- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT07560800
Effect of Beetroot Juice on Cardiovascular and Autonomic Responses to Exercise in Adults With Type 2 Diabetes (DiaBEET)
Effect of Beetroot Juice on Cardiovascular and Autonomic Responses During and After Exercise in Adults With Type 2 Diabetes
This study will investigate whether a single dose of beetroot juice can improve cardiovascular responses and recovery after exercise in adults with Type 2 Diabetes.
Type 2 Diabetes is associated with higher blood pressure, impaired blood vessel function, and reduced autonomic control of the heart, all of which increase cardiovascular risk and may affect how the body responds to and recovers from physical activity. Beetroot juice is naturally rich in dietary nitrate, which is converted in the body into nitric oxide, a molecule that helps blood vessels relax and improve blood flow. While these effects have been demonstrated in healthy individuals, less is known about their impact in people with Type 2 Diabetes.
In this study, approximately 16 to 20 adults aged 40 to 65 years with Type 2 Diabetes will take part. After an online screening and consent process, eligible participants will attend two laboratory visits at Oxford Brookes University. In a randomised, double-blind, placebo-controlled crossover design, participants will receive beetroot juice during one visit and a nitrate-depleted placebo during the other visit.
During each visit, participants will undergo physiological measurements, including blood pressure, heart rate, oxygen saturation, and capillary blood glucose. Participants will then complete a short session of supervised, light-to-moderate cycling exercise. Measurements will continue during the recovery period to assess how quickly the cardiovascular system returns to resting levels.
The main outcomes are systolic blood pressure and heart rate variability during recovery, which reflect cardiovascular regulation and autonomic function. Secondary outcomes include diastolic blood pressure, heart rate, blood glucose, and markers related to nitric oxide availability.
This study may help determine whether a simple, dietary-based intervention such as beetroot juice can support cardiovascular function and improve recovery after exercise in people living with Type 2 Diabetes.
Study Overview
Status
Intervention / Treatment
Detailed Description
Type 2 diabetes mellitus (T2DM) is characterised by endothelial dysfunction, elevated blood pressure and impaired autonomic regulation, all of which contribute to increased cardiovascular risk. In particular, reduced cardiovagal modulation and delayed recovery of cardiovascular parameters following exercise are associated with adverse clinical outcomes. These disturbances are closely linked to reduced nitric oxide bioavailability.
Dietary inorganic nitrate, abundant in beetroot juice, is converted via the entero-salivary nitrate-nitrite-nitric oxide pathway into nitric oxide, promoting vasodilation, improved endothelial function and reductions in blood pressure. Acute supplementation with nitrate-rich beetroot juice has been shown to enhance nitric oxide bioavailability within approximately 2 to 3 hours after ingestion, making it suitable for investigating short-term physiological responses. However, evidence in individuals with T2DM remains limited, particularly regarding post-exercise autonomic recovery.
This study is designed as a randomised, double-blind, placebo-controlled crossover trial to evaluate the acute effects of nitrate-rich beetroot juice on cardiovascular and autonomic responses to exercise in adults with T2DM not treated with insulin. Each participant will complete two experimental conditions, receiving nitrate-rich beetroot juice and a nitrate-depleted placebo in random order, separated by an adequate washout period. Randomisation will be performed using a computer-generated sequence by an independent researcher, and both participants and investigators will remain blinded to allocation.
All procedures will be conducted in a controlled laboratory environment under supervision by trained research staff. Continuous physiological monitoring will be performed to capture cardiovascular responses at rest, during exercise and throughout the recovery period. The exercise protocol consists of a standardised, light-to-moderate intensity cycling task designed to provide a consistent physiological stimulus while minimising risk.
The primary focus of the study is on post-exercise recovery, with particular emphasis on heart rate variability as an index of autonomic (vagal) modulation and systolic blood pressure as a marker of haemodynamic regulation. The crossover design allows each participant to serve as their own control, improving statistical efficiency and reducing inter-individual variability.
Safety procedures are integrated throughout the protocol, including pre-participation screening, standardised preparation requirements and continuous monitoring during all experimental phases. The study is conducted as a low-risk laboratory protocol, with predefined procedures for the management of any adverse or unexpected physiological responses.
The findings of this study are expected to contribute to the understanding of whether acute dietary nitrate supplementation can improve cardiovascular regulation and autonomic recovery following exercise in individuals with T2DM, providing mechanistic insight and potential implications for non-pharmacological strategies to support cardiovascular health in this population.
Study Type
Enrollment (Estimated)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Bruno M Candeloro, MSc
- Phone Number: +447523113252
- Email: diabeet.study@brookes.ac.uk
Study Locations
-
-
Oxfordshire
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Oxford, Oxfordshire, United Kingdom, OX3 0BP
- Clinical Physiology Laboratory, Oxford Brookes University
-
Contact:
- Bruno M Candeloro, MSc
- Phone Number: +447523113252
- Email: diabeet.study@brookes.ac.uk
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Clinically diagnosed Type 2 Diabetes Mellitus
- Aged 40 to 65 years
- Not treated with insulin
- Stable diabetes medication regimen for at least 3 months
- Able to understand the study information and provide informed consent
- Able to safely perform light-to-moderate cycling exercise
Exclusion Criteria:
- Current or recent use of insulin
- Use of organic nitrates (e.g., glyceryl trinitrate) or phosphodiesterase-5 inhibitors (e.g., sildenafil, tadalafil)
- Use of systemic antibiotics within the specified preparation period or regular use of antiseptic/antibacterial mouthwash during study participation
- Use of supplements known to interfere with nitric oxide metabolism within the defined preparation period
- Unstable or clinically significant cardiovascular disease
- Uncontrolled hypertension or any condition that makes exercise unsafe
- Chronic kidney disease, history of kidney stones, or other relevant renal conditions
- Neurological, musculoskeletal or systemic disorders that impair safe participation
- Known or suspected allergy or intolerance to beetroot, lemon or any component of the study products
- Pregnancy or breastfeeding
- Inability to comply with study preparation requirements
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Experimental: Beetroot Juice Then Placebo
Participants receive nitrate-rich beetroot juice during the first visit and a nitrate-depleted placebo during the second visit, with a washout period of at least 48 hours between visits.
|
A single dose of approximately 70 mL of nitrate-rich beetroot juice providing approximately 400 mg of inorganic nitrate will be administered.
The product consists of concentrated beetroot juice with a small amount of lemon juice and is consumed prior to exercise testing.
The timing of ingestion is standardized to allow peak nitrate-nitrite-nitric oxide conversion within approximately 2 to 3 hours.
This intervention is intended to increase nitric oxide bioavailability and assess its acute effects on cardiovascular and autonomic responses.
Other Names:
A nitrate-depleted beetroot juice placebo matched for appearance, taste and packaging will be administered in a single dose of approximately 70 mL.
The placebo is identical to the active intervention in all aspects except for nitrate content.
It is consumed under the same standardized conditions and timing as the active intervention to maintain blinding and allow controlled comparison of physiological responses.
Other Names:
|
|
Experimental: Placebo Then Beetroot Juice
Participants receive a nitrate-depleted placebo during the first visit and nitrate-rich beetroot juice during the second visit, with a washout period of at least 48 hours between visits.
|
A single dose of approximately 70 mL of nitrate-rich beetroot juice providing approximately 400 mg of inorganic nitrate will be administered.
The product consists of concentrated beetroot juice with a small amount of lemon juice and is consumed prior to exercise testing.
The timing of ingestion is standardized to allow peak nitrate-nitrite-nitric oxide conversion within approximately 2 to 3 hours.
This intervention is intended to increase nitric oxide bioavailability and assess its acute effects on cardiovascular and autonomic responses.
Other Names:
A nitrate-depleted beetroot juice placebo matched for appearance, taste and packaging will be administered in a single dose of approximately 70 mL.
The placebo is identical to the active intervention in all aspects except for nitrate content.
It is consumed under the same standardized conditions and timing as the active intervention to maintain blinding and allow controlled comparison of physiological responses.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Systolic Blood Pressure During Post-Exercise Recovery
Time Frame: During post-exercise recovery mean value at 0-10 minutes, 10-20 minutes, 20-30 minutes, and 50-60 minutes.
|
Systolic blood pressure will be measured continuously during the post-exercise recovery period following submaximal cycling using beat-to-beat monitoring.
This measure will be used to assess haemodynamic regulation after exercise under each intervention condition.
|
During post-exercise recovery mean value at 0-10 minutes, 10-20 minutes, 20-30 minutes, and 50-60 minutes.
|
|
Heart Rate Variability (RMSSD) During Post-Exercise Recovery
Time Frame: During post-exercise recovery at 0-10 minutes, 10-20 minutes, 20-30 minutes, and 50-60 minutes.
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Heart rate variability, expressed as the root mean square of successive differences (RMSSD), will be derived from continuous electrocardiogram recordings during the post-exercise recovery period following submaximal cycling.
This measure will be used to assess autonomic (vagal) recovery after exercise under each intervention condition.
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During post-exercise recovery at 0-10 minutes, 10-20 minutes, 20-30 minutes, and 50-60 minutes.
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Diastolic Blood Pressure During Post-Exercise Recovery
Time Frame: During post-exercise recovery mean value at 0-10 minutes, 10-20 minutes, 20-30 minutes, and 50-60 minutes.
|
Diastolic blood pressure will be measured continuously during the post-exercise recovery period following submaximal cycling using beat-to-beat monitoring.
This measure will be used to assess haemodynamic responses and vascular regulation after exercise under each intervention condition.
|
During post-exercise recovery mean value at 0-10 minutes, 10-20 minutes, 20-30 minutes, and 50-60 minutes.
|
|
Heart Rate During Post-Exercise and Recovery
Time Frame: During post-exercise recovery mean value at 0-10 minutes, 10-20 minutes, 20-30 minutes, and 50-60 minutes.
|
Heart rate will be measured continuously during submaximal cycling exercise and throughout the post-exercise recovery period using electrocardiogram monitoring.
This measure will be used to assess cardiovascular response to exercise and the rate of recovery toward resting levels under each intervention condition.
|
During post-exercise recovery mean value at 0-10 minutes, 10-20 minutes, 20-30 minutes, and 50-60 minutes.
|
|
Capillary Blood Glucose Response
Time Frame: Pre-ingestion; 15, 30, 45, 60, 90, and 120 minutes post-ingestion; and 5 and 60 minutes post-exercise
|
Capillary blood glucose will be measured using finger-prick sampling at predefined time points, including pre-ingestion, 15, 30, 45, 60, 90 and 120 minutes post-ingestion, and at 5 and 60 minutes post-exercise.
These measurements will be used to assess glycaemic response to the intervention and exercise under each experimental condition.
|
Pre-ingestion; 15, 30, 45, 60, 90, and 120 minutes post-ingestion; and 5 and 60 minutes post-exercise
|
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Salivary Nitric Oxide-Related Response
Time Frame: Baseline, 1 hour post-ingestion, and 2 hours post-ingestion.
|
Salivary nitric oxide-related response will be assessed using test strips that estimate nitrate and nitrite concentrations in saliva.
Measurements will be performed at baseline, 1 hour post-ingestion, and 2 hours post-ingestion.
This measure will be used as an indicator of nitric oxide bioavailability following dietary nitrate supplementation under each experimental condition.
|
Baseline, 1 hour post-ingestion, and 2 hours post-ingestion.
|
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Perceived Exertion During Exercise
Time Frame: On both test days (beetroot juice and placebo days) perceived exertion will be recorded every minute during the submaximal cycling ramp test from timepoint M3 (2 hours post-ingestion) to timepoint M4 (peak exercise)
|
Perceived exertion will be assessed during the submaximal cycling ramp test using the Borg Rating of Perceived Exertion (6-20 scale).
The scale ranges from 6 (no exertion) to 20 (maximal exertion), with higher scores indicating greater perceived effort.
Ratings will be collected every minute during the exercise test and at peak exercise under each intervention condition.
|
On both test days (beetroot juice and placebo days) perceived exertion will be recorded every minute during the submaximal cycling ramp test from timepoint M3 (2 hours post-ingestion) to timepoint M4 (peak exercise)
|
Collaborators and Investigators
Sponsor
Publications and helpful links
General Publications
- Colberg SR, Sigal RJ, Yardley JE, Riddell MC, Dunstan DW, Dempsey PC, Horton ES, Castorino K, Tate DF. Physical Activity/Exercise and Diabetes: A Position Statement of the American Diabetes Association. Diabetes Care. 2016 Nov;39(11):2065-2079. doi: 10.2337/dc16-1728. No abstract available.
- Sun H, Saeedi P, Karuranga S, Pinkepank M, Ogurtsova K, Duncan BB, Stein C, Basit A, Chan JCN, Mbanya JC, Pavkov ME, Ramachandaran A, Wild SH, James S, Herman WH, Zhang P, Bommer C, Kuo S, Boyko EJ, Magliano DJ. IDF Diabetes Atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045. Diabetes Res Clin Pract. 2022 Jan;183:109119. doi: 10.1016/j.diabres.2021.109119. Epub 2021 Dec 6.
- Lara J, Ashor AW, Oggioni C, Ahluwalia A, Mathers JC, Siervo M. Effects of inorganic nitrate and beetroot supplementation on endothelial function: a systematic review and meta-analysis. Eur J Nutr. 2016 Mar;55(2):451-459. doi: 10.1007/s00394-015-0872-7. Epub 2015 Mar 13.
- Zunkovic B, Kejzar N, Bajrovic FF. Standard Heart Rate Variability Parameters-Their Within-Session Stability, Reliability, and Sample Size Required to Detect the Minimal Clinically Important Effect. J Clin Med. 2023 Apr 25;12(9):3118. doi: 10.3390/jcm12093118.
- Yang DR, Wang MY, Zhang CL, Wang Y. Endothelial dysfunction in vascular complications of diabetes: a comprehensive review of mechanisms and implications. Front Endocrinol (Lausanne). 2024 Apr 5;15:1359255. doi: 10.3389/fendo.2024.1359255. eCollection 2024.
- Benjamim CJR, Porto AA, Valenti VE, Sobrinho ACDS, Garner DM, Gualano B, Bueno Junior CR. Nitrate Derived From Beetroot Juice Lowers Blood Pressure in Patients With Arterial Hypertension: A Systematic Review and Meta-Analysis. Front Nutr. 2022 Mar 15;9:823039. doi: 10.3389/fnut.2022.823039. eCollection 2022.
- Tyler AP, Linder BA, Ricart K, Behrens CE Jr, Ovalle F, Patel RP, Fisher G. The Effects of Acute Beetroot Juice Intake on Glycemic and Blood Pressure Responses When Controlling for Medication in Individuals with Type 2 Diabetes: A Pilot Study. Nutrients. 2024 Aug 10;16(16):2636. doi: 10.3390/nu16162636.
- Liu S, Cui Y, Chen M. Heart rate variability: a multidimensional perspective from physiological marker to brain-heart axis disorders prediction. Front Cardiovasc Med. 2025 Nov 6;12:1630668. doi: 10.3389/fcvm.2025.1630668. eCollection 2025.
- Fejes R, Lutnik M, Weisshaar S, Pilat N, Wagner KH, Stuger HP, Peake JM, Woodman RJ, Croft KD, Bondonno CP, Hodgson JM, Wolzt M, Neubauer O. Increased nitrate intake from beetroot juice over 4 weeks affects nitrate metabolism, but not vascular function or blood pressure in older adults with hypertension. Food Funct. 2024 Apr 22;15(8):4065-4078. doi: 10.1039/d3fo03749e.
- Eleftheriadou A, Spallone V, Tahrani AA, Alam U. Cardiovascular autonomic neuropathy in diabetes: an update with a focus on management. Diabetologia. 2024 Dec;67(12):2611-2625. doi: 10.1007/s00125-024-06242-0. Epub 2024 Aug 9.
- Benjamim CJR, S Junior FW, de Figueiredo MILS, Benjamim CJR, Cavalcante TCF, da Silva AAM, Monteiro LRL, Santana MDR, Garner DM, Valenti VE. Beetroot (Beta Vulgaris L.) Extract Acutely Improves Heart Rate Variability Recovery Following Strength Exercise: A Randomized, Double-Blind, Placebo-Controlled Crossover Trial-Pilot Study. J Am Coll Nutr. 2021 May-Jun;40(4):307-316. doi: 10.1080/07315724.2020.1774441. Epub 2020 May 29.
- Aliahmadi M, Amiri F, Bahrami LS, Hosseini AF, Abiri B, Vafa M. Effects of raw red beetroot consumption on metabolic markers and cognitive function in type 2 diabetes patients. J Diabetes Metab Disord. 2021 Apr 21;20(1):673-682. doi: 10.1007/s40200-021-00798-z. eCollection 2021 Jun.
Study record dates
Study Major Dates
Study Start (Estimated)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- UREC-261968
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Access Criteria
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
- CSR
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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