Replicated blood-based biomarkers for ME/CFS not explained by inactivity [preprint], 2024, Beentjes et al
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Why?
I wonder if widespread endothelium dysfunction manifests in the liver to a large degree just as it does with reduced blood flow to the brain.
Would you say that brain changes are faster? Because rapid and temporary changes in lucidity and temperament are fairly well-known to occur in dementia.
Mary
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Actually, I think Chris Ponting is a bit fuzzy on this - he says:
I think he might be distinguishing between people who he considers to have ME/CFS ("post-viral chronic fatigue") and people with other fatiguing conditions - e.g., liver dysfunction. At least that's how it appears to me.
I think the real problem is we don't have a definitive biomarker. We badly need one. He says it's a massive mess:
Everything I read says that PEM is the hallmark of ME/CFS. And there is a test for this - 2-day CPET - only it's expensive, and very difficult for persons with ME/CFS to do and can cause further harm. So not possible for most of us. And PEM is not a hallmark of liver disease.
I agree.
I don't think so. Here's a list of of symptoms of liver disease provided by AI when I googled "liver disease symptoms":
Most of these don't apply to most posters here, or at least they're not posting about them. And people here do post about everything. I think they would be posting their lab results with abnormal liver markers, etc., as well as symptoms of liver dysfunction.
Anyways, I guess we're not going to agree on the role of the liver in ME/CFS. You and Mario Vitali could be right, though I doubt it . . . hopefully someday in the not too distant future we'll get some definitive answers achieved with testing done with rigorously screened patient cohorts - we can always hope, right?
His paper is on ME/CFS, if he thinks there are people in his sample who don't have ME/CFS, I would think that he would make it clear.
No, I think he thinks there are ME/CFS patients in his sample who have liver disease.
By the same token, dementia is not a hallmark of cardiovascular disease, but cardiovascular disease is a risk factor for dementia.
The symptoms you listed are those typically seen in severe liver disease. Milder forms of liver disease often have no clinical symptoms. Liver disease is often found incidentally when a scan is performed for other suspected conditions.
As I said previously, most people think that the liver is just involved in digestion and detoxification, so they would not think to test their liver function, much less post the results.
Remember though, absence of evidence is not evidence of absence.
You're free to have your doubts, but I'd just say that mariovitali and I have done quite a bit of research on the liver. This paper provides us with another piece of evidence pointing in the same direction and I think it would be a pity if people dismiss it for weak reasons.
linusbert
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for me checking the list, non applys except sometimes nausea, sometimes no appetite, a bit hair loss, minor memory problems, confusion very rarely and usually can be attributed to a certain environmental trigger.
BUT i still believe we or i could have a functional liver deficiency (no known name of a disease) of some sort. that means due to energy deficiency, the liver does not work properly, like most other organs as well. so it kinda works enough to not get the symptoms of liver failure, but enough so that the body is not detoxifying properly and bad stuff accumulates.
I think so. Don't some tranquilizers work very rapidly? While not brain cells, electric shock has immediate effect on nerves. Glial cells are sending out processes and pulling them back in very rapidly, I think it's thousands of times a second, so there's very rapid processing going on. If a drug affected those processes, it would affect brain function as soon as those molecules reached the cells.
I haven't heard of the liver changing states in that sort of time frame, although I haven't had any reason to read much about liver function, so that might just be ignorance.
Does the liver produce any signalling molecules that have dramatic effects on brain function? For all I know (and don't know), some squishy organ somewhere in the body does produce some rapid brain-altering signals, which could cause the observed switching of ME state.
Sure, if you're talking about drugs. Many drugs are designed to work rapidly, and not just on the brain.
In fact, the brain is the most difficult organ for drugs to get to because of the blood brain barrier.
Bile acids, for one, directly as well as through the gut. It also affects the metabolism of molecules that affect the brain, like insulin and cortisol.
All right, but how rapid is the effect on the brain? Also, how rapid is the change in bile acids? If the hypothesis is chronic liver dysfunction, how likely is taking some spice or nutrient going to result in a switch to full non-ME state half an hour later?
It's possible for many organs to have some pathway that would result in a rapid change in brain function through some possibly convoluted biochemical pathway. However, the likelihood may be very small, especially if it also requires that the organ not show any obvious sign of dysfunction. I'm just not seeing any reason why the liver should be more likely involved than the gut, which has direct connections to the brain.
Statistics might help decide the worthiness of the liver hypothesis. Is there an abnormally high number of PWME who also have comorbid liver disease? Alcohol affects liver function, so does drinking affect ME symptoms? There are probably other simple tests of the liver-ME hypothesis.
Your questions are not necessarily relevant because a substance can resolve a symptom without addressing the root cause. For example, in diabetes caused by obesity, blood glucose is raised because of increased insulin resistance and/or increased glucose production. A sulfonylurea drug can rapidly reduce blood glucose by increasing insulin secretion but that does not address the root cause, which requires the slow process of weight loss.
Diseases of the brain, kidney and liver can all progress to a late stage without being recognised. And "not recognised" is not exactly the same as "not obvious". A symptom may be obvious but the underlying cause is not recognised.
The liver affects the gut.
You are on a thread that is discussing a paper that found pwme have traits that are indicative of liver disease.
I checked the paper and didn't find evidence that convinced me that liver disease was involved. If ME is screwing up people's immune system and various organs depending on the individual, it seems reasonable that the liver would show some abnormal function. I wouldn't call "elevated ALT, ALP, and GGT, and low urea levels" as traits, but rather "something might be wrong somewhere in the body". If a group of people ingested a toxin, wouldn't that result in abnormal liver factors, without it being liver disease?
I'm unaware of any abnormal readings for glial cells. I suspect they're involved, since they influence brain function, are affected by immune activation elsewhere in the body, and respond very rapidly, so they logically fit the symptoms and responses of ME. I don't see liver disease as such a good fit for ME.
Also, even if that was a counter to my favorite theory, it wouldn't affect what I see as a weakness in the claim that liver disease displays traits matching ME. I'm no liver expert, but those elevated readings don't convince me that they only show up with genuine liver disease.
Also, even if that was a counter to my favorite theory, it wouldn't affect what I see as a weakness in the claim that liver disease displays traits matching ME. I'm no liver expert, but those elevated readings don't convince me that they only show up with genuine liver disease.
Does the liver disease theory fit with the rapid onset of ME symptoms for some people? I think plenty of people feel flu-like symptoms one day and eventually realize they're not going away, but instead fit the criteria of ME. Are there liver diseases that switch on (and temporarily off) that rapidly?
For any theory of ME, it's important to consider the fit for timing, development (gradual increase vs abrupt), responses to other factors, etc, rather than just having a few symptoms match (lethargy matches a vast number of diseases) or a few measured quantities that might be caused by other conditions.
If they provided evidence that the measured abnormalities only fit genuine liver disease, I'd take the theory more seriously. With ME, I expect some organs will show some minor abnormalities. We're simply not 100% healthy, so something is abnormal, and given the complex interactions in the body, that means that there might be a large number of downstream abnormalities, some common to most PWME, and some varying with individuals.
For any theory of ME, it's important to consider the fit for timing, development (gradual increase vs abrupt), responses to other factors, etc, rather than just having a few symptoms match (lethargy matches a vast number of diseases) or a few measured quantities that might be caused by other conditions.
If they provided evidence that the measured abnormalities only fit genuine liver disease, I'd take the theory more seriously. With ME, I expect some organs will show some minor abnormalities. We're simply not 100% healthy, so something is abnormal, and given the complex interactions in the body, that means that there might be a large number of downstream abnormalities, some common to most PWME, and some varying with individuals.