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

8 Participants Needed

Trial Summary

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).

What data supports the effectiveness of the treatment Nitrate Rich Beetroot Juice for Microvascular Angina?

Research shows that beetroot juice, which is rich in nitrates, can improve exercise performance and lower blood pressure in various groups, including those with chronic conditions like COPD and type 2 diabetes. This suggests it might also help with microvascular angina by improving blood flow and reducing heart strain. ^{1 2 3 4 5}

Is beetroot juice safe for human consumption?

Beetroot juice, which is rich in nitrates, has been shown to be generally safe for human consumption. Studies have reported that it can lower blood pressure and improve exercise performance without significant adverse effects. ^{1 3 6 7 8}

How does beetroot juice treatment for microvascular angina differ from other treatments?

Beetroot juice is unique for microvascular angina because it is rich in nitrates, which are converted in the body to nitric oxide, a molecule that helps improve blood flow and reduce blood pressure. This natural approach differs from standard medications by using dietary supplementation to enhance cardiovascular function. ^{1 3 5 9 10}

What is the purpose of this 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. The main questions it aims to answer are: AIM 1: Test the hypothesis that fourteen days of nitrate rich beetroot juice will increase cardiac perfusion and improve quality of life compared to placebo. AIM 2: Test the hypothesis that fourteen days of nitrate rich beetroot juice will increase physical fitness and reduce angina and dyspnea symptoms compared to placebo. Exploratory AIM 3: Test the hypothesis that fourteen days of nitrate rich beetroot juice will improve vascular health and function. Participants will: * Take study beverage for 4 weeks total. * Stress Cardiac magnetic resonance imaging and 12 lead electrocardiograms * Complete questionnaires * Cycling exercise test * Non invasive vascular testing * Blood draws

Research Team

Patricia Rodriguez-Lozano, MD

Principal Investigator

University of Virginia

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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 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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Dietary nitrate supplementation improves exercise performance and decreases blood pressure in COPD patients. [2018]

2. Canada pubmed.ncbi.nlm.nih.gov

Cardiorespiratory function associated with dietary nitrate supplementation. [2021]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of Nitrate and Nitrite Following Beetroot Juice Drink Consumption. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Dietary Inorganic Nitrate/Nitrite Supplementation Reduces Central and Peripheral Blood Pressure in Patients With Type 2 Diabetes Mellitus. [2023]

5. England 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. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

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

7. England pubmed.ncbi.nlm.nih.gov

Efficacy and Variability in Plasma Nitrite Levels during Long-Term Supplementation with Nitrate Containing Beetroot Juice. [2023]

8. England pubmed.ncbi.nlm.nih.gov

The effect of nitrate supplementation on muscle contraction in healthy adults. [2015]

9. United States pubmed.ncbi.nlm.nih.gov

Dietary nitrate load lowers blood pressure and renal resistive index in patients with chronic kidney disease: A pilot study. [2018]

10. United States pubmed.ncbi.nlm.nih.gov

Effect of dietary nitrate on blood pressure, endothelial function, and insulin sensitivity in type 2 diabetes. [2022]