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Glutathione causing anxiety/irritability

Mr. Cat

Senior Member
Messages
156
Location
Nothern California
Hello PR,

I just started taking liposomal glutathione, which initially had some positive effects of clearing brain fog, and a feeling of well-being. However, soon it started causing anxiety, and then irritability, without the positive symptoms I experienced earlier. I'm pretty sure this doesn't happen to most users, and tried to research it. I came across something saying that a subset of glutathione users may experience anxiety/irritability, and that taking selinium, magnesium, and zinc before, as well as well as magnesium, niacin, zinc, and molybdenum afterward may get rid of these symptoms. That's a lot of supplements to buy just to see if it works, so I'm going to keep reducing the dose and see what happens. I initially tried 700mg, then 350mg, then 175mg, all of which were too much for me. I also experienced strong irritability after taking undenatured whey, which I understand is a glutathione precursor. The positive effects I have experienced sporadically have made me want to continue experimenting despite the negative ones. Anyone have an idea of what's going on with glutathione causing anxiety/irritability, and what to do about it?
 

Treeman

Senior Member
Messages
774
Location
York, England
Hi, I've just started taking glutathione and have had no such problems. I have however found a slight improvement in my conditions. The most noticeable thing is that its flipped my IBS-C to IBS-D. I eat dates and figs with food to aid digestion, however I'm now going remove them over a couple of days to see if my habits, "normalise".
 

Pyrrhus

Senior Member
Messages
4,172
Location
U.S., Earth
I just started taking liposomal glutathione, which initially had some positive effects of clearing brain fog, and a feeling of well-being. However, soon it started causing anxiety, and then irritability, without the positive symptoms I experienced earlier.

I have never tried liposomal or IV glutathione, but I have taken N-acetyl-cysteine (NAC) to boost my glutathione levels. This caused 8-12 weeks of various symptoms, including anxiety and irritability. Then all those symptoms went away and I feel so much better afterwards. (I take 1000mg NAC daily, half in the morning and half at night)

Hope this helps.
 

gbells

Improved ME from 2 to 6
Messages
1,491
Location
Alexandria, VA USA
I have never tried liposomal or IV glutathione, but I have taken N-acetyl-cysteine (NAC) to boost my glutathione levels. This caused 8-12 weeks of various symptoms, including anxiety and irritability. Then all those symptoms went away and I feel so much better afterwards. (I take 1000mg NAC daily, half in the morning and half at night)

Hope this helps.

Older people can't boost glutathione with NAC. They lose the ability to synthesize it.
 

Pyrrhus

Senior Member
Messages
4,172
Location
U.S., Earth
For anyone interested, the lowered production of glutathione that is seen in aging has been found to be due to a deficiency of the precursors, especially cysteine, needed to make glutathione.

Basically, in a nutshell, the oxidative damage that comes with aging gradually depletes glutathione, which at the same time depletes cysteine faster than it can be replenished by the diet.

So taking promoters of glutathione, such as cysteine or NAC, can boost glutathione production in older adults. (NAC is converted into cysteine in the intestines.)

If you're interested, here are some scientific publications on the subject:

Reference 1 said:
There is growing evidence that oxidative stress increases with age. ... Clinical studies confirmed that supplementation of the glutathione precursor cysteine decreases insulin responsiveness in the fasted state. In several clinical trials, cysteine supplementation improved skeletal muscle functions, decreased the body fat/lean body mass ratio, decreased plasma levels of the inflammatory cytokine tumour necrosis factor α (TNF-α), improved immune functions, and increased plasma albumin levels. As all these parameters degenerate with age, these findings suggest: (i) that loss of youth, health and quality of life may be partly explained by a deficit in cysteine and (ii) that the dietary consumption of cysteine is generally suboptimal and everybody is likely to have a cysteine deficiency sooner or later.

Reference 2 said:
Aging is a chronic oxidation process in which the immune system is involved. Because leukocyte function is a good health marker and longevity predictor, the effects of daily oral administration of N-acetylcysteine (NAC, 600 mg) on several lymphocyte and neutrophil functions, as well as cytokine levels, were studied in 36 healthy postmenopausal women: 18 aged 50–69 years and 18 aged >69 years. In addition, plasma and leukocyte oxidative stress markers (glutathione, superoxide, malondialdehyde) were evaluated. ... NAC administration significantly improved the parameters studied, bringing their values closer to those of younger women and thus exerting a modulatory, rather than a merely stimulatory, action on the immune system. These effects were also observed 3 months after the end of supplementation. The present findings suggest that a short period of NAC supply (i.e., 2–4 months) at the dose used may lead to prolonged strengthening of immune defenses in postmenopausal women, likely by increasing the leukocyte glutathione pool. Thus, NAC could contribute to maintenance of good health and quality of life in postmenopausal women by decreasing the probability of immune system-related diseases, such as infections, in aging.

Reference 3 said:
First, [NAC] can act as a precursor for glutathione synthesis as well as a stimulator of the cytosolic enzymes involved in glutathione regeneration. ... And finally, N-acetylcysteine also increases mitochondrial complex I and IV specific activities both in vitro and in vivo in synaptic mitochondrial preparations from aged mice. In view of the above, and because of the ease of its administration and lack of toxicity in humans, the potential usefulness of N-acetylcysteine in the treatment of age-associated mitochondrial neurodegenerative diseases deserves investigation.

Hope this helps.

References
[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1569588/
[2] https://www.infona.pl/resource/bwmeta1.element.elsevier-6833adf5-072f-3fc1-86ef-41e373a56fb5
[3] https://www.sciencedirect.com/science/article/abs/pii/S0306987700911940
 

Mr. Cat

Senior Member
Messages
156
Location
Nothern California
I have never tried liposomal or IV glutathione, but I have taken N-acetyl-cysteine (NAC) to boost my glutathione levels. This caused 8-12 weeks of various symptoms, including anxiety and irritability. Then all those symptoms went away and I feel so much better afterwards. (I take 1000mg NAC daily, half in the morning and half at night)

Hope this helps.
That's interesting, Pyrrhus that the negative symptoms disappeared after 8-12 weeks. I tried NAC in the past, and I experienced negative side effects (increased brain fog, I think, maybe anxiety too). I'm not sure I could handle 8-12 weeks of the anxiety/irritability I was feeling!
 

Judee

Psalm 46:1-3
Messages
4,461
Location
Great Lakes
Glutathione is also a sulfur/thiol. Is it possible you have problems with sulfur/thiols? Some of us do.

Do you react similarily to things like garlic and onions, or veggies in the broccoli family? Do you get headaches after you take the glutathione or eat any of those type of things?
 

Mr. Cat

Senior Member
Messages
156
Location
Nothern California
Glutathione is also a sulfur/thiol. Is it possible you have problems with sulfur/thiols? Some of us do.

Do you react similarily to things like garlic and onions, or veggies in the broccoli family? Do you get headaches after you take the glutathione or eat any of those type of things?

Yes, I just heard about thiols, and got a recommendation to try glutamine or glycine instead, as they are thiol-free, which I may do. I seem to handle garlic, onions, and cruciferous vegetables ok - in fact those are the main vegetables I can eat. I'd hate to discover that I have a sulfer problem, as my diet is already extremely limited!
 

percyval577

nucleus caudatus et al
Messages
1,302
Location
Ik waak up
Symptoms might also develop because when you have supplemented after a while the effect should lessen, and then other actions would come up again, which are now not anymore countered until the next supplementation dose, or not anymore surrounded by a countering environment. I had this with Iboprofen (which I took for tooth pain).
 

Pyrrhus

Senior Member
Messages
4,172
Location
U.S., Earth
I'm not sure I could handle 8-12 weeks of the anxiety/irritability I was feeling!

Yeah, it was pretty hellish. To be honest, I took a lot of Ativan to get through those weeks, and I might not have made it through without the Ativan. But I am certainly glad I made it through, as I feel so much better now. My body must have been quite drained of glutathione!

Oh, and if you're interested, here's a study that talks about glutathione in ME:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3896084/

Symptoms might also develop because when you have supplemented after a while the effect should lessen, and then other actions would come up again, which are now not anymore countered until the next supplementation

That reminds me of one thing- the first dose I took caused symptoms lasting a week. When the symptoms started to subside, I took the next dose. I had to gradually increase the dose by taking only one dose in the first week (on Monday), two doses in the second week (Monday and Friday), three doses in the third week, etc. Even after I was able to tolerate it daily, it took a couple more weeks for the symptoms to subside and to start seeing the real benefits.
 

percyval577

nucleus caudatus et al
Messages
1,302
Location
Ik waak up
That reminds me of one thing- the first dose I took caused symptoms lasting a week.
The whole thing will be complex enough (I guess). When I started my low manganese diet, I had at the first day two effects: a good one, and in a sense a bad one. This often happened during the last year, sometimes with some good influences.
 

Mr. Cat

Senior Member
Messages
156
Location
Nothern California
Yeah, it was pretty hellish. To be honest, I took a lot of Ativan to get through those weeks, and I might not have made it through without the Ativan. But I am certainly glad I made it through, as I feel so much better now. My body must have been quite drained of glutathione!

Oh, and if you're interested, here's a study that talks about glutathione in ME:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3896084/



That reminds me of one thing- the first dose I took caused symptoms lasting a week. When the symptoms started to subside, I took the next dose. I had to gradually increase the dose by taking only one dose in the first week (on Monday), two doses in the second week (Monday and Friday), three doses in the third week, etc. Even after I was able to tolerate it daily, it took a couple more weeks for the symptoms to subside and to start seeing the real benefits.

That sounds like a good plan, Pyrrhus, to take a (smallish)dose once symptoms have calmed down, which they have for me today. I think I have sort of been doing that on by own anyway, but may do that more systematically, as you did. It sounds like a better approach than either flooding the system with glutathione and having constant intense symptoms, or giving up on glutathione altogether. Glad to hear it eventually worked for you.
 
Messages
31
I have has the same experience(irritability/anxiety) with any sulphur/thiol based supplements.
I have had it with
- NAC Alpha Lipoic acid and Glutathione - makes me irritable tired and foggy.
- NT Factor - makes me irritable but with energy

I havent tried to push through them for weeks. If there is any over the counter medicine that can give me boost to my mood. I would try it.
There isnt anything powerful enough to offset the effects. If there are any please post here.

There is andy cutler chelation protocol which say we need to dose in small frequent doses. Like starting from 5mg for every 3 hours to move mercury out of your system. Read about it.

ACC was too difficult for me to follow. But the symptoms are in-line with what they describe. But their solutions never work.

So thats my experience so far
 
Messages
3
Yeah, it was pretty hellish. To be honest, I took a lot of Ativan to get through those weeks, and I might not have made it through without the Ativan. But I am certainly glad I made it through, as I feel so much better now. My body must have been quite drained of glutathione!

Pyrrhus, I'm suffering terribly from the usage of an oral Glutathione spray. My symptoms amount to autonomic neuropathy. I can barely climb the stairs, I'm having bouts of delirium, severe anxiety and more. Could you expound more on your own hellish experiences? How long did they last. Were you able to recover? Aside from the Benzodiazepines, did you do anything to facilitate coping/healing?


I found this somewhat difficult to comprehend. Would you be willing to summarize or highlight the key points?

Grateful, for any help.
 

YippeeKi YOW !!

Senior Member
Messages
16,047
Location
Second star to the right ...
it started causing anxiety, and then irritability, without the positive symptoms I experienced earlier.
Glutathione metabolism can increase glutamate, the major excitatory neurotransmitter in the central nervous system, which can lead to GABA/glutamate imbalances, which in turn can lead to anxiety, irritability, and insomnia, among other effects.
I also experienced strong irritability after taking undenatured whey, which I understand is a glutathione precursor.
First off, there's no such thing as 'undenatured whey'. It's a sales tool.

Whey is hydrolized protein. Hydrolization severs the links between amino acids and provides an almost endless supply of free glutamic acid, another precursor to excess glutamate. Whey protein is hydrolyzed either thru high-heat processing, or by using various acids to sever the amino links, so in short, it's denatured by its extensive processing into whey protein.
 

Pyrrhus

Senior Member
Messages
4,172
Location
U.S., Earth
Pyrrhus, I'm suffering terribly from the usage of an oral Glutathione spray. My symptoms amount to autonomic neuropathy. I can barely climb the stairs, I'm having bouts of delirium, severe anxiety and more. Could you expound more on your own hellish experiences? How long did they last. Were you able to recover? Aside from the Benzodiazepines, did you do anything to facilitate coping/healing?

You're not alone. A lot of people have pretty hellish start-up effects on N-acetyl-cysteine or glutathione. For me, it mostly involved muscle weakness, air hunger, insomnia, and delayed constipation followed by diarrhea. Other symptoms included brain fog, night sweats, and aches.

I generally start at a low dose, and only raise the dose slowly. ("start low and go slow")

I started with a single 500mg dose of N-acetyl-cysteine on a Monday. That was all I took for the first week.

By the following Monday, the effects from the first dose wore off, so I took another 500mg dose, and then another dose on that Friday. So I took 2 doses in the second week.

The third week I took three doses, on Monday, Wednesday, and Friday. The fourth week I took four doses, etc.

By the 8th week, I was taking 500mg N-acetyl-cysteine every day.

But this was a pretty hellish eight weeks, and I didn't start to feel the positive effects of the increased glutathione until week 12.

After week 12, though, I had a clear improvement in most of my symptoms. In fact, boosting my glutathione is one of the greatest long-lasting improvements I have had, reducing all of my core ME symptoms noticeably.

Hope this answers your questions.
 
Last edited:

bread.

Senior Member
Messages
499
You're not alone. A lot of people have pretty hellish start-up effects on N-acetyl-cysteine or glutathione. For me, it mostly involved muscle weakness, air hunger, insomnia, and delayed constipation followed by diarrhea. Other symptoms included brain fog, night sweats, and aches.

The most important piece of advice I can give is to start at a low dose, and only raise the dose slowly. ("start low and go slow")

I started with a single 500mg dose of N-acetyl-cysteine on a Monday. That was all I took for the first week.

By the following Monday, the effects from the first dose wore off, so I took another 500mg dose, and then another dose on that Friday. So I took 2 doses in the second week.

The third week I took three doses, on Monday, Wednesday, and Friday. The fourth week I took four doses, etc.

By the 8th week, I was taking 500mg N-acetyl-cysteine every day.

But this was a pretty hellish eight weeks, and I didn't start to feel the positive effects of the increased glutathione until week 12.

After week 12, though, I had a clear improvement in most of my symptoms. In fact, boosting my glutathione is one of the greatest long-lasting improvements I have had, reducing all of my core ME symptoms noticeably.

Hope this answers your questions.

wow, how severe are you?