Effect of Blueberries on Immunity and Response to Flu Vaccination

Study Overview
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Brief Summary
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This research study will test the effects of almonds on immune functions and immune response to influenza vaccine in overweight older men and postmenopausal women

Detailed Description
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A free-living parallel, single-blind, RCT will be utilized. There will be two phases: Phase 1 - to examine the effects of Blueberries on plasma markers of immune strength, and Phase 2 - to assess the response to influenza vaccine following blueberry intake. Subjects will either consume their usual diet with (Blueberry group) or a placebo(control group) blueberries for 8 weeks, receive the influenza vaccination, and continue the intervention for another 4 weeks. The test food will be freeze-dried powder (FDP) (  to 1 cup fresh blueberries) per day with the usual diet. The control will be the placebo powder with some guidelines to restrict all berries and other polyphenol-rich foods. The entire study will last 12 weeks. Participants will attend a baseline clinic at which time they will be randomized to one of the two groups. Clinic visits will occur at baseline, weeks 4 and 8 before, and week 4 after vaccination.

Official Title
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Immune Benefits of Blueberry Consumption and Response to Influenza Vaccination in Overweight Older Men and Postmenopausal Women: A Randomized Trial

Conditions
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Immune Response, Inflammation

Intervention / Treatment
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* Dietary Supplement: Blueberry powder group
* Dietary Supplement: Placebo powder group


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Older men and post-menopausal women aged 50-70 year 2. Have BMI of 25-32 3. Able to commute to Loma Linda University 3. Not taking medication or supplements that affect immunity 4. Agree to get vaccinated for Flu Exclusion Criteria: Intolerance or allergy to Blueberries Regular intake of Blueberries and other berried (>2 ounces/week) Immune system insufficiency or disease Using immune boosting supplements Exposure to antibiotics and corticoids immediately prior to study Uncontrolled chronic diseases and relevant psychiatric illness, including major depression Flu vaccination less than 10 months ago from the start of the study

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 70 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: his will be a parallel, free-living, randomized controlled trial, where 52 overweight men and postmenopausal women will be randomized to receive either the freeze dried blueberries or a placebo powder
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Blueberry powder group<br>Participants in the blueberry powder group will receive freeze dried blueberries in form of a powder | Dietary Supplement: Blueberry powder group<br>* Participants in the blueberry powder group will receive freeze dried blueberries in form of a powder<br>Dietary Supplement: Placebo powder group<br>* Participants in the placebo powder group will receive an isocaloric placebo powder<br>|
| Placebo Comparator: Placebo powder group<br>Participants in the placebo group will receive an isocaloric placebo powder. | Dietary Supplement: Blueberry powder group<br>* Participants in the blueberry powder group will receive freeze dried blueberries in form of a powder<br>Dietary Supplement: Placebo powder group<br>* Participants in the placebo powder group will receive an isocaloric placebo powder<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| changes in lymphocyte populations | Immunophenotyping will be performed by flow cytometry to measure the number of T helper, T cytotoxic, Naïve and memory cells and B cells | baseline to 8 weeks | 
| changes in cytokine production | PBMC cells will be separated from blood, activated and cultured using phytohemagglutinin (PHA). Inflammatory cytokine production will be measured in the resulting supernatant using ELISA | baseline to 8 weeks | 
| changes in natural killer (NK) cell activity | The NK degranulation assay will be performed on blood samples. The test will be conducted using a modified flow cytometry method that measures the expression of CD107a | baseline to 8 weeks | 
| changes in serum inflammatory cytokine concentration | Changes in the concentrations of the inflammatory cytokines will be performed on serum using enzyme-linked immunoassay (ELISA) | baseline to 8 weeks | 
| changes in complete blood count (CBC) | changes in the complete blood count will be performed on whole blood with the use of an automated hematology analyzer at a certified clinical facility | baseline to 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| changes in neutralizing antibody titers against hemagglutinin and neuraminidase of the vaccine strain | Neutralizing antibody titers in the serum against the hemagglutinin and neuraminidase of the vaccine strain will be measured using the standard commercial ELISA kits | week 8 to week 12 | 
| changes in the viral load in response to vaccination | viral load in blood will be measured using a quantitative polymerase chain reaction | week 8 to week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Almonds, Immunity, Inflammation