Acceptability and Tolerability of Ketone Supplements and Effects of BHB Concentrations in Young Adults

Study Overview
=================
Brief Summary
-----------------
Assess the acceptability and tolerability of two different commercially available ketone supplements and determine their effects on capillary blood concentrations of the ketone beta-hydroxybutyrate and glucose in young adults.

Detailed Description
-----------------
Past findings suggest that raising ketone concentrations through the use of a ketogenic diet (high-fat, moderate-protein, low-carbohydrate) is effective for preventing weight gain and decreasing appetite. However, strict adherence to this diet is difficult, and ending the diet can result in the regaining of body weight. Our group has investigated the effects of various ketone supplements in both rodents and humans. Past results of our group and that of our colleagues suggest that ketone supplements have the ability to increase ketone concentrations in the blood, decrease appetite, lower body weight, and maintain lean body mass. Exogenous ketones may serve as an alternative to the ketogenic diet by increasing concentrations of ketones without the need for adherence to a strict diet. However, little is known about ketone supplements as it relates to their tolerability and efficacy. For example, the taste of these supplements is unacceptable to some individuals and it is unclear if ketone supplements provide an adequate approach to raise and maintain circulating ketone concentrations as observed with the ketogenic diet. This information will be valuable before launching larger-scale human trials. Ketone supplements (KE1 and KE4) will be obtained from KetoneAid (Falls Church, VA). Participants will be asked to drink (5g and 10g) of each supplement separated by at least 3 days. Capillary blood samples will be measured using a handheld device to measure circulating beta-hydroxybutyrate (BHB) and glucose concentrations while a questionnaire will be used to assess the acceptability and tolerability of the ketone supplements.

Official Title
-----------------
Acceptability and Tolerability of Ketone Supplements and Their Effects on Capillary Beta-hydroxybutyrate Concentrations in Young Adults

Conditions
-----------------
Exogenous Ketosis

Intervention / Treatment
-----------------
* Dietary Supplement: KE1 5g
* Dietary Supplement: KE1 10g
* Dietary Supplement: KE4 5g
* Dietary Supplement: KE 10g
* Other: Placebo drink


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adult 18-25 years of age In generally good health Able and willing to attend study visits (once every 3 days for  2 weeks) BMI 18.5-29.9 Exclusion Criteria: Pregnant Has preexisting medical conditions, including Type 2 diabetes, heart disease, or cancer BMI ≥ 30

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 25 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Participants will each undergo all five treatments, in randomized order. The five treatments include the control placebo, 5g of KE1, 10g of KE1, 5g of KE4, and 10g of KE4. There will be a minimum of two days washout period between treatments.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Control placebo<br> | Other: Placebo drink<br>* Flavor-matched control placebo drink (KetoneAid, Falls Church, VA), 4 ounces<br>|
| Experimental: KE1 5g<br> | Dietary Supplement: KE1 5g<br>* 5g of KE1 (KetoneAid, Falls Church, VA), diluted to 4 ounces<br>|
| Experimental: KE1 10g<br> | Dietary Supplement: KE1 10g<br>* 10g of KE1 (KetoneAid, Falls Church, VA), equal to 4 ounces<br>|
| Experimental: KE4 5g<br> | Dietary Supplement: KE4 5g<br>* 5g of KE4 (KetoneAid, Falls Church, VA), diluted to 4 ounces<br>|
| Experimental: KE4 10g<br> | Dietary Supplement: KE 10g<br>* 10g of KE4 (KetoneAid, Falls Church, VA), diluted to 4 ounces<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Supplement tolerability and acceptability | The ketone supplements being used have been described as having strong, disagreeable flavors. Therefore, the first outcome measure will be understanding how the flavors and gastrointestinal effects of both supplements may impact subjects. This outcome measure will be assessed by measuring the symptoms experienced, the time at which each symptom occurred, and the duration of each symptom using a scaled symptom questionnaire titled Symptom Questionnaire. The questionnaire rates symptoms on an ordinal scale from absent, mild, moderate, to severe, with absent being the minimum value and better outcome, and severe being the maximum value and worst outcome. The questionnaire will assess the time that each symptom occurred, on a scale from immediately, one hour, and two hours after supplement consumption. The questionnaire will assess the duration of each symptom, on a scale of less than thirty minutes, one hour, and two hours after each symptom occurred. | 2 hours | 
| Capillary beta-hydroxybutyrate concentrations | Exogenous ketone supplements are now widely available at the commercial level, so it is important to understand the concentration-dependent effects of these supplements on circulating ketone concentrations, measured by concentrations of beta-hydroxybutyrate following a capillary blood fingerstick. | 2 hours | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
exogenous ketones, ketone supplementation, ketone monoester, ketone salt, tolerability, acceptability, beta-hydroxybutyrate