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Insights into myalgic encephalomyelitis/chronic fatigue syndrome phenotypes through comprehensive metabolomics, 2018, Lipkin et al

Discussion in 'BioMedical ME/CFS Research' started by Andy, Jul 4, 2018.

  1. Andy

    Andy Committee Member & Outreach

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    Open access at https://www.nature.com/articles/s41598-018-28477-9
     
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  2. Sasha

    Sasha Senior Member (Voting Rights)

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    Just makes me realise that if anyone ever unlocks this disease, I'm not going to understand what they're talking about... :confused:
     
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  3. strategist

    strategist Senior Member (Voting Rights)

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    There doesn't seem to be any unlocking of the disease here. It seems that every research group is seeing somewhat different metabolite profiles. There seems to be a broad agreement that energy production is affected but the details vary.
     
    Last edited: Jul 4, 2018
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  4. Wonko

    Wonko Senior Member (Voting Rights)

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    Does it mean anything?, or is it another in the sea of apparently meaningless papers that can't be put together yet.

    If it does mean something then what? and what would be the implications, what's the cause, what pharmacy of pills, potions, poisons and supplements should I be taking (and are any bacon sandwiches and doughnuts included in the treatment regime?)

    other things.............
     
    Last edited: Jul 4, 2018
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  5. Andy

    Andy Committee Member & Outreach

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    Which is why we will need the blog on this from @Simon M :)

    To unlock ME surely the odds are we will need a series of papers that refine/advance the theories from the previous ones, rather than just one or two. They do talk about antidepressants and supplement consumption as things to take into account in this paper which might affect the findings.
     
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  6. Trish

    Trish Moderator Staff Member

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    I don't have the energy to read it all yet. Maybe never.

    From a rapid glance through:

    Lots of familiar names among the authors.

    They are finding differences between pwme and healthy controls and claim potential biomarkers, but this will need lots of validation on bigger samples.

    They are finding stuff related to altered energy metabolism.

    Some of their test results were probably distorted by the fact that some of the patients and controls were taking drug treatments, specifically antidepressants, and supplements, specifically B vitamins.

    I'm surprised they don't either ask the patients to stop all drugs and supplements for a month (or however long is necessary) before study samples are taken, or find sufficient patients not on any medication or supplements - for metabolomics. Surely 'clean' samples are essential.

    My conclusion - it looks like a potentially useful step forward, but not a giant leap.
     
    Last edited: Jul 4, 2018
  7. strategist

    strategist Senior Member (Voting Rights)

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    Another limitation is the sample size of 50 patients and 50 controls. It feels a bit small for the hundreds of things they're measuring. Women and men have different metabolite profies and the men in the sample are too few to say anything about them. The other metabolomics studies had similar numbers I believe.

    Maybe we will see more consistency between larger studies.

    Fluge and Mella had 200 patients and they measured 20 amino acids rather than hundreds of metabolites.
     
    Last edited: Jul 4, 2018
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  8. Andy

    Andy Committee Member & Outreach

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    Thing I've learned today. From Wikipedia: Mannitol [which was found at higher levels in patients in this study] is popularly used as a cutting agent in cocaine...
     
    Last edited: Jul 4, 2018
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  9. Solstice

    Solstice Senior Member (Voting Rights)

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    Does this make us valuable to the cartels? I'm boarding up my house just in case.
     
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  10. Manganus

    Manganus Established Member (Voting Rights)

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    First of all, I think all of us see the same:
    Finally, there is flow!
    It's no longer only one odd study here, and one odd study there. They actually start to relate to each other, and papers come every now and then instead of just occasionally, as it used to be.

    This is a pity! :(

    This is a valid point. But not necessarily easy to accomplish, as it may make participation in studies less ..."inviting" in lack of a better word.

    Another similar point is that cultural factors also may be relevant. I mean: medical culture. It's easy to see the difference between the UK and the US, where treatment seems to be considerably more "active" or "engaged" in the US. But then we can guess that there are other differences with regard to societal or medical culture, that we not even think of (for instance between Norway and Australia). This is a factor that may explain some differences between research reports.

    Still, with the growing number of reports, a picture ought to crystallize. But I prefer to leave this judgement to the scientists, who have a much clearer head than I have.

    Being male myself, I start to think that maybe the bulk of work necessarily has to be done on females (for several reasons). But I'm really ambivalent when it comes to the issue of women-only studies. I am not good enough at statistic theory to conclude whether it's meaningful or not to have, like 15-20% males just in order to test if the significant results for women seem relevant for males too.

    In this report, it seems to have been just a waste. :(
     
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  11. Forbin

    Forbin Senior Member (Voting Rights)

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    Not that I claim to fully understand this, but I think a major take-a-way here is to be found in chart S3 in the Supplementary Figures & Tables.

    They take their previous work on bacteria and combine it with the top 10 predictive metabolites found in this study and find that they can differentiates (A): ALL ME/CFS, (B): ME/CFS with IBS, and (C):ME/CFS w/o IBS from controls with a high degree of accuracy. "ALL ME/CFS vs Controls" seems to be the most accurate comparison, most likely because the IBS/no-IBS subsets have fewer members in them by definition (i.e. because they're subsets).

    If this stands up with larger groups, it's really quite important because it's a biomarker. It might not be practical in a clinical setting, but, for research purposes, it could be invaluable for ensuring that the subjects involved in future studies are indeed a distinct cohort.
     
    Last edited: Jul 6, 2018
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  12. Simon M

    Simon M Senior Member (Voting Rights)

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    Nice try! Sorry, don't even have the energy to read the paper.

    However, I'm relying on the summary from @Trish , and over at PR Murf posted this:

    Six thoughts

    1. They confirm some of the previous metabolomic findings - ceramides and phospholipids.
    2. They find (yet) another subgroup that can confound metabolomic findings - having IBS.
    3. Gut Bacteria matter - they can help identify the disease.
    4. They include 9 men in the 50 patients and 9 in the 50 controls, and this adds no statistical power on the male side, while diminishing statistical power on the female side. Not sure it's worth it.
    5. A treatment idea: They find some possible reasons to take b-vitamins.
    6. These topological maps are interesting to look at but I can't get much out of them in terms of actionable ideas, beyond the fact that the connections look mostly non-random (i.e. There's *something* there.)

    And the free full text is now available here (thanks to Dr Ian Lipkin for this link)

    Indeed, and the new Columbia collablorative is taking numerous approaches alongside the microbiome work. I started working on a blog about this 2 months ago, and have spoken to Ian Lipkin, but my health is rubbish so progress is intermittent. With luck, a blog will appear next week. Some of the science looks pretty impressive.

    [This will be my last big blog for the forseeable future; my recent HLA blog was based on something I wrote 4 years ago, and the one before that was a guest blog from Chris P.]
     
    Last edited: Jul 6, 2018
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  13. Trish

    Trish Moderator Staff Member

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    Sorry to hear you're so ill at the moment, @Simon M. Rest well.

    I don't think I'd rely on my impressions. I hope others with more understanding will sort out a better summary.
     
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  14. Esther12

    Esther12 Senior Member (Voting Rights)

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    Link broken for me - is Lipkin playing with us?!
     
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  15. Andy

    Andy Committee Member & Outreach

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    No, Simon's link embedding skills obviously went a bit wonky for that bit - it doesn't link anywhere.
     
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  16. Simon M

    Simon M Senior Member (Voting Rights)

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    Whoops: https://www.nature.com/articles/s41598-018-28477-9
    Original post corrected.

    Thanks. And I'll rest better once the blog is finally out of the door. Pacing perfectly in the meantime, of course...
     
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  17. Sunshine3

    Sunshine3 Senior Member (Voting Rights)

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    @Simon M sorry too to hear you are having a rough patch at present..... hopefully it will lift a little again. You are in our thoughts :hug:
     
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  18. Snow Leopard

    Snow Leopard Senior Member (Voting Rights)

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    I haven't spent the time making sense of this yet, but the supplementary tables look interesting as mentioned by @Forbin.

    I will say that on first glance I have noticed several errors with the references referring to the wrong papers, which is disappointing, perhaps publishing errors?
     
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  19. Sing

    Sing Established Member (Voting Rights)

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    I question when I hear again of fever and swollen lymph nodes. Didn’t this originally come from a definiton from the US based on a post Epstein Barr illness? I am forgetting. I certainly have neither. My understanding is that most of us have low body temperature and low other things in keeping with what’s been found as a downturn in metabolism, autonomic functions, etc. There is also the matter of how many years someone has been sick. The first three years were found (Mady Hornig, etc.) to be characterized by higher than normal infections and symptoms of active infection, whereas in the later years, this is not the case. That would be my experience too, after 22 years of ME.

    Please, anyone, correct me where my understanding might be faulty.
     
  20. Forbin

    Forbin Senior Member (Voting Rights)

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    Sort of along the same lines, I noticed that ceramides were mentioned, but only becasue I first heard of ceramides last winter when my dermatologist prescribed a ceramide-based cream for my hands that were chapped to the point of bleeding.

    Ceramides are a waxy lipid molecule that help to retain moisture in the uppermost layer of the skin. They also perform a number of other functions inside the body, including involvement in the cell signaling that leads to programmed cell death (apoptosis).

    The paper indicates that the levels of some ceramide species are higher than normal in ME/CFS patients with IBS and lower than controls in ME/CFS patients without IBS. According to the paper, there are possible links between ceramides and IBS and metabolic disorders and increased levels may be associated with an altered gut microbiome. They suggest that blocking the ceramide precursor molecule might decrease inflammation by lowering ceramide levels.

    In the same paragraph, they mention mannitol:
     
    Last edited: Jul 7, 2018

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