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Triggering the Cholinergic Antiinflammatory Pathway to Inhibit NF-kB

nf-kb cholinergic inflammation

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#1 HighDesertWizard

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Posted 02 February 2015 - 04:14 AM


The Vagus Nerve, Heart Rate Variability, Cholinergic Antiinflammatory Pathway Nexus is, to my knowledge, our bodies' major, Innate mechanism for inflammation inhibition via the inhibition of NF-kB. 

 

The purpose of that Longecity thread above is to discuss the science. Recently, I've become more determined to focus on all the practical means to trigger it in myself and discussion of those means is the purpose of this thread.

 

For now, in this first post, I'll just note that it's important to consider the complete set of types of CAIP agonists...

  • Diet
  • Physical activity
  • Supplements
  • Positive Cognition
  • Biofeedback
  • Brain Wave Stimulation
  • Electrical Stimulation
  • ?

At this date, the best graphic figure that depicts the various kinds of CAIP agonists is this one... I'll find the link and post it later...

3cEBJIb.png

 

I look forward to the discussion.


Edited by HighDesertWizard, 02 February 2015 - 04:51 AM.

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#2 HighDesertWizard

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Posted 02 February 2015 - 04:17 AM

In another thread, Logic asked about a means for triggering the CAIP...

 

Will supplementing Acetylcholine have an effect?

"...Acetylcholine inhibits cytokine production in macrophages via α7 nicotinic acetylcholine receptor (α7nAChR), and nicotine is a more stable agonist to control cytokine production..."
http://www.nature.co...cr2013128a.html
 

 

Logic... 

 

I haven't tried Acetylcholine. I have tried other Acetylcholine agonists. They work. And I bet Acetylcholine would work... Let us know about your experience if you do try it.
 
I have just ordered Galantamine powder from my current favorite powder supplier, PowderCity.com based on a few studies Tracey himself was involved in.
 

Galantamine Alleviates Inflammation and Other Obesity-Associated Complications in High-Fat Diet–Fed Mice

Brain acetylcholinesterase activity controls systemic cytokine levels through the cholinergic anti-inflammatory pathway

Central cholinergic activation of a vagus nerve-to-spleen circuit alleviates experimental colitis

 

I will post about my experience with Galantamine once I try it...


Edited by HighDesertWizard, 02 February 2015 - 04:19 AM.

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#3 HighDesertWizard

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Posted 07 February 2015 - 02:23 PM

The story of how I happened upon the scientific literature of the Vagus-HRV-Cholinergic Antiinflammatory Pathway Nexus is relevant to the discussion of how to Trigger the CAIP to inhibit NF-kB...

 

In late 2011, I was experimenting with, both, HeartMath's emWave device that assists with exercises to increase Heart Rate Variability (HRV) and with a Cognitive enhancement supplement, Excelerol, that does feel like it increases cognitive ability for a short time.

 

Without intending to do it, I mixed up the timing of my experiments... I took Excelerol about an hour before an emWave session. After doing that, I noticed that it was significantly easier to maintain the green light on the emWave device (i.e., keep my HRV higher). I repeated the combining of these two n=1 experiments on myself several times. There was no doubt about it. I could more easily maintain In-The-Moment-Higher-HRV after I had taken a couple Excelerol capsules.

 

After becoming clear about that fact, I began doing google scholar searches of each Excelerol ingredient along with the phrase "Heart Rate Variability." Within 15 minutes, I had come across so many references to the Cholinergic Antiinflammatory Pathway in general and the name, Kevin Tracey, specifically, that I knew I had what was likely the best Explanation of the Excelerol-emWave device effect.

 

It took me several months to digest the literature until, in April of 2012, I felt comfortable establishing the LongeCity thread about the Vagus-HRV-CAIP Nexus. I'm not a professional scientist or a medical professional. I don't always articulate as well as others can about the science of a subject. But I strongly felt at the time that LongeCity needed a thread about this topic...

 

My n=1 anecdotal experience highlights a Key Point... The Cholinergic Antiinflammatory Pathway is triggered at the a7 SubUnit of the Nicotinic Acetylcholine Receptor. This can be done, essentially, in two different ways...

  • Vagus Nerve Stimulation is our Innate Mechanism for targeting that receptor. There are foods, supplements, drugs, cognitive practices, physical activities, etc. that Stimulate the Vagus Nerve.
  • There are also Foods, Supplements, Drugs that are intended to target that receptor directly. (I confess that I'm unclear about Vagus Nerve Stimulation impact in taking this second approach. Still, this second approach can work as my anecdotal experience demonstrates.)

A terrific graphic figure from a 2012 Kevin Tracey study makes these two means clear...

 

Enjoy!

 

1sE7S6l.png


Edited by HighDesertWizard, 07 February 2015 - 02:39 PM.

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#4 HighDesertWizard

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Posted 07 February 2015 - 06:16 PM

It turns out that Alpha-rhythm stimulation using brain entrainment enhances heart rate variability in subjects with reduced HRV. The abstract...

 

In the present research, we have used the brain entrainment (BWE) treatment simultaneously recording time series data of R-R intervals of the ECG during rest condition. In detail, we have used alpha brain stimulation and we have found that it induces an enhancement of HRV, particularly in Total Variability and Vagal Modulation activities. The experiment has been performed by us on ten subjects with age ranging from 20 to 70 years old. The risk induced from low HRV is by this time well known in literature. Therefore, the obtained result promises to be of valuable interest not only in terms of the basic neurological investigation but also because it delineates new possibilities in terms of clinical application.

 

I thought I had found other studies showing an association of Acetylcholine expression with Alpha Waves... Can't find the studies at the moment... Will keep trying...



#5 HighDesertWizard

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Posted 08 February 2015 - 10:00 PM

One of the easiest ways to increase Vagal Tone, and probably the cheapest, are various breathing techniques. Here's a study that shows both Vagal Tone and Sleep Quality are increased with 20 minutes of paced breathing before sleep among insomniacs.

 

Efficacy of paced breathing for insomnia: Enhances vagal activity and improves sleep quality



#6 Flex

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Posted 15 February 2015 - 12:08 AM

You could try chinese skullcap.

For more details, look into my post

Battling neurological and musculoskeletal inflammation, or why does Ibuprofen feel like an opiate high?

http://www.longecity...gh/#entry713700



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#7 Razor444

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Posted 15 February 2015 - 02:20 AM

GTS-21 is an a7nAChR agonist.

 

It's available from THT.co.

 

To clarify. 'Effect of the a7nAChR agonist GTS-21 on inflammation during human endotoxemia':

 

Introduction

Activation of the cholinergic anti-inflammatory pathway via vagus nerve stimulation or a7nAChR agonists improves outcome in animal models of endotoxemia, sepsis and experimental arthritis. This vagal anti-inflammatory pathway is mediated by the nicotinergic a7nACh receptor that can be selectively stimulated by GTS-21. Up to now, the anti-inflammatory effects of oral administration of GTS-21 in humans in vivo have not been investigated. The aim of this study was to investigate the anti-inflammatory effects of oral administration of GTS-21 on the inflammatory response in the human endotoxemia model.

 

...

 

Conclusion

GTS-21 suppresses TNFα and stimulates IL-10 release during human endotoxemia in healthy human volunteers, resulting in a shift towards a more anti-inflammatory pattern. This effect may have potential for in vivo modulation of the innate immune response.

 

Edit: Just noticed GTS-21 on the image from the original post!


Edited by Razor444, 15 February 2015 - 02:23 AM.


#8 HighDesertWizard

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Posted 21 February 2015 - 03:58 PM

GTS-21 is an a7nAChR agonist.

 

It's available from THT.co.

 

To clarify. 'Effect of the a7nAChR agonist GTS-21 on inflammation during human endotoxemia':

 

Introduction

Activation of the cholinergic anti-inflammatory pathway via vagus nerve stimulation or a7nAChR agonists improves outcome in animal models of endotoxemia, sepsis and experimental arthritis. This vagal anti-inflammatory pathway is mediated by the nicotinergic a7nACh receptor that can be selectively stimulated by GTS-21. Up to now, the anti-inflammatory effects of oral administration of GTS-21 in humans in vivo have not been investigated. The aim of this study was to investigate the anti-inflammatory effects of oral administration of GTS-21 on the inflammatory response in the human endotoxemia model.

 

...

 

Conclusion

GTS-21 suppresses TNFα and stimulates IL-10 release during human endotoxemia in healthy human volunteers, resulting in a shift towards a more anti-inflammatory pattern. This effect may have potential for in vivo modulation of the innate immune response.

 

Edit: Just noticed GTS-21 on the image from the original post!

 

Razor... Thanks for the info on purchasing GTS-21... Galantamine works well but is expensive.

 

I've got a lot more info on Triggering the CAIP and will be posting about it over time.



#9 HighDesertWizard

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Posted 21 February 2015 - 05:30 PM

I need some assistance. I've been thinking through what kind of Vagus Nerve or direct CAIP Stimulation "dosing" to do to reduce inflammation. To put the question more specifically...

 

How often and at what intensity, should either Vagus Nerve Stimulation and/or Acetylcholine Agonist "dosing"  take place?

 

I can't seem to find the full study of a study referenced by Kevin Tracey that sheds light on this question. It's this one...

 

Stimulated production of proinflammatory cytokines covaries inversely with heart rate variability

 

Can anyone help me out with this? Thx...



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#10 HighDesertWizard

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Posted 21 February 2015 - 05:50 PM

You could try chinese skullcap.

For more details, look into my post

Battling neurological and musculoskeletal inflammation, or why does Ibuprofen feel like an opiate high?

http://www.longecity...gh/#entry713700

 

Flex... Thanks... You know a good deal about various antiinflammatories... I'm wondering if they're all acetylcholine agonists or otherwise stimulate the Vagus Nerve.


Edited by HighDesertWizard, 21 February 2015 - 05:51 PM.


#11 StevesPetRat

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Posted 21 February 2015 - 06:24 PM

Thank you for posting this thread. I have been very interested in this pathway as well since recognizing that my cognitive implosion and many physical symptoms were cholinergic in nature. Exploring further revealed that vagus nerve stimulation is being investigated for the treatment of arthritis and tinnitus, both of which I have (as well as residual dry eye, sinusitis, and cellulite, all possibly helped by ACh as well). The cognitive issues resolved back to around 75% of baseline rather quickly, but the physical inflammatory problems linger months later.

Do you knew how galantamine compared to huperzine A? I have not yet started messing with AChEI's, as I would prefer to increase the gene expression of choline acetyltransferase (ChAT) and vesicular acetylcholine transporter (VAChT) rather than take the "blunt" approach. But, there's not much info on how to do that; current candidates are αGPC, BDNF, NGF, and CDNF.

#12 HighDesertWizard

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Posted 21 February 2015 - 06:51 PM

I've been trying to develop a simple, graphic approach to presentation of the profound health benefits of Triggering the Cholinergic Antiinflammatory Pathway. The first few slides need to grab a person by the throat and hook them in. Here's the current version...

 

https://docs.google....T6WqCdvgIRJ8gig

 

Any and all feedback about how to make it better much appreciated.


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#13 ceridwen

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Posted 14 April 2015 - 02:17 PM

Steve's pet rat I think you should try all 4 things you mention in your message all at once. That's what I intend to do.

#14 ceridwen

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Posted 14 April 2015 - 02:22 PM

I have been wary of getting rid of my tinnitus as I thought a reduction in tinnitus is a clear and immediate indicator that a new substance/treatment is working but it has always come back so maybe not.

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#15 Flex

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Posted 14 April 2015 - 04:19 PM

 

You could try chinese skullcap.

For more details, look into my post

Battling neurological and musculoskeletal inflammation, or why does Ibuprofen feel like an opiate high?

http://www.longecity...gh/#entry713700

 

Flex... Thanks... You know a good deal about various antiinflammatories... I'm wondering if they're all acetylcholine agonists or otherwise stimulate the Vagus Nerve.

 

 

Sory for my late response, I´ve forgot it.

 

I dont know, would have to take a look.

 

If its in any way helpful, heres how the Scientists do a recherche:

 

Using cerebral ischemia (OR ischemic stroke) AND herb (OR
traditional Chinese medicine) AND inflammation (OR inflammatory OR immunity) as the keywords, we search
the English databases including PudMed, Medline, and
Cochrane library from 1980 to 2010, generating 77 articles from the initial search.

Anti-inflammatory effects of Chinese medicinal herbs on cerebral ischemia

http://www.cmjournal...9-8546-6-26.pdf







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