Ketone Ester Supplementation on Neuro-cardiovascular Responses to Stress in Humans

Ketone ester supplementation has become increasingly popular as an athletic supplement. However, the metabolic effects of these supplements on exercise performance are controversial. One potential reason for lack of an ergogenic benefit could be the effects of ketone bodies on other bodily systems, such as the sympathetic nervous system. During exercise and stress the body increases the activity of the sympathetic nervous system. This causes blood vessels to constrict (get smaller) and can increase blood pressure. Studies have shown that ketone bodies can suppress the sympathetic nervous system in mice. Additionally, ketone ester supplementation can reduce blood pressure in healthy adults. In humans, direct measures of sympathetic activity are usually made from sympathetic outflow to muscle, also called muscle sympathetic nerve activity (MSNA). Using a ketone ester supplement, the investigators plan to measure blood pressure and sympathetic outflow to muscle at rest and during handgrip exercise and a mathematical task stress test to investigate the effect of ketones on neuro-cardiovascular stress responses.

Study Overview

• Status: Completed
• Conditions: Ketosis
• Intervention / Treatment: Dietary supplement: D-beta-hydroxybutyrate; Dietary supplement: Placebo

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Guelph, Ontario, Canada, N1G2W1
      • University of Guelph - Human Cardiovascular Physiology Laboratory

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• 18 to 40 years of age
• Healthy, free of known cardiovascular, metabolic, or musculoskeletal disease

Exclusion Criteria:

• History of smoking (within 3 months), diagnosed cardiovascular or metabolic disease, recent musculoskeletal injury preventing handgrip exercise, prescription of chronic medications other than oral contraceptives.
• Current or recent (within 6 months) use of ketone ester supplementation or participation in a ketogenic diet.
• Inability to abstain from drugs, caffeine, alcohol, or strenuous physical activity prior to the study visit.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo drink	Dietary supplement: Placebo; Isocaloric flavored water with medium-chain triglyceride oil.
Active Comparator: Ketone ester drink	Dietary supplement: D-beta-hydroxybutyrate; Drink containing D-beta-hydroxybutyrate administered at a dose of 395 mg/kg.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Muscle sympathetic nerve activity	Microneurography of fibular nerve	Baseline - Immediately before active and control interventions
Muscle sympathetic nerve activity	Microneurography of fibular nerve	Post-intervention - Immediately following active and control interventions
Blood pressure	Finger plethysmography	Baseline - Immediately before active and control interventions
Blood pressure	Finger plethysmography	Post-intervention - Immediately following active and control interventions

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Forearm blood flow	Brachial artery Doppler ultrasound	Baseline - Immediately before active and control interventions
Forearm blood flow	Brachial artery Doppler ultrasound	Post-intervention - Immediately following active and control interventions

Collaborators and Investigators

• Sponsor: University of Guelph
• Investigators: Principal Investigator: Philip Millar, PhD, University of Guelph

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2021
• Primary Completion (Actual): October 1, 2022
• Study Completion (Actual): December 1, 2022

Study Registration Dates

• First Submitted: May 5, 2021
• First Submitted That Met QC Criteria: May 5, 2021
• First Posted (Actual): May 11, 2021

Study Record Updates

• Last Update Posted (Actual): September 22, 2023
• Last Update Submitted That Met QC Criteria: September 20, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Acid-Base Imbalance; Acidosis; Ketosis
• Other Study ID Numbers: 21-02-019

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