Cholesterol malabsorption caused by sitostanol ester feeding and neomycin in pravastatin-treated hypercholesterolaemic patients

Abstract

Serum cholesterol values were insufficiently reduced by pravastatin in two different patient populations. Therefore, we studied whether further cholesterol reduction could be achieved by inhibiting both cholesterol synthesis (by pravastatin) and absorption (by neomycin or sitostanol ester). Thus, we measured serum cholesterol, cholesterol precursors (reflecting cholesterol synthesis), cholestanol and plant sterols (reflecting cholesterol absorption and biliary secretion) for up to 6 weeks in pravastatin-treated patients with familial hypercholesterolaemia (FH, n = 13) and with and without ileal bypass during addition of neomycin (1.5 g per day) and in another patient population of non-FH (n = 14) subjects during addition of sitostanol ester (1.5 g per day). Addition of neomycin lowered serum total, LDL and HDL cholesterol by a further 20%, and increased the pravastatin-lowered precursor:cholesterol ratios by 20% (irrespective of ileal bypass). It also reduced by 20% the plant sterol:cholesterol ratio (irrespective of ileal bypass) which was markedly increased by pravastatin alone. Pravastatin and neomycin in combination lowered total, LDL and HDL cholesterol by 45%, 53% and 17%, respectively. This combined regimen reduced the serum lathosterol:cholesterol ratio to about half of the reduction caused by pravastatin, while the elevation of the plant sterols:cholesterol ratio was less with the combination than with pravastatin alone. Changes in serum cholesterol precursor:cholesterol and plant sterol:cholesterol ratios during the combined treatment were smaller in the subgroup with ileal bypass. Addition of sitostanol ester did not lower serum total or LDL cholesterol nor the precursor:cholesterol ratios significantly, while the reduction observed in the plant sterols:cholesterol ratios was similar to that achieved with neomycin addition.(ABSTRACT TRUNCATED AT 250 WORDS)

Beyond blood lipids: phytosterols, statins and omega-3 polyunsaturated fatty acid therapy for hyperlipidemia

“…A series of randomised, controlled trials [74][75][76] combining phytosterols with statin medication show a 4.5±2.4% additive effect, which translates to an additional 9-14% reduction in cardiovascular events, using risk modelling equations [77,78]. Accordingly, statin-induced inhibition of cholesterol synthesis may insufficiently reduce LDL cholesterol, produce adverse effects and may be uneconomical, such that suboptimal doses may be required [79].…”

Support of drug therapy using functional foods and dietary supplements: focus on statin therapy

“…Effects of combination therapy with plant sterols and/or stanols and statins Vanhanen (35) was the first to conduct a clinical trial towards the effects of sitostanol esters on lipid levels in patients on pravastatin treatment. It was found that the daily addition of 1·5 g sitostanol ester did not lower serum total or LDL-cholesterol after 6 weeks of supplementation.…”

“…These authors suggest that plant sterols and stanols have an additive (35) DB, PC, R 3 HC on pravastatin therapy $ 1 year (n 14)…”

Cholesterol-lowering phytosterols: factors affecting their use and efficacy

“…The first study to examine combined treatments used a low dose of phytosterols (0.9 g/d) and showed no further reduction in LDL cholesterol with phytosterol addition. 102 When consumed at higher doses (1.8-3.0 g/d), phytosterol addition to statin therapy lowered LDL cholesterol an additional 6%-20%. [103][104][105][106][107][108][109][110][111] Because these studies were relatively short term lasting 4-12 weeks, De Jong et al 112 …”