title: Potential metabolic consequences of statins in sepsis.
abstract: OBJECTIVE
  Statins may be important for the prevention and management of sepsis; however, through their impact on ubiquinone synthesis, they may impair mitochondrial and organ function in the septic patient. Here we provide a narrative review of the function and roles of ubiquinone in cellular metabolism, the interactions with statins, and the potential consequences in the critically ill.
  
  
  METHODS
  Literature search using the PubMed database. Search terms included statins, mitochondria, ubiquinone, and sepsis.
  
  
  CONCLUSIONS
  Statins are 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors and act by decreasing mevalonate levels, a precursor for cholesterol synthesis. However, mevalonate is also a precursor for ubiquinone, an integral component of the mitochondrial respiratory chain and an important antioxidant. Plasma ubiquinone is inversely related to statin levels, and impaired statin metabolism or excretion can decrease ubiquinone levels markedly. This is potentially important as critical illness markedly impairs statin metabolism. As mitochondrial dysfunction may be a major contributor to sepsis-induced organ failure, it is plausible that low ubiquinone levels may exacerbate mitochondrial and organ dysfunction. Furthermore, although the clinical relevance of low ubiquinone levels is currently unknown in the critically ill, this is often cited as a possible cause of the myopathy and rhabdomyolysis associated with statin use.
authors.affiliation: University College Hospitals NHS Foundation Trust, University College London, London, United Kingdom.
authors.forename: David A
authors.initials: DA
authors.lastname: Brealey
authors.forename: Mervyn
authors.initials: M
authors.lastname: Singer
authors.forename: Marius
authors.initials: M
authors.lastname: Terblanche
mesh_terms: D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D018805:Sepsis / Q000150:complications* / Q000378:metabolism* / Q000628:therapy; D014451:Ubiquinone / Q000502:physiology
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D014451:Ubiquinone