-
Frontiers in Immunology 2022Memory T cells play an essential role in infectious and tumor immunity. Vitamin A metabolites such as retinoic acid are immune modulators, but the role of vitamin A...
Memory T cells play an essential role in infectious and tumor immunity. Vitamin A metabolites such as retinoic acid are immune modulators, but the role of vitamin A metabolism in memory T-cell differentiation is unclear. In this study, we identified retinol dehydrogenase 10 (Rdh10), which metabolizes vitamin A to retinal (RAL), as a key molecule for regulating T cell differentiation. T cell-specific Rdh10 deficiency enhanced memory T-cell formation through blocking RAL production in infection model. Epigenetic profiling revealed that retinoic acid receptor (RAR) signaling activated by vitamin A metabolites induced comprehensive epigenetic repression of memory T cell-associated genes, including TCF7, thereby promoting effector T-cell differentiation. Importantly, memory T cells generated by Rdh deficiency and blocking RAR signaling elicited potent anti-tumor responses in adoptive T-cell transfer setting. Thus, T cell differentiation is regulated by vitamin A metabolism and its signaling, which should be novel targets for memory T cell-based cancer immunotherapy.
Topics: Alcohol Oxidoreductases; Immunotherapy; Memory T Cells; Neoplasms; Tretinoin; Vitamin A
PubMed: 35844620
DOI: 10.3389/fimmu.2022.935465 -
Frontiers in Endocrinology 2024The first evidence of the existence of vitamin A was the observation 1881 that a substance present in small amounts in milk was necessary for normal development and... (Review)
Review
The first evidence of the existence of vitamin A was the observation 1881 that a substance present in small amounts in milk was necessary for normal development and life. It was not until more than 100 years later that it was understood that vitamin A acts as a hormone through nuclear receptors. Unlike classical hormones, vitamin A cannot be synthesized by the body but needs to be supplied by the food as retinyl esters in animal products and ß-carotene in vegetables and fruits. Globally, vitamin A deficiency is a huge health problem, but in the industrialized world excess of vitamin A has been suggested to be a risk factor for secondary osteoporosis and enhanced susceptibility to fractures. Preclinical studies unequivocally have shown that increased amounts of vitamin A cause decreased cortical bone mass and weaker bones due to enhanced periosteal bone resorption. Initial clinical studies demonstrated a negative association between intake of vitamin A, as well as serum levels of vitamin A, and bone mass and fracture susceptibility. In some studies, these observations have been confirmed, but in other studies no such associations have been observed. One meta-analysis found that both low and high serum levels of vitamin A were associated with increased relative risk of hip fractures. Another meta-analysis also found that low levels of serum vitamin A increased the risk for hip fracture but could not find any association with high serum levels of vitamin A and hip fracture. It is apparent that more clinical studies, including large numbers of incident fractures, are needed to determine which levels of vitamin A that are harmful or beneficial for bone mass and fracture. It is the aim of the present review to describe how vitamin A was discovered and how vitamin A is absorbed, metabolized and is acting as a ligand for nuclear receptors. The effects by vitamin A in preclinical studies are summarized and the clinical investigations studying the effect by vitamin A on bone mass and fracture susceptibility are discussed in detail.
Topics: Humans; Bone Density; Vitamin A; Animals; Fractures, Bone; Signal Transduction; Osteoporosis; Vitamin A Deficiency; Bone and Bones
PubMed: 38711977
DOI: 10.3389/fendo.2024.1298851 -
Arquivos Brasileiros de Oftalmologia Feb 2016Clinical presentations associated with vitamin A deficiency persist in poor regions globally with the same clinical features as those described centuries ago. However,... (Review)
Review
Clinical presentations associated with vitamin A deficiency persist in poor regions globally with the same clinical features as those described centuries ago. However, new forms of vitamin A deficiency affecting the eyes, which have become widespread, as a result of modern societal habits are of increasing concern. Ophthalmic conditions related to vitamin A deficiency require the combined attention of ophthalmologists, pediatricians, internists, dermatologists, and nutritionists due to their potential severity and the diversity of causes. As the eyes and their adnexa are particularly sensitive to vitamin A deficiency and excess, ocular disturbances are often early indicators of vitamin A imbalance. The present review describes the clinical manifestations of hypovitaminosis A with an emphasis on so-called modern dietary disorders and multidisciplinary treatment approaches. The present review also discusses the relationship between retinoic acid therapy and dry eye disease.
Topics: Acne Vulgaris; Aged; Child, Preschool; Chronic Disease; Eye Diseases; Humans; Male; Vitamin A; Vitamin A Deficiency; Young Adult
PubMed: 26840172
DOI: 10.5935/0004-2749.20160018 -
In Vitro Cellular & Developmental... Feb 2023Human periodontal ligament cells (hPDLCs) are known as ideal seed cells for the regeneration of periodontal tissues. Several factors (i.e., vitamin D, luteolin, and...
Human periodontal ligament cells (hPDLCs) are known as ideal seed cells for the regeneration of periodontal tissues. Several factors (i.e., vitamin D, luteolin, and 6-bromoindirubin-3'-oxime) have been shown to promote osteogenic differentiation of hPDLCs. In this study, we aim to investigate the effect of vitamin A on cell proliferation, migration, and osteogenic differentiation of hPDLCs. hPDLCs were cultured in osteogenic induction medium supplemented with different concentrations of vitamin A. Cell proliferation and migration assays were conducted after 24, 48, and 72 h of incubation, whereas osteogenic differentiation and osteogenesis-related gene expression were assessed after 21 d only. Our results demonstrated that 1-µM vitamin A stimulation exerted the most potent promotion effect on cell proliferation, migration, and osteogenic differentiation of hPDLCs. It also induced significant upregulation of osteogenic differentiation-related genes and mitochondrial complexes II and IV in hPDLCs. Vitamin A may serve as a promising potential candidate for periodontal tissue regeneration.
Topics: Humans; Animals; Osteogenesis; Vitamin A; Periodontal Ligament; Cells, Cultured; Cell Differentiation; Cell Proliferation
PubMed: 36947388
DOI: 10.1007/s11626-023-00754-6 -
International Journal of Pharmaceutics Jul 2023Topical administration of active substances may be promoted by optimizing not only the vehicle formulation but also the application protocol. The formulation aspects are...
Topical administration of active substances may be promoted by optimizing not only the vehicle formulation but also the application protocol. The formulation aspects are widely studied in the literature while a few works are dedicated to the development of application methods. In this context, we studied an application protocol usable as a part of skincare routine by investigating the effect of massage on the skin penetration of retinol. Retinol is a lipophilic molecule widely used as an anti-ageing firming agent in cosmetic formulations. Massage was applied to pig skin explants mounted to Franz diffusion cells after or before the deposit of the retinol-loaded formulation. Thetype of skin massage (roll or rotary type) and its duration were varied.The massage protocol had a significant influence on retinol skin penetration. Due to its highly lipophilic character, retinol accumulated into the stratum corneum but, depending on the massage protocol, a significant retinol concentration was obtained after 4 h in epidermis and dermis layers. Results showed that the roll-type massage was significantly more efficient than the rotary process that exhibited little effect on retinol cutaneous penetration. Such results could be interesting for the development of massage devices in association with cosmetic formulations.
Topics: Animals; Swine; Vitamin A; Skin Absorption; Skin; Administration, Cutaneous; Cosmetics; Massage
PubMed: 37279867
DOI: 10.1016/j.ijpharm.2023.123106 -
The Cochrane Database of Systematic... Feb 2017Vitamin A deficiency is a major public health problem in low and middle income countries. Vitamin A supplementation in children six months of age and older has been... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Vitamin A deficiency is a major public health problem in low and middle income countries. Vitamin A supplementation in children six months of age and older has been found to be beneficial, but no effect of supplementation has been noted for children between one and five months of age. Supplementation during the neonatal period has been suggested to have an impact by increasing body stores in early infancy.
OBJECTIVES
To evaluate the role of vitamin A supplementation for term neonates in low and middle income countries with respect to prevention of mortality and morbidity.
SEARCH METHODS
We used the standard search strategy of the Cochrane Neonatal Review Group to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 2), MEDLINE via PubMed (1966 to 13 March 2016), Embase (1980 to 13 March 2016) and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to 13 March 2016). We also searched clinical trials databases, conference proceedings and reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials.
SELECTION CRITERIA
Randomised and quasi-randomised controlled trials. Also trials with a factorial design.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trial quality and extracted study data. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess the quality of evidence.
MAIN RESULTS
We included 12 trials (168,460 neonates) in this review, with only a few trials reporting disaggregated data for term infants. Therefore, we analysed data and presented estimates for term infants (when specified) and for all infants.Data for term neonates from three studies did not show a statistically significant effect on the risk of infant mortality at six months in the vitamin A group compared with the control group (typical risk ratio (RR) 0.80; 95% confidence interval (CI) 0.54 to 1.18; I = 63%). Analysis of data for all infants from 11 studies revealed no evidence of a significant reduction in the risk of infant mortality at six months among neonates supplemented with vitamin A compared with control neonates (typical RR 0.98, 95% CI 0.89 to 1.07; I = 47%). We observed similar results for infant mortality at 12 months of age with no significant effect of vitamin A compared with control (typical RR 1.04, 95% CI 0.94 to 1.15; I = 47%). Limited data were available for the outcomes of cause-specific mortality and morbidity, vitamin A deficiency, anaemia and adverse events.
AUTHORS' CONCLUSIONS
Given the high burden of death among children younger than five years of age in low and middle income countries, and the fact that mortality in infancy is a major contributory cause, it is critical to obtain sound scientific evidence of the effect of vitamin A supplementation during the neonatal period on infant mortality and morbidity. Evidence provided in this review does not indicate a potential beneficial effect of vitamin A supplementation among neonates at birth in reducing mortality during the first six months or 12 months of life. Given this finding and the absence of a clear indication of the biological mechanism through which vitamin A could affect mortality, along with substantial conflicting findings from individual studies conducted in settings with potentially varying levels of maternal vitamin A deficiency and infant mortality, absence of follow-up studies assessing any long-term impact of a bulging fontanelle after supplementation and the finding of a potentially harmful effect among female infants, additional research is warranted before a decision can be reached regarding policy recommendations for this intervention.
Topics: Developing Countries; Humans; Infant; Infant Mortality; Infant, Newborn; Morbidity; Randomized Controlled Trials as Topic; Vitamin A; Vitamin A Deficiency; Vitamins
PubMed: 28234402
DOI: 10.1002/14651858.CD006980.pub3 -
Nutrients Feb 2019A total of 12 trials have tested the effect of neonatal vitamin A supplementation (NVAS) on mortality. Overall, NVAS had no effect on mortality, but results were... (Review)
Review
A total of 12 trials have tested the effect of neonatal vitamin A supplementation (NVAS) on mortality. Overall, NVAS had no effect on mortality, but results were heterogeneous. Two competing hypotheses have been put forward to explain the divergent effects: A) NVAS works by preventing vitamin A deficiency (VAD) and not all countries have VAD; B) NVAS interacts negatively with subsequent diphtheria-tetanus-pertussis (DTP) vaccine, increasing mortality in females; in countries with low DTP coverage NVAS may have a beneficial effect. Only hypothesis A was tested in a recent meta-analysis; there is no strong empirical support for hypothesis A and it would not explain observed negative effects in some settings. Hypothesis B accounts for most observations. However, so far it has only been tested properly in a few trials. If hypothesis B is correct, it has major consequences for the understanding of the effects of vitamin A, and for the VAS policy in older children. As a WHO priority, the DTP coverage is bound to increase, and therefore hypothesis B urgently needs to be tested.
Topics: Dietary Supplements; Diphtheria-Tetanus-Pertussis Vaccine; Drug Interactions; Female; Humans; Infant; Infant Mortality; Infant, Newborn; Male; Postnatal Care; Vaccination Coverage; Vitamin A; Vitamin A Deficiency; Vitamins
PubMed: 30795563
DOI: 10.3390/nu11020449 -
The American Journal of Clinical... Apr 2021Reduction of vitamin A deficiency (VAD) in Malawi coincided with introduction of vitamin A-fortified staple foods, alongside continued biannual high-dose vitamin A...
BACKGROUND
Reduction of vitamin A deficiency (VAD) in Malawi coincided with introduction of vitamin A-fortified staple foods, alongside continued biannual high-dose vitamin A supplementation (VAS).
OBJECTIVE
We describe coverage of vitamin A interventions and vitamin A status in the 2015-2016 Malawi Micronutrient Survey.
METHODS
Food samples and biospecimens were collected within a representative household survey across 105 clusters. Retinol was measured using ultraviolet excitation fluorescence (sugar) and photometric determination (oil). Preschool children (PSC, aged 6-59 mo, n = 1102), school-age children (SAC, aged 5-14 y, n = 758), nonpregnant women (n = 752), and men (n = 219) were initially assessed for vitamin A status using retinol binding protein (RBP) and modified relative dose response (MRDR). Randomly selected fasted MRDR participants (n = 247) and nonfasted women and children (n = 293) were later assessed for serum retinol, retinyl esters, and carotenoids. Analyses accounted for complex survey design.
RESULTS
We tested sugar and oil samples from 71.8% and 70.5% of the households (n = 2,112), respectively. All of the oil samples and all but one of the sugar samples had detectable vitamin A. National mean retinol sugar and oil contents were 6.1 ± 0.7 mg/kg and 6.6 ± 1.4 mg/kg, respectively. Receipt of VAS in the previous 6 mo was reported by 68.0% of PSC. VAD prevalence (RBP equivalent to <0.7µmol retinol/L) was 3.6% in PSC, and <1% in other groups. One woman and no children had MRDR ≥0.060 indicating VAD. Among fasted PSC and SAC, 18.0% (95% CI: 6.4, 29.6) and 18.8% (7.2, 30.5) had >5% of total serum vitamin A as retinyl esters, and 1.7% (0.0, 4.1) and 4.9% (0.0, 10.2) had >10% of total serum vitamin A as retinyl esters. Serum carotenoids indicated recent intake of vitamin A-rich fruits and vegetables.
CONCLUSIONS
Near elimination of VAD in Malawi is a public health success story, but elevated levels of vitamin A among children suggests that vitamin A interventions may need modification.
Topics: Adolescent; Adult; Carotenoids; Child; Child, Preschool; Dietary Supplements; Female; Food, Fortified; Humans; Infant; Malawi; Male; Middle Aged; Nutritional Status; Retinol-Binding Proteins; Retinyl Esters; Vitamin A; Vitamin A Deficiency; Young Adult
PubMed: 33751046
DOI: 10.1093/ajcn/nqab004 -
Pharmacology & Therapeutics Feb 2022Vitamin A is an important micro-essential nutrient, whose primary dietary source is retinyl esters. In addition, β-carotene (pro-vitamin A) is a precursor of vitamin A... (Review)
Review
Vitamin A is an important micro-essential nutrient, whose primary dietary source is retinyl esters. In addition, β-carotene (pro-vitamin A) is a precursor of vitamin A contained in green and yellow vegetables that is converted to retinol in the body after ingestion. Retinol is oxidized to produce visual retinal, which is further oxidized to retinoic acid (RA), which is used as a therapeutic agent for patients with promyelocytic leukemia. Thus, the effects of retinal and RA are well known. In this paper, we will introduce (1) vitamin A circulation in the body, (2) the actions and mechanisms of retinal and RA, (3) retinoylation: another RA mechanism not depending on RA receptors, (4) the relationship between cancer and actions of retinol or β-carotene, whose roles in vivo are still unknown, and (5) anti-cancer actions of vitamin A derivatives derived from fenretinide (4-HPR). We propose that vitamin A nutritional management is effective in the prevention of cancer.
Topics: Cell Differentiation; Delivery of Health Care; Humans; Neoplasms; Receptors, Retinoic Acid; Tretinoin; Vitamin A
PubMed: 34175370
DOI: 10.1016/j.pharmthera.2021.107942 -
Nutrients Dec 2016Embryonic development is orchestrated by a small number of signaling pathways, one of which is the retinoic acid (RA) signaling pathway. Vitamin A is essential for... (Review)
Review
Embryonic development is orchestrated by a small number of signaling pathways, one of which is the retinoic acid (RA) signaling pathway. Vitamin A is essential for vertebrate embryonic development because it is the molecular precursor of the essential signaling molecule RA. The level and distribution of RA signaling within a developing embryo must be tightly regulated; too much, or too little, or abnormal distribution, all disrupt embryonic development. Precise regulation of RA signaling during embryogenesis is achieved by proteins involved in vitamin A metabolism, retinoid transport, nuclear signaling, and RA catabolism. The reversible first step in conversion of the precursor vitamin A to the active retinoid RA is mediated by retinol dehydrogenase 10 (RDH10) and dehydrogenase/reductase (SDR family) member 3 (DHRS3), two related membrane-bound proteins that functionally activate each other to mediate the interconversion of retinol and retinal. Alcohol dehydrogenase (ADH) enzymes do not contribute to RA production under normal conditions during embryogenesis. Genes involved in vitamin A metabolism and RA catabolism are expressed in tissue-specific patterns and are subject to feedback regulation. Mutations in genes encoding these proteins disrupt morphogenesis of many systems in a developing embryo. Together these observations demonstrate the importance of vitamin A metabolism in regulating RA signaling during embryonic development in vertebrates.
Topics: Alcohol Oxidoreductases; Animals; Embryonic Development; Humans; Signal Transduction; Tretinoin; Vertebrates; Vitamin A
PubMed: 27983671
DOI: 10.3390/nu8120812