The Effect of Different Macronutrients on Ileal Brake Activation

• Measurements in plasma and/or platelet poor plasma Plasma levels of the gut hormone Cholecystokinin (CCK) [ Time Frame: 1 day ] [ Designated as safety issue: No ]
• Gastric emptying by using the C13 stable isotope breath test [ Time Frame: 1 day ] [ Designated as safety issue: No ]
• Small bowel transit time by using lactulose hydrogen breath test [ Time Frame: 1 day ] [ Designated as safety issue: No ]
• Gallbladder volumes by gallbladder ultrasound [ Time Frame: 1 day ] [ Designated as safety issue: No ]
• Measurements in plasma and/or platelet poor plasma Plasma levels of the gut hormone Glucagon Like Peptide-1 (GLP-1) [ Time Frame: 1 day ] [ Designated as safety issue: No ]
• Measurements in plasma and/or platelet poor plasma Plasma levels of the gut hormone peptide YY (PYY) [ Time Frame: 1 day ] [ Designated as safety issue: No ]

• Measurements in plasma and/or platelet poor plasma Plasma levels of the gut hormone Cholecystokinin (CCK) [ Time Frame: 1 day ] [ Designated as safety issue: No ]
• Gastric emptying by using the C13 stable isotope breath test [ Time Frame: 1 day ] [ Designated as safety issue: No ]
• Small bowel transit time by using lactulose hydrogen breath test [ Time Frame: 1 day ] [ Designated as safety issue: No ]
• Gallbladder volumes by gallbladder ultrasound [ Time Frame: 1 day ] [ Designated as safety issue: No ]
• Measurements in plasma and/or platelet poor plasma Plasma levels of the gut hormone Glucagon Like Peptide-1 (GLP-1) [ Time Frame: 1 day ] [ Designated as safety issue: No ]
• Measurements in plasma and/or platelet poor plasma Plasma levels of the gut hormone peptide YY (PYY) [ Time Frame: 1 day ] [ Designated as safety issue: No ]
• Difference in food intake as measured during an ad libitum meal [ Time Frame: 1 day ] [ Designated as safety issue: No ]

The appearance of a food matrix into the duodenum, both during a meal and during the postprandial phase results in a feed-back from different parts of the intestine to the stomach, to the small intestine and to the central nervous system. All these processes inhibit, in concert, food processing in the gastrointestinal tract, satiation and appetite sensations and, consequently, food intake. These processes are involved in the so-called intestinal brake. The location at which the feedback process is initiated determines the severity of the brake effect; the entry of nutrients into the duodenum and jejunum activates the so-called duodenal and jejunal "brakes": negative feedback mechanisms that influence the function of more proximal parts of the gastrointestinal tract. Activation of both of these feedback mechanisms results in reduction of food intake and inhibition of hunger, probably partly by inhibition of gastric emptying rate (thus contributing to enhanced and prolonged gastric distension) and small intestinal transit time. More distal in the small intestine, the ileal brake is a feedback mechanism that results in inhibition of proximal gastrointestinal motility and secretion and increase feelings of satiation and reduction of ad libitum food intake.These results all point to a potentially powerful role of the ileal brake in the regulation of digestion, with direct or indirect impact upon eating behaviour and satiation.

The current scientific data strongly suggest that activation of the ileal brake provides the most powerful feedback mechanism to gastrointestinal transit and, especially, satiety signals and food intake. Most studies have used fat as macronutrient. The effects of several amounts, types and preparations of fat on the ileal brake have previously been investigated and reported.

Until present, the effects of the other macronutrients to induce the ileal brake remain largely unknown. There is evidence that carbohydrates induce the ileal brake. Proteins may also exert effects, although data are scarce and not convincing. However, it becomes more and more accepted that proteins may induce stronger effects on satiation and food intake than fat or carbohydrates.

In this study we're going to investigate the effect of intraileal infusion of casein and sucrose on ileal brake activation.

• Obesity
• Overweight

• Dietary Supplement: Casein
  Ileal infusion of low dose casein (5 gram)
• Dietary Supplement: Casein
  Ileal infusion of high dose casein (15 gram)
• Dietary Supplement: Sucrose
  Ileal infusion of low dose sucrose (4.3 gram)
• Dietary Supplement: Sucrose
  Ileal infusion of high dose sucrose (12.9 gram)
• Other: Saline
  Ileal infusion with saline (180mL in total)
• Dietary Supplement: Safflower oil
  Ileal infusion with safflower oil (6gr safflower oil in water)

• Experimental: Low dose casein
  Ileal infusion of low dose casein
  Intervention: Dietary Supplement: Casein
• Experimental: High dose casein
  Ileal infusion of high dose casein
  Intervention: Dietary Supplement: Casein
• Experimental: Low dose sucrose
  Ileal infusion of low dose sucrose
  Intervention: Dietary Supplement: Sucrose
• Experimental: High dose sucrose
  Ileal infusion of high dose sucrose
  Intervention: Dietary Supplement: Sucrose
• Placebo Comparator: Placebo
  Ileal infusion saline
  Intervention: Other: Saline
• Active Comparator: Safflower oil
  Ileal infusion safflower oil
  Intervention: Dietary Supplement: Safflower oil

Inclusion Criteria:

• Based on medical history and previous examination, no gastrointestinal complaints can be defined.
• Age between 18 and 55 years. This study will include healthy adult subjects (Male and Female), Women must be taking oral contraceptives. Subjects over 55 years have an increased risk for comorbidities, therefore, subjects over 55 years will not be included.
• BMI between 18 and 29 kg/m2
• Less then 2 'yes' responses in the SCOFF questionnaire (see appendix F1)
• Weight stable over at least the last 6 months

Exclusion Criteria:

• History of severe cardiovascular, respiratory, urogenital, gastrointestinal/ hepatic, hematological/immunologic, HEENT (head, ears, eyes, nose, throat), dermatological/connective tissue, musculoskeletal, metabolic/nutritional, endocrine, neurological/psychiatric diseases, allergy, major surgery and/or laboratory assessments which might limit participation in or completion of the study protocol. The severity of the disease (major interference with the execution of the experiment or potential influence on the study outcomes) will be decided by the principal investigator.
• Use of medication, including vitamin supplementation, except oral contraceptives, within 14 days prior to testing
• Administration of investigational drugs or participation in any scientific intervention study which may interfere with this study (to be decided by the principle investigator), in the 180 days prior to the study
• Major abdominal surgery interfering with gastrointestinal function (uncomplicated appendectomy, cholecystectomy and hysterectomy allowed, and other surgery upon judgement of the principle investigator)
• Dieting (medically prescribed, vegetarian, diabetic, macrobiological, biological dynamic)
• Pregnancy, lactation
• Excessive alcohol consumption (>20 alcoholic consumptions per week)
• Smoking
• Blood donation within 3 months before the study period
• Self-admitted HIV-positive state
• Eating disorders detected using the 'SCOFF questionnaire' (in Dutch translation)
• Lactose or cow milk intolerance