Effect of Supplementation with Saccharomyces Boulardii on Academic Examination Performance and Related Stress in Healthy Medical Students: A Randomized, Double-Blind, Placebo-Controlled Trial

Abstract

In recent years, bacterial probiotic dietary supplementation has emerged as a promising way to improve cognition and to alleviate stress and anxiety; however, yeast probiotics have not been tested. The aim of the present study was to determine whether 30-day supplementation with Saccharomyces boulardii enhances academic performance under stress and affects stress markers. The trial was retrospectively registered at clinicaltrials.gov (NCT03427515). Healthy medical students were randomized to supplement their diet with Saccharomyces boulardii CNCM I-1079 or placebo before sitting for an academic examination, which served as a model of stress. The grades of a final examination adjusted to subject knowledge tested in non-stressful conditions was used as a primary outcome measure. Psychometrically evaluated state anxiety, cortisol and metanephrine salivary levels, and pulse rate were tested at a non-stressful time point before the intervention as well as just before the stressor. Fifty enrolled participants (22.6 ± 1.4 years of age, 19 males) completed the trial in the Saccharomyces and placebo arms. Supplementation with Saccharomyces did not significantly modify examination performance or increase in state anxiety, salivary cortisol, and metanephrine. However, the intervention resulted in higher increase in pulse rate under stress as compared to placebo by 10.4 (95% CI 4.2–16.6) min−1 (p = 0.0018), and the effect positively correlated with increase in salivary metanephrine (Pearson’s r = 0.35, 95% CI 0.09–0.58, p = 0.012). An intention-to-treat analysis was in line with the per-protocol one. In conclusion, supplementation with Saccharomyces boulardii CNCM I-1079 appears largely ineffective in improving academic performance under stress and in alleviating some stress markers, but it seems to increase pulse rate under stress, which may hypothetically reflect enhanced sympathoadrenal activity.

Decrease in Salivary Serotonin in Response to Probiotic Supplementation With Saccharomyces boulardii in Healthy Volunteers Under Psychological Stress: Secondary Analysis of a Randomized, Double-Blind, Placebo-Controlled Trial

“…boulardii ( Saccharomyces boulardii , Sb ) has also been found to have probiotic properties ( 32 ). Sb has been extensively tested and widely used in gastroenterology ( 32 , 33 ); however, it is a subject of very little research in neuroscience ( 34 , 35 ), particularly in relation to its serotonergic effect. Intriguingly, fungal probiotics significantly differ from bacterial ones in their biological characteristics, mechanism of action and beneficial properties ( 36 , 37 ), and the effects of probiotic bacteria cannot be easily extrapolated to yeasts ( 35 ).…”

“…Sb has been extensively tested and widely used in gastroenterology ( 32 , 33 ); however, it is a subject of very little research in neuroscience ( 34 , 35 ), particularly in relation to its serotonergic effect. Intriguingly, fungal probiotics significantly differ from bacterial ones in their biological characteristics, mechanism of action and beneficial properties ( 36 , 37 ), and the effects of probiotic bacteria cannot be easily extrapolated to yeasts ( 35 ). Therefore, there is a need to determine the serotonergic effect of yeast probiotics and its potential therapeutic implications.…”

“…The secondary aim was to test whether salivary 5-HT concentration is associated with selected psychological (depression, anxiety, eating attitudes, information retrieval), physiological (pulse rate, body-mass index), biochemical (salivary cortisol and metanephrine) and sociodemographic parameters. The study serves as a secondary analysis of a randomized, double-blind, placebo-controlled trial aimed at evaluating the pro-cognitive and anti-anxiety effects of Sb dietary supplementation (original study) ( 35 ).…”

Active ingredient ‘Better gut microbiome function’

“…Caution is warranted with this study however, since errors in the statistical analysis in the initial manuscript warranted a subsequent correction which significantly altered the initially promising reported outcome (Tran 2019). By far the most common study design for both pre- and probiotics involved following a cohort of selected and unselected university students before, during, and after final exams (Marcos, Warnberg et al 2004, Andersson, Tullberg et al 2016, Culpepper, Christman et al 2016, Kato-Kataoka, Nishida et al 2016, Kato-Kataoka, Nishida et al 2016, Takada, Nishida et al 2016, Karbownik, Kreczynska et al 2020). These studies often only used stress or anxiety as a secondary outcome, focussing on stress-related GI problems or immune performance, mostly with salivary cortisol as the main outcome.…”

“…Furthermore, the literature currently does not support their use in reducing anxiety, and two studies reported adverse effects, e.g. increased BAI (Tran, Zhebrak et al 2019) and increased pulse rate (Karbownik, Kreczynska et al 2020).…”