Ketone Supplementation, Glucose Control, and Cardiovascular Function

NCT03817749 | Completed

• 1 other identifier: H18-02930
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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.

Conditions

Hyperglycemia, Postprandial; Overweight and Obesity; Diabetes Mellitus Risk

Keywords

Flow mediated dilation; Glucose control; Inflammation; Immune cell function; Cognition; Oxidative stress; Cardiovascular function

Outcome Measures

Primary Outcomes (1)

• Glucose control

  Post-prandial glucose excursions will be measured by continuous glucose monitoring using the iPro2 CGM by Medtronic in both the active and placebo supplement conditions. Post-prandial glucose following breakfast, lunch, and dinner will be averaged together.

  2 hours after a meal

Secondary Outcomes (9)

• Change from baseline flow mediated dilation at 14 days

  Day 0 (Pre-intervention) and Day 14 (post-intervention)

• Change from baseline histone acetylation at 14 days

  Day 0 (Pre-intervention) and Day 14 (post-intervention)

• Change from baseline mitochondrial superoxide production at 14 days

  Day 0 (Pre-intervention) and Day 14 (post-intervention)

• Change from baseline cognition (executive functions) at 14 days

  Day 0 (Pre-intervention) and Day 14 (post-intervention)

• Change from baseline plasma glucose at 14 days

  Day 0 (Pre-intervention) and Day 14 (post-intervention)

Study Arms (2)

Experimental

EXPERIMENTAL

* Participants will consume 20 g of an active oral exogenous ketone monoester supplement 15 minutes prior to each meal of the day for a 14-day period. * Pre-intervention (baseline) and post-intervention measurements will be obtained before and immediately after the 14-day period. * All meals will be provided throughout the supplementation period * Participants will wear a continuous glucose monitor for 6 consecutive days during the supplementation period.

Dietary Supplement: Exogenous ketone monoester

Placebo

PLACEBO COMPARATOR

Participants will consume a flavor matched placebo drink and undergo the same procedures described in the Experimental Arm

Dietary Supplement: Exogenous ketone monoester

Interventions

Exogenous ketone monoester DIETARY_SUPPLEMENT

Participants will consume 20g of the oral ketone monoester supplement 15 minutes prior to each meal of the day for 14 days. All meals will be provided throughout the 14-day supplementation period.

Also known as: HVMN ketone monoester supplement

Experimental; Placebo

Eligibility Criteria

• Age: 30 Years - 69 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of British Columbia: lead

Study Sites (1)

University of British Columbia, Okanagan.

Kelowna, British Columbia, V1V 1V7, Canada

Location

Related Publications (2)

• 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.

  PMID: 34605026 DERIVED

• 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.

  PMID: 33367782 DERIVED

MeSH Terms

Conditions

Hyperglycemia; Overweight; Obesity; Inflammation

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Pathologic Processes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: December 6, 2018
• First Posted: January 25, 2019
• Study Start: February 6, 2019
• Primary Completion: March 1, 2020
• Study Completion: December 31, 2020
• Last Updated: April 28, 2021

Record last verified: 2021-04

Locations

CA (1)