MitoQ and Exercise Effects on Vascular Health

Summary

An impairment in vascular function can lead to the development of age-associated cardiovascular disease (CVD), the leading cause of death in postmenopausal women. Regular aerobic exercise (AE) benefits vascular function in older men by reducing oxidative stress, however, similar AE training improvements are diminished or absent in postmenopausal women. not using estrogen-based hormone therapy. Vascular function and oxidative stress are improved with AE training in postmenopausal women treated with E2, suggesting an essential role of E2 in vascular adaptations to AE in women. Clinical use of E2 is contraindicated for this purpose, thus establishing alternative pharmacological approaches that could be administered as a substitute for E2 to improve AE signaling for vascular benefits and reducing CVD risk in E2-deficient postmenopausal women is biomedically important. The mitochondrial-targeted antioxidant MitoQ may be an alternative to E2 for restoring AE benefits in E2-deficient postmenopausal women given its recently established effectiveness for reducing oxidative stress and improving vascular function in that population. Accordingly, the overall aim of this application is to assess the efficacy of a 12-week randomized controlled trial of moderate intensity AE training combined with oral MitoQ (20 mg/d) compared to AE+oral placebo (PL) or No AE+MitoQ on vascular vasodilatory function (brachial artery flow-mediated dilation; FMD) in healthy E2-deficient postmenopausal women. Insight into the causes for the improvement related to molecules (e.g., nitric oxide) that promote vasodilation, mitochondrial function, oxidative stress, and the influence of "circulating factors" will also be obtained. We hypothesize that AE+MitoQ will improve both FMD \> AE+PL and \> No AE+MitoQ, and that No AE+MitoQ will improve FMD \> AE+PL. The greater improvements in endothelial function with AE+MitoQ vs. both AE+PL and No AE+MitoQ, and with No AE+MitoQ vs. AE+PL will be mediated by greater improvements in nitric oxide production, mitochondrial function, and mitochondrial and oxidative stress linked, at least in part, to changes in "circulating factors". The expected results from this study will establish the efficacy of MitoQ for restoring AE-vascular signaling in E2-deficient postmenopausal women and will provide the foundation for development of evidence-based guidelines for sex-specific AE programs for improving vascular health and preventing CVD in postmenopausal women.

Conditions

• Aging
• Menopause

Interventions

DIETARY_SUPPLEMENT

MitoQ

MitoQ is a biochemically modified form of ubiquinol

DIETARY_SUPPLEMENT

Placebo

Each placebo capsule contains inert excipient and is identical in appearance

BEHAVIORAL

Aerobic exercise

Moderate intensity aerobic exercise on the treadmill

Sponsors & Collaborators

• National Institute on Aging (NIA)

  collaborator NIH

• University of Colorado, Denver

  lead OTHER

Principal Investigators

• Kerrie L Moreau, PhD · University of Colorado, Denver

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

TRIPLE

Model

PARALLEL

Eligibility

Min Age

50 Years

Max Age

120 Years

Sex

FEMALE

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2023-01-16

Primary Completion

2024-09-30

Completion

2025-11-30

FDA Drug

Yes

Countries

• United States

Study Locations