Creatine Kinetics, Synthesis From Glycine and Response to Creatine and Amino Acid Supplement in Healthy Humans
Condition: Creatine Synthesis in Healthy Subjects
Study type: Interventional

Summary: 
      The goal of the present study is to quantify the rate of synthesis of creatine in healthy
      controls and endurance trained subjects. In addition, the effect of oral creatine supplement
      for seven days on creatine kinetics will be examined.

      Ten healthy controls (age 20-35 years) and ten endurance trained subjects will be recruited
      by advertisement. Endurance trained subjects will be recruited from health clubs. They will
      be screened for absence of any chronic disease (history, physical examination, CBC, metabolic
      and liver panel, urinalysis). A DEXA measurement will be done to quantify whole body skeletal
      muscle mass.

      For five (5) days prior to the study, they will be placed on a creatine-free (essentially
      meat-free) diet. Dietary compliance will be ensured by repeated communication with the
      subject, by nurse coordinator and the CRU Nutritionist. Subject will maintain daily record of
      the food intake for validation. On the last day, i.e. 24 hours prior to the tracer study,
      subject will collect the 24 hours urine sample and bring it to the CRU on the day of the
      study.
    

Detailed description: 
      Creatine and phosphocreatine are the major intracellular buffers for adenosine triphosphate.
      They also function as the energy shuttle for high energy phosphate from the mitochondrial
      site of production to the cytoplasmic site of utilization. In addition, creatine has been
      shown to affect satellite cell proliferation and differentiation and increase cell mitotic
      activity during compensatory hypertrophy in rat skeletal muscle. Creatine is synthesized from
      three amino acids: glycine, arginine and methionine. Although creatine metabolism has been
      studied extensively in the rat, the data regarding the kinetics of creatine and their
      regulation in humans are limited. This is in part due to a large and slow turning over pool
      of creatine and lack of good tracer methods. Using a recently developed stable isotopic
      tracer method (by us), we propose to quantify the rate of synthesis of creatine and its
      regulation in healthy subjects and in those with large skeletal muscle mass as a result of
      endurance training. In addition, the response to oral creatine administration on creatine
      kinetics will be quantified. The site of regulation will be identified by the relative rate
      of appearance of tracer glycine in guanidinoacetic acid and creatine. It is hypothesized that
      the fractional rate of synthesis of creatine will be higher in endurance trained subjects,
      and that creatine will suppress the rate of synthesis of creatine. Since creatine is critical
      for the maintenance of skeletal muscle mass and satellite cell proliferation, these data will
      provide the normative physiological data for future studies of subjects with manifest
      sarcopenia, such as aging, and those with chronic diseases, e.g. cirrhosis of liver. These
      data will form the basis for the studies of creatine metabolism in neurodegenerative
      disorders where creatine is being increasingly used as a therapeutic agent.
    

Intervention name(s): Creatine and Amino Acid supplement
Intervention type(s): Dietary Supplement
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: creatine synthesis