Classification & Nature
- Classification: It is a tripeptide (a small protein-like molecule).
- Composition: Composed of three amino acids: Cysteine, Glutamic Acid, and Glycine.
- Endogenous Status: Naturally produced by the liver and found in nearly every cell in the body.
Key Benefits
- Oxidative Stress Neutralizer: Directly scavenges free radicals.
- Detoxification: Binds to toxins, heavy metals, and pollutants in the liver for excretion.
- Immune Support: Enhances T-cell proliferation and function.
- Skin Brightening: Inhibits tyrosinase activity (reducing melanin production).
- Mitochondrial Protection: Guards the “powerhouse” of the cell from DNA damage.
Pathways & Mechanism
- Primary Pathway: The Glutathione-Ascorbate Cycle.
- Enzymatic Activity: Works via Glutathione Peroxidase (GPx) to convert hydrogen peroxide into water.
- Recycling: After “disarming” a free radical, it becomes oxidized (GSSG) and must be reduced back to its active state (GSH) using the enzyme Glutathione Reductase and NADPH.
Dosing Range & Strategy
- Oral (Standard): 250mg – 1,000mg daily. (Note: Standard oral has poor bioavailability).
- Liposomal/S-Acetyl: 100mg – 600mg daily (Highly preferred for superior absorption).
- IV/IM Injection: 600mg – 2,400mg (Usually administered 1–2 times weekly).
- Strategy: Best taken on an empty stomach (for oral/liposomal) or during periods of high oxidative stress (illness, post-workout, or detox cycles).
Pharmacokinetics (Half-life & Saturation)
- Half-life: Very short in the blood (approx. 1.5 to 10 minutes for IV/bolus), as it is rapidly taken up by cells or broken down.
- Peak Saturation: * IV: Immediate peak.
- Liposomal Oral: 1–3 hours for plasma peak.
- Tissue Saturation: Consistent daily dosing typically takes 2–3 weeks to significantly elevate systemic cellular levels.
Genomic vs. Non-Genomic
- Non-Genomic: Direct chemical neutralization of reactive oxygen species (ROS) in the cytoplasm and mitochondria.
- Genomic: Influences gene expression by modulating NF-κB (inflammation) and Nrf2 (the body’s antioxidant response element).
Synergy & Performance Enhancers
- Vitamin C: Recycles oxidized Glutathione back to its active state.
- Selenium: A required cofactor for the enzyme Glutathione Peroxidase.
- Alpha-Lipoic Acid (ALA): Directly aids in regenerating Glutathione levels.
- NAC (N-Acetyl Cysteine): The rate-limiting precursor; provides the cysteine needed to build more Glutathione.
- Milk Thistle (Silymarin): Protects the liver and prevents Glutathione depletion.
Side Effects & Interactions
- Side Effects: Bloating, abdominal cramps (rare with oral), or zinc depletion with long-term high-dose use.
- What to Avoid: * Alcohol: Rapidly depletes Glutathione stores.
- Acetaminophen (Tylenol): One of the primary causes of Glutathione depletion in the liver.
- Chemotherapy: Since Glutathione protects cells, it may interfere with the efficacy of certain oxidative chemo drugs (always consult an oncologist).
Duration of Use & Detectability
- Duration: Can be used long-term (maintenance) or in “bursts” (4–8 weeks) during detox.
- Detectability: Not a banned substance in most athletic contexts (WADA), but IV infusions over 100mL may be restricted due to “infusion volume” rules, not the substance itself.
General Notes & Summary
Glutathione is often called the “Master Antioxidant” for a reason: without it, your other antioxidants like Vitamin C and Vitamin E couldn’t be recycled and would quickly become useless. While it is naturally occurring, our levels decline with age, poor diet, and environmental toxins. This makes supplementation attractive, but the delivery method is everything.
Traditional oral Glutathione is frequently broken down by stomach enzymes before it ever reaches the bloodstream. For a knowledge base, it is vital to emphasize that Liposomal or S-Acetyl Glutathione are the “gold standards” for oral intake, as they bypass the digestive hurdles that render standard powders ineffective.
Lastly, remember that Glutathione is a “team player.” It works best in an environment rich in Selenium and Vitamin C. If you are taking high doses of Glutathione without supporting its precursors or cofactors, you are essentially buying an expensive car but forgetting the spark plugs.