Low-Carbohydrate and Plant-Based Dietary Effects on Vascular Health

Study Overview
=================
Brief Summary
-----------------
This is a randomized trial with a crossover design to investigate the short-term effects of two different dietary patterns on markers of vascular health. A low-carbohydrate diet and a whole-food, plant-based diet will be used. In addition to more traditional markers (cholesterol, blood pressure, inflammation), endothelial progenitor cells and trimethylamine N-oxide will be assessed.

Detailed Description
-----------------
This study is an investigation of the short-term effects of two different diets on both conventional as well as newer markers of vascular health among subjects over the age of 50 who have a cardiovascular risk factor. The low-carbohydrate diet will be consistent with low-carbohydrate diet maintenance plans, with net carbs kept under 50g per day. The whole-food, plant-based diet will exclude animal foods, oils, and solid fats. Meals will be provided, and subjects will consume each diet for 2 weeks, with a 4-6 week washout period between dietary phases. Subjects will be randomized 1:1 to start with either the plant-based diet or the low-carbohydrate diet. Its primary aim is to assess the short-term effect of a whole-food, plant-based diet and a low-carbohydrate diet on levels of endothelial progenitor cells and trimethylamine N-oxide among this population. Secondarily, we will assess more conventional measures of vascular risk, including cholesterol, weight, blood pressure, insulin resistance, and inflammatory marker, as well as fullness and changes in nutritional intake.

Official Title
-----------------
Short-term Effects of a Low-carbohydrate Diet and a Whole-food, Plant-based Diet on Newer Markers of Vascular Health

Conditions
-----------------
Heart Disease, Ischemic, Hyperlipidemias, Hypertension

Intervention / Treatment
-----------------
* Other: Whole-Food, Plant-Based Diet and Low-Carbohydrate Diet


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age >50 Diagnosis of any of the following cardiovascular risk factors: hypertension (Diagnosis present in chart or use of antihypertensive medications); hyperlipidemia/dyslipidemia (non-HDL cholesterol ≥ 130 within the past year or current use of antihyperlipidemic medication); prediabetes (HbA1c ≥ 5.7% and < 6.5% in the past year); diabetes (HbA1c ≥ 6.5% in the past year); obesity (body mass index ≥ 30). Willing and able to comply with the protocol for the duration of the study, including food provision, scheduled meetings and testing visits. Able to speak and read English fluently because counseling and education is only available in English. Exclusion Criteria: Active malabsorption syndrome (celiac disease, history of gastric bypass within the past year, uncontrolled Crohn's disease, protein-losing enteropathy, etc…) Use of any of the following medications that require close monitoring and adjustment during major dietary change: insulin, sulfonylureas, or warfarin Chronic or acute kidney disease, with eGFR < 50 on two or more lab tests in the past 6 months Diagnosis of cirrhosis or liver failure Hyperkalemia (defined as potassium >5.4 on two or more lab tests in the past 6 months) Major surgery in the past 3 months Myocardial infarction in the past 6 months Current, active eating disorder as determined by chart review, investigator assessment, or subject history Food allergies or intolerances that would interfere with eating study food or require special accommodation as determined by subject history, investigator assessment, or chart review Consuming a current diet described by the subject as vegetarian, vegan, very low-carbohydrate, or ketogenic Illicit drug use (not including marijuana) High risk alcohol use, based on subject history (defined as greater than 7 drinks/week for women and greater than 14 drinks/week for men)

Ages Eligible for Study
-----------------
Minimum Age: 50 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: All subjects will consume two separate diets, with a 4-6 washout in between. They will be randomized 1:1 to determine which diet they start with.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Whole-Food, Plant-Based Start<br>This group starts with the whole-food, plant-based diet, then gets the low-carbohydrate diet after the washout period. | Other: Whole-Food, Plant-Based Diet and Low-Carbohydrate Diet<br>* Participants will consume two weeks of each diet, with a 4-6 week washout period in between. Meals and snacks are provided for convenience to enhance adherence to each dietary pattern, but subjects can add or include their own home-prepared foods as long as they meet dietary guidelines. Each dietary intervention will include an education session via Zoom teleconference, and at least 2 individual contacts by phone to address questions and assess for adverse events.<br>|
| Experimental: Low-Carbohydrate Start<br>This group starts with the low-carbohydrate diet, then gets the whole-food, plant-based diet after the washout period. | Other: Whole-Food, Plant-Based Diet and Low-Carbohydrate Diet<br>* Participants will consume two weeks of each diet, with a 4-6 week washout period in between. Meals and snacks are provided for convenience to enhance adherence to each dietary pattern, but subjects can add or include their own home-prepared foods as long as they meet dietary guidelines. Each dietary intervention will include an education session via Zoom teleconference, and at least 2 individual contacts by phone to address questions and assess for adverse events.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Endothelial Progenitor Cells |  | 2 weeks | 
| trimethylamine N-oxide |  | 2 weeks | 
| HDL function |  | 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cholesterol Panel | Total, LDL, HDL, non-HDL cholesterol, and triglycerides | 2 weeks | 
| Blood Pressure |  | 2 Weeks | 
| Resting Heart Rate |  | 2 weeks | 
| Weight |  | 2 weeks | 
| Insulin resistance | HOMA-IR | 2 weeks | 
| Insulin |  | 2 weeks | 
| Blood Glucose |  | 2 weeks | 
| Inflammatory Markers | hsCRP, TNF-a, IL-6 | 2 weeks | 
| Satiety Assessment | Adapted SLIM (satiety labeled intensity magnitude) | 2 weeks | 
| Food liking | 5 food liking factor scales adapted from 5-Factor Satiety Questionnaires | 2 weeks | 
| Change in nutritional intake | assessed by 3 day food records at baseline and in second week of dietary phase | 2 weeks |