Glutathione (GSH) is a tripeptide composed of glutamate, cysteine, and glycine and is often referred to as the "master antioxidant." It plays a crucial role in detoxification, oxidative stress regulation, and immune function.
Key Functions of Glutathione
- Neutralization of Reactive Oxygen Species (ROS): Glutathione helps eliminate free radicals, reducing oxidative damage at the cellular level.
- Detoxification via GST (Glutathione S-Transferases): The GST family of enzymes facilitates the conjugation of glutathione to toxins, making them more water-soluble for excretion.
- Antioxidant Recycling: GSH regenerates oxidized vitamin C and vitamin E, maintaining the antioxidant balance.
- Immune System Regulation: It supports white blood cell function, helping fight infections and inflammation.
- Mitochondrial Protection: It safeguards mitochondria from oxidative stress, preserving cellular energy production.
GSH vs. GST: How They Relate and Differ
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Glutathione (GSH): A crucial antioxidant that directly neutralizes free radicals and supports cellular detoxification.
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Glutathione S-Transferases (GSTs): A family of enzymes that utilize GSH to bind and remove harmful compounds from the body.
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Key Difference: GSH is the antioxidant itself, while GST enzymes act as catalysts, allowing glutathione to effectively detoxify a wide range of substances.
Forms of Glutathione
- Reduced Glutathione (GSH): The active form that combats oxidative stress.
- Oxidized Glutathione (GSSG): The inactive form, which is converted back to GSH by glutathione reductase.
- Liposomal & Acetylated Glutathione: These are supplemental forms with enhanced bioavailability.
Factors Affecting Glutathione Synthesis
- Limiting Factor: Cysteine (the scarcest amino acid in synthesis)
- Depleting Agents: Chronic stress, aging, toxins, infections, and excessive paracetamol (acetaminophen)
Paracetamol and NAC in Relation to Glutathione
Paracetamol metabolism consumes large amounts of cysteine, depleting glutathione stores and leading to potential liver toxicity. Conversely, N-Acetyl-Cysteine (NAC) serves as a precursor to cysteine, replenishing glutathione levels and protecting the liver.
The GSTM Gene Family: Genetic Variations and Detoxification
The GSTM1 gene family encodes glutathione S-transferases (GSTs), responsible for detoxifying heavy metals, carcinogens, and pollutants.
- Highly Polymorphic Variants: Some individuals have lower GST activity due to genetic mutations.
- Whole Gene Deletions: A large portion of the population lacks GSTM1 entirely, reducing detoxification efficiency.
- Ethnic Variations: Studies show that 50-60% of Europeans and 20-30% of Asians have a GSTM1 deletion.
Impact of GSTM1 Deletion (DD Result)
If you have a GSTM1 deletion (DD result), congratulations! You've joined an exclusive club where detoxing is now an extreme sport. 🚴♂️ This means your body struggles to clear toxins efficiently, increasing susceptibility to oxidative stress. To counteract this, you should prioritize:
- Boosting glutathione levels: Consume sulfur-rich foods (broccoli, garlic, onions).
- Using antioxidants: Vitamin C, E, NAC, alpha-lipoic acid.
- Reducing toxin exposure: Limit alcohol, processed foods, and environmental pollutants.
Below you can see a DNA test result where the GSTM1 gene is absent.

Glutathione Depletion and Disease Risk
Chronic glutathione deficiency has been linked to several diseases:
- Neurodegenerative Disorders: Parkinson’s, Alzheimer’s, multiple sclerosis (due to oxidative stress in neurons)
- Liver Disease: Fatty liver, cirrhosis, and hepatotoxicity from drug metabolism
- Cardiovascular Disease: Increased oxidative damage leading to atherosclerosis
- Cancer Susceptibility: Impaired detoxification of carcinogens
- Chronic Inflammatory Diseases: Asthma, arthritis, and autoimmune conditions
The Antioxidant Cascade: Maintaining Balance
Since GSH is the central hub of antioxidant defense, its depletion weakens the recycling of:
- Vitamin C & E (critical for neutralizing free radicals)
- Coenzyme Q10 (vital for mitochondrial function)
- Alpha-lipoic Acid (important for cellular energy production)
How to Maintain Optimal Glutathione Levels
- Dietary Support: Eat glutathione-rich foods (spinach, avocado, asparagus).
- Supplementation: NAC, liposomal glutathione, and selenium.
- Exercise: Moderate-intensity workouts boost glutathione production.
- Stress Management: Reduce chronic inflammation with mindfulness and sleep.
Conclusion
Glutathione is a powerful antioxidant that is essential for health and longevity. Genetic factors like GSTM1 deletions impact detoxification, requiring individuals to be proactive in maintaining GSH levels. By understanding glutathione metabolism and implementing lifestyle strategies, one can optimize health and resilience against chronic diseases.