Serum lipids, plant sterols, and cholesterol kinetic responses to plant sterol supplementation in phytosterolemia heterozygotes and control individuals

Background: Plant sterol (PS) supplementation is increasingly accepted as a dietary strategy to lower plasma cholesterol concentrations. However, information is scarce about the effect of increased PS intake in potentially vulnerable groups, such as phytosterolemia heterozygotes (HET). Objective: This study assessed the responsiveness of circulating PS and lipid concentrations and cholesterol kinetics (absorption and synthesis) to daily PS supplementation in HET (ABCG8 S107X mutation) compared with a healthy control cohort. Design: A double-blind, randomized, crossover, placebo-controlled study was conducted in 10 HET and 15 control subjects. The participants had a mean (+/- SEM) age of 34 +/- 2 y and a BMI (in kg/m(2)) of 29.9 +/- 1.1 and consumed similar to 1.6 g PS or placebo capsules daily with supper for 4 wk. Cholesterol absorption and synthesis were assessed by using [C-13]cholesterol and deuterium oxide, respectively. Results: Plasma LDL-cholesterol concentrations decreased (P = 0.006) in both groups after PS supplementation (HET: 2.73 +/- 0.19 mmol/L; control: 3.11 +/- 0.19 mmol/L) compared with placebo (HET: 3.12 +/- 0.20 mmol/L; control: 3.50 +/- 0.21 mmol/L), whereas PS concentrations (campesterol+beta-sitosterol) increased (P = 0.03) in both groups after PS supplementation (HET: 39.72 +/- 6.05 mu mol/L; control: 24.03 +/- 1.65 mu mol/L) compared with placebo (HET: 27.32 +/- 3.80 mu mol/L; control: 21.12 +/- 2.05 mu mol/L). Cholesterol absorption efficiency decreased (P = 0.010) by similar to 22% and similar to 17% and synthesis rates increased (P = 0.040) by similar to 20% and similar to 24% in the HET and control groups, respectively, in response to PS consumption compared with placebo. Conclusion: These data suggest that heterozygosity for the ABCG8 S107X mutation does not influence the action of dietary PS on circulating cholesterol concentrations but may affect sterol absorption. This trial was registered at clinicaltrials.gov as NCT01102647. Am J Clin Nutr 2012;95:837-44.