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Concept: Vitamin A

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Vitamin A or retinol is arguably the most multifunctional vitamin in the human body as it is essential from embryogenesis to adulthood. The pleiotropic effects of vitamin A are exerted mainly by one active metabolite, all-trans retinoic acid (atRA), which regulates the expression of a battery of target genes through several families of nuclear receptors (RARs, RXRs and PPARβ/δ), polymorphic retinoic acid (RA) response elements and multiple coregulators. It also involves extra nuclear and non-transcriptional effects such as the activation of kinase cascades, which are integrated in the nucleus via the phosphorylation of several actors of RA signaling. However, vitamin A itself proved recently to be active and RARs to be present in the cytosol to regulate translation and cell plasticity. All these new concepts expand the scope of the biologic functions of vitamin A and RA.

Concepts: Cell nucleus, Cell, Signal transduction, Retinol, Vitamin A, Retinoic acid, Tretinoin, Retinoid

148

Vitamin A supplementation (VAS) programs targeted at children aged 6-59 months are implemented in many countries. By improving immune function, vitamin A (VA) reduces mortality associated with measles, diarrhea, and other illnesses. There is currently a debate regarding the relevance of VAS, but amidst the debate, researchers acknowledge that the majority of nationally-representative data on VA status is outdated. To address this data gap and contribute to the debate, we examined data from 82 countries implementing VAS programs, identified other VA programs, and assessed the recentness of national VA deficiency (VAD) data. We found that two-thirds of the countries explored either have no VAD data or data that were >10 years old (i.e., measured before 2006), which included twenty countries with VAS coverage ≥70%. Fifty-one VAS programs were implemented in parallel with at least one other VA intervention, and of these, 27 countries either had no VAD data or data collected in 2005 or earlier. To fill these gaps in VAD data, countries implementing VAS and other VA interventions should measure VA status in children at least every 10 years. At the same time, the coverage of VA interventions can also be measured. We identified three countries that have scaled down VAS, but given the lack of VA deficiency data, this would be a premature undertaking in most countries without appropriate status assessment. While the global debate about VAS is important, more attention should be directed towards individual countries where programmatic decisions are made.

Concepts: Immune system, Measurement, Vitamin, Vitamin C, Implementation, Intervention, Vitamin A, Internet Explorer

34

The unified global efforts to mitigate the high burden of vitamin and mineral deficiency, known as hidden hunger, in populations around the world are crucial to the achievement of most of the Millennium Development Goals (MDGs). We developed indices and maps of global hidden hunger to help prioritize program assistance, and to serve as an evidence-based global advocacy tool. Two types of hidden hunger indices and maps were created based on i) national prevalence data on stunting, anemia due to iron deficiency, and low serum retinol levels among preschool-aged children in 149 countries; and ii) estimates of Disability Adjusted Life Years (DALYs) attributed to micronutrient deficiencies in 136 countries. A number of countries in sub-Saharan Africa, as well as India and Afghanistan, had an alarmingly high level of hidden hunger, with stunting, iron deficiency anemia, and vitamin A deficiency all being highly prevalent. The total DALY rates per 100,000 population, attributed to micronutrient deficiencies, were generally the highest in sub-Saharan African countries. In 36 countries, home to 90% of the world’s stunted children, deficiencies of micronutrients were responsible for 1.5-12% of the total DALYs. The pattern and magnitude of iodine deficiency did not conform to that of other micronutrients. The greatest proportions of children with iodine deficiency were in the Eastern Mediterranean (46.6%), European (44.2%), and African (40.4%) regions. The current indices and maps provide crucial data to optimize the prioritization of program assistance addressing global multiple micronutrient deficiencies. Moreover, the indices and maps serve as a useful advocacy tool in the call for increased commitments to scale up effective nutrition interventions.

Concepts: Malaria, Africa, Sub-Saharan Africa, North Africa, Iron deficiency anemia, Malnutrition, Vitamin A, Millennium Development Goals

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The objectives of the present study were to investigate the effects of acute exposure to PBDEs on retinoid signaling in fish. Zebrafish embryos (2h post-fertilization, hpf) were exposed to DE-71 (0, 31.0, 68.7, and 227.6μg/L) until 120hpf. Retinoid profiles showed the content of retinal and retinoic acid was reduced significantly. While a significant up-regulation was observed in the transcription of retinal dehydrogenase (raldh2), the transcription of retinol binding protein (rbp1a), retinol dehydrogenase (rdh1), cellular retinoic acid binding protein (crabp1a and crabp2a) and retinoic acid receptor subunit (raraa) were down-regulated significantly, indicating disruption of retinoid signaling. However, the transcriptions of five opsin genes (zfrho, zfuv, zfred, zfblue, and zfgr1) were up-regulated. Furthermore, whole mount immunostaining and western blotting demonstrated increased rhodopsin protein expression in the exposure groups. Overall, the results indicated that acute exposure to PBDEs could disturb retinoid signaling and may impact on eye development of zebrafish larvae.

Concepts: Protein, Gene, Molecular biology, Retinol, Vitamin A, Retinal, Retinoic acid receptor, Retinoic acid

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OBJECTIVE: Calcific aortic valve disease (CAVD) is a major public health problem with no effective treatment available other than surgery. We previously showed that mature heart valves calcify in response to retinoic acid (RA) treatment through downregulation of the SRY transcription factor Sox9. In this study, we investigated the effects of excess vitamin A and its metabolite RA on heart valve structure and function in vivo and examined the molecular mechanisms of RA signaling during the calcification process in vitro. METHODS AND RESULTS: Using a combination of approaches, we defined calcific aortic valve disease pathogenesis in mice fed 200 IU/g and 20 IU/g of retinyl palmitate for 12 months at molecular, cellular, and functional levels. We show that mice fed excess vitamin A develop aortic valve stenosis and leaflet calcification associated with increased expression of osteogenic genes and decreased expression of cartilaginous markers. Using a pharmacological approach, we show that RA-mediated Sox9 repression and calcification is regulated by classical RA signaling and requires both RA and retinoid X receptors. CONCLUSIONS: Our studies demonstrate that excess vitamin A dietary intake promotes heart valve calcification in vivo. Therefore suggesting that hypervitaminosis A could serve as a new risk factor of calcific aortic valve disease in the human population.

Concepts: Gene, In vitro, Aortic valve, Retinol, Vitamin A, Valvular heart disease, Valves, Aortic valve stenosis

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Alitretinoin (9-cis-retinoic acid) is a synthetic vitamin A derivative with immunomodulatory and anti-inflammatory activity recently licensed as a treatment for refractory chronic hand eczema(1) . Here, we report the successful use of oral alitretinoin in two women of childbearing age with Darier’s disease (DD). DD (OMIM 124200) is an autosomal dominant disorder of keratinisation characterised by multiple discrete or confluent warty papules and plaques in seborrhoeic areas, palmoplantar pits and distinctive nail dystrophy(2) of teenage or adult onset.

Concepts: Pregnancy, Childbirth, Energy, Folic acid, Multiple birth, Retinol, Vitamin A

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The genus Capsicum (pepper) comprises a large number of wild and cultivated species. The plants are grown all over the world, primarily in tropical and subtropical countries. The fruits are an excellent source of health-related compounds, such as ascorbic acid (vitamin C), carotenoids (provitamin A), tocopherols (vitamin E), flavonoids, and capsaicinoids. Pepper fruits have been used for fresh and cooked consumption, as well as for medicinal purposes, such as treatment of asthma, coughs, sore throats, and toothache. Depending on its uses, there are several main characters important for product quality; pungency, bright attractive colors, highly concentrated extracts, and a small number of seeds are the main characters on which quality is based and priced. Herein, a general overview of biochemical composition, medical properties of these compounds, and characteristics of quality attributes of pepper fruits is presented.

Concepts: Nutrition, Antioxidant, Plant, Vitamin, Vitamin C, Vitamin A, Ascorbic acid, Capsicum

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There is increasing evidence that vitamin A deficiency in utero correlates with abnormal airway smooth muscle (SM) function in postnatal life. The bioactive vitamin A metabolite retinoic acid (RA) is essential for formation of the lung primordium; however, little is known about the impact of early fetal RA deficiency on postnatal lung structure and function. Here, we provide evidence that during murine lung development, endogenous RA has a key role in restricting the airway SM differentiation program during airway formation. Using murine models of pharmacological, genetic, and dietary vitamin A/RA deficiency, we found that disruption of RA signaling during embryonic development consistently resulted in an altered airway SM phenotype with markedly increased expression of SM markers. The aberrant phenotype persisted postnatally regardless of the adult vitamin A status and manifested as structural changes in the bronchial SM and hyperresponsiveness of the airway without evidence of inflammation. Our data reveal a role for endogenous RA signaling in restricting SM differentiation and preventing precocious and excessive SM differentiation when airways are forming.

Concepts: Asthma, Function, Embryo, Uterus, Developmental biology, Cellular differentiation, Vitamin A, Retinoic acid

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Micronutrient deficiencies are common in locales where people must rely upon sorghum as their staple diet. Sorghum grain is seriously deficient in provitamin A (β-carotene) and in the bioavailability of iron and zinc. Biofortification is a process to improve crops for one or more micronutrient deficiencies. We have developed sorghum with increased β-carotene accumulation that will alleviate vitamin A deficiency among people who rely on sorghum as their dietary staple. However, subsequent β-carotene instability during storage negatively affects the full utilization of this essential micronutrient. We determined that oxidation is the main factor causing β-carotene degradation under ambient conditions. We further demonstrated that coexpression of homogentisate geranylgeranyl transferase (HGGT), stacked with carotenoid biosynthesis genes, can mitigate β-carotene oxidative degradation, resulting in increased β-carotene accumulation and stability. A kinetic study of β-carotene degradation showed that the half-life of β-carotene is extended from less than 4 wk to 10 wk on average with HGGT coexpression.

Concepts: Photosynthesis, Nutrition, Redox, Vitamin, Zinc, Cereal, Vitamin A, Rice

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A 10-year-old boy with no notable medical history presented with ocular burning. A lesion consisting of a dry, scaly patch with a foamy appearance was observed on the temporal conjunctiva of the left eye.

Concepts: Vitamin A