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| Name | Class |
|---|---|
| Milton S. Hershey Medical Center | OTHER |
| Wake Forest University Health Sciences | OTHER |
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In this study the investigators will test the hypothesis that short-term consumption of inorganic nitrate (supplied in concentrated beetroot juice) enhances coronary blood flow responses, large artery hemodynamics, and leg oxygenation/exercise tolerance in patients with peripheral arterial disease (PAD). Understanding and improving blood flow regulation in the heart and skeletal muscles of patients with PAD is important because exercise triggers symptoms of leg pain and substantially raises blood pressure and myocardial demand in these patients.
Peripheral arterial disease (PAD) is a strong predictor of cardiovascular mortality and negatively affects functional capacity and quality of life for as many as 14 million patients in the U.S. alone. One open-label study showed that acute consumption of beetroot juice improved 6 min walk performance, reduced blood pressure, and enhanced leg muscle oxygenation in PAD patients. However, no studies have rigorously confirmed these findings in a double-blind manner, nor have the effects of this supplement been investigated (acutely or short-term) in the coronary circulation of PAD patients.
In addition to studying its effects on graded treadmill walking performance and consequent large artery vasodilation, the present study will examine the effects of short-term beetroot juice consumption (twice/day) on both coronary and leg vasodilator (graded calf flexion) and vasoconstrictor (isometric handgrip, voluntary apnea) responses in patients with PAD. Participants will randomly consume either nitrate-rich or nitrate-depleted beetroot juice with a 7 to 14 day wash-out period between. Effects of beetroot juice consumption on plasma nitrate, nitrite and methemoglobin will also be assessed.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Beetroot juice (Beet-It Organic Shot) | Active Comparator | Subjects will consume 70 ml of beetroot juice (Beet-It Organic Shot) twice per day (morning, afternoon) for 5 to 7 days to assess the short term effects of this nitrate supplement on graded treadmill walking responses (day 4) and vasodilator/vasoconstrictor responses in the coronary and lower leg circulations (day 5 or 6 or 7). On both study visits, subjects will consume their morning dose 1 hour 45 min before experiments begin. |
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| Beetroot juice placebo (Beet-It Organic Placebo) | Placebo Comparator | Subjects will consume 70 ml of beetroot juice placebo (Beet-It Organic Placebo) twice per day (morning, afternoon) for 5 to 7 days to assess the short term effects of this nitrate supplement on graded treadmill walking responses (day 4) and vasodilator/vasoconstrictor responses in the coronary and lower leg circulations (day 5 or 6 or 7). On both study visits, subjects will consume their morning dose 1 hour 45 min before experiments begin. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Beetroot juice | Drug | This beverage contains 0.3 g of inorganic nitrate per 70 ml container, and is bottled and supplied by James White Drinks (UK). |
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| Measure | Description | Time Frame |
|---|---|---|
| Exercise performance | Exercise capacity will be assessed using a graded treadmill walking test to peak exertion with expired gas analysis and determination of peak oxygen uptake, calf muscle oxygenation, blood pressure, claudication onset time, and peak walking time. | 5 to 7 days after initiating daily ingestion of beetroot juice |
| Measure | Description | Time Frame |
|---|---|---|
| Coronary vascular function | Coronary artery (transthoracic ultrasound) blood flow responses to plantar flexion and handgrip exercise. | 4 days after initiating daily ingestion of beetroot juice |
| Leg vascular function |
| Measure | Description | Time Frame |
|---|---|---|
| Blood measures of nitrate absorption and conversion | Venous blood will be withdrawn (venipuncture) for determination of plasma nitrate, nitrite and methemoglobin levels | 4 to 7 days after initiating ingestion of beetroot juice |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Urs A Leuenberger, MD | Penn State University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Milton S. Hershey Medical Center | Hershey | Pennsylvania | 17033 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39027664 | Derived | Kim DJ, Gao Z, Luck JC, Brandt K, Miller AJ, Kim-Shapiro D, Basu S, Leuenberger U, Gardner AW, Muller MD, Proctor DN. Effects of short-term dietary nitrate supplementation on exercise and coronary blood flow responses in patients with peripheral artery disease. Front Nutr. 2024 Jul 3;11:1398108. doi: 10.3389/fnut.2024.1398108. eCollection 2024. |
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| Type | Date | Date Unknown |
|---|---|---|
| Release | Jul 27, 2024 | |
| Reset | Aug 19, 2024 | |
| Release | Jun 13, 2025 | |
| Reset | Jul 1, 2025 | |
| Release | Jun 8, 2026 | |
| Reset | Jul 2, 2026 |
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| Release Date | Unrelease Date | Unrelease Date Unknown | Reset Date | MCP Release Number |
|---|---|---|---|---|
| Jul 27, 2024 | Aug 19, 2024 | |||
| Jun 13, 2025 |
| ID | Term |
|---|---|
| D058729 | Peripheral Arterial Disease |
| ID | Term |
|---|---|
| D050197 | Atherosclerosis |
| D001161 | Arteriosclerosis |
| D001157 | Arterial Occlusive Diseases |
| D014652 | Vascular Diseases |
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| Beetroot juice placebo | Drug | 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). |
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Popliteal artery and near infrared spectroscopy (NIRS) responses to plantar flexion and handgrip exercise.
| 4 days after initiating daily ingestion of beetroot juice |
| Jul 1, 2025 |
| Jun 8, 2026 | Jul 2, 2026 |
| D002318 |
| Cardiovascular Diseases |
| D016491 | Peripheral Vascular Diseases |