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

Study Overview
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Brief Summary
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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.

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

Conditions
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Ketosis

Intervention / Treatment
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* Dietary Supplement: D-beta-hydroxybutyrate
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 |