Postmenopausal Women
Conditions
Keywords
Dietary nitrate supplementation, Beetroot juice
Brief summary
In this study the investigators will test the hypothesis that acute consumption of inorganic nitrate (supplied in concentrated beetroot juice) reduces artery stiffness and resting blood pressure, and lessens the rise in blood pressure during handgrip exercise in postmenopausal women. Understanding and improving artery function and blood pressure regulation in women is important because they undergo accelerated arterial stiffening after menopause and have much larger increases in blood pressure when they exercise compared with either premenopausal women or men of similar age.
Detailed description
Postmenopausal women have stiff central arteries and exaggerated blood pressure (BP) responses during exercise compared with either premenopausal women or men of similar age. Arterial stiffness and exaggerated BP responses to exercise are prognostic for heart wall thickening, future hypertension, adverse cardiovascular events, and mortality. Previous studies have reported that acute consumption of nitrate-rich beetroot juice can lower resting and exercising BP responses in older adults. However, these studies included both sexes and did not compare the effects of beetroot juice to a nitrate-depleted placebo (a true control). Thus, the potential BP lowering effects of nitrate supplementation per se have not been established in postmenopausal women. The present study examines the acute (single dose) effects of nitrate-rich beetroot juice on resting hemodynamics (peripheral and central BP, arterial wave properties, etc), and physiological responses to handgrip exercise in metabolically healthy post-menopausal women.
Interventions
DRUGBeetroot juice
This beverage contains 0.3 g of inorganic nitrate per 70 ml container, and is bottled and supplied by James White Drinks (UK).
This beverage is identical in look and taste to the Beet-It organic shot, but has the nitrate removed. It is also bottled and supplied by James White Drinks (UK).
Sponsors
Penn State University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Masking description
Treatment order will be randomly assigned to participants by Clinical Research Center (CRC) staff using computer-based mathematical software. The generated list that determines each participants treatment order will be kept in a secure location in the CRC which cannot be accessed directly by research team members.
Eligibility
Sex/Gender
FEMALE
Age
55 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
* Resting systolic blood pressure less than or equal to 160 mmHg * Resting diastolic blood pressure less than or equal to 100 mmHg
Exclusion criteria
* Overt cardiovascular, metabolic, hematologic, pulmonary, renal, musculoskeletal, and/or neurological disease(s) * Users of any tobacco and/or nicotine products (smokers, chewing tobacco, nicotine-containing patches/gum, smokeless cigarettes) * Body mass index greater than 35 * Total cholesterol greater than 239 mg/dl * LDL cholesterol greater than 159 mg/dl * Fasting blood triglycerides greater than 199 mg/dl * Fasting blood glucose greater than 109 mg/dl and HbA1c greater than 6.0% * Individuals currently taking any of the following medications: 1. blood pressure lowering medication (e.g., beta blockers, ACE inhibitors, angiotensin antagonists, calcium channel blockers, diuretics) 2. lipid-lowering medication (e.g., statins) 3. nitrates (e.g. nitroglycerin) for angina 4. phosphodiesterase inhibitors (e.g., Viagra) 5. anti-inflammatory drugs * Individuals currently taking hormone replacement therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Resting Aortic Blood Pressures | Resting systolic blood pressure at 90 minutes after beetroot juice ingestion | Aortic Blood pressures were measured in the arm (cuff) and estimated in the aorta (radial artery tonometry). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Handgrip Exercise Blood Pressure Responses (Relative Change From Baseline) | Approximately 180 minutes after ingestion of beetroot juice | Beat-to-beat blood pressure (finger cuff) will be assessed at rest and during handgrip exercise to volitional fatigue. |
| Handgrip Exercise Tolerance | Approximately 90 minutes after ingestion of beetroot juice | Time to fatigue (seconds) was assessed during a progressive blood flow restricted handgrip exercise protocol. |
| Peak Rate of Perceived Exertion Scores During Handgrip Exercise | Approximately 90 minutes after ingestion of beetroot juice | The Borg Rating of Perceived Exertion Scale (RPE) was used to assess exercise intensity during handgrip exercise. The RPE scale ranges from a minimum of 6 (no exertion at all) to a maximum of 20 (maximal exertion) units on a scale. |
| Blood Measures of Nitrate Absorption and Conversion | Change from baseline measures of plasma nitrate and nitrite at 90 minutes and at approximately 6 hours | Venous blood will be withdrawn (venipuncture) for determination of plasma nitrate and nitrite. |
| Resting Arterial Stiffness/Wave Properties | Change from baseline resting pulse wave velocity at 90 minutes after beet root juice ingestion | Carotid to femoral artery pulse wave velocity will be assessed using arterial tonometry. |
Countries
United States
Participant flow
Recruitment details
20 healthy postmenopausal women were screened for eligibility between October 15, 2013 and January 1, 2020 at State College community in State College, PA.
Pre-assignment details
16 of 20 participants were randomized. Of those not randomized, 3 did not meet inclusion criteria and 1 withdrew after the familiarization visit.
Participants by arm
| Arm | Count |
|---|---|
| Randomized, Nitrate-rich or -Depleted Beetroot Juice on Two Separate Days Subjects consumed 140 ml of beetroot juice (Beet-It Organic Shot) approximately 90 min before physiological testing.
Nitrate-rich Beetroot juice: This beverage contains 0.3 g of inorganic nitrate per 70 ml container, and is bottled and supplied by James White Drinks (UK).
Nitrate-depleted Beetroot juice (placebo): This beverage is identical in look and taste to the Beet-It organic shot, but has the nitrate removed. It is also bottled and supplied by James White Drinks (UK). | 13 |
| Total | 13 |
Baseline characteristics
| Characteristic | Randomized, Nitrate-rich or -Depleted Beetroot Juice on Two Separate Days |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 4 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants |
| Age, Continuous | 63 year STANDARD_DEVIATION 4.1 |
| Mean arterial pressure | 91 mmHg |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 13 Participants |
| Region of Enrollment United States | 13 participants |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 13 | 0 / 13 |
| other Total, other adverse events | 0 / 13 | 0 / 13 |
| serious Total, serious adverse events | 0 / 13 | 0 / 13 |
Outcome results
Primary
Resting Aortic Blood Pressures
Aortic Blood pressures were measured in the arm (cuff) and estimated in the aorta (radial artery tonometry).
Time frame: Resting systolic blood pressure at 90 minutes after beetroot juice ingestion
Population: This was a crossover study where the same group of subjects was intervened with both nitrate-rich beetroot juice and nitrate depleted beetroot juice
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Randomized, Nitrate Rich Beetroot Juice | Resting Aortic Blood Pressures | 113.3 mmHg | Standard Error 4.1 |
| Randomized, Nitrate Depleted Beetroot Juice | Resting Aortic Blood Pressures | 116.9 mmHg | Standard Error 6.3 |
Secondary
Blood Measures of Nitrate Absorption and Conversion
Venous blood will be withdrawn (venipuncture) for determination of plasma nitrate and nitrite.
Time frame: Change from baseline measures of plasma nitrate and nitrite at 90 minutes and at approximately 6 hours
Population: This study is a crossover study. Same subjects for nitrate-rich beetroot juice were intervened for nitrate-depleted beetroot juice.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Randomized, Nitrate Rich Beetroot Juice | Blood Measures of Nitrate Absorption and Conversion | Plasma nitrate concentration | 643.9 uM | Standard Error 45.7 |
| Randomized, Nitrate Rich Beetroot Juice | Blood Measures of Nitrate Absorption and Conversion | Plasma Nitrite concentration | 0.402 uM | Standard Error 0.077 |
| Randomized, Nitrate Depleted Beetroot Juice | Blood Measures of Nitrate Absorption and Conversion | Plasma nitrate concentration | 39.2 uM | Standard Error 9.3 |
| Randomized, Nitrate Depleted Beetroot Juice | Blood Measures of Nitrate Absorption and Conversion | Plasma Nitrite concentration | 0.115 uM | Standard Error 0.027 |
Secondary
Handgrip Exercise Blood Pressure Responses (Relative Change From Baseline)
Beat-to-beat blood pressure (finger cuff) will be assessed at rest and during handgrip exercise to volitional fatigue.
Time frame: Approximately 180 minutes after ingestion of beetroot juice
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Randomized, Nitrate Rich Beetroot Juice | Handgrip Exercise Blood Pressure Responses (Relative Change From Baseline) | 25 percentage of change from baseline | Standard Error 3 |
| Randomized, Nitrate Depleted Beetroot Juice | Handgrip Exercise Blood Pressure Responses (Relative Change From Baseline) | 30 percentage of change from baseline | Standard Error 5 |
Secondary
Handgrip Exercise Tolerance
Time to fatigue (seconds) was assessed during a progressive blood flow restricted handgrip exercise protocol.
Time frame: Approximately 90 minutes after ingestion of beetroot juice
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Randomized, Nitrate Rich Beetroot Juice | Handgrip Exercise Tolerance | 602.8 seconds | Standard Deviation 48.61 |
| Randomized, Nitrate Depleted Beetroot Juice | Handgrip Exercise Tolerance | 541.0 seconds | Standard Deviation 48.66 |
Secondary
Peak Rate of Perceived Exertion Scores During Handgrip Exercise
The Borg Rating of Perceived Exertion Scale (RPE) was used to assess exercise intensity during handgrip exercise. The RPE scale ranges from a minimum of 6 (no exertion at all) to a maximum of 20 (maximal exertion) units on a scale.
Time frame: Approximately 90 minutes after ingestion of beetroot juice
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Randomized, Nitrate Rich Beetroot Juice | Peak Rate of Perceived Exertion Scores During Handgrip Exercise | 17.3 units on a scale | Standard Deviation 2.8 |
| Randomized, Nitrate Depleted Beetroot Juice | Peak Rate of Perceived Exertion Scores During Handgrip Exercise | 17.7 units on a scale | Standard Deviation 1.7 |
Secondary
Resting Arterial Stiffness/Wave Properties
Carotid to femoral artery pulse wave velocity will be assessed using arterial tonometry.
Time frame: Change from baseline resting pulse wave velocity at 90 minutes after beet root juice ingestion
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Randomized, Nitrate Rich Beetroot Juice | Resting Arterial Stiffness/Wave Properties | 7.328 m/s | Standard Error 0.407 |
| Randomized, Nitrate Depleted Beetroot Juice | Resting Arterial Stiffness/Wave Properties | 7.572 m/s | Standard Error 0.384 |