Short Term Choline and Cardiovascular Health

Short Term Choline Supplementation and Cardiovascular 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 increase TMAO, impairs vascular function.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Virginia
    • Blacksburg, Virginia, United States, 24061
      • Virginia Polytechnic and State University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• 18-65 years old, healthy, non-smoking weight stable for previous 6 months (±2.0 kg), BMI<35 kg/m^2, verbal and written informed consent, approved for participation by study medical director (Jose Rivero, M.D.)

Exclusion Criteria:

• Smoking, pregnancy, obese (BMI>35 kg/m^2), altered dietary patterns within the last month of recruitment, vegetarians, vegans, unstable heart disease or diabetes, untreated high blood pressure or high cholesterol, allergies to choline supplement, taking any medications that could affect the results (ex., aspirin, antibiotics, pre/probiotics 1 month prior to enrollment), those with trimethylaminuria

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
Experimental: Short Term Choline Supplementation; Participants will be asked to consume 1000 mg of choline bitartrate for 4 weeks prior to and during the testing period.	Dietary supplement: Choline; Participants will consume 1000 mg (2x500 mg) of choline bitartrate (over-the-counter supplement) for 28 consecutive days. At baseline, some participants will also be randomly assigned to consume 1000 mg of choline bitartrate the evening before the third testing session to study its acute effects.
Placebo Comparator: Short Term Placebo Supplementation; Participants will be asked to consume 1000 mg of placebo (maltodextrin) for 4 weeks prior to and during the testing period.	Dietary supplement: Placebo; Participants will consume 1000 mg (2x500 mg) of placebo for 28 consecutive days. At baseline, some participants will also be randomly assigned to consume 1000 mg of placebo the evening before the third testing session to study its acute effects.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in brachial artery function after supplementation	Brachial artery function or flow mediated dilation (FMD), the blood flow and diameter of the brachial artery in the forearm (fMD), will be measured using a duplex ultrasound machine before and after the inflation of a blood pressure cuff on the forearm for 5 minutes and after placing a nitroglycerine tablet (0.4 mg) under the participant's tongue. This test will be conducted once at baseline and then once after each 5-day period of the randomly-assigned supplement (choline or placebo), including a 1-week washout period (crossover design). Off-line analysis of baseline and post-reactive hyperemic diameters and velocities will be performed using edge detection software (Vascular Analysis Tools, Medical Imaging Applications, Inc.).	30-minute measurement in laboratory

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in arterial stiffness after supplementation	The blood flow and diameter in the common arteries in the neck will be measured from the image obtained from an ultrasound unit (GE Vivid S6) equipped with a high resolution linear array transducer. For applanation tonometry, the carotid, brachial, radial and femoral artery pressure waveform and amplitude will be obtained by a fingertip probe incorporating a high-fidelity strain gauge transducer. Each of these measures are used to calculate arterial stiffness. These tests will be conducted once at baseline and then once after each 5-day period of the randomly-assigned supplement (choline or placebo), including a 1-week washout period (crossover design).	45-minute measurement in laboratory
Change in gut-mediated TMAO levels after supplementation	At baseline, a fasting blood sample will be collected to measure plasma TMAO concentration after supplementation consumption 8 hours prior to the third testing session.	5-minute measurement in laboratory

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): May 8, 2019
• Primary Completion (Actual): December 2, 2022
• Study Completion (Actual): November 21, 2023

Study Registration Dates

• First Submitted: October 5, 2017
• First Submitted That Met QC Criteria: October 26, 2017
• First Posted (Actual): October 31, 2017

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: Choline; Trimethylamine N-Oxide; Vascular health
• 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: 18-535

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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