Methionine Tolerance in Healthy Human Adults
Condition: Healthy
Study type: Interventional

Summary: 
      Participants will receive four different doses of methionine through four month long
      interventions with a two week wash-out period in between intervention. The dose will increase
      with each intervention. Two visits during each intervention will also involve receiving
      stable isotope infusion to determine the metabolism of methionine in the body. Participants
      will also be monitored via blood work and questionnaires regarding overall health.
    

Detailed description: 
      Study subjects: Healthy volunteers (40 - 79 years) will be included in the study. Informed
      consent will be obtained before any study related procedures will be performed. All subjects
      will be extensively screened by research nurses / physician. Exclusion criteria are any
      condition that interfere with the definition 'healthy" according to the study physician's
      judgement based on medical history, lab testing, use of medication, and physical exam.

      Study design: To establish the Upper Level of Safe intake (USLI) of methionine intake, it is
      essential to create a dose-response approach of possible negative effects of methionine. To
      define the Lowest-Observed-Adverse-Effect Level (LOAEL), the investigators suggest a 4 weeks
      intervention and 2 to 4 weeks washout in healthy volunteers with free methionine at 10 mg/kg
      body weight/day (=requirement), 25 mg/kg body weight/day, 50 mg/kg body weight/day and 100
      mg/kg body weight/day. Pure methionine will be provided by ICAAS. The 4-week intervention
      period is based on a study in pigs (6). Methionine will be consumed in 3 daily doses.
      Participants will be advised about their daily dietary intake during the study. Besides the
      screening visit, each subjects will come back for up to 13 study visits (up to 5 Short study
      Days (SD, approx. 30 min) and 8 Long study Days (LD, approx. 5 h). On all study days (both SD
      and LD) the investigators will check parameters of toxicity and measure metabolites of
      methionine catabolism on the day before each dose intervention, during intervention (2 weeks
      after the start of each dose intervention; range: +/- 3 days), on the last day of each dose
      intervention, and 2 weeks after the last dose intervention. Because methionine as a dietary
      supplement clearly rises a safety issue, we will conduct this experiment in steps. First,
      subjects will receive the 10 mg/kg body weight/day. The investigators then will analyse all
      parameters of toxicity, interpret the data and when there are no safety concerns, continue
      with the next intake level. The study will be stopped at the level when there are apparent
      safety concerns.

      The study will take place at the research facility of the Center for Translational Research
      on Aging and Longevity (CTRAL), Texas A&M University. The subject will be asked to arrive in
      the fasted state on both the screening and all study days. On the screening day, body weight
      and height will be measured and Dual-energy X-ray absorptiometry (DXA) will be performed to
      measure body composition. On both SD and LD a medical interview will be performed and a
      toxicity questionnaire completed (see attached protocol). Furthermore on a SD two blood
      samples will be taken (up to 30 ml). On a LD, one catheter will be inserted in the peripheral
      vein of an arm for blood sampling (18 samples in total, up to 80 ml per LD) and
      questionnaires related to cognition, health status and well being may or may not be completed
      by the subject (see attached protocol). After a baseline blood sample is taken, a stable
      isotope pulse is provided through the same line. The baseline sample will be used to test
      toxicity parameters in blood, plasma homocysteine concentration, the plasma concentrations of
      products of the methionine degrading transamination and sulfoxidation route, and to establish
      background enrichment of stable isotopes. Samples obtained after the pulse will provide
      information about transmethylation of methionine, and GSH synthesis. Subjects will be called
      every week to check compliance regarding supplement intake and to answer questions regarding
      health and well-being. Subjects who discontinue the study during the study will not be
      replaced.
    

Intervention name(s): methionine
Intervention type(s): Dietary Supplement
Intervention description(s): 4 weeks intervention and 2 to 4 weeks washout in healthy volunteers with free methionine at 10 mg/kg body weight/day (=requirement), 25 mg/kg body weight/day, 50 mg/kg body weight/day and 100 mg/kg body weight/day.
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Other
Keywords: Dietary Supplements