The March of the Probiotics

The battle between good and evil is a concept most people can grasp, which is one reason why probiotics have enjoyed increasing popularity in the past five to 10 years. With digestive systems struggling to keep up with modern diets and lifestyles, the beneficial bacteria that work to preserve certain areas of the gastrointestinal (GI) tract have taken the stage as the next big thing in the nutrition and health markets.

Whether they knew it or not, the yogurt-eating populations were the early adopters of probiotic health; and it was yogurt that kicked started the focus on functional probiotic foods, as well as the use of specific or proprietary strains for either health or marketing benefits. Sure, probiotic supplements wet around, but that market was always niche until more recently. According to BCC Research, of the $21.6 billion in global sales of probiotic ingredients and finished products in 2010, probiotic foods accounted for a dominating 91 percent ($19.6B), and supplements, at 6.4 percent ($1.3B), accounted for the next biggest chunk. The firm predicts 2015 global probiotics sales will reach $31.1 billion, a 7.8-percent compound annual growth rate (CAGR)a 7.5-percent CAGR is expected for functional products, and a 9.6-percent CAGR for supplements.

This is not to say that probiotics have outgrown their niche moniker, but the potential has been teasing at the edge of stardom, if only research would catch up. The European Food Safety Authority (EFSA) has lead the way in probiotic claims resistance, essentially claiming a lack of sufficient research to prove claims for digestive and other health benefits. Notably, Dannon and Nestle were mad to remove claims that consumption of their probiotic functional foods would confer immune benefits, especially involving colds and the flu.

While the industry and supporting scientistswho have published numerous research results in peer-reviewed journalshave ramped up the pressure to get some kind of digestive claim approved, it appears there will not be a claim for digestive, immune or any other health benefit from probiotic consumption approved anytime soon.  For now, the industry continues to focus on filling research gaps relative to these health benefits.

Its true that probiotics have long been studied for digestive health, and that continued research supports their efficacy in this area, said Peggy Steele, global business director for Danisco Health and Nutrition, who noted the researchers at Daniscos dedicated health and nutrition center are bringing consistency and repeatability to the science in order to further establish the benefits. In addition, we are bringing the same methodological approach to immune health benefits, which have been made difficult with the regulatory interpretations of the available science. She assured Danisco continues to publish the results of clinical trials in respected, peer-reviewed journals, including several publications in the last few years; more have been accepted this year and are awaiting publication, and additional studies are currently underway. Newer areas where probiotics may provide a benefitincluding oral health, urinary tract health and vaginal healthare also being evaluated.

Isabelle Champié, global marketing director for Institut Rosell-Lallemand, agreed oral care and womens health are burgeoning areas for probiotics, as are stress management, atopic dermatitis and general wellness. There is a variable level of scientific documentation published for these conditions, she said. Immunity and stress by far have the most supportive scientific documentation, while the other health areas are more emerging, but research is growing quickly in those fields.

While there is a wealth of research on the primary digestive health benefits of probiotics, digestive health also contributes in many ways to overall health and wellness by a variety of mechanisms, explained Tim Gamble, president and CEO of Nutraceutix. Increasingly, science is documenting the systemic benefits of probiotics, including research and compelling evidence in the areas of immunity, as was documented in research on the Immunobiotix® product, he noted.

Still, the probiotic evidence pool is filled largely by digestive studies, so the GI benefits will likely stay front and center, according to Michael Shahani, director of operations for Nebraska Cultures.  In the digestive system, beneficial bacteria contribute to a healthy GI function by competing with potentially harmful bacteria in the intestines.

However, you cant just throw any old probiotic into the intestinal flora cauldron and expect all the promised benefits publicized. Champié explained strain specificity is critical because published clinical and pre-clinical data is based on research conducted on specific strains, and not all strains are equal.  By knowing the specific strains, formulators can use the scientific studies done on that strain to back up the benefits, she said.

Albert Dahbour, chief sales officer at Wakunaga of America, explained different strains are thought to colonize in different parts of the body, notably in the intestines, and they also perform various functions based on their genus and species. However, certain strains are classified in a unique genus (family) and species because of characteristics they exhibit, he said, noting when you get down to the species level, different strains in the same genus will have some similar benefits.  More importantly, other aspects of efficacy are equally important: strain source, strain type, acid resistance, heat resistance, stability, etc. Therefore, when formulating, companies should look at the complete picture of efficacy and not just strain specificity.

Shanani advised strain specificity is important if you are making specific claims based on specific research done with a specific strain. For example, Dr. Shahanis® Lactobacillus acidophilus DDS-1 strain, manufactured by Nebraska Cultures, is supported by a large body of research, he said. It is unknown if other strains of L. acidophilus would have those exact characteristics and benefits.  However, it is likely that many strains of a certain species will have at least some of the same characteristics.

Gamble took a less rigid approach to strain specificity, reasoning it is important but, to-date, most research demonstrating the potential merits of individual strains does not usually rule out the possibility that other closely matching strains may deliver the same benefits of those shown in individual strain research.  Most commercially funded research is going to focus on that providers strains, and exclude testing and/or documentation and publication of third-party strains, for obvious cost and competitive reasons, he explained, but added strain-specific research is important.  Historically, in a sense, benefits have been a bit generalized.  As the library of conducted research continues to flesh out, we should see new research working hard to identify more precise mechanisms of action and the contributions to health that will bring strain-specific benefits into stronger focus.

Kevin Mehring, global business director from Danisco, agreed with the mantra all strains are not equal, citing the specificity of the research.  Determining which strains are effective and at what levels is an important component of our ongoing research program, he said. But simply demonstrating the efficacy of a strain is not enough. To deliver the specific health benefit, the dose must meet or exceed that used in the clinical studies. 

This issue of dose and delivery is important for formulators of probiotic-based products, especially functional foods. Unlike other natural products ingredients, probiotics are living microorganisms and are measured in unique ways. Like an army of health soldiers, probiotics are counted, with many products labeling the total number of bacteria alive at time of manufacture. A common unit of measure for this has been colony-forming units (CFUs).

Unfortunately, historical research and even store shelves dont reveal much in terms of just how much of a given probiotic should be consumed to achieve desired results, Gamble said, pointing out the increased CFU counts on labels in recent years has had more to do with marketing competition than research.  

However, Shahani reasoned it is pretty clear that at least 1 billion probiotic bacteria need to be ingested to achieve a benefit. We recommend 5 to 10 billion CFU/d as a maintenance dose, twice that for someone recovering from food poisoning or antibiotic therapy, he said. For formulators, he warned manufacturing processes can affect the potency of probiotic products significantly. It is possible to kill all the bacteria in processing if proper steps arent taken, he explained, noting certain processes such as tableting can easily kill probiotic bacteria. It is important to keep probiotic bacteria cool and dry during all phases of processing.

Champié added to the dosage recommendations, reporting it is generally recognized one would use 1 billion CFUs for maintenance and 10 billion CFUs to address a specific condition. Again, this will depend on the strain and how much was used in the published clinical studies, and it can vary greatly from strain to strain, she advised. Echoing the concerns over the potential negative effects of processing, she urged good-quality probiotics should always guarantee and state the number of live probiotics (in CFUs) in the finished product and at the end of shelf life.  It is the responsibility of the manufacturer to ensure its product stability because if the probiotic is not stable, it wont be effective.

Steele agreed the doses reflecting existing research can depend greatly on strain used and benefits investigated. However, she noted when it comes to providing a specific health benefit, the delivery of live probiotics to the site of action is critical. This means probiotics not only have to remain viable throughout the shelf life of the dietary supplement or nutritional product, they also have to survive transit in the acid and bile conditions of the GI tract, she explained.  HOWARU® Premium probiotics have been shown to have strong performance in all of these criteria.

Delivery may well be the biggest issue in the probiotics market outside of health claims approval struggles. This is important, Champié explained, because probiotics are microorganisms that must remain alive to be effective.  She called stability a critical issue and advised manufacturers must carefully monitor processing conditions. Key processing conditions that affect probiotic survival would be temperature, pressure and compression, humidity level or pH, and how the probiotic interacts with the other ingredients, she said. For example, some ingredients can be bacteriostatic or even bactericidal.  In this instance, microencapsulation, which protects the probiotics from harsh processing conditions and ingredient interactions, is often used.  Institut Rosell-Lallemand has developed a microencapsulation technology (Probiocap®), that we use in our ProbioStick to protect the probiotic on its journey through the digestive tract into the stomach and the intestines.

Mike Bush, vice president of business development at Ganeden Biotech, noted spore-forming Bacillus coagulans can go through manufacturing, storage and shipping conditions traditional probiotics couldnt previously endure. For some applications formulators had previously tried, they found themselves using 300 percent to 400 percent overages just to meet their target shelf life, he said. With Ganeden BC30, we hit spec every time with little to no overage needed.

Gamble punctuated the critical importance of delivery. From our perspective, in the research and commercial manufacturing worlds, there has been a disturbing lack of consideration given to addressing this issue, particularly when it is proven and widely recognized that traditional, natural probiotics are perishable on the shelf and are greatly denatured by stomach acids, therefore hindering the effectiveness of inexpertly manufactured and poorly delivered probiotics in a dramatic way, Gamble said. He explained Nutraceutix created strain-independent processes and technologies designed to deliver viable organisms to the consumer at the point of purchase, and then deliver viable organisms past damaging stomach acids, creating probiotic supplements that are more potent than other forms of probiotics like powders, capsules and foods.  Consider that just one BIO-tract® caplet with LiveBac processing can deliver more live organisms to the intestinal tract than dozens of capsules or cups of yogurt (and that is assuming that those capsules or yogurts are consumed freshly after being manufactured, whereas LiveBac/BIO-tract caplets can be formulated to meet label claim after 18 months when bottled and kept at room temperature or better).

These characteristics factor into what kinds of products can effectively contain probiotics. The single most potent and efficacious format for probiotics is in dietary supplement form, Gamble stated. Its not even close. There are no particularly effective, palatable or economical ways for functional foods, beverages, personal care products or even cultured dairy products to even approach the therapeutic potential of probiotics in dietary supplement form.

Steele agreed supplements are an ideal delivery vehicle for probiotics. You can easily control the amount delivered and the environment, she said, noting HOWARU probiotics are very stable and have good survivability. Daniscos patented stabilization technology keeps our probiotics in top condition without the need for refrigeration. They also provide industry-leading shelf stability, along with the necessary robustness to arrive at the site of action viable and ready to work.

Still, Steele and Mehring contend probiotics can and are added successfully to many foods and beverages. In this category, products traditionally refrigerated have been the starting point. Obvious candidates are yogurts and other dairy-based beverages where probiotics are already widely used, the pair confirmed. As probiotics move beyond the dairy aisle, beverages are the next logical format, because of the good stability of probiotics in various beverage applications.

Consider Champié another champion of supplements as the ideal vehicle for probiotics. Supplements are easier to formulate, the matrix is more readily adaptable and there arent any problems with ingredient interaction or manufacturing issues, she reasoned.  However, while additional R&D work is needed to successfully include probiotics in foods and beverages, there are some products that are well-suited to probiotics, such as breakfast cereals and juice for children, she offered. Some strains are also more adaptable than others, and the emergence of spore-forming strains (i.e., B. subtilis ) offer an enormous amount of new possibilities.

Bush said Ganeden BC30 probiotics needs three  things to activateheat above 30 degrees, lots of moisture and a substrate to feed on (carbon-based, such as sugars)and are, thus, currently limited to refrigerated beverages. However, because the bacteria have a spore inside that protects the bacterias genetic material from harsh conditions, the ingredient can withstand the heat and pressure of processing, he said, adding the ingredient is used in a wide range of applications including baked goods, ready to drink (RTD) beverages such as hot tea, soup mixes, oatmeal mixes, confections, pasta and many other food items. 

Shahani summed up the task of bringing probiotics to various applications, explaining probiotics are best utilized in products that are designed to preserve the probiotic potency and keep them alive; and are perceived as products that can confer a probiotic benefit. For example, Kraft tried to market a probiotic cheese some years ago, he recalled. It was a very good vehicle for probiotics, but consumers didnt perceive cheese as a product that should have probiotics in it, so the product failed. Another example, he said, are softel supplement products: Probiotics are easily killed in the manufacturing process of softgels, so they are not a good vehicle for probiotics although consumers would probably consider softgels a good vehicle for probiotic supplements.

Among the more interesting applications outside of the staple refrigerated dairy and drink products, probiotics in chocolate is a surprisingly good match, Shahani said. Dark chocolate is perceived as having health benefits, and chocolate fortified with probiotics could be a great success. He also noted probiotics in powdered meal replacements or sports drinks is also an interesting and viable application. 

In other trends, Gamble noted fielding an increase in requests for combination products, those involving probiotics with other actives to address particular conditions or market segments.  With the flexible and patented BIO-tract delivery technology, we can formulate some very creative combination products that capture consumer interest, and foster loyalty through simplified dosing and heightened bioavailability.

Considering probiotics are such vulnerable cargo and their use in innovative applications is tricky, formulators may rely on probiotic suppliers for guidance. Proprietary strains, patented technologies and research support, as well as expertise in handling and using probiotic ingredients, are just a few of the ways  probiotic suppliers assist formulators and manufacturers. 

According to Shahani, Nebraska Cultures provides protocols for storage, manufacturing and testing of probiotics. We help arrange for third-party testing of products, he added, We also make our science and marketing personnel available for consultation with our customers if they need or want that.

Similarly, Champie noted Institut Rosell Lallemand works closely with its customers to provide them with full technical, marketing and regulatory support. We guarantee the quality of our products in terms of stability, consistency and safety, she assured. In fact, at Supplyside West Trade show in Las Vegas, October 2011, the company launched a new comprehensive guide for formulators, to help them design their own probiotic formulation, using the best of our scientific and technical expertise, Champie said.

Good probiotic suppliers are invested in their customers success, Mehring assured. As such, we start with formulation assistance: helping them to select the most appropriate stains, excipients, processing aids and flavors, he explained, noting Danisco also offers advice on which finished format to choose, along with the requirements for ensuring optimum probiotic efficacy and survival during shelf life. Another step is making certain our enumeration procedure is suited to the end product; our scientists work closely with a customers chosen lab to ensure consistency.

Another critical area for support is in regulatory guidance. With the scientific substantiation of food and supplement claims under significant and lengthy review by regulatory agencies, customers also rely on Danisco for claims language guidance, he said. Our team of regulatory experts can help navigate todays complex regulatory landscape.

Given the increased attention probiotics have garneredalbeit primarily in conjunction with growing awareness of digestive health issues and solutionsthe market for probiotic products still has numerous obstacles, including regulatory (health claims), technology (probiotics are sensitive to many environmental and processing factors) and marketing (consumers can be finicky about which functional foods should contain probiotics). Continued research on health benefits, technological innovations and market focus data will help this small-but-expanding market niche reach its potential.