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      Coenzyme q10 liquid supplementation in dyslipidemic subjects with statin-related clinical symptoms: a double-blind, randomized, placebo-controlled study

      research-article
      1 , 2 , 3 , 2 , 1
      Drug Design, Development and Therapy
      Dove
      coenzyme Q10, myalgia, statins

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          Abstract

          Introduction

          Statin-associated myalgia occurs in about 1–3% of patients in the medical literature. Plasma CoQ10 levels are reduced in patients undergoing statin.

          Objective

          The primary outcome was the detection of clinical symptoms and the perception of pain evaluated throughout specific questionnaires. The secondary outcome was the variation in lipid profile and the variation in safety parameters.

          Methods

          We enrolled 60 Caucasian patients, intolerant to statins. During the run-in period, patients underwent a 1-month wash-out period during which statins were stopped. At the end of the wash-out period, if CPK and/or transaminases returned within an acceptable range, statins were re-introduced at half of the previously taken dose. After one month, patients were randomized to take either a liquid CoQ10 supplement or a placebo for three months at 100 mg/day.

          Results

          The Clinical Index Score for myalgia assessment was lower after 3 months with CoQ10, while it did not change with the placebo. The VAS score was lower after 3 months of CoQ10 supplementation, while no variation was recorded with the placebo. In the group treated with the dietary supplement, CoQ10 plasma concentrations were inversely correlated with CPK levels, Clinical Index Score absolute values, and VAS.

          Conclusion

          The addition of CoQ10 with half dosage statin in patients with previous intolerance to statins improves the perception of clinical symptoms such as asthenia, myalgia or pain.

          Most cited references31

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          The distribution and chemical composition of ultracentrifugally separated lipoproteins in human serum.

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            An assessment by the Statin Muscle Safety Task Force: 2014 update.

            The National Lipid Association's Muscle Safety Expert Panel was charged with the duty of examining the definitions for statin-associated muscle adverse events, development of a clinical index to assess myalgia, and the use of diagnostic neuromuscular studies to investigate muscle adverse events. We provide guidance as to when a patient should be considered for referral to neuromuscular specialists and indications for the performance of a skeletal muscle biopsy. Based on this review of evidence, we developed an algorithm for the evaluation and treatment of patients who may be intolerant to statins as the result of adverse muscle events. The panel was composed of clinical cardiologists, clinical lipidologists, an exercise physiologist, and a neuromuscular specialist.
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              Statin therapy and plasma coenzyme Q10 concentrations--A systematic review and meta-analysis of placebo-controlled trials.

              Statin therapy may lower plasma coenzyme Q10 (CoQ10) concentrations, but the evidence as to the significance of this effect is unclear. We assessed the impact of statin therapy on plasma CoQ10 concentrations through the meta-analysis of available RCTs. The literature search included selected databases up to April 30, 2015. The meta-analysis was performed using either a fixed-effects or random-effect model according to I(2) statistic. Effect sizes were expressed as weighted mean difference (WMD) and 95% confidence interval (CI). The data from 8 placebo-controlled treatment arms suggested a significant reduction in plasma CoQ10 concentrations following treatment with statins (WMD: -0.44 μmol/L, 95%CI: -0.52, -0.37, p<0.001). The pooled effect size was robust and remained significant in the leave-one-out sensitivity analysis. Subgroup analysis suggested that the impact of statins on plasma CoQ10 concentrations is significant for all 4 types of statins studied i.e. atorvastatin (WMD: -0.41 μmol/L, 95%CI: -0.53, -0.29, p<0.001), simvastatin (WMD: -0.47 μmol/L, 95% CI: -0.61, -0.33, p<0.001), rosuvastatin (WMD: -0.49 μmol/L, 95%CI: -0.67, -0.31, p<0.001) and pravastatin (WMD: -0.43 μmol/L, 95%CI: -0.69, -0.16, p=0.001). Likewise, there was no differential effect of lipophilic (WMD: -0.43 μmol/L, 95%CI: -0.53, -0.34, p<0.001) and hydrophilic statins (WMD: -0.47 μmol/L, 95%CI: -0.62, -0.32, p<0.001). With respect to treatment duration, a significant effect was observed in both subsets of trials lasting <12 weeks (WMD: -0.51 μmol/L, 95%CI: -0.64, -0.39, p<0.001) and ≥12 weeks (WMD: -0.40 μmol/L, 95%CI: -0.50, -0.30, p<0.001). The meta-analysis showed a significant reduction in plasma CoQ10 concentrations following treatment with statins. Further well-designed trials are required to confirm our findings and elucidate their clinical relevance.
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                Author and article information

                Journal
                Drug Des Devel Ther
                Drug Des Devel Ther
                DDDT
                dddt
                Drug Design, Development and Therapy
                Dove
                1177-8881
                21 October 2019
                2019
                : 13
                : 3647-3655
                Affiliations
                [1 ]Center of Diabetes and Metabolic Diseases, Department of Internal Medicine and Therapeutics, University of Pavia and Fondazione IRCCS Policlinico San Matteo , Pavia, Italy
                [2 ]Laboratory of Molecular Medicine, University of Pavia , Pavia, Italy
                [3 ]Center for Prevention, Surveillance, Diagnosis and Treatment of Rare Diseases, Fondazione IRCCS Policlinico San Matteo , Pavia, Italy
                Author notes
                Correspondence: Giuseppe DerosaDepartment of Internal Medicine and Therapeutics, University of Pavia, Fondazione IRCCS Policlinico San Matteo , Pavia, P.le C. Golgi, 2, Pavia27100, ItalyTel +39 038 252 6217Fax +39 038 252 6259 Email giuseppe.derosa@unipv.it
                Article
                223153
                10.2147/DDDT.S223153
                6814351
                31695332
                cb7d31cf-2335-4d81-bbe8-8be94b196792
                © 2019 Derosa et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 14 July 2019
                : 07 August 2019
                Page count
                Figures: 2, Tables: 4, References: 42, Pages: 9
                Categories
                Original Research

                Pharmacology & Pharmaceutical medicine
                coenzyme q10,myalgia,statins
                Pharmacology & Pharmaceutical medicine
                coenzyme q10, myalgia, statins

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