Functional Cupcake for Preventing Vitamin A Deficiency and Correlated Anemia and Oxidative Stress.

<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.

Small-Quantity Lipid-Based Nutrient Supplements Do Not Affect Plasma or Milk Retinol Concentrations Among Malawian Mothers, or Plasma Retinol Concentrations among Young Malawian or Ghanaian Children in Two Randomized Trials.

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.

Development of sub-tropically adapted diverse provitamin-A rich maize inbreds through marker-assisted pedigree selection, their characterization and utilization in hybrid breeding.

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 ß-carotene (BC: 8.72µg/g), ß-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.

Adequate vitamin A rich food consumption and associated factors among lactating mothers visiting child immunization and post-natal clinic at health institutions in Gondar Town, Northwest Ethiopia.

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.

Vitamin A and iron status of children before and after treatment of uncomplicated severe acute malnutrition.

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.

Pro-vitamin A carotenoid content of 48 plantain (Musa AAB genome) cultivars sourced from eastern Democratic Republic of Congo.

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.

Strategies to achieve adequate vitamin A intake for young children: options for Cameroon.

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.

Vitamin A intakes remain higher among intervention participants 3 years after a biofortification intervention in Mozambique.

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 deficiency impairs contextual fear memory in rats: Abnormalities in the glucocorticoid pathway.

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 11ß-hydroxysteroid dehydrogenase type 1 (11ß-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 11ß-HSD1 expression following a novelty-induced stress. We also examined whether vitamin A supplementation or a single injection of UE2316, a selective 11ß-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 11ß-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 11ß-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 11ß-HSD1.

A Randomized Crossover Study to Evaluate Recipe Acceptability in Breastfeeding Mothers and Young Children in India Targeted for a Multiple Biofortified Food Crop Intervention.

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.

An Overview of Carotenoids, Apocarotenoids, and Vitamin A in Agro-Food, Nutrition, Health, and Disease.

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).

Systematic review and meta-analysis approach on vitamin A fortified foods and its effect on retinol concentration in under 10 year children.

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 (I2 = 97%, τ2(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.

Improving Blood Retinol Concentrations with Complementary Foods Fortified with Moringa oleifera Leaf Powder - A Pilot Study.

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.

Enhanced CD103 Expression and Reduced Frequencies of Virus-Specific CD8+ T Cells Among Airway Lymphocytes After Influenza Vaccination of Mice Deficient in Vitamins A + D.

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 PA224-233/Db epitope were compared with T cells specific for the NP366-374/Db 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.

Estimating Lives Saved by Achieving Dietary Micronutrient Adequacy, with a Focus on Vitamin A Intervention Programs in Cameroon.

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.

The change in retinoic acid receptor signaling induced by prenatal marginal vitamin A deficiency and its effects on learning and memory.

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 Ca2+ influx and eventually caused learning and memory deficits.

Mortality Benefits of Vitamin A Are Not Affected by Varying Frequency, Total Dose, or Duration of Supplementation.

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.