Strategies for the prevention and treatment of statin-induced myopathy: Is there a role for ubiquinone supplementation?

Koumis, Tina; Nathan, Joseph P.; Rosenberg, Jack M.; Cicero, Lorraine A.

doi:10.1093/ajhp/61.5.515

Cited by 22 publications

(5 citation statements)

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“…There are only some case reports suggesting that CoQ administration may reduce the severity (but not the incidence) of myopathy in patients receiving statins [95,96]. In addition, no systematic studies investigated whether CoQ supplementation alleviates symptoms of statin-induced myopathy.…”

Section: Mechanism Of Statin-induced Myopathymentioning

confidence: 99%

Adverse Effects of Statins - Mechanisms and Consequences

Bełtowski¹,

Wójcicka²,

Jamróz-Wiśniewska

2009

CDS

192

119

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Statins inhibit 3-hydroxy-3-methylglutarylcoenzyme A (HMG-CoA) reductase, the rate-limiting enzyme in cholesterol biosynthesis, which converts HMG-CoA to mevalonate. Statins lower plasma low-density lipoprotein (LDL) cholesterol by causing intracellular cholesterol depletion and upregulating the expression of LDL receptors. Apart from cholesterol, mevalonate is also the substrate for the synthesis of nonsteroid isoprenoids including farnesylpyrophosphate, geranylgeranylpyrophosphate (both attached to small GTP-binding proteins by protein prenyltransferases), coenzyme Q, dolichol, isopentenyladenosine, etc. Depletion of these isoprenoids results in so called "pleiotropic" effects of statins which are independent of cholesterol lowering. Although statins are generally well-tolerated, adverse effects may occur in some patients. These effects result from impaired protein prenylation, deficiency of coenzyme Q involved in mitochondrial electron transport and antioxidant protection, abnormal protein glycosylation due to dolichol shortage, or deficiency of selenoproteins. Myopathy is the most frequent side effect of statins and in some cases may have a form of severe rhabdomyolysis. Less common adverse effects include hepatotoxicity, peripheral neuropathy, impaired myocardial contractility and autoimmune diseases. The risk of these unfavorable effects is largely outweighed by great reduction of cardiovascular events in statin users. However, due to increasing number of patients taking statins, monitoring for any side effects, intense research to recognize their mechanisms and to identify susceptible patients, as well as rational management of these complications are mandatory to further improve safety of these excellent drugs.

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Section: Mechanism Of Statin-induced Myopathymentioning

confidence: 99%

Adverse Effects of Statins - Mechanisms and Consequences

Bełtowski¹,

Wójcicka²,

Jamróz-Wiśniewska

2009

CDS

192

119

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“…It has been proposed by several authors that CoQ10 supplementation could counteract the side effects of statins. Several studies assessed the potential beneficial role of CoQ10 supplementation in statin‐treated patients with myopathic symptoms, with promising 97,100,101 or less promising results 102 . In particular, Langsjoen et al 97 .…”

Section: Coenzyme Q As An Adjuvant In Drug Treatment: the Example Of mentioning

confidence: 99%

Is there a place for coenzyme Q in the management of metabolic disorders associated with obesity?

Sohet¹,

Delzenne²

2012

Nutrition Reviews

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Coenzyme Q (CoQ), a lipophilic cofactor of the electron transport chain in the mitochondria, can be synthesized endogenously or provided by food. The aim of this review is to summarize the in vitro cell culture studies, the in vivo animal studies, and the human studies investigating the impact of CoQ supplementation on the occurrence of obesity and related disorders (diabetes, hypertension, lipemia, and atherosclerosis). The antioxidative properties of CoQ have been observed in different experimental models of atherosclerosis, obesity, and diabetes. The recent discovery of the anti-inflammatory effect of CoQ, mostly described in vitro, has generated increased interest in CoQ supplementation, but it needs to be confirmed in vivo in pathological situations. CoQ intervention studies in humans failed to show reproducible effects on body weight, fat mass, or glycemia, but CoQ supplementation does seem to have an antihypertensive effect. The molecular mechanism to explain this effect has only recently been discovered.

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“…Poor coenzyme Q10 status and antioxidant status in the body are also predisposing factors for statin toxicity [6][7][8][9][10]. One of the most important factors for predicting risk of myopathy is also way of metabolization of statins.…”

Section: Epidemiology and Risk Factors Of Statin Myopathymentioning

confidence: 99%

“…The antioxidant status of our body depends on the presence of coenzyme Q10, vitamin A, E, and C and beta-carotine, superoxide dismutase, catalase and ceruloplasmin. Apart from these antioxidants, flavonoids, anthrocyclins, minerals; selenium, chromium and copper and w-3 fatty acids may also provide protection against oxidative stress predisposed by statins [6][7][8]. It also has been shown that increased levels of CoQ10 may protect cells from chemotherapy-induced oxidative stress [52].…”

Section: Coq10mentioning

confidence: 99%

“…Finally, the depletion of CoQ10 in muscle mitochondria during the statin therapy is to increase muscle cell fluidity and thus possibly cause myopathy [4,5]. Poor coenzyme Q10 status and antioxidant status in the body are also predisposing factors for statin toxicity [6][7][8][9][10]. A number of observations suggest that statin toxicity may be due to the metabolic effects of lipid lowering in patients with minor muscle disorders [11][12][13].…”

Section: Introductionmentioning

confidence: 99%

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Is there is Need for Ubiquinone (CoQ10) Supplementation in Statin- Associated Myopathy?

Skripova¹,

Daniel²,

Katarina³

et al. 2010

TONUTRAJ

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Statins are currently the most effective drugs in reducing low-density lipoprotein cholesterol (LDL-C). With their mechanism of action, by inhibiting 3-hydroxy-3 methylglutharyl coenzyme A reductase, statins decrease cholesterol production. The same biosynthetic pathway is shared by ubiquinone or coenzyme Q10. Statins block production of dekaprenyl-4-benzoate, a precursor of coenzyme Q10 (CoQ10), which is an essential component in mitochondrial transport system. Ubiquinone deficiency may affect oxidative phosphorylation and adenosine triphosphate production, which can subsequently result in impairing of muscle energy metabolism and contribute to development of myopathy. Statin therapy also decreases antioxidant status in the body, resulting in to increase in free radical damage to cells in various parts of body; liver, nerves, muscles. Statins can decrease natural antioxidant protection present in our body and predispose toxicity. Statin-associated myopathy is the most common side effect of statin treatment often lead to statin dose reduction, or therapy cessation, which can negatively affect cardiovascular risk management. The spectrum of statin-related myopathy ranges from common but clinically benign myalgia to rare but life-threatening rhabdomyolysis. Observational studies suggest that myalgia can occur in up to 10% of persons prescribed statins, whereas rhabdomyolysis continues to be rare. Statins lower circulating levels of CoQ10 up to 54%, whereas several studies did not confirmed a lowering of CoQ10 levels in muscles during statin therapy and the evidence was given also on low dose of statin therapy, which did not appear to reduce intramuscular levels of CoQ10 in symptomatic patients with statin myopathy. The conflicting results have been published on the impaired mitochondrial function, which was found during the analysis of the myocyte cells in patients treated with statins. The supplementation of CoQ10 results in increasing of serum CoQ10, but it is not clear if it relieves myopatic symptoms in statin treated patients. Yet available intervention studies reported contrasting results and just two of them proved benefit of CoQ10 supplementation. Hence coenzyme Q10 supplementation is not currently recommended for routine use in the prophylaxis of statin toxicity.

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Strategies for the prevention and treatment of statin-induced myopathy: Is there a role for ubiquinone supplementation?

Cited by 22 publications

References 0 publications

Adverse Effects of Statins - Mechanisms and Consequences

Adverse Effects of Statins - Mechanisms and Consequences

Is there a place for coenzyme Q in the management of metabolic disorders associated with obesity?

Is there is Need for Ubiquinone (CoQ10) Supplementation in Statin- Associated Myopathy?

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