High-dose ubiquinol supplementation in multiple-system atrophy: a multicentre, randomised, double-blinded, placebo-controlled phase 2 trial, 2023

Multiple System Atrophy:

-slowness of movement, tremor, or stiffness
-clumsiness or lack of coordination
-impaired speech
-croaky quivering voice
-fainting or lightheadedness due to orthostatic hypotension

Summary
Background
Functionally impaired variants of COQ2, encoding an enzyme in biosynthesis of coenzyme Q10 (CoQ10), were found in familial multiple system atrophy (MSA) and V393A in COQ2 is associated with sporadic MSA. Furthermore, reduced levels of CoQ10 have been demonstrated in MSA patients.
Methods
This study was a multicentre, randomised, double-blinded, placebo-controlled phase 2 trial. Patients with MSA were randomly assigned (1:1) to either ubiquinol (1500 mg/day) or placebo. The primary efficacy outcome was the change in the unified multiple system atrophy rating scale (UMSARS) part 2 at 48 weeks. Efficacy was assessed in all patients who completed at least one efficacy assessment (full analysis set). Safety analyses included patients who completed at least one dose of investigational drug. This trial is registered with UMIN-CTR (UMIN000031771), where the drug name of MSA-01 was used to designate ubiquinol.
Findings
Between June 26, 2018, and May 27, 2019, 139 patients were enrolled and randomly assigned to the ubiquinol group (n = 69) or the placebo group (n = 70). A total of 131 patients were included in the full analysis set (63 in the ubiquinol group; 68 in the placebo group). This study met the primary efficacy outcome (least square mean difference in UMSARS part 2 score (−1.7 [95% CI, −3.2 to −0.2]; P = 0.023)). The ubiquinol group also showed better secondary efficacy outcomes (Barthel index, Scale for the Assessment and Rating of Ataxia, and time required to walk 10 m). Rates of adverse events potentially related to the investigational drug were comparable between ubiquinol (n = 15 [23.8%]) and placebo (n = 21 [30.9%]).
Interpretation
High-dose ubiquinol was well-tolerated and led to a significantly smaller decline of UMSARS part 2 score compared with placebo.

https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(23)00097-4/fulltext

 

Note, reduced levels of CoQ10 have been demonstrated in MSA patients.

Some pwME have stated that PEM was ameliorated from taking high dose Ubiquinol.

It helped me years ago but over time it made my sleep worse.

 

Ubiquinol seems to boost my energy. It doesn't have a tremendous effect, but it helps a little. After about 7 to 10 days of not taking it, I become more fatigued.

I've gone through this ABA cycle several times now with the same effect.

 

I'm suggesting that CoQ10 Ubiquinol might be helpful for symptoms such as orthostatic intolerance and improved heat tolerance which was most likely the case for me during PEM.

My CoQ10 blood test results were low.

 

What are the supplements helping exactly? OI? Coq10 didn't give more energy per se, but I was able to function better until it disrupted my sleep so I discontinued.

Effect of Dietary Coenzyme Q10 Plus NADH supplementation on Fatigue Perception and Health-Related QOL in individuals of M.E/CFS: A prospective, randomized, double-blind, placebo-controlled trial.

Abstract
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex, multisystem, and profoundly debilitating neuroimmune disease, probably of post-viral multifactorial etiology. Unfortunately, no accurate diagnostic or laboratory tests have been established, nor are any universally effective approved drugs currently available for its treatment.

This study aimed to examine whether oral coenzyme Q10 and NADH (reduced form of nicotinamide adenine dinucleotide) co-supplementation could improve perceived fatigue, unrefreshing sleep, and health-related quality of life in ME/CFS patients. A 12-week prospective, randomized, double-blind, placebo-controlled trial was conducted in 207 patients with ME/CFS, who were randomly allocated to one of two groups to receive either 200 mg of CoQ10 and 20 mg of NADH (n = 104) or matching placebo (n = 103) once daily. Endpoints were simultaneously evaluated at baseline, and then reassessed at 4- and 8-week treatment visits and four weeks after treatment cessation, using validated patient-reported outcome measures.

A significant reduction in cognitive fatigue perception and overall FIS-40 score (p < 0.001 and p = 0.022, respectively) and an improvement in HRQoL (health-related quality of life (SF-36)) (p < 0.05) from baseline were observed within the experimental group over time. Statistically significant differences were also shown for sleep duration at 4 weeks and habitual sleep efficiency at 8 weeks in follow-up visits from baseline within the experimental group (p = 0.018 and p = 0.038, respectively).

Overall, these findings support the use of CoQ10 plus NADH supplementation as a potentially safe therapeutic option for reducing perceived cognitive fatigue and improving the health-related quality of life in ME/CFS patients. Future interventions are needed to corroborate these clinical benefits and also explore the underlying pathomechanisms of CoQ10 and NADH administration in ME/CFS.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8399248/

 

Well, if that gene comes up in our results as one that many of participants share a variant of then we will of course report it.