Chronic oral treatment with MitoQ for 3 months significantly improved brachial artery flow-mediated dilation in older adults compared to placebo (7.0% vs 5.8%; p=0.0002).
RCT (n=92)
randomized parallel-group
Does oral MitoQ 20mg/day improve vascular endothelial function in healthy older adults?
Three months of oral MitoQ supplementation significantly improved vascular endothelial function in healthy older adults by reducing mitochondrial oxidative stress.
Absolute Event Rate: 7% vs 5.8%
p-value: p=0.0002
BACKGROUND: Vascular endothelial dysfunction with aging, characterized by reduced nitric oxide (NO) bioavailability, is mediated by excessive production of mitochondrial reactive oxygen species (mitoROS). The excessive mitoROS, in turn, is stimulated in part by age-related changes to the circulating milieu (serum). In a small crossover design pilot trial in older adults (n=20), we found that 6 weeks of oral treatment with the mitochondria-targeted antioxidant MitoQ improved endothelial function by reducing mitoROS, while favorably altering the circulating milieu. However, these findings need to be extended to a randomized parallel design trial in a larger cohort of older adults using a clinically relevant treatment period. HYPOTHESES: Compared with placebo (PLA), 3 months of chronic oral treatment with MitoQ in older adults would: 1) improve vascular endothelial function by reducing mitoROS; and 2) induce changes to the circulating milieu that reduce mitoROS and increase NO bioavailability. METHODS: Ninety-two healthy older men and postmenopausal women (age 60+ yrs) underwent 3 months of supplementation with MitoQ (20mg/day) (N=45, 30 women; 69±1 yrs) or PLA (N=47, 26 women; 68±1 yrs) in a randomized parallel-group design Phase IIa clinical trial (NCT04851288). Endothelial function was assessed by brachial artery flow-mediated dilation (FMDBA). Smooth muscle sensitivity to NO was quantified by brachial artery dilation to sublingual nitroglycerin. Administration of a supratherapeutic dose of MitoQ (160mg) was employed to acutely inhibit mitoROS-related oxidative stress in vivo (N=38-39/group); the difference in FMDBA after vs before the acute 160mg dose was taken as the tonic suppression of endothelial function by mitoROS. In preclinical experiments, common carotid arteries and aortic rings (~1 mm) were obtained from young sex-matched, intervention naïve C57BL/6J mice (3-6 mo). Excised common carotid arteries were exposed for 24 hr and aortic rings for 48 hr to 5% participant serum collected before and after chronic MitoQ or PLA treatment. Acetylcholine-stimulated endothelium-dependent dilation (EDD; carotid artery pressure myography) and aortic ROS bioactivity (electron resonance spectroscopy, CMH spin probe) were assessed (N=9-10, 5 women/group). The contribution of mitoROS to EDD was determined by perfusion of carotid arteries with participant serum in the presence vs. absence of MitoQ. RESULTS: FMDBA increased by 22% with chronic MitoQ treatment (pre: 5.7±0.4%, post: 7.0±0.5%) but did not change with PLA (pre: 5.5±0.3%, post: 5.8±0.3%) (interaction: p=0.0002). The improvement with chronic MitoQ was associated with a 61% reduction in the mitoROS-related suppression of FMDBA (p=0.0015). Traditional cardiometabolic risk factors and smooth muscle sensitivity to NO were unchanged. Compared with exposure to baseline serum, peak carotid EDD was greater (MitoQ: +4.8±1.0%, PLA: +0.5±1.1%; p=0.0024) and aortic ROS bioactivity was lower (MitoQ: -38.8%±4.0%, PLA +5.5±3.7%; p< 0.0001) in arteries after exposure to serum collected after chronic MitoQ treatment. MitoQ incubation following serum exposure enhanced peak EDD at baseline and after PLA but led to no further improvement in peak EDD in arteries exposed to serum collected after chronic MitoQ (p=0.0006). CONCLUSION: Chronic oral treatment with MitoQ improves endothelial function in older adults by lowering mitoROS-related oxidative stress via favorable changes to the circulating milieu. Targeting excessive mitoROS is a promising strategy for enhancing endothelial function with aging. FUNDING: R01AG066730; F32HL167552; F31AG087709; NIH/NCATS CTSA UL1TR002535. MitoQ and placebo pills provided by MitoQ Limited. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.
Murray et al. (Fri,) conducted a rct in Healthy older adults (n=92). MitoQ vs. Placebo was evaluated on Brachial artery flow-mediated dilation (FMDBA) (p=0.0002). Chronic oral treatment with MitoQ for 3 months significantly improved brachial artery flow-mediated dilation in older adults compared to placebo (7.0% vs 5.8%; p=0.0002).