Plant Stanol Esters and Influenza Vaccination

Study Overview
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Brief Summary
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Plant stanols are known to lower low-density lipoprotein cholesterol (LDL-C). However, recent studies have suggested that these compounds also beneficially influence the immune system, e.g. increasing vaccine-specific antibody titers. BMI and age have previously been negatively associated to vaccination responses. If plant stanols indeed have beneficial effects on the immune system, people with overweight or obesity and higher age might benefit from consuming plant stanols prior to receiving the influenza vaccination.

Official Title
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Evaluating the Effect of Different Daily Plant Stanol Ester Intakes 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: Plant stanol soft chews (2g per day)
* Dietary Supplement: Plant stanol soft chews (3g per day)
* Dietary Supplement: Plant stanol soft chews (4g per day)
* Dietary Supplement: Control soft chews


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women Aged 60 years or older (or 59, but turning 60 years during influenza season 2022/2023 (in line with RIVM guidelines)) BMI between 20 and 35 kg/m2 Currently not using products containing plant sterols or stanols (products with a cholesterol lowering claim of Becel ProActiv, Benecol, Danacol, store brands) Willing to abstain from products containing plant sterols or stanols during the study (products with a cholesterol lowering claim of Becel ProActiv, Benecol, Danacol, store brands) Willing to keep the intake of fish oil and vitamin supplements constant Exclusion Criteria: Already received influenza vaccination in 2022 Already had influenza in 2022 Allergy to an ingredient of the chews 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

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: Plant stanol group (2 grams per day)<br>Dietary Supplement: 4 soft chews containing 0.5g plant stanols each (delivered as plant stanol esters) Soft chews containing 0.5g plant stanols each delivered as plant stanol esters | 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: Plant stanol soft chews (2g per day)<br>* Participants have to consume 4 soft chews per day containing 0.5g plant stanols each (delivered as plant stanol esters), corresponding to a total plant stanol intake of 2g daily<br>|
| Experimental: Plant stanol group (3 grams per day)<br>Dietary Supplement: 6 soft chews containing 0.5g plant stanols each (delivered as plant stanol esters) Soft chews containing 0.5g plant stanols each delivered as plant stanol esters | 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: Plant stanol soft chews (3g per day)<br>* Participants have to consume 6 soft chews per day containing 0.5g plant stanols each (delivered as plant stanol esters), corresponding to a total plant stanol intake of 3g daily<br>|
| Experimental: Plant stanol group (4 grams per day)<br>Dietary Supplement: 8 soft chews containing 0.5g plant stanols each (delivered as plant stanol esters) Soft chews containing 0.5g plant stanols each delivered as plant stanol esters | 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: Plant stanol soft chews (4g per day)<br>* Participants have to consume 8 soft chews per day containing 0.5g plant stanols each (delivered as plant stanol esters), corresponding to a total plant stanol intake of 4g daily<br>|
| Placebo Comparator: Placebo group<br>Dietary Supplement: 6 placebo soft chews Soft chews that do not contain plant stanols | 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 soft chews<br>* Participants have to consume 6 control soft chews per day that does not contain plant stanols<br>|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vaccine specific IgG antibody titer | The response to the Influenza vaccine will be measured by quantifying the specific IgG antibody titer | T=0 (day before vaccination), weekly in the month after vaccination (T1-T4) | 
| 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) | 
| 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 plant stanols and/or sterols outside the intervention | Day - 1 (start study), T=4 weeks after vaccination (end of study) | 
| Liver elastography | Fibroscan | Day - 1 (start study), T=0 (day before vaccination), T=4 weeks after vaccination (end of study) | 
| Liver fat content | Fibroscan | Day - 1 (start study), T=0 (day before vaccination), 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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Plant Stanols, Immune system, Influenza vaccination