Coenzyme Q10 dose-escalation study in hemodialysis patients: safety, tolerability, and effect on oxidative stress

Abstract

Background: Coenzyme Q10 (CoQ10) supplementation improves mitochondrial coupling of respiration to oxidative phosphorylation, decreases superoxide production in endothelial cells, and may improve functional cardiac capacity in patients with congestive heart failure. There are no studies evaluating the safety, tolerability and efficacy of varying doses of CoQ10 in chronic hemodialysis patients, a population subject to increased oxidative stress.

Methods: We performed a dose escalation study to test the hypothesis that CoQ10 therapy is safe, well-tolerated, and improves biomarkers of oxidative stress in patients receiving hemodialysis therapy. Plasma concentrations of F2-isoprostanes and isofurans were measured to assess systemic oxidative stress and plasma CoQ10 concentrations were measured to determine dose, concentration and response relationships.

Results: Fifteen of the 20 subjects completed the entire dose escalation sequence. Mean CoQ10 levels increased in a linear fashion from 704 ± 286 ng/mL at baseline to 4033 ± 1637 ng/mL, and plasma isofuran concentrations decreased from 141 ± 67.5 pg/mL at baseline to 72.2 ± 37.5 pg/mL at the completion of the study (P = 0.003 vs. baseline and P < 0.001 for the effect of dose escalation on isofurans). Plasma F2-isoprostane concentrations did not change during the study.

Conclusions: CoQ10 supplementation at doses as high as 1800 mg per day was safe in all subjects and well-tolerated in most. Short-term daily CoQ10 supplementation decreased plasma isofuran concentrations in a dose dependent manner. CoQ10 supplementation may improve mitochondrial function and decrease oxidative stress in patients receiving hemodialysis.

Trial registration: This clinical trial was registered on clinicaltrials.gov [NCT00908297] on May 21, 2009.

Figures

Fig. 1

CoQ10 dose escalation study design. *Measurement of plasma CoQ10, comprehensive metabolic panel, creatine phosphokinase, and oxidative stress biomarkers

Fig. 2

Overview of study subject participation and study withdrawal

Fig. 3

Effect of Coenzyme Q10 supplementation on plasma concentrations of total CoQ10 (a) and CoQ10(H2):CoQ10 ratios (b) (mean ± SD) in study subjects and unmatched healthy controls. Sample numbers for baseline (0 mg), 300 mg, 600 mg, 1200 mg, 1800 mg, and healthy controls were 20, 19, 19, 18, 15, and 10, respectively

Fig. 4

Effect of hemodialysis (HD) on plasma concentrations of CoQ10 in study subjects administered 1800 mg of CoQ10 for 14 days (n = 10). Dark bars indicate total CoQ10 levels prior to standard hemodialysis treatment, lighter bars are following hemodialysis. Error bars indicate SD of the means (paired T-test for means p = 0.72)

Fig. 5

Effect of CoQ10 dose escalation (a–c) and total CoQ10 plasma concentrations (d–f) on plasma concentrations of F2-isoprostanes, isofurans, and isofuran:F2-isoprostane ratios

Fig. 6

Effect of CoQ10 dose escalation (a) and total CoQ10 plasma concentrations (b) on plasma concentrations of interleukin-6

Fig. 7

Effect of CoQ10 supplementation (following 1200 mg dosing period) on levels of oxidized methionine (mean ± SD) in apolipoprotein A-I of high density lipoprotein (all p-values > 0.5)