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Advances in Nutrition (Bethesda, Md.) Jun 2021A systematic review was conducted to summarize the absorption, transport, storage, and metabolism of oral neonatal vitamin A supplementation (NVAS). This review focused...
A systematic review was conducted to summarize the absorption, transport, storage, and metabolism of oral neonatal vitamin A supplementation (NVAS). This review focused specifically on the neonatal period (first 28 d of life for humans) to inform guidance by WHO on recommendations related to NVAS. A systematic search of international and regional databases was conducted. Inclusion criteria were human or animal studies that gave oral vitamin A as a single or limited number of doses to apparently healthy neonates. Studies evaluating fortification or food-based approaches, dosing with retinoic acid, or studies of neonatal models of disease were excluded. The search retrieved 8847 unique records. After screening by title and abstract, 88 were screened using the full text, and 35 records met inclusion criteria: 13 human and 22 animal studies. Studies indicate that high-dose NVAS is absorbed well by neonates, typically mirroring fat absorption. Doses were primarily stored in the liver and transiently increased in the lung, kidney, spleen, adrenal glands, brain, skin, and adipose tissue, generally with a dose-response. Serum retinol and retinyl esters also transiently increased following NVAS. Although minimal acute adverse effects are noted, there is a lack of data supporting NVAS for improving organ maturation or sustained delivery to target organs. Research gaps include the physiological effects of the short-term increase of vitamin A concentrations in extrahepatic tissues, or whether there are unknown adverse effects over time.
Topics: Animals; Dietary Supplements; Humans; Infant, Newborn; Liver; Retinyl Esters; Vitamin A; Vitamin A Deficiency
PubMed: 33216111
DOI: 10.1093/advances/nmaa137 -
BMJ Global Health Jul 2020WHO recommends vitamin A supplementation (VAS) programmes for children 6-59 months where vitamin A deficiency is a public health problem. However, resources for VAS are... (Review)
Review
WHO recommends vitamin A supplementation (VAS) programmes for children 6-59 months where vitamin A deficiency is a public health problem. However, resources for VAS are falling short of current needs and programme coverage is suffering. The authors present the case for considering the options for shifting efforts and resources from a generalised approach, to prioritising resources to reach populations with continued high child mortality rates and high vitamin A deficiency prevalence to maximise child survival benefits . This includes evaluating where child mortality and/or vitamin A deficiency has dropped, as well as using under 5 mortality rates as a proxy for vitamin A deficiency, in the absence of recent data. The analysis supports that fewer countries may now need to prioritise VAS than in the year 2000, but that there are still a large number of countries that do. The authors also outline next steps for analysing options for improved targeting and cost-effectiveness of programmes. Focusing VAS resources to reach the most vulnerable is an efficient use of resources and will continue to promote young child survival.
Topics: Child; Cost-Benefit Analysis; Dietary Supplements; Humans; Prevalence; Vitamin A; Vitamin A Deficiency; Vulnerable Populations
PubMed: 32718947
DOI: 10.1136/bmjgh-2019-001997 -
The Journal of Biological Chemistry Sep 2021Impaired dark adaptation (DA), a defect in the ability to adjust to dimly lit settings, is a universal hallmark of aging. However, the mechanisms responsible for...
Impaired dark adaptation (DA), a defect in the ability to adjust to dimly lit settings, is a universal hallmark of aging. However, the mechanisms responsible for impaired DA are poorly understood. Vitamin A byproducts, such as vitamin A dimers, are small molecules that form in the retina during the vitamin A cycle. We show that later in life, in the human eye, these byproducts reach levels commensurate with those of vitamin A. In mice, selectively inhibiting the formation of these byproducts, with the investigational drug C20D-vitamin A, results in faster DA. In contrast, acutely increasing these ocular byproducts through exogenous delivery leads to slower DA, with otherwise preserved retinal function and morphology. Our findings reveal that vitamin A cycle byproducts alone are sufficient to cause delays in DA and suggest that they may contribute to universal age-related DA impairment. Our data further indicate that the age-related decline in DA may be tractable to pharmacological intervention by C20D-vitamin A.
Topics: Aging; Animals; Dark Adaptation; Eye; Humans; Macular Degeneration; Male; Mice; Mice, Inbred ICR; Retina; Retinal Degeneration; Retinal Pigment Epithelium; Visual Acuity; Vitamin A
PubMed: 34391781
DOI: 10.1016/j.jbc.2021.101074 -
Poultry Science Dec 2021This study evaluated the level and length of time of vitamin A supplementation and its effects on carcass and cuts yield, meat quality, and myopathies in 42-day-old...
This study evaluated the level and length of time of vitamin A supplementation and its effects on carcass and cuts yield, meat quality, and myopathies in 42-day-old broilers. A total of 1,920 birds were divided into 6 groups, and each group received a different level of vitamin A: 0; 6,000; 16,000; 26,000; 36,000 and 46,000 IU/ kg. From d 1 to 21, the treatments were distributed among 16 replicates with 20 birds. From the 22nd d on, 8 repetitions remained with the initial treatment and the others received diets with no vitamin A supplementation. Twelve birds were slaughtered per treatment to evaluate carcass and cuts yield, shear force, cooking loss, water holding capacity, and the presence of substances reactive to thiobarbituric acid. The remaining birds were slaughtered and evaluated in loco for Wooden Breast (WB) and White Striping (WS). Wings weight was affected by vitamin A levels. The duration of the vitamin A supplementation process had effects on the weight of breast, legs with a dorsal portion, and meat color in the yellow intensity (b*). Incidence of WB had higher scores in birds supplemented until 42 d of age. WS showed a quadratic response and a lower response with supplementation of 29,700 IU/ kg. Even for WS, a higher occurrence of the normal score was found in birds supplemented until 21 d of age. Minimal quadratic responses were obtained for normal, moderate, and severe scores, in supplementations of 29,301; 29,959, and 29,827 IU/ kg, respectively. WB had lower occurrence rates in birds supplemented until 21 d of age. Consequently, the severe score was more frequent when supplementation was provided until 42 d of age. The level of vitamin A and the length of time during which this supplementation was provided had influence on cuts yield, meat color and the incidence of WB and WS of the 42-day-old birds.
Topics: Animal Feed; Animals; Chickens; Diet; Meat; Pectoralis Muscles; Vitamin A
PubMed: 34768044
DOI: 10.1016/j.psj.2021.101490 -
Translational Psychiatry Feb 2023The small, hormone-like molecule retinoic acid (RA) is a vital regulator in several neurobiological processes that are affected in depression. Next to its involvement in...
The small, hormone-like molecule retinoic acid (RA) is a vital regulator in several neurobiological processes that are affected in depression. Next to its involvement in dopaminergic signal transduction, neuroinflammation, and neuroendocrine regulation, recent studies highlight the role of RA in homeostatic synaptic plasticity and its link to neuropsychiatric disorders. Furthermore, experimental studies and epidemiological evidence point to the dysregulation of retinoid homeostasis in depression. Based on this evidence, the present study investigated the putative link between retinoid homeostasis and depression in a cohort of 109 patients with major depressive disorder (MDD) and healthy controls. Retinoid homeostasis was defined by several parameters. Serum concentrations of the biologically most active Vitamin A metabolite, all-trans RA (at-RA), and its precursor retinol (ROL) were quantified and the individual in vitro at-RA synthesis and degradation activity was assessed in microsomes of peripheral blood-derived mononuclear cells (PBMC). Additionally, the mRNA expression of enzymes relevant to retinoid signaling, transport, and metabolism were assessed. Patients with MDD had significantly higher ROL serum levels and greater at-RA synthesis activity than healthy controls providing evidence of altered retinoid homeostasis in MDD. Furthermore, MDD-associated alterations in retinoid homeostasis differed between men and women. This study is the first to investigate peripheral retinoid homeostasis in a well-matched cohort of MDD patients and healthy controls, complementing a wealth of preclinical and epidemiological findings that point to a central role of the retinoid system in depression.
Topics: Male; Humans; Female; Retinoids; Depressive Disorder, Major; Leukocytes, Mononuclear; Tretinoin; Vitamin A; Homeostasis
PubMed: 36813763
DOI: 10.1038/s41398-023-02362-0 -
Nutrients Apr 2022The vitamin A metabolite all-trans retinoic acid (RA) plays a key role in tissue homeostasis and mucosal immunity. RA is produced by gut-associated dendritic cells,... (Review)
Review
The vitamin A metabolite all-trans retinoic acid (RA) plays a key role in tissue homeostasis and mucosal immunity. RA is produced by gut-associated dendritic cells, which are among the first cells encountered by HIV. Acute HIV infection results in rapid reduction of RA levels and dysregulation of immune cell populations whose identities and function are largely controlled by RA. Here, we discuss the potential link between the roles played by RA in shaping intestinal immune responses and the manifestations and pathogenesis of HIV-associated enteropathy and similar conditions observed in SIV-infected non-human primate models. We also present data demonstrating the ability of RA to enhance the activation of replication-competent viral reservoirs from subjects on suppressive anti-retroviral therapy. The data suggest that retinoid supplementation may be a useful adjuvant for countering the pathologic condition of the gastro-intestinal tract associated with HIV infection and as part of a strategy for reactivating viral reservoirs as a means of depleting latent viral infection.
Topics: Animals; HIV Infections; Humans; Immunity, Mucosal; Tretinoin; Virus Replication; Vitamin A
PubMed: 35458172
DOI: 10.3390/nu14081611 -
Biochimica Et Biophysica Acta.... Nov 2020The nutritional requirements of the developing embryo are complex. In the case of dietary vitamin A (retinol, retinyl esters and provitamin A carotenoids), maternal... (Review)
Review
The nutritional requirements of the developing embryo are complex. In the case of dietary vitamin A (retinol, retinyl esters and provitamin A carotenoids), maternal derived nutrients serve as precursors to signaling molecules such as retinoic acid, which is required for embryonic patterning and organogenesis. Despite variations in the composition and levels of maternal vitamin A, embryonic tissues need to generate a precise amount of retinoic acid to avoid congenital malformations. Here, we summarize recent findings regarding the role and metabolism of vitamin A during heart development and we survey the association of genes known to affect retinoid metabolism or signaling with various inherited disorders. A better understanding of the roles of vitamin A in the heart and of the factors that affect retinoid metabolism and signaling can help design strategies to meet nutritional needs and to prevent birth defects and disorders associated with altered retinoid metabolism. This article is part of a Special Issue entitled Carotenoids recent advances in cell and molecular biology edited by Johannes von Lintig and Loredana Quadro.
Topics: Carotenoids; Embryonic Development; Heart; Humans; Nutritional Requirements; Organogenesis; Retinoids; Retinyl Esters; Signal Transduction; Tretinoin; Vitamin A
PubMed: 31978553
DOI: 10.1016/j.bbalip.2020.158636 -
Methods in Enzymology 2020Vitamin A signaling pathways are predominantly driven by the cellular concentrations of all-trans-retinoic acid (atRA), as the main mechanism of retinoid signaling is...
Vitamin A signaling pathways are predominantly driven by the cellular concentrations of all-trans-retinoic acid (atRA), as the main mechanism of retinoid signaling is via activation of retinoic acid receptors. atRA concentrations are in turn controlled by the storage of vitamin A and enzymatic processes that synthesize and clear atRA. This has resulted in the need for robust and highly specific analytical methods to accurately quantify retinoids in diverse biological matrices. Tissue-specific differences in both the quantity of retinoids and background matrix interferences can confound the quantification of retinoids, and the bioanalysis requires high performance instrumentation, such as liquid chromatography mass-spectrometry (LC-MS). Successful bioanalysis of retinoids is further complicated by the innate structural instability of retinoids and their relatively high lipophilicity. Further, in vitro experiments with retinoids require attention to experimental design and interpretation to account for the instability of retinoids due to isomerization and degradation, sequential metabolism to numerous structurally similar metabolites, and substrate depletion during experiments. In addition, in vitro biological activity is often confounded by residual presence of retinoids in common biological reagents such as cell culture media. This chapter identifies common biological and analytical complexities in retinoid bioanalysis in diverse biological matrices, and in the use of retinoids in cell culture and metabolic incubations. In addition, this chapter highlights best practices for the successful detection and quantification of the vitamin A metabolome in a wide range of biological matrices.
Topics: Receptors, Retinoic Acid; Retinoids; Signal Transduction; Tretinoin; Vitamin A
PubMed: 32359651
DOI: 10.1016/bs.mie.2020.02.010 -
Progress in Retinal and Eye Research Mar 2023The eye is an ideal organ for imaging by a multi-photon excitation approach, because ocular tissues such as the sclera, cornea, lens and neurosensory retina, are highly... (Review)
Review
The eye is an ideal organ for imaging by a multi-photon excitation approach, because ocular tissues such as the sclera, cornea, lens and neurosensory retina, are highly transparent to infrared (IR) light. The interface between the retina and the retinal pigment epithelium (RPE) is especially informative, because it reflects the health of the visual (retinoid) cycle and its changes in response to external stress, genetic manipulations, and drug treatments. Vitamin A-derived retinoids, like retinyl esters, are natural fluorophores that respond to multi-photon excitation with near IR light, bypassing the filter-like properties of the cornea, lens, and macular pigments. Also, during natural aging some retinoids form bisretinoids, like diretinoid-pyridiniumethanolamine (A2E), that are highly fluorescent. These bisretinoids appear to be elevated concurrently with aging. Vitamin A-derived retinoids and bisretinoidss are detected by two-photon ophthalmoscopy (2PO), using a new class of light sources with adjustable spatial, temporal, and spectral properties. Furthermore, the two-photon (2P) absorption of IR light by the visual pigments in rod and cone photoreceptors can initiate visual transduction by cis-trans isomerization of retinal, enabling parallel functional studies. Recently we overcame concerns about safety, data interpretation and complexity of the 2P-based instrumentation, the major roadblocks toward advancing this modality to the clinic. These imaging and retina-function assessment advancements have enabled us to conduct the first 2P studies with humans.
Topics: Humans; Mice; Animals; Vision, Ocular; Vitamin A; Retina; Retinoids; Retinal Pigment Epithelium
PubMed: 36787681
DOI: 10.1016/j.preteyeres.2023.101170 -
Journal of Nutritional Science 2021Countries are increasingly transitioning from event-based vitamin A supplementation (VAS) distribution to delivery through routine health system contacts, shifting also... (Review)
Review
Countries are increasingly transitioning from event-based vitamin A supplementation (VAS) distribution to delivery through routine health system contacts, shifting also to administrative, electronic-based monitoring tools, a process that brings certain limitations affecting the quality of administrative VAS coverage. At present, there is no standardised methodology for measuring the coverage of VAS delivered through routine health services. To address this gap, we conducted a systematic review of the literature to identify and recommend methods to measure VAS coverage, with the aim of providing guidance to countries on the collection of consistent data for planning, monitoring and evaluating VAS programmes integrated into routine health systems. We searched the PubMed®, Embase®, Scopus, Google Scholar and World Health Organization (WHO) Global Index Medicus databases for studies published from 1 January 2000 to 1 January 2021, reporting original data on VAS coverage and methodologies used for measurement. We screened 2371 original titles and abstracts, assessed twenty-seven full-text articles and ultimately included eighteen studies. All but two studies used a coverage cluster survey (CCS) design to measure VAS coverage, adapting the WHO Vaccination Coverage Cluster Surveys methodology, by modifying sample size and sampling parameters. Annual two-dose VAS coverage was reported from only four studies. Until electronic-based systems to collect and analyse VAS data are equipped to measure routine two-dose VAS coverage using administrative data, CCSs that comply with the 2018 WHO Vaccination Coverage Cluster Surveys Reference Manual represent the gold-standard method for effective VAS programme monitoring.
Topics: Dietary Supplements; Humans; Surveys and Questionnaires; Vitamin A; Vitamin A Deficiency
PubMed: 34527226
DOI: 10.1017/jns.2021.65