Glutathione is often called the body’s “master antioxidant”—and for good reason. It plays a central role in detoxification, immune defense, energy production, and protection against oxidative stress. While you can support your glutathione levels through diet and supplements, your body actually makes it on its own—through a finely tuned internal process known as glutathione synthesis.
This process depends not only on specific amino acids and nutrients but also on a network of genes and enzymes. In this article, we’ll explore how glutathione is made, the genes involved (including the often-overlooked CTH gene), and how to support your body’s natural antioxidant system.
What Is Glutathione?
Glutathione is a tripeptide, made up of three amino acids:
- Glutamate
- Cysteine
- Glycine
It exists in two forms:
- Reduced glutathione (GSH) – the active antioxidant form
- Oxidized glutathione (GSSG) – the used form, which can be recycled
Glutathione neutralizes free radicals, supports detoxification (especially in the liver), and helps regenerate other antioxidants like vitamins C and E.
How Is Glutathione Synthesized?
Glutathione is created inside your cells through a two-step enzymatic process:
- Step 1: Glutamate + Cysteine → γ-Glutamylcysteine
- Enzyme: Glutamate-cysteine ligase (GCL)
- Genes involved:
- GCLC (catalytic subunit)
- GCLM (modifier subunit)
- GCLC (catalytic subunit)
- This is the rate-limiting step in glutathione production.
- Enzyme: Glutamate-cysteine ligase (GCL)
- Step 2: γ-Glutamylcysteine + Glycine → Glutathione (GSH)
- Enzyme: Glutathione synthetase (GSS)
- Adds glycine to complete the tripeptide.
- Enzyme: Glutathione synthetase (GSS)
But here’s the catch: cysteine is often the limiting amino acid in this process. That’s where the CTH gene comes in.
🧬 The Role of the CTH Gene
The CTH gene encodes cystathionine gamma-lyase, an enzyme that converts cystathionine into cysteine as part of the transsulfuration pathway. This pathway links the methionine cycle to glutathione synthesis by supplying the cysteine needed for step one of the process.
If the CTH enzyme isn’t working efficiently—due to genetic variants or nutrient deficiencies—your body may struggle to make enough cysteine, especially during periods of stress or toxin exposure. And without cysteine, glutathione production stalls.
🧬 Key Genes Involved in Glutathione Synthesis
Why Glutathione Is So Important
Glutathione supports nearly every major system in the body:
- ✅ Neutralizes free radicals
- ✅ Detoxifies heavy metals and xenobiotics
- ✅ Regenerates other antioxidants (e.g., vitamin C, E, CoQ10)
- ✅ Supports immune health and cell repair
- ✅ Maintains mitochondrial function and energy
- ✅ Reduces inflammation and cellular damage
What Depletes Glutathione?
- Chronic psychological or oxidative stress
- Infections or high inflammation
- Environmental toxins and pollutants
- Smoking, alcohol, poor diet
- Certain medications (e.g., acetaminophen)
- Nutrient deficiencies (B6, B12, folate, selenium)
- Genetic polymorphisms (especially in GCLC, CTH, or GST genes)
How to Support Glutathione Synthesis Naturally
🔹 Supply the building blocks:
- Cysteine – from protein, eggs, poultry, or NAC (N-acetylcysteine)
- Glutamate – found in bone broth, fermented foods
- Glycine – from collagen, gelatin, or bone broth
🔹 Key cofactors and nutrients:
- Vitamin B6 – supports the CTH enzyme
- B12 and folate – aid upstream methylation and transsulfuration
- Selenium – essential for glutathione peroxidase
- Magnesium & zinc – support enzymatic function
🔹 Lifestyle tips:
- Reduce toxin exposure (clean air, clean water, clean food)
- Prioritize sleep, rest, and recovery
- Manage stress to reduce oxidative burden
- Exercise moderately to stimulate endogenous antioxidant activity
- Consider glutathione-boosting supplements (e.g., NAC, liposomal glutathione, alpha-lipoic acid)
Genetics & Testing
If you suspect low glutathione levels or poor detox capacity, genetic testing can help identify polymorphisms in GCLC, GCLM, GSS, CTH, or GST genes. Knowing your genetic blueprint can help guide personalized nutrition and lifestyle strategies to optimize your antioxidant defense system.
Conclusion
Glutathione synthesis is one of your body’s most important protective processes—guarding your cells, supporting your liver, and helping you handle everyday stress and toxins. And it all starts with a handful of critical enzymes and the genes behind them—including the often-overlooked CTH gene, which supplies the cysteine needed to kick off the process.
By supporting these pathways with the right nutrients, lifestyle habits, and (when needed) personalized testing, you give your body the tools it needs to heal, detox, and thrive.