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Journal of Molecular Endocrinology Oct 2022Vitamin A (retinol) is an essential, fat-soluble vitamin that plays critical roles in embryonic development, vision, immunity, and reproduction. Severe vitamin A... (Review)
Review
Vitamin A (retinol) is an essential, fat-soluble vitamin that plays critical roles in embryonic development, vision, immunity, and reproduction. Severe vitamin A deficiency results in profound embryonic dysgenesis, blindness, and infertility. The roles of bioactive vitamin A metabolites in regulating cell proliferation, cellular differentiation, and immune cell function form the basis of their clinical use in the treatment of dermatologic conditions and hematologic malignancies. Increasingly, vitamin A also has been recognized to play important roles in cardiometabolic health, including the regulation of adipogenesis, energy partitioning, and lipoprotein metabolism. While these roles are strongly supported by animal and in vitro studies, they remain poorly understood in human physiology and disease. This review briefly introduces vitamin A biology and presents the key preclinical data that have generated interest in vitamin A as a mediator of cardiometabolic health. The review also summarizes clinical studies performed to date, highlighting the limitations of many of these studies and the ongoing controversies in the field. Finally, additional perspectives are suggested that may help position vitamin A metabolism within a broader biological context and thereby contribute to enhanced understanding of vitamin A's complex roles in clinical cardiometabolic disease.
Topics: Adipogenesis; Animals; Cardiovascular Diseases; Female; Homeostasis; Humans; Pregnancy; Vitamin A; Vitamin A Deficiency
PubMed: 35900842
DOI: 10.1530/JME-22-0078 -
Nutrients Apr 2024This review aims to evaluate the efficacy of any vitamin administration(s) in preventing and managing COVID-19 and/or long-COVID. Databases were searched up to May 2023... (Meta-Analysis)
Meta-Analysis Review
The Efficacy of Multivitamin, Vitamin A, Vitamin B, Vitamin C, and Vitamin D Supplements in the Prevention and Management of COVID-19 and Long-COVID: An Updated Systematic Review and Meta-Analysis of Randomized Clinical Trials.
This review aims to evaluate the efficacy of any vitamin administration(s) in preventing and managing COVID-19 and/or long-COVID. Databases were searched up to May 2023 to identify randomized clinical trials comparing data on the effects of vitamin supplementation(s) versus placebo or standard of care on the two conditions of interest. Inverse-variance random-effects meta-analyses were conducted to estimate pooled risk ratios (RRs) and 95% confidence intervals (CIs) for all-cause mortality between supplemented and non-supplemented individuals. Overall, 37 articles were included: two regarded COVID-19 and long-COVID prevention and 35 records the COVID-19 management. The effects of vitamin D in preventing COVID-19 and long-COVID were contrasting. Similarly, no conclusion could be drawn on the efficacy of multivitamins, vitamin A, and vitamin B in COVID-19 management. A few positive findings were reported in some vitamin C trials but results were inconsistent in most outcomes, excluding all-cause mortality (RR = 0.84; 95% CI: 0.72-0.97). Vitamin D results were mixed in most aspects, including mortality, in which benefits were observed in regular administrations only (RR = 0.67; 95% CI: 0.49-0.91). Despite some benefits, results were mostly contradictory. Variety in recruitment and treatment protocols might explain this heterogeneity. Better-designed studies are needed to clarify these vitamins' potential effects against SARS-CoV-2.
Topics: Humans; Dietary Supplements; COVID-19; Vitamins; Vitamin D; Randomized Controlled Trials as Topic; Ascorbic Acid; SARS-CoV-2; Vitamin A; COVID-19 Drug Treatment; Vitamin B Complex
PubMed: 38732592
DOI: 10.3390/nu16091345 -
Developmental Biology Jul 2021Vertebrate rod and cone photoreceptors detect light via a specialized organelle called the outer segment. This structure is packed with light-sensitive molecules known... (Review)
Review
Vertebrate rod and cone photoreceptors detect light via a specialized organelle called the outer segment. This structure is packed with light-sensitive molecules known as visual pigments that consist of a G-protein-coupled, seven-transmembrane protein known as opsin, and a chromophore prosthetic group, either 11-cis retinal ('A') or 11-cis 3,4-didehydroretinal ('A'). The enzyme cyp27c1 converts A into A in the retinal pigment epithelium. Replacing A with A in a visual pigment red-shifts its spectral sensitivity and broadens its bandwidth of absorption at the expense of decreased photosensitivity and increased thermal noise. The use of vitamin A-based visual pigments is strongly associated with the occupation of aquatic habitats in which the ambient light is red-shifted. By modulating the A/A ratio in the retina, an organism can dynamically tune the spectral sensitivity of the visual system to better match the predominant wavelengths of light in its environment. As many as a quarter of all vertebrate species utilize A, at least during a part of their life cycle or under certain environmental conditions. A utilization therefore represents an important and widespread mechanism of sensory plasticity. This review provides an up-to-date account of the A/A chromophore exchange system.
Topics: Animals; Opsins; Photoreceptor Cells, Vertebrate; Retina; Retinal Cone Photoreceptor Cells; Retinal Pigment Epithelium; Retinal Pigments; Retinal Rod Photoreceptor Cells; Rod Opsins; Vitamin A
PubMed: 33684435
DOI: 10.1016/j.ydbio.2021.03.002 -
Methods in Enzymology 2022Macrophages are critical players in the development of atherosclerotic lesions, where they promote local and systemic inflammation. Macrophages engulf lipoproteins and...
Macrophages are critical players in the development of atherosclerotic lesions, where they promote local and systemic inflammation. Macrophages engulf lipoproteins and cell debris upon entry into the arterial wall, becoming lipid-laden foam cells. While most lipids found in foam cells are triglyceride and cholesterol, these cells accumulate several other lipids with bioactive properties, such as vitamin A and carotenoids. Vitamin A has strong immunomodulatory actions in macrophages and other immune cells. For example, macrophages release vitamin A as retinoic acid to modulate T cell differentiation, but the implication of intracellular vitamin A stores in this process remains elusive due to the lack of an adequate experimental model to load vitamin A into macrophages. The purpose of this study was to develop a reliable method to deliver vitamin A to cultured murine macrophages. Our results show that thioglycolate-elicited peritoneal macrophages fail to take up significant levels of vitamin A when provided as free retinol. Cultured macrophages and macrophages in the peritoneal cavity can take up retinyl esters, either as retinyl ester-loaded serum or retinyl esters infused directly into the peritoneal cavity. HPLC analyses in macrophage lysates revealed that the intraperitoneal injection method results in a fourfold greater vitamin A loading efficiency than retinyl ester-loaded serum added to cultured cells. These two alternative methods provide an efficient and reliable methodology to load macrophages with vitamin A for downstream applications such as studies of gene regulation trafficking of intracellular vitamin A, and vitamin A release from macrophages.
Topics: Animals; Cells, Cultured; Lipoproteins; Macrophages; Mice; Retinyl Esters; Triglycerides; Vitamin A
PubMed: 36008013
DOI: 10.1016/bs.mie.2022.04.008 -
Hepatology Communications May 2023Vitamin A, a fat-soluble vitamin that includes retinol and carotenoids, is implicated in liver fibrosis, whereas its deficiency has been associated with various liver...
INTRODUCTION
Vitamin A, a fat-soluble vitamin that includes retinol and carotenoids, is implicated in liver fibrosis, whereas its deficiency has been associated with various liver diseases and higher overall mortality. This study aims to determine the relationship between levels of vitamin A species and liver fibrosis, as well as liver-related mortality in the population of the US.
METHODS
A total of 12,299 participants from the National Health and Nutrition Examination Survey III (NHANES III) were analyzed to provide nationally representative estimates of the relationship between the levels of vitamin A species and liver fibrosis measured by Fibrosis-4 (FIB-4) index and liver-related mortality.
RESULTS
A low blood level of retinol, but not other retinoid derivatives, was associated with significant liver fibrosis after adjustment for demographics, anthropometric measurements, medical history, retinol, and carotene intakes. Compared with vitamin D and E, retinol deficiency demonstrated much stronger associations with a high FIB-4 score. Individuals with known risks of chronic liver disease (CLD) and the lowest pentile of retinol levels had ORs of 3.12 (95% CI, 1.64-5.91) for possible fibrosis and 19.7 (95% CI, 5.71-67.7) for likely fibrosis, and an HR of 7.76 (95% CI, 1.19-50.5) for liver-related mortality compared with those in the highest retinol-level pentile. These relationships were more pronounced among individuals with known risks of chronic liver disease than without.
CONCLUSIONS
A low circulating retinol level is associated with liver fibrosis and liver-related mortality in chronic liver disease. This relationship is potentially driven by a mechanistic link rather than the malabsorption of fat-soluble vitamins and may be leveraged for disease prognostication and have therapeutic implications.
Topics: Humans; Vitamin A; Nutrition Surveys; Cohort Studies; Carotenoids; Liver Diseases; Liver Cirrhosis
PubMed: 37058112
DOI: 10.1097/HC9.0000000000000124 -
Frontiers in Immunology 2023Vitamin A has long been associated with bladder cancer, and many exogenous vitamin A supplements, vitamin A derivatives, and synthetic drugs have been investigated over... (Review)
Review
Vitamin A has long been associated with bladder cancer, and many exogenous vitamin A supplements, vitamin A derivatives, and synthetic drugs have been investigated over the years. However, the effectiveness of these strategies in clinical practice has not met expectations, and they have not been widely adopted. Recent medical research on intestinal flora has revealed that bladder cancer patients exhibit reduced serum vitamin A levels and an imbalance of gut microbiota. In light of the close relationship between gut microbiota and vitamin A, one can speculate that a complex regulatory mechanism exists between the two in the development and occurrence of bladder cancer. As such, further exploration of their interaction in bladder cancer may help guide the use of vitamin A for preventive purposes. During the course of this review, attention is paid to the influence of intestinal microbiota on the vitamin A metabolism and the RA signaling pathway, as well as the mutual promotion relationships between them in the prevention of bladder cancer, In addition, it emphasizes the importance of intestinal microbiota for bladder cancer prevention and treatment.
Topics: Humans; Gastrointestinal Microbiome; Vitamin A; Urinary Bladder Neoplasms; Biomedical Research; Dietary Supplements
PubMed: 37711628
DOI: 10.3389/fimmu.2023.1252616 -
Archivum Immunologiae Et Therapiae... Dec 2019The skin is the largest epithelial surface protecting the body from invading microbes. Vitamin A plays vital roles in the host defence of the skin, including promoting... (Review)
Review
The skin is the largest epithelial surface protecting the body from invading microbes. Vitamin A plays vital roles in the host defence of the skin, including promoting epithelial cell integrity, proliferation, and differentiation and even mediating immune responses. Furthermore, vitamin A derivatives, retinoid drugs, are widely used to treat skin diseases, such as acne and psoriasis. However, the immunoregulatory mechanisms of retinoids in dermatology have not been systematically described. In this paper, we discuss the immunological functions of retinoids during disease treatment, especially in skin disorders caused by exogenous infections.
Topics: Animals; Dermatology; Epithelial Cells; Humans; Immunity; Immunologic Factors; Retinoids; Skin; Skin Diseases; Vitamin A
PubMed: 31552446
DOI: 10.1007/s00005-019-00562-5 -
Sichuan Da Xue Xue Bao. Yi Xue Ban =... Jan 2023Keeping the immune system healthy forms an effective way to fight infections. Past experience has shown that, in addition to effective interventions including... (Review)
Review
Keeping the immune system healthy forms an effective way to fight infections. Past experience has shown that, in addition to effective interventions including vaccination, drug therapy, and non-pharmaceutical intervention (NPI), dietary nutrition and mental health are also key factors in maintaining immune system health and combating emerging and sudden outbreaks of infections. As the main dietary nutrients, vitamins are active regulators of the immune response and exert a critical impact on the immunity of the human body. Vitamin deficiency causes increased levels of inflammation and decreased immunity, which usually starts in the oral tissues. Appropriate vitamin supplementation can help the body optimize immune function, enhance oral immunity, and reduce the negative impact of pathogen infection on the human body, which makes it a feasible, effective, and universally applicable anti-infection solution. This review focuses on the immunomodulatory effects of vitamin A, B, C, D, and E and proposes that an omics-based new systemic approach will lead to a breakthrough of the limitations in traditional single-factor single-pathway research and provide the direction for the basic and applied research of vitamin immune regulation and anti-infection in all aspects.
Topics: Humans; Vitamins; Vitamin A; Immune System; Vitamin K; Inflammation; Dietary Supplements
PubMed: 36647636
DOI: 10.12182/20230160107 -
Nutrients Dec 2019Vitamin A (all--retinol), its active derivatives retinal and retinoic acid, and their synthetic analogues constitute the group of retinoids. It is obtained from diet... (Review)
Review
Vitamin A (all--retinol), its active derivatives retinal and retinoic acid, and their synthetic analogues constitute the group of retinoids. It is obtained from diet either as preformed vitamin A or as carotenoids. Retinal plays a biological role in vision, but most of the effects of vitamin A are exerted by retinoic acid, which binds to nuclear receptors and regulates gene transcription. Vitamin A deficiency is an important nutritional problem, particularly in the developing world. Retinol and carotenoids from diet during pregnancy and lactation influence their concentration in breast milk, which is important in the long term, not only for the offspring, but also for maternal health. In this study, we review the role of vitamin A in mammary gland metabolism, where retinoid signaling is required not only for morphogenesis and development of the gland and for adequate milk production, but also during the weaning process, when epithelial cell death is coupled with tissue remodeling.
Topics: Animals; Carotenoids; Diet; Female; Humans; Lactation; Mammary Glands, Animal; Mammary Glands, Human; Milk, Human; Nutritional Requirements; Pregnancy; Vitamin A; Vitamin A Deficiency; Weaning
PubMed: 31892157
DOI: 10.3390/nu12010080 -
Methods in Enzymology 2020Generation of the autacoid all-trans-retinoic acid (ATRA) from retinol (vitamin A) relies on a complex metabolon that includes retinol binding-proteins and enzymes from...
Generation of the autacoid all-trans-retinoic acid (ATRA) from retinol (vitamin A) relies on a complex metabolon that includes retinol binding-proteins and enzymes from the short-chain dehydrogenase/reductase and aldehyde dehydrogenase gene families. Serum retinol binding-protein delivers all-trans-retinol (vitamin A) from blood to cells through two membrane receptors, Stra6 and Rbpr2. Stra6 and Rbpr2 convey retinol to cellular retinol binding-protein type 1 (Crbp1). Holo-Crbp1 delivers retinol to lecithin: retinol acyl transferase (Lrat) for esterification and storage. Lrat channels retinol directly into its active site from holo-Crbp1 by protein-protein interaction. The ratio apo-Crbp1/holo-Crbp1 directs flux of retinol into and out of retinyl esters, through regulating esterification vs ester hydrolysis. Multiple retinol dehydrogenases (Rdh1, Rdh10, Dhrs9, Rdhe2, Rdhe2s) channel retinol from holo-Crbp1 to generate retinal for ATRA biosynthesis. β-Carotene oxidase type 1 generates retinal from carotenoids, delivered by the scavenger receptor-B1. Retinal reductases (Dhrs3, Dhrs4, Rdh11) reduce retinal into retinol, thereby restraining ATRA biosynthesis. Retinal dehydrogenases (Raldh1, 2, 3) dehydrogenate retinal irreversibly into ATRA. ATRA regulates its own concentrations by inducing Lrat and ATRA degradative enzymes. ATRA exhibits hormesis. Its effects relate to its concentration as an inverted J-shaped curve, transitioning from beneficial in the "goldilocks" zone to toxicity, as concentrations increase. Hormesis has distorted understanding physiological effects of ATRA post-nataly using chow-diet fed, ATRA-dosed animal models. Cancer, immune deficiency and metabolic abnormalities result from mutations and/or insufficiency in Crbp1 and retinoid metabolizing enzymes.
Topics: Animals; Retinol-Binding Proteins; Retinol-Binding Proteins, Cellular; Tretinoin; Vitamin A
PubMed: 32359649
DOI: 10.1016/bs.mie.2020.02.003