Creatine as a Candidate to Prevent Statin Myopathy
Abstract
:1. Introduction
2. Common Hypothesis on Pathogenesis
3. Statins Decrease Creatine Synthesis
4. Functions of Creatine in the Muscle
5. Decreasing Creatine Content Harms Muscular Function
- Decreased levels of phosphocreatine near cytoplasmic ATPase, which is therefore limiting the substrate (ATP) that is readily available for their function.
- Decreased differentiation of myoblasts into myocytes.
- Lack of sufficient creatine to take up the phosphate from ATP in the mitochondria. This may lead to reduced ATP turnover in the mitochondria, which in turn might be the cause of the mitochondrial dysfunction that was often hypothesized to be the cause of statin myopathy (Table 1).
6. Statins Reduce Synthesis of ATP in the Muscle
7. Creatine Administration Prevents Statin Myopathy
8. Discussion and Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Paper | Mechanisms Proposed |
---|---|
Tomaszewski et al., 2011 [24] | Altered membrane function due to lower cholesterol content. Altered mitochondrial function due to decreased muscle coenzyme Q10 (CoQ10). Impairment of calcium homeostasis. Induction of apoptosis. Genetic determinants. |
Vrablik et al., 2014 [25] | Decreased intracellular concentrations of cholesterol. Reduced production of coenzyme Q10 and related ubiquinones. Decreased production of prenylated proteins. Increased uptake of cholesterol from the extracellular space. Increased uptake of phytosterols. Disruption of calcium metabolism in myocytes. Decreased renewal of damaged muscle cells via the ubiquitin pathway. Inhibition of selenoprotein synthesis. Genetic factors 1. Unmasking of pre-existing muscular disorders |
Apostolopoulou et al., 2015 [26] | Impairment of mitochondrial function. Decreased muscle coenzyme Q10 (CoQ10). Genetic susceptibility. |
Laufs et al., 2015 [27] | Reduction of cholesterol/isoprenoid concentrations in specific cellular and subcellular compartments. Reduced sarcolemmal and/or sarcoplasmic reticular cholesterol. Alterations of myocellular fat and/or sterol concentration. Increased catabolism of muscular proteins or decreased catabolism of damaged proteins. Failure to repair damaged muscle. Leakage of sarcolemmal calcium into the cytoplasm. Impairment of mitochondrial function 2. |
Muntean et al., 2017 [28] | Increased fatty acid synthesis and induced triacylglycerol and phospholipid accumulation in lipid droplets 3. Inhibition of the mevalonate pathway and subsequent decrease in availability of isoprenoid intermediates, leading to decreased synthesis of cholesterol, ubiquinone and dolichols, and to impaired prenylation of structural proteins. Calcium release from sarcoplasmic reticulum and mitochondria. Impairment of oxidative phosphorylation. Decrease in mitochondria density and biogenesis. Apoptosis and calpain-mediated cell death. Impairment of muscle regeneration and the remodeling of cytoskeletal architecture. |
du Souich et al., 2017 [29] | Increased statin accumulation in the myocyte, resulting from the reduced function of the transporters carrying statins into cells or their metabolites out of them. Altered mitochondrial function causing reduced production of ATP, excess production of reactive oxygen species (ROS) and apoptosis. Reduced ubiquinone levels. Toxic effect of statins on mitochondrial function. Direct effect of statins on sarcoplasma chloride and lactate. |
Selva-O’Callaghan et al., 2018 [30] | Mitochondrial dysfunction. Oxidative stress. Impaired mevalonate metabolism. Isoprenylation of small G-proteins. Genetic susceptibility (polymorphisms of the SLCO1B1 gene 4, alterations in genes coding for plasma membrane calcium transporting ATPase and alterations of the CoQ2 gene 5) 6. |
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Balestrino, M.; Adriano, E. Creatine as a Candidate to Prevent Statin Myopathy. Biomolecules 2019, 9, 496. https://doi.org/10.3390/biom9090496
Balestrino M, Adriano E. Creatine as a Candidate to Prevent Statin Myopathy. Biomolecules. 2019; 9(9):496. https://doi.org/10.3390/biom9090496
Chicago/Turabian StyleBalestrino, Maurizio, and Enrico Adriano. 2019. "Creatine as a Candidate to Prevent Statin Myopathy" Biomolecules 9, no. 9: 496. https://doi.org/10.3390/biom9090496