Metabolic Analysis in Human Sulfur Amino Acid Deficiency

Not Applicable

Completed

• Conditions: Oxidative Stress; Heart Diseases; Diabetes

• Registration Number: NCT00253760
• Lead Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Brief 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.

Study Timeline

• Study Start: 2004-02
• Study First Submitted: 2005-11-14
• Study First Submitted QC: 2005-11-14
• Study First Posted: 2005-11-15
• Study Completion: 2007-02
• Status Verified: 2010-03
• Last Update Submitted: 2010-03-17
• Last Update Posted: 2010-03-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 15

Inclusion Criteria

• Normal weight
• Males or females

Exclusion Criteria

• Smokers
• Pregnancy
• Chronic illness other than hypertension
• Age less than 18 and greater than 40 years

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
redox state of the two central low molecular weight thiol-disulfide pools, i.e., GSH/GSSG and cysteine (Cys)/cystine (CySS)
a global metabolic spectrum detectable by H-NMR

Trial Locations

Locations (1)

Emory University Hospital; 🇺🇸 Atlanta, Georgia, United States