Metabolic Analysis in Human Sulfur Amino Acid Deficiency
Condition: Oxidative Stress; Diabetes; Heart Diseases
MeSH terms: Heart Diseases
Study type: Interventional

Summary: 
      Varied food intake, disease, and genetic differences result in complex diet-health
      interactions. In principle, information-rich metabolic analyses combined with bioinformatic
      tools provide an approach to explore these interactions. This project is a feasibility study
      of the use of high-resolution 1H-nuclear magnetic resonance (NMR) to study metabolic
      perturbations induced by a deficiency in sulfur amino acids (SAA). The investigators will 1)
      test the hypothesis that deficient dietary intake of SAA in humans results in oxidation of
      reduced glutathione (GSH)/oxidized glutathione (GSSG) redox and 2) determine whether 1H-NMR
      of blood and urine detects metabolic changes due to SAA deficiency.
    

Detailed description: 
      Varied food intake, disease, and genetic differences result in complex diet-health
      interactions. In principle, information-rich metabolic analyses combined with bioinformatic
      tools provide an approach to explore these interactions. This project is a feasibility study
      of the use of high-resolution 1H-NMR to study metabolic perturbations induced by deficiency
      in sulfur amino acids (SAA). In cell culture, sulfur amino acid (SAA) deficiency results in
      substantial oxidation of glutathione (GSH) redox state. Because GSH redox affects central
      homeostatic and cell defense mechanisms, redox changes in vivo due to SAA deficiency could
      induce complex physiologic effects that are not easily predictable by more traditional
      metabolic analyses. We will 1) test the hypothesis that deficient dietary intake of SAA in
      humans results in oxidation of GSH/GSSG redox and 2) determine whether 1H-NMR of blood and
      urine detects metabolic changes due to SAA deficiency. Studies will be performed on 12
      healthy individuals (6 males, 6 females) in the Emory General Clinical Research Center (GCRC)
      using a crossover design (replete, deficient, replete). Kinetic and balance studies will
      establish the time course and magnitude of changes in SAA and metabolites in blood and urine
      in response to SAA intake. Plasma GSH/GSSG and cysteine/cystine redox will be measured to
      determine whether variation in intake of SAA affects steady-state thiol-disulfide redox
      state. 1H-NMR spectra of blood and urine samples will be used to determine whether metabolic
      changes unrelated to the direct SAA metabolites can be detected in association with variation
      in SAA intake. The results will show whether variation in SAA intake is likely to affect
      health risks associated with thiol-disulfide redox and oxidative stress. Furthermore, because
      NMR analysis of biofluids can be performed with a high throughput (e.g., 300 samples/day with
      a flow cell), results will show whether this approach could be useful for nutritional
      assessment of complex metabolic effects of SAA intake.
    

Intervention name(s): dietary amino acids; cysteine and methionine
Intervention type(s): Drug
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Diagnostic
Keywords: redox; sulfur amino acids; glutathione; aging