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Comprehensive Circulatory Metabolomics in ME/CFS Reveals Disrupted Metabolism of Acyl Lipids and Steroids: Levine,Hanson et al 2020

Discussion in 'BioMedical ME/CFS Research' started by Sly Saint, Jan 14, 2020.

  1. Sly Saint

    Sly Saint Senior Member (Voting Rights)

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    Article. PDF
    Received: 20 December 2019; Accepted: 12 January 2020; Published: 14 January 2020
    https://www.google.com/url?sa=t&rct.../10/1/34/pdf&usg=AOvVaw2V_YUpD2lnE2NHCJAMQr0M
     
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  2. lansbergen

    lansbergen Senior Member (Voting Rights)

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    Another class of lipids with farreaching activity on virtually all organ systems are steroids; androgenic, progestin, and corticosteroids are broadly reduced in our patient cohort.

    https://ammes.org/tag/dexamethasone/
     
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  3. lansbergen

    lansbergen Senior Member (Voting Rights)

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  4. lansbergen

    lansbergen Senior Member (Voting Rights)

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  5. Andy

    Andy Committee Member & Outreach

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  6. Jaybee00

    Jaybee00 Senior Member (Voting Rights)

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    So can we use supplements to increase
    Docosahexaenoyl-choline?
     
  7. Lidia

    Lidia Senior Member (Voting Rights)

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    Yes. Why is this metabolism disrupted? This is the key.
     
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  8. alktipping

    alktipping Senior Member (Voting Rights)

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    where did they get the 65 million figure from for the last decade the only figures I have seen where 17-25 million . considering many countries chose not to acknowledge the disease at all I don't think there will ever be an accurate figure for this
     
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  9. Hutan

    Hutan Moderator Staff Member

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    There was a disappointingly significant difference in the ages of the controls and the women with ME/CFS:
    Screen Shot 2020-01-15 at 7.12.57 PM.png

    Median of 43 for the controls and 52 for the ME/CFS group.

    It's not surprising then that differences in androgenic steroids were found (with the ME/CFS group having lower levels).

    Here's a graph of the normal levels of testosterone steroids in women at various ages:
    Screen Shot 2020-01-15 at 7.11.31 PM.png
    The levels of these steroids should be lower in an older female cohort. I'm surprised there was no mention of the age difference in the two samples in the discussion of this. I wouldn't be surprised if the age difference affected levels of quite a few of the metabolites.

    Edited to add - the study found that progestin was lower in the ME/CFS group. Again predictable from the age difference - men, menopausal women and women at certain times in their menstrual cycle have levels that are one-tenth or even one twentieth of the levels that occur in women at other times during their menstrual cycle. Again - I didn't see any discussion of the effect of the age difference in the study.
     
    Last edited: Jan 15, 2020
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  10. Milo

    Milo Senior Member (Voting Rights)

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    Thank you NIH and NINDS but special thank you to the generous private donor.
     
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  11. Hutan

    Hutan Moderator Staff Member

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    Re sphingolipids and ceramides - we've seen these come up quite often, so at first that seemed positive.

    This study found increases in both, unlike Naviaux who found lower levels.
    So, looks like we forget about those.

    The authors of this study comment that they were able to process the samples very quickly, unlike their previous study where samples waited maybe 24 hours. They think the processing time accounts for some differences between studies. So it's great that they were able to process these samples so fast.
     
    Last edited: Jan 15, 2020
  12. Hutan

    Hutan Moderator Staff Member

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    I don't want to seem negative - I rate the Hanson team highly. They don't hype their results and seem to be working systematically to improve ME/CFS research.

    Hopefully there is something in the acyl choline finding:
    Screen Shot 2020-01-15 at 8.08.41 PM.png
     
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  13. Aslaug

    Aslaug Senior Member (Voting Rights)

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    What Hutan said. I haven't got to read the study except glanced at the participants and I'm skeptical. But I like metabolomics so I look forward to read this in more detail when I can spare the energy.
     
  14. mariovitali

    mariovitali Senior Member (Voting Rights)

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    I wonder whether it is possible that many metabolites have a temporal aspect which is not taken into consideration. So there may be metabolites that :

    -Increase / decrease at specific times of the day
    -Increase / decrease momentarily (e.g for 1 hour)

    If any of the above takes place then this would be a problem for replication of results. I do not know if the above make sense so it's just a thought.
     
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  15. Michiel Tack

    Michiel Tack Senior Member (Voting Rights)

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    The paper is a bit difficult to comprehend (might have to read it again), but I also got the impression that the study showed mostly null results. The authors write:
     
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  16. spinoza577

    spinoza577 Senior Member (Voting Rights)

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    I wonder this too, aside from individuel differences there might be differences due to areas, seasons, and daytime. It could also point simply to an exaggeration.

    My personal impression is that it is pretty unlikely that the findings in metabolism and the immune system give a direct cause. They might reflect a disturbed homeostasis, or are downstream effects.


    I would say, an interesting result, that in itself doesn´t tell much, instead is asking for interpretations, and technically for more details.

    They say as well:
    (from the conclusions)


    The main tendencies - if I am allowed to put like so - are:
    • decreased Acyl Cholines (which are still obscure although providing already a variety of links to ME symptoms)
    • decreased Dipedtides (which are not well understood)
    • increased Sphingolipids (at odds with Naviaux [who found them decreased in ME, though increased in GWS], and with Nagy-Szakal et al [who found only some of them decreased in ME without IBS].)
    • decreased Steroids, three classes of them (referring to de Vega et al with guessing hypersensitivity and reduced HPA-axis, which is not fully understood).
     
    Last edited: Jan 15, 2020
  17. mariovitali

    mariovitali Senior Member (Voting Rights)

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    @Hutan

    Thank you for the analysis you provided. I was not able to read very closely the paper but i wanted to ask regarding the following reference to cholate (=cholic acid) on page 5:


    which was not found elsewhere in the text. Why this is so?
     
  18. Hutan

    Hutan Moderator Staff Member

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    Yes, interesting point @mariovitali.
    There is Figure 3 later in the document.
    Extending the quote you gave a bit further - the authors note that all of the other metabolites in the same pathway were also considerably lower.
    You can see the dot for the 'Primary Bile Acid Metabolism' pathway with 9 metabolites. So, it looks like something to keep an eye on.

    Screen Shot 2020-01-18 at 12.37.24 PM.png
     
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  19. Snow Leopard

    Snow Leopard Senior Member (Voting Rights)

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  20. Hutan

    Hutan Moderator Staff Member

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    Checking that the mean age difference between the control and ME/CFS sample might explain the bile acid differences, specifically cholic acid, I thought this 2016 paper was an interesting read.
    Age-Related Changes of Plasma Bile Acid Concentrations in Healthy Adults—Results from the Cross-Sectional KarMeN Study

    They did find differences in bile acid concentrations in plasma with age and with sex, but those differences probably don't explain the differences found in the ME/CFS study. Concentrations didn't vary between pre- and post-menopausal women and, if anything, concentrations slightly increased with age in women.

    It looks as though there is a lot of variability in levels between individuals though and diet does affect levels. I didn't find any mention of the ME/CFS study requiring participants to fast, so the differences found perhaps can be explained by different diets and perhaps time since last eating.

    Maybe there should be some standardisation of food intake prior to blood collection in these studies e.g. participants should be required to eat specified meals the day before, and fast before a morning collection.
     
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