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Glutathione: Is more better?

Messages
296
An interesting article on Glutathione.

"
Now, let’s actually think this through:

  1. GSH is a good thing, the body’s most important endogenous antioxidant/detoxification molecule.
  2. The liver makes more GSH in response to oxidative/toxic chemical stress.
  3. Substances which raise blood levels of GSH—even a precursor like cysteine—may do so because they increase (or reflect an increase in) oxidative/toxic chemical stress, the body making more GSH to neutralize the increased stress.
  4. Therefore, we might actually make things worse with cysteine supplementation.
So it’s possible that adding a supplement that increases GSH might do more harm than good, if we fail to consider the body’s exquisite natural system of checks and balances.

Let’s consider an analogous situation: Red blood cells are the indispensable oxygen carriers in the blood. If you don’t have enough of them, you have anemia. The body will compensate and make more of them if you deprive it of oxygen. You can do this by, say, moving from New York (close to sea level) to Denver (a mile high), where the oxygen content of the air is lower, and it works. You can also do it by smoking cigarettes, subjecting your body to chronic carbon monoxide poisoning. Ergo, smoking cigarettes can cure anemia!"

Read the rest here

Let's discuss :)!
 

PeterPositive

Senior Member
Messages
1,426
Hi,
I have experimented with oral GSH for a while (2 years), starting at 500mg and raising to 1500mg, then settling at 1000mg / day.

Regardless of the known issues, such as oral GSH not being well absorbed in the GI tract and unlikely to make it to the cell, it has helped dealing with inflammation and provided a 15-20% extra well being.

I can stop the GSH for a while without setbacks, but after roughly 3 weeks I usually get worst again with increased intensity of symptoms such as pain and inflammation.

According to someone GSH supplements are just an expensive way to provide the necessary aminoacids to the body to build its own GSH, meaning that the GSH gets broken down by the digestion and then reassembled by the metabolism... Maybe that's the case... I was initially skeptical of oral GSH but I do see some benefits so now I am equally skeptical of the oral GSH skepticism :)

I also have low stomach acid, so maybe my digestion is not efficient enough to break the GSH down? It's difficult to say, too many variables.

It's also worth mentioning that a number of people in this board have reported nasty side effects both from GSH precursors and GSH itself, so it may represent a crapshoot for some people.

my 2c
 

Gingergrrl

Senior Member
Messages
16,171
I read the link with great interest as I am currently doing a detailed glutathione protocol until I noticed the bottom which was an advertisement to buy his own supplement which lost credibility for me!
 

PeterPositive

Senior Member
Messages
1,426
I read the link with great interest as I am currently doing a detailed glutathione protocol until I noticed the bottom which was an advertisement to buy his own supplement which lost credibility for me!
Really? I don't see any ads at the bottom of the page. I turned the ad-blocker off, still nada...
 

Gingergrrl

Senior Member
Messages
16,171
Really? I don't see any ads at the bottom of the page. I turned the ad-blocker off, still nada...

How weird! On my phone it is a promotion twice in article and at bottom for the authors own supplement "sweetamine." Bizarre if not there for others!
 

PeterPositive

Senior Member
Messages
1,426
How weird! On my phone it is a promotion twice in article and at bottom for the authors own supplement "sweetamine." Bizarre if not there for others!
Interesting... I checked it with chrome on an iMac. Maybe the ads are targeted only at mobile phones... who knows :)
 

Gingergrrl

Senior Member
Messages
16,171
Interesting... I checked it with chrome on an iMac. Maybe the ads are targeted only at mobile phones... who knows :)

Weird and I did not click further on ad link so no clue what it says. But in any case IMO glutathione is a great product although of course it is not for everyone.
 

ahmo

Senior Member
Messages
4,805
Location
Northcoast NSW, Australia
Data like these, which so clearly confirm the theory, put glutathione and its precursors in proper perspective, and helped drive me to formulate and sell the glycine supplement Sweetamine
First sentence of last para. I haven't read the body yet, wonder if glycine and other aminos will do the job. I used glycine for several years.

I also consider myself as one who had a bad reaction to glutathione. I can't be certain, there were layers of irritation to my brain, but I'd been taking denatured whey for at least 6 months, had a toxic psychosis. I attribute it to combination of sulfur, histamines, glutathione. I may be incorrect.
 

Gingergrrl

Senior Member
Messages
16,171
I also consider myself as one who had a bad reaction to glutathione.

@ahmo I am so sorry that you had a bad response (which is the norm for me with most things that I try LOL.)

I am having a very positive response to glutathione and it's been about 19 days. The detox became strong with flu-like symptoms that I have not had before so I stopped for one day as per my doctor but back on the protocol today as the symptoms are gone. I am going to do a more thorough post on the whole experience after a few months when I have more to report and am still in the very early stages and don't want to jinx myself.
 

alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
Like most things, glutathione has an optimal dose response range, somewhat variable person by person. I think it can be good, and more better, but too much is worse.

The body has many essential oxidative chemical processes. Too much glutathione might disturb those and cause secondary negative effects.

Cysteine has its own problems. Most who want to boost cysteine use NAC, the acetylated version.
 

Gingergrrl

Senior Member
Messages
16,171
Like most things, glutathione has an optimal dose response range, somewhat variable person by person. I think it can be good, and more better, but too much is worse.

The body has many essential oxidative chemical processes. Too much glutathione might disturb those and cause secondary negative effects.

@alex3619 Can you (or anyone else with this info!) explain this when you get a chance (in beginner's lingo!) I'm now getting horrible flu-like symptoms from the nebulized glutathione even though for the first 18 or so days, it was working really well. I was wondering, how do you know when you have crossed the threshold that you are triggering a positive immune response that is getting rid of toxins vs. a dangerous response that you want to slow down?

Flu-like symptoms have never been a part of my illness (chills, feeling flu-ish and feverish, joint/muscle pain, and overall just sick, etc) and it's being triggered by the glutathione but not sure if this is good or bad? I suspect I've always been more autoimmune plus the severe autonomic issues, POTS, shortness of breath, and then the severe MCAS/allergies. In trying to treat the mold toxicity, which I believe was the final trigger behind everything, I am triggering this detox reaction (that I read is "normal" but is still alarming!)

I know you cannot give medical advice and not asking for any but was just curious if you could explain what you said above re: glutathione and the secondary negative effects?
 

JPV

ɹǝqɯǝɯ ɹoıuǝs
Messages
858
There's been much talk on the forum on how direct supplementation of glutathione has had negative effects on many of us suffering from ME/CFS. I know I had a bad reaction from it when I experimented with the liposomal form. I think the general consensus is that boosting it indirectly, via methods such as increasing methylation, seems to be the safer approach.

That said, I stumbled across this interesting post from Ken Lassesen's blog, which I found to be very interesting and may prove to be an important piece of the puzzle...
Lactobacillus Reuteri and recommendations on how to take it (CFS Remission)

Glutathione
Glutathione is one of L.Reuteri essential foods (http://www.ncbi.nlm.nih.gov/pubmed/21585317 ) so make sure that you supplement with it (I would suggest taking that 1 hr before the L.Reuteri) . This feeding of L. Reuteri may be one reason that it has positive effects on CFS patients (although the why of taking it comes from a different model).
The reason that some people may be non-responders to Gluthathione could be as simple as having no L.Reuteri left to feed!

Bottom line: L Reuteri and Glutathione should be taken together – taking one without the other may result in little or no effect.
 

Gingergrrl

Senior Member
Messages
16,171
@JPV Thanks for the info and I really appreciate it. In my case, the glutathione is nebulized and in a much smaller dose than in IV form. My mold doc is against the glutathione IV's that so many on PR have responded negatively to b/c they give a huge dose all at once and overwhelm the body (in her opinion) and then quickly leave.

I have inflammation in my lungs and the nebulized glutathione is the first thing in three years to directly help my breathing. It was miraculous until I started getting the detox/flu-like symptoms and I suspect the mold binders that I am tolerating are not strong enough. I am very interested in trying CSM (the pure powdered form with no additives, sugar, or colors) in a micro dose as it is the gold standard for binders and I don't feel I have a lot to lose right now.

I tried the methylation supplements when I saw an ME/CFS specialist in 2014 and had a horrible over-methylation reaction. The dose was way too high but even at a micro dose, I did not tolerate them at all. I know this is the hypothesis to indirectly raise glutathione but my body does not tolerate it. My mold doc said that from my SNP's right now it is better not to open up the methylation pathway and leave it alone (and I'd have to check my notes to explain her thinking on this one as I lack the science to explain it coherently.)

I did my first dose of nebulized glutathione at the hospital just in case of a negative reaction but I did not have one. I think it has now just built up in my system so I need to slow the detox process down (my plan had been to increase the dose to 2x/day but now I am thinking to do it every other day or whatever my doc advises.)

I have not taken the L. Reuteri that you sited above but my understanding (which could be wrong!) is that I should not take lactobacillus probiotics b/c of having MCAS and if I take any, they should be the Bifido strain. At present, I am not taking any probiotics out of fear how I could react MCAS/allergy-wise.
 

alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
Can you (or anyone else with this info!) explain this when you get a chance (in beginner's lingo!) I'm now getting horrible flu-like symptoms from the nebulized glutathione even though for the first 18 or so days, it was working really well.
I really don't think we know enough. I have been trying to explain the glutathione paradox for about 13 years now. There are some hypotheses, sure, but they are not proven, and might be right in some cases and wrong in others. That is, some of the theories are right, maybe more than one, but which? What is it we are missing?

I go with the empirical on this. If one specific dose is good, and more is worse, you have found a soft limit. That limit might later rise or lower, but you know there is a limit for you, individually, as a patient.

This effect plus sudden start and stop of short remission make me think its all under dynamic regulation. When you push hard there is a delay and then it pushes back. Soooo many treatments in ME are like this. Finding one that does not do this is a hard search, and one which many of us engage in. When this happens I strongly suspect you are pushing at the edge of the disease, not the core, and it fights back. However when the body pushes back I think you do have a clue, its just that we don't know how to interpret the clue.

As usual, we need more and better science.

Now there may indeed be cases of pathogen die off. I am just suspicious that this is common. One thing I want to try more is glutathione, or perhaps NAC, directly onto the nasal membranes. There are nasal gluthathione sprays for example. However this has risks too. The reason I want to try it is for sinus issues which became much worse for me recently, and I am probably only kicking out of it due to antibiotics.

Fortunately, a good number of searchers find something that helps them, such as methylation therapy or antivirals, while perhaps the majority of us are still looking.

The issue with glutathione and loss of oxidative stress below a hard to define threshold is that this will effect many many biochemical pathways, variable patient by patient due to individual chemistry, and most probably felt hardest in the brain. In other words, its theoretically sound but we still do not know the full impact.

The other issue is that improved function with more glutathione may give rise to secondary consequences, and start using up other substances you have in short supply. It might be a clue as to other things that need fixing. Again, many speculate about what, but to date we have no certainty. So we try things.
 

PeterPositive

Senior Member
Messages
1,426
There are nasal gluthathione sprays for example. However this has risks too. The reason I want to try it is for sinus issues which became much worse for me recently, and I am probably only kicking out of it due to antibiotics.
Is the nasal GSH supposed to act locally or is it expected to be absorbed in the system?
In other words, could it substitute the oral form?

thanks
 

alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
Is the nasal GSH supposed to act locally or is it expected to be absorbed in the system?
In other words, could it substitute the oral form?

thanks
I do not know for sure. One thing it should due is increase the immune capacity in the nasal region , with possible increase in resistance to the kinds of infection we sometimes get. The evidence for this is weak, and based on old animal models, but its theoretically fair. Absorption is probably, and I am guessing here, weaker than sublingual, and much weaker than nebulized into the lungs. However if someone has side effects this might be a good thing. In any case whatever result someone has would take precedent over theory.
 

Gingergrrl

Senior Member
Messages
16,171
This might make a difference. It might be that it changes your lung vascular chemistry too much. If you absorb it via the lung, and you use the nebulizer only under the tongue instead, does this make a difference?

@alex3619 When you say "changes to my lung vascular chemistry", do you mean that more blood is able to perfuse my lungs or that the lung inflammation is decreasing or something else? It sounds like this would be a good versus a bad thing?

Also, the nebulizer piece goes above the tongue (not under) so am confused by this, too? Am I using it wrong? My doc said that it is predominantly in the lungs yet it also goes systemic to the body. I am also using a glutathione skin cream but am not using any of the stronger methods and have never done the IV form.
 

Gingergrrl

Senior Member
Messages
16,171
Absorption is probably, and I am guessing here, weaker than sublingual, and much weaker than nebulized into the lungs. However if someone has side effects this might be a good thing. In any case whatever result someone has would take precedent over theory.

@alex3619 Sorry, that all these quotes are separate and I normally use multi-quote! It sounds like you are saying nebulization is one of the stronger methods and that if someone has side effects, it might be a good thing? I need to read your longer response and try to take it in, but am I understanding this correctly?
 

Gingergrrl

Senior Member
Messages
16,171
I really don't think we know enough. I have been trying to explain the glutathione paradox for about 13 years now. There are some hypotheses, sure, but they are not proven, and might be right in some cases and wrong in others. That is, some of the theories are right, maybe more than one, but which? What is it we are missing?

Okay, am using multi-quote now! I did not realize that you have been trying to explain the glutathione hypothesis for 13 years so I am definitely asking the right person!

I go with the empirical on this. If one specific dose is good, and more is worse, you have found a soft limit. That limit might later rise or lower, but you know there is a limit for you, individually, as a patient.

This is exactly what I am doing (trying to find the right limit) and still feel hopeful that I can find it. It initially felt like a miracle treatment but I guess I hit the soft limit as you said. This one requires a lot of experimentation and I think often of your "lemon rule" and already used it to eliminate other things I have been trying but I feel the glutathione is still right for me, I just need to play with the dosing schedule.

This effect plus sudden start and stop of short remission make me think its all under dynamic regulation. When you push hard there is a delay and then it pushes back. Soooo many treatments in ME are like this. Finding one that does not do this is a hard search, and one which many of us engage in. When this happens I strongly suspect you are pushing at the edge of the disease, not the core, and it fights back. However when the body pushes back I think you do have a clue, its just that we don't know how to interpret the clue.

I totally agree that I am pushing at the limit (and in my case it is stirring up the mold toxins in my body and trying to detox them out) so I am pushing at this, too. I am not smart enough to interpret it all but am still trying.

As usual, we need more and better science.

Agreed!

Fortunately, a good number of searchers find something that helps them, such as methylation therapy or antivirals, while perhaps the majority of us are still looking.

I am hoping to become one of those searchers that finds something that improves my quality of life but for now am still actively looking and trying things.

The issue with glutathione and loss of oxidative stress below a hard to define threshold is that this will effect many many biochemical pathways, variable patient by patient due to individual chemistry, and most probably felt hardest in the brain. In other words, its theoretically sound but we still do not know the full impact.

Am glad that you think it is theoretically sound (b/c I do as well) and more an issue of finding the right amounts.

The other issue is that improved function with more glutathione may give rise to secondary consequences, and start using up other substances you have in short supply. It might be a clue as to other things that need fixing. Again, many speculate about what, but to date we have no certainty. So we try things.

How would I figure out the other things that I need to add if the glutathione is using up other things? Am still planning to do the NutrEval test which might give my doctor some ideas.