Glutathione

Grades and forms of glutathione

Glutathione, in bulk almost always reduced L-glutathione (GSH), is a tripeptide of glutamic acid, cysteine and glycine. In the EU its novel food status must be confirmed; where a Union list entry applies, both the raw material and the finished supplement must match it. This page covers the grades buyers specify, that regulatory position and the handling points that follow from its free thiol group.

CAS 70-18-8 identifies the reduced form, γ-L-glutamyl-L-cysteinylglycine. Oxidised glutathione (GSSG), the disulfide formed from two molecules, is a different substance with its own identity and regulatory position. Check which one a specification describes before comparing offers.

Supplement-grade glutathione powder is typically made by fermentation and purified to a crystalline solid. Grades differ in assay, the limit for oxidised glutathione and other related substances, microbiological limits and particle size. Particle size affects flow and blend uniformity in capsule filling and direct compression.

Three questions usually decide the choice:

• Where a Union list entry applies, does the specification match it, including the production method?
• Is the assay reported for reduced glutathione, with oxidised glutathione given as a separate limit?
• Does the particle size suit the format: a fine powder for drink mixes, a free-flowing grade for capsules and tablets?

SoleChem sends the specification sheet and certificate of analysis with its quote; these state the assay, impurity limits and physical data for the lot. Ask for the grade you need in the quote form.

EU regulatory status

Glutathione is not a vitamin or mineral, so Annexes I and II of Directive 2002/46/EC do not apply to it. Its status under Regulation (EU) 2015/2283 on novel foods must be confirmed against the Union list before use.

Where an entry exists in the Union list, Implementing Regulation (EU) 2017/2470, it sets the specification and, where appropriate, conditions of use such as food categories, target population and maximum use levels. The ingredient must meet that specification, and the finished product must stay within the authorised conditions of use. Check whether the entry also sets specific labelling requirements or data protection that limits who may place it on the market. The novel food guide explains how to read an entry.

National rules still apply alongside the authorisation. Many member states require notification of a food supplement before sale, using the option in Article 10 of Directive 2002/46/EC. Rules on substances other than vitamins and minerals also differ by member state, so confirm the position in each target market.

Claims on the finished product fall under Regulation (EC) No 1924/2006. Check the EU Register of nutrition and health claims and the health-claims guide before writing any claim.

Formulation notes

The free thiol (-SH) group of the cysteine residue drives most handling decisions. It oxidises to the disulfide in the presence of oxygen, moisture, heat and trace metals such as iron and copper. Oxidation lowers the reduced-glutathione assay over shelf life, so real-time stability data matter. The same precautions apply to other thiol ingredients such as N-acetyl-L-cysteine.

• Capsules: dry fill in HPMC or gelatin hard capsules is the simplest route. Fine grades may need a flow aid such as silicon dioxide. Packs with low oxygen and moisture transmission, or a desiccant, protect the assay. See ingredients for capsules.
• Tablets: direct compression avoids the water and heat of wet granulation. In multi-ingredient tablets, keep glutathione apart from iron and copper salts where the design allows. See ingredients for tablets.
• Powders and drinks: glutathione dissolves readily in water but oxidises faster in solution than in the dry state. It has a sulphurous note and a sour taste that the flavour system must cover. Ready-to-drink liquids are the most demanding format.

Glutathione is declared as the substance itself, so there is no elemental conversion. The quantity weighed per serving is the label claim divided by the assay fraction, plus any stability overage. For example, a 250 mg claim with a lot assay of 98.0 % needs about 255 mg before overage. The overage calculator handles the stability allowance. The molar mass of 307.33 g/mol is needed only when converting between mass and molar quantities.

Label rules for the finished product, including the name under which glutathione is declared, are covered in the labelling guide.