Keep in mind that LDL-C is not a measurement of actual LDL particles; LDL-C is only an estimate (not measured from the individual's blood sample) of how much cholesterol is being transported by all LDL particles; either a smaller concentration of large particles or a high concentration of small particles. Also keep in mind that LDL particles carry many fat molecules (typically 3,000 to 6,000 fat molecules per LDL particle); this includes cholesterol, triglycerides, phospholipids and others. Thus even if the hundreds to thousands of cholesterol molecules within an average LDL particle were measured, this does not reflect the other fat molecules or even the number of LDL particles.
One study found increased levels of plant sterols in skeletal muscle in patients treated with high-dose statins [ 5 ]. Specifically, sitosterol was increased by approximately 50 percent. The authors of the study proposed that these increased cellular levels could contribute to the muscle toxicity of statins. Beta-sitosterol is an activator of AMP-activated protein kinase, which inhibits acetyl-CoA carboxylase. This results in reduced fat synthesis and increased beta-oxidation. Preliminary evidence suggests that statin-intolerant patients demonstrate increased fatty acid oxidation (FAO) in response to lovastatin, implicating an intrinsic FAO abnormality [ 10 ]. Statins increase the expression of mitochondrial carnitine acylcarnitine translocase and this effect may contribute to the alteration in FAO [ 11 ].