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Chronic Microglial Activation in ME/CFS, And Its Possible Treatment Using Microglial Inhibitors

heapsreal

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australia (brisbane)
@heapsreal
I added memantine to the list of microglial activation inhibitors. Thanks.

I havent looked into it too far but many meds for alzhiemers and parkinsons seem to be targeted at neuroinflammation which may be helpful for ME, I also think many dopamine agonists which are also used in these treatments may have anti neuroinflammatory effects also??
 

Hip

Senior Member
Messages
17,992
I havent looked into it too far but many meds for alzhiemers and parkinsons seem to be targeted at neuroinflammation which may be helpful for ME, I also think many dopamine agonists which are also used in these treatments may have anti neuroinflammatory effects also??

I know that drugs which agonize dopamine D2 receptors on astrocytes significantly lower brain inflammation.1 This may in part explain why I find very low dose amisulpride helpful for ME/CFS: in very low doses only, amisulpride acts to stimulate dopamine D2 receptors.


@Hip are u going to have a section of neuro inflammation treatments in the cfs road map?

I try to keep the roadmap evidenced-based, and only include treatments that either studies or ME/CFS doctors have found helpful for ME/CFS. That's so that people can know that the listed treatments in the roadmap have been proven effective, rather than being speculative. I can't think at the moment of any specific anti-brain inflammation treatments used by ME/CFS doctors, apart from LDN and Valcyte (which are in the roadmap).
 

Hip

Senior Member
Messages
17,992
A word of caution: these microglial activation inhibitors may have caused me to crash.

Last week I took a set of these microglial activation inhibitors as an experiment. On the first day taking them, I found I had a rapid boost in energy and enthusiasm, and this led me to spend 5 intense hours doing lots of house cleaning and dusting, washing floors, moving furniture around, etc. I don't usually get much PEM from physical activity, so the next day after this cleaning spree I felt a little tired, but nothing more than that. I took the microglial activation inhibitors for a second time on that second day. Later on that second day, I went out socially for the evening (I usually find socializing more exhausting than physical activity).

On the third day, I found myself much more exhausted than I would normally be after socializing. I was concerned that the microglial activation inhibitors might have been the cause of this increased PEM, so I stopped taking them entirely. However, as the week progressed, I found that the increased fatigue remained, so I realized I had precipitated a mini crash.

It is possible that these microglial activation inhibitors I took may have caused this mini crash, which I am still not really recovered from 1 week later.

The set of microglial activation inhibitors that I took for those two days in a row were:

Microglial activation inhibitors:
Hyaluronic acid 400 mg transdermal
Lithium orotate 60 mg
Vitamin D 10,000 IU
Turmeric 1000 mg
Vitamin E 400 IU
Chinese skullcap (4:1 extract) 400 mg
Genistein 56 mg
Lycopene 10 mg
Sulforaphane 400 mcg
N-acetyl-glucosamine 750 mg
Sesame seed oil 10 ml
Acetate (vinegar 2 tablespoons)
Siberian ginseng 5 grams
Terminalia chebula 1000 mg
Vinpocetine 10 mg
Reishi 600 mg
Curcumin 900 mg
Horny goat weed (Epimedium) 900 mg
Luteolin 100 mg
Fisetin 100 mg

I took the above just because I happened to have all of these supplements in stock from previous supplement experiments.

Given my experience with these microglial activation inhibitors, I am just sounding a note of caution for anyone considering taking them. It's possible, as @Marco suggested earlier in this thread, that by strongly inhibiting microglial activation, you are lowering the ill effects of brain inflammation (which is good), but you may also be reducing antiviral defenses in the brain (which is bad).

Though I cannot rule out the possibility that my intense 5 hour house cleaning spree may have played a role in my mini crash.



When I recover, I may try these microglial activation inhibitors again, but this time using a smaller set of them (perhaps only taking say 6 or 7 of the above supplements, rather than the full set of 20 I took).
 
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adreno

PR activist
Messages
4,841
Microglial activation inhibitors:
Hyaluronic acid 400 mg transdermal
Lithium orotate 60 mg
Vitamin D 10,000 IU
Turmeric 1000 mg
Vitamin E 400 IU
Chinese skullcap (4:1 extract) 400 mg
Genistein 56 mg
Lycopene 10 mg
Sulforaphane 400 mcg
N-acetyl-glucosamine 750 mg
Sesame seed oil 10 ml
Acetate (vinegar 2 tablespoons)
Siberian ginseng 5 grams
Terminalia Chebula 1000 mg
Vinpocetine 10 mg
Reishi 600 mg
Curcumin 900 mg
Horny goat weed (Epimedium) 900 mg
Luteolin 100 mg
Fisetin 100 mg
Given that set of supplements, with hundreds of biochemical reactions, it seems irrational to even speculate that your crash was due to microglial inhibition.
 

A.B.

Senior Member
Messages
3,780
@Hip If I had to guess, I would say it's the lithium orotate. I took a small dose, about 10 mg, and it almost immediately reduced my energy levels.
 

Hip

Senior Member
Messages
17,992
Given that set of supplements, with hundreds of biochemical reactions, it seems irrational to even speculate that your crash was due to microglial inhibition.

I certainly agree that any attempts we make to try to figure out the biochemical mechanisms behind the benefits or ill effects we observe for drugs or supplements are just guesses — educated ones at best.

But I don't think my speculation is irrational: each individual supplement has multiple (and usually mild) effects in the body. However, when like me you simultaneously take 20 supplements, where each has been shown to induce effect X in the body, then you can be sure that, in addition the numerous mild biochemical effects the supplements have, on top of that "noise," you are also definitely going to get a powerful induction of effect X.

This is actually a technique I have used a lot in my ME/CFS treatment experiments. For example, when I wanted to test whether boosting natural killer cell function might be beneficial, I took not one, but half a dozen drugs and supplements known to boost NK cells (this led to mild improvements in my ME/CFS symptoms, in case you want to know).


I should mention that I have used all the above supplements extensively before, both individually and mixed with other supplements and drugs, and they have all proved benign and beneficial for one or more of my symptoms. These supplements are all on my list of regulars that I know do me good.
 
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Marco

Grrrrrrr!
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Near Cognac, France
When I recover, I may try these microglial activation inhibitors again, but this time using a smaller set of them (perhaps only taking say 6 or 7 of the above supplements, rather than the full set of 20 I took).

That's still a lot of supplements doing who know what as @adreno said. Personally I wouldn't take more than one at a time otherwise you're just compounding the uncertainty.

Two other possible issues are : often dose/response with meds supplements isn't monotonic and at higher doses antioxidants can become pro-oxidant. The recently published paper on CoQ10 for GWI found the 100mg dose far superior to 300mg (and some symptoms worsened at 300mg. Secondly its generally the case that while too much of a thing (inc microglial activation) is a bad thing, so too is too little. Don't forget that glia are happy little housekeepers clearing away cellular debris etc on a daily basis quite apart from their role in tackling infection or damage.

There's no reason to conclude that you may have re-exposed a virus. Either of the above causes (or neither) could be at work as well as your own admission that you kind of overdid things.

Good luck.
 

melamine

Senior Member
Messages
341
Location
Upstate NY
Two other possible issues are : often dose/response with meds supplements isn't monotonic and at higher doses antioxidants can become pro-oxidant.

This is what seems to have happened to me when I tried Martin Pall supplements, taken as directed. There have been other instances using antioxidants in so-called normal doses that seemed to be the cause of similar symptoms.
 

melamine

Senior Member
Messages
341
Location
Upstate NY
@Hip If I had to guess, I would say it's the lithium orotate. I took a small dose, about 10 mg, and it almost immediately reduced my energy levels.
Lithium orotate makes me feel better or the same, but definitely not worse. I noticed minimal to no effect with luteolin or vinpocetine.
There is at least one thing on your list, Hip, that I would not take because of autoimmune issues: oxymatrine. Maybe in smaller doses it loses its stimulating effect, but then does it lose its microglial inhibiting effect as well?
I also see that elevated IL-6 is listed as a marker for neuroinflammation. I've only had mine tested once and it was on the low side. My brain symptoms were not as bad at the time of the test as at other times (else I would probably have cancelled the doctor app't.!) but I am reminded of it every time I read that it is expected to be elevated, if anything, and wonder whether my body was overcorrecting in some way...
 

Hip

Senior Member
Messages
17,992
I also see that elevated IL-6 is listed as a marker for neuroinflammation. I've only had mine tested once and it was on the low side.

IL-6 crosses the blood-brain barrier poorly, so if you had a blood test, I think it would have measured blood levels of IL-6, rather than IL-6 levels in the brain.

There is at least one thing on your list, Hip, that I would not take because of autoimmune issues: oxymatrine.

Yes oxymatrine is contraindicated for patients with autoimmune issues, or a family history of autoimmunity.
 

Hip

Senior Member
Messages
17,992
That's still a lot of supplements doing who know what as @adreno said. Personally I wouldn't take more than one at a time otherwise you're just compounding the uncertainty.

I can appreciate that if someone hasn't taken a dozen or more supplements at the same time before, they might be a little concerned about doing so. But in the many treatment experiments I have performed over the years, I often took a dozen supplements at the same time, and in nearly all cases without any ill effects, sometimes with mild benefits, and occasionally with excellent benefits.

For example, when I devised a treatment protocol to support mitochondria, I found nearly two dozen supplements that were beneficial for various aspects of mitochondrial functioning and mitochondrial biogenesis. I took these two dozen supplements all at the same time with no ill effects at all (I saw some improvements in my ME/CFS, but nothing significant).

My mitochondrial cocktail was this: Deprenyl 5 mg, Rhodiola rosea 350 mg, Lecithin 1200 mg, IGF-1 Nutronics Labs (139ng/drop) 4 drops sublingual, Lithium orotate 125 mg, 7-keto DHEA 50 mg, Leucine 5 grams, Glutamine 5 grams , Niacinamide 1000 mg, Ginkgo biloba (24%) 60 mg, Piracetam 2 grams, Q10 200 mg, Magnesium (as malate) 280 mg, Lauricidin (monolaurin) ½ scoop, Taurine 1000 mg, Acetyl-L-carnitine 800 mg, Alpha lipoic acid 250 mg, Pyrroloquinoline quinone (PQQ) 20 mg, Benfotiamine 80 mg, Carnosine 1000 mg, Sodium bicarbonate ¼ tsp, Creatine monohydrate 2 grams.

So I have plenty of experience trying supplement cocktails, and rarely had any ill effects from any combination.


Though I am not immune to certain specific supplements causing me ill effects. I cannot take the mineral boron for example. A daily dose of just 3 mg of boron will soon produce very strange emotional effects, making me become extremely sad for no reason, making me feel extremely lonely, even when I am with people. It's horrible. So I avoid boron like the plague. Molybdenum can also do strange things to me in higher doses.
 

melamine

Senior Member
Messages
341
Location
Upstate NY
I appreciate your experiments, Hip! I am not good at identifying things like you did with the boron and molybdenum. Interesting and totally unexpected reactions.
 

lansbergen

Senior Member
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2,512

Hip

Senior Member
Messages
17,992
I appreciate your experiments, Hip! I am not good at identifying things like you did with the boron and molybdenum. Interesting and totally unexpected reactions.

I realized several years ago that with the brain fog and terrible memory you get with ME/CFS, the only way I was going to reliably observe any effects of taking supplements or drugs for ME/CFS was by keeping a daily supplement diary, where I would note down what supplements or drugs I took each day, along with the dose taken.

I just use a basic word processor document on my computer for this diary. It's very easy to do this, because if you are taking regular supplements each day, you just copy yesterday's supplements and paste them into today's diary entry. This diary also reminds me what to take each day, as I am apt to forget what I am supposed to be taking.

On each day, or at the end of a week, you also note down in the diary any significant changes in symptoms. For example, at the end of the week, looking back, I may realize that I had noticeably lower levels of brain fog, such that all week I had engaged in projects that I would not normally be able to do. When you observe something like this, note it down in the diary. You can then look back at the supplements or drugs you took over that week, and the week before, to see if any new ones were introduced which might explain why your brain fog had improved that week.

All the supplements and drugs that turned out to be beneficial for me I would have totally missed if I had not used this diary system. You cannot rely on your memory once you have ME/CFS.


Here is a screenshot of my supplement diary entry for today (13 December):
Hip's Supplement Diary.png

All the supplements and drugs you see listed on the left are my regular daily supplements that I take all the time, which help with various ME/CFS, anxiety and depression symptoms.

If I am testing any new supplements or drugs, I will add them to this list on the left.

On the right in the "Results" section I write any observations that I may have, for example: "My depression has improved a lot today," or "Brain fog much worse today."

I use this simple table format as it is easy to read, and you can just copy and paste yesterday's table, change the date, and it becomes today's table. So my supplements diary is just a word processor document with lots of these tables, one after the other, with one table for each day.
 
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