The effects of 3 weeks of oral glutathione supplementation on whole body insulin sensitivity in obese males with and without type 2 diabetes: a randomized trial.

The effect of oral glutathione (GSH) supplementation was studied in obese subjects with and without type 2 diabetes (T2DM) on measures of glucose homeostasis and markers of oxidative stress. Twenty subjects (10 patients with T2DM and 10 obese subjects) were recruited for the study, and randomized in a double-blinded placebo-controlled manner to consume either 1000 mg GSH per day or placebo for 3 weeks. Before and after the 3 weeks insulin sensitivity was measured with the hyperinsulinemic-euglycemic clamp and a muscle biopsy was obtained to measure GSH and skeletal muscle mitochondrial hydrogen peroxide (H2O2) emission rate. Whole body insulin sensitivity increased significantly in the GSH group. Skeletal muscle GSH was numerically increased (∼19%) in the GSH group; no change was seen in GSH to glutathione disulfide ratio. Skeletal muscle mitochondrial H2O2 emission rate did not change in response to the intervention and neither did the urinary excretion of the RNA oxidation product 8-oxo-7,8-dihydroguanosine or the DNA oxidation product 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), although 8-oxodG decreased as a main effect of time. Oral GSH supplementation improves insulin sensitivity in obese subjects with and without T2DM, although it does not alter markers of oxidative stress. The study has been registered in clinicaltrials.gov (NCT02948673). Novelty: Reduced glutathione supplementation increases insulin sensitivity in obese subjects with and without T2DM. H2O2 emission rate from skeletal muscle mitochondria was not affected by GSH supplementation.

Inflammatory biomarkers in patients in Simvastatin treatment: No effect of co-enzyme Q10 supplementation.

PURPOSE: Atherosclerosis is a major risk factor for cardiovascular disease (CVD) and is known to be an inflammatory process. Statin therapy decreases both cholesterol and inflammation and is used in primary and secondary prevention of CVD. However, a statin induced decrease of plasma concentrations of the antioxidant coenzyme Q10 (CoQ10), may prevent the patients from reaching their optimal anti-inflammatory potential. Here, we studied the anti-inflammatory effect of Simvastatin therapy and CoQ10 supplementation. METHODS: 35 patients in primary prevention with Simvastatin (40 mg/day) were randomized to receive oral CoQ10 supplementation (400 mg/d) or placebo for 8 weeks. 20 patients with hypercholesterolemia who received no cholesterol-lowering treatment was a control group. Plasma concentrations of lipids and inflammatory biomarkers (interleukin-6 (IL6); -8 (IL8); -10 (IL10), tumor necrosis factor-α (TNFα); high-sensitivity C reactive protein (hsCRP)) as well as glycated hemoglobin (HbA1c) were quantified before and after the intervention. RESULTS: No significant change in inflammatory markers or lipids was observed after CoQ10 supplementation Patients in Simvastatin therapy had significantly (P < 0.05) lower baseline concentration of IL6 (0.31 ±â€¯0.03 pg/ml), IL8 (1.6 ±â€¯0.1 pg/ml) IL10 (0.16 ±â€¯0.02 pg/ml) and borderline (P = 0.053) lower TNFα (0.88 ±â€¯0.05 pg/ml), but not hsCRP (1.34 ±â€¯0.19 mg/l) compared with the control group (0.62 ±â€¯0.08, 2.6 ±â€¯0.2, 0.25 ±â€¯0.01, 1.07 ±â€¯0.09, and 1.90 ±â€¯0.35, respectively). CONCLUSIONS: Simvastatin therapy has beneficial effects on inflammatory markers in plasma, but CoQ10 supplementation seems to have no additional potentiating effect in patients in primary prevention. In contrast, glucose homeostasis may improve with CoQ10 supplementation.

Time course for the recovery of physical performance, blood hemoglobin, and ferritin content after blood donation.

BACKGROUND: It is widely accepted that blood donation negatively affects endurance performance, but data on physical recovery after a standard blood donation are scarce. This study aimed to elucidate the temporary impact of blood donation on endurance performance, measured as peak oxygen uptake (VO2peak ) and time trial (TT) performance. STUDY DESIGN AND METHODS: VO2peak , TT performance, blood, iron, and anthropometric variables were determined before (baseline) and 3, 7, 14, and 28 days after blood donation in 19 healthy men. RESULTS: VO2peak was reduced by 6.5% from 49.7 ± 2 mL/kg/min at baseline to 46.3 ± 2 mL/kg/min on Day 3 (p < 0.001), and TT performance was reduced by 5.2% from 13:31 ± 00:42 to 14:13 ± 00:50 min:sec (p < 0.001). Both VO2peak and TT performance were back to baseline 14 days after blood donation. Blood hemoglobin (Hb) concentration declined 7.9% from 9.3 ± 0.11 mmol/L at baseline to 8.6 ± 0.1 mmol/L on Day 3 (p < 0.001) and was not different from baseline 28 days after blood donation. The hematocrit (Hct) was reduced from 43.8 ± 0.5% at baseline to 40.6 ± 0.6% on Day 3 (p < 0.001). On Day 28 Hct was 42.8 ± 0.5% and still reduced below baseline (p = 0.028). Ferritin concentration was reduced 46% from 113 ± 23 µg/L at baseline to a minimum of 61 ± 14 µg/L on Day 14 (p = 0.008). CONCLUSION: The individual recovery was variable, but physical performance was recovered 14 days after a standard blood donation, despite blood Hb concentration remaining lower than at baseline.

Erythropoietin treatment enhances muscle mitochondrial capacity in humans.

Erythropoietin (Epo) treatment has been shown to induce mitochondrial biogenesis in cardiac muscle along with enhanced mitochondrial capacity in mice. We hypothesized that recombinant human Epo (rhEpo) treatment enhances skeletal muscle mitochondrial oxidative phosphorylation (OXPHOS) capacity in humans. In six healthy volunteers rhEpo was administered by sub-cutaneous injection over 8 weeks with oral iron (100 mg) supplementation taken daily. Mitochondrial OXPHOS was quantified by high-resolution respirometry in saponin-permeabilized muscle fibers obtained from biopsies of the vastus lateralis before and after rhEpo treatment. OXPHOS was determined with the mitochondrial complex I substrates malate, glutamate, pyruvate, and complex II substrate succinate in the presence of saturating ADP concentrations, while maximal electron transport capacity (ETS) was assessed by addition of an uncoupler. rhEpo treatment increased OXPHOS (from 92 ± 5 to 113 ± 7 pmol·s(-1)·mg(-1)) and ETS (107 ± 4 to 143 ± 14 pmol·s(-1)·mg(-1), p < 0.05), demonstrating that Epo treatment induces an upregulation of OXPHOS and ETS in human skeletal muscle.