Effects of Glutathione (an Antioxidant) and N-Acetylcysteine on Inflammation

Stanford University

Status: Completed

Conditions: Hypertension; Hyperlipidemia; Insulin Resistance; Obesity

Treatments: Dietary Supplement: N-Acetylcysteine; Other: Placebo; Dietary Supplement: Glutathione

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT01550432

R21AT004475 (U.S. NIH Grant/Contract)

SU-03252010-5442

Details and patient eligibility

About

The rationale for the potential role of antioxidants in the prevention of cardiovascular diseases (CVD) remains strong despite the disappointing results of recent trials with a few select antioxidant vitamins. Glutathione (GSH) is one of the body's most powerful antioxidant agents but there is a surprising paucity of data on its use as an interventional therapy.

Glutathione, when taken orally, is immediately broken down into its constituent amino acids, of which cysteine is the only one to be essential. Available cysteine is the critical determinant of intracellular GSH concentrations. N-acetyl cysteine (NAC) is an antioxidant supplement that has been used to provide a source of cysteine to replete GSH levels. By replenishing endogenous glutathione, it is possible that NAC would exert the same effect(s) as exogenous GSH.

However, there is a new delivery system, liposomal GSH, which keeps glutathione intact. In this study, the investigators propose to match the cysteine content of NAC and GSH and compare the effects of these two supplements, at two different doses, on markers of inflammation and oxidative stress.

Enrollment: 78 patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

1. Gender: Both women and men

2. Age: > or = 18 years

3. Ethnicity and race: All ethnic and racial backgrounds welcome

4. Presence of Metabolic Syndrome: As defined in ATP III of the National 5.Cholesterol Education program, the metabolic syndrome will be diagnosed as presence of at least three of the following, which will be measured at the screening clinic visit:

   • Central obesity as measured by waist circumference:

     • Men: Greater than 40 inches
     • Women: Greater than 35 inches

   • Fasting blood triglycerides greater than or equal to 150 mg/dL

   • Blood HDL cholesterol:

     • Men: Less than 40 mg/dL
     • Women: Less than 50 mg/dL

   • Blood pressure greater than or equal to 130/85 mmHg

   • Fasting glucose greater than or equal to 100 mg/dL

6.Planning to be available for clinic visits and bottle pick-ups for the 8 weeks of study participation 7.Ability and willingness to give written informed consent 8.No known active psychiatric illness.

Exclusion criteria

1. Daily intake of dietary supplements containing antioxidants or omega-3 FAs

2. Fasting blood glucose > 140 mg/dL

3. Significant liver enzyme abnormality

   • AST or ALT more than 2 times the upper limit of normal and/or
   • Bilirubin more than 50% the upper limit of normal
   • Renal disease as measured at baseline:
   • Serum creatinine > 1.30 mg/dL, or
   • Calculated creatinine clearance < 71 mL/min

4. Self reported personal history of:

   • Clotting disorders
   • Clinically significant atherosclerosis (e.g., CAD, PAD)
   • Malignant neoplasm
   • Ongoing infection
   • Inflammatory disease (e.g., rheumatoid arthritis)

5. Subjects currently receiving the following medications (self report):

   • Anti-Inflammatory drugs
   • Lipid lowering drugs including statins
   • Anti-hypertensive drugs
   • Anti-coagulant drugs

6. Body Mass Index (BMI) greater than or equal to 40.

7. Pregnant or Lactating

8. Inability to communicate effectively with study personnel

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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78 participants in 5 patient groups, including a placebo group

High-Dose Glutathione

Experimental group

Description:

2,260 mg/day

Treatment:

Dietary Supplement: Glutathione

Low-Dose Glutathione

Experimental group

Description:

1,130 mg/day

Treatment:

Dietary Supplement: Glutathione

High-Dose N-Acetylcysteine

Experimental group

Description:

1,200 mg/day

Treatment:

Dietary Supplement: N-Acetylcysteine

Low-Dose N-Acetylcysteine

Experimental group

Description:

600 mg/day

Treatment:

Dietary Supplement: N-Acetylcysteine

Placebo

Placebo Comparator group

Description:

Volume of liquid placebo product comparable to glutathione and 1 or 2 placebo pills/day.

Treatment:

Other: Placebo