Serum plant sterols and biliary cholesterol secretion in humans

Abstract

Ratios of cholestanol, campesterol, and sitosterol to cholesterol in serum are known to reflect cholesterol absorption efficiency. Here, a possible link between these ratios and biliary secretion rates of cholesterol was investigated. Biliary lipid secretion rates and serum sterols were determined in 13 patients with gallstones. Seven were treated with ursodeoxycholic acid (UDCA) (1,000 mg/d). Serum cholesterol and non-cholesterol sterols were also measured in a cross over study in 20 healthy volunteers, who received either placebo or UDCA (750 mg/d). Biliary cholesterol secretion was significantly lower, whereas the non-cholesterol sterols and their ratio to cholesterol were higher in patients with gallstones treated with UDCA. A highly significant negative linear correlation between the ratios of non-cholesterol sterols to cholesterol and biliary cholesterol secretion was observed. In volunteers, administration of UDCA for 4 weeks was followed by a significant increase in non-cholesterol sterols and their ratios. Even 4 weeks after discontinuing UDCA administration, campesterol and sitosterol were still significantly higher than pretreatment levels, which was also true for the campesterolcholesterol ratio after 8 weeks. The results suggest that the ratios of cholestanol, campesterol, and sitosterol to cholesterol can be used as indicators of changes in biliary cholesterol secretion rates. Cholestanol and the two plant sterols campesterol and sitosterol are present in low concentrations in human blood (1, 2), but their concentrations are 400-to 1,000-fold lower than cholesterol (1). The concentrations in serum are the results of synthesis (for cholestanol only), absorption efficiency (campesterol and sitosterol), lipoprotein metabolism, and rate of hepatic excretion into bile (3). They are absorbed from the intestine to a much lesser extent than cholesterol (4, 5). Cholestanol is synthesized in the liver from cholesterol (6), and is almost absent from the diet. Whereas sitosterol is not metabolized to a significant extent in humans (7), a conversion of cholestanol to bile acids has been reported (6). The ratios of cholestanol, campesterol, and sitosterol to cholesterol in serum have been shown to correlate positively with the cholesterol absorption efficiency (2, 8), and have therefore been regarded as markers for changes in the absorption of cholesterol (8-10).Recently it has been reported that treatment with ursodeoxycholic acid (UDCA), a bile acid known to reduce the hepatic secretion of cholesterol (11-14), increases serum concentrations of plant sterols and cholestanol in patients with primary biliary cirrhosis (15) and patients with radiolucent gallstones (16,17). Considering that cholesterol absorption is not affected or even reduced by UDCA (13,14,(18)(19)(20)(21), we thought that these results were not consistent with the observation that the ratio of plant sterols to cholesterol are only markers of cholesterol absorption efficiency. The purpose of the present study was to examine whether the ...

Phytosterol and cholesterol precursor levels indicate increased cholesterol excretion and biosynthesis in gallstone disease

“…Previously, it has been postulated that in selected patients ratios of serum campesterol and sitosterol to cholesterol reflect the biliary cholesterol secretion rates 43. Because in our study we used the surrogate markers for cholesterol transport and synthesis, which indicated a link between cholesterol homeostasis and GSD, we further strengthened our findings by analysis of biliary lipid compositions, demonstrating that gallstone patients display increased biliary levels of both phytosterols and cholesterol.…”

Relationships between cholesterol homoeostasis and triacylglycerol-rich lipoprotein remnant metabolism in the metabolic syndrome

“…This is supported by demonstrations that weight reduction or statin therapy decreases cholesterol synthesis and biliary cholesterol, resulting in an increase in cholesterol absorption efficiency [19,21]. A recent study [22] also showed that biliary cholesterol secretion is inversely associated with plasma plant sterol levels. In the present study, we used the campesterol : cholesterol and lathosterol : cholesterol ratios to estimate cholesterol absorption and synthesis respectively.…”

Specific Loss of Brain ABCA1 Increases Brain Cholesterol Uptake and Influences Neuronal Structure and Function

“…However, reduced desmosterol conversion would be associated with reduced levels of 3beta-hydroxysterol Delta24-reductase (DHCR24) also known as seladin-1 and increased levels of all precursors carrying a double bond at C-24 including lanosterol (Waterham et al, 2001). We also measured the levels of dihydrolanosterol, the post-lanosterol step and a lathosterol precursor (Lindenthal et al, 2002) and found no changes in ABCA1 -B/-B cortex or hippocampus (data not shown). This suggests that the increase in cholesterol precursors is not due to their decreased degradation.…”