Mild NAC success story. Anyone else?

[Gzephyr]

Background: Moderate CFS for 3 years post mono. I suspect a lingering EBV infection drives the majority of my symptoms. I take 3 grams of valacyclovir a day to suppress replication. I get very sick with mono-like symptoms and PEM if I miss a dose.


I took NAC for close to 2 months earlier this year (600mg a day.) I noticed I felt a whole lot better within a month or so but wasn't exactly sure it was the NAC helping me because I had a few other supplements in my stack. A few weeks later, I decided to drop all my supplements and see how I felt without them. Stopped NAC, l-lysine, zinc, and monolaurin. I did not drop my 3 grams per day Valacyclovir because it's the only drug I've found that stops my chronic EBV from replicating. I felt horrible again for a little over a month and assumed the combination of supplements I was taking were actually providing some benefit.

That month went by and then I started back on NAC alone and I was back to feeling much better. My lymph nodes weren't as swollen, my inflamed tonsils and sinuses were much better, I had more energy, and my activity threshold for triggering PEM had increased tremendously. I first expected a crash after exerting myself more than usual but it never came. I kept slightly over-exerting myself with short walks and even a quick mini-tennis session that led to no PEM. I was so happy to have a small part of my life back !

These benefits lasted the entire month I was back on NAC. I'm fairly confident I would have crashed hard several times with that much exertion if it weren't for the NAC.

Unfortunately, it's not a perfect fairytale story. A week ago, I came off the NAC again because it makes me pretty apathetic if I take it everyday for too long and I'm back to feeling pretty yucky within a couple days off it. Not completely terrible but noticeably worse. This could be a coincidence but I truly believe NAC helps my CFS. I also started back on L-lysine and it definitely helps with brain fog. No question. These are the only two supplements that have provided some CFS relief. I believe it more than ever that lingering EBV is to blame for a majority of my symptoms. I'll try to adjust my NAC dose so it doesn't make me apathetic while also provided CFS relief.

Here is some research I've found regarding NAC and EBV inflammation.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5724866/

The extra glutathione production from NAC could be the reason it helps me so much. I do I suspect it helps with the inflammation directly related to the EBV but I wouldn't doubt it to be more complex than that.

Has anyone else noticed a strong benefit from NAC?

 

[cfs since 1998]

I think NAC (combined with Vitamin C) helped me recover from Covid and swine flu, but only back to where I was before. But of course that could have been a coincidence.

 

[datadragon]

Nac inhibits the NLRP3 inflammasome pathway and NLRP3 inflammasome activation normally can lead to reactivating Epstein-Barr Virus, while inhibiting NLRP3 efficiently represses EBV reactivation so maybe that is part of why that helped you related to a lingering EBV infection. Hopefully the NIH and other researchers will eventually give more info on the mechanisms of ME/CFS so that drugs can be found, created or other treatments can be more effectively targeted.

NLRP3 inflammasome activation reactivates Epstein-Barr Virus. NLRP3 inflammasome inhibitors can efficiently repress EBV reactivation.
https://forums.phoenixrising.me/thr...n-efficiently-repress-ebv-reactivation.90835/

NAC has been shown to inhibit the NLRP3 inflammasome pathway (IL1β and IL18) in vitro, and decrease plasma TNF-ɑ in human clinical trials. NAC has been used to replenish glutathione stores and increase the proliferative response of T cells - N-Acetylcysteine (NAC) is an antioxidant and a precursor of the synthesis of glutathione (GSH). https://www.sciencedirect.com/science/article/pii/S0306987720308811 https://pubmed.ncbi.nlm.nih.gov/32504923/

Glutathione Transferase Omega-1 Regulates NLRP3 Inflammasome Activation through NEK7 Deglutathionylation - NLRP3 Inflammasome activation is limited by Exogenous GSH (Glutathione) and augmented in the presence of GSTO1-1 which suggests deglutathionylation as a possible process required for NLRP3 activation. https://www.cell.com/cell-reports/pdf/S2211-1247(19)31127-1.pdf

Added Note: NAC also appeared to be helpful for blood clotting, even in an ADAMTS13 deficient state. N-Acetylcysteine (NAC) was able to reduce the size of large Von Willebrand Factor (VWF) multimers, and inhibits platelet activation and formation of platelet-monocyte complexes. Injection of NAC into ADAMTS13-deficient mice led to the rapid resolution of thrombi and reduced plasma vWF multimers. Some people however it mentioned do have adverse allergic reactions in response to intravenous NAC infusion, and in those specific cases, they only showed concordant and rapid marked INCREASES in factor VIII activity and vWf antigen, rather than decrease, unless they took it with an antihistamine so that is important information for anyone who uses it if they get adverse reactions. https://gut.bmj.com/content/54/4/515

 

[Gzephyr]

Nac inhibits the NLRP3 inflammasome pathway and NLRP3 inflammasome activation normally can lead to reactivating Epstein-Barr Virus, while inhibiting NLRP3 efficiently represses EBV reactivation so maybe that is part of why that helped you related to a lingering EBV infection. Hopefully the NIH and other researchers will eventually give more info on the mechanisms of ME/CFS so that drugs can be found, created or other treatments can be more effectively targeted.

NLRP3 inflammasome activation reactivates Epstein-Barr Virus. NLRP3 inflammasome inhibitors can efficiently repress EBV reactivation.
https://forums.phoenixrising.me/thr...n-efficiently-repress-ebv-reactivation.90835/

NAC has been shown to inhibit the NLRP3 inflammasome pathway (IL1β and IL18) in vitro, and decrease plasma TNF-ɑ in human clinical trials. NAC has been used to replenish glutathione stores and increase the proliferative response of T cells - N-Acetylcysteine (NAC) is an antioxidant and a precursor of the synthesis of glutathione (GSH). https://www.sciencedirect.com/science/article/pii/S0306987720308811 https://pubmed.ncbi.nlm.nih.gov/32504923/

Glutathione Transferase Omega-1 Regulates NLRP3 Inflammasome Activation through NEK7 Deglutathionylation - NLRP3 Inflammasome activation is limited by Exogenous GSH (Glutathione) and augmented in the presence of GSTO1-1 which suggests deglutathionylation as a possible process required for NLRP3 activation. https://www.cell.com/cell-reports/pdf/S2211-1247(19)31127-1.pdf

Added Note: NAC also appeared to be helpful for blood clotting, even in an ADAMTS13 deficient state. N-Acetylcysteine (NAC) was able to reduce the size of large Von Willebrand Factor (VWF) multimers, and inhibits platelet activation and formation of platelet-monocyte complexes. Injection of NAC into ADAMTS13-deficient mice led to the rapid resolution of thrombi and reduced plasma vWF multimers. Some people however it mentioned do have adverse allergic reactions in response to intravenous NAC infusion, and in those specific cases, they only showed concordant and rapid marked INCREASES in factor VIII activity and vWf antigen, rather than decrease, unless they took it with an antihistamine so that is important information for anyone who uses it if they get adverse reactions. https://gut.bmj.com/content/54/4/515

Amazing stuff. Thanks again for sharing your findings. Makes a lot of sense. I plan on really diving into these studies when I have the energy and maybe I'll share some of my findings. Just bought Liposomal Glutathione today to replace NAC so we'll see how that goes. Thanks !

 

[datadragon]

Amazing stuff. Thanks again for sharing your findings. Makes a lot of sense. I plan on really diving into these studies when I have the energy and maybe I'll share some of my findings. Just bought Liposomal Glutathione today to replace NAC so we'll see how that goes. Thanks !

Perhaps someone can also consider looking at trying S-Acetyl L-Glutathione I mentioned here, and can see if NAC vs Glutathione shows any benefit differences.
https://forums.phoenixrising.me/thr...elp-me-so-much-momentarily.89782/post-2438411

 

[Gzephyr]

Back on NAC 600mg and I feel amazing again. It brings me from moderate severity to mild within a week every time I start taking it and it usually stays that way for as long as I’m on it. It’s that big of a change.

However, I don’t take it consistently because it makes me very emotionally flat to the point where I can’t stand it. It’ll build up in my system and I’ll need to take a few weeks off to feel mentally normal. It works as an incredible anxiolytic for the first few weeks before making me too numb. I need to tinker with the dosing and then maybe I can avoid this. I’m currently experiencing the sweet spot at the time of this post and it’s been nice not having to be worried all the time about my health.

Another reason I don’t take it consistently is because I’ll feel too good on it and will over exert myself physically pretty much every day. I’ll start to feel numbed out by the NAC so I stop taking it and then boom I have horrible PEM for a month and oh boy it is NOT fun.

I just need to focus on not overdoing it while taking NAC. I won’t be able to be super physically active like I want to be but perhaps I can avoid some daily pain and fatigue long term.

It’s not a fix but man it’s a huge huge huge quality of life booster.

 

[Gzephyr]

So, Valacyclovir and NAC are still the only two drugs/supplements that provide any kind of sustained, drastic relief.

I’m adding glycine and curcumin to my stack by the end of the week. Gonna see if I can lower inflammation any further which will maybe allow for my immune system to heal up a little. It still hasn’t been able to kick ebv dormant.

 

[Violeta]

Back on NAC 600mg and I feel amazing again. It brings me from moderate severity to mild within a week every time I start taking it and it usually stays that way for as long as I’m on it. It’s that big of a change.

However, I don’t take it consistently because it makes me very emotionally flat to the point where I can’t stand it. It’ll build up in my system and I’ll need to take a few weeks off to feel mentally normal. It works as an incredible anxiolytic for the first few weeks before making me too numb. I need to tinker with the dosing and then maybe I can avoid this. I’m currently experiencing the sweet spot at the time of this post and it’s been nice not having to be worried all the time about my health.

Another reason I don’t take it consistently is because I’ll feel too good on it and will over exert myself physically pretty much every day. I’ll start to feel numbed out by the NAC so I stop taking it and then boom I have horrible PEM for a month and oh boy it is NOT fun.

I just need to focus on not overdoing it while taking NAC. I won’t be able to be super physically active like I want to be but perhaps I can avoid some daily pain and fatigue long term.

It’s not a fix but man it’s a huge huge huge quality of life booster.

It sounds as if it's affecting neurotransmitters. I looked it up and it does affect glutamate and dopamine, but I don't know how or why its effect after consistent use would make you feel numb. Maybe someone else can figure that part out.

• Glutamate:
  This is a primary target for NAC.
  • Mechanism: NAC stimulates the cystine-glutamate antiporter (Sxc–). This process moves cysteine into the cell and releases glutamate into the extracellular space, which then stimulates inhibitory metabotropic glutamate receptors (like mGlu2) on presynaptic neurons.
    
    
  • Result: This action ultimately reduces the amount of glutamate released into the synapse, helping to normalize glutamatergic signaling and balance glutamate levels in conditions like neuropsychiatric disorders.

Elevated glutamate levels are observed in patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Long COVID, suggesting that this crucial brain neurotransmitter, which can become toxic at high levels, may play a role in post-exertional malaise (PEM) and other symptoms. Research indicates a link between these conditions and disrupted glutamate metabolism, with imbalances potentially contributing to the complex neurological symptoms experienced by affected individuals.

Dopamine is the gatekeeper.
Dopamine may still play a role in this scenario. Despite the recent focus on glutamate, the ‘dopamine hypothesis’ of schizophrenia is well established and compounds that raise dopamine levels (e.g. Ritalin and Adderall) are standard treatments for ADHD and have also shown some promise in relieving fatigue and concentration difficulties in ME/CFS (Blockmans et al, 2006). It appears that dopamine plays a key role in regulating glutamate neurotransmission. Dopamine acts as a sort of ‘gatekeeper’ of glutamatergic input, boosting strong glutamate signals while suppressing weaker ones (Horvitz, 2002).
N-Acetylcysteine (NAC) has been shown to influence dopamine levels in the brain, with studies indicating both increases and decreases depending on dosage and context. NAC can modulate dopamine release by affecting glutamatergic neurotransmission and glutathione levels, which are linked to dopamine regulation.

 

[alcasa]

If someone responds strongly to NAC, the chances are that the mechanism is glutamatergic. As Violeta already pointed out, NAC delivers cysteine to the brain very efficiently thanks to its N-acetyl group. This increases the exchange of cysteine with extracellular glutamate, reducing the synaptic glutamate pool while at the same time activating mGluRs outside the neurons.

Chronic NAC intake enhances glutamate uptake—especially when combined with aspirin or in cases where uptake has been downregulated, as many studies have shown. But I see that more as a long-term effect.

Have you ever tried NAG? Or any benzodiazepine? Or alcohol? If any of those help, then the chances are very high that my profile picture is the answer to the question.

 

[Gzephyr]

If someone responds strongly to NAC, the chances are that the mechanism is glutamatergic. As Violeta already pointed out, NAC delivers cysteine to the brain very efficiently thanks to its N-acetyl group. This increases the exchange of cysteine with extracellular glutamate, reducing the synaptic glutamate pool while at the same time activating mGluRs outside the neurons.

Chronic NAC intake enhances glutamate uptake—especially when combined with aspirin or in cases where uptake has been downregulated, as many studies have shown. But I see that more as a long-term effect.

Have you ever tried NAG? Or any benzodiazepine? Or alcohol? If any of those help, then the chances are very high that my profile picture is the answer to the question.

That could be why it’s helping but I was under the impression that the glutathione raising effect is what helps me so much. My body is definitely chronically inflamed from ebv and low on glutathione.

Never tried NAG but benzos don’t make me feel much better nor does alcohol. Alcohol makes me feel much worse, actually. I’ve also tried Phenibut but I can’t say it does much for my physical health.

 

[alcasa]

That could be why it’s helping but I was under the impression that the glutathione raising effect is what helps me so much. My body is definitely chronically inflamed from ebv and low on glutathione.

Never tried NAG but benzos don’t make me feel much better nor does alcohol. Alcohol makes me feel much worse, actually. I’ve also tried Phenibut but I can’t say it does much for my physical health.

If benzodiazepines don’t help at all, alcohol doesn’t make you feel better, and phenibut is useless, then glutamate may not be the mechanism. I'd give NAG a try anyway, since it has a similar mechanism—in that I think it increases the O-GlcNAcylation of glutamate receptors.


I only consider myself an expert in metabolism, glutamate and brain excitation, so I’m not sure how glutathione could be helping you beyond preventing ROS excess, limiting peroxidation, and assisting in the detoxification and in the handling of vitamins C and E.

Results should be consistent, if glutamate is a problem for you then the majority of interventions that oppose it should improve you. There could be a one-off or even two, but the incosistency points toward other places.

 

[Violeta]

I am awake at 3:45 AM and have been awake almost all night. I started think about glutamate, and was wondering what foods are high in glutamate. So I googled.

Other sources of glutamate are peas, nuts, grapes, eggs, milk, and certain seafood.
LOL, I had salmon for dinner and then ate grapes.
Eggs make my postherpetic neuralgia worse.
(In postherpetic neuralgia (PHN), glutamate, a major excitatory neurotransmitter, plays a significant role by increasing the excitability of neurons in the pain-transmitting spinal cord, especially through the activation of NMDA glutamate receptors. )

I have to reread this thread.

And what on earth am I going to eat.

 

[godlovesatrier]

NAC is and always will be one of my primary supplements. I take 1.2g twice a day.

In my most recent antibiotic relapse (which reactivated much of my long COVID symptoms?!) NAC was the main thing allowing me to function. It still lets me recover from the worst of PEM.

But considering the latest reach that isn't surprising at all. ME CFS bodies when they exercise cannot produce antioxidants properly nor energy and the whole mechanism for this in the body breaks down. If every 3 hours you give your body the antioxidants it's not making it has a massive impact on the disease. I suspect the effect might be much stronger in men owing to the fact that women suffer far worse cytokine levels in this diseases when exerting than men do (proven several times).

https://www.healthrising.org/blog/2...inds-me-cfs-systems-folding-under-the-stress/

If anyone isn't taking it and wants to try it you must start at a very low dose. I started on 25mg before bed back in 2022 and after about a month I could tolerate 500mg. The redox state in ME and LC cells is on a hair trigger and if your body isn't ready for it you'll reactivate a lot of viruses when you depress the ROS in these cells by taking the antioxidants. This causes much worse fatigue and general symptoms. But if you take it very slowly that won't happen and if you're lucky your body will gradually adapt.

You might also find l actyle glutathione by jarrow worth trying. It's much stronger than NAC and some people will tell you not to bother with it but I honestly find it to be another fantastic add on. Not only does it provide another energy boost but it's very good at giving mental energy and improving cognitive focus. Again split a tablet into four parts or less before attempting one tablet per day.

 

[Rufous McKinney]

NAC is and always will be one of my primary supplements.

I don't notice effects taking this. I"m tossing down 600 mgs a day...lately. I was probably taking none for a very long time.

Most of the time I take things and notice nothing. Then, I take a tiny bit of something and get really wiped out from it. Maddening.

 

[Gzephyr]

https://www.clinicaltrials.gov/study/NCT04542161

They’re recruiting if anyone is interested. I bet they’ll find that it helps many.

I think you’re pretty spot on with how it works for CFSers and why there are start up symptoms @godlovesatrier. I strongly believe the benefits I get are from the glutathione boost.

I forgot to mention that it gives me really bad PEM if I take too much at the start of another course.

 

[cfs since 1998]

I took NAC for about a year at 600-1200mg/day, no noticeable difference.

 

[godlovesatrier]

@Rufous McKinney I go through phases like that. Maybe it's possible your body just doesn't need that specific thing right now. I go through phases with things where the benefit is neglible. But in this flare NAC has been a godsend. Pre COVID too it was very reliable. Post COVID still useful but sometimes I need other stuff too.

I should say I take everything on an empty stomach now too and have for tbr last two years. Long COVID pharma (Martha) recommends that approach so I have continued work it.

 

[hapl808]

Chronic NAC intake enhances glutamate uptake—especially when combined with aspirin or in cases where uptake has been downregulated, as many studies have shown. But I see that more as a long-term effect.

Have you ever tried NAG? Or any benzodiazepine? Or alcohol? If any of those help, then the chances are very high that my profile picture is the answer to the question.

I find NAC helpful, but probably more for its effect on my breathing. Maybe helpful for brain fog, but hard to tell.

NAG doesn't seem to do anything for me. Benzos relax me temporarily and maybe improve muscle pain, but a very long 'hangover' period from just one 5mg Valium. Even 2.5mg will leave me even more burnt out than usual for a day or two.

Alcohol interestingly has one of the better impacts on my brain fog and headaches, but it is extremely short acting and then lowers my HRV and impacts my sleep. I probably have half a drink every month or two, but haven't figured out how to enjoy even a moderate level without the negative impacts.

All this seems like it should be diagnostic, but even with the help of AI, I've found no interventions that give any lasting real improvement.