Probiotics' 15 Minutes of Fame, and Counting

Before 2006 when Dannon marketed the heck out of its probiotic strain via Activiatouting digestive reliefconsumers werent really speaking up about their belly woes. Digestion was a hush-hush subject and was mainly dealt with behind closed doors; but, after 2006, that door opened, and probiotics got more than just 15 minutes of nutritional fame. Activia, and others, have opened the door for an honest conversation (not verbal, but conversing via their purchasing habits) between consumers and food and beverage formulators about digestion, which has paved the way for more probiotic innovation, conversations and demand proliferation.
The increased promotional efforts by large corporations, especially yogurt manufacturers, have not only resulted in increased sales for these companies, but has helped smaller companies, such as Oragenics, in some degree to get the message out, and be understood, that not all bacteria are harmful and that probiotics for a niche application, including oral care, can provide certain health benefits for consumers, said Robert Zahradnik, Ph.D., vice president of product development, Oragenics.
According to the Natural Marketing Institutes (NMI) Health and Wellness Trends Survey (2008 HWTD), awareness of the term "probiotics" has grown from a mere 9 percent in 2002 to 60 percent of American adults in 2009a 567-percent increase in awareness in only eight years. Three years after Activias launch, probiotics got another boost in 2009 when Proctor & Gamble launched its daily probiotic supplement, Align. Mintel said Aligns success may also have paved the way for more probiotic products to go mainstream.
In 2009, we noticed through our Nielsen Reports the market took a dramatic upturn with the launch of [Align], said Glenn A. Guadi, sales manager, consumer healthcare, Capsugel Americas Region. Its emphasis on educating the consumer helped other brands as well during the launch period.
Sure, kefirs been sold on street corners across Asia for many years, but it was a best kept secret rather than a go-to product for healthy digestion and a strong immune system. But thats all changing. In January 2010, Mintel asked 1,083 adults 18 and older: Do you eat any of the following food/drink types specifically for fiber/digestive health/regularity benefits? Thirty-one percent of males and 49 percent of female said they eat yogurt with probiotics. To build on this, Mintel also reported in its report Gastrointestinal Remedies: Digestive and Immunity Health U.S. April 2010, respondents showed a preference for more natural solutions to gastrointestinal (GI) problems. In fact, roughly half of the respondents who experienced a digestive issue in the last year said they would prefer to manage their digestive health through diet alone.
Consumers are concerned about the antibiotic residues in milk, meat and eggs and more concerned about antibiotic-resistant bacteria, said S. K. Dash, Ph.D., president of UAS Labs. This has made consumers prefer probiotics instead of antibiotics. Probiotics are safe to use and support digestive health and promote immune functions.

Outside the Dairy Carton

As a result of new advances in technology, probiotics unstable nature is finding its footing and opening up a world of new applications.
 There has been some improvement in understanding about how probiotics can be kept stable in food and beverage applications, so the new products appearing are more successful than those in the past, said Michael Shahani, director of operations for Nebraska Cultures Inc. Nebraska Cultures DDS-1 strain of L. acidophilus was recently used in a human clinical study at the University of Nebraska, showing the DDS-1 strain does persist in the human gut. We are getting numerous inquiries about putting probiotics in dried meal replacement and energy beverage mixes, infant formula, frozen yogurt mixes, chocolate and other foods. We expect quite a bit of new business for these applications, Shahani added.
Joanie Dion, technical representative, Lallemand Nutritional Food Ingredients, said: Probiotics in foods are still strong in the dairy industry, but are also being seen in beverages, long shelf-life products and even in baked goods. This is thanks to technical progress on the stability front, in particular the development of microencapsulation technologies and the selection of new, highly resistant probiotic strains. She cited Bacillus subtilis as an example, as it is resistant to baking, making it possible to bake probiotic breads, muffins, pastries and more.
Mike Bush, vice president of business development, Ganeden Biotech Inc., echoed Dion, stating: In addition to new microencapsulation technologies, which add to the stability of traditionally frail strains, the use of spore-formers such as Bacillus coagulans have allowed companies to develop shelf-stable probiotic products such as bread, pasta, tea and nutrition bars. This expansion, which has been in part driven by the availability of shelf-stable probiotics such as GanedenBC30, has been great for Ganeden. With more than 50 product launches and dozens more in the queue, we are offering product options to satisfy a wide variety of consumer tastes and interests.
The popularity of probiotics has also affected another probiotic vehiclecapsules. First, we saw a surge in demand for our vegetarian capsule Vcaps®, and we think the upswing in preference was linked in part to the increase in demand for probiotics, Guadi said. Second, the increased demand for probiotics has spurred innovation in our capsule delivery offerings. In conversations with manufacturers and marketers, Capsugel learned of the unique challenges associated with the manufacture of consumer health care products containing probiotics. They indicated a need for capsules with a lower moisture content. They also said they needed a way to protect probiotics from the acidic environment of the stomach so they could release in the intestinal tract. As a result of these conversations, Capsugel created new capsule technologiesDRcaps capsules, LWAcaps capsules and Vcaps® Plus capsulesto address these issues. Manufacturers and/or marketers can choose a capsule from Capsugels portfolio of choices that can be customized to their manufacturing, marketing and distribution needs, budget and consumer desires. For example, its DRcaps are made with hydroxypropyl methycellulose (HPMC) to slow down the capsule opening after swallowing, which helps protect ingredients in the capsules after swallowing from early activation caused by stomach acid.

From Macro to Micro

In addition to probiotics application expansion, research on their physiological benefits is also mounting. Digestion is just a macro look at probiotics. The micro view of probiotics is increasingly revealing, as research and science is finding more beneficial roles beyond digestion including oral care, skin care and immunity.
Isabelle Champié, deputy manager and global marketing director for Institut Rosell-Lallemand, said one reason the probiotics market has seen growth is because of the broadening of probiotics science. If gut health is still strong, other applications substantiated by scientific research have appeared such as immunity, womens health and more emerging segments such as lactose intolerance, atopic dermatitis, stress, etc., she said. In fact, Institut Rosell-Lallemand has been researching probiotics effects on stress and anxiety. Based on the understanding of the brain-gut axis concept, it is now obvious the gut microflora, and probiotics that interact with it, have the potential to interact with the gut-brain communication. A study using its Probio'Stick®a combination of Lactobacillus Rosell-52 and Bifidobacterium Rosell-175revealed its effectiveness in reducing the GI symptoms experienced by individuals suffering with chronic stress (Nutr Res. 2008;28(1):1-5). A 2010 clinical study with its Probio'Stick, which used several validated psychological self-assessment scales, showed it significantly alleviated psychological distress in volunteers (Br J Nutr. 2010;26:1-9) and was reinforced by a pre-clinical behavioral study that also demonstrated the anxiolytic-like effects of ProbioStick in rats.
The expansion of the traditional applications involving gut health into potentially new applications such as oral health, urinary tract health, upper respiratory health and immune health has also helped focus everyone on the many new areas where probiotics may help to promote health benefits, Zahradnik noted. With regard to the new application of probiotics to oral health, recently published peer-reviewed research regarding the three probiotics strains in the food ingredient, ProBiora3 from Oragenics, has suggested these strains are both safe (Int J Toxicol. 2009;28:357-67) and beneficial (J App Microbiol. 2009;107:682-90) for maintaining fresh breath and oral health not only in humans, but by extension, for companion pets.
Dash is another advocate for probiotics beyond digestion. UAS Labs has completed clinical studies on atopic dermatitis, which have been published, he said. A clinical trial on urinary tract infections is underway and expected to be completed by end of May.

Probiotic Confusion

As the numbers have proved, probiotic sales are up, application innovation is expanding and their beneficial health effects are broadening; but, are consumers really probiotic savvy and are they really diligent in meeting their bacteria needs? According to recent research data, consumer awareness is much stronger now, but theres still some work to be done.
While awareness has shown some dramatic gains, use of probiotic foods is much lower, with only 17 percent of the U.S. population indicating they have used probiotic-enriched foods in the past 30 days, said Steve French, managing partner, NMI. There may be several opportunities to increase the aforementioned probiotic usage rates. Most importantly, many consumers simply lack clear understanding of the benefits. This factor may be one of the major barriers to consumer usage; NMI research reveals consumers show very low and fragmented understanding of how probiotics can benefit their health. In addition, continued product expansion outside dairy should help probiotics in foods and beverages.
Champié agreed with French, comparing probiotic wisdom to vitamin wisdom back in the day. It seems that our understanding of probiotics is where the vitamin industry was decades ago, she said. Consumers understand probiotics are healthy, but are not aware of strain specificity and the variety of benefits of a strain. Going back to vitamins, we have now moved from the idea that vitamins are good for your health toward the understanding that they are all different and have very distinct effects: for example, consumers easily distinguish vitamin D from vitamin C. The same is true for probiotics; each strain is different and can have very different, or even antagonistic effects, and we need to educate consumers about this.
Zahradnik added: I believe there is a segment of informed consumers in the United States that seek out probiotic-containing products for purchase, but this percentage is still relatively small in America. Todays growth in the probiotics market is more a direct response to the level of national advertising by the large food companies than to an active understanding, and search for probiotics benefits, by the majority of purchasers.
Education is an important aspect of the probiotic market. From specified label claims to focused marketing campaigns, little by little, the industry is able to educate consumers on the full spectrum of probiotic benefits.

Stable on a Tightrope

Since probiotics are live bacteria, they are highly unstable by nature, and ensuring their efficacy and stability is one of the challenges in working with probiotics. Fortunately, many companies have made technological leaps in stabilization.
Traditional probiotics are inherently unstable, Bush said. They are living organisms that, unless stored in the perfect environment, are easily destroyed. So stability becomes an issue in manufacturing, shipping, storing and through gastric transit. Ganedens patented probiotic strain is inherently stable due to structure of the cells, which contain a small endospore. That spore is highly stable through heat, pressure, gastric acidity, and germinates and grows well when it reaches the gut. And this is accomplished without encapsulation, coating or otherwise augmenting the natural cell.

Oragenics has also worked to stabilize its probiotics and ensure their efficacy. The ability to stabilize probiotics that are freeze-dried or lyophilized for room temperature storage has helped Oragenics to provide viable probiotics in compressed tablets, Zahradnik said. Since the manufacturing steps during processing into tablets and then packaging can reduce the numbers of viable cells in the finished product, Oragenics adds a sufficient excess or overage of viable cells to account for these losses. A further overage is added to the probiotics tablets to address any losses in viable cell counts that might occur during normal storage at room temperature. The labeled amount of live probiotics in Oragenics mints/tablets is the amount that has been clinically tested for safety and effectiveness. The overage needed to maintain at least the labeled amount of live bacteria throughout the Best By period stamped on the product container has been determined through in-house long-term stability testing of finished and packaged product. Zahradnik said packaging can also play a role in stability. Every effort has been made to ensure the primary packaging is sufficient to protect Oragenics oral care products, especially from humidity, during long-term storage at room temperature, he added.
Institut Rosell-Lallemand tackled the stability issues by developing protection technologies. We have developed patented protection technologies for our probiotic strains (Probiocap®), and this has helped to extend the applications of our probiotics, Champié said, noting a couple application examples such long-shelf life food productschocolate or powdered food supplements. In terms of efficacy, we have an important R&D program that involves both pre-clinical and human studies run in partnership with leading research institutes, hospitals and universities around the world, she added. In our clinical trials, we test the finished products formula and not the individual strains so that our formulation doesnt change when its brought to market, thus providing efficacy data for the market and end-users.
From the shelf to the gut, its a struggle to ensure the stability of probiotics strains remain intact from ingredient supplier to manufacturer to retailer. We constantly strive to educate our customers and the general public about the need to handle probiotics appropriately in order to ensure their stability, Shahani said. We ship our raw materials only overnight or by refrigerated truck. We strongly recommend to manufactures that they put Store in a cool, dry place. For best results, refrigerate after opening. on their labels. In addition, we recommend manufacturers over-formulate sufficiently to maintain their label claim of potency, and that they do not put unrealistic shelf life or expiration dates on their labels.
Companies such as Capsugel know how unstable probiotics can be and have worked to develop stable delivery systems for probiotic suppliers. The pressure and heat from the tableting process is harsh and can compromise the stability of probiotics, Guadi said. This is less of a concern with encapsulation in general, but the low moisture content of Vcapswhich are made of hydroxypropyl methycellulose (HPMC)provide a distinct advantage. Probiotics are sensitive to moisture. Normal HPMC has a 4-percent to 6-percent moisture content at 50-percent relative humidity compared to 12 percent to 14 percent for gelatins. This means Vcaps capsules can help protect the probiotics from activating in the package.

As unstable as probiotics are in the formulation process, their market growth is stable. And as the industry continues to introduce new applications and spread the word on probiotics many health benefits, the market will continue to prove its stability and its right for more than just 15 minutes of fame.