Effects of Almond Consumption on Cardiovascular, Metabolomic, and Microbiome Profiles in Millennials

Study Overview
=================
Brief Summary
-----------------
The purpose of the study is to examine the effects of almond snacking on metabolic, cardiovascular and microbiome profiles in college freshmen.

Detailed Description
-----------------
Nut (principally almond) consumption helps ameliorate cardiovascular disease, reduce the risk of type II diabetes mellitus (T2DM). Recent studies have demonstrated improvements in glycemic control in T2DM and impaired glucose tolerant (IGT) subjects as well as in healthy adults. The association between nut consumption and diabetes prevalence is largely mediated by changes in body mass (adiposity). The application of metabolomic and lipidomic approaches to better asses the mechanisms regulating carbohydrates and lipids in an almond-based study has not been performed. Additionally, the gut microbiota has been proposed to contribute to a number of metabolic disorders including insulin sensitivity, glucose metabolism, and other cardiometabolic risk factors. However, data demonstrating the complex interactions among dietary interventions, gut microbiome, glucose regulation, and cardiovascular phenotype are lacking. Furthermore, because all the studies on nut consumption and health have been performed on adults (median age of subjects: +40 years) and given the increasing incidence of metabolic disorders (obesity, insulin resistance, etc.) at much younger stages of life especially in the Central Valley of California, no data exist on the potential benefits of almonds in ameliorating metabolic disorders at a much earlier life stage. This may be clinically more important than studies in adults because the transition from adolescence to adulthood is associated with a number of potential risk factors unique to this age group, especially in those that enter their first year of college. The fixed age of the participants contributes to a more homogeneous population than has been previously studied, which greatly minimizes the potential for age-dependent alterations in physiology to either potentiate or mask the effects of the almonds on metabolic mechanisms. The nutritional independence that is associated with going away to college poses many potential health challenges, for example the phenomenon, Freshman 15. The increased prevalence of overweight and obesity is greatest in 18-29 year olds, especially among those reporting some college education (10.6%-17.8% vs 7.1%-12.1% in 18-29 year olds overall) suggesting that some aspect of the collegiate experience is associated with weight gain. While almond-supplemented diets have been shown to reduce body mass or ameliorate weight gain, the evidence substantiating the benefits of functional foods in addressing the weight gain commonly associated with the transition to college is scarce and an untapped area of research. Furthermore, this transition to nutritional independence makes new college students vulnerable to additional alterations in eating patterns. Among these concerns are the relatively high number of college freshmen that reported skipping breakfast (20%-43%), which is by far the most skipped meal among those studies reviewed. This is important because chronically skipping breakfast in adolescents has detrimental outcomes on cardiometabolic health and has negative impacts on academic performance. Additionally, most college students snack, with snacking common both in the morning and the afternoon. Data suggest a benefit to snacking on peanuts and almonds. However, the benefits of snacking in young college students who routinely skip a meal (breakfast here) are not defined. Therefore, being able to demonstrate the benefits of almonds in college breakfast skippers would have significant implications for young adults in their first year of college, and thus, provide an ideal opportunity to further address this line of inquiry. Lastly, the application of metabolomic and lipidomic approaches to better assess the mechanisms regulating carbohydrates and lipids in an almond-based study has not been performed. Advancements in high-throughput analytical techniques have initiated a renaissance in the study of metabolism on a grand scale that allow for robust assessment of nutritional status and cellular responses. These approaches provide an advantage of mapping metabolites in such a fashion that changes in mechanisms can be elucidated as demonstrated by the SuGAR Project.

Official Title
-----------------
Effects of Almond Consumption on Cardiovascular, Metabolomic, and Microbiome Profiles in Millennials: Implications of Systemic Glucoregulatory Mechanisms

Conditions
-----------------
Diet Intervention

Intervention / Treatment
-----------------
* Dietary Supplement: Almonds
* Dietary Supplement: Graham crackers


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 18-22 years of age Newly enrolled, 1st-year college students at University of California, Merced Willing to eat almonds and study snacks Willing to comply with the study protocol Consistent diet and activity patterns Non-smoker >1 year or more Exclusion Criteria: Nut allergies Illicit drug use Medications that affect metabolism or appetite Anti-inflammatory medications, analgesics and antibiotics Diabetes or pre-diabetes, uncontrolled hypertension, cardiovascular disease or dyslipidemia requiring drug therapy Gastrointestinal disease and/or bariatric surgery

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 22 Years

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

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

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

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Almond group<br>2 oz. of almonds everyday for 8 weeks | Dietary Supplement: Almonds<br> <br> |
| Active Comparator: Control group<br>Isoenergetic control group 5 graham cracker sheets everyday for 8 weeks | Dietary Supplement: Graham crackers<br> <br> |

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in fasting blood glucose |  | Change from baseline at 8 weeks | 
| 2-hour oral glucose tolerance test |  | At the end of 8 week intervention | 
| Change in fasting blood insulin |  | Change from baseline at 8 weeks | 
| Change in stool microbiome profiles |  | Change from baseline at 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Weight |  | Every 2 weeks over the 8 week intervention | 
| Body composition |  | Every 2 weeks over the 8 week intervention | 
| Waist circumference |  | Every 2 weeks over the 8 week intervention | 
| Blood pressure |  | Every 2 weeks over the 8 week intervention | 
| 24-hour appetite ratings |  | Baseline, 4 weeks into intervention and end of 8 week intervention | 
| Hip circumference |  | Every 2 weeks over the 8 week intervention | 
| Flow Mediated Dilation (FMD) | As a measure of endothelial function | At the end of 8 week intervention | 
| Urinary 8-isoprostane |  | Baseline and end of 8 week intervention | 
| Urinary electrolytes |  | Baseline and end of 8 week intervention | 
| Urinary angiotensinogen |  | Baseline and end of 8 week intervention | 
| Urinary creatinine clearance |  | Baseline and end of 8 week intervention | 
| Fasting lipid profile |  | Baseline, 4 weeks into intervention and end of 8 week intervention | 
| Physical activity | Research Tracker 6 (RT6) accelerometers | Baseline, 4 weeks into intervention and end of 8 week intervention | 
| Hepatic glucose metabolism | Isotopic dilution | End of 8 week intervention |