Statin treatment and coenzyme Q10 (ubiquinone)

• statins mechanism of action is inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG CoA Reductase), the rate-limiting enzyme in the biosynthesis of cholesterol from acetyl-Coenzyme A via mevalonate and subsequent intermediates
  • inhibition of HMG CoA reductase also leads to a decrease the synthesis of nonsterol derivatives of mevalonate, including coenzyme Q10 (also known as ubiquinone)
  • studies have consistently shown that HMG CoA reductase inhibitors lower plasma coenzyme Q10 levels
• coenzyme Q10
  • is an important redox component of the mitochondrial respiratory transport chain
    • role in the generation of high-energy products such as adenosine triphosphate (ATP)
    • ATP-bioavailability is a crucial factor regulating myocardial contractility
      • ATP-content correlating positively with systolic and diastolic left ventricular indices in diseased human myocardium
    • myocardial tissue levels of coenzyme Q10 are reduced in heart failure (1)
    • the reduced form of coenzyme Q10, is ubiquinol
      • ubiquinol is an antioxidant and free radical scavenger
    • vitamin E (a-tocopherol) and coenzyme Q10 are carried by LDL
• coenzyme Q10 and statin treatment:
  • a study investigating the effect of treatment with simvastatin 20mg per day for a period of 6 months (2) showed
    • serum lipids showed the expected reductions.
    • plasma vitamin E and coenzyme Q10 levels were reduced by 17 ± 4% (P < 0·01) and 12 ± 4% (P < 0·03) at 6 months. However, the coenzyme Q10/LDL-cholesterol ratio and vitamin E/LDL-cholesterol ratio increased significantly
    • left ventricular ejection fraction (EF) decreased transiently after 1 month, while no significant change was observed at 3 and 6 months. Other markers of left ventricular function did not change significantly at any time point
    • the authors concluded that:
      • despite reduced plasma vitamin E and coenzyme Q10, 20 mg of simvastatin therapy is associated with a significantly increased coenzyme Q10/LDL-cholesterol ratio and vitamin E/LDL-cholesterol ratio
      • simvastatin treatment is not associated with impairment in left ventricular systolic or diastolic function in hypercholesterolaemic subjects after 6 months of treatment

Notes:

• the transient reduction in a population with normal left ventricular ejection fraction was not associated with clinical evidence for reduced cardiac function (1)
• in contrast to the findings of this single study statins have been shown to improve left ventricular function in several trials
  • atorvastatin therapy improved left ventricular ejection fraction in hypercholesteraemic patients with coronary artery disease (CAD) by 13% after 2 years of treatment (3)
  • simvastatin has been shown to reduce the occurrence of heart failure in a cohort of CAD patients without previous evidence of congestive heart failure (4)
  • the improvement in cardiac function in heart failure in patients with CAD is perhaps not surprising as it is most commonly owing to progression of coronary atherosclerosis and myocardial infarction – both of which are decreased by statin treatment

In 2024 a systematic review analysed one meta-analysis and four randomized controlled trials. All of these studies were conducted between 2010 and 2023, involving a total of 800 patients. All randomized controlled trials showed improvement in statin-associated myopathy with CoQ10 supplementation, along with or without a reduced dosage of statins, without any notable side effects of CoQ10. It was deduced by the authors that CoQ10 supplementation significantly ameliorates statin-induced musculoskeletal symptoms. (5)

Reference:

1. Folkers K et al. Biochemical rationale and myocardial tissue data on the effective therapy of cardiomyopathy with coenzyme Q10. Proc Natl Acad Sci USA 1985;82: 901–4.
2. Colquhoun DM et al. Effects of simvastatin on blood lipids, vitamin E, coenzyme Q10 levels and left ventricular function in humans. Eur J Clin Invest. 2005 Apr;35(4):251-8.
3. Kontopoulos AG et al. Long-term treatment effect of atorvastatin on aortic stiffness in hypercholesterolemic patients. Curr Med Res Opin 2003;19: 22–7.
4. Kjekshus J et al. The effects of simvastatin on the incidence of heart failure in patients with coronary heart Disease. J Card Fail 1997;3: 249–54.
5. Ahmad K et al. Effectiveness of Coenzyme Q10 Supplementation in Statin-Induced Myopathy: A Systematic Review. Cureus. 2024 Aug 31;16(8):e68316