Plant Stanol Esters and COVID-19 Vaccination Response

The Effect of Plant Stanol Ester Consumption on the Vaccination Response to a COVID-19 Vaccine

Plant stanols are known to lower low-density lipoprotein cholesterol (LDL-C). However, studies have suggested that these compounds also beneficially influence the immune system, e.g. increasing vaccine-specific antibody titers. BMI has previously been negatively associated to vaccination responses. If plant stanols indeed have beneficial effect on the immune system, people with overweight or obesity might benefit from consuming plant stanols prior to receiving the COVID-19 vaccination. The primary objective of this study is to demonstrate clinical benefits of consumption of plant stanols (delivered via products enriched with plant stanol esters) on the vaccination response to a COVID-19 vaccine in overweight or obese patients. The main study endpoint is vaccination response to a COVID-19 vaccine. Secondary endpoints include amongst others hematological, inflammatory and immunological parameters (e.g. hs-CRP, leukocyte differential count) and metabolic markers (e.g. blood lipid profiles, plasma glucose, serum insulin, HOMA-IR).

Study Overview

• Status: Terminated
• Conditions: Overweight and Obesity
• Intervention / Treatment: Dietary supplement: Plant stanol mini drinks; Biological: COVID-19 vaccine; Dietary supplement: Placebo mini drinks

• Study Type: Interventional
• Enrollment (Actual): 48
• 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: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Men and women
• Aged 18 years or older
• BMI between 27 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 COVID-19 vaccination
• Already had a positive test for COVID-19 (this includes all types of tests, e.g. PCR tests or antibody tests)
• Allergy to an ingredient of the mini drinks
• Having donated blood within one month prior to the start of the study, or planning to donate blood during the study
• Pregnant women
• Breastfeeding women
• Excessive alcohol use (>20 consumptions per week)
• Regular use of soft 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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Plant stanol group; This arm receives 4g of plant stanols per day (delivered as plant stanol esters) by consuming mini drinks (100 mL each).	Dietary supplement: Plant stanol mini drinks; Oat milk based mini drinks (100 mL) containing 2g plant stanols each (delivered as plant stanol esters).; Biological: COVID-19 vaccine; First dose of one of the COVID-19 vaccines. Participants have to wait until they are invited to receive the vaccine by the government; this study does not interfere with national planning of the vaccines.
Placebo Comparator: Placebo group; This arm receives mini drinks without added plant stanols (delivered as plant stanol esters).	Biological: COVID-19 vaccine; First dose of one of the COVID-19 vaccines. Participants have to wait until they are invited to receive the vaccine by the government; this study does not interfere with national planning of the vaccines.; Dietary supplement: Placebo mini drinks; Oat milk based mini drinks (100 mL) without added plant stanols (delivered as plant stanol esters).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Vaccine specific antibody titers	The response to the COVID-19 vaccine will be measured by quantifying specific antibody titers (vaccine specific IgG and IgM). These titers will be measured in blood samples collected weekly during the month after vaccination by suitable ELISAs.	Change T=0 and 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	T=-1 (start study), T=0 (day before vaccination), T=4 weeks after vaccination
Immune parameters (2)	hsCRP	T=-1 (start study), T=0 (day before vaccination), weekly in the month after vaccination (T1-T4)
Leukocyte count	Number of leukocytes measured in EDTA plasma	T=-1 (start study), T=0 (day before vaccination), weekly in the month after vaccination (T1-T4)
Leukocyte differential count	Number of subgroups of leukocytes measured in EDTA plasma	T=-1 (start study), T=0 (day before vaccination), weekly in the month after vaccination (T1-T4)
Fasted metabolism (1)	Serum non-cholesterol sterols and stanols	T=-1 (start study), T=0 (day before vaccination), weekly in the month after vaccination (T1-T4)
Fasted metabolism (2)	Serum lipid and lipoprotein profile	T=-1 (start study), T=0 (day before vaccination), weekly in the month after vaccination (T1-T4)
Fasted metabolism (3)	Glucose metabolism (including e.g. plasma glucose, serum insulin and calculated HOMA-IR)	T=-1 (start study), T=0 (day before vaccination), weekly in the month after vaccination (T1-T4)
Anthropometry (1)	Body weight	T=-1 (start study), T=0 (day before vaccination), weekly in the month after vaccination (T1-T4)
Anthropometry (2)	Height	T=-1 (start study)
Anthropometry (3)	Waist circumference	T=-1 (start study), T=0 (day before vaccination), weekly in the month after vaccination (T1-T4)
Anthropometry (4)	Hip circumference	T=-1 (start study), T=0 (day before vaccination), weekly in the month after vaccination (T1-T4)
Anthropometry (5)	Waist-to-hip ratio	T=-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	T=-1 (start study) and T=4 weeks after vaccination (end study)
Diary outcomes (1)	General illness	T=-1 (start study) until T=4 weeks after vaccination (end of study)
Diary outcomes (2)	Side effects COVID-19 vaccine	T=0 (day before vaccination) until T=4 weeks after vaccination (end of study)
Diary outcomes (3)	Medication intake	T=-1 (start study) until 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): April 22, 2021
• Primary Completion (Actual): January 11, 2022
• Study Completion (Actual): January 11, 2022

Study Registration Dates

• First Submitted: April 13, 2021
• First Submitted That Met QC Criteria: April 13, 2021
• First Posted (Actual): April 14, 2021

Study Record Updates

• Last Update Posted (Actual): March 2, 2022
• Last Update Submitted That Met QC Criteria: February 11, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: Obesity; Overweight; COVID-19 vaccine; Immune system; Vaccination response
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Body Weight; COVID-19; Overweight
• Other Study ID Numbers: METC 21-013

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No