Almonds to Improve Gut Health and Decrease Inflammation

Study Overview
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Brief Summary
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Almonds are a good source of beneficial compounds. This study will investigate if eating almonds everyday for 12 weeks can affect gut health and inflammation in persons with metabolic syndrome. Investigators will measure changes in metabolism, heart health, and the levels of vitamins and other compounds from almonds.

Detailed Description
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Metabolic Syndrome (MetS) affects over a billion people world-wide. MetS progression and further health complications are driven by chronic inflammation. Major causes of inflammation in MetS are gut barrier breakdown and the absorption of harmful bacteria. What causes the gut barrier breakdown is not clear, but a poor diet, especially low micronutrient intakes like vitamin E, is implicated by propagating a vicious cycle that promotes oxidative stress, inflammation and further gut barrier damage. This study will assess the impact of daily consumption of 2 ounces of almonds for 12 weeks on gut health, markers of inflammation and cardiometabolic health, and micronutrient status in persons with MetS.

Official Title
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Almonds to Improve Gut Health and Decrease Inflammation in Metabolic Syndrome

Conditions
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Metabolic Syndrome, Dysbiosis, Inflammation

Intervention / Treatment
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* Other: Almond
* Other: Crackers


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 35-60 years 3 or more of the following: hypertension (systolic BP 130-179 mmHg or diastolic BP 85-119 mmHg); hyperglycemia (fasting glucose 100-599 mg/dL); central obesity [waist circumference greater than 40.1 inches (M) or 34.6 inches (F); hypertriglyceridemia (150-499 mg/dL); low HDL [lower than 40 mg/dL (M) or 50 mg/dL (F)] Willing to restrict consumption of nuts other than study nuts for 1 week prior to and throughout the study (13 weeks) Willing to stop probiotic supplements one week prior to and during the study (13 weeks) Willing to stop multivitamins and supplements containing vitamin E, magnesium, calcium, iron, zinc and copper one week prior to and during the study (13 weeks) Willing to complete intake diaries during the study Willing to maintain current eating patterns (no significant diet change during study) Exclusion Criteria: Weekly consumption of almonds, hazelnuts, peanuts and sunflower seeds combined greater than 2 servings (about 2 oz) in the past 3 months Nut, wheat, or gluten allergy/intolerance Regular use of vitamin E supplements Consume more than 2 alcoholic drinks daily Tobacco use, including e-cigarettes, or smoking of any substance (e.g. cannabis) in the past 3 months Pregnancy, breastfeeding, or planning to become pregnant before completing the study Vigorous exercise greater than 7 hours/week History of cardiovascular disease, liver disease or cancer Have had bariatric surgery (e.g. gastric bypass, gastric banding, sleeve gastrectomy, etc.), other gastrointestinal procedures (e.g. cholecystectomy), disorders (e.g. Crohn's disease, celiac disease, ulcerative colitis) or chronic diarrhea Diagnosis of hemochromatosis Chronic use (daily intake in past 30 days) of anti-inflammatory medication (steroid or NSAID) Use of ezetimibe or orlistat Use of oral antibiotic medication within the past month Body Mass Index (BMI) <25.0 or >35.0 kg/m2 Regular use of multivitamin supplements in the past 3 months Physician prescribed use of probiotic, vitamin E, magnesium, calcium, iron, zinc or copper supplements

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 60 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: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Almonds<br>Daily consumption of 2 ounces of unsalted, dry roasted almonds for 12 weeks | Other: Almond<br>* Daily consumption of 2 ounces of unsalted, dry roasted almonds for 12 weeks<br>|
| Placebo Comparator: Crackers<br>Daily consumption of non-whole grain crackers for 12 weeks (caloric equivalent to 2 ounces of dry roasted almonds) | Other: Crackers<br>* Daily consumption of non-whole grain crackers for 12 weeks (caloric equivalent to 2 ounces of dry roasted almonds)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gut permeability and health: Serum endotoxin | Change from baseline at week 4: Marker of gut barrier function and health, serum endotoxin | 0 and 4 weeks | 
| Gut permeability and health: Short chain fatty acids | Change from baseline at week 4: Markers of gut barrier function and health fecal short chain fatty acids profiles | 0 and 4 weeks | 
| Gut permeability and health: Inflammatory biomarkers | Change from baseline at week 4: Gut inflammatory biomarkers calprotectin and myeloperoxidase | 0 and 4 weeks | 
| Biomarkers of inflammation | Change from baseline at week 4: Plasma inflammatory markers (ex. TNF and IL-6) | 0 and 4 weeks | 
| Oxidative stress status: malondialdehyde | Change from baseline at week 4: Plasma malondialdehyde | 0 and 4 weeks | 
| Oxidative stress status: isoprostanes | Change from baseline at week 4: Urinary isoprostanes | 0 and 4 weeks | 
| Cardiometabolic health | Change from baseline at week 12: Total cholesterol, LDL, HDL, and triglycerides | 0 and 12 weeks | 
| Vitamin E status | Change from baseline at week 4 and week 12: Plasma α-tocopherols | 0, 4 and 12 weeks | 
| Vitamin E status: Urinary catabolite | Change from baseline at week 4 and week 12: Urinary vitamin E catabolite (α-CEHC) | 0, 4 and 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood pressure | Change from baseline at week 4 and week 12: Systolic, and diastolic blood pressure | 0, 4 and 12 weeks | 
| Weight | Change from baseline at week 4 and week 12: Weight | 0, 4 and 12 weeks | 
| BMI | Change from baseline at week 4 and week 12: BMI (weight and height will be combined to report BMI in kg/m^2) | 0, 4 and 12 weeks | 
| Waist circumference | Change from baseline at week 4 and week 12: Waist circumference | 0, 4 and 12 weeks | 
| Glycemic control: glucose | Change from baseline at week 12: Fasting blood glucose | 0 and 12 weeks | 
| Glycemic control: Insulin | Change from baseline at week 12: Insulin | 0 and 12 weeks | 
| Glycemic control: HOMA-IR | Change from baseline at week 12: HOMA-IR | 0 and 12 weeks | 
| Other almond-based bioactives (polyphenol levels) | Change from baseline at week 12: Urinary metabolites of flavonoids like (+)-catechin, (-)-epicatechin and naringenin | 0 and 12 weeks | 
| Mineral status | Change from baseline at week 12: Plasma magnesium, calcium, iron, zinc, and copper (microgram/mL) | 0 and 12 weeks |