Phytosterol ester processing in the small intestine: impact on cholesterol availability for absorption and chylomicron cholesterol incorporation in healthy humans

Abstract

Phytosterols (plant sterols and stanols) can lower intestinal cholesterol absorption, but the complex dynamics of the lipid digestion process in the presence of phytosterol esters (PEs) are not fully understood. We performed a clinical experiment in intubated healthy subjects to study the time course of changes in the distribution of all lipid moieties present in duodenal phases during 4 h of digestion of meals with 3.2 g PE (PE meal) or without (control meal) PE. In vitro experiments under simulated gastrointestinal conditions were also performed. The addition of PE did not alter triglyceride (TG) hydrolysis in the duodenum or subsequent chylomicron TG occurrence in the circulation. In contrast, cholesterol accumulation in the duodenum aqueous phase was markedly reduced in the presence of PE (-32%, P < 0.10). In vitro experiments confirmed that PE reduces cholesterol transfer into the aqueous phase. The addition of PE resulted in a markedly reduced presence of meal-derived hepta-deuterated cholesterol in the circulation, i.e., in chylomicrons (-43%, PE meal vs. control; P < 0.0001) and plasma (-54%, PE meal vs. control; P < 0.0001). The present data show that addition of PE to a meal does not alter TG hydrolysis but displaces cholesterol from the intestinal aqueous phase and lowers chylomicron cholesterol occurrence in humans.

Fig. 1.

Apparent lipolysis rate expressed as AUC 240 min ratios of released FFAs in the aqueous phase (± pellet) to intact TGs in the oil phase. Results shown are the mean (± SEM) of ratios after a meal with PEs (gray) or without PE as control (white).

Fig. 2.

Incorporation of FFAs, free cholesterol, and free phytosterols in the aqueous (micellar) phase formed during in vitro digestion of a control and a phytosterol esters-containing meal. For experimental details, see the Materials and Methods section. Time represents the time of incubation under duodenal conditions. Y-axis represents the aqueous phase concentration for each lipid species relative to the initial concentration.

Fig. 3.

Distribution expressed in AUC240 (mmol/min/l) of free cholesterol and CEs in the different duodenum phases (aqueous, oil, and pellet) after a meal with PEs (gray) or without PE as control (white). Results are the mean (± SEM) of AUC240 min.

Fig. 4.

Distribution (ratios) of sterol species in the different duodenum phases (aqueous, oil, and pellet) after a meal with PE (gray) or without PE as control (white). A: Phytosterol esters/phytosterols and phytosterols/cholesterol ratios. B: Cholesterol aqueous phase/pellet ratio. Results are the mean (± SEM) of AUC240 min ratios.

Fig. 5.

Kinetics of occurrence of absorbed meal D7C in chylomicrons after a meal with PE (solid line) or without PE as control (dashed line). For experimental details, see the Materials and Methods section. Results are means (± SEM). * Significantly different values, P < 005.

Fig. 6.

A: D7C AUCs 480 min in chylomicrons after a meal with PE (gray) and without PE as control (white); as shown, mean value (± SEM) after the meal with PE significantly different from the one after the control meal, P < 0.0001. B: TG AUCs for 240 min and 480 min, means (± SEM); as shown, no significant differences (ns) between the meal with PE (gray) and without PE (white) values were found. All data shown are means (± SEM).

Fig. 7.

A: Tracer (D7C)/tracee ratios (isotopic enrichement, °/_°°) of plasma cholesterol. B: D7C AUCs 480 min in plasma after a meal with PE (gray) or without PE as control (white); as shown, values after the meal with PE significantly different from those after the control meal, P < 0.0001. All data shown are means (± SEM).