Request for Inosine startup effects experiences

Violeta

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Actually I eat quite a lot of meat. Ray Peat encourages a lot of protein in the diet while minimizing PUFA, amongst other things.
I guess I was going by the recommendations of people who run Ray Peat forums where they seem to mostly recommend a very high carbohydrate diet with a lot of milk and orange juice. I know that he ate more meat than is being reported now.

Did you see that meat is an important source of adenosine? I'm not saying one should avoid meat. I would think the problem is not metabolizing the adenosine into inosine and the other things that it gets converted into.
 

halcyon

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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 can't comment on long-term effects as I had to stop taking it, but the initial start up effects were malaise, low-grade fever, sore throat/tonsillitis, and headache for me (starting at 100mg and increasing to 500mg over 2 weeks). The sore throat went away after about a week and a half. I took it for about 3 months, but combined with other immune modulators I was on at the time, it seemed to cause too much inflammation.
 

godlovesatrier

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That's really interesting @halcyon because I think it causes too much inflammation as well.

Are you able to describe what inflamation symptoms you had? For me it's mainly my neck which seems to be getting very stiff and hasn't been like that in a very long time indeed, about 10 months. It only got bad after taking inosine, I say bad it's mild and only comes on in the afternoon but that's enough to make me wary as it was a symptom I had gotten rid of.

One thing I will say is it's given me a nice energy boost even at the lower doses (100mg) and it's fixed my absolutely dead sex drive. But I am sure the sex drive being dead is a product of taking reishi every day.

Thanks for the info,
 

godlovesatrier

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Interesting, everyone's definition is different, thanks for the extra info.

I've gone off the Inosine for now, my sleep is just totally trashed, however maybe not surprising considering I can normally sleep ok. So maybe the inosine just brought a healthy nk response to a much higher level, which meant a real lack of sleep ensued.

Also my sore throats just got a lot worse, could be allergies but I think it's just ME.
 

Shanti1

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The Inosine is likely boosting NK cell activity and that's why I feel worse
In Dec I tested my NK function and it was a 2 (range 7-125 Lu30), so my NK cells are definitely snoozing at the wheel.

After my post last week saying I had discontinued the Inosine due to flu symptoms, I decided to try it again. Today is day 5 of 500mg tid and I am tolerating it much better than the first time around. I think this is because I've been on Oxy and Valac for 8 months now and my viral load is probably much lower than the first time I tried it.

I am having intermittent low-grade fever, slight lymphadenopathy that was worse the first day and now almost gone, slight sore throat. I'm not sure yet if the Inosine is helping or not. I can feel some of the "heart tiredness mentioned by @Judee. Sometimes I feel that the inosine is making me more fatigued and other times it seems to help with cognition. I can't take it too close to bed or it will keep me up. This is probably related to its ability to inhibit adenosine production.

Anyhow, I am sticking with it for now and will report back.

ADA breaks down adenosine when the levels become excessive. It converts adenosine to inosine, ADA breaks down adenosine when the levels become excessive. It converts adenosine to inosine, which signals to the body to stop producing adenosine.
@Violeta Thanks for bringing up adenosine and its relationship to inosine. High adenosine sure fits the signature of a lot of ME symptoms like fatigue, sleepiness, immune dysfunction, and increased BBB permeabiity. It does seem worth investigating.

I couldn't find much on adenosine in ME/CFS, but I did find this:

A map of metabolic phenotypes in patients with myalgic encephalomyelitis/chronic fatigue syndrome
This study looked at 3 metabolic phenotypes in 83 people with ME/CFS (MEall, ME1, ME2, ME3) and 35 healthy controls (HC). The study mentions adenosine being increased in pwME. When I pulled the sublemental data for the study, I found this showing an almost 5 fold increase in adenosine pwME.

1646875153575.png


This link (related to the Self Hacked link already posted) has additional suggestions on how to increase Adenosine Deaminase activity: https://selfhack.com/blog/about-adenosine-and-the-adenosine-deaminase-gene-rs73598374/

Great link @SlamDancin Could you let us know the name of the lab you used to test adensosine? Are you in the US? I would like to test mine and the two major labs here, Labcorp and Quest do not offer it. I also checked a couple of functional labs and didn't see it offered
 

Violeta

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Shanti, thank you. And I'm really tired but I just want to quick add before I forget that the selfhacked article says that caffeine helps because it is a phosphodiesterase inhibitor, and I have a paper that says that boron is a PDE inhibitor, too. I have to think about that.
 

Shanti1

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selfhacked article says that caffeine helps because it is a phosphodiesterase inhibitor
Yes, I LOVE caffeine, lol. Not only is it a phosphdiesterase inhibitor, but it directly blocks adenosine from binding to adenosine receptors in the brain, keeping us awake. Hope you feel better soon @Violeta :heart:
 

Violeta

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Thank you, @Shanti!

I have been allowing myself some caffeine, and it is very helpful if I get the amount just right. So I make my coffee with mostly decaf and a little regular, and try not to drink it too late in the day. It's like a desert!

I forget who has high SAH and low SAM-e, but boron also is important for SAM-e. Coffee is actually listed as a source of boron, but sounds like you have to drink a lot to get a decent amount. "Boron is found in leafy greens like spinach and kale, but the most common sources are apples, coffee, potatoes, milk, and beans. Coffee and milk actually don’t have that high of boron content, but we consume enough of them to drive them into the top five sources for boosting boron levels."

"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."

"Adenosine kinase (ADK) is the key enzyme regulating the intracellular and extracellular metabolism of adenosine by phosphorylation of adenosine to adenosine 5'-monophosphate (AMP)."


Adenosine kinase is activated by zinc, too.

This information gives me a lot of hope that I can turn things around. But we'll see.
 
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Tried 30mg Inosine today, still very stimulating. But maybe not enough to stop me sleeping? Wonder what it is in Inosine that's so potent for insomnia to be induced.

I slept great last night, only got woke up once, valerian and melatonin worked and kicked in after 30 minutes like they normall do.

But with equilibrant and/or inosine it seems that isn't the case.

Also I spoke to Prusty briefly last night about my immune modulator induced neutropenia, all he could think of was lupus - just a thought but maybe my terrible back pain and that are related.

Anyway back on topic I'll update about Inosine again if I keep taking it. Neck stiffness seems to have got a lot better since I stopped the 100mg Inosine dose.

Within a week I noticed at 200mg that I had lots more energy and was enjoying things because of it - moods been a bit flat the last 6 months. Also didn't crash (that I can remember) in social situations, only crashed doing physical activity, that was at the higher dose of 500mg Inosine. But it totally fucks my sleep over at that dose - pardon my french!
 
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Agreed could well be. Plus metabolic changes would be fast. Within 10 minutes of taking it I can feel the changes.

I might just take low doses and try larger doses as a PEM buffer on busy days. Not sure if that will actually work but it's worth a little experiment I think.

I just hope it doesn't make the neutropenia worse. That would be bad!
 

Shanti1

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Ask and you shall receive!
Thank you! Interesting lab, I hadn't heard of them before.

I have been allowing myself some caffeine, and it is very helpful if I get the amount just right.
I know what you mean, too much will push me to a bad place. Plus, one can build up some tolerance to it. I usually use green tea and pick a couple of days out of the week to have a little coffee when I need an extra boost.

@godlovesatrier
Thought I would give an update that yesterday I woke up with a marked "tired heart" feeling, heavy limbs, and sore throat and decided to stop the Inosine. I just can't tell if I would really come out ahead if I try to push through this one. Since I have been feeling relatively better the last couple of months, I decided it wasn't worth the risk. It is now late in the day here and I am feeling better since stopping.
 

SlamDancin

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@Shanti1 Youre welcome! You are way more knowledgeable than me so I’m extra glad to share info with you if I can. Do you think you can deduce more about the connection between methylation and adenosine? I purchased some Zinc but I’d like to know more about how to lower adenosine levels further.
 

Shanti1

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@SlamDancin I definitely feel that it is the collective knowledge of all of us together that helps to untangle the ME/CFS web.

Here is an image of how adenosine is tied in with the methylation pathway.

SAMe is the master methyldonor in the body. The methylated B vitamines (methylfolate and methylcobalamin) are there to help generate SAMe. SAMe is found in every cell in the body. It donates methygroups to actuate the thousands of pathways that rely on methylation. It also methylates DNA to turn genes on and off.

After SAMe donates a methyl group it becomes SAH. SAH (S-Adenosyl Homocysteine) is broken down into Adenosine and Homocysteine by the SAHH enzyme.

If Adenosine builds up in the body, it causes SAH to build up. SAH directly inhibits the Methyltransferase enzymes which convert SAMe to SAH when a methygroup is dontated to help with mportant body process.

Effectively, high adenosine slows down methylation reactions in the body by inhibiting methylation by SAMe.


1647044562949.png
 
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SlamDancin

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Sorry if this should be clear from the diagram but I’m wondering if the relationship goes both ways between SAH and Adenosine. Would Folate/B12 lower adenosine by lowering SAH? Do they even lower SAH? Does anything about this seem treatable to you?
 

Shanti1

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Good questions. Yes, adenosine could join back with homocysteine and turn back into SAH, but SAH can not turn back into SAMe, so ultimately, SAH needs to break into homocysteine and adenosine to metabolize through the pathway.

Supporting the movement of the Methylation cycle through the use of methylfolate/B12 can lower SAH by helping it metabolize to homocysteine and adenosine (SAH is made of adenosine and homocysteine linked and it gets split by the SAHH enzyme).

I don't see how Methylfolate/B12 would lower adenosine. However, increasing methylation pathways in those who are deficient can help with serotonin, dopamine, epinephrine, and norepinephrine production, which can help with alertness and mood (this is likely why SAMe works for depression).

As far as ways to lower adenosine. After looking at the literature, I think Inosine balances out the action of adenosine more than inhibiting its production. In fact, Inosine inhibits the Adenosine Deaminase Enzyme, so taking too much of it, while balancing the action of adenosine, could also increase adenosine (ref). Maybe that is why those of us experimenting with inosine feel like it both helps and harms us at the same time.
1647053456682.png


So back to lowering adenosine, the Self-Hacked posts give the following suggestions:

  • Zinc is the only cofactor necessary for ADA activity, so adequate zinc is needed for the enzyme to work well [2].
  • Estradiol is one of the few inducers of adenosine deaminase [13].
  • IGF-1 is another inducer of adenosine deaminase [14].
  • Simvastatin (and probably other statins) increases ADA production when it’s suppressed by IL-13 [15].

The other input pathway to adensoine is from AMP (via the 5-nucleotidase enzyme), which is something we haven't explored, maybe a project for tomorrow. @Violeta noted earlier that Caffeine inhbits Phosphodiesterase and she found somewhere that boron does too.

1647054693269.png
 

SlamDancin

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Yes! A project for tomorrow I love the sound of that. From the self hacked article, and a two second pubmed search, looks like the ENT1 is also involved in adenosinergic tone. The selfhacked article mentioned this a possible target of benzodiazepines which is another topic of great interest to me because of how effective they are in the short run for me and others here. I’ll let you know what I find!