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Background: Evidence of the effectiveness of biofortified maize with higher provitamin A (PVA) to address vitamin A deficiency in rural Africa remains scant., Objectives: This study projects the impact of adopting PVA maize for a diversity of households in an area typical of rural Zimbabwe and models the cost and composition of diets adequate in vitamin A., Methods: Household-level weighed food records were generated from 30 rural households during a week in April and November 2021. Weekly household intakes were calculated, as well as indicative costs of diets using data from market surveys. The impact of PVA maize adoption was modeled assuming all maize products contained observed vitamin A concentrations. The composition and cost of the least expensive indicative diets adequate in vitamin A were calculated using linear programming., Results: Very few households would reach adequate intake of vitamin A with the consumption of PVA maize. However, from a current situation of 33%, 50%-70% of households were projected to reach ≥50% of their requirements (the target of PVA), even with the modest vitamin A concentrations achieved on-farm (mean of 28.3 μg RAE per 100 g). This proportion would increase if higher concentrations recorded on-station were achieved. The estimated daily costs of current diets (mean ± standard deviation) were USD 1.43 ± 0.59 in the wet season and USD 0.96 ± 0.40 in the dry season. By comparison, optimization models suggest that diets adequate in vitamin A could be achieved at daily costs of USD 0.97 and USD 0.79 in the wet and dry seasons, respectively., Conclusions: The adoption of PVA maize would bring a substantial improvement in vitamin A intake in rural Zimbabwe but should be combined with other interventions (e.g., diet diversification) to fully address vitamin A deficiency., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Vitamin A (VA) deficiency is prevalent in preschool-aged children in sub-Saharan Africa., Objectives: We assessed the effect of small-quantity lipid-based nutrient supplements (SQ-LNS) given to women during pregnancy and lactation and their children from 6 to 18 mo of age on women's plasma and milk retinol concentrations in Malawi, and children's plasma retinol concentration in Malawi and Ghana., Methods: Pregnant women (≤20 wk of gestation) were randomized to receive daily: 1) iron and folic acid (IFA) during pregnancy only; 2) multiple micronutrients (MMN; 800 μg retinol equivalent (RE)/capsule), or 3) SQ-LNS (800 μg RE/20g) during pregnancy and the first 6 mo postpartum. Children of mothers in the SQ-LNS group received SQ-LNS (400 μg RE/20 g) from 6 to 18 mo of age; children of mothers in the IFA and MMN groups received no supplement. Plasma retinol was measured in mothers at ≤20 and 36 wk of gestation and 6 mo postpartum, and in children at 6 and 18 mo of age. Milk retinol was measured at 6 mo postpartum. VA status indicators were compared by group., Results: Among Malawian mothers, geometric mean (95% CI) plasma retinol concentrations at 36 wk of gestation and 6 mo postpartum were 0.97 μmol/L (0.94, 1.01 μmol/L) and 1.35 μmol/L (1.31, 1.39 μmol/L), respectively; geometric mean (95% CI) milk retinol concentration at 6 mo postpartum was 1.04 μmol/L (0.97, 1.13 μmol/L); results did not differ by intervention group. Geometric mean (95% CI) plasma retinol concentrations for Malawian children at 6 and 18 mo of age were 0.78 μmol/L (0.75, 0.81 μmol/L) and 0.81 μmol/L (0.78, 0.85 μmol/L), respectively, and for Ghanaian children they were 0.85 μmol/L (0.82, 0.88 μmol/L) and 0.88 μmol/L (0.85, 0.91 μmol/L), respectively; results did not differ by intervention group in either setting., Conclusions: SQ-LNS had no effect on VA status of mothers or children, possibly because of low responsiveness of the VA status indicators., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Malnutrition has emerged as one of the major health problems worldwide. Traditional yellow maize has low provitamin-A (proA) content and its genetic base in proA biofortification breeding program of subtropics is extremely narrow. To diversify the proA rich germplasm, 10 elite low proA inbreds were crossed with a proA rich donor (HP702-22) having mutant crtRB1 gene. The F2 populations derived from these crosses were genotyped using InDel marker specific to crtRB1. Severe marker segregation distortion was observed. Seventeen crtRB1 inbreds developed through marker-assisted pedigree breeding and seven inbreds generated using marker-assisted backcross breeding were characterized using 77 SSRs. Wide variation in gene diversity (0.08 to 0.79) and dissimilarity coefficient (0.28 to 0.84) was observed. The inbreds were grouped into three major clusters depicting the existing genetic diversity. The crtRB1-based inbreds possessed high β-carotene (BC: 8.72μg/g), β-cryptoxanthin (BCX: 4.58μg/g) and proA (11.01μg/g), while it was 2.35μg/g, 1.24μg/g and 2.97μg/g in checks, respectively. Based on their genetic relationships, 15 newly developed crtRB1-based inbreds were crossed with five testers (having crtRB1 gene) using line × tester mating design. 75 experimental hybrids with crtRB1 gene were evaluated over three locations. These experimental hybrids possessed higher BC (8.02μg/g), BCX (4.69μg/g), proA (10.37μg/g) compared to traditional hybrids used as check (BC: 2.36 μg/g, BCX: 1.53μg/g, proA: 3.13μg/g). Environment and genotypes × environment interaction had minor effects on proA content. Both additive and dominance gene action were significant for proA. The mean proportion of proA to total carotenoids (TC) was 44% among crtRB1-based hybrids, while 11% in traditional hybrids. BC was found to be positively correlated with BCX (r = 0.68) and proA (r = 0.98). However, no correlation was observed between proA and grain yield. Several hybrids with >10.0 t/ha grain yield with proA content >10.0 μg/g were identified. This is the first comprehensive study on development of diverse proA rich maize hybrids through marker-assisted pedigree breeding approach. The findings provides sustainable and cost-effective solution to alleviate vitamin-A deficiency., Competing Interests: The authors have declared that no competing interests exist.

<b>Background and Objective:</b> Vitamin A Deficiency (VAD) is a critical public health problem that affects the health of kids worldwide and may induce anemia and oxidative stress. The current study aimed to pre-clinically assess the effect of a cupcake, prepared to be served for primary school children, on vitamin A deficiency and related anemia and oxidative stress in rats. <b>Materials and Methods:</b> Flour of flash orange sweet potatoes, as a rich source of pro-vitamin A, was used to prepare the cupcake. The chemical composition, amino acids and sensory evaluation of the cupcake were done. The biological evaluation was carried out using 18 weaning rats in three groups (control group, vitamin A-deficient group and vitamin A-deficient group fed on a diet fortified with 20% of the prepared cupcake for two months). <b>Results:</b> The results indicated the high value of vitamin A in the prepared cupcake. Excellent sensory characteristics were noticed. Feeding on the VDA diet fortified with the prepared cupcake suppressed the reduction in Retinol-Binding Protein (RBP), hemoglobin and iron. Total Iron Binding Capacity (TIBC) increased in the VAD group. Also, feeding on the prepared cupcake suppressed the reduction in Superoxide Dismutase (SOD) and Glutathione Peroxidase (GPx) and the elevation of Malondialdehyde (MDA). <b>Conclusion:</b> It can be suggested that the prepared cupcake is promising in preventing of vitamin A deficiency and related anemia and oxidative stress. Thus, the prepared cupcake may be efficient for children to prevent vitamin A deficiency.

Background & Aims: Treatment of children with uncomplicated severe acute malnutrition (SAM) is based on ready-to-use therapeutic foods (RUTF) and aims for quick regain of lost body tissues while providing sufficient micronutrients to restore diminished body stores. Little evidence exists on the success of the treatment to establish normal micronutrient status. We aimed to assess the changes in vitamin A and iron status of children treated for SAM with RUTF, and explore the effect of a reduced RUTF dose., Methods: We collected blood samples from children 6-59 months old with SAM included in a randomised trial at admission to and discharge from treatment and analysed haemoglobin (Hb) and serum concentrations of retinol binding protein (RBP), ferritin (SF), soluble transferrin receptor (sTfR), C-reactive protein (CRP) and α1-acid glycoprotein (AGP). SF, sTfR and RBP were adjusted for inflammation (CRP and AGP) prior to analysis using internal regression coefficients. Vitamin A deficiency (VAD) was defined as RBP < 0.7 μmol/l, anaemia as Hb < 110 g/l, storage iron deficiency (sID) as SF < 12 μg/l, tissue iron deficiency (tID) as sTfR > 8.3 mg/l and iron deficiency anaemia (IDA) as both anaemia and sID. Linear and logistic mixed models were fitted including research team and study site as random effects and adjusting for sex, age and outcome at admission., Results: Children included in the study (n = 801) were on average 13 months of age at admission to treatment and the median treatment duration was 56 days [IQR: 35; 91] in both arms. Vitamin A and iron status markers did not differ between trial arms at admission or at discharge. Only Hb was 1.7 g/l lower (95% CI -0.3, 3.7; p = 0.088) in the reduced dose arm compared to the standard dose, at recovery. Mean concentrations of all biomarkers improved from admission to discharge: Hb increased by 12% or 11.6 g/l (95% CI 10.2, 13.0), RBP increased by 13% or 0.12 μmol/l (95% CI 0.09, 0.15), SF increased by 36% or 4.4 μg/l (95% CI 3.1, 5.7) and sTfR decreased by 16% or 1.5 mg/l (95% CI 1.0, 1.9). However, at discharge, micronutrient deficiencies were still common, as 9% had VAD, 55% had anaemia, 35% had sID, 41% had tID and 21% had IDA., Conclusion: Reduced dose of RUTF did not result in poorer vitamin A and iron status of children. Only haemoglobin seemed slightly lower at recovery among children treated with the reduced dose. While improvement was observed, the vitamin A and iron status remained sub-optimal among children treated successfully for SAM with RUTF. There is a need to reconsider RUTF fortification levels or test other potential strategies in order to fully restore the micronutrient status of children treated for SAM., Competing Interests: Conflict of interest HF has received research grants from ARLA Food for Health Centre, Danish Dairy Research Foundation and also has research collaboration with Nutriset. Other authors declare no conflicts of interest., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Vitamin A deficiency is highly prevalent in low-income countries and is a major public health problem worldwide. Lactating mothers are the most vulnerable population group to vitamin A deficiency. Despite this, there is limited study on vitamin A-rich food consumption by lactating mothers in Ethiopia. Therefore, this study aimed to assess adequate vitamin A rich food consumption and associated factors among lactating mothers visiting child immunization and postnatal care centers in health institutions of Gondar Town., Methods: An Institution-based cross-sectional study design was employed at a health institution in Gondar Town from February to March 2019, and included 631 study participants. Simple random sampling followed by a systematic sampling technique was used to select participants. The data were collected using the Helen Keller International Food Frequency Questionnaire, entered using Epi-Info 7 statistical software and exported to STATA version 14 for analysis. A multivariable logistic regression analysis was used to identify factors associated with the outcome variable and variables with p-value <0.05 were considered as statistically significant., Result: A total of 624 lactating mothers participated in the study giving a response rate of 98.89%. The study shows adequate consumption of vitamin A-rich food was 38.94% (95% CI: 35%- 43%). Predictors such as attending college diploma and above (AOR = 2.26, 95% CI; 1.02-4.99), having household family size ≤ 3 (AOR = 4.04, 95% CI; 1.60-10.17), being in higher economic class (AOR = 1.93, 95% CI; 1.18-3.14), having dietary diversity score of ≥ 5 (AOR = 1.59, 95% CI; 1.09-2.32) and meal frequency of ≥ 4 (AOR = 1.64, 95% CI; 1.09-2.32) were statistically significant., Conclusion and Recommendation: The majority of respondents had inadequate consumption of foods rich in vitamin A. Educational status, family size, wealth index, dietary diversity, and meal frequency were found to be factors that affect adequate consumption of vitamin A-rich foods. Encouraging and educating lactating mothers to consume foods rich in vitamin A is crucial., Competing Interests: The authors have declared that no competing interests exist.

Meeting children's vitamin A (VA) needs remains a policy priority. Doing so efficiently is a fiscal imperative and protecting at-risk children during policy transitions is a moral imperative. Using the Micronutrient Intervention Modeling tool and data for Cameroon, we predict the impacts and costs of alternative VA intervention programs, identify the least-cost strategy for meeting targets nationally, and compare it to a business-as-usual (BAU) strategy over 10 years. BAU programs effectively cover ∼12.8 million (m) child-years (CY) and cost ∼$30.1 m; ∼US$2.34 per CY effectively covered. Improving the VA-fortified oil program, implementing a VA-fortified bouillon cube program, and periodic VA supplements (VAS) in the North macroregion for 3 years effectively cover ∼13.1 m CY at a cost of ∼US$9.5 m, or ∼US$0.71 per CY effectively covered. The tool then identifies a sequence of subnational policy choices leading from the BAU toward the more efficient strategy, while addressing VA-attributable mortality concerns. By year 4, fortification programs are predicted to eliminate inadequate VA intake in the South and Cities macroregions, but not the North, where VAS should continue until additional delivery platforms are implemented. This modeling approach offers a concrete example of the strategic use of data to follow the Global Alliance for VA framework and do so efficiently., (© 2019 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals, Inc. on behalf of New York Academy of Sciences.)

Background: Vitamin A deficiency (VAD) is widespread in sub-Saharan Africa (SSA). Unlike in developed countries, where the main source of vitamin A comes from meat, the diet of poor populations in SSA is largely plant based. It is thus important to identify local / popular plants with higher vitamin A content for combating VAD. Banana (including plantains) is an important staple food crop in this region. The identification and promotion of vitamin A-rich banana cultivars could contribute significantly to the alleviation of VAD in areas heavily dependent on the crop. We assessed pro-vitamin A carotenoid (pVACs) content in the fruit pulp of 48 local plantains from eastern Democratic Republic of Congo, to identify cultivars that could help reduce VAD, especially among young children and women of reproductive age., Results: Mean pVACs content varied from 175-1756 μg/100 gfw in ripe fruits. Significant increases (P < 0.001) in total pVACs content occurred after ripening in all cultivars except 'UCG II'. Retinol activity equivalents (RAE) in ripe fruits ranged from 12-113 μg/100 gfw. Fifteen plantain cultivars, including 'Adili II', 'Nzirabahima', 'Mayayi', 'Buembe', and 'Sanza Tatu' (associated with RAE values of 44 μg/100 gfw and above) can be considered as good sources of pVACs. Modest consumption (250 or 500 gfw) of the fruit pulp of the five best plantain cultivars at ripening stage 5 meets between 39-71% and 44-81% of vitamin A dietary reference intake (DRI) respectively, for children below 5 years old and women of reproductive age., Conclusion: The 15 best plantain cultivars (especially the top 5) could potentially be introduced / promoted as alternative sources of pro-vitamin A in banana-dependent communities, and help to reduce cases of VAD substantially. © 2019 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry., (© 2019 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.)

Background: A multiple biofortified food crop trial targeting iron, zinc, and vitamin A deficiencies among young children and their breastfeeding mothers is planned in India., Objective: To determine the acceptability of recipes prepared with control and biofortified pearl millet, wheat, lentils, and sweet potato., Methods: Children (6-24 months) and their mothers were enrolled as pairs (n = 52). Weight and height/length were determined. Mothers and children were separately, individually randomized in a crossover design to control or biofortified recipes. Children's 3-day intake was measured per recipe and crop variety. For mothers, a 9-point hedonic scale evaluated color, odor, taste, and overall acceptability., Results: Children's mean (SD) length-/height-for-age Z -score was -1.2 (1.7), with 27% < -2 (stunted). Mean weight-for-length Z -score was -0.6 (1.2) with 9.6% < -2 (wasted). Mother's body mass index showed 17% <18.5 and 38% >25. There was no difference in the children's intake of biofortified versus control varieties of any recipe ( P ≥ .22); overall median daily intake was 75 g (Q1: 61, Q3: 100). Mother's hedonic scores for color, odor, taste, or overall acceptability did not demonstrate any notable differences ( P ≥ .23 for overall acceptability); combined median overall acceptability score was 8.5 (Q1: 8.0, Q3: 9.0)., Conclusions: Recipes were consumed readily, were rated as highly acceptable, and did not show any differences between biofortified and control varieties.

The Reaching End Users (REU) project introduced orange sweet potatoes (OSP) to farmers in northern Mozambique between 2006 and 2009, and the associated cluster randomised control trial found increased vitamin A intake among targeted children and women of child-bearing age and reduced prevalence of inadequate vitamin A intake. Yet little is known about whether successful agricultural-nutrition interventions have lasting effects. This study measures the lasting effects of the REU project, 3 years after the project ended, on vitamin A intake. To do so, dietary intake data were collected in the same thirty-six villages as the original study, focusing on both women of child-bearing age and children under 6 years old, the latter including both children who had been measured before and younger children (under 3 years old) in the same farmer groups. The dietary intake is then converted to micronutrient intake to compare treated households with control households. Vitamin A intake remains higher in treated villages than in control villages among both children under 3 years old, who had not been born when the original intervention ended, and mothers of child-bearing age. Differences in vitamin A intake can wholly be attributed to differences in OSP intake. Therefore, the REU project appears to have had lasting impacts on vitamin A intake beyond the intervention period. Had the vine retention component been enhanced, lasting impacts could have been even larger.

Vitamin A and its active metabolite, retinoic acid (RA), play a key role in the maintenance of cognitive functions in the adult brain. Depletion of RA using the vitamin A deficiency (VAD) model in Wistar rats leads to spatial memory deficits in relation to elevated intrahippocampal basal corticosterone (CORT) levels and increased hippocampal 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) activity. All of these effects are normalised by vitamin A supplementation. However, it is unknown whether vitamin A status also modulates contextual fear conditioning (CFC) in a glucocorticoid-associated fear memory task dependent on the functional integrity of the hippocampus. In the present study, we investigated the impact of VAD and vitamin A supplementation in adult male rats on fear memory processing, plasma CORT levels, hippocampal retinoid receptors and 11β-HSD1 expression following a novelty-induced stress. We also examined whether vitamin A supplementation or a single injection of UE2316, a selective 11β-HSD1 inhibitor, known to modulate local glucocorticoid levels, had any beneficial effects on contextual fear memory and biochemical parameters in VAD rats. We provide evidence that VAD rats exhibit a decreased fear conditioning response during training with a poor contextual fear memory 24 hours later. These VAD-induced cognitive impairments are associated with elevated plasma CORT levels under basal conditions, as well as following a stressful event, with saturated CORT release, altered hippocampal retinoid receptors and 11β-HSD1 expression. Vitamin A supplementation normalises VAD-induced fear conditioning training deficits and all biochemical effects, although it cannot prevent fear memory deficits. Moreover, a single injection of UE2316 not only impairs contextual fear memory, but also reduces plasma CORT levels, regardless of the vitamin A status and decreases slightly hippocampal 11β-HSD1 activity in VAD rats following stress. The present study highlights the importance of vitamin A status with respect to modulating fear memory conditioning in relation to plasma CORT levels and hippocampal 11β-HSD1., (© 2019 British Society for Neuroendocrinology.)

Carotenoids are fascinating compounds that can be converted into many others, including retinoids that also play key roles in many processes. Although carotenoids are largely known in the context of food science, nutrition, and health as natural colorants and precursors of vitamin A (VA), evidence has accumulated that even those that cannot be converted to VA may be involved in health-promoting biological actions. It is not surprising that carotenoids (most notably lutein) are among the bioactives for which the need to establish recommended dietary intakes have been recently discussed. In this review, the importance of carotenoids (including apocarotenoids) and key derivatives (retinoids with VA activity) in agro-food with relevance to health is summarized. Furthermore, the European Network to Advance Carotenoid Research and Applications in Agro-Food and Health (EUROCAROTEN) is introduced. EUROCAROTEN originated from the Ibero-American Network for the Study of Carotenoids as Functional Food Ingredients (IBERCAROT)., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objective: To carry out a systematic review and meta-analysis of the trials to identify as well as quantify the effect of vitamin A fortified food on serum vitamin A concentration among children under 10 year., Study Design: All the relevant studies has been retrieved by MEDLINE, PubMed, Embase, ProQuest and the Cochrane Library and secondary referencing. A random effects model was applied to compute the pooled effect size of effect of serum retinol. Meta regression was performed to detect the sources of heterogeneity and moderator variables on the study effect. We included all the relevant randomized control trials. These studies were assessed for inclusion and validity, with independent duplication., Results: Out of 648 published studies, fourteen were included and evaluated. These studies were covering 6153 children and the duration of feeding for the fortified foods ranged between 3 and 12 months. A pooled effect size of vitamin A fortification on retinol in children was estimated (N 6153; Standard Mean Difference = 0.47; 95% CI 0.16, 0.78). However, there was evidence of substantial heterogeneity of estimate on effect (I 2  = 97%, τ 2 (tau-squared) = 0.55, p < 0.01)., Conclusion: This study suggests that consumption of Vitamin A fortified foods results in increased concentration of retinol and thereby results in reduction of Vitamin A deficiency among the children., (Copyright © 2019 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Vitamin A deficiency (VAD) remains a major public health issue and is reported to be the cause of about 6 percent of child deaths under the age of 5 years in Africa. Inadequate dietary intake of vitamin A-rich foods is a major cause of VAD. Moringa oleifera leaf powder (MLP) is rich in nutrients particularly vitamin A and its use in infant feeding has been explored. This pilot study was designed to test the efficacy of MLP in improving blood retinol concentrations among infants in a rural district in Ghana. A subset of infants participating in a randomized controlled trial (ISRCTN14377902) were randomly assigned to receive one of the three study foods ( MCL-35g and MS-5g both of which were fortified with MLP, and a third food, CF-35g , a cereal legume blend which served as the control food) in a feeding intervention that lasted for 6 weeks. Primary outcome of the pilot study was retinol levels measured in 5 ml of whole blood at baseline and endline using the iCheck™ Fluoro device. A total of 103 infant-mother pairs were recruited at baseline, of which 65 completed the study. All the infants in the study were vitamin A deficient at both baseline and endline when compared to the World Health Organization (WHO) threshold of 0.70µmol/l. There was however a marginal non-significant increase in blood vitamin A concentrations for all three groups at endline, with higher numerical increases seen in the two Moringa supplemented groups. VAD is a significant public health problem and MLP could be an affordable and sustainable means of combatting the issue. The efficacy of MLP in improving vitamin A status of infants however needs to be ascertained in well-designed trials involving larger numbers of infants and which will last for longer periods. Such studies will also be beneficial in helping to establish the long-term acceptability of complementary foods that incorporate MLP in the target population.

Competing Interests: Competing interests: We have read and understood BMJ’s policy on declaration of interests and declare the following: JBM, CSB, and HPSS have no competing interests, KPW Jr, ACP, and AS receive academic programme support and periodic gratis supplement manufacture for intervention trials have been provided by the multinational science company DSM through the Sight and Life Foundation to the Johns Hopkins Bloomberg School of Public Health.

Previous research has evaluated antibody responses toward an influenza virus vaccine in the context of deficiencies for vitamins A and D (VAD+VDD). Results showed that antibodies and antibody-forming cells in the respiratory tract were reduced in VAD+VDD mice. However, effectors were recovered when oral supplements of vitamins A + D were delivered at the time of vaccination. Here we address the question of how vaccine-induced CD8 + T cell responses are affected by deficiencies for vitamins A + D. VAD+VDD and control mice were vaccinated with an intranasal, cold-adapted influenza virus A/Puerto Rico/8/34 vaccine, with or without oral supplements of vitamins A + D. Results showed that the percentages of vaccine-induced CD8 + T cell and total CD4 + T cell responses were low among lymphocytes in the airways of VAD+VDD animals compared to controls. The CD103 membrane marker, a protein that binds e-cadherin (expressed on respiratory tract epithelial cells), was unusually high on virus-specific T cells in VAD+VDD mice compared to controls. Interestingly, when T cells specific for the PA 224-233 /D b epitope were compared with T cells specific for the NP 366-374 /D b epitope, the former population was more strongly positive for CD103. Preliminary experiments revealed normal or above-normal percentages for vaccine-induced T cells in airways when VAD+VDD animals were supplemented with vitamins A + D at the time of vaccination and on days 3 and 7 after vaccination. Our results suggest that close attention should be paid to levels of vitamins A and D among vaccine recipients in the clinical arena, as low vitamin levels may render individuals poorly responsive to vaccines.

Background: The most common micronutrient deficiencies in Ecuadorian schoolchildren are vitamin A (VA), zinc, and iron. The objective of the present study was to test the efficacy of cow's milk as a vehicle for VA, zinc, and iron supplementation., Methods: Three hundred twenty-eight children aged 6-10 years were included in a randomized, double blind controlled study; 173 children received 480 mL of whole milk (300 Kcals; G1) daily and 155 children received fortified milk (300 Kcals; G2) daily for 23 weeks. Participants had a nutritional evaluation before and after supplementation. Both treatment groups were comparable for gender, age, weight and height at the beginning of the study., Results: Both types of milk were well accepted by the participating children. Data showed that serum concentrations of VA, zinc, and iron significantly increased within both treatment groups. The increase in serum concentrations of the indicated micronutrients was significantly greater in children with deficiencies than in non-deficient ones. There were not significant differences in serum concentrations of VA, zinc, and iron between groups after supplementation. Data also showed that there was an increase in the percentage of children with normal BMI at the expense of a decrease of the percentage of children with excess weight at the end of the treatment period in G1 whereas in G2 it remained unchanged. Blood lipid profiles were normal before and after milk supplementation in both treatment groups., Conclusions: These data indicated that fortified and non-fortified milk are excellent options to increase serum VA, zinc, and iron concentration in schoolchildren.

Background: We previously compared the potential effects of different intervention strategies for achieving dietary vitamin A (VA) adequacy. The Lives Saved Tool (LiST) permits estimates of lives saved through VA interventions but currently only considers periodic VA supplements (VASs). Objective: We aimed to adapt the LiST method for estimating the mortality impact of VASs to estimate the impact of other VA interventions (e.g., food fortification) on child mortality and to estimate the number of lives saved by VA interventions in 3 macroregions in Cameroon. Methods: We used national dietary intake data to predict the effects of VA intervention programs on the adequacy of VA intake. LiST parameters of population affected fraction and intervention coverage were replaced with estimates of prevalence of inadequate intake and effective coverage (proportion achieving adequate VA intake). We used a model of liver VA stores to derive an estimate of the mortality reduction from achieving dietary VA adequacy; this estimate and a conservative assumption of equivalent mortality reduction for VAS and VA intake were applied to projections for Cameroon. Results: There were 2217-3048 total estimated VA-preventable deaths in year 1, with 58% occurring in the North macroregion. The relation between effective coverage and lives saved differed by year and macroregion due to differences in total deaths, diarrhea burden, and prevalence of low VA intake. Estimates of lives saved by VASs (the intervention common to both methods) were similar with the use of the adapted method (in 2012: North, 743-1021; South, 280-385; Yaoundé and Douala, 146-202) and the "usual" LiST method (North: 697; South: 381; Yaoundé and Douala: 147). Conclusions: Linking effective coverage estimates with an adapted LiST method permits estimation of the effects of combinations of VA programs (beyond VASs only) on child mortality to aid program planning and management. Rigorous program monitoring and evaluation are necessary to confirm predicted impacts., Competing Interests: Author disclosures: RE-S, AP, AC, NW, MJH, SAV, and KHB, no conflicts of interest., (© 2017 American Society for Nutrition.)

This study investigated the prenatal marginal vitamin A deficiency (mVAD)-related impairment in learning and memory and the interactions between RARα, Src and NR1. Learning and memory were assessed in adult rats that were exposed to prenatal mVAD with Morris water maze. The average escape time was longer in mVAD rats, and they passed the hidden platform fewer times during the memory retention test than normal vitamin A intake (VAN) rats. The mRNA and protein levels of RARα, Src and NR1 in mVAD rats were significantly lower than those in VAN rats. RARα and Src, but not NR1, were in the same protein complex. RA treatment-induced increase in RARα, Src and NR1 expressions in mVAD neurons was much lower than that in VAN neurons. Overexpression of RARα gene in VAN neurons induced an increase in RARα, Src and NR1 expressions, while silencing of RARα gene induced a decrease in expressions of RARα and Src, but not that of of NR1. In mVAD neurons, however, overexpression of RARα did not induce an increase in NR1 expression, while silencing of RARα gene had no effect on Src and NR1 expressions. Furthermore, inhibition of Src was associated with a decrease in NR1 expression but not that of RARα. Prenatal mVAD was associated with impaired learning and memory in adult rats. It is possible that mVAD-related decrease in RARα led to a decrease in Src expression, which in turn down-regulated NR1 expression and Ca 2+ influx and eventually caused learning and memory deficits., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Few studies have examined the impact of local animal-source foods (ASFs) on the nutritional status of reproductive-age women in developing countries. Objective: We hypothesized that a midmorning snack of local ASF for 6 mo would reduce dietary micronutrient deficiencies [usual intake less than the estimated average requirement (EAR)] and improve blood biomarkers of iron, zinc, and vitamins A and B-12 status among nonpregnant, reproductive-age women in rural Vietnam. Methods: One hundred seventeen women, 18-30 y old, were randomly assigned to receive either an ASF (mean: 144 kcal, 8.9 mg Fe, 2.7 mg Zn, 1050 μg retinoic acid equivalent vitamin A, and 5.5 μg vitamin B-12) or a control snack (mean: 150 kcal, 2.0 mg Fe, 0.9 mg Zn, 0 μg retinoic acid equivalent vitamin A, and 0 μg vitamin B-12) 5 d/wk for 6 mo. Usual nutrient intakes were estimated by repeated 24-h dietary recalls. Blood samples were collected at baseline and 3 and 6 mo. Because of the relation between nutritional status and inflammation, serum C-reactive protein, α-1-acid-glycoprotein, and urinary tract infections (UTIs) were also monitored. Results: Eighty-nine women (47 in the ASF group and 42 controls) completed the study. In the ASF group, intakes of iron and vitamins A and B-12 below the EAR were eliminated, and the prevalence of a low zinc intake was reduced to 9.6% compared with 64.7% in controls ( P < 0.001). At 6 mo, a modest increase ( P < 0.05) in hemoglobin and iron status occurred in the ASF group compared with the control group, but plasma zinc, retinol, and serum vitamin B-12 concentrations did not differ. UTI relative risk was 3.9 ( P < 0.05) among women assigned to the ASF group who had a low whole-body iron status at baseline. Conclusions: Adding a small amount of locally produced ASF to the diets of reproductive-age Vietnamese women improved micronutrient intakes and iron status. However, the increased UTI incidence in women in the ASF group with initially lower iron stores warrants further investigation., Competing Interests: 2: Author disclosures: AG Hall, T Ngu, HT Nga, PN Quyen, PT Hong Anh, and JC King, no conflicts of interest., (© 2017 American Society for Nutrition.)

Background: Although vitamin A supplementation reduces child mortality, it remains unclear whether dosing frequency, total dose, or duration modifies effectiveness., Objective: Determine whether mortality effects of vitamin A vary by dosing frequency, total dose, or duration., Methods: Meta-analysis of randomized controlled trials, identified by systematic review and expert opinion, utilizing relatively standard World Health Organization doses in children <5 years. Meta-regression evaluated whether mortality effects varied by dosing frequency, total dose, or supplementation duration., Results: Identified 17 trials, including 1,180,718 children, mean (standard deviation [SD]) age 31.5 (15.4) months at baseline. Supplementation frequency ranged every 3 months-every 2 years, supplementation duration 4-60 months (mean = 15.4; SD = 12.8), and total dose 134,361-2,200,000 IU (mean = 667,132 IU; SD = 540,795). Compared with control, vitamin A reduced mortality 22% (95% confidence interval [CI] = 10-32; P = 0.002). This protective effect was not modified by increasing supplementation frequency (dose/year: relative risk [RR] = 1.02; 95% CI = 0.98-1.06; P = .22), total dose (per 200,000 IU: RR = 1.02; 95% CI = 0.97-1.06; P = .31), nor supplementation duration (per year: RR = 1.06; 95% CI = 0.97-1.15; P = 0.14). Multivariate meta-regression showed similar results. Sensitivity analyses excluding 1 controversial trial (Aswathi 2013) did not alter findings., Conclusion: Results confirm benefits of vitamin A supplementation in children <5 years in nations with vitamin A deficiency, without influence of frequency, total dose, or dosing duration within ranges evaluated. These findings inform design and efficiency of vitamin A supplementation policies.

Deposition of amyloid β protein (Aβ) to form neuritic plaques in the brain is the unique pathological hallmark of Alzheimer's disease (AD). Aβ is derived from amyloid β precursor protein (APP) by β- and γ-secretase cleavages and turned over by glia in the central nervous system (CNS). Vitamin A deficiency (VAD) has been shown to affect cognitive functions. Marginal vitamin A deficiency (MVAD) is a serious and widespread public health problem among pregnant women and children in developing countries. However, the role of MVAD in the pathogenesis of AD remains elusive. Our study showed that MVAD is approximately twofold more prevalent than VAD in the elderly, and increased cognitive decline is positively correlated with lower VA levels. We found that MVAD, mostly prenatal MVAD, promotes beta-site APP cleaving enzyme 1 (BACE1)-mediated Aβ production and neuritic plaque formation, and significantly exacerbates memory deficits in AD model mice. Supplementing a therapeutic dose of VA rescued the MVAD-induced memory deficits. Taken together, our study demonstrates that MVAD facilitates AD pathogenesis and VA supplementation improves cognitive deficits. These results suggest that VA supplementation might be a potential approach for AD prevention and treatment.

Background: Orange-fleshed sweet potato (OFSP) improves vitamin A (VA) status of young children; research with pregnant and lactating women is limited. Objective: We examined the effectiveness of the Mama SASHA (Sweetpotato Action for Security and Health in Africa) program to improve nutrition knowledge, diets, and nutritional status of pregnant and lactating women (PLW) in Western Kenya. Methods: Eight health facilities were allocated to the Mama SASHA intervention or comparison arms. PLW in intervention facilities received enhanced nutrition counseling at health clinics, were linked with community-based maternal support groups, and received vouchers for OFSP vine cuttings. Control PLW received clinic-based nutrition counseling only. A total of 505 women in early and midpregnancy, attending their first antenatal care visit, and with no previous engagement in project activities were enrolled from the 8 facilities. Nutrition and health-seeking knowledge, food security, dietary patterns, and anthropometric measurements were collected at 4 time points at ≤9 mo postpartum. VA intakes were assessed with multipass 24-h recalls in a subsample of 206 mothers at 8-10 mo postpartum. VA status was assessed by using serum retinol-binding protein (RBP). Impacts were estimated with multilevel mixed models adjusted for clustering and differences at enrollment. Results: At enrollment, 22.9% of women had RBP <1.17 μmol/L. By 9 mo postpartum, intervention women had significantly higher intakes of VA [adjusted difference = 297.0 retinol activity equivalent (RAE) units; 95% CI: 82, 513 RAE units; P = 0.01; n = 206], greater consumption of VA-rich fruit and vegetables in the previous 7 d (difference-in-difference estimate: 0.40 d; 95% CI: 0.23, 0.56 d; P < 0.01), and a 45% reduction in the odds of RBP <1.17 μmol/L (OR: 0.55; 95% CI: 0.33, 0.92; P = 0.01). Conclusion: Promotion of OFSP to PLW through health services is a feasible strategy to improve women's nutrition knowledge, VA intakes, and maternal RBP., Competing Interests: 2: Author disclosures: A Webb Girard, F Grant, M Watkinson, HS Okuku, R Wanjala, D Cole, C Levin, and J Low, no conflicts of interest.

Background: Despite evidence for the benefits of vitamin A supplementation (VAS) among children 6 to 59 months of age, the feasibility of introduction and potential benefit of VAS in the neonatal period in public health programmes is uncertain., Objective: The primary objective was to evaluate the feasibility and effectiveness of early neonatal VAS (single dose of 50 000 international units within 48-72 hours after birth) delivered through the public sector Lady Health Worker (LHW) programme in rural Pakistan and to document its association with a reduction in mortality at 6 months of age., Methods: A community-based, cluster randomised, placebo-controlled trial was undertaken in two districts of rural Pakistan. LHWs dispensed vitamin A/placebo in identical capsules to newborn infants within 48-72 hours of birth. Follow-up visits were undertaken at 1 week of age and every 4 weeks thereafter until 6 months of age., Results: Of a total of 15 433 consecutive pregnancies among eligible women of reproductive age, 13 225 pregnancies were registered, 12 218 live births identified and 11 028 newborn infants reached by LHWs. Of these, 5380 (49%) received neonatal VAS and 5648 (51%) placebo. The LHWs successfully delivered the capsules to 79% of newborns within 72 hours of birth with no significant adverse effects. Although the proportion of days observed with symptoms of fever, diarrhoea or rapid breathing were lower with neonatal VAS, these differences were not statistically significant. Mortality rates in the two groups were comparable at 6 months of age., Conclusions: While our study demonstrated that neonatal VAS was safe and could be feasibly delivered by LHWs in Pakistan as part of their early postnatal visits, the overall lack of benefit on neonatal and 6-month morbidity and mortality in our population suggests the need for further evaluation of this intervention in populations at risk., Trial Registration Number: ClinicalTrials.gov NCT00674089., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Background: Impaired dark adaptation is an early functional indicator of vitamin A deficiency that may be prevented by regular dietary intake of foods containing provitamin A carotenoids., Objective: We tested the impact of provitamin A carotenoid-biofortified maize consumption (∼15 μg β-carotene/g) on dark adaptation in Zambian children., Methods: We used a cluster-randomized trial of children aged 4-8 y (n = 1024) in Mkushi District, Zambia, and compared the regular consumption (2 meals/d, 6 d/wk for 6 mo) of biofortified orange maize (OM) to white maize (WM). The primary outcome was the serum retinol response. In a random sample (n = 542), we used a digital pupillometer to test pre- and postintervention responses to graded light stimuli (-2.9 to 0.1 log cd/m 2 ) in a dark-adapted state., Results: At baseline, 11.7% of the children had serum retinol <0.7 μmol/L, 14.4% had impaired dark adaptation (pupillary threshold ≥ -1.11 log cd/m 2 ), and 2.3% had night blindness. The mean ± SD pupillary responsiveness to light stimuli was poorer at baseline in the OM group (16.1% ± 6.6%) than the WM group (18.1% ± 6.4%) (P = 0.02) but did not differ at follow-up (OM: 17.6% ± 6.5%; WM: 18.3% ± 6.5%). Among children with serum retinol <1.05 μmol/L at baseline, there was greater improvement in pupillary responsiveness in the OM group (2.2%; 95% CI: 0.1%, 4.3%) than the WM group (0.2%; 95% CI: -1.1%, 1.5%; P = 0.01), but there were no differences in children with adequate baseline status. We found no effect of treatment on pupillary threshold or night blindness., Conclusions: The regular consumption of provitamin A carotenoid-biofortified maize increased pupillary responsiveness among children with marginal or deficient vitamin A status, providing evidence of a functional benefit to consuming this biofortified crop. This trial was registered at clinicaltrials.gov as NCT01695148., (© 2016 American Society for Nutrition.)

Background: Vitamin A deficiency continues to be a major public health problem affecting developing countries where people eat mostly rice as a staple food. In Asia, rice provides up to 80% of the total daily energy intake., Objective: We used existing data sets from Bangladesh, Indonesia, and the Philippines, where dietary intakes have been quantified at the individual level to 1) determine the rice and vitamin A intake in nonpregnant, nonlactating women of reproductive age and in nonbreastfed children 1-3 y old and 2) simulate the amount of change that could be achieved in the prevalence of inadequate intake of vitamin A if rice biofortified with β-carotene were consumed instead of the rice consumed at present., Design: We considered a range of 4-20 parts per million (ppm) of β-carotene content and 10-70% substitution levels for the biofortified rice. Software was used to estimate usual rice and vitamin A intake for the simulation analyses., Results: In an analysis by country, the substitution of biofortified rice for white rice in the optimistic scenario (20 ppm and 70% substitution) decreased the prevalence of vitamin A inadequacy from baseline 78% in women and 71% in children in Bangladesh. In Indonesia and the Philippines, the prevalence of inadequacy fell by 55-60% in women and dropped by nearly 30% in children from baseline., Conclusions: The results of the simulation analysis were striking in that even low substitution levels and modest increases in the β-carotene of rice produced a meaningful decrease in the prevalence of inadequate intake of vitamin A. Increasing the substitution levels had a greater impact than increasing the β-carotene content by >12 ppm.

Background: Vitamin A deficiency remains a nutritional concern in sub-Saharan Africa. Conventionally bred maize hybrids with high provitamin A carotenoid concentrations may have the potential to improve vitamin A status in maize-consuming populations., Objective: We evaluated the efficacy of regular provitamin A carotenoid-biofortified "orange" maizemeal (∼15 μg β-carotene/g) consumption in improving vitamin A status and reducing vitamin A deficiency in children., Design: This was a cluster-randomized controlled trial in the rural farming district of Mkushi, Zambia. All 4- to 8-y-old children in an ∼400-km(2) area were identified and grouped by proximity into clusters of ∼15-25 children. We randomly assigned clusters to 1) orange maizemeal (n = 25), 2) white maizemeal (n = 25), or 3) a parallel, nonintervention group (n = 14). Children in intervention clusters (n = 1024) received 200 g maizemeal for 6 d/wk over 6 mo; the maizemeal was prepared according to standardized recipes and served in cluster-level kitchens. Staff recorded attendance and leftovers. We collected venous blood before and after the intervention to measure serum retinol, β-carotene, C-reactive protein, and α1-acid glycoprotein., Results: Intervention groups were comparable at baseline, and vitamin A status was better than anticipated (12.1% deficient on the basis of serum retinol <0.7 μmol/L). Although attendance at meals did not differ (85%), median daily maize intake was higher in white (154 g/d) than in orange (142 g/d) maizemeal clusters. At follow-up, mean serum β-carotene was 0.14 μmol/L (95% CI: 0.09, 0.20 μmol/L) higher in orange maizemeal clusters (P < 0.001), but mean serum retinol (1.00 ± 0.33 μmol/L overall) and deficiency prevalence (17.1% overall) did not differ between arms., Conclusion: In this marginally nourished population, regular biofortified maizemeal consumption increased serum β-carotene concentrations but did not improve serum retinol. This trial was registered at clinicaltrials.gov as NCT01695148., (© 2016 American Society for Nutrition.)

In Cambodia, micronutrient deficiencies remain a critical public health problem. Our objective was to evaluate the impact of multi-micronutrient fortified rice (MMFR) formulations, distributed through a World Food Program school-meals program (WFP-SMP), on the hemoglobin concentrations and iron and vitamin A (VA) status of Cambodian schoolchildren. The FORISCA-UltraRice+NutriRice study was a double-blind, cluster-randomized, placebo-controlled trial. Sixteen schools participating in WFP-SMP were randomly assigned to receive extrusion-fortified rice (UltraRice Original, UltraRice New (URN), or NutriRice) or unfortified rice (placebo) six days a week for six months. Four additional schools not participating in WFP-SMP were randomly selected as controls. A total of 2440 schoolchildren (6-16 years old) participated in the biochemical study. Hemoglobin, iron status, estimated using inflammation-adjusted ferritin and transferrin receptors concentrations, and VA status, assessed using inflammation-adjusted retinol-binding protein concentration, were measured at the baseline, as well as at three and six months. Baseline prevalence of anemia, depleted iron stores, tissue iron deficiency, marginal VA status and VA deficiency were 15.6%, 1.4%, 51.0%, 7.9%, and 0.7%, respectively. The strongest risk factors for anemia were hemoglobinopathy, VA deficiency, and depleted iron stores (all p < 0.01). After six months, children receiving NutriRice and URN had 4 and 5 times less risk of low VA status, respectively, in comparison to the placebo group. Hemoglobin significantly increased (+0.8 g/L) after three months for the URN group in comparison to the placebo group; however, this difference was no longer significant after six months, except for children without inflammation. MMFR containing VA effectively improved the VA status of schoolchildren. The impact on hemoglobin and iron status was limited, partly by sub-clinical inflammation. MMFR combined with non-nutritional approaches addressing anemia and inflammation should be further investigated.

Carotenoids are essential components for human nutrition and health, mainly due to their antioxidant and pro-vitamin A activity. Foods with enhanced carotenoid content and composition are essential to ensure carotenoid feasibility in malnourished population of many countries around the world, which is critical to alleviate vitamin A deficiency and other health-related disorders. The pathway of carotenoid biosynthesis is currently well understood, key steps of the pathways in different plant species have been characterized and the corresponding genes identified, as well as other regulatory elements. This enables the manipulation and improvement of carotenoid content and composition in order to control the nutritional value of a number of agronomical important staple crops. Biotechnological and genetic engineering-based strategies to manipulate carotenoid metabolism have been successfully implemented in many crops, with Golden rice as the most relevant example of β-carotene improvement in one of the more widely consumed foods. Conventional breeding strategies have been also adopted in the bio-fortification of carotenoid in staple foods that are highly consumed in developing countries, including maize, cassava and sweet potatoes, to alleviate nutrition-related problems. The objective of the chapter is to summarize major breakthroughs and advances in the enhancement of carotenoid content and composition in agronomical and nutritional important crops, with special emphasis to their potential impact and benefits in human nutrition and health.

Food fortification is a cost-effective and sustainable strategy to prevent or correct micronutrient deficiencies. A double-blind cluster (bari) randomised controlled trial was conducted in a rural community in Bangladesh to evaluate the impact of consumption of chapatti made of micronutrient-fortified wheat flour for 6 months by school-aged children on their vitamin A, haemoglobin and iron status. A total of 43 baris (group of households) were randomly selected. The baris were randomly assigned to either intervention or control group. The intervention group received wheat flour fortified with added micronutrients (including 66 mg hydrogen-reduced elemental iron and 3030 μg retinol equivalent as retinyl palmitate per kilogram of flour), while the control group received wheat flour without added micronutrients. A total of 352 children were enrolled in the trial, 203 in the intervention group and 149 in the control group. Analyses were carried out on children who completed the study (191 in the intervention group and 143 in the control group). Micronutrient-fortified wheat flour chapatti significantly increased serum retinol concentration at 6 months by 0.12 μmol L(-1) [95% confidence interval (CI): 0.06, 0.19; P < 0.01]. The odds of vitamin A deficiency was significantly lower for children in the intervention group at 3 months [odds ratio (OR) = 0.26; 95% confidence interval (CI): 0.07, 0.89; P < 0.05] and 6 months (OR = 0.21; 95% CI: 0.06, 0.68; P < 0.01). No demonstrable effect of fortified chapatti consumption on iron status, haemoglobin levels or anaemia was observed. Consumption of fortified chapattis demonstrated a significant improvement in the vitamin A status, but not in iron, haemoglobin or anaemia status., (© 2013 John Wiley & Sons Ltd.)

Diabetes has emerged as the biggest pandemic of our times, growing parallel to obesity. Insulin treatment regimens have been unable to completely inhibit protein glycation, which is responsible for the development of increased oxidative stress in diabetic tissues. Coupled with recent evidences that highlight the role of reactive oxygen species in the onset and progression of type 2 diabetes mellitus (T2DM), the antioxidants have taken prime focus as a possible intervention strategy. Studies have established a role of antioxidant vitamins C and E in improving patient condition in the past. Vitamin A, in addition to its role as an antioxidant, boasts a pleiotropic role in cell regulation through its action on gene regulation, maintenance of epithelial cell integrity, and resistance to infection. Studies have also ascribed a role to vitamin A in up-regulating the antioxidant enzyme functions in the body. Additionally, a link has been found between diabetes and deficient vitamin A levels indicating vitamin A supplementation may have a role in T2DM biology. This review therefore focuses on the vitamin A intervention in T2DM patients having deficient in vitamin A., (Copyright © 2015 Elsevier Inc. All rights reserved.)

We report a case of acquired night blindness in a developed country (Spain) without risk factors for nutritional deficiency disease or family history of hereditary retinal disease. A 76-year-old woman presented with acquired night blindness of 6-month progression. After a thorough inquiry about eating patterns she becomes suspicious of vitamin A low dietary intake, which is analytically confirmed and successfully treated. Despite being very uncommon in our environment and even more in patients without digestive problems, in a patient reporting acquired night blindness vitamin A deficiency should not be discarded until eating patterns have been investigated. It might be especially relevant in certain socioeconomic situations and eating disorders such as bulimia or anorexia nervosa.

Objective: Vitamin A deficiency (VAD) is associated with the progression of chronic liver disease (CLD). The aim in this study was to assess levels of serum retinol and retinol-binding protein (RBP) as well as liver vitamin A stores in the presence of liver cirrhosis and hepatocellular carcinoma., Methods: We ascertained the serum retinol and RBP levels of randomly selected CLD patients divided into two groups, one given 1500 UI (n = 89) and the other receiving 2500 UI (n = 89) doses of retinyl palmitate for the relative dose response test. Blood samples were collected in a fasting state and 5 and 7 h after supplementation., Results: The prevalence of VAD was 62.4%. There was a progressive drop in serum retinol (P < 0.001) and RBP (P = 0.002) according to the severity of the liver disease, and a greater prevalence of severe VAD was noted in cirrhosis Child & Pugh C (52.8%). Fifty percent of the patients presented a low availability of RBP relative to retinol concentration, and there was no peak in RBP levels regardless of the dose of retinyl palmitate administered., Conclusions: Our findings suggest serum retinol and RBP are relevant as indicators of vitamin A nutritional status in the presence of CLD. Liver vitamin A store cannot be evaluated using the RDR test because CLD causes a reduction in RBP synthesis and interferes with the mobilization of endogenous vitamin A. Considering how the patients already showed a drop in RBP relative to retinol concentrations, it is reasonable to assume vitamin A supplementation may trigger harmful effects in CLD patients., (Published by Elsevier Inc.)

Objective: Vitamin A deficiency is a serious health problem in Bangladesh. The 2011-12 Bangladesh Micronutrient Survey found 76·8% of children of pre-school age were vitamin A deficient. In the absence of nationally representative, individual dietary assessment data, we use an alternative--household income and expenditure survey data--to estimate the potential impact of the introduction of vitamin A-fortified vegetable oil in Bangladesh., Design: Items in the household income and expenditure survey were matched to food composition tables to estimate households' usual vitamin A intakes. Then, assuming (i) the intra-household distribution of food is in direct proportion to household members' share of the household's total adult male consumption equivalents, (ii) all vegetable oil that is made from other-than mustard seed and that is purchased is fortifiable and (iii) oil fortification standards are implemented, we modelled the additional vitamin A intake due to the new fortification initiative., Setting: Nationwide in Bangladesh., Subjects: A weighted sample of 12,240 households comprised of 55,580 individuals., Results: Ninety-nine per cent of the Bangladesh population consumes vegetable oil. The quantities consumed are sufficiently large and, varying little by socio-economic status, are able to provide an important, large-scale impact. At full implementation, vegetable oil fortification will reduce the number of persons with inadequate vitamin A intake from 115 million to 86 million and decrease the prevalence of inadequate vitamin A intake from 80% to 60%., Conclusions: Vegetable oil is an ideal fortification vehicle in Bangladesh. Its fortification with vitamin A is an important public health intervention.

Iron deficiency anemia, zinc and vitamin A deficiencies are serious public health problems in Cameroon, as in many developing countries. Local vegetables which are sources of provitamin A carotenoids (PACs) can be used to improve vitamin A intakes. However, traditional meals are often unable to cover zinc and iron needs. The aim of this study was to determine the bioavailability of 3 PACs (α-carotene, β-carotene, and β-cryptoxanthin) in young men, who were fed with a vitamin A-free diet and received iron and zinc supplementation. Twelve healthy participants were divided into three groups and were supplemented with elemental iron (20 mg of iron fumarate), 20 mg of zinc sulfate or iron+zinc (20 mg of iron in the morning and 20 mg of zinc in the evening) for 11 d. They were given a vitamin A- and PAC-free diet from the 6th to the 11th day, followed by a test meal containing 0.55 kg of freshly peeled papaya as a source of PACs. Blood samples were collected four times successively on the 11th day (the test meal day), at T0 (just after the test meal), after 2 h (T2), after 4 h (T4) and after 7 h (T7). Ultracentrifugation was used to isolate serum chylomicrons. Retinol appearance and PAC postprandial concentrations were determined. The supplementation with zinc, iron and iron+zinc influenced the chylomicron appearance of retinol and PACs differently as reflected by retention times and maximum absorption peaks. Iron led to highest retinol levels in the chylomicron. Zinc and iron+zinc supplements were best for optimal intact appearance of α-carotene, β-carotene and β-cryptoxanthin respectively. Supplementation with iron led to the greatest bioavailability of PACs from papaya and its conversion to retinol.

Vitamin A is a critical micronutrient for regulating immunity in many organisms. Our previous study demonstrated that gestational or early-life vitamin A deficiency decreases the number of immune cells in offspring. The present study aims to test whether vitamin A supplementation can restore lymphocyte pools in vitamin A-deficient rats and thereby improve the function of their intestinal mucosa; furthermore, the study aimed to identify the best time frame for vitamin A supplementation. Vitamin A-deficient pregnant rats or their offspring were administered a low-dose of vitamin A daily for 7 days starting on gestational day 14 or postnatal day 1, day 14 or day 28. Serum retinol concentrations increased significantly in all four groups that received vitamin A supplementation, as determined by high-performance liquid chromatography. The intestinal levels of secretory immunoglobulin A and polymeric immunoglobulin receptor increased significantly with lipopolysaccharide challenge in the rats that received vitamin A supplementation starting on postnatal day 1. The rats in this group had higher numbers of CD8+ intestinal intraepithelial lymphocytes, CD11C+ dendritic cells in the Peyer's patches and CD4+CD25+ T cells in the spleen compared with the vitamin A-deficient rats; flow cytometric analysis also demonstrated that vitamin A supplementation decreased the number of B cells in the mesenteric lymph nodes. Additionally, vitamin A supplementation during late gestation increased the numbers of CD8+ intestinal intraepithelial lymphocytes and decreased the numbers of B lymphocytes in the mesenteric lymph nodes. However, no significant differences in lymphocyte levels were found between the rats in the other two vitamin A supplement groups and the vitamin A-deficient group. In conclusion, the best recovery of a subset of lymphocytes in the offspring of gestational vitamin A-deficient rats and the greatest improvement in the intestinal mucosal immune response are achieved when vitamin A supplementation occurs during the early postnatal period.

Background: Biofortification is a strategy to relieve vitamin A (VA) deficiency. Biofortified maize contains enhanced provitamin A concentrations and has been bioefficacious in animal and small human studies., Objective: The study sought to determine changes in total body reserves (TBRs) of vitamin A with consumption of biofortified maize., Design: A randomized, placebo-controlled biofortified maize efficacy trial was conducted in 140 rural Zambian children. The paired (13)C-retinol isotope dilution test, a sensitive biomarker for VA status, was used to measure TBRs before and after a 90-d intervention. Treatments were white maize with placebo oil (VA-), orange maize with placebo (orange), and white maize with VA in oil [400 μg retinol activity equivalents (RAEs) in 214 μL daily] (VA+)., Results: In total, 133 children completed the trial and were analyzed for TBRs (n = 44 or 45/group). Change in TBR residuals were not normally distributed (P < 0.0001); median changes (95% CI) were as follows: VA-, 13 (-19, 44) μmol; orange, 84 (21, 146) μmol; and VA+, 98 (24, 171) μmol. Nonparametric analysis showed no statistical difference between VA+ and orange (P = 0.34); both were higher than VA- (P = 0.0034). Median (95% CI) calculated liver reserves at baseline were 1.04 (0.97, 1.12) μmol/g liver, with 59% >1 μmol/g, the subtoxicity cutoff; none were <0.1 μmol/g, the deficiency cutoff. The calculated bioconversion factor was 10.4 μg β-carotene equivalents/1 μg retinol by using the middle 3 quintiles of change in TBRs from each group. Serum retinol did not change in response to intervention (P = 0.16) but was reduced with elevated C-reactive protein (P = 0.0029) and α-1-acid glycoprotein (P = 0.0023) at baseline., Conclusions: β-Carotene from maize was efficacious when consumed as a staple food in this population and could avoid the potential for hypervitaminosis A that was observed with the use of preformed VA from supplementation and fortification. Use of more sensitive methods other than serum retinol alone, such as isotope dilution, is required to accurately assess VA status, evaluate interventions, and investigate the interaction of VA status and infection. This trial was registered at clinicaltrials.gov as NCT01814891., (© 2014 American Society for Nutrition.)

Vitamin A must be adequately distributed within the body to maintain the functions of retinoids in the periphery and chromophore production in the eyes. Blood transport of the lipophilic vitamin is mediated by the retinol-binding protein, RBP4. Biochemical evidence suggests that cellular uptake of vitamin A from RBP4 is facilitated by a membrane receptor. This receptor, identified as the Stimulated by retinoic acid gene 6 (Stra6) gene product, is highly expressed in epithelia that constitute blood-tissue barriers. Here we established a Stra6 knockout mouse model to analyze the metabolic basis of vitamin A homeostasis in peripheral tissues. These mice were viable when bred on diets replete in vitamin A, but evidenced markedly reduced levels of ocular retinoids. Ophthalmic imaging and histology revealed malformations in the choroid and retinal pigmented epithelium, early cone photoreceptor cell death, and reduced lengths of rod outer segments. Similar to the blood-retina barrier in the RPE, vitamin A transport through the blood-cerebrospinal fluid barrier in the brain's choroid plexus was impaired. Notably, treatment with pharmacological doses of vitamin A restored vitamin A transport across these barriers and rescued the vision of Stra6(-/-) mice. Furthermore, under conditions mimicking vitamin A excess and deficiency, our analyses revealed that STRA6-mediated vitamin A uptake is a regulated process mandatory for ocular vitamin A uptake when RBP4 constitutes the only transport mode in vitamin A deficiency. These findings identifying STRA6 as a bona fide vitamin A transporter have important implications for disease states associated with impaired blood vitamin A homeostasis., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Vitamin A deficiency (VAD) has been recognized as a public-health issue in developing countries. Economic constraints, sociocultural limitations, insufficient dietary intake, and poor absorption leading to depleted vitamin A stores in the body have been regarded as potential determinants of the prevalence of VAD in South Asian developing countries. VAD is exacerbated by lack of education, poor sanitation, absence of new legislation and enforcement of existing food laws, and week monitoring and surveillance system. Several recent estimates confirmed higher morbidly and mortality rate among children and pregnant and non-pregnant women of childbearing age. Xerophthalmia is the leading cause of preventable childhood blindness with its earliest manifestations as night blindness and Bitot's spots, followed by blinding keratomalacia, all of which are the ocular manifestations of VAD. Children need additional vitamin A because they do not consume enough in their normal diet. There are three general ways for improving vitamin A status: supplementation, fortification, and dietary diversification. These approaches have not solved the problem in South Asian countries to the desired extent because of poor governmental support and supervision of vitamin A supplementation twice a year. An extensive review of the extant literature was carried out, and the data under various sections were identified by using a computerized bibliographic search via PubMed, Web of Science, and Google Scholar. All abstracts and full-text articles were examined, and the most relevant articles were selected for screening and inclusion in this review. Conclusively, high prevalence of VAD in South Asian developing countries leads to increased morbidity and mortality among infants, children, and pregnant women. Therefore, stem efforts are needed to address this issue of public-health significance at local and international level in lower- and middle-income countries of South Asia.

Background: The potential of β-cryptoxanthin (CX)-rich foods to form vitamin A (VA) in humans in not well understood., Objective: We measured the effects of consuming CX- and β-carotene (BC)-rich foods on plasma and breast milk VA and carotenoids in lactating women with low VA status., Design: Participants were randomly assigned to 4 groups (n = 34, 34, 34, and 33, respectively) receiving orange-fleshed sweet potatoes (OFSPs) (12 mg BC/d), tangerines (5.3 mg CX/d), white-fleshed sweet potatoes (WFSPs) with a VA supplement (0.5 mg/d), or WFSPs 2 times/d, 6 d/wk for 3 wk. All except the VA group received placebo capsules identical in appearance to VA supplements. Changes in plasma and breast milk VA, BC, and CX were measured., Results: Plasma retinol increased in the VA group. Plasma BC in the OFSP group and CX in the tangerine group increased 250% and 830%, respectively; apparent relative absorption in the CX group, considering the amounts consumed, was 4 times that in the BC group. Mean (±SEM) changes in milk VA in the OFSP (0.028 ± 0.074 μmol/L) and tangerine (0.067 ± 0.091 μmol/L) groups did not differ from those in the control (-0.077 ± 0.068 μmol/L) or VA (0.277 ± 0.094 μmol/L) group. Milk CX increased in the tangerine group., Conclusions: VA capsules increased plasma and milk VA concentrations. The greater change in CX concentrations in the tangerine group than in BC concentrations in the OFSP group suggests that CX in tangerines was better absorbed, but both foods failed to increase milk VA concentrations. This trial was registered at clinicaltrials.gov as NCT01420406.

Background: World Health Organization (WHO) guidelines recommend for children with severe acute malnutrition (SAM), high-dose vitamin A (VA) supplements be given on day 1 of admission, and on days 2 and 14 in the case of clinical signs of vitamin A deficiency (VAD). Daily low-dose VA follows, delivered in a premix added to F-75 and F-100. This study aimed to systematically review the evidence for safety and effectiveness of high-dose VA supplementation (VAS) in treatment of children with SAM., Methods: A comprehensive literature review was undertaken for all relevant randomized controlled trials (RCT) and observational studies from 1950 to 2012. Studies identified for full review were evaluated using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology using a set of pre-defined criteria: indirectness; inconsistency; imprecision; and study limitations. A quality rating of high, moderate, or low was then assigned to each study, and only those attaining moderate to high were considered in making recommendations., Results: Of the 2072 abstracts screened, 38 met criteria for full review, and 20 were rated moderate to high quality. Only one study replicated the WHO VA protocol in children with SAM. Indirectness was a critical limitation, as studies were not exclusive to children with SAM. There was inconsistency across trials for definitions of malnutrition, morbidities, and ages studied; and imprecision arising from sub-group analyses and small sample sizes. Evidence showed improved outcomes associated with low-dose compared to high-dose VAS, except in cases presenting with signs of VAD, measles, and severe diarrhea or shigellosis. Adverse outcomes related to respiratory infection, diarrhea, and growth were associated with high-dose VAS in children who were predominantly adequately nourished. No adverse effects of the high dose were found in children with SAM in the trial that replicated the WHO VA guideline., Conclusion: This is the first systematic review of the safety and efficacy of high-dose VAS in treatment of SAM. We recommend a low-dose VAS regimen for children with SAM, except in cases presenting with measles, severe diarrhea (shigellosis), and any indication of VAD. Further research is needed in exclusively malnourished children and to explore alternate delivery strategies.

Objective: To examine the effects of three different school snacks on morbidity outcomes., Design: Twelve schools were randomized to either one of three feeding groups or a Control group. There were three schools per group in this cluster randomized trial. Children in feeding group schools received school snacks of a local plant-based dish, githeri, with meat, milk or extra oil added. The oil used was later found to be fortified with retinol. Physical status, food intake and morbidity outcomes were assessed longitudinally over two years., Setting: Rural Embu District, Kenya, an area with high prevalence of vitamin A deficiency., Subjects: Standard 1 schoolchildren (n 902; analytic sample) enrolled in two cohorts from the same schools one year apart., Results: The Meat and Plain Githeri (i.e. githeri+oil) groups showed the greatest declines in the probability of a morbidity outcome (PMO) for total and severe illnesses, malaria, poor appetite, reduced activity, fever and chills. The Meat group showed significantly greater declines in PMO for gastroenteritis (mainly diarrhoea) and typhoid compared with the Control group, for jaundice compared with the Plain Githeri group, and for skin infection compared with the Milk group. The Milk group showed the greatest decline in PMO for upper respiratory infection. For nearly all morbidity outcomes the Control group had the highest PMO and the least decline over time., Conclusions: The intervention study showed beneficial effects of both animal source foods and of vitamin A-fortified oil on morbidity status.

Vitamin A deficiency is one of the major causes of mortality and morbidity in the developing World. This deficiency can be prevented by alimentary or pharmaceutical supplementation. However, both vitamin A oxidation and isomerization should be prevented, as these phenomenons result in loss of nutritional efficacy. The aim of this study was to investigate the effect of a food protein matrix, β-lactoglobulin (β-Lg) aggregates produced by high pressure (HP), on the stabilization of β-carotene during storage and gastro-duodenal digestion and therefore on its bioavailability. In vitro gastro-duodenal digestion of β-Lg aggregates entrapping β-carotene showed that up to 12% and 33% of total β-carotene was released after peptic and pancreatic digestion, respectively. Overall, our study showed that β-Lg aggregates are efficient for caging and stabilization of β-carotene during storage and digestion. Hence, it may be an interesting approach for the protection and the delivery of vitamin A., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Biofortification of cassava with the provitamin A carotenoid β-carotene is a potential mechanism for alleviating vitamin A deficiency. Cassava is a staple food in the African diet, but data regarding the human bioavailability of β-carotene from this food are scarce. The objective of the present study was to evaluate provitamin A-enhanced cassava as a source of β-carotene and vitamin A for healthy adult women. The study was a randomised, cross-over trial of ten American women. The subjects consumed three different porridges separated by 2 week washout periods. Treatment meals (containing 100 g cassava) included: biofortified cassava (2 mg β-carotene) porridge with added oil (15 ml peanut or rapeseed oil, 20 g total fat); biofortified cassava porridge without added oil (6 g total fat); unfortified white cassava porridge with a 0·3 mg retinyl palmitate reference dose and added oil (20 g total fat). Blood was collected six times from - 0·5 to 9·5 h post-feeding. TAG-rich lipoprotein (TRL) plasma was separated by ultracentrifugation and analysed using HPLC with coulometric array electrochemical detection. The AUC for retinyl palmitate increased after the biofortified cassava meals were fed (P< 0·05). Vitamin A conversion was 4·2 (sd 3·1) and 4·5 (sd 3·1) μg β-carotene:1 μg retinol, with and without added oil, respectively. These results show that biofortified cassava increases β-carotene and retinyl palmitate TRL plasma concentrations in healthy well-nourished adult women, suggesting that it is a viable intervention food for preventing vitamin A deficiency.

Vitamin A (VA) deficiency (VAD) continues to be a major nutritional problem in developing countries, including Central America. In Mexico, milk is a well-accepted vehicle for the administration of micronutrients, including VA, to preschoolers. Thus, we conducted a randomized, controlled, clinical trial to investigate the efficacy of daily consumption of 250 mL of VA-fortified milk (which provided 196 retinol equivalents/d) for 3 mo on VA stores in mildly to moderately VAD (serum retinol concentration 0.35-0.7 μmol/L) preschoolers who were not enrolled in a food assistance program. Twenty-seven mildly to moderately VAD children were randomly assigned based on screening measurements to either the intervention (n = 14) or control group (n = 13) (children in the control group did not receive placebo). All children in the control group and 79% (n = 11) of the children in the intervention group completed the study. The total body VA (TBVA) pool size was estimated using the deuterated retinol dilution technique before and after the intervention. After 3 mo, median changes in the serum retinol concentration for the intervention and control groups were 0.13 and -0.21 μmol/L, respectively (P = 0.009). Median changes in the TBVA stores were 0.06 and 0.01 mmol, respectively (P = 0.006) and estimated median changes in the liver VA concentration were 0.09 and 0.01 μmol/g, respectively (P = 0.002). The VA-fortified milk was well accepted among preschoolers and significantly increased TBVA stores, liver VA stores, and serum retinol concentration, indicating that it may be an effective means to ameliorate VAD in young Mexican children.

Prospective studies have indicated an age-related impairment of the immune response. Carotenoids have been hypothesised to enhance immune cell function. The aim of the present study was to describe the age-related effects and the impact of in vivo dietary carotenoid depletion and repletion on specific and non-specific immunity. A total of ninety-eight healthy male subjects (aged 20-75 years) received a carotenoid-depleted diet for 3 weeks and were then supplemented daily for 5 weeks with 30 mg β-carotene, 15 mg lycopene and 9 mg lutein. Blood samples were collected at study entry, after depletion and supplementation, and biomarkers of immune status were determined. We found that serum IgA levels were positively correlated with ageing. Lymphocyte phenotyping indicated an increase with age in the memory T-helper cell subpopulation (CD4⁺CD45RO⁺) concomitantly with a decrease in naive T-helper cells (CD4⁺CD45RA⁺). A significant increase in the natural killer cells subpopulation and a small decrease in B lymphocytes were also observed, especially for the oldest volunteers. From ex vivo cell function exploration, a positive correlation was observed between age and IL-2 production of phytohaemagglutinin-stimulated lymphocytes. Neutrophils' bactericidal activity was significantly impaired with age (from 50 years) and was modulated by carotenoid status. An age effect was found on neutrophils' spontaneous migration but not on directed migration. Immune response in healthy human subjects is mostly affected by age rather than by dietary carotenoid depletion and repletion. Even in carefully selected healthy volunteers, some age-related immune changes occur predominantly from 50 years onwards. This immunosenescence could generate a loss in the immune system adjustment capacity.