Adverse event data are often lacking or inadequate in clinical trials of probiotics and prebiotics, making it impossible to make broad conclusions about the safety of interventions aimed at modifying gut microbiota, authors of a systematic review have concluded.

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Out of 384 randomized clinical trials, nearly a third gave no information on potential harms associated with probiotics, prebiotics, or products that combine the two, according to authors of the review, which appears in Annals of Internal Medicine.

Only 2% of the trials adequately reported all key safety components, said the authors, led by Aïda Bafeta, PhD, Centre d’Épidémiologie Clinique, Hôpital Hôtel-Dieu, Paris.

“The inadequacy in reporting harms-related results may lead to an inaccurate safety profile and erroneous decision making, with major consequences for patients,” Dr. Bafeta and her colleagues wrote in their review.

While some may assume detailed safety evaluation is unnecessary, caution is especially needed when considering use of probiotics and prebiotics in patients who are vulnerable or critically ill, according to the authors.

“More worrying is that potential risks have been described in case reports and clinical trial results,” they wrote.

Dr. Bafeta and her coauthors cited a 2008 randomized, placebo-controlled trial published in The Lancet showing an increased risk of mortality associated with a particular combination of probiotic strains administered as prophylaxis in patients with predicted severe acute pancreatitis.

A 2011 report by the Agency for Healthcare Research and Quality found that current literature at that time was “not well equipped” to answer with confidence on the safety of probiotics as administered in clinical trials.

In the present report, Dr. Bafeta and her colleagues conducted a systematic review of 384 published randomized trials assessing probiotics, prebiotics, or synbiotics, which are products that combine probiotics and probiotics.

They found that 28% (106 trials) gave no information at all related to harms, while 90% (347) failed to define adverse events, and 97% (372) left out any mention of methods for collecting harms-related information.

Out of 53 studies including hospitalized or critical care patients, 7 reported the number of serious adverse events per study group, they said.

When safety data were included, reporting was often inadequate, according to Dr. Bafeta and her colleagues. Generic statements were used in 37% of the randomized trials, while 5% gave only global statistical comparisons.

Only 2% (nine trials) reported all safety-related parameters recommended by guidelines, such as adverse event definitions, seriousness of adverse events, and number of participant withdrawals due to harms, the reviewers found.

“The safety profile of an intervention should never be presumed,” they wrote. “Rather, it should be rigorously evaluated and reported.”

Probiotics and prebiotics are of increasing interest as treatments that may modify gut microbiota, potentially resulting in health benefits, they said. Probiotics are live microorganisms administered to confer a health benefit in the gut, while prebiotics are ingredients that change the composition or activity of gut microbiota.

No reviews previous to this one have assessed the adequacy of reporting adverse effects in trials of probiotics, prebiotics, and synbiotics, according to Dr. Bafeta and her colleagues, who reported no conflicts of interest associated with their review.

SOURCE: Bafeta A et al. Ann Intern Med. 2018 Jul 17.

Probiotics RCTs lack needed safety data, report says