Metabolic Effect of New Foods Through Gut-brain Axis
Condition: Obesity; Overweight
MeSH terms: Overweight
Study type: Interventional

Summary: 
      A diet high in easily obtained energy-dense foods leads to the problems of overweight and
      obesity common in the developed world. Foods enriched with fiber or bitter compounds may
      increase satiety and decrease energy intake. This intervention will measure the effectiveness
      of coffee melanoidins, bread melanoidins, beta-glucans, and a Gentiana lutea L. extract in
      both a free or encapsulated form to decrease energy intake and modify the physiological
      markers of satiety in the short term. In particular bread (fiber) and a pudding (Gentiana
      lutea L. extract) will be used as tasty food matrices in the study.
    

Detailed description: 
      Overweight and obesity are health problems of utmost importance to the world population. The
      continuous development and consumption of high-energy foods at a low cost is correlated with
      an increased risk of diabetes and insulin resistance in addition to weight gain. To maintain
      body weight, a balance between energy intake and energy expenditure must be obtained. Since
      weight gain is a common outcome with an energy-dense diet, the best approach to reduce
      caloric intake is through the consumption of fruits and vegetables. However, this approach is
      usually unsatisfactory in the long-term as the loss of tasty food and the low reward of
      healthy meals often undermines the nutritionally prudent diet. A possible alternative
      approach is to produce tasty foods with low caloric density and satiety-inducing compounds
      that can reduce caloric intake and increase the sensation of satiety.

      The human body regulates energy intake through a complex and interconnected biological system
      involving gut-brain axis, the endocannabinoid system and the hypothalamic-pituitary-adrenal
      axis. Biomarkers in the hypothalamic-pituitary-adrenal axis regulate food intake and the
      physiological response to stress. In the absence of food, the brain senses hunger through the
      elevation of the gastrointestinal hormone ghrelin. Once food is ingested, ghrelin levels
      decrease while other biomarkers in the gut-brain axis are released to increase feelings of
      satiety through the delay of gastric emptying, decrease in appetite and the decrease in food
      intake. Recent studies in mice have linked the endocannabinoid system with the
      hypothalamic-pituitary-adrenal axis through physiological stress and energy homeostasis.
      Furthermore, the endocannabinoids anandamide and 2-arachidonoylglycerol are both elevated
      during hunger but decrease after feeding.

      Natural foods with low energy density, such as fruits and vegetables, usually contain a high
      amount of dietary fiber. Dietary fiber is classified as either soluble fiber (beta-glucans)
      or insoluble fiber (wheat bran) but both soluble and insoluble fiber have been strongly
      linked to increased satiety sensation. Dietary fiber is important for a properly functioning
      gastrointestinal tract by providing a nutrient source for bacteria in the large intestine.
      When a 3% portion of barley beta-glucans were added to a fruit drink or to bread and consumed
      at breakfast, a reduction in energy intake of 30% over 24 hours was observed along with
      beneficial changes in post-prandial gastrointestinal hormones involved in the biological
      control of hunger and satiety. Intake of insoluble fiber improves insulin sensitivity and
      enriched barley fiber bread or wheat fiber bread improved ghrelin and peptide YY (PYY)
      hormone response compared to control bread. A recently characterized class of food compounds,
      melanoidins, have been found to exhibit similar properties to dietary fiber in the
      gastrointestinal tract. Melanoidins are formed by the Maillard reaction process through the
      reaction of proteins with reduced carbohydrates and sugars during the cooking of heat-treated
      foods. Melanoidins are large insoluble or partially insoluble complexes that are present in
      coffee, bread, cocoa, and beer. However, the main sources of melanoidins in the diet are from
      coffee and bread with a contribution of 0.5-2.0 g/day of coffee melanoidins and 1.8-15 g/day
      of bread melanoidins. Research has shown that coffee melanoidins are fermented in the
      gastrointestinal tract while bread melanoidins stimulate bifidobacteria in the large
      intestine.

      Bitter compounds have also been recently implicated in increasing satiety and having a
      beneficial effect on gastrointestinal tract hormones. Recent research in animals indicates
      that several bitter compounds can reduce the rate of gastric emptying, induce the secretion
      of satiety-inducing hormones cholecystokinin and glucagon-like peptide 1 (GLP-1), and
      decrease food intake. However, the animal experiments required the bitter compounds to be
      delivered directly to the stomach for action. A few bitter tasting vegetables, including
      broccoli and chicory, show beneficial health effects. Some natural phytochemicals are
      polyphenols known to possess different biological mechanisms and to have a bitter taste. The
      plant species Gentiana lutea L. produces several biologically active bitter phytochemicals,
      including the iridoid (loganic acid) and the secoiridoids (swertiamarin, gentiopicroside,
      amarogentin, sweroside). Gentiana lutea L. is used most often for the production of herbal
      teas and liqueurs.

      In this randomized, crossover trial, the hunger and satiety feelings will be measured while
      blood will be collected at specific time points during the seven arms. Since this
      intervention is to develop tasty foods that both increase satiety and decrease energy intake
      in the short term, the bitter compounds will also be encapsulated in a protective coating.
      Encapsulation is commonly used to protect pharmaceuticals during passage through the oral
      cavity or stomach to enable the active compounds to be properly absorbed in the body. The
      coating used in one arm will allow the Gentiana lutea L. extract to pass through the oral
      cavity, allowing the volunteers to not taste the bitter compounds, for target in the stomach
      and duodenum.

      All volunteers will participate in the seven arms of the study. Three different
      fiber-enriched breads and a control bread will be consumed in addition to skim milk at
      breakfast in four interventions. In the other three interventions, participants will consume
      a control pudding, Gentiana lutea L. extract pudding and the encapsulated Gentiana lutea L.
      extract pudding. A one-week washout period will be included between two separate
      interventions. The hedonic feelings of satiety, hunger, and appetite will be measured with a
      questionnaire at time 0 (baseline) and at 0.5, 1, 2, and 3 hours after breakfast. After 3
      hours, the volunteers will consume lunch until they are satiated and then keep a food diary
      to record their intake throughout the rest of the day. In addition, blood will be collected
      at each time point and the amount of the specific hormones, neuropeptides, and
      endocannabinoids will be measured as part of the secondary outcomes.
    

Intervention name(s): Satiety of breads; Satiety of puddings
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): One separate breakfast session to consume each bread along with 125 mL skim milk. The session will start after an overnight fast followed by 5 separate blood draws over a 3 hour period before a provided lunch.; One separate breakfast session will be used to evaluate satiating efficacy of puddings after an overnight fast. After pudding consumption, five separate blood draws will be taken over a 3 hour period before a provided lunch.
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Single (Participant)
Primary purpose: Basic Science
Keywords: beta-Glucans; Bitter; Bread; Coffee; Gentiana lutea; Melanoidins; Microencapsulation