t_wrex
Bluelighter
- Joined
- Jul 29, 2019
- Messages
- 141
I've been reading recently on antioxidant supplementation, specifically to counteract the potentially high levels of reactive oxygen (ROS) molecules generated during metabolism of various recreational drugs. I've used doses of NAC with the intention of counteracting the oxidative stress of MDMA metabolism, though of course ROSs are involved in a myriad of destructive biological processes (NAC was recently looked at in a COVID-19 study.)
Glutathione is referred to as one of the more powerful antioxidants present in the body, capable of rendering a good number of ROS's inert. A prodrug for it, N-acetylcysteine, is promoted by many as helping augment the body's natural glutathione production. I have asked on this forum and elsewhere whether this is truly pharmacologically sound, and have unfortunately not received very many substantial responses; lots of glowing anecdotal reports of success, in addition to a repeated claim that since NAC is so cheap you "might as well" take it even if it doesn't do much of anything. More than one anecdote claimed that you could get nearly the same level of benefit from NAC as you could by just maintaining good diet and exercise; this agrees with what my GP told me when I asked him about it during my last doctor visit. He said that there are rate-limiting mechanisms that prevent antioxidants from being taken up too quickly, and that if precursors exceeded that threshold the body would just eliminate them unchanged. He also said that the thing that concerned him most with MDMA was the toxic effects on the heart, which he said NAC wouldn't help with.
Recent studies from the past few years identify the amide derivative of NAC as being a better candidate for glutathione supplement than NAC, highly increasing its bioavailbility and blood-brain barrier penetration. I have read that the ethyl ester of glutathione (often named "GSH-EE") might be an even better candidate, as it is just glutathione with one of the terminating carboxylic acid groups changed to a carboxylic ester. This apparently allows it to cross the blood brain barrier where plain glutathione cannot, while retaining the same radical scavenging properties. Seems to me you would always want the thing that's closest to the parent drug rather than a prodrug precursor.
The studies I found these compounds in are at most a decade old, and I could only find samples available in research quantities from Sigma Aldrich/Cayman etc. Anyone have any thoughts on this?
Glutathione is referred to as one of the more powerful antioxidants present in the body, capable of rendering a good number of ROS's inert. A prodrug for it, N-acetylcysteine, is promoted by many as helping augment the body's natural glutathione production. I have asked on this forum and elsewhere whether this is truly pharmacologically sound, and have unfortunately not received very many substantial responses; lots of glowing anecdotal reports of success, in addition to a repeated claim that since NAC is so cheap you "might as well" take it even if it doesn't do much of anything. More than one anecdote claimed that you could get nearly the same level of benefit from NAC as you could by just maintaining good diet and exercise; this agrees with what my GP told me when I asked him about it during my last doctor visit. He said that there are rate-limiting mechanisms that prevent antioxidants from being taken up too quickly, and that if precursors exceeded that threshold the body would just eliminate them unchanged. He also said that the thing that concerned him most with MDMA was the toxic effects on the heart, which he said NAC wouldn't help with.
Recent studies from the past few years identify the amide derivative of NAC as being a better candidate for glutathione supplement than NAC, highly increasing its bioavailbility and blood-brain barrier penetration. I have read that the ethyl ester of glutathione (often named "GSH-EE") might be an even better candidate, as it is just glutathione with one of the terminating carboxylic acid groups changed to a carboxylic ester. This apparently allows it to cross the blood brain barrier where plain glutathione cannot, while retaining the same radical scavenging properties. Seems to me you would always want the thing that's closest to the parent drug rather than a prodrug precursor.
The studies I found these compounds in are at most a decade old, and I could only find samples available in research quantities from Sigma Aldrich/Cayman etc. Anyone have any thoughts on this?