Short Term Choline and Cardiovascular Health

NCT03327805 | Completed

• 1 other identifier: 18-535
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Cardiovascular Risk Factor

Keywords

Choline; Trimethylamine N-Oxide; Vascular health

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Change in arterial stiffness after supplementation

  45-minute measurement in laboratory

• Change in gut-mediated TMAO levels after supplementation

  5-minute measurement in laboratory

Study Arms (2)

Short Term Choline Supplementation

EXPERIMENTAL

Participants will be asked to consume 1000 mg of choline bitartrate for 4 weeks prior to and during the testing period.

Dietary Supplement: Choline

Short Term Placebo Supplementation

PLACEBO COMPARATOR

Participants will be asked to consume 1000 mg of placebo (maltodextrin) for 4 weeks prior to and during the testing period.

Dietary Supplement: Placebo

Interventions

Choline DIETARY_SUPPLEMENT

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.

Short Term Choline Supplementation

Placebo DIETARY_SUPPLEMENT

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.

Short Term Placebo Supplementation

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.)

You may not qualify if:

• 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

Sponsors & Collaborators

• Virginia Polytechnic Institute and State University: lead

Study Sites (1)

Virginia Polytechnic and State University

Blacksburg, Virginia, 24061, United States

Location

MeSH Terms

Interventions

Choline

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Trimethyl Ammonium Compounds; Quaternary Ammonium Compounds; Onium Compounds

Study Officials

• Kevin Davy, PhD

  Virginia Polytechnic Institute and State University

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: Double-blind, placebo-controlled, crossover design

Study Record Dates

• First Submitted: October 5, 2017
• First Posted: October 31, 2017
• Study Start: May 8, 2019
• Primary Completion: December 2, 2022
• Study Completion: November 21, 2023
• Last Updated: March 27, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)