Safety of probiotics used to reduce risk and prevent or treat disease.

Susanne Hempel, Sydne Newberry, Alicia Ruelaz, Zhen Wang, Jeremy N V Miles, Marika J. Suttorp, Breanne Johnsen, Roberta Shanman, Wendelin Slusser, Ning Fu, Alex Smith, Beth Roth, Joanna Polak, Aneesa Motala, Tanja Perry, Paul G. Shekelle

Research output: Contribution to journalReview article

97 Citations (Scopus)

Abstract

To catalog what is known about the safety of interventions containing Lactobacillus, Bifidobacterium, Saccharomyces, Streptococcus, Enterococcus, and/or Bacillus strains used as probiotic agents in research to reduce the risk of, prevent, or treat disease. We searched 12 electronic databases, references of included studies, and pertinent reviews for studies addressing the safety of probiotics from database inception to August 2010 without language restriction. We identified intervention studies on probiotics that reported the presence or absence of adverse health outcomes in human participants, without restriction by study design, participant type, or clinical field. We investigated the quantity, quality, and nature of adverse events. The search identified 11,977 publications, of which 622 studies were included in the review. In 235 studies, only nonspecific safety statements were made ("well tolerated"); the remaining 387 studies reported the presence or absence of specific adverse events. Interventions and adverse events were poorly documented. A number of case studies described fungemia and some bacteremia potentially associated with administered probiotic organisms. Controlled trials did not monitor routinely for such infections and primarily reported on gastrointestinal adverse events. Based on reported adverse events, randomized controlled trials (RCTs) showed no statistically significantly increased relative risk (RR) of the overall number of experienced adverse events (RR 1.00; 95% confidence interval [CI]: 0.93, 1.07, p=0.999); gastrointestinal; infections; or other adverse events, including serious adverse events (RR 1.06; 95% CI: 0.97, 1.16; p=0.201), associated with short-term probiotic use compared to control group participants; long-term effects are largely unknown. Existing studies primarily examined Lactobacillus alone or in combination with other genera, often Bifidobacterium. Few studies directly compared the safety among different intervention or participant characteristics. Indirect comparisons indicated that effects of delivery vehicles (e.g., yogurt, dairy) should be investigated further. Case studies suggested that participants with compromised health are most likely to experience adverse events associated with probiotics. However, RCTs in medium-risk and critically ill participants did not report a statistically significantly increased risk of adverse events compared to control group participants. There is a lack of assessment and systematic reporting of adverse events in probiotic intervention studies, and interventions are poorly documented. The available evidence in RCTs does not indicate an increased risk; however, rare adverse events are difficult to assess, and despite the substantial number of publications, the current literature is not well equipped to answer questions on the safety of probiotic interventions with confidence.

Original languageEnglish (US)
Pages (from-to)1-645
Number of pages645
JournalEvidence report/technology assessment
Issue number200
StatePublished - Apr 2011
Externally publishedYes

Fingerprint

Probiotics
Safety
Bifidobacterium
Randomized Controlled Trials
Lactobacillus
Publications
Databases
Confidence Intervals
Fungemia
Yogurt
Control Groups
Saccharomyces
Enterococcus
Health
Bacteremia
Infection
Streptococcus
Critical Illness
Bacillus
Language

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Hempel, S., Newberry, S., Ruelaz, A., Wang, Z., Miles, J. N. V., Suttorp, M. J., ... Shekelle, P. G. (2011). Safety of probiotics used to reduce risk and prevent or treat disease. Evidence report/technology assessment, (200), 1-645.

Safety of probiotics used to reduce risk and prevent or treat disease. / Hempel, Susanne; Newberry, Sydne; Ruelaz, Alicia; Wang, Zhen; Miles, Jeremy N V; Suttorp, Marika J.; Johnsen, Breanne; Shanman, Roberta; Slusser, Wendelin; Fu, Ning; Smith, Alex; Roth, Beth; Polak, Joanna; Motala, Aneesa; Perry, Tanja; Shekelle, Paul G.

In: Evidence report/technology assessment, No. 200, 04.2011, p. 1-645.

Research output: Contribution to journalReview article

Hempel, S, Newberry, S, Ruelaz, A, Wang, Z, Miles, JNV, Suttorp, MJ, Johnsen, B, Shanman, R, Slusser, W, Fu, N, Smith, A, Roth, B, Polak, J, Motala, A, Perry, T & Shekelle, PG 2011, 'Safety of probiotics used to reduce risk and prevent or treat disease.', Evidence report/technology assessment, no. 200, pp. 1-645.
Hempel S, Newberry S, Ruelaz A, Wang Z, Miles JNV, Suttorp MJ et al. Safety of probiotics used to reduce risk and prevent or treat disease. Evidence report/technology assessment. 2011 Apr;(200):1-645.
Hempel, Susanne ; Newberry, Sydne ; Ruelaz, Alicia ; Wang, Zhen ; Miles, Jeremy N V ; Suttorp, Marika J. ; Johnsen, Breanne ; Shanman, Roberta ; Slusser, Wendelin ; Fu, Ning ; Smith, Alex ; Roth, Beth ; Polak, Joanna ; Motala, Aneesa ; Perry, Tanja ; Shekelle, Paul G. / Safety of probiotics used to reduce risk and prevent or treat disease. In: Evidence report/technology assessment. 2011 ; No. 200. pp. 1-645.
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