NAC benefits and side effects

[Dane12]

Dear all,

I am currently investigating the possibility to start an anti-inflammatory treatment based on NAC (on top of Besremi). Looking over the NAC side effects, I run into some materials that show there is a potential downside of using this aminoacid, by promoting the expansion of some cancers (especially lung).

pubmed.ncbi.nlm.nih.gov/315...

cellandbioscience.biomedcen...

There are also other publications.

Is anyone more knowledgeable about this topic?

Thank you in advance for your response.

[EPguy]

I am on Besremi and taking NAC (1200mg/day sustained release) I feel the NAC does help my symptoms.

There are many discussions on NAC on this forum, by searching posts for NAC.

--

The reports you have are not what we like to see of course. There is this one also directed to liver cancer looking at IFN+ NAC:

"NAC may be enhancing the effect of IFN through inhibition of NF-kB"

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

They don't seen to address or be aware of the downside in your references. Maybe it's less a concern with the IFN combo?

--

You likely have seen the mouse studies for MPN with NAC. They showed very good results. One example:

"N-acetylcysteine inhibits thrombosis in a murine model of myeloproliferative neoplasm"

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

But this study used equivalent of 100%VAF, so there were no wild type (good) Jak2 cells to replace them with which is required for IFN (and apparently NAC) to reduce allele.

In contrast: "Marty et al23 previously reported that NAC reduced spleen weight and blood counts and reduced the frequency of JAK2V617F progenitors in a competitive transplantation JAK2V617F murine model. The impact of NAC on blood counts and spleen size by Marty et al23 could possibly be explained by the selective reduction of JAK2V617F cells. Because hematopoiesis in our model is made up entirely of JAK2V617F cells, (100%VAF) this could explain why we did not see the same impact on blood counts or spleen weight as Marty et al.23"

--

Here is the "Marty" study, it used an equiv of 30% VAF of Jak2 mutants, and they saw a reduction in allele and other benefits:

"Mice engrafted with 30% of Jak2(V617F) KI bone marrow (BM) cells developed a polycythemia vera-like disorder. Treatment with the anti-oxidant N-acetylcysteine (NAC) substantially restored blood parameters and reduced damages to DNA. Furthermore, NAC induced a marked decrease in splenomegaly with reduction in the frequency of the Jak2(V617F)-positive hematopoietic progenitors in BM and spleen"

"Targeting ROS accumulation might prevent the development of JAK2(V617F) MPNs. "

pubmed.ncbi.nlm.nih.gov/235...

--

In your references there is trouble with reducing ROS (reactive oxygen species). In our case excess ROS is a known complication of MPN as quoted above so maybe we benefit more by reducing them.

At least the reference you provide suggests one should check for "JunD-deficiency" if starting NAC as this was a clear risk factor.

--

The NAC/MPN trial ongoing will give some early answers, but it is not testing IFN combo.

clinicaltrials.gov/ct2/show...

You can see they are using doses of 1200-3600/day.

[Dane12 in reply to EPguy]

Thank you for your well documented answer! There is a clear benefit in reducing the ROS with the help of NAC. It remains to see if , in special circumstances, NAC does not inhibit too much the ROS, which our body use them in our immune response.

[Snook37 in reply to EPguy]

I’ve also started taking NAC 1200 mg/day (600 mg twice a day) starting 3-4 weeks ago. We’ll see if it makes a difference. Ready for preliminary results from Dr. Fleischman’s study, but as you mentioned I wish they were looking at combo therapy with interferon. Would probably provide more insight. I always read it was liver protective and not liver toxic.

[EPguy in reply to Snook37]

You're right about the liver in general, NAC is used to prevent liver damage with Tylenol overdose. This is its FDA approved medical use.

[SoledadBarcelona]

I read about it, NAC+ is no good for us but a precursor of NAC + can be well. I have been taking Nicotinamide Riboside Chloride. Happy with it. .. until now.

[Dane12 in reply to SoledadBarcelona]

Thank you for the information!

[EPguy in reply to SoledadBarcelona]

I think you might be referring to NAD+ :

"Nicotinamide riboside (NR) is a newly discovered nicotinamide adenine dinucleotide (NAD+) precursor vitamin"

nature.com/articles/s41598-...

--

This seems to be not related to NAC, which does not normally have a + version. Could be both these supps are useful, but likely in very different ways.

[Dane12]

Thank you for the information!

[NegritOcho]

You’ll be fine. The latest research indicates that NAC shoukd be taken with Glycine:

pubmed.ncbi.nlm.nih.gov/337...

m.youtube.com/watch?v=EvX6i...(Not working as expected?)

[Dane12 in reply to NegritOcho]

Thank you for the information!

[EPguy in reply to NegritOcho]

I've seen this too. It's directed to complications of aging, which seems a broad idea of being useful. Related reports note NAC alone is less useful for this. How it translates to our MPN need is a question. I plan to ask my Dr whether Gly can be harmful, he's not inclined to agree any of these are useful but at least clearing it as not harmful with my specialist is a start.

This study found it not of much effect except for those with high ROS (oxidative stress) That's us. But I don't know whether we have low GSH-T, but this does decline with age:

"analyses revealed that a subset of subjects characterized by high oxidative stress (above the median for MDA) and low baseline GSH-T status (below the median), who received the medium and high doses of GlyNAC, presented increased glutathione generation "

frontiersin.org/articles/10...