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The Role of Vitamin A in Retinal Diseases.
Sajovic, J, Meglič, A, Glavač, D, Markelj, Š, Hawlina, M, Fakin, A
International journal of molecular sciences. 2022;(3)
Abstract
Vitamin A is an essential fat-soluble vitamin that occurs in various chemical forms. It is essential for several physiological processes. Either hyper- or hypovitaminosis can be harmful. One of the most important vitamin A functions is its involvement in visual phototransduction, where it serves as the crucial part of photopigment, the first molecule in the process of transforming photons of light into electrical signals. In this process, large quantities of vitamin A in the form of 11-cis-retinal are being isomerized to all-trans-retinal and then quickly recycled back to 11-cis-retinal. Complex machinery of transporters and enzymes is involved in this process (i.e., the visual cycle). Any fault in the machinery may not only reduce the efficiency of visual detection but also cause the accumulation of toxic chemicals in the retina. This review provides a comprehensive overview of diseases that are directly or indirectly connected with vitamin A pathways in the retina. It includes the pathophysiological background and clinical presentation of each disease and summarizes the already existing therapeutic and prospective interventions.
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The Transcriptional Role of Vitamin A and the Retinoid Axis in Brown Fat Function.
Herz, CT, Kiefer, FW
Frontiers in endocrinology. 2020;:608
Abstract
In recent years, brown adipose tissue (BAT) has gained significance as a metabolic organ dissipating energy through heat production. Promotion of a thermogenic program in fat holds great promise as potential therapeutic tool to counteract weight gain and related sequelae. Current research efforts are aimed at identifying novel pathways regulating brown fat function and the transformation of white adipocytes into BAT-like cells, a process called "browning." Besides numerous genetic factors some circulating molecules can act as mediators of adipose tissue thermogenesis. Vitamin A metabolites, the retinoids, are potent regulators of gene transcription through nuclear receptor signaling and are thus involved in a plethora of metabolic processes. Accumulating evidence links retinoid action to brown fat function and browning of WAT mainly via orchestrating a transcriptional BAT program in adipocytes including expression of key thermogenic genes such as uncoupling protein 1. Here we summarize the current understanding how retinoids play a role in adipose tissue thermogenesis through transcriptional control of thermogenic gene cassettes and potential non-genomic mechanisms.
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Retinoids in health and disease: A role for hepatic stellate cells in affecting retinoid levels.
Haaker, MW, Vaandrager, AB, Helms, JB
Biochimica et biophysica acta. Molecular and cell biology of lipids. 2020;(6):158674
Abstract
Vitamin A (retinol) is important for normal growth, vision and reproduction. It has a role in the immune response and the development of metabolic syndrome. Most of the retinol present in the body is stored as retinyl esters within lipid droplets in hepatic stellate cells (HSCs). In case of liver damage, HSCs release large amounts of stored retinol, which is partially converted to retinoic acid (RA). This surge of RA can mediate the immune response and enhance the regeneration of the liver. If the damage persists activated HSCs change into myofibroblast-like cells producing extracellular matrix, which increases the chance of tumorigenesis to occur. RA has been shown to decrease proliferation and metastasis of hepatocellular carcinoma. The levels of RA and RA signaling are influenced by the possibility to esterify retinol towards retinyl esters. This suggests a complex regulation between different retinoids, with an important regulatory role for HSCs.
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Predictive role of vitamin A serum concentration in psoriatic patients treated with IL-17 inhibitors to prevent skin and systemic fungal infections.
Campione, E, Cosio, T, Lanna, C, Mazzilli, S, Ventura, A, Dika, E, Gaziano, R, Dattola, A, Candi, E, Bianchi, L
Journal of pharmacological sciences. 2020;(1):52-56
Abstract
The use of biological drugs in psoriasis is replacing traditional therapies due to their specific mechanism and limited side effects. However, the use of Interleukin 17 inhibitors and the modification of its cytokine pathway could favor the risk of fungal infections. All-trans retinoic acid is an active metabolite of vitamin A with anti-inflammatory and immunoregulatory properties through its capacity to stimulate both innate and adaptive immunity and to its effects on proliferation, differentiation and apoptosis in a variety of immune cells. Furthermore, it has been recently discovered that All-trans retinoic acid has a direct fungistatic effect against Candida and Aspergillus Fumigatus. On the basis of these new insights, in the current review, we suggest that the evaluation of serum level of All-trans retinoic acid or vitamin A should be considered as a predictive marker for the development of fungal infections among psoriatic patients treated with Interleukin 17 inhibitors. In clinical practice, vitamin A test could be added in the routine hospital diagnostic management for a better selection of psoriatic patients eligible to Interleukin 17 inhibitors.
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5.
The Potential of Integrating Provitamin A-Biofortified Maize in Smallholder Farming Systems to Reduce Malnourishment in South Africa.
Zuma, MK, Kolanisi, U, Modi, AT
International journal of environmental research and public health. 2018;(4)
Abstract
Biofortification interventions have the potential to combat malnutrition. This review explored the use of provitamin A-biofortified maize (PVABM) as a vitamin A deficiency (VAD) reduction agricultural-based strategy. Maize has been identified as one of the key staple crops for biofortification to reduce hidden hunger in Africa. Most nutrition interventions have not been successful in reducing hunger because rural communities, who mainly rely on agriculture, have been indirectly excluded. The biofortification intervention proposed here aims to be an inclusive strategy, based on smallholder farming systems. Vitamin A is a micronutrient essential for growth, immune function, reproduction and vision, and its deficiency results in VAD. VAD is estimated to affect more than 250 million children in developing countries. In Africa, especially sub-Saharan Africa, maize is a staple food for rural communities, consumed by most household members. Due to carotenoids, PVABM presents an orange color. This color has been reported to lead to negative perceptions about PVABM varieties. The perceived agronomic traits of this maize by smallholder farmers have not been explored. Adoption and utilization of PVABM varieties relies on both acceptable consumer attributes and agronomic traits, including nutritional value. It is therefore important to assess farmers' perceptions of and willingness to adopt the varieties, and the potential markets for PVABM maize. It is essential to establish on-farm trials and experiments to evaluate the response of PVABM under different climatic conditions, fertilizer levels and soils, and its overall agronomic potential. For the better integration of PVABM with smallholder farming systems, farmer training and workshops about PVABM should be part of any intervention. A holistic approach would enhance farmers' knowledge about PVABM varieties and that their benefits out-compete other existing maize varieties.
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Vitamin A supplements for reducing mother-to-child HIV transmission.
Wiysonge, CS, Ndze, VN, Kongnyuy, EJ, Shey, MS
The Cochrane database of systematic reviews. 2017;(9):CD003648
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Abstract
BACKGROUND Strategies to reduce the risk of mother-to-child transmission of the human immunodeficiency virus (HIV) include lifelong antiretroviral therapy (ART) for HIV-positive women, exclusive breastfeeding from birth for six weeks plus nevirapine or replacement feeding plus nevirapine from birth for four to six weeks, elective Caesarean section delivery, and avoiding giving children chewed food. In some settings, these interventions may not be practical, feasible, or affordable. Simple, inexpensive, and effective interventions (that could potentially be implemented even in the absence of prenatal HIV testing programmes) would be valuable. Vitamin A, which plays a role in immune function, is one low-cost intervention that has been suggested in such settings. OBJECTIVES To summarize the effects of giving vitamin A supplements to HIV-positive women during pregnancy and after delivery. SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase, and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) up to 25 August 2017, and checked the reference lists of relevant articles for eligible studies. SELECTION CRITERIA We included randomized controlled trials conducted in any setting that compared vitamin A supplements to placebo or no intervention among HIV-positive women during pregnancy or after delivery, or both. DATA COLLECTION AND ANALYSIS At least two review authors independently assessed study eligibility and extracted data. We expressed study results as risk ratios (RR) or mean differences (MD) as appropriate, with their 95% confidence intervals (CI), and conducted random-effects meta-analyses. This is an update of a review last published in 2011. MAIN RESULTS Five trials met the inclusion criteria. These were conducted in Malawi, South Africa, Tanzania, and Zimbabwe between 1995 and 2005 and none of the participants received ART. Women allocated to intervention arms received vitamin A supplements at a variety of doses (daily during pregnancy; a single dose immediately after delivery, or daily doses during pregnancy plus a single dose after delivery). Women allocated to comparison arms received identical placebo (6601 women, 4 trials) or no intervention (697 women, 1 trial). Four trials (with 6995 women) had low risk of bias and one trial (with 303 women) had high risk of attrition bias.The trials show that giving vitamin A supplements to HIV-positive women during pregnancy, the immediate postpartum period, or both, probably has little or no effect on mother-to-child transmission of HIV (RR 1.07, 95% CI 0.91 to 1.26; 4428 women, 5 trials, moderate certainty evidence) and may have little or no effect on child death by two years of age (RR 1.06, 95% CI 0.92 to 1.22; 3883 women, 3 trials, low certainty evidence). However, giving vitamin A supplements during pregnancy may increase the mean birthweight (MD 34.12 g, 95% CI -12.79 to 81.02; 2181 women, 3 trials, low certainty evidence) and probably reduces the incidence of low birthweight (RR 0.78, 95% CI 0.63 to 0.97; 1819 women, 3 trials, moderate certainty evidence); but we do not know whether vitamin A supplements affect the risk of preterm delivery (1577 women, 2 trials), stillbirth (2335 women, 3 trials), or maternal death (1267 women, 2 trials). AUTHORS' CONCLUSIONS Antepartum or postpartum vitamin A supplementation, or both, probably has little or no effect on mother-to-child transmission of HIV in women living with HIV infection and not on antiretroviral drugs. The intervention has largely been superseded by ART which is widely available and effective in preventing vertical transmission.
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Provitamin A biofortification of crop plants: a gold rush with many miners.
Giuliano, G
Current opinion in biotechnology. 2017;:169-180
Abstract
Carotenoids are synthesized de novo by plants, where they play fundamental physiological roles as photosynthetic pigments and precursors for signaling molecules. They are also essential components of a healthy diet, as dietary antioxidants and vitamin A precursors. Vitamin A deficiency is a public health problem in developing countries, which has prompted a series of efforts toward the biofortification of plant-derived foods with provitamin A carotenoids (mainly β-carotene), giving rise to 'golden' crops. Since the 'golden rice' exploit, a number of biofortified crops have been generated, using transgenic approaches as well as conventional breeding. Bioavailability studies have demonstrated the efficacy of several 'golden' crops in maintaining vitamin A status. This review presents the state of the art and the areas that need further experimentation.
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Vitamin A Supplementation Programs and Country-Level Evidence of Vitamin A Deficiency.
Wirth, JP, Petry, N, Tanumihardjo, SA, Rogers, LM, McLean, E, Greig, A, Garrett, GS, Klemm, RD, Rohner, F
Nutrients. 2017;(3)
Abstract
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.
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Experience of integrating vitamin A supplementation into polio campaigns in the African Region.
Chehab, ET, Anya, BM, Onyango, AW, Tevi-Benissan, MC, Okeibunor, J, Mkanda, P, Mihigo, R
Vaccine. 2016;(43):5199-5202
Abstract
INTRODUCTION Vitamin A deficiency is a public health problem that affects children across the WHO African Region. Countries have integrated vitamin A supplementation in different child health interventions, most notably with polio campaigns. The integration of vitamin A in polio campaigns was documented as a best practice in Angola, Chad, Cote d'Ivoire, Tanzania, and Togo. There are potential risks to vitamin A supplementation associated with the polio endgame and certification in the African Region. METHODS We reviewed the findings from the documentation of best practices assessment that was conducted by the WHO Regional Office for Africa in 2014 and 2015 in the five countries that noted integration of vitamin A with polio as a best practice. In addition, we reviewed the coverage rates for oral poliovirus vaccine and vitamin A supplementation in Angola, Chad, Cote d'Ivoire, Tanzania, and Togo in 2014 and 2015. RESULTS Vitamin A deficiency in 2004 ranged from 35% in Togo to as high as 55% in Angola. All five countries integrated vitamin A supplementation in at least one campaign in 2013-2014 and all achieved over 80% coverage for vitamin A supplementation when it was integrated with polio. DISCUSSION Given the progress of the polio program, and decreasing campaigns, there is a risk that fewer children will be reached each year with vitamin A supplementation. We recommend that for countries strengthen the integration of vitamin A supplementation with routine immunization services.
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10.
Optical Coherence Tomography Assessment Before and After Vitamin Supplementation in a Patient With Vitamin A Deficiency: A Case Report and Literature Review.
Saenz-de-Viteri, M, Sádaba, LM
Medicine. 2016;(6):e2680
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Abstract
Vitamin A is an essential fat-soluble vitamin important for the function of various body systems. In the eye, vitamin A is essential for the synthesis of visual pigments in photoreceptors. Vitamin A deficiency is a rare condition in the developed countries and might follow bariatric or intestinal bypass surgery.We present the case of a 67-year-old male that complained of visual loss and nyctalopia. Patient had bariatric surgery 15 years before for weight loss. Low serum levels of vitamin A confirmed the diagnosis and patient started vitamin A supplementation. Visual fields, macular thickness, and ganglion cell layer thickness were recorded and monitored 1 month, 6 months, and 1 year after the beginning of therapy. Visual fields were significantly altered and central macular thickness and ganglion cell layer thickness were reduced, but the first 2 showed a significant recovery with vitamin supplementation therapy. By the 1st month of treatment patient referred a complete remission of visual symptoms. Further, we observed hyperreflective material accumulating beneath a partially disrupted ellipsoid band in the high definition optical coherence tomography that also improved progressively with vitamin repletion.Newer and more sophisticated imaging systems have increased our knowledge of the mechanisms responsible for retinal diseases. To our knowledge, this is the first description of the effect of vitamin A deficiency and vitamin supplementation on macular thickness. This case also highlights the importance of considering bariatric bypass surgery as a cause of vitamin A deficiency in developed countries.