Aging
Conditions
Keywords
nitrate, blood flow, blood pressure, vascular function, hypoxia
Brief summary
The main purpose/s of this study is to examine the effects of 4 weeks of dietary nitrate supplementation on peripheral chemoreceptor sensitivity, spontaneous baroreflex sensitivity, and blood pressure responsiveness to a variety of physiological stressors in older healthy adults. We will also examine the effect of dietary nitrate supplementation on measures of central artery stiffness and aortic blood pressure in older adults. Lastly, we will also recruit a group of young subjects in order to help characterize the age-related changes associated with the physiological outcome measures of the present study.
Detailed description
1 in 3 adults in the U.S. have hypertension which is known to increase the risk of heart disease and stroke. Blood pressure regulation is mediated by many factors including but not limited to metabolic factors, pressure/stretch sensing receptors located in the aorta and carotid arteries, endothelial cell function, and kidney function (via water and sodium absorption/excretion). It has been shown that many of these regulatory mechanisms are altered and/or become dysfunctional with aging. Specifically older adults commonly demonstrate a decreased sensitivity in pressure receptors and/or endothelial dysfunction. Additionally with aging, there is an increase in sympathetic nervous system activity and arterial stiffness which can contribute to higher blood pressure. The important vasodilator, nitric oxide (NO), has been implicated as a key signaling molecule involved in several of the mechanisms in blood pressure regulation outlined above. A decreased NO production or bioavailability is thought to contribute to several of the physiologic changes that come with aging. Therefore, the overall aim of this study is to use a randomized, double-blind crossover, placebo controlled study to examine the effects of acute dietary nitrate supplementation (to boost bioavailable NO) on various parameters of blood pressure regulation and responsiveness in normal healthy older adults. Our main hypothesis is that 4 weeks of dietary nitrate supplementation will decrease the blood pressure responses in older adults in response to a variety of physiological stressors.
Interventions
DIETARY_SUPPLEMENTSuper Beets Placebo
Nitrate deficient beetroot powder (10g/day) for 4 weeks
DIETARY_SUPPLEMENTSuper Beets
Nitrate rich beetroot powder (10g/day) for 4 weeks
Sponsors
Neogenis Laboratories
Darren P Casey
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
Yes
Inclusion criteria
Two separate age groups were included. Inclusion Criteria: * Healthy young adults 18-35 years of age (comparison group) * Healthy older adults 60-85 years of age (intervention group)
Exclusion criteria
* Hypertension, hyperlipidemia, current smoker or smoker within the last year, heart disease, diabetes, Chronic obstructive pulmonary disease, asthma, sleep apnea, Raynaud's disease, body mass index (BMI) \> 30 kg/m2, allergy medication, clinical depression, autonomic disorders and other conditions or medications that might normally alter cardiovascular function, exercise tolerance, and/or blood pressure responses.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Carotid Chemosensitivity Following 4 Weeks of Dietary Nitrate Supplementation and Placebo in Older Adults | Pre and post 4 weeks dietary nitrate supplementation and pre and post 4 weeks of placebo. | Carotid chemosensitivity examined by measuring hypoxia ventilatory responsiveness in older adults before and after 4 weeks of beet root juice supplementation and placebo. Chemoreflex sensitivity was quantified as the change in ventilation in relation to the change in pulse oxygen saturation. |
| Change in Systolic Blood Pressure During Metaboreflex Testing Following 4 Weeks of Dietary Nitrate Supplementation and Placebo in Older Adults. | Pre and post 4 weeks dietary nitrate supplementation and pre and post 4 weeks of placebo. | Muscle metaboreflex examined by measuring systolic blood pressure responses to ischemic isometric muscle contraction in older adults before and after 4 weeks of beet root juice supplementation and placebo. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Nitrate First Arm Subjects consumed beet root juice with nitrate for 4 weeks during the first arm of the study. After a 4 week washout period, subjects consumed beetroot juice without nitrate (placebo) for 4 weeks. | 7 |
| Placebo First Arm Subjects consumed beet root juice without nitrate (placebo) for 4 weeks during the first arm of the study. After a 4 week washout period, subjects consumed beetroot juice with nitrate for 4 weeks. | 6 |
| Young Comparison Group Young control group, used for age-related comparisons. This group did not go through any intervention. | 10 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Post 1 | Comparison only group. No intervention. | 0 | 0 | 10 |
Baseline characteristics
| Characteristic | Nitrate First Arm | Placebo First Arm | Young Comparison Group | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 6 Participants | 6 Participants | 0 Participants | 12 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 0 Participants | 10 Participants | 11 Participants |
| Age, Continuous Older Adults | 68 years STANDARD_DEVIATION 3 | 66 years STANDARD_DEVIATION 2 | — | 67 years STANDARD_DEVIATION 3 |
| Age, Continuous Young Adults | — | — | 25 years STANDARD_DEVIATION 4 | 25 years STANDARD_DEVIATION 4 |
| Body Mass Index Older Adults | 26 kg/m^2 STANDARD_DEVIATION 4 | 25 kg/m^2 STANDARD_DEVIATION 3 | — | 26 kg/m^2 STANDARD_DEVIATION 3 |
| Body Mass Index Young Adults | — | — | 24 kg/m^2 STANDARD_DEVIATION 3 | 24 kg/m^2 STANDARD_DEVIATION 3 |
| Diastolic Blood Pressure Older Adults | 76 mmHg STANDARD_DEVIATION 5 | 75 mmHg STANDARD_DEVIATION 6 | — | 76 mmHg STANDARD_DEVIATION 5 |
| Diastolic Blood Pressure Young Adults | — | — | 72 mmHg STANDARD_DEVIATION 5 | 72 mmHg STANDARD_DEVIATION 5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants | 6 Participants | 10 Participants | 23 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Glucose Older Adults | 97 mg/dl STANDARD_DEVIATION 7 | 96 mg/dl STANDARD_DEVIATION 4 | — | 96 mg/dl STANDARD_DEVIATION 5 |
| Glucose Young Adults | — | — | 89 mg/dl STANDARD_DEVIATION 5 | 89 mg/dl STANDARD_DEVIATION 5 |
| HDL Older Adults | 57 mg/dl STANDARD_DEVIATION 19 | 49 mg/dl STANDARD_DEVIATION 21 | — | 53 mg/dl STANDARD_DEVIATION 19 |
| HDL Young Adults | — | — | 60 mg/dl STANDARD_DEVIATION 15 | 60 mg/dl STANDARD_DEVIATION 15 |
| LDL Older Adults | 98 mg/dl STANDARD_DEVIATION 33 | 107 mg/dl STANDARD_DEVIATION 33 | — | 102 mg/dl STANDARD_DEVIATION 32 |
| LDL Young Adults | — | — | 82 mg/dl STANDARD_DEVIATION 23 | 82 mg/dl STANDARD_DEVIATION 23 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 7 Participants | 6 Participants | 9 Participants | 22 Participants |
| Region of Enrollment United States | 7 participants | 6 participants | 10 participants | 23 participants |
| Sex: Female, Male Female | 2 Participants | 4 Participants | 5 Participants | 11 Participants |
| Sex: Female, Male Male | 5 Participants | 2 Participants | 5 Participants | 12 Participants |
| Systolic Blood Pressure Older Adults | 126 mmHg STANDARD_DEVIATION 12 | 118 mmHg STANDARD_DEVIATION 5 | — | 122 mmHg STANDARD_DEVIATION 10 |
| Systolic Blood Pressure Young Adults | — | — | 119 mmHg STANDARD_DEVIATION 8 | 119 mmHg STANDARD_DEVIATION 8 |
| Total Cholesterol Older Adults | 171 mg/dl STANDARD_DEVIATION 40 | 184 mg/dl STANDARD_DEVIATION 31 | — | 177 mg/dl STANDARD_DEVIATION 35 |
| Total Cholesterol Young Adults | — | — | 153 mg/dl STANDARD_DEVIATION 22 | 153 mg/dl STANDARD_DEVIATION 22 |
| Triglycerides Older Adults | 84 mg/dl STANDARD_DEVIATION 39 | 144 mg/dl STANDARD_DEVIATION 84 | — | 111 mg/dl STANDARD_DEVIATION 69 |
| Triglycerides Young Adults | — | — | 53 mg/dl STANDARD_DEVIATION 12 | 53 mg/dl STANDARD_DEVIATION 12 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 13 | 0 / 13 | 0 / 10 |
| other Total, other adverse events | 0 / 13 | 0 / 13 | 0 / 10 |
| serious Total, serious adverse events | 0 / 13 | 0 / 13 | 0 / 10 |
Outcome results
Primary
Change in Carotid Chemosensitivity Following 4 Weeks of Dietary Nitrate Supplementation and Placebo in Older Adults
Carotid chemosensitivity examined by measuring hypoxia ventilatory responsiveness in older adults before and after 4 weeks of beet root juice supplementation and placebo. Chemoreflex sensitivity was quantified as the change in ventilation in relation to the change in pulse oxygen saturation.
Time frame: Pre and post 4 weeks dietary nitrate supplementation and pre and post 4 weeks of placebo.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nitrate Pre | Change in Carotid Chemosensitivity Following 4 Weeks of Dietary Nitrate Supplementation and Placebo in Older Adults | -0.13 L/min/%SpO2 | Standard Error 0.04 |
| Nitrate Post | Change in Carotid Chemosensitivity Following 4 Weeks of Dietary Nitrate Supplementation and Placebo in Older Adults | -0.05 L/min/%SpO2 | Standard Error 0.02 |
| Placebo Pre | Change in Carotid Chemosensitivity Following 4 Weeks of Dietary Nitrate Supplementation and Placebo in Older Adults | -0.10 L/min/%SpO2 | Standard Error 0.05 |
| Placebo Post | Change in Carotid Chemosensitivity Following 4 Weeks of Dietary Nitrate Supplementation and Placebo in Older Adults | -0.11 L/min/%SpO2 | Standard Error 0.05 |
Primary
Change in Systolic Blood Pressure During Metaboreflex Testing Following 4 Weeks of Dietary Nitrate Supplementation and Placebo in Older Adults.
Muscle metaboreflex examined by measuring systolic blood pressure responses to ischemic isometric muscle contraction in older adults before and after 4 weeks of beet root juice supplementation and placebo.
Time frame: Pre and post 4 weeks dietary nitrate supplementation and pre and post 4 weeks of placebo.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nitrate Pre | Change in Systolic Blood Pressure During Metaboreflex Testing Following 4 Weeks of Dietary Nitrate Supplementation and Placebo in Older Adults. | 19.2 mmHg | Standard Error 2.1 |
| Nitrate Post | Change in Systolic Blood Pressure During Metaboreflex Testing Following 4 Weeks of Dietary Nitrate Supplementation and Placebo in Older Adults. | 13 mmHg | Standard Error 2.5 |
| Placebo Pre | Change in Systolic Blood Pressure During Metaboreflex Testing Following 4 Weeks of Dietary Nitrate Supplementation and Placebo in Older Adults. | 16.1 mmHg | Standard Error 1.8 |
| Placebo Post | Change in Systolic Blood Pressure During Metaboreflex Testing Following 4 Weeks of Dietary Nitrate Supplementation and Placebo in Older Adults. | 17 mmHg | Standard Error 1.9 |