Prebiotics as a category exist in something of a regulatory limbo at the moment. When the agency issued the final rule on the updates for the nutrition and supplements facts panels in May of this year, what could be labeled as a ‘dietary fiber’ was defined as “non-digestible soluble and insoluble carbohydrates (with 3 or more monomeric units), and lignin that are intrinsic and intact in plants; isolated or synthetic non-digestible carbohydrates (with 3 or more monomeric units) determined by FDA to have physiological effects that are beneficial to human health.”
What’s a prebiotic?
This left a number of products on market, such as inulin, out in the cold until manufacturers submit petitions to FDA to be included in this definition. And in any case, there is no formal regulatory definition of what a ‘prebiotic’ is, though there is a mention of the concept in a footnote from an agency communication in 2006. By applying this term to what can be found in the marketplace we might produce our own definition that goes something like this: “A prebiotic is an isolated or purified fiber of plant origin that can lay claim to a digestive health benefit by fostering the growth of beneficial microbes.”
At the root, any dietary fiber ought to be able to claim in a general way to foster the growth of microbial species. After all, a significant portion of fecal mass is composed of microorganisms and if one of the end goals of fiber supplementation is to increase fecal mass, two would seem to equal two in this case. The marketers of prebiotics, however, make a more focused claim to boost certain species—bifidobacteria, for example—with the use of their products. This had led to the rise of synbiotics, where specific prebiotics are paired with a few billion CFUs of the type of probiotic organism they are claimed to support.
Dim view of fermentation
All that is fine and good, but in the draft guidance titled “Scientific Evaluation of the Evidence on the Beneficial Physiological Effects of Isolated or Synthetic Non-digestible Carbohydrates Submitted as a Citizen Petition (21 CFR 10.30): Guidance for Industry” FDA was somewhat standoffish about those sorts of claims. “Fermentation and changes in the microbiota in the large intestine are considered to be processes, rather than beneficial physiological effects. While physiological effects that are beneficial to human health may be an outcome of fermentation or changes in the colonic microbiota, we do not consider either to be valid and measurable predictors of these effects in humans,” the guidance reads.
But according to Kantha Shelke, PhD, principal in the Chicago-based food consultancy CorvusBlue LLC, not having a precise regulatory definition of what a prebiotic fiber is and what isn’t could actually work to the benefit of the marketers of these ingredients as they work to put together their citizen’s petitions.
“The FDA recognizes changes in the microbiome to be a multifactorial process that cannot be regarded a measurable ‘physiological benefit’ for marketing purposes. The FDA does not, however, prohibit the positioning of ingredients as prebiotics, only as dietary fibers until proven via human intervention studies,” Shelke told NutraIngredients-USA.
Loss of microbiome modulation as a claim
Jacqueline Kuler is an attorney who’s a partner in the firm Amin Talati Upadhye who’s been working on this issue for clients since FDA dropped the fiber gauntlet in May. She said the exclusion of microflora proliferation as a benefit from official regulatory language was a blow.
“It is unfortunate that the FDA has taken the position that modulation of microbiota is not a beneficial physiological benefit in and of itself, but rather, may be a process that is associated with a physiological endpoint like laxation or attenuation of blood glucose or cholesterol levels. This means that in order for prebiotic fibers to be considered “dietary fibers” they must be shown to have health benefits beyond microbiome changes,” she said.
“Laxation effects and attenuation of blood glucose or cholesterol levels are often secondary outcome measures in prebiotic microflora studies, however, the robustness of the data for these outcomes remains to be seen, and a review of FDA’s initial conclusions is somewhat pessimistic. Microflora claims can still be made for prebiotics, assuming they are supported, it’s just a matter of whether these ingredients can be included in the calculation for dietary fiber,” Kuler concluded.
Studies in like populations
In providing the information to FDA on whether a product has a fiber-like benefit, FDA cautioned that the studies used should be closely relevant to the US population. While this is always desirable in a general sense for any ingredient and any indication, the agency viewed this as especially important in the fiber realm, as diet is everything in this case.
“Differences in nutrition, diet, and beneficial physiological effects between the United States and the country where a study was done may mean that the study results cannot be extrapolated to the US population. It may be difficult, for example, to draw scientific conclusions about the physiological effects of an added non-digestible carbohydrate in a population that consumes much higher or much lower levels of dietary fiber or other nutrients that have an effect on the physiological endpoint,” the guidance said.
“Kudos to the FDA for the sophisticated concept of human intervention studies as evidence of the causal relationship between ingredients and their physiological effects wherever possible, and for recognizing that physiological manifestation of digestive, laxative, and blood glucose effects depend on several variables including diet and population and must be demonstrated appropriately,” Shelke said.
“The data used to support claims must be relevant to the intended population and this would be no different for studies supporting digestive health claims,” Kuler said.
Research guide
In addition to issuing the draft guidance, the agency also issued a science review on a number of isolated or purified fibers as a way to help direct the assembly of dossiers. The review omits several popular ingredients, such as isomalto-oligosaccharides (IMOs), but Shelke said it’s a guide, not fait accompli.
“The research guide is a review of the scientific literature on clinical studies conducted with some 26 isolated/synthetic non-digestible carbohydrates. The guide is not meant to be an exhaustive list, rather a working document of the main physiological end-points for carbohydrates that the FDA has yet to categorize as dietary fiber. Expect the guide to grow as more scientific data emerges on other physiological endpoints affected by non-digestible carbohydrate to allow for acceptance as a dietary fiber,” Shelke said.