-
New Forum Software Installed (Still a few issues but reopening the forum) More details.
What was the unit of measure @Mij?
A supplement manufacturer partly funded the study.
Open label study:
20 participants, 8 weeks, 150 mg CoQ10 per day.
The patients were evaluated before and after the 8-week period with a questionnaire to assess fatigue and depression symptoms; blood samples to measure CoQ10 concen- trations [total CoQ10, ubiquinol, ubiquinone, and ubiquinol/ ubiquinone ratio (%)], oxidation activity and antioxidant activity; an arithmetic task, a sleep-wake cycle study, and an autonomic nervous function test.
Selection criteria was the 1994 CDC criteria - I forget exactly what this is but I don't think PEM is mandatory.
It isn't reported how long participants were required to not supplement with CoQ10 before the start of the trial, but it must have been some time as all of the baseline CoQ10 levels were lower than those after the trial supplementation.
At baseline, 'approximately 95% of the patients had significantly lower total plasma ubiquinol levels (0.66 6 0.23) as compared to the reference data (0.8–0.9)'.
10 of the 20 participants took psychoactive substances
Double blinded study
43 patients enrolled, only ended up with 17 in treatment arm and 14 in placebo arm
12 week study; 4 week wash-out prior for those taking CoQ10; 150 mg/day
Evaluations as per the open label study: questionnaires to assess fatigue and depression symptoms; blood samples to measure CoQ10 concen- trations [total CoQ10, ubiquinol, ubiquinone, and ubiquinol/ ubiquinone ratio (%)], oxidation activity and antioxidant activity; an arithmetic task, a sleep-wake cycle study, and an autonomic nervous function test.
Lower levels of CoQ10 in ME/CFS serum is starting to look like a solid finding. But, as most of the CoQ10 is produced endogenously, it's not clear that that necessarily means much in terms of health. Could it be that we aren't producing chemicals of lots of sorts particularly efficiently, and so there isn't the usual surplus of CoQ10 sitting in the plasma, but there's still enough in the tissues?
Could it be that those joining a trial on CoQ10 are more likely to be supplementing prior to the trial and the body gets used to the higher exogenous supply and reduces endogenous production, and so a period of no supplement results in these lower levels? (If that is true, then the effect seems to last at least 16 weeks, which seems a bit implausible.)
But this trial doesn't provide evidence that CoQ10 supplementation helps with ME/CFS symptoms or measures of plasma oxidative stress.
Yes, I guess lots of teams have done open label trials to see if there might be anything in an idea and to see if the treatment is safe before following up with a blinded study, which is what happened here. But combining the results of both in one paper really muddles things. It's a difficult paper to read.
A supplement manufacturer partly funded the study.
Open label study:
20 participants, 8 weeks, 150 mg CoQ10 per day.
The patients were evaluated before and after the 8-week period with a questionnaire to assess fatigue and depression symptoms; blood samples to measure CoQ10 concen- trations [total CoQ10, ubiquinol, ubiquinone, and ubiquinol/ ubiquinone ratio (%)], oxidation activity and antioxidant activity; an arithmetic task, a sleep-wake cycle study, and an autonomic nervous function test.
Selection criteria was the 1994 CDC criteria - I forget exactly what this is but I don't think PEM is mandatory.
It isn't reported how long participants were required to not supplement with CoQ10 before the start of the trial, but it must have been some time as all of the baseline CoQ10 levels were lower than those after the trial supplementation.
At baseline, 'approximately 95% of the patients had significantly lower total plasma ubiquinol levels (0.66 6 0.23) as compared to the reference data (0.8–0.9)'.
10 of the 20 participants took psychoactive substances
8 weeks of supplementation substantially increased CoQ10 plasma levels.
"No clinical outcomes changed over the course of the 8-week supplementation in the patients". This is remarkable - an open label trial and subjective assessments of fatigue (Chalder Fatigue scores) did not improve.
The only outcome that was significant was an increase in sleep hours with an increase in the ubiquinone/ubiquinol ratio (but it doesn't sound as though there was any significant change in the ubiquinone/ubiquinol ratio)
Reductions in depressive symptoms were correlated with increased CoQ10 plasma levels (P=0.02) - however, a small increase in CoQ10 levels was associated with worse depressive symptoms and only the lucky ones with a big increase in CoQ10 were more likely to have less depressive symptoms (and even then, some had worse depressive symptoms). So it's probably just a random finding.
"The increases in total CoQ10 levels were negatively correlated with decreases in plasma oxidative stress (i.e., dROMs levels; q 5 20.49, p 5 0.03)". So, as CoQ10 levels increased, plasma oxidative stress (as measured with dROMs) went up! This is also a remarkable finding considering how much has been written about oxidative stress being the cause of ME/CFS. Taking CoQ10 appeared to make things worse. The authors used a double negative to report this, making the outcome less than clear.
No change in Biological Antioxidant Potential of serum
The only outcome that was significant was an increase in sleep hours with an increase in the ubiquinone/ubiquinol ratio (but it doesn't sound as though there was any significant change in the ubiquinone/ubiquinol ratio)
Reductions in depressive symptoms were correlated with increased CoQ10 plasma levels (P=0.02) - however, a small increase in CoQ10 levels was associated with worse depressive symptoms and only the lucky ones with a big increase in CoQ10 were more likely to have less depressive symptoms (and even then, some had worse depressive symptoms). So it's probably just a random finding.
"The increases in total CoQ10 levels were negatively correlated with decreases in plasma oxidative stress (i.e., dROMs levels; q 5 20.49, p 5 0.03)". So, as CoQ10 levels increased, plasma oxidative stress (as measured with dROMs) went up! This is also a remarkable finding considering how much has been written about oxidative stress being the cause of ME/CFS. Taking CoQ10 appeared to make things worse. The authors used a double negative to report this, making the outcome less than clear.
No change in Biological Antioxidant Potential of serum
Double blinded study
43 patients enrolled, only ended up with 17 in treatment arm and 14 in placebo arm
12 week study; 4 week wash-out prior for those taking CoQ10; 150 mg/day
Evaluations as per the open label study: questionnaires to assess fatigue and depression symptoms; blood samples to measure CoQ10 concen- trations [total CoQ10, ubiquinol, ubiquinone, and ubiquinol/ ubiquinone ratio (%)], oxidation activity and antioxidant activity; an arithmetic task, a sleep-wake cycle study, and an autonomic nervous function test.
Levels of CoQ10 did increase markedly in the serum (0.76 to 2.96 micrograms per ml).
No difference between Chalder Fatigue scores or depressive symptoms between placebo and treatment. Means of both were actually worse in the treatment arm.
Patients in the treatment arm did better in some aspects of the arithmetic task and had slightly less awakenings during sleep.
With the autonomic function, it was actually the placebo group that got worse, not the treatment arm getting better. And it was only one aspect of heart rate variability. And the treatment arm's figure for that measure got a bit worse than baseline too, just not as much as in the placebo.
"The other variables (CES-D, Chalder’s fatigue scale, arithmetic tasks [correct rate and response time per answer], sleep-wake cycle [sleep effectiveness, sleeping hours, day and nighttime activity levels, sleep efficacy, and sleep latency], daytime BAP, dROMs, and autonomic nervous function [LF power, LF/HF, CVa-a%]) did not show statistically significant differences between the supplementation groups."
No difference between Chalder Fatigue scores or depressive symptoms between placebo and treatment. Means of both were actually worse in the treatment arm.
Patients in the treatment arm did better in some aspects of the arithmetic task and had slightly less awakenings during sleep.
With the autonomic function, it was actually the placebo group that got worse, not the treatment arm getting better. And it was only one aspect of heart rate variability. And the treatment arm's figure for that measure got a bit worse than baseline too, just not as much as in the placebo.
"The other variables (CES-D, Chalder’s fatigue scale, arithmetic tasks [correct rate and response time per answer], sleep-wake cycle [sleep effectiveness, sleeping hours, day and nighttime activity levels, sleep efficacy, and sleep latency], daytime BAP, dROMs, and autonomic nervous function [LF power, LF/HF, CVa-a%]) did not show statistically significant differences between the supplementation groups."
Lower levels of CoQ10 in ME/CFS serum is starting to look like a solid finding. But, as most of the CoQ10 is produced endogenously, it's not clear that that necessarily means much in terms of health. Could it be that we aren't producing chemicals of lots of sorts particularly efficiently, and so there isn't the usual surplus of CoQ10 sitting in the plasma, but there's still enough in the tissues?
Could it be that those joining a trial on CoQ10 are more likely to be supplementing prior to the trial and the body gets used to the higher exogenous supply and reduces endogenous production, and so a period of no supplement results in these lower levels? (If that is true, then the effect seems to last at least 16 weeks, which seems a bit implausible.)
But this trial doesn't provide evidence that CoQ10 supplementation helps with ME/CFS symptoms or measures of plasma oxidative stress.
Last edited:
Mij
Senior Member (Voting Rights)
It doesn't say.
wigglethemouse
Senior Member (Voting Rights)
@Hutan there was a phase 1/2 CoQ10 study in Gulf War Illness that may be worth looking at
https://www.mitpressjournals.org/doi/10.1162/NECO_a_00659
Men experienced more improvement whereas women showed little - from Page 18 of this presentation
https://www.va.gov/RAC-GWVI/meetings/aug2017/KlimasAUG2017.pdf
It lead to Klimas's 200 people double blind RCT that is predicted to complete at the end of 2020
https://clinicaltrials.gov/ct2/show/NCT02865460
https://www.mitpressjournals.org/doi/10.1162/NECO_a_00659
Men experienced more improvement whereas women showed little - from Page 18 of this presentation
https://www.va.gov/RAC-GWVI/meetings/aug2017/KlimasAUG2017.pdf
It lead to Klimas's 200 people double blind RCT that is predicted to complete at the end of 2020
https://clinicaltrials.gov/ct2/show/NCT02865460
Thanks very much @wigglethemouse
Re the Gulf War Illness study:
Coenzyme Q10 Benefits Symptoms in Gulf War Veterans: Results of a Randomized Double-Blind Study
2014
Beatrice A. Golomb, Matthew Allison, Sabrina Koperski, Hayley J. Koslik,
This seems to be the problem with many of these studies; the investigators are quite convinced they should work, because you know, all that inflammation in ME/CFS/Gulf War Illness and CoQ10 is an anti-oxidant. So when it doesn't work
The idea in this GWI paper that CoQ10 helps only males with Gulf War Illness rather than females would be a whole lot more believable if the treatment arm with 300 mg of CoQ10 had shown some improvement as well as the 100 mg arm. It did not. The authors have explained this by suggesting that if you have too much CoQ10, it becomes pro-oxidant.
It would be really nice if CoQ10 did help; it's an easy treatment and it fits with the (often hand-wavey) theories that are so often talked about of mitochondria and inflammation and oxidation. But I'm not seeing it yet.
Re the Gulf War Illness study:
Coenzyme Q10 Benefits Symptoms in Gulf War Veterans: Results of a Randomized Double-Blind Study
2014
Beatrice A. Golomb, Matthew Allison, Sabrina Koperski, Hayley J. Koslik,
Abstract
We sought to assess whether coenzyme Q10 (CoQ10) benefits the chronic multisymptom problems that affect one-quarter to one-third of 1990–1 Gulf War veterans, using a randomized, double-blind, placebo-controlled study. Participants were 46 veterans meeting Kansas and Centers for Disease Control criteria for Gulf War illness. Intervention was PharmaNord (Denmark) CoQ10 100 mg per day (Q100), 300 mg per day (Q300), or an identical-appearing placebo for 3.5
0.5 months.
General self-rated health (GSRH), the primary outcome, differed across randomization arms at baseline, and sex significantly predicted GSRH change, compelling adjustment for baseline GSRH and prompting sex-stratified analysis. GSRH showed no significant benefit in the combined-sex sample.
Among males (85% of participants), Q100 significantly benefited GSRH versus placebo and versus Q300, providing emphasis on Q100. Physical function (summary performance score, SPS) improved on Q100 versus placebo. A rise in CoQ10 approached significance as a predictor of improvement in GSRH and significantly predicted SPS improvement. Among 20 symptoms each present in half or more of the enrolled veterans, direction-of-difference on Q100 versus placebo was favorable for all except sleep problems; sign test 19:1,
) with several symptoms individually significant. Significance for these symptoms despite the small sample underscores large effect sizes, and an apparent relation of key outcomes to CoQ10 change increases prospects for causality.
In conclusion, Q100 conferred benefit to physical function and symptoms in veterans with Gulf War illness. Examination in a larger sample is warranted, and findings from this study can inform the conduct of a larger trial.
Sci-HubWe sought to assess whether coenzyme Q10 (CoQ10) benefits the chronic multisymptom problems that affect one-quarter to one-third of 1990–1 Gulf War veterans, using a randomized, double-blind, placebo-controlled study. Participants were 46 veterans meeting Kansas and Centers for Disease Control criteria for Gulf War illness. Intervention was PharmaNord (Denmark) CoQ10 100 mg per day (Q100), 300 mg per day (Q300), or an identical-appearing placebo for 3.5
General self-rated health (GSRH), the primary outcome, differed across randomization arms at baseline, and sex significantly predicted GSRH change, compelling adjustment for baseline GSRH and prompting sex-stratified analysis. GSRH showed no significant benefit in the combined-sex sample.
Among males (85% of participants), Q100 significantly benefited GSRH versus placebo and versus Q300, providing emphasis on Q100. Physical function (summary performance score, SPS) improved on Q100 versus placebo. A rise in CoQ10 approached significance as a predictor of improvement in GSRH and significantly predicted SPS improvement. Among 20 symptoms each present in half or more of the enrolled veterans, direction-of-difference on Q100 versus placebo was favorable for all except sleep problems; sign test 19:1,
In conclusion, Q100 conferred benefit to physical function and symptoms in veterans with Gulf War illness. Examination in a larger sample is warranted, and findings from this study can inform the conduct of a larger trial.
This seems to be the problem with many of these studies; the investigators are quite convinced they should work, because you know, all that inflammation in ME/CFS/Gulf War Illness and CoQ10 is an anti-oxidant. So when it doesn't work
there is a post-hoc stratification to find one combination that does. And then the conclusion just steps over the null results and carries on as planned.
It seems that there is always a reason why hope should remain alive and people should keep buying the supplements. (A study of CoQ10 in bipolar depression that had a very clear null result blamed a range of things including the participants in the trial ‘patients volunteering for trials tend to be more burdened by psychological, social and personality co-morbidities’.)
The idea in this GWI paper that CoQ10 helps only males with Gulf War Illness rather than females would be a whole lot more believable if the treatment arm with 300 mg of CoQ10 had shown some improvement as well as the 100 mg arm. It did not. The authors have explained this by suggesting that if you have too much CoQ10, it becomes pro-oxidant.
It would be really nice if CoQ10 did help; it's an easy treatment and it fits with the (often hand-wavey) theories that are so often talked about of mitochondria and inflammation and oxidation. But I'm not seeing it yet.
Last edited by a moderator:
wigglethemouse
Senior Member (Voting Rights)
It's been a while since I read the study, and watched the talk, but I seem to remember with Complex V broken, some of the other complexes were upregulated to compensate, which led to the use of more raw material across many metabolites.
If that is the case maybe many metabolites would be needed not just one.
Interesting new study connecting coq10, glutathione and methylation
Coenzyme Q10 modulates sulfide metabolism and links the mitochondrial respiratory chain to pathways associated to one carbon metabolism (Gonzalez-Garcia, 2020)
Coenzyme Q10 modulates sulfide metabolism and links the mitochondrial respiratory chain to pathways associated to one carbon metabolism (Gonzalez-Garcia, 2020)
Effect of Dietary Coenzyme Q10 Plus NADH Supplementation on Fatigue Perception and Health-Related QoL in ... ME/CFS, 2021, Castro-Marrero et al.
A new study out from the Castro-Marrero team, who did an earlier study of CoQ10 and NADH supplementation - discussed earlier in this thread.
A new study out from the Castro-Marrero team, who did an earlier study of CoQ10 and NADH supplementation - discussed earlier in this thread.
Ravn
Senior Member (Voting Rights)
I had the weirdest effect from high-dose CoQ10 (1200mg in split doses, plus single 20mg dose NADH).
Every time I started it, my Polar heart rate monitor would start counting actual heart beats 1.5 to 2 times (so a heart rate of 60 would be counted as 90 or 120). And every time I stopped the CoQ10, the overcounting would stop, too (there was a delay of a few hours to a day at each stop and start, presumably CoQ10 building up/taking time to be excreted).
I repeated this quite a few times because I found it so curious, 2 weeks on, 2 weeks off (with NADH taken continuously). I also checked with three other devices and they all counted normally at the same time the Polar was overcounting. So something about the Polar, whether its sensor or algorythm, is different. Because I repeated the experiment so many times I'm confident the Polar was genuinely picking up on some change, just what?
I haven't found any explanation for the overcounting. The only thing that comes up on searches for HR monitors overcounting is pacemaker interference and I don't have one of those. And the only thing that comes up for CoQ10's effect on the heart is that it's supposed to be good for it. Most unenlightening.
Eventually though I could take the CoQ10 without my HR going funny, I think it was after 4 or 5 on/off cycles. Didn't notice any other difference though so stopped again after 3 months, and didn't notice any difference from stopping either.
Every time I started it, my Polar heart rate monitor would start counting actual heart beats 1.5 to 2 times (so a heart rate of 60 would be counted as 90 or 120). And every time I stopped the CoQ10, the overcounting would stop, too (there was a delay of a few hours to a day at each stop and start, presumably CoQ10 building up/taking time to be excreted).
I repeated this quite a few times because I found it so curious, 2 weeks on, 2 weeks off (with NADH taken continuously). I also checked with three other devices and they all counted normally at the same time the Polar was overcounting. So something about the Polar, whether its sensor or algorythm, is different. Because I repeated the experiment so many times I'm confident the Polar was genuinely picking up on some change, just what?
I haven't found any explanation for the overcounting. The only thing that comes up on searches for HR monitors overcounting is pacemaker interference and I don't have one of those. And the only thing that comes up for CoQ10's effect on the heart is that it's supposed to be good for it. Most unenlightening.
Eventually though I could take the CoQ10 without my HR going funny, I think it was after 4 or 5 on/off cycles. Didn't notice any other difference though so stopped again after 3 months, and didn't notice any difference from stopping either.
Mij
Senior Member (Voting Rights)
I had an increase in heart rate when I first took CoQ10 in the 90's from a small dose of 50 mg.
Around 15 years later I tried again and had no problem taking 100mg/day, the problem over time though was that it gave me false energy and I had difficulty falling asleep. Wired/tired.
Around 15 years later I tried again and had no problem taking 100mg/day, the problem over time though was that it gave me false energy and I had difficulty falling asleep. Wired/tired.
[Preprint] Coenzyme Q10 as Treatment of Post COVID-19 Condition, 2022, Hansen et al
A well-conducted study of CoQ10 for Long Covid by a Danish team - they found CoQ10 made no difference to number or severity of symptoms.
A well-conducted study of CoQ10 for Long Covid by a Danish team - they found CoQ10 made no difference to number or severity of symptoms.
The registration for Nancy Klimas's CoQ10 phase III trial for gulf war illness shows that the study was completed in 2020, and they subsequently added the results to that page.
The differences mostly seem modest and aren't consistent across outcomes (e.g. SF-36 - more improvement in CoQ10 group, but brief visual memory test - more improvement in placebo). No p values reported.
Does anyone know if this was published? If it's a null result, it's good that they at least posted the numbers on the registration page, but currently if you search for "CoQ10 gulf war" in PubMed, the only trial listed is the 2014 RCT posted above, which might make doctors overconfident in this supplement's usefulness.
The differences mostly seem modest and aren't consistent across outcomes (e.g. SF-36 - more improvement in CoQ10 group, but brief visual memory test - more improvement in placebo). No p values reported.
Does anyone know if this was published? If it's a null result, it's good that they at least posted the numbers on the registration page, but currently if you search for "CoQ10 gulf war" in PubMed, the only trial listed is the 2014 RCT posted above, which might make doctors overconfident in this supplement's usefulness.