Author, year [reference] Study design/country Population (age, sex)/sample size Biological sample/other markers Main outcome Results Conclusion Paolisso G. et al., 1996 [33 ] Experimental study with free fatty acids (FFA) infusions/Italy Adults ( Plasma/MDA, LOOH Effect of FFA on OS The GSH/GSSG ratio diminished after 6 h of FFA infusion and continued to 24 h, although the better effect was at 6 h. After a wash-out period, the ratio returns to basal value. The OS intensifies with the increase of FFA, inferring that the ratio measures the OS. Abramson JL. et al., 2005 [34 ] Cross-sectional/USA Adults ( Plasma/FORT Association between OS and high sensitivity CRP (hsCRP) The GSH/GSSG ratio showed little association with hsCRP. The ratio was not strongly associated with CRP. Gherghel D. et al., 2005 [35 ] Cross-sectional/UK Older adults ( Blood/none Glutathione status in primary open-angle glaucoma (POAG) The GSH/GSSG ratio was similar in both sexes. No differences between study group and control were observed in redox index, after correction for age and gender. The authors did not conclude about the ratio because the results were not significant. Yeh CC. et al., 2006 [36 ] Cross-sectional/Taiwan Adults (27-83 y, female)/112 women with BC Blood, tumor tissue/none Glutathione status in breast cancer (BC) GSH/TGSSG ratio was decreased in the blood of the patients with breast cancer, and breast cancer tissue was increased, especially in stage II. There was an imbalance in the glutathione redox status in the breast tumor patients. Ashfaq S. et al., 2006 [37 ] Cross-sectional/USA Adults (30-65 y, both sexes)/114 healthy subjects Blood/cysteine and its redox state Thiols status and early atherosclerosis After adjusting for traditional risk factors and hs-CRP, the GSH/GSSG ratio is an independent predictor of intima-media thickness. Glutathione redox state is an independent predictor for the presence of early atherosclerosis. Nikolaidis MG. et al., 2007 [38 ] Experimental of isokinetic exercise/Greece Adults ( Blood/MDA, TAC, PC Effect of repeated muscle-damaging exercise on the time-course changes in indices of muscle damage Exercise decreased the GSH/GSSG ratio at several time points after both exercise bouts. The authors did not conclude directly with the ratio but shown an effect across it. Harzallah O. et al., 2008 [39 ] Cross-sectional/Tunisia Adults (22–61 y, both sexes)/40 subjects with BD Blood/MDA, CAT, SOD, GPx Association between OS and Behçet’s disease (BD) The GSH/GSSG ratio was reduced in BD patients. Exist an OS in BD as shown by the diminution of the ratio. Youssef H. et al., 2009 [40 ] Cross-sectional postexercise effect/Lebanon Adolescents (14-19 y, female)/29 overweight girls Blood/F2-Iso, LOOH, ox-LDL, SOD, GPx, vit. C, vit. E, β -carot. Effect of incremental ergocycle exercise on OS The overweight adolescents presented the GSH/GSSG ratio lower. Exercise exacerbates OS in the overweight adolescents; GSH/GSSG ratio is a good marker. Tsai SM. et al., 2009 [41 ] Cross-sectional/Taiwan Adults (31-81 y, both sexes)/54 HBV-associated HCC patients Blood/2 ⋅ −, MDA, SOD, GPx, vit. A, C, E Changes in OS in chronic hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) patients The ratio of GSH/GSSG of HBV-associated HCC patients was lower than that of controls. Changes in the GSH demonstrated that HBV-associated HCC patients had undergone OS during their clinical disease progression. Huang YS. et al., 2009 [30 ] Cross-sectional/China Adults (41-76 y, both sexes)/56 patients plaque-forming Plasma/MDA, ox-LDL Relationship between glutathione redox status and the atherosclerosis GSH/GSSG redox status was positively correlated with the intima thickness. Peroxidative glutathione redox status may be a sensitive and reliable index for monitoring OS in atherosclerosis. Kleinsorge EC. et al., 2011 [42 ] Cross-sectional/Argentina Adults ( Erythrocyte/MDA, CAT, DICA To determinate the oxidative damage in photocopier operators GSH/GSSG is similar between operators and controls. The authors did not discuss or conclude about the ratio. Patel RS. et al., 2011 [43 ] Cross-sectional/USA Adults and elderly (20-70 y, both sexes)/169 healthy subjects Plasma/cysteine ratio, dROMs Relationship between novel markers of OS and arterial elastic properties The redox potential of GSH/GSSG showed modest association with carotid-femoral pulse wave velocity. After multivariate adjustment for confounders, GSH/GSSG is not associated with impaired arterial elasticity. Zepeda RJ. et al., 2012 [44 ] Prospective randomized single blind clinical trial/Chile Adults (30-75 y, both sexes)/23 patients with EH in carvedilol therapy Erythrocyte/NOx, FRAP, MDA, 8-Iso Effect of carvedilol and nebivolol on the OS and endothelial function in patients with essential hypertension (EH) In patients with carvedilol, GSH/GSSG ratio was higher compared with patients who received nebivolol. As part of the antihypertensive mechanism, carvedilol seems to reinforce the antioxidant system. Llorente-Cantarero FJ. et al., 2012 [45 ] Cross-sectional/Spain Children (7-12 y, both sexes)/138 healthy subjects Erythrocyte/MDA, 4-HNE, PC, NOx, SOD, GPx To identify gender-based biomarkers for OS in children Girls had a lower GSH/GSSG ratio than boys. The authors did not conclude about the ratio directly. Ntalapascha M. et al., 2013 [46 ] Observational prospective/Greece Adults (30-65 y, male)/18 patients with severe OSAS Erythrocyte/MDA, PC, 8-Iso, CAT, SOD, TAC Assess the OS in patients with obstructive sleep apnea syndrome (OSAS) The overnight (morning–night) change (%) of GSH/GSSG ratio was different between OSAS and controls. OSAS might be associated with increased OS possibly via GSH/GSSG pathway. Shah D. et al., 2013 [47 ] Cross-sectional/India Adults ( Erythrocyte/MDA, SOD, CAT, GPx, ROS production, total thiols Association between glutathione pathway and systemic lupus erythematosus (SLE) severity Altered redox state (GSH/GSSG) was found in SLE patients. GSH depletion may be coupled with the severity of the disease. Victor VM. et al., 2014 [48 ] Observational prospective of testosterone (T) therapy/Spain Adults ( Polymorpho-nuclear cells/mitochondrial O2 consumption, membrane potential, ROS production The effect of T treatment on the redox state of leukocytes of FtMs subjects GSH/GSSG ratio was lower in patients post-T treatment Treatment of FtMs with T can induce a state of OS. Enns GM. et al., 2014 [49 ] Cross-sectional/USA All ages (0.5-50 y, both sexes)/62 subjects with mitochondrial disease (MitD) Blood/none To determine the redox status in mitochondrial diseases and if the redox imbalance is an indicator of clinical status The GSH/GSSG ratio was lower in MitD patients, and redox potential was higher compared with controls. GSH and GSSG levels may be biomarkers of mitochondrial dysfunction, and the evaluation of redox potential may be useful in monitoring of clinical status in MitD. Schmitt B. et al., 2015 [50 ] Randomized crossover trial/France Adults (38-67 y, both sexes)/20 subjects with metabolic syndrome Blood/reduced thiols, vit. E To compare the effect on glutathione status of a sublingual form of GSH, compared with oral GSH and N-acetylcysteine (NAC) A higher GSH/GSSG ratio was observed in sublingual GSH group compared with oral GSH and NAC groups. The authors conclude about the effectivity of the treatments based in the GSH results. Karimi R. et al., 2016 [51 ] Cross-sectional/USA Adults ( Blood/none Seafood Hg exposure is related to a shift in redox status (low GSH/GSSG or high redox potential (h )) Blood Hg concentration was associated with changes in GSH/GSSG ratio and redox potential. Hg exposure from seafood is linked to a shift in redox status toward OS. Atkin M. et al., 2016 [52 ] A double-blind, placebo-controlled crossover pilot/UK Adults (18-70 y, both sexes)/26 subjects with T2DM Blood/LOOH, TAS Aged garlic extract (AGE) may improve OS in high-risk cardiovascular subjects with type 2 diabetes (T2DM) No difference was found in GSH/GSSG ratio. There is no clinical benefit of adding AGE, in the short term, to usual medical therapy in patients with T2DM. Galicia-Moreno M. et al., 2016 [53 ] Cross-sectional/Mexico Adults ( Blood/MDA, PC To evaluate the role of OS in alcoholic liver cirrhosis (ALC) There were no differences in the GSH/GSSG ratio between groups. ALC subjects have an increase in OS in the early stages of disease severity and abstinence from alcohol consumption favors GSH in patients with advanced disease severity. Moreno-Solís G. et al., 2017 [54 ] Observational/Spain Infants (1-11 months, both sexes)/45 infants with RSV-AB Erythrocyte/MDA, 4-HNE, GPx Association between OS and acute bronchiolitis caused by respiratory syncytial virus (RSV-AB) and its severity The GSH/GSSG ratio was lower in RSV-AB infants and decrease if the infants need oxygen therapy. The authors propose the use of GSSG and the GSH/GSSG ratio as biomarkers linked to the pathogenesis of RSV-AB. Vacchi-Suzzi C. et al., 2018 [55 ] Cross-sectional cohort/USA Adults (≥18 y, both sexes)/282 healthy Blood/none Association between blood lead level (BLL) and glutathione (GSH) redox biomarkers Increasing exposure to Pb was associated with lower levels of GSH/GSSG ratio and more positive GSH redox potential. Blood Pb is associated with lower levels of GSH and the GSH/GSSG ratio.
