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Antioxidant Vitamins and Prebiotic FOS and XOS Differentially Shift Microbiota Composition and Function and Improve Intestinal Epithelial Barrier In Vitro.
Pham, VT, Calatayud, M, Rotsaert, C, Seifert, N, Richard, N, Van den Abbeele, P, Marzorati, M, Steinert, RE
Nutrients. 2021;(4)
Abstract
Human gut microbiota (HGM) play a significant role in health and disease. Dietary components, including fiber, fat, proteins and micronutrients, can modulate HGM. Much research has been performed on conventional prebiotics such as fructooligosaccharides (FOS) and galactooligosaccharides (GOS), however, novel prebiotics or micronutrients still require further validation. We assessed the effect of FOS, xylooligosaccharides (XOS) and a mixture of an antioxidant vitamin blend (AOB) on gut microbiota composition and activity, and intestinal barrier in vitro. We used batch fermentations and tested the short-term effect of different products on microbial activity in six donors. Next, fecal inocula from two donors were used to inoculate the simulator of the human microbial ecosystem (SHIME) and after long-term exposure of FOS, XOS and AOB, microbial activity (short- and branched-chain fatty acids and lactate) and HGM composition were evaluated. Finally, in vitro assessment of intestinal barrier was performed in a Transwell setup of differentiated Caco-2 and HT29-MTX-E12 cells exposed to fermentation supernatants. Despite some donor-dependent differences, all three tested products showed beneficial modulatory effects on microbial activity represented by an increase in lactate and SCFA levels (acetate, butyrate and to a lesser extent also propionate), while decreasing proteolytic markers. Bifidogenic effect of XOS was consistent, while AOB supplementation appears to exert a specific impact on reducing F. nucleatum and increasing butyrate-producing B. wexlerae. Functional and compositional microbial changes were translated to an in vitro host response by increases of the intestinal barrier integrity by all the products and a decrease of the redox potential by AOB supplementation.
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The Effect of Corrected Inflammation, Oxidative Stress and Endothelial Dysfunction on Fmd Levels in Patients with Selected Chronic Diseases: A Quasi-Experimental Study.
Yilmaz, MI, Romano, M, Basarali, MK, Elzagallaai, A, Karaman, M, Demir, Z, Demir, MF, Akcay, F, Seyrek, M, Haksever, N, et al
Scientific reports. 2020;(1):9018
Abstract
While the pathophysiology of chronic disorders varies there are three basic mechanisms - inflammation, oxidative stress and endothelial dysfunction - that are common in many chronic diseases. However, the failure of these mechanisms to work synchronously can lead to morbidity complicating the course of many chronic diseases. We analyzed data of 178 patients from cohorts with selected chronic diseases in this quasi-experimental study. Endothelial dysfunction was determined by flow-mediated dilatation (FMD) and asymmetric dimethylarginine (ADMA) levels. Serum ADMA, high sensitive C-reactive protein (hs-CRP), serum PTX3, malondialdehyde (MDA), Cu/Zn-superoxide dismutase (Cu/Zn-SOD), glutathione peroxidase (GSH-Px) levels and FMD were studied in baseline and after 12 weeks of Morinda citrifolia (anti-atherosclerotic liquid- AAL), omega-3 (anti-inflammatory capsules- AIC) and extract with Alaskan blueberry (anti-oxidant liquid- AOL). Stepwise multivariate regression analysis was used to evaluate the association of FMD with clinical and serologic parameters. Serum ADMA, MDA, PTX3, hsCRP and albumin levels, and proteinuria were significantly decreased while CuZn-SOD, GSH-Px and FMD levels were significantly increased following AAL, AIC and AOL therapies. The FMD was negatively correlated with serum ADMA, MDA, PTX3, and hsCRP levels and positively correlated with CuZn-SOD and eGFR levels. ADMA and PTX3 levels were independently related to FMD both before and after AAL, AIC and AOL therapies. Our study shows that serum ADMA, MDA, PTX3 levels are associated with endothelial dysfunction in patients with selected chronic diseases. In addition, short-term AAL, AIC and AOL therapies significantly improves a number of parameters in our cohort and can normalize ADMA, PTX3, hsCRP and MDA levels.
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A longitudinal study of pre-pregnancy antioxidant levels and subsequent perinatal outcomes in black and white women: The CARDIA Study.
Harville, EW, Lewis, CE, Catov, JM, Jacobs, DR, Gross, MD, Gunderson, EP
PloS one. 2020;(2):e0229002
Abstract
BACKGROUND Although protective associations between dietary antioxidants and pregnancy outcomes have been reported, randomized controlled trials of supplementation have been almost uniformly negative. A possible explanation is that supplementation during pregnancy may be too late to have a beneficial effect. Therefore, we examined the relationship between antioxidant levels prior to pregnancy and birth outcomes. METHODS AND FINDINGS Serum carotenoids and tocopherols were assayed in fasting specimens at 1985-86 (baseline) and 1992-1993 (year 7) from 1,215 participants in Coronary Artery Risk Development in Young Adults (CARDIA) study. An interviewer-administered quantitative food-frequency questionnaire assessed dietary intake of antioxidants. Pregnancy outcome was self-reported at exams every 2 to 5 years. Linear and logistic regression modeling was used to assess relationships of low birthweight (LBW; <2,500 g), continuous infant birthweight, preterm birth (PTB; <37 weeks) and length of gestation with antioxidant levels adjusted for confounders, as well as interactions with age and race. RESULTS In adjusted models, lycopene was associated with higher odds of LBW (adjusted odds ratio for top quartile, 2.15, 95% confidence interval 1.14, 3.92) and shorter gestational age (adjusted beta coefficient -0.50 weeks). Dietary intake of antioxidants was associated with lower birthweight, while supplement use of vitamin C was associated with higher gestational age (0.41 weeks, 0.01, 0.81). CONCLUSIONS Higher preconception antioxidant levels are not associated with better birth outcomes.
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Biomarker Identification, Safety, and Efficacy of High-Dose Antioxidants for Adrenomyeloneuropathy: a Phase II Pilot Study.
Casasnovas, C, Ruiz, M, Schlüter, A, Naudí, A, Fourcade, S, Veciana, M, Castañer, S, Albertí, A, Bargalló, N, Johnson, M, et al
Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics. 2019;(4):1167-1182
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Abstract
X-Adrenoleukodystrophy (X-ALD) and its adult-onset, most prevalent variant adrenomyeloneuropathy (AMN) are caused by mutations in the peroxisomal transporter of the very long-chain fatty acid ABCD1. AMN patients classically present spastic paraparesis that can progress over decades, and a satisfactory treatment is currently lacking. Oxidative stress is an early culprit in X-ALD pathogenesis. A combination of antioxidants halts the clinical progression and axonal damage in a murine model of AMN, providing a strong rationale for clinical translation. In this phase II pilot, open-label study, 13 subjects with AMN were administered a high dose of α-tocopherol, N-acetylcysteine, and α-lipoic acid in combination. The primary outcome was the validation of a set of biomarkers for monitoring the biological effects of this and future treatments. Functional clinical scales, the 6-minute walk test (6MWT), electrophysiological studies, and cerebral MRI served as secondary outcomes. Most biomarkers of oxidative damage and inflammation were normalized upon treatment, indicating an interlinked redox and inflammatory homeostasis. Two of the inflammatory markers, MCP1 and 15-HETE, were predictive of the response to treatment. We also observed a significant decrease in central motor conduction time, together with an improvement or stabilization of the 6MWT in 8/10 subjects. This study provides a series of biomarkers that are useful to monitor redox and pro-inflammatory target engagement in future trials, together with candidate biomarkers that may serve for patient stratification and disease progression, which merit replication in future clinical trials. Moreover, the clinical results suggest a positive signal for extending these studies to phase III randomized, placebo-controlled, longer-term trials with the actual identified dose. ClinicalTrials.gov Identifier: NCT01495260.
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Potential Benefits of Nitrate Supplementation on Antioxidant Defense System and Blood Pressure Responses after Exercise Performance.
Menezes, EF, Peixoto, LG, Teixeira, RR, Justino, AB, Puga, GM, Espindola, FS
Oxidative medicine and cellular longevity. 2019;:7218936
Abstract
Nitrate (NO3 -) supplementation is associated with exercise performance, oxygen uptake, blood flow, and blood pressure improvement, and it can act as an antioxidant agent. This study evaluated the effects of sodium nitrate supplementation on oxidative stress markers and blood pressure responses after aerobic exercise performance in physically active males. Fourteen subjects aged 22 ± 3 years and with a BMI of 23 ± 1 kg/m2 were submitted to four exercise tests in intervals of 5 days. Nitrate supplementation (NO session) and placebo supplementation (PL session) were acute (AC) and over a period of 5 days (FD) in random order with a crossover design. Saliva was collected at basal (0'); 60 min after supplementation (60'); immediately after exercise (90'); and 15, 30, and 60 min after the test (105', 120', and 150'). The NO session had higher concentrations (P < 0.05) of salivary nitrite in both AC and FD treatments when compared with the PL session. There was a reduction in systolic blood pressure (SBP) only after FD in the NO session. Furthermore, uric acid and total antioxidant capacity (FRAP) salivary concentrations increased, while SOD activity and TBARS levels decreased after FD but not after AC in the NO session. The results suggest that nitrate supplemented over a period of 5 days reduced SBP and indirectly acted as an antioxidant in healthy nonsedentary young men.
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Association of Rare Predicted Loss-of-Function Variants in Cellular Pathways with Sub-Phenotypes in Age-Related Macular Degeneration.
Pietraszkiewicz, A, van Asten, F, Kwong, A, Ratnapriya, R, Abecasis, G, Swaroop, A, Chew, EY
Ophthalmology. 2018;(3):398-406
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Abstract
PURPOSE To investigate the association of rare predicted loss-of-function (pLoF) variants within age-related macular degeneration (AMD) risk loci and AMD sub-phenotypes. DESIGN Case-control study. PARTICIPANTS Participants of AREDS, AREDS2, and Michigan Genomics Initiative. METHODS Whole genome sequencing data were analyzed for rare pLoF variants (frequency <0.1%) in the regions of previously identified 52 independent risk variants known to be associated with AMD. Frequency of the rare pLoF variants in cases with intermediate or advanced AMD was compared with controls. Variants were assigned to the complement, extracellular matrix (ECM), lipid, cell survival, immune system, metabolism, or unknown/other pathway. Associations of rare pLoF variant pathways with AMD sub-phenotypes were analyzed using logistic and linear regression, and Cox proportional hazards models. MAIN OUTCOME MEASURES Differences in rare pLoF variant pathway burden and association of rare pLoF variant pathways with sub-phenotypes within the population with AMD were evaluated. RESULTS Rare pLoF variants were found in 298 of 1689 cases (17.6%) and 237 of 1518 controls (15.6%) (odds ratio [OR], 1.11; 95% confidence interval [CI], 0.91-1.36; P = 0.310). An enrichment of rare pLoF variants in the complement pathway in cases versus controls (OR, 2.94; 95% CI, 1.49-5.79; P = 0.002) was observed. Within cases, associations between all rare pLoF variants and choroidal neovascularization (CNV) (OR, 1.34; 95% CI, 1.04-1.73; P = 0.023), calcified drusen (OR, 1.33; 95% CI, 1.04-1.72; P = 0.025), higher scores on the AREDS Extended AMD Severity Scale (Standardized Coefficient Beta (β)=0.346 [0.086-0.605], P = 0.009), and progression to advanced disease (hazard ratio, 1.25; 95% CI, 1.01-1.55; P = 0.042) were observed. At the pathway level, there were associations between the complement pathway and geographic atrophy (GA) (OR, 2.17; 95% CI, 1.12-4.24; P = 0.023), the complement pathway and calcified drusen (OR, 3.75; 95% CI, 1.79-7.86; P < 0.001), and the ECM pathway and more severe levels in the AREDS Extended AMD Severity Scale (β = 0.62; 95% CI, 0.04-1.20; P = 0.035). CONCLUSIONS Rare pLoF variants are associated with disease progression. Variants in the complement pathway modify the clinical course of AMD and increase the risk of developing specific sub-phenotypes.
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CFH and ARMS2 genetic risk determines progression to neovascular age-related macular degeneration after antioxidant and zinc supplementation.
Vavvas, DG, Small, KW, Awh, CC, Zanke, BW, Tibshirani, RJ, Kustra, R
Proceedings of the National Academy of Sciences of the United States of America. 2018;(4):E696-E704
Abstract
We evaluated the influence of an antioxidant and zinc nutritional supplement [the Age-Related Eye Disease Study (AREDS) formulation] on delaying or preventing progression to neovascular AMD (NV) in persons with age-related macular degeneration (AMD). AREDS subjects (n = 802) with category 3 or 4 AMD at baseline who had been treated with placebo or the AREDS formulation were evaluated for differences in the risk of progression to NV as a function of complement factor H (CFH) and age-related maculopathy susceptibility 2 (ARMS2) genotype groups. We used published genetic grouping: a two-SNP haplotype risk-calling algorithm to assess CFH, and either the single SNP rs10490924 or 372_815del443ins54 to mark ARMS2 risk. Progression risk was determined using the Cox proportional hazard model. Genetics-treatment interaction on NV risk was assessed using a multiiterative bootstrap validation analysis. We identified strong interaction of genetics with AREDS formulation treatment on the development of NV. Individuals with high CFH and no ARMS2 risk alleles and taking the AREDS formulation had increased progression to NV compared with placebo. Those with low CFH risk and high ARMS2 risk had decreased progression risk. Analysis of CFH and ARMS2 genotype groups from a validation dataset reinforces this conclusion. Bootstrapping analysis confirms the presence of a genetics-treatment interaction and suggests that individual treatment response to the AREDS formulation is largely determined by genetics. The AREDS formulation modifies the risk of progression to NV based on individual genetics. Its use should be based on patient-specific genotype.
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Dietary total antioxidant capacity (TAC) among candidates for coronary artery bypass grafting (CABG) surgery: Emphasis to possible beneficial role of TAC on serum vitamin D.
Abbasalizad Farhangi, M, Najafi, M
PloS one. 2018;(12):e0208806
Abstract
AIMS: Recently, the clinical importance of total antioxidant capacity (TAC) and its protective role against several chronic diseases like cardiovascular disease, osteoporosis and several types of cancers has been reported. However, its association with cardio-metabolic risk factors among patients candidate for coronary artery bypass graft surgery (CABG) has not been evaluated yet. CABG is associated with increased oxidative stress and free radicals; so, the current study was aimed to evaluate the potential association of TAC with cardiovascular risk factors among patients candidate for CABG. METHODS AND MATERIALS In the current cross-sectional study, 454 patients aged 35-80 years as candidates of CABG and hospitalized in Tehran Heart Center were enrolled. Anthropometric and demographic characteristics were obtained from all participants. Total dietary antioxidant capacity (TAC) was calculated according to the findings of semi-quantitative food-frequency questionnaire (FFQ). Biochemical parameters including serum lipids, albumin, creatinine, HbA1C, C-reactive protein (CRP), lipoprotein (a), creatinine, blood urea nitrogen (BUN) and serum vitamin D concentrations were also assessed by commercial laboratory methods. RESULTS Male patients in the top quintiles of TAC had significantly lower prevalence of hypertension (35.1% vs 45.9%). Moreover, male patients at fifth quintile of TAC were 2% more serum vitamin D concentrations, 3% lower serum cholesterol concentrations compared with lowest quintile. Top quintiles of TAC make patients more likely to have low hematocrit and high serum albumin concentrations compared with lowest quintiles (P < 0.05). However, in female participants, only serum creatinine concentration was in negative association with TAC. In comparison of clinical parameters, females in the fifth quintile of TAC had 9% higher EF compared with patients in the first quintile (P = 0.021). CONCLUSION To our findings, higher dietary antioxidant capacity was associated with lower prevalence of hypertension, lower hematocrit, total cholesterol and higher albumin and vitamin D concentrations. Therefore, high dietary TAC could be considered as a potent protective tool against cardio-metabolic risk factors in patients CABG candidate for especially in male patients.
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Immune cell response to strenuous resistive breathing: comparison with whole body exercise and the effects of antioxidants.
Asimakos, A, Toumpanakis, D, Karatza, MH, Vasileiou, S, Katsaounou, P, Mastora, Z, Vassilakopoulos, T
International journal of chronic obstructive pulmonary disease. 2018;:529-545
Abstract
BACKGROUND/HYPOTHESIS Whole body exercise (WBE) changes lymphocyte subset percentages in peripheral blood. Resistive breathing, a hallmark of diseases of airway obstruction, is a form of exercise for the inspiratory muscles. Strenuous muscle contractions induce oxidative stress that may mediate immune alterations following exercise. We hypothesized that inspiratory resistive breathing (IRB) alters peripheral blood lymphocyte subsets and that oxidative stress mediates lymphocyte subpopulation alterations following both WBE and IRB. PATIENTS AND METHODS Six healthy nonathletes performed two WBE and two IRB sessions for 45 minutes at 70% of VO2 maximum and 70% of maximum inspiratory pressure (Pimax), respectively, before and after the administration of antioxidants (vitamins E, A, and C for 75 days, allopurinol for 30 days, and N-acetylcysteine for 3 days). Blood was drawn at baseline, at the end of each session, and 2 hours into recovery. Lymphocyte subsets were determined by flow cytometry. RESULTS Before antioxidant supplementation at both WBE end and IRB end, the natural killer cell percentage increased, the T helper cell (CD3+ CD4+) percentage was reduced, and the CD4/CD8 ratio was depressed, a response which was abolished by antioxidants only after IRB. Furthermore, at IRB end, antioxidants promoted CD8+ CD38+ and blunted cytotoxic T-cell percentage increase. CD8+ CD45RA+ cell percentage changes were blunted after antioxidant supplementation in both WBE and IRB. CONCLUSION We conclude that IRB produces (as WBE) changes in peripheral blood lymphocyte subsets and that oxidative stress is a major stimulus predominantly for IRB-induced lymphocyte subset alterations.
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Intravenous vitamin C in the treatment of allergies: an interim subgroup analysis of a long-term observational study.
Vollbracht, C, Raithel, M, Krick, B, Kraft, K, Hagel, AF
The Journal of international medical research. 2018;(9):3640-3655
Abstract
UNLABELLED Objective Oxidative stress appears to be a key factor in the pathogenesis of allergic diseases and a potential therapeutic target in allergy treatment. Allergic diseases are reportedly associated with reduced plasma levels of ascorbate, which is a key physiological antioxidant. Ascorbate prevents excessive inflammation without reducing the defensive capacity of the immune system. Methods An interim analysis of a multicenter, prospective, observational study was conducted to investigate the change in disease-specific and nonspecific symptoms (fatigue, sleep disorders, depression, and lack of mental concentration) during adjuvant treatment with intravenous vitamin C (Pascorbin®; Pascoe, Giessen, Germany) in 71 patients with allergy-related respiratory or cutaneous indications. Results Between the start and end of treatment, the mean sum score of three disease-specific symptoms decreased significantly by 4.71 points and that of four nonspecific symptoms decreased significantly by 4.84 points. More than 50% of patients took no other allergy-related medication besides vitamin C. Conclusions Our observations suggest that treatment with intravenous high-dose vitamin C reduces allergy-related symptoms. Our observations form a basis for planning a randomized controlled clinical trial to obtain more definitive evidence of the clinical relevance of our findings. We also obtained evidence of ascorbate deficiency in allergy-related diseases. TRIAL REGISTRATION Clinical Trials NCT02422901.