The Influence of Honey-flavored Yogurt on Low-grade Inflammation and Gut Health in Middle to Older Aged Women.

Study Overview
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Brief Summary
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A randomized, double-blind, crossover dietary intervention trial will test the effects of 4 weeks of daily honey-flavored yogurt intake on markers of inflammation (Th17 cytokines) and oxidative stress (NOX2, UA, RSNO) and associative changes with microbial derived metabolites (SCFAs, BAs, ellagitannins), metabolism and the fecal microbiome. The above suite of selected markers will capture diet-induced systemic changes in inflammation and oxidative stress, while assessing associated microbial changes.

Detailed Description
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Those qualified for enrollment will be randomized into a double-blind crossover study to consume 2 morning servings of a 0.6 cup (150g) of plain yogurt with : A) cane sugar added in an isocaloric level as the honey or, B) 1 tbsp of phenolic-rich honey for 4 weeks. A one-month washout between periods will be used. The participants will be instructed to consume one yogurt in replacement of or as part of breakfast, and as a late morning snack. They will also be instructed to not add any additional items to the yogurt. Therefore, each study participant will consume 2 tbsp. of honey a day for four weeks, which is a realistic amount typically consumed by honey users.

Official Title
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The Influence of Honey-flavored Yogurt on Low-grade Inflammation and Gut Health in Middle to Older Aged Women.

Conditions
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Overweight

Intervention / Treatment
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* Other: Honey sweetened yogurt
* Other: Sugar sweetened yogurt


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Postmenopausal female: 45-65 years Women: lack of menses for at least two years. Subject is willing and able to comply with the study protocols. Subject is willing to participate in all study procedures BMI 25.0 - 30.0 kg/m2 Exclusion Criteria: BMI ≥ 31 kg/m2 Food allergies Self-reported use of daily anticoagulation agents including aspirin, NSAIDs Vegan, Vegetarians, food faddists or those consuming a non-traditional diet Use of concentrated food supplements/powders and extracts Fruit consumption > 2 cups/day Vegetable consumption >3 cups/day Self-reported restriction of physical activity due to a chronic health condition Self-reported chronic/routine high intensity exercise Self-reported diabetes Blood pressure ≥ 140/90 mm Hg Self-reported renal or liver disease Self-reported heart disease, which includes cardiovascular events and stroke Abnormal Metabolic or CBC panels (laboratory values outside the reference range) if determined to be clinically significant by the study physician. Self-reported cancer within past 5 years Self-reported malabsorption Currently taking prescription drugs or supplements. Supplement use other than a general formula of vitamins and minerals that meet the RDA Not willing to stop any supplement use, including herbal, plant or botanical, fish oil, oil supplements a month prior to study enrollment. Indications of substance or alcohol abuse within the last 3 years Cannabis use Screening LDL ≥ 190 mg/dl for those who have 0-1 major risk factors apart from LDL cholesterol (i.e. family history of premature coronary artery disease (male first degree relative < 55 years; CHD in female first degree relative < 65 years), cigarette smoker, HDL-C ≤ 40 mg/dL]. (using NCEP calculator http://cvdrisk.nhlbi.nih.gov/calculator.asp) Screening LDL ≥ 160 mg/dl for those who have 2 major risk factors apart from LDL cholesterol [i.e. family history of premature coronary artery disease (male first degree relative < 55 years; CHD in female first degree relative < 65 years), cigarette smoker, HDL-C ≤ 40 mg/dL]. (using NCEP calculator http://cvdrisk.nhlbi.nih.gov/calculator.asp); Screening LDL ≥ 130 mg/dl for those who have 2 major risk factors apart from LDL cholesterol [i.e. family history of premature coronary artery disease (male first degree relative < 55 years; CHD in female first degree relative < 65 years), cigarette smoker, HDL-C ≤ 40 mg/dL], and a Framingham 10-year Risk Score 10-20% (using NCEP calculator http://cvdrisk.nhlbi.nih.gov/calculator.asp). Current enrollee in a clinical research study.

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Female

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: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Randomized single-blind 2-arm crossover trial. Each arm will be 4 weeks in length, with a 4 week washout between arms.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Honey sweetened yogurt<br>1 tbsp. of honey in 0.6 cup (150g) of plain yogurt. The participants will be asked to consume 2 morning servings of the yogurt for a total of 2 tbsp. of the assigned honey per day. | Other: Honey sweetened yogurt<br>* 2 tbsp. of daily honey intake in 1.2 cups of yogurt per day, split into two equal portions<br>|
| Placebo Comparator: Sugar sweetened yogurt<br>Sugar will be added to 0.6 cup (150g) of plain yogurt in an isocaloric amount compared to the honey. The participants will be asked to consume 2 morning servings of the yogurt per day. | Other: Sugar sweetened yogurt<br>* sugar added, in an isocaloric fashion to the honey, to 1.2 cups of yogurt per day, split into two equal portions<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentration of CD4+ T Helper (TH)17 cytokines | Cytokines included in the panel are: Il-1b, IL-4, IL-6, IL-10, IL-17a, IL-21, IL-22, IL-23, IL-31, IL-33, IFN-gamma, TNF-alpha, IL-17f. | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentration of Secondary bile acids | plasma microbial metabolites | 4 weeks | 
| Concentration of Short chain fatty acids | Fecal microbial metabolites | 4 weeks | 
| Concentration of urolithins and other ellagitannin-derived metabolites | microbial metabolites | 4 weeks | 
| Concentration of soluble NADPH oxidase (NOX2) | plasma marker oxidative stress | 4 weeks | 
| Concentration of uric acid | plasma marker oxidative stress | 4 weeks | 
| Concentration of total Nitrate/Nitrite and Nitric Oxide related metabolites (RSNO) | dietary nitrate and NO metabolites | 4 weeks | 
| Concentration of untargeted metabolomics | metabolism | 4 weeks | 
| Determination of microbial populations | stool bacterial population | 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phenolic, Honey, Inflammation, Yogurt, Microbiome