Choline and Cardiometabolic Health

Study Overview
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Brief Summary
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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.

Official Title
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Short Term Choline Supplementation and Cardiometabolic Health in Adults

Conditions
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Cardiovascular Risk Factor

Intervention / Treatment
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* Dietary Supplement: Choline capsule
* Dietary Supplement: Placebo capsule


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 79 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Double-blind, placebo-controlled, crossover design
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Choline supplementation<br>Participants will consume 1000 mg of choline per day for 4 weeks. | Dietary Supplement: Choline capsule<br>* 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.<br>|
| Placebo Comparator: Placebo supplementation<br>Participants will consume 1000 mg of placebo per day for 4 weeks. | Dietary Supplement: Placebo capsule<br>* 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.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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insulin sensitivity, vascular function, blood pressure, continuous glucose monitoring, trimethylamine N-oxide (TMAO)