Reduction of Obesity-Associated Intestinal Inflammation by Low-Fat Dairy Yogurt

The main objective of this work is to conduct a clinical trial in obese and non-obese individuals testing the ability of low-fat dairy yogurt to improve gastrointestinal health and reduce chronic inflammation. Our central hypothesis is that short and long-term consumption of low-fat dairy yogurt will reduce inflammation to a greater extent in obese individuals by improving intestinal barrier function.

Study Overview

• Status: Completed
• Conditions: Chronic Inflammation; Intestinal Barrier Function
• Intervention / Treatment: Other: Low fat dairy yogurt; Other: Soy pudding

• Study Type: Interventional
• Enrollment (Actual): 128
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53706
      • Department of Food Science, Babcock Hall

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• premenopausal women
• BMI from 18.5-27 and 30-40 kg/m2
• resting blood pressure <140/90 mmHg
• not taking medication to control hypertension
• stable body weight for the previous 2 months
• willing to maintain a normal exercise level and avoid exercise 24 h prior to blood sampling
• willing to avoid yogurt and probiotic-containing foods or consume 2 servings of yogurt for the duration of the study

Exclusion Criteria:

• previous diagnoses of cardiovascular disease (CVD), diabetes, or arthritis (except for osteo-arthritis)
• currently being treated for cancer (i.e., chemotherapy, radiation therapy)
• prescribed estrogen replacement therapy
• practicing weight-loss, vegetarian, kosher, or vegan diets
• currently taking dietary supplements
• exceed alcohol consumption more than moderate drinking (1 drink/day or a total of 7/week)
• actively using antibiotics
• taking anti-inflammatory drugs
• have allergies to soy, egg or milk
• perimenopausal or menopausal symptoms

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Non-obese individuals; Daily consumption of 12 oz lowfat yogurt or soy pudding for 9 weeks.	Other: Low fat dairy yogurt; Consumption of 12 oz of low fat dairy yogurt daily for 9 weeks; Other: Soy pudding; Consumption of 12 oz of low fat soy pudding daily for 9 weeks.
Experimental: Obese individuals; Consumption of 12 oz of soy pudding or low fat dairy yogurt daily for 9 weeks.	Other: Low fat dairy yogurt; Consumption of 12 oz of low fat dairy yogurt daily for 9 weeks; Other: Soy pudding; Consumption of 12 oz of low fat soy pudding daily for 9 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma soluble cluster of differentiation 14 (sCD14)	Fasting plasma sCD14 (change from baseline)	0, 3, 6, and 9 wk

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fasting plasma interleukin-6 (IL-6)	Fasting plasma IL-6 (change from baseline)	0, 3, 6, 9 wk
Postprandial sCD14	Postprandial plasma sCD14 following a high-fat, high-calorie challenge meal (area under curve)	0 and 9 wk
Postprandial interleukin-6 (IL-6)	Postprandial plasma IL-6 following a high-fat, high-calorie challenge meal (area under curve)	0 and 9 wk

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fasting lipopolysaccharide binding protein (LBP)	Determined by immunoassay	0 and 9 wk
Fasting plasma endotoxin (LPS, lipopolysaccharide)	Determined by limulus amebocyte lysate assay	0, 9 wk
Fasting plasma core antibodies to endotoxin	Immunoglobulin M Endotoxin-core antibody (IgM EndoCAb)	0 and 9 wk
Fasting plasma anandamide (AEA)	Determined by LC-MS	0, 9 wk
Fasting plasma 2-arachidonoylglycerol (2-AG)	Determined by LC-MS	0, 9 wk
Fasting plasma IL-10	Determined by immunoassay	0, 9 wk
Fasting plasma high-sensitivity C-reactive protein (hsCRP)	Determined in fasting plasma	0, 9 wk
Fasting plasma Tumor Necrosis Factor-alpha (TNF-α)	Determined in fasting plasma	0, 9 wk
Fasting plasma Soluble TNF-Receptor II (sTNF-RII)	Determined in fasting plasma	0, 9 wk
TNF-alpha/sTNF-RII ratio	Determined in fasting plasma	0, 9 wk
Fasting plasma glucose	Determined in fasting plasma	0, 9 wk
Fasting plasma triglycerides	Determined in fasting plasma	0, 9 wk
Fasting plasma insulin	Determined in fasting plasma	0, 9 wk
Fasting plasma soluble cluster of differentiation 14 (sCD14)	Determined in fasting plasma	0, 9 wk
Body weight		0, 3, 6, 9 wk
Body mass index		0, 3, 6, 9 wk
Waist circumference		0, 3, 6, 9 wk
Systolic blood pressure		0, 3, 6, 9 wk
Diastolic blood pressure		0, 3, 6, 9 wk
Fasting RPLP0, encoding ribosomal protein large P0	mRNA expression of peripheral blood mononuclear cell normalized to encoding 18s rRNA (RNA18S5)	0, 9 wk
TLR4, encoding Toll-like receptor 4	mRNA expression of peripheral blood mononuclear cell normalized to encoding 18s rRNA (RNA18S5)	0, 9 wk
RELA, encoding p65 subunit of nuclear factor kappa B	mRNA expression of peripheral blood mononuclear cell normalized to encoding 18s rRNA (RNA18S5)	0, 9 wk
NFKBIA, encoding nuclear factor kappa B inhibitor alpha	mRNA expression of peripheral blood mononuclear cell normalized to encoding 18s rRNA (RNA18S5)	0, 9 wk
PTGS2, encoding cyclooxygenase-2 (COX-2)	mRNA expression of peripheral blood mononuclear cell normalized to encoding 18s rRNA (RNA18S5)	0, 9 wk
NCF1,encoding the p47 subunit of nicotinamide adenine dinucleotide phosphate-oxidase, (NADPH oxidase)	mRNA expression of peripheral blood mononuclear cell normalized to encoding 18s rRNA (RNA18S5)	0, 9 wk
TNF, encoding tumor necrosis factors (TNF)	mRNA expression of peripheral blood mononuclear cell normalized to encoding 18s rRNA (RNA18S5)	0, 9 wk
IFNG, encoding interferon-γ	mRNA expression of peripheral blood mononuclear cell normalized to encoding 18s rRNA (RNA18S5)	0, 9 wk
TGFB1, encoding transforming growth factor beta 1 (TGFβ1)	mRNA expression of peripheral blood mononuclear cell normalized to encoding 18s rRNA (RNA18S5)	0, 9 wk
Postprandial plasma glucose	Postprandial plasma glucose following a high-fat, high-calorie challenge meal (area under curve)	0, 9 wk
Postprandial plasma triglycerides	Postprandial plasma triglycerides following a high-fat, high-calorie challenge meal (area under curve)	0, 9 wk
Postprandial lipopolysaccharide binding protein (LBP)	Postprandial plasma LBP following a high-fat, high-calorie challenge meal (area under curve)	0, 9 wk
Postprandial lipopolysaccharide (LPS)	Postprandial plasma LPS following a high-fat, high-calorie challenge meal determined by limulus amebocyte lysate assay (area under curve)	0, 9 wk
Postprandial lipopolysaccharide binding protein (LBP)/soluble cluster of differentiation 14 (sCD14) ratio	Postprandial LBP/sCD14 ratio following a high-fat, high-calorie challenge meal (area under curve)	0, 9 wk
Postprandial plasma insulin	Postprandial plasma insulin following a high-fat, high-calorie challenge meal (area under curve)	0, 9 wk
Energy intake (kcal)	Self-reported food intake determined by dietary records	0, 9 wk
Total fat (g)	Self-reported nutrient intake determined by dietary records	0, 9 wk
Carbohydrate (g)	Self-reported nutrient intake determined by dietary records	0, 9 wk
Total protein (g)	Self-reported nutrient intake determined by dietary records	0, 9 wk
Total fat (%)	Self-reported nutrient intake determined by dietary records	0, 9 wk
Carbohydrate (%)	Self-reported nutrient intake determined by dietary records	0, 9 wk
Total protein (%)	Self-reported nutrient intake determined by dietary records	0, 9 wk
Cholestrol (mg)	Self-reported nutrient intake determined by dietary records	0, 9 wk
Saturated fatty acids (g)	Self-reported nutrient intake determined by dietary records	0, 9 wk
Vitamin D (μg)	Self-reported nutrient intake determined by dietary records	0, 9 wk
Calcium (mg)	Self-reported nutrient intake determined by dietary records	0, 9 wk
Sodium (mg)	Self-reported nutrient intake determined by dietary records	0, 9 wk
Potassium (mg)	Self-reported nutrient intake determined by dietary records	0, 9 wk
Total sugars (g)	Self-reported nutrient intake determined by dietary records	0, 9 wk
Added sugars (g)	Self-reported nutrient intake determined by dietary records	0, 9 wk

Collaborators and Investigators

• Sponsor: University of Wisconsin, Madison
• Collaborators: Dairy Research Institute
• Investigators: Principal Investigator: Bradley W Bolling, PhD, University of Wisconsin, Madison

Publications and helpful links

General Publications

• Pei R, DiMarco DM, Putt KK, Martin DA, Chitchumroonchokchai C, Bruno RS, Bolling BW. Premeal Low-Fat Yogurt Consumption Reduces Postprandial Inflammation and Markers of Endotoxin Exposure in Healthy Premenopausal Women in a Randomized Controlled Trial. J Nutr. 2018 Jun 1;148(6):910-916. doi: 10.1093/jn/nxy046. Erratum In: J Nutr. 2018 Oct 1;148(10):1698.
• Pei R, DiMarco DM, Putt KK, Martin DA, Gu Q, Chitchumroonchokchai C, White HM, Scarlett CO, Bruno RS, Bolling BW. Low-fat yogurt consumption reduces biomarkers of chronic inflammation and inhibits markers of endotoxin exposure in healthy premenopausal women: a randomised controlled trial. Br J Nutr. 2017 Dec;118(12):1043-1051. doi: 10.1017/S0007114517003038. Epub 2017 Nov 28.

Study record dates

Study Major Dates

• Study Start: September 1, 2012
• Primary Completion (Actual): September 30, 2016
• Study Completion (Actual): March 31, 2017

Study Registration Dates

• First Submitted: September 12, 2012
• First Submitted That Met QC Criteria: September 12, 2012
• First Posted (Estimate): September 17, 2012

Study Record Updates

• Last Update Posted (Actual): October 3, 2017
• Last Update Submitted That Met QC Criteria: September 29, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: Inflammation; Obese; Intestine; Yogurt
• Additional Relevant MeSH Terms: Pathologic Processes; Inflammation
• Other Study ID Numbers: 2014-0669