Beetroot Juice for Peripheral Arterial Disease
(BEET PAD Trial)
Recruiting in Palo Alto (17 mi)
+3 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: Northwestern University
Must not be taking: Oral nitrates, Nitrites
Disqualifiers: Amputation, Critical limb ischemia, Wheelchair, Major surgery, others
Trial Summary
What is the purpose of this trial?The BEET PAD Trial is a multi-centered double-blind randomized clinical trial designed to determine whether beetroot juice, compared to placebo, improves six-minute walk distance at four month follow-up in people with lower extremity peripheral artery disease (PAD). Investigators hypothesize that by simultaneously increasing lower extremity perfusion, gastrocnemius muscle mitochondrial activity, and myofiber health and regeneration, beetroot juice will significantly improve walking performance in people with PAD. The primary aim is to determine whether beetroot juice significantly improves six-minute walk distance at 4-month follow-up in people with PAD, compared to placebo. Preliminary evidence suggests that beetroot juice has both acute and chronic effects on walking performance in PAD. The primary outcome will measure the combined acute and chronic effect of beetroot juice (i.e. the maximal effect) on change in 6-minute walk at 4-month follow-up. In secondary aims, investigators will distinguish between acute and chronic effects of beetroot juice on six-minute walk and delineate biologic pathways by which beetroot juice improves walking performance in PAD, by measuring change in gastrocnemius muscle perfusion (MRI arterial spin labeling) and gastrocnemius muscle health. The trial will assess the durability of beetroot juice effects on six-minute walk. Nitrate in beetroot juice is metabolized to nitrite and subsequently to NO, attaining peak nitrite levels 2.5 hours after ingestion. The trial will determine whether a higher peak or a greater increase in plasma nitrite at 2.5 hours after beetroot juice consumption at baseline has a greater effect on six-minute walk at 4-month follow-up, compared to a lower peak or a smaller increase, respectively.
Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications, but you must stop consuming beetroot juice, oral nitrate or nitrite, and beetroot supplements for 30 days before the trial and throughout its duration.
What data supports the effectiveness of the treatment Beetroot Juice for Peripheral Arterial Disease?
Research shows that beetroot juice, which is high in dietary nitrate, can improve blood flow and exercise performance in patients with peripheral arterial disease. It helps increase walking distance and improve muscle function, making it easier for patients to walk longer without pain.
12345Is beetroot juice safe for human consumption?
Research shows that beetroot juice, which is high in dietary nitrate, is generally safe for human consumption. It has been used in studies to lower blood pressure and improve cardiovascular function without significant adverse effects.
12567How is beetroot juice treatment different from other treatments for peripheral arterial disease?
Beetroot juice is unique because it is rich in dietary nitrate, which the body converts to nitric oxide, a molecule that helps improve blood flow and oxygen delivery to muscles. This can enhance exercise tolerance and walking distance in patients with peripheral arterial disease, offering a natural alternative to traditional medications.
12468Eligibility Criteria
This trial is for people over 50 with peripheral artery disease (PAD), which means they have poor blood flow in their legs. They must have specific test results showing PAD and be able to walk a certain distance. People can't join if they've had major leg amputations, severe limb issues, need walkers or wheelchairs, have other conditions limiting walking, recent surgeries or heart events, mental impairment scores below a threshold, allergies to beetroot juice, don't speak English, are in another study recently or consume lots of beets.Inclusion Criteria
I am 50 years old or older.
I have been diagnosed with PAD based on vascular tests or angiography.
My ABI is between 0.90 and 1.00, and it drops by 20% or more after a physical test.
+2 more
Exclusion Criteria
I have severe leg pain at rest due to poor blood flow.
I have a current foot ulcer on the bottom of my foot.
I haven't been in a clinical trial for at least 3 months, or 6 months if it was for stem cell/gene therapy.
+18 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive beetroot juice or placebo twice daily to assess its effects on six-minute walk distance and other health metrics
16 weeks
Regular visits for monitoring and assessments
Follow-up
Participants are monitored for safety and effectiveness after treatment, including assessments of walking performance and muscle health
4 weeks
2 visits (in-person)
Participant Groups
The BEET PAD Trial is testing whether drinking beetroot juice improves walking ability after four months compared to a placebo drink. The idea is that the natural compounds in beetroot juice might help increase blood flow and muscle health in the legs of those with PAD.
2Treatment groups
Active Control
Placebo Group
Group I: Beetroot juiceActive Control1 Intervention
The beetroot juice intervention comes in a single 70 ml drink and is manufactured by James White Drinks. Each drink contains beetroot juice and 2% lemon juice, made from concentrates. Each serving of 70 mL of beetroot juice contains 400 mgs (6.45 millimoles) of nitrate and will be taken twice daily for a total daily dose of 800 mgs (12.90 millimoles) of nitrate.
Group II: PlaceboPlacebo Group1 Intervention
The placebo comes in a single 70 ml drink and is manufactured by James White Drinks. The placebo contains beetroot juice and 2% lemon juice, made from concentrates, and is filtered to remove nitrate.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of ChicagoChicago, IL
University of VirginiaCharlottesville, VA
Northwestern University Feinberg School of MedicineChicago, IL
University of MinnesotaMinneapolis, MN
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Who Is Running the Clinical Trial?
Northwestern UniversityLead Sponsor
University of VirginiaCollaborator
University of ChicagoCollaborator
National Institute on Aging (NIA)Collaborator
References
Acute dietary nitrate supplementation does not augment submaximal forearm exercise hyperemia in healthy young men. [2018]Despite the popularity of dietary nitrate supplementation and the growing evidence base of its potential ergogenic and vascular health benefits, there is no direct information about its effects on exercising limb blood flow in humans. We hypothesized that acute dietary nitrate supplementation from beetroot juice would augment the increases in forearm blood flow, as well as the progressive dilation of the brachial artery, during graded handgrip exercise in healthy young men. In a randomized, double-blind, placebo-controlled crossover study, 12 young (22 ± 2 years) healthy men consumed a beetroot juice (140 mL Beet-It Sport, James White Juice Company) that provided 12.9 mmol (0.8 g) of nitrate or placebo (nitrate-depleted Beet-It Sport) on 2 study visits. At 3 h postconsumption, brachial artery diameter, flow, and blood velocity were measured (Doppler ultrasound) at rest and during 6 exercise intensities. Nitrate supplementation raised plasma nitrate (19.5-fold) and nitrite (1.6-fold) concentrations, and lowered resting arterial pulse wave velocity (PWV) versus placebo (all p
Acute Effects of Dietary Nitrate on Exercise Tolerance, Muscle Oxygenation, and Cardiovascular Function in Patients With Peripheral Arterial Disease. [2022]Previous studies have used supplements to increase dietary nitrate intake in clinical populations. Little is known about whether effects can also be induced through vegetable consumption. Therefore, the aim of this study was to assess the impact of dietary nitrate, through nitrate-rich vegetables (NRV) and beetroot juice (BRJ) supplementation, on plasma nitrate and nitrite concentrations, exercise tolerance, muscle oxygenation, and cardiovascular function in patients with peripheral arterial disease. In a randomized crossover design, 18 patients with peripheral arterial disease (age: 73 ± 8 years) followed a nitrate intake protocol (∼6.5 mmol) through the consumption of NRV, BRJ, and nitrate-depleted BRJ (placebo). Blood samples were taken, blood pressure and arterial stiffness were measured in fasted state and 150 min after intervention. Each intervention was followed by a maximal walking exercise test to determine claudication onset time and peak walking time. Gastrocnemius oxygenation was measured by near-infrared spectroscopy. Blood samples were taken and blood pressure was measured 10 min after exercise. Mean plasma nitrate and nitrite concentrations increased (nitrate; Time × Intervention interaction; p
Dietary nitrate supplementation improves exercise performance and decreases blood pressure in COPD patients. [2018]Dietary nitrate (NO3(-)) supplementation via beetroot juice has been shown to increase the exercise capacity of younger and older adults. The purpose of this study was to investigate the effects of acute NO3(-) ingestion on the submaximal constant work rate exercise capacity of COPD patients. Fifteen patients were assigned in a randomized, single-blind, crossover design to receive one of two treatments (beetroot juice then placebo or placebo then beetroot juice). Submaximal constant work rate exercise time at 75% of the patient's maximal work capacity was the primary outcome. Secondary outcomes included plasma NO3(-) and nitrite (NO2(-)) levels, blood pressure, heart rate, oxygen consumption (VO2), dynamic hyperinflation, dyspnea and leg discomfort. Relative to placebo, beetroot ingestion increased plasma NO3(-) by 938% and NO2(-) by 379%. Median (+interquartile range) exercise time was significantly longer (p = 0.031) following the ingestion of beetroot versus placebo (375.0 + 257.0 vs. 346.2 + 148.0 s, respectively). Compared with placebo, beetroot ingestion significantly reduced iso-time (p = 0.001) and end exercise (p = 0.008) diastolic blood pressures by 6.4 and 5.6 mmHg, respectively. Resting systolic blood pressure was significantly reduced (p = 0.019) by 8.2 mmHg for the beetroot versus the placebo trial. No other variables were significantly different between the beetroot and placebo trials. These results indicate that acute dietary NO3(-) supplementation can elevate plasma NO3(-) and NO2(-) concentrations, improve exercise performance, and reduce blood pressure in COPD patients.
Moderate dose of dietary nitrate improves skeletal muscle microvascular function in patients with peripheral artery disease. [2023]Peripheral artery disease (PAD) is an atherosclerotic disease characterized by compromised lower-extremity blood flow that impairs walking ability. We showed that a moderate dose of dietary nitrate in the form of beetroot juice (BRJ, 0.11 mmol/kg) can improve macrovascular function and maximal walking distance in patients with PAD. However, its impacts on the microcirculation and autonomic nervous system have not been examined. Therefore, we investigated the impacts of this dose of dietary nitrate on skeletal muscle microvascular function and autonomic nervous system function and further related these measurements to 6-min walking distance, pain-free walking distance, and exercise recovery in patients with PAD. Patients with PAD (n = 10) ingested either BRJ or placebo in a randomized crossover design. Heart rate variability, skeletal muscle microvascular function, and 6-min walking distance were performed pre- and post-BRJ and placebo. There were significant group × time interactions (P < 0.05) for skeletal muscle microvascular function, 6-min walking distance, and exercise recovery, but no changes (P > 0.05) in heart rate variability or pain-free walking distance were noted. The BRJ group demonstrated improved skeletal muscle microvascular function (∆ 22.1 ± 7.5 %·min-1), longer 6-min walking distance (Δ 37.5 ± 9.1 m), and faster recovery post-exercise (Δ -15.3 ± 4.2 s). Furthermore, changes in skeletal muscle microvascular function were positively associated with changes in 6-min walking distance (r = 0.5) and pain-free walking distance (r = 0.6). These results suggest that a moderate dose of dietary nitrate may support microvascular function, which is related to improvements in walking distance and claudication in patients with PAD.
Dietary nitrate load lowers blood pressure and renal resistive index in patients with chronic kidney disease: A pilot study. [2018]Beetroot has a high concentration of inorganic nitrate, which can serially reduced to form nitrite and nitric oxide (NO) after oral ingestion. Increased renal resistive index (RRI) measured by Doppler ultrasonography is associated with higher cardiovascular mortality in hypertensive patients with reduced renal function over time defined as chronic kidney disease (CKD). Our aim was to investigate whether the supplementation of dietary nitrate by administration of beetroot juice is able to reduce blood pressure and renal resistive index (RRI) as prognostic markers for cardiovascular mortality in CKD patients. In a cross-over study design, 17 CKD patients were randomized to either a dietary nitrate load (300 mg) by highly concentrated beetroot juice (BJ) or placebo (water). Hemodynamic parameters as well as plasma nitrate concentration and RRI were measured before and 4 h after treatment. In this cohort, CKD was mainly caused by hypertensive or diabetic nephropathy. The mean eGFR was 41.6 ± 12.0 ml/min/m2. Plasma nitrate concentrations were significantly increased after ingestion of BJ compared to control. Peripheral systolic and diastolic blood pressure as well as mean arterial pressure (MAP) were significantly reduced secondary to the dietary nitrate load compared to control (e.g. ΔMAPBJ = -8.2 ± 7.6 mmHg vs. ΔMAPcontrol = -2.2 ± 6.0 mmHg, p = 0.012). BJ also led to significantly reduced RRI values (ΔRRIBJ = -0.03 ± 0.04 versus ΔRRIcontrol = 0.01 ± 0.04; p = 0.017). Serum potassium levels were not altered secondary to the treatment. In this study, administration of the nitrate donor BJ led to significantly reduced RRI values and peripheral blood pressure which might be explained by release of the vasodilatator NO after oral intake. Whether supplementation of dietary nitrate in addition to routine pharmacologic therapy is able to decelerate progression of cardiovascular and renal disease in CKD, remains to be investigated.
Pharmacokinetics of Nitrate and Nitrite Following Beetroot Juice Drink Consumption. [2021]Label="BACKGROUND" NlmCategory="BACKGROUND">Nitrate (NO3 -)-rich beetroot (BR) juice supplementation has been shown to improve cardiovascular function via reduction to nitrite (NO2 -) and then to the bioactive molecule nitric oxide (NO). However, limited research exists for the role of inorganic NO2 - that is contained naturally within BR.
Nitrate-rich beet juice intake on cardiovascular performance in response to exercise in postmenopausal women with arterial hypertension: study protocol for a randomized controlled trial. [2023]There is no evidence of the use of beetroot juice with a previously recommended dose of nitrate (NO3) (> 300 mg) on the cardiovascular performance during and recovery following exercise in postmenopausal women with systemic arterial hypertension (SAH).
Dietary nitrate supplementation enhances exercise performance in peripheral arterial disease. [2021]Peripheral arterial disease (PAD) results in a failure to adequately supply blood and oxygen (O(2)) to working tissues and presents as claudication pain during walking. Nitric oxide (NO) bioavailability is essential for vascular health and function. Plasma nitrite (NO(2)(-)) is a marker of vascular NO production but may also be a protected circulating "source" that can be converted to NO during hypoxic conditions, possibly aiding perfusion. We hypothesized that dietary supplementation of inorganic nitrate in the form of beetroot (BR) juice would increase plasma NO(2)(-) concentration, increase exercise tolerance, and decrease gastrocnemius fractional O(2) extraction, compared with placebo (PL). This was a randomized, open-label, crossover study. At each visit, subjects (n = 8) underwent resting blood draws, followed by consumption of 500 ml BR or PL and subsequent blood draws prior to, during, and following a maximal cardiopulmonary exercise (CPX) test. Gastrocnemius oxygenation during the CPX was measured by near-infrared spectroscopy. There were no changes from rest for [NO(2)(-)] (152 ± 72 nM) following PL. BR increased plasma [NO(2)(-)] after 3 h (943 ± 826 nM; P ≤ 0.01). Subjects walked 18% longer before the onset of claudication pain (183 ± 84 s vs. 215 ± 99 s; P ≤ 0.01) and had a 17% longer peak walking time (467 ± 223 s vs. 533 ± 233 s; P ≤ 0.05) following BR vs. PL. Gastrocnemius tissue fractional O(2) extraction was lower during exercise following BR (7.3 ± 6.2 vs. 10.4 ± 6.1 arbitrary units; P ≤ 0.01). Diastolic blood pressure was lower in the BR group at rest and during CPX testing (P ≤ 0.05). These findings support the hypothesis that NO(2)(-)-related NO signaling increases peripheral tissue oxygenation in areas of hypoxia and increases exercise tolerance in PAD.