Low Fat Vegan or American Heart Association Diets & Cardiovascular Risk in Obese 9-18 y.o. With Elevated Cholesterol

Study Overview
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Brief Summary
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The purpose of this study is to investigate the short-term effects of a reduced fat plant-based diet on biomarkers of inflammation, oxidative stress and cardiovascular risk. This plant-based diet consists of whole grains, fruits and vegetables and little amounts of nuts and seeds, with no limitations on the amount of food intake. Animal products are not allowed. The results of the plant-based diet will be compared with the diet recommended by American Heart Association. This diet also emphasizes fruits and vegetables, but allows healthy fats, low-fat meats, fish and low-fat dairy in moderation. The results of the study might be useful in understanding whether or not plant-based diets are protective against cardiovascular disease.

Detailed Description
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Scientific Question: In obese, hypercholesterolemic (>169 mg/dl) 9-18 year olds and one of their parents are biomarkers of inflammation, oxidative stress and cardiovascular risk significantly reduced after a randomized 4 week trial of a reduced fat, vegan diet, or the American Heart Association (AHA) diet (which also encourages fruits, vegetables and whole grains, but permits low fat meat and dairy, and fish)? Rationale: Cardiovascular disease remains the leading cause of death in North Americans, but manifest disease in childhood and adolescence is rare. By contrast, risk factors and risk behaviors that accelerate the development of atherosclerosis begin in childhood, and there is increasing evidence that risk reduction delays progression toward clinical disease. Myeloperoxidase is an early biomarker of inflammation, oxidative stress and cardiovascular risk in prepubertal obese children and is over expressed in children with hypercholesterolemia. Trimethylamine N-oxide, global arginine bioavailability ratio, arginine methylation index, paraoxonase 1 gene, and F2-isoprostane are all also associated with future major adverse cardiovascular events. Studies have suggested that a low-fat, vegan diet is effective in promoting weight loss, lowering body mass index, improving lipoprotein profiles, insulin sensitivity and in preventing cardiovascular disease in overweight individuals. Vegetarian diets have been shown to not only prevent but also to reverse heart disease in adults. Dietary habits (e.g. vegan/vegetarian versus omnivore/carnivore) are associated with significant alterations in intestinal microbiota composition and function. The diet-microbe interaction may play a significant role in the cardiovascular protective effects of a vegan/vegetarian diet. One small report of 15 adults on a reduced fat, vegan Engine 2 Diet for four weeks reported decreases in mean total cholesterol from 197 mg/dl to 135 mg/dl and mean LDL cholesterol falling from 124 mg/dl to 74 mg/dl. Innovation: This is the first randomized trial comparing a low fat vegan diet to the standard AHA diet. If one diet proves superior in this brief pilot study, future larger long term studies will be needed to clearly define the health implications of our results. Methods: Obese hypercholesterolemic children ages 9-18 will be identified by reviewing medical records and recruited initially by letters. Child, parent/guardian pairs will be randomly assigned to either the reduced fat vegan diet or the AHA diet. During the 4-week study, participants will be asked to attend a group teaching and cooking session once a week on Saturday to learn about their assigned diets. The participants will also be requested to record their diet history on 2 weekdays and 1 weekend day before and again during the 4 weeks of the study.

Official Title
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Low Fat Vegan Diet or American Heart Association Diet, Impact on Biomarkers of Inflammation, Oxidative Stress and Cardiovascular Risk in Obese 9-18 y.o. With Elevated Cholesterol: A Four Week Randomized Trial

Conditions
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Cardiovascular Disease, Hypercholesterolemia, Obesity, Fatty Liver

Intervention / Treatment
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* Other: American Heart Association Diet
* Other: Reduced Fat Vegan Diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Children ages 9-18 BMI > 95th percentile Hypercholesterolemia (>169 mg/dl) Exclusion Criteria: Pregnant women Patients already on vegetarian diets

Ages Eligible for Study
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Minimum Age: 9 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Reduced Fat Vegan Diet<br>Plant based diet with as few added oils and fats as possible. | Other: Reduced Fat Vegan Diet<br> <br> |
| Active Comparator: American Heart Association Diet<br>Diet emphasizing fruits, vegetables and whole grains but also low fat dairy, low fat meat and fish. | Other: American Heart Association Diet<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Body Mass Index BMI Percentile |  | baseline, 4 weeks | 
| Children Change in BMI Z Score | Body mass index z-scores, also called BMI standard deviation (s.d.) scores, are measures of relative weight adjusted for child age and sex. Given a child's age, sex, BMI, and an appropriate reference standard, a BMI z-score (or its equivalent BMI-for-age percentile) can be determined. Negative BMI z-scores indicate a BMI that is lower than the population mean, while positive BMI scores indicate a value that is higher than the population mean. A decrease in the BMI z-score over time indicate a lowering of the BMI. Z-scores of 1.03 and 1.64 correspond to the 85th and 95th percentiles of BMI-for-age, which are the definitions of overweight and obesity in children. | baseline, 4 weeks | 
| Change in Blood Pressure (BP) |  | baseline, 4 weeks | 
| Change in Weight |  | baseline, 4 weeks | 
| Change in Circumference |  | baseline, 4 weeks | 
| Change in PAQ (Physical Activity Questionnaire) | PAQ self reported questions based on activity level from 1 (low activity) to 5 (high activity), overall PAQ score is a mean of the questions. | baseline, 4 weeks | 
| Change in Lipid Profile |  | baseline, 4 weeks | 
| Change in Glucose |  | baseline, 4 weeks | 
| Change in hsCRP (High-sensitivity C-reactive Protein) |  | baseline, 4 weeks | 
| Change in Liver Enzymes |  | baseline, 4 weeks | 
| Change in IL-6 (Interleukin-6) |  | baseline, 4 weeks | 
| Change in MPO (Myeloperoxidase) |  | baseline, 4 weeks | 
| Change in HgbA1c (Hemoglobin A1c) |  | baseline, 4 weeks | 
| Change in Insulin |  | baseline, 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PB/AHA - Adjusted Mean Difference BMI |  | Baseline, 4 weeks | 
| PB/AHA - Adjusted Mean Difference BMI Z Score Children |  | Baseline, 4 weeks | 
| PB/AHA - Adjusted Mean BP |  | Baseline, 4 weeks | 
| PB/AHA - Adjusted Mean Difference Weight |  | Baseline, 4 weeks | 
| PB/AHA - Adjusted Mean Difference Circumference |  | Baseline, 4 weeks | 
| PB/AHA - Adjusted Mean Difference PAQ Children | PAQ self reported questions based on activity level from 1 (low activity) to 5 (high activity), overall PAQ score is a mean of the questions. | Baseline, 4 weeks | 
| PB/AHA - Adjusted Mean Lipid Profile |  | Baseline, 4 weeks | 
| PB/AHA - Adjusted Mean Ratio Glucose |  | Baseline, 4 weeks | 
| PB/AHA - Adjusted Mean Ratio hsCRP |  | Baseline, 4 weeks | 
| PB/AHA - Adjusted Mean Ratio Liver Enzymes |  | Baseline, 4 weeks | 
| PB/AHA - Adjusted Mean Ratio IL-6 |  | Baseline, 4 weeks | 
| PB/AHA - Adjusted Mean Ratio MPO |  | Baseline, 4 weeks | 
| PB/AHA - Adjusted Mean Ratio HgbA1c |  | Baseline, 4 weeks | 
| PB/AHA - Adjusted Mean Ratio Insulin |  | Baseline, 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vegan Diet, Hypercholesterolemia, American Heart Association Diet, Cardiovascular Risk, Obesity