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Comment Vol 3 September 2015 e
Vitamin A defi ciency: slow progress towards elimination
Gretchen Stevens and colleagues’ study1 in The Lancet
Global Health analyses 134 reports from 83 countries
of population-representative data for serum retinol
concentration and shows several trends in vitamin A
defi ciency. First, prevalence is diminishing in a statistically
signifi cant way in east and southeast Asia and Oceania.
Second, Latin America and Caribbean nations might be
making progress. Third, prevalence remains unchanged
in sub-Saharan Africa and south Asia. Stevens and
colleagues’ most interesting conclusion is that this
“evidence for both prevalence and absolute burden of
vitamin A defi ciency should be used to reconsider, and
possibly revise, the list of priority countries for high-dose
vitamin A supplementation”.
However, several caveats need to be considered,
including the use of cross-sectional data, exclusion of
children younger than 6 months, absence of clinical
vitamin A defi ciency assessments, gaps in serum retinol
data for certain populations and for 55 countries, use
of mortality data from randomised controlled trials of
vitamin A supplementation for diarrhoea and malaria
rather than population-level data, the assumption
that all post-neonatal measles deaths occur in children
aged 6–59 months old, and use of serum retinol as the
biomarker of defi ciency.
Nonetheless, we might need to focus on retinol
concentration not mortality to assess and guide
our eff orts to eliminate vitamin A defi ciency, as
recommended by WHO for population-level surveys,
even though this measure can be problematic in
individuals because of the well known eff ects of acute
infl ammation due to infection or injury on serum retinol
concentrations.2 Controlling for acute infl ammation
by including biomarkers for it3 might not be necessary
at the population level, because adequate vitamin A
status might, by itself, diminish infl ammation through
a reduction in the frequency or severity of infections in
these populations.
Despite these limitations, the authors provide
important estimates, with uncertainty distributions,
for the prevalence of vitamin A defi ciency, and a clear
picture of trends from 1991 to 2013. The association
between vitamin A defi ciency and eye pathology and all-
cause mortality is well known, as is the contribution of
vitamin A defi ciency to reduced resistance to infections,
especially diarrhoea and measles, and increased mortality
in children younger than 5 years.4 These benefi ts have
driven the scale-up of vitamin A supplementation
programmes as preventative public health measures
around the world. However, the coverage of these
programmes has not been effi cient in east or southern
Africa (67%) and south Asia (53%).5 Lagging coverage
and continued evidence of vitamin A defi ciency is the
basis for the suggestion by Stevens and colleagues that
future eff orts refocus on these regions. This suggestion
makes sense if we are confi dent that progress elsewhere
would not be compromised as a result.
During the past two decades, mortality from
diarrhoeal disease has substantially decreased and
measles has been eliminated as a public health issue
wherever eff ective immunisation programmes fl ourish.
Continued eff orts to control diarrhoeal disease and
enhance measles vaccine coverage per se suggest
that vitamin A supplementation programmes should
now focus on the reduction of defi ciency rather than
diarrhoea or measles morbidity or mortality as the
What then should be done to accelerate progress
towards elimination of vitamin A defi ciency in children?
Initiation of supplementation programmes where
they do not exist and strengthening of programmes
where coverage is poor is step one. However, high-dose
supplementation only provides protection from hypo-
retinolaemia for 2–3 months in children younger than
5 years and favourably shifts the distribution of serum
retinol for less than 2 months,6 indicating that biannual
supplementation is not suffi cient by itself to prevent
vitamin A defi ciency. Improvement of dietary intake of
foods rich in vitamin A (eg, animal products) or beta-
carotene is a more sustainable solution, but high-cost,
access, and cultural dietary practices have restricted
its potential to alleviate vitamin A defi ciency. Other
options have been tested or are under development,
such as fortifi cation of centrally processed foods
(although these might not reach poor populations in
rural areas); addition of vitamin A sprinkles to food in
the home, day-care centres, and schools;7 promotion of
beta-carotene rich foods such as sweet potatoes;8 and
genetically engineered crops with high concentrations
of beta-carotene such as golden rice.9 By addressing
See Articles page e528
e503 Vol 3 September 2015
gaps in vitamin A suffi ciency around the world,
redirecting attention to areas of the world struggling
to make progress while continuing to monitor other
regions through systematic population-representative
sampling of serum retinol, promotion of research into
sustainable dietary solutions including a campaign to
legitimise genetically modifi ed crops high in vitamin A
or precursors, and alignment of all of these eff orts with
Sustainable Development Goal 2 to “end hunger, achieve
food security and improved nutrition and promote
sustainable agriculture”,10 we can not only sustain the
favourable trends described by Stevens and colleagues
but also hasten progress in other parts of the world.
*Davidson H Hamer, Gerald T Keusch
Center for Global Health and Development, Boston University
School of Public Health (BUSPH), Boston, MA 02118, USA (DHH);
Department of Global Health, BUSPH, Boston, MA, USA (DHH);
Section of Infectious Diseases, Department of Medicine, Boston
Medical Center, Boston, MA, USA (DHH, GTK); Tufts University
Friedman School of Nutrition Science and Policy, Boston, MA, USA
(DHH); and National Emerging Infectious Diseases Laboratories,
Boston University School of Medicine, Boston, MA, USA (GTK)
We declare no competing interests.
Copyright © Hamer et al. Open Access article distributed under the terms of
1 Stevens GA, Bennett JE, Hennocq Q, et al. Trends and mortality eff ects of
vitamin A defi ciency in children in 138 low-income and middle-income
countries between 1991 and 2013: pooled analysis of population-based
surveys. Lancet Glob Health 2015; 3: e528–36.
2 Thurnham DI, McCabe GP, Northrop-Clewes CA, Nestel P. Eff ects of
subclinical infection on plasma retinol concentrations and assessment of
prevalence of vitamin A defi ciency: meta-analysis. Lancet 2003;
362: 2052–58.
3 Bresnahan KA, Chileshe J, Arscott S, et al. The acute phase response aff ected
traditional measures of micronutrient status in rural Zambian children
during a randomized, controlled feeding trial. J Nutr 2014; 144: 972–78.
4 Mayo-Wilson E, Imdad A, Herzer K, Yakoob MY, Bhutta ZA. Vitamin A
supplements for preventing mortality, illness and blindness in children
aged under 5: systematic review and meta-analysis. Br Med J 2011;
343: 1–19.
5 UNICEF. UNICEF Global Databases. Nutrition: vitamin A supplementation.
October, 2014. (accessed
June 13, 2015).
6 Palmer AC, West KP, Dalmiya N, Schultink W. The use and interpretation of
serum retinol distributions in evaluating the public health impact of
vitamin A programmes. Public Health Nutr 2012; 15: 1201–15.
7 Varma JL, Das S, Sankar RS, Mannar MGV, Levinson FJ, Hamer DH.
Community-level micronutrient fortifi cation of a food supplement in
India: a controlled trial with pre-school children aged 36-66 months.
Am J Clin Nutr 2007; 85: 1127–33.
8 Hotz C, Loechl C, Lubowa A, et al. Introduction of ß-carotene rich orange
sweet potato in rural Uganda resulted in increased vitamin A intakes
among children and women and improved vitamin A status among
children. J Nutr 2012; 142: 1871–80.
9 Tang G, Qin J, Dolnikowski GG, Russell RM, Grusak MA. Golden Rice is an
eff ective source of vitamin A. Am J Clin Nutr 2009; 89: 1776–83.
10 Dubé L, Pingali P, Webb P. Paths of convergence for agriculture, health,
and wealth. Proc Natl Acad Sci U S A 2012; 109: 12294–301.
... After being declared safe for consumption in four countries (Australia, New Zealand, Canada and the United States) (Greedy, 2018), it is the Philippines that was the first to approve its cultivation, which is expected to happen in Bangladesh soon, too. Since Potrykus and Beyer developed its first version in 1999 (Qamar et al., 2020;Ye et al., 2000), Golden Rice has been facing sustained criticism that undoubtedly delayed the progress of this humanitarian project to help alleviate the health and economic burden of vitamin A deficiency (Wesseler and Zilberman, 2014). ...
... It is important to emphasize that this crop is not, or should not, be framed as a silver bullet-or a golden bullet, as it were-for ending micronutrient malnutrition. Rather, it has an important role in addressing a particular micronutrient deficiency that still imposes a considerable burden on public health and that requires innovative but cost-effective and culturally appropriate interventions that go beyond conventional vitamin A supplementation programs that typically target high priority population groups (children of 6-59 months old) (Hamer and Keusch, 2015). Implementing food-based solutions is particularly important as these are less vulnerable to disruptions caused by funding shortfalls or catastrophes, as shown most recently by the drop in vitamin A supplementation rates due to COVID-19 (HKI, 2020). ...
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Following its approval in the Philippines in July 2021, provitamin A-rich “Golden Rice” is set to become the worlds' first commercialized genetically modified crop with direct consumer benefits. Despite supplementation and fortification programs, the burden of micronutrient deficiencies remains high. For Golden Rice to be successful in reducing vitamin A deficiency, it needs to be taken up by food systems and integrated into consumer diets. Despite negative information often being associated with genetic engineering, evidence suggests that consumers react positively to Golden Rice. Thus, it offers policy makers and public health stakeholders a new, powerful option to address micronutrient malnutrition that they can integrate as a cost-effective component in broader nutrition strategies and tailor it to consumers’ heterogeneous socio-economic contexts and needs to promote “Golden Diets”. For this to happen, the right framing of the pathway from policy to consumption is crucial.
... A study revealed that Vitamin A deficiency prevails, and 30% of preschool children in Developing Countries have vitamin A deficiency in sub-Saharan Africa despite National supplementation and food fortification programs, (UNSSCN, 2010). Hamer and Keusch (2015) in their study observed that Vitamin A deficiency (VAD) is a widespread nutritional disorder in the Developing Countries, and is still a public health concern globally. It is seen as main causative factor of preventable blindness in children. ...
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Cassava is a staple crop that is consumed in almost every Community in Nigeria. It is a high perishable crop that deteriorates within few days after harvesting. Processing cassava into chips and flours reduces the moisture content to a very low level thus reducing post-harvest losses. It has been shown that biofortified yellow root cassava possesses great potential to alleviate vitamin A deficiency complementary to other interventions such as vitamin A supplementation and fortification. This study therefore, investigated the effects of processing methods and packaging materials on the shelf-life of yellow root cassava flour. Yellow root cassava (UMUCASS 36 (TMS 01/1368) was harvested, cleaned and processed into flour by chipping and grating. Flour samples obtained from each method was stored for 6 weeks in tin and black polyethylene, and evaluated weekly. Result of a preliminary study conducted on the moisture content of the raw cassava root and flour samples showed that both chipped and grated flour samples had lower moisture content (2.36% and 3.20% respectively) compared to the raw cassava root (71.63%). The results of the chemical properties of the flour samples showed no significant difference (p˃0.05) in week 0. However, the physicochemical and functional properties of the grated and chipped flour samples packaged in tin and polyethylene varied significantly from week 1 through week 6. Carotenoids retention was highest (72.1%) in chipped flour sample packaged in polyethylene. Chipped flour sample in polyethylene had the lowest mould count (34.33-66.67 cfu/g). Moisture retention was highest in grated sample packaged in both tin and polythene. The result of this study revealed that flour processed from dried chips and packaged in black polythene was the best for storage stability and longer shelf-life.
... It is clear that progress in combatting VAD has been significant, a reduction from 23 to 34% of under-five child deaths in the 1990s to circa 2% in these two countries in 2013, the latest data available [31]. The 2013 data are useful as a proxy for comparison between countries, but has limitations [32] including that the "total VAD" deaths reported are actually solely deaths where measles or diarrhea are reported on a death certificate. But these are not the only causes of death due to immune system insufficiency due to VAD, and reporting may anyway be patchy in remote, poor districts. ...
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On July 21, 2021, Golden Rice was registered in the Philippines allowing cultivation and consumption. Research, as an intervention to combat vitamin A deficiency (VAD), started in 1991, and proof of concept for what was to become Golden Rice, was achieved in 1999. In the 1990s, 23-34% deaths globally of children less than 5 years old were caused by VAD, and in developing countries, the percentage was even higher. By 2013, progress against the Millennium Development Goals had reduced <5-y child deaths globally from VAD to about 2% of all such deaths. The progress included significant vaccination programs against measles, and better access to clean water, as well as vitamin A supplementation, all delivered through community health programs. Economic development and education about diet reduced food insecurity. In contrast to continuing VAD deaths, the Covid-19 pandemic has attracted huge political attention, including in low-and middle-income countries. Community health programs have been adversely affected by the pandemic. There is a danger that as a result VAD rates, child and maternal mortality climbs again toward 1990's levels. Adoption of Golden Rice provides a safe, culturally simple amelioration and is costless. Other countries should seize the opportunity. Bangladesh is first in line, possibly followed by Indonesia and India.
... VAD is the leading cause of preventable blindness in children. It leads to an increased risk of disease and death from diseases such as malaria, diarrhea and measles [2]. ...
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Biofortified yellow-fleshed cassava is important in countries with high cassava consumption, to improve the vitamin A status of their populations. Yellow- and white-fleshed cassava were evaluated over three locations for proximate composition and cyanide content as well as retention of carotenoids after boiling. There was significant variation in the crude fiber, fat, protein and ash content of the genotypes. All but one of the yellow-fleshed cassava genotypes recorded higher protein values than the white-fleshed local genotypes across locations. The cyanide content of the genotypes varied between locations but was within the range of sweet cassava genotypes, but above the maximum acceptable recommended limit. Micronutrient retention is important in biofortified crops because a loss of micronutrients during processing and cooking reduces the nutritional value of biofortified foods. Total carotenoid content (TCC) ranged from 1.18–18.81 μg.g−1 and 1.01–13.36 μg.g−1 (fresh weight basis) for fresh and boiled cassava, respectively. All the yellow-fleshed cassava genotypes recorded higher TCC values in both the fresh and boiled state than the white-fleshed genotypes used as checks.
... Previously, food fortification, dietary diversification, and supplementation were tried to reduce VAD (Tanumihardjo and Furr 2013). Despite these initiatives, the problem of VAD remains the same in South Asia and sub-Saharan belt of Africa due to budget constraints and other reasons (Hamer and Keusch 2015). These limitations lead to the emergence of new strategy like biofortification for nutrient improvement of the staple crops. ...
Malnutrition is a severe public health challenge in several underdeveloped countries worldwide. Thus, sustainable plant productivity and its easy availability in the coming years shall be a major constraint for food and nutritional security for the teeming millions. Moreover, various abiotic and biotic stresses in plants contribute to yield penalty. The conventional breeding techniques for improvement/enhancement of growth, yield, and quality traits are tedious, time-consuming, and impermanent. On the contrary, microbe-assisted genetic manipulation of crop plants has revolutionized the crop improvement through incorporation of value-added traits of agronomic and nutritional importance. It is now possible to transfer genes(s) of interest, irrespective of its origin to crop plants through direct or indirect (vector or vectorless) approaches. Indeed, Agrobacterium has become the most effective vector for gene transfer in the arena of transgenic technology. The success of a transgene of nutritional importance depends upon its high expression level and stability in plant system. To give effect to this hypothesis, various strategies have been deployed including elimination of destabilizing elements of the transgene; removal of putative polyadenylation sequences, cryptic splicing sites, and codon biasness; and incorporation of elements for high-level expression (strong promoter(s), 5′ untranslated leader sequence, translation initiation context). In this chapter, we have discussed the importance of Agrobacterium and various genetic engineering approaches for enhancing the expression of foreign genes including the current scenario and advancements in the biofortification of crops. This chapter also summarizes state of the art of nutrition enhancement in crops, major challenges, and future prospects.
... The major consequences of VAD include visual impairment, xerophthalmia and night blindness, and VAD significantly increases the risk of severe infections and diseases, and can even result in death. United Nations International Children's Emergency Fund (UNICEF), in partnership with World Health Organization (WHO), has recommended vitamin A supplementation programs and food fortification strategies to alleviate VAD issues [5][6][7]. Unfortunately, these nutritional interventions have progressed slowly due to a low coverage rate, and there is the persistent concern that delivering excess preformed vitamin A to consumers may result in hypervitaminosis A, which can be lethal or contribute to teratogenic mutations [8]. ...
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Provitamin A and pre-formed vitamin A compounds are essential micronutrients for humans. However, vitamin A deficiency (VAD) affects the health status of nearly 50% of populations in Southeast Asia and sub-Saharan Africa and is especially pronounced in preschool children and pregnant women. The objective of this research was to determine an acceptable flavor/ingredient combination to produce a palatable food product that incorporates sweet potatoes, peanut paste, and chickpeas. We sought to determine the acceptability of the three product formulations and to determine the influence of demographic data on ratings for the sensory attributes of each sample. To address VAD issues, three formulations of a product incorporating sweet potato puree (to increase β-carotene content), pure peanut butter (to provide fat for β-carotene absorption), and chickpeas (to provide a complete protein source), were developed: (1) an unflavored control, and two formulations with added natural seasonings: (2) curry-flavored, and (3) pumpkin spice-flavored. Sensory analysis of the three products showed that the curry-flavored product received the highest acceptability in terms of overall liking, flavor, texture, and appearance (p < 0.001). Since the demographic effect was not statistically significant (p > 0.05), it is highly likely that the curry-flavored product can be implemented in other countries or areas with high acceptability.
... Whereas many signaling ligands (eg, Notch, Wnt) are encoded by endogenous genes, bioactive RA is wholly derived from dietary vitamin A. Vitamin A deficiency is especially common in developing regions, and 1 in 6 pregnant women globally are vitamin A deficient (World Health Organization Global Database on Vitamin A Deficiency, 2009). Vitamin A deficiency remains a prevalent health burden in sub-Saharan Africa, south Asia, and rural China (55,56), and maternal vitamin A deficiency increases the risk for visual impairments and facial clefting in children (57,58). Although pituitary gland dysfunction was not specifically assessed in these epidemiology studies, it often presents together with visual impairment and midline defects such as clefting (59). ...
Dietary vitamin A is metabolized into bioactive retinoic acid in vivo and regulates the development of many embryonic tissues. Retinoic acid signaling is active in the oral ectoderm-derived tissues of the neuroendocrine system, but its role there has not yet been fully explored. We show here that retinoic acid signaling is active during pituitary organogenesis and dependent on the pituitary transcription factor Prop1.Prop1-mutant mice show reduced expression of the aldehyde dehydrogenase gene Aldh1a2, which metabolizes the vitamin A-intermediate retinaldehyde into retinoic acid. In order to elucidate the specific function of RA signaling during neuroendocrine development, we studied a conditional deletion of Aldh1a2 and a dominant-negative mouse model of inhibited retinoic acid signaling during pituitary organogenesis. These models partially phenocopy Prop1-mutant mice by exhibiting embryonic pituitary dysmorphology and reduced hormone expression, especially thyroid-stimulating hormone. These findings establish the role of retinoic acid in embryonic pituitary stem cell progression to differentiated hormone cells and raise the question of gene-by-environment interactions as contributors to pituitary development and disease.
This “case study” documents the ways in which a variety of epidemiologic studies and the data they generated (which challenged existing beliefs and public health constructs) were greeted by established “experts” in relevant fields. Just as Virchow described over a century ago, results of an initial observational study, which raised the issues, were entirely ignored. Prominent publication of a randomized clinical trial, which both supported the observational study’s associations and proved that they were causal, was greeted with intense hostility, disbelief, and rejection. Only the subsequent accrual of additional, similar RCTs slowly changed scientific opinion, especially when replications were eventually conducted by others than the original investigators. A halt was brought to this slowly changing scientific climate by the timely gathering of those involved in a week-long meeting that evaluated the quality and interpretation of all available data and discussed their relevance and validity. That many investigators had not understood the importance of the context in which their own studies had been conducted was startling, particularly regarding the two variables of greatest relevance: the study population’s baseline risk of vitamin A deficiency and mortality. Investigators of some of the best conducted studies misinterpreted their own data. The resulting 10-year effort eventually changed global health policy, but some “deniers,” without a shred of evidence to back their claims, still refuse to accept this outcome.
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Crude palm oil (CPO) is extracted from the mesocarp of oil palm (Elaeis guineensis) fruits. CPO is widely consumed in many African countries. Due to its high provitamin A carotenoid content, it is also widely used in programmes designed to prevent vitamin A deficiency. Elaeis guineensis occurs naturally across a wide geographical range in Africa. We investigated the carotene, tocochromanol (vitamin E) and fatty acid composition of a large set of genotypes representative of this genetic and geographic diversity. We found considerable intraspecific diversity in most lipid traits. Populations from Côte d'Ivoire were distinguished from other origins by their very low palmitate content and high tocochromanol content. Genotypes from Benin, Côte d'Ivoire and Nigeria were characterized by high carotene contents. Finally, hybrids of crosses between genotypes from Côte d'Ivoire and Nigeria produce CPO with exceptionally high provitamin A and vitamin E contents together with low palmitate content.
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Vitamin A deficiency is a risk factor for blindness and for mortality from measles and diarrhoea in children aged 6-59 months. We aimed to estimate trends in the prevalence of vitamin A deficiency between 1991 and 2013 and its mortality burden in low-income and middle-income countries. We collated 134 population-representative data sources from 83 countries with measured serum retinol concentration data. We used a Bayesian hierarchical model to estimate the prevalence of vitamin A deficiency, defined as a serum retinol concentration lower than 0·70 μmol/L. We estimated the relative risks (RRs) for the effects of vitamin A deficiency on mortality from measles and diarrhoea by pooling effect sizes from randomised trials of vitamin A supplementation. We used information about prevalences of deficiency, RRs, and number of cause-specific child deaths to estimate deaths attributable to vitamin A deficiency. All analyses included a systematic quantification of uncertainty. In 1991, 39% (95% credible interval 27-52) of children aged 6-59 months in low-income and middle-income countries were vitamin A deficient. In 2013, the prevalence of deficiency was 29% (17-42; posterior probability [PP] of being a true decline=0·81). Vitamin A deficiency significantly declined in east and southeast Asia and Oceania from 42% (19-70) to 6% (1-16; PP>0·99); a decline in Latin America and the Caribbean from 21% (11-33) to 11% (4-23; PP=0·89) also occurred. In 2013, the prevalence of deficiency was highest in sub-Saharan Africa (48%; 25-75) and south Asia (44%; 13-79). 94 500 (54 200-146 800) deaths from diarrhoea and 11 200 (4300-20 500) deaths from measles were attributable to vitamin A deficiency in 2013, which accounted for 1·7% (1·0-2·6) of all deaths in children younger than 5 years in low-income and middle-income countries. More than 95% of these deaths occurred in sub-Saharan Africa and south Asia. Vitamin A deficiency remains prevalent in south Asia and sub-Saharan Africa. Deaths attributable to this deficiency have decreased over time worldwide, and have been almost eliminated in regions other than south Asia and sub-Saharan Africa. This new evidence for both prevalence and absolute burden of vitamin A deficiency should be used to reconsider, and possibly revise, the list of priority countries for high-dose vitamin A supplementation such that a country's priority status takes into account both the prevalence of deficiency and the expected mortality benefits of supplementation. Bill & Melinda Gates Foundation, Grand Challenges Canada, UK Medical Research Council. © 2015 World Health Organization; licensee Elsevier. This is an Open Access article published without any waiver of WHO's privileges and immunities under international law, convention, or agreement. This Article should not be reproduced for use in association with the promotion of commercial products, services, or any legal entity. There should be no suggestion that WHO endorses any specific organisation or products. The use of the WHO logo is not permitted. This notice should be preserved along with the Article's original URL.
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The acute phase response (APR) to infection can alter blood-based indicators of micronutrient status. Data from a 3-mo randomized, controlled feeding trial in rural Zambian children (n = 181, aged 3-5 y) were used to determine the impact of the APR on indicators of vitamin A and iron status using baseline and final blood samples. Concentrations of acute phase proteins were categorized as raised C-reactive protein (CRP; >5 and >10 mg/L) only, both raised CRP and α1-acid glycoprotein (AGP; >1.2 g/L), raised AGP only, and neither CRP nor AGP raised to identify the respective stages of infection: incubation, early convalescence, convalescence, and healthy state. Data were insufficient to examine the incubation stage of infection. A CRP concentration of >5 mg/L was an effective elevation cutoff point in this population to show impact on micronutrient markers. Time did not affect hemoglobin, serum ferritin, or serum retinol concentrations (P > 0.05). During early convalescence, hemoglobin decreased (14-16%; P ≤ 0.05), serum ferritin increased (279-356%; P ≤ 0.05), and serum retinol decreased (20-30%; P ≤ 0.05). Serum retinol concentrations did not change during convalescence; however, hemoglobin remained depressed (4-9%) and serum ferritin was elevated (67-132%) (both P ≤ 0.05). Modified relative dose response values were unaffected by the APR (P > 0.05) but increased between time points (16%; P ≤ 0.05), indicating a decrease in liver vitamin A reserves on the background of a semiannual vitamin A supplementation program. The observed prevalence of anemia and vitamin A deficiency assessed by serum retinol concentration was higher during the APR (P ≤ 0.05). It is important to consider the impact of infection on dietary interventions and to adjust for acute phase proteins when assessing iron status or vitamin A status by serum retinol concentration alone in children.
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Vitamin A deficiency (VAD) persists in Uganda and the consumption of β-carotene-rich orange sweet potato (OSP) may help to alleviate it. Two large-scale, 2-y intervention programs were implemented among Ugandan farmer households to promote the production and consumption of OSP. The programs differed in their inputs during year 2, with one being more intensive (IP) and the other being reduced (RP). A randomized, controlled effectiveness study compared the impact of the IP and RP with a control on OSP and vitamin A intakes among children aged 6-35 mo (n = 265) and 3-5 y (n = 578), and women (n = 573), and IP compared with control on vitamin A status of 3- to 5-y-old children (n = 891) and women (n = 939) with serum retinol <1.05 μmol/L at baseline. The net OSP intake increased in both the IP and RP groups (P < 0.01), accounting for 44-60% of vitamin A intake at follow-up. The prevalence of inadequate vitamin A intake was reduced in the IP and RP groups compared with controls among children 6-35 mo of age (>30 percentage points) and women (>25 percentage points) (P < 0.01), with no differences between the IP and RP groups of children (P = 0.75) or women (P = 0.17). There was a 9.5 percentage point reduction in prevalence of serum retinol <1.05 μmol/L for children with complete data on confounding factors (n = 396; P < 0.05). At follow-up, vitamin A intake from OSP was positively associated with vitamin A status (P < 0.05). Introduction of OSP to Ugandan farming households increased vitamin A intakes among children and women and was associated with improved vitamin A status among children.
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This special feature calls for forward thinking around paths of convergence for agriculture, health, and wealth. Such convergence aims for a richer integration of smallholder farmers into national and global agricultural and food systems, health systems, value chains, and markets. The articles identify analytical innovation, where disciplines intersect, and cross-sectoral action where single, linear, and siloed approaches have traditionally dominated. The issues addressed are framed by three main themes: (i) lessons related to agricultural and food market growth since the 1960s; (ii) experiences related to the integration of smallholder agriculture into national and global business agendas; and (iii) insights into convergence-building institutional design and policy, including a review of complexity science methods that can inform such processes. In this introductory article, we first discuss the perspectives generated for more impactful policy and action when these three themes converge. We then push thematic boundaries to elaborate a roadmap for a broader, solution-oriented, and transdisciplinary approach to science, policies, and actions. As the global urban population crosses the 50% mark, both smallholder and nonsmallholder agriculture are keys in forging rural-urban links, where both farm and nonfarm activities contribute to sustainable nutrition security. The roadmaps would harness the power of business to reduce hunger and poverty for millions of families, contribute to a better alignment between human biology and modern lifestyles, and stem the spread of noncommunicable chronic diseases.
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Developing countries have adopted universal, high-potency vitamin A (VA) supplementation and food fortification as major strategies to control deficiency, prevent nutritional blindness and reduce child mortality. Yet questions persist regarding how best to measure impact and when to phase out supplementation. The present paper provides guidance on the use and interpretation of serum retinol (SROL) distributions as indicators of both programme impact and adequate VA intake in a population. We reviewed extant data on SROL's response to high-potency VA supplementation and VA-fortified foods in children. Supplementation virtually eliminates xerophthalmia and reduces child mortality; however, it shifts the SROL distribution only transiently (<2 months). Regular consumption of VA-fortified foods prevents xerophthalmia, lowers mortality and sustainably improves SROL distributions, from which both compliance and public health impact can be inferred. Given SROL's limited responsiveness to high-potency VA supplementation, target population coverage remains the preferred performance indicator. However, periodic SROL surveys do reflect underlying dietary risk and can guide programming: low or marginal SROL distributions in areas with high supplementation coverage do not signify programme failure, but rather suggest the need to continue supplementation while working to effectively raise dietary VA intakes. We propose that a sustained rise in the SROL distribution, defined as ≤5 % prevalence of SROL < 0·70 μmol/l among vulnerable population groups in at least two consecutive surveys (≥1 year apart), be used as an indicator of stable and adequate dietary VA intake and status in a population, at which point programmes may re-evaluate the need for continued universal supplementation.
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To determine if vitamin A supplementation is associated with reductions in mortality and morbidity in children aged 6 months to 5 years. Systematic review and meta-analysis. Two reviewers independently assessed studies for inclusion. Data were double extracted; discrepancies were resolved by discussion. Meta-analyses were performed for mortality, illness, vision, and side effects. Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, Medline, Embase, Global Health, Latin American and Caribbean Health Sciences, metaRegister of Controlled Trials, and African Index Medicus. Databases were searched to April 2010 without restriction by language or publication status. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised trials of synthetic oral vitamin A supplements in children aged 6 months to 5 years. Studies of children with current illness (such as diarrhoea, measles, and HIV), studies of children in hospital, and studies of food fortification or β carotene were excluded. 43 trials with about 215,633 children were included. Seventeen trials including 194,483 participants reported a 24% reduction in all cause mortality (rate ratio=0.76, 95% confidence interval 0.69 to 0.83). Seven trials reported a 28% reduction in mortality associated with diarrhoea (0.72, 0.57 to 0.91). Vitamin A supplementation was associated with a reduced incidence of diarrhoea (0.85, 0.82 to 0.87) and measles (0.50, 0.37 to 0.67) and a reduced prevalence of vision problems, including night blindness (0.32, 0.21 to 0.50) and xerophthalmia (0.31, 0.22 to 0.45). Three trials reported an increased risk of vomiting within the first 48 hours of supplementation (2.75, 1.81 to 4.19). Vitamin A supplementation is associated with large reductions in mortality, morbidity, and vision problems in a range of settings, and these results cannot be explained by bias. Further placebo controlled trials of vitamin A supplementation in children between 6 and 59 months of age are not required. However, there is a need for further studies comparing different doses and delivery mechanisms (for example, fortification). Until other sources are available, vitamin A supplements should be given to all children at risk of deficiency, particularly in low and middle income countries.
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Children participating in the Integrated Child Development Service (ICDS) in India have high rates of iron and vitamin A deficiency. The objective was to assess the efficacy of a premix fortified with iron and vitamin A and added at the community level to prepared khichdi, a rice and dal mixture, in increasing iron and vitamin A stores and decreasing the prevalence of iron deficiency, anemia, and vitamin A deficiency. This cluster, randomized, double-blind, controlled trial was initiated in 30 Anganwadi centers (daycare centers) in West Bengal state, India. Children aged 36-66 mo (n = 516) attending village-based ICDS centers were randomly assigned to receive either a fortified or a nonfortified premix for 24 wk. Blood was drawn at 0 and 24 wk by venipuncture for the measurement of hemoglobin, serum ferritin, and serum retinol. The change in the hemoglobin concentration of anemic children was significantly different between fortified and nonfortified khichdi groups (P < 0.001). Prevalence rates of anemia, iron deficiency, and iron deficiency anemia were significantly lower after 24 wk in the fortified-khichdi group than in the nonfortified-khichdi group (P < 0.001). There were no significant differences in serum retinol concentrations or in the prevalence of vitamin A deficiency between the fortified- and nonfortified-khichdi groups. A premix fortified with iron, vitamin A, and folic acid and added to supplementary food at the community level can be effective at increasing iron stores and reducing the prevalence of iron deficiency and anemia.
Genetically engineered "Golden Rice" contains up to 35 microg beta-carotene per gram of rice. It is important to determine the vitamin A equivalency of Golden Rice beta-carotene to project the potential effect of this biofortified grain in rice-consuming populations that commonly exhibit low vitamin A status. The objective was to determine the vitamin A value of intrinsically labeled dietary Golden Rice in humans. Golden Rice plants were grown hydroponically with heavy water (deuterium oxide) to generate deuterium-labeled [2H]beta-carotene in the rice grains. Golden Rice servings of 65-98 g (130-200 g cooked rice) containing 0.99-1.53 mg beta-carotene were fed to 5 healthy adult volunteers (3 women and 2 men) with 10 g butter. A reference dose of [13C10]retinyl acetate (0.4-1.0 mg) in oil was given to each volunteer 1 wk before ingestion of the Golden Rice dose. Blood samples were collected over 36 d. Our results showed that the mean (+/-SD) area under the curve for the total serum response to [2H]retinol was 39.9 +/- 20.7 microg x d after the Golden Rice dose. Compared with that of the [13C10]retinyl acetate reference dose (84.7 +/- 34.6 microg x d), Golden Rice beta-carotene provided 0.24-0.94 mg retinol. Thus, the conversion factor of Golden Rice beta-carotene to retinol is 3.8 +/- 1.7 to 1 with a range of 1.9-6.4 to 1 by weight, or 2.0 +/- 0.9 to 1 with a range of 1.0-3.4 to 1 by moles. Beta-carotene derived from Golden Rice is effectively converted to vitamin A in humans. This trial was registered at as NCT00680355.
Background: Vitamin A deficiency adversely affects child morbidity and survival. This deficiency is estimated by measurement of plasma retinol concentrations, but because plasma retinol is reduced by clinical and subclinical infection, this proxy measure can lead to overestimation. Infection and trauma are accompanied by rises in concentrations of acute-phase proteins in plasma. We aimed to estimate vitamin A deficiency more accurately by measuring changes in plasma retinol and acute-phase proteins associated with subclinical infection or convalescence. Methods: We analysed data for concentrations of plasma retinol and one or more acute-phase proteins (alpha1-acid-glycoprotein, alpha1-antichymotrypsin, C-reactive protein, or serum amyloid A) from 15 studies of apparently healthy individuals. We generated summary estimates of differences in retinol concentrations for incubation, early, and late convalescent phases of infection between people with none and those with one or more raised acute-phase proteins. We compared these groups in two, three, and four group analyses. We also compared a subgroup of apparently healthy preschool (1-5 years) children with results from all other studies. Findings: For all four proteins, retinol values were much higher in people with normal concentrations of protein, than in individuals with raised concentrations (16% higher for alpha1-antichymotrypsin, 18% for alpha1-acid-glycoprotein, 25% for C-reactive protein, and 32% for serum amyloid A). Estimates of the reduction in plasma retinol for individuals with infection compared with healthy individuals, were 13% (incubation), 24% (early convalescent), and 11% (late convalescent). Estimates of vitamin A deficiency in individuals with no raised acute-phase proteins (healthy group) were much the same as those obtained by adjustment of plasma retinol concentrations in the whole group using acute-phase proteins. Interpretation: We recommend that surveys to estimate vitamin A deficiency should include measurements of serum C-reactive protein and alpha1-acid-glycoprotein concentrations. Information about acute-phase proteins will enable plasma retinol concentrations to be corrected where sub-clinical infection exists, and the healthy sub-group to be identified.