Intestinal Ketone Bodies Interfere With the Glycemic Control
Condition: Healthy Adult Volunteers
Study type: Interventional

Summary: 
      The ketone body (KB) ß-hydroxybutyrate will be given to eight fasting healthy volunteers of
      both sexes in order to observe the effects after an oral glucose tolerance test (OGTT) over 2
      h. Then, a standard lunch will be served at 12.00, as well as an afternoon snack at 15.00.
      Each participant will be its own control and participates in a randomised two-way cross over
      design; the KB are released in the stomach-duodenum, or in the ileum-colon. Peripheral blood
      samples are taken for endpoint GLP-1 analyses.
    

Detailed description: 
      It has been shown in man that a fatty diet in people with obesity stimulated the release of
      ketone bodies (KB) in the small intestinal mucosa. This observation was partly explained by
      an increased level of the ketogenic enzyme 3-hydroxy-3-methylglutaryl-CoA synthase (HMGCS2)
      in the jejunum of the obese people.

      Glucagon-like peptide 1 (GLP-1) is a peptide that is released from the intestinal mucosa and
      mediates among other things, satiation, as well as insulin-secretion and insulin-sensitivity.
      In patients with obesity, GLP-1 response to food is attenuated, but it increases following
      bariatric surgery.

      The question arose if the increased KB could be linked to the decreased level of meal-induced
      GLP-1. Indeed, in mice and rats the increased production of KB could be related to a
      decreased level of GLP-1. However, such a close relationship has never been shown in man.

      The present study tests, therefore, if release of the ketone body beta-hydroxybutyric acid
      into the intestine on two levels (stomach/duodenum and ileum/colon) of healthy volunteers
      influences the blood concentration of GLP-1 following an oral glucose tolerance test (OGTT).
      Glucose, insulin and KB are determined in peripheral plasma according to OGTT-routine.

      KB are lipid-derived organic molecules that can serve a circulating energy source during
      starvation/fasting (or pronged exercise). Beta-hydroxybutyrate (BHB), acetoacetate (AcAc) and
      acetone ("ketone bodies") are products of acetyl-CoA derived from fatty acids converted to
      via hepatic mitochondria. The three KB are connected to each by proteolytic interconnection.
      BHB is the most important source of energy, while AcAc is approximately 25-30% of BHB.
      Acetone is gas-soluble and is exhaled if ketonemia increases.

      The present study utilises ingestion of one KB (BHB) to get an acute, rapid increase in
      ketonemia. An encapsulation technology is used to differentiate the effect of KB on the small
      intestine from the effect mainly in the colon. Microcapsules with 1./ alginate, will release
      the KB in proximal stomach/duodenal intestine, and 2./ pea protein will release in the distal
      part of the intestine, mainly colon. The microcapsules are of food grade and are produced
      according to Good Manufacturing Process (GMP) standards (AnaBio Technologies LTD, Cork,
      Ireland). The KB in the microcapsules will contain 18 g BHB- and Ca+, Mg2+. Together with the
      encapsulation material (alginate or pea-protein) the total weight will be 20g per dose.
    

Intervention name(s): Alginate; Pea-protein
Intervention type(s): Other; Other
Intervention description(s): BHB covered in alginate will be realised in stomach-duodenum; BHB covered in pea-protein will be released in ileum-colon
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Basic Science