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

Official title

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

Overview

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.

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.

Interventions

• Dietary supplement Beetroot juice
  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
• Dietary supplement Nitrate-depleted Beetroot Juice Placebo
  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.

Primary outcome measures

• 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.]
• 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.]

Secondary outcome measures (5)

• 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.]
• 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.]
• 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]
• Salivary Nitric Oxide-Related Response [Time frame: Baseline, 1 hour post-ingestion, and 2 hours post-ingestion.]
• 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)]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Crossover

Masking

Triple blind

Primary purpose

Basic science

Study locations

United Kingdom · 1 center

• Clinical Physiology Laboratory, Oxford Brookes University — Oxford

Publications

• 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
• 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
• 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
• 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
• 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
• 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 PMID 34879977
• 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
• 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

Identifiers

NCT: NCT07560800 · UREC-261968

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗