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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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Development of sub-tropically adapted diverse provitamin-A rich maize inbreds through marker-assisted pedigree selection, their characterization and utilization in hybrid breeding.
Duo, H, Hossain, F, Muthusamy, V, Zunjare, RU, Goswami, R, Chand, G, Mishra, SJ, Chhabra, R, Gowda, MM, Pal, S, et al
PloS one. 2021;(2):e0245497
Abstract
Malnutrition has emerged as one of the major health problems worldwide. Traditional yellow maize has low provitamin-A (proA) content and its genetic base in proA biofortification breeding program of subtropics is extremely narrow. To diversify the proA rich germplasm, 10 elite low proA inbreds were crossed with a proA rich donor (HP702-22) having mutant crtRB1 gene. The F2 populations derived from these crosses were genotyped using InDel marker specific to crtRB1. Severe marker segregation distortion was observed. Seventeen crtRB1 inbreds developed through marker-assisted pedigree breeding and seven inbreds generated using marker-assisted backcross breeding were characterized using 77 SSRs. Wide variation in gene diversity (0.08 to 0.79) and dissimilarity coefficient (0.28 to 0.84) was observed. The inbreds were grouped into three major clusters depicting the existing genetic diversity. The crtRB1-based inbreds possessed high β-carotene (BC: 8.72μg/g), β-cryptoxanthin (BCX: 4.58μg/g) and proA (11.01μg/g), while it was 2.35μg/g, 1.24μg/g and 2.97μg/g in checks, respectively. Based on their genetic relationships, 15 newly developed crtRB1-based inbreds were crossed with five testers (having crtRB1 gene) using line × tester mating design. 75 experimental hybrids with crtRB1 gene were evaluated over three locations. These experimental hybrids possessed higher BC (8.02μg/g), BCX (4.69μg/g), proA (10.37μg/g) compared to traditional hybrids used as check (BC: 2.36 μg/g, BCX: 1.53μg/g, proA: 3.13μg/g). Environment and genotypes × environment interaction had minor effects on proA content. Both additive and dominance gene action were significant for proA. The mean proportion of proA to total carotenoids (TC) was 44% among crtRB1-based hybrids, while 11% in traditional hybrids. BC was found to be positively correlated with BCX (r = 0.68) and proA (r = 0.98). However, no correlation was observed between proA and grain yield. Several hybrids with >10.0 t/ha grain yield with proA content >10.0 μg/g were identified. This is the first comprehensive study on development of diverse proA rich maize hybrids through marker-assisted pedigree breeding approach. The findings provides sustainable and cost-effective solution to alleviate vitamin-A deficiency.
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Vitamin A Plasma Levels in COVID-19 Patients: A Prospective Multicenter Study and Hypothesis.
Tepasse, PR, Vollenberg, R, Fobker, M, Kabar, I, Schmidt, H, Meier, JA, Nowacki, T, Hüsing-Kabar, A
Nutrients. 2021;(7)
Abstract
COVID-19 is a pandemic disease that causes severe pulmonary damage and hyperinflammation. Vitamin A is a crucial factor in the development of immune functions and is known to be reduced in cases of acute inflammation. This prospective, multicenter observational cross-sectional study analyzed vitamin A plasma levels in SARS-CoV-2 infected individuals, and 40 hospitalized patients were included. Of these, 22 developed critical disease (Acute Respiratory Distress Syndrome [ARDS]/Extracorporeal membrane oxygenation [ECMO]), 9 developed severe disease (oxygen supplementation), and 9 developed moderate disease (no oxygen supplementation). A total of 47 age-matched convalescent persons that had been earlier infected with SARS-CoV-2 were included as the control group. Vitamin A plasma levels were determined by high-performance liquid chromatography. Reduced vitamin A plasma levels correlated significantly with increased levels of inflammatory markers (CRP, ferritin) and with markers of acute SARS-CoV-2 infection (reduced lymphocyte count, LDH). Vitamin A levels were significantly lower in hospitalized patients than in convalescent persons (p < 0.01). Of the hospitalized patients, those who were critically ill showed significantly lower vitamin A levels than those who were moderately ill (p < 0.05). Vitamin A plasma levels below 0.2 mg/L were significantly associated with the development of ARDS (OR = 5.54 [1.01-30.26]; p = 0.048) and mortality (OR 5.21 [1.06-25.5], p = 0.042). Taken together, we conclude that vitamin A plasma levels in COVID-19 patients are reduced during acute inflammation and that severely reduced plasma levels of vitamin A are significantly associated with ARDS and mortality.
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Vitamin A and D Absorption in Adults with Metabolic Syndrome versus Healthy Controls: A Pilot Study Utilizing Targeted and Untargeted LC-MS Lipidomics.
Chatelaine, H, Dey, P, Mo, X, Mah, E, Bruno, RS, Kopec, RE
Molecular nutrition & food research. 2021;(2):e2000413
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SCOPE Persons with metabolic syndrome (MetS) absorb less vitamin E than healthy controls. It is hypothesized that absorption of fat-soluble vitamins (FSV) A and D2 would also decrease with MetS status and that trends would be reflected in lipidomic responses between groups. METHODS AND RESULTS Following soymilk consumption (501 IU vitamin A, 119 IU vitamin D2 ), the triglyceride-rich lipoprotein fractions (TRL) from MetS and healthy subjects (n = 10 age- and gender-matched subjects/group) are assessed using LC-MS/MS. Absorption is calculated using area under the time-concentration curves (AUC) from samples collected at 0, 3, and 6 h post-ingestion. MetS subjects have ≈6.4-fold higher median vitamin A AUC (retinyl palmitate) versus healthy controls (P = 0.07). Vitamin D2 AUC is unaffected by MetS status (P = 0.48). Untargeted LC-MS lipidomics reveals six phospholipids and one cholesterol ester with concentrations correlating (r = 0.53-0.68; P < 0.001) with vitamin A concentration. CONCLUSIONS The vitamin A-phospholipid association suggests increased hydrolysis by PLB, PLRP2, and/or PLA2 IB may be involved in the trend in higher vitamin A bioavailability in MetS subjects. Previously observed differences in circulating levels of these vitamins are likely not due to absorption. Alternate strategies should be investigated to improve FSV status in MetS.
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Retinol-binding protein, retinol, and modified-relative-dose response in Ugandan children aged 12-23 months and their non-pregnant caregivers.
Whitehead, RD, Ford, ND, Mapango, C, Ruth, LJ, Zhang, M, Schleicher, RL, Ngalombi, S, Halati, S, Ahimbisibwe, M, Lubowa, A, et al
Experimental biology and medicine (Maywood, N.J.). 2021;(8):906-915
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Abstract
Retinol-binding protein (RBP), retinol, and modified-relative-dose response (MRDR) are used to assess vitamin A status. We describe vitamin A status in Ugandan children and women using dried blood spot (DBS) RBP, serum RBP, plasma retinol, and MRDR and compare DBS-RBP, serum RBP, and plasma retinol. Blood was collected from 39 children aged 12-23 months and 28 non-pregnant mothers aged 15-49 years as a subsample from a survey in Amuria district, Uganda, in 2016. DBS RBP was assessed using a commercial enzyme immunoassay kit, serum RBP using an in-house sandwich enzyme-linked immunosorbent assay, and plasma retinol/MRDR test using high-performance liquid chromatography. We examined (a) median concentration or value (Q1, Q3); (b) R2 between DBS-RBP, serum RBP, and plasma retinol; and (c) Bland-Altman plots. Median (Q1, Q3) for children and mothers, respectively, were as follows: DBS-RBP 1.15 µmol/L (0.97, 1.42) and 1.73 (1.52, 1.96), serum RBP 0.95 µmol/L (0.78, 1.18) and 1.47 µmol/L (1.30, 1.79), plasma retinol 0.82 µmol/L (0.67, 0.99) and 1.33 µmol/L (1.22, 1.58), and MRDR 0.025 (0.014, 0.042) and 0.014 (0.009, 0.019). DBS RBP-serum RBP R2 was 0.09 for both children and mothers. The mean biases were -0.19 µmol/L (95% limits of agreement [LOA] 0.62, -0.99) for children and -0.01 µmol/L (95% LOA -1.11, -1.31) for mothers. DBS RBP-plasma retinol R2 was 0.11 for children and 0.13 for mothers. Mean biases were 0.33 µmol/L (95% LOA -0.37, 1.03) for children, and 0.29 µmol/L (95% LOA -0.69, 1.27) for mothers. Serum RBP-plasma retinol R2 was 0.75 for children and 0.55 for mothers, with mean biases of 0.13 µmol/L (95% LOA -0.23, 0.49) for children and 0.18 µmol/L (95% LOA -0.61, 0.96) for mothers. Results varied by indicator and matrix. The serum RBP-retinol R2 for children was moderate (0.75), but poor for other comparisons. Understanding the relationships among vitamin A indicators across contexts and population groups is needed.
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Should Vitamin A Injections to Prevent Bronchopulmonary Dysplasia or Death Be Reserved for High-Risk Infants? Reanalysis of the National Institute of Child Health and Human Development Neonatal Research Network Randomized Trial.
Rysavy, MA, Li, L, Tyson, JE, Jensen, EA, Das, A, Ambalavanan, N, Laughon, MM, Greenberg, RG, Patel, RM, Pedroza, C, et al
The Journal of pediatrics. 2021;:78-85.e5
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OBJECTIVE To determine whether infants at higher risk of bronchopulmonary dysplasia (BPD) or death benefit more from vitamin A therapy than those at lower risk. STUDY DESIGN We conducted a post hoc reanalysis of a landmark phase III randomized controlled trial conducted from January 1996 to July 1997 at 14 university-affiliated neonatal intensive care units in the US. Data analysis was performed from October 2019 to October 2020. Infants born weighing 401-1000 g and receiving respiratory support at 24 hours of age were assigned to intramuscular vitamin A 5000 IU or sham procedure 3 times weekly for 4 weeks. The primary outcome was BPD, defined as use of supplemental oxygen, or death at 36 weeks postmenstrual age. An externally validated model for predicting BPD or death was used to estimate the risk of these outcomes for each infant. RESULTS As previously reported, 222 of 405 infants (54.8%) assigned vitamin A therapy and 248 of 402 infants (61.7%) in the control group developed BPD or died (relative risk [RR], 0.89 [95% CI, 0.80-0.99]; risk difference [RD], -6.9% [95% CI, -13.0 to -0.7]). The predicted individual risks of BPD or death ranged from 7.1% to 98.6% (median, 61.5%; mean, 60.9%). The effect of vitamin A therapy on BPD or death depended on infants' risk of the primary outcome (P = .03 for interaction): for example, a RR of 0.73 (RD, -14.5%) for infants with a 25% predicted risk and a RR of 0.96 (RD, -1.0%) for infants with a 75% risk. There was no difference in the decrease in vitamin A deficiency across risk groups. CONCLUSIONS Contrary to expectations, the effect of vitamin A therapy on BPD or death was greater for lower risk than higher risk infants. TRIAL REGISTRATION ClinicalTrials.gov NCT01203488.
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Clinical Olfactory Working Group consensus statement on the treatment of postinfectious olfactory dysfunction.
Addison, AB, Wong, B, Ahmed, T, Macchi, A, Konstantinidis, I, Huart, C, Frasnelli, J, Fjaeldstad, AW, Ramakrishnan, VR, Rombaux, P, et al
The Journal of allergy and clinical immunology. 2021;(5):1704-1719
Abstract
BACKGROUND Respiratory tract viruses are the second most common cause of olfactory dysfunction. As we learn more about the effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with the recognition that olfactory dysfunction is a key symptom of this disease process, there is a greater need than ever for evidence-based management of postinfectious olfactory dysfunction (PIOD). OBJECTIVE Our aim was to provide an evidence-based practical guide to the management of PIOD (including post-coronavirus 2019 cases) for both primary care practitioners and hospital specialists. METHODS A systematic review of the treatment options available for the management of PIOD was performed. The written systematic review was then circulated among the members of the Clinical Olfactory Working Group for their perusal before roundtable expert discussion of the treatment options. The group also undertook a survey to determine their current clinical practice with regard to treatment of PIOD. RESULTS The search resulted in 467 citations, of which 107 articles were fully reviewed and analyzed for eligibility; 40 citations fulfilled the inclusion criteria, 11 of which were randomized controlled trials. In total, 15 of the articles specifically looked at PIOD whereas the other 25 included other etiologies for olfactory dysfunction. CONCLUSIONS The Clinical Olfactory Working Group members made an overwhelming recommendation for olfactory training; none recommended monocycline antibiotics. The diagnostic role of oral steroids was discussed; some group members were in favor of vitamin A drops. Further research is needed to confirm the place of other therapeutic options.
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Vitamin A supplementation prevents the bronchopulmonary dysplasia in premature infants: A systematic review and meta-analysis.
Ding, Y, Chen, Z, Lu, Y
Medicine. 2021;(3):e23101
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Abstract
BACKGROUND It is necessary to evaluate the effectiveness and safety of vitamin A supplementation on the bronchopulmonary dysplasia (BPD) in premature infants. METHODS Randomized controlled trials (RCTs) on the role of supplemental vitamin A in preterm infants were searched. The Medline et al databases were manually searched from inception to April 30, 2020. Related outcomes including incidence of BPD, retinopathy of prematurity (ROP), necrotizing enterocolitis (NEC), intraventricular hemorrhage (IVH), sepsis and mortality were assessed with Review Manager 5.3 software, and Random-effect model was applied for all conditions. RESULTS A total of 9 RCTs with 1409 patients were included. The analyzed results showed that the incidence of BPD in vitamin A group was significantly less than that of control group (OR = 0.67, 95%CI [0.52-0.88]). There was no significant difference in the incidence of ROP (OR = 0.65, 95%CI [0.29-1.48]), NEC (OR = 0.88, 95%CI [0.59-1.30]), IVH (OR = 0.90, 95%CI [0.65-1.25]), sepsis (OR = 0.84, 95%CI [0.64-1.09]) and mortality (OR = 0.98, 95%CI [0.72-1.34]) among two groups. CONCLUSION Vitamin A supplementation is beneficial to the prophylaxis of BPD in premature infants, further studies on the administration approaches and dosages of vitamin A in premature infants are warranted.
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Observation for clinical effect of acupuncture combined with conventional therapy in the treatment of acne vulgaris.
Kou, L, Yu, N, Ren, J, Yang, B, Tao, Y
Medicine. 2020;(18):e19764
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INTRODUCTION Acne vulgaris is a chronic inflammatory disease of the sebaceous glands that occurs in adolescent men and women. In recent years, the incidence of acne has increased year by year, so it is of great significance to find a precise and effective treatment and further explore its possible mechanism of action. The purpose of this study will be to explore a treatment method that has both traditional Chinese medicine characteristics and significant effects, and provides a higher level of evidence for acupuncture for acne vulgaris. It also provides patients with more treatment options. METHODS/DESIGN The study will be a randomized controlled trial divided into 2 parallel groups. This pragmatic randomized controlled trial will recruit 66 patients who are diagnosed with acne vulgaris. 30-minutes acupuncture sessions will be provided to patients assigned to the intervention group. All participants will continue to receive conventional treatment. The selection of outcomes will be evaluated by the skin lesions score scale. DISCUSSION This trial may provide evidence regarding the clinical effectiveness, safety, and cost-effectiveness of acupuncture for patients with acne vulgaris. TRIAL REGISTRATION NUMBER CTR2000030427.
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Dietary vitamin A intake and the risk of ovarian cancer: a meta-analysis.
Wang, Q, He, C
Bioscience reports. 2020;(4)
Abstract
BACKGROUND Previous studies have demonstrated some associations between dietary vitamin A intake and ovarian cancer risk with an inconsistent relationship. We therefore performed the present study to further explore the association between them. METHODS Databases of PubMed, Embase, and Web of Science were retrieved up to September 1, 2019. Summarized relative risk (RR) with corresponding 95% confidence intervals (CI) were calculated. Stata 14.0 software was used for data analysis. RESULTS Fifteen articles involving 4882 cases and 443,179 participants were included in this meta-analysis. A positive association between dietary vitamin A intake and ovarian cancer risk was found (RR = 0.816, 95%CI = 0.723-0.920, I2 = 48.4%, Pfor heterogeneity = 0.019). Significant association was also found in case-control studies (RR = 0.769, 95%CI = 0.655-0.902), but not in cohort studies. When we performed the analysis between ovarian cancer risk and geographic locations, we found an inverse association in North American populations (RR = 0.825, 95%CI = 0.720-0.946), instead of other populations. CONCLUSIONS In summary, findings from the present study suggested that higher dietary intake of vitamin A may contribute to the lower development of ovarian cancer, especially among North Americans.