NO/ONOO Theory and Treatment


Senior Member
When I first read about Martin Paul’s theory, I kinda figured it was bullshit and I still think for the majority of CFS patients that it likely is or at least one I don’t subscribe too.

However, given my experiences this last year, and lack of other demonstrable causes, I think it could apply to me. Still chasing down many other options but nothing has shown up yet as a viable alternative cause.

The last two and a half months or so Ive been targeting neuroinflammation and glutamate excess along with methylation and oxidative stress/redox imbalances and have made surprising headway.

It’s yet to be seen if this continues once I d/c what I’m doing but right now I’d say I went from severe/moderate to mild in about 10 weeks.

Pharmalogically Ive used primarily lamotrigine and selegiline/rasagiline - also played with memantine, nitrous oxide, ketamine, and LSD - but these two/three have been the best so far.

The other portion has been IV infusions which Ive detailed in another thread but consist of
• 10-15g vitamin c
• 5-10g glutathione
• 3,000mg SAM-e
• 1,000mg phosphatidylcholine
• 500-1,000mg NAD+
• Multivitamin and multimineral mixes

• on the first one I added 10ml DMSO for anti inflammatory effects and this last one I added the SAM-e which I’ll continue

I’m planning to continue the infusions for at least 12 weeks and also add HBOT.

I’m trying to think of anything else I could add to the infusions to support neutralization of peroxynitrate and further stabilization of redox balances so does anyone else have anything they would add in a perfect world?

Water soluble components are best but I am going to try some fat soluble emulsions as well soon.

I’m considering:
BH4 (this is probably highest on the list
Uric acid?

Also considering some others like resveratrol and curcumin but need to work on my compounding first.

Additional thoughts helpful since I’m guinea pigging myself right now haha.


nucleus caudatus et al
Ik waak up
I came across some inhibitory influence, which act against NO, not sure about the first one though, and need to look it up anew, in some future.

  • Citrate
  • Acetate (in vinegar)
  • Vit C
  • Vit B12
I take them not together, instead it plainly seems, that they act at different sides in the brain preferably, and I want/need to structure the alteration which they induce. Low amounts, on top of manganese restriction.

Other main groups are: B5 - (B7) - B1 - B2
Cl (with hydrogencarbonate), K,
Mg + Vit D, as well in sips in conjunction with some black tea (luckily! containing some Mn)
Se - Zinc (both in normal amounts, retarding supps) - other metals in chocolate

So it partly matches with your experience. Thanks for sharing!


Senior Member
Keep in mind that a theory can be completely wrong, but still match a few observations in reality. If the theory says that NO inhibitors should reduce symptoms, an NO inhibitor might reduce your symptoms ... by some other effect of that treatment that doesn't involve NO. I expect that most chemicals will have multiple potential effects on an organism. Apply the scientific principle by predicting what effect a treatment will have based on the theory, and then testing it. However, this is where observer bias sneaks in, and people look for the results they want to see and ignore any results that contradict it.

Experiment away! :)
Most of the times, I am in read-only mode but as a parent of a child with autism, I have looked into this a bit. I see a lot of similarities between autism and ME/CFS. I hope it is OK to post.

I am just wondering if anyone looked into,

- While most of this cycle takes place extramitochondrial region, superoxides do affect mitochondrial energy production. I am curious if anyone looked into optimizing mitochondrial function by using Levocarnitine, Co-Q10 and other mito supplements. Table 3 of lists all supplements needed.

- ONOO is a potent activator of NK-kB. Do folks try out steroids to see if it helps them? Prednisone blocks NF-kB activity. This is, of course, a short term solution, just to check if you fit into this theory.

- Bupropion (immediate release) has TNFa blocking activity. Has anyone tried using it? (While other pro-inflammatory cytokines are also involved, I don't know contribution of each to the overall effect. I focused on TNFa because of its involvement in many other disorders is proven.)

- There is increased intracellular Ca. Is there any thought of using Ca-channel blockers to limit intracellular Ca?
This comes from type II diabetes treatment options. Plasma membrane calcium-ATPase get inactivated in type II diabetes as well as a result of increased oxidative stress. Hypertension is common in type II diabetic patients. *dipine types of Ca channel blockers seems to be a preferred treatment.

- BH4 is a great idea but Kuvan costs a small fortune, even if you can pay for it. AFAIK, it is not easy to acquire.

I could be totally off the sensible path. Oxidative stress and Mito dysfunction is extremely common in autism. So I am always on a lookout for a novel idea for addressing it. If my understanding is correct, the crux of addressing NO/ONOO is to quench progression of the Fenton reaction triggered by ONOO.


Senior Member
I see a lot of similarities between autism and ME/CFS
I've seen this too, autism and bipolar disorder have come up multiple times in my research.

I don't know much about autism, and haven't done much research on the nitric oxide or peroxynitrite aspects of oxidative stress. But I think it's important to note that excessive free radicals, oxidative stress, and mitochondria dysfunction can be tied to autoimmune conditions.

You're probably already aware of this, but there seems to be increasing evidence for Autism as a potential autoimmune disease.

Autism – A Potential Autoimmune Disease: Neurodegeneration-Induced Autoantibodies against Neural Proteins

I believe oxidative stress, etc are related more towards the production of auto-antibodies, whereas mito dysfunction can be the result of auto-antibodies.


Senior Member
@deltaforce I have heard some people improving with bupropion, (someone Here I think had a huge improvement for 2 weeks and then relapsed again) I tried it and I felt better right away but it gave me pretty bad tinnitus instantly so I only lasted 2 days on it and it took 3 months for the tinnitus to reduce. Ritalin is also helpful but I can’t seem to take it more than once a month for a couple of days in a row I wish I understood why it stops working so fast, all I can think is that it tips the balance the other way.


Senior Member
The more I've read, I think the NO/ONOO hypothesis is a piece of many CFS/ME cases but that its an effect, not a cause. If it were a cause, it wouldn't be impossible to reverse the cycle and there would have been successful cases of treatment by now of which I haven't seen.

The doc I've been seeing (Dr Kaiser) has actually been very knowledgable and to his point, CFS/ME is a big bus and everyone got on it in different ways. Cellular dysfunction is a root effect though it almost all patients. Just have to find your cause, and treat that if possible, while addressing cellular dysfunction in tandem.