The Impact of Inorganic Nitrate-rich Beetroot Juice on Microvascular Blood Flow and Cognitive Function

The Impact of Inorganic Nitrate-rich Beetroot Juice on Microvascular Blood Flow, Cognitive Function and Other Hemodynamic Outcomes in Postmenopausal Women

Cardiovascular disease (CVD) is one of the leading causes of mortality worldwide. Inorganic nitrate found in beetroot and green leafy vegetables has been demonstrated to reduce cardiovascular disease risk factors including reducing blood pressure and the stiffness of blood vessels by increasing levels of a compound called nitric oxide. Much of the research to date has focused on the large blood vessels, and little is known about the impact of inorganic nitrate on smaller blood vessels which could be related to cognitive function.

The majority of beneficial effects with inorganic nitrate have been observed within young healthy populations. However, it is known that after the menopause women are at an increased risk of cardiovascular disease and have reduced levels of nitric oxide in their body; this could also contribute to the cognitive decline also observed post-menopause. This trial will investigate the impact of inorganic nitrate from beetroot juice on the blood flow in small blood vessels and on cognitive function in postmenopausal women. The hypothesis of the study is that the nitrate in beetroot juice will increase circulating nitric oxide that will then increase blood flow in small blood vessels and improve cognitive function.

Study Overview

• Status: Completed
• Conditions: Post Menopausal
• Intervention / Treatment: Dietary supplement: Concentrated beetroot juice; Dietary supplement: Nitrate depleted beetroot juice + potassium nitrate (KNO3); Dietary supplement: Nitrate depleted beetroot juice

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • UK
    • Reading, UK, United Kingdom, RG6 6AH
      • University of Reading

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Apparently healthy post-menopausal women (age over 45)
• Able to understand information sheet and willing to comply with the study protocol and able to give informed consent
• Not having menstrual period for 12 months

Exclusion Criteria:

• Blood pressure <90/60 or > 140/90 mmHg
• Medical history of myocardial infarction, angina, thrombosis, stroke, cancer, high cholesterol, liver, renal, respiratory or bowel diseases or diabetes or other endocrine disorder
• BMI>30
• Any tobacco and/or nicotine users (or quit within the last 6 months)
• Current use of antihypertensive medication
• Alcohol intake > 14 units/week
• Vigorous exercise > 3 times/ week
• Antihypertensive medication users
• People who have had hysterectomy
• Currently taking hormone replacement therapy or selective oestrogen receptor modulator

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Concentrated beetroot juice	Dietary supplement: Concentrated beetroot juice; Subjects will consume 70ml shot (Beet-it Sport nitrate 400 shot, James White Drinks) and this drink contains 0.4g inorganic nitrate
Active Comparator: Nitrate depleted beetroot juice + potassium nitrate (KNO3)	Dietary supplement: Nitrate depleted beetroot juice + potassium nitrate (KNO3); Nitrate-depleted beetroot juice (70ml) and 0.4g KNO3- will be mixed. (Same appearance and taste with Beet-it sport shot)
Placebo Comparator: Nitrate-depleted beetroot juice	Dietary supplement: Nitrate depleted beetroot juice; Subjects will consume 70ml of (Beet-it Placebo shot, James White Drinks). This drink is the same as the Beet-it Sport nitrate shot but has the nitrate removed.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline endothelial dependent microvascular function as laser Doppler imaging (LDI) with iontophoresis	Measurements will be taken by LDI with iontophoresis of endothelium-dependent (acetylcholine (ACh))	At baseline (t= 0.5 hours) and t= 3 hours
Change from baseline endothelial independent microvascular function as laser Doppler imaging (LDI) with iontophoresis	Measurements will be taken by LDI of endothelium-independent (sodium nitroprusside (SNP))	At baseline (t= 0.5 hours) and t= 3 hours
Change from baseline cognitive function. Domain: Episodic memory	-Rey Auditory Verbal Learning Test (RAVLT) task Cognitive domains will be assessed by using the Gorilla online research tools.	At baseline (t= 0 hours) and t=2.5 hours
Change from baseline cognitive function. Domain: Executive function 1	-Digit Span Task	At baseline (t= 0 hours) and t=2.5 hours
Change from baseline cognitive function. Domain: Executive function 2	-Stroop Task	At baseline (t= 0 hours) and t=2.5 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in blood pressure	Systolic and Diastolic Blood pressure measurement by automated device	[Time Frame: At baseline (t= 0 hours) and 15 minute intervals until t= 2.5 hours.]

Collaborators and Investigators

• Sponsor: University of Reading

Study record dates

Study Major Dates

• Study Start (Actual): March 14, 2023
• Primary Completion (Actual): July 7, 2023
• Study Completion (Actual): August 7, 2023

Study Registration Dates

• First Submitted: February 8, 2023
• First Submitted That Met QC Criteria: April 11, 2023
• First Posted (Actual): April 13, 2023

Study Record Updates

• Last Update Posted (Estimated): November 22, 2024
• Last Update Submitted That Met QC Criteria: November 20, 2024
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: Cognition; NO; Beetroot; Nitrate; Microvascular function
• Other Study ID Numbers: -TBC-

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No