Glutathione and Its Precursors in HIV-Infected Patients

Study Overview
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Brief Summary
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The aim of this study is to investigate the responses of the serum amyloid A (SAA) pathway to dietary supplements of glutamine (Gln) and cysteine (Cys) together with methionine (Met)-overloading in HIV+ patients comparatively to healthy controls.

Detailed Description
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Introduction: Among the 4 sulphur-containing amino acids (SAA), only Met and Cys are incorporated into proteins, but Hcy and Tau are related to oxidative stress and glutathione (GSH), the major intracellular hydro-soluble anti-oxidant agent. HIV+ patients present low levels of antioxidant nutrients, including GSH and its precursors. Objective: To investigate the responses of the SAA pathway to dietary supplements of Gln and Cys together with Met-overloading in HIV+ patients comparatively to healthy controls. Methods: Twelve HIV+ (6 males and 6 females, 25-36 yrs old) patients under HAART (one HIV protease inhibitor in combination with two nucleoside analogs) for at least one year and 20 (10M and 10F, 23-28 yrs old) healthy controls were randomly assigned to 7-day diets containing either NAC (N-acetylcysteine, 1g/d) or Gln (20g/d), with a 7-day washout period with their usual diet (UD). Blood samples were drawn after overnight fast before and after (2h and 4h) ingesting the Met (100 mg/kg) overload (Met-OL) with determination of the area under the curve (AUC). HPLC plasma analysis of SAA (Met, Hcy, Cys and Tau), GSH and GSSG and Ser, Gly, Glu and Gln was carried out at moments before (MO) and after 7-day diets (M1). Additionally, at baseline, both groups were assessed for anthropometry (BMI, kg/m2; body fat %) and plasma biochemistry (creatinine, urea, γ-glutamyl transpeptidase, glucose, triglycerides, cholesterol, uric acid, albumin, folic acid and vitamin B12).The HIV+ group (G2) was also characterized by the viral load, CD4+ and CD8+ lymphocytes counts. Statistical comparisons were undertaken among diets between groups with p = 0.05.

Official Title
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The Effect of Substrate Supply on Modulating Plasma GSH Levels in Treated HIV+ Patients

Conditions
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HIV Infection

Intervention / Treatment
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* Dietary Supplement: Glutathione precursors


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HIV infection antiretroviral therapy for at least one year Exclusion Criteria: presence of any renal or liver failure ingestion of either vitamins B or GSH precursors

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Patient Group<br>Dietary supplement:N-acetylcysteine 1g/day and Glutamine 20g/day for 7 consecutive days. The dietary supplements were intermediated by 7 days of washout with usual diet. | Dietary Supplement: Glutathione precursors<br>* HIV+ patients were assigned to 7 day diets containing either NAC or Gln<br>* Other names: NAC (N-acetyl-L-cysteine);|
| Active Comparator: Control Group<br>Healthy HIV negative subjects submitted to the same dietary supplement than experimental group: N-acetylcysteine 1g/day and Glutamine 20g/day for 7 consecutive days. The dietary supplements were intermediated by 7 days of washout with usual diet. | Dietary Supplement: Glutathione precursors<br>* HIV+ patients were assigned to 7 day diets containing either NAC or Gln<br>* Other names: NAC (N-acetyl-L-cysteine);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma glutathione |  | 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma sulfur amino acids |  | 7 days |