Earlier this month, the Council for Responsible Nutrition and the International Probiotics Association (IPA) announced the publication of probiotic guidelines. This is not the first effort to develop probiotic guidelines. Those were developed in May of 2002, by a panel of experts convened by the FAO/WHO. This panel met the day before the inaugural meeting of the International Scientific Association for Probiotics and Prebiotics (ISAPP) and the resulting guidelines were published on the FAO/WHO website.
Adoption by probiotic producers of legitimate verification programs would be far more meaningful to consumers and healthcare providers than another set of voluntary guidelines. Verification programs verify producers’ compliance with quality and label standards, assuring consumers receive high-quality and accurately represented products. Organizations such as U.S. Pharmacopeia (USP) and Underwriter Laboratories offer these programs. Such credible, independent, third parties are better suited to assure transparency and consistency of probiotic products than companies are for their own products.
However, since new guidelines are what have been recently released, it is of value to consider them within the context of the FAO/WHO guidelines, which we will consider first.
The 2002 FAO/WHO guidelines offered simple but enduring principles for responsible probiotic product development, and its bedrock principles applied to all probiotic categories including foods, supplements and drugs:
1. Strain identification by current methods (both phenotypic and genotypic). This included requirements for use of current nomenclature, identification at the strain level and deposit of the strain into an international culture collection. The deposit requirement was established for two reasons. First, it enables independent research on commercial probiotic strains, and second, it provides reference material for claims of identity to a commercial strain.
2. Functional characterization, including in vitro and animal testing.
3. Safety assessment.
4. Controlled human studies to document health effects. Probiotics by definition require evidence of health benefit in the target host. These guidelines emphasized the need for such evidence, although the discussion about the need for phase 1, 2 and 3 studies suggests a path more suitable for a new drug than probiotic foods or supplements. Phase 1 studies may not be needed based on history of safe use of many probiotics used in food. Randomized, controlled phase 2 or 3 trials may be needed, depending on regulatory requirements and the type of claim being made.
5. Proper labeling of products, to include:
• Contents, including genus, species and strain;
• Minimum numbers of each strain of probiotic contained in the product at the end of shelf life;
• Proper storage conditions;
• Corporate contact details for consumer information.
Over the 15 years since those guidelines were published, the probiotic field has grown widely as evidenced by more strains, more types of products, more regulatory categories of probiotic products and more clinical evidence for a broader range of health effects. This growth prompted the ISAPP to convene a consensus panel of experts in 2013 to consider if the concept of probiotics had changed. The results were published by Hill et al. (2014) in Nature Reviews in Gastroenterology and Hepatology (NRGH), in an open access paper that has been downloaded over 30,000 times (the most downloaded paper in NRGH).
Some key updates to the probiotic concept from this paper are:
1. An update (which reflected a grammatical correction but no substantive change) of the 2001 FAO/WHO definition of a probiotic: Probiotics are “live microorganisms that, when administered in adequate amounts, confer a health benefit on the host”.
2. Reiteration that the term probiotic spans many regulatory categories, including foods, supplements, drugs (AKA live biotherapeutic agents) and infant formula.
3. A conclusion that the undefined nature of fecal microbial transplants and cultures used in fermented foods—even if some have been shown to benefit health—do not meet the essential criteria of a probiotic.
4. A conclusion, based on consideration of the large number of studies conducted on some well-studied probiotic species that general digestive probiotic benefits exist at the species level. “If the goal of probiotic consumption is to support digestive health, perhaps many different probiotic preparations containing adequate numbers of well-studied species will be sufficient.”
As can be seen in the table above, the CRN/IPA guidelines provide expanded insight into approaches to measuring stability but are silent on many important issues addressed in the FAO/WHO guidelines. The absence of recommendations on substantiation of claims and safety are noteworthy. Another difference is the requirement for labeling total CFU for multiple strain products. Although methods to test levels of individual strains after blending are often not available, especially for products formulated with widely different levels of different strains, it is reasonable to propose that expected levels of each strain, based on stability data for individual strains, be disclosed. This would meet the goal of transparency much better than labels with only total counts, where consumers could not differentiate products formulated with one dominant strain from products with equivalent numbers of multiple strains.
All stakeholders benefit when probiotic products comply with quality and labeling expectations. Published voluntary guidelines are useful for outlining key principles for quality probiotic manufacture. Third party verification programs provide the transparency needed for consumers and healthcare provides to trust that these guidelines—and more—are being followed.