Nitrate, Exercise and Vascular Function in Midlife Women
NCT Number: NCT06527248
Acronym: Women's-Beet
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: NA
Conditions: Healthy|Menopause|Hypertension|Inflammation
Interventions: DIETARY_SUPPLEMENT: Nitrate group|DIETARY_SUPPLEMENT: Placebo group
Sponsor: University of Vienna
Collaborators: Medical University of Vienna|Danube University Krems|University of Giessen|Edith Cowan University|Flinders University
Sex: FEMALE
Age: ADULT, OLDER_ADULT
Enrollment: 54
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: TRIPLE (PARTICIPANT, INVESTIGATOR, OUTCOMES_ASSESSOR)|Primary Purpose: PREVENTION
Start Date: 2025-01-01
Completion Date: 2027-03

Summary:
The purpose of this clinical study in women after menopause is to investigate whether the daily intake of nitrate from beetroot juice over 12 weeks enhances the positive effect of exercise training on vascular function, blood pressure and physical performance.

The risk of cardiovascular diseases (CVD) increases with advancing age and women are particularly affected. In women, the decline in the sex hormone oestrogen in the blood circulation with menopause contributes to impaired vascular function and an increased CVD risk; in part through increased inflammatory processes, oxidative stress, and a reduced body's own production of nitric oxide (NO). NO is a signaling molecule that is important for vascular function. Endurance-based exercise training is a key lifestyle strategy to prevent CVD. However, studies indicate that exercise is less effective in terms of its health-promoting adaptations in women after menopause as compared with men of similar age.

This study investigates the effect of exercise training in combination with the intake of nitrate-rich beetroot juice on functions of the cardiovascular system. Nitrate is a nitrogen compound that is found naturally in plant foods (e.g. beetroot juice) and is converted to NO in the human body. Results of previous studies indicate vasodilatory, blood pressure-lowering and performance-enhancing effects as well as positive influences on inflammatory processes and oxidative stress following nitrate intake. The hypothesis is that nitrate intake concomitant to training promotes training adaptations and further improves vascular function, blood pressure and physical performance compared to training without nitrate intake.

For the study, 54 untrained postmenopausal women (with the ages between 45 and 65 years) will be recruited and randomly allocated into two groups. Both groups will undergo 12 weeks of endurance-based exercise training. One group will receive nitrate-rich beetroot juice, and the other nitrate-depleted beetroot juice (as placebo). Vascular function, blood pressure, maximum oxygen uptake, and blood biomarkers for nitrate metabolism, inflammation status and oxidative stress will be examined.

The anticipated study results will provide new insights into whether nitrate as a 'training adjunct' improves health-promoting training adaptations in women after menopause. The overall aim is to improve the cardiovascular health and performance of middle-aged women and reduce their increased CVD risk.

Primary Outcome Measures: Forearm blood flow (FBF) response to acetylcholine (FBFACh), Endothelial-dependent microvascular function, Change from baseline FBFACh to after the 12-week intervention period
Secondary Outcome Measures: 24-hour ambulatory systolic blood pressure, Ambulatory blood pressure monitoring, Change from baseline 24 hour-ambulatory systolic blood pressure to after the 12-week intervention period|Maximal oxygen uptake (V̇O2 max), Cardiorespiratory fitness: V̇O2 max, Change from baseline V̇O2 max to after the 12-week intervention period
Other Outcome Measures: FBF response to glyceryltrinitrate (FBFGTN), Endothelial-independent microvascular function, Change from baseline FBFGTN to after the 12-week intervention period|Clinic blood pressure, Clinic blood pressure monitoring, Change from baseline clinic blood pressure to after the 12-week intervention period|Plasma and saliva nitrate and nitrite, Nitrate metabolism: biomarker for nitrate bioavailability and functioning of the enterosalivary nitrate-nitrite-nitric oxide (NO) pathway, Change from baseline plasma and saliva nitrate and nitrite to after the 12-week intervention period|Serum hsCRP, Systemic inflammation status: serum high-sensitive C-reactive protein, Change from baseline hsCRP to after the 12-week intervention period