Metabolic Analysis in Human Sulfur Amino Acid Deficiency

NCT ID: NCT00253760

Last Updated: 2010-03-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-02-29
• Study Completion Date: 2007-02-28

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.

Conditions

Oxidative Stress; Diabetes; Heart Diseases

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Interventions

dietary amino acids; cysteine and methionine

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role: lead

Principal Investigators

Dean P Jones, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Emory University

Locations

Emory University Hospital

Atlanta, Georgia, United States

Countries

United States

Other Identifiers

R03DK066008

Identifier Type: NIH

Identifier Source: secondary_id

View Link

R03 DK66008 (completed 2007)

Identifier Type: -

Identifier Source: org_study_id