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Mitochondrial impairment but not peripheral inflammation predicts greater Gulf War illness severity, 2023, Patel et al

Discussion in 'Gulf War Illness' started by rvallee, Jul 13, 2023.

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  1. rvallee

    rvallee Senior Member (Voting Rights)

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    Mitochondrial impairment but not peripheral inflammation predicts greater Gulf War illness severity
    https://www.nature.com/articles/s41598-023-35896-w
    Published: 12 July 2023


    Gulf War illness (GWI) is an important exemplar of environmentally-triggered chronic multisymptom illness, and a potential model for accelerated aging. Inflammation is the main hypothesized mechanism for GWI, with mitochondrial impairment also proposed. No study has directly assessed mitochondrial respiratory chain function (MRCF) on muscle biopsy in veterans with GWI (VGWI).

    We recruited 42 participants, half VGWI, with biopsy material successfully secured in 36. Impaired MRCF indexed by complex I and II oxidative phosphorylation with glucose as a fuel source (CI&CIIOXPHOS) related significantly or borderline significantly in the predicted direction to 17 of 20 symptoms in the combined sample.

    Lower CI&CIIOXPHOS significantly predicted GWI severity in the combined sample and in VGWI separately, with or without adjustment for hsCRP. Higher-hsCRP (peripheral inflammation) related strongly to lower-MRCF (particularly fatty acid oxidation (FAO) indices) in VGWI, but not in controls. Despite this, whereas greater MRCF-impairment predicted greater GWI symptoms and severity, greater inflammation did not.

    Surprisingly, adjusted for MRCF, higher hsCRP significantly predicted lesser symptom severity in VGWI selectively. Findings comport with a hypothesis in which the increased inflammation observed in GWI is driven by FAO-defect-induced mitochondrial apoptosis. In conclusion, impaired mitochondrial function—but not peripheral inflammation—predicts greater GWI symptoms and severity.
     
    rvallee, Jul 13, 2023
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    Hoopoe, Sean, Hutan and 5 others like this.
  2. Amw66

    Amw66 Senior Member (Voting Rights)

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    Mitochondrial complex 1- a wee bit familiar sounding .
    No compensatory complex 5 uprating ?.
     
    Amw66, Jul 13, 2023
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  3. RedFox

    RedFox Senior Member (Voting Rights)

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    I can't believe people with GWI have suffered for so long (30+years) with so little research. I know pwME have done the same, but I've only been ill 5 years and entered the ME world in 2021, when LC was well-known and the new NICE guidelines came out.
     
    RedFox, Jul 14, 2023
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  4. Hutan

    Hutan Moderator Staff Member

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    Acetylcholinesterase inhibitors might be the common factor in illnesses like GWI, including in ME/CFS and chronic ciguatera.

    Ref #9
    Golomb, B. A. et al. Coenzyme Q10 benefits symptoms in Gulf War veterans: Results of a randomized double-blind study. Neural Comput.26, 2594–2651. https://doi.org/10.1162/NECO_a_00659 (2014).
    I'll be surprised if this report of CoQ10 helping GWI checks out, but maybe it will. I'll make a thread.

    Edit:
    Thread here: Coenzyme Q10 Benefits Symptoms in Gulf War Veterans: Results of a Randomized Double-Blind Study, 2014, Golomb et al
    No significant benefit for primary outcome (self-rated general health) for both the 100mg and 300mg CoQ10 treatment arms.
     
    Last edited: Jul 14, 2023
    Hutan, Jul 14, 2023
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  5. Amw66

    Amw66 Senior Member (Voting Rights)

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    There's the common Wessley factor
     
    Amw66, Jul 14, 2023
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  6. butter.

    butter. Senior Member (Voting Rights)

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    Nobody should be surprised about this. It will be a similar picture in ME/CFS, despite what has been said (on this forum) about (secondary) mitochondrial diseases and how they differ from what we call ME/CFS.
     
    butter., Jul 14, 2023
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  7. Hutan

    Hutan Moderator Staff Member

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    Cells from a muscle biopsy: 19 GWI; 17 controls
    14 matched pairs for a subset analysis
    There was some missing data - actual numbers contributing to reported means isn't reported.

    There were 19 different assessments made of mitochondrial function (results in Supplementary Table 1); hsCRP was also assessed.
    5 measures are reported in Table 2.
    None were anywhere near significant in the total sample. Two (listed below) were only just significant in the paired analysis (p=0.05 and p=0.04)

    I think there has to be a fair amount of doubt about the importance of these findings, due to the number of assessments made, the relatively small number of participants and the low level of significance.

    CI&CII&FAOCI/CIIOXPHOS
    Paired analysis: P=0.039. Means(SD) GWI=46 (24); HC=72 (30)
    Whole analysis: P=0.23. Means(SD) GWI=51 (24); HC = 63 (30)
    Substantial standard deviations

    FAOMaxUC
    Determined by using fatty acids as the fuel source with FCCP as an uncoupler
    Paired analysis: P=0.049. Means(SD) GWI=68 (27); HC=102 (46)
    Whole analysis: P=0.20. Means(SD) GWI=75(30); HC = 92 (42)
    Substantial standard deviations

    There might be something in here, but the study needs to be repeated with a substantially larger sample, so that there is the potential to identify participant subsets. Possibly the findings are a result of lower activity levels (and therefore lower regular demands on energy production) in the GWI participants.

    Interestingly, they found a good negative relationship between CI&CII&FAOCI/CIIOXPHOS and 'post-exertional fatigue' (p=0.014). hsCRP was not associated with post-exertional fatigue but was with 'tiredness'.

    They conclude, on the basis of the lack of a difference in hsCRP that inflammation pays no role in GWI. This may be true, but I think we have seen recently that there can still be elements of inflammation without elevated hsCRP. (I've deleted this point as I'm not sure now what the paper claims about inflammation; it might say both it might and might not be important. I don't have the energy to go back and check.)
     
    Last edited: Jul 14, 2023
    Hutan, Jul 14, 2023
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  8. RedFox

    RedFox Senior Member (Voting Rights)

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    Definitely. I predict we'll discover their pathology is very similar, if we can unravel GWI before most of their cohort passes away and can't be studied anymore.
     
    RedFox, Jul 14, 2023
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  9. rvallee

    rvallee Senior Member (Voting Rights)

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    Or the next cohort comes along. Guaranteed. Probably not identical, but issues like this are sadly common, and they are very rarely studied at all.
     
    rvallee, Jul 16, 2023
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  10. RedFox

    RedFox Senior Member (Voting Rights)

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    The next cohort is long Covid.
     
    RedFox, Jul 17, 2023
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