Choline and Cardiometabolic Health

Short Term Choline Supplementation and Cardiometabolic Health in Adults

Trimethylamine-N-oxide (TMAO), a metabolite produced by gut microbial metabolism of dietary choline, has recently been causally linked to atherosclerosis in animal models and has been shown to be predictive of cardiovascular disease (CVD) risk in some but not all cohort studies. The relevance of observations in animals to humans is unclear and little information is available on the mechanisms linking TMAO to increased CVD risk. Vascular dysfunction plays a critical role in the initiation and progression of atherothrombotic disease. Whether TMAO impairs vascular function in humans is not known. The purpose of this study is to determine if short term supplementation of dietary choline, which increases TMAO, affects CVD risk factors, such as glucose homeostasis and vascular function.

Study Overview

• Status: Completed
• Conditions: Cardiovascular Risk Factor
• Intervention / Treatment: Dietary supplement: Choline capsule; Dietary supplement: Placebo capsule

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Virginia
    • Blacksburg, Virginia, United States, 24060
      • Virginia Polytechnic and State University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Age 18-79 years
• Weight stable for previous 6 months (+2.0kg)
• Sedentary to recreationally active (<30 min aerobic exercise <2x/wk)
• No plans to gain/lose weight or change physical activity level
• Verbal and written informed consent
• Willing to be randomized to treatment order
• Fully vaccinated against COVID-19

Exclusion Criteria:

• BMI > 35 kg/m2
• Smoking
• Pregnant or plans of becoming pregnant
• Vegetarian or Vegan
• Changed dieatry patterns within the last month
• Diabetes (or use of diabetes medications) or unstable heart disease
• Untreated high blood pressure or high cholesterol
• Health problems that mide it unsafe to participate
• Taking medications, vitamins or supplements that could affect study outcomes (including but not limited to aspirin, antibiotics, prebiotics, and probiotics)
• Known allergy, hypersensitivity, intolerance to choline supplement or its ingredients
• Trimethylaminuria or "fish odor" syndrome

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Choline supplementation; Participants will consume 1000 mg of choline per day for 4 weeks.	Dietary supplement: Choline capsule; Participants will consume 1000 mg (2 x 500 mg) of choline bitartrate (over-the-counter supplement) for 28 consecutive days. They will continue to consume 1000 mg of choline bitartrate during the post-testing period.
Placebo Comparator: Placebo supplementation; Participants will consume 1000 mg of placebo per day for 4 weeks.	Dietary supplement: Placebo capsule; Participants will consume 1000 mg (2 x 500 mg) of placebo (maltodextrin) for 28 consecutive days. They will continue to consume 1000 mg of placebo during the post-testing period.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Insulin Sensitivity after Supplementation	Participants will complete a slucose tolerance test at baseline, after a 2-week washout, and immediately following each intervention. A catheter will be placed in one of the participant's arms. After a baseline blood draw to measure fasting levels of glucose, insulin, cholesterol and other factors, participants will drink a glucose beverage (75 g). Blood will be collected in small amounts (less than one half teaspoon) at eight timepoints over a three-hour period. Insulin sensivity will be calculated using Matsuda's index. This test will be conducted two times separated by about 4 weeks for each intervention (choline, placebo).	3-hour test in laboratory at 4 timepoints; baseline, week 4, week 6, and week 10

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in 24-hour Area Under the Curve for Glucose Levels after Supplementation	Glucose will be monitored by a Continuous Glucose Monitor (CGM) sensor (Enlite Sensor; Medtronic, Inc. or FreeStyle Libre Pro; Abbott) and this will be placed on the participant's abdomen or back of the upper arm in order to measure glucose continuously. The measured glucose levels will be assessed by an iPro2 Professional CGM; Medtronic, Inc. or FreeStyle Libre Pro reader; Abbott; and the CGM will be worn for 4 consecutive days. This test will be conducted two times separated by about 4 weeks for each intervention (choline, placebo).	4-day measurement during free living

Collaborators and Investigators

• Sponsor: Virginia Polytechnic Institute and State University
• Investigators: Principal Investigator: Kevin Davy, PhD, Virginia Polytechnic Institute & State University

Study record dates

Study Major Dates

• Study Start (Actual): August 20, 2021
• Primary Completion (Actual): December 2, 2022
• Study Completion (Actual): November 21, 2023

Study Registration Dates

• First Submitted: February 17, 2021
• First Submitted That Met QC Criteria: February 17, 2021
• First Posted (Actual): February 21, 2021

Study Record Updates

• Last Update Posted (Actual): February 20, 2024
• Last Update Submitted That Met QC Criteria: February 18, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: insulin sensitivity; blood pressure; vascular function; continuous glucose monitoring; trimethylamine N-oxide (TMAO)
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Antimetabolites; Gastrointestinal Agents; Hypolipidemic Agents; Lipid Regulating Agents; Nootropic Agents; Lipotropic Agents; Choline
• Other Study ID Numbers: VT18-535-568(TRX)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No