NAC (N-Acetylcysteine) at the FDA and vs oral glutathione

[EPguy]

Some of us are taking NAC supplement for its antinflammatory effects. It's also subject of this phase 1-2 MPN trial looking for dose and MPN-TSS symptom improvements:

clinicaltrials.gov/ct2/show...

In the US, FDA had been considering removing it from allowed supplements, but it seems they are rationally ready to let it stay in some way as of Apr 2022. Before seeing that good news I checked the alternative, glutathione.

Glutathione has two versions in the body GSH and GSSG. GSH is the good one, GSSG is oxidized and not good. It seems regular oral glutathione has troubles with bio-availability of the good one while NAC cause the body to create GSH glutathione internally. I found this report:

ncbi.nlm.nih.gov/pmc/articl...

It's done by a company that makes a bioavailable version of glutathione and with volunteers with metabolic syndrome. With that bias, they conclude that regular oral glut makes more of the not-good kind, GSSG, while both NAC and their new product makes more of the good one GSH. In essence they conclude their Glut is as good as NAC and better than oral glut. They used NAC as the reference and I see it also as an indirect endorsement of NAC for the purpose of obtaining active glutathione.

--"The relative amounts of each form determine the cellular redox status (GSH/GSSG ratio) which is often used as a marker of antioxidative capacity of cells...In our study, the GSH/GSSG ratios in the NAC and sublingual GSH arms are significantly higher than oral GSH one."--

Problem is their "patented" glut is expensive, more than $2/day.

amazon.com/Euromedica-Clini...

But if their report is relevant, it's best to use either their expensive glutathione or NAC. With NAC being available it would be the cheaper option.

-There may be other glut formulas that are equal to NAC for the "good" GSH. If so that is also a good option for the goal of these supplements which seems to be getting high GSH/GSSG ratios in the body..

--

[Planti]

Hiya, Thanks for posting that.

I had heard before that NAC was more likely to boost glutathione than oral glutathione. It is interesting that they did not assay against other sublingual forms of glutathione. Not that the liquid/sublingual one that I used to buy was much less expensive than their sublingual tabs.

Problem now for me with NAC is that my stomach has become much more sensitive and NAC is causing heartburn even when I take it after a meal.

Oh, darn, always something.

[EPguy in reply to Planti]

Looking deeper, there is another type of glutathione, S-Acetyl-Glutathione (SAG) for which << SAG significantly restored, GSH levels..., while it strongly reduced GSSG levels>>

Interesting that it also has "Acetyl" in it as with NAC.

The promotions on Amazon are consistent with the higher bio-availability. It is not expensive.

pubmed.ncbi.nlm.nih.gov/354...

The subligual guys didn't look for competitors because they are promoting their version (with a plausible study) . But your comment suggests that sub-lingual category is known and effective.

I had some issues with NAC in my 1st round, weird stomach and stinky gas. The gas is a known effect. I stopped for a couple months. Upon restarting it's been totally easy. But I also started Besremi before restarting NAC, so that might somehow be relevant. I use a time release NAC.

[Paul123456 in reply to EPguy]

I’ve now concluded that the NAC was not responsible for my reduced Pegasys efficacy. Think it was simply the most obvious conclusion, that I reduced dosage Pegasys too much as I tried to boost my WBC. This may have let the MPN genie out of the lamp and I’m now trying to get myJAK2 back under control. At least my blood counts are rising with the JAK2 (unsurprisingly?) so I have a bit more latitude re dose increases.

[EPguy in reply to Paul123456]

That is reassuring regarding NAC, and fits the idea: look in the obvious place 1st. I disobeyed this once seeking a roof leak (it was right where the drip came from, who would think?)

But I hope you can regain that allele progress. You did have tight responses to the changes. Will you have another AB reading soon?

Re CBCs vs AB, I have posted in fine detail on that see post here, and am having discussions with my Dr. There is a clear correlation of CHR to AB. You are seeing that connection well it seems. Is your CBC still in range?

My Dr wants to blindly go for a numeric Bes dose value rather than a result based titration.

healthunlocked.com/mpnvoice...

Re WBC I recently posted my latest CBCs etc. My MPN specialist is ok with near zero Lymph since there are redundant sources in Lymph nodes (seems reasonable) and also the spleen. He said he has lymphoma pts with zero Lymph but no infection troubles. But blood Neut should not go too low since it has no other source.

[Paul123456 in reply to EPguy]

That’s interesting info re Lymphocytes, I was aware that Lymph nodes acted as a top up but did not realise to that extent.

How low is your Hem prepared to allow Neuts to fall? Mine wants them above 1.5 but definitely not below 1. I tend to range between the two.

[EPguy in reply to Paul123456]

I did not ask since I'm so far in range (1.8-2.5) and didn't want to press off subject item. But I have now added that to my question list for next visit. It did bottom out when i was on HU+ Bes at 1.58. But if Bes dose continues rising it could decline again.

For lymph I found this ref which matches his expert knowledge, note "small proportion":

merckmanuals.com/profession...

<< It is also important to note that the lymphocytes in the blood represent only a small proportion of the total lymphocyte pool and may not always correlate with the composition and numbers of lymphocytes in other lymphoid (eg, nodes, spleen) and non-lymphoid (eg, lung, liver) tissues.>>

[Planti in reply to EPguy]

I must look for time release NAC. I have two dogs I can blame for the SG which I do experience too. How much NAC do you take?

First I heard of SL Glutathione was from a friend who was told to take the regular tabs and put them under tongue, by his hepatologist. Sublingual forms were not readily available at the time. Must have been some early evidence of increasing the absorption by that means. Friend still alive, took the INF tx for hep C when it was covered by medical plan.

Thanks for your post, they are always very interesting and informative.

L

[PhysAssist in reply to Planti]

In researching further, I also found this study:"Oral supplementation with liposomal glutathione elevates body stores of glutathione and markers of immune function"

ncbi.nlm.nih.gov/pmc/articl...

But I'm not sure exactly what, if anything it adds to the conversation.

[EPguy in reply to PhysAssist]

That study points to a third Glut form that may have high bio-avail, liposomal glutathione. Lipo Glut is available for sale.

It also considered the ratio of GSH/GSSG, so that is relevant in glut studies.

So we have four possible good ways to get the good type GSH glut: sub-lingual, liposomal glutathione, S-Acetyl-Glutathione, and NAC.

Lipids are used in other drugs, including the mRNA vaxes to get the agent into cells. This was a key innovation in these shots.

[EPguy in reply to Planti]

Agree, dogs don't need NAC to stir up the air.

I take 600mg. It's whole foods brand. NAC is not easily avail online in US because the FDA issue is still not fully resolved.

Interesting your friend was explicitly instructed to take NAC. It is well established to help liver troubles. Is the Hep C all better? There are now actual cures for most Hep C, it's what we are hoping for with MPN.

[PhysAssist in reply to EPguy]

Yup, that's why I'm actually pushing to get switched from Hydroxyurea, which as a non-specific DNA inhibitor [cytotoxic agent] doesn't address the underlying causes of PV or enable molecular remission/"minimal residual disease", to Besremi, which, if I understood all the studies I have been reviewing had the best tolerability of the interferon preparations, and did [over time= average of 3 years] induce both cellular and molecular remission i.e., reduce both overproduction of downstream blood products and JAK2 mutation allele burden].

Again, if I understood my reading correctly- the JAK2 allele burden is perhaps as important to disease treatment as is cytoreduction, due to the pro-inflammatory nature of the JAK2 mutation causing increased risk for leukemic transformation, myelofibrosis, etc.

see:

ncbi.nlm.nih.gov/pmc/articl...

[Roles of JAK2 in Aging, Inflammation, Hematopoiesis and Malignant Transformation]

and:

ncbi.nlm.nih.gov/pmc/articl...

[Inflammatory Pathophysiology as a Contributor to Myeloproliferative Neoplasms]

[EPguy in reply to PhysAssist]

The 1st report there discusses jak2 mutations that are from age and don't necessarily turn into MPN. But that inflammation + mutation can lead to MPN. Hence interest in anti-inflams. This research group is esp focused on this area:

mpnlab.org/participate-in-s...

You're right that INF, including besremi, can stop progression and even reverse disease. There's three key aspects of MPN control, blood counts (CHR) allele burden (AB) and marrow histology (fibrosis, cellularity...) INF can help all of these. I've posted reports on the close relation between CHR and AB reductions. There seems to be less prediction of marrow improvements by these other two. But HU is far more limited in fixing any of them.

Here is the 5 year Besremi AB results. They also had better progression results, although small n on that. But the value of AB reductions is not agreed by all practitioners, even while it is growing among them. As I say, I'd rather try to get AB reduced and find it didn't matter than not try and find it would have mattered.

Ropeg 5 year allele

[PhysAssist]

Hi,Agree with all of that.

I would point out that the first article also mentions the general overall increase in disease processes caused by the uncontrolled systemic inflammation caused by having a JAK2 mutation, which led me to wonder even more whether it might be significantly beneficial to reduce that allele burden positing a likely direct relationship between them [AB and systemic inflammation].

We know that systemic inflammation increases both cancer risk and the process of cardiovascular disease, i.e., atherosclerosis, so it seems to me that decreasing that [AB] should also decrease the associated risks.

...and this all ties into the primary discussion of this thread, because that's essentially the whole point of trying to increase systemic glutathione levels- to help mitigate the effects of inflammatory changes associated w/ MPN's and JAK2 mutations.