CoQ10 - Coenzyme Q10

What was the unit of measure @Mij?

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​

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."​

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.

 

Another bit of evidence relating to CoQ10 is the finding by Paul Fisher's team (Daniel Missailidis) that it seems to be only Complex 5 that is broken in mitochondria. The rest of the ATP process, including the bit requiring CoQ10, seemed to be working fine.

 

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,

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-Hub

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.

 

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.

 

This latest Castro-Marrero trial is of a good size (70 participants in each arm after dropouts). Despite what the abstract says, the data does not suggest the CoQ10 +NADH treatment is helpful for people with ME/CFS, at least when taken for two months.

 

[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.