Evidence Trace, complete trial record
In plain terms
In plain terms: MitoQ (Mitoquinone Mesylate) shows early signals in human research but the evidence is limited -- small trials, surrogate endpoints, or not yet independently replicated. It is an emerging area, not yet a proven one.
MitoQ (Mitoquinone Mesylate)
C
Limited: small, mixed or unreplicated trials
The endpoint this grade is based on: Surrogate biomarker endpoint, Brachial artery flow-mediated dilation in older adults at 20 mg/day, a measured vascular marker that is not an established stand-in for a clinical outcome, improved in a 20-person crossover in older adults and an 18-person kidney disease pilot (C). Physical function in healthy older adults and endurance performance were tested at the same dose without benefit (D Route 2). Parkinson's disease progression was unchanged over a year at 40 to 80 mg.
The evidence as the record states it
Rossman et al. (Hypertension, 2018; PMID 29661838): 20 healthy adults aged 60 to 79 with impaired endothelial function, 20 mg/day for 6 weeks, randomized double-blind crossover; brachial flow-mediated dilation 42 percent higher than after placebo, aortic stiffness lower only in those with elevated baseline values; funded by NIH, MRC and Wellcome grants with an industry contract from the manufacturer, which supplied the capsules. Kirkman et al. (Am J Physiol Renal Physiol, 2023; PMID 37560769): randomized pilot, 18 patients with chronic kidney disease, 20 mg/day for 4 weeks; flow-mediated dilation improved, exercise capacity did not. Murray et al. (J Physiol, 2026; PMID 41733122): randomized placebo-controlled crossover, 18 healthy adults aged 60 to 79, 20 mg/day for 6 weeks; no convincing effect on physical function, with exploratory subgroup signals in those aged 70 and over; NIH-funded. Gonzalo-Skok et al. (Sports Med Open, 2024; PMID 38981985): meta-analysis of 8 trials, 188 subjects; MitoQ reduced exercise-induced oxidative damage and did not improve endurance performance. Shill et al. (J Physiol, 2016; PMID 27501153): 3 weeks of endurance training with MitoQ or placebo in young men, no difference in training adaptations or maximal oxygen uptake. Broome et al. (Redox Biol, 2022; PMID 35623315): 23 untrained men, 20 mg/day across 3 weeks of interval training; VO2peak, 20 km time trial and mitochondrial content gains no different from placebo, peak power gain larger; funded by a New Zealand government innovation agency in partnership with the manufacturer. Broome et al. (Appl Physiol Nutr Metab, 2022; PMID 35201920): 32 untrained men, 20 mg/day for 14 days; muscle soreness and recovery of maximal strength after eccentric exercise unchanged. Hughes et al. (Physiol Rep, 2023; PMID 38061764): a single 80 mg dose lowered VO2max in nine inactive women. Snow et al. (Mov Disord, 2010; PMID 20568096): 128 newly diagnosed untreated patients with Parkinson's disease, two doses against placebo for 12 months; no difference on any measure of progression; MRC-funded, with developers of the compound among the authors. Gane et al. (Liver Int, 2010; PMID 20492507): phase II, 30 hepatitis C patients, 40 or 80 mg for 28 days; aminotransferases fell within the treated groups, a different dose and population. Ras et al. (Int J Cardiol, 2013; PMID 23041097): 23 cohort studies, 14,753 people; cardiovascular risk about 8 percent lower per 1 point higher flow-mediated dilation, an observational association, not a treatment effect. Grade C on flow-mediated dilation: two small randomized trials on a marker that is not an established stand-in for a clinical outcome; functional and exercise outcomes are D on Route 2.
PMID 29661838 PMID 35623315 PMID 20492507 PMID 41733122 PMID 37560769 PMID 20568096 PMID 38981985 PMID 38061764 PMID 35201920 PMID 27501153 PMID 23041097
Evidence by specific use
Brachial artery flow-mediated dilation in older adults
Grade C
Rossman et al. (Hypertension, 2018; PMID 29661838): 20 older adults with impaired endothelial function, 20 mg/day for 6 weeks in a double-blind crossover; flow-mediated dilation 42 percent higher than after placebo, with an industry contract from the manufacturer stated beside the letter. Kirkman et al. (Am J Physiol Renal Physiol, 2023; PMID 37560769): an 18-patient pilot in chronic kidney disease, 4 weeks; flow-mediated dilation improved against placebo (p = 0.04), but the groups started apart (2.4 against 4.2 percent) and part of the difference is the placebo group falling. Flow-mediated dilation predicts cardiovascular events in cohort studies, but no trial has shown that raising it with a treatment prevents an event, so it is not an established stand-in for a clinical outcome under the B definition. Two small trials on a marker that does not qualify for B: C.
PMID 29661838 PMID 37560769
Physical function in healthy older adults
Grade D
Murray et al. (J Physiol, 2026; PMID 41733122): 6 weeks of 20 mg/day in 18 healthy older adults, no convincing effect on any measure of physical function; the authors' own conclusion is that the mouse findings did not translate. Tested at the record's dose and no benefit: D on Route 2, at low certainty given the trial's size.
PMID 41733122
Endurance exercise performance and training adaptation
Grade D
Tested without benefit. Gonzalo-Skok et al. (Sports Med Open, 2024; PMID 38981985) pooled 8 trials and found no improvement in endurance performance. Shill et al. (J Physiol, 2016; PMID 27501153) found no effect on training adaptations or maximal oxygen uptake, and Broome et al. (Redox Biol, 2022; PMID 35623315) found VO2peak and time-trial gains no different from placebo, in a trial co-funded with the manufacturer. Broome et al. (Appl Physiol Nutr Metab, 2022; PMID 35201920): no effect on soreness or strength recovery. Hughes et al. (Physiol Rep, 2023; PMID 38061764): a single 80 mg dose lowered VO2max in nine inactive women, a possible harm at a higher dose. D on Route 2.
PMID 38981985 PMID 27501153 PMID 35623315 PMID 35201920 PMID 38061764
Why Grade C and not Grade B
Grade C reflects early or limited human evidence -- small trials, surrogate endpoints, or preliminary findings not yet independently replicated. The evidence points in a promising direction but does not yet meet the standard for Grade B. A single well-powered, independently replicated trial with a meaningful endpoint would move this to Grade B or higher.
What this grade covers and what it does not
Grade C, the record's best use: brachial artery flow-mediated dilation at 20 mg/day, improved against placebo in Rossman et al. (Hypertension, 2018; PMID 29661838), 20 older adults, and in Kirkman et al. (Am J Physiol Renal Physiol, 2023; PMID 37560769), an 18-patient kidney disease pilot whose groups started apart. WHY NOT B: the B definition admits a biomarker only when it is an established stand-in for a clinical outcome, such as HbA1c, LDL, blood pressure or bone density. Flow-mediated dilation predicts cardiovascular events in cohorts (Ras et al., Int J Cardiol, 2013; PMID 23041097), but no trial has shown that raising it with a treatment prevents one. Listed beneath it: physical function in healthy older adults and endurance performance, tested at the same dose without benefit, D on Route 2. WHAT THIS GRADE DOES NOT COVER: blood pressure, heart attack, stroke or any clinical event, which no trial measured; and doses other than 20 mg/day.
What would move this grade
A well-powered randomized trial with an objective, clinically meaningful primary endpoint and at least one independent replication would support Grade B or higher.
How to track whether this is working
For vascular use, repeat the same endothelial-function or arterial-stiffness measure used at baseline, such as brachial flow-mediated dilation or pulse-wave velocity where available. Blood pressure can be followed as a conventional clinical measure. Liver enzymes are not an efficacy marker here, only a safety one where there is a separate clinical indication.