Nitrate, Exercise and Vascular Function in Midlife Women

Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexFemale
Age45-65
SponsorUniversity of Vienna

About this trial

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.

Eligibility criteria

This trial accepts healthy volunteers

Qualifiers

Postmenopausal women (amenorrhoeic ≥1 year), between the ages of 45 and 65 years, inclusive, who are either normotensive or are medically treated for stage 1 hypertension

Written informed consent

Disqualifiers

Current or recent (within previous 3 months) engagement in exercise training (i.e., planned, structured, and regular exercise) with an average net exercise time of >2 hours per week

Above-average cardiorespiratory fitness levels (i.e., a V̇O2 max max above the 75th percentile of age- and sex-specific normative data: ≥43 mL/kg/min for women aged 45-49 years, ≥38 mL/kg/min for women aged 50-59 years, ≥35 mL/kg/min for women aged 60-65 years)

Any evidence of acute or chronic diseases such as symptomatic cardiovascular or peripheral vascular disease, moderate or severe chronic kidney disease (estimated glomerular filtration rate (GFR) <50 mL/min), pulmonary, neural, or musculoskeletal disease, osteoporotic fractures, cancer, or type 1 or 2 diabetes mellitus

Fasting glucose >7.0 mmol/L or HbA1c > 6.5 rel. %

Trial design

Design model

Parallel

Treatments tested in this trial

  • Nitrate group

    Dietary supplement

    Daily consumption of 70 mL beetroot juice containing \~400 mg nitrate over an intervention period of 12 weeks concomitant to exercise training, either 3 hours pre-exercise on training days or with breakfast on non-training days.

  • Placebo group

    Dietary supplement

    Daily consumption of 70 mL nitrate-depleted beetroot juice (placebo) over an intervention period of 12 weeks concomitant to exercise training, either 3 hours pre-exercise on training days or with breakfast on non-training days.

Treatment groups

54 Participants
are divided into 2 treatment groups
Group A: Nitrate groupActive comparator 1 intervention
Group B: Placebo groupPlacebo comparator 1 intervention

Trial outcomes

Primary outcomes

1

Forearm blood flow (FBF) response to acetylcholine (FBFACh)

Endothelial-dependent microvascular function

Time frame
Change from baseline FBFACh to after the 12-week intervention period

Secondary outcomes

1

24-hour ambulatory systolic blood pressure

Ambulatory blood pressure monitoring

Time frame
Change from baseline 24 hour-ambulatory systolic blood pressure to after the 12-week intervention period
2

Maximal oxygen uptake (V̇O2 max)

Cardiorespiratory fitness: V̇O2 max

Time frame
Change from baseline V̇O2 max to after the 12-week intervention period

Other outcomes

1

FBF response to glyceryltrinitrate (FBFGTN)

Endothelial-independent microvascular function

Time frame
Change from baseline FBFGTN to after the 12-week intervention period
2

Clinic blood pressure

Clinic blood pressure monitoring

Time frame
Change from baseline clinic blood pressure to after the 12-week intervention period
3

Plasma and saliva nitrate and nitrite

Nitrate metabolism: biomarker for nitrate bioavailability and functioning of the enterosalivary nitrate-nitrite-nitric oxide (NO) pathway

Time frame
Change from baseline plasma and saliva nitrate and nitrite to after the 12-week intervention period
4

Serum hsCRP

Systemic inflammation status: serum high-sensitive C-reactive protein

Time frame
Change from baseline hsCRP to after the 12-week intervention period

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

University of Vienna

Lead sponsor

Medical University of Vienna

Collaborator

Danube University Krems

Collaborator

University of Giessen

Collaborator

Edith Cowan University

Collaborator

Flinders University

Collaborator