Industry Defends Probiotics Against Accusations of Being Unregulated, Ineffective

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The supplements industry is defending probiotics on multiple fronts, against new guidelines from the American Gastroenterological Association (AGA) and a segment on the show 60 Minutes.

The new guidelines from AGA were formed by a guideline panel and technical review panel, wherein the members were selected by the AGA Governing Board. The guidelines and technical review underwent independent peer review, and a 30-day open public comment period. The document calls the probiotic industry “largely unregulated,” and opines that “marketing of [the] product is often geared directly at consumers without providing direct and consistent proof of effectiveness.” When it comes to studies, the guidelines note that forming a cohesive opinion is difficult—“studies have been extremely varied including differences in the strain of microbe(s) used, dose, and route of administration, as well as the research methodology, including differences in the reporting of endpoints and outcomes… Conclusions drawn from meta-analyses or systemic reviews can be misleading if different studies with different patient populations, different reported endpoints and outcomes, or different strains or combinations of probiotics are grouped together inappropriately.”

AGA prioritized certain health conditions—IBD, IBS, infectious gastroenteritis, necrotizing enterocolitis, and Clostridioides difficile associated diseases, and focused on outcomes including treatment of disease, prevention of sepsis, and all-cause mortality.

The guidelines include:

  • Adults and children on antibiotic treatment may use boulardii or one of three provided combinations of strains for prevention of C. difficile infection. However, patients who place a high value on the “potential harms” or on cost and a low value on the small risk of C. difficile development would reasonably select no probiotics.
  • Adults and children with Crohn’s disease, ulcerative colitis, and IBS are only recommended to use probiotics in the context of a clinical trial.
  • AGA suggested the use of a combination of eight strains for adults and children with pouchitis, but noted that patients for whom the feasibility and cost of using that specific combination of probiotics is problematic can reasonably select no probiotics.
  • There are several combinations of probiotics recommended for preterm, low birth weight infants, to protect against necrotizing enterocolitis.
  • AGA suggests against the use of probiotics in children with acute infectious gastroenteritis.

The National Products Association hit back against the guidelines, saying in a press release that they “ignore the bulk of scientific evidence related to the health benefits of probiotics. The guidelines also falsely claim that the natural products industry is unregulated, despite being over seen by not one but two federal agencies to protect consumers from false advertising and bad actors.”

The press release says that “thousands of studies” have supported the safe use and efficacy of probiotics for a range of treatments and patient populations, including flu-like respiratory tract infections and IBS.

“These guidelines are at odds with the overwhelming number of studies supporting the safety and efficacy of probiotics in modern medicine. Consumers should always consult with their doctors or medical professionals before using probiotics, but these guidelines will only lead to more confusion for consumers,” said Sibyl Swift, NPA’s SVP for Scientific and Regulatory Affairs, in the press release. “Probiotics are among the most popular supplement products, primarily because consumers trust their safety and the important role they play in supporting their health.”

Meanwhile, 60 Minutes released a segment titled “Do Probiotics Actually Do Anything?” The segment recognizes the importance of the microbiome, and recognizes that altering it can make changes to health, but it contends that probiotics meet a lower safety standard than drugs, and concludes that probiotic supplements are useless.

The Council for Responsible Nutrition (CRN) released a statement from Andrea Wong, Ph.D., SVP Scientific & Regulatory Affairs at CRN, in response to this segment. She summed up the segment: The vigorous body of scientific research exploring the benefits of probiotics is providing increased understanding of the role probiotics play, not only for digestive health, but for immune function, brain health and even bone health. Probiotic use is supported both by a long history of safe use and rigorous clinical trials, and CRN underscores those beneficial effects and the safety of these products. But unfortunately, the recent news segment highlights the developing nature of the science and the lack of scientific certainty with regard to their beneficial health effects, pitting one scientist’s view against another’s and leaving viewers confused about the category.”

Dr. Jon LaPook interviewed several doctors and researchers, the majority of whom were anti-probiotic. Dr. Patricia Hibberd, a Professor of Medicine at Boston University, told Dr. LaPook: “The whole idea that maybe throwing in good bacteria that we would take by mouth that hopefully would land in the right places in the GI tract and work with the immune system. We just don’t know how to do any of that.”

Dr. Hibberd opines that there is no science backing the use of probiotics for IBS or after antibiotics; Dr. Dan Merenstein, Professor of Family Medicine at Georgetown University, tells Dr. LaPook immediately afterward that “I think the data is there. I recommend probitoics mainly for people who are on antibiotics and for people with irritable bowel disease.” He’s currently working on a clinical trial, backed by the National Institutes of Health, testing a probiotic cocktail to see if it can prevent diarrhea in children taking antibiotics.

On the subject of safety, the segment says: “The Food and Drug Administration, the FDA, does not classify probiotic capsules as drugs. That means they do not have to be proven ‘safe and effective.’ When added to anything, including infant formula, probiotics only need to meet a lower standard: ‘generally recognized as safe.’ In rare cases, probiotics have been linked to severe infections in critically ill patients and those with weakened immune systems. Otherwise, they appear to be safe.”

Dr. Wong’s take: “The safety of probiotics is well-established through their long history of use and safety studies. Moreover, probiotic products marketed as dietary supplements are subject to comprehensive dietary supplement regulations that include current Good Manufacturing Practices (cGMPs), testing procedures, labeling and storage requirements, and other practices enforced by regulatory agencies at both the federal and state levels. Many of the clinical endpoints questioned in the news segment involve treatment of serious diseases and medical conditions that are far beyond the purview of dietary supplements without refuting their beneficial effects for maintaining a healthy gut.”

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Dr. LaPook then interviews Professors Eran Elinav and Eran Segal, from Israel’s Weizmann Institute of Science, who performed a trial on a small group of adult volunteers who underwent multiple endoscopies and colonoscopies. Half the volunteers were given “a very large combination of probiotics that are out there in your supermarket,” according to Professor Elinav, and half were given a placebo. Professor Segal summed up the results: “What we’re seeing is that half the people take the probiotics and the probiotics, as they go in, they just go out and they don’t populate the gut.”

Dr. Wong opined that the research noted was cherry-picked. “The segment does not feature any new research and only highlights previously published scientific studies, each with their own limitations. For example, one of the featured studies reviewed the effects of a specific combination of probiotic strains on how they modify the microbiome of the host, but did not measure important clinical endpoints, like the prevention of diarrhea after taking antibiotics.”

Dr. Wong concluded: “Probiotics have been shown to support good health and continue to be a growing category with consumers. Their repeated purchases and positive consumer outcomes undercut the reporter’s supposition that benefits can be attributed to a placebo effect. This segment and its featured research reinforces that probiotics work through a variety of mechanisms beyond changing the composition of the microbiome and we encourage more research into the benefits and safety of this category. CRN reminds consumers to consult their healthcare providers if they have questions about the probiotic supplements they are taking or thinking about taking in the future.

UPDATE 7/2: The United Natural Products Alliance (UNPA) and the International Probiotics Association (IPA) have both responded to the 60 Minutes segment.

The IPA statement says: “Probiotic effects are usually strain-specific, and well-characterized probiotics are safe for the general healthy population… However, the program… creates confusion and misimpressions in consumers by failing to present balanced information.”

IPA notes that, with regards to scientific backing, independent clinical organizations WGO and AGA recommend specific probiotics for antibiotic-associated diarrhea, and the WGO recommends specific probiotics for IBS. The statement also acknowledges that the placebo effect can play a role in how probiotic users feel—but that that doesn’t impact positive results researchers have gotten: “Studies conducted according to accepted scientific standards, including those conducted on many probiotics, are usually able to differentiate positive outcomes from a placebo effect through the randomization and blinding process.”

IPA further discusses specific studies mentioned in the segment. “The results from one undocumented product in an exploratory study from the Weizmann Institute… was technologically advanced, [but] it included only a small number of subjects, and was not investigating any clinical endpoints. Just because the intervention did not recover the microbiota under the study conditions, does not mean that probiotics as a whole are ineffective (Suez et al., 2018). While the researchers were ‘surprised’ that the probiotics did not ‘settle’, it is important to understand that the scientific community widely acknowledges that probiotics do not colonize (Taverniti et al., 2019).”

The other interview IPA questions is one with Dr. Frank Greer, who questions the safety and efficacy of probiotics in infant forula. “In 2011, the European Society for Paediatric Gastroenterology Hepatology and Nutrition concluded that there were no safety concerns in these populations (Braegger et al., 2011). It is always difficult to document a benefit in a generally healthy population, and this is also true for probiotic infant formulas. A further comment is made on the absence of long-term studies. One can discuss what long-term is, but the IPA would like to remind the reader that there are several longitudinal studies that have followed children from birth for 11 years or more (Wickens et al., 2018) and cancer patients for more than 20 years (Mutoh et al., 2020), none of which have raised safety concerns over these extensive periods.”

UNPA’s comment was short and to the point: “It’s disappointing to continue to see such coverage but as we all know controversy surrounding the benefits of supplements is an evergreen story. Judging from recent sales figures, it is fair to say that the consumers have spoken.”

Perhaps the takeaway here should be this: “Probiotics” are not a monolith, and whether you’re a formulator or a retailer, you should choose your ingredients and products with care.

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