Abstracts

Approach for Substantiating a Claim of Digestive Health for Probiotics

Yehuda Ringel, PhD, University of North Carolina at - Chapel Hill

The probiotic concept suggests that supplementation of the intestinal microbiota with the right types and numbers of microbes can improve the microflora characteristics and promote health. Public interest in the relationship between diet and health together with direct-to-consumer advertising contributed to a dramatic increase in the functional food and probiotics market. Probiotic produces are available in different preparations including fermented milk drinks, yoghurts, food products, capsules, pills, and powders. The number, variability and availability of these products are increasing as new products are constantly being developed and marketed with various beneficial health claims.

The issue of probiotics has recently taken on a higher profile as the makers of probiotic and nutritional supplements have launched high-profile marketing campaigns, claiming their products can help relieve and prevent common digestive problems such as constipation, bloating, abdominal discomfort and diarrhea. As a result, people who suffer from these ailments are now taking probiotics or asking their doctors whether or not they should give probiotic products a try. In theory, certain probiotics (at the right dose and in the right formulation) can help restoring the proper balance of the intestinal microbiota, lead to better digestive function and possibly improve gastrointestinal symptoms. However, the current scientific data to support these claims and particularly the benefit of probiotic use in certain disease or illness conditions is limited. Indeed, most of the probiotic products currently available on the market have not been scientifically tested for their effectiveness in particular conditions.

The regulatory authorities regard probiotics as dietary supplements that are not intended to diagnose, treat, cure, or mitigate the effects of diseases and recommend that consumers will consult with a health care professional before using these products. However, studies have shown that despite this recommendation only a minority (less than 30%) of probiotics consumers does so with the advice of their health care provider. Furthermore, the ability of health care provider to provide knowledgeable advice with the regard to the appropriate use of probiotics is very limited due of the lack of high quality evidence based data on the currently available probiotic products.

Further detailed and accurate information on the content, safety, benefits and possibly mechanisms of action of available probiotic products is greatly needed. This information should arise from high quality research. However, the area of clinical and translational research in probiotics is currently facing several obstacles that delay production/delivery of this information. Some of these difficulties relate to the lack of clear guidelines from the regulatory authorities with regard to the needed requirements, lack of available funding from federal resources to support high quality research in this area, discrepancies in endpoints terminology between marketing professionals, researchers, health care providers and consumers.Resolving these difficulties will promote the research in this area and will help providing the needed information to appropriately support probiotics claims, increasing their beneficial effects and customers' satisfaction with their use.

Probiotics and Label Claims: Communicating the Health Benefits of Foods That Can Promote Health

Elizabeth Rahavi, RD, International Food Information Council

Foods that can provide benefits remain a hot food and nutrition topic. The media continues to chronicle trends in food and health and consumers remain enthusiastic about the benefits these foods offer. Research shows that many consumers believe the link between nutrition and health, and are looking for actionable advice. This is especially true for probiotics where findings from the 2009 International Food Information Council (IFIC) Functional Foods/Foods for Health survey shows that nearly three quarters of Americans are aware of the health benefits of probiotics for maintaining a healthy digestive and immune systems, a significant increase from 2007. Recent findings from the 2009 IFIC Food & Health survey also shows that consumers cite the food label as an important factor guiding their food and beverage choices. However, claims on food packages are just one vehicle for informing consumers about foods that promote health. Consumers bring a number of factors into their decisions to purchase a food or beverage, including prior experience, knowledge, and influence from family, friends and others. Therefore, effective communication is a critical element in realizing the public health benefits that probiotics offer, without presenting them as “magic bullets.” IFIC and the IFIC Foundation will present a body of comprehensive consumer research that provides a look at consumer interest in foods that can promote health, probiotics and label claims, which all point to communication implications for disussing probiotics with consumers.

Substantiating Structure /Function Claims Made for Dietary Supplements

Kenneth M. Taylor, PhD, Center for Food Safety and Applied Nutrition, United States Food and Drug Administration 

The Federal Food, Drug, and Cosmetic Act (the Act) provides that nutrition support statements may be made for dietary supplements. However, the Act also stipulates that such structure/function claims that are made in accordance with 21 U.S.C. 343(r)(6) must be substantiated to demonstrate that the statements are truthful and not misleading. To articulate its position toward adequate substantiation of structure/function claims, FDA has developed a guidance which describes the amount, type, and quality of supporting evidence that may be considered appropriate or acceptable. By applying a substantiation standard of “competent and reliable scientific evidence”, relevant matters such as the meaning of the claim(s), the relationship of evidence to the claim(s), the quality of the evidence, and the totality of the evidence should be considered when assessing if a structure/function claim is supported within the context of a surrounding body of evidence. This approach provides flexibility for the variety of evidence that may constitute adequate substantiation. In addition to addressing the statutory requirement, having a defined substantiation standard may also help to promote consumer confidence in products which make nutrition support statements.

Substantiation of Health Claims in Advertising

Richard L. Cleland, JD, Federal Trade Commission

Propelled by media attention, big budget advertising campaigns, and boomers’ never ending quest to stay healthy for as long as possible, probiotics are fast approaching star status. But, from an advertising perspective, are probiotics really ready for prime time. Federal law prohibits unsubstantiated health claims in advertising. Disease claims, as well as structure function claims, must be supported by competent are reliable scientific evidence that is sufficient in quality and quantity based on standards generally accepted in the relevant scientific fields, when considered in light of the entire body of relevant and reliable scientific evidence, to substantiate that the representation is true. To meet this standard, studies must meet the basic requirements of sound science. In general, this standard will require human clinical studies that are randomized, double-blind, placebo-controlled, and conducted by persons qualified by training and experience to conduct such studies. Studies must be strain specific and measure endpoints that support the advertising claims. Dosages used in the studies must be comparable to the dose users would receive under the minimum recommended use directions. Measurements must be valid and statistical analysis should be based on between group comparisons. Results must be both statistically and clinically significant. So far, probiotics have had difficulty meeting these standards, both in the E.U. and U.S.

FDA Ingredient Labeling Regulations

Geraldine June, MS, Food Labeling and Standards Staff

FDA food labeling regulations require several pieces of information on a food label. This information about a food is necessary to inform consumers about the attributes of the food product to assist them in making informed purchase decisions. The statement of identity, which is the name of the food and should be one of the principal pieces of information on a food product, can be a name prescribed by a regulation such as a standard of identity, a common or usual name, an appropriately descriptive term, or when the nature of the food is obvious, a fanciful name. In addition to the statement of identity, food labels must include a list of ingredients by their common or usual names in descending order of predominance by weight. Thus, it is very important to have an appropriate truthful and non misleading name for a food and its ingredients to inform the consumer what the food product is and what it contains. This presentation will provide an overview of FDA labeling requirements for foods, including dietary supplements, with an emphasis on FDA requirements and policies on how common or usual names are established. The presentation will also provide some examples of how some common or usual names were established.

Probiotic Nomenclature for Product Labels: Recommendations from Lactobacillus and Bifidobacterium Nomenclature Committees

Charles Franz, PhD, Max Rubner-Institut, Federal Institute of Nutrition and Food

Probiotics are live microorganisms which, when administered in adequate amounts, confer a health benefit on the host. The European Food Safety Authority (EFSA) recommends that microorganisms used in foods, including probiotics, should undergo a safety assessment; correct identification and taxonomy of the probiotic microorganism is a pre-requisite for this. Health Canada (2009) also demands that the correct identity of microorganisms should be declared on probiotic products. As is well known that the probiotic properties are strain, condition and dose dependent, the correct identification and labeling of probiotic strains is therefore essential. Lactobacilli and bifidobacteria are Gram-positive bacteria of which specific species are most often used as probiotics. While bifidobacteria belong to the Actinomycete subdivision of the Gram-positive bacteria, the lactobacilli can be grouped in the clostridial subdivision, the Firmicutes. The Lactobacillus species groups which containing probiotic species include the L. acidophilus group, the L. casei group, the L. reuteri group, the L. salivarius group and the L. plantarum group. Bacterial systematics embraces classification (taxonomy), identification and nomenclature, which are all essential for studying novel probiotic microorganisms or existing strains for which the taxonomy is under revision. Taxonomy is a dynamic science and for the lactobacilli it is far from satisfactory. The wide range of genome mol%GC content (32 to 54%) is twice as much as that normally accepted for a well-defined genus. This indicates that taxonomical changes are likely. This unsatisfactory taxonomy also applies to probiotic species such as in the case of L. casei and L. paracasei, for which the taxonomy is still quite controversial. Nevertheless, product labeling with the correct species identification and nomenclature are increasingly important issues. The recommendations to producers of probiotic microorganisms thus are to be cognisant of the unsatisfactory taxonomy of the lactobacilli and to continually update their knowledge on the current taxonomy of these bacteria from appropriate sources.

The Role Of International Biological Resource Centers in Identifying and Curating Bacterial Strains for Commercial Use

Brian J. Beck, PhD, American Type Culture Collection

As a Biological Resource Center (BRC), ATCC supports research discovery and application by academic, government and private sectors through a combination of products and services. ATCC’s mission is to acquire, authenticate, preserve, develop and distribute biological materials, information, technology, intellectual property and standards for the advancement and application of scientific knowledge. ATCC maintains four types of Collections (Contract, General, Patent, and Safe Deposit) that offer the depositor and users different levels of control and access. Biological materials held by these collections range from bacterial cultures and cell lines to derivatives such as proteins, genomic DNA and antibodies. Acquisition priorities include type strains, sequenced genomes, model research strains, reference strains used for quality control purposes and organisms with interesting functionality. Cultures are replicated with minimal passages and preserved to limit genetic drift and maintain the phenotype as close to the original as possible. Authentication/quality control is achieved by characterizing strains using genotypic and phenotypic testing to determine a contemporary phylogenetic assignment. Cryopreserved cultures are shipped world-wide through a network of distributors. Although new technologies such as phenotypic microarray and next-generation sequencing of genomes will likely revolutionize the identification and discrimination of strains, BRC’s must continue to balance time and cost-effective methodologies with maximum strain resolution.

Delimiting the Boundaries of the “Strain” in an Ever-Evolving Bacterial World

Eric W. Brown, PhD, US Food and Drug Administration

The ever-increasing introduction of live bacterial food and supplement ingredients into US markets has fostered an intense and renewed scientific interest among regulatory microbiologists for accurate strain identification and nomenclature. A precise taxonomic evaluation of a bacterium deployed in probiotic form can provide substantial insight into its overall safety for human consumption. Analyses of this nature also allow a delimiting of strain and species boundaries among closely related isolates along with a snapshot of the genetic and phylogenetic stability of a particular “strain”. This latter endeavor becomes even more important given the evolutionary implications for long-term application of specific bacterial isolates as probiotics in specific food or supplement commodities. The evolutionary landscape of bacterial strains often is dappled with numerous examples of vertical and horizontal change resulting in an isolate swarm. In certain instances, selection for specific clonal variants within the swarm can lead to the emergence of highly adapted individuals and ultimately new strains or subspecies. Such implications may confound stability among commercialized bacterial cultures over time. Facile genotypic and phenotypic approaches are now available that are capable of capturing and estimating this diversity. In addition, phylogenetic applications can provide further insight into the microevolution of strains. Here, we present several examples for this paradigm among pathogenic species known to associate with the food supply along with some of the widely applied genetic and genomic technologies now available that readily document this evolution. Finally, the implications of phylogenetic analysis of strains and species designated as live microbial ingredients will be discussed.

Naming and Marketing of Strains - An Industry Perspective

Duane Charbonneau, PhD, Procter & Gamble

Appropriate taxonomic identification of probiotics is an essential component of strain commercialization. It is necessary for regulatory submissions, patents placements and quality assurance. Establishment of strain-typing protocols is an important component and necessary for probiotic development. Taxonomic identification is valuable to assure appropriate lineages of newly discovered strains to those with a safe history of use in the host of choice. Several methods are available for determining taxonomic relationships: these include phenotypic determinations, structural lipid analysis, functional genomics and DNA sequencing of the 16S rRNA gene. Strain-typing methods such as bacterial barcode (rep-PCR) and Pulsed Field Gel Electrophoresis have also been utilized. Each method has limitations with respect to the precise taxonomic identification of any particular strain. Next generation sequencing of whole genome offers great promise for taxonomic elucidation in the future; however, current genome databases are limited in size. Thus bacterial nomenclature remains in a state of flux as new tools to assess taxonomic relationships are developed. Many commercial suppliers of probiotics utilize trade names in addition to scientific names to avoid the need to constantly modify product information and not confuse consumers as well as regulatory agencies. Trade names assure the consumer that the probiotic strain or strains in the product remain constant. Bacterial nomenclature name changes although sometimes necessary can become confusing to the scientist, regulator and consumer. Bacterial taxonomy is important but until definitive tools for taxonomic relationships are established more emphasis should be placed on strain typing, preclinical data, clinical safety and efficacy evaluations.