Assessment of TMAO Formation With Egg Intake Versus Choline Supplement in a Healthy Population

Study Overview
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Brief Summary
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The objective of this study is to determine the effects of consuming either 3 eggs per day as compared to a daily choline supplement (choline bitartrate, 397.5 mg choline/day) on plasma concentrations of High Density Lipoprotein-cholesterol (HDL-C), trimethylamine N-oxide (TMAO), and other biomarkers of cardiovascular disease risk in young, healthy individuals. The goal is to determine if choline given as phosphatidylcholine (eggs) will lead to a different TMAO response when compared to choline in free supplemental form.

Detailed Description
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Epidemiological data in short term studies, suggests that egg intake does not increase risk for cardiovascular disease (CVD). In fact, eggs are a great source of phospholipids (phosphatidylcholine) where choline has many metabolic roles, specially in lipid metabolism and cell membrane structure. Choline is present in the diet as free choline, which is absorbed in the small intestines, or choline esters, which is absorbed intact primarily through the lymphatic system. In addition, recent evidence suggests that the choline found in eggs may be metabolized by intestinal microbes into trimethylamine N-oxide (TMAO), a compound that may increase the risk for CVD. However, it is not known to what extent egg intake may contribute to plasma TMAO concentrations. Therefore, the objective of this study is to determine the impacts of daily intake of 3 eggs versus a choline supplement on plasma TMAO as well as other biomarkers for CVD risk, with the goal of determining if the same amount of choline given as phosphatidylcholine from eggs will increase plasma choline levels without a concomitant increase in plasma TMAO, such that CVD risk is not negatively impacted.

Official Title
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Assessment of TMAO Formation With Egg Intake Versus Choline Supplement in a Healthy Population

Conditions
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Cardiovascular Risk Factor

Intervention / Treatment
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* Other: Eggs
* Dietary Supplement: Choline Supplement


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women (18-30 years), BMI 18.5 - 29.9 kg/m2, proficient in English, and willing to consume 3 eggs per day or 397.5 mg of choline supplement (1½ tablets/day) for 4 weeks each. Exclusion Criteria: Self-reported diabetes mellitus, cardiovascular disease, history of stroke, renal problems, liver disease, cancer, or a diagnosed eating disorder Taking any glucose-lowering prescriptions or supplements, triglyceride-lowering medications, bile acid sequestrants, or high dose chromium or cinnamon supplements Taken antibiotics in the previous 1 months, or if they are vegetarian or vegan BMI ≤ 18.4 or ≥ 30 kg/m2, or extreme clinical values, such as plasma triglycerides > 500 mg/dL, plasma glucose > 126 mg/dL, plasma cholesterol > 240 mg/dL, plasma creatinine ≤ 0.5 or ≥ 0.9 mg/dL for females and ≤ 0.7 or ≥ 1.2 mg/dL for males, or blood pressure > 140/90 mm Hg (average of 3 readings) Allergic to eggs or any component of the choline supplement

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 30 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Egg intake<br>Consumption of 3 eggs per day for breakfast, 4 weeks | Other: Eggs<br>* Consumption of 3 eggs per day for breakfast, 4 weeks<br>|
| Experimental: Choline Supplement intake<br>Consumption of choline supplement, 1 1/2 tablet (395mg choline), with breakfast for 4 weeks | Dietary Supplement: Choline Supplement<br>* Consumption of choline supplement, 1 1/2 tablet (395mg choline), with breakfast for 4 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Eggs of Egg Consumption on Plasma Biochemical Parameters | Using plasma form each participant, an automated spectrophotometer is able to analyze at once plasma lipids [total colesterol, triglycerides, HDL (mg/dL)], glucose (mg/dL), CRP (mg/dL, and liver enzymes [alanine aminotransferase and aspartate aminotransferase (U/L)]. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effects of Intervention on Gene Expression using RT-PCR | PBMC will be isolated from whole blood. RNA will be isolated from these cells, and then cDNA will be synthesized using a specific kit. Finally a RT-PCR will be used to analyze the expression of genes, such as: GAPDH, HMG-CoA reductase, LDL-r, CD36, SRA, FMO3, SRB1, PPAR-gama. All results will be presented based on house keeping gene GAPDH. | 1 year |