Russ Brook As I dietitian who has researched toxicology, I can't speak on how supplemental affects inflammatory bowel disease conditions, but I do know that the problem with supplemental glutathione has to do with it's poor absorption. It is better to enhance the body's natural production of glutathione and spare it's just as a direct antioxidant so it can be used in detoxification (an indirect anti oxidative process). You can do this by taking foods rich in cysteine, e.g. eggs, and having adequate dietary antioxidants like vitamin C and E as well as phytochemicals from vegetables, fruits, and sprouts.

Glutathione (GSH) has a very short half-life of around 1.3 minutes and as a tripeptide is readily degraded in the stomach. As GSH must be manufactured continuously to provide for enzymes like GPx and the GSTs, it is unlikely that a GSH supplement can keep pace with cellular demands - even if it manages to bypass degradation in the gut. All the GSH-related genes are Nrf2 target genes and so upregulation of Nrf2 by potent phytochemicals such as sulforaphane will provide cells with a supply of GSH in the manner cells are genetically accustomed to. Interestingly, supplement direct-acting antioxidant vitamins like vitamins C, E and beta-carotene can mask the signalling processes used to activate Nrf2. To directly answer your question, I think it is unlikely that supplemental GSH has sufficient impact to inhibit synthesis in any cell type, tissue or organ.

Agree with Christine, i think is really unusefull to supplement glutathione due to is short half-life and poor bioavalability, in my practice i strongly suggest DHA and EPA, antiosxidant and polyphenols......

Great points Christine and Roberto. What are your thoughts on sublingual Glutathione and rectal suppository Glutathioine? The patient had a lot of success for Ulcerative Colitis using sublingual Glutathiones and inquired about purchasing a Glutathione rectal suppository which he is able to purchase at his local compounding pharmacy. He is interested in using this rectal suppository of Glutathione to treat his rectal inflammation caused by Ulcerative Colitis as the sublingual version has helped tremendously.

Again, I see no point in supplementing with pre-formed GSH. I prefer to mimic the cell's endogenous mechanisms by activation of Nrf2 with subsequent induction of a battery of cytoprotective genes, which act in concert to protect cells. GSH is just one player in this huge cell-defensive orchestra.

Sulforaphane is acknowledged as the most potent food-derived Nrf2 activator; moderate exercise is beneficial in using the same mechanism as at least one means of cytoprotection.

And if ulcerative colitis is the primary reason for seeking GSH, then I'd suggest the patient should be investigating the value of pre-biotic butyrate-producing soluble fibres as a wider programme to enhance the populations of microbiota. This will have a far greater benefit than GSH suppositories which I doubt will have any benefit at all. Combine a high sulforaphane-yielding whole broccoli sprout supplement with a prebiotic like beta-glucan or partially-hydrolysed guar gum plus a diet rich in plant polyphenols - such as the classical Mediterranean diet.

Thank you Christine. Patient has seen a rapid and strong benefit from GSH sublingual in ulcerative colitis disease activity. There is some research that GSH can help reduce oxidative damage in ulcerative colitis.

But, Russ there are more rounded longer-term solutions. UC is known to be correlated with lack of diversity in the microbiome and with low butyrate-producing species.

Christine, I think you are correct that one of the many causes of UC is microbiome. But, I believe the GI inflammatory diseases, although all under the same title or umbrella of ulcerative colitis or crohn's, are in reality several different diseases all with the common symptom of inflammation in the colon or small intestine or other parts of the digestive system. There might be a subset of ulcerative colitis diseases that are caused by microbiome, there might be others caused by a malfunction of the immune system without stimuli, there might be others caused by harmful toxins resulting in degradation (or oxidative damage) of the intestinal lining and tight junctions, and perhaps other causes. I don't think there is a one size fit all treatment for these diseases. Just my opinion and observation.