Role of HIV on Glutathione Synthesis and Oxidative Stress
Study Details
Study Description
Brief Summary
HIV infection is associated the development of increased oxidative stress and deficiency of glutathione (GSH), the dominant endogenous antioxidant protein, but the underlying mechanisms contributing to GSH deficiency are hitherto unknown. Furthermore GSH metabolism has not been studied in HIV patients, in whom the burden of risk factors promoting oxidative stress is highest. Our previous studies in non-HIV human subjects with diabetes-related oxidative stress and GSH deficiency have demonstrated that the latter is due to decreased synthesis of GSH. Importantly, short-term dietary supplementation with the simple GSH precursor amino-acids cysteine and glycine, boosted GSH synthesis and cellular concentrations, corrected GSH deficiency, and reduced oxidative stress and oxidant damage. The current proposal will study whether (1) defective synthesis underlies GSH deficiency in patients with HIV, and will test a simple, inexpensive and rational therapy based on protein supplementation to improve GSH synthesis and concentrations and lower markers of oxidative stress and oxidant damage in these patients; (2) study if correction of GSH deficiency is asssociated with any changes in (a) impaired mitochondrial fuel oxidation in the fasted and insulin stimulated states; (b) insulin sensitivity; (c) body composition and anthropometry; (d) forearm muscle strength; (e) plasma biochemistry, and (f) quality of life indices in these subjects.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Cysteine/glycine Subjects will be studied before and after receiving oral cysteine (as n-acetylcysteine) and glycine for 2 weeks |
Dietary Supplement: Cysteine (as n-acetylcysteine) and glycine
Cysteine and glycine will be supplemented at doses of 0.81 mmol/kg/d and 1.31 mmol/kg/d for 2 weeks each
Dietary Supplement: Cysteine/glycine
Subjects will receive oral dietary amino-acids (cystiene as n-acetylcysteine, and glycine)
|
Outcome Measures
Primary Outcome Measures
- Glutathione synthesis rates and concentrations [9 hours]
Fractional and absolute synthesis rates of glutathione and its concentrations
Secondary Outcome Measures
- Mitochondrial fuel oxidation [Twice over 9 hours of the study on 2 occassions]
Lipolysis, fuel oxidation, and a hyperinsulinemic euglycemic clamp.
- Rates of fuel kinetics [3 hours]
Measure rate of lipolysis (from infused 13C-palmitate) and recovery of 13CO2 (from infused acetate tracer)
- Insulin sensitivity [3 hours]
Measure insulin sensitivity using a hyperglycemic euglycemic clamp
- Muscle strength [Done once in each 9-hour study]
- Quality of life by SF36 questionnaire [Before and after]
Eligibility Criteria
Criteria
Inclusion Criteria:
(1) HIV infected patients with GSH deficiency
Exclusion Criteria:
-
renal impairment (serum Creatinine above 1.5mg/dL), liver impairment (ALT and AST > 2x upper limit of normal)
-
any hormonal disorders such as hypothyroidism, hypercortisolemia, hypogonadism, or diabetes mellitus on pharmacotherapy
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evidence of infections other than HIV in the preceding 3 months
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subjects with plasma triglyceride concentrations of ≥ 500mg/dL on triglyceride lowering therapy
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BMI < 20
-
established heart disease
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Co-existing viral hepatitis B and C
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Baylor GCRC | Houston | Texas | United States | 77030 |
Sponsors and Collaborators
- Baylor College of Medicine
Investigators
- Principal Investigator: R V Sekhar, MD, Baylor College of Medicine
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- HIV and glutathione