I am fascinated w/ the potential for sodium bicarbonate in #MECFS + #Fibromyalgia.
Used by athletes + studied for decades + there is OK evidence of weak performance gains
BUT @remissionbiome is interested in myalgia, muscle soreness, DOMS. 1/n
Four things have really captured my attention. A new topical delivery version that makes the GI effects a non-issue. 2. Vagal nerve connections. 3. DOMS (delayed-onset muscle soreness) is reduced. 4. direct lactate effects are seen (very common in #MECFS). 2/n
Characterization of the Human Skeletal Muscle Metabolome for Elucidating the Mechanisms of Bicarbonate Ingestion on Strenuous Interval Exercise pubs.acs.org/doi/pdf/10.102… 3/n
I am surprised how well this stuff seems to help muscle pain. Its a bit odd actually. It really really helps and its super fast. I am more than a bit miffed as while there is decent literature on bicarb on muscle soreness - that the topical version works well its surprising. 6/n
@PeterAttiaMD tweeted re: PR lotion + was on fence for performance BUT its muscle soreness that I am interested in here.
If lactic acid/lactate is one of the main culprits of myalgia and the topical lotion affects it - maybe this makes a lot of sense? 8/n
There is some evidence that the oral bicarbonate does affect DOMS (delayed onset muscle soreness) for athletes. I have often wondered if the myalgia soreness of #MECFS and #Fibromyalgia is biochemically similar to DOMS in athletes. 9/n
Because lactate is an important marker for us in @remissionbiome this is really key for us. We will be using lactate meters throughout the experiment and there is a possibility that lactate consuming bacteria triggered the 'event'. 10/n
We will be trying out PR lotion (I have been experimenting for a week) + using oral bicarbonate for the vagal trigger benefit.
"Can a basic solution activate the inflammatory reflex? A review of potential mechanisms, opportunities, and challenges" 11/n
It is possible to have normal oxygen saturation and pathological hypoxia at the same time? In certain conditions like #ME and #LongCovid this is likely what is actually occurring. Some tissues (like brain and muscles) are not getting enough oxygen.
To make matters worse it is possible that epigenetic 'memory' of the sick state is part of what might keep us sick (even when an acute illness ends) - and that changes in oxygen gradients in tissues (pathological hypoxia) is a trigger for these epigenetic changes.
We don't have a definitive answer yet but interactions between inflammation + the immune system + pathological hypoxia (low oxygen) may provide some clues that this is indeed occurring.
It can be hard to wrap ones head around having low oxygen or hypoxia when your smart watch shows normal oxygen saturation.
BUT! It is oxygen USE that is the issue, not that it is there is the first place. When we look at oxygen getting to the brain and oxygen use in the muscles, we see a different story.
It is obvious that hypoxia would interact with the immune response and inflammation and changes oxygen gradients in different tissues.
"These changing oxygen gradients are exaggerated during inflammation, where oxygenation is often depleted owing to alterations in tissue perfusion and increased cellular activity."
Pathological hypoxia also interacts with Mast Cells - causing them to degranulate and release inflammatory meditators. Obviously those that have MCAS might need to pay particular attention to hypoxia as a risk factor to help manage Mast Cells.
If activity also restricts oxygen in brain and muscles this could be one reason why physical activity can lead not just to crashes but also MCAS flares and its maintenance when all other triggers have been removed. (note: mast cells can also release interferon-gamma!!).
Hypoxia potentially interacts with ME and LC disease processes in many ways, affecting inflammation, immune responses including mast cells, and even epigenetics. Hypoxia might induce epigenetic changes in immune cells, such as chromatin remodeling, which can have long-lasting effects leading to 'immune memory' and a change of state from pre-illness that is hard to turn back.
Practically, this means that immune cells exposed to hypoxia may retain a "memory" of this exposure, affecting their response to future infections or inflammatory signals.
"How oxygenation shapes immune responses: emerging roles for physioxia and pathological hypoxia"
We all know that too much screen time can be hard on the eyes and brain, but if you have #ME or #LC it can be a major element of daily life that needs to be managed.
This is because screens both indirectly and directly are related to neuroinflammation - which we already suffer from.
I wish this paper focused less on healthy people/kids and developmental patterns and more on disease conditions and biology - but regardless - I copied the relevant sections on neuroinflammation and circadian cycle disruption (article is paywalled).
This is a topic that really needs to be covered for #ME specifically given our underlying neuro-issues. Using larger screens, blue light blockers, e-ink readers, special eye safe screens, screens with low flicker frequency and checking your tech to make sure if is not one of those units that people complain about are all options. I also wear 'Avulux' migraine glasses.
I upgraded to a 15.6" laptop with a high resolution screen a year ago and this was a great move for me. The smaller the screen is the harder I 'look'.
Search my feed for previous discussions of screen usage: "screens (from:chydorina)"
Interconnections of screen time with neuroinflammation (2024)
Have you ever felt like your brain was on fire? This feeling is often linked to "Glutamate Excitotoxicity" - a process where neurons are exposed too high concentrations of the excitatory neurotransmitter glutamate leading to neuronal cell death.
Read paper: "Excitotoxicity Revisited: Mitochondria on the Verge of a Nervous Breakdown" (linked in comments)
Its probably quite common in #MECFS but then again it is super widespread across many neurodegenerative conditions and psychological disorders - which means that it would great to treat it but in and of itself treating it is not going to 'cure' MECFS.
Because it is SO widespread across so many conditions it has been heavily studied and there have been major research efforts to see if interventions could be developed to manage it (see image below).
Unfortunately (or maybe even fortunately as messing with fundamental pathways like this could have major unknown consequences) it has not been very amendable to direct treatment interventions.
There is however a way to help manage dysfunctions in this system. A backdoor so to speak. This is because the problem is not so much the glutamate itself, it is that the mitochondria are doing a poor job of processing it.
So, instead of trying to mess around with the glutamate levels directly or affect the clearance of glutamate we could instead focus on the mitochondria - which we know are struggling in MECFS.
"Therefore, one possibility might be to couple drugs that impact the glutamate responses with interventions that support mitochondrial bioenergetics, for example by promoting mitochondrial biogenesis or supporting intermediary metabolism, impacting both the mechanisms that may contribute to neurodegeneration in these diseases."
Check out the linked paper: it will really flesh out for you why glutamate has been such a heavily researched subject.
The bottom line is that mitochondrial function is probably where we should be focusing our intervention effort.
Methylene Blue, Photobiomodulation (PBM), the NAD pathway, Ellagic Acid and Urolithin a, as well as comprehensive protocols that address energy processing, amino acids, ALCAR and mitochondrial cocktails such as are used in mitochondrial disorders.
The Born Free protocol is also EXPLICITLY designed to modulate mitochondrial function.
Astaxanthin might also be worth looking into for these indications. see paper link below in comments.
Astaxanthin Protection against Neuronal Excitotoxicity via Glutamate Receptor Inhibition and Improvement of Mitochondrial Function (2022)
This makes me a little sick just considering this but I would not be surprised if Auvelity (a mix of dextromethorphan and bupropion) starts being pushed like crazy in #MECFS #LongCovid.
Given the big SSRI - serotonin/LC papers that hit in the last year you can actually see the lead up to these new psych meds being released for LC.
Adding an NMDA receptor antagonist to an anti-depressant is really insidious. If Auvelity worked for LC it would be the "dex" component and not the bupropion. We have known for ages that NDMA receptor antagonists might be helpful - other options are ketamine, memantine, as well as safer stuff like Magnesium, Zinc, L-theanine, NAC.
NMDA receptor antagonists are used for glutamate ecotoxicity (brain on fire) symptoms. We do have glutamate excitotoxicity but it is also present across most neurological conditions and many other diseases including depression. It is not a lever that will 'fix' MECFS in and of itself.
I have been hearing a lot about 'dextromethorphan' lately on X and while it is available OTC in cough syrup - its obviously not helpful to Pharma that needs it to be RX. So? A new drug mixing it with an SSRI (bupropion). If you want to try 'dex' just try the OTV version. Dont give in and get pushed into an SSRI.
Repeat: If you must try 'dextromethorphan' - please just get the OTC drug store stuff. Adding SSRIs just to try in post-viral conditions could have negative consequences. These are not disorders that will be fixed with psych meds.
I first tried "dex" back in 2014. All these interventions just keep going through cycles - we all try them - most fail and many have baseline decreases. It is not a miraculous PEM buster but it can lower glutamate ecotoxicity.
Its obvious the media is going to promote the #$%^& out of this:
What wont fail? Basic foundational optimization: nutrition, minerals, electrolytes, microbiome. Until our biochemistry is less dysfunctional and we actually are getting nutrients from food - nothing is going to work 'properly'. Doing this above is an intervention that will always be worthwhile. It may not make you better in and of itself, but it will set you up for it when 'disease modifying interventions' come down the pipeline.x.com/search?q=dextr…
This is pretty interesting (and actually somewhat surprising). I have known that plasmalogens were going to get major attention in the coming years for a wide range of conditions, from #LongCovid and #MECFS to autoimmune conditions like #MS, neurodegenerative conditions like #Alzheimers #Parkinsons and also cardiovascular conditions but this new paper (out of Australia) suggests that in the coming years we might be seeing a new standard cardiovascular marker based on plasmalogen levels.
I am not surprised by the evidence or usefulness of plasmalogen supplements - suggesting that plasmalogen levels should be used more generally as cardiovascular markers suggests that the potential importance of plasmalogens is really reaching the mainstream.
In this paper they discuss using shark liver oil. I am obviously not a fan of this source (I actually supervised a PhD thesis on shark biology and the consequences of shark fisheries on declines in top down control in oceans when I was a prof). Dr. Goodenowe has pioneered the production of synthetic plasmalogens which I believe are the best choice for a wide variety of reasons.
Development and validation of a plasmalogen score as an independent modifiable marker of metabolic health: population based observational studies and a placebo-controlled cross-over study (2024)