Mitochondrial-Targeted Antioxidant (MitoQ) Improves Vascular Function in Healthy Late Middle-Aged and Older Adults

Excess reactive oxygen species production by mitochondria (mtROS) is a key mechanism of vascular dysfunction with aging. Our laboratory has shown that supplementation with the mitochondrial‐targeted antioxidant MitoQ improves vascular endothelial function by reducing mtROS and ameliorates arterial stiffening in old mice, but the effects in humans are unknown. Here we sought to translate our preclinical findings to humans, while also determining the safety and efficacy of MitoQ. Twenty healthy late middle‐aged and older adults (60–79 years) with impaired endothelial function (baseline brachial artery flow‐mediated dilation [FMD] <6%) underwent six weeks of oral supplementation with MitoQ (20 mg/day) or placebo in a randomized, placebo‐controlled, double‐blind, crossover design study. MitoQ was well tolerated, and no treatment‐related serious adverse events occurred. Plasma MitoQ concentrations were higher after the treatment vs. placebo period (P<0.05). Brachial artery FMD was 42% higher after MitoQ vs. placebo (P<0.05); this improvement was associated with complete amelioration of tonic mtROS‐related suppression of endothelial function (assessed as the increase in FMD with acute 160 mg dose of MitoQ, n=9, P<0.05). Aortic stiffness (carotid‐femoral pulse wave velocity [PWV]) was lower after MitoQ vs. placebo (P<0.05) in participants with elevated baseline levels (carotid‐femoral PWV >7.60 m/s, n=11). Plasma oxidized low‐density lipoprotein, a marker of oxidative stress, also was lower after MitoQ vs. placebo (P<0.05), whereas participant characteristics, endothelium‐independent dilation (sublingual nitroglycerin) and circulating markers of inflammation were not different (all P>0.1). These findings in humans support earlier preclinical observations and suggest that MitoQ and other therapeutic strategies targeting mtROS may hold promise for treating age‐related vascular dysfunction. Support or Funding Information Clinicaltrials.gov Identifier: NCT02597023 Funding: Supported by NIH R21 AG049451, T32 AG000279, F32 AG053009, Colorado CTSA UL1 TR001082 and an industry contract with MitoQ Limited. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .