The thing about mecfs is that it appears to be stimulation intolerance rather than excertion intolerance. Patients are hypersensitive to all sorts of stuff, foods, sounds, light, excertion, emotions etc all cause fatigue. So there seems to be a frailty at the center of it that could be explained by cellular & organelle membranes being near the breaking point and therefore any stimulus that can cause an upset is not allowed.
First im throwing in how the cytoskeleton and the membrane is related. I think some results on the cytoskeleton in mecfs could be a hint thats pointing at the cellular membrane. Basically if there is something wrong with the cytoskeleton then it could affect the membrane negatively.
Genetic study from 2022 found the TPPP gene region to be the most associated with the disease although the result was not statistically significant, maybe because GWAS studies usually need alot more people to get results.
Quote about this gene from GeneCards
Another finding reported in 2022 from the NIH was the WASF3 gene overexpression which led them to do a follow up study.
I found the following quote at GeneCards
Research from 2020 by Missialidis et al shown below indicated a problem keeping an electric potential across the mitochondrial membrane, maybe because of proton leakage.
From 2019 there is the paper from Ron Davis that showed reduced deformability of red blood cells in mecfs patients, here is their conclusion:
Extracellular vesicles are blobs made from membrane lipids, i imagine that if the cell has inadequate membrane lipids then the vesicles it produces will be affected somehow. Here is a quote from a 2017 study
Here is another study on EVs that is supposed to show a relative abundance difference in charged groups in the membrane, im just putting in is a quote from its abstract:
Then there is the study from Lipkin et al where they found lower levels of many phospholipids in the blood, particularly plasmalogens seems to be at very low levels. Have a look at the chart in this post. This seems like a very important finding in my view, here is what wikipedia says:
Also there is this study that found association of worse health related to what lipids was found in the blood.
There are also indications that some patients may have low BH4. According to wiki BH4 is a cofactor for ether lipid oxidase. As mentioned above, plasmalogens are important members of cellular membranes, these are ether phospholipids and therefore possibly affected by low BH4 levels.
Me/cfs has also been associated with antiphospholipid syndrome, these lipids are important constituent of cellular membranes.
Further the recent poll on supplements revealed that a subset of pwme respond positively to carnitine. The most important job of carnitine is simply to transport actyl groups across one of the mitochondrial membranes. If mitochondrial membranes are compromised in a way that reduces the effectiveness of carnitine transporters in the mitochondrial membrane then its possible that increased concentration of carnitine could alleviate this effect. So again its possible to construct a membrane failure narrative for the carnitine signal.
The cellular membranes are the command center of the cell, they receive signals from everywhere that stimulate the extracellular receptors and thus cause changes to occur inside the cell. I imagine that dysfunctional membranes are leading to all sorts of cellular signaling failures. One speculation is that this type of signaling failure could be the cause of brain fog. A couple of examples include calcium signaling failure as researched by Staines & Gradisnik, or the Nf-Kb - redox - wnt/beta catenin signalling as reported by Maes, or the dysregulation of ephrin-eph signalling as reported by Hanson. I think these problems probably could cause a vicious cycle where the membranes are negatively affected leading to more signalling problems.
So thats the case i can make for membrane failure of cells and organelles as the cause of mecfs. Can be caused by alot of factors and therefore people with mecfs improve on very different sorts of treatments. Doesnt have to be e.g oxidative stress even if that would be a common way there. Anything that cause altered membrane composition in such a way that it becomes dysfunctional. E.g i imagine lack of certain lipids or just a dysregulation of lipid metabolism could affect what gets put into the membrane. The membrane is in constant flux, lipids coming and going all the time.
So if this theory holds up then there are probably lots of ways to end up with mecfs. Some autoimmune, some persistent virus etc.
First im throwing in how the cytoskeleton and the membrane is related. I think some results on the cytoskeleton in mecfs could be a hint thats pointing at the cellular membrane. Basically if there is something wrong with the cytoskeleton then it could affect the membrane negatively.
Genetic study from 2022 found the TPPP gene region to be the most associated with the disease although the result was not statistically significant, maybe because GWAS studies usually need alot more people to get results.
Quote about this gene from GeneCards
Another finding reported in 2022 from the NIH was the WASF3 gene overexpression which led them to do a follow up study.
I found the following quote at GeneCards
Research from 2020 by Missialidis et al shown below indicated a problem keeping an electric potential across the mitochondrial membrane, maybe because of proton leakage.
From 2019 there is the paper from Ron Davis that showed reduced deformability of red blood cells in mecfs patients, here is their conclusion:
Extracellular vesicles are blobs made from membrane lipids, i imagine that if the cell has inadequate membrane lipids then the vesicles it produces will be affected somehow. Here is a quote from a 2017 study
Here is another study on EVs that is supposed to show a relative abundance difference in charged groups in the membrane, im just putting in is a quote from its abstract:
Then there is the study from Lipkin et al where they found lower levels of many phospholipids in the blood, particularly plasmalogens seems to be at very low levels. Have a look at the chart in this post. This seems like a very important finding in my view, here is what wikipedia says:
Also there is this study that found association of worse health related to what lipids was found in the blood.
There are also indications that some patients may have low BH4. According to wiki BH4 is a cofactor for ether lipid oxidase. As mentioned above, plasmalogens are important members of cellular membranes, these are ether phospholipids and therefore possibly affected by low BH4 levels.
Me/cfs has also been associated with antiphospholipid syndrome, these lipids are important constituent of cellular membranes.
Further the recent poll on supplements revealed that a subset of pwme respond positively to carnitine. The most important job of carnitine is simply to transport actyl groups across one of the mitochondrial membranes. If mitochondrial membranes are compromised in a way that reduces the effectiveness of carnitine transporters in the mitochondrial membrane then its possible that increased concentration of carnitine could alleviate this effect. So again its possible to construct a membrane failure narrative for the carnitine signal.
The cellular membranes are the command center of the cell, they receive signals from everywhere that stimulate the extracellular receptors and thus cause changes to occur inside the cell. I imagine that dysfunctional membranes are leading to all sorts of cellular signaling failures. One speculation is that this type of signaling failure could be the cause of brain fog. A couple of examples include calcium signaling failure as researched by Staines & Gradisnik, or the Nf-Kb - redox - wnt/beta catenin signalling as reported by Maes, or the dysregulation of ephrin-eph signalling as reported by Hanson. I think these problems probably could cause a vicious cycle where the membranes are negatively affected leading to more signalling problems.
So thats the case i can make for membrane failure of cells and organelles as the cause of mecfs. Can be caused by alot of factors and therefore people with mecfs improve on very different sorts of treatments. Doesnt have to be e.g oxidative stress even if that would be a common way there. Anything that cause altered membrane composition in such a way that it becomes dysfunctional. E.g i imagine lack of certain lipids or just a dysregulation of lipid metabolism could affect what gets put into the membrane. The membrane is in constant flux, lipids coming and going all the time.
So if this theory holds up then there are probably lots of ways to end up with mecfs. Some autoimmune, some persistent virus etc.
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Im eating 3 eggs per day attempting to get proper fats but seems like thats not enough since upper tolerable limit of PC is 3,5grams and one egg is like 120 mg or something.