Probiotics and Examination-related Stress in Healthy Medical Students

Effect of Supplementation With Saccharomyces Boulardii and Lactobacillus Rhamnosus on Examination-related Stress in Healthy Medical Students: a Randomised, Double-blind, Placebo-controlled Trial

Probiotics are live microorganisms exhibiting multiple properties beneficial to health. An increasing body of evidence indicates that probiotics may support healthy brain function and may relieve stress. Recent research in this area has examined lactic acid bacteria in detail, but little is known about the stress-relieving effects of Saccharomyces, a yeast with probiotic properties.

Psychological stress is a factor that allows people to successfully cope with various daily life situations. On the other hand, excessive stress may lead to bodily harm and decrease performance, e.g. academic achievements. Probiotics may help manage stress, but little is known whether probiotics improve performance under stress.

The aim of this trial is to examine whether the healthy medical students may demonstrate better performance in academic examinations when supplementing their diet with a yeast probiotic strain Saccharomyces boulardii (CNCM I-1079) or bacterial probiotic strain Lactobacillus rhamnosus GG (ATCC 53103). The secondary aim of the trial is to evaluate the potential effects of this supplementation on state anxiety as well as on biochemical and physiological stress markers.

Study Overview

• Status: Completed
• Conditions: Healthy; Anxiety; Stress-related Problem
• Intervention / Treatment: Dietary supplement: Lactobacillus rhamnosus GG (ATCC 53103); Dietary supplement: Placebo; Dietary supplement: Saccharomyces boulardii (CNCM I-1079)

• Study Type: Interventional
• Enrollment (Actual): 92
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 30 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Being a third year medical student of the Faculty of Medicine or Faculty of Military Medicine, Medical University of Lodz

Exclusion Criteria:

• formal inability to sit the first attempt of the final examination of Basic Medical Pharmacology
• chronic diseases: neurological, psychiatric, cardiological, gastroenterological, immunological, endocrine or infectious
• state of immunosuppression
• history of hospitalization (< 3 months before entrance to the study)
• presence of central venous catheter
• parenteral nutrition
• current pregnancy or intention to become pregnant within 3 months from the entrance to the study
• current lactation
• allergic reaction (< 3 months before entrance to the study)
• hypersensitivity to yeast, maltodextrins, potato starch, magnesium stearate, hypromellose, gelatin, glycerol or titanium dioxide
• body mass index over 30
• chronic medication use (current or < 3 months before entrance to the study)
• systemic antibacterial or antifungal medication use (current or < 3 months before entrance to the study)
• overuse of alcohol or psychoactive substances (current or < 3 months before entrance to the study)
• tobacco smoking - more than 5 cigarettes (or equivalents) a day (currently or < 3 months before entrance to the study)
• pro- or prebiotic preparations intake (< 3 months before entrance to the study)
• vegan or other atypical diet
• doing professional or extreme sports

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lactobacillus; Lactobacillus rhamnosus GG (ATCC 53103) - encapsulated	Dietary supplement: Lactobacillus rhamnosus GG (ATCC 53103); 30 days of supplementation, 6x10^9 CFU/day
Placebo Comparator: Placebo; Placebo - encapsulated mixture of maltodextrins	Dietary supplement: Placebo; 30 days of supplementation
Experimental: Saccharomyces; Saccharomyces boulardii (CNCM I-1079) - encapsulated	Dietary supplement: Saccharomyces boulardii (CNCM I-1079); 30 days of supplementation, 5x10^9 CFU/day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Performance under examination-related stress	Number of correctly-answered questions in the final examination in Basic Medical Pharmacology	The examination is held on the 30th day of the trial.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
State anxiety under examination-related stress	State anxiety measured with State-Trait Anxiety Inventory (STAI)	30 minutes before the final examination in Basic Medical Pharmacology
Cortisol	Salivary cortisol level	Measured a day before the final examination in Basic Medical Pharmacology
Pulse rate	Individual, instructed measurement of pulse rate	30 minutes before the final examination in Basic Medical Pharmacology
Metanephrine	Salivary metanephrine level	Measured a day before the final examination in Basic Medical Pharmacology

Collaborators and Investigators

• Sponsor: Medical University of Lodz
• Investigators: Principal Investigator: Michał S. Karbownik, PhD, Medical University of Lodz

Publications and helpful links

General Publications

• McFarland LV. Systematic review and meta-analysis of Saccharomyces boulardii in adult patients. World J Gastroenterol. 2010 May 14;16(18):2202-22. doi: 10.3748/wjg.v16.i18.2202.
• Dinan TG, Stilling RM, Stanton C, Cryan JF. Collective unconscious: how gut microbes shape human behavior. J Psychiatr Res. 2015 Apr;63:1-9. doi: 10.1016/j.jpsychires.2015.02.021. Epub 2015 Mar 3.
• Foster JA, Rinaman L, Cryan JF. Stress & the gut-brain axis: Regulation by the microbiome. Neurobiol Stress. 2017 Mar 19;7:124-136. doi: 10.1016/j.ynstr.2017.03.001. eCollection 2017 Dec.
• Karbownik MS, Kreczynska J, Kwarta P, Cybula M, Wiktorowska-Owczarek A, Kowalczyk E, Pietras T, Szemraj J. Effect of Supplementation with Saccharomyces Boulardii on Academic Examination Performance and Related Stress in Healthy Medical Students: A Randomized, Double-Blind, Placebo-Controlled Trial. Nutrients. 2020 May 19;12(5):1469. doi: 10.3390/nu12051469.

Study record dates

Study Major Dates

• Study Start (Actual): April 20, 2016
• Primary Completion (Actual): June 20, 2016
• Study Completion (Actual): June 20, 2016

Study Registration Dates

• First Submitted: February 2, 2018
• First Submitted That Met QC Criteria: February 7, 2018
• First Posted (Actual): February 9, 2018

Study Record Updates

• Last Update Posted (Actual): February 9, 2018
• Last Update Submitted That Met QC Criteria: February 7, 2018
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Keywords: Stress; Probiotics; Psychobiotics; Examination
• Other Study ID Numbers: 502-03/5-108-03/502-54-157

Drug and device information, study documents

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