Plant Stanol Esters and Influenza Vaccination

Evaluating the Effect of Different Daily Plant Stanol Ester Intakes on the Vaccination Response to an Influenza Vaccine

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.

Study Overview

• Status: Completed
• Conditions: Immune Response
• Intervention / Treatment: 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

• Study Type: Interventional
• Enrollment (Actual): 137
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Limburg
    • Maastricht, Limburg, Netherlands, 6229ER
      • Maastricht University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 59 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Plant stanol group (2 grams per day); 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; 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; Dietary supplement: Plant stanol soft chews (2g per day); 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
Experimental: Plant stanol group (3 grams per day); 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; 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; Dietary supplement: Plant stanol soft chews (3g per day); 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
Experimental: Plant stanol group (4 grams per day); 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; 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; Dietary supplement: Plant stanol soft chews (4g per day); 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
Placebo Comparator: Placebo group; Dietary Supplement: 6 placebo soft chews Soft chews that do not contain plant stanols	Biological: Influenza vaccine; 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; Dietary supplement: Control soft chews; Participants have to consume 6 control soft chews per day that does not contain plant stanols

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Maastricht University Medical Center
• Collaborators: Raisio Nutrition Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): October 11, 2022
• Primary Completion (Actual): December 20, 2022
• Study Completion (Actual): December 20, 2022

Study Registration Dates

• First Submitted: January 11, 2023
• First Submitted That Met QC Criteria: January 20, 2023
• First Posted (Actual): January 31, 2023

Study Record Updates

• Last Update Posted (Actual): January 31, 2023
• Last Update Submitted That Met QC Criteria: January 20, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: Immune system; Influenza vaccination; Plant Stanols
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human
• Other Study ID Numbers: METC 22-048

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No