“Probiotics” are all about life—the word itself means “for life.” It juxtaposes with antibiotics, which are designed to kill antagonistic microorganisms—and often take several “good guys” along with the bad.
 

Perhaps most critical, probiotics improve and maybe even preserve the lives of users. But, in order for this to happen, the probiotics microorganisms—beneficial bacteria—must stay alive themselves. Michael Shahani, chief operations officer, Nebraska Cultures, Inc., Walnut Creek, CA, says, “Maintaining the stability of probiotic bacteria is one of the most important issues—if not the most important—being worked on by the probiotics industry.”
 

He went on to discuss the four elements that are detrimental to the stability of probiotic bacteria—moisture, heat, oxygen and light. “In processing or using probiotics in functional foods, these four elements must be eliminated or at least reduced as much as possible,” he explained. “In addition, most lactic acid bacteria will slowly die off over time at room temperature, and even at refrigerated temperature, although at a much slower rate.”
 

Unfortunately, Mr. Shahani noted, “There is no ‘magic bullet’ to insure stability at this point; just keeping the products as cool and dry as possible is the best way to maintain their effectiveness.”
 

But introducing refrigeration adds a barrier to regular usage. If all other nutrients in a consumer’s regimen are kept in a medicine chest or pantry closet, then it takes extra effort to procure the probiotics supplement from the refrigerator. And many consumers just won’t do it.

So the quest for a truly room temperature-stable probiotics delivery system goes on. According to Mr. Shahani, whose company supplies the DDS-1 strain of Lactobacillus acidophilus, “Various kinds of coatings or microencapsulation techniques are being tried, but nothing works as well as refrigeration.” He suggests that manufacturers “get used to over-formulating so that enough live bacteria are available in a product even if some or most die off over time.”
 

These are the physical challenges confronting the efficacy of probiotics. A completely different kind of threat became prominent about a year ago—and even though it was deflected, it is still lurking. This was the NDI Draft Guidance proposed by FDA, provisions of which could have proved fatal to the probiotics category.
 

Specifically, the Guidance took the position that “not all bacterial microorganisms are dietary ingredients, and a microorganism that is not a dietary ingredient cannot be a NDI. … Bacteria that have never been consumed as food are unlikely to be dietary ingredients.” (Section IV, C, Question 4).
 

The document further stated, “FDA considers each strain of a bacterial or yeast species to be a separate ingredient.” (Section VI, A, Question 17). Thus, any new strain of bacteria used in a probiotic product might be disallowed as a dietary ingredient.
 

Happily, the regulators withdrew this initial interpretation. But they didn’t go away completely, and in June announced that a revised Draft Guidance would be submitted near the end of this year. Wondering what version 2.0 might contain is enough to keep some probiotics suppliers up at night.
 

Despite these negative forces, however, probiotics sales continue to mount, and the category’s infiltration into mainstream food lines is nothing if not impressive. Activia is the most recognized supermarket product boasting probiotic benefits. Also note, however, that in July, Minnesota-based General Mills started shipping the first of 40 new yogurt products in an attempt to hold its own against newly popular Greek-style yogurts, which feature an extra-thick and creamy texture. 
 

Included in the launch package are Yoplait Greek 100, a 100-calorie Greek yogurt that has been endorsed by Weight Watchers International, Inc., and Yoplait Fruplait, which, according to General Mills, has twice as much fruit as most other leading brands.
 

Foods vs. Supplements

Yogurt is—clearly—the most accessible of probiotics delivery mechanisms. The only problem, according to industry pundits, is that it is virtually impossible to pack enough probiotic punch into a cup of yogurt, sell it at a competitive price, and expect it to do much good for the user.
 

Tony Blanch, director of quality for Nutraceutix, Redmond, WA, said, “Conventional whole foods, if available and eaten consistently, might be sufficient to promote a balanced digestive microbiota. However, today’s hectic lifestyles, limited good food availability, and poor diet choices routinely lead to digestive issues. Probiotic-supplemented foods, although an improvement, cannot typically supply enough probiotic organisms to provide a therapeutic correction to the gut ecosystem. Dietary supplements with significantly higher potency are clearly the treatment of choice to correct and maintain proper balance in the GI tract.”

Mr. Blanch describes his company as  “an NSF-certified GMP contract manufacturer of probiotics in bulk powder and finished dietary supplement forms, including standard capsules and advanced tablets and caplets in bulk and in fully finished bottles.”
 

The quality control executive points out, “In foods, there are material shelf life and dose limitations for probiotics. In the dietary supplement sector, the best shelf-stable viability and consistent dosing through expiration are found in tablet and caplet forms. Two-piece hard shell capsules, although they are relatively inexpensive to produce, generally suffer from poor shelf stability, which can negate their often-high initial (claimed) potencies. Powdered forms offer some flexibility in application but, like capsules, may only be of benefit if packaged and stored to maintain viability through expiration.” 
 

‘Sick’ Transit Gloria Mundi

Unlike a cruise aboard a luxury liner, the trip made by probiotics organisms from mouth to intestines is rarely half the fun. More often, it is no fun at all, but a journey fraught with peril.

Mr. Blanch of Nutraceutix says, “Technologies to get live probiotics through the harsh conditions of the stomach and deliver them in a viable state to the intestinal tract should be a primary consideration for researchers, brands and consumers seeking truly therapeutic forms of probiotic products.”
 

“All forms of delivery are possible: food, drinks, supplements in any form. I would not say that one is better than the other but rather that it depends on the consumer’s habits and lifestyle,” said Isabelle Champié, deputy manager/global marketing director at Montreal, Canada-based Lallemand Health Solutions. 
 

“Whatever the way of delivery, the main criterion is survival,” she emphasized. “Let’s always keep in mind that the probiotic should be alive when reaching the gut, its site of action. It is essential to verify that product manufacturers ensure appropriate bacterial count by the end of the product shelf life.”
 

According to Ms. Champié, Lallemand offers both finished product formulations, backed with human and animal study data, as well as individual strains for custom-made blends, either for supplements or food products. The company offers numerous products with digestive system benefits, including: Lacidofil, a blend of two specific probiotic strains, Lactobacillus Rosell-52 and Lactobacillus Rosell-11, shown to be effective in preventing and treating antibiotic associated diarrhea in children and reducing lactose intolerance; Protecflor, which combines the complementary activities of documented probiotic yeast and bacteria; pharmaceutical grade Saccharomyces boulardii, which has been named in more than 300 publications as helping to prevent diarrhea; and B. subtilis R0179, a heat-stable strain that is said to be naturally part of the human microflora. 
 

Other Lallemand products appear to improve immunity. Ms. Champié calls Lafti L10 “feel-good” bacteria because they support immune defenses and improve general well-being. ProbioKid combines three probiotic strains (Lactobacillus helveticus Rosell-52, Bifidobacterium bifidum Rosell-71, Bifidobacterium infantis Rosell-33), and a prebiotic (fructooligosaccharide-FOS). In a randomized, double-blind, placebo-controlled pilot study, this synbiotic formula reduced the incidence of common winter infections (ENT, bronchopulmonary or gastric disorders) in school-aged children 25%. ProbioKid VitaC adds vitamin C to the mix.
 

Stress, Anxiety and the ‘Gut-Brain’ Axis

Stress and anxiety are the more novel areas where probiotic interventions are being studied. In June, a Lallemand press release reported on a gathering of neurobiologists, behavioral experts, gastroenterologists and animal nutritionists, which assembled in Chantilly, France to explore various aspects of the “gut-brain axis.” The scientists discussed conditions such as autism, anxiety and depression, in which the microbiota is altered. Research is now under way to try to link some of these conditions to a particular microbiota profile. 
 

In an animal model for anxiety and depression, a team led by Professor Stephen Collins, from McMaster University, in Hamilton, Ontario, Canada, showed that behavioral changes or stress alter the gut microbiota and that a particular neurotransmitter involved in the stress-response (the corticotrophin-releasing hormone, or CRH) could play a role by altering the gut physiology and hence the habitat of the microbiota.
 

Enter Rx

It probably was inevitable that aggressive natural strategies in the use of probiotic products would attract the attention of pharmaceutical manufacturers. No longer is it true, as Mike Bush, vice president of Cleveland, OH-based Ganeden Biotech, recently commented, that  “As a category, probiotics basically doesn’t exist at the pharmaceutical level.”
 

This past June, Enterologics, Inc., located in St. Paul, MN, cited the “remarkable increase in … scientific publications related to probiotics over the past five years” as its motivation for “developing probiotics as biologic drugs for specific gastrointestinal disease indications.”
 

Bob Hoerr, MD, PhD, the company’s president, said, “New techniques in molecular biology are making it feasible to better understand how probiotics interact with our bodies and the mechanisms through which they exert their effects. We believe that Probactrix, our E. coli M17 probiotic, … holds great promise and [we] look forward to demonstrating its potential role for treating specific disease conditions through clinical trials.”
 

In the meantime, however, the time-honored delivery systems—conventional foods like yogurt, supplements in tablet/capsule/powder formats and functional and/or fortified foods—continue to be the way most probiotics are ingested.
 

Mr. Bush, whose company sold its supplement business to Schiff in June 2011, favors functional foods as the “easiest choice for consuming probiotics without changing one’s lifestyle too much.”
 

Ganeden’s flagship product is BC30, a “patented strain of probiotic bacteria, Bacillus coagulans GBI-30, 6086,” which, he says, is “available as a powder and can be incorporated into virtually any processed food.”
 

Gregory Bonfilio, director of business development for Pharmachem Laboratories in Kearny, NJ, says several characteristics combine in probiotic products with the greatest market potential: “condition-specific applications and general well-being, immune and overall health support; [blending of] certain strains of lactobacilli and bifidus so that the result of the combination is greater than the individual; and the ability to administer those strains in a more consumer friendly or unique manner.”
 

His company, through an exclusive distributorship with Italy’s Probiotical, S.p.A., offers Bifiver, which was developed to deliver support against the number, intensity and duration of respiratory infective episodes such as cold, pharyngitis and flu, especially during the winter season.
 

Mr. Bonfilio says Bifiver is covered by two international patents and is microencapsulated with a “lipid system that coats the powders to protect them during manufacturing, through shelf life as well as through the gastric barrier, so they may adhere where they are supposed to, in the GI tract.” He cites a crossover study comparing so-called normal strains with microencapsulated strains. “The study showed the microencapsulated strains had five times greater absorption in the GI than the conventional strains, which allows our customers to use far less of a more potent product, thereby reducing costs,” Mr. Bonfilio explained.
 

The Pharmachem executive expresses pride in a delivery mechanism that uses a device similar to the well-known Pixie Stick candy package that allows probiotic powder to be introduced directly into the user’s mouth with no handling of the product, only its container. He is also high on an “unflavored probiotic that can go directly into yogurt so that the yogurt itself is the delivery form, providing enhanced probiotic value beyond its ‘live culture’ content.”
 

Into the Future

Looking forward, Rodger Jonas, director of national sales for P.L. Thomas Company, Morristown, NJ, said, “The ability to impact immunity, as a preventative measure, is a huge factor in utilizing probiotics. Alleviating symptoms such as gas is another application area. The targets of probiotics remain varied and will allow different segments to be targeted. Probiotics will change from a general good health product to a niche application approach. This is due to improved probiotics and new clinical studies.”
 

Mr. Jonas added, “You will see probiotics that survive in the gut and provide multiple benefits.” Some will be aimed at maintaining good digestive health. Others will be targeted for gas, or immunity, or colitis and Crohn’s disease. Other functional targets [might] include improving serotonin levels (mood) and formation of specific compounds in the gut (such as carotenoids and polyphenols).
 

According to Anurag Pande, PhD, vice president, scientific affairs, East Windsor, NJ-based Sabinsa Corp., his company has two ingredients in the probiotic range—LactoSpore and LactoWise. Both contain Bacillus coagulans as a probiotic strain. 
 

Dr. Pande says LactoSpore was launched as a room temperature-stable probiotic, obtained self-affirmed GRAS status in 2008, and has become an industry staple. 
 

LactoWise could be considered a “next-generation” probiotic product, he suggests. “It is a synbiotic that contains both probiotic and prebiotic components. The prebiotic portion contains fenugreek galactomannans, which provide nutrition for growth of the probiotic bacteria. Both LactoWise and LactoSpore are stable at room temperature with shelf life exceeding any non-spore forming lactic acid bacteria in similar conditions.”
 

In Dr. Pande’s view, for probiotics to attain its full market potential, shelf life stability is essential. “Probiotics requiring refrigeration suffer from limitations in terms of the products that can be formulated with them. Further, the activity also is not assured if the proper cold chain is not maintained,” he said. “These shortcomings can be overcome by use of spore-forming bacteria. The spore-forming bacterial such as B. coagulans have a longer shelf life at room temperature, so they are able to sustain their beneficial effect even in a harsh environment or throughout manufacturing processes without loss of activity.”

About the author: New Jersey-based freelance writer Alan Richman is the former editor/associate publisher of Whole Foods Magazine and a regular contributor to Nutraceuticals World. He can be reached at 609-619-3395 or alanrichman@yahoo.com.

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