Potential metabolic consequences of statins in sepsis

TY - JOUR

T1 - Potential metabolic consequences of statins in sepsis

AU - Brealey, David A.

AU - Singer, Mervyn

AU - Terblanche, Marius

PY - 2011/6

Y1 - 2011/6

N2 - 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.Data Source: Literature search using the PubMed database. Search terms included statins, mitochondria, ubiquinone, and sepsis.Conclusion: 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.

AB - 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.Data Source: Literature search using the PubMed database. Search terms included statins, mitochondria, ubiquinone, and sepsis.Conclusion: 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.

KW - sepsis

KW - statins

KW - ubiquinone

KW - mitochondria

KW - antioxidant

KW - organ dysfunction

KW - COA REDUCTASE INHIBITORS

KW - CHRONIC HEART-FAILURE

KW - COENZYME Q(10) SUPPLEMENTATION

KW - CRITICALLY-ILL PATIENTS

KW - SKELETAL-MUSCLE

KW - DOUBLE-BLIND

KW - UBIQUINONE CONCENTRATIONS

KW - HEALTHY-VOLUNTEERS

KW - SERUM UBIQUINONE

KW - NITRIC-OXIDE

U2 - 10.1097/CCM.0b013e31820eb74f

DO - 10.1097/CCM.0b013e31820eb74f

M3 - Article

SN - 0090-3493

VL - 39

SP - 1514

EP - 1520

JO - Critical Care Medicine

JF - Critical Care Medicine

IS - 6

ER -