Choline and Cardiometabolic Health

NCT04764162 | Completed Results DMC

• 2 other identifiers: 25-521R21AG067380
• Study Type: interventional
• Target: 14
• 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 increases TMAO, affects CVD risk factors, such as glucose homeostasis and vascular function.

Conditions

Cardiovascular Risk Factor

Keywords

insulin sensitivity; vascular function; blood pressure; continuous glucose monitoring; trimethylamine N-oxide (TMAO)

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Insulin Sensitivity at 4 Weeks

  Participants will complete a 2-hour glucose tolerance test at baseline, immediately following the first intervention, after a 2-week washout, and immediately following the second 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 2-hour period. Insulin sensitivity will be calculated using Matsuda's index (a ratio with no units). This test will be conducted two times separated by about 4 weeks for each intervention (choline, placebo).

  Calculated difference between the baseline and 4-week testing session for each intervention

Secondary Outcomes (1)

• Change in 24-hour Area Under the Curve for Glucose Levels After Supplementation

  Difference in 24-hour glucose levels during free living at baseline and 4 weeks

Study Arms (2)

Choline, then Placebo

EXPERIMENTAL

Participants will consume 1000 mg (2 x 500 mg) of choline supplement per day for 4 weeks, including post-testing sessions. A 2-week washout period will follow the first intervention. Then the participants will consume 1000 mg (2 x 500 mg) of placebo per day for 4 weeks, including post-testing sessions.

Dietary Supplement: Choline; Dietary Supplement: Placebo

Placebo, then Choline

EXPERIMENTAL

Participants will consume 1000 mg (2 x 500 mg) of placebo per day for 4 weeks, including post-testing sessions. A 2-week washout period will follow the first intervention. Then the participants will consume 1000 mg (2 x 500 mg) of choline supplement per day for 4 weeks, including post-testing sessions.

Dietary Supplement: Choline; Dietary Supplement: Placebo

Interventions

Choline DIETARY_SUPPLEMENT

1000 mg (2 x 500 mg) choline bitartrate capsules (over-the-counter supplement)

Choline, then Placebo; Placebo, then Choline

Placebo DIETARY_SUPPLEMENT

Choline-matched 1000 mg (2 x 500 mg) placebo (maltodextrin) capsules

Choline, then Placebo; Placebo, then Choline

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• BMI \> 35 kg/m2
• Smoking
• Pregnant or plans of becoming pregnant
• Vegetarian or Vegan
• Changed dietary 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

Sponsors & Collaborators

• Virginia Polytechnic Institute and State University: lead
• National Institute on Aging (NIA): collaborator

Study Sites (1)

Virginia Polytechnic and State University

Blacksburg, Virginia, 24060, United States

Location

MeSH Terms

Conditions

Insulin Resistance

Interventions

Choline

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Dr. Kevin Davy
• Organization: Virginia Tech

kdavy@vt.edu

(540)231-3487

Study Officials

• Kevin Davy, PhD

  Virginia Polytechnic Institute & State University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

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: February 17, 2021
• First Posted: February 21, 2021
• Study Start: August 20, 2021
• Primary Completion: December 2, 2022
• Study Completion: November 21, 2023
• Last Updated: May 31, 2025
• Results First Posted: November 29, 2024

Record last verified: 2025-05

Locations

US (1)