Clinical trial NCT01550432: Effects of Glutathione (an Antioxidant) and N-Acetylcysteine on Inflammation
Official title: Effects of GSH and N-Acetylcysteine on Inflammatory Markers Among Adults With CVD Risk
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Obesity
Hyperlipidemia
Insulin Resistance
Hypertension
Lead sponsor: Stanford University
Sponsor class: OTHER
Collaborators: name: National Center for Complementary and Integrative Health (NCCIH)
First posted: 2012-03-12
Enrollment: 78
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Inflammatory Markers
timeFrame: 8 weeks
Secondary outcomes:
measure: Oxidized LDL
timeFrame: 8 weeks
measure: Insulin Sensitivity
timeFrame: 8 weeks
measure: Weight
timeFrame: 8 weeks
measure: Blood pressure
timeFrame: 8 weeks
measure: Serum lipids
timeFrame: 8 weeks
measure: Insulin
timeFrame: 8 weeks
measure: Glucose
timeFrame: 8 weeks
measure: Plasma Glutathione levels
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University School of Medicine
state: California
Study officials:
affiliation: Stanford University
name: Christopher D Gardner
role: PRINCIPAL_INVESTIGATOR
References: