Author Topic: Information about Cytokines and other biological substances  (Read 6353 times)

Quantum

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Re: Information about Cytokines and other biological substances
« Reply #30 on: March 08, 2019, 11:24:49 PM »
So do you guys think Quinolinic acid serum level have any meaning in POIS? When should this be measured?
https://drive.google.com/file/d/1nLgk-A7TpkU1k7Z3GTeH9kPrR3siqKcW/view

Hi Muon,

I feel it would be a loss of money, because the serum value will say nothing about what is happening in the microglia ( for quinolinic acid) and in the astrocytes ( for kynurenic acid), in the brain, behind the blood brain barrier.
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demografx

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Re: Information about Cytokines and other biological substances
« Reply #31 on: March 08, 2019, 11:49:24 PM »
Hi Nas, sorry for the delay, but as I have said in my previous post, I was on vacations, and just got back yesterday to do on return.  Whenever you have a question for me, please be patient, it will usually takes far less than one month before I get back to you ;)
Hope you know I was joking.
10 years of significant POIS-reduction, treatment consisting of daily (365 days/year) testosterone patches.

TRT must be checked out carefully with your doctor due to fertility, cardiac and other risks.

40+ years of severe 4-days-POIS, married, raised a family, started/ran a business

Nas

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Re: Information about Cytokines and other biological substances
« Reply #32 on: March 09, 2019, 12:00:07 PM »
Hi Nas, sorry for the delay, but as I have said in my previous post, I was on vacations, and just got back yesterday to do on return.  Whenever you have a question for me, please be patient, it will usually takes far less than one month before I get back to you ;)
Sorry I might've been inpatient, I get frustrated when I waste time not fighting against this curse.
About what you see as a paradox, I refer you again at the diagram I have linked to my January 2015 post, at http://fr.slideshare.net/adonissfera/tryptophan-and-madness/17-Cytokines_Come_in_Two_FlavorsProInflammatory   .  If you look carefully, you will see that the 2 kynurenine pathways tryptophan is shunt to happen in two different cell types: 

the KMO enzyme leading to quinolinic acid is active in the microglia and produces quinolinic acid, and causes emotional symptoms

 and the KAT enzyme is present in the astrocytes, leading to kynurenic acid production, and cause cognitive symptoms

so, 2 different cell types, having a different distribution in the brain.

both enzymes, KMO and KAT, have kynurenine as substrate ( = "input" substance).
Thanks Quantum, makes perfect seance but since I have depression and pure OCD I don't know if agitating NMDAr would be a good idea, we'll see.
Back in 2015, I search a lot to find natural KMO inhibitor, which would have been great to test my hypothesis on quinolinic acid causing my emotional symptoms , but did not find any ( KAT inhibitor were not interesting for me since I have no cognitive symptoms).  So, I then went back up in the chain and decided to work on blocking TDO and IDO, so there would be less tryptophan turned into kynurenine, so less substrate available for KMO and KAT, to turn TRP in QUIN or kynureninc acid, as explained above.
Nanna recently proposed NAD+ as a good IDO inhibitor, maybe this would be a better test then Glycine.

So about NMDAr agonists, there is a guy in FB who tried Glutamic acid and it didn't work for him, I wonder since Kyneurenic acid is a glyicne site antagonist, won't glutamate be effective on NMDAr in this case?

Quantum

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Re: Information about Cytokines and other biological substances
« Reply #33 on: March 09, 2019, 06:44:19 PM »
I saw that when I read about kynurenic acid and all the rest, but never found any reference stating that glutamate was helping cognitive functions, and many references states its excitotoxic properties, so I am not a fan of glutamate.   And, for years, I have stayed away of anything containing monosodium glutamate ( MSG), as it is not healthy for the brain.

However, you can find many reference stating that D-serine, which is a glycine derivative substance, does help cognitive functions:  https://examine.com/supplements/d-serine/   .   Phosphatidylserine is proven to help as well ( https://examine.com/supplements/phosphatidylserine/) , and lecithin is a very cheap source of it   ( there is lecithin in eggs....would that be what is helping Bulbo and others who are getting better with one or more eggs a day ? )


When it comes to IDO inhibitors, my favorite is rosmarinic acid ( which I take from rosemary essential oil, one or 2 drops in a glass of water) . .  A high quality, organic rosemary oil is rather cheap here, and will last a long time, as I use it 2 drops at a time.
« Last Edit: March 09, 2019, 06:52:27 PM by Quantum »
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Nas

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Re: Information about Cytokines and other biological substances
« Reply #34 on: March 10, 2019, 04:38:09 AM »
Thanks Quantum,
For now I've ordered Glycine powder, we'll see if it does the trick.

About lecithin, I tried sunflower lecithin but it did nothing as I recall.

I also tried rosemary extract way when I first joined this forum and saw your post about IDO/TDO inhibitors. It also did nothing.

I think taking more direct action supplements for me is better, because if they didn't work, I can scratch them off and move on to a new theory.

Nas

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Re: Information about Cytokines and other biological substances
« Reply #35 on: March 12, 2019, 12:16:10 PM »
Hi Quantum,
I wonder how effective are Cox-2 inhibitors on IDO suppression?  I personally had zero success with NSAID's so I'm looking forward for your response.
Thanks. 

Quantum

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Re: Information about Cytokines and other biological substances
« Reply #36 on: March 12, 2019, 10:22:11 PM »
Hi Quantum,
I wonder how effective are Cox-2 inhibitors on IDO suppression?  I personally had zero success with NSAID's so I'm looking forward for your response.
Thanks.


NSAIDS are not part of my pre-pack, but some initial versions of my pack had ibuprofen in them.  Because of stomach irritation effect, I have chosen not to include it as a "regular" member of my pre-pack.   I prefer using turmeric and rosemary essential oil as IDO inhibitor, in addition to TDO inhibitors too. 

And, I eat some pumpkin seeds every day, to sustain good tryptophan levels.   For tryptophan, I also have 5-HTP in my pre-pack, which is the direct precursor of serotonin and of course a source of tryptophan, and the green tea in my pre-pack help lower the peripheral metabolism of 5-htp, so more of it make it to the brain.   More Trp in the brain helps if much of it have been shunt to the kynurenine pathway  ( some new Trp is needed to resume serotonin synthesis and rebalance things, in my hypothesis ).
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Nas

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Re: Information about Cytokines and other biological substances
« Reply #37 on: March 13, 2019, 05:33:48 AM »
Yes but I have tried them personally many times and they don't seem to work, that's problematic since they're supposed to down regulate IDO.

Quantum

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Re: Information about Cytokines and other biological substances
« Reply #38 on: March 13, 2019, 07:16:38 AM »
I I take only rosemary and curcumin, and a few others, it would not work,   I need my whole pre-pack to have a real protection.

Maybe you could try adding different things together, that you think may help you, if no single supplement seems to do the job.   I see POIS like a multi-headed beast, so it calls for action on different pathways at the same time.  That is how I reached some results.  It toolk a few months of adding and subtracting and testing, but it lead to something effective.
You are 100% responsible for what you do with anything I post on this forum and of any consequence it could have for you.  Forum rule: ""Do not use POISCenter as a substitute for, or to give, medical advice" Read the remaining part at http://poiscenter.com/forums/index.php?topic=1.msg10259#msg10259

Nas

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Re: Information about Cytokines and other biological substances
« Reply #39 on: March 13, 2019, 10:47:09 AM »
Quantum I'm strictly talking about NSAID not the supplements.

Nas

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Re: Information about Cytokines and other biological substances
« Reply #40 on: March 13, 2019, 05:34:11 PM »
So do you guys think Quinolinic acid serum level have any meaning in POIS? When should this be measured?
https://drive.google.com/file/d/1nLgk-A7TpkU1k7Z3GTeH9kPrR3siqKcW/view
Actually B3 levels after orgasm would be a very good indicator of the validity of this theory.
Isn't it crazy that no one actually tested their B3 levels in this form, yet?

Nas

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Re: Information about Cytokines and other biological substances
« Reply #41 on: March 14, 2019, 03:50:01 PM »
Quoted from Nanna on the topic of kynurenic acid:


Here is some background information that might help you with the kynurenine pathway:
  Glutamate (excitation) and GABA (inhibition) act as on/off switches for neurons. When the neuron is on (glutamate-NMDA) there is increased energy consumption and NAD+/NADH cycling. When the neuron is turned off (GABA) energy is conserved and there is very little cellular activity.

  The main purpose of the kynurenine pathway is to produce niacin and ultimately NADH and NADPH (Ref). NADH and NADPH are a key energy redox antioxidants that allow the body to used calories as energy (ATP). NAD+ is also a required cofactor along with poly(ADP-ribose) polymerase-1 (PARP-1) for DNA repair. But if there is too much DNA damage then PARP-1 will consume and deplete NAD+, which depletes the energy of the cell/neuron and kills it. For example:
Blockade of PARP activity attenuates poly(ADP-ribosyl)ation but offers only partial neuroprotection against NMDA-induced cell death in the rat retina.

  As long as everything is normal in a neuron/cell, then the kynurenine pathway is only producing niacin/NAD as the end-product. However, there are several ways that the neuron can detect DNA damage. If a small amount of DNA damage occurs then NAD+ is consumed by PARP-1 to repair DNA. But if a large amount of DNA damage is suddenly detected, the cell goes into safe-mode by shutting down cellular activity (block NMDA, reduce PARP-1 activity, and increase GABA). This is partially accomplished by diverting kynurenine metabolism away from niacin production and into kynurenic acid. Kynurenic acid then blocks cellular activity by blocking glutamate receptors (NMDA, AMPA, etc...) (Ref). The increase in kynurenic acid prevents further DNA damage and stress induced toxicity.

  Kynurenic acid production is a safety-switch in the kynurenine pathway to prevent DNA damage and cell death. The side-effect of this is that it prevents DNA damage by shutting down the neuron (inhibiting glutamate receptors) so that it is no longer excited/firing (brain fog). Kynurenic acid prevents excitotoxicity at the expense of cognition. If you want to decrease kynurenic acid and brain fog, you should answer the question, "Why is there an increase in DNA damage?" Different stressors (cancer, infection, poison, emotional stress) can cause DNA damage. So I do not consider kynurenic acid a cause of anything, but rather it is a safety-reaction to a cause.

  The true cause of brain fog is likely something that has nothing to do with the kynurenine pathway, but the body uses changes in the kynurenine pathway to prevent irreversible DNA damage. You can always recover from kynurenic acid induced brain fog, but you cannot recover from neuron loss (brain cell death) due to DNA damage.

In terms of autoimmune diseases, "N-acetylcysteine (NAC) treatment significantly reduced kynurenine levels relative to placebo in vivo" -Comprehensive metabolome analyses reveal N-acetylcysteine-responsive accumulation of kynurenine in systemic lupus erythematosus: implications for activation of the mechanistic target of rapamycin

Sure you can share that explanation. If you do, you may also want to share this quote:
"Kynurenic acid shows neuroprotective properties. (Ref12) Some researchers have posited that the increased levels found in cases of neurological degradation is due to a failed attempt to protect the cells. (Ref13)" -Kynurenic acid: Role in disease

Muon

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Re: Information about Cytokines and other biological substances
« Reply #42 on: March 15, 2019, 09:20:15 AM »
Some of us do feel better on a ketogenic diet:
https://en.wikipedia.org/wiki/Kynurenic_acid#Link_to_ketogenic_diet

Nas

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Re: Information about Cytokines and other biological substances
« Reply #43 on: March 18, 2019, 09:41:34 PM »
From wiki:

KYNA has been proposed to act on four targets:

As an antagonist at ionotropic AMPA, NMDA and Kainate glutamate receptors in the concentration range of 0.1-2.5 mM.[2]

As a noncompetitive antagonist at the glycine site of the NMDA receptor.

As an antagonist of the α7 nicotinic acetylcholine receptor.[3] However, recently (2011) direct recording of α7 nicotinic acetylcholine receptor currents in adult (noncultured) hippocampal interneurons by the Cooper laboratory [4] validated a 2009 study [5] that failed to find any blocking effect of kynurenic acid across a wide range of concentrations, thus suggesting that in noncultured, intact preparations from adult animals there is no effect of kynurenic acid on α7 nicotinic acetylcholine receptor currents.[4][5]

As a ligand for the orphan G protein-coupled receptor GPR35.[6] Another tryptophan metabolite, 5-hydroxyindoleacetic acid exerts its effects via the orphan G protein-coupled receptor GPR35.[7]

It seems that Glycine is only going to work on agonising the NMDA receptor from the Glycine site, but what about the ionotropic site? Or the AMPA and kainate receptors?

b_jim

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Re: Information about Cytokines and other biological substances
« Reply #44 on: March 19, 2019, 10:46:34 AM »
I think we are VERY CLOSE of the Pois secret.
it's hard for me to understand all these elements. I need some hours to work on this.
Taurine = Anti-Pois
Suffering from lyme disease