CoQ10 - Coenzyme Q10

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).

 

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).

 

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:



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:


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.

 

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.



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.




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.

 

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.

 

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.

 

There is the Mendus study on MitoQ

The influence of Mitoq on symptoms and cognition in fibromyalgia, myalgic encephalomyelitis and chronic fatigue
Johnson and Grant. I can't find the date on the document yet, but I think it happened in 2015.

http://docs.wixstatic.com/ugd/a420b5_bbb1cc70f8a54e949a08432ac76690fc.pdf

We don't seem to have a thread on this?

 

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:

 

I found this:

Do you have some information about the two forms or dosage @Amw66?

 

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?

 

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.

 

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.
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Scihub