"Exercise Tests Suggest Autoimmunity..." Cort Johnson

[echobravo]

From my understanding, IVIG mostly contains IgG, with only small amount of the other immunoglobulins. Have you had your IgG subclasses tested? If they are low, then IVIG may help.

Thanks! The concept of "IgG subclasses" is new to me, and was not mentioned by my "state assigned" doctor either, will look into it.

 

[Demepivo]

Mestinon is a prescription acetylcolinesterase inhibitor (not a beta blocker). Huperzine A is an OTC version that is freely available and probably just as effective.

For anybody interested in researching Huperzine A. Examine have a page looking at various studies.

https://examine.com/supplements/huperzine-a/

Examine is usually more reliable and objective than say Selfhacked....

Huperzine-A is a compound extracted from the herbs of the Huperziceae family. It is known as an acetylcholinesterase inhibitor, which means that it stops an enzyme from breaking down acetylcholine which results in increases in acetylcholine.

Acetylcholine is known as the learning neurotransmitter, and is involved in muscle contraction as well. Increasing levels of acetylcholine is routinely used as a technique amongst weight-lifters and scholars.

Huperzine-A appears to be a relatively safe compound from animal studies of toxicity and studies in humans showing no side-effects at dosages routinely supplemented with. Huperzine-A is in preliminary trials for usage in fighting Alzheimer's Disease as well.

Hope this helps

 

[Gingergrrl]

[I lurk these days but still enjoy reading the forum on and off, and seeing you all in action!]

@Sasha, it's good to see you and to know that you are still around even if just lurking these days!

Has anyone actually tried the drug mestonin here?

I tried it in 2014 (1/8th of a Mestinon pill) and had a horrible reaction and my doctor told me never to take it again.

I am sure you can confidently answer this question yourself, having like me read the rituximab discussions on this forum for many years.

I wish I could confidently answer the question but I honestly have no idea if my improvements will last after I am done with IVIG and Rituximab. I have read the forum and talked to many people but many have different symptoms, diagnoses, and treatment protocols than I do, so it is very hard to compare and come to any conclusion beyond faith and guessing!

I am a bit confused by the story here and have not looked in detail but antibodies to acetyl choline would not really do anything and probably do not exist. There are antibodies to acetyl choline receptors in myasthenia.

I thought it was proven that there are autoantibodies to the acetylcholine receptors? I thought the anti-nicotinic ones are what are found in myasthenia gravis, and some cases of LEMS, and the anti-muscarinic are what are currently being tested by Cell Trend. Even if there is no cure to these illnesses yet, I thought the existence of the autoantibodies were proven? Is this incorrect?

 

[Jonathan Edwards]

I thought it was proven that there are autoantibodies to the acetylcholine receptors? I thought the anti-nicotinic ones are what are found in myasthenia gravis, and some cases of LEMS, and the anti-muscarinic are what are currently being tested by Cell Trend. Even if there is no cure to these illnesses yet, I thought the existence of the autoantibodies were proven? Is this incorrect?

You have misread what i put GG. I said there is no evidence for antibodies to ACh itself as far as I know. The antibodies are to receptors. The anti-nicotinic ones are cast iron. The anti-muscarinic ones make Prof Vincent pull a face and raise her eyebrows, and when Angela raises her eyebrows there is usually a good reason. They certainly do not seem to be much more common in ME than normal.

 

[Gingergrrl]

You have misread what i put GG. I said there is no evidence for antibodies to ACh itself as far as I know. The antibodies are to receptors.

I apologize and for some reason, I struggle to grasp/remember that the autoantibodies are not to acetylcholine vs. to the receptors. I think I have got it now .

The anti-nicotinic ones are cast iron.

That's what I thought, thanks for confirming.

The anti-muscarinic ones make Prof Vincent pull a face and raise her eyebrows, and when Angela raises her eyebrows there is usually a good reason.

You have no idea how badly I would love to talk to Prof Vincent re: these autoantibodies (and this topic in general) but my attempts at contacting her have not been successful. Do you know if she feels that anti-muscarinic autoantibodies do not exist or just that there is not yet a valid measurement tool?

They certainly do not seem to be much more common in ME than normal.

I actually have no opinion on this and only know that I test positive for the autoantibodies on two tests but remain unclear if ME will ultimately be my diagnosis.

 

[adreno]

Antibodies towards AChRs is hardly news. Neither is treating POTS with Mestinon. I suspect only a few will benefit from this, and many will find the high levels of ACh intolerable. Many probably need more vasoconstriction, not less, such as can be achieved through alpha-1 adrenoceptor agonism. Remember that antibodies towards adrenoceptors have also been found in POTS/OI.

 

[jimmy86]

Antibodies towards AChRs is hardly news. Neither is treating POTS with Mestinon. I suspect only a few will benefit from this, and many will find the high levels of ACh intolerable. Many probably need more vasoconstriction, not less, such as can be achieved through alpha-1 adrenoceptor agonism. Remember that antibodies towards adrenoceptors have also been found in POTS/OI.

Yes, there was a thread on Mestinon, which I tried myself for POTS/ME with only very mild effects.

http://forums.phoenixrising.me/index.php?threads/mestinon.21483/

Definitely not a magic treatment.

 

[AdamS]

While not completely new, I find this hypothesis and the way Cort explains it really interesting. For me, the first warning signs I started to get at the gym (a few weeks before my decline into ME) were breathlessness, tachycardia and lightheadedness...It was like my heart & lungs were playing serious catch up, even after exercises I could easily tolerate normally.

I know that has been research into dysregulation of aceytlcholine and adrenergic signalling in the past with some evidence of autoantibodies.

I'm not going to speculate about that research, but for anyone interested, i've tried the following treatments with guidance from my POTS consultant:

Treatment one: Midodrine 2.5mg x 3 per day (Alpha Agonist, vasopressor).
My Anecdotal Experience: Seemed to help with OI in the beginning. Made headaches worse. Had bad reaction at 5mg. Overall, found very little benefit and stopped taking it.

Treatment two: Ivabradine (Lowers heart rate through different mechanism than beta blockers).
My Anecdotal Experience: Definitely lowered heart rate and made it feel very stable but made me feel very tired/lethargic so I stopped taking it.

Treatment three: Propranolol 10-20mg (beta blocker). I read here that low doses can help POTS. Alan Light also suggested that it may help in low doses.
My Anecdotal Experience: I definitely noticed that I felt less out of breath when walking/doing mild exercise on propranolol in the beginning, but it didn't seem to help me significantly enough to justify continuing it. The impact really was minimal.

*I've also tried Ivabradine/Midodrine in combination as well as Propranolol/Midodrine and neither helped me much.

So the puzzle for me still goes on, I have to say that Cort's article made a lot of sense to me, I hope we find some answers soon. Fluge & Mella's mention of Arginine a while back and the anecdotal reports about the benefits of NO2 Black/Isordil on here do make me think that for some of us, there is a problem with vasodilation/constriction.

 

[Diwi9]

So the puzzle for me still goes on, I have to say that Cort's article made a lot of sense to me, I hope we find some answers soon. Fluge & Mella's mention of Arginine a while back and the anecdotal reports about the benefits of NO2 Black/Isordil on here do make me think that for some of us, there is a problem with vasodilation/constriction.

I think we've had an exchange about vasodilators and vasoconstrictors in the past, as alcohol and arginine improves both of us. Maybe we're candidates for Mestinon??? I do better on beta-blockers too.

It seems that if we are going to get anywhere with research, sub-typing is a must. We need more large studies to accomplish this; the NIH Intra-mural study is already de facto sub-typing through its strict criteria for participation.

 

[Jesse2233]

Curious about mestinon as well. The autoimmune implications are fascinating

 

[Learner1]

@AdamS @Diwi9 You might take a look at citrulline instead of arginine. My doctor has me on 3g a day. I take it just before going to the gym to lift weights, along with a few other things.

Here's an article I found describing why you'd want to use it, with references at the end:

http://www.jimstoppani.com/home/articles/citrulline-vs-arginine

 

[Forbin]

I don't know if it is relevant, but, in 1975, there was an outbreak of cases resembling ME/CFS at Mercy San Juan Hospital in Carmichael, California, a suburb of Sacramento. These cases, however, were distinguished by severe vascular involvement, leading investigator Erich D. Ryll, M.D. to term the illness "Infectious Venulitis."

The CDC investigated and documented 45 cases. The largest percentage of cases by occupation were among ICU nurses. Four cases were non-hospital contacts of employees. One case was an ICU patient. Additional cases were reported later.

Below is a link to Dr. Ryll's 30-year-follow-up report on this outbreak:

http://iacfsme.org/portals/0/pdf/Summer2011-Ryll-30YearReview-2-46.pdf

 

[bertiedog]

Many probably need more vasoconstriction, not less

I am definitely one of those, Sumatriptan being the only thing that will work on the severe migraines I get (its a strong vasoconstrictor). I have had POTS for nearly 15 years now and benefit from low dose Propananol but it doesn't stop the problem of too much vasodilation.

Many times I have run into trouble when trying different herbs which always end up to be vasodilators when I start searching to see why I am having such issues.

Pam

 

[bertiedog]

I read here that low doses can help POTS. Alan Light also suggested that it may help in low doses.

I take 10 mg Propananol twice a day and have been on this med for 20 years without any ill effects. It always makes me feel a bit better.

Pam

 

[adreno]

There are at least two different types of POTS, low-flow and high-flow. The low-flow type likely involves low NO and vasoconstriction, while high-flow type involves high NO and vasodilation. I seem to be mostly the high-flow type.

IME, beta blockers and angiotensin II inhibitors improves tachycardia, but worsens standing tolerance, likely by causing too much venal dilation. OTOH, adrenergic agonists worsens tachycardia, but improves standing tolerance.

It seems to me that things are vastly more complex than just adding more ACh or NE. If both ACh and NE receptors are disturbed/malfunctioning, blood flow regulation is generally screwed. Perhaps we need simultaneous venal constriction and arterial dilation? I don't know, but shotgun approaches (i.e. mestinon, etc) are unlikely to work.

I think it will be more productive to focus on the problems upstream, and figure out why the immune cells are pumping out antibodies. Removing, or reducing the source of this is likely to be the only really effective treatment IMO.

 

[user9876]

I thought that there was an interesting story here which was clouded by discussions of anti-bodies. David Systrom seems to be able to monitoring blood flow during exercise and then see if it is normal or if it changes in different patterns with one suggesting a failure to pump blood or a failure to take up blood. What I didn't get from the article is a sense of how much this has been tested on patients but he seems to have funding to look further into this.

He may have various theories about why but to me it looks like the really interesting thing will be the simple observations that he can make. It feels like that could tell us something really important about mechanism (but not cause).

Its important not to mix up interesting observations and tests with theories about why.

 

[voner]

I took Mestinon for years back in the late 90s and early 2000's.I kept using it because it's seemed to dampen down the "postexertional malaise" which in those days I didn't know existed and I just called "the kickback the days after". my symptoms pretty much match the symptoms that Cort describes in his blog.... ME/CFS/FM with autonomic dysfunction, POTS, IBS and some severe myofascial pain and allodynia. My memory is pretty horrendous, so I really can't give any other details unless I could find some old notes. I do remember it did not dampen down any other symptoms (i.e. pain, flue like feeling,etc), it just seem to affect PEM.

for me, it accelerated the parasympathetic system and thus I would immediately have my nose start watering and it causesd some very significant speeding up of gut motility and also caused significant gut/stomach issues. I happened to be taking methadone during the same time and so the two seemed to counteract each other as far as gut motility..

in the past five years I've tried going back on Mestinon a couple times without using Methadone along side and it's been pretty disastrous because of the severe side effects like the gut motility, diarrhea, cramping etc.

for anyone that's actually considering trying this pharmaceutical, I recommend you also consider trying the time release version of it which is actually less expensive and it was easier for me to tolerate.

 

[Stretched]

Has this been discussed? I'm blown away with this turn of events.

https://www.healthrising.org/blog/2...ts-chronic-fatigue-fibromyalgia-autoimmunity/

It seems to me that an argument can be made for stress being a CFS causative factor coincidental to Systrom’s findings of blood vessel and endothelial constriction, as stress is a known systemic constrictor. Further reasoning might lead that there is a limit or threshold where stress enters the picture as the causitive factor which continues the described process even after the originating stress is removed, but further constriction progresses when stress returns, causing vacillations in severity… .

Further, when ‘uber-stress’ re enters the PWC’s lifestyle the result is PEM. IOW, it's at this point I suppose Sysrom can record excessive alterations in his Pulmonary measurements, i.e. greater constrictions.

 

[alex3619]

I am wondering if blood thinners can be helpfull, anybody use this drug?

Its been tried, including formal testing I think in the 90s. This class of drugs is one of the worst you can give me, it triggers whole body neuropathy in me.

 

[Research 1st]

Lets see what Dr David Kem comes up with in the next year or so.
He's helping create a decoy drug to block the antibodies to receptors found in POTS.
Either it will work or it won't.