Request for Inosine startup effects experiences

Violeta

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

Inosine would be the turn off signal for production of adenosine.
So the body would have enough inosine (because of supplementing with it).

However, you would come up short on AMP, and since...
"As discussed previously, AMPs have been shown to participate in alerting, mobilizing and amplifying innate and adaptive immune responses of the host, and will confer protection against microbial infections. Decreased expression of AMPs can increase susceptibility to infectious diseases."

you would start to have disease symptoms.

I don't know what virus you are susceptible to, but I am susceptible to herpesviruses. Look at this.

"Adenosine monophosphate (AMP) is one of 3 forms of adenosine present in human cells. It has been used to treat shingles and nerve pain. It can be taken as a pill or powder or injected into muscle by a healthcare provider."

I am not saying one should take AMP, but that both adenosine deaminase and adenosine kinase are important to keep adenosine levels from getting too high and also providing inosine and adenosine monophosphate.
 

Violeta

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And then we have to get back to excess production of adenosine caused by stress, hypoxia being a big one.

Beneficial and detrimental role of adenosine signaling in diseases and therapy

https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC4839494/


Adenosine is a major signaling nucleoside that orchestrates cellular and tissue adaptation under energy depletion and ischemic/hypoxic conditions by activation of four G protein-coupled receptors (GPCR). The regulation and generation of extracellular adenosine in response to stress are critical in tissue protection. Both mouse and human studies reported that extracellular adenosine signaling plays a beneficial role during acute states. However, prolonged excess extracellular adenosine is detrimental and contributes to the development and progression of various chronic diseases. In recent years, substantial progress has been made to understand the role of adenosine signaling in different conditions and to clarify its significance during the course of disease progression in various organs. These efforts have and will identify potential therapeutic possibilities for protection of tissue injury at acute stage by upregulation of adenosine signaling or attenuation of chronic disease progression by downregulation of adenosine signaling. This review is to summarize current progress and the importance of adenosine signaling in different disease stages and its potential therapeutic effects.
 
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Marylib

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It doesn't agree with some people but you guys are trying to work out the reason - that's good. It never did anything for me one way or the other, but isoprinosine does. It got me out of bed once. It's hard to get or very expensive, unfortunately. At some point, someone on this forum developed a hack to turn inosine into isoprinosine.
 
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So I had to stop Inosine again. I took 30mg and it still made sleep difficult and then woke me up at 4am where I laid in a dozed but awake state for 2 hours.

Plus my sore throat and sinus type symptoms which are 100% like ebv came back only really when I took Inosine. Not straight away but generally in the evening.

Higher doses did allow me to do quite a lot but I was restless and sleep was really bad in the evenings.

Suzan Jackson swears by it but I do think some people can tolerate the stimulation and are still able to sleep. That was me in the first three years of the illness. But it's much harder now.

Hope you guys figure out the other side of things.

@Marylib hello. I think I remember this will have to see if I can find the thread. Interesting that you got on better with the drug. Maybe there are some big differences. With myself I've noticed any immune stimulation apart from beta glucans causes ebv to reactivate.
 
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https://forums.phoenixrising.me/threads/warning-about-inosine-plus-dmae.81113/#post-2293139

I believe this is the thread Marylib is referring to.

One thing Hip says here which I forgot is that Imunovir can make some people a lot worse. I personally think if your body had ebv and other viruses and maybe even enteroviruses in a good place and then you took Inosine and it allowed some of them to replicate. You'd 100% go backwards. That's my theory anyway.

All I know is I do feel worse at present and I'm not responding very well to Joshua protocol at getting me back to where I was. Tree pollen may be a confounding factor. Hormonally my t is lowish and my oestradol is below the low range which may well be making me ultimately worse.
 

Shanti1

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

Inosine would be the turn off signal for production of adenosine.
So the body would have enough inosine (because of supplementing with it).
@Violeta I love the Self-Hacked blogs and use them myself as a source of info, but when I checked the reference used for the statement that inosine signals the body to stop producing adenosine, I found the reference doesn't support the statement.

Here is the Self-Hacked post where the statement is made:
https://selfhacked.com/blog/adenosine-risks/

Here is the reference that is cited for the statement:
Adenosine Kinase: Exploitation for Therapeutic Gain
The paper mentions that inosine analogs can inhibit the ADK enzyme (which would increase adenosine). Nowhere does the paper discuss inosine inhibition of SAHH or 5'-Nuceotidase, or any other mechanism through which Inosine could lower adenosine.

Sadly, when I did an internet search for SAHH or 5'Nucleotidase inhibition by inosine, I also came up empty-handed. If you are able to find anything, please share it with us.

I was able to find that inosine inhibits ADA (ref), which would increase adenosine, but also that Inosine is an adenosine antagonist at some adenosine receptors and that it balances out adenosine activity (ref). So, my current thought is that inosine may increase adenosine, but it also balances its activity, which could be partially responsible for the mixed responses we have to it.




1647106129450.png
 

Shanti1

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I don't know what virus you are susceptible to, but I am susceptible to herpesviruses.
The herpes virus EBV is what I battle with. Thankfully, none of the others have shown up.

"Adenosine monophosphate (AMP) is one of 3 forms of adenosine present in human cells. It has been used to treat shingles and nerve pain. It can be taken as a pill or powder or injected into muscle by a healthcare provider."
Interesting. I found this older study:
The Treatment and Prevention of Neuralgia With Adenosine Monophosphate

I am not saying one should take AMP, but that both adenosine deaminase and adenosine kinase are important to keep adenosine levels from getting too high and also providing inosine and adenosine monophosphate.
Yes, this seems to be the case.
I wonder also about inhibiting 5'-Nucleotidase, but I haven't looked into what else that enzyme does yet.
 

SlamDancin

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@Shanti1 Read some about the adenosine-benzodiazepine connection last night. Benzos have long been known to inhibit the reuptake of Adenosine and adenosine receptors are responsible for some of the effects and side effects. Here's a 2020 study looking at Midazolam;

A Role for the Adenosine ADORA2B Receptor in Midazolam Induced Cognitive Dysfunction - PubMed (nih.gov)
Results: Midazolam treatment significantly downregulated Adora2b or Per2 mRNA in the hippocampus of C57BL/6J mice, and hippocampal PER2 protein expression or T-maze alternation was significantly reduced in Adora2b-/- mice. ADORA2B agonist BAY-60-6583 restored midazolam mediated reduction in spontaneous alternation in C57BL/6J mice. Analysis of hippocampal Tnf-α or Il-6 mRNA levels in Adora2b-/- mice did not reveal an inflammatory phenotype. However, C-fos, a critical component of hippocampus-dependent learning and memory, was significantly downregulated in the hippocampus of Adora2b-/- mice.
Conclusion: These results suggest a role of ADORA2B in midazolam induced cognitive dysfunction. Further, our data demonstrate that BAY-60-6583 treatment restores midazolam induced cognitive dysfunction, possibly via increases of Per2. Additional mechanistic studies hint towards C-FOS as another potential underlying mechanism of memory impairment in Adora2b-/- mice. These findings suggest the ADORA2B agonist as a potential therapy in patients with midazolam induced cognitive dysfunction.
 

Marylib

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https://forums.phoenixrising.me/threads/warning-about-inosine-plus-dmae.81113/#post-2293139



One thing Hip says here which I forgot is that Imunovir can make some people a lot worse. I personally think if your body had ebv and other viruses and maybe even enteroviruses in a good place and then you took Inosine and it allowed some of them to replicate. You'd 100% go backwards. That's my theory anyway.

All I know is I do feel worse at present and I'm not responding very well to Joshua protocol at getting me back to where I was. Tree pollen may be a confounding factor. Hormonally my t is lowish and my oestradol is below the low range which may well be making me ultimately worse.
@godlovesatrier
Yes, that's the thread. Immune-modulators are a double-edged sword. You never know where you will end up. Your theory makes sense to me. I hope you can climb out of this. Going backwards after feeling better is a horrible feeling.
 

Shanti1

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One thing Hip says here which I forgot is that Imunovir can make some people a lot worse. I personally think if your body had ebv and other viruses and maybe even enteroviruses in a good place and then you took Inosine and it allowed some of them to replicate. You'd 100% go backwards.
I have started and stopped Inosine twice now. Both times it felt like an EBV reactivation rather than the type of herx/immune recognition I had with valac and oxy. Hope you recover soon.
 

Violeta

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I was able to find that inosine inhibits ADA (ref)
Yes, the link supplied by selfhacked surely didn't have the information it was said to have had.

But the link you supplied, that inosine inhibits ADA, (which I'm trying to wrap my mind around, because ADA metabolizes adenosine to inosine) must be the negative feedback loop. So I suppose this would mean that a rise in inosine shuts off ADA and temporarily stops metabolism of adenosine. I wonder if this works on a gradient basis.

So if one takes inosine but needs ADA to breakdown adenosine, would that be putting the brakes on that process?

So while that process would not cause a rise in adenosine, it would stop the breakdown of adenosine, which is what we're going for if we have symptoms of excess adenosine, which would include fatigue, unrefreshing sleep.

Adenosine kinase is also part of the metabolism of the adenosine, but that's another story.

Although if adenosine kinase and adenosine deaminase are both not working up to par, that might leave a lot of adenosine hanging around making one sleepy all day long. And this could be caused by a zinc deficiency.
 

Shanti1

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So I suppose this would mean that a rise in inosine shuts off ADA and temporarily stops metabolism of adenosine. I wonder if this works on a gradient basis.
So while that process would not cause a rise in adenosine, it would stop the breakdown of adenosine, which is what we're going for if we have symptoms of excess adenosine, which would include fatigue, unrefreshing sleep.
Yes, it would happen on a gradient, the more inosine you have, the more inhibition. The body's way of saying, "hey, we already have a lot of inosine, don't need any more!"

Although inosine doesn't cause increased synthesis of adenosine, levels could build up as one of its breakdown pathways is blocked, leaving all the work to ADK.


1647125548082.png


I am finding that, while zinc is a cofactor for ADA, magnesium is the cofactor for adenosine kinase, so you would need enough of both minerals for optimal enzyme function.

https://www.uniprot.org/uniprot/P55263
https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC6123718/
 
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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.
I just started it today, and have been wired tired and wired tired today. Restlessness. I took 1/4 of the tablet, not 1/2. (so, I took 125 mg) I think if I took 1/2 it would be too intense. I did "a lot" of chores today, and my legs are killing me. I hope there isn't mean long term payback from this. I also msg'd Sue, and she couldn't remember what her 1st days were like...as it's been so long.

I was wondering if anyone else was trying it, and longer term responsiveness.
 
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Based on my experience with Famvir and Valtrex I'd say it's working but possibly not in the most ideal way. Famvir got me quite a bit better, but 9 days of valtrex seemed to put the ebv genie back in the bottle. Sadly my kidneys become very inflamed on the valtrex, doesn't effect kidney function but I get stones and other things, it's not very pleasant.

Anyway I guess my point is, if you are feeling worse but having more energy then that might confer an antiviral effect is occuring through immune modulation. In which case antivirals could have a good effect.
 
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Anyway I guess my point is, if you are feeling worse but having more energy then that might confer an antiviral effect is occuring through immune modulation. In which case antivirals could have a good effect.
Bad PEM today. Wasn't able to fall asleep til after 2, really resteless and alert like you'd mentioned. I'm not sure I want to mess around with inosine again. I didn't take any today - my legs are pretty shot from the big amp up yesterday. Hard for me to read stuff like Sue Jackson doing so well on it, walking, driving, etc. and continuing to feel so hopeless for myself. I follow her on Twitter and see how comparatively very high functioning she is.
 
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Yeah it's bizzare how some severe patients can do well on things and then other patients who are milder take it and have no reaction, but the two do appear to be the same subset.

Well I think Sue has her viral load under control and that's vital in this disease but can often be elusive. Also she's had covid recently and has not been the same since, she crashes constantly, whereas normally she does not. Also she's taking valtrex to try and get back to her former baseline, but really struggling.

I'm not that different myself these days, on the valtrex/famvir I am able to do all sorts. But prior to this I wouldn't say anything's really worked. Apart from the Josh Leisk protocol that's in my signature.

It's frustrating I know but I've tried all sorts, I just don't think anything's been potent enough for viral replication. That's the conclusion I've come to anyway.
 

ChrisD

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Forgive my ignorance but are we talking about the supplement Inosine as opposed to Pranobex?

I have Just started a small amount of Inosine after one month of Oxymatrine (along side) to try to enhance the small but good effects I've been having from Oxy, but also to mitigate for a few side effects like muscle aches
 

godlovesatrier

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We are yes.

Also your approach is a good one. Dr chia recommends that approach if patients can tolerate oxy and Inosine together. As it coaxes the entereoviruses out so they are more easily killed off.

Good luck.
 

ChrisD

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We are yes.

Also your approach is a good one. Dr chia recommends that approach if patients can tolerate oxy and Inosine together. As it coaxes the entereoviruses out so they are more easily killed off.

Good luck.
Thank you. For 3 days of taking a quarter of a capsule, I felt a bit better - daytime energy and respiration etc. But on day 4 I got immense upper right arm ache and shoulder pain.

I think this may be to do with increased Uric acid levels as I have also been doing a niacin protocol for a while which is know to increase Uric. So I may have to stop that.

I also have Taxi folin to try alongside Oxy soon.