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Antioxidant interventions in autism spectrum disorders: A meta-analysis.
Liu, Y, Yang, Z, Du, Y, Shi, S, Cheng, Y
Progress in neuro-psychopharmacology & biological psychiatry. 2022;:110476
Abstract
BACKGROUND Autism spectrum disorder (ASD) might be associated with oxidative stress, and antioxidants are commonly used in the treatment of young people with ASD. However, the evidence about the effectiveness of these interventions remains debatable. We performed a meta-analysis to evaluate the effect of antioxidants on the symptoms of patients with autism. METHODS Data sources: PubMed and Web of Science databases. STUDY SELECTION We selected placebo-controlled, double-blind, randomized clinical trials published until February 2021 to evaluate the efficacy of antioxidant interventions on ASD. DATA ANALYSIS Aberrant Behavior Checklist (ABC), Repetitive Behavior Scale-Revised (RBS), Social Responsiveness Scale (SRS), Developmental Behavior Checklist (DBC) and Clinical Global Impressions Severity scale (CGIS) were used to evaluate the 22 different symptom outcomes. The Hedges-adjusted g value was used to estimate the effect of each dietary intervention relative to the placebo. RESULTS In this meta-analysis, we examined 13 double-blind randomized clinical trials, comprising a total of 570 patients with ASD: 293 in the intervention group and 277 in the placebo group. Antioxidants (N-acetylcysteine (NAC), other antioxidants) are more effective than placebos in improving the irritability among symptoms in the ABC and communication disturbance symptoms in the DBC. There was a good trend of improvement in the stereotypic behavior symptoms in the ABC. Treatment with NAC antioxidants showed a good trend of improvement in irritability in the ABC and symptoms of hyperactivity. The effect size was small, and there was a low risk of statistical heterogeneity and publication bias. LIMITATIONS The number of studies in this meta-analysis was small and the sample size was small. CONCLUSION This meta-analysis suggests that antioxidant intervention has a potential role in the management of some symptoms in patients with ASD, and indicates the feasibility of using antioxidants to treat autism in the future.
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Systematic Review and Meta-Analysis of Oxidative Stress and Antioxidant Markers in Oral Lichen Planus.
Wang, J, Yang, J, Wang, C, Zhao, Z, Fan, Y
Oxidative medicine and cellular longevity. 2021;:9914652
Abstract
BACKGROUND Oral lichen planus (OLP) is a relatively common chronic inflammatory disease of unknown etiology, which might be caused by oxidative stress and impaired antioxidant defense. OBJECTIVE To systematically investigate the markers of oxidative stress and antioxidant systems in the saliva and blood from OLP patients and healthy controls. METHODS The PubMed, Cochrane Library, and Embase were systematically queried to collect data from studies in which oxidative stress/antioxidant markers from OLP and healthy subjects had been evaluated until March 10, 2021. RESULTS A total of 28 studies fulfilled inclusion criteria, and 25 of them, having 849 OLP patients and 1,052 control subjects and analyzing 12 oxidative stress and antioxidant state marker levels, were subjected to meta-analysis. We found a significant decrease in total antioxidant capacity (TAC) and uric acid (UA) and a significant increase in malondialdehyde (MDA) and nitric oxide (NO) levels in the saliva and serum/plasma of OLP patients. Moreover, a significant elevation of 8-hydroxy-deoxyguanosine (8-OHdG) and advanced oxidation protein product (AOOP) level and a decrease in vitamin C were also observed in the saliva of the OLP group. In contrast, salivary vitamin A, zinc, glutathione peroxidase (GPx), vitamin E, and nitrite were not significantly different between the two groups. In single studies, markers of oxidative stresses such as superoxide dismutase (SOD) and 8-isoprostanelevels were elevated in OLP, and antioxidant parameters such as glutathione (GSH) and total protein (TP) levels were dysregulated. CONCLUSION This meta-analysis helps to clarify the profile of oxidative stress and antioxidant state markers in OLP patients although existing evidence is rather heterogeneous and many studies are affected by several limitations. Larger and more standardized studies are warranted to ascertain whether these markers are potential causes or effects of OLP and whether antioxidant therapy improving oxidative stress will be useful.
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Vitamin C and COVID-19 treatment: A systematic review and meta-analysis of randomized controlled trials.
Rawat, D, Roy, A, Maitra, S, Gulati, A, Khanna, P, Baidya, DK
Diabetes & metabolic syndrome. 2021;(6):102324
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Abstract
BACKGROUND AND AIMS Vitamin C has been used as an anti-oxidant in various diseases including viral illnesses like coronavirus disease (COVID-19). METHODS Meta-analysis of randomized controlled trials (RCT) investigating the role of vitamin C supplementation in COVID-19 was carried out. RESULTS Total 6 RCTs including n = 572 patients were included. Vitamin C treatment didn't reduce mortality (RR 0.73, 95% CI 0.42 to 1.27; I2 = 0%; P = 0.27), ICU length of stay [SMD 0.29, 95% CI -0.05 to 0.63; I2 = 0%; P = 0.09), hospital length of stay (SMD -0.23, 95% CI -1.04 to 0.58; I2 = 92%; P = 0.57) and need for invasive mechanical ventilation (Risk Ratio 0.93, 95% CI 0.61 to 1.44; I2 = 0%; P = 0.76). Further sub-group analysis based on severity of illness (severe vs. non-severe), route of administration (IV vs. oral) and dose (high vs. low) failed to show any observable benefits. CONCLUSION No significant benefit noted with vitamin C administration in COVID-19. Well-designed RCTs with standardized control group needed on this aspect.
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The role of probucol preventing contrast-induced nephropathy in patients undergoing invasive coronary procedures - Systematic review and meta-analysis of randomized controlled trials.
Pranata, R, Yonas, E, Vania, R, Lukito, AA
Turk Kardiyoloji Dernegi arsivi : Turk Kardiyoloji Derneginin yayin organidir. 2021;(1):51-59
Abstract
OBJECTIVE The aim of this meta-analysis was to synthesize the latest evidence on the effect of probucol on the incidence of contrast-induced nephropathy (CIN) in patients undergoing coronary angiography (CAG)/percutaneous coronary intervention (PCI). METHODS A systematic literature search of PubMed, ScienceDirect, EuropePMC, ProQuest, and Clinicaltrials. gov was performed to retrieve studies that assessed probucol and CIN in CAG/PCI. RESULTS Four studies that compared probucol with hydration alone, comprising 1270 subjects, were identified and analyzed. There was no significant difference between probucol and control groups in the baseline level of creatinine and at 48 hours; however, a significant difference was observed at 72 hours (mean difference: -3.87 μmol/L; 95% confidence interval [CI]: -6.58, -1.15; p=0.005). The meta-analysis indicated that probucol did not reduce the CIN incidence (odds ratio [OR]: 0.46; 95% CI: 0.20, 1.08; p=0.08). After performing a leave-one-out sensitivity analysis, removal of a study resulted in a lower risk of CIN (OR: 0.33; 95% CI: 0.19, 0.56; p<0.001). Probucol did not reduce the CIN incidence in a pooled adjusted effect estimate (OR: 0.75; 95% CI: 0.15, 3.87; p=0.73). There was no significant difference in the rate of major adverse events between the 2 groups (OR: 0.39; 95% CI: 0.05, 3.05; p=0.37). Funnel plot results were asymmetrical, indicating possible publication bias. Grading of Recommendations, Assessment, Development and Evaluations qualification demonstrated a low and very low certainty of evidence in unadjusted and adjusted effect estimates, respectively. CONCLUSION Probucol did not reduce the incidence of CIN; however, due to the low certainty of evidence, further study is required for a definite conclusion. Although the p value was not significant, the confidence interval showed a nonsignificant trend toward benefit. However, this trend might have been due to publication bias.
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Oxidative and antioxidative stress markers in keratoconus: a systematic review and meta-analysis.
Navel, V, Malecaze, J, Pereira, B, Baker, JS, Malecaze, F, Sapin, V, Chiambaretta, F, Dutheil, F
Acta ophthalmologica. 2021;(6):e777-e794
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PURPOSE To conduct a systematic review and meta-analysis on the levels of oxidative stress markers and antioxidants in keratoconus compared to healthy subject. METHOD The PubMed, Cochrane Library, Embase, Science Direct and Google Scholar databases were searched on 1st June 2020 for studies reporting oxidative and antioxidative stress markers in keratoconus and healthy controls. Main meta-analysis was stratified by type of biomarkers, type of samples (tears, cornea, aqueous humour and blood) and type of corneal samples (stromal cells, epithelium and endothelium). RESULTS We included 36 articles, for a total of 1328 keratoconus patients and 1208 healthy controls. There is an overall increase in oxidative stress markers in keratoconus compared with healthy controls (standard mean deviation (SMD) = 0.94, 95% confidence interval (95% CI) 0.55-1.33), with a significant increase in reactive oxygen and nitrogen species (1.09, 0.41-1.78) and malondialdehyde (1.78, 0.83-2.73). There is an overall decrease in antioxidants in keratoconus compared with healthy controls (-0.63, -0.89 to -0.36), with a significant decrease in total antioxidant capacity/status (-1.65, -2.88 to -0.43), aldehyde/NADPH dehydrogenase (-0.77, -1.38 to -0.17), lactoferrin/transferrin/albumin (-1.92, -2.96 to -0.89) and selenium/zinc (-1.42, -2.23 to -0.61). Oxidative stress markers were higher in tears and in cornea of keratoconus than in aqueous humour, and antioxidants were decreased in tears, aqueous humour and blood without difference between sample type. Oxidative stress markers increased in stromal cells and antioxidants decreased in endothelium. CONCLUSION Oxidative stress markers and antioxidants were dysregulated in keratoconus, involving an imbalance of redox homeostasis in tears, cornea, aqueous humour and blood.
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Antioxidant micronutrient supplementation in critically ill adults: A systematic review with meta-analysis and trial sequential analysis.
Gudivada, KK, Kumar, A, Shariff, M, Sampath, S, Varma, MM, Sivakoti, S, Krishna, B
Clinical nutrition (Edinburgh, Scotland). 2021;(3):740-750
Abstract
BACKGROUND The role of antioxidant micronutrient (AxM) supplementation in the critically ill patients has been controversial, and recent trials have suggested a tendency to harm. Therefore, we performed a systematic review with meta-analysis and trial sequential analysis (TSA) of randomized controlled trials (RCT) to examine the effect of AxM supplementation on clinical outcomes among critically ill adults. METHODS PubMed, EMBASE, Cochrane, CINAHL, LILACS, DARE, SCOPUS, and Web of sciences databases were searched from inception to March 2019. RCTs that compared AxM supplements with placebo in adult critically ill patients and reporting mortality as an outcomes were included. Trial quality was assessed using updated cochrane risk of bias (RoB-II) tool. Primary outcome was all-cause mortality. Secondary outcomes were 28-day mortality, intensive care unit (ICU) and hospital length of stay (LOS), ventilator days and infection between the two groups. Outcomes were summarised using random-effects estimators. Quality of evidence (QOE) was rated using Grading of Recommendations, Assessment, Development and Evaluation. Prior to final analysis, we repeated the search through September 2019. R version 3.6.2 and STATA version 13 were used for all statistical analyses. RESULTS Pooled analysis of 34 trials with 4678 patients revealed that AxM supplementation was associated with possible reduction in all-cause mortality (relative risk [RR], 0.89 [95%CI 0.79 to 0.99], TSA adjusted CI 0.77 to 1.03; Low QOE). Fragility index and number needed to treat were 1 and 41, respectively. Eight studies with low RoB (RR, 1.08; 95%CI 0.95 to 1.23; TSA CI, 0.64 to 1.82; moderate QOE) did not show mortality reduction with AxM supplementation. SECONDARY OUTCOMES ICU LOS (weighted mean difference [WMD], -0.84; 95%CI -1.50 to -0.18; moderate QOE), hospitalization days (WMD, -2.83; 95%CI -3.91to -1.75; low QOE) and ventilator days (WMD, -1.87; 95%CI -3.60 to -0.14; very low QOE) showed a statistically significant benefit with AxM supplementation. In meta-regression analysis, neither the duration of AxM therapy nor the dosage of selenium, which was the most widely studied AxM, reported an association with mortality. CONCLUSION Although AxM supplementation was associated with possible reduction in all-cause mortality, results from the TSA and studies with low RoB showing null effect suggest that the evidence of benefit is questionable. Secondary outcomes attained statistically significant benefit with AxM supplements, but the certainity of evidence was low. To summarize, current evidence does not justify administration of AxM in critically ill patients. REGISTRATION PROSPERO, CRD42019125898.
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Redox signaling and antioxidant therapies in acute respiratory distress syndrome: a systematic review and meta-analysis.
Bo, L, Jin, F, Ma, Z, Li, C
Expert review of respiratory medicine. 2021;(10):1355-1365
Abstract
Objectives: No pharmacologic treatment that targets the pathophysiologic alterations of acute respiratory distress syndrome (ARDS) has proven effective. Previous studies have revealed overactive oxidative stress as a potential therapeutic target. Thus we conducted this systematic review to assess the efficacyof antioxidant therapy on the clinical outcomes of ARDS patients.Methods: We retrieved clinical trials from electronic databases. Articles and conference abstracts about antioxidant therapies for patients with ARDS were identified in which the overall effect of each antioxidant therapy on the mortality of ARDS patients was summarized.Results: We identified 18 relevant studies that met the inclusion criteria, including 899 patients in the experimental group and 870 patients in the control group. The pooled results indicated that most antioxidant therapies could not improve all-cause mortality and might even be harmful in ARDS patients at low risk of death.Conclusion: Unclassified patients could not benefit from the antioxidant therapies, and thus discretion must be exercised when using these therapies.Abbreviations ARDS Acute respiratory distress syndrome; ICU: Intensive care unit; NAC: N-acetylcysteine; ROS: Reactive oxygen species; RNS: Reactive nitrogen species; RR: Relative risk; CI: Confidence interval; OTC: L-2-oxothiazolidine-4-carboxylic acid; EPA: Eicosapentaenoic acid; DHA: Docosahexaenoic acid; GLA: Gamma-linolenic acid; NA: Not applicable; PaO2/FiO2 ratio: The ratio of partial pressure arterial oxygen and fraction of inspired oxygen; ALI: Acute lung injury.
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Effects of resveratrol supplementation on bone quality: a systematic review and meta-analysis of randomized controlled trials.
Li, Q, Yang, G, Xu, H, Tang, S, Lee, WY
BMC complementary medicine and therapies. 2021;(1):214
Abstract
BACKGROUND The results from clinical trials have revealed that the effects of resveratrol supplementation on bone mineral density (BMD) and bone biomarkers are inconsistent. Our objective was to determine the effects of resveratrol supplementation on BMD and serum bone biomarkers. METHODS PubMed, Cochrane library, EMBASE, Web of science and Scopus were searched up to August 24, 2020. Two reviewers independently performed the articles search and screen according to defined selection criteria. The study quality of the randomized controlled trials (RCTs) was evaluated with the Cochrane scoring system. Heterogeneity among studies was examined by Cochrane Q test. Retrieved data were pooled after mean differences (MD) were computed between two groups for BMD and serum biomarkers. Subgroup analyses were performed to evaluate a potential difference in terms of dose of resveratrol and intervention duration. Sensitivity analysis was executed by omitting studies with imputed values in order to evaluate the influence of these studies on the overall results. RESULTS Ten eligible studies involving 698 subjects were included in this meta-analysis with 401 participants receiving resveratrol and 297 receiving placebo. Supplementation of resveratrol had no statistically significant effects on areal bone mineral density (aBMD) at lumbar spine (MD: -0.02, 95% CI: - 0.05, 0.01, p = 0.26, I2 = 6%), total hip BMD (MD: -0.01, 95% CI: - 0.04, 0.02, p = 0.65, I2 = 0%), and whole body BMD (MD: 0.00, 95% CI: - 0.02, 0.02, p = 0.74, I2 = 0%). Supplementation of resveratrol also did not result in significant change in bone serum markers, including serum alkaline phosphatase (ALP), bone alkaline phosphatase (BAP), osteocalcin (OCN), procollagen I N-terminal propeptide (PINP), C-terminal telopeptide of type I collagen (CTX) and parathyroid hormone (PTH). Subgroup analysis showed the effect of resveratrol supplementation on BMD and serum bone markers were similar in trails of different doses, intervention duration, and pathological conditions of the participants. CONCLUSION Resveratrol supplementation did not show any significant effect on BMD or serum bone markers with the current evidence. Further investigation with more well-organized multicentre randomized trial is warranted.
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Post-Diagnosis use of Antioxidant Vitamin Supplements and Breast Cancer Prognosis: A Systematic Review and Meta-Analysis.
Li, Y, Lin, Q, Lu, X, Li, W
Clinical breast cancer. 2021;(6):477-485
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Abstract
Antioxidant vitamin supplements (AVSs) are widely used among breast cancer survivors. Whether post-diagnosis use of AVSs would impair cancer survival is unclear. To assess the association between breast cancer survival and post-diagnosis AVSs use. We performed a literature search using PubMed, Cochrane Library, and Embase from their inception to October 1, 2020. Studies that investigated the association between breast cancer survival and post-diagnosis AVS use included. The AVSs included 1 or more of the following: vitamin A, C, or E. The meta-analysis included 8 studies with 17,062 patients. There was no significant difference between AVS use or not after diagnosis (HR 0.92, 95% CI 0•82-1•03) or during chemotherapy (HR 1.15, 95% CI 0.78-1.68) in overall survival (OS). Whenever during chemotherapy or after diagnosis, AVS users had a worse prognosis in the later studies. There was no significant inverse association between post-diagnosis vitamin A or E supplements use and OS. Vitamin C intake after breast cancer diagnosis was significantly associated with better OS (HR 0.84, 95% CI 0.76-0.93). Our findings suggest that post-diagnosis AVSs use would not worsen breast cancer survival, while vitamin C use after diagnosis might benefit OS. The discrepancy of survivals associated with post-diagnosis AVS use between earlier and later studies may cast doubt on the recommendation on guidelines. RCTs with large sample sizes are needed.
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Systematic review with meta-analysis: The effect of vitamin E supplementation in adult patients with non-alcoholic fatty liver disease.
Vadarlis, A, Antza, C, Bakaloudi, DR, Doundoulakis, I, Kalopitas, G, Samara, M, Dardavessis, T, Maris, T, Chourdakis, M
Journal of gastroenterology and hepatology. 2021;(2):311-319
Abstract
BACKGROUND AND AIM Νon-alcoholic fatty liver disease (NAFLD) is estimated to be the most common cause of end-stage liver disease in the next years. Vitamin E has shown beneficial effects as a possible "scavenger" of oxidative stress products, which play a major role in pathogenesis of the disease. The purpose of the present meta-analysis is to investigate the effects of vitamin E supplementation in biochemical and histological parameters in adult patients with NAFLD. METHODS Literature search was performed in major electronic databases (MEDLINE, CENTRAL, and Embase) up to June 2020 for randomized clinical trials, which examined vitamin E versus placebo treatment in adults with NAFLD. Changes in liver enzymes were considered as primary outcomes while changes in histological, biochemical, and metabolic parameters as secondary. Quality of evidence was assessed through risk of bias according to the Cochrane risk of bias tool. RESULTS Eight studies were included in qualitative analysis and seven in quantitative analysis. Vitamin E reduced the values of liver enzymes compared with placebo (-7.37 IU/L, 95% confidence interval: -10.11 to -4.64 for alanine aminotransferase, and -5.71 IU/L, 95% confidence interval: -9.49 to -1.93 for aspartate aminotransferase). Additionally, vitamin E improved statistically significantly liver pathology in every individual histological parameter as well as low-density lipoprotein cholesterol, fasting blood glucose, and serum leptin values. CONCLUSIONS Vitamin E can improve biochemical and histological characteristics of NAFLD patients, especially of non-alcoholic steatohepatitis patients. The results indicate that vitamin E could be a promising choice and be considered as a treatment option in patients with NAFLD.