Clinical trial NCT01574417: Plant Stanols and Gene Expression Profile
Official title: The Effects of Plant Stanol Esters on Intestinal Mucosal Gene Expression Profiles and Microbiota Composition in Healthy Human Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Hypercholesterolemia
Keywords: Plant stanols
Gene expression profile
Microbiota
Lead sponsor: Maastricht University Medical Center
Sponsor class: OTHER
Collaborators: name: Raisio Group
First posted: 2012-04-10
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: PREVENTION

Brief summary: Plant sterols and stanols are dietary components that are naturally present in plants. Their biological function in plants is comparable with these of cholesterol in animals. They are structurally related to cholesterol, but are absorbed by enterocytes to a much lesser extent. It is generally accepted that they inhibit intestinal cholesterol absorption and consequently lower serum low-density lipoprotein (LDL) cholesterol concentrations up to 10% at daily intakes of 2.5 g. The exact underlying mechanism of the plant sterol/stanol mediated reduction in intestinal cholesterol absorption is still unknown. It has been suggested that they lower the activity of sterol uptake transporters like Niemann-Pick C1 like 1 protein (NPC1L1) in enterocytes, otherwise several studies indicated that these compounds could activate the liver X receptor (LXR) in enterocytes, thereby activating the ABC transporters involved in the intestinal cholesterol metabolism, whereas recently suggestions have been made that plant sterols and stanols activate transintestinal cholesterol excretion (TICE). This is the direct cholesterol secretion from the blood into the intestinal lumen, in which the enterocytes play a central role. None of these assumptions have so far been evaluated in humans.

Objective: The major objective of the present study is to examine the acute effects of dietary plant stanol esters on the intestinal mucosal gene expression profiles in intestinal biopsies in healthy volunteers. The minor objective is to investigate whether semi-long-term use (3 weeks) of plant stanol esters have an effect on microbiota composition.

Detailed description: lant sterols and stanols are dietary components that are naturally present in plants. Their biological function in plants is comparable with these of cholesterol in animals. They are structurally related to cholesterol, but are absorbed by enterocytes to a much lesser extent. It is generally accepted that they inhibit intestinal cholesterol absorption and consequently lower serum low-density lipoprotein (LDL) cholesterol concentrations up to 10% at daily intakes of 2.5 g. The exact underlying mechanism of the plant sterol/stanol mediated reduction in intestinal cholesterol absorption is still unknown. It has been suggested that they lower the activity of sterol uptake transporters like Niemann-Pick C1 like 1 protein (NPC1L1) in enterocytes, otherwise several studies indicated that these compounds could activate the liver X receptor (LXR) in enterocytes, thereby activating the ABC transporters involved in the intestinal cholesterol metabolism, whereas recently suggestions have been made that plant sterols and stanols activate transintestinal cholesterol excretion (TICE). This is the direct cholesterol secretion from the blood into the intestinal lumen, in which the enterocytes play a central role. None of these assumptions have so far been evaluated in humans.

Objective: The major objective of the present study is to examine the acute effects of dietary plant stanol esters on the intestinal mucosal gene expression profiles in intestinal biopsies in healthy volunteers. The minor objective is to investigate whether semi-long-term use (3 weeks) of plant stanol esters have an effect on microbiota composition.

Eligibility criteria: Inclusion Criteria:

* Aged between 18-60 years
* BMI between 20-30kg/m2
* mean serum total cholesterol \< 7.8mmol/L

Exclusion Criteria:

* unstable body weight
* active cardiovascular diseases
* gastrointestinal diseases
* use of cholesterol-lowering drugs
* use of lipid-lowering therapy
* abuse of drug or alcohol
* pregnant or breast-feeding women
* current smoker

Primary outcomes:
measure: intestinal mucosal gene expression profiles
timeFrame: Measured at day 8 and day 64. Changes will be calculated between day 8 and day 64.
Secondary outcomes:
measure: microbiota composition
timeFrame: measured after 3 weeks consumption of controle margarine and the plant stanol-enriched margarine. Changes will be calculated between these 2 interventions.
measure: lipoprotein profile
timeFrame: measured at baseline and after 3 weeks
measure: plasma glucose concentration
timeFrame: measured at day 8 and day 64, on 8 time points
measure: plasma plant stanol concentration
timeFrame: measured at baseline and after 3 weeks
Other outcomes:
Locations:
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Centre
state: Limburg
Study officials:
affiliation: Maastricht University Medical Centre
name: Jogchum Plat, Dr
role: PRINCIPAL_INVESTIGATOR
References: