Effects of High-fat and Low-fat Diet on the Gut
Condition: Metabolic Syndrome X
MeSH terms: Metabolic Syndrome
Study type: Interventional

Summary: 
      Rationale: The prevalence of the metabolic syndrome is strongly increasing in developed
      countries. The role of the small intestine seems important in the development of the
      metabolic syndrome. Although it is known that a high-fat Western-style of diet has
      deleterious effects on (post-prandial) lipidemia and glucose homeostases, effects of such a
      diet on the small intestine is not known. To elucidate the role of the small intestine on the
      early development of the metabolic syndrome, the effects of a high-fat (HF) and a low-fat
      (LF) diet will be examined on gene expression in the small intestine and early biomarkers in
      blood of healthy subjects.

      Objective: The objective of this study is to compare in healthy subjects the effects of a HF
      diet (40 En% fat) with those of a LF diet (20 En% fat) on early biomarkers and parameters of
      metabolic stress in blood and on expression of genes in the small intestine.

      Additional research objectives are:

        -  To compare the diet-induced changes in transcriptome profile of the small intestine with
           more easily accessible peripheral blood mononuclear cells (PBMC)

        -  To establish effects of HF and LF diet on basal gut permeability and after a
           chenodeoxycholic acid (CDCA) load (second hit).

      Study design: Randomised crossover design. The duration of the experimental periods (HF and
      LF diet) will be 28 days, separated by a wash out period of at least 3 weeks. At day 21 of
      each intervention period a postprandial test will be performed and duodenum biopsies will be
      taken. At day 25 and 28 of each intervention period, respectively, basal gut permeability and
      gut permeability after a CDCA load will be determined with a sugar recovery test.

      Study population: Ten healthy men in the age of 18-60 years, without a history of any
      gastrointestinal disorders or complaints.

      Intervention: Subjects will consume in random order:

        -  a HF diet (40 En% fat, 45 En% carbohydrates and 15 En% proteins)

        -  a LF diet (20 En% fat, 65 En% carbohydrates and 15 En% proteins)

      Primary study parameters/endpoints: Potential early biomarkers of the metabolic syndrome in
      blood and gene expression profiles in the small intestine.

      Secondary study parameters/endpoints: Parameters of the metabolic syndrome in blood, gene
      expression profiles in PBMC and gut permeability.
    


Intervention name(s): high fat diet followed by low fat diet; low fat diet followed by high fat diet
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): High fat diet : 40 Energy (En)% fat, 45 En% carbohydrates, 15 En% proteins, 250 mg cholesterol,4 weeks, daily Low fat diet : 20 Energy (En)% fat, 65 En% carbohydrates, 15 En% proteins, 250 mg cholesterol,4 weeks, daily; Low fat diet : 20 Energy (En)% fat, 65 En% carbohydrates, 15 En% proteins, 250 mg cholesterol,4 weeks, daily High fat diet : 40 Energy (En)% fat, 45 En% carbohydrates, 15 En% proteins, 250 mg cholesterol,4 weeks, daily
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Prevention