Beetroot Juice for Microvascular Angina

(NO-ANOCA Trial)

Overseen By Shuo Wang

Age: 18+

Sex: Female

Trial Phase: Academic

Sponsor: University of Virginia

Must not be taking: Nitroglycerine, PDE-5 inhibitors

Disqualifiers: Cardiomyopathy, Heart failure, Diabetes, Stroke, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 5 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether beetroot juice, rich in inorganic nitrate, can improve blood flow and physical fitness in women with certain heart conditions. Specifically, it examines whether this juice can ease chest pain, enhance exercise ability, and boost overall heart health. Participants will consume both nitrate-rich beetroot juice and nitrate-depleted beetroot juice (placebo) for two weeks each, undergoing various tests such as stress imaging and exercise assessments. Women who experience chest pain but have no major artery blockages might be suitable candidates. As an unphased trial, this study offers participants the chance to contribute to groundbreaking research that could lead to new insights and treatments for heart health.

Do I have to stop taking my current medications for the trial?

The trial requires that you stop taking certain medications, specifically nitroglycerine, PDE-5 inhibitors (like Cialis or Viagra), and xanthine oxidase inhibitors (like Allopurinol).

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that beetroot juice, rich in nitrates, is generally safe for consumption. Studies have found that it can help lower blood pressure, benefiting heart health. Those who drink beetroot juice with nitrates often experience a significant increase in blood nitrate levels, indicating good absorption.

Reports of side effects are rare, and most people tolerate the juice well, suggesting its safety. Although researchers continue to explore new applications, its use in other health areas supports its safety. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using beetroot juice for microvascular angina because it introduces an entirely natural approach by using nitrate-rich beetroot juice. Unlike standard treatments like beta-blockers, calcium channel blockers, and nitrates, which primarily aim to improve blood flow and reduce heart workload, beetroot juice works by increasing nitric oxide levels in the blood. This can help relax and dilate blood vessels, potentially offering a new, non-pharmaceutical option that might have fewer side effects. Plus, the convenience of consuming it as a simple drink makes it an appealing alternative for patients.

What evidence suggests that nitrate rich beetroot juice might be an effective treatment for microvascular angina?

Research has shown that beetroot juice, rich in nitrates, can enhance heart and blood vessel health. Some studies have found that it increases blood flow by making blood vessels more flexible, with a 24% improvement from the starting point. This improvement is crucial because better blood flow can aid conditions like microvascular angina, which affects the small blood vessels in the heart. One study found that beetroot juice might help lower both systolic and diastolic blood pressure in older adults, boosting overall heart health. In this trial, participants will receive either nitrate-rich beetroot juice or a placebo (nitrate-depleted beetroot juice) to evaluate its effects on blood flow and physical fitness in individuals with heart-related conditions. ^{1 2 4 6 7}

Who Is on the Research Team?

Patricia Rodriguez-Lozano, MD

Principal Investigator

University of Virginia

Are You a Good Fit for This Trial?

This trial is for women with ANOCA and CMD, conditions affecting heart blood flow and muscle function. Participants will undergo various tests including cardiac imaging, ECGs, exercise testing, vascular assessments, and blood draws over a 4-week period.

Inclusion Criteria

Willing and able to provide written informed consent

I am female.

I was referred for a heart check-up due to suspected blockage within the last 2 years.

Exclusion Criteria

History of reaction to iodinated contrast agents

Pregnancy or women who are breast-feeding

Greater than first degree heart block

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive either nitrate-rich beetroot juice or placebo for 14 days, followed by a 7-day washout, then the alternate treatment for another 14 days

5 weeks

Baseline and end of each treatment period visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Nitrate Rich Beetroot Juice
• Placebo (Nitrate depleted beetroot juice)

Trial Overview The study is examining if drinking nitrate-rich beetroot juice can improve heart blood flow, physical fitness, quality of life, reduce chest pain (angina), shortness of breath (dyspnea), and enhance vascular health compared to a placebo beetroot juice.

How Is the Trial Designed?

Group I: Placebo followed by Beetroot juice Experimental Treatment 1 Intervention

Placebo (70 mL nitrate depleted beetroot juice) for 14 days followed by Nitrate rich Beetroot juice for 14 days

Group II: Beetroot juice followed by placebo Experimental Treatment 1 Intervention

70mL Nitrate Rich Beetroot Juice for 14 days followed by placebo (70mL nitrate depleted beetroot juice) for 14 days

Who Is Running the Clinical Trial?

University of Virginia

Lead Sponsor

Trials

802

Recruited

1,342,000+

Published Research Related to This Trial

Ingesting beetroot juice rich in nitrate (NO3-) significantly increases plasma levels of both nitrate and nitrite (NO2-), which can positively affect cardiovascular measures like mean arterial pressure (MAP).

While both NO3- and NO2- have the potential to lower MAP, the expected reduction in systolic and diastolic blood pressure was not observed, suggesting that the role of NO2- in blood pressure regulation alongside NO3- needs further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of Nitrate and Nitrite Following Beetroot Juice Drink Consumption. Jakubcik, EM., Rutherfurd-Markwick, K., Chabert, M., et al.[2021]

This study will evaluate the effects of beetroot juice, rich in nitrates, on cardiovascular performance in 25 postmenopausal women with systemic arterial hypertension, using both acute (800 mg) and daily doses (400 mg) over a week.

The research aims to provide insights into how beetroot juice can improve cardiovascular health during exercise, potentially leading to specific nutritional recommendations for women with hypertension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Benjamim, CJR., Sousa, YBA., Porto, AA., et al.[2023]

In a 12-week study with adults, those consuming beetroot juice containing 380 mg of nitrate showed a significant increase in plasma nitrite levels (273.2% change) compared to a placebo group (4.9% change).

Long-term consumption of beetroot juice effectively enhances the body's ability to convert dietary nitrate into plasma nitrate and nitrite, indicating its potential benefits for cardiovascular health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Variability in Plasma Nitrite Levels during Long-Term Supplementation with Nitrate Containing Beetroot Juice. Miller, GD., Collins, S., Ives, J., et al.[2023]

Supplementation with inorganic nitrate/nitrite from beetroot juice for eight weeks significantly reduced both peripheral and central systolic blood pressure in patients with type 2 diabetes mellitus, indicating a potential therapeutic benefit for managing hypertension in this population.

The treatment also improved arterial stiffness, as evidenced by a reduction in augmentation index, suggesting that increasing nitric oxide bioavailability may enhance cardiovascular health in individuals with elevated blood pressure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dietary Inorganic Nitrate/Nitrite Supplementation Reduces Central and Peripheral Blood Pressure in Patients With Type 2 Diabetes Mellitus. Bock, JM., Hughes, WE., Ueda, K., et al.[2023]

In a study involving 12 healthy young African-American females, beetroot juice significantly increased plasma nitric oxide (NO) levels, which is linked to improved cardiovascular function during exercise.

The consumption of beetroot juice led to decreased oxygen consumption, systolic blood pressure, and heart rate during exercise, suggesting it may reduce cardiac workload and improve efficiency in healthy individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiorespiratory function associated with dietary nitrate supplementation. Bond, V., Curry, BH., Adams, RG., et al.[2021]

In a study involving 17 chronic kidney disease (CKD) patients, supplementation with beetroot juice, which is high in dietary nitrate, significantly reduced blood pressure and renal resistive index (RRI), suggesting potential cardiovascular benefits.

The reduction in blood pressure and RRI after beetroot juice consumption may be attributed to the release of nitric oxide (NO), a vasodilator, indicating that dietary nitrate could be a useful adjunct therapy for managing hypertension in CKD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dietary nitrate load lowers blood pressure and renal resistive index in patients with chronic kidney disease: A pilot study. Kemmner, S., Lorenz, G., Wobst, J., et al.[2018]

In a study involving 15 COPD patients, acute ingestion of beetroot juice significantly improved exercise capacity, allowing patients to exercise longer at a submaximal workload compared to a placebo.

Beetroot juice also led to notable reductions in both resting and exercise-induced blood pressure, indicating potential cardiovascular benefits alongside improved exercise performance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dietary nitrate supplementation improves exercise performance and decreases blood pressure in COPD patients. Berry, MJ., Justus, NW., Hauser, JI., et al.[2018]

A study analyzing 45 different lots of 24 beetroot juice products found significant variability in nitrate (NO3-) content, with a mean variation of 30% within the same product and up to a 50-fold difference between different products.

Only five of the tested products consistently provided the recommended dose of ≥5 mmol of NO3- per serving, which is necessary for enhancing exercise performance, highlighting the importance of product selection for athletes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

What's in Your Beet Juice? Nitrate and Nitrite Content of Beet Juice Products Marketed to Athletes. Gallardo, EJ., Coggan, AR.[2021]

In a study with 18 healthy participants, four days of dietary supplementation with inorganic nitrate from beetroot juice significantly reduced muscular fatigue during exercise with blood flow restriction, showing better force retention compared to a placebo.

The observed benefits in muscle performance are likely due to improved calcium handling or enhanced blood flow during low-oxygen conditions, indicating that nitrate supplementation can help maintain muscle function during intense physical activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of nitrate supplementation on muscle contraction in healthy adults. Hoon, MW., Fornusek, C., Chapman, PG., et al.[2015]

Citations

1. nature.com nature.com/articles/s41430-022-01115-4

No effect of nitrate-rich beetroot juice on microvascular ... Conclusions. Beetroot juice had no effect on blood pressure or microvascular endothelial function in young and older individuals. Dosage and ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6722817/

The Effects of Beetroot Juice on Blood Pressure ... This pilot study demonstrated that medium-term BRJ ingestion potentially improves SBP, DBP and large-vessel EF in healthy older adults.

3. withpower.com withpower.com/trial/beetroot-juice-for-microvascular-angina-3e563

Beetroot Juice for Microvascular Angina (NO-ANOCA Trial) The purpose of this study is to see if inorganic nitrate in the form of beetroot juice helps blood flow and physical fitness in women with ANOCA and CMD.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05810974

The Impact of Inorganic Nitrate-rich Beetroot Juice on ... Inorganic nitrate found in beetroot and green leafy vegetables has been demonstrated to reduce cardiovascular disease risk factors including reducing blood ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0002916523120971

Dietary nitrate improves vascular function in patients with ... Dietary nitrate resulted in an absolute increase in the FMD response of 1.1% (an ∼24% improvement from baseline) with a worsening of 0.3% in the placebo group ( ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S0891584924005501

Effects of increased nitrate intake from beetroot juice on ... Briefly, plasma nitrate and nitrite concentrations increased significantly (∼4- to 5-fold) at 3H POST and 4WK POST following nitrate-rich beetroot juice ...

7. frontiersin.org frontiersin.org/journals/physiology/articles/10.3389/fphys.2019.00047/full

A Double-Blind Placebo-Controlled Crossover Study of the ... We found minimal effects of nitrate-containing beetroot juice on brachial systolic BP, so our data suggest that measurement of brachial BP as ...