Products with Probiotics

Products With Probiotics

In the United States, most probiotic products are either foods or dietary supplements. A few probiotics are marketed as medical foods. Although fermented dairy products such as yogurt and kefir are typically associated with delivery of “beneficial cultures”, the types of foods claiming to deliver probiotics has expanded to include granola and candy bars, frozen yogurt, cereal, juice and cookies. Whether or not any given product, even ones that claim to contain “probiotics”, actually deliver adequate amounts of efficacious probiotic strains cannot be ascertained from just looking at the product. Consumers can contact the manufacturer to determine what studies have been conducted on their specific product as formulated and what health benefits should be expected. Products are required by law to be labeled in a truthful and not misleading fashion, safe for their intended use, and be manufactured under Good Manufacturing Practices. However, it is not practical for regulatory authorities to verify compliance with these laws for all products.

In food products, the probiotics used are primarily Lactobacillus, Bifidobacterium and Streptococcus thermophilus, and more recently Bacillus. Yogurt is a primary food vehicle for probiotics. It is produced by fermentation of milk by two starter cultures, Lactobacillus bulgaricus and Streptococcus thermophilus. In the United States, post-fermentation heat treatment of yogurt, which kills all live cultures, is allowed. To help consumers distinguish between yogurts that contain live active cultures and those that have been heat treated, the National Yogurt Association established a “Live Active Culture” seal. The seal is available for use by any yogurt manufacturer on packaging and requires refrigerated yogurt to contain 108 viable lactic acid bacteria per gram at the time of manufacture. The seal also can be used on frozen yogurts containing 107 viable lactic acid bacteria per gram at time of manufacture. However, these counts do not differentiate probiotic bacteria from starter culture bacteria (L. bulgaricus and S. thermophilus), and therefore the seal is not useful in determining if adequate levels of added probiotic bacteria are present in a yogurt. In other words, the standard refers to a total number of live cultures and levels of each microbe present do not have to individually meet the standard.

The dietary supplement market for probiotic cultures seems to be a more diverse market than probiotics for dairy. The supplement market contains many different product formats and contents, including capsules, liquids, powders and tablets. If properly prepared and stored, probiotic bacteria can remain viable in dried form and reach the intestine alive when consumed. A diverse array of bacterial genera and species are represented in these products, including Lactobacillus, Bifidobacterium, Saccharomyces, Bacillus and Enterococcus.

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Regulatory Considerations

Probiotics could potentially be regulated as a variety of different products in the United States:

  • Conventional foods (For consumption by general population)
  • Dietary supplements (A subcategory of foods, the dietary supplement category was created in 1994 by the Dietary Supplement Health and Education Act. The products are meant to be used as oral supplements to the diet, and are not to be represented as meals. However, labels can stipulate target population.)
  • Medical foods (Foods used under medical supervision for patients needing special dietary support for medical condition.)
  • Drugs (A drug is meant to cure, treat, mitigate, prevent, diagnose or cure disease. Drugs composed of live microbes are deemed “biologics” by the FDA’s Center for Biological Evaluation and Research.)
    • Drugs for animal use
    • Drugs for human use
  • Feed additives (Termed “Direct fed microbials” by the USDA.)

The same probiotic strain could in theory be used in any of these regulatory categories, assuming that evidence for efficacy is available. The regulatory category of a probiotic product is determined by:

  • Intended use (which is largely defined by the nature of the claims made)
  • Formulation (for example, capsules and pills cannot be conventional foods)
  • Route of administration (foods and supplements must be orally administered)
  • Target consumers (conventional foods are meant to be consumed by the general public; animal vs. humans)
  • Safety (foods must be comprised of GRAS substances or approved food additives only; no “risk vs. benefit” analysis is allowed for foods, but is acceptable with drugs)

If a product claims to have an effect on the cure, treatment, prevention, mitigation or diagnosis of a disease (e.g., “helps treat ulcerative colitis”), the product is a drug. Claims of health benefits on foods foods or dietary supplements must be of one of two types:

  • Health claims. Under US law, the term “health claim” has a specific definition. It refers to a claim that the food can reduce the risk of disease. Such claims are allowed, but only if approved by FDA or an authoritative body. These claims may be qualified. Evidence to support these claims should be generated on the general or at-risk population and must be published. Currently, there are no approved health claims for probiotics.
  • Structure function claims. These claims relate the food or ingredient to normal functioning of the human body. No approval or notification is required for such claims to be used on foods. For use on dietary supplements, FDA notification is required.

In the United States, a product must have scientific substantiation for structure/function claims. The burden of proof rests with the manufacturer. Although the FDA does not require premarket approval of such statements, the manufacturer must provide scientific justification for use of any health statements if asked by the FDA. In December 2008, the FDA Center for Food Safety and Applied Nutrition published a Guidance for Industry on “Substantiation for Dietary Supplement Claims“. This document describes the amount, type, and quality of evidence FDA recommends a manufacturer have to substantiate a claim. Although targeted toward dietary supplements, the concepts are applicable for structure/function statements made on food.

Some useful references on regulatory issues with probiotics:

With regard to the regulations on product quality, the FDA issued (August 24, 2007) a final ruling establishing regulations to require current good manufacturing practices for dietary supplements to be phased in over the next few years. Although these regulations don’t address verification of efficacy claims, they will hopefully improve the compositional quality (identity, purity, and strength) of probiotic supplements on the U.S. market. This ruling, however, does not apply to conventional foods, only dietary supplements.

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Safety

Although the use of traditional lactic starter bacteria for foods and dietary supplements is considered safe, the more recent use of intestinal isolates of bacteria delivered in high numbers to consumers with potentially compromised health has raised the question of safety. In the U.S., Title 21 of the Code of Federal Regulations (21 CFR) and the FDA Office of Premarket Approval lists microorganisms which are approved food additives or which enjoy Generally Recognized as Safe (GRAS) status. It should be kept in mind, however, that “GRAS” status is only for a specified food use. (It is not a term that applies to dietary supplements.) The microbes themselves are not considered GRAS, but their use as agents of fermentation in dairy foods is. This list specifies that harmless lactic acid producing bacteria, including Lactobacillus acidophilus, used as optional ingredients in specified standardized foods (such as yogurt and buttermilk) are sanctioned. In addition, this list specifically includes Streptococcus (thermophiluscremorislactis, and lactis subsp.diacetylactis), Lactobacillus (bulgaricusfermentumlactis), and three Leuconostoc species. Note that several probiotic Lactobacillus species (e.g., reutericasei,paracaseigasseriplantarum) and bifidobacteria are not specifically on this GRAS list. However, the acknowledged nature of this list is that it is partial and the absence of a microbe on this list does not imply it is not safe for use. These species are accepted as safe in Japan and Europe.

Several probiotics have been assessed for GRAS status by qualified experts. As of January 2012, the following GRAS notifications for probiotics are on file with the FDA:

  • Bifidobacterium longum BB536, for use as a food ingredient and in infant formula
  • Lactobacillus casei subsp. rhamnosus GG, for use in infant formula
  • Lactobacillus reuteri DSM 17938, for use in food
  • Bifidobacterium lactis Bb12 + Streptococcus thermophilus Th4, for use in infant formula
  • Lactobacillus rhamnosus HN001, for use in infant formula
  • Bifidobacterium animalis ssp. lactis Bf-6, for use as a food ingredient

The FDA GRAS notification process is optional. Self-determination of GRAS status can be conducted by a company and kept confidential. The GRAS notification process entails submission of the documents supporting the conclusion of GRAS status to the FDA, allowing them to comment. The notification process is public and available on the FDA website.

The safety of lactobacilli and bifidobacteria has been considered by qualified experts in the field in a variety of forums. The general conclusion is that the pathogenic potential of lactobacilli and bifidobacteria is quite low. This is based on the prevalence of these microbes in fermented food, as normal colonizers of the human body, and the low level of infection attributed to them. However, reports of association of lactobacilli and bifidobacteria with human infection (commonly endocarditis) in patients with compromised health suggest that these microbes have rare opportunistic capability. In 2011, a report by the Agency for Healthcare and Research Quality published a comprehensive report on the safety of probiotics. The report concluded that reporting of adverse events in probiotic intervention studies was inadequate and that rare adverse events are difficult to assess from the published literature.

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Commercial Strains Sold As Probiotics

Selected probiotic strains and products available in the US and Europe.

This table does not constitute an endorsement of any of these products, nor does it include all strains/mixtures currently available.
1Parenthetic entries indicate alternative strain designations; B. lactis is a shorthand designation for Bifidobacterium animalis subsp lactis.
2
Strains sold as ingredients are available in numerous consumer products; contact responsible company for product list. Products listed are examples and do not reflect a comprehensive list of available products containing the indicated strain.

Strain1 Product containing strain2 Sold by
L. acidophilus NCFM
B. lactis
Bi-07
B. lactis HN019 (DR10)
L. rhamnosus HN001 (DR20)
Sold as ingredient DuPont Nutrition Biosciences ApS
(Madison WI)
Saccharomyces cerevisiae  boulardii Florastor Biocodex (Creswell OR)
B. infantis 35624 Align Procter & Gamble (Mason OH)
L. rhamnosus R0011
L. acidophilus R0052
Sold as ingredient Lallemand (Montreal, Canada)
B. lactis Bb-12
L. acidophilus
LA5
L. paracasei CRL 431
L. fermentum VRI003 (PCC)
L. reuteri RC-14
L. rhamnosus GR-1
L. paracasei F19
Sold as ingredient Chr. Hansen (Milwaukee WI)
L. casei Shirota
B. breve Yakult
Yakult Yakult (Torrence, CA)
L. casei DN-114 001
B. animalis DN-173 010
DanActive fermented milk
Activia yogurt
Dannon (Tarrytown, NY)
L. johnsonii Lj-1 (NCC533; L. acidophilus La-1) Nestlé (Lausanne, Switzerland)
L. plantarum299V
Sold as ingredient
Good Belly
Nature Made Digestive Probiotic Health
Probi AB (Lund, Sweden)
NextFoods (Boulder, Colorado)
Pharmavite
L. reuteri ATCC 55730 (“Protectis”) BioGaia Probiotic chewable tablets or drops Biogaia (Stockholm, Sweden)
L. rhamnosus GG (“LGG”) Culturelle Valio Dairy (Helsinki, Finland)
L. rhamnosus LB21
Lactococcus lactis L1A
Sold as ingredient Essum AB (Umeå, Sweden)
L. salivarius UCC118 University College (Cork, Ireland)
B. longum BB536 Sold as ingredient Morinaga Milk Industry Co., Ltd.
(Zama-City, Japan)
L. acidophilus LB Sold as ingredient Lacteol Laboratory (Houdan, France)
Bacillus coagulans BC30 Sustenex, Digestive Advantage
Ingredient for food use
Schiff Nutrition InternationalGaneden Biotech Inc. (Cleveland, OH)