Abstract

The validation of the use of plasma plant sterols as a marker of cholesterol absorption is frail. Nevertheless, plant sterol concentrations are routinely used to describe treatment-induced changes in cholesterol absorption. Their use has also been advocated as a clinical tool to tailor cholesterol-lowering therapy. Prior to wider implementation, however, the validity of plant sterols as absorption markers needs solid evaluation. Therefore, we compared plasma plant sterol concentrations to gold-standard stable isotope-determined cholesterol absorption. Plasma campesterol/TC concentrations (camp/TC) were measured in a population of 175 mildly hypercholesterolemic individuals (age: 59.7 ± 5.6 years; BMI: 25.5 ± 2.9 kg/m(2); LDL-C: 4.01 ± 0.56 mmol/l). We compared cholesterol absorption according to the plasma dual-isotope method in subjects with the highest camp/TC concentrations (N = 41, camp/TC: 2.14 ± 0.68 μg/mg) and the lowest camp/TC concentrations (N = 39, camp/TC: 0.97 ± 0.22 μg/mg). Fractional cholesterol absorption did not differ between the groups (24 ± 12% versus 25 ± 16%, P = 0.60), nor was it associated with plasma camp/TC concentrations in the total population of 80 individuals (β = 0.13; P = 0.30, adjusted for BMI and plasma triglycerides). Our findings do not support a relation between plasma plant sterol concentrations and true cholesterol absorption and, therefore, do not favor the use of these sterols as markers of cholesterol absorption. This bears direct consequences for the interpretation of earlier studies, as well as for future studies targeting intestinal regulation of cholesterol metabolism.

Highlights

  • The validation of the use of plasma plant sterols as a marker of cholesterol absorption is frail

  • We found significant negative correlations between plasma absorption markers on the one hand and plasma lathosterol/total cholesterol (TC) concentrations on the other (R = Ϫ0.39 for campesterol/TC; R = Ϫ0.42 for sitosterol/TC; and R = Ϫ0.39 for cholestanol/TC; P < 0.001 for all)

  • These markers were unable to distinguish between “high and low cholesterol absorbers,” as we found comparable Fractional cholesterol absorption (FCA) rates in individuals despite 3-fold varying plasma campesterol/TC concentrations

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Summary

Introduction

The validation of the use of plasma plant sterols as a marker of cholesterol absorption is frail. Plant sterol concentrations are routinely used to describe treatment-induced changes in cholesterol absorption. Our findings do not support a relation between plasma plant sterol concentrations and true cholesterol absorption and, do not favor the use of these sterols as markers of cholesterol absorption. This bears direct consequences for the interpretation of earlier studies, as well as for future studies targeting intestinal regulation of cholesterol metabolism.—Jakulj, L., H. We revalidated plasma plant sterol concentrations as markers of cholesterol absorption in a population of 80 mildly hypercholesterolemic subjects. Our results do not favor their use as valid markers of human cholesterol absorption

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