Effect of Beetroot Juice on Cardiovascular and Autonomic Responses to Exercise in Adults With Type 2 Diabetes

NCT07560800 | Not Yet Recruiting

• 1 other identifier: UREC-261968
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Hypertension; Type 2 Diabetes Mellitus; Autonomic Nervous System Diseases

Keywords

Beetroot juice; Dietary nitrate; Nitric oxide; Heart rate variability; Autonomic function; Blood pressure; Exercise recovery; Submaximal exercise; Endothelial function; Crossover trial

Outcome Measures

Primary Outcomes (2)

• Systolic Blood Pressure During Post-Exercise Recovery

  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

  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.

  During post-exercise recovery at 0-10 minutes, 10-20 minutes, 20-30 minutes, and 50-60 minutes.

Secondary Outcomes (5)

• Diastolic Blood Pressure During Post-Exercise Recovery

  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

  During post-exercise recovery mean value at 0-10 minutes, 10-20 minutes, 20-30 minutes, and 50-60 minutes.

• Capillary Blood Glucose Response

  Pre-ingestion; 15, 30, 45, 60, 90, and 120 minutes post-ingestion; and 5 and 60 minutes post-exercise

• Salivary Nitric Oxide-Related Response

  Baseline, 1 hour post-ingestion, and 2 hours post-ingestion.

• Perceived Exertion During Exercise

  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)

Study Arms (2)

Beetroot Juice Then Placebo

EXPERIMENTAL

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.

Dietary Supplement: Beetroot juice; Dietary Supplement: Nitrate-depleted Beetroot Juice Placebo

Placebo Then Beetroot Juice

EXPERIMENTAL

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.

Dietary Supplement: Beetroot juice; Dietary Supplement: Nitrate-depleted Beetroot Juice Placebo

Interventions

Beetroot juice DIETARY_SUPPLEMENT

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.

Also known as: Nitrate-rich beetroot juice

Beetroot Juice Then Placebo; Placebo Then Beetroot Juice

Nitrate-depleted Beetroot Juice Placebo DIETARY_SUPPLEMENT

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.

Also known as: Placebo beetroot juice

Beetroot Juice Then Placebo; Placebo Then Beetroot Juice

Eligibility Criteria

• Age: 40 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Oxford Brookes University: lead

Study Sites (1)

Clinical Physiology Laboratory, Oxford Brookes University

Oxford, Oxfordshire, OX3 0BP, United Kingdom

Location

Related Publications (12)

• 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.

  PMID: 37176559 BACKGROUND

• 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.

  PMID: 38645427 BACKGROUND

• 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.

  PMID: 27926890 BACKGROUND

• 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.

  PMID: 35369064 BACKGROUND

• 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.

  PMID: 39203773 BACKGROUND

• 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.

  PMID: 34879977 BACKGROUND

• 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.

  PMID: 41282340 BACKGROUND

• 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.

  PMID: 25764393 BACKGROUND

• 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.

  PMID: 38546454 BACKGROUND

• 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.

  PMID: 39120767 BACKGROUND

• 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.

  PMID: 32469260 BACKGROUND

• 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.

  PMID: 34222085 BACKGROUND

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Hypertension; Autonomic Nervous System Diseases

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Vascular Diseases; Cardiovascular Diseases; Nervous System Diseases

Central Study Contacts

Bruno M Candeloro, MSc

CONTACT

+447523113252; diabeet.study@brookes.ac.uk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: An independent laboratory technician, not involved in data collection or analysis, is responsible for generating the randomization sequence and preparing and labeling the study drinks using participant ID codes. This individual is the only unblinded member of the study team. The intervention and placebo are matched for appearance, taste and packaging to maintain blinding throughout the study.
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: This is a randomized, double-blind, placebo-controlled crossover study in which each participant completes two experimental conditions. Participants receive nitrate-rich beetroot juice in one visit and a nitrate-depleted placebo in the other visit, in a randomized order. The two conditions are separated by a washout period of at least 48 hours. Each participant serves as their own control to reduce inter-individual variability.

Study Record Dates

• First Submitted: April 2, 2026
• First Posted: May 1, 2026
• Study Start: April 2, 2026
• Primary Completion (Estimated): July 31, 2026
• Study Completion (Estimated): July 31, 2026
• Last Updated: May 1, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, CSR
• Time Frame: At the time of submission for journal publication of results
• Access Criteria: RADAR shares the intellectual product of Oxford Brookes University freely and openly, either with the staff and students of Oxford Brookes or with the general public and global academic community.

Locations

GB (1)