Exercise Training Intensity and Nitrate Supplementation in Post-Menopausal Females
- Conditions
- Menopause
- Interventions
- Dietary Supplement: Berkeley Life Pro Nitrate CapsulesBehavioral: High Intensity ExerciseBehavioral: Moderate Intensity Exercise
- Registration Number
- NCT06480695
- Lead Sponsor
- University of Virginia
- Brief Summary
Menopause greatly increases cardiovascular disease risk (CVD). Current exercise guidelines are inadequate to ameliorate this risk and higher intensity exercise may be necessary for cardiovascular benefits in postmenopausal females. Oral nitrate supplementation enhances exercise performance and CVD risk profile in several clinical conditions. The investigators recently reported that 3-days of nitrate supplementation in postmenopausal females enhances acute post-exercise vascular function, in an intensity dependent manner. The effects of nitrate supplementation and exercise training over a longer training program remains unexplored. This investigation will examine the impact of exercise training intensity with and without inorganic nitrate supplementation, on CVD and fitness outcomes. Postmenopausal females will be tested for maximal oxygen uptake and lactate threshold before randomization to one of four groups: that inorganic nitrate-rich tablets, or tablets with nitrate extracted; and assigned to one-month of calorie matched high-intensity or moderate-intensity exercise training. Vascular function and fitness will be evaluated before and after training.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- Female
- Target Recruitment
- 40
- Post-menopausal female (greater than age 45 but less than age 75)
- Sedentary (does not exercise regularly or less than 2 bouts of exercise per week)
- No major changes in medication in the last 3 months
- Smokers within last 5 years
- Weight unstable (loss/gain of more than 3kg in the past 3 months)
- Any medical condition that prevents the subject from exercising safely
- Hormone replacement therapy (current or within last 3 months)
- Diabetes
- Currently or recently on vasoactive medications (i.e., calcium channel blockers, statins, ACE or renin inhibitors, ARBs, nitrates, alpha- or beta-blockers, diuretics, proton pump inhibitors, etc.)
- Oral antibiotic use within previous four weeks
- Oral disease or poor oral health as determined by the Oral Health Questionnaire
- Using an antibacterial mouthwash or a mouthwash containing chlorhexidine and unwilling to discontinue use
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Berkeley Life Nitrate-Rich Pro Capsules + High Intensity Exercise (HIE) High Intensity Exercise Participants assigned to this group will be instructed to take 6 capsules rich in nitrate (\~157mg of nitrate each) 2x a day (morning a night) starting 2-hours before the first exercise session. Participants will complete a supervised bout of exercise on a treadmill 3x a week for 1-month. Participants will exercise at an RPE of 15-17 based on the participant's VO2peak test. Berkeley Life Nitrate-Rich Pro Capsules + High Intensity Exercise (HIE) Berkeley Life Pro Nitrate Capsules Participants assigned to this group will be instructed to take 6 capsules rich in nitrate (\~157mg of nitrate each) 2x a day (morning a night) starting 2-hours before the first exercise session. Participants will complete a supervised bout of exercise on a treadmill 3x a week for 1-month. Participants will exercise at an RPE of 15-17 based on the participant's VO2peak test. Berkeley Life Nitrate-Rich Pro Capsules + Moderate Intensity Exercise (MIE) Moderate Intensity Exercise Participants assigned to this group will be instructed to take 6 capsules rich in nitrate (\~157mg of nitrate each) 2x a day (morning a night) starting 2-hours before the first exercise session. Participants will complete a supervised bout of exercise on a treadmill 3x a week for 1-month. Participants will exercise at an RPE of 10-12 based on the participant's VO2peak test. Berkeley Life Placebo Capsules + High Intensity Exercise (HIE) High Intensity Exercise Participants assigned to this group will be instructed to take 6 capsules rich in nitrate-depleted placebo 2x a day (morning a night) starting 2-hours before the first exercise session. Participants will complete a supervised bout of exercise on a treadmill 3x a week for 1-month. Participants will exercise at an RPE of 15-17 based on the participant's VO2peak test. Berkeley Life Nitrate-Rich Pro Capsules + Moderate Intensity Exercise (MIE) Berkeley Life Pro Nitrate Capsules Participants assigned to this group will be instructed to take 6 capsules rich in nitrate (\~157mg of nitrate each) 2x a day (morning a night) starting 2-hours before the first exercise session. Participants will complete a supervised bout of exercise on a treadmill 3x a week for 1-month. Participants will exercise at an RPE of 10-12 based on the participant's VO2peak test. Berkeley Life Placebo Capsules + Moderate Intensity Exercise (MIE) Moderate Intensity Exercise Participants assigned to this group will be instructed to take 6 capsules rich in nitrate-depleted 2x a day (morning a night) starting 2-hours before the first exercise session. Participants will complete a supervised bout of exercise on a treadmill 3x a week for 1-month. Participants will exercise at an RPE of 10-12 based on the participant's VO2peak test.
- Primary Outcome Measures
Name Time Method Cardiorespiratory Fitness Baseline and after 1-month of exercise training Peak aerobic capacity (VO2peak) will be assessed using a symptom-limited graded exercise test on a treadmill. An IV will be placed and lactate measured during rest and after the completion of every 3-minute stage to determine lactate threshold at VO2peak.
Vascular Endothelial Function (Flow-Mediated Dilation [FMD]) Baseline and after 1-month of exercise training Participants will be placed in a supine position with their left forearm slightly extended and supinated with legs straight. The arteries will be imaged using a high-resolution 7.5MHz linear array transducer at rest, during 5 minutes of forearm occlusion via cuff inflation, and continuously for 3 minutes post-occlusion; an EKG trigger will be used to capture images during end-diastole of the cardiac cycle.
- Secondary Outcome Measures
Name Time Method Lipids Baseline and after 1-month of exercise training A blood sample will be obtained to measure lipids.
Hemoglobin Baseline and after 1-month of exercise training A blood sample will be obtained to measure hemoglobin.
Oral Nitrate Reducing Capacity Baseline and after 1-month of exercise training Assessment of the oral microbiome's ability to reduce nitrate to nitrite. This will be measured through a swab on the dorsal surface of the tongue, an unstimulated saliva sample, and a rinse of a standard nitrate solution.
Skeletal muscle perfusion Baseline and after 1-month of exercise training Skeletal Muscle Blood Flow (straight gauge plethysmography) will be measured non-invasively using venous occlusion/strain-gauge plethysmography both at rest and during reactive hyperemia following 5-minutes of occlusion via the Hokanson A16. A strain gauge device will be place around the widest part of the participant's right calf. A blood pressure place around participant's ankle will be inflated for 60 seconds to eliminate foot circulation from the measurement. At the same time, a cuff placed on the thigh will be inflated to block venous blood flow. The cuff occlusion will be held for \~60 seconds ((several cardiac cycles (4-6 cycles)) to obtain resting blood flow measurements.
Peripheral and Central Blood Pressures Baseline and after 1-month of exercise training Brachial artery blood pressures will be obtained using a standard sphygmomanometer. Aortic blood pressures will be obtained using applanation tonometry (SphygmoCor version 8.0, AtCor Medical).
24-hour ambulatory blood pressure Baseline and after 1-month of exercise training Blood pressure will be monitored using a standard ambulatory brachial artery blood pressure cuff (SunTech Oscar 2, SunTech Medical). Blood pressure measurements are programmed to be taken every 30-minutes during the day and every hour at night. This allows for monitoring of nighttime blood pressure changes and variations throughout the day.
Skeletal muscle microvascular perfusion (near-infra-red- spectroscopy) Baseline and after 1-month of exercise training Tissue oxygenation will be captured noninvasively using non-invasive, near-infrared spectrometry (NIRS, PortaMon, Artinis Medical Systems B.V., The Netherlands) positioned on the gastrocnemius or vastus lateralis muscle.
Plasma Nitrate Baseline and after 1-month of exercise training A fasting blood draw will be taken. Following the blood draw, the participant will take one dose of Beetroot juice. The participant will then return to the lab three hours later for a second blood draw to assess level of nitrate in the plasma.
Plasma Nitrite Baseline and after 1-month of exercise training A fasting blood draw will be taken. Following the blood draw, the participant will take one dose of Beetroot juice. The participant will then return to the lab three hours later for a second blood draw to assess level of nitrite in the plasma.