Effect of the Diet on Urinary Excretion of Alpha-ketoglutarate
Condition: Acid Base Disorder
Study type: Interventional

Summary: 
      -  The G coupled-protein receptors 99 (GPR99) was discovered in 2002 by Wittenberg et al.
           and is involved as a metabolic receptor. It has been shown that the natural ligand of
           GPR99 is an intermediate in the Krebs cycle, alpha-ketoglutarate (aKG). Studies done on
           rats have shown that aKG is measurable in the blood, freely filtered by the glomerulus
           and highly reabsorbed in the proximal tubule in metabolic acidosis, while it is not
           reabsorbed in metabolic alkalosis. No absorption or secretion of aKG intervene between
           the end of the proximal tubule and the final urine. Thus, having a receptor aKG in the
           distal tubule creates a paracrine communication with the proximal tubule, informing
           about the acid-base status of the body and allows adjustment of the urinary excretion of
           acid or base.

        -  The hypothesis is that GPR99 is aKG sensor in the distal tubules and allow to report the
           acid-base status (determined by the metabolic activity of the proximal tubule) of the
           body to the distal tubule. This can then adapt the urinary excretion of acid or base in
           the final urine. Acidifying the body by a high meat consumption associated with a test
           of acidification, the kidney should reduce its aKG excretion and the concentration of
           this metabolite should be even lower in the urine. And vice versa in the case of
           alkalizing the body through a vegetarian diet associated with an alkalizing test.

        -  Twelve healthy omnivorous volunteers will be selected. First inclusion visit includes
           verification of inclusion/exclusion criteria and signed informed consent. Urine and
           plasma baseline measurements will be performed and volunteers will meet a dietician.
           This person will tell them concerning meat and vegetarian diet as well as how to have a
           diet with 6g of salt per day.Volunteers are then randomized in order to determine which
           diet they will start first.The first phase will last during 4 days. The diet is followed
           during 3 days, and a 24-hour urine collection will begin on the third day at 7: 00 am.
           The fourth day, volunteers will have an investigational's day at the investigation's
           center after completing their urine collection at home (7:00 am). During the day of
           investigation, volunteers will give their urine (8: 00 am, corresponding to the baseline
           urine), and then the "meat" arm will receive a tablet of 50meq of NH4Cl and the
           "vegetarian" arm will receive a tablet of 1g of NaHC03. Volunteers will stay in the
           investigation center for 6h. Each hour since 8:00am, a urine sample will be taken, and
           at 3 hours and 6 hours post-tablet, a blood sample will also be made.This
           investigational's day will be followed by one to two weeks of treatment washing out.
           After that, the second phase will begin and will as the first phase excepted that the
           diet will be inversed.

           5 other healthy vegetarian or vegan volunteers are recruited. Inclusion visit is the
           same as omnivorous volunteers. Only investigational's day at the investigation's center
           will be performed (no diet, no urine collection).
    


Intervention name(s): Meat and vegetable diet
Intervention type(s): Other
Intervention description(s): After having a diet of 3 days and the investigational's day, the volunteers will have the other diet
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: G protein-coupled receptor 99; 2-oxoglutarate receptor 1; alpha-ketoglutarate; urine; pH; acidosis; alkalosis; Healthy volunteers