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Eye (London, England) May 2023Spectral-domain optical coherence tomography (SD-OCT) and full-field electroretinography (ERG) allow retinal assessment with vitamin A deficiency (VAD). Using SD-OCT,...
BACKGROUND
Spectral-domain optical coherence tomography (SD-OCT) and full-field electroretinography (ERG) allow retinal assessment with vitamin A deficiency (VAD). Using SD-OCT, this study aimed to characterize and follow a novel retinal abnormality in patients with VAD and intramuscular supplementation.
METHODS
Patients with VAD were retrospectively reviewed, including SD-OCT and electroretinography.
RESULTS
Three patients had VAD following bariatric or colon surgery and varying supplementation. All had nyctalopia, extinguished scotopic rod-specific function with ERG, and decreased serum vitamin A. None demonstrated surface abnormalities. All received intramuscular vitamin A with subjective resolution of symptoms. On SD-OCT, four of six eyes exhibited homogenous foveal hyperreflectivity anterior to retinal pigment epithelium-Bruch complex, reminiscent of a "double carrot", which improved following supplementation. ERG findings demonstrated improved scotopic rod-specific function in all cases; however, photopic function remained diminished in two cases.
CONCLUSIONS
Structural improvement of the proposed "double carrot" sign occurs soon after vitamin A supplementation. While scotopic function improves rapidly following supplementation, cone function recovers more slowly. Therefore, foveal changes such as the "double carrot" sign suggest that structural recovery of cones precedes functional recovery.
Topics: Humans; Electroretinography; Retina; Retrospective Studies; Tomography, Optical Coherence; Visual Acuity; Vitamin A; Vitamin A Deficiency
PubMed: 35840717
DOI: 10.1038/s41433-022-02137-9 -
Pediatric Research Apr 2022India has an unacceptably high burden of vitamin A deficiency (VAD) among children aged 6-59 months. To mitigate VAD and its adverse effects on child health, the Indian...
BACKGROUND
India has an unacceptably high burden of vitamin A deficiency (VAD) among children aged 6-59 months. To mitigate VAD and its adverse effects on child health, the Indian government runs a nationwide vitamin A supplementation (VAS) programme. However, the effect of VAS in reducing child morbidity and mortality remains inconclusive and has been debated globally. In this paper, we estimate the effect of VAS on two indicators of child nutrition-anaemia (categorized into any anaemia, and mild/moderate anaemia) and anthropometric failure (categorized into stunting, wasting, and underweight) among children aged 6-59 months.
METHODS
Using the nationally representative 2015-2016 National Family Health Survey data set from India, we set up a quasi-experimental study design and estimated household and mother fixed-effects of VAS on select types of child anaemia and anthropometric failure.
RESULTS
Findings from both the household fixed-effects and mother fixed-effects analysis showed that VAS does not influence any types of childhood anaemia and anthropometric failure in India. We discussed the findings considering existing literature and possible limitations of the study.
CONCLUSIONS
The infirm effect of Vitamin A on anaemia and anthropometric failure is probably indicative of targeted VAS intervention, as opposed to a universal VAS programme.
IMPACT
Effects of vitamin A supplementation (VAS) in treating child morbidity and mortality remain inconclusive, which calls for further rigorous studies. This study set up a quasi-experimental research design and estimated the null effect of VAS on child anaemia and childhood anthropometric failure. While the cautious interpretation of findings is urged, this study reliably supports targeted intervention of VAS, instead of the universal VAS programme. The use of nationally representative data and robust research protocol are the primary strengths of this study.
Topics: Anemia; Child; Child Nutritional Physiological Phenomena; Dietary Supplements; Female; Humans; Infant; Prevalence; Vitamin A; Vitamin A Deficiency
PubMed: 35140334
DOI: 10.1038/s41390-022-01969-1 -
The Cochrane Database of Systematic... Jun 2020Retinitis pigmentosa (RP) comprises a group of hereditary eye diseases characterized by progressive degeneration of retinal photoreceptors. It results in severe visual... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Retinitis pigmentosa (RP) comprises a group of hereditary eye diseases characterized by progressive degeneration of retinal photoreceptors. It results in severe visual loss that may lead to blindness. Symptoms may become manifest during childhood or adulthood which include poor night vision (nyctalopia) and constriction of peripheral vision (visual field loss). Visual field loss is progressive and affects central vision later in the disease course. The worldwide prevalence of RP is approximately 1 in 4000, with 100,000 individuals affected in the USA. At this time, there is no proven therapy for RP.
OBJECTIVES
The objective of this review was to synthesize the best available evidence regarding the effectiveness and safety of vitamin A and fish oils (docosahexaenoic acid (DHA)) in preventing the progression of RP.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), which contains the Cochrane Eyes and Vision Trials Register (2020, Issue 2); Ovid MEDLINE; Embase.com; PubMed; Latin American and Caribbean Health Sciences Literature Database (LILACS); ClinicalTrials.gov; the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP); and OpenGrey. We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 7 February 2020.
SELECTION CRITERIA
We included randomized controlled trials that enrolled participants of any age diagnosed with any degree of severity or type of RP, and evaluated the effectiveness of vitamin A, fish oils (DHA), or both compared to placebo, vitamins (other than vitamin A), or no therapy, as a treatment for RP. We excluded cluster-randomized trials and cross-over trials.
DATA COLLECTION AND ANALYSIS
We prespecified the following outcomes: mean change from baseline visual field, mean change from baseline electroretinogram (ERG) amplitudes, and anatomic changes as measured by optical coherence tomography (OCT), at one-year follow-up, and mean change in visual acuity, at five-year follow-up. Two review authors independently extracted data and evaluated risk of bias for all included trials. We also contacted study investigators for further information when necessary.
MAIN RESULTS
In addition to three trials from the previous version of this review, we included a total of four trials with 944 participants aged 4 to 55 years. Two trials included only participants with X-linked RP and the other two included participants with RP of all forms of genetic predisposition. Two trials evaluated the effect of DHA alone; one trial evaluated vitamin A alone; and one trial evaluated DHA and vitamin A versus vitamin A alone. Two trials recruited participants from the USA, and the other two recruited from the USA and Canada. All trials were at low risk of bias for most domains. We did not perform meta-analysis due to clinical heterogeneity. Four trials assessed visual field sensitivity. Investigators found no evidence of a difference in mean values between the groups. However, one trial found that the annual rate of change of visual field sensitivity over four years favored the DHA group in foveal (-0.02 ± 0.55 (standard error (SE)) dB versus -0.47 ± 0.03 dB, P = 0.039), macular (-0.42 ± 0.05 dB versus -0.85 ± 0.03 dB, P = 0.031), peripheral (-0.39 ± 0.02 versus -0.86 ± 0.02 dB, P < 0.001), and total visual field sensitivity (-0.39 ± 0.02 versus -0.86 ± 0.02 dB, P < 0.001). The certainty of the evidence was very low. The four trials evaluated visual acuity (LogMAR scale) at a follow-up of four to six years. In one trial (208 participants), investigators found no evidence of a difference between the two groups, as both groups lost 0.7 letters of the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity per year. In another trial (41 participants), DHA showed no evidence of effect on visual acuity (mean difference -0.01 logMAR units (95% confidence interval -0.14 to 0.12; one letter difference between the two groups; very low-certainty evidence). In the third trial (60 participants), annual change in mean number of letters correct was -0.8 (DHA) and 1.4 letters (placebo), with no evidence of between-group difference. In the fourth trial (572 participants), which evaluated (vitamin A + vitamin E trace) compared with (vitamin A trace + vitamin E trace), decline in ETDRS visual acuity was 1.1 versus 0.9 letters per year, respectively. All four trials reported electroretinography (ERG). Investigators of two trials found no evidence of a difference between the DHA and placebo group in yearly rates of change in 31 Hz cone ERG amplitude (mean ± SE) (-0.028 ± 0.001 log μV versus -0.022 ± 0.002 log μV; P = 0.30); rod ERG amplitude (mean ± SE) (-0.010 ± 0.001 log μV versus -0.023 ± 0.001 log μV; P = 0.27); and maximal ERG amplitude (mean ± SE) (-0.042 ± 0.001 log μV versus -0.036 ± 0.001 log μV; P = 0.65). In another trial, a slight difference (6.1% versus 7.1%) in decline of ERG per year favored vitamin A (P = 0.01). The certainty of the evidence was very low. One trial (51 participants) that assessed optical coherence tomography found no evidence of a difference in ellipsoid zone constriction (P = 0.87) over two years, with very low-certainty evidence. The other three trials did not report this outcome. Only one trial reported adverse events, which found that 27/60 participants experienced 42 treatment-related emergent adverse events (22 in DHA group, 20 in placebo group). The certainty of evidence was very low. The rest of the trials reported no adverse events, and no study reported any evidence of benefit of vitamin supplementation on the progression of visual acuity loss.
AUTHORS' CONCLUSIONS
Based on the results of four studies, it is uncertain if there is a benefit of treatment with vitamin A or DHA, or both for people with RP. Future trials should also take into account the changes observed in ERG amplitudes and other outcome measures from trials included in this review.
Topics: Adolescent; Adult; Child; Child, Preschool; Combined Modality Therapy; Disease Progression; Docosahexaenoic Acids; Electroretinography; Female; Fish Oils; Humans; Male; Middle Aged; Randomized Controlled Trials as Topic; Retinitis Pigmentosa; Visual Acuity; Visual Fields; Vitamin A; Vitamins; Young Adult
PubMed: 32573764
DOI: 10.1002/14651858.CD008428.pub3 -
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 -
Mucosal Immunology Apr 2022Vitamin A and its derivative retinoic acid (RA) play important roles in the regulation of mucosal immunity. The effect of vitamin A metabolism on T lymphocyte immunity... (Review)
Review
Vitamin A and its derivative retinoic acid (RA) play important roles in the regulation of mucosal immunity. The effect of vitamin A metabolism on T lymphocyte immunity has been well documented, but its role in mucosal B lymphocyte regulation is less well described. Intestinal immunoglobulin A (IgA) is key in orchestrating a balanced gut microbiota composition. Here, we describe the contribution of RA to IgA class switching in tissues including the lamina propria, mesenteric lymph nodes, Peyer's patches and isolated lymphoid follicles. RA can either indirectly skew T cells or directly affect B cell differentiation. IgA levels in healthy individuals are under the control of the metabolism of vitamin A, providing a steady supply of RA. However, IgA levels are altered in inflammatory bowel disease patients, making control of the metabolism of vitamin A a potential therapeutic target. Thus, dietary vitamin A is a key player in regulating IgA production within the intestine, acting via multiple immunological pathways.
Topics: Humans; Immunity, Mucosal; Immunoglobulin A; Intestinal Mucosa; Peyer's Patches; Tretinoin; Vitamin A
PubMed: 35418672
DOI: 10.1038/s41385-022-00509-8 -
Biological & Pharmaceutical Bulletin 2022Vitamin A is an important trace essential nutrient. Vitamin A is present as a retinyl ester in animal foods and as β-carotene (provitamin A), which is a precursor of... (Review)
Review
Vitamin A is an important trace essential nutrient. Vitamin A is present as a retinyl ester in animal foods and as β-carotene (provitamin A), which is a precursor of vitamin A, in plant foods such as green and yellow vegetables. After ingestion and absorption in the body, these are converted into retinol and stored as retinyl esters in stellate cells in the liver. The stored retinyl esters are decomposed into retinol as needed, and converted into the aldehyde retinal, which plays an important role in vision. Retinoic acid (RA) has a variety of effects. In particular, RA is used as a therapeutic agent for acute promyelocytic leukemia. This review will cover (1) elucidation of anti-refractory cancer effects of retinol (vitamin A) not mediated by RA receptors, (2) elucidation of anti-cancer effects of RA not mediated by RA receptors and (3) the development of candidate new anti-cancer agents that combine the actions of RA and retinol. Lessons learned from these findings are that vitamin A has anti-cancer activity not mediated by RA receptors; that nutritional management of vitamin A leads to prevention and treatment of cancer, and that new compounds developed from RA derivatives represent good anti-cancer drug candidates that are in various stages of clinical trials.
Topics: Animals; Antineoplastic Agents; Cell Transformation, Neoplastic; Liver; Neoplasms; Receptors, Retinoic Acid; Retinyl Esters; Tretinoin; Vitamin A
PubMed: 36047189
DOI: 10.1248/bpb.b22-00315 -
Nutrients Jan 2022Vitamin A, a fat-soluble essential vitamin, is implicated in a large range of physiological processes. Up to now, the associations between vitamin A and metabolic...
Vitamin A, a fat-soluble essential vitamin, is implicated in a large range of physiological processes. Up to now, the associations between vitamin A and metabolic syndrome (MetS) or other metabolic risk factors are controversial in children and adolescents. Thus, we aimed to dig into the relationship of vitamin A with MetS and many other metabolic risk factors. This was a cross-sectional study derived from the China National Nutrition and Health Surveillance of Children and Lactating Mothers. A total of 3025 school-aged (7-17 years) children and adolescents were selected by applying multistage stratified cluster random sampling methods in the Jiangsu Province of eastern China. Through enquiry survey, anthropometric measurement and laboratory examination, relevant information and blood biochemical indexes of the participants were collected in this study. MetS was identified according to the modified criteria of the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III). Multivariate logistic analysis and the generalized additive model (GAM) were used to analyze the relationship between vitamin A and various metabolic risk factors. The overweight, obesity and MetS prevalence of children and adolescents in this study was 14.0%, 11.9% and 5.1%, respectively. The risk of prevalent MetS, general obesity, high low-density lipoprotein (LDL), high total cholesterol (TC) and hyperuricemia increased with vitamin A in a dose-dependent way. Logistic regression analysis showed that serum vitamin A Z scores were positively associated with MetS and central obesity, elevated blood pressure (BP) and elevated triglyceride (TG). Sex stratification analysis showed that both in male and female participants, the risk of prevalent MetS, general obesity, high LDL, high TC and hyperuricemia still increased with vitamin A levels. MetS was at a high prevalence level in children and adolescents in Jiangsu that were 7-17 years old. Vitamin A was positively associated with obesity, MetS, dyslipidemia and hyperuricemia. More public health measures and new visions should focus on the effects of retinol on children and adolescents.
Topics: Adolescent; Adult; Child; China; Cross-Sectional Studies; Female; Humans; Lactation; Male; Risk Factors; Vitamin A
PubMed: 35276969
DOI: 10.3390/nu14030610 -
A review on vitamin A deficiency and depleted immunity in South Asia: From deficiency to resilience.Nutrition (Burbank, Los Angeles County,... Aug 2024In the developing world, the twin challenges of depleted health and growing issue of food waste management loom large, demanding simultaneous attention and innovative... (Review)
Review
In the developing world, the twin challenges of depleted health and growing issue of food waste management loom large, demanding simultaneous attention and innovative solutions. This review explores how these issues can be effectively mitigated while shedding light on the transformative impact of food waste valorization on health management. A spotlight is cast on vitamin A deficiency (VAD), an acute public health concern, especially prevalent in South Asia, driven by economic constraints, sociocultural factors, inadequate diets, and poor nutrient absorption. VAD's devastating effects are exacerbated by limited education, lack of sanitation, ineffective food regulations, and fragile monitoring systems, disproportionately affecting children and women of childbearing age. Recent studies in South Asian countries have revealed rising rates of illness and death, notably among children and women of childbearing age, due to VAD. To address inadequate dietary intake in children utilizing vegetable waste, particularly from carrots and beetroot, which are rich in β-carotene, and betalains, respectively, offers a sustainable solution. Extracting these compounds from vegetable waste for supplementation, fortification, and dietary diversification could significantly improve public health, addressing both food waste and health disparities economically. This approach presents a compelling avenue for exploration and implementation. In summary, this review presents an integrated approach to tackle health and food waste challenges in the developing world. By tapping into the nutritional treasure troves within vegetable waste, we can enhance health outcomes while addressing food waste, forging a brighter and healthier future for communities in need.
Topics: Humans; Vitamin A Deficiency; Asia; Diet; Vitamin A; Female; Vegetables; Child; Developing Countries; Asia, Southern
PubMed: 38669831
DOI: 10.1016/j.nut.2024.112452 -
Experimental Biology and Medicine... May 2021Vitamin A is a fat-soluble vitamin involved in essential functions including growth, immunity, reproduction, and vision. The vitamin A Dietary Reference Intakes (DRIs)... (Review)
Review
Vitamin A is a fat-soluble vitamin involved in essential functions including growth, immunity, reproduction, and vision. The vitamin A Dietary Reference Intakes (DRIs) for North Americans suggested that a minimally acceptable total liver vitamin A reserve (TLR) is 0.07 µmol/g, which is not explicitly expressed as a vitamin A deficiency cutoff. The Biomarkers of Nutrition for Development panel set the TLR cutoff for vitamin A deficiency at 0.1 µmol/g based on changes in biological response of several physiological parameters at or above this cutoff. The criteria used to formulate the DRIs include clinical ophthalmic signs of vitamin A deficiency, circulating plasma retinol concentrations, excretion of vitamin A metabolites in the bile, and long-term storage of vitamin A as protection against vitamin A deficiency during times of low dietary intake. This review examines the biological responses that occur as TLRs are depleted. In consideration of all of the DRI criteria, the review concludes that induced biliary excretion and long-term vitamin A storage do not occur until TLRs are >0.10 µmol/g. If long-term storage is to continue to be part of the DRI criteria, vitamin A deficiency should be set at a minimum cutoff of 0.10 µmol/g and should be set higher during times of enhanced requirements where TLRs can be rapidly depleted, such as during lactation or in areas with high infection burden. In population-based surveys, cutoffs are important when using biomarkers of micronutrient status to define the prevalence of deficiency and sufficiency to inform public health interventions. Considering the increasing use of quantitative biomarkers of vitamin A status that indirectly assess TLRs, i.e. the modified-relative-dose response and retinol-isotope dilution tests, setting a TLR as a vitamin A deficiency cutoff is important for users of these techniques to estimate vitamin A deficiency prevalence. Future researchers and policymakers may suggest that DRIs should be set with regard to optimal health and not merely to prevent a micronutrient deficiency.
Topics: Biomarkers; Humans; Liver; Reference Values; Vitamin A; Vitamin A Deficiency
PubMed: 33765844
DOI: 10.1177/1535370221992731 -
International Journal of Molecular... Mar 2021Bladder cancer (BC) is the tenth most common cancer worldwide with a high recurrence rate, morbidity and mortality. Therefore, chemoprevention and improved treatment of... (Review)
Review
Bladder cancer (BC) is the tenth most common cancer worldwide with a high recurrence rate, morbidity and mortality. Therefore, chemoprevention and improved treatment of BC are of paramount importance. Epidemiological studies suggest that adequate vitamin A intake may be associated with reduced BC risk. In addition, retinoids, natural and synthetic derivatives of vitamin A, are intensively studied in cancer research due to their antioxidant properties and their ability to regulate cell growth, differentiation, and apoptosis. Findings from in vivo and in vitro models of BC show great potential for the use of retinoids in the chemoprevention and treatment of BC. However, translation to the clinical practice is limited. In this narrative review we discuss: (i) vitamin A and retinoid metabolism and retinoic acid signalling, (ii) the pathobiology of BC and the need for chemoprevention, (iii) the epidemiological evidence for the role of dietary vitamin A in BC, (iv) mechanistic insights obtained from in vivo and in vitro models, (v) clinical trials of retinoids and the limitations of retinoid use, (vi) novel systems of retinoid delivery, and (vii) components of retinoid signalling pathways as potential novel therapeutic targets.
Topics: Animals; Anticarcinogenic Agents; Antineoplastic Agents; Apoptosis; Cell Differentiation; Humans; Retinoids; Signal Transduction; Urinary Bladder Neoplasms; Vitamin A
PubMed: 33805295
DOI: 10.3390/ijms22073510