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

[tango]

@Gondwanaland my understanding is that silymarin, soy and the seeds you mentioned are all phytoestrogens. I wonder if the issue you have is with lectins??? Perhaps it would be worth trying sprouted activated seeds to see how you respond

EPO is also estrogenic so I'm lost with your comment.

What is the connection between avocados and choline with estrogen

 

[tango]

Dr Weil suggests that milk thistle might interfere with HRT. As I'm on bioidentical estrogen I wonder if I should stop the milk thistle?
https://www.drweil.com/vitamins-supplements-herbs/herbs/milk-thistle/

 

[Gondwanaland]

I am on bioidentical estrogen.

Me too

I also take a supplement with soy isoflavones and black cohosh.

I tried those and my thyroid hated them. I read somewhere that Black Cohosh stimulates FSH and that is something I don't need since my levels are very high already.

Mood, pain and energy all improve.

Mine too

Soy isn't really an estrogen antagonist. It's simpler a weaker form of estrogen. So it should be helpful. Have you tried isoflavones supplements?

I did. I read that these phytoestrogens supress endogenous estrogen formation. I am not sure what is the reason I feel worse on them. When I first tried red clover sprouts I got a cycle , but then it was the last one.

Progesterone and zinc I understand as zinc supports progesterone and lowers copper

I seem to need copper a lot.

 

[Gondwanaland]

issue you have is with lectins???

Very likely

Perhaps it would be worth trying sprouted activated seeds to see how you respond

Sprouted linseeds are the worst offenders

EPO is also estrogenic so I'm lost with your comment.

AFAIK it is progesterogenic, and progesterone is also an estrogen precursor, but my conversion seems to be blocked. I think I have too many aromatase inhibitors in my diet (paper enclosed on natural aromatase inhibitors) - or possibly a Niacin deficiency?

What is the connection between avocados and choline with estrogen

I think avocados are progesterogenic
Choline accelerates estrogen breakdown, Niacin antagonizer (just putting together scattered info I read on many different places)

Dr Weil suggests that milk thistle might interfere with HRT. As I'm on bioidentical estrogen I wonder if I should stop the milk thistle?
https://www.drweil.com/vitamins-supplements-herbs/herbs/milk-thistle/

Because extracts from the milk thistle plant can act like estrogen, women should avoid them if they have estrogen-related conditions including uterine fibroids, endometriosis or a history of hormone-related cancers (breast, uterine, ovarian). Extracts from milk thistle seeds do not have estrogenic effects.

EDIT-- It seems to be counter-indicated for estrogen dominance

I am on bioidentical estrogen as well and feel only benefits from Milk Thistle, but I only take it 1x every 10 days or so for adrenal support - when I have chills and my body temperature seems to oscillate it helps a lot to stabilize and suppressses the chills.

 

[tango]

@Gondwanaland I am on mobile so can't quote properly but bioidentical also stops endogenous production of estrogen as it's an exogenous source

EDIT: I was sure EPO is estrogenic

I need to read up on choline. I'm not sure about it breaking down estrogen.

 

[Gondwanaland]

EDIT: I was sure EPO is estrogenic

EPO is a source of GLA and (just like CLA from chia seeds) uses B6 to convert it to arachidonic acid, which forms prostaglandins. I think that taking EPO depleted me of B6 and at the same time left me with an excess of inflammatory protaglandins. I took it for almost 4 weeks and when I stopped I had a gout crisis. I measured uric acid one month later and it was still elevated at 6.2 (2.4 - 5.7 mg/dL).

Many women take it to balance estrogen dominance, I think precisely because it activates that specific B6 pathway it tends to favor progesterone while breaking down estrogen more quickly. Healthy women can turn progesterone into estrogen as the body needs, but I seem to have a block precisely there (B3 deficiency?)

The fact is that after taking EPO my estrogen levels got so low that I just couldn't get rid of uric acid and starting estrogen replacement saved me from the horrors of the gout crisis.

I am really not sure about the whole mechanism, and miss having someone to discuss with about it.

 

[tango]

I am really not sure about the whole mechanism, and miss having someone to discuss with about it.

Maybe post your query as a separate question and get some help?

 

[pattismith]

thank you for this thread!

 

[pattismith]

@Hip

Seems to me that PPI are also microglial inhibitors but I didn't see it in your list:


Proton pump inhibitors can reduce the inflammatory state of microglia

Since some PPIs like omeprazole can rapidly penetrate the BBB [87], they would have the potential to interact with microglial cells. Activation of microglial cells may play an important role in the regulation of autoimmune inflammation in EAE and MS [103,104]. Activated microglia are thought to exert toxicity towards neurons via the production of potentially neurotoxic molecules such as proinflammatory cytokines and superoxide radicals [105]. For example, lipopolysaccharide (LPS)- and IFN-γ-stimulated human microglia show significant toxicity towards neurons in culture [106]. However, when LPS- and IFN-γ-activated human microglial cells were exposed to lansoprazole or omeprazole, they displayed less toxicity towards neuroblastoma cells in culture [107]. Microglia may also perform protective functions, such as secretion of neurotrophic factors and the protective cytokines TGF-β and IL-10 [103], thus the role of PPIs on these functions deserves further study.

 

[Hip]

Seems to me that PPI are also microglial inhibitors but I didn't see it in your list:

Thanks. However, looking at the paper and the paragraph you quoted, I can't see where the authors have cited any papers demonstrating that omeprazole or other PPIs can inhibit microglial activation.

But I found this paper which says:

PPIs possess anti-inflammatory effects and can decrease human microglial and monocytic neurotoxicity. They suggest that PPIs combined with NSAIDs may be effective in the treatment of a broad spectrum of neurodegenerative diseases associated with activated microglia.

So I added PPIs to the list.

 

[pattismith]

Thanks. However, looking at the paper and the paragraph you quoted, I can't see where the authors have cited any papers demonstrating that omeprazole or other PPIs can inhibit microglial activation.

But I found this paper which says:


So I added PPIs to the list.

you may be right according to my own experience.

15 years ago, I was hit by a sudden painful syndrome around my hips, pelvis and upper legs/sacrum; it was not clear if tendons or joints or muscles or other substructures were involved.

It was permanent, with no difference between standing or lying positions.

I saw some specialists, but no one helped. I finally had a kind of diagnosis "neuropathic pain"...that's it and good luck...

This was 2 years after the bigining of my syndrome. So I started to experiment with some meds.

I found that opioids could releave my pain, and I started also NAIDS (Piroxicam) + Omeprazole.

I took it for three years at low dose because my stomach was upset, and 3-4 years after, I was able to stop all my medications.

The effect was very slow, so I didn't notice any difference at first, but it worked...

I am not totally cured from this pain, because it can show up from time to time but it never come back as strong (of course I never pushed myself as much as I did just before it hit me).

So I believe these drugs have helped, although it was slow....And after that I was exhausted, I think my B12 level was very bad....

I would advise to take B12 shots during such a treatment.

Now it is advised to kill Helicobacter Pylori before long AINS courses, but of course I didn't at that time...

 

[knackers323]

@Hip did you get much benefit from bromantane, mood or otherwise?

 

[Hip]

@Hip did you get much benefit from bromantane, mood or otherwise?

I have not yet tried it properly, but in one brief test at a low dose of 12.5 mg, it seemed to increase mental focus and concentration a bit.

 

[frederic83]

Seems to me that PPI are also microglial inhibitors but I didn't see it in your list

I'm not sure if it is relevant but I took PPIs for five years, and once I stopped it I noticed I needed to sleep more (around two hours) and it takes longer to fall asleep with the melatonin.

 

[pattismith]

@Hip ,

your great work mentions Vinpocetine.
Interestingly, Vinpocetine appears to be a potent blocker of NaV1.8 voltage gate channels.

https://www.researchgate.net/public...tion_in_neuroprotection_Effect_of_vinpocetine

http://jpet.aspetjournals.org/content/306/2/498

One other NaV1.8 blocker is Ambroxol, which was shown to improve Fibromyalgia in open studies.

Ambroxol, beyond is also a cytokine modulator

https://www.ncbi.nlm.nih.gov/pubmed/14504727

https://www.karger.com/Article/Pdf/56297

 

[Hip]

Vinpocetine is also a cerebral vasodilator, which might combat the reduce brain blood flow in ME/CFS.

 

[Ema]

@Hip ,

your great work mentions Vinpocetine.
Interestingly, Vinpocetine appears to be a potent blocker of NaV1.8 voltage gate channels.

https://www.researchgate.net/public...tion_in_neuroprotection_Effect_of_vinpocetine

http://jpet.aspetjournals.org/content/306/2/498

One other NaV1.8 blocker is Ambroxol, which was shown to improve Fibromyalgia in open studies.

Ambroxol, beyond is also a cytokine modulator

https://www.ncbi.nlm.nih.gov/pubmed/14504727

https://www.karger.com/Article/Pdf/56297

Looks like ouabain, which I widely (perhaps erroneously?) credit with resolving my POTS symptoms also works on this NaV1.8 channel. I did not notice an effect on pain with it though. Hmmm.

 

[Hip]

Looks like ouabain, which I widely (perhaps erroneously?) credit with resolving my POTS symptoms also works on this NaV1.8 channel.

Ouabain looks like a very interesting compound! I see you wrote a blog on it.

 

[pattismith]

Interestingly, Lithium seems to be a voltage gated sodium channel blocker in some cells, (I wonder if brain cells are concerned)

Looks like ouabain, which I widely (perhaps erroneously?) credit with resolving my POTS symptoms also works on this NaV1.8 channel. I did not notice an effect on pain with it though. Hmmm.

Thank you for the link, it is not clear to me if Ouabain has an effect on Nav1.8 (sounds like it is only an indirect one), but if it has some, it is not clear to me if the nociceptive effect is mediated by this effect or by the inhibition of the Na/K ATPase pump...

 

[renski]

Some good info here re neuroinflammation: https:// www.youtube.com / watch?v=IV9oEZ1aUGY (46:32)