Short Term Ketone Supplementation and Cardiometabolic Health
Condition: Cardiovascular Risk Factor
Study type: Interventional

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Ketone drink; Placebo drink
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): Pre- and post-testing will be completed before and after participants receive 42 doses of ketone supplement drink over a 2-week period (3x/day for 14 days).; Pre- and post-testing will be completed before and after participants receive 42 doses of placebo supplement drink over a 2-week period (3x/day for 14 days).
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Prevention
Keywords: D-β-hydroxybutyrate; low carbohydrate high fat diet; blood pressure; cognitive function; flow mediated dilation