Plant sterol supplementation does not inhibit intestinal cholesterol absorption in subjects with obesity

Introduction: Plant sterols (PS) have a recognized cholesterol-lowering effect at daily doses of 1.5–3 g, but their effects in subjects with obesity remain scarcely studied. PS mainly lower cholesterol by inhibiting intestinal absorption; however, this process is already reduced in subjects with obesity, raising concerns about PS efficacy in this population. Serum sterols provide valuable information on intestinal PS and cholesterol absorption, and on endogenous cholesterol synthesis. Only one study has measured serum sterols in overweight/obesity individuals after PS supplementation (phytostanols, BMI=28.4 kg/m², n=11). Methodology: Randomized, double-blind, placebo-controlled, crossover clinical trial was conducted in 23 subjects with overweight/class I–III obesity and mild hypercholesterolemia (LDL>115 mg/dL) (NCT06481020). Participants received 2 g/day of PS or placebo for 8 weeks (6-week washout). Serum β-sitosterol, campesterol (PS absorption markers), lathosterol and desmosterol (cholesterol synthesis markers) were quantified at baseline and after each treatment. Results and Discussion: After PS supplementation, serum β-sitosterol significantly increased by 28.8% (absolute) and 36.0% (cholesterol-normalized ratio) (p<0.05), and campesterol by 19.5% and 31.2% (p=0.098 and p=0.0522), confirming intestinal absorption. Lathosterol and desmosterol did not change significantly (p>0.05), indicating the absence of compensatory cholesterol synthesis due to PS-induced inhibition of intestinal cholesterol absorption. This is consistent with the non-significant changes in serum cholesterol after PS supplementation (201.9 ± 27.6 vs. 199.3 ± 29.6 mg/dL, p= 0.499). In contrast, the previous study in overweight/obesity showed compensatory cholesterol synthesis and total cholesterol reduction after PS supplementation. These discrepancies are likely attributable to the markedly higher BMI of our study (36.4 vs. 28.4 kg/m²). Conclusions: This is the first study evaluating PS supplementation in subjects with obesity class I–III. Cholesterol intestinal absorption was not reduced, explaining the lack of total cholesterol lowering, contrary to studies with lower-BMI individuals. Further studies are needed to confirm these findings.