Short Term Ketone Supplementation and Cardiometabolic Health
Short Term Ketone Supplementation and Cardiometabolic Health
The purpose of this research study is to determine if short-term consumption of a dietary
 ketone drink, which increases the blood circulation concentrations of beta-hydroxybutyrate, a
 ketone, affects blood vessel health and cognitive health in adults. Ketones are normally
 produced by the liver when people fast longer than 16-24 hours or eat a diet low in
 carbohydrates. Participants will be asked to randomly consume a dietary ketone drink and
 placebo (flavored water) for a 2-week period each in a crossover fashion with a 2-week
 washout period while maintaining habitual diet and physical activity patterns.

 The investigators hypothesize that consumption of a ketone drink will reduce BP and improve
 vascular health by reducing aortic pulse wave velocity and increasing brachial artery flow
 mediated dilation. Furthermore, they hypothesize that ketone consumption will improve
 cognitive health by increasing attention and processing speed.
Objective: The objective of this study is threefold: 1) To establish feasibility and
 proof-of-concept for the efficacy of ketone supplementation in reducing blood pressure and
 improving vascular and cognitive function in older adults; 2) Establish proficiency and
 feasibility with the proposed cognitive function measurements; and 3) Obtain preliminary data
 for effect size generation.

 Background: Age is the primary risk factor for cardiovascular disease. Middle age is a
 vulnerable period where cardiovascular risk factors, such as BP, begin to emerge and signs
 and symptoms of disease first becomes evident. Hypertension is present in 60-75% of adults in
 this demographic and associated with vascular dysfunction and cognitive decline. Low
 Carbohydrate High Fat (LCHF) ketogenic diets have become increasingly popular for improving
 cardiometabolic health but adherence is suboptimal due to their restrictive nature.
 Supplementation with ketone drinks increase plasma β-hydroxybutyrate and mimics the metabolic
 effects of LCHF ketogenic diets as well as lowers BP and improves vascular and cognitive
 function in rodent models. Whether ketone supplementation lowers BP and improves vascular and
 cognitive health in humans of any age is unknown.

 Approach: A double-blind randomized 2x2 crossover design with 2 repeated measures in each
 period will be used. Pre-/post-test evaluation in each period will be used to evaluate the
 benefits to vascular and cognitive health ingestion with consumption of a ketone
 drink/placebo drink.
Inclusion Criteria:

 -  Ability to provide informed consent

 -  50-75 years of age

 -  Systolic blood pressure 120-159 mmHg

 -  Diastolic blood pressure <100 mmHg

 -  Sedentary to recreationally active

 -  Body Mass Index <35 kg/m^2

 -  Postmenopausal women must be >1 year since last menses

 Exclusion Criteria:

 -  Current smoker

 -  Pregnant or planning to become pregnant

 -  Dyslipidemia (Total cholesterol >240 mg/dL, LDL >160 mg/dL)

 -  Chronic clinical disease (e.g., inflammatory bowel disease/irritable bowel syndrome,
 unstable coronary heart disease, stroke, heart failure, diabetes, neurological
 disorders)

 -  Taking a medication or supplement that would impact study outcomes

 -  Following an extreme dietary pattern or planning to change to one (e.g., low
 carbohydrate, carnivore, vegetarian/vegan)

 -  Not weight stable in the prior 3 months (>2 kg weight change)