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

Am J Clin Nutr. 2012 Apr;95(4):837-44. doi: 10.3945/ajcn.111.028985. Epub 2012 Feb 29.

Abstract

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/m²) of 29.9 ± 1.1 and consumed ∼1.6 g PS or placebo capsules daily with supper for 4 wk. Cholesterol absorption and synthesis were assessed by using [¹³C]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+β-sitosterol) increased (P = 0.03) in both groups after PS supplementation (HET: 39.72 ± 6.05 μmol/L; control: 24.03 ± 1.65 μmol/L) compared with placebo (HET: 27.32 ± 3.80 μmol/L; control: 21.12 ± 2.05 μmol/L). Cholesterol absorption efficiency decreased (P = 0.010) by ∼22% and ∼17% and synthesis rates increased (P = 0.040) by ∼20% and ∼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.

Trial registration: ClinicalTrials.gov NCT01102647.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily G, Member 8
  • ATP-Binding Cassette Transporters / chemistry
  • ATP-Binding Cassette Transporters / genetics*
  • Adolescent
  • Adult
  • Aged
  • Amino Acid Substitution
  • Cholesterol / biosynthesis
  • Cholesterol / blood
  • Cholesterol / metabolism*
  • Cohort Studies
  • Cross-Over Studies
  • Dietary Supplements*
  • Double-Blind Method
  • Female
  • Heterozygote
  • Humans
  • Hypercholesterolemia / diet therapy*
  • Hypercholesterolemia / etiology
  • Hypercholesterolemia / genetics
  • Hypercholesterolemia / metabolism
  • Hypercholesterolemia / physiopathology
  • Hypercholesterolemia / prevention & control
  • Intestinal Absorption
  • Intestinal Diseases / diet therapy*
  • Intestinal Diseases / genetics
  • Intestinal Diseases / metabolism
  • Intestinal Diseases / physiopathology
  • Kinetics
  • Lipid Metabolism, Inborn Errors / diet therapy*
  • Lipid Metabolism, Inborn Errors / genetics
  • Lipid Metabolism, Inborn Errors / metabolism
  • Lipid Metabolism, Inborn Errors / physiopathology
  • Lipids / blood*
  • Male
  • Middle Aged
  • Mutant Proteins / chemistry
  • Mutant Proteins / genetics
  • Phytosterols / adverse effects
  • Phytosterols / blood
  • Phytosterols / genetics
  • Phytosterols / metabolism
  • Phytosterols / therapeutic use*
  • Young Adult

Substances

  • ABCG8 protein, human
  • ATP Binding Cassette Transporter, Subfamily G, Member 8
  • ATP-Binding Cassette Transporters
  • Lipids
  • Mutant Proteins
  • Phytosterols
  • Cholesterol

Supplementary concepts

  • Sitosterolemia

Associated data

  • ClinicalTrials.gov/NCT01102647