Facilitated Vegan Diet on Cardiometabolic Endpoints and Trimethylamine N-oxide

Study Overview
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Brief Summary
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Vegan meal kit delivery offers consumer convenience and has shown benefit in cardiometabolic parameters such as low-density lipoprotein cholesterol (LDL-c) and weight. The purpose of this study is to evaluate the impact of meal kit facilitated vegan diet on LDL-c and trimethylamine N-oxide (TMAO) when compared to an omnivorous diet control.

Detailed Description
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This study will compare the impact of a vegan diet to a non-vegan diet, when provided with meal kits in participants who are overweight. A vegan diet includes foods that come from plants and excludes foods that come from animals like meat, dairy, and eggs. Dietary modifications such as adopting a vegan diet are associated with significant improvements in cardiometabolic parameters, making it one of the preferred treatment options for obesity and preventing associated health conditions. Meal kits are packages that include: a quick ( 30-45 minutes) and simple recipe, all the recipe's required ingredients, and are conveniently delivered to patient homes. In this study, a facilitated vegan diet is defined as a change from an omnivorous diet to a vegan diet with the aid of boxed vegan meal kit delivery. A facilitated vegan diet has shown LDL-c and weight improvements over continuing an omnivorous diet in a preliminary study. TMAO, changes in gut microbiome, and compliance to dietary modification impact cardiovascular and overall health. TMAO is a diet dependent biomarker for CVD, as elevated TMAO levels are associated with a 62% increased risk of heart attack, stroke, or death. TMAO increases platelet hyperactivity, inflammation, and foam cell generation, all of which contribute to atherosclerosis and may explain the increased risk of CVD. Additionally, TMAO predicts risk of major adverse cardiovascular events independently of other cardiovascular risk factors. Consumption of animal products elevate TMAO levels due to its abundance of TMAO precursors: choline and carnitine. Chronic dietary red meat was associated with increased TMAO levels over white meat and non-meat protein. One study found that consuming plant-based alternative meat products improved TMAO levels over a mostly red meat diet. Both study interventions replaced protein sources but did not remove animal products such as eggs and dairy, which have conflicting evidence relative to TMAO. This study intervention will have participants adopt a full vegan diet, eliminating animal products. The gut microbiome plays a crucial role in converting dietary precursors into TMAO. TMAO levels post l-carnitine ingestion were significantly higher in patients on a long-term omnivorous diet vs patients on a long-term vegan or vegetarian diet. This suggests that the gut microbiome in a plant-based diet lowers the formation of TMAO via the diet. This study will explore changes in gut microbiome from a dietary intervention in relation to TMAO and explore if these changes are sustained after discontinuing a 4-week facilitated vegan diet. Additionally, changes in gut microbiome will be explored in relation to microbiota changes seen in other disease states such as anxiety, irritable bowel disease, and other inflammatory diseases. The impact of dietary modifications on controlling obesity and associated health conditions has room for improvement. Dietary modifications have long been one of the preferred treatments in obesity and CVD prevention, yet the obesity rates continue to rise. One potential area of improvement is compliance to dietary modification. This study will explore changes in food group restricted free diet patterns after a 4-week vegan meal kit intervention.

Official Title
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Impact of Facilitated Vegan Diet on Cardiometabolic Endpoints and Trimethylamine N-oxide

Conditions
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Cardiometabolic Risk Factors

Intervention / Treatment
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* Other: Facilitated Vegan Diet
* Other: Omnivorous Diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years old BMI ≥ 25kg/m^2 Consume ≥ 5 servings red meat per week Active duty military and Department of Defense (DoD) Beneficiaries with active Tricare insurance Willing and able to adopt a vegan or standard omnivorous diet for 4 weeks Willing and able to track meal patterns, nutritional intake, exercise activity, and adverse events for 13 weeks Willing and able to come to David Grant USAF Medical Center for 4 blood draws Able to receive weekly emails and receive and prepare meal kits Exclusion Criteria: Currently on a vegetarian, vegan, or food-group restricted diet Currently taking or planning to initiate medications or supplements that significantly affect TMAO levels, carnitine, choline, or gut microbiome (Systemic antibiotics, antifungals, antivirals, antiparasitic, corticosteroids, methotrexate, cytokines, or immunosuppressive cytotoxic agents, laxatives, proton pump inhibitors, resveratrol, meldonium, or metformin) Currently consuming the following ≥ 2 times per week: probiotics/prebiotics, probiotic enhanced foods (eg. enhanced yogurt, kefir, kombucha), or energy drinks, multivitamins, or supplements with choline, carnitine, or betaine (Acceptable to consume: non-probiotic enhanced yogurts, energy drinks and multivitamins without choline, carnitine, or betaine) Participants will have the option to delay study start if they express interest in the study and have permanently discontinued one of the excluded diet, medication, or supplement listed previously within the past 4 weeks (minimum 4 week time between discontinuation of excluded item and study start) Clinically significant or unstable cardiovascular, gastrointestinal, hepatic, or renal disease states defined as requiring on-going changes to medication or medical management Consumption of smoking or chewing tobacco, or other nicotine-containing products for >1 day per week Consumption of >14 alcohol drinks per week Pregnant, breastfeeding, or plan to become pregnant

Ages Eligible for Study
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Minimum Age: 18 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: Parallel Assignment
Interventional Model Description: Randomized, controlled, prospective clinical trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Facilitated Vegan Diet<br>The facilitated vegan participants will self-prepare and consume 2 vegan meal kits per day for 4 weeks | Other: Facilitated Vegan Diet<br>* Vegan boxed meal kits<br>|
| Active Comparator: Standard Omnivorous Diet<br>The standard omnivorous arm will self-prepare and consume 2 non-vegan meal kits per day for 4 weeks | Other: Omnivorous Diet<br>* Non-vegan boxed meal kits<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change between intervention arms in baseline adjusted LDL-c at 4 weeks | Change in LDL-c | 4 weeks | 
| Change between intervention arms in baseline adjusted TMAO at 4 weeks | Change in TMAO | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change between intervention arms in baseline adjusted LDL-c at 8 weeks | Change in LDL-c | 8 weeks | 
| Change between intervention arms in baseline adjusted LDL-c at 12 weeks | Change in LDL-c | 12 weeks | 
| Change between intervention arms in baseline adjusted TMAO at 8 weeks | Change in TMAO | 8 weeks | 
| Change between intervention arms in baseline adjusted TMAO at 12 weeks | Change in TMAO | 12 weeks | 
| Change between intervention arms in baseline adjusted lipid panel parameters at 4 weeks | Change in lipid panel | 4 weeks | 
| Change between intervention arms in baseline adjusted lipid panel parameters at 8 weeks | Change in lipid panel | 8 weeks | 
| Change between intervention arms in baseline adjusted lipid panel parameters at 12 weeks | Change in lipid panel | 12 weeks | 
| Change between intervention arms in baseline adjusted BMI at 4 weeks | Weight and height will be combined to report BMI in kg/m^2 | 4 weeks | 
| Change between intervention arms in baseline adjusted BMI at 8 weeks | Weight and height will be combined to report BMI in kg/m^2 | 8 weeks | 
| Change between intervention arms in baseline adjusted BMI at 12 weeks | Weight and height will be combined to report BMI in kg/m^2 | 12 weeks | 
| Change between intervention arms in baseline adjusted blood pressure at 4 weeks | Measured with Sphygmocor device, both systolic and diastolic blood pressures | 4 weeks | 
| Change between intervention arms in baseline adjusted blood pressure at 8 weeks | Measured with Sphygmocor device, both systolic and diastolic blood pressures | 8 weeks | 
| Change between intervention arms in baseline adjusted blood pressure at 12 weeks | Measured with Sphygmocor device, both systolic and diastolic blood pressures | 12 weeks | 
| Change between intervention arms in baseline adjusted hemoglobin A1c at 4 weeks | Change in hemoglobin A1c | 4 weeks | 
| Change between intervention arms in baseline adjusted hemoglobin A1c at 8 weeks | Change in hemoglobin A1c | 8 weeks | 
| Change between intervention arms in baseline adjusted hemoglobin A1c at 12 weeks | Change in hemoglobin A1c | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vegan, boxed meal kit, trimethylamine N-oxide, cardiometabolic