Role of Antioxidant Therapy in the Treatment and Prognosis of COVID-19: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

Background: A significant aspect of the SARS-CoV-2 pathology involves oxidative stress, characterized by an imbalance between the production of harmful free radicals and the body's antioxidant defenses. With the ongoing evolution of SARS-CoV-2, the investigation into non-virus-specific therapeutic options, such as antioxidant therapy, has gained importance. Objectives: This systematic review and meta-analysis aimed to summarize data from randomized control trials (RCTs) to evaluate the effectiveness and safety of antioxidant therapy in patients with SARS-CoV-2 infection. Methods: We searched the peer-reviewed indexed literature on MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), CINAHL, EMBASE, International Pharmaceutical Abstracts, and Scopus, from inception to July 2023. Results: The search identified 3306 articles from which 25 were included for quantitative synthesis, with 5 studies eligible for meta-analysis. Antioxidant therapies included zinc, vitamin A, vitamin C, and combination treatments. Zinc interventions showed mixed results regarding intensive care unit admissions and hospital stays. Vitamin A studies indicated improvements in inflammatory markers. Vitamin C studies displayed inconsistent effects on clinical improvement and hospitalization. Combination treatments suggested benefits in symptom clearance and cytokine storm reduction. Meta-analysis of vitamin C studies found no significant difference in C-reactive protein concentrations (-0.50; 95% CI: -3.63, 2.63; I2 = 0%), intensive care unit stay duration (pooled mean difference: 1.44; 95% CI: 0.07, 2.81; I2 = 0%), or mortality (pooled odds ratio: 0.55; 95% CI: 0.28, 1.09; I2 = 0%), with a slight trend favoring reduced hospitalization duration (pooled mean difference: -2.37; 95% CI: -2.99, -1.76; I2 = 49%). Of the 25 studies, 8 were high quality with low bias, 6 had some concerns, and 11 were low quality with high bias. Conclusions: The review presents mixed efficacy of antioxidant therapies for SARS-CoV-2, with some studies indicating potential benefits. Further well-designed large-scale RCTs are warranted to determine the definitive role of antioxidants in SARS-CoV-2 treatment.This systematic review was registered at PROSPERO as CRD42023430805.

Dietary pattern in autism increases the need for probiotic supplementation: A comprehensive narrative and systematic review on oxidative stress hypothesis.

Autism spectrum disorders (ASDs) are associated with specific dietary habits, including limited food selection and gastrointestinal problems, resulting in an altered gut microbiota. Autistic patients have an elevated abundance of certain gut bacteria associated with increased oxidative stress in the gastrointestinal tract. Probiotic supplementation has been shown to decrease oxidative stress in a simulated gut model, but the antioxidant effects of probiotics on the oxidative stress of the gut in autistic patients have not been directly studied. However, it is speculated that probiotic supplementation may help decrease oxidative stress in the gastrointestinal tract of autistic patients due to their specific dietary habits altering the microbiota. PubMed, Scopus and Web of Science databases and Google Scholar were searched up to May 2023. This systematic-narrative review aims to present the latest evidence regarding the changes in eating habits of autistic children which may further increase the gut microbiota induced oxidative stress. Additionally, this review will assess the available literature on the effects of probiotic supplementation on oxidative stress parameters.

Concordance in COVID-19 serology, bone mineralization, and inflammatory analytes between venous and self-collected capillary blood samples exposed to various pre-analytical conditions.

BACKGROUND: The COVID-19 has led to a significant increase in demand for remote blood sampling in clinical trials. This study aims to ascertain the concordance between venous versus capillary samples, processed immediately or exposed to various pre-analytical conditions. METHODS: Participants (≥12 years old) provided a venous blood sample (processed immediately) and capillary samples allocated to one of the following conditions: processed immediately or exposed to 12-, 24-, or 36-h delays at room temperature or 36-h delays with a freeze-thaw cycle. The analytes of interest included SARS-CoV-2 IgG, 25-hydroxy vitamin D (25(OH)D), alkaline phosphate (ALP), calcium (Ca), phosphate (Ph), and c-reactive protein (CRP). Paired samples were considered interchangeable if they met three criteria: minimal within-subject mean difference, 95% of values within desirable total errors, and inter-class correlation (ICC) > 0.90. RESULTS: 90 participants (44.1% male) were enrolled. When comparing rapidly processed venous with capillary samples, 25(OH)D, ALP, and CRP met all three criteria; SARS-CoV-2 IgG met two criteria (mean difference and ICC); and Ca and Ph met one criterion (mean difference). When considering all three criteria, concentrations of 25(OH)D, CRP, and ALP remained unchanged after delays of up to 36 h; SARS-CoV-2 IgG met two criteria (mean difference and ICC); Ca and Ph met one criterion (mean difference). CONCLUSION: These findings suggest that remote blood collection devices can be used to measure anti-SARS-CoV-2 IgG, 25(OH)D, CRP, and ALP. Further analysis is required to evaluate the interchangeability between venous and capillary testing in Ca and Ph levels, which are more sensitive to pre-analytical conditions.

Oral vitamin D supplemental therapy to attain a desired serum 25-hydroxyvitamin D concentration in essential healthcare teams.

BACKGROUND: The study objectives were to ascertain the efficacy of vitamin D supplementation in rapidly increasing serum vitamin D and of implementation of a hybrid (virtual and in-person) trial. METHODS: In a randomized triple-blind controlled trial, healthcare workers were allocated to receive an oral bolus of 100,000 IU with 10,000 IU/week of vitamin D3 or placebo. The co-primary outcomes were the change from baseline in serum 25-hydroxyvitamin D [(Δ) 25(OH)D] and proportion with vitamin D sufficiency (25(OH)D ≥ 75 nmol/L), at endpoint. Adherence to supplements and procedures as well as adverse event rates were documented. RESULTS: Thirty-four (19 intervention, 15 control) subjects were randomized, with 28 (41%) virtual visits. After 44.78 ± 11.00 days from baseline, a significant adjusted group difference of 44.2 (34.7, 53.8) nmol/L was observed in the Δ 25(OH)D (95% CI) in favor of supplementation; 77.8% of intervention, and 13.3% of control, patients were vitamin D sufficient (OR:6.11, 95% CI:1.6, 22.9). The adherence to intervention was 94.7% in the intervention and 100% in the control groups. Irrespective of visit type, high adherence was observed in sampling procedures and completion of fortnightly online questionnaire. No adverse events attributable to vitamin D were reported. CONCLUSION: The vitamin D supplementation rapidly and safely raised 25(OH)D levels to sufficient levels for a biological effect. Similarly high adherence to study procedures was observed with virtual and in-person participation. TRIAL REGISTRATION: This trial was registered at https://clinicaltrials.gov on July 23, 2020 (# NCT04483635 ).

Reply to Leong et al. Comment on "Hosseini et al. Effects of Vitamin D Supplementation on COVID-19 Related Outcomes: A Systematic Review and Meta-Analysis. Nutrients 2022, 14, 2134".

We thank Drs. Leong et al. for their comments [...].

Children With Asthma Have Impaired Innate Immunity and Increased Numbers of Type 2 Innate Lymphoid Cells Compared With Healthy Controls.

Background: Asthma is the most frequent cause of hospitalisation among children; however, little is known regarding the effects of asthma on immune responses in children. Objective: The present study aimed to evaluate cytokine responses of peripheral blood mononuclear cells (PBMCs), PBMC composition and lung function in children with and without asthma. Methods: Using a case-control design, we compared 48 children with asthma aged 3-11 years with 14 age-matched healthy controls. PBMC composition and cytokine production including interferon (IFN)-γ, interleukin (IL)-1ß, IL-5 and lL-6 following stimulation with rhinovirus-1B (RV1B), house dust mite (HDM) and lipopolysaccharide (LPS) were measured. Lung function was assessed using impulse oscillometry and nitrogen multiple breath washout. Results: The frequency of group 2 innate lymphoid cells were significantly higher in asthmatics and PBMCs from asthmatics had deficient IFN-γ production in response to both RV1B and LPS compared with controls (P<0.01). RV1B-induced IL-1ß response and HDM-stimulated IL-5 production was higher in asthmatics than controls (P<0.05). In contrast, IL-1ß and IL-6 were significantly reduced in response to HDM and LPS in asthmatics compared to controls (P<0.05). Children with asthma also had reduced pulmonary function, indicated by lower respiratory reactance as well as higher area of-reactance and lung clearance index values compared with controls (P<0.05). Conclusion: Our study indicates that children with asthma have a reduced lung function in concert with impaired immune responses and altered immune cell subsets. Improving our understanding of immune responses to viral and bacterial infection in childhood asthma can help to tailor management of the disease.

The effects of increasing fruit and vegetable intake in children with asthma: A randomized controlled trial.

BACKGROUND: A high fruit and vegetable (F&V) diet reduces asthma exacerbations in adults; this has not been examined in children to date. OBJECTIVE: To investigate the effect of a 6-month, high F&V diet on the time to first asthma exacerbation in children with asthma, in a parallel-group, randomized, controlled trial. METHODS: Children (aged 3-11 years) with asthma, history of exacerbations and usual low F&V intake (≤3 serves/day) were randomized to the intervention (high F&V diet) or control group (usual diet) for 6 months. The primary outcome was time to first exacerbation requiring medical intervention. Secondary outcomes included exacerbation rate, lung function, plasma TNF-α, CRP, and IL-6, faecal microbiota and peripheral blood mononuclear cell (PBMC) histone deacetylase (HDAC) activity and G-protein coupled receptor (GPR) 41/43 and HDAC (1-11) expression. RESULTS: 67 children were randomized between September 2015 and July 2018. F&V intake (difference in change (∆): 3.5 serves/day, 95% CI: [2.6, 4.4] p < 0.001) and plasma total carotenoids (∆: 0.44 µg/ml [0.19, 0.70] p = 0.001) increased after 6 months (intervention vs control). Time to first exacerbation (HR: 0.81, 95% CI: [0.38, 1.69], p = 0.569; control vs. intervention) and exacerbation rate (IRR: 0.84, [0.47, 1.49], p = 0.553; control vs. intervention) were similar between groups. In per-protocol analysis, airway reactance z-scores increased in the intervention versus control group (X5 ∆: 0.76 [0.04, 1.48] p = 0.038, X20 ∆: 0.93 [0.23, 1.64] p = 0.009) and changes in faecal microbiota were observed though there was no difference between groups in systemic inflammation or molecular mechanisms. In the control group, CRP and HDAC enzyme activity increased, while GPR41 expression decreased. No adverse events attributable to the interventions were observed. CONCLUSION & CLINICAL RELEVANCE: A high F&V diet did not affect asthma exacerbations over the 6-month intervention, though warrants further investigation as a strategy for improving lung function and protecting against systemic inflammation in children with asthma.

The Effect of Omega-3 Fatty Acids, EPA, and/or DHA on Male Infertility: A Systematic Review and Meta-analysis.

The objective was to evaluate the effect of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) on sperm parameters including total sperm concentration, sperm motility, sperm DHA, and seminal plasma DHA concentration in infertile men. The literature search was conducted in PubMed, Google Scholar, and Scopus from January 1, 1990 to December 20, 2017. The systematic review and meta-analysis were based on randomized controlled trials in infertile men with DHA or EPA treatments, either alone or in combination with other micronutrients. Three studies met the inclusion criteria: 147 patients in the intervention group and 143 patients in the control group. The analysis showed that omega-3 treatments significantly increased the sperm motility (RR 5.82, 95% CI [2.91, 8.72], p <. 0001, I2 = 76%) and seminal DHA concentration (RR 1.61, 95% CI [0.15, 3.07], p =. 03, I2 = 98%). Compared with the controls, the interventions did not affect the sperm concentration (RR 0.31, 95% CI [-8.13, 8.76], p =. 94, I2 = 95%) or sperm DHA (RR 0.50, 95% CI [-4.17, 5.16], p =. 83, I2 = 99%). The observed heterogeneity may be due to administration period and dosage of omega-3 fatty acids across the studies. Funnel plot shows no evidence of publication bias. This meta-analysis indicates that supplementing infertile men with omega-3 fatty acids resulted in a significant improvement in sperm motility and concentration of DHA in seminal plasma.

A Meta-analysis of Randomized Control Trials: The Impact of Vitamin C Supplementation on Serum CRP and Serum hs-CRP Concentrations.

OBJECTIVE: The present meta-analysis was designed to assess the effects of vitamin C supplementation on serum C-reactive Protein (CRP) levels. METHODS: We conducted a comprehensive systematic search of the literature in Scopus, PubMed and Google Scholar until May 2018. The pooled Weighted Mean Difference (WMD) and its 95% Confidence Interval (CI) in baseline and at the end of the trial were calculated to assess the net change in serum CRP by using random-effects model. The heterogeneity was assessed by I2 test. Combined and stratified analyses were used in the metaanalysis. RESULTS: From 306 articles found and screened in our initial search, 12 studies were included with 446 participants in supplementation groups and 447 in control groups. The pooled effect size analysis showed a significant reducing effect of vitamin C supplementation on circulating CRP level (-0.23 mg/L, 95% CI, -0.44, -0.03, p=0.02), with a significant heterogeneity effect across the studies involved. Subgroup analyses showed that vitamin C supplementation significantly lowered CRP among trials. The most significant effect was found 1) on hs- CRP as the representative inflammatory marker (-0.43 mg/L, 95% CI -0.76, -0.1) 2) in subjects with a baseline CRP≥3 (-1.48 mg/L, 95% CI -2.84, -0.11) 3) in subjects under <60 years old of age (-0.23 mg/L, 95% CI -0.44,- 0.01) 4) or using intravenous administration of vitamin C (-0.89 mg/L, 95% CI -1.49,-0.3). CONCLUSION: The present meta-analysis shows that vitamin C supplementation reduces serum CRP level, particularly in younger subjects, with higher CRP baseline level, at a lower dosage and intravenous administration.

Effects of fruit and vegetable consumption on inflammatory biomarkers and immune cell populations: a systematic literature review and meta-analysis.

BACKGROUND: Inflammation is associated with an increased risk of a range of chronic diseases. A diet high in fruit and vegetables may help to reduce inflammation, as fruit and vegetables are rich sources of antioxidants and other biologically active substances, which may improve immune function. OBJECTIVE: To summarize the evidence, we executed a systematic review and meta-analysis examining the effects of fruit and/or vegetable intake on inflammatory biomarkers and immune cells in humans with different diseases and conditions. Design: Electronic databases including PubMed, Cochrane, CINAHL, and EMBASE were systematically searched up to March 2018. RESULTS: Eighty-three studies were included. Of these, 71 (86%) were clinical trials, and 12 were observational studies (n = 10 cross-sectional and n = 2 cohort). Amongst the observational research, n = 10 studies found an inverse association between intakes of fruit or vegetables and inflammatory biomarkers. Similarly, the majority of the intervention studies (68%, n = 48) reported beneficial effects of fruit or vegetable intake on ≥1 biomarker of systemic or airway inflammation. A meta-analysis of included studies showed that fruit or vegetable intake decreased circulating levels of C-reactive protein and tumor necrosis factor-α (P < 0.05) and increased the γδ-T cell population (P < 0.05). Conclusions: In conclusion, this review suggests that higher intakes of fruit and vegetables lead to both a reduction in proinflammatory mediators and an enhanced immune cell profile.

Vitamin D Receptor Gene Variation, Dietary Intake and Bone Mineral Density in Obese Women: A Cross Sectional Study.

Osteoporosis and fragility fractures have been regarded as important public health concerns. We investigated their possible association with vitamin D receptor (VDR) FOK1 polymorphisms (rs10735810) and dietary parameters such as calcium and vitamin D intake. A total of 264 Iranian obese women (BMI>30 kg/m2) were categorized based on the FOK1 genotype and divided into two groups: group one with the FF genotype (n=184) and the f allele carrier group with the Ff or ff genotype (n=80). The body composition, dietary intake and bone mineral density were assessed for all cases. The frequency of the F and f alleles for FOK1 in the study were 71.5% and 28.5%, respectively. Women with the f allele had a higher BMI (p=0.05), as well as parathyroid hormone (PTH) and tumor necrosis factor alpha (TNF-α) concentration (p=0.05, p=0.01, respectively). Participants with calcium intakes of more than 1,000 mg/d and the ff genotype had a higher L2_L4 Z-score. Moreover, women with vitamin D intakes of less than 600 IU/d and the ff genotype had a higher total T-score and total Z-score. Although women whose dietary intake of vitamin D was higher than the recommended dietary allowance (RDA>600 IU/d) and had the FF genotype had a higher total T-score and total Z-score, as well. Our findings suggest that interactions between FOK1 polymorphisms in Iranian obese women and dietary intake of calcium and vitamin D may play a decisive role in bone mineral density and osteoporosis among these women.

Effects of Fruit and Vegetable Consumption on Risk of Asthma, Wheezing and Immune Responses: A Systematic Review and Meta-Analysis.

Abstract: Evidence suggests that reduced intake of fruit and vegetables may play a critical role in the development of asthma and allergies. The present review aimed to summarize the evidence for the association between fruit and vegetable intake, risk of asthma/wheeze and immune responses. Databases including PubMed, Cochrane, CINAHL and EMBASE were searched up to June 2016. Studies that investigated the effects of fruit and vegetable intake on risk of asthma/wheeze and immune responses were considered eligible (n = 58). Studies used cross-sectional (n = 30), cohort (n = 13), case-control (n = 8) and experimental (n = 7) designs. Most of the studies (n = 30) reported beneficial associations of fruit and vegetable consumption with risk of asthma and/or respiratory function, while eight studies found no significant relationship. Some studies (n = 20) reported mixed results, as they found a negative association between fruit only or vegetable only, and asthma. In addition, the meta-analyses in both adults and children showed inverse associations between fruit intake and risk of prevalent wheeze and asthma severity (p < 0.05). Likewise, vegetable intake was negatively associated with risk of prevalent asthma (p < 0.05). Seven studies examined immune responses in relation to fruit and vegetable intake in asthma, with n = 6 showing a protective effect against either systemic or airway inflammation. Fruit and vegetable consumption appears to be protective against asthma.

Association Between Antioxidant Intake/Status and Obesity: a Systematic Review of Observational Studies.

The global prevalence of obesity has doubled in recent decades. Compelling evidences indicated that obesity was associated with lower concentrations of specific antioxidants which may play a role in the development of obesity-related diseases such as cardiovascular disease. The present review aimed to synthesize the evidence from studies on the association between obesity and antioxidant micronutrients in a systematic manner. Data bases including MEDLINE, Science Direct, and Cochrane were searched from inception to October 2015. Thirty-one articles were reviewed using the MOOSE checklist. Lower concentrations of antioxidants have been reported in obese individuals among age groups worldwide. Circulatory levels of carotenoids, vitamins E and C, as well as zinc, magnesium, and selenium were inversely correlated with obesity and body fat mass. However, studies demonstrated inconsistencies in findings. Lower status of carotenoids, vitamins E and C, zinc, magnesium, and selenium appears to be associated with adiposity. Intervention studies may be needed to establish the causality of these associations.

Association between Micronutrients Intake/Status and Carotid Intima Media Thickness: A Systematic Review.

BACKGROUND: Carotid intima media thickness (IMT) is a noninvasive marker of the extent and severity of subclinical atherosclerosis. Micronutrient intake may affect atherosclerosis and play a major role in the development of cardiovascular diseases (CVDs). OBJECTIVE: The primary aim of this review was to synthesize the evidence regarding the association between carotid IMT and selected micronutrients. METHOD: The authors searched PubMed, Cochrane, and EMBASE databases from inception to June 2016 for selected micronutrients, CVD, carotid IMT, and antioxidants. Thirty-five original studies met the inclusion criteria and were reviewed following preferred reporting items for systematic review and meta-analysis guidelines. RESULTS: Although not all studies found consistent results, the weight of the evidence suggests that high intakes and/or circulatory levels of magnesium, as well as vitamin D and the vitamin B group, may be associated with lower carotid IMT or reduced progression of carotid IMT. The majority of studies did not find any significant association between vitamin E and C and carotid IMT. Less evidence was available for associations of retinol, zinc, and iron with carotid IMT. CONCLUSIONS: In general, the current evidence concerning micronutrient intake and carotid IMT is largely inconclusive. Pragmatic clinical trials are required to determine whether dietary or supplemental intake of specific micronutrients alters carotid IMT, which is a surrogate measure of cardiovascular risk.

Diet quality in obese/overweight individuals with/without metabolic syndrome compared to normal weight controls.

BACKGROUND: Metabolic syndrome (MetS) is a serious public health concern worldwide; however, the pathogenesis of this disease has not been yet cleared. This study aimed to compare diet quality in obese/overweight participants with/without metabolic syndrome with normal weight controls. METHODS: This was a comparative study on 147 Iranian adults under treatment at the Endocrinology Center of Tehran University of Medical Sciences. They were assigned into three groups (normal weight, obese weight with/without MetS) according to the inclusion- exclusion criteria. Metabolic syndrome was defined according to the NCEP ATPIII consensus criteria. Healthy Eating Index Data were obtained from the validated FFQ to determine the diet quality index scores, using the Healthy Eating Index-2010. RESULTS: Our findings demonstrated that FBS, TG, SBP, WC and weight were higher among MetS patients compared to the both weight matched and non-weight matched participants, while HDL-c was lowest in this group (p<0.05). A statistically significant difference was found between healthy weight controls and obese/overweight participants with/without MetS in HEI-2010, and 9 of the 12 HEI-2010 components score (p<0.05). CONCLUSION: Our study revealed that low diet quality was a risk factor in developing MetS.

Effects of pomegranate extract supplementation on inflammation in overweight and obese individuals: A randomized controlled clinical trial.

The study was designed to determine the effect of thirty days of pomegranate extract oral supplementation on plasma inflammatory and oxidative stress biomarkers as well as serum metabolic profiles, in overweight and obese individuals. In this randomized, double-blind, placebo-controlled study 48 obese and overweight participants were randomly assigned to receive either 1000 mg of pomegranate extract, or a placebo, daily for 30 days. At baseline, and after 30 days of treatment, anthropometric parameters, dietary intake, plasma concentrations of malondialdehyde, interleukin-6 and hyper sensitive-C reactive protein and levels of serum lipids, glucose and insulin were assessed. Thirty days of PE supplementation resulted in a significant decrease in mean serum levels of glucose, insulin, total cholesterol, LDL-C, and plasma MDA, IL-6 and hs-CRP. HDL-C significantly increased following the PE versus the PL intervention. Our study suggests that pomegranate extract consumption may reduce complications linked with obesity.

Changes of left ventricular mass index among end-stage renal disease patients after renal transplantation.

PURPOSE: The aim of this study was to determine left ventricular (LV) mass index via echocardiography in end-stage renal disease patients (ESRD) before and after renal transplantation, and its association with one-year survival. MATERIALS AND METHODS: Forty-seven patients with ESRD who were candidate for renal transplantation were evaluated with echocardiography before and 4 months after the operation. Left ventricular ejection fraction (EF), LV mass, and LV mass index were determined. All of the patients were followed up for 1 year. RESULTS: Mean LVEF was 51.6% which increased to 53.7% after renal transplantation (P = .001). Mean LV mass was 209 gr before the operation which decreased to 189 gr after the operation (P = .001). Mean LV mass index before the operation was 120 gr/m2 which decreased to 110 gr/m2 following the operation (P = .002). All of the patients survived during 1-year follow-up, and no death was reported. CONCLUSION: Renal transplantation had beneficial effects in terms of LV function in young patients with ESRD.