Glutathione

What glutathione does in your body

Glutathione (GSH) is a tripeptide made from glutamic acid, cysteine, and glycine. It is the most abundant antioxidant in human cells, present in millimolar concentrations in virtually every tissue. Your liver produces it continuously, and it serves three critical functions: neutralizing reactive oxygen species, detoxifying harmful compounds, and recycling other antioxidants like vitamins C and E back to their active forms ^[1].

Unlike antioxidants you get from food, glutathione is endogenous—your cells make it themselves. This matters because it can reach places dietary antioxidants cannot, including the inside of mitochondria where energy production generates damaging free radicals. Glutathione levels decline roughly 35-50% between youth and old age, and this drop correlates with increased oxidative stress markers and reduced detoxification capacity ^[2].

How glutathione protects your cells

The glutathione system works through two main enzymes. Glutathione peroxidases (GPX) use GSH to neutralize hydrogen peroxide and lipid peroxides before they form damaging free radicals. The glutathione S-transferases (GST) attach glutathione to toxins, drugs, and heavy metals, marking them for elimination. This conjugation is the rate-limiting step in Phase II detoxification ^[3].

A 2024 study found that dopamine neuron degeneration linked to aging is glutathione-dependent in model organisms, with reduced GSH synthesis accelerating neuronal death and shortening lifespan ^[4]. In humans, low glutathione levels appear in virtually every age-related disease: cardiovascular disease, neurodegeneration, diabetes, and cancer. The association is strong enough that some researchers propose glutathione depletion as a biomarker of biological aging.

Why levels drop with age

Several factors contribute to age-related glutathione decline. Cysteine availability becomes limiting as dietary protein intake often drops in older adults. The enzymes that synthesize and recycle glutathione lose efficiency. Chronic inflammation increases glutathione consumption. And accumulated oxidative damage impairs the cellular machinery that produces it.

The consequences extend beyond antioxidant defense. Low glutathione compromises immune function, reduces mitochondrial efficiency, slows toxin clearance, and impairs protein synthesis. Maintaining adequate levels through midlife and beyond appears protective against multiple age-related pathologies.

Strategies to support glutathione levels

Direct glutathione supplementation has poor bioavailability—most is broken down in the digestive tract before reaching cells. More effective approaches target the synthesis pathway:

• N-acetylcysteine (NAC) provides cysteine, the rate-limiting amino acid for GSH synthesis. Multiple studies show NAC raises glutathione levels in deficient individuals ^[5].
• Whey protein is rich in cysteine and cystine. Regular consumption supports glutathione production, particularly in older adults with low protein intake.
• Cruciferous vegetables (broccoli, Brussels sprouts, kale) contain sulforaphane, which activates the Nrf2 pathway and upregulates glutathione synthesis enzymes.
• Selenium and folate are cofactors for glutathione peroxidases and synthesis enzymes. Adequate intake ensures the machinery works efficiently.
• Exercise transiently increases oxidative stress, which signals cells to upregulate glutathione production as an adaptive response.

Liposomal glutathione and S-acetyl-L-glutathione show better absorption than standard oral forms in limited studies, though evidence for clinical outcomes remains preliminary ^[6].