Plant Stanols and Gene Expression Profile

Hypercholesterolemia Clinical Trial

Official title:

The Effects of Plant Stanol Esters on Intestinal Mucosal Gene Expression Profiles and Microbiota Composition in Healthy Human Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01574417
• Other study ID #: METC 12-3-005
• Status: Completed
• Phase: N/A
• First received: March 20, 2012
• Last updated: October 24, 2012
• Start date: March 2012
• Est. completion date: October 2012

Study information

• Verified date: October 2012
• Source: Maastricht University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: October 2012
• Est. primary completion date: October 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

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

Study Design

Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Hypercholesterolemia

Intervention

Dietary Supplement:
• control margarine
Subjects will undergo a postprandial test for 5.5 hours, in which 26.7gram of the control margarine is consumed together with a high-fat milkshake. Daily consumption of 20 gram of a control margarine (providing daily 3.0 gram of plant stanols), for a period of 3 weeks.
• plant stanol-enriched margarine
Subjects will undergo a postprandial test for 5.5 hours, in which 26.7gram of the plant stanol-enriched margarine is consumed together with a high-fat milkshake. Daily consumption of 20 gram of a plant stanol-enriched margarine (providing daily 3.0 gram of plant stanols), for a period of 3 weeks.

Locations

Country	Name	City	State
Netherlands	Maastricht University Medical Centre	Maastricht	Limburg

Sponsors (2)

Lead Sponsor	Collaborator
Maastricht University Medical Center	Raisio Group

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	intestinal mucosal gene expression profiles		Measured at day 8 and day 64. Changes will be calculated between day 8 and day 64.	No
Secondary	microbiota composition		measured after 3 weeks consumption of controle margarine and the plant stanol-enriched margarine. Changes will be calculated between these 2 interventions.	No
Secondary	lipoprotein profile		measured at baseline and after 3 weeks	No
Secondary	plasma glucose concentration		measured at day 8 and day 64, on 8 time points	No
Secondary	plasma plant stanol concentration		measured at baseline and after 3 weeks	No