Clinical trial NCT03817749: Ketone Supplementation, Glucose Control, and Cardiovascular Function
Official title: The Effects of Exogenous Ketone Supplementation on Cardiovascular Function and Glucose Control
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Hyperglycemia, Postprandial
Overweight and Obesity
Diabetes Mellitus Risk
Keywords: Flow mediated dilation
Glucose control
Inflammation
Immune cell function
Cognition
Oxidative stress
Cardiovascular function
Lead sponsor: University of British Columbia
Sponsor class: OTHER
First posted: 2019-01-25
Enrollment: 15
Sex: ALL
Minimum age (years): 30
Maximum age (years): 69
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: PREVENTION

Brief summary: Post-prandial hyperglycemic excursions induce a cascade of deleterious effects on the body, including increased inflammation, production of reactive oxygen species, and impaired cardiovascular function. Ingestion of an exogenous oral ketone supplement blunts hyperglycemia in response to an oral glucose tolerance test. Accordingly, it is hypothesized that exogenous ketone supplement ingestion prior to a meal could be an effective strategy for blunting postprandial hyperglycemia. Therefore, the purpose of this study is to investigate the effect of short-term (14-days) pre-meal exogenous ketone supplementation on glucose control, cardiovascular function, inflammation, and oxidative stress in individuals at an elevated risk of type 2 diabetes.


Eligibility criteria: Inclusion Criteria:

* Elevated waist circumference (\>102 cm for males, \>88 cm for females) and/or Obesity (BMI \> 30 kg/m2) and/or Diagnoses of prediabetes based on A1C (5.7-6.4%) and/or fasting plasma glucose (5.6-6.9 mmol/l) using ADA criteria

Exclusion Criteria:

* Competitively trained endurance athlete
* Actively attempting to lose weight
* History of mental illness or existing neurological disease(s)
* Previous cardiovascular events (i.e., heart attack, stroke)
* Diagnoses of diabetes
* Hypoglycemia
* Irritable bowel syndrome or inflammatory bowel disease
* Taking medication that may interfere with insulin sensitivity
* Currently following a ketogenic diet or taking ketone supplements
* Unable to commit for 2 separate 14-day trials and unable to follow a controlled diet

Primary outcomes:
measure: Glucose control
timeFrame: 2 hours after a meal
Secondary outcomes:
measure: Change from baseline flow mediated dilation at 14 days
timeFrame: Day 0 (Pre-intervention) and Day 14 (post-intervention)
measure: Change from baseline histone acetylation at 14 days
timeFrame: Day 0 (Pre-intervention) and Day 14 (post-intervention)
measure: Change from baseline mitochondrial superoxide production at 14 days
timeFrame: Day 0 (Pre-intervention) and Day 14 (post-intervention)
measure: Change from baseline cognition (executive functions) at 14 days
timeFrame: Day 0 (Pre-intervention) and Day 14 (post-intervention)
measure: Change from baseline plasma glucose at 14 days
timeFrame: Day 0 (Pre-intervention) and Day 14 (post-intervention)
measure: Change from baseline plasma insulin at 14 days
timeFrame: Day 0 (Pre-intervention) and Day 14 (post-intervention)
measure: Change from baseline plasma free fatty acids at 14 days
timeFrame: Day 0 (Pre-intervention) and Day 14 (post-intervention)
measure: Change from baseline interleukin-1(IL)-1beta at 14 days
timeFrame: Day 0 (Pre-intervention) and Day 14 (post-intervention)
measure: Change from baseline caspase-1 activation at 14 days
timeFrame: Day 0 (Pre-intervention) and Day 14 (post-intervention)
Other outcomes:
Locations:
city: Kelowna
country: Canada
facility: University of British Columbia, Okanagan.
state: British Columbia
Study officials:
References:
citation: Walsh JJ, Caldwell HG, Neudorf H, Ainslie PN, Little JP. Short-term ketone monoester supplementation improves cerebral blood flow and cognition in obesity: A randomized cross-over trial. J Physiol. 2021 Nov;599(21):4763-4778. doi: 10.1113/JP281988. Epub 2021 Oct 4.
citation: Walsh JJ, Neudorf H, Little JP. 14-Day Ketone Supplementation Lowers Glucose and Improves Vascular Function in Obesity: A Randomized Crossover Trial. J Clin Endocrinol Metab. 2021 Mar 25;106(4):e1738-e1754. doi: 10.1210/clinem/dgaa925.