Facilitated Vegan Diet on Cardiometabolic Endpoints and Trimethylamine N-oxide

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Cardiometabolic Risk Factors
• Intervention / Treatment: Other: Facilitated Vegan Diet; Other: Omnivorous Diet

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 70
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Travis Air Force Base, California, United States, 94535
      • David Grant U.S. Air Force Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Facilitated Vegan Diet; The facilitated vegan participants will self-prepare and consume 2 vegan meal kits per day for 4 weeks	Other: Facilitated Vegan Diet; Vegan boxed meal kits
ACTIVE_COMPARATOR: Standard Omnivorous Diet; The standard omnivorous arm will self-prepare and consume 2 non-vegan meal kits per day for 4 weeks	Other: Omnivorous Diet; Non-vegan boxed meal kits

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference between intervention arms in baseline adjusted gut microbiome at 4 weeks	Change in alpha diversity	4 weeks
Change between intervention arms in baseline adjusted gut microbiome at 8 weeks	Change in alpha diversity	8 weeks
Change between intervention arms in baseline adjusted gut microbiome at 12 weeks	Change in alpha diversity	12 weeks
Change between intervention arms in baseline adjusted complete blood count	Change in complete blood count	12 weeks
Change between intervention arms in baseline adjusted serum C-reactive protein	Change in C-reactive protein	12 weeks
Change between intervention arms in baseline adjusted serum high sensitivity C-reactive protein	Change in high sensitivity C-reactive protein	12 weeks
Change between intervention arms in baseline adjusted serum vitamin B12 level	Change in vitamin B12	12 weeks
Change between intervention arms in baseline adjusted serum iron	Change in serum iron	12 weeks
Change in calorie intake	Change in calorie intake	12 weeks
Change in meal patterns post vegan meal kit intervention	Change in percent of vegan meals per week	12 weeks

Collaborators and Investigators

• Sponsor: David Grant U.S. Air Force Medical Center

Publications and helpful links

General Publications

• Koeth RA, Wang Z, Levison BS, Buffa JA, Org E, Sheehy BT, Britt EB, Fu X, Wu Y, Li L, Smith JD, DiDonato JA, Chen J, Li H, Wu GD, Lewis JD, Warrier M, Brown JM, Krauss RM, Tang WH, Bushman FD, Lusis AJ, Hazen SL. Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat Med. 2013 May;19(5):576-85. doi: 10.1038/nm.3145. Epub 2013 Apr 7.
• Tang WH, Wang Z, Levison BS, Koeth RA, Britt EB, Fu X, Wu Y, Hazen SL. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N Engl J Med. 2013 Apr 25;368(17):1575-84. doi: 10.1056/NEJMoa1109400.
• Wang Z, Bergeron N, Levison BS, Li XS, Chiu S, Jia X, Koeth RA, Li L, Wu Y, Tang WHW, Krauss RM, Hazen SL. Impact of chronic dietary red meat, white meat, or non-meat protein on trimethylamine N-oxide metabolism and renal excretion in healthy men and women. Eur Heart J. 2019 Feb 14;40(7):583-594. doi: 10.1093/eurheartj/ehy799.
• The Vegan Diet. National Health Service website. Updated Aug 2018. Accessed 10 Jan 2021.
• Najjar RS, Moore CE, Montgomery BD. A defined, plant-based diet utilized in an outpatient cardiovascular clinic effectively treats hypercholesterolemia and hypertension and reduces medications. Clin Cardiol. 2018 Mar;41(3):307-313. doi: 10.1002/clc.22863. Epub 2018 Mar 25.
• Heianza Y, Ma W, Manson JE, Rexrode KM, Qi L. Gut Microbiota Metabolites and Risk of Major Adverse Cardiovascular Disease Events and Death: A Systematic Review and Meta-Analysis of Prospective Studies. J Am Heart Assoc. 2017 Jun 29;6(7):e004947. doi: 10.1161/JAHA.116.004947.
• Crimarco A, Springfield S, Petlura C, Streaty T, Cunanan K, Lee J, Fielding-Singh P, Carter MM, Topf MA, Wastyk HC, Sonnenburg ED, Sonnenburg JL, Gardner CD. A randomized crossover trial on the effect of plant-based compared with animal-based meat on trimethylamine-N-oxide and cardiovascular disease risk factors in generally healthy adults: Study With Appetizing Plantfood-Meat Eating Alternative Trial (SWAP-MEAT). Am J Clin Nutr. 2020 Nov 11;112(5):1188-1199. doi: 10.1093/ajcn/nqaa203.

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 1, 2022
• Primary Completion (ANTICIPATED): June 1, 2022
• Study Completion (ANTICIPATED): June 1, 2022

Study Registration Dates

• First Submitted: September 2, 2021
• First Submitted That Met QC Criteria: September 27, 2021
• First Posted (ACTUAL): October 8, 2021

Study Record Updates

• Last Update Posted (ACTUAL): April 1, 2022
• Last Update Submitted That Met QC Criteria: March 30, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Vegan; cardiometabolic; trimethylamine N-oxide; boxed meal kit
• Other Study ID Numbers: FWH20210097H

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No