Brain Fog is likely mast cell and glial inflammation.

cherubim

Well-Known Member
I am familiar with dex...I took a low dose of it when I was diagnosed with adrenal insufficiency, but I've since stopped it.

It does not activate nrf2...if anything, it inhibits it.
Did you recover from adrenal insufficiency? I'm currently trying DHEA - another anti-inflammatory which helps adrenal insufficiency. Why did you stop - did you have a bad response?

PubMed: "Anti-inflammatory efficacy of dexamethasone and Nrf2 activators in the CNS using brain slices as a model of acute injury." Maybe someone else can read it and decipher the article. it's anti-inflammatory - but the article was difficult to comprehend. I get very weary trying to sort it all out myself - which is why I came here. Sometimes supplements can help to a degree - other times one may need a heavy-hitter pharmaceutical. It would be interesting to know if anyone has found a pharmaceutical to up-regulate Nrf2. There is a neurologist - can't recall his name, who recommends Nrf2 activators.
 

cherubim

Well-Known Member
I read so much that my brain doesn't work after awhile. I thought it said something like that. Don't know what cAMP is.

You're familiar with dexamethasone? Have you ever tried it? That was one of the next things I was thinking of trying. I believe it has some Nrf2 activation properties, which I thought might help. I found a good research paper on it on PubMed.

I tried an Nrf2 booster on Amazon - Antioxidant Boost. Probably everyone has some type of oxidative stress going on that needs to be addressed - this is what I gathered from research.

I'm wondering what inciting factor would cause a system to continue to pump out glial cells, when there was no need. Unless there was prolonged stress, and the normal shutoff mechanism wasn't working - in which event, meds like ibudilast are needed. I suppose it is hoped that when one's system is calmed, then the medications are no longer needed.

I wish I had some type of medical background so that I already understood the basics. Wouldn't it be nice to be a doctor to at least write your own prescriptions, instead of pleading with a doctor to try you on one?

God help us.
Here is a link I was researching on Dexamethasone: http://link.springer.com/article/10.1007/s11481-011-9338-8

Maybe someone else can decipher it. It looks like a good bet.
 

rebar

Active Member
@Lostfalco, @Remy or whoever can answer. I'm concerned about ibudilast being anticholinergic like Benadryl or Seroquel. There has been association with dementia for some time now. In 2015 and this year studies have shown a direct link in the elderly. I'm concerned because I took for over 10 years Seroquel to help my insomnia, I've got memory issues now, could be ME or could be the anticholinergic I previously took. I reread everything here on ibudilast and can't determine.
Is the ibudilast anticholinergic?
 

Lostfalco

Active Member
@Lostfalco, @Remy or whoever can answer. I'm concerned about ibudilast being anticholinergic like Benadryl or Seroquel. There has been association with dementia for some time now. In 2015 and this year studies have shown a direct link in the elderly. I'm concerned because I took for over 10 years Seroquel to help my insomnia, I've got memory issues now, could be ME or could be the anticholinergic I previously took. I reread everything here on ibudilast and can't determine.
Is the ibudilast anticholinergic?
Hey rebar, there is no evidence that ibudilast is anti-cholinergic. Its primary effects are mediated through phosphodiesterase 4 inhibition (PDE4i) which has actually been connected with cholinergic release/facilitation in animal models.

"The facilitating effect of prucalopride on cholinergic neurotransmission in pig gastric circular muscle is regulated by phosphodiesterase 4." http://www.ncbi.nlm.nih.gov/pubmed/22266217

"Synergistic effect between 5-HT4 receptor agonist and phosphodiesterase 4-inhibitor in releasing acetylcholine in pig gastric circular muscle in vitro." http://www.ncbi.nlm.nih.gov/pubmed/27060014
 

Remy

Administrator
@Lostfalco, @Remy or whoever can answer. I'm concerned about ibudilast being anticholinergic like Benadryl or Seroquel. There has been association with dementia for some time now. In 2015 and this year studies have shown a direct link in the elderly. I'm concerned because I took for over 10 years Seroquel to help my insomnia, I've got memory issues now, could be ME or could be the anticholinergic I previously took. I reread everything here on ibudilast and can't determine.
Is the ibudilast anticholinergic?
I concur. I can usually tell when something is anticholinergic by its effect on my HRV and with ibudilast there has been zero change.
 

rebar

Active Member
Any link from ibudilast/galantamine and developing sleep issues. I'm also doing the nasal insulin, and I started the memantine.
I stopped the memantine after staying awake for most of 2 nights. It relaxed me, but felt very awake, or "on", not a wired feeling.

I struggle with insomnia, but this has gone from 5 to 6 hours to 3. Now off the memantine but no improvement.

Any ideas.

thanks
 

Remy

Administrator
Any link from ibudilast/galantamine and developing sleep issues. I'm also doing the nasal insulin, and I started the memantine.
I stopped the memantine after staying awake for most of 2 nights. It relaxed me, but felt very awake, or "on", not a wired feeling.

I struggle with insomnia, but this has gone from 5 to 6 hours to 3. Now off the memantine but no improvement.

Any ideas.

thanks
The memantine did the same to me...and it has a super long half life. Maybe give it a few more days?
 

Remy

Administrator
I know they do. But I don't expect them to know the local import rules for every Country ;)
Actually, it's in their interests to know the rules because if the package gets stopped, they are out the money, if they are reputable. If too many packages get stopped, they stop shipping to that country.
 

rebar

Active Member
I had noticed the half life I believe it to be 36 hours, I thought at the time it may complicate dosage, Remy are you still on it.
 

Remy

Administrator
I had noticed the half life I believe it to be 36 hours, I thought at the time it may complicate dosage, Remy are you still on it.
No, I gave up on the memantine. It gave me the worst tired but unable to sleep problems after a few days. Things are better now but I'm still a little restless, especially through the first half of the night.
 

cherubim

Well-Known Member
No, I gave up on the memantine. It gave me the worst tired but unable to sleep problems after a few days. Things are better now but I'm still a little restless, especially through the first half of the night.

I ordered it and was going to try it. Did you try taking Melatonin with it about an hour before bed?
 

cherubim

Well-Known Member
Why is that? You seem like you're well-informed. I tried the melatonin myself, but don't like it - but thought maybe someone else might benefit. It seems you can research hours and still miss some things.
 

Remy

Administrator
Why is that? You seem like you're well-informed. I tried the melatonin myself, but don't like it - but thought maybe someone else might benefit. It seems you can research hours and still miss some things.
I believe Jack Kruse when he says that you shouldn't take hormones you can make. I think before people start taking melatonin, they need to make the environmental changes that will allow them to make it themselves. I believe that exogenous melatonin mixed with blue light from screens has been conclusively shown to cause eye damage and glaucoma.

I also don't believe that megadosing hormones is usually a good idea and people regularly do that with melatonin...taking mgs when we only make mcgs a day.
 

cherubim

Well-Known Member
I hadn't heard that. I think I came across Jack Kruse's website - if I got the name right. He believes in sunlight. I read that sitting in the sun helps vitamin D disperse in the body - helping pain. It works differently than oral vitamin D.

I don't like taking any chemicals - but sometimes life circumstances force your hand. I didn't research the memantine well - but I hope it helps. It's good to hear of other's experiences - so that if you have that same reaction you won't attribute it to something else. Especially doing multiple therapies.
 
Fog/inattention/low alertness/cognitive issues are my no.1 complaint, precluding any useful endeavor most of the time. If there is one thing I could improve while waiting for the super-star scientists to come up with a full CFS 'cure', this would be it. So colour me interested! However, living in the 51st state (i.e. the UK) I'm skeptical about trying to acquire most of the substances you've discussed here: galantamine, Ibudilast, intranasal insulin (memantimine, cromolyn sodium, dexamethasone... etc). International Amazon delivery is irksome enough for me, heh (let alone extra customs delays and charges, uncertainty and unknowns about product quality and actually sorting out the purchases). Anyway...

I was using a choline/inositol supplement for awhile, initially it helped with energy and brain fog but over time the positive effects lessoned.

Alpha gpc is another cholinergic supplement i used a few years ago which was helpful. Then last year tried it again but got nothing out of it.
Very similar experiences here. A few years back I pinned some temporary improvements on choline bitartrate, with a correlated reduced need of sleep duration. Shortly after I managed 3 months of almost regular 24 hour sleep cycle for the first time in years of 25 hour long, progressing rhythm (now 26 hours).

I pinned this fix potentially on re-establishing the last, actylcholine dependent, link of the SCN clock resetting chain (from retina light detection). Although I was taking a lot of other supplements then too (including morning tyrosine, night time 5-HTP and (small dose) melatonin) which were too cumbersome to continue, given no other functional benefits and declining mood.

Also, a couple of weeks ago I tried out Alpha-GPC and felt like I was half-fixed for 3 days. Much more physically active and capable, reduced fog. Until I got cocky and tried half an avocado with a squeeze of lemon and got knocked down for 3 days (histamine delayed fatigue reaction, longer than normal). Haven't recovered that peak response since. (Although, that type of one time revelationary response has been fairly common for me, with various supplements, going all the way back 10 years to a delicious 2 day bout of hypomania when I first tried 5-HTP, but never recurred - the metabolic memory there, fascinating.) Interestingly, the positives only kicked in with the full 300mg capsule, nothing notable with sprinkling half (150mg) on my breakfast. Doubling up from this didn't seem to suit me, but it's always a bit tricky to tell against the background 'noise'.

I personally hit upon alpha-GPC as an ingredient in @Diana Driscoll's Parasym Plus https://vagusnervesupport.com/ (one that I'd not tried before), after reading through her interesting interview with Yasmina Ykelenstam: http://thelowhistaminechef.com/dr-diana-driscoll-interview-vagus-nerve-and-potsmast-cell-activation/
Parasym Plus Label.jpg

Unfortunately I don't seem to tolerate (even sunflower) phosphatidylcholine pills (and am excluding eggs), so have been looking for a way to boost my choline in general. Also a little wary about supplementing it after reading about particular, common, gut bacteria that turn choline into TMAO (although not so much from a heart disease perspective, for me).

Neuroprotek
I got through a whole bottle of NeuroProtek (60 capsules) and noticed nothing, so stopped - pretty expensive and not suspicious of mast cell activation for myself.

------------------------​

Overall, with inhibiting microglia, is there likely to be a risk of reducing their capacity to do other of their many, still fairly ill defined other duties? I think I was reading that they seem to be increasingly found to be closely involved in synaptic functioning - plasticity, pruning, etc - as well as their contextually specialised immune functions. (e.g. quickly googled).
------------------------​

@Lostfalco - thanks for your article and popping in here. Regarding "What is brain fog", I think it's interesting talking about histamine release triggering an almost paradoxical action, via autoinhibitory (H3) receptors. Histamine circuits in the hypothalamus are central to alertness (along with orexin ones knocked out in narcolepsy) and possibly circadian rhythm entrainment. When I took Mirtazapine for a couple of days (many years back) it totally knocked me out, Kleine Levin syndrome style, for 20 hours of sleep per day. The hypersomnolence is a fairly well known side effect, and via inhibition of CNS histamine action, there.

So, much later (a few years ago), when I first figured out (from dietary reaction tracking) that I seemed to be histamine intolerant, I wondered if my primary symptom, of next day fatigue, was down to some kind of high histamine counter-balancing reaction in my CNS, like that, suppressing the alerting effects of histamine as a neurotransmitter... But then I decided that was overly complex speculation. Apparently "Histamine hardly passes the blood-brain barrier..." http://physrev.physiology.org/content/88/3/1183.full. But those parts of the hypothalamus are, anyway (I think), purposefully not protected from inflammatory signals in the blood, so as to induce the 'sickness behaviour', when ill (which conserves energy and whatever group evolutionary benefits from avoiding socialization, perhaps).

Is that kind of global brain effect the type of mechanism you talk about (and reference) as causing brain fog? Or is there instead/also localised histamine mediated effects (from glia/mast cells) that might only impact some parts of the brain and therefore various specific faculties?

"The H1 and H4 receptors are thought to increase permeability in the blood-brain barrier, thus increasing infiltration of unwanted cells in the central nervous system." Wikipedia. I think chemotherapy and ultrasound can also open up the BBB like this, with the main immune system leaking in, causing fog. (Perhaps interestingly, adenosine, which Naviaux found raised in his CFS metabolic study can also open up the BBB epithelia.)

All sounds very murky, cloudy, etc, but what is the actual mechanism of action in terms changes to neuron firing patterns, changing cognition? Can it not just be that the energy output of neurons is being capped by reduced mitochondrial output? Globally. When I think about the study of brain EEG readings, that what they seem to show is increasingly high frequency firing patterns for higher levels of cognition. Also, distant neurons communicate by synchronizing their frequencies, like radio channels. Then the more complex a task the brain performs, the more different brain resources (areas) will need to be connected at the same time, requiring more frequency bandwidth, pushing up the envelope of the highest frequency needed to hold the show together. So if cellular energy is handicapping firing rate, then cognitive complexity would be constrained too...? At least, that what it kinda feel like to me, when I can't hold a thought together for long enough to execute it, or bits of my working memory keep falling off the map...

Sorry, much rampant blathering again. Any coherence?
 

cherubim

Well-Known Member
I had a bad reaction to sunflower lecithin also. I take non-GMO soy lecithin every once in awhile to keep cell lipids intact.
 

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