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A map of metabolic phenotypes in patients with myalgic encephalomyelitis/chronic fatigue syndrome, 2021, Fluge, Mella et al
- Thread starter Sly Saint
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I don't know what they mean, but maybe being too sedetary could make our condition worse? I guess being somewhat active, being careful not to trigger PEM, could be beneficial. At least I can say it is that way for me. Needless to say this wouldnt work if you are severe / bedbound, but if you are moderate / mild, trying to take a few short walks every day might help.
ukxmrv
Senior Member (Voting Rights)
The energy to do the "few short walks" has to come from somewhere though and they may need to stop useful things like housework or personal care or earning a living in order to save the strength to walk. Even moderate and mild patients may already be acting at the top of their available energy resources with a big "wish list" of useful things they would love to do.
Yep exactly as someone with mild end of moderate ME for me any physical activity has to have a practical purpose in support of daily living needs like washing my clothes or cooking, social activity like meeting friends occasionally usually involves some walking. Based on the activity I need to do each day, or week, I have to limit social activity to probably once a week because it requires walking. Also have to spread out appointments so doing walking solely for exercise is not a realistic option.
Kalliope
Senior Member (Voting Rights)
Two articles today about this study. One from a news site about research and one from the Medical Faculty at the University in Bergen. I am grateful for some comprehensible summaries of the study, and hope the google translations are not too bad.
Forskning.no Forskere i Bergen foreslår at ME kan kobles til svikt i energi-forsyningen til cellene
google translation: Researchers in Bergen suggest that ME can be linked to a failure in the energy supply to the cells
Quotes:
- What we believe may be an explanation is that a restriction in the blood flow during activity means that the cells receive too little oxygen, and that this leaves metabolic traces over time, says Karl Johan Tronstad.
...
Ola Didrik Saugstad is a pediatrician and professor of pediatrics. Among other things, he researches ME. Saugstad is impressed with the researchers' work.
- It is a very exciting and very thorough study, he says.
- I think you can use big words and say that it shows that this group is completely in the international lead when it comes to ME research.
University in Bergen - ME kan knyttes til energisvikt i cellene
google translation: - ME can be linked to energy failure in the cells
Quote:
What Tronstad and his colleagues have found supports a theory that ME disease is linked to a persistent disruption of the cells' ability or ability to satisfy energy needs.
That some changes are expressed in different ways in the different patients, Tronstad explains that the body has different methods of dealing with threatening situations. He mentions fasting as an example: When one fasts, the normal supply of nutrients to the cells is limited and the body will then react by supplying the cells with alternative energy sources via the blood. Such metabolic compensation mechanisms can be affected by disease, and can then vary somewhat from person to person.
- In ME patients, we found characteristic features of two types of metabolic adaptations in particular, where one seemed to be associated with a more serious symptom picture. Factors that may come into play are diet, medication, genes, and lack of physical activity, says Tronstad.
The findings also fit well with the fact that the symptoms are often aggravated by physical activity. During physical activity, there are higher requirements for energy supply to the cells. If the energy supply does not work properly, the stress on the cells increases.
That the error in the energy supply is due to a failure in the immune system is only a hypothesis, but it also agrees well with the findings:
- Specifically, it may be an autoimmune mechanism that weakens the blood supply under load. When we do something active, the blood supply is adjusted to enable activity, but in ME patients this self-regulation may be blocked, says Tronstad.
Forskning.no Forskere i Bergen foreslår at ME kan kobles til svikt i energi-forsyningen til cellene
google translation: Researchers in Bergen suggest that ME can be linked to a failure in the energy supply to the cells
Quotes:
- What we believe may be an explanation is that a restriction in the blood flow during activity means that the cells receive too little oxygen, and that this leaves metabolic traces over time, says Karl Johan Tronstad.
...
Ola Didrik Saugstad is a pediatrician and professor of pediatrics. Among other things, he researches ME. Saugstad is impressed with the researchers' work.
- It is a very exciting and very thorough study, he says.
- I think you can use big words and say that it shows that this group is completely in the international lead when it comes to ME research.
University in Bergen - ME kan knyttes til energisvikt i cellene
google translation: - ME can be linked to energy failure in the cells
Quote:
What Tronstad and his colleagues have found supports a theory that ME disease is linked to a persistent disruption of the cells' ability or ability to satisfy energy needs.
That some changes are expressed in different ways in the different patients, Tronstad explains that the body has different methods of dealing with threatening situations. He mentions fasting as an example: When one fasts, the normal supply of nutrients to the cells is limited and the body will then react by supplying the cells with alternative energy sources via the blood. Such metabolic compensation mechanisms can be affected by disease, and can then vary somewhat from person to person.
- In ME patients, we found characteristic features of two types of metabolic adaptations in particular, where one seemed to be associated with a more serious symptom picture. Factors that may come into play are diet, medication, genes, and lack of physical activity, says Tronstad.
The findings also fit well with the fact that the symptoms are often aggravated by physical activity. During physical activity, there are higher requirements for energy supply to the cells. If the energy supply does not work properly, the stress on the cells increases.
That the error in the energy supply is due to a failure in the immune system is only a hypothesis, but it also agrees well with the findings:
- Specifically, it may be an autoimmune mechanism that weakens the blood supply under load. When we do something active, the blood supply is adjusted to enable activity, but in ME patients this self-regulation may be blocked, says Tronstad.
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Kitty
Senior Member (Voting Rights)
This has been talked about for years, hasn't it. I remember reading (I think in the 90s?) about theories that the burning in our muscles after activity, which doesn't feel like a muscle strain or the soreness that follows unaccustomed exercise, might possibly be due to a mild reperfusion injury.
Let's hope they're able to progress the work further. If they're right, it would be great to have good evidence on which other research groups could base funding applications too.
Kalliope
Senior Member (Voting Rights)
One of the Norwegian articles about the study has now been translated into English. I thought the article was good in explaining for general readers what was found and what it means:
Science Norway ME/CFS may be linked to failure in energy supply to the cells
Invisible Woman
Senior Member (Voting Rights)
Equally, as a hypothesis that could be harmful for some.
That's how I tried to manage my ME once I understood the pattern caused by PEM as I experienced it. I sacrificed a lot to keep physical function up.
However (& I'm sorry folks I know I bang on about this) we know that we can already trigger PEM and be in the early stages of it up to 3 days before symptoms may become noticeable. So it is entirely possible that there is a stage where cumulative damage or deterioration may be caused without triggering PEM. This could lead to a gradual decline in function & an increase in disease severity over time for some people.
I have no doubt that some movement is needed for the body to stay healthy but I think there are some of us for whom the damage that might be caused by activity even without overt PEM may be worse than the problems caused by inactivity.
For some there may not be that sweet spot of getting it just right no matter how careful we are.
The big problem is we don't know what processes drive PEM . We don't know who is at most risk of long term deterioration.
Either way, whether you try to do something little and often or not there's risk and not enough information for us to make informed decisions.
That's before we consider that ME is a fluctuating condition so a 5 minute walk that takes up ½ spoon of energy today may take 5 spoons of energy on Saturday.
How would you suggest to correct these dysfunctions if we do not understand why they occur, and the source of the problem? It is more complex than “ your potassium is low, eat bananas”.
Well, i just speculate, i dont have any scientific background. Some weeks ago i read a paper that 90 % of metabolic dysfunctions are treatable. There are many diseases where you dont understand the source of the problem but you are able to treat the consequences of the problem. Maybe it's not the cure but you can often improve the patient´s health. Just your example the potassium level is low, you dont know why but you take supplements and your potassium level is normal. Sometimes it improve your health sometimes it is more complex and you dont see any improvement.
Here I try to speculate if Fluge/Mela identified the phenotypes with specific metabolic problems if it´s not worth to try to fix these metabolic problems and to see if it improves patients health. But how you say maybe it´s more complex and it wouldn´t do anything but without trying we dont know.
Murph
Senior Member (Voting Rights)
A long time ago I compared the findings of this study to those of Germain, Hanson et al 2018. You can see the results below. Agreement between the two studies is moderate and that's a consistent feature of metabolomic studies. I hope to do more like this.
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please do
ME/CFS Skeptic
Senior Member (Voting Rights)
Thanks for the interseting comparison @Murph
A (likely stupid) question from someone with no experience with metabolomics: I noticed that you plotted 'level in cases divided by level in controls': would it make sense to plot the concentrations in each study directly so that they are not influenced by the controls?
Do you mean in the field of ME/CFS or in general?
That would be great.
A (likely stupid) question from someone with no experience with metabolomics: I noticed that you plotted 'level in cases divided by level in controls': would it make sense to plot the concentrations in each study directly so that they are not influenced by the controls?
Simon M
Senior Member (Voting Rights)
This is great, thanks. Can you tell us the R and p values (if p values are appropriate comparing between studies)
It makes me happy to see your choice of theme for your ggplots @Murph, and your use of labs and captions 
I don't remember naming conventions in these studies, but are they the same so you could compare all the compounds they tested for without having to do some changes? I had to do a workaround with metabolic workbench to standardise metabolite names a few years ago when I wanted to compare findings from metabolomic diet pattern studies.
I wish more studies would provide their data so we could do these types of things ourselves..
I don't remember naming conventions in these studies, but are they the same so you could compare all the compounds they tested for without having to do some changes? I had to do a workaround with metabolic workbench to standardise metabolite names a few years ago when I wanted to compare findings from metabolomic diet pattern studies.
I wish more studies would provide their data so we could do these types of things ourselves..
Murph
Senior Member (Voting Rights)
Thanks for the kind feedback and intelligent questions.
just the few mecfs studies I've looked at. I started this project expecting to find a great deal of agreement. One reason I fizzled out is that all I couldn't find much agreement. What's more despite the studies often measuring thousands of molecules, overlap between them was slight. There sure are a lot of metabolites a person can measure~
IN some studies we only get standardised fold change data so it's not possible to compare in raw terms. And sample handlgin differences are likely to mean that raw values aren't too meaningful.
I recently found a way to very simply put the r^2 right on the plot so if I ever re-run these i'll do so. As i think you can tell by eyeballing them the results aren't good.
Yeah the different names of metabolites are a nightmare. I used a "fuzzy matching" program and then manually double checked to make sure it wasn't mixing up things. Some studies provide CHEMID and other meta-labels for the compounds. But there's more than one standard for labels and not every standard includes every metabollite! I'm not able to be sure i've found every match.
I see you also use R for data analysis! Possibly there's a package in R for matching metabolites. I haven't seen it but I wouldn't be surprised.
There seem to be a few R users here. I saw a few ggplots in the thread on EEfRT. Perhaps we could set up a github for sharing code to run analyses.
just the few mecfs studies I've looked at. I started this project expecting to find a great deal of agreement. One reason I fizzled out is that all I couldn't find much agreement. What's more despite the studies often measuring thousands of molecules, overlap between them was slight. There sure are a lot of metabolites a person can measure~
IN some studies we only get standardised fold change data so it's not possible to compare in raw terms. And sample handlgin differences are likely to mean that raw values aren't too meaningful.
I recently found a way to very simply put the r^2 right on the plot so if I ever re-run these i'll do so. As i think you can tell by eyeballing them the results aren't good.
It makes me happy to see your choice of theme for your ggplots @Murph, and your use of labs and captions
I don't remember naming conventions in these studies, but are they the same so you could compare all the compounds they tested for without having to do some changes? I had to do a workaround with metabolic workbench to standardise metabolite names a few years ago when I wanted to compare findings from metabolomic diet pattern studies.
I wish more studies would provide their data so we could do these types of things ourselves..
Yeah the different names of metabolites are a nightmare. I used a "fuzzy matching" program and then manually double checked to make sure it wasn't mixing up things. Some studies provide CHEMID and other meta-labels for the compounds. But there's more than one standard for labels and not every standard includes every metabollite! I'm not able to be sure i've found every match.
I see you also use R for data analysis! Possibly there's a package in R for matching metabolites. I haven't seen it but I wouldn't be surprised.
There seem to be a few R users here. I saw a few ggplots in the thread on EEfRT. Perhaps we could set up a github for sharing code to run analyses.
Not sure how often this would be possible with the available data, but sub-grouping by sex may be helpful.
I may be mistaking @Murph here, but I read it as a problem of studies not including the same metabolites and thus one can't compare the studies findings since they are looking at different metabolites. This problem is compounded by studies often only referring to their "top different" metabolites between groups, without providing any sort of raw data so one can look at the other metabolites in the study.