Statin therapy depresses total body fat oxidation in the absence of genetic limitations to fat oxidation

Abstract

Cholesterol lowering drugs are associated with myopathic side effects in 7% of those on therapy, which is reversible in most, but not all patients. This study tested the hypothesis that total body fat oxidation (TBFO) is reduced by statins in patients with genetic deficiencies in FO, determined by white blood cells (FOwbc) and by molecular analysis of common deficiencies, and would cause intolerance in some patients. Six patients on statin therapy without myopathic side effects (tolerant) and 7 patients who had previously developed statin-induced myopathic symptoms (intolerant) (age = 58 +/- 8.25 yrs, ht. = 169 +/- 11 cm, and wt. = 75.4 +/- 14.2 kg) were tested for TBFO (Respiratory Exchange Ratio, RER) pre- and during exercise. FOwbc was not significantly different between tolerant and intolerant (0.261 +/- 0.078 vs. 0.296 +/- 0.042 nmol/h per 10(9) wbc), or normals (0.27 +/- 0.09 nmol/h per 10(9) wbc) and no common molecular abnormalities were found. Pre-exercise RER (0.73 +/- 0.05 vs. 0.84 +/- 0.05) was significantly lower in the intolerant group and the VO2 at RER = 1.0 (1.27 +/- 0.32 vs. 1.87 +/- 0.60 L/min) greater than the tolerant. Post-exercise lactates were not different between groups. Although dietary fat intake was not different, blood lipoprotein levels, particularly triglycerides were 35% lower in tolerant than previously intolerant. TBFO and blood lipoproteins were reduced in tolerant patients in spite of the absence of genetic limitations, but not in the intolerant group as hypothesized. Although not conclusive, these data suggest the need for a prospective study of the effects of statins on fat oxidation.

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.…”

Serum Oxidized‐LDL is Associated with Diabetes Duration Independent of Maintaining Optimized Levels of LDL‐Cholesterol

“…Of note, it has been demonstrated that statins reduce ox-LDL production [38,39], and decrease total body fat oxidation [40]. A study by Van Tits et al [41] reported a decrease of 35-43% in ox-LDL by therapeutic intervention with statins in patients with familial hypercholesterolemia.…”

A Randomized Clinical Trial to Assess the Effect of Statins on Skeletal Muscle Function and Performance: Rationale and Study Design

“…14 Interestingly, in the latter study, the resting respiratory exchange ratio (RER; an index of fat and carbohydrate metabolism) increased with statin therapy in both asymptomatic and symptomatic statin users, consistent with other reports suggesting that statins decrease or impair fat oxidation. [15][16][17] An altered RER attributable to statins could alter exercise metabolism and diminish aerobic exercise performance.…”