th ACN and Singapore The “GMO foods” (S13) symposium was almost selected as the venue for the next Congress, it is not entirely devoted to issues of safety in relation to surprising that issues of chronic disease and long-term biotechnology products in the human and animal food health are beginning to dominate the scientific agenda chain. The discussion covered perspectives on safety, of the region’s scientists, given the highly urbanized aspects of detection of genetic modification, and regu - settings and rising prosperity of these fast-growing lation and labeling issues. economies.

The “Assessment and evaluation of diet in the Asian However, it is also clear that there remain great eco - region” (S17) symposium included two topics of cen - nomic, social, and environmental disparities between tral relevance to micronutrient nutrition. These includ - the countries of this region, and there will be increas - ed how to adapt and apply the US Dietary Reference ing stresses from the double burden of under and over- Intake approach to Asian countries, and a commentary nutrition as the disparities widen. This is a region on the limitations and resolution of dietary assess - where the spectrum of nutritional disorders and ments for micronutrient intake. chronic as well as infectious diseases will likely affect the greatest numbers of people. Looking forward, Workshop sessions these problems look set to be further exacerbated by the nutrition and health impacts of progressive climate Six workshops were offered, covering prac - change. tical areas related to policy issues, institu - tional feeding programs, nutrition education SIGHT AND LIFE through the mass media, metabolic and continues to support nutritional aspects of glutamate, innovation the fight against mi- in food science, and improving nutrition cronutrient malnutri - research. Within these, two presentations tion by nurturing the emerged as highly relevant to SIGHT AND skills and knowledge LIFE’s readers. Dr Patanee Winichagoon, that can make a differ - of the Institute of Nutrition at the Mahidol ence in communities University in Bangkok, presented on the the world over, and “Co-existence of micronutrient malnutri - providing program - tion: implication for nutrition policy and matic and other sup - programs in Asia.” Dr Winichagoon noted port to relevant inter - that multiple nutrients are often deficient in ventions. This report persons or populations; whether formula - is part of this ongoing tion of multiple micronutrient supplements support to our network or concerted food-based strategies are more of stakeholders around feasible and appropriate is a regional policy the world, to help question. Dr Eileen Kennedy, dean of the connect us to the latest Tufts University Friedman School of thinking in our field Nutrition Science and Policy in the US, pre - and make our work sented on “Public-private sector collabora - Impressions from Taipei stronger. tions,” which looked at the opportunities for

46 Inside SIGHT AND LIFE Magazine Issue 3/2007

Inside SIGHT AND LIFE

Hua Jing is a PhD student at the Department of International Health – Human Nutrition, Johns Hopkins Bloomberg School of Public Health in Baltimore, Maryland. From 18 June to 17 August 2007, she worked as an intern in the SIGHT AND LIFE team in Kaiseraugst, Switzerland.

In the first of a new series, Inside SIGHT AND LIFE, Hua Jing describes her impressions of working with the Kaiseraugst team – shortly after arriving in Switzerland and shortly before returning to the USA two months later.

degree in Nutritional Sciences at SAL: So what will you be doing in the University of Wisconsin- the SIGHT AND LIFE team for Madison. If what I’ve learned in the next two months? the course of my studies can help HJ: As I’m sure you’re aware, victims of malnutrition in some SIGHT AND LIFE receives many way, I’ll be very happy. requests to fund work in the field of micronutrition. Writing an SAL: You currently have a DSM appropriately formulated proposal Fellowship in Micronutrient Re- can be very challenging, however Hua Jing search at Johns Hopkins Uni- – and so can trying to evaluate pro- versity. What does this involve? posals that don’t meet the funding HJ: At the University of Wis- criteria. It was therefore decided to The view from outside consin-Madison from July 2004 to develop standard guidelines for (June 2008) July 2006 I conducted research submitting proposals and also a into the bioavailability of pro-vita - standard approach to evaluating SIGHT AND LIFE (SAL): Hua min A carotenoids, and these stud - these. My tasks within SIGHT Jing, welcome to Switzerland and ies sparked my interest in the sub - AND LIFE include drawing up an welcome to SIGHT AND LIFE! ject of public health. It was also at evaluation grid to facilitate the Let me start by asking what made Wisconsin that I received intensive process, evaluating individual pro - you want to work in the field of training in analytic laboratory posals, and developing the criteria nutritional science? techniques such as HPLC (high- and format for proposals to be sub - Hua Jing (HJ): I simply want to performance liquid chromatogra - mitted in 2008. Our hope is that by use my knowledge of medicine phy). At Johns Hopkins, where giving people better instructions as and public health, and of laborato - I’ve been since August 2006, I’m to how to meet our criteria, we’ll ry techniques too, to help people applying these techniques and also encourage a general improvement who are suffering the effects of going a stage further, for I’m in the quality of proposals submit - poor nutrition in developing coun - receiving intensive academic ted, which will result in more pro - tries. My first degree was a Bach- training as a research assistant posals achieving their aim of elor of Medicine from Peking from Professor Keith West. My receiving funding. University Health Science Center, focus is on identifying micronutri - which I followed with Master of ent levels in serum and processing SAL: What are your first impres - Medical Science from the Depart- the accompanying data. Next year sions of the SIGHT AND LIFE ment of Food Science and Nutri- I shall commence my own re- team? Have you settled well into tion at the School of Public Health search into micronutrient deficien - your new working environment? at Peking University. I then em- cy, working towards a PhD. HJ: I have indeed settled in well, barked on a Master of Science and I’m thoroughly enjoying the

47 SIGHT AND LIFE Inside SIGHT AND LIFE

Hua Jing BM, MMS. Honors and awards 1996 Beijing Medical University Academic Excellence Scholarship 1997 Beijing Medical University Academic Excellence Scholarship 1999 Peking University Academic Excellence Scholarship 2000 Peking University Guanghua Scholarship (topmost) 2000 Peking University Outstanding Student Honor (super honor) 2006 Johns Hopkins School of Public Health Adele Diaz Scholarship 2007 Johns Hopkins School of Public Health DSM Fellowship

Publications

Hua Jing, Yong Li. Effects of ethanol on mouse embryonic brain development and heat shock protein 73 expression. Toxicology In Vitro. 2004 Oct; 18(5): 601 –7.

Hua Jing, Mingxi Zang, Yong Li. Effects of ethanol on mouse embryonic brain development: an in vitro study. China Reproductive Health. 2004, 15(2): 107 –110.

Zang, MX, Li, Y, Xue, LX, Jia, HT, Jing, H . Cooperative activation of atrial naturetic peptide promoter by Dhand and MEF2C. J Cell Biochem. 2004 Dec; 93(6):1255 –66.

Christopher Davis, Hua Jing, Julie A.Howe, Torbert Rocheford, and Sherry A. Tanumihardjio. Cryproxanthin from supplements or biofortified maize enhances liver vitamin A in mongolian gerbils more than or equal to carotene supplements. (submitted) experience of applying my academic training to real- HJ: Chinese medicine looks at people holistically, life situations. Although small, the SIGHT AND balancing various factors such as food intake, sleep LIFE team is embedded within DSM and therefore and emotional state. Western medicine focuses by enjoys global leverage. We collaborate with major contrast on curing individual symptoms, especially global institutions such as the World Food Program, acute disease. I think the two approaches have much so it’s a very stimulating working environment to be to learn from each other. Chinese medicine could in. The team has all been very welcoming and helpful benefit from the rigor of the Western approach, while – and they’re passionately committed to fighting Western medicine could benefit from the all-encom - micronutrient deficiencies in developing countries. passing view taken by Chinese medicine. That said, my qualifications are in Western medicine, not SAL : You come from China, you’ve been studying in Chinese! the USA and are now working in Switzerland. How do you manage to cope with the cultural differences The view from inside (August 2008) between these countries? HJ: At the beginning I did experience some culture SAL: Hua Jing, we first spoke almost two months shocks, I must confess, but I’ve found inspiration in ago, just after you had joined the SIGHT AND LIFE the words of Stephan Tanda, the member of DSM’s team as an intern. That period has now come to an Managing Board with responsibility for DSM’s end. Were your expectations of the internship Nutrition cluster. He says, “Think local, leverage fulfilled? global.” So wherever I live, I strive to live and think HJ: Very much so. My time here gave me the global. This allows me to incorporate positive ele - opportunity to apply my university learning to an ments of the new cultures that I encounter into my industrial context and to greatly broaden my general own culture – which helps me to develop personal understanding of industry. global leverage. SAL: So you had plenty to do? SAL : Chinese medicine is growing increasingly pop - HJ: Oh, I was kept very busy! I completed the new ular in the Western world; Chinese food has long document standard as planned, developed grant appli - been so. What, in your view, can the West learn from cation guidelines for use in 2008, participated in the China’s understanding of the relationship between editorial work of the SIGHT AND LIFE team, sup - nutrition and health? And what can China learn from ported the dissemination of the SIGHT AND LIFE the West? Nutritional Anemia Guidebook for review by special -

48 Inside SIGHT AND LIFE Magazine Issue 3/2007

ist journals, and had the chance to meet various got along very well for a period of two months and experts in the field of nutritional science. had achieved a great deal together during that time. I found myself beginning to miss my SIGHT AND SAL: What were your impressions of DSM, the LIFE colleagues even before leaving them! I must sponsor of SIGHT AND LIFE? confess that I’d been looking forward to returning to HJ: What impressed me most was the diversity of the the USA, but in the end I found it extremely difficult company, not just within the SIGHT AND LIFE team to say goodbye to my new colleagues in Switzerland. but throughout the organization. It was inspiring to see so many people from such widely differing cul- SAL : What will be the focus of your work in tural backgrounds working so closely together. Baltimore next year? HJ: I’ll take more classes in how to develop propos - SAL: Did you experience any problems during your als and will also sit various exams so that I can com - stay in Switzerland? mence my own research and embark on the associat - HJ: I did have some problems with the local lan- ed field work in June 2008. My topic hasn’t been guages – not at work, where everyone spoke English, defined as yet, but I’m currently exploring various but in daily life outside. I remember having terrible ideas together with my supervisors. Dr Klaus difficulty trying to ask for hair conditioner in a partic - Kraemer’s input here has also been extremely help - ular shop: no-one seemed to understand the term! So ful. I would advise prospective interns to learn some of the local languages before coming here. I did pick up SAL: Hua Jing, Many thanks for talking with SIGHT a few words myself, of course: gruezi, guten Tag, AND LIFE MAGAZINE, and the best of luck with all bonjour, merci, voilà and ciao. you do. HJ: Thank you. Having the chance to crystallize my SAL: Is there one experience that sums up your thoughts in this way is a very satisfying conclusion to sojourn with SIGHT AND LIFE? an important phase in my professional and personal HJ: Yes, it was my last day in Kaiseraugst. Everyone development. from the SIGHT AND LIFE team gathered together to bid me farewell, which was very touching. We had Interview by Jonathan Steffen

SIGHT AND LIFE is a humanitarian initiative of DSM covering a wide range of activities in colla boration with global and local partners and co operating with leading universities. To ensure a sustain able and significant improvement in human nutrition and health, SIGHT AND LIFE encourages partnerships, the exchange of scienti fic information and the crea tion of networks. For more information please visit www.sightandlife.org

DSM Nutritional Products DSM Nutritional Products is the world’s leading supplier of vitamins, carotenoids and other fine chemicals to the feed, food, pharmaceutical and personal care industries. The business has sales of over EUR 2 billion and a long tradition as a pioneer in the discovery of new products, new formula- tions and attractive applications for all industry segments. For further com- pany information please visit www.dsmnutritionalproducts.com UNLIMITED RESPONSIBILITY SIGHT AND LIFE IS A HUMANITARIAN INITIATIVE OF DSM

DSM DSM creates innovative products and services in life sciences and materials es on accelerating profitable and innovative growth of the company’s special - sciences, contributing to the quality of life. DSM’s products and services are ties portfolio. The key drivers of this strategy are market-driven growth and used globally in a wide range of markets and applications, supporting a innovation, an increased presence in emerging economies and operational healthier, more sustainable and enjoyable way of living. End markets include excellence. DSM has annual sales of almost EUR 9 billion and employs some human and animal nutrition and health, personal care, pharmaceuticals, 22,000 people worldwide. The company is headquartered in the automotive, coatings and paint, electrics & electronics, life protection and Netherlands, with locations in Europe, Asia, the Americas, Africa and housing. The company strategy, Vision 2010 – Building on Strengths, focus- Australia. More information about DSM can be found at www.dsm.com

DSM Nutritional Products Ltd. P.O. Box 3255, CH-4002 Basel Switzerland

49 SIGHT AND LIFE Recent literature

Multiple micronutrient literature

David I. Thurnham University of Ulster, Northern Ireland Centre for Food and Health, Coleraine Northern Ireland, UK Email: [email protected]

Vitamin A and cornea in 16.1%. The major underlying etiology of BL/SVI was undetermined in 32.7%, hereditary fac - Prevalence and causes of childhood blindness in tors in 31.9% (mainly retinal dystrophies), and child - camps for displaced persons in Khartoum: hood disorders in 28.5%. Avoidable causes of BL/SVI results of a household survey. Zeidan Z, Hashim K, accounted for 59.9% of the total students (measles- Muhit MA, Gilbert C. East Mediterr Health J related 23.1%; cataract (15.5%) and glaucoma 2007;13:580–5. (Department of Community Medi - (8.2%)). Comparisons of trends of SVI/BL among cine, Faculty of Medicine, University of Khartoum, <16 y and Ն 16 y, suggested that childhood disorders Khartoum, Sudan. Email: [email protected]) and corneal factors have declined, while hereditary disorders have increased. Optic nerve disorder, The prevalence and causes of visual impairment and although not counted as a major cause of blindness, blindness were determined in 29 048 children < 16 seems to be on the increase. Conclusions: The tempo - years in all households of 5 camps for internally dis - ral changes could reflect improved vitamin A supple - placed people in Khartoum State, Sudan. After house- mentation, measles vaccination and socioeconomic to-house visits by trained health care workers, 916 development in Indonesia. children received further assessment, 2.7% of whom were found to be blind, 1.6% to be severely visually Out-of-home food intake is often omitted from impaired and 5.5% to be visually impaired, according mothers’ recalls of school children’s intake in to WHO criteria. The prevalence of blindness in chil - rural Kenya. Gewa CA, Murphy SP, Neumann CG. dren in the camps was estimated as 1.4 per 1000 chil - J Nutr 2007;137:2154–9. (Department of Community dren. The leading causes of blindness were found to be Health Sciences, School of Public Health, University corneal opacities (40.0%), mainly due to vitamin A of California, Los Angeles, CA 90095, USA. Email: deficiency, followed by amblyopia (32.5%) [email protected])

Causes and temporal trends of childhood blind - The objectives of this study were to describe the types ness in Indonesia: study at schools for the blind and composition of foods consumed outside the home in Java. Sitorus RS, Abidin MS, Prihartono J Br J (OH) by rural school-aged Kenyan children, to assess Ophthalmol 2007;91:1109–13. (Department of Oph - their contribution to the daily intake of the child, and thal mology, Faculty of Medicine, University of to evaluate the ability of the mother to estimate intake Indonesia. Jakarta. Salemba 6, Jakarta-10430. Indo- of OH foods. To capture any seasonal differences, the nesia. Email: [email protected]) study was conducted twice, once during a food short - age season (FSS) and again during the subsequent har - From a total of 504 students in schools for the blind in vest season (HS). OH foods contributed 13 and 19% of Java, 479 were examined using a modified WHO daily energy intake in the FSS & HS, respectively, but Prevention of Blindness (WHO/PBL) procedure. mothers missed 77 and 41% of the OH energy intake. Authors found a majority of the students (95%) were Nutrients most likely to be under-reported on the blind (BL) and 4.6% were severely visually impaired mothers’ recalls were vitamin C (59 and 26% was (SVI). The major anatomical site of BL/SVI was missed in the FSS & HS, respectively) and vitamin A whole globe in 35.9%, retina in 18.9%, lens in 16.4% (~22% was missed in both seasons). To ensure that all

50 Recent literature Magazine Issue 3/2007

food intake is recalled, it is important that school chil - innate immune response, and (3) describe recent work dren be included in dietary assessment interviews on the relevance of the vitamin D intracrine-autocrine- about their own intakes. paracrine system in a model of a common and devastat - ing human disease, tuberculosis. Authors suggest that Improved vitamin A supplementation regimen there is a long history of studies that show that host- for breastfed very low birth weight infants. defenses against Mycobacterium tuberculosis is Aurvåg AK, Henriksen C, Drevon CA et al. Acta dependent on serum 25-OHD levels of the host and not Paediatr 2007;96:1296–302. (Department of Pedia - on the action of 1-25(OH)2D. trics, Akershus University Hospital and Akershus Faculty Division, University of Oslo, Norway. Email: Vitamin D deficiency. Holick MF. New Engl J Med [email protected]) 2007;357:266–81. (Department of Medicine, Section of Endocrinology, Nutrition, and Diabetes, the Vitamin D, Authors observed that preterm infants usually have Skin, and Bone Research Laboratory, Boston University low retinol concentrations at birth and at discharge Medical Center, Boston, MA 02118, USA. Email: from hospital and report a new protocol designed to [email protected]) raise plasma retinol in very low birth weight infants (VLBW: birth weight < 1500 g). An open intervention A useful general review on what is currently known of trial was conducted on 53 VLBW infants in which a the metabolism of vitamin D. . The author believes that daily dose of vitamin A was given mixed with human vitamin D deficiency is more common than generally milk instead of as a bolus and varied according to recognized. His cut-off for deficiency is 75 nmol/L for bodyweight. Blood samples were collected at inclu - serum 25-OHD concentrations – a threshold the author sion and discharge from hospital, and plasma retinol maintains is necessary for anti-fracture efficiency in was analyzed using HPLC. At discharge from hospital, post-menopausal women. A lower threshold of 50 the reference group had lower median plasma retinol nmol/L may be sufficient for the immunomodulatory concentrations compared to the modified group (0.30 actions of 25-OHD. The author associated poor vs. 0.49 mmol/L, p = 0.008). Fewer infants in the mod - vitamin D status with osteoporosis, chronic disease and ified group had plasma retinol levels below 0.35 some common cancers. Readers will be aware however mmol/L compared to infants in the reference group that low concentrations of 25-OHD found in patients (44% vs. 69%, p = 0.04). [DIT: Infants are born with with cancer may well be a consequence of the condition low concentrations of serum retinol (<1.0 mmol/L) but rather than a cause. However, the author describes the values in VLBW infants are particularly low even evidence to suggest that persons with better vitamin D at discharge. It would be interesting to know whether status may be better able to exert local control on cancer the intervention group achieved normal values more cell growth, so delaying development of the disease. quickly than the reference group.] The author emphasizes the need for sunlight to promote vitamin D synthesis in the skin and provides details on Vitamin D vitamin D supplements needed where sunlight sources are poor. Vitamin D in defense of the human immune response. Adams JS, Liu P, Chun R et al. Ann N Y Vitamin D and prevention of breast cancer. Welsh Acad Sci 2007; 26 July, ahead of print. (Cedars-Sinai J. Acta Pharmacologica Sinica 2007;28:1373–82. Medical Center, 8700 Beverly Blvd, Los Angeles, (Department of Biological Sciences, University of California, USA. Email: [email protected]) Notre Dame, Notre Dame, IN 46556, USA. Email: [email protected]) Defensin is a generic name reserved for an endoge - nously synthesized antimicrobial agent. The authors Epidemiologic data have demonstrated that breast can - reviewed a series of discoveries that led to the proposal cer incidence is inversely correlated with indices of vita - that 25-hydroxylated metabolite of vitamin D is a key min D status, including ultraviolet exposure, which intracellular regulator of the synthesis and action of nat - enhances epidermal vitamin D synthesis. The vitamin D urally occurring defensin molecules against bacterial receptor (VDR) is expressed in mammary epithelial antigens. Key elements of the discussion include (1) the cells, suggesting that vitamin D may directly influence basic element of the human immune response that is sensitivity of the gland to transformation. Consistent responsive to vitamin D, (2) describe work relevant to with this concept, in vitro studies have demonstrated the extrarenal expression of the vitamin D-1-hydroxlase that the VDR ligand, 1,25-dihydroxyvitamin D (CYP27b1) in the macrophage as an initiator of the (1,25D), exerts negative growth regulatory effects on

51 SIGHT AND LIFE Recent literature

mammary epithelial cells that contribute to maintenance are important functional, surgical and financial reasons of the differentiated phenotype. Furthermore, deletion to study relationships between risk for ARC/ARM and of the VDR gene in mice alters the balance between pro - nutrition, particularly given the rapidly growing elder - liferation and apoptosis in the mammary gland, which ly segment of our population. It is clear that oxidative ultimately enhances its susceptibility to carcinogenesis. stress is associated with compromises to the lens and In addition, dietary supplementation with vitamin D, or retina and over 70 studies have attempted to relate chronic treatment with synthetic VDR agonists, reduces antioxidant intake to risk for ARC and ARM. This arti - the incidence of carcinogen-induced mammary tumors cle reviews epidemiological literature about ARC and in rodents. Collectively, these observations have rein - ARM with emphasis on roles for vitamins C and E and forced the need to further define the human requirement carotenoids. Since glycation and glycoxidation are for vitamin D and the molecular actions of the VDR in major molecular insults which involve an oxidative relation to prevention of breast cancer. stress component, the authors also review new litera - ture that relates dietary carbohydrate intake to risk for Vitamin E ARC and ARM. To evaluate dietary effects as a whole, several studies have tried to relate dietary patterns to Maternal food consumption during pregnancy risk for ARC. Authors note that data from the observa - and asthma, respiratory and atopic symptoms in tional studies generally support a protective role for 5-year-old children. Willers SM, Devereux G, Craig antioxidants or supplements but results from interven - LCA et al. Thorax 2007;62:772–8. (Institute for Risk tion trials are less encouraging with respect to limiting Assessment Sciences, Division of Environmental risk for ARC/ARM prevalence. Likewise it is difficult Epidemiology, Utrecht University, P O Box 80178, to determine why the various types of studies are not 3508 TD Utrecht, The Netherlands. yielding similar results. The authors speculate that Email: [email protected]) there are many common insults and mechanistic com - promises that are associated with aging, and proper Because maternal vitamin E, vitamin D and zinc nutrition early in life may address some of these com - intakes during pregnancy have been associated with promises and provide for extended youthful function asthma, wheeze and eczema in 5-year-old children, the later in life. Whether it is possible to identify an effec - authors investigated maternal intake during pregnancy tive nutritional strategy to prevent or delay the devel - by food frequency questionnaire (FFQ) in a longitudi - opment and progress of ARC/ARM and the age when nal cohort study. 1253 cohort children participated at the supplementation should begin needs further study. 5 y and maternal FFQ data were available for 1212. No consistent associations were found between childhood Vitamin E: inflammation and atherosclerosis. outcomes and maternal intake of the analyzed foods Singh U, Devaraj S. Vitam Horm 2007;76:519–49. except for apples and fish. Maternal apple intake was (Department of Pathology, Laboratory for Athero- beneficially associated with wheeze (odds ratio [OR] sclerosis and Metabolic Research, UC Davis Medical highest vs lowest tertile 0.63), asthma (OR 0.54) and Center, Sacramento, California 95817, USA. Email: doctor-confirmed asthma (OR 0.47) in the children. [email protected]) Maternal fish consumption was beneficially associated with doctor-confirmed eczema (OR Ն 1/week vs never Cardiovascular disease (CVD) is the leading cause of 0.57). Conclusion: Consumption of apples and fish morbidity and mortality in the western world with its during pregnancy may have a protective effect against incidence increasing lately in developing countries and the development of childhood asthma and allergic dis - evidence suggests inflammation is involved in its ease. etiology. The authors report recent emerging data on ␣-tocopherol as well as gamma-tocopherol and toco - Nutritional antioxidants and age-related cata- trienols especially with regards to their effect on ract and maculopathy. Chiu C, Taylor A. Exp Eye inflammation as it relates to CVD. Authors point out Res 2007;84:229–45. (The Laboratory for Nutrition that vitamin E is a potent antioxidant and comprises and Vision Research, USDA Human Nutrition eight different isoforms. The anti-inflammatory prop - Research Center on Aging, Tufts University, 711 erties of ␣-tocopherol have been assessed in terms of Washington Street, Boston, MA 02111, USA. Email: decreasing C-reactive protein (CRP) and proinflamma - [email protected]) tory cytokines especially at high doses. They also dis - cuss work showing gamma-tocopherol decreases reac - Age-related cataract (ARC) and maculopathy (ARM) tive nitrogen species and also appears to have anti- are two major causes of blindness worldwide. There inflammatory properties; however, there are scanty

52 Recent literature Magazine Issue 3/2007

data examining pure gamma-T preparations. They sug - Vitamin K gest that tocotrienols (alpha and gamma) may prevent CVD but the data are conflicting. [DIT: There is still Vitamin K status in the elderly Booth SL. Curr much to learn about vitamin E and its functions in the Opin in Clin Nutr Metabol Care 2007;10:20–3. body. However readers may also want to consult the (Vitamin K Laboratory, Jean Mayer USDA Human paper below and others in the literature that find no Nutrition Research Center on Aging at Tufts benefits of vitamin E supplements against CVD.] University, Boston, Massachusetts 02111, USA. Email: [email protected]) A randomized factorial trial of vitamins C and E and ␤-carotene in the secondary prevention of Poor vitamin K nutrition has recently been linked to cardiovascular events in women: Results from several chronic diseases associated with abnormal cal - the Women’s Antioxidant Cardiovascular Study cification in the elderly. To understand the impact of (NCT00000541). Cook NR, Albert CM, Gaziano JM vitamin K nutrition on healthy aging it is necessary to et al. Arch Intern Med 2007;167:1610–8. (Division of assess both the determinants and the adequacy of vita - Preventive Medicine, Brigham and Women’s Hospital, min K nutritional status. Recent work suggests elderly Harvard Medical School, 900 Commonwealth Ave E, persons consume more vitamin K than young adults: Boston, MA 02215, USA. however, a subgroup of the elderly population does not Email: [email protected]) meet the current recommended dietary intakes. The first meta-analysis evaluating the data on the role of Randomized trials have largely failed to support an vitamin K and bone health concluded that increased effect of antioxidant vitamins on the risk of cardiovas - intakes of vitamin K are warranted to reduce bone loss cular disease (CVD). Few trials have examined inter - and fracture risk among the elderly. Other work sug - actions among antioxidants, and, to our knowledge, no gests that non-dietary determinants of vitamin K status previous trial has examined the individual effect of need to be factored into any discussion on the adequa - vitamin C on CVD. The Women’s Antioxidant cy of nutritional status of the elderly and a promising Cardiovascular Study tested the effects of vitamin C area of research is the interrelationship between estro - (500 mg/d), vitamin E (600 IU every other day), and gen and vitamin K. Thus some elderly persons may ␤-carotene (50 mg every other day) on the combined benefit from increased intakes of vitamin K to reduce outcome of myocardial infarction, stroke, coronary bone loss and fracture risk but much more research is revascularization, or CVD death among 8171 female required to identify non-dietary determinants of vita - health professionals at increased risk, in a 2 x 2 x 2 fac - min K status, and their impact on the elderly. torial design. Participants were Ն 40 years with a his - tory of CVD or 3 or more CVD risk factors and were HPLC method for plasma vitamin K1: effect of followed up for a mean duration of 9.4 y, from plasma triglyceride and acute-phase response on 1995 –1996 to 2005. A total of 1450 women experi - circulating concentrations. Azharuddin MK, enced 1 or more CVD outcomes. There was no overall O’Reilly DS, Gray A, Talwar D. Clin Chem 2007; effect of vitamin C (relative risk [RR], 1.02; [P=0.71]), 53:1706–13. (Scottish Trace Element and Micro- vitamin E (RR, 0.94; [P=0.23]), or ␤-carotene (RR, nutrient Reference Laboratory, Department of Clinical 1.02; [P=0.71]) on the primary combined end point or Biochemistry, Royal Infirmary, Glasgow, UK. Email: on the individual secondary outcomes of myocardial [email protected]) infarction, stroke, coronary revascularization, or CVD death. A marginally significant reduction in the pri - The plasma concentration of vitamin K1 (K1, phyllo - mary outcome with active vitamin E was observed quinone) is the most reliable index for assessing vita - among the pre-specified subgroup of women with min K status. Authors validated an HPLC method to prior CVD (RR, 0.89; 95% CI, 0.79–1.00 [P=0.04]; P quantify plasma K1 and examined the effect of plasma value for interaction, 0.07). There were no significant triglyceride concentration on the K1 reference interval interactions between agents for the primary end point, and any effects of inflammation using C-reactive pro - but those randomized to both active vitamins C and E tein (CRP) on K1 concentration in plasma. K1 was experienced fewer strokes (P value for interaction, extracted from fasting plasma samples by depro - 0.03). There were no overall effects of vitamins C and teinization and C18 solid-phase extraction, separated E or ␤-carotene on cardiovascular events among by reversed-phase HPLC, and detected fluorometrical - women at high risk for CVD. ly after postcolumn reduction with a platinum catalyst using a novel internal calibrator, docosyl naphthoate. The recovery of K1 was > 90%. Between-run impreci -

53 SIGHT AND LIFE Recent literature

sion was 8.7%–9.0%, and within-run imprecision was Folate and vitamin B 12 status in relation to ane - 3.8%–7.0%. The linearity was up to 44.8 nmol/L, limit mia, macrocytosis, and cognitive impairment in of detection 0.08 nmol/L, and limit of quantification older Americans in the age of folic acid fortifi- 0.14 nmol/L. The correlation between plasma K 1 and cation. Morris MS, Jacques PF, Rosenberg IH, Selhub triglyceride concentrations was r = 0.7 in the reference J. Am J Clin Nutr. 2007;85:193–200. (Jean Mayer population. The 95% reference interval for the US Department of Agriculture, Human Nutrition K1:triglyceride ratio was 0.20 to 2.20 nmol/mmol. Research Center on Aging, Tufts University, Boston, After surgery, plasma concentrations of CRP were sig - MA 02111, USA. Email: [email protected]) nificantly increased, whereas triglyceride and K1 but not the K1:triglyceride ratio were transiently decreased Vitamin B12 deficiency causes pernicious anemia and > 50%. K1 population reference intervals should be affects many seniors. Historic reports on the treatment expressed as a ratio of the triglyceride concentration. of pernicious anemia with folic acid (FA) suggest that K1 concentrations in plasma are decreased by inflam - high-level FA fortification delays the diagnosis of or mation and, unless corrected for plasma triglyceride exacerbates the effects of vitamin B12 deficiency. This concentration, are unlikely to be a reliable index of idea is controversial, however, because observational vitamin K status. [DIT: This work adds yet another data are few and inconclusive. Furthermore, experi - nutrient to the growing list of micronutrients that are mental investigation is unethical. Authors examined influenced by inflammation.] the relations between serum folate and vitamin B12 status relative to anemia, macrocytosis, and cognitive B vitamins impairment (i.e., Digit Symbol-Coding score < 34) in senior participants in the 1999–2002 US National Trends in blood folate and vitamin B 12 concen - Health and Nutrition Examination Survey. The sub - trations in the United States, 1988 2004. Pfeiffer jects had normal serum creatinine concentrations and CM, Johnson CL, Jain RB et al. Am J Clin Nutr reported no history of stroke, alcoholism, recent ane - 2007;86:718–27. (National Center for Environmental mia therapy, or diseases of the liver, thyroid, or Health, Centers for Disease Control and Prevention, coronary arteries (n = 1459). Low vitamin B12 status Atlanta, GA. Email: [email protected]) was defined as a serum B12 < 148 pmol/L or a serum methylmalonic acid concentration > 210 nmol/L Monitoring the folate status of US population groups – the maximum of the reference range for serum over time has been a public health priority for the past vitamin B12-replete participants with normal creati - 2 decades especially since the implementation of a nine. After control for demographic characteristics, folic acid fortification program in the mid-1990s. low versus normal vitamin B12 status was more likely Authors measured blood indicators of folate and vita - to be associated with anemia (2.7 x), macrocytosis min B12 status pre-fortification in ~23 000 partici - (1.8 x), and cognitive impairment (2.5 x). In addition, pants in NHANES III (1988–1994) and post-fortifica - in those with a low vitamin B12 status, a high serum tion in ~8000 participants in 3 NHANES periods folate (> 59 nmol/L – 80th percentile) was more likely (1999–2004). Serum and RBC folate concentrations to be associated with anemia (3.1 x) and cognitive increased substantially (by 119–161% and 44–64%, impairment (2.6 x). The authors concluded that in respectively) in each age group in the first post-fortifi - seniors with low vitamin B12 status, high serum folate cation survey period and then declined slightly (by was associated with anemia and cognitive impairment. 5–13% and 6–9%, respectively) in most age groups However when vitamin B12 status was normal, high between the first and third post-fortification survey serum folate was found to be associated with protec - periods. Serum vitamin B12 concentrations did not tion against cognitive impairment (0.4 x). change. Prevalence estimates of low serum and RBC folate concentrations declined in women of childbear - Maternal nutrient supplementation counteracts ing age from before to after fortification (from 21% to bisphenol A-induced DNA hypomethylation in < 1% and from 38% to 5%, respectively) but remained early development. Dolinoy DC, Huang D, Jirtle unchanged thereafter. Prevalence estimates of high RL. Proc Natl Acad Sci USA 2007;104:13056–61. serum folate concentrations increased in children and (Department of Radiation Oncology and University older persons from before to after fortification (from Program in Genetics and Genomics, Duke University, 5% to 42% and from 7% to 38%, respectively) but Durham, NC 27710, USA. decreased later after fortification. Conclusions: The Email: [email protected]) small fall-off in folate concentrations post-fortification does not raise concerns about inadequate status.

54 Recent literature Magazine Issue 3/2007

The hypothesis of fetal origins of adult disease sug - increasing urinary DMAs. The implications of this gests that early developmental exposures involve epi - study need to be explored to determine if folate supple - genetic modifications, such as DNA methylation, that mentation as a public health strategy in countries influence adult disease susceptibility. In utero or where arsenic intake is a problem can prevent arsenic- neonatal exposure to bisphenol A (BPA), a high-pro - induced illnesses. duction-volume chemical used in the manufacture of polycarbonate plastic, is associated with higher body Very low oral doses of vitamin B-12 increase weight, increased breast and prostate cancer, and serum concentrations in elderly subjects with altered reproductive function. BPA has been detected food-bound vitamin B-12 malabsorption. Blacher in 95% of human urine samples of a reference popula - J, Czernichow S, Raphaël M et al. J.Nutr 2007; tion of adults in the USA. Authors describe a study in 137:373–8. (INSERM U 258, Hôpital Paul Brousse, which adult pregnant mice were exposed to BPA and a Villejuif, France. Email: [email protected]) gene (agouti) that determines coat color was moni - tored. In wild-type mice, coat color is predominantly The BOSSANOVA study, a randomized double-blind black but hypomethylation of the agouti gene by expo - trial, was designed to determine the amount of oral sure of the mice to BPA shifted the distribution of coat vitamin B12 that would increase the serum vitamin color and produced yellow offspring. However, mater - B12 concentration by 37 pmol/L (50 ng/L) and deter - nal dietary supplementation, with either methyl donors mine whether there was a dose response. The authors like folic acid or the phytoestrogen genistein, negated also aimed to quantify the most efficient dose to be the DNA hypomethylating effect of BPA. Thus, the added to flour in addition to folic acid (flour co-fortifi - authors present compelling evidence that early de- cation with vitamin B12 and folic acid). Sixty-seven velopmental exposure to BPA can change offspring patients were randomly assigned to I of 6 groups phenotype by stably altering the epigenome, an effect receiving various daily oral doses of vitamin B12 (i.e., that can be counteracted by maternal dietary supple - 2.5, 5, 10, 20, 40 or 80 mg/d) for 30 d. The dose ments. response was tested for different biological variables using a mixed model, taking into account the vari - Folic acid supplementation lowers blood arsenic. able’s initial value (between-subject effect), a linear Gamble MV, Liu X, Slavkovich V et al. Am J Clin log-dose effect, and a linear log (dose x time) interac - Nutr 2007;86:1202–9. (Departments of Environmental tion, where time was d 15 or d 30. Significant Health Sciences, Mailman School of Public Health, between-subject effects were found for serum vitamin Columbia University, New York, NY. B12, plasma homocysteine, and methylmalonic acid Email: [email protected]) concentrations, but a log-dose effect was found only for serum vitamin B12 (P < 0.001). The slope of the Chronic arsenic exposure currently affects >100 mil - line tended to be higher (P = 0.07) at d 30 than at d 15. lion persons worldwide. Authors investigated whether For a mean serum vitamin B12 increase of 37 pmol/L, in vivo metabolism by folate-dependent one-carbon a dose of 5.9 (95% CI, 0.9–12.1) µg/d was needed. metabolism, would detoxify ingested inorganic arsenic Authors concluded that very low oral doses of vitamin (InAs) by methylation to monomethylarsonic (MMAs) B12 increased serum vitamin B12 concentrations in and dimethylarsinic (DMAs) acids to facilitate urinary elderly subjects with sub-clinical vitamin B12 defi - arsenic elimination. In a randomized, double-blind, ciency, following a log-dose pattern, and the results placebo-controlled trial, 130 arsenic-exposed Bangla- should assist the design of public health program for deshi adults with low plasma folate (< 9 nmol/L) were safe flour co-fortification with folic acid. supplemented with folic acid. Blood InAs, MMAs, and DMAs were measured before and after 12 wk of sup - Vitamin C plementation with folic acid (400 mg/d) or placebo. MMAs in blood were reduced by a mean (SE) of Old world meets modern: a case report of 22.2% (2.9) in the folic acid group and by 1.2% (3.6) scurvy. Wang AH, Still C. Nutr Clin Pract 2007; in the placebo group (P < 0.0001). There was no 22:445–8. (Department of Gastroenterology and change in blood DMAs but rapid excretion was indi - Nutrition, Geisinger Medical Center, 100 N. Academy cated by an increase in urinary DMAs (P = 0.0099). Ave., Danville, PA 17822, USA. Total blood arsenic was reduced by 13.6% in the folic Email: [email protected]) acid supplementation group and by 2.5% in the place - bo group (P = 0.0199). Folic acid supplementation Authors describe a case of scurvy (vitamin C deficien - acted primarily by decreasing blood MMAs and cy) in a 65-year-old man. The patient reported heavy

55 SIGHT AND LIFE Recent literature

alcohol abuse over the last several years. He also Efficacy of topical vitamin C derivative (VC- reported that his diet consisted of cheese pizzas only. PMG) and topical vitamin E in prevention and On physical examination, he was noted to have spon - treatment of UVA suntan skin. Puvabanditsin P, taneous ecchymosis (bruises) of his lower extremities Vongtongsri R. J Med Assoc Thai 2006;89:S65–S68. (denying any history of trauma); poor dentition; and (Division of Dermatology, Department of Medicine, corkscrew hairs on his chest, abdomen, and legs, with Faculty of Medicine, Chulalongkorn University, Rama associated perifollicular petechia (small hemorrhages IV Rd, Bangkok 10330, Thailand. at the base of hair follicles). Punch biopsy of his skin Email: [email protected]) lesions revealed perivascular lymphohistiocytic inflammation, with some focal perifollicular erythro - Exposure of the skin to ultraviolet radiation (UVA) is cyte extravasation. Serum ascorbic acid concentration known to induce reactive oxygen species and cause tis - was < 7 µmol/L (<1.2 mg/L) (normal range, 11– sue damage and inflammation. In 20 volunteers, the 80 µmol/L). The patient was successfully treated with authors tested whether two well-known antioxidants 1 g/d vitamin C for the first 5 d, followed by a dose of (topical 10% vitamin C derivative (VC-PMG) and top - 500 mg/d. [DIT: I agree with the authors that scurvy is ical 5% vitamin E) would inhibit these mediators and rarely seen in modern times but it does still occur. I reduce UVA-induced skin reaction. Prior to 30 Joules have found that the hemorrhages and unusual dietary UVA exposures, volunteers were asked to apply both habits are almost always present.] agents twice daily for 3 days. Treatments had no effects on the melanin index measured immediately Oxidative stress in sepsis in children. Cherian S, after irradiation using the Maxemeter. After continu - Jameson S, Rajarajeswari C et al. Indian J Med Res ing the cream application for 12 weeks, there were also 2007;125:143–8. (Departments of Biochemistry, no bleaching effects observed after 2, 4, 6, 8, 10 and 12 Kasturba Medical College & Hospital, Manipal weeks compared to the placebo. The treatment was 576104, India.) found to have no effects on prevention or treatment of effects of UVA irradiation. Authors assessed the levels of certain antioxidants in blood of children with sepsis to investigate oxidative Minerals damage. Thirty-eight children with sepsis (1 to 5 y) and 39 age- and sex-matched controls were admitted to Distribution of anemia associated with micronu - a tertiary care hospital. Red cell glutathione (GSH), trient deficiencies other than iron in a proba - superoxide dismutase (SOD) and thiobarbituric acid bilistic sample of Mexican children. Villalpando S, reactive substance (TBARS) and plasma vitamin C Pérez-Expósito AB, Shamah-Levy T, Rivera JA. Ann were estimated by standard techniques. There was no Nutr Metab 2006;50:506–11 (Center for Research on significant differences in erythrocyte GSH, SOD and Nutrition and Health, Instituto Nacional de Salud TBARS levels in children with sepsis when compared Pública, Cuernavaca, Mexico. to controls. However, plasma vitamin C levels were Email: [email protected]) significantly lower in the patients. The authors suggest that active phagocytosis may reduce vitamin C due to The workers explored the associations among anemia its role as a free radical scavenger. The authors suggest (Hb and percent transferrin saturation (PTS)) and vita - that children affected by sepsis probably adapt to the mins A, C, and folate deficiencies in a probabilistic free radical toxicity induced by this condition. [DIT: It sample of 0.5–11 y (n = 1770) Mexican children from has been known for many years that there is an active the National Nutrition Survey (1999). Overall, 16.6% uptake of vitamin C from plasma by leukocytes emerg - of children were anemic and of these 62% were iron ing from the bone marrow with the onset of infection. deficient (PTS<16). Vitamin A deficiency was more Whether the process is primarily to boost antioxidant frequent in children with iron deficiency (ID) than protection within the leukocytes or reduce the concen - non-ID children both with (40.6 vs. 16%) and without trations of a potential pro-oxidant in the plasma or both anemia (27.7 vs. 11.9%, both p < 0.05). In addition is not clear. If vitamin C is not removed from damaged non-anemic, ID children had lower hemoglobin folate tissues, it can react with iron to produce ferrous iron (11.5 vs. 22%, p < 0.05) than their non-ID counter - which may promote tissue damage by Fenton chem - parts. Mean concentrations of serum iron (p < 0.01), istry.] folate (p < 0.001) and retinol (p < 0.0001), but not ascorbic acid (p < 0.6), were significantly lower in anemic than in non-anemic children. In a linear regres - sion model, 15% of hemoglobin variation in children

56 Recent literature Magazine Issue 3/2007

was explained by retinol, folate and PTS, but not vita - Although there is much interest in using sodium iron min C (p < 0.0001). Authors concluded anemia was (III) ethylenediaminetetraacetic acid ( EDTA) in food mostly associated with iron deficiency and with a less - fortification programs to tackle the global problem of er proportion of folate and vitamin A deficiencies. iron deficiency and its anemia, the authors found that Interventions aimed to reduce anemia in this popula - synthesis methods of stable isotope-labeled sodium tion must consider interactions between those iron (III) EDTA for use in human bioavailability stud - micronutrients in designing strategies. [DIT: 14% of ies are incomplete, incorrect or totally lacking. To the probabilistic sample was excluded with CRP meet this need, the authors devised a simplified and >3 mg/L; the hemoglobin folate value was determined optimized synthesis of sodium iron (III) EDTA from a from whole blood folate and hemoglobin measured in block of isotopically enriched iron metal that can be dried blood spots and expressed as µg folate/L erythro - easily and cheaply reproduced using simple basic lab - cytes.] oratory apparatus. The resulting product is of high purity (499.0%), and may be used for human stable Sex differences in prevalence of anaemia and isotope bioavailability studies. The authors argue that iron deficiency in infancy in a large multi-coun - the simplicity of the method allows workers to perform try trial in South-East Asia. Wieringa FT, Berger J, their own syntheses and that greater uniformity in this Dijkhuizen MA et al. Br J Nutr. 2007;98:1070–1076. synthesis will reduce the variation observed between (University Medical Center Nijmegen, The Nether- studies. lands, and Nutrition Research and Development Centre, Bogor, Indonesia. Iron status of inner-city African-American Email: [email protected]) infants. Lozoff B, Lu Angelilli M, Zatakia J et al. Am J Hematol. 2007;82(2):112–21. (Center for Human Biochemical data from 4 parallel, randomized, double- Growth and Development, University of Michigan, blind trials with Fe and/or Zn supplementation in Ann Arbor, Michigan 48109, USA. infants (n 2452) in Indonesia, Thailand and Vietnam Email: [email protected]) was pooled to evaluate effects of Fe supplementation and sex on the prevalence of anemia and Fe status in The Fe status of African-American infants continues to infants in SE Asia,. At recruitment (5 mo of age), Hb be subject to debate. Authors characterized the Fe, lead concentrations were slightly but significantly lower in and inflammation status of 198 9-mo inner-city infants boy infants compared with girl infants (108.7 v. 111.4 (94% fed Fe-fortified formula). The proportion with g/L, P = 0.04). At 11 mo of age, boy infants not receiv - Fe deficiency was calculated based on three approach - ing Fe had significantly lower Hb (106.2 v. 111.0 g/L, es ( Ն 2 abnormal iron measures with or without ane - P < 0.001) and lower serum ferritin concentrations mia for MCV model; NHANES II, ferritin model and (14.3 v. 21.1 mg/L, P < 0.001) than girl infants not NHANES III, or Sweden/Honduras study) and a prom - receiving Fe. Consequently, boy infants had a higher ising new measure – body iron, calculated from ferritin relative risk of anemia (1.6, 95 % CI 1.3, 2.1) and of and transferrin receptor (TfR). There were no sex dif - Fe-deficiency anemia (3.3, 95 % CI 2.1, 5.0) than girl ferences for any iron measure. Hb < 110 g/L was infants. Fe supplementation significantly increased Hb observed in 25%; Hb Յ 105 g/L in 10.1%. Free ery - concentrations in both boys and girls and there was no throcyte protoporphyrin (FEP) values were elevated sex difference in Fe status in infants receiving Fe for without elevated lead concentrations or an inflamma - 6 mo. Authors suggest that standard infant feeding tory response: mean FEP = 866 mg/L red blood cells practices in SE Asia do not provide sufficient Fe to (75.5 µmol/mol heme); 52.3% were > 800 mg/L (1.42 meet requirements and that Fe requirements for boy µmol/L), almost half of whom had a second abnormal infants are ~0.9 mg/d higher than for girl infants espe - Fe measure. The estimated prevalence of Fe deficien - cially in the second half of infancy. cy was 14.4, 5.3, and 2.5% for the MCV, ferritin, and Sweden/Honduras models, respectively, and 4.1% for Sodium iron(III) ethylenediaminetetraacetic acid body Fe < 0 mg/kg. Regulation of iron storage is synthesis to reduce iron deficiency globally. Loots immature at < 1 year of age, making estimates of Fe D, van Lieshout M, Lachmann G. Eur J Clin Nutr deficiency that depend on ferritin, including body Fe, 2007;61:287–9. (Department of Nutrition, School of suspect in this age period. Thus, the "true" prevalence Physiology, Nutrition and Consumer Sciences, North- of Fe deficiency could not be established with confi - West University, Potchefstroom, South Africa. Email: dence and functional indicators of poor Fe status in [email protected]) young infants are urgently needed.

57 SIGHT AND LIFE Recent literature

Sensory characteristics and iron dialyzability of Hepcidin deficiency plays a central role in most Fe- gluten-free bread fortified with iron. Kiskini A, overload disorders. The role of hepcidin abnormalities Argiri K, Kalogeropoulos M et al. Food Chem in anemias that are associated with renal disease and in 2007;102: 309–316. (Laboratory of Engineering, resistance to erythropoietic therapies remains to be Processing and Preservation of Foods, Department of elucidated. Food Science and Technology, Agricultural University of Athens, Iera Odos 75, Athens 11855, Greece. Nutritional iron deficiency: an evolutionary per - Email: [email protected]) spective. Denic S, Agarwal MM. Nutrition 2007; 23:603–14. (Faculty of Medicine & Health Sciences, The objectives of the present study were (a) to produce UAE University, Al Ain, Abu Dhabi, United Arab gluten-free bread, fortified with Fe (GFB-Fe), using Emirates. Email: [email protected]) selected Fe compounds (ferric pyrophosphate, ferric pyrophosphate with emulsifiers, NaFeEDTA, elec - Iron deficiency, with or without Fe-deficiency anemia, trolytic iron, ferrous gluconate, ferrous lactate and fer - is so ubiquitous that it affects all populations of the rous sulfate), (b) to test sensory characteristics of the world irrespective of race, culture, or ethnic back - GFB-Fe (feel-mouth texture, crumb color, aroma and ground. Despite all the latest advances in modern med - taste), and (c) to compare iron dialyzability of various icine, improved nutrition, and the ready availability of iron compounds in GFB-Fe. The most acceptable prod - cheap oral Fe, there is still no good explanation for the ucts were those fortified with ferric pyrophosphate with widespread persistence of Fe deficiency. It is possible emulsifiers and ferric pyrophosphate. Ferrous dialyz - that the Fe deficiency phenotype is very prevalent able iron (ferrous iron with molecular weight lower because of many factors other than the commonly than 8000 Da, an index for prediction of Fe bioavail - cited causes such as a decreased availability or an ability) was measured under simulated gastrointestinal increased utilization of Fe. Several thousand years ago, conditions. Ferrous dialyzable iron in GFB-Fe forti- human culture changed profoundly with the agrarian fied with ferric pyrophosphate with emulsifiers, revolution, when humans turned to agriculture. Their NaFeEDTA, ferrous bis-glycinate, ferrous gluconate or diet became Fe deficient and new epidemic infections ferrous sulfate was higher than that in GFB-Fe fortified emerged due to crowding and lifestyle changes. There with electrolytic iron, ferrous lactate or ferric pyrophos - is convincing evidence that Fe deficiency protects phate (P < 0.05). These results are promising for the against many infectious diseases such as malaria, development of GFB-Fe products in the future. plague, and tuberculosis as shown by diverse medical, historical, and anthropologic studies. Thus, this change Molecular control of iron transport. Ganz, T. J of diet increased the frequency of Fe deficiency, and Am Soc Nephrol. 2007;18:394–400. (Departments of epidemic infections exerted a selection pressure under Medicine and Pathology, David Geffen School of which the Fe deficiency phenotype survived better. Medicine, 10833 Le Conte Avenue, CHS 37-055, Multiple evolutionary factors have contributed in mak - University of California, Los Angeles, CA 90095- ing Fe deficiency a successful phenotype. Authors 1690, USA. Email: [email protected]) analyze some of the recent findings on Fe metabolism, the theories explaining excessive menstruation in The Fe-regulatory hormone hepcidin is a 25-amino human primates, the unexplained relative paucity of acid peptide that is synthesized in hepatocytes. hemochromatosis genes, the former medical practice Hepcidin binds to the cellular Fe export channel ferro - of “blood-letting,” and other relevant historical data to portin and causes its internalization and degradation fully understand the phenomenon of Fe deficiency. and thereby decreases Fe efflux from Fe exporting tis - They suggest that, due to a long evolutionary persist - sues into plasma. By this mechanism, hepcidin inhibits ence of Fe deficiency, efforts at its prevention will take dietary Fe absorption, the efflux of recycled Fe from a long time to be effective. splenic and hepatic macrophages, and the release of Fe from storage in hepatocytes. Hepcidin synthesis is Effect of zinc supplementation on child morta- stimulated by plasma Fe and Fe stores and is inhibited lity. Lazzerini M. Lancet 2007;370:1194–5. (Dept of by erythropoietic activity, ensuring that extracellular Pediatrics, Institute of Child Health, IRCCS Burlo plasma Fe concentrations and Fe stores remain stable Garofolo, Trieste, Italy. and the erythropoietic demand for Fe is met. During Email: [email protected]) inflammation, increased hepcidin concentrations cause Fe sequestration in macrophages, resulting in hypofer - Author comments on the accompanying article by remia and eventually anemia of inflammation. Tielsch and colleagues and suggests that when exam -

58 Recent literature Magazine Issue 3/2007

ining the results of intervention trials, readers should A mathematical model of zinc absorption in look at the confidence intervals (CI) of potential bene - humans as a function of dietary zinc and phytate. fits. She suggests that although the overall result may Miller LV, Krebs NF, Hambidge KM. J Nutr 2007; not reach statistical significance, “if the upper bound - 137:135–41. (Section of Nutrition, Department of ary of the CI includes an important benefit, the possi - Pediatrics, University of Colorado Health Sciences bility that treatment still might be worthwhile has not Center, Denver, CO 80262, USA. been ruled out”. In other words the investigators might Email: [email protected]) have missed a true treatment effect and the stronger the non-significant trend in favor of the experimental The quantities of zinc and phytate in the diet are the treatment, the more likely the investigators missed a primary factors determining zinc absorption. A mathe - true treatment effect and that zinc can reduce mortali - matical model of zinc absorption as a function of ty in children over 12 mo. She accepts however that dietary zinc and phytate can be used to predict dietary establishing the size of the effect and the influence of zinc requirements and, potentially, enhance our under - malaria may now be difficult to investigate as inclu - standing of zinc absorption. Authors described a sion of a placebo group in future trials would be ethi - model relating total zinc absorption to total dietary cally questionable, at least in areas with malaria. zinc and total dietary phytate, fitted it to 21 mean data from whole day absorption studies using nonlinear Effect of daily zinc supplementation on child regression analysis and found it to have an R-squared mortality in southern Nepal: a community-based, of 0.82. The model was judged to be valid and of cluster randomised, placebo-controlled trial. immediate value for studying and predicting absorp - Tielsch JM, Khatry SK, Stoltzfus RJ et al. Lancet tion. A version of the model incorporating a passive 2007;370:1230–9. (Dept of Intl Health, Johns Hopkins absorption mechanism was not supported by the avail - University, Baltimore, MD, USA. able data. Email: [email protected]) Plant breeding to control zinc deficiency in Zinc supplementation can reduce subsequent morbidi - India: how cost-effective is biofortification? Stein ty in children recovering from diarrhea and respiratory AJ, Nestel P, Meenakshi JV et al. Pub Hlth Nutr illness in developing countries. Authors assessed the 2007;10:492-–501. (Division of International Agri- effect of daily zinc supplementation on morbidity and cultural Trade and Food Security, University of mortality in children in southern Nepal. The trial com - Hohenheim (490b), 70593 Stuttgart, Germany. prised a community-based, cluster-randomized, dou - Email: [email protected]) ble-masked, placebo-controlled, 2x2 factorial trial in children aged 1–35 mo (NCT00109551). Treatment The survey aimed to estimate the potential impact of groups were placebo, Fe and folic acid, Zn, and Fe and Zn biofortification of rice and wheat on public health folic acid with Zn (12.5 mg Fe, 50 mg folic acid and in India and to evaluate its cost-effectiveness com - 10 mg Zn). All children received vitamin A supple - pared with alternative interventions and international mentation twice per year. Only the Zn arm of the study standards. The burden of Zn deficiency (ZnD) in India was reported in the manuscript. 41 276 children (place - was expressed in disability-adjusted life years bo n=20 308 or Zn n=20 968) were followed-up for 60 (DALYs) lost. Current Zn intakes were derived from a 636.3 person-years. The primary outcome was child nationally representative household food consumption mortality but daily reports of common morbidities in survey (30-day recall) and attributed to household stratified random subsamples of children were members based on adult equivalent weights. Using a assessed every week for 12 mo. Authors reported that dose-response function, projected increased Zn intakes total mortality of children receiving zinc supplementa - from biofortified rice and wheat were translated into tion was not significantly different from that of chil - potential health improvements for pessimistic and dren receiving placebo. Further data are needed from optimistic scenarios. After estimating the costs of other populations with endemic Zn deficiency to developing and disseminating the new varieties, the confirm a potential beneficial effect in children over cost-effectiveness of Zn biofortification was calculated 12 mo (135 Zn vs 165 placebo; 0.80, 0.60–1.06). The for both scenarios and compared with alternative frequency and duration of diarrhea, persistent diarrhea, micronutrient interventions and international reference dysentery, and acute lower respiratory infections did standards. From representative household survey data not differ between the groups. (n = 119 554) authors calculated the annual burden of ZnD in India is 2.8 million DALYs lost. Zn biofortifi - cation of rice and wheat may reduce this burden by

59 SIGHT AND LIFE Recent literature

20–51% and save 0.6–1.4 million DALYs each year, Prevalence of iron deficiency and anemia among depending on the scenario. The cost for saving one healthy women of reproductive age in Bhakta- DALY amounts to $US 0.73–7.31, which is very cost- pur, Nepal. Chandyo RK, Strand TA, Ulvik RJ et al. effective by the standards of the World Bank and the Eur J Clin Nutr 2007;61:262–9. (Department of Child WHO, and is lower than that of most other micronutri - Health, Institute of Medicine, Tribhuvan University, ent interventions. Kathmandu, Nepal. Email: [email protected])

Interaction of lead with some essential trace This cross-sectional study used a cluster sampling pro - metals in the blood of anemic children from cedure to randomly recruit 500 apparently healthy Lucknow, India. Ahamed M, Singh S, Behari JR et women of reproductive age (13–35 years) to explore al. Clin Chim Acta 2007;377:92–7. (Analytical associations between markers of Fe status and Fe Toxicology Division, Industrial Toxicology Research intake. Plasma concentration of hemoglobin (Hb), fer - Centre, P.O. Box 80, M.G. Marg, Lucknow-226 001, ritin and transferrin receptors was measured. Dietary India. Email: [email protected]) information was obtained by a food frequency ques - tionnaire and two 24-h dietary recalls. The prevalence Lead inhibits heme synthesis, can cause anemia and of anemia (Hb concentration < 120 g/L) was 12% (n may affect the absorption and metabolism of essential 58). The prevalence of depleted Fe stores (plasma fer - trace metals. There is little information from northern ritin <15 µg/l) was 20% (n 98) whereas the prevalence India on high blood lead levels ( Ն 100 µg/L) and ane - of Fe deficiency anemia (anemia, depleted Fe stores mia in children. A cross-sectional study recruited 75 with elevated transferrin receptor (tfr) i.e. > 1.54 mg/l) children from Lucknow aged 1–7 y (50 anemic (Hb Յ was 6% (n 30). Seven percent (n 35) of women had Fe 80 g/L) and 25 non-anemic (Hb > 80 g/L)) to evaluate -deficient erythropoiesis (depleted Fe stores and ele - the association of blood lead levels Ն 100 µg/L with vated transferrin receptor but normal Hb). Out of the anemia. In addition, blood levels of lead, iron, zinc, 58 anemic women, 41 (71%) and 31 (53%) also had copper, and calcium, hemoglobin (Hb), hematocrit, elevated plasma tfr and depleted Fe stores, respective - ascorbic acid and delta-aminolevulinic acid dehy - ly. 54% of the women ate less than the recommended dratase (delta-ALAD) were measured. Children were average intake of Fe. The main foods contributing to categorized into those with blood lead Ն 100 µg/L dietary Fe were rice, wheat flour and green and dry (6.89 ± 2.44; n=19, GI) and those with blood lead vegetables. The prevalence of anemia in our study was >100 mg/L (21.86 ± 7.58; n=56, GII). After adjust - substantially lower than the national figure for non- ment for child’s age, sex, and area of residence, chil - pregnant women. Only about half of the women with dren with blood lead levels. Ն 100 µg/L were 2.87 anemia also had depleted Fe stores, suggesting that (95% CI: 1.60–2.87) times as likely to have anemia as other causes of anemia may be prevalent in this popu - children with blood lead levels <100 mg/L. The differ - lation. ences of the adjusted mean values of Hb, delta-ALAD, and hematocrit were significantly lower in children Plasma carotenoid levels and cognitive perform - from the GII group when compared to children from ance in an elderly population: results of the EVA the GI group (p < 0.01, p < 0.01, and p < 0.05, respec - Study. Akbaraly NT, Faure H, Gourlet V et al. tively). Among essential trace metals, adjusted mean Gerontol A Biol Sci Med Sci 2007;62:308–16. levels of blood iron, zinc, and calcium were signifi - (NSERM U888, Hôpital La Colombière, 39 Avenue cantly lower in GII as compared to GI (P < 0.05 each). Charles Flahault, BP 34493, 34093 Montpellier, There were significant negative correlations of blood Cedex 5, France. Email: [email protected]) lead levels with delta-ALAD (r = -0.612, p < 0.01), hematocrit (r = -0.427, p < 0.05), iron (r = -0.552, p < The authors hypothesized that because carotenoids 0.05) zinc (r = -0.427, p < 0.05), and calcium (r = - have antioxidant properties, they may have a role in 0.324, p < 0.05). Conclusion: Results indicate that ele - preventing cognitive impairment. In a cross-sectional vated blood lead levels ( Ն 100 µ/L) in children were analysis on a healthy elderly population (the EVA, significantly associated with risk of anemia and that “Etude du Vieillissement Artériel,” study; n = 589, age blood lead levels also influenced the status of essential = 73.5 +/- 3 years), the relationships between cognitive trace metals. performance (assessed by the Mini-Mental State Examination, Trail Making Test Part B, Digit Symbol Substitution, Finger Tapping Test, and Word Fluency Test) and different plasma carotenoid concentrations (lutein, z eaxanthin, ␤-cryptoxanthin, lycopene, ␣-caro -

60 Recent literature Magazine Issue 3/2007

tene, and trans- ␤-carotene and cis- ␤-carotene) were mins or vitamin A/ ␤-carotene supplements during examined. Logistic regression showed that participants pregnancy and lactation to HIV-infected women on with the lowest cognitive functioning (< 25th per - their children’s risk of malaria up to 2 years of age, in centile) had a higher probability of having low levels a randomized, placebo-controlled trial. Tanzanian of specific plasma carotenoids (< 1st quartile): women (N = 829) received one of four daily oral lycopene and zeaxanthin. For zeaxanthin, odds ratios regimens during pregnancy and after delivery: 1) vita - ranged from 1.70 to 1.97 for the different tests and for mins B, C, and E (M); 2) vitamin A and ␤-carotene lycopene, from 1.64 to 1.93. The authors recognized (VA/BC); 3) multivitamins including VA/BC that there is no way of knowing if the low levels of (M+VA/BC); or 4) placebo. After 6 mo, all children carotenoids precede or are a consequence of cognitive received 6-mo oral VA supplements irrespective of impairment but suggest further research is needed to treatment arm. The incidence of childhood malaria investigate their observations. was assessed through 3-mo blood smears and at monthly and interim clinic visits from birth to 24 mo Multi-micronutrient supplements of age. Compared with placebo the incidence of clini - cal malaria was 71% lower (P < 0.02) in group M, 43% A multiple-micronutrient-fortified beverage (P = 0.04) lower in M+VA/BC and 63% (P = 0.06) affects hemoglobin, iron, and vitamin A status lower in VA/BC. The effects did not vary according to and growth in adolescent girls in rural Bangla- the children’s HIV status. Supplementation of preg - desh. Ziauddin Hyder SM, Haseen F, Khan M et al. J nant and lactating HIV-infected women with vitamins Nutr 2007;137:2147–53. (Department of Public Health B, C, and E might be a useful, inexpensive intervention Sciences, University of Toronto and Research to decrease the burden of malaria in children born to Institute, the Hospital for Sick Children, Toronto, HIV-infected women in sub-Saharan Africa. [DIT: It Ca nada M5G 1X8. Email: [email protected]) seems unlikely that nutritional status would influence the frequency of being bitten by mosquitoes suggest - The authors tested whether a multiple-micronutrient- ing that better nutritional status may help children to fortified beverage given 6d/wk for 12 mo could recover more quickly.] improve hemoglobin (Hb) concentrations, micronutri - ent status, and growth among adolescent girls in rural Randomized comparison of 3 types of micronu - Bangladesh. A total of 1125 girls (Hb Ն 70 g/L) trient supplements for home fortification of com - enrolled in a randomized, double-blind, placebo-con - plementary foods in Ghana: Effects on growth trolled trial and were allocated to either a fortified or and motor development. Adu-Afarwuah S, Lartey non-fortified beverage of similar taste and appearance. A, Brown KH et al. Am J Clin Nutr 2007;86:412–20. The fortified beverage increased Hb, serum ferritin (Program in International Nutrition and Community (sFt) and retinol concentrations and had greater Nutrition, University of California, Davis, CA increases in weight, MUAC, and BMI at 6 mo (P < 95616–8669, USA. Email: [email protected]) 0.01). Consuming the beverage for an additional 6 mo did not further improve the Hb concentration, but the A low micronutrient content of complementary foods sFt level continued to increase (P = 0.01). The use of a is associated with growth faltering in many popula - multiple-micronutrient-fortified beverage can con - tions. A potential low-cost solution is the home fortifi - tribute to the reduction of anemia and improvement of cation of complementary foods with Sprinkles (SP) micronutrient status and growth in adolescent girls in powder, crushable Nutritabs (NT) tablets, or energy- rural Bangladesh dense (108 kcal/d), fat-based Nutributter (NB). Authors investigated whether multiple micronutrients Effects of maternal vitamin supplements on added to home-prepared complementary foods would malaria in children born to HIV-infected increase growth and if the effect would be greatest in women. Villamor E, Msamanga G, Saathoff E et al. the presence of added energy from fat. Ghanaian Am J Trop Med Hyg 2007;76:1066–71. (Department infants (n= 313) were randomly assigned to receive of Nutrition, Harvard School of Public Health, Boston, SP, NT, or NB containing 6, 16, and 19 vitamins and Massachusetts 02115, USA. minerals, respectively, daily from 6 to 12 mo of age. Email: [email protected]) Anthropometric status; micronutrient status; motor development; and morbidity were assessed at inter - The effects of maternal multivitamin supplementation vals. Infants (n = 96) not randomly selected for the on the risk of malaria in children are unknown. intervention (non-intervention; NI) were assessed at 12 Authors examined the impact of providing multivita - mo. The groups did not differ significantly at baseline,

61 SIGHT AND LIFE Recent literature

except that the NB group had a higher proportion of multiple-micronutrient foodLET providing the RNI boys and weighed slightly more. The dropout rate during infancy may be one strategy to improve iodine (15/313) was low. At 12 mo, after control for initial status. size, the NB group had a significantly greater mean weight-for-age z score (WAZ) (-0.49) and length-for- Non-provitamin A carotenoids age z score (LAZ) (-0.20) than did the NT group (WAZ: -0.67; LAZ: -0.39) and the NT and SP groups The relationship of dietary carotenoid and vita - combined (WAZ: -0.65; LAZ: -0.38); the difference min A, E, and C intake with age-related macular with the NI group (WAZ: -0.74; LAZ: -0.40) was not degeneration in a case-control study: Age-Related significant. A lower percentage of the NI infants (25%) Eye Disease Study Research Group. AREDS Report than of the intervention groups (SP: 39%; NT: 36%; No. 22. Arch Ophthalmol 2007;125:1225–32. NB: 49%) could walk independently by 12 mo. All 3 (The EMMES Corporation, 401 N Washington St, Ste supplements had positive effects on motor milestone 700, Rockville, MD 20850-1707. acquisition by 12 mo compared with no intervention, Email: [email protected]) but only NB affected growth. Relationships between dietary carotenoids, vitamin A, Efficacy of daily and weekly multiple micronu - alpha-tocopherol, and vitamin C and prevalent age- trient food-like tablets for the correction of related macular degeneration (AMD) in the Age- iodine deficiency in Indonesian males aged 6–12 Related Eye Disease Study (AREDS) were assessed mo. Wijaya-Erhardt M, Untoro J, Karyadi E et al. Am using logistic regression analyses. Stereoscopic color J Clin Nutr. 2007 85:137–43. (SEAMEO-TROPMED fundus photographs were used to categorize 4519 Regional Center for Community Nutrition, University AREDS participants aged 60 to 80 years at enrolment of Indonesia, Jakarta, Indonesia. into 4 AMD severity groups and a control group (par - Email: [email protected]) ticipants with < 15 small drusen). Nutrient intake was estimated from a self-administered semi-quantitative Infants are highly vulnerable to iodine deficiency, and food frequency questionnaire at enrolment. Intake val - little data exist on the effect of multiple-micronutrient ues were energy adjusted and classified by quintiles. supplementation on their iodine status. Authors com - Dietary lutein/zeaxanthin intake was inversely associ - pared the efficacy of daily and weekly multiple ated with neovascular AMD (odds ratio [OR], 0.65; micronutrient food-like tablets (foodLETs) to increase 95% confidence interval [CI], 0.45–0.93), geographic iodine status in infants. In a double-blind, placebo- atrophy (OR, 0.45; 95% CI, 0.24–0.86), and large or controlled trial, 133 Indonesian males aged 6–12 mo extensive intermediate drusen (OR, 0.73; 95% CI, were randomly assigned to 1 of 4 groups: a daily mul - 0.56–0.96), comparing the highest vs lowest quintiles tiple-micronutrient foodLET providing the Recom- of intake, after adjustment for total energy intake and mended Nutrient Intake (RNI)(DMM), a weekly mul - non-nutrient-based covariates. Other nutrients were tiple-micronutrient foodLET providing twice the RNI not independently related to AMD. In conclusion high - (WMM), a daily 10-mg Fe foodLET (DI), or placebo. er dietary intake of lutein/zeaxanthin was independent - Urinary iodine (UI) concentrations were measured at ly associated with decreased likelihood of having neo - baseline and at 23 wk. At baseline, the average UI con - vascular AMD, geographic atrophy, and large or centration (1.37 µmol/L) was within the normal range extensive intermediate drusen. but 30.8% of subjects had iodine deficiency (UI < 0.79 µmol/L). At 23 wk, initial UI correlated inversely with the changes in UI (P < 0.001) but after baseline adjust - ment, the changes in UI were not significantly differ - ent between the 4 groups (P = 0.39). The DMM group appeared to be the most effective in reducing iodine deficiency and avoiding iodine excess, but the differ - ences were not significant. Daily consumption of a

62 Alumni in Community Eye Health Magazine Issue 3/2007

Experiences of SIGHT AND LIFE Alumni in Community Eye Health at the International Centre for Eye Health

Editor’s note: Since 1991, SIGHT AND LIFE has been supporting training of students – with a special interest in vitamin A and nutrition – in Community Eye Health at the International Centre for Eye Health (ICEH) at the London School of Hygiene and Tropical Medicine. We were interested to hear from the alumni – most of them returned to their home countries after the course – about what the course has meant to their professional life and daily work. We are very grateful to Mrs Adrienne Burrough of ICEH who went back to the files and tracked down most of the former students to obtain their comments. Here we publish a selection of responses of more than 40 students from more than 20 different nations.

Dr Felix Ezepue, 1991 Dr Do Seiha, 1994 training program at the Malawi Qualifications: Ophthalmologist Qualifications: Ophthalmologist College of Health Sciences in Country: Nigeria Country: Cambodia Lilongwe, Malawi. The training program has been upgraded to I am a member of the National I am currently working in the Preah diploma level. Future plans include Advisory Committee on Micro - Ang Duong Eye Hospital in Phnom introducing other programs aimed nutrient Deficiency. I am also a Penh. I am the Coordinator for the at addressing the human resource member of the National Committee National Prevention of Blindness & component of VISION 2020: The for the Prevention of Blindness. I VISION 2020 in Cambodia. Right to Sight. The programs being have conducted and supervised targeted are cataract surgery, oph - others in the conducting of blind - Mrs Hilda Kazembe, 1995 –1996 thalmic nursing, and refraction. ness and low vision surveys. In all Qualifications: Ophthalmic Nurse These are going to be offered at these, the knowledge and skills Country: Malawi advanced diploma level. gained on the course were found to be very useful. Since my return from training at I will always be very grateful to ICEH, I have continued to teach SIGHT AND LIFE, this great Mr Michael Bassu, 1993 and coordinate the ophthalmic organization that has dedicated Qualifications: Ophthalmic Nurse itself to eradicating blindness Country: Tanzania caused by VAD, for funding my training. It is true that the course changed our approach to eye care. The Mr Bakary Ceesay, 1995 –1996 improved quality of eye care Qualifications: Cataract surgeon attracted more patients to our clin - Country: The Gambia ics and the number of surgical cases went up. Many school chil - Since completing the course, I have dren were screened at their school been promoted to Deputy Program health clinics and educated on vita - Manager (DPM) for the National min A deficiency and other dis - Mrs Hilda Kazembe Eye Care Program of the Gambia. I eases. go to hospitals or secondary units

63 SIGHT AND LIFE Alumni in Community Eye Health

In addition to my present job in the ophthalmologist in Nigeria and the government sector, I am currently whole of West Africa. attached to the University of South Asia as a course coordinator for the Mr Momodou Bah, 1999 –2000 Master of Public Health in Oph - Course: Master of Science (M.Sc.) thal mology (MPHO). I enjoy shar - in Community Eye Health, ing my knowledge and views with Country: The Gambia students who also want to follow Dr Muhit with a patient careers in blindness prevention in Mr Bakary Ceesay examining a Bangladesh. patient I thank all the staff at the ICEH for the fantastic time I had during my to operate on cataract patients or to stay in London, and especially for see eye patients. the scholarship provided by SIGHT AND LIFE, without which I would The course in Community Eye not have come to ICEH to study. Health has assisted me a great deal. It has made my work easier and I Dr Mansur Rabiu, 1998 –1999 am now able to apply the skills Qualifications: Ophthalmologist gained during the training. In the Country: Nigeria Mr Bah about to board a dug-out canoe in Gambia, receipt of vitamin A is Guinea Bissau now recorded in the infant and wel - fare card given to children during Since my return home from studies, their visits. We also have a moni - I have been engaged in blind- toring unit checking on the nutri - ness prevention activities in the tional status of infants. Gambia, Guinea-Bissau, Senegal and Guinea-Conakry. Dr Dipak Kumar Nag, 1996 –1997 Qualifications: Ophthalmologist I am the project officer for Sight Country: Bangladesh Savers International’s Gambia Dr Mansur Rabiu country office. My Master’s in When I look back 10 years, I recall Community Eye Health has ade - that terms such as ‘avoidable blind - Presently, I am heading the Nige- quately prepared me for the tasks ness’ and ‘community eye care’ rian National Blindness and Low and challenges I now face in bring - were not a part of my day-to-day Vision Survey Project. This is a ing eye care to underserved and conversations. Completing the three year multi-million dollar proj - poor communities. M.Sc. course in Community Eye ect that involves conducting a pop - Health in 1997 changed my vocab - ulation-based survey on blindness, Dr Mohammad Muhit, 1999-2000 ulary and my life. visual impairment, normative para - Qualifications: Ophthalmologist meters, socioeconomic, and quali - Country: Bangladesh tative measures across Nigeria. The result of the survey is expected to The Master’s in Community Eye be applicable to most parts of West Health program has helped me to Africa. re-orient myself from clinical oph - thalmology to a Community Eye I have indeed benefited immensely Health approach, and also provided from the Master’s course in Com- me with the necessary skills and munity Eye Health. The course has knowledge to practice Community prepared me to be able to head the Eye Health to help solve the prob - above-mentioned project. Since lem of blindness in developing completing the course, I have countries. Since then, I have con - Dr Dipak Kumar Nag become more of a community tinued to focus my work on child - ophthalmologist than a clinical hood blindness in Bangladesh. The

64 Alumni in Community Eye Health Magazine Issue 3/2007

Since completing the course in 2002, I have worked for the Nepal Red Cross Society and Shri Janaki Eye Hospital, Janakpur (in collabo - ration with the Swiss Red Cross). We work in four districts in Nepal and three districts in India. The populations we serve number Dr Muhit with a patient approximately 2.8 million in Nepal and 3 million in India. Community Eye Health course also taught me how to translate research Dr Kuldeep Dole, 2002 –2003 into policy and programs in devel - Qualifications: Ophthalmologist Dr Kuldeep Dole examining a child oping countries. Country: India Dr Mansyur Syumarti, 2003 –2004 My training at ICEH on Com - I am currently working as a com - Qualifications: Ophthalmologist munity Eye Health enabled me to munity ophthalmologist at H.V. Country: Indonesia develop a public health approach Desai Eye Hospital in Pune, India. for prevention of blindness among This job involves working at outpa - Before undertaking the Masters children and I am continuously tient clinics and conducting opera - course, I had no idea about Com - using those skills in my work to tions. munity Eye Health and only treated achieve the goals of VISION 2020. patients with eye problems individ - ually, without a community per - Mr Jib Acharya, 2001 –2002 spective of the problem. Qualifications: Ophthalmic Assistant On returning to Indonesia after Country: Nepal completing the Master’s in Com- munity Eye Health, I worked as a program coordinator in the commu - nity ophthalmology unit of Cicendo Eye Hospital. In this job, I have been involved in various activities to develop community eye care Dr Kuldeep Dole programs in Indonesia. I am able to carry out these activities because of I am also involved in project what I learned on the Community planning and implementation. Cur- Eye Health course. ren tly, we are working on a project for pediatric eye care services for this region in collaboration with Mr Jib Acharya ORBIS International. Since it began in March 2004, I have been a Firstly, I would like to convey my technical consultant to this project. sincere thanks to SIGHT AND This job involves leading a team of LIFE for funding my Masters in health workers to accomplish set Community Eye Health at the objectives, coordinating with part - Inter national Center for Eye Health ner NGOs, reporting, developing (ICEH) in London in 2001. I was strategies, controlling the budget, the first person with this qualifica - and undertaking public relations. tion in Nepal in the field of preven - This work is possible because of tive ophthalmology. The course at the training that I received at the ICEH has equipped me as an expert London School of Hygiene and in the field of Community Eye Tropical Medicine through support Dr Syumarti in the field, conducting a survey Health. from SIGHT AND LIFE.

65 SIGHT AND LIFE Alumni in Community Eye Health

Dr Funmi Bankole, 2003 –2004 programs and surgical expeditions of these products that meets the Qualifications: Ophthalmologist to various communities in Lagos specified levels of vitamin A. Country: Nigeria State, focusing on the less privi - leged people. Given this opportunity to connect with the wide range of SIGHT Dr Kahaki Kimani, 2003 –2004 AND LIFE’s readership, I would Qualifications: Ophthalmologist like to request assistance, in check - Country: Kenya ing the level of vitamin A in local - ly available grains, which are used What I learned during the Masters for preparing semi-solid food for in Community Eye Health course at children being weaned off breast the London School of Hygiene and milk. This forms the staple food for Centre for Women and Child Health, where Tropical Medicine has proven to be most children from around the age vitamin A capsules, oral polio vaccine, and immensely useful in my career as of 4 months to 2 years or more. anthelmintic drugs were distributed to children well as in my daily work. The post - on National Immunization Day in 2006 graduate students in our department of Ophthalmology, University of Dr Funmi Bankole beside the project vehicle Nairobi, have also benefited from during a survey the Community Eye Health mod - ules and I am sure this will be very useful to them once they qualify The course afforded me the oppor - and go to work in their own coun - tunity to acquire skills in designing, tries. analyzing and carrying out field work in population-based research. This has helped me in building my career in preventive ophthalmology Dr Kimani and colleagues with a patient in my country.

I am presently back in Lagos State Dr Lutful Husain, 2005 –2006 in Nigeria with the State Pre- Qualifications: Ophthalmologist vention of Blindness program, Country: Bangladesh where I take part in planning and implementing free eye screening I am currently working at the Centre for Women and Child Dr Kimani operating Health (CWCH), an NGO-based clinical and research organization in Dhaka with the aim of improving I hope to publish the work I did on maternal and child health at the the vitamin A situation in children's community level through nutrition, homes in Nairobi for my disserta - clinical, and research activities. tion during the course. My plans for the future are to initi - ate a school-based screening pro - Dr Perpetua Odugbo, 2004 –2005 gram to detect refractive error and Qualifications: Ophthalmologist other eye diseases at the communi - Country: Nigeria ty level, and to carry out research to detect subclinical vitamin A defi - An area in which I am involved is ciency among pregnant women liv - monitoring of the food fortification ing in the vicinity of CWCH by Dr Funmi Bankole at the registration point, program, which includes assessing measuring serum retinol levels. where she participated in supervising the availability of vitamin A-forti - an enumerator fied foods in selected markets in the study area, and the percentage

66 Alumni in Community Eye Health Magazine Issue 3/2007

dren. This is an extension of my MSc dissertation. I will be taking this up in London with ICEH at the London School of Hygiene and Tropical Medicine in September 2007.

Prof. Iftikhar Hussain, 2006 –2007 Qualifications: Public Health Doctor Country: Bangladesh Centre for Women and Child Health, where vitamin A capsules, oral polio vaccine, and Teaching population based survey methods anthelmintic drugs were distributed to children with our MPH students on National Immunization Day in 2006 My training in Community Eye Dr Khumbo Kalua, 2005 –2006 Health has given me the opportuni - Qualifications: Ophthalmologist ty to take a close look at the course Country: Malawi and address the issues regarding community eye care. We started our course in June 2006, after my Prof. Iftikhar Hussain return from London, and six stu - dents have enrolled for the MPH in Ophthalmology. In the current ses - My aim in joining the Diploma sion, Spring 2007, 12 more stu - Course in Community Eye Health dents have enrolled, including three at the London School of Hygiene students from Nepal. and Tropical Medi cine was to acquire the skills to develop a course curriculum for the Master of Public Health in Community Oph - Dr Kalua examining a child with thal mology at the University of cornea disease South Asia School of Public Health and Life Sciences in Dhaka, Bangladesh. I am currently in the process of establishing a resource centre for our region here in Blantyre and hope to send out a proposal for pos - sible funding assistance from ICEH or any of the donors, including SIGHT AND LIFE, that sponsored me for the training. I would like to focus more on childhood blindness and conduct more research in the area. The Healthy Eyes Activity Book I have just received news that I can be ordered from have been awarded funding from SIGHT AND LIFE, the British Council for the Pre - www.sightandlife.org vention of Blindness to pursue a Ph.D. on Key Informant Methods in Africa for identifying blind chil - SIGHT AND LIFE News

diseases. But the provision of a News nutritionally complete diet also has long-term health benefits, includ - ing im proving cognitive develop - ment and reducing the risk of Sprinkles Workshop chronic diseases. Multi-micronutrient powders pack- Quality criteria for multi-micronutrient powders ed into individual sachets (Sprink - les™) are a new solution to fortify foods with essential vitamins and minerals in an effective way. Multi-micronutrient powders have been used for 10 years in a number of trials and are proven to reduce anemia and improve the micronu - trient status of children. The con - tent of a sachet (containing 1 RNI of most vitamins and trace ele - ments) is usually added by the mother or caregiver to the porridge of a child at home, and is thus Participants of the workshop called “in-home” or “point of use” fortification. Although the quality of the original Sprinkles™ is Quality criteria for multi-micronutrient powders was the only agenda controlled through a technology item of a workshop hosted by the Sprinkles Global Health Initiative transfer agreement with a limited (SGHI) on September 27–28, 2007 in Toronto. Representatives from UN number of licensed manufacturers, agencies (World Food Programme, UNICEF), donors (US Agency for other formulations of uncertain International Development), NGOs quality are also available on the (Micronutrient Initiative, Global market. There is hence a need Alliance for Improved Nutrition), to agree on quality criteria the private sector (DSM Nutri - for production of all multi- tional Products, Fortitech), private micronutrient powders. initiatives (Sprinkles Global Health Ini tia tive, Heinz Company According to the organizers of Foundation, SIGHT AND LIFE) the workshop, Stanley Zlotkin and academia (Tufts University, (SGHI) and Martin Bloem Hospital for Sick Children) (World Food Programme), the reviewed quality criteria for the meeting went far beyond composition, manufacturing, sharing knowledge, ex pertise packaging and labeling of and experiences; it raised sever - multi-micronutrient powders al issues regarding the durability (Sprinkles™ and Sprinkles™- of some of the more sensitive type products), and proposed micronutrients in their powdered guidelines for their wide-scale form in the harsh climatic production and distribution. conditions of many developing coun tries. The outcomes of the Micronutrient malnutrition is common among people in resource-poor deli berations will be made public countries who live largely on grain-based diets with no or little access to and published in a peer-review animal-derived or fortified food. Young children, pregnant and lactating scientific journal. women and schoolchildren are particularly vulnerable to micro nutrient malnutrition. Nutritious foods with adequate amounts of micronutrients help children grow and develop normally and ward off fatal infectious

68 News Magazine Issue 3/2007

Healthy Eyes Activity Book The Hindi version of HEAB was released on Oct o ber 11, 2007 in Bhubaneswar, Orissa, by India’s Union (HEAB), 2nd edition in Hindi Minister of State for Health Mrs Panabaaga Lakshmi and Telugu in the presence of the President of the International Agency for the Prevention of Blindness (IAPB) SIGHT AND LIFE gave a generous grant to the Cen- Dr Gullapalli Nageswara Rao. Dr Rao, who is also tral Audio Visual Unit at LV Prasad Eye Institute, the Founder-Chairman of LV Prasad Eye Institute India, for the translation and printing in Hindi and (LVPEI) in Hyderabad, India, was keen to have the Telugu of 9,000 copies of the 2nd edition of ‘Healthy Hindi HEAB book released at natio nal level to mark Eyes Activity Book (HEAB) – A Health Teaching World Sight Day (WSD). Significantly, WSD, which Book for Primary Schools.’ HEAB is authored by Dr is observed every year on the second Thursday of Victoria Francis and Dr Boateng Wiafe and published October, is dedicated this year to the eye care of jointly by the International Centre for Eye Health, children. London and SIGHT AND LIFE. Marking WSD in Hyderabad, the Telugu HEAB was released jointly by up-and-coming youth icon and film actor Navdeep (of the box- office hit Telugu movie Chanda- mama fame) and Mr Ramesh Prasad, Chair man of Prasad Film Labor - atories and Prasad’s Group, India, at the inauguration of an eye care exhi - bition arranged by LV Prasad Eye Institute in Prasad’s IMAX in the heart of Hyderabad. Introducing the book at the book release function, Mr Sam J Balasundaram, Public From left to right: Dr Somasheila Murthy, Consultant, LV Prasad Eye Relations Officer and Administrator Institute; Mr Ashish Vohra, Head of Commercial Mass Market, Fullerton India Credit Company Ltd. (FICCL); Upcoming Telugu film star of LVPEI, highlighted the role of Navadeep; Mr Ramesh Prasad, Managing Director, Prasad Media SIGHT AND LIFE in making the Corporation Ltd.; Dr V S Sangwan, Associate Director, LV Prasad Eye book translations and printing possi - Insti tute; Samuel J Balasundaram, Administrator, LV Prasad Eye Insti tute ble.

Our heartfelt thanks go to SIGHT AND LIFE for reaching out to serve the Indian population through the book translation and bulk printing of HEAB.

To receive copies of the HEAB in Hindi and Telugu please contact Mrs Shobha Mocherla, Central Audio Visual Unit at LV Prasad Eye Institute, Hyderabad 500 034, A.P., India E-mail: [email protected]

Mr Ramesh Prasad, Managing Director, Prasad Media Corporation Ltd, releases the new Telugu HEAB during the World Sight Day in Hyderabad

69 SIGHT AND LIFE News

Highlights from India’s third antenatal iron supplement use is low, with only 23% of women on average reporting having consumed 90 or National Family Health Survey more iron-folate tablets during a previous pregnancy. The mean prevalence of anemia among men 2 was The report of the third National Family Health Survey 24%. While lower than that in children and women, (NFHS-3) conducted in India during 2005–2006 was this rate may be higher than in other settings, although released on October 11, 2007. The NFHS-3, carried comparable nationally representative data on this are out 7 years after the NFHS-2, was conducted in scant. 29 states including the three new states of Jharkhand, Uttaranchal and Chhattisgarh of India. The sample A national vitamin A supplementation program calls for comprised households selected to be representative a large dose of vitamin A to be delivered to children nationally as well as by state. A total of about 199,000 from nine months to three years of age once every six married women aged 15–49 years and, for the first months. NFHS-3 found a modest increase in vitamin A time, men aged 15–54 years and unmarried women supplementation coverage from 17% in NFHS-2 to 25% were interviewed. Nutritional status assessment is an in NFHS-3. This level of coverage is far below being important component of the NFHS providing valuable universal and is unlikely to impact on either the preva - data and trends in the prevalence of wasting and stunt - lence of xeropthalmia or lead to reductions in child ing malnutrition in young children and women as well mortality. A 25% reduction in the prevalence of night as the extent of micronutrient deficiencies such as that blindness among pregnant women was noted (from of vitamin A and iron. The NFHS-3 included nutrition - 12% in NFHS-2 to 9% in NFHS-3). al status assessment of men for the first time. Also worth noting was the addition of HIV-1 testing among The NFHS-3 estimates of the prevalence of under - more than 100,000 women and men during the house - weight (<-2 z-score weight for age), wasting (<-2 z- hold survey in seven high HIV-1 prevalent states of the score weight for height) and stunting (<-2 z-score, country. A few highlights related to the nutritional height for age) malnutrition among children under 5 status from the report are described below. years were based on the new WHO re ference standards 3. Approxi mately half India harbors one of the highest were stunted, 43% were under - rates of anemia in young children weight, and 20% were wasted. and women of reproductive age, The NFHS-3 report also pro - especially during pregnancy. Data vides tables on secular trends from NFHS-3 reveals continuing using data from the previous high rates of anemia in these popu - survey which were collected lations and a small but clear in - only among under three year crease in the prevalence of anemia olds. After applying the new in both women and children from WHO reference standards to the the previous survey. The overall previous data, the prevalence of prevalence of anemia among chil - stunting and underweight was dren and women of reproductive found to have reduced from age 1 increased from 74% and 52%, 51% to 45% and 43% to 40%, respectively, in NFHS-2 (conduct - respectively. How ever, the pre- ed in 1998–99) to 79% and 56%, valence of wasting increased by respectively, in NFHS-3. At least 3%, from 20% to 23%, in part half of these cases of anemia may due to the decline in stunting. be attributable to iron deficiency. India is one of the few countries The NFHS-3 data also reveal that has a policy for iron supple - the dual burden of malnutrition mentation in children. However, faced by the Indian population, data collected during NFHS-3 re - a trend likely to continue to veal a dismally low national cover - increase with the ongoing nutri - age of 5%, providing in part an tion transition occurring on the explanation for the continuing and subcontinent, un less strong pre - even increasing rates of anemia in ventive action is taken. Wasting this population group. Similarly, under nutrition among women

70 News Magazine Issue 3/2007

defined as thinness (BMI<18.5 kg/m 2) increased from A copy of the report is available at: 21% in NFHS-2 to 28% in NFHS-3. Twenty seven http://www.nfhsindia.org/nfhs3_national_report.html percent of men were also thin (BMI<18.5 kg/m 2). Although the mean body mass index (BMI) was simi - Communicated by Veena Singh and Parul Christian, lar among men and women (20.2 and 20.5 kg/m 2), Johns Hopkins School of Public Health, Baltimore, 15% of men and 21% of women were overweight or USA, E-mail: [email protected] obese (BMI ≥25 kg/m 2). Among women this rate was higher than the 17% found during NFHS-2. 1 Defined as hemoglobin <11 g/dL for pregnant and <12 g/dL for non-pregnant women. 2 Overall, the new NFHS data reveal that despite some Defined as hemoglobin <13 g/dL and adjusted for altitude and smoking status. modest improvements in child malnutrition there is a 3 WHO Child Growth Standards based on length/height, growing burden of micronutrient deficiencies and weight and age. Acta Paediatr Suppl 2006;450:76–85. under as well as overnutrition among adults.

Flour fortification trial A flour fortification trial was SIGHT AND LIFE donated premix launched in reforested areas of for the three-year project. in reforestation areas China in 2002, with support from of China is done with UNICEF and implemented by the The trial data show that micronutri - conference organizers. The purpose ent deficiencies among populations great success of the project was to assess the consuming fortified flour have been effectiveness of flour fortification reduced significantly. Officials from where it was currently being done in the SGA and MOH concluded that A conference on flour fortification China, and offer evidence to scale flour fortification is a cost-effective was organized by the Chinese up the project nationwide. DSM and and safe way to improve micronutri - Ministry of Health (MOH), the ent wellbeing without having to State Grain Administration (SGA), make changes to the diet. the Chinese Center for Disease Control and Prevention, and the DSM received an award as a valu - Public Nutrition and Development able partner of the flour fortification Center of China in Lanzhou, Gansu trial. Province, in Northwestern China on September 14, 2007. Represen - tatives from DSM, UNICEF, and the local CDC and Grain Bureau of Chengde and Lanzhou attended the View into the conference hall conference.

The Nutritional Anemia book and guidebook can be ordered from SIGHT AND LIFE, www.sightandlife.org

ISBN 3-906412-33-4 SIGHT AND LIFE News

Global consultation on weekly iron and folic acid supplemen- tation for anemia prevention in women of reproductive age organized by Dr Tommaso Cavalli- Sforza, Nutrition Adviser of WHO Regional Office for the Western Pacific and Dr Brunno de Benoist, Participants of the global consultation on iron and folic acid Coordinator, Micronutrient Unit, supplementation WHO, held last 25 –27 April 2007 in Manila. and folate status, before, during and 3. Decide on possible recommen - after pregnancy; dations and guidelines to apply this The objectives of the consultative approach on a large scale in order meeting were as follows: 2. Based on the above evidence, to increase the effectiveness of specify the conditions under which programs to prevent and control 1. Review the evidence of the effi - weekly iron and folic acid supple - anemia and iron deficiency; and cacy, effectiveness, safety and fea - mentation could be successfully sibility of preventive supplementa - implemented as measures to pre - 4. Identify and prioritize knowl - tion with weekly iron and folic acid vent anemia at population level in edge gaps for which additional supplementation in improving iron women of reproductive age; research is needed.

First regional flour fortification workshop for East and Southeast Asia

More than 70 experts from govern - ments, international agencies, pub - lic health institutions and the flour industry gathered in Kuala Lum - pur, Malaysia, on August 18 –20, 2007, for the first Regional Flour Participants of the flour fortification workshop Fortification Workshop for East and Southeast Asia. The objective ed. Efficacy trials in the Phili p - fortification in Malaysia, Vietnam, of the workshop was to accelerate pi nes showed significant improve - and Thailand. The workshop pro - the pace of collaborations between ments in iron and vitamin A status vided a platform to assess the status the public and private sector toward as a result of consuming bread of current national flour fortifica - achieving and sustaining national made from iron and vitamin A-for - tion efforts, analyze challenges in flour fortification. tified wheat flour. achieving universal flour fortifica - tion, and share lessons learned from At present, Indonesia and the The participants, representing national flour fortification initia - Philippines are the only countries 20 countries, considered strategies tives. where flour fortification is mandat - to achieve the full promise of flour

72 Letters to the editor Magazine Issue 3/2007

Letters to the editor

Dear Sir, I am doing my best to help all the people around here, especially in the areas of health education, medical I have been regularly receiving and writing in to your treatment and data management. Nonetheless, there Magazine for three years now and, like many of your are still many challenges and much to learn – with sup - readers, would like to express my thanks to SIGHT port from SIGHT AND LIFE, I look forward to being AND LIFE. fully equipped to work efficiently as a community clinician.

Children awaiting vitamin A dosing Child receives vitamin A capsule

Since I first wrote in to the magazine, I have been We truly appreciate the very useful information work ing at the same dispensary at Mtambo in SIGHT AND LIFE has given us on vitamin A and Tanzania, where patients are brought for medical treat - other important nutrition and health topics. I hope you ment and services. Underfive children are also brought will continue to support me in increasing my know l - in for weighing and vaccinations, and we still give edge and providing better health education so that I deworming tablets and vitamin A drops to all children may help the community in Mtambo and all other aged one year and above. This has been achieved by Tanzanians more effectively. the excellent team work and dedication of my three full-time village health workers. I will always be grate - Sincerely, ful to my staff, the staff of SIGHT AND LIFE, and Almandus John Bosco everyone in Mtambo and around the world who has Mtambo Dispensary supported us. Mpanda, Tanzania

Dir Sir, We have so far administered vitamin A capsules over On behalf of the Sunbie Project in Ghana, I would like a 10 day campaign to 3,000 children aged six months to share with your readers how privileged we feel to be to five years. This was done by first distributing the a partner of SIGHT AND LIFE. We are grateful for capsules to the children attending the Lemu your assistance to this program, which aims to Community Public School, then visiting the homes of eradicate vitamin A de ficiency (VAD) among the poor children who do not go to school. The community was and vulnerable in the Lemu community, in Sene very excited because their children received vitamin A District – Kwame Danso. capsules, as did the teachers. While administering the

73 SIGHT AND LIFE Letters to the editor

vitamin A, I came across four children with serious eye problems that needed im mediate attention, which was be yond my own ability to help.

I hope to continue the project to assist the people in my community to do away with vitamin A deficien - cy with the help of SIGHT AND LIFE. The Sunbie Project’s resources, such as personnel and funding, are limited and we appeal to SIGHT AND LIFE to continue helping the project because the demand for help is overwhelming.

In future, I would like to realize my plan to extend services to the in terior villages around the Lemu community, which I think may have even more seri - ous eye problems. However, the means to reach such villages is itself a problem. I hope with your assistance I can overcome these constraints and continue to help my community.

Yours faithfully,

Esther Pegree Bayuo, Northern School of Esther Pegree Bayuo dosing vitamin A Business, PO Box 482, Tamale, Northern Region, Ghana

Doreen Mwintero, 6 years old, Tamale, Ghana

74 Publications Magazine Issue 3/2007

Publications

Editor’s note: SIGHT AND LIFE presents recent publications which may be of particular interest to our readers. However, no publications other than SIGHT AND LIFE publications are available from us, nor do we have any priviledged access to them.

Home-gardens to address Hills in KwaZulu-Natal during the 1990s. This home-garden project, vitamin A deficiency in South which was aimed at the production and consumption of vitamin A-rich Africa: a food based approach fruits and vegetables together with nutrition education, proved to be suc - cessful in improving the vitamin A status of 2 to 5-year-old children. The High rates of micronutrient malnu - home-garden approach can complement both fortification and supplemen - trition persist despite commitments tation programs and provides a sustainable means of achieving food and made globally to reduce this nutritional security. People in rural areas often have limited access to serious problem. Hunger and mal- commercially available fortified foods. Rural areas will therefore benefit nutrition and their devastating con - most from the inclusion of vitamin A-rich vegetables in gardening proj - sequences can be dramatically re- ects. duced through well conceived and carefully developed and imple - The purpose of this manual is to assist organizations in implementing mented programs. Vitamin A defi - home-garden projects to improve vitamin A status. This manual will ciency is of public health signi- prove to be useful, not only to those interested in food-based programs, ficance, and affects mostly women but also to those concerned with health and nutrition education. It will also and children in developing coun - encourage and facilitate the design and implementation of effective food- tries. In an attempt to address vita - based projects to improve nutrition. min A deficiency in South Africa, the authors Mieke Faber, Sunette For further information on the publication, please visit the website of the Laurie and Sonja Venter from the Agricultural Research Council of South Africa www.arc.agric.za Medical Research Council (MRC) and the Agricultural Research Eye care in developing nations Council developed, monitored and evaluated an integrated household The prevention of blindness is known to food production and growth moni - be one of the most cost-effective health toring project in a rural village bor - interventions that can be undertaken. It dering the Valley of a Thousand should start at the indivi dual, family, and community levels. Primary eye care, as part of primary health care, has thus been strongly advocated by the World Health organization’s Program for the Pre - vention of Blindness and Deafness in its long-standing partnership with the International Eye Foundation and other non-governmental organizations. To be meaningful, primary eye care must respond to local needs and resources and must use opportunities for com - munity support. This book, now in its 4th edition, responds particularly well to the need for practical, innovative, and affordable solutions to bring eye care to those populations most in

75 SIGHT AND LIFE Publications

need in the developing world. The editions has proved this book’s As examples, apparent vitamin- most common ocular disorders and popularity and value. We are in - dependent modifications that are their management are described, debted to Dr Schwab for bringing important to epigenetic events and including public health perspectives forth this expanded and updated genomic stability are described, as and appropriate guidelines. The edition.” well as new information on the role book contributes greatly to increas - and importance of maintaining ing the access to basic eye care For further information on this optimal vitamin status for anti - services in developing countries. book please visit oxidant and anti-inflammatory de - Such services, along with appropri - www.manson-publishing.co.uk fense. Important analytical advan - ate public health interventions, con - ces in vitamin analysis and assess - stitute the key to eliminating unnec - Handbook of vitamins ment are discussed in a chapter essary visual loss in future genera - dealing with accelerated mass tions. The existence of effective In keeping with the tradition of pre - spectrometry (AMS) applications. public/private partnerships for the vious editions, the 4th edition of the prevention of blinding diseases, Handbook of Vitamins was assem - It is also important to emphasize along with the rapid progress of bled to update and provide contem - that much of the interest in vita - Vision 2020: the ‘Right to Sight’ porary perspectives on vitamins. mins stems from an appreciation global movement should make it One of the of the editors’ chal - that there regrettably remain siz - possible to achieve that goal. lenges (Janos Zempleni, Robert B. able populations at risk of vitamin Rucker, Donald B. McCormick, deficiencies. In this regard, classic Alfred Sommer, Dean Emeritus John W. Suttie) was to maintain the examples are included along with and Professor, Johns Hopkins clinical focus of previous editions, examples of vitamin-related poly - University on this book: “It is the while addressing important con - morphisms and genetic factors that eye health worker’s guide to deliv - cepts that have evolved in recent influence the relative needs for ering services to low-resource pop - years owing to the advances in given vitamins. ulations, whether they be pockets of molecular and cellular biology as poverty in otherwise affluent well as those in analytical chem - This volume is written by a group nations or broadly deprived popu - istry and nanotechnology. The of authors who have made major lations living in the developing reader will find comprehensive contributions to our understanding world. Demand for the first three summaries that focus on chemical, of vitamins. Dr Janos Zempleni physiological, and joins the group of editors who nutritional relation - assembled the third edition. ships and highlights Dr Zempleni brings a molecular of newly described biology perspective to complement and identified func - the biochemical and physiological tions for all the rec - expertise of the other editors. ognized vitamins. Dr Lawrence Machlin who was The goal was to sole editor of the first two editions assemble the best in this series and who died shortly currently available after the release of the 3rd edition reference text on would be pleased with the progress vitamins for an and advances in vitamin research audience ranging summarized in the 4th edition. from basic scien - tists to clinicians to For further information on this vol - advanced students ume please visit the website of the and educators with publisher www.crcpress.com a commitment to better understand - ing vitamin func - tion.

76 Publications Magazine Issue 3/2007

Community-based management of severe acute Nutrition education in primary schools – malnutrition a planning guide for nutrition education in primary schools

Educating school children in healthy nutrition is one of the most effective strategies for overcoming malnutri - tion and chronic diet-related diseases, but has been neglected for far too long. Chronic diet-related dis - eases, such as excess weight and obesity, diabetes, hypertension and cardiovascular diseases are not restricted to rich countries. They are increasing around the globe as a result of new lifestyles and eating habits. Two out of three overweight and obese people now live in low- and middle-income countries, with the vast majority in emerging markets and transition eco - nomies, according to the WHO. Certainly, hunger and undernutrition remain a major public health problem for some 820 million people in developing countries that do not have the means to buy or produce sufficient good quality food. But globalization and economic development have introduced new foods and altered dietary habits and lifestyle patterns in many develop - ing countries as well. A joint statement by the WHO, WFP, SCN and UNICEF It is not only the amount of food, but the quality of a diet that has a critical effect on children’s growth, Severe acute malnutrition remains a major killer of health and learning capacity. Eating is not just a children under five years of age. Until recently treat - ment has been restricted to facility-based approaches, greatly limiting its coverage and impact. New evi - dence suggests, however, that large numbers of chil - dren with severe acute malnutrition can be treated in their communities without being admitted to a health facility or a therapeutic feeding centre.

Children with severe acute malnutrition need safe, palatable foods with an energy content and adequate amounts of vitamins and minerals. Ready-to-use ther - apeutic foods (RUTF) are soft or crushable foods that can be consumed easily by children from 6 months without adding water. At least half of the proteins con - tained should come from milk. The community-based approach involves timely detection of severe acute malnutrition in the community and provision of treat - ment for those without medical complications with RUTF or other nutrient-dense foods at home. If prop - erly combined with a facility-based approach for those malnourished children with medical complications and implemented on a large scale, community-based management of severe acute malnutrition could pre - vent the deaths of hundreds of thousands of children.

For further information please visit the WHO website www.who.int

77 SIGHT AND LIFE Publications

biological process; it depends on is that the adoption of a healthy diet these stu dies through dietary sup - learned habits and perceptions, on as a major life-long habit will like - plementation may have great the cultural and social environ - ly have an impact on reducing a importance as the population ages ment. Good nutrition education can substantial proportion of visual and the burden of such chro nic con - make children aware of how to impairment and blindness. A major ditions increases. achieve a nourishing diet with lim - problem facing ophthalmology will ited means; how to prepare and be the large increase in diabetic Dr Semba’s text covers the broad handle food safely and how to retinopathy that is expec ted to fol - field of nutrition and ophthalmolo - avoid food-related risks. low the worldwide epidemic of gy. The content of the 12 chapters type 2 diabetes and obesity. The covers specific disease entities e.g., FAO has published a new compre - second theme is that a historical AMD and cataract, diabetic hensive guide for curriculum devel - perspective is essential to under - retinopathy, and inborn errors of opment addressing nutrition educa - standing current challenges in oph - metabolism and specific nutrients tion in primary schools. The new thalmology, medicine, and public (e.g., vitamins C, E, A, and B-com - guide is aimed at ministry officials, health. Many of the eye diseases plex, zinc, fatty acids) and their teachers, nutrition experts, health caused by nutritional deficiencies relation to ocular disease. It is a professionals and others involved were well described when malnu - unique text, in that all chapters in the planning of nutrition educa - trition was more highly prevalent in were written by one author and tion programs for primary schools. some parts of the world. In situa - cover a large area of material rang - Although it also contains a section tions of conflict, famine, and natu - ing from an historical overview, on the basics of healthy nutrition, ral disasters, the same eye diseases epidemiology, pathology and treat - the guide is not a teaching aid for are seen repeatedly. Vitamin A ment of the condition. The text pro - nutrition education itself. It is a deficiency was once a major cause vides important and new authorita - resource package comprising three of childhood blindness in devel - tive information on the relation of elements: a book that explains the oped countries and today still nutrition to ocular disorders which key ideas and processes in nutri - remains the leading cause of blind - will reward the reader with a tion, health and education; a set of ness among children in the devel - wealth of insightful information. worksheets taking the user through oping world. The third theme in the the entire planning exercise; a handbook is that many nutrients For further information please visit classroom curriculum chart, pro - play a role in oxidative stress and the website of the publisher viding learning objectives for nutri - inflammation. This idea has www.humanapress.com tion education in primary schools emerged as a major underlying in developing countries. hypothesis in the pathogenesis of eye diseases. The guide is available in English and French. For further information Xerophthalmia is an ancient please visit the FAO website scourge and there is perhaps www.fao.org more known about vitamin A and nutritional blindness Handbook of nutrition and than is known collectively ophthalmology about aIl the other nutrition - al deficiencies and eye In the last three decades, substantial health. The relationship progress has been made in demon - between the B-com plex strating the importance of good vitamins and nutritional nutrition to eye health. Nutrition am blyopia is complex. The plays a major role from early role of caro tenoids, infant development through child - antioxidant vitamins, zinc, hood and on through older age as a and other nutrients in determinant of visual function and chronic eye disease, e.g. eye disease. The author Richard age-related macular de - Semba has emphasized three broad generation and cataract is themes in the Handbook of Nutri - still evolving. The appli - tion and Ophthalmology . The first cation of findings from

78 Publications Magazine Issue 3/2007

Doreen Mwintero, 6 years old, Tamale, Ghana

79 Photo credits US CDC: Cover page, 2, 7, address sheet; Tobias Vogt: page 2, 8, 10, 11

Colophon

SIGHT AND LIFE Magazine Layout and graphics: SIGHT AND LIFE Incorporating the Xerophthalmia GAS - graphic art studio, Dr Klaus Kraemer Club Bulletin Grenzach-Wyhlen Secretary General PO Box 2116 Publisher: SIGHT AND LIFE Printer: Burger Druck, 4002 Basel, Switzerland Editor: Klaus Kraemer Waldkirch Phone: +41 61 688 7494 Editorial team: Anne-Catherine Fax: +41 61 688 1910 Frey, Svenia Sayer-Ruehmann, Opinions, compilations and figures Email: [email protected] Federico Graciano contained in the signed articles do www.sightandlife.org not necessarily represent the point Translation and language: of view of SIGHT AND LIFE and ISBN 3-906412-40-7 transparent language solutions are solely the responsibility of the GmbH, Berlin authors.