title: Absence of adverse events in healthy individuals using probiotics--analysis of six randomised studies by one study group.
abstract: Consumption of live bacteria as probiotic supplements is increasing. There is, however, a lack of information on the safety of ingested probiotics. The main objective of this study was to investigate the adverse events (AEs) of specific probiotics (Lactobacillus rhamnosus GG (LGG) alone or LGG in combination with L. rhamnosus Lc705, Propionibacterium freudenreichii JS, Bifidobacterium lactis BB12, or Bifidobacterium breve 99) studied in six of our study groups' clinical trials, by analysing individual participant data. A secondary objective was to study AEs associated with the consumed probiotic species and mixtures in three specific categories; 'gastrointestinal disorders', 'respiratory, thoracic and mediastinal disorders' and 'infections and infestations'. Six randomised, double-blind, placebo-controlled clinical studies by our study group were included in this AE analysis (study population n=1,909). All AE data were classified according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) v4.0. From the 26 CTCAE System Organ Classes, we identified AEs in 20 classes among 1,909 subjects. Probiotic ingestion did not result in statistically significant differences in AEs in different groups, when compared to placebo. A subgroup analysis of gastrointestinal, respiratory, thoracic and mediastinal disorders, infections and infestations, found no differences between the intervention groups or for different probiotic combinations (risk ratio (RR) = 0.97, 95% confidence interval (CI): 0.93-1.02, P=0.30; RR=0.99, 95% CI: 0.97-1.01, P=0.35; RR=0.99, 95% CI: 0.93-1.06, P=0.62, respectively). As a conclusion, ingestion of probiotic supplementations containing LGG alone, or LGG in combination with L. rhamnosus Lc705, P. freudenreichii JS, B. breve 99, or B. lactis BB12 did not seem to cause AEs in young and elderly subjects in this analysis.
authors.affiliation: 1 Otorhinolaryngology, University of Helsinki and Helsinki University Hospital, P.O. Box 220, 00290 Helsinki, Finland.
authors.forename: L
authors.initials: L
authors.lastname: Tapiovaara
authors.affiliation: 2 Medical Nutrition Physiology, Pharmacology, Faculty of Medicine, University of Helsinki, P.O. Box 64, 00014 Helsinki, Finland.
authors.forename: L
authors.initials: L
authors.lastname: Lehtoranta
authors.affiliation: 3 STAT-Consulting, Vahverokatu 6, 37130 Nokia, Finland.
authors.forename: T
authors.initials: T
authors.lastname: Poussa
authors.affiliation: 4 Mäkivuokko Consulting, Kaksosvuorentie 20, 02400 Kirkkonummi, Finland.
authors.forename: H
authors.initials: H
authors.lastname: Mäkivuokko
authors.affiliation: 2 Medical Nutrition Physiology, Pharmacology, Faculty of Medicine, University of Helsinki, P.O. Box 64, 00014 Helsinki, Finland.
authors.forename: R
authors.initials: R
authors.lastname: Korpela
authors.affiliation: 1 Otorhinolaryngology, University of Helsinki and Helsinki University Hospital, P.O. Box 220, 00290 Helsinki, Finland.
authors.forename: A
authors.initials: A
authors.lastname: Pitkäranta
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001644:Bifidobacterium / Q000502:physiology; D002675:Child, Preschool; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D007223:Infant; D007778:Lactobacillus / Q000502:physiology; D052201:Lacticaseibacillus rhamnosus / Q000502:physiology; D008297:Male; D019936:Probiotics / Q000008:administration & dosage / Q000009:adverse effects*; D011424:Propionibacterium / Q000502:physiology; D016032:Randomized Controlled Trials as Topic; D055815:Young Adult
keywords: Bifidobacterium; Lactobacillus; probiotics; safety