Glutathione-producing probiotics: the science behind ME-3®

Most glutathione products ask you to swallow glutathione. A glutathione-producing probiotic is a different idea: a bacterial strain that makes the molecule itself. The strain that put this concept on the map is Limosilactobacillus fermentum ME-3® (formerly Lactobacillus fermentum ME-3®), described in the scientific literature as an antioxidative probiotic with a complete glutathione system. This article explains what that means, what the evidence supports, and what an EU formulator may and may not say about it. VF Bioscience supplies ME-3®, with documentation, to food supplement, functional food and pharmaceutical manufacturers worldwide.

Can a probiotic produce glutathione?

Glutathione (GSH) is a tripeptide of glutamate, cysteine and glycine, and “the most abundant non-protein thiol that defends against oxidative stress” in mammalian cells (Lu, Biochimica et Biophysica Acta, 2013). Some lactic acid bacteria can synthesize it. ME-3® is notable because it does more than synthesize: it “was reported to have a complete glutathione system characterized by glutathione synthesis, uptake and redox turnover” (Pophaly et al., Microbial Cell Factories, 2012). That combination, making glutathione, taking it up, and recycling it between its reduced and oxidized forms, is what distinguishes the strain.

What is Limosilactobacillus fermentum ME-3®?

ME-3® was isolated and characterized by Professor Marika Mikelsaar and colleagues at the University of Tartu in Estonia, and deposited as strain DSM-14241. Its first description, in 2002, used the in-laboratory acronym E-3; the designation ME-3 came later, so older papers referring to E-3 concern the same strain (Kullisaar et al., International Journal of Food Microbiology, 2002). A point of nomenclature matters here: in the 2020 reclassification of the genus Lactobacillus, the species became Limosilactobacillus fermentum (Zheng et al., 2020). The correct current name is therefore Limosilactobacillus fermentum ME-3®, though the historical literature cites Lactobacillus fermentum ME-3®.

How does ME-3® make glutathione?

The mechanism is intracellular and belongs to the bacterium. A review of the strain describes it as “characterized by a complete glutathione system: synthesis, uptake and redox turnover”, with “high total antioxidative activity (TAA) and total antioxidative status (TAS) of intact cells and lysates” (Mikelsaar and Zilmer, Microbial Ecology in Health and Disease, 2009). The original work reported that the strain contains a remarkable level of glutathione, expresses manganese superoxide dismutase (relevant to countering lipid peroxidation), and survives exposure to reactive oxygen species (Kullisaar et al., 2002).

How is a glutathione probiotic different from a glutathione supplement?

The two approaches are not interchangeable. An oral glutathione supplement delivers the molecule directly. A glutathione-producing strain is studied for its own intracellular glutathione system. For a formulator, the relevant fact is that ME-3® is a documented strain with an unusual and well-described antioxidant biochemistry, which is a specification and sourcing consideration, not a health claim.

What can you claim in the EU?

Nothing on the antioxidant front. EFSA has rejected general antioxidant claims: among its stated reasons for rejection was a “lack of evidence that the claimed effect is indeed beneficial … (for example, food with ‘antioxidant properties’)”, alongside claims on probiotics (EFSA, 2011). There is no authorized EU health claim for probiotics, and the term probiotic is itself treated as an implied health claim. There is no authorized claim specific to ME-3®. On the safety side, Limosilactobacillus fermentum is on EFSA’s Qualified Presumption of Safety list, but QPS is a safety pre-assessment at species level, not an efficacy or claims approval. So the strain science is presented as technical information, and any consumer-facing wording is confirmed per market.