Aging, Sarcopenia
Conditions
Keywords
nitric oxide
Brief summary
The purpose of this study is to see if drinking beetroot juice (BRJ) is beneficial for aging patients. We hope to determine the effect of BRJ on exercise performance. BRJ improves exercise performance in athletes and normal people. We are trying to determine if BRJ improves exercise performance in aging patients. We will be comparing the effects of BRJ versus the effects of a placebo (BRJ without the nitrates that are naturally occurring in beets and other similar foods). It is thought that the benefits of BRJ may come from its natural nitrate content. Although BRJ is available for purchase in grocery stores, for the purposes of this study it is considered investigational, which means that it has not been approved as a medical therapy.
Detailed description
This study consists of two parts separated by a 14 day wash-out. Subjects will be randomly assigned to receive either the BRJ or placebo during the first part. During the second part they will receive the opposite of what they had during the first part. This is considered a double-blind study, which means neither the subjects nor the investigators will know what form (BRJ or placebo) a subject is receives. Study Visit One (Screening) 1-2 hours The purpose of the screening visit is to explain all aspects of the study. It will also determine if subjects can participate in the study. Subjects will provide a complete medical history and undergo a physical exam. They will have their blood drawn (about 1.5 teaspoons) and provide a urine sample. They will also practice the entire neuromuscular function exercise test. During this test, the strength of their muscles will be determined by having them kick, push and/or pull back as hard as you can while their leg is strapped to an exercise device. A vital signs monitor will measure your blood pressure, heart rate, and rhythm. During the remainder of the study subjects will be instructed to consume their normal diet. However, they will be asked to avoid eating foods high in nitrate such as beets, spinach, and collard greens the evening before each visit. They will be asked to refrain from the use of antibacterial mouthwash, such as Listerine or Cepacol, during the study. Chewing gum, alcohol, and food and drinks containing caffeine (coffee, tea, chocolate, and soft drinks) should be avoided 24 hours prior to each visit. They will be asked to fast for 12 hour prior to each study visit. Study Visit Two - Approximately 5 hours At the beginning of this visit a catheter (small, flexible, sterile plastic tube) will be placed through a vein in one of the subject's arms. This is for collection of blood samples. Blood will be drawn four times during this visit. Each draw will be 6 mL or about 1.2 teaspoons. The first blood draw will check nitrate and nitrite levels. They will then have a breath test to check nitric oxide. They will then drink 140 mL (about 2/3 of a cup) of BRJ (or placebo). Blood and breath samples will be obtained every hour. Heart rate and blood pressure will be measured at the same times the blood and breath samples are obtained. Subjects will then rest quietly in a private room for about 2 hours after ingestion of BRJ (or placebo) then will perform: * The neuromuscular function test that was practiced during the screening visit. * After completing the exercise test they will undergo a muscle biopsy of their thigh muscle. First, the area will be sterilized and numbed with an injection. Next, a small incision (about ¼ inch) will be made and a small biopsy needle will be used to collect a small sample of your muscle (about the size of a pencil eraser). This will be performed on the leg opposite of that used during the neuromuscular test. * One final blood and breath sample will then be obtained. * Subjects will then be provided a 7 day supply of BRJ (or placebo) and will continue to drink two bottles (about 5 oz) every morning. * Subjects will also be provided with an activity tracker. This will be worn at the hip during all waking hours except when bathing or swimming. This monitor will measure total activity time and sedentary time. Study Visit Three - 1-2 hours Subjects will return to the research center with the empty BRJ bottles. At this visit a single blood (1.2 teaspoon) and breath sample will be collected. Subjects will then complete a questionnaire to rate how tired they felt during the previous week. They will be provided another 7 day supply of BRJ (or placebo) and will continue to drink two bottles every morning. Study Visit Four - Approximately 5 hours Subjects will return to the research center and undergo the same procedures as they did in Study Visit Two. They will also complete a questionnaire that will rate how tired they felt during the previous week. Washout After visit four subjects will undergo a 14 day washout period where they will not drink the BRJ (or placebo). There are no dietary restrictions at this time; subjects may consume caffeine, alcohol, gum, mouthwash, etc. Subjects will then repeat Study Visits Two, Three, and Four again. However, during this they will be given the opposite form of BRJ you had received before. Study Visit Five Subjects will repeat the procedures completed during Study Visit Two. Study Visit Six Subjects will repeat the procedures completed during Study Visit Three. Study Visit Seven Subjects will repeat the procedures completed during Study Visit Four.
Interventions
2 x 70 mL concentrated beet root juice depleted of nitrate per day for 14 days.
2 x 70 mL concentrated beet root juice per day for 14 days.
Sponsors
Study design
Intervention model description
Double-blind, placebo-controlled, crossover
Eligibility
Inclusion criteria
In good health, as determined by the investigator's review of history (provided by subject at screening visit), physical examination, and routine blood and urine tests (done at screening visit)
Exclusion criteria
Men and women \<65 or \>79 years of age * Unable to provide informed consent * Currently pregnant or lactating (given the age range for the study, verbal confirmation by subject is believed to be sufficient) * Current smokers * Significant orthopedic limitations or other contraindications to strenuous exercise * Those taking phosphodiesterase inhibitors (e.g., Viagra) * Those taking proton pump inhibitors, antacids, xanthine oxidase inhibitors, or on hormone replacement therapy * Those taking anti-coagulants (e.g., Coumadin) or on anti-platelet therapy * History of neuromuscular disease (e.g., cervical spondylotic radiculomyelpathy, lumbar spondylosis, amyotrophic lateral sclerosis, Guillain-Barré syndrome, and acquired demyelinating polyneuropathies), cardiovascular disease (e.g., \> stage I hypertension, heart failure, myocardial infarction/ischemia, significant myocardial or pericardial diseases (e.g. amyloidosis, constriction), moderate or severe valvular disease, renal disease, liver disease, or anemia
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximal Knee Extension Velocity | 1 day | \*Maximal\* knee extension velocity was determined by having participants perform knee extensions at velocities of 0, 1.57, 3.14, 4.57, and 6.14 radians per second on an isokinetic dynamometer (device that controls velocity while measuring torque). Peak power at each velocity was calculated by multiplying the measured torque by that velocity, then a parabolic function was fit to these calculated data to predict \*maximal\* knee extensor velocity. Higher values are better. |
| Muscle Knee Extensor Power | 1 day | This outcome was determined by having participants perform knee extensions at velocities of 0, 1.57, 3.14, 4.57, and 6.14 radians per second on an isokinetic dynamometer (device that controls velocity while measuring torque). \*Peak\* power at each velocity was calculated by multiplying the measured torque by that velocity, then a parabolic function was fit to these calculated data to predict \*maximal\* knee extensor power. Higher values are better. |
| Maximal Knee Extension Power | 14 days | \*Maximal\* knee extension power was determined by having participants perform knee extensions at velocities of 0, 1.57, 3.14, 4.57, and 6.14 rad/s on an isokinetic dynamometer (device that controls velocity while measuring torque). \*Peak\* power at each velocity was calculated by multiplying the measured torque by that velocity, then \*maximal\* power was determined by fitting a parabolic function to these data. Higher values are better. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Plasma Nitrate | 0,1,2,3 hours after treatment at 1 day | Plasma nitrate concentrations were measured using high performance liquid chromatography. |
| Physical Function | 1,14 days of treatment | Patient-Reported Outcomes Measurement Information System physical function questionnaire (PROMIS 20a). Results given as T-score with mean of 50 and standard deviation of 10. Higher is better. |
| Plasma Nitrite | 0,1,2,3 hours after treatment at 1 day | Plasma nitrite concentrations were measured using high performance liquid chromatography. |
| Perceived Fatigue | 1 and 14 days of treatment | Patient-Reported Outcomes Measurement Information System perceived fatigue questionnaire (PROMIS 8a). Results given as T-score with mean of 50 and standard deviation of 10. Lower is better. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants All study participants | 16 |
| Total | 16 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| First Intervention (14 Days) | Screen failure | 15 | 16 |
Baseline characteristics
| Characteristic | All Study Participants |
|---|---|
| Age, Continuous | 71 years STANDARD_DEVIATION 5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 4 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 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 | 1 Participants |
| Race (NIH/OMB) White | 14 Participants |
| Region of Enrollment United States | 16 Participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 47 | 0 / 16 | 0 / 16 |
| other Total, other adverse events | 27 / 47 | 5 / 16 | 4 / 16 |
| serious Total, serious adverse events | 0 / 47 | 0 / 16 | 0 / 16 |
Outcome results
Maximal Knee Extension Power
\*Maximal\* knee extension power was determined by having participants perform knee extensions at velocities of 0, 1.57, 3.14, 4.57, and 6.14 rad/s on an isokinetic dynamometer (device that controls velocity while measuring torque). \*Peak\* power at each velocity was calculated by multiplying the measured torque by that velocity, then \*maximal\* power was determined by fitting a parabolic function to these data. Higher values are better.
Time frame: 14 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Maximal Knee Extension Power | 4.23 W/kg | Standard Deviation 1.21 |
| Nitrate | Maximal Knee Extension Power | 4.31 W/kg | Standard Deviation 1.26 |
Maximal Knee Extension Velocity
\*Maximal\* knee extension velocity was determined by having participants perform knee extensions at velocities of 0, 1.57, 3.14, 4.57, and 6.14 rad/s on an isokinetic dynamometer (device that controls velocity while measuring torque). Peak power at each velocity was calculated by multiplying the measured torque by that velocity, then \*maximal\* knee extensor velocity was determined by fitting a parabolic function to these data (\*maximal\* knee extension velocity = 2 x fitted velocity at which \*maximal\* power is developed). Higher values are better.
Time frame: 14 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Maximal Knee Extension Velocity | 12.2 rad/s | Standard Deviation 1.8 |
| Nitrate | Maximal Knee Extension Velocity | 12.7 rad/s | Standard Deviation 1.8 |
Maximal Knee Extension Velocity
\*Maximal\* knee extension velocity was determined by having participants perform knee extensions at velocities of 0, 1.57, 3.14, 4.57, and 6.14 radians per second on an isokinetic dynamometer (device that controls velocity while measuring torque). Peak power at each velocity was calculated by multiplying the measured torque by that velocity, then a parabolic function was fit to these calculated data to predict \*maximal\* knee extensor velocity. Higher values are better.
Time frame: 1 day
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Maximal Knee Extension Velocity | 12.2 radians per second | Standard Deviation 1.9 |
| Nitrate | Maximal Knee Extension Velocity | 12.7 radians per second | Standard Deviation 2.1 |
Muscle Knee Extensor Power
This outcome was determined by having participants perform knee extensions at velocities of 0, 1.57, 3.14, 4.57, and 6.14 radians per second on an isokinetic dynamometer (device that controls velocity while measuring torque). \*Peak\* power at each velocity was calculated by multiplying the measured torque by that velocity, then a parabolic function was fit to these calculated data to predict \*maximal\* knee extensor power. Higher values are better.
Time frame: 1 day
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Muscle Knee Extensor Power | 3.98 Watts per kilogram body mass | Standard Deviation 1.18 |
| Nitrate | Muscle Knee Extensor Power | 4.26 Watts per kilogram body mass | Standard Deviation 1.37 |
Perceived Fatigue
Patient-Reported Outcomes Measurement Information System perceived fatigue questionnaire (PROMIS 8a). Results given as T-score with mean of 50 and standard deviation of 10. Lower is better.
Time frame: 1 and 14 days of treatment
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Perceived Fatigue | 1 d | 42.3 T-score | Standard Deviation 9.1 |
| Placebo | Perceived Fatigue | 14 d | 39.3 T-score | Standard Deviation 7.1 |
| Nitrate | Perceived Fatigue | 1 d | 43.2 T-score | Standard Deviation 8.9 |
| Nitrate | Perceived Fatigue | 14 d | 40.8 T-score | Standard Deviation 6.6 |
Physical Function
Patient-Reported Outcomes Measurement Information System physical function questionnaire (PROMIS 20a). Results given as T-score with mean of 50 and standard deviation of 10. Higher is better.
Time frame: 1,14 days of treatment
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Physical Function | 1 day | 53.0 T-score | Standard Deviation 6.8 |
| Placebo | Physical Function | 14 days | 54.7 T-score | Standard Deviation 6.8 |
| Nitrate | Physical Function | 1 day | 52.2 T-score | Standard Deviation 7.4 |
| Nitrate | Physical Function | 14 days | 57.0 T-score | Standard Deviation 6.3 |
Plasma 4-hydroxynonenal
4-hydroxynonenal is an indicator of oxidative damage to lipids (fats). It was measured using a commercial enzyme-linked immunosuppressant assay kit. Lower is better.
Time frame: 1 and 14 days of treatment
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Plasma 4-hydroxynonenal | Pre-treatment | 43.9 ug/mL | Standard Deviation 25 |
| Placebo | Plasma 4-hydroxynonenal | Post-treatment | 38.4 ug/mL | Standard Deviation 26.6 |
| Nitrate | Plasma 4-hydroxynonenal | Pre-treatment | 38.1 ug/mL | Standard Deviation 24.6 |
| Nitrate | Plasma 4-hydroxynonenal | Post-treatment | 35.7 ug/mL | Standard Deviation 24 |
Plasma 8-hydroxydeoxyguanosine
Plasma 8-hydroxydeoxyguanosine is an indicator of oxidative damage to DNA/RNA. It was measured using a commercial enzyme-linked immunosuppressant assay kit. Lower is better.
Time frame: 1 and 14 days of treatment
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Plasma 8-hydroxydeoxyguanosine | Pre-treatment | 11.4 mg/mL | Standard Deviation 4 |
| Placebo | Plasma 8-hydroxydeoxyguanosine | Post-treatment | 11.6 mg/mL | Standard Deviation 3.9 |
| Nitrate | Plasma 8-hydroxydeoxyguanosine | Pre-treatment | 11.5 mg/mL | Standard Deviation 4.5 |
| Nitrate | Plasma 8-hydroxydeoxyguanosine | Post-treatment | 11.7 mg/mL | Standard Deviation 4.5 |
Plasma Nitrate
Plasma nitrate concentrations
Time frame: 0,1,2,3 hours after treatment at 14 days
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Plasma Nitrate | 0 h | 37 umol/L | Standard Deviation 20 |
| Placebo | Plasma Nitrate | 1 h | 35 umol/L | Standard Deviation 13 |
| Placebo | Plasma Nitrate | 2 h | 35 umol/L | Standard Deviation 11 |
| Placebo | Plasma Nitrate | 3 h | 35 umol/L | Standard Deviation 14 |
| Nitrate | Plasma Nitrate | 3 h | 780 umol/L | Standard Deviation 292 |
| Nitrate | Plasma Nitrate | 0 h | 190 umol/L | Standard Deviation 153 |
| Nitrate | Plasma Nitrate | 2 h | 815 umol/L | Standard Deviation 281 |
| Nitrate | Plasma Nitrate | 1 h | 740 umol/L | Standard Deviation 241 |
Plasma Nitrate
Plasma nitrate concentrations were measured using high performance liquid chromatography.
Time frame: 0,1,2,3 hours after treatment at 1 day
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Plasma Nitrate | 0 h | 35 umol/L | Standard Deviation 24 |
| Placebo | Plasma Nitrate | 1 h | 35 umol/L | Standard Deviation 22 |
| Placebo | Plasma Nitrate | 2 h | 33 umol/L | Standard Deviation 20 |
| Placebo | Plasma Nitrate | 3 h | 33 umol/L | Standard Deviation 16 |
| Nitrate | Plasma Nitrate | 3 h | 661 umol/L | Standard Deviation 247 |
| Nitrate | Plasma Nitrate | 0 h | 39 umol/L | Standard Deviation 19 |
| Nitrate | Plasma Nitrate | 2 h | 698 umol/L | Standard Deviation 214 |
| Nitrate | Plasma Nitrate | 1 h | 601 umol/L | Standard Deviation 258 |
Plasma Nitrite
Plasma nitrite concentrations were measured using high performance liquid chromatography.
Time frame: 0,1,2,3 hours after treatment at 14 days
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Plasma Nitrite | 0 h | 0.307 umol/L | Standard Deviation 0.294 |
| Placebo | Plasma Nitrite | 1 h | 0.308 umol/L | Standard Deviation 0.247 |
| Placebo | Plasma Nitrite | 2 h | 0.353 umol/L | Standard Deviation 0.344 |
| Placebo | Plasma Nitrite | 3 h | 0.275 umol/L | Standard Deviation 0.286 |
| Nitrate | Plasma Nitrite | 3 h | 0.989 umol/L | Standard Deviation 1.039 |
| Nitrate | Plasma Nitrite | 0 h | 0.615 umol/L | Standard Deviation 0.671 |
| Nitrate | Plasma Nitrite | 2 h | 1.053 umol/L | Standard Deviation 1.144 |
| Nitrate | Plasma Nitrite | 1 h | 0.972 umol/L | Standard Deviation 1.039 |
Plasma Nitrite
Plasma nitrite concentrations were measured using high performance liquid chromatography.
Time frame: 0,1,2,3 hours after treatment at 1 day
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Plasma Nitrite | 0 h | 0.364 umol/L | Standard Deviation 0.283 |
| Placebo | Plasma Nitrite | 1 h | 0.382 umol/L | Standard Deviation 0.338 |
| Placebo | Plasma Nitrite | 2 h | 0.379 umol/L | Standard Deviation 0.401 |
| Placebo | Plasma Nitrite | 3 h | 0.374 umol/L | Standard Deviation 0.376 |
| Nitrate | Plasma Nitrite | 3 h | 1.243 umol/L | Standard Deviation 1.078 |
| Nitrate | Plasma Nitrite | 0 h | 0.400 umol/L | Standard Deviation 0.356 |
| Nitrate | Plasma Nitrite | 2 h | 1.104 umol/L | Standard Deviation 0.847 |
| Nitrate | Plasma Nitrite | 1 h | 0.904 umol/L | Standard Deviation 0.826 |
Plasma Protein Carbonyls
Protein carbonyls are an indicator of oxidative damage to proteins. It was measured using a commercial enzyme-linked immunosuppressant assay kit. Lower is better.
Time frame: 1 and 14 days of treatment
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Plasma Protein Carbonyls | Pre-treatment | 3.71 nmol/mg | Standard Deviation 1.4 |
| Placebo | Plasma Protein Carbonyls | Post-treatment | 3.79 nmol/mg | Standard Deviation 1.67 |
| Nitrate | Plasma Protein Carbonyls | Pre-treatment | 4.00 nmol/mg | Standard Deviation 1.67 |
| Nitrate | Plasma Protein Carbonyls | Post-treatment | 4.46 nmol/mg | Standard Deviation 2.17 |