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/
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).
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.
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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).
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@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?
