Determine How Consumption of Dairy Fat Fractions Rich in Phospholipids and Proteins Influence Inflammation in the Fed State-Phase 1

Study Overview
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Brief Summary
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Phase 1 of this study involves determining how consumption of dairy fat fractions rich in milk fat globule membrane influences postprandial inflammation in participants with metabolic syndrome or obesity during a high dietary fat challenge in a six-hour period.

Detailed Description
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Phase 1 is a randomized crossover study designed to determine how inclusion of dairy fractions rich in milk fat globule membrane (MFGM) to shakes rich in dairy or palm fat influence postprandial inflammation. Participants who have 2 or more risk factors of metabolic syndrome or BMI ≥ 30 will consume four shakes on separate days. The four shakes are: high dairy fat, high dairy fat + MFGM, high palm fat, high palm fat + MFGM. Eligible participants will arrive to the Western Human Nutrition Research Center (WHNRC) at the University of California (UC) Davis campus on the morning of each test day after a 10-12-hr overnight fast. Upon arrival participants will fill out a questionnaire about their dietary and medication intakes and physical activity for the past 72 hours to ensure compliance. Compliant participants' weight and blood pressure will be measured and a fasting blood draw will be taken before participants consume their test meal. Participants will only consume this test meal and water freely for the duration of the test day. Blood will be drawn serially at 1, 3 and 6 hours postprandially. Participants will be tested on the additional three arms on three different spaced apart by two weeks. On the third or fourth test day, participants' body composition and bone mineral density will be measured by dual x-ray absorptiometry.

Official Title
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Effects of Dairy Fat on Postprandial Inflammation- Phase 1

Conditions
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Metabolic Syndrome, Obesity

Intervention / Treatment
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* Dietary Supplement: Dairy fat
* Dietary Supplement: Dairy fat + MFGM
* Dietary Supplement: Palm fat
* Dietary Supplement: Palm fat + MFGM


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-65 years Two or more components of metabolic syndrome: Central obesity (waist circumference greater than 40 inches for men and 35 inches for women); fasting blood triglycerides greater than or equal to 150 mg/dL; plasma HDL cholesterol (Less than 40 mg/dL for men and less than 50 mg/dL for women); blood pressure greater than or equal to 130/85 mmHg; fasting glucose greater than or equal to 100 mg/dL or - BMI equal to or greater than 30 Exclusion Criteria: Metabolic Disorders: BMI > 40 Body weight more than 400 lbs. Any immune related diseases such as autoimmune disease, rheumatoid arthritis, asthma, Gastrointestinal disorders including Crohn's Disease, colitis, diverticulitis, irritable bowel disease, celiac, malabsorption syndrome Cancer Known presence of significant metabolic disease which could impact the results of the study (i.e. hepatic, renal disease) Type II diabetes Use of over-the-counter anti-obesity agents (e.g. containing phenylpropanolamine, ephedrine, and/or caffeine) within the last 12 weeks Use of corticoid steroids within the last 12 weeks Daily use of anti-inflammatory pain medication Self report of eating disorder Poor vein assessment determined by WHNRC's phlebotomist Dietary/supplements: Known allergy or intolerance to study food (lactose intolerance, dairy, wheat allergies) Vegetarian (defined as abstinence from consumption of eggs, dairy, poultry, beef and pork) More than 1 serving of fish per week More than 14 grams of fiber per 1000 kcal per day Less than 16:1 of total dietary omega 6: Omega 3 ratio More than 1% of daily energy as trans fats Initiation of anti-inflammatory supplemental fish, krill, flax, borage and primrose seed oils within the last 12 weeks Dietary supplements consisting of concentrated soy isoflavones, resveratrol, other polyphenols identified as modulators of inflammation Medications Initiation of statin therapy within the last 12 weeks Lifestyle More than 10% weight loss or gain during the past 6 months Recent initiation (past 4 weeks) of exercise program Plan to become pregnant in the next 6 months Pregnancy or lactation Recent initiation or cessation of hormonal birth control or change in hormonal birth control regimen within the last 12 weeks Use of tobacco products More than 2 standard alcoholic drinks per day.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Palm fat<br>The amount of calories in the shake will be equivalent to 30% of each participant's calculated energy expenditure. The macronutrient composition of the shake as a percent of energy will be: 45% fat, 40% carbohydrate and 15% protein. The shake will contain palm fat, frozen fruit, glucose polymer, and protein powder. | Dietary Supplement: Palm fat<br> <br> |
| Experimental: Palm fat + MFGM<br>The amount of calories in the shake will be equivalent to 30% of each participant's calculated energy expenditure. The macronutrient composition of the shake as a percent of energy will be: 45% fat, 40% carbohydrate and 15% protein. The shake will contain palm fat, frozen fruit, glucose polymer, and BPC50, a dairy fraction rich in milk fat globule membrane proteins and phospholipids. Fifty percent of the shake's fat will be derived from BPC50. | Dietary Supplement: Palm fat + MFGM<br>* BPC50, a dairy fraction rich in milk fat globule membrane proteins and phospholipids manufactured by Fonterra, will make up 50% of the shake's total fat.<br>|
| Active Comparator: Dairy fat<br>The amount of calories in the shake will be equivalent to 30% of each participant's calculated energy expenditure. The macronutrient composition of the shake as a percent of energy will be: 45% fat, 40% carbohydrate and 15% protein. The shake will contain whipping cream, frozen fruit, glucose polymer, and protein powder. | Dietary Supplement: Dairy fat<br> <br> |
| Experimental: Dairy fat + MFGM<br>The amount of calories in the shake will be equivalent to 30% of each participant's calculated energy expenditure. The macronutrient composition of the shake as a percent of energy will be: 45% fat, 40% carbohydrate and 15% protein. The shake will contain whipping cream, frozen fruit, glucose polymer, and BPC50, a dairy fraction rich in milk fat globule membrane proteins and phospholipids. Fifty percent of the shake's fat will be derived from BPC50. | Dietary Supplement: Dairy fat + MFGM<br>* BPC50, a dairy fraction rich in milk fat globule membrane proteins and phospholipids manufactured by Fonterra, will make up 50% of the shake's total fat.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma inflammatory mediators | Plasma cytokines will be measured using a multi-plex immunoassay and plasma oxylipins will be measured by mass spectroscopy. | Change from 0 hour up to 6 hours postprandial | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma lipid profile | Plasma lipids (triglycerides, total cholesterol, LDL-C, HDL-C) will be measured by enzymatic analysis by UC Davis Pathology Lab. | Change from 0 hour up to 6 hours postprandial | 
| Plasma bone markers | Plasma N-terminal telopeptide (NTX), C-terminal telopeptide (CTX) and propeptide of type I collagen (P1NP) will be measured by multi-plex immunoassay. | Change from 0 hour up to 6 hours postprandial | 
| Urinary metabolites | Urinary metabolites will be measured by nuclear magnetic resonance (NMR) spectroscopy. | Change from 0 hour up to 6 hours postprandial | 
| Plasma glucose | Plasma glucose will be measured by enzymatic analysis by UC Davis Pathology Lab. | Change from 0 hour up to 6 hours postprandial | 
| Red blood cell functionality | Red blood cells isolated from whole blood will be measured for sheer stress using an in-vitro microfluidic assay. | Change from 0 hour up to 6 hours postprandial |