The Acute Effect of Beetroot Juice in Normal and Hypertensive Subjects

The Acute Effect of Beetroot Juice on Circulating Nitrate and Nitrite Levels and Blood Pressure in Normotensives and Hypertensives

Inorganic nitrate can be converted to nitrite and thence nitric oxide in humans. Nitric oxide is normally produced by the inner lining of blood vessels and helps keep blood vessels open and therefore blood pressure lower. In subjects with high blood pressure, the inner lining of the blood vessels does not function adequately. The investigators wish to investigate whether elevating systemic levels of inorganic nitrate (through provision of dietary nitrate-rich vegetables) can elevate levels of nitrate/nitrite in hypertensive subjects, and whether this has a beneficial effect on blood pressure.

Study Overview

• Status: Completed
• Conditions: Hypertension
• Intervention / Treatment: Dietary supplement: Beetroot juice; Dietary supplement: Water

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, EC1M 6BQ
    • Queen Mary University London

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Adult male and females between 18 and 85 years of age, inclusive.
2. To be eligible, female subjects will be required to state that they are not pregnant, and will not become pregnant during the course of the study.
3. Body mass index (BMI) between 18 and 40 kg/m2
4. A signed and dated written informed consent prior to admission to the study
5. The subject is able to understand and comply with protocol requirements, instructions and protocol-stated restrictions.
6. Grade 1 hypertensive SBP 140-159 or DBP 90-99 on no anti-hypertensives, no target organ damage (TOD), low cardiovascular disease (CVD) risk

Exclusion Criteria:

1. History of symptomatic coronary artery disease, stroke, or other known atherosclerotic disease.
2. History of chronic viral hepatitis (including presence of hepatitis B surface antigen or hepatitis C antibody), or other chronic hepatic disorders.
3. History of increased liver function tests (ALT, AST) due to acute or chronic liver conditions, 3x above the upper limit of normal or bilirubin 1.5x above the upper limit of normal at screening.
4. Renal impairment with creatinine clearance (eGFR) of <50 ml/min at screening.
5. Current poorly controlled diabetes mellitus, defined as HbA1c >10% at Screen.
6. Subjects with LDLc, >7.5 mmol/l. Fasting TG level >6mmol/l.
7. History of heart failure defined as NYHA class II - IV or those with known severe LV dysfunction (EF<30%) regardless of symptomatic status
8. History of malignancy within the past 5 years, other than non-melanoma skin cancer.
9. Current life-threatening condition other than vascular disease (e.g., very severe chronic airways disease, HIV positive, life-threatening arrhythmias) that may prevent a subject from completing the study.
10. Alcohol or drug abuse within the past 6 months.
11. Use of an investigational device or investigational drug within 30 days or 5 half-lives (whichever is the longer) preceding the first dose of study medication.
12. Subjects who will commence or who are likely to commence treatment with non-steroidal anti-inflammatory drugs (NSAIDs) (other than aspirin), from screening until study completion.
13. Any non-stable dosing of ongoing medication regimens throughout the study trial.
14. The subject has a three month prior history of regular alcohol consumption exceeding an average weekly intake of > 28 units (or an average daily intake of greater than 3 units) for males, or an average weekly intake of > 21 units (or an average daily intake of greater than 2 units) for females. 1 unit is equivalent to a halfpint (284mL) of beer/lager; 25mL measure of spirits or 125mL of wine; or a positive alcohol breath test at the screening visit
15. A positive urine test for drugs of abuse (not related to known medications the subject is taking, ie, codeine for pain management) or alcohol at screening or prior to study medication administration.
16. Any other subject whom the Investigator deems unsuitable for the study (e.g., due to either medical reasons, laboratory abnormalities, expected study medication noncompliance, or subject's unwillingness to comply with all study-related study procedures).
17. Subjects with rheumatoid arthritis, connective tissue disorders and other conditions known to be associated with chronic inflammation (e.g. Inflammatory Bowel Disease).
18. Subjects with any acute infection, or significant trauma (burns, fractures).
19. Subjects who have donated more than 500 mL of blood within 56 days prior to the initiation of the study.

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Beetroot juice; 250ml beetroot juice ingestion	Dietary supplement: Beetroot juice; 250ml once of beetroot juice
Placebo Comparator: Water; 250ml low-nitrate water placebo	Dietary supplement: Water; 250ml once of low-nitrate mineral water

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Changes in circulating nitrate/nitrite/cGMP levels	24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in blood pressure		24 hours
arterial stiffness	pulse wave velocity	3hours

Collaborators and Investigators

• Sponsor: Queen Mary University of London
• Collaborators: University College, London
• Investigators: Principal Investigator: Amrita Ahluwalia, QMUL

Publications and helpful links

General Publications

• Webb AJ, Patel N, Loukogeorgakis S, Okorie M, Aboud Z, Misra S, Rashid R, Miall P, Deanfield J, Benjamin N, MacAllister R, Hobbs AJ, Ahluwalia A. Acute blood pressure lowering, vasoprotective, and antiplatelet properties of dietary nitrate via bioconversion to nitrite. Hypertension. 2008 Mar;51(3):784-90. doi: 10.1161/HYPERTENSIONAHA.107.103523. Epub 2008 Feb 4.
• Kapil V, Milsom AB, Okorie M, Maleki-Toyserkani S, Akram F, Rehman F, Arghandawi S, Pearl V, Benjamin N, Loukogeorgakis S, Macallister R, Hobbs AJ, Webb AJ, Ahluwalia A. Inorganic nitrate supplementation lowers blood pressure in humans: role for nitrite-derived NO. Hypertension. 2010 Aug;56(2):274-81. doi: 10.1161/HYPERTENSIONAHA.110.153536. Epub 2010 Jun 28. Erratum In: Hypertension. 2010 Sep;56(3):e37-9. Hypertension. 2017 Feb;69(2):e1.

Study record dates

Study Major Dates

• Study Start: December 1, 2009
• Primary Completion (Actual): December 1, 2010
• Study Completion (Actual): December 1, 2010

Study Registration Dates

• First Submitted: November 8, 2010
• First Submitted That Met QC Criteria: November 8, 2010
• First Posted (Estimate): November 9, 2010

Study Record Updates

• Last Update Posted (Estimate): August 8, 2011
• Last Update Submitted That Met QC Criteria: August 4, 2011
• Last Verified: July 1, 2011

More Information

Terms related to this study

• Keywords: Aortic stiffness; Vegetable; Nitrate; Nitrite
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension
• Other Study ID Numbers: 08/H0703/91 Acute