Glutathione causing anxiety/irritability

Pyrrhus

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do you do anything else that helped?
I've tried many things that produced temporary improvement, but only B vitamins and NAC have led to clear, sustained improvement for me personally.

Have you described somewhere what B vitamins you are taking now?
For me, personally, I take "B minus" from the company Seeking Health:
https://www.seekinghealth.com/products/b-minus-100-capsules

And then I add 400mcg of methyl-folate per day and 250mcg of Hydroxy-B12 per week.
(I happen to be extremely sensitive to B12, hence the low dosage.)

As always, everyone is different and the ideal supplementation for you may vary...

Hope this helps.
 

HABS93

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Started with 500mg of NAC but didn't learn till later to take this amino acid powder that has glycine and other great ones to help boost it. After I increase the dose a month ago too 1500mg of NAC . Feel calmly hands . Feels like I'm trying to sweet toxins and whatever else . Brain fog much worse but I'm plowing through it. I've done my job so much I can go into auto pilot . I also smoke weed before bed so .
As for B vitamins I definitely found a nice mix right now. B complex plus a mitchrondria supplements and NAC. This has given stronger out burst or energy. I was running around at a park yesterday throwing a football around. I'm going to try transdermal B12 do it's more absorbed.
 

Lieselotte

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@Mr. Cat I had the same thing happen to me. I started taking liposomal glutathione (500mg/day I believe), and after a few weeks, I was a total wreck! I was literally ON EDGE every minute. Snapped at my boss at work and thank God it was out of character for me so she let it slide. I went off the glutathione and the symptoms went away. This was probably a year before I came down with ME.

Now, I'm back on glutathione (250mg for now) and have no issues with it. So, what is the difference? Well, I could have had my Mycoplasma infection at the time I took it the first time. So the glut could have stirred up more than I could handle to detox at the time because of that.
Or... someone on here mentioned that problems taking glut could mean I need detox heavy metals. I have since undergone some chelation for metals - mainly Lead and Mercury. It's possible the glut was stirring them up and I couldn't get rid of them efficiently.

Just some thoughts. :)
 

Pyrrhus

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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/
I found this somewhat difficult to comprehend. Would you be willing to summarize or highlight the key points?
Sorry, I don't know how I missed your question! The following is the abstract from the paper. Note that "GSH" is a nickname for glutathione, and "MRS" is an abbreviation for Magnetic Resonance Spectroscopy.


Increased ventricular lactate in chronic fatigue syndrome. III. Relationships to cortical glutathione and clinical symptoms implicate oxidative stress in disorder pathophysiology
Shungu et al 2012 said:
Chronic fatigue syndrome (CFS) is a complex illness, which is often misdiagnosed as a psychiatric illness. In two previous reports, using 1H MRS, we found significantly higher levels of ventricular cerebrospinal fluid (CSF) lactate in patients with CFS relative to those with generalized anxiety disorder and healthy volunteers (HV), but not relative to those with major depressive disorder (MDD).

In this third independent cross-sectional neuroimaging study, we investigated a pathophysiological model which postulated that elevations of CSF lactate in patients with CFS might be caused by increased oxidative stress, cerebral hypoperfusion and/or secondary mitochondrial dysfunction. Fifteen patients with CFS, 15 with MDD and 13 HVs were studied using the following modalities: (i) 1H MRSI to measure CSF lactate; (ii) single-voxel 1H MRS to measure levels of cortical glutathione (GSH) as a marker of antioxidant capacity; (iii) arterial spin labeling (ASL) MRI to measure regional cerebral blood flow (rCBF); and (iv) 31P MRSI to measure brain high-energy phosphates as objective indices of mitochondrial dysfunction.

We found elevated ventricular lactate and decreased GSH in patients with CFS and MDD relative to HVs. GSH did not differ significantly between the two patient groups. In addition, we found lower rCBF in the left anterior cingulate cortex and the right lingual gyrus in patients with CFS relative to HVs, but rCBF did not differ between those with CFS and MDD. We found no differences between the three groups in terms of any high-energy phosphate metabolites. In exploratory correlation analyses, we found that levels of ventricular lactate and cortical GSH were inversely correlated, and significantly associated with several key indices of physical health and disability. Collectively, the results of this third independent study support a pathophysiological model of CFS in which increased oxidative stress may play a key role in CFS etiopathophysiology.
(emphasis and spacing added)

So, in a nutshell, the researchers used a technique called Magnetic Resonance Spectroscopy to measure the levels of lactic acid (lactate) and glutathione (GSH) in the brains of ME/cfs patients.

They found elevated lactic acid and low glutathione in the brains of ME/cfs patients, which together indicated higher levels of oxidative stress in the brains of ME/cfs patients compared to healthy people.
 
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Pyrrhus

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Increased ventricular lactate in chronic fatigue syndrome. III. Relationships to cortical glutathione and clinical symptoms implicate oxidative stress in disorder pathophysiology
The above 2012 publication is from researcher Dikoma Shungu at Cornell University.
The following is some information on Dikoma Shungu's current clinical trial of NAC. (Remember that "GSH" is a nickname for glutathione.)


Assessment of N-Acetylcysteine as Therapy for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (NAC ME/CFS)
https://clinicaltrials.gov/ct2/show/NCT04542161
Excerpt:
Shungu said:
This phase two, single-site study will utilize a double-blind, placebo-controlled, randomized, pre-/post-treatment design to investigate the effect of NAC dosing on brain GSH levels and measure temporally concordant plasma levels of several established circulating markers of oxidative stress. Three study groups, of 20 subjects each (for a total of 60 who completed all components of the study), will each be administered a different dose (0 mg/day, 900mg/day, 3600mg/day) of the study intervention over a four week period; N-acetylcysteine (NAC) treatment. Subjects receiving 0 mg/day dose will be administered a placebo. Baseline visit assessments will include blood collection, survey questionnaires, MRI and MRS imaging. Subjects whose initial screening confirms low GSH level at baseline will be provided with a 4-week supplement of anonymized NAC or placebo caplets. After 4 weeks, subjects will then undergo a follow-up visit to repeat the baseline assessments.
 

gbells

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It won't have any effect. Glutathione is an antioxidant so it has nothing to do with energy loss in ME. I wouldn't approve funding for it.

That said, at age 50 I use reduced glutathione myself for longevity purposes. But it has no effect on ME.
 

bread.

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Before taking B vitamins and NAC, I was moderately severe.

After B vitamins and NAC, just moderate.

May not sound like much of an improvement, but I can objectively do much more than I could do before.
Would you think this could be helpful in me/cfs? This combination seems to upregulate fatty acid oxidation and downregulate glucose usage? Could this be detrimental in me/cfs? Especially in severe cases? Could this explain why some people get worse on NAC?

https://www.bcm.edu/news/glynac-improves-strength-and-cognition-in-older-humans
 

Pyrrhus

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Would you think this could be helpful in me/cfs? This combination seems to upregulate fatty acid oxidation and downregulate glucose usage? Could this be detrimental in me/cfs? Especially in severe cases? Could this explain why some people get worse on NAC?

https://www.bcm.edu/news/glynac-improves-strength-and-cognition-in-older-humans
The trial described in your link used a combination of Glycine and NAC in order to boost glutathione, and it reported an improvement in cognition in the elderly. I don't know what doses they used and I have not reviewed the study completely, but combining Glycine and NAC is a perfectly rational approach to boosting glutathione.

Note that Glycine and Cysteine (NAC) are natural components of dietary protein, and if supplemented in reasonable amounts, it's hard to see how they might have a negative impact on health, even if someone experiences intolerable start-up effects when they first start taking them.

Unfortunately, I don't think we are in a position to say for certain why some people experience such intolerable start-up effects when they first start supplementing to boost glutathione.

Hope this helps.
 
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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.
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wow, you are my superhero! first time i tried nac the first capsule knocked me down like i had a full on flu with body aches, fatigue, fog, general misery. i tried one more time to make sure and same. itʻs been several years and iʻm now trying again with these tiny little d-hist jr. tablets that only have 12.5mg nac, lol. sounds silly but i know it might be good for me if only i can learn to tolerate it. seem ok on one of those so will gradually add an extra each day. today was a total of 25mg nac and then i (wasnʻt thinking) and added in a new liquid methyl b12, at 1/4 dose of 1250mcg but oooooof. i donʻt know which one triggered this massive agitation, air hunger and crawling out of my skin. later on heartrate was off the charts, iʻm sure itʻs the b12 and not excited about trying it again. HOW in the world did you manage to keep going week after week despite hellish effects? i feel like iʻve got so little wiggle room that iʻm unable to sacrifice much to things that kick me down at the get-go... need some of your inspiration :)

also, some people with virus and biofilm can apparently have pretty gnarly "nac-flu" reactions, so not sure if itʻs die-off or some other reaction but it sure packs a punch.
 
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Pyrrhus

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HOW in the world did you manage to keep going week after week despite hellish effects? i feel like iʻve got so little wiggle room that iʻm unable to sacrifice much to things that kick me down at the get-go... need some of your inspiration :)
Lots of super-calming YouTube videos played in a loop, I guess. ;)
Fires in a fireplace. Beaches. Fires on beaches...
 
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Couldn't find this thread before. Just wanted to say I've been on 5g glycine 4x a day and 1800mg NAC 3x a day for the last 20 days. In a bit of a slump currently but I always take the NAC and glycine away from the other things I'm taking and don't notice any bad effects after the 20 minute period has elapsed for it to be metabolised. So still seems to be doing me some good.
 

Shanti1

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Great thread, I was wondering about others who feel worse with glutathione. I react to NAC and glutathione, but keep thinking they should be helpful. In my case, they both make me feel "thinned out", Bilbo Baggins said it best, "like butter spread over too much bread." Not a terrible reaction, but uncomfortable enough that I stop after one day. Anyhow, I am going to try to micro-dose myself into a good relationship with glutathione. Already taking B vits and Minerals.

@Sophiedw Based on the the NAC --> glutathione pathway, that list looks reasonable. Someone on this thread also mentioned zinc, but I think that info may be based on super high IV doses: https://pubmed.ncbi.nlm.nih.gov/1529808/
This study seems to indicate that chelation of our minerals by NAC may not be a concern:
https://pubmed.ncbi.nlm.nih.gov/2276385/
My thought is that we ME/CSF folks need to make sure we are nutritionally replete, so good to make sure we are getting/taking minerals regardless.
 
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Interesting, I have been struggling with difficulty sleeping and bad anxiety. I never even though it could be the glutathione itself causing this. Thank god for this thread! I was taking out all sorts of other things.

Did anyone ever manage a micro dose that worked.

@Learner1 did you experience this?

I started liposomal glutathione 2 weeks ago and the anxiety began last week. I've been considering quitting my job, over thinking my ability to do it, questioning everything about myself, now I've started questioning my relationship and other things. So it feels like it's getting worse.

Oh well at least I have probably figured it out now, phew!

Just a note I take 6g of NAC per day and have been for over 3 months and it does not cause any anxiety (for me).
 
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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 selenium, 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?
Just a quick note to say I've been taking zinc, selenium and lots of magnesium (the latter for 2 months) the formers for 2-3 weeks and that hasn't helped the anxiety. In fact I mistakenly believed the selenium and zinc might be the cause as I've never really taken zinc before but I have taken selenium long term and I remember it causing insomnia. Anxiety doesn't always go hand in hand with insomnia for me but sometimes it does. Just in case that helps anyone.