Setria® Glutathione: The Molecule, the Form and the Absorption Question
What glutathione is
Glutathione is a tripeptide, made from three amino acids: glutamate, cysteine and glycine. It is synthesised inside cells in two enzymatic steps, and it is one of the most abundant small molecules in the intracellular environment, present at millimolar concentrations in many tissues.
It cycles between two states.
GSH, the reduced form, in which a free thiol group is available
GSSG, the oxidised form, in which two glutathione molecules are joined by a disulfide bridge
The ratio between the two is one of the most widely used laboratory indicators of cellular redox state. The enzyme glutathione reductase regenerates GSH from GSSG, and the cycle runs continuously.
Glutathione is also a substrate for the glutathione S-transferase enzyme family, which is involved in phase II conjugation reactions in the liver.
The absorption debate
For a long time the orthodox position was that oral glutathione was pointless. The reasoning was that a tripeptide would be hydrolysed by peptidases in the gut into its three constituent amino acids, arriving in circulation as glutamate, cysteine and glycine rather than as glutathione. Early studies supported this, finding no meaningful rise in plasma glutathione after oral dosing.
That position has been revisited rather than overturned.
Richie and colleagues conducted a six-month randomised placebo-controlled trial of oral glutathione in healthy adults and reported increases in glutathione in blood, erythrocytes, plasma and buccal cells at both dose levels tested, with the effect dose and time dependent. Sinha and colleagues subsequently examined a liposomal glutathione preparation over one month and reported increases in body stores alongside changes in certain functional markers.
Reduced form, and why Setria is specified
Setria is a branded reduced L-glutathione produced by fermentation rather than chemical synthesis or extraction.
Two things are being specified by that name. The first is that the material is the reduced form, GSH, rather than oxidised glutathione or a precursor such as N-acetylcysteine. The second is manufacturing identity: a defined fermentation process, a documented specification and the analytical backing to demonstrate both.
Glutathione is a reactive molecule. It oxidises readily, which makes both manufacturing and formulation stability real technical problems rather than theoretical ones. A material with a verified reduced-form specification at the point of manufacture is a meaningful starting point, and the formulation then has to preserve it.
Delivery
This is a dry liposomal capsule using the SAIFx system, with sunflower lecithin phospholipids and acacia gum.
The rationale for phospholipid encapsulation of glutathione follows directly from the absorption debate above. If the obstacle is peptidase hydrolysis in the gut, then presenting the intact tripeptide within a phospholipid structure addresses that obstacle directly. The Sinha study cited above used a liposomal preparation for exactly this reason.
Dose and practical considerations
One capsule provides 250 mg of reduced L-glutathione. Published human studies have used doses in the range of roughly 250 mg to 1,000 mg daily, over durations from four weeks to six months.
Glutathione has a good tolerability record in the published trials. As with any supplement, anyone pregnant, breastfeeding or taking prescribed medication should speak to their GP or pharmacist before starting.
Common questions
Is oral glutathione absorbed? This was long assumed not to be the case on the basis of gut hydrolysis. More recent randomised human studies have reported increases in body stores after sustained oral dosing. The evidence base is small and includes manufacturer involvement, so it is best described as developing.
What is the difference between reduced and oxidised glutathione? Reduced glutathione, GSH, has a free thiol group. Oxidised glutathione, GSSG, is two molecules joined by a disulfide bridge. The ratio between them is used as a laboratory measure of cellular redox state.
How is glutathione different from NAC? N-acetylcysteine is a precursor supplying cysteine, which is the rate-limiting amino acid in glutathione synthesis. Glutathione is the assembled tripeptide.
Does the body make its own glutathione? Yes. It is synthesised inside cells in two enzymatic steps and is among the most abundant intracellular small molecules.
Why does glutathione need a delivery system? Because it is a peptide facing digestive hydrolysis, and because it oxidises readily, which makes stability a formulation challenge.
References
- Meister A, Anderson ME. Glutathione. Annual Review of Biochemistry. 1983;52:711-760.
- Wu G, Fang YZ, Yang S, Lupton JR, Turner ND. Glutathione metabolism and its implications for health. Journal of Nutrition. 2004;134(3):489-492.
- Richie JP Jr, Nichenametla S, Neidig W, et al. Randomized controlled trial of oral glutathione supplementation on body stores of glutathione. European Journal of Nutrition. 2015;54(2):251-263. doi:10.1007/s00394-014-0706-z
- Sinha R, Sinha I, Calcagnotto A, et al. Oral supplementation with liposomal glutathione elevates body stores of glutathione and markers of immune function. European Journal of Clinical Nutrition. 2018;72(1):105-111.
- Witschi A, Reddy S, Stofer B, Lauterburg BH. The systemic availability of oral glutathione. European Journal of Clinical Pharmacology. 1992;43(6):667-669.
- Allen J, Bradley RD. Effects of oral glutathione supplementation on systemic oxidative stress biomarkers in human volunteers. Journal of Alternative and Complementary Medicine. 2011;17(9):827-833.
- Forman HJ, Zhang H, Rinna A. Glutathione: overview of its protective roles, measurement, and biosynthesis. Molecular Aspects of Medicine. 2009;30(1-2):1-12.
- Great Britain Nutrition and Health Claims Register. Department of Health and Social Care, gov.uk.
Food supplements are not a substitute for a varied and balanced diet and a healthy lifestyle.