Request for Inosine startup effects experiences

[godlovesatrier]

Hi all,

We've got several threads on inosine but it doesn't seem very clear whether it has early startup symptom flare like many (working) treatments do or not.

Inosine is an immune modulator for those that aren't aware. But it's very stimulating. Which is a potentially good/bad thing.

So with the Joshua Leisk protocol beta glucans are also used as an immune modulator of sorts. It works very well but the first few weeks on it are rough! Worsened mouth ulcers, sore throat, flu like symptoms etc. This passes after a few weeks.

The thing is I'd like to know if Inosine is the same. The first few weeks you feel worse and then after that you start to feel better.

My fatigues come back and I just feel dizzier and more rubbish. I have had my sore throat flare too but not had that issue today.

So hopefully those that are still taking Inosine can comment on the long-term effects. I've contacted Suzan Jackson to try and understand what the early weeks/months were like on it.

I still find it hard to scientifically understand why some stimulants simply make ME much worse. Although not from an energy deficit perspective.

Thanks in advance.

 

[Judee]

I tried it in the beginning of 2020, I believe. I was (and still am) using Oxymatrine and I also had read Sue's posts so I added inosine.

At first I was getting good results from it but then it quickly turned on me and was exacerbating my ME/CFS to probably the worst that it had ever been (at that point). My heart pain was increasing and I was getting what I call "heart tiredness" to the point that I was having dreams about it.

It was bad so I didn't continue on it so I'm sorry, I can't tell you if it would have gotten better.

They were talking about immunovir/isoprinosine on this page:
https://forums.phoenixrising.me/thr...cmafplus-com-in-hong-kong.79370/#post-2275989 (I know it's not exactly the same thing but the response might be similar on the Inosine.) ??

I think that's where I got some of the info on uric acid. MrMichaelFreedmen said something about, "a reported increase with il6 in relation to acute increased uric acid."

I did later find out that I have a gene rs1800795 GG that can predespose a person to making more IL-6 anyway.

Like I said, I know immunovir/isoprinosine is not the same as Inosine exactly but where you said you were not finding much data on Inosine, maybe that at least would give you a clue as to whether what you're going through now, is in line with what others have experienced.

Also, Webmd had some reviews for the medication (not the supplement) but they were from ME/CFS patients.

Just a thought. (shrug )

One more thing: It was interesting that ChooChoo noted in this THREAD that, "...IL-6 production has been a potential diagnostic marker for severe CFS for some time."

Hope you can figure this all out. I know you keep trying, @godlovesatrier.

 

[godlovesatrier]

Thank you Judee.

Are you able to tell me (and anyone else that replies) how long it was before you had to stop? This would help me a lot.

Funny how your still on oxy. Maybe it's simply more reliable and effective to take low doses of that than say taking immunvir/Inosine. I never even took a low dose of oxy I assumed it might make me worse. Although if I went down that route I think I'd have to get myself some equilibrant.

Anyway thanks for the reply. My hrv has gone way up but I did dabble with some high dose nicotanimide at the weekend. No Inosine on weekends.

Let me know how long it was before you stopped.

Thanks!

 

[Judee]

Honestly, I can't remember. I think I was on it about or less than a month maybe.

I was trying to do that rotation that Sue mentions and then I saw that Webmd comment and that person said she did a slightly different rotation (again iirc). So I may have switched to that for a while to see if it would get any better because I think my experiment was already starting to tank at that point.

The thing that is really helping me with HRV is that Swanson GHR. I have to take that or the Piping Rock version every night before bed or the next day I have high heart rates and crash badly. I bought the 2nd kind because it doesn't have the mucuna or the alpha-GPC. I think those two make my brain swelling worse but ironically, the Swanson's seems a little more potent for me. ???

With the niacinamide, I really do think it helps and I'm going to reserve it for days when I have to do more like leave the house but I don't think I can use it all the time because it seems to have a rebound effect where I crash more the next day.

Of course, that could be because I pushed more but I think, I've observed that rebound effect even on days where I didn't do more.

(It's nice taking it before bed though because it has the added benefit of making me very sleepy. Too bad like so many other things, it causes other issues. )

With the oxymatrine, I now only feel the effect if I miss taking it. i.e I feel worse but it isn't giving me the boost that it did at the beginning either.

I should either up the dose significantly one more time for a while or stop taking it altogether, but Hip said Dr Chia said if it ever worked for us we shouldn't stop it. Well, women that is...men can stop after a year or two. ??? So since it did once give me a boost, I don't want to stop using it.

I know,

Edit: Also I forgot to add that I think I find niacinamide works better when I take it with zinc. (I got that idea from this article: https://www.rosecottagedoc.co.uk/post/the-nad-deficiency-hypothesis where it's talking about NAD+ and zinc.)

 

[godlovesatrier]

Yeah a month is a reasonable time. So it turns out Sue did see amelioration of side effects and startup effects after either a few weeks or a few months, it's not that clear on her blog - I've messaged her directly to try to find out.

To be honest the last week or so I've had insomnia and I don't really ever get it this bad without having taken something, going to see how I get on this week. Going to take extra valerian tonight!

As for the oxy yep you probably need to increase the dosage. I beleve it's 6 months for men, but for women they have to stay on it. They also say it only works once. I suspect that if you give the body a 12 month break it might be possible to restart it again from scratch. You don't need to do this though as you're already on it, I think titration of the dose up to the recommended dose is prob your best bet.

The Inosine is likely boosting NK cell activity and that's why I feel worse:

From Sue's blog:

“We started with just 1 pill a day for 5 days (always take weekends off) and stuck with just 1-2 pills a day for the first few weeks. Note that you may have to start out very low with the dosing until you get used to it and you may see an increase in immune-related symptoms in the first weeks (if so, start even lower, with a 1/2 pill). You MUST keep changing the dose around to keep it effective - this is true for all immune modulators.”

https://me-pedia.org/wiki/Imunovir

https://www.tandfonline.com/doi/abs/10.1300/J092v11n02_06

"Chronic fatigue syndrome is associated with systemic and cognitive symptoms and with several immune abnormalities. The clinical impact of Isoprinosine(r) was evaluated in sixteen CFS patients, followed for 28 weeks in a single-blind, placebo controlled trial. Patients were also monitored for various immune parameters. Improvement based on clinical staging was observed in six of ten treated patients (60%). Clinically improved patients showed significantly enhanced natural killer (NK) cell activity, which correlated with the duration of Isoprinosine treatment (p >0.03). Treatment with Isoprinosine resulted in significantly increased numbers of CD4+ T helper cells (p >0.03). Treatment with Isoprinosine for 12 weeks did not appreciably influence the in vitro production of IFN-y, IL-1oc, IL-10 or IL-12. However, IL-12 was significantly increased at week 28 (p >0.02) in patients who improved after treatment with Isoprinosine. These results suggest that taking Isoprinosine may benefit a subgroup of patients with CFS, and this clinical improvement is associated with enhanced NK cell function and IL-12 levels. Further trials to evaluate the use of Isoprinosine in the treatment of CFS patients are warranted. "

That's probably as good as it's going to get I guess.

I think all the PR members who tried Inosine in 2010's may no longer be active. Spoken to heaps about his experiences but he primarily took famvir to get to a good place not Inosine.

 

[Shanti1]

I tried valacyclovir, Oxymatrine, and inosine all around the same time. I still take valacyclovir and oxy (8 months now) and could sense that they were helping me even though I initially had low-grade fever and increased fatigue with them. With Inosine, I started to get full-on flu symptoms, return of lymphadenopathy, and sore throat within 2 days and wasn't brave enough to take the gamble that it would pass and was a herx as opposed to just making me worse. I may try it again at some point.

 

[Violeta]

Has anyone tried working on inosine from the angle of increasing adenosine deaminase so that adenosine is changed to inosine?

 

[godlovesatrier]

One thing I've noitced is that within only a few days of taking 1g now down to 500mg my body temp has gone up a lot and so has my hrv. I think my immune system must have gone on the offensive. When I took oxy I never really had the increase in body temp. Taking oxy was more akin to taking valac aka valtrex.

Thanks for the replies.

 

[godlovesatrier]

So I reviewed my beta glucan diary from the first 60 days of the joshua leisk protocol and all the startup reactions to inosine are almost identical, I'd say they are possibly just a bit stronger as my sleep is much worse than it was initially on josh's protocol and I feel sicker and more disorientated/lethargic as the days go on. I think this actually bodes quite well.

I can only assume that the beta glucans stopped working or were not working nearly as well a few months ago, combined with infections just made me sicker.

Still interested to hear others experiences, but I am continuing at 500mg a day weekdays.

 

[Learner1]

My fatigues come back and I just feel dizzier and more rubbish. I have had my sore throat flare too but not had that issue today.

Worsened mouth ulcers, sore throat, flu like symptoms

Sounds like a flare of EBV or other herpesviruses.

in relation to acute increased uric acid."

This is a half get problem.

think those two make my brain swelling worse

Have you tried boswellia or LDN to reduce it?

With the niacinamide, I really do think it helps and I'm going to reserve it for days when I have to do more like leave the house but I don't think I can use it all the time because it seems to have a rebound effect where I crash more the next day

Have you tried NMN or NAD+?

I've had insomnia and I don't really ever get it this bad without having taken something, going to see how I get on this week

did you increase ammonia level inadvertently? Could you be short of citrulline or ornithine?

 

[godlovesatrier]

@Learner1 I can try benzoate and ALA for the insomnia tonight. If it's ammonia then those two shoulder lower it.

But I react this way to all immune modulators Inc beta glucans and antivirals Inc valtrex and oxymatrine. So personally I think it's more likely stimulation of the immune system keeping me awake. As my body temp is maybe a degree higher than normal.

Not sure about the citruline. I think I've got ornithine here somewhere.

Well Joshua used to say that you have to get a little worse before you'll get any better. I think the immune system has to aggrevate the herpes viruses to start killing them and it's on the attack more efficiently than usual. Combination of the two makes you feel like crap. Going to give it 3 weeks. As I normally see results within 15 days. If I don't overdo the dosing.

 

[godlovesatrier]

So I spoke to Suzan Jackson again and she confirmed that her sore throat and swollen glands were almost entirely eliminated on Inosine. I'd say it took her a few months to see really good improvements.

She says her PEM, fatigue and what not were vastly reduced by Inosine over the years and she's been on it 11 years. She worked up to 5 a day very gradually. She does not take it every day she has a dosing schedule in her blog for those that are interested.

She says she can now do 50 minute walks a few times a week. Funnily enough this is the exact same place I was at on beta glucans from June to October 2021. But she did say she can do a 3 and a half hour drive these days but needs a nap and food at the end. I mean I've done 3 and a half hours once I did crash but it only lasted 3 hours but this was in July. I think symptoms being what they are there's not a cat in hell's chance I could do that in the autumn or winter. Well I know I can't because my max at the moment is 30 minutes before getting crash like symptoms (driving) and 10 minutes is my max for walking.

Maybe famvir would assist over the autumn and winter.

Thanks for all the responses. Hopefully someone else will find this info useful.

 

[Violeta]

Has anyone tried working on inosine from the angle of increasing adenosine deaminase so that adenosine is changed to inosine?

It seems as though there must be something about ME/CFS that causes a adenosine deaminase deficiency.

The only reason I can find in literature is genetic.

Does anyone have a clue?

The only other thing I can think of is a zinc deficiency, because zinc activates it, which might be common in ME/CFS.

 

[SlamDancin]

@Violeta I’m going to be doing some research into this and I’ll let you know if I find a reason for my own high Adenosine levels (from 2015).

 

[Violeta]

@Violeta I’m going to be doing some research into this and I’ll let you know if I find a reason for my own high Adenosine levels (from 2015).

Oh thank you. What test measures that? Do they measure the inosine or any of the other things related to it?

Do you mind if I ask what type of diet you are on?

 

[SlamDancin]

@Violeta Its kind of hard to describe my diet. I don’t subscribe to any one school of thought but I do take a lot of advice on the subject from Dr Ray Peat.

The adenosine measurement came from a panel that measured Folate and it’s metabolites and Glutathione. I’ll dig it up and see if I’m forgetting anything but I’m sure there was no measurement of Inosine or other nucleosides. I was also low on Folate and it’s metabolites and Reduced Glutathione (GSH) and I had high oxidized Glutathione (GSSG).

Does anyone know the connection here?

 

[SlamDancin]

Here’s a decent article on Adenosine;

https://selfhacked.com/blog/adenosine-risks/

It discusses methylation and Inosine towards the bottom. Adenosine blocks methylation and is associated with high SAH levels, which is why it was included in the panel I took. My SAH was high and SAM-E was low. Also there is a connection between Adenosine and benzos that I would like to look into.

 

[Violeta]

@Violeta Its kind of hard to describe my diet. I don’t subscribe to any one school of thought but I do take a lot of advice on the subject from Dr Ray Peat.

The adenosine measurement came from a panel that measured Folate and it’s metabolites and Glutathione. I’ll dig it up and see if I’m forgetting anything but I’m sure there was no measurement of Inosine or other nucleosides. I was also low on Folate and it’s metabolites and Reduced Glutathione (GSH) and I had high oxidized Glutathione (GSSG).

Does anyone know the connection here?

A Ray Peat diet does explain it well enough, so not a lot of meat, which is what I was wondering.

 

[Violeta]

Here’s a decent article on Adenosine;

https://selfhacked.com/blog/adenosine-risks/

It discusses methylation and Inosine towards the bottom. Adenosine blocks methylation and is associated with high SAH levels, which is why it was included in the panel I took. My SAH was high and SAM-E was low. Also there is a connection between Adenosine and benzos that I would like to look into.

That is a very helpful article.

This is what I keep going back to..."ADA breaks down adenosine when the levels become excessive. It converts adenosine to inosine"

I was wondering what the feedback inhibitor was, and there it is...inosine.

ADA breaks down adenosine when the levels become excessive. It converts adenosine to inosine, which signals to the body to stop producing adenosine.

Adenosine kinase deficiency would also cause elevated adenosine.

Of course there may be other causes.

 

[SlamDancin]

Actually I eat quite a lot of meat. Ray Peat encourages a lot of protein in the diet while minimizing PUFA, amongst other things.