Mitochondrial-targeted Antioxidant Supplementation for Improving Age-related Vascular Dysfunction in Humans

  • End date
    Dec 3, 2025
  • participants needed
  • sponsor
    University of Colorado, Boulder
Updated on 4 October 2022


The majority of cardiovascular diseases (CVD) occur in men and women 60 years of age. Vascular dysfunction, including endothelial dysfunction, as assessed by reduced endothelium-dependent dilation (EDD), and stiffening of the large elastic arteries (i.e., aortic and carotid artery stiffening), is a major mechanism of increased risk of CVD in older adults. Excess production of ROS (reactive oxygen species) by mitochondria (mtROS) has emerged as a central feature of vascular oxidative stress with aging and driver of age-related vascular dysfunction. As such, identifying novel strategies to decrease mtROS and improve vascular function, to ultimately reduce the risk of age-related CVD, is an important biomedical objective.

MitoQ is a mitochondria-targeted antioxidant that accumulates at the inner mitochondrial membrane where it is optimally positioned to reduce mtROS. Preclinical findings showed that 4 weeks of oral MitoQ supplementation completely restored EDD in old mice, ameliorated mtROS-associated suppression of EDD, and was associated with reduced arterial mtROS, oxidative stress, and improved mitochondrial health. MitoQ therapy also reduced aortic stiffness in old mice. A recent small pilot study of older adults (n=20) found that supplementation with MitoQ was well-tolerated, improved endothelial function, and reduced plasma levels of oxidized low-density lipoprotein, a circulating biomarker of oxidative stress. Consistent with the preclinical findings, preliminary mechanistic assessments in subsets of subjects from the pilot study suggested that improved endothelial function with MitoQ was mediated by reduced endothelial cell mtROS production, associated reductions in tonic mtROS-related suppression of EDD, and improved mitochondrial health, linked in part to changes in circulating factors in the serum induced by chronic MitoQ supplementation. Lastly, MitoQ reduced aortic stiffness in older adults who exhibited age-related aortic stiffening at baseline.

The investigators are conducting a randomized, placebo-controlled, double-blind clinical trial to establish oral MitoQ (20 mg/day; MitoQ, Ltd.) for 3 months vs. placebo (n=56/group) for improving endothelial function in older men and women (60 years), and determine the mechanisms by which MitoQ improves endothelial function. The investigators will also assess the effect of MitoQ on aortic stiffness.

Condition Senility, Aging, Aging
Treatment Placebo, MitoQ
Clinical Study IdentifierNCT04851288
SponsorUniversity of Colorado, Boulder
Last Modified on4 October 2022


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Inclusion Criteria

Age 60 years and over
Ability to provide informed consent
Willing to accept random assignment to condition
Body mass index <40 kg/m2
Weight stable in the prior 3 months (<2 kg weight change) and willing to remain weight stable throughout the study
Free from alcohol dependence or abuse
Mini-mental stage examination score 21

Exclusion Criteria

Uncontrolled thyroid disease
Regular vigorous aerobic (>6 bouts/week, >60 min/bout at a workload >6 METS)
Blood donation within 8 weeks prior to enrolling in the study
Clear my responses

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