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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.

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  • Authors+Show Affiliations

    ,

    Department of Pharmacy, University of Washington School of Pharmacy, Box 357630, Seattle, WA, 98195, USA. cathyy@uw.edu. Department of Medicine, Kidney Research Institute, University of Washington School of Medicine, Box 359606, Seattle, WA, 98195, USA. cathyy@uw.edu.

    ,

    Division of Critical Care Medicine, Department of Anesthesiology, Vanderbilt University Medical Center, 1211 21st Avenue South, 526 Medical Arts Building, Nashville, TN, 37205, USA. frederic.t.billings@vanderbilt.edu.

    ,

    Department of Pharmacy, University of Washington School of Pharmacy, Box 357630, Seattle, WA, 98195, USA. adam.claessens@tu.edu.

    ,

    Department of Medicine, Kidney Research Institute, University of Washington School of Medicine, Box 359606, Seattle, WA, 98195, USA. broshanr@uw.edu.

    ,

    Department of Medicine, Kidney Research Institute, University of Washington School of Medicine, Box 359606, Seattle, WA, 98195, USA. loril@nwkidney.org.

    ,

    Division of Nephrology, Department of Medicine, Vanderbilt University Medical Center, 1161 21st Avenue South, S-3223 Medical Center North, Nashville, TN, 37232, USA. mary.b.sundell@vanderbilt.edu.

    ,

    Department of Medicine, Kidney Research Institute, University of Washington School of Medicine, Box 359606, Seattle, WA, 98195, USA. sahmad@uw.edu.

    ,

    Diabetes and Obesity Center of Excellence, Department of Medicine, University of Washington, Box 358055, Seattle, WA, USA. bhshao@u.washington.edu.

    ,

    Department of Pharmacy, University of Washington School of Pharmacy, Box 357630, Seattle, WA, 98195, USA. ds@uw.edu.

    ,

    Division of Nephrology, Department of Medicine, Vanderbilt University Medical Center, 1161 21st Avenue South, S-3223 Medical Center North, Nashville, TN, 37232, USA. alp.ikizler@vanderbilt.edu.

    Department of Medicine, Kidney Research Institute, University of Washington School of Medicine, Box 359606, Seattle, WA, 98195, USA. himmej@u.washington.edu.

    Source

    BMC nephrology 16: 2015 Nov 03 pg 183

    MeSH

    Administration, Oral
    Adolescent
    Adult
    Aged
    Aged, 80 and over
    Dietary Supplements
    Dose-Response Relationship, Drug
    Drug Tolerance
    Female
    Humans
    Kidney Failure, Chronic
    Male
    Maximum Allowable Concentration
    Middle Aged
    Oxidative Stress
    Renal Dialysis
    Ubiquinone
    United States
    Young Adult

    Pub Type(s)

    Journal Article
    Multicenter Study
    Randomized Controlled Trial
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    26531095

    Citation

    Yeung, Catherine K., et al. "Coenzyme Q10 Dose-escalation Study in Hemodialysis Patients: Safety, Tolerability, and Effect On Oxidative Stress." BMC Nephrology, vol. 16, 2015, p. 183.
    Yeung CK, Billings FT, Claessens AJ, et al. Coenzyme Q10 dose-escalation study in hemodialysis patients: safety, tolerability, and effect on oxidative stress. BMC Nephrol. 2015;16:183.
    Yeung, C. K., Billings, F. T., Claessens, A. J., Roshanravan, B., Linke, L., Sundell, M. B., ... Himmelfarb, J. (2015). Coenzyme Q10 dose-escalation study in hemodialysis patients: safety, tolerability, and effect on oxidative stress. BMC Nephrology, 16, p. 183. doi:10.1186/s12882-015-0178-2.
    Yeung CK, et al. Coenzyme Q10 Dose-escalation Study in Hemodialysis Patients: Safety, Tolerability, and Effect On Oxidative Stress. BMC Nephrol. 2015 Nov 3;16:183. PubMed PMID: 26531095.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Coenzyme Q10 dose-escalation study in hemodialysis patients: safety, tolerability, and effect on oxidative stress. AU - Yeung,Catherine K, AU - Billings,Frederic T,4th AU - Claessens,Adam J, AU - Roshanravan,Baback, AU - Linke,Lori, AU - Sundell,Mary B, AU - Ahmad,Suhail, AU - Shao,Baohai, AU - Shen,Danny D, AU - Ikizler,T Alp, AU - Himmelfarb,Jonathan, Y1 - 2015/11/03/ PY - 2015/04/01/received PY - 2015/10/29/accepted PY - 2015/11/5/entrez PY - 2015/11/5/pubmed PY - 2016/6/29/medline SP - 183 EP - 183 JF - BMC nephrology JO - BMC Nephrol VL - 16 N2 - 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. SN - 1471-2369 UR - https://www.unboundmedicine.com/medline/citation/26531095/Coenzyme_Q10_dose_escalation_study_in_hemodialysis_patients:_safety_tolerability_and_effect_on_oxidative_stress_ L2 - https://www.biomedcentral.com/1471-2369/16/183 DB - PRIME DP - Unbound Medicine ER -