High‐Dose Statin Treatment Does Not Alter Plasma Marker for Brain Cholesterol Metabolism in Patients With Moderately Elevated Plasma Cholesterol Levels

Abstract

Statins inhibit endogenous cholesterol synthesis, up-regulate low-density lipoprotein (LDL) receptor expression in mammalian liver cells, and thus decrease circulating LDL-cholesterol concentrations. As cholesterol seems to play a role in the development of neurodegenerative diseases, it is of interest to evaluate the effect of high dosages of statins (eg, atorvastatin or simvastatin) on brain cholesterol metabolism. Plasma samples from 44 participants (aged 30-69 years, 16 men and 18 women) of an earlier randomized, placebo-controlled, double-blind trial, who took 40 mg atorvastatin or 80 mg simvastatin daily for 2 months, were used to analyze total cholesterol, its precursor lathosterol, and its metabolites 24(S)-hydroxycholesterol and 27-hydroxycholesterol. Despite a significant decrease in absolute plasma concentrations of oxysterols, total cholesterol, and its endogenous synthesis rate, indicated by a decreased ratio of lathosterol to cholesterol, the plasma 24(S)-hydroxycholesterol to cholesterol ratio, a surrogate marker of brain cholesterol homeostasis, remained unchanged. Short-term high-dose atorvastatin and simvastatin treatment does not seem to influence brain cholesterol metabolism in patients with moderately elevated plasma cholesterol levels.

ApoE and cholesterol in schizophrenia and bipolar disorder: comparison of grey and white matter and relation with APOE genotype

“…However, animal studies indicate that administration of high doses of simvastatin or pravastatin does not change total brain cholesterol levels 52,53 Furthermore, a study of human volunteers showed that administration of a highdose of either simvastatin or pravastatin did not change plasma 24(S)-hydroxycholesterol to cholesterol ratio, a surrogate marker of brain cholesterol homeostasis. 54 In addition, moderate or heavy past or present alcohol use was reported in a significant proportion of the psychiatric patients. In this group of patients, we found a significant deficit in cholesterol levels in white matter but not in grey matter relative to patients reported to have no or only social alcohol use.…”

Postprandial plasma oxyphytosterol concentrations after consumption of plant sterol or stanol enriched mixed meals in healthy subjects

“…Sitosterol and campesterol concentrations were analyzed using gas chromatography-flame ion detection (GC-FID) as described previously [12] and concentrations are expressed as mg/dL. 7b-Hydroxy(OH)-campesterol, 7b-OH-sitosterol, 7-keto-campesterol and 7-keto-sitosterol were analyzed by gas chromatography-mass spectrometry (GC-MS-MS) according to the procedure as described by Husche et al [13] with minor modifications related to the use of a GC-MS triplequad instead of a GC-MS singlequad and are expressed as ng/mL.…”

Statins and their influence on brain cholesterol

“…Because its measurement is easier in humans, the authors of nine different clinical studies have measured 24S-hydroxycholesterol, and majority of them demonstrated its reduction both in plasma and in CSF. [16][17][18][19][20][21][22][23] There were just two exceptions. In a study in which the authors used hydrophilic pravastatin, concentrations of 24S-hydroxycholesterol in plasma were decreased only nonsignificantly.…”

“…Only three recent clinical studies have measured 27-hydroxycholesterol in plasma 21,22,24 and one also in CSF. 23 In all of them 21,22,24 the authors found a significant reduction in plasma level of 27-OH-cholesterol after statin treatment, whereas the CSF levels were nonsignificantly reduced (in the study by Hoglund et al 24 ).…”