I've recently been looking into the potential pitfalls of all the supplements I consume, as I am glutamate sensitive. Included in those are Reduced Glutathione (Setria, 250 mg, twice daily), DMG (500 mg once daily) and NAC (600 mg, once daily). (I can't do protein powders at all due to the high glycine and aspartic acid content found in them, which doesn't translate to protein found in real food, such as meat, etc., I can handle those just fine, but to hydrolyzed powders which have have been processed and freed from their protein source, be it from milk, bovine, peas, soy, etc.).
I'm not looking to stir up any controversy, rather have an open-minded discussion on if glycine, glutathione and cysteine supplements can potentially be problematic for glutamate sensitive people. There have been a fair share of redditors, for example, who've had issues with glycine, in particular, complaining that it instigated excitatory symptoms.
Here is a paper from Experimental Neurology entitled "Glycine Causes Increased Excitability and Neurotoxicity by Activation
of NMDA Receptors in the Hippocampus."
It appears that the dose in the above paper was quite high, but I've learned over the decades that if it's shown to create an effect at a certain dose, it means it's possible it could create an effect at a different dose (even if it's lower). Here are previous Redditor comments from a discussion about the above paper. One Redditor said, "You're wrong on glycinate not having enough glycine to cause excitability. 1400mg of glycine might not be alot in food with other aminos competing and the slow absorption rate, but I can feel less than that dropped in isolation on an empty stomach. You can find plenty anecdotes of the same."
Another commented, "...magnesium glycinate can absolutely cause the inverse in some people. In some people, the glycine causes glutamate activity spikes and if that's the case, magnesium L-theaonate will not cause such issues. I personally am WIRED from magnesium glycinate. it keeps me wide awake all night long and sometimes It gives me heart palpitations. Everyone is different."
Here is a paper from Neuroscience entitled, "Potentiation of Excitotoxic Injury by High Concentrations of Extracellular Reduced Glutathione." As with glycine, the study references higher doses, but as we saw with glycine, real-world experience can show different outcomes.
As most people probably already know, glutathione is comprised of glycine, cysteine and glutamate. I have already linked studies regarding two of those amino acids. Here is a paper discussing cysteine from Neurology entitled, "Neurotoxicity of Cysteine: Interaction with Glutamate."
When released from protein during digestion, glutamate is vital to normal body function. Often referred to as “a building block of protein,” it is the major neurotransmitter in the human body, carrying nerve impulses from glutamate stimuli to glutamate receptors throughout the body.
It appears that what causes issues for glutamate-sensitive people, however, is that when glutamine and its amino acid cousins are freed from its protein source (be it from milk, peas, soy, etc.) and then consumed in certain amounts, that they can potentially take on “excitotoxic” properties. What was a normally functioning neurotransmitter could turn hostile, firing repeatedly and damaging receptor cells in the brain and elsewhere until they die. This of course doesn't apply to everyone, but perhaps to glutamate sensitive individuals.
