L-Glutathione

Glutathione is a tripeptide made from glutamate, cysteine and glycine, synthesised inside cells throughout the body and present at particularly high concentrations in the liver. It is often described as the master antioxidant, reflecting its central position in cellular redox defence.

The long-standing objection to oral supplementation is that glutathione is a peptide and should be broken into its constituent amino acids during digestion, making it no more useful than supplying those amino acids directly.

That objection has softened somewhat. Trials using specific stabilised or liposomal preparations have reported increases in body stores over sustained supplementation. Whether that holds for ordinary unprotected glutathione powder is much less clear, which makes the form a more consequential choice here than for most ingredients.

Glutathione neutralises reactive oxygen species directly and serves as the substrate for glutathione peroxidase, which detoxifies hydrogen peroxide and lipid peroxides. In doing so it is oxidised, then recycled back to its reduced form by glutathione reductase.

It is also central to the liver's second-phase clearance processes, binding to a wide range of compounds to make them water-soluble for excretion. This is the basis of its role in clearing substances the body wants rid of.

Cysteine availability is the rate-limiting factor in glutathione synthesis. This is why N-acetylcysteine is often the more efficient and cheaper route to raising glutathione, and why comparing the two is a fair question rather than a technicality.

Trials using stabilised oral glutathione over several months have reported increases in blood and tissue glutathione markers, which is meaningful evidence that absorption is possible with the right preparation. Sample sizes have been modest and independent replication limited.

What is far less established is whether raising glutathione produces any noticeable benefit in someone who is already well. Most outcome research involves people with documented oxidative stress or depleted glutathione, and results there do not automatically extend to a healthy person topping up a functioning system.

Skin lightening is a widely marketed application, principally in Asian markets, with some trial support at high doses. It is worth noting that this represents a cosmetic use and sits well outside how the product is positioned in sports nutrition.

Oral glutathione is well tolerated, with trials reporting few adverse effects. Occasional complaints include mild digestive upset and, rarely, headache.

A consideration worth understanding rather than fearing: antioxidant supplementation around training may blunt some of the adaptive signalling that exercise-induced oxidative stress provides. This has been shown more clearly for high-dose vitamin C and E than for glutathione, but the principle applies, and taking it away from training sessions is a sensible precaution for anyone training for adaptation.

Injectable and intravenous glutathione, widely marketed for cosmetic purposes, carries a different and considerably higher risk profile than oral use and has drawn safety warnings from several regulators.