Serum cholesterol precursor sterols in coeliac disease: effects of gluten free diet and cholestyramine

Abstract

Enhanced biliary secretion and high faecal excretion of cholesterol are associated with increased cholesterol synthesis in coeliac disease. We have further investigated cholesterol synthesis in coeliac disease by determining the concentrations of faecal steroids and cholesterol precursors in serum, with and without a gluten free diet and while taking cholestyramine. The levels of unesterified methyl sterols and free and esterified lathosterol, but not those of squalene and desmosterol, were increased in proportion to the level of cholesterol synthesis, as measured with the sterol balance technique. Serum esterified methyl sterol concentrations were also slightly higher but, unlike free methyl sterols or lathosterol, they were not significantly correlated with cholesterol synthesis. The gluten free diet decreased the level of cholesterol synthesis, and the levels of lathosterol and free methyl sterols. There was less decrease in the concentration of esterified methyl sterols, and an insignificant decrease in the concentrations of squalene and desmosterol. Cholestyramine lowered the serum cholesterol concentration and increased that of serum free methyl sterols less in the patients than in the controls, and the increase was proportionate to increase of cholesterol elimination (or synthesis). The increase of serum free methyl sterols per unit of the increase of cholesterol elimination (or synthesis) was three times higher in the bile acid malabsorption caused by cholestyramine than in the cholesterol malabsorption caused by gluten enteropathy. On the other hand, the decrease in the level of serum cholesterol relative to the increase in cholesterol elimination (or synthesis) was higher in cholesterol malabsorption due to coeliac disease than in cholestyramine induced bile acid malabsorption. Effective secretion of newly synthesised and/or absorbed cholesterol directly into the bile could be a factor in the marked decrease of the serum cholesterol concentration in coeliac disease.