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CoQ10 - Coenzyme Q10

Discussion in 'Other: Methylation; B12; Glutathione; GcMAF' started by Hutan, Feb 13, 2020.

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  1. Hutan

    Hutan Moderator Staff Member

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    I'm writing an article on CoQ10 and MitoQ for my local group's newsletter; these supplements are often recommended by both people with ME/CFS and clinicians. We don't seem to have a thread specifically on this yet.

    I'm interested in the evidence for CoQ10 supplementation being helpful for people with ME/CFS (along with the evidence for any side effects).
     
  2. Hutan

    Hutan Moderator Staff Member

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    Systematic review of randomized controlled trials for (CFS/ME) (2020) Kim et al
    Thread here
    full paper

    Articles were screened according to the following inclusion criteria: (1) RCTs or randomized controlled crossover trials, (2) patients with CFS/ME as participants, (3) an evaluation of the efficacy of the intervention for CFS/ME treatment, and (4) fatigue-related primary measurement or main outcome. The exclusion criteria were as follows: (1) articles with no full text, (2) the number of participants was less than 45 (less than 23 in a crossover trial), (3) studies without mention of the case definition or the characteristics of participants and (4) studies with a Jadad score less than 3 points.

    Found only 1 study on CoQ10:
    Does oral coenzyme Q10 plus NADH supplementation improve fatigue and biochemical parameters in chronic fatigue syndrome? (2015).
    Castro-Marrero J, Cordero MD, Segundo MJ, Sáez-Francàs N, Calvo N, Román-Malo L, Aliste L, de Fernández Sevilla T, Alegre J.

    (The KPAX002 study with its blend of micronutrients for mitochondrial support did not contain any CoQ10).
     
    Last edited: Feb 14, 2020
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  3. Mij

    Mij Senior Member (Voting Rights)

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    My levels were measured over 10 years ago, I was at 50% and was advised to supplement. I didn't notice much difference at 100mg, but I did feel an improvement at 300mg/day as far as being upright longer. I had to discontinue after 4 months because it was negatively affecting my sleep, but I continue take a small amount from time to time because I tested high for oxidative stress.

    I'm wondering if there is a difference between measuring levels in plasma and in cells?
     
  4. Hutan

    Hutan Moderator Staff Member

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    Does oral coenzyme Q10 plus NADH supplementation improve fatigue and biochemical parameters in chronic fatigue syndrome? (2015) Castro-Marrero et al

    8 week
    Double blind, placebo controlled
    oral CoQ10 (200 mg/day) plus NADH (20 mg/day) supplementation
    73 Spanish CFS patients, all female - Fukuda criteria

    (We don't have a thread on this study yet.)

    A significant improvement of fatigue showing a reduction in fatigue impact scale total score (p<0.05) was reported in treated group versus placebo.

    NAD+/NADH (p<0.001), CoQ10 (p<0.05), ATP (p<0.05), and citrate synthase (p<0.05) were significantly higher, and lipoperoxides (p<0.05) were significantly lower in blood mononuclear cells of the treated group.

    No adverse impacts seen, or reported by patients

    Although the improvement fatigue is reported as significant (p<0.05), the changes are quite small:

    Screen Shot 2020-02-14 at 2.57.38 PM.png

    Just looking at the different baseline Fatigue Impact Scores and the standard deviations, I think there'd need to be more studies before you could say that there is a real difference. There was a 5.6% improvement in the treatment group and a 2.7% improvement in the placebo group. It wouldn't take much in the way of some patients knowing which group they are in, or a couple of small decisions about whether some data is left in or excluded to account for that.

    This seems a bit odd:
    Screen Shot 2020-02-14 at 3.04.59 PM.png

    So, in the treatment group during the trial, mean body weight went up by 1% and mean BMI went up by 1%. But in the placebo group, mean body weight decreased by 0.03%, but BMI increased by 5%. Heights of participants don't change - so would that suggest something happened to the composition of the placebo group over the study?

    Potential conflict of interest:
    The supplements were from this company.
     
    Last edited: Feb 14, 2020
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  5. Hutan

    Hutan Moderator Staff Member

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    Castro-Marrero study continued:

    So, the diagram with numbers of participants at each point in the trial does not show that the composition of the placebo group changed during the trial. But, given the 5% increase in mean BMI with no change in mean weight, I think then either there was an error in the weight or BMI data, or there were different placebo participants at baseline and follow-up.

    Screen Shot 2020-02-14 at 3.36.12 PM.png

    A big problem when we are trying to work out if CoQ10 helps is that this study supplemented with both CoQ10 and NADH. So we don't know the impact of each supplement on its own.


    Supplementation does seem to increase NADH and CoQ10 in blood mononuclear cells. But there is no discussion of what normal values are and what happens in healthy people with supplementation.


    Screen Shot 2020-02-14 at 4.03.32 PM.png

    The authors also found that intracellular ATP and citrate synthase (they say this is a marker of mitochondrial mass) increased, and lipid peroxidation levels decreased.
     
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  6. Hutan

    Hutan Moderator Staff Member

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    Castro-Marrero study

    So, in summary, there are some interesting findings. But it's just one study that has not been replicated. The decrease in the fatigue measure after accounting for the placebo effect was about 3% - hardly clinically significant. And, even if there is a real benefit, we don't know if it was the CoQ10 or the NADH, or some synergy between them.

    And there are potential conflict of interest issues, with the producer of the supplements supporting the study.
     
    Last edited: Feb 14, 2020
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  7. Hutan

    Hutan Moderator Staff Member

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    MitoQ
    Professor Tate at the University of Otago in NZ is currently studying MitoQ in ME/CFS. MitoQ was developed by University of Otago researchers. Prof Tate said late last year that his team have found that MitoQ does get into cells/mitochondria better than CoQ10. The problem is that, and I'm going on memory here - I'll fix it when I find my notes - the change of shape that makes it easier for the MitoQ to get into the mitochondria results in it not being able to 'fit into the groove' in order to participate in the processes that make ATP.

    Fortunately, CoQ10 has two jobs in the mitochondria: to help make ATP and to mop up the free radicals that are the waste byproduct of ATP production. So, while MitoQ seems to be physically unable to help with ATP production, perhaps it can still mop up free radicals and reduce oxidation damage.

    To me though, there's the possibility that loading up your mitochondria with molecules that look like CoQ10 but don't do the job might actually make energy production worse. Because whatever feedback loops there are for the body to provide CoQ10 when levels are low might not work.
     
    Last edited: Feb 14, 2020
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  8. Hutan

    Hutan Moderator Staff Member

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  9. Hutan

    Hutan Moderator Staff Member

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    So the key finding from the Mendus study is
    The study had two arms - one was a blinded crossover study of 51 people with ME/CFS, people were provided a 6 week supply of 20 mg capsules (one a day) without knowing whether it was MitoQ or a placebo and then later received a 6 week supply of the other. In the second arm, 43 people with ME/CFS bought their own MitoQ - (the commercial form with 5 mg capsules and guidelines suggesting a dosage of 10 mg/day). Both sets of participants completed the same surveys and online tests.

    Of course, with this being an online study, we can't know for sure if the participants all had ME/CFS. The study was supported by the company producing MitoQ; they provided the free supply and they paid one of the authors to do the analysis.

    Participants completed online assessments of fatigue, pain, sleep quality, mental clarity, gastrointestinal issues, depression and overall wellbeing, as well as an assessment of how active they had been. These were subjective assessments from 0 to 10, and were to cover the previous week. Participants also did three online cognitive tests.

    Participants in the blinded study therefore were in the study for 2 x 6weeks. Participants in the unblinded study could provide data up until the 90 day mark.

    Results
    Blinded study: No effects were observed for the MitoQ group on any measures above that observed in the placebo group.
    Open label study: Significant (indeed, large) positive effects were observed for many of the measures including decreased pain and increased energy, sleep quality, mental clarity, activity, well being and verbal reasoning. Many of these effects were observed at 6-weeks and continued to grow at two follow-up points of 2 and 3 months. At 6 weeks, energy was reported to have increased by an average of 26% (versus both the blinded placebo and the blinded MitoQ participants reporting decreases in energy at 6 weeks). This is despite the open dosage being probably half of what the blinded study participants were taking.

    It's certainly interesting, as an example of how easy it is for people to convince themselves that something is helping.

    (This study also had a fibromyalgia blinded arm - some positive effects were found for this. I haven't looked at those. But, in the ME/CFS study, the mean pain rating on a scale from 0 to 10 increased slightly from about 3.7 to 4 during the 6 weeks of MitoQ.)

    There was some discussion about the possibility that the higher dose in the blinded study caused sleep problems and nausea.

    6 people discontinued the blinded study due to side effects (it's not clear if this includes the fibromyalgia study) - but of these 6, 5 were taking the placebo.

    The authors conclude:
     
    Last edited: Feb 15, 2020
  10. Amw66

    Amw66 Senior Member (Voting Rights)

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    Is this ubiquinol or ubiquinone - there seems to be a difference in response for people.

    Dosage is also a significant variable. Some use high dosage to mitigate effects of PEM.
     
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  11. Hutan

    Hutan Moderator Staff Member

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    I found this:
    Do you have some information about the two forms or dosage @Amw66?
     
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  12. Amw66

    Amw66 Senior Member (Voting Rights)

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    Anecdotal info - and given the dual function the effectiveness will depend on what it is being used for and how acute the need is?
    This thread from PR may offer an insight
    https://forums.phoenixrising.me/blo...-now-how-it-helps-and-general-me-advice.1737/

    ____________________

    Moderator note: The blog linked above contains medical advice that is not compliant with our Rule 5 (no medical advice). Please do your research before deciding what is best for you.
     
    Last edited by a moderator: Feb 17, 2020
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  13. Mij

    Mij Senior Member (Voting Rights)

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  14. Sisyphus

    Sisyphus Senior Member (Voting Rights)

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    My MD reccomends CQ10 for cardio health.

    Then again, the office email 'news' recommended dark chocolate (iirc, no net benefit but lotta calories). I seriously doubt any net health benefit, it seems like those pop 'eat this magic stuff' things that circulate on social media and cynical clickbait sites.

    Net: Confused. I'm going with my GP recommendation but not convinced it's actually of any use.
     
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  15. TiredSam

    TiredSam Moderator Staff Member

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    I tried CQ10 for a few days some years ago, and convinced myself that it was blowing my head off, by which I think I mean it made my brain even foggier, so I stopped.
     
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  16. Invisible Woman

    Invisible Woman Senior Member (Voting Rights)

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    Not sure whether anecdotal information is what you want, but if it helps...

    I was advised to try CQ10 shortly after I first became ill. I spent a few months on it as I recall. I didn't notice any difference at all so it was discontinued.
     
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  17. Hutan

    Hutan Moderator Staff Member

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    https://www.ncbi.nlm.nih.gov/pubmed/20010505

    2009

    Coenzyme Q10 deficiency in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is related to fatigue, autonomic and neurocognitive symptoms and is another risk factor explaining the early mortality in ME/CFS due to cardiovascular disorder.
    Maes M1, Mihaylova I, Kubera M, Uytterhoeven M, Vrydags N, Bosmans E.

    Abstract

    INTRODUCTION:
    Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a medical illness characterized by disorders in inflammatory and oxidative and nitrosative (IO&NS) pathways.

    METHODS:
    This paper examines the role of Coenzyme Q10 (CoQ10), a mitochondrial nutrient which acts as an essential cofactor for the production of ATP in mitochondria and which displays significant antioxidant activities. Plasma CoQ10 has been assayed in 58 patients with ME/CFS and in 22 normal controls; the relationships between CoQ10 and the severity of ME/CFS as measured by means of the FibroFatigue (FF) scale were measured.

    RESULTS:
    Plasma CoQ10 was significantly (p=0.00001) lower in ME/CFS patients than in normal controls. Up to 44.8% of patients with ME/CFS had values beneath the lowest plasma CoQ10 value detected in the normal controls, i.e. 490 microg/L. In ME/CFS, there were significant and inverse relationships between CoQ10 and the total score on the FF scale, fatigue and autonomic symptoms. Patients with very low CoQ10 (<390 microg/L) suffered significantly more from concentration and memory disturbances.

    DISCUSSION:
    The results show that lowered levels of CoQ10 play a role in the pathophysiology of ME/CFS and that symptoms, such as fatigue, and autonomic and neurocognitive symptoms may be caused by CoQ10 depletion. Our results suggest that patients with ME/CFS would benefit from CoQ10 supplementation in order to normalize the low CoQ10 syndrome and the IO&NS disorders. The findings that lower CoQ10 is an independent predictor of chronic heart failure (CHF) and mortality due to CHF may explain previous reports that the mean age of ME/CFS patients dying from CHF is 25 years younger than the age of those dying from CHF in the general population. Since statins significantly decrease plasma CoQ10, ME/CFS should be regarded as a relative contraindication for treatment with statins without CoQ10 supplementation.

    I find this puzzling. The Castro-Marrero supplementation study found that serum levels of CoQ10 increased with supplementation, but there was not really improvement in symptoms. Is anyone aware of any measures of CoQ10 levels in ME/CFS serum other than this Maes study?
     
    Last edited: May 12, 2020
  18. Hutan

    Hutan Moderator Staff Member

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    CoQ10: What a nightmare of different units, some per litre and some per gram, some mol per quantity of cholesterol...

    I found a population reference of 360 to 1590 micrograms/litre in serum. Maes reported that in his sample, the lowest value of the controls was 490 micrograms/litre. I found a reference with a mean of 490 micrograms/litre for un-supplemented healthy young male athletes (1360 when supplemented).

    So, it's interesting that many people with ME/CFS in the Maes sample had lower CoQ10 than the healthy controls and there seemed to be an inverse relationship between ME/CFS severity and CoQ10 levels. I'm not sure that what Maes calls 'very low' (<390 micrograms/L) necessarily is.
     
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  19. Hutan

    Hutan Moderator Staff Member

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    https://www.ncbi.nlm.nih.gov/pubmed/27125909
    2016

    Ubiquinol-10 supplementation improves autonomic nervous function and cognitive function in chronic fatigue syndrome.
    Fukuda S1,2,3, Nojima J4, Kajimoto O5, Yamaguti K3,6, Nakatomi Y3,6, Kuratsune H1,3,6, Watanabe Y2,3.

    Abstract

    The aim of this study was to evaluate the benefit of oral ubiquinol-10 supplementation in CFS patients using an open-label study and a randomized, double-blinded, placebo-controlled (RCT) study.

    Twenty patients with CFS were randomly enrolled in an 8-week open-label oral ubiquinol-10 (150 mg ubiquinol-10/day) study. The patients and the attending physicians were not blinded to the supplementation.

    Forty-three patients with CFS were randomly assigned to receive either ubiquinol-10 (150 mg/day) or placebo every day for 12 weeks. The patients and the attending physicians were blinded to the supplementation, and a total of 31 patients (N = 17 in the ubiquinol group and 14 in the placebo group) completed the study.

    The beneficial effects of ubiquinol-10 were observed in the open-label study we conducted prior to the RCT. The RCT results suggest that supplementation with ubiquinol-10 for 12 weeks is effective for improving several CFS symptoms.
    Scihub
     
    Last edited: May 12, 2020
  20. Arnie Pye

    Arnie Pye Senior Member (Voting Rights)

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    That's rather a strange way of testing something. First do a small study where everyone knows what the subjects are taking, including the subjects themselves. Then follow this with a proper RCT.

    Why not just combine the two pools of subjects and do a larger RCT?
     
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