Dairy Fat and Fermentation Study

Study Overview
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Brief Summary
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The purpose of the study is to compare the effect of consuming full-fat (regular) and fat-free (skim) milk, as well as full-fat and fat-free yogurt (a fermented dairy product), on microorganisms in your gut as well as the products produced by the gut microbes. We will also determine whether consuming these dairy products affects risk factors for heart disease.The findings of the study will help us determine if heart disease risk factors are modified by the fat content and fermentation of milk. The results may facilitate refinement of public health dietary guidance for cardiovascular disease risk reduction.

Detailed Description
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A randomized-controlled cross-over trial will be conducted to compare the effect of two servings per day of full-fat and fat-free milk, and full-fat and fat-free yogurt (hence forth referred to as dairy food items) on the gut microbiome, fecal and serum metabolome, and determine their relation to cardiometabolic risk factors (CMRF) and functional pathways associated with the differences identified. Participants will be provided with 2 servings per day of the test dairy products and requested not to consume additional bovine (cow) milk or yogurt during each 3-week diet phase.They will be allowed to use dairy substitutes such as plant-based milk alternatives and consume other types of dairy products (e.g. cheese). The study consists of four diet phases: fat-free milk phase, full-fat milk phase, fat-free yogurt phase and full-fat yogurt phase. Each diet phase is 3 weeks in duration, separated by a 2 week break. Participants will be provided with 2 servings of a dairy based food item per day specific to their assigned phase and asked to consume them at two separate times during the day - morning and evening. Weight, waist circumference and blood pressure will be measured, blood and stool samples will be collected, and participants will complete two 24-hr food recall questionnaires during each phase.

Official Title
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Effect of Full-Fat and Fat-Free Dairy, With and Without Fermentation, on Fecal Microbiome, Fecal and Serum Metabolome, and Host Cardiometabolic Risk Status

Conditions
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Heart Diseases, Microbial Colonization, Inflammation

Intervention / Treatment
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* Other: Milk or yogurt beverage


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age >50 years Men and postmenopausal women BMI >25 and <35 kg/m2 No milk allergy, lactose intolerance or adherence to vegan or other dietary pattern that excludes dairy products Non-smoker Usual pattern of bowel movements at least every other day. Exclusion Criteria: Women and men <50 years Women, pre- or peri-menopausal BMI <25 and >35 kg/m2 Current smokers or former smoker who quit < 6 months Use of nicotine replacement products within last 6 months Replacement or gender affirming hormonal therapy use Weight gain of >15 pounds within last 6 months Infrequent bowel movements History of anemia within past 2 years or confirmation of anemia at first study visit Blood donation within last 2 months Untreated hypertension Oral antibiotics use within 2 weeks of study entry Steroid use (including dental prophylaxis use within 2 wks prior to or during study, except non-prescription topical and nasal steroids, e. g. Flonase) Use of lipid lowering medications Chronic use of aspirin, non-steroidal anti-inflammatory medications (NSAIDS), laxatives, anti-diarrheal medication Regular use (>2 times per week) of acid lowering medication: antacids, proton pump inhibitors, or H2 Blockers. Use of dietary supplements other than multi-vitamins, including pre- and probiotics, within 2 months of study entry Milk allergy, lactose intolerance or adherence to vegan or other dietary patterns that exclude dairy products Colonoscopy within 3 weeks of study entry or during study period Diagnosis of malabsorption, inflammatory bowel disease (ulcerative colitis or Crohn's Disease), cirrhosis, history of gastrointestinal resection (other than appendectomy), chronic pancreatitis or any other chronic GI disease that in the opinion of the study physician would alter the study results Chronic heart, liver, thyroid, renal or kidney disease Type I or type II diabetes Alcohol consumption >7 drinks/week for women and >14 drinks/week for men Inadequate refrigerator storage capacity to store 21 8-oz containers of milk or yogurt Participation in other dietary intervention research study during the same time No social security number Not willing to commit to adhering to the protocol

Ages Eligible for Study
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Minimum Age: 50 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: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: randomized crossover design
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Full-fat milk beverage<br>Beverage made with full-fat milk | Other: Milk or yogurt beverage<br>* Commercially available milk or yogurt (depending on experimental arm) will be incorporated into flavored drinks/smoothies to minimize perceived differences among these items, preserving the double-blind nature of the study design.<br>|
| Experimental: Fat-free milk beverage<br>Beverage made with fat-free milk | Other: Milk or yogurt beverage<br>* Commercially available milk or yogurt (depending on experimental arm) will be incorporated into flavored drinks/smoothies to minimize perceived differences among these items, preserving the double-blind nature of the study design.<br>|
| Experimental: Full-fat yogurt beverage<br>Beverage made with full-fat yogurt | Other: Milk or yogurt beverage<br>* Commercially available milk or yogurt (depending on experimental arm) will be incorporated into flavored drinks/smoothies to minimize perceived differences among these items, preserving the double-blind nature of the study design.<br>|
| Experimental: Fat-free yogurt beverage<br>Beverage made with fat-free yogurt | Other: Milk or yogurt beverage<br>* Commercially available milk or yogurt (depending on experimental arm) will be incorporated into flavored drinks/smoothies to minimize perceived differences among these items, preserving the double-blind nature of the study design.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| gut microbiome | Determine the effects of dairy fat in milk, with and without fermentation, on gut microbiome | 3 weeks | 
| fecal metabolome | Determine the effects of dairy fat in milk, with and without fermentation, on fecal metabolome | 3 weeks | 
| serum metabolome | Determine the effects of dairy fat in milk, with and without fermentation, on serum metabolome | 3 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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gut microbiome, gut microbiota, yogurt, milk, heart disease