Statin Therapy Depresses Fat Metabolism in Older Individuals

Abstract

Although statin therapy normalizes blood lipoproteins, it reduced fat metabolism in older individuals, which cannot be a result of lower availability from blood.

Simvastatin-Induced Insulin Resistance May Be Linked to Decreased Lipid Uptake and Lipid Synthesis in Human Skeletal Muscle: the LIFESTAT Study

“…In the present study, the fat oxidation rate was similar between simvastatin-treated patients and control subjects. This is in line with the studies of short treatment (5 days–8 weeks) [ 15 , 16 ], but not those of longer treatment [ 17 – 19 ]. However, in the long-term studies, it is possible that a different plasma lipid profile [ 17 , 19 ], VO 2 max, or age [ 18 ] between the treatment and control groups may have caused the reported difference in fat oxidation rate.…”

“…In the light of the study by Phillips et al [ 4 ] and the preclinical data by Langhi et al [ 5 ], the question arises as to whether chronic simvastatin use changes fatty acid storage and oxidation in humans. The literature on the effect of statins on FA oxidation rate in humans is conflicting with studies reporting either no effect [ 15 , 16 ] or simvastatin-induced impaired fat oxidation [ 17 – 20 ]. One explanation for controversy could be that the studies that report no effect of statins on fat oxidation (FO) only use treatments of shorter duration (5 days to 8 weeks) [ 15 , 16 ].…”

Inhibition of the mevalonate pathway affects epigenetic regulation in cancer cells

“…However, this could also be due to a lack of NADPH, because the following NADPH-producing reactions are downregulated by statins: 1) glycolysis, including the NADPH-producing pentose-phosphate cycle as well as the KREBS or tricarbonic acid cycle (39) , 2) the fatty acid oxidation (40) , 3) the OCM, which was identified as a major producer of NADPH by quantitative flux analysis (41) , and 4) TYMS , which is among the most downregulated genes analyzed in our transcriptomic study, is known to convert dUMP to dTMP in the presence of NADPH and serine (42) . Thus, a lack of NADPH could be responsible for the downregulation of this gene in responsive cell lines ( Table 4 ).…”

Statins Do Not Impair Whole-body Fat Oxidation During Moderate-intensity Exercise in Dyslipidemic Adults

“…Other conflicting results include reports in humans of increased resting RER with statins, indicating a possible shift from fat to CHO metabolism [13,35]. A 12-week aerobic training study measured a greater increase in VO2max in a -statin, compared with +statin group.…”

“…The available research in patients undergoing exercise has produced conflicting results, with studies confounded by the co-administration of a kaleidoscope of other cholesterol-lowering agents, or with β-blockers, which inhibit the release of FFA from adipose tissue and complicate the interpretation of the data [11,12]. One study in patients has reported reduced fat oxidation with atorvastatin, during lower-intensity exercise [13]. Patients have also self-reported increased fatigue with exertion after taking simvastatin for a period of 6 months [14].…”