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Switch to turn off inflammation.

Cort

Cort

Phoenix Rising Founder
Messages
7,390
Location
Arizona in winter & W. North America otherwise
neweimear said:
https://www.irishtimes.com/news/hea...-for-inflammatory-diseases-1.3443334?mode=amp. @Ben H @Janet Dafoe (Rose49)
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Metabolism and inflammation - that's a interesting combination given the possible glucose connection in ME/CFS.

Teams led by immunologist Prof Luke O’Neill, who is based in Trinity, and Dr Mike Murphy, of the University of Cambridge, have discovered that “itaconate” – a molecule derived from glucose – “acts as a powerful off switch for macrophages”, which are cells operating at the heart of the the immune system where inflammation occurs.

“My lab has been exploring metabolic changes in macrophages for the past six years, and we’ve come across what we think is the most important finding yet,” said Prof O’Neill.
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The onset of inflammatory is of course huge interest to ME/CFS. Montoya's results strongly suggest ME/CFS is an inflammatory disease. There must be a switch somewhere! Could this be it or one of them? I'll bet there are multiple switches in the immune system

Macrophages have not been identified in ME/CFS but I don't know if they've been studied either.

Prof O’Neill and his collaborators are exploring its relevance to the onset and development of inflammatory and infectious diseases. They are also keen to explore whether the findings can be exploited in the effort to develop new anti-inflammatory medicines.
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ljimbo423

ljimbo423

Senior Member
Messages
4,705
Location
United States, New Hampshire
It looks like itaconate is made in the TCA cycle. If Fluge and Mella are right about impaired pyruvate dehydrogenase (PDH) function in CFS, then itaconate could be low in CFS. Because the TCA cycle is slow from the impaired PDH.
Metabolic-pathway-for-itaconic-acid-production-via-the-different-compartments-in-the.png
 
Learner1

Learner1

Senior Member
Messages
6,305
Location
Pacific Northwest
My lactate and pyruvate are at the very end of low normal, and cis-acotinic acid is low, while citric acid and other Krebs metabolites are normal. I do seem to have a PDH block and am burning amino acids.

The NutrEval notes that iron and glutathione are needed to get from citric acid to cis-acotinic acid and fluoride, arsenic, mercury, and tin can inhibit the conversion, so there are likely more factors at play.

@Nine lives Have you had a mycotoxins or heavy metals test?
 
N

Nine lives

Messages
90
Nice to meet someone with a similar profile!

I am on CIRS protocol which I started soon after this OAT test last summer. So mycotoxins have been one strand for me. Hair metals all relatively low now.

I had noted the fluoride as a block in that part of cycle and indeed in 2010 2 full doses of Levaquin to "settle down" my root canals.

I believe I was taking liposomal glutathione at the time, but I can' swear to it. I try to take this when I can - I think it helps me sweat, which is something I have struggled with since all this started.
 
N

Nine lives

Messages
90
No - last summer I was actually eating carbs - about 80-100 a day in the hope of raising gut diversity. Nevertheless, my hydroxybutyrate was flagged in that OAT as high 5.2 when it should be less than 3.1.

I think my body thinks it is starving and yet I am as heavy in weight as I became post-pregnancy.

Yet, I am one of those helped by thiamine derivatives. At that time I was just using AUTHIA cream with Thiamin Tetrahydrofurfuryl Disulfide (but that also has methyl B12 which I find overstimulating). Moved to benfothiamine, sulbutiamine, allithiamine.
 
nanonug

nanonug

Senior Member
Messages
1,709
Location
Virginia, USA
Nine lives said:
No - last summer I was actually eating carbs - about 80-100 a day in the hope of raising gut diversity. Nevertheless, my hydroxybutyrate was flagged in that OAT as high 5.2 when it should be less than 3.1.
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How's your blood sugar? Any hint of diabetes? It's too bad the test you did says nothing about glycolysis. There is a bunch of potential roadblocks from glucose to pyruvate that are just unknown.
 
N

Nine lives

Messages
90
So, looked back at 2016 OAT had same low aconitic.

At that time, blood sugar was good at 90 (dropping now with benfothiamine etc). BUT I rarely eat any sweets, fruit etc. Sugary foods make me feel light headed. At my worst any carbs did that. Definitely something going on for me in that pathway but strangely it is not showing up in my blood sugar.
 
Wayne

Wayne

Senior Member
Messages
4,307
Location
Ashland, Oregon
Janet Dafoe (Rose49) said:
Thanks. Sent to Ron.
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Hi @Janet Dafoe (Rose49),

Yesterday, I ran across what I thought was a remarkable article that has similarities to the article linked in this thread. Perhaps Ron might be interested in it, as it refers to not only stopping inflammation, but "resetting the immune system" as well (which stops the inflammation).

It's quite a long article, but one area they highlighted was how some rheumatoid arthritis patients were completely recovering simply from having a vagus nerve stimulation device implanted in their bodies, and turning it on for 30 seconds 6 times a day. IIRC, they say toward the end they believe it has applications/implications for pw/CFS.

There's a Single Nerve That Connects All of Your Vital Organs — And It Might Just Be the Future of Medicine

Here's a 4-paragraph snippet from the article, with the last one being the most important (right after Cort's quote):

"Operating far below the level of our conscious minds, the vagus nerve is vital for keeping our bodies healthy. It is an essential part of the parasympathetic nervous system, which is responsible for calming organs after the stressed 'fight-or-flight' adrenaline response to danger. Not all vagus nerves are the same, however: some people have stronger vagus activity, which means their bodies can relax faster after a stress.

The strength of your vagus response is known as your vagal tone and it can be determined by using an electrocardiogram to measure heart rate. Every time you breathe in, your heart beats faster in order to speed the flow of oxygenated blood around your body. Breathe out and your heart rate slows.

... so the bigger your difference in heart rate when breathing in and out, the higher your vagal tone. Research shows that a high vagal tone makes your body better at regulating blood glucose levels, reducing the likelihood of diabetes, stroke and cardiovascular disease. Low vagal tone, however, has been associated with chronic inflammation.

Cort said:
There must be a switch somewhere! Could this be it or one of them? I'll bet there are multiple switches in the immune system
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As part of the immune system, inflammation has a useful role helping the body to heal after an injury, for example, but it can damage organs and blood vessels if it persists when it is not needed. One of the vagus nerve's jobs is to reset the immune system and switch off production of proteins that fuel inflammation. Low vagal tone means this regulation is less effective and inflammation can become excessive"​
 
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K

kangaSue

Senior Member
Messages
1,851
Location
Brisbane, Australia
Wayne said:
As part of the immune system, inflammation has a useful role helping the body to heal after an injury, for example, but it can damage organs and blood vessels if it persists when it is not needed. One of the vagus nerve's jobs is to reset the immune system and switch off production of proteins that fuel inflammation. Low vagal tone means this regulation is less effective and inflammation can become excessive"
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Hmm, wonder if that switch involves antibodies to alpha7-nicotinic acetylcholine receptor (alpha7nAChR) causing dysfunction in the cholinergic anti-inflammatory pathway. That could explain the involvement of GI problems too.
https://physoc.onlinelibrary.wiley.com/doi/full/10.1113/JP271537
https://www.ncbi.nlm.nih.gov/pubmed/16056392
 
N

Nine lives

Messages
90
On the Genova Metabolic Analysis Profile (MAP) that I took in 2008 (pre-onset) the equivalent marker is cis-aconitic acid with a range of 1.4 to 76.8. My reading was 41.9, which was perfectly in the middle of the range.

To me, this states an environmental insult took place between 2008 (normal) and 2016, 2017 (low flag). I stated that I took 2 RXs of Levaquin in 2010, but I had a nice remission for a good year. Moved into temporary apartment for 3 months (horrendous VOCs and probably mold) hence I am on mold protocol. Maybe there is more than one thing that can hit production of this.

Anyway, I feel the dental work has helped move up my PEM threshold. I hope to take another OAT this summer and see where this marker lies.
 
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