Agaricus Bisporus and Influenza Vaccination Response

Study Overview
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Brief Summary
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There are numerous in vitro and animal studies that suggested that mushrooms beneficially influence the immune system. We have recently shown that a wild isolate of the edible Agaricus bisporus mushroom had a clear effect on parameters reflecting a better function of the immune system, both in vitro and in vivo in animals. The question now is whether this efficacy can also be translated to humans. In humans, measuring the antibody response is the golden standard to evaluate immune function. If Agaricus bisporus powder indeed has beneficial effects on the immune system, people with overweight or obesity and higher age might benefit from consuming Agaricus bisporus powder prior to receiving the influenza vaccination.

Official Title
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Mushboost: Evaluating the Effect of Agaricus Bisporus Powder Intake on the Vaccination Response to an Influenza Vaccine

Conditions
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Immune Response

Intervention / Treatment
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* Biological: Influenza vaccine
* Dietary Supplement: Agaricus bisporus capsules
* Dietary Supplement: Control capsules


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 60 years or older during influenza season 2023/2024 (in line with RIVM guidelines) BMI between 20 and 35 kg/m2 Willing to abstain from mushrooms other than the capsules containing a mushroom powder as provided by us during the study period. Willing to keep the intake of fish oil, Zinc, Selenium and (vitamin) supplements constant Willing to abstain from products / supplements enriched with Vitamin D Willing to abstain from products / supplements enriched with plant sterols or stanols Willing to abstain from products / supplements enriched with (β)glucans or fungi. Willing to abstain from products / supplements that are mentioned to boost your immune system Willing to abstain from (products enriched in) pre/pro-biotics Willing to abstain from products/supplements enriched with ergothioneine Exclusion Criteria: Already received influenza vaccination in 2023 Allergy to mushrooms Known allergic reaction to an active component or other components of the vaccine (e.g. Chicken Eggs) Having donated blood within one month prior to the start of the study, or planning to donate blood during the study Excessive alcohol use (>20 consumptions per week) Regular use of soft and/or hard drugs Using medication for diseases known to affect inflammation/immunity (e.g. inhaled corticosteroids and prednisone)

Ages Eligible for Study
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Minimum Age: 59 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
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Agaricus bisporus group<br>Dietary supplement: 10 capsules containing 500 mg Agaricus bisporus powder each | Biological: Influenza vaccine<br>* Single dose of the Influenza vaccine Participants have to wait until they are invited to receive the vaccine by the general practitioner; this study does not interfere with national planning of the vaccine<br>Dietary Supplement: Agaricus bisporus capsules<br>* Participants have to consume 10 capsules per day containing 500 mg Agaricus bisporus powder each, corresponding to a total Agariicus bisporus powder intake of 5 g daily<br>|
| Placebo Comparator: Placebo group<br>Dietary supplement: 10 placebo capsules, capsules that do not contain Agaricus bisporus powder | Biological: Influenza vaccine<br>* Single dose of the Influenza vaccine Participants have to wait until they are invited to receive the vaccine by the general practitioner; this study does not interfere with national planning of the vaccine<br>Dietary Supplement: Control capsules<br>* Participants have to consume 10 capsules per day containing 500 mg maltodextrin each, corresponding to a total maltodextrin intake of 5 g daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vaccine specific antibody titer | The response to the Influenza vaccine will be measured by quantifying the specific antibody titer | Maximal change form T=0 (change T=0 to T=3 weeks or T=4 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immune parameters (1) | Cytokine production by PBMCs after stimulation with antiCD3-antiCD28 antiCD28 antibodies using the TruCulture system | Day - 1 (start study), T=0 (day before vaccination), T=4 weeks after vaccination (end of study) | 
| Immune parameters (2) | hsCRP | Day - 1 (start study), T=0 (day before vaccination), T=4 weeks after vaccination (end of study) | 
| Leukocyte count | Number of leukocytes measured in EDTA plasma | Day - 1 (start study), T=0 (day before vaccination), T=4 weeks after vaccination (end of study) | 
| Leukocyte differential count | Number of subgroups of leukocytes measured in EDTA plasma | Day - 1 (start study), T=0 (day before vaccination), T=4 weeks after vaccination (end of study) | 
| Fasted metabolism (1) | Serum non-cholesterol sterols and stanols | Day - 1 (start study), T=0 (day before vaccination), T=4 weeks after vaccination (end of study) | 
| Fasted metabolism (2) | Serum lipid and lipoprotein profile | Day - 1 (start study), T=0 (day before vaccination), T=4 weeks after vaccination (end of study) | 
| Fasted metabolism (3) | Plasma glucose | Day - 1 (start study), T=0 (day before vaccination), T=4 weeks after vaccination (end of study) | 
| Fasted metabolism (4) | Ergothioneine | Day - 1 (start study), T=0 (day before vaccination), T=4 weeks after vaccination (end of study) | 
| Fasted metabolism (5) | Glutathione | Day - 1 (start study), T=0 (day before vaccination), T=4 weeks after vaccination (end of study) | 
| Fasted metabolism (6) | Malondialdehyde | Day - 1 (start study), T=0 (day before vaccination), T=4 weeks after vaccination (end of study) | 
| Anthropometry (1) | Body weight | Day - 1 (start study), T=0 (day before vaccination), weekly in the month after vaccination (T1-T4) | 
| Anthropometry (2) | Height | Day -1 (start study) | 
| Anthropometry (3) | Waist circumference | Day - 1 (start study), T=0 (day before vaccination), weekly in the month after vaccination (T1-T4) | 
| Anthropometry (4) | Hip circumference | Day - 1 (start study), T=0 (day before vaccination), weekly in the month after vaccination (T1-T4) | 
| Anthropometry (5) | Waist-to-hip ratio | Day - 1 (start study), T=0 (day before vaccination), weekly in the month after vaccination (T1-T4) | 
| Diet | Food frequency questionnaire is used to determine if the participants maintain their habitual diet and to determine if the participants do not consume mushrooms outside the intervention | Day - 1 (start study), T=4 weeks after vaccination (end of study) | 
| Quality of life questionnaire | Quality of life questionnaire is used to determine the participants overall wellbeing and quality of life | Day - 1 (start study), T=4 weeks after vaccination (end of study) | 
| Diary outcomes (1) | Adverse events as assessed by the diary | Day - 1 (start study), T=4 weeks after vaccination (end of study) | 
| Diary outcomes (2) | Medication intake as assessed by the diary | Day - 1 (start study), T=4 weeks after vaccination (end of study) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Agaricus bisporus, Immune system, Influenza vaccination, Mushroom