Marian Zboraj04.01.07
One of the top 10 key trends for 2007, according to the "Ten Key Trends in Food, Nutrition & Health 2007" by Julian Mellentin, published by U.K.-based New Nutrition Business, is digestive health. More specifically, the future looks bright for makers of probiotics and dietary fiber.
Probiotics, also known as "friendly" bacteria, are used around the world to help support healthy digestion, provide immune support (or "natural defense") and maintain optimal health and wellness. Having originally been taught that bacteria are essentially bad for their health, it's hard for consumers to grasp the fact that bacteria actually keeps them alive, so although probiotics have gained consumer acceptance over the past few years, Todd Klaenhammer, PhD, distinguished university professor in the departments of Food Science, Microbiology and Genetics at North Carolina State University, still feels the category has a long way to go. "What people don't realize is that bacteria account for over 90% of the 'cells' associated with our body," he said. "So, in terms of pure numbers, we're mostly bacteria. Most of the bacteria associated with our bodies are very protective, aiding our digestion, modulating our immune system and protecting us from pathogens."
In 2001, the World Health Organization (WHO) defined probiotics as "live micro-organisms, which when administered in adequate amounts, confer health benefits on the host." Probiotics balance/restore intestinal microbiota, and according to Susan Abeln, principal scientist in research & development, P&G, Cincinnati, OH, in a balanced state, these bacteria perform a number of important functions that contribute to human health, including the synthesis of vitamins and other nutrients, and the secretion of digestive enzymes.
"Beneficial bacterial species protect against a state of 'dysbiosis,' which is an upset in the equilibrium that can cause digestive upsets," explained Dr. Abeln. Common factors that can trigger an imbalanced state include changes in diet, travel, stress, illness, aging, and the use of some medications, primarily antibiotics.
"The composition of the microflora is dominated by four types of bacteria: Bacteroides, Bifidobacterium, Eubacterium and Peptostreptoccocus," Dr. Abeln continued. "Bifidobacteria are widely thought to be the most important gram positive organism in the digestive environment. Bifidobacterial species remain primary residents of the digestive microflora throughout most of an individual's life."
Dr. Abeln also pointed out that there is evidence to suggest that the intestinal microflora of people with Irritable Bowel Syndrome (IBS) differs from that of healthy people, supporting the notion that imbalances in the types of bacteria residing in the gastrointestinal tract can trigger digestive symptoms. Importantly, she says, studies have found reduced levels of Bifidobacteria species in individuals meeting the diagnostic criteria for IBS.
While probiotics are living microorganisms, prebiotics are stable, non-digestible food ingredients that serve as a food source for probiotic bacteria. "The purpose of a prebiotic is to foster the growth of good bacteria (probiotics) and decrease bad bacteria (pathogens)," said Coni Francis, PhD, RD, senior manager of science, marketing and technical services, GTC Nutrition, Golden, CO. "As the balance of healthy bacteria is tipped in the right direction, we experience numerous health benefits, such as increased calcium absorption, enhanced digestive function and a stronger immune system.
"When comparing prebiotic fiber ingredients, glucose termination and short-chain length are extremely important considerations to the fermentation profile and ingredient functionality," added Dr. Francis. "In other words, the chemical structure and chain length of a prebiotic will determine how easily it can be utilized by probiotic bacteria."
Joseph O'Neill, executive vice president of sales and marketing, Orafti-Active Food Ingredients, Malvern, PA, says based upon the totality of the available published human data, there is convincing scientific evidence from human interventional trials pointing to a clear correlation between the ingestion of the prebiotics inulin and/or oligofructose and a statistically significant increase in Bifidobacterium levels in the human colon. As a result, he believes inulin and oligofructose are the most widely demonstrated prebiotic fibers available.
Aside from the fact that pre/probiotics can help support human digestion, there is also evidence to indicate they may aid in other health conditions. Lactobacillus and Bifidobacterium have shown positive effects in improving lactose digestion, reducing cholesterol, reducing yeast infections, reducing colon cancer and boosting the immune system. And some of the new pre/probiotic products are capitalizing on these condition-specific benefits.
Other recent studies undertaken amongst children in daycare have shown that those whose diet was supplemented with live probiotic L. reuteri suffered less from fever, stomach infection and common colds than other children in the same daycare setting.
Dr. S.K. Dash, president, UAS Laboratories, Eden Prairie, MN, discussed the anti-carcinogenic effects of his company's Lactobacillus acidophilus DDS-1 probiotic. "The mechanism of DDS-1 induced suppression of tumors was evaluated," he said. "Using a mouse macrophage cell line, investigators determined that DDS-1 was able to stimulate the production of im-mune components (interleukin-1a and tumor necrosis factor-a), which are known killers or inhibitors of tumor cells."
Women's health is another opportunity for probiotics, which can restore and maintain vaginal microflora balance. Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 have both been shown to support vaginal health in studies.
There is also growing evidence suggesting that probiotics can be effective in the prevention of recurrent urinary tract infection (UTI). "The proposed mechanism of action includes inhibition of growth and adhesion of pathogens at the vaginal and urethral mucosa before ascension of these pathogens into the bladder," said Dr. Dash. In a case study, UAS' DDS-1 was administered twice daily for a month. When investigators followed up with subjects, Dr. Dash said there were positive effects.
Valérie Delahaye, global marketing and sales director, Institut Rosell, Montreal, Canada, also noted that a clinical study in healthy volunteers affected by chronic stress demonstrated the beneficial role of a probiotic preparation in reducing gastrointestinal symptoms linked to stress. Allergy prevention, in particular atopic dermatitis, is another promising field of application, she said.
A synbiotic represents the combination of prebiotic(s) and prebiotic(s), which Mr. Mr. O'Neill claims offers a great opportunity to provide a targeted benefit. "Prebiotics selectively promote the growth of the health promoting Bifidobaceria in the digestive tract," he explained. "Targeted synbiotics offer a potential means of preventing or treating many socially important health concerns, including osteoporosis and obesity."
Speaking of obesity, Orafti-Active Food Ingredients' Beneo oligofructose, a prebiotic ingredient from the chicory root, has been shown to promote satiety. According to the company, an "intervention trial in human volunteers has confirmed that BeneoP95 can enhance satiety as well as lower energy and food intake. BeneoP95 and BeneoSynergy1 could thus play a key role as a new tool helping to fight the obesity epidemic."
Not all probiotics are created equal. Indeed, there are literally thousands of different kinds of friendly bacteria with unique health attributes. It is therefore important to make sure that probiotic strains are well tested and documented to ensure that they are safe and impart a desired health benefit.
"Different strains of the same species have been noted to differ in several ways, including stability, expression of enzymes and production of inhibitory substances, ability to colonize the GI tract and, perhaps most important, clinical efficacy," said P&G's Dr. Abeln. "Therefore, the recommendation is that all probiotics be independently tested and evaluated in clinical trials-it is never appropriate to extrapolate clinical benefit from an individual strain to other strains. It is especially important that probiotics that make claims of health benefits be studied in well-controlled clinical trials in humans. Currently, many health claims rely on data from non-clinical laboratory (in vitro) methods, which may not be predictive of the actual clinical benefits (in vivo)." In other words, laboratory experiments are considered insufficient on their own to define a probiotic organism.
"The fields of DNA research and genome sequencing are becoming very important in probiotic bacteria research," said Michael Shahani, director of operations, Nebraska Cultures, Inc., Walnut Creek, CA. "As these research techniques help us understand more specifically how probiotics work, and which bacteria work most effectively, it may be possible to target more specifically how probiotics can be used to improve health."
NC State's Dr. Klaenhammer agrees that genomics research in this area will likely have a huge impact. "We must be able to examine a strain of probiotic bacteria and determine what genes are present and if they can impact survival or functionality, or support a specific health benefit," he said. "That data are exploding and will continue to accumulate over the next five years. Ultimately, strain comparisons on the basis of genetic content will help answer industry questions about how to pick the right probiotic strains for specific purposes and products."
While reviews of the safety of the bacterial species Lactobacilli and Bifidobacteria have concluded they pose no health risks to consumers, making them generally recognized as safe (GRAS), not all strains of probiotic bacteria are as widely accepted. Claims of probiotic benefits are wide ranging and for the most part, not supported by clinical data-or in some cases, any data at all.
According to Tine Westerdahl, head of marketing, Human Health & Nutrition, Chr. Hansen, Hørsholm, Denmark, scientific evidence for safety and efficacy are some of the most important issues for consumers to consider. This is because they continue to increase their knowledge of different products and are aiming to derive specific effects from these products.
Having clinical evidence has become even more crucial in the European market. "In the EU, since January 2007, the regulation on the use of nutrition and health claims for foods (Regulation EC 1924/2006 of the 20th of December 2006) is now in force and has drawn a strict framework for nutraceutical products such as pre/probiotics," said Institut Rosell's Ms. Delahaye. "Any claim must be backed up by strong clinical evidence."
Quality control is also a major concern, especially with probiotic products in the U.S. Recent reviews have found that many probiotic supplements do not contain what they claim, making credibility a major issue facing the market. It is critical that finished products contain the promised amount of viable bacteria. Because quality control is a major concern with probiotic supplements, P&G has made a significant investment in understanding the science of probiotic manufacturing and stability. One solution is a bacterial bar coding methodology, which P&G uses to ensure the purity and quality of the Bifantis bacteria in its Align probiotic supplement. This method is so specific that it can discriminate between the Bifantis strain of Bifidobacteria and 30 other very closely related strains.
Traditionally, consumers have gravitated to the dairy aisle, specifically yogurt, to obtain the health benefits found in probiotics. Evidence of this trend can be found in the recent report "What's Hot Around the Globe: Insights on Growth in Food & Beverage Products," released by AC-Nielsen Global Services, an operating unit of The Nielsen Co. The report noted that Drinkable Yogurts was the fastest-growing food and beverage category purchased by consumers worldwide (between mid-2005 and mid-2006). In fact, annual sales of drinkable yogurt rose over 18% to $7.8 billion during the same period, according to the survey.
Additional proof about growing yogurt consumption can be found in the "Functional Food and Beverages, November 2006" report published by Mintel International Group,Chicago, IL, which revealed the results of its survey of 566 adults who had purchased a functional food recently (28% of the total). The report found that in the past three months, 11% bought prebiotic and/or probiotic yogurt.
On a global scale, in 2005, retail sales of probiotic dairy products were conservatively estimated at $3 billion in Japan, $3 billion in Europe and $300 million in the U.S., according to "Ten Key Trends in Food, Nutrition & Health 2007." Mr. Mellentin, the report author, says "consumer researchers and industry executives assert that the U.S. consumer wasn't interested in digestive health to the same extent as Europeans or Asians (despite the peculiar fact that America has the world's highest per capita consumption of laxatives)…Danone is now, with its Activia brand, showing just how wrong those market researchers were."
Previously launched in Europe, Danone(Dannon) Activia debuted in the U.S. in January last year, bringing with it a new approach to yogurt in the U.S. market. "The yogurt carried an overt, very explicitly communicated health message about digestion. Messages describe how consumers can relieve constipation, and help speed up intestinal transit time," according to Mr. Mellentin. Activia contains the probiotic culture Bifidus Regularis, which has been clinically proven to help regulate the digestive system in two weeks.
"There are several reasons why dairy foods are the preferred choice for getting probiotic bacteria," explained Michael Neuwirth, senior director of public relations, The Dannon Company, White Plains, NY. "Because dairy helps to buffer stomach acids, probiotics in dairy are more likely to survive the journey through the digestive system." Dairy forms are also ideal since short shelf life and refrigeration allows the living microorganisms to remain as active living cultures.
Mr. Neuwirth added that fermented dairy products like yogurt are also a source of calcium, riboflavin, vitamin B12, potassium and certain amino acids, all nutrients that are critical for good health. "In addition, during the fermentation of dairy foods, new products such as functional peptides are formed, which research shows may have beneficial effects," he said.
As competition heats up, several companies are working behind the scenes with a variety of new delivery methods/technologies to enhance the survival, viability and health benefits of probiotics, particularly in functional foods. As a result of these innovative technologies and strong formulations surrounding the viability of the probiotic bacteria throughout the industrial process and in non-refrigerated environments, non-dairy probiotic products are starting to give dairy products a run for their money. Probiotics can now be found in infant formulas, biscuits, oral care products, chocolate and fruit juices.
"Many probiotic producers have developed protective technologies, mainly based on microencapsulation of the dried live bacteria, providing them increased resistance to the temperature and pressure environments typical of many food processes. These technologies also protect them from acidity," said Institut Rosell's Ms. Delahaye. "Each different probiotic strain has a different stability profile, and for every new probiotic application, stability studies are key to guarantee the proper probiotic count to the customer."
With the rise in reduced sugar and sugar-free applications, Mr. O'Neil says many foods formulated with high intensity sweeteners could use the help of inulin and oligofructose to mask the "licorice" off-notes associated with them, particularly sucralose. In addition, he said, oligofructose enhances fruit/berry flavors in fruit preparations, while reduced sugar and sugar-free chocolate applications benefit from inulin due to its bulking effect.
Cereals and wellness bars are only two examples of new probiotic delivery forms that consumers can now benefit from. Last year, Kashi Co., La Jolla, CA, launched the shelf-stable Kashi Vive Probiotic Digestive Wellness Cereal. According to the company, Lactobacillus probiotics become live and active in the body and can thrive in the human intestine over an extended period of time, ultimately improving the balance of good and bad bacteria in the digestive system.
Attune Foods, San Francisco, CA, recently introduced Attune Yogurt & Granola Wellness Bars, which feature more than five times the beneficial probiotics found in yogurt. They contain three different, specially formulated Lafti probiotic strains (a range supplied by DSM Food Specialties, Inc.). Each Attune bar contains more than 10 billion probiotic bacteria, which are proven to survive in the digestive tract in an amount shown to provide optimal results. Attune wellness bars also include the prebiotic inulin.
With the existence of a wide variety of probiotic strains, any company wanting to formulate a probiotic product has many factors to consider. Gregory Miller, PhD, MACN, executive vice president, science and innovation, Dairy Management Inc. (DMI), Rosemont, IL, discussed some of these issues, including: What bacteria are going to be in the product? How many bacteria constitute an effective dose? How long must the probiotics remain viable to deliver the dose? And, perhaps most important of all, What claims or benefits will be associated with this product? Securing documentation of the bacteria's type, potency and purity, as well as any nutrition research published on that strain, is very important.
"Processing conditions offer additional considerations," said Dr. Miller. "How well will a certain strain tolerate acid, shear force and varying oxygen levels? Would additional ingredients enhance bacteria viability, suggesting a pre- and probiotic combination?"
As mentioned previously, the bacteria's ability to survive the stomach and bile acid is important. Not all strains can withstand the acid environment to the same extent, so it is important that each strain is tested for survival throughout the gastrointestinal tract.
"Studies have shown that unprotected probiotic forms can suffer significantly from exposure to stomach acids, losing as much as 99% of their viability before reaching optimal locations in the intestines," said Tim Gamble, vice president, sales and marketing, Nutraceutix, Inc., Redmond, WA. "Freeze dried probiotic organisms, like those in supplements, are activated when hydrated and, unless in a fertile environment, will quickly expire. As such, probiotic-containing foods, beverages and other high-moisture forms present some formidable challenges, primarily in terms of shelf-life and viability through time of consumption. Probiotic manufacturing expertise and novel delivery technologies are a must."
According to Nebraska Cultures' Mr. Shahani, probiotic bacteria are damaged by heat, moisture, light and exposure to air. "Minimizing these four factors are the key to keeping probiotic bacteria alive both during and after manufacturing," he said. "The required amount of probiotics must be present at the time you eat the product-not just when the product was manufactured."
According to GTC's Dr. Francis, the main challenge in working with synbiotics is the limited number of systems probiotics can be added to. "The probiotics industry is currently working to overcome this limitation by finding ways to maintain the stability of cultures in systems that are not traditionally known to contain probiotics," she said.
With the success of Activia, The Dannon Company recently introduced a reduced-calorie version called Activia Light. The company also reformulated its Danimals kids products to include one of the most widely researched probiotic strains, Lactobacillus GG (LGG), which is a product of Valio, Helsinki, Finland. Most recently, the company launched DanActive, a probiotic dairy drink that "helps strengthen the body's defenses" through a proprietary culture called L. casei Immunitas. "It is too early to assess the public's reaction, but we are hopeful that DanActive will also be a significant success," said Mr. Neuwirth. According to the company, L. casei Immunitas has been clinically proven to work in the digestive track where 70% of a person's immune system is located.
Valio recently launched A+Express, a yogurt enriched with prebiotic galacto-oligosaccharides (GOS) for a better maintained digestive system. "GOS are a heterogeneous group of milk-derived carbohydrates that are able to enhance gut function by acting as soluble fiber in the colon," said Kaarle (Kalle) Leporanta, marketing manager, Valio. "Human clinical studies show that GOS improves regularity and increases the number of beneficial bifido-bacteria in the gut." In fact, Valio teamed up with healthcare professionals to develop A+ Express, two cups of which contain 8 grams of GOS-an optimal amount for everyday gut well-being, according to Mr. Leporanta.
In other developments, Valio and Chr. Hansen A/S recently agreed to strengthen their cooperation in the manufacturing and commercialization of LGG for food supplements. Chr. Hansen A/S will now directly handle processes related to manufacturing and selling LGG for the food supplement segment. As a result, Chr. Hansen A/S will also develop and sell food supplement products where LGG is combined with BB-12 or other Chr. Hansen probiotic strains.
Valio has also developed a method to produce a non-dairy fruit juice drink with probiotics. These products are successfully on the market in Finland, Estonia, Latvia and Lithuania. "Tine in Norway is also producing similar products under license from Valio," said Mr. Leporanta. "These products offer an opportunity to develop a totally new kind of drink category."
On the supplement side, P&G recently introduced Align, a new probiotic supplement containing Bifantis (Bifidobacterium infantis 35624), which was developed to appeal to a consumer that prefers to take a dietary probiotic supplement as a capsule once a day, every day.
In the January 2007 edition of Nature Medicine, researchers from Inserm (French National Institute of Health and Medical Research) and Danisco, Madison, WI, released the results of a study demonstrating for the first time that the oral administration of Lactobacillus acidophilus NCFM mediates analgesic functions in the gut equivalent to morphine effects. These results suggest that the microbiology of the intestinal tract influences visceral pain perception, and open new perspectives in the treatment of abdominal pain and IBS with this unique probiotic strain.
"When we put intestinal epithelial cells in contact with various lactic acid bacteria, Lactobacillus acidophilus NCFM induce a significant expression of µ opioid receptor (MOR) and receptors for cannabinoid (CB2) that exert an analgesic effect," said Dr. Pierre Desreumaux, head of the Department of Gastrointestinal Diseases and Nutrition at Lille Hospital, France, research director at Inserm and principal author of the study. "One could envision NCFM to be prescribed for intestinal functional disorders or co-administered with morphine to relieve serious gastrointestinal pathologies, therefore reducing the morphine doses and related side effects."
On the dairy front, DMI is funding research looking into the components of milk, which enhance the ability of probiotic organisms to survive and deliver their benefits. "We are trying to find out if dairy components or the dairy environment positively impact the bacteria," explained Dr. Klaenhammer. "What are the components in milk that appear to enhance bacteria's ability to survive and deliver those benefits? For instance, research by the Nestlé Research Center has already shown that lactose, or milk sugar, is the preferred food source for Bifidobacterium longum. There may be some noteworthy traits in lactobacilli that are turned on by lactose as well. This is interesting because human infants get lactose as they ingest milk and Bifidobacteria become one of the predominant bacteria present in the newborn gut."
Given the rapid development of the pre/probiotic market of late, many companies felt a need to gather under one umbrella to further research and educate the public. Recognizing this strong need, Institut Rosell aided in the launch of the International Probiotics Association (IPA) at the end of 2006. "Its mission is to provide a forum for the exchange of new clinical research and advances in product development, to establish scientific standards for probiotic products within the international marketplace, and to promote the health benefits of probiotics," said Ms. Delahaye. In November 2007, the IPA will hold its first Congress in Beverly Hills, CA.
Experts agree that the pre/probiotics market has a strong future as the battle between good versus bad bacteria continues to rage on in the human body. While today's main areas for pre/probiotics are gut, female, immune and dental health, there will probably be an expansion of these areas in the future. "There is great potential for the prebiotic/probiotic market to grow in terms of awareness," saidGTC's Dr. Francis. "As consumers be-come more knowledgeable about the health benefits associated with pre/probiotics, demand for food, beverage and supplement products enriched with these ingredients will only increase."
Dannon's Mr. Neuwirth agreed. "We anticipate there will continue to be new product introductions, which will serve to increase public awareness of the benefits of probiotics. Additionally, we are hopeful that consumer awareness of the strain-specific benefits of probiotics will improve. This is key in order for consumers to differentiate among products based on the clinical research that supports a specific strain's claims."
The presence of synbiotics will also increase in many new foods and beverages. Dr. Jan Van Loo, senior manager, New Business Development and Information, Orafti Group, Tienen, Belgium, points out that there are already a number of products on the market with pre- and probiotics, including Symbi from Priegola in Spain, Muller Vitality in the U.K., Healthier Synbiotic Yogurt in Ireland and Bio+ from Yoplait in Ireland-all of which claim on pack the synbiotic effect. "Ninety-five percent of the products currently on sale are dairy products like yogurts and dairy drinks, which is largely due to the chilled environment requirement," said Dr. Van Loo, adding, "But there is still huge potential for product development, including the introduction of other chilled drinks such as fruit and vegetable juices, cheeses and chilled baby foods."
"We're seeing just the tip of the iceberg today in the development of probiotic products that provide a consumer benefit," said DMI's Dr. Miller. "Consumers have demonstrated their strong interest in functional foods focused on health benefits and a lot of industry leaders are looking at the available science and considering the possibilities. And based on what could eventually emerge in this area, I think the door is just starting to open."
Probiotics, also known as "friendly" bacteria, are used around the world to help support healthy digestion, provide immune support (or "natural defense") and maintain optimal health and wellness. Having originally been taught that bacteria are essentially bad for their health, it's hard for consumers to grasp the fact that bacteria actually keeps them alive, so although probiotics have gained consumer acceptance over the past few years, Todd Klaenhammer, PhD, distinguished university professor in the departments of Food Science, Microbiology and Genetics at North Carolina State University, still feels the category has a long way to go. "What people don't realize is that bacteria account for over 90% of the 'cells' associated with our body," he said. "So, in terms of pure numbers, we're mostly bacteria. Most of the bacteria associated with our bodies are very protective, aiding our digestion, modulating our immune system and protecting us from pathogens."
Bacteria Benefits
In 2001, the World Health Organization (WHO) defined probiotics as "live micro-organisms, which when administered in adequate amounts, confer health benefits on the host." Probiotics balance/restore intestinal microbiota, and according to Susan Abeln, principal scientist in research & development, P&G, Cincinnati, OH, in a balanced state, these bacteria perform a number of important functions that contribute to human health, including the synthesis of vitamins and other nutrients, and the secretion of digestive enzymes.
"Beneficial bacterial species protect against a state of 'dysbiosis,' which is an upset in the equilibrium that can cause digestive upsets," explained Dr. Abeln. Common factors that can trigger an imbalanced state include changes in diet, travel, stress, illness, aging, and the use of some medications, primarily antibiotics.
"The composition of the microflora is dominated by four types of bacteria: Bacteroides, Bifidobacterium, Eubacterium and Peptostreptoccocus," Dr. Abeln continued. "Bifidobacteria are widely thought to be the most important gram positive organism in the digestive environment. Bifidobacterial species remain primary residents of the digestive microflora throughout most of an individual's life."
Dr. Abeln also pointed out that there is evidence to suggest that the intestinal microflora of people with Irritable Bowel Syndrome (IBS) differs from that of healthy people, supporting the notion that imbalances in the types of bacteria residing in the gastrointestinal tract can trigger digestive symptoms. Importantly, she says, studies have found reduced levels of Bifidobacteria species in individuals meeting the diagnostic criteria for IBS.
While probiotics are living microorganisms, prebiotics are stable, non-digestible food ingredients that serve as a food source for probiotic bacteria. "The purpose of a prebiotic is to foster the growth of good bacteria (probiotics) and decrease bad bacteria (pathogens)," said Coni Francis, PhD, RD, senior manager of science, marketing and technical services, GTC Nutrition, Golden, CO. "As the balance of healthy bacteria is tipped in the right direction, we experience numerous health benefits, such as increased calcium absorption, enhanced digestive function and a stronger immune system.
"When comparing prebiotic fiber ingredients, glucose termination and short-chain length are extremely important considerations to the fermentation profile and ingredient functionality," added Dr. Francis. "In other words, the chemical structure and chain length of a prebiotic will determine how easily it can be utilized by probiotic bacteria."
Joseph O'Neill, executive vice president of sales and marketing, Orafti-Active Food Ingredients, Malvern, PA, says based upon the totality of the available published human data, there is convincing scientific evidence from human interventional trials pointing to a clear correlation between the ingestion of the prebiotics inulin and/or oligofructose and a statistically significant increase in Bifidobacterium levels in the human colon. As a result, he believes inulin and oligofructose are the most widely demonstrated prebiotic fibers available.
Aside from the fact that pre/probiotics can help support human digestion, there is also evidence to indicate they may aid in other health conditions. Lactobacillus and Bifidobacterium have shown positive effects in improving lactose digestion, reducing cholesterol, reducing yeast infections, reducing colon cancer and boosting the immune system. And some of the new pre/probiotic products are capitalizing on these condition-specific benefits.
Other recent studies undertaken amongst children in daycare have shown that those whose diet was supplemented with live probiotic L. reuteri suffered less from fever, stomach infection and common colds than other children in the same daycare setting.
Dr. S.K. Dash, president, UAS Laboratories, Eden Prairie, MN, discussed the anti-carcinogenic effects of his company's Lactobacillus acidophilus DDS-1 probiotic. "The mechanism of DDS-1 induced suppression of tumors was evaluated," he said. "Using a mouse macrophage cell line, investigators determined that DDS-1 was able to stimulate the production of im-mune components (interleukin-1a and tumor necrosis factor-a), which are known killers or inhibitors of tumor cells."
Women's health is another opportunity for probiotics, which can restore and maintain vaginal microflora balance. Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 have both been shown to support vaginal health in studies.
There is also growing evidence suggesting that probiotics can be effective in the prevention of recurrent urinary tract infection (UTI). "The proposed mechanism of action includes inhibition of growth and adhesion of pathogens at the vaginal and urethral mucosa before ascension of these pathogens into the bladder," said Dr. Dash. In a case study, UAS' DDS-1 was administered twice daily for a month. When investigators followed up with subjects, Dr. Dash said there were positive effects.
Valérie Delahaye, global marketing and sales director, Institut Rosell, Montreal, Canada, also noted that a clinical study in healthy volunteers affected by chronic stress demonstrated the beneficial role of a probiotic preparation in reducing gastrointestinal symptoms linked to stress. Allergy prevention, in particular atopic dermatitis, is another promising field of application, she said.
A synbiotic represents the combination of prebiotic(s) and prebiotic(s), which Mr. Mr. O'Neill claims offers a great opportunity to provide a targeted benefit. "Prebiotics selectively promote the growth of the health promoting Bifidobaceria in the digestive tract," he explained. "Targeted synbiotics offer a potential means of preventing or treating many socially important health concerns, including osteoporosis and obesity."
Speaking of obesity, Orafti-Active Food Ingredients' Beneo oligofructose, a prebiotic ingredient from the chicory root, has been shown to promote satiety. According to the company, an "intervention trial in human volunteers has confirmed that BeneoP95 can enhance satiety as well as lower energy and food intake. BeneoP95 and BeneoSynergy1 could thus play a key role as a new tool helping to fight the obesity epidemic."
Quality Research
Not all probiotics are created equal. Indeed, there are literally thousands of different kinds of friendly bacteria with unique health attributes. It is therefore important to make sure that probiotic strains are well tested and documented to ensure that they are safe and impart a desired health benefit.
"Different strains of the same species have been noted to differ in several ways, including stability, expression of enzymes and production of inhibitory substances, ability to colonize the GI tract and, perhaps most important, clinical efficacy," said P&G's Dr. Abeln. "Therefore, the recommendation is that all probiotics be independently tested and evaluated in clinical trials-it is never appropriate to extrapolate clinical benefit from an individual strain to other strains. It is especially important that probiotics that make claims of health benefits be studied in well-controlled clinical trials in humans. Currently, many health claims rely on data from non-clinical laboratory (in vitro) methods, which may not be predictive of the actual clinical benefits (in vivo)." In other words, laboratory experiments are considered insufficient on their own to define a probiotic organism.
"The fields of DNA research and genome sequencing are becoming very important in probiotic bacteria research," said Michael Shahani, director of operations, Nebraska Cultures, Inc., Walnut Creek, CA. "As these research techniques help us understand more specifically how probiotics work, and which bacteria work most effectively, it may be possible to target more specifically how probiotics can be used to improve health."
NC State's Dr. Klaenhammer agrees that genomics research in this area will likely have a huge impact. "We must be able to examine a strain of probiotic bacteria and determine what genes are present and if they can impact survival or functionality, or support a specific health benefit," he said. "That data are exploding and will continue to accumulate over the next five years. Ultimately, strain comparisons on the basis of genetic content will help answer industry questions about how to pick the right probiotic strains for specific purposes and products."
While reviews of the safety of the bacterial species Lactobacilli and Bifidobacteria have concluded they pose no health risks to consumers, making them generally recognized as safe (GRAS), not all strains of probiotic bacteria are as widely accepted. Claims of probiotic benefits are wide ranging and for the most part, not supported by clinical data-or in some cases, any data at all.
According to Tine Westerdahl, head of marketing, Human Health & Nutrition, Chr. Hansen, Hørsholm, Denmark, scientific evidence for safety and efficacy are some of the most important issues for consumers to consider. This is because they continue to increase their knowledge of different products and are aiming to derive specific effects from these products.
Having clinical evidence has become even more crucial in the European market. "In the EU, since January 2007, the regulation on the use of nutrition and health claims for foods (Regulation EC 1924/2006 of the 20th of December 2006) is now in force and has drawn a strict framework for nutraceutical products such as pre/probiotics," said Institut Rosell's Ms. Delahaye. "Any claim must be backed up by strong clinical evidence."
Quality control is also a major concern, especially with probiotic products in the U.S. Recent reviews have found that many probiotic supplements do not contain what they claim, making credibility a major issue facing the market. It is critical that finished products contain the promised amount of viable bacteria. Because quality control is a major concern with probiotic supplements, P&G has made a significant investment in understanding the science of probiotic manufacturing and stability. One solution is a bacterial bar coding methodology, which P&G uses to ensure the purity and quality of the Bifantis bacteria in its Align probiotic supplement. This method is so specific that it can discriminate between the Bifantis strain of Bifidobacteria and 30 other very closely related strains.
Dairy Vs. Non-Dairy
Traditionally, consumers have gravitated to the dairy aisle, specifically yogurt, to obtain the health benefits found in probiotics. Evidence of this trend can be found in the recent report "What's Hot Around the Globe: Insights on Growth in Food & Beverage Products," released by AC-Nielsen Global Services, an operating unit of The Nielsen Co. The report noted that Drinkable Yogurts was the fastest-growing food and beverage category purchased by consumers worldwide (between mid-2005 and mid-2006). In fact, annual sales of drinkable yogurt rose over 18% to $7.8 billion during the same period, according to the survey.
Additional proof about growing yogurt consumption can be found in the "Functional Food and Beverages, November 2006" report published by Mintel International Group,Chicago, IL, which revealed the results of its survey of 566 adults who had purchased a functional food recently (28% of the total). The report found that in the past three months, 11% bought prebiotic and/or probiotic yogurt.
On a global scale, in 2005, retail sales of probiotic dairy products were conservatively estimated at $3 billion in Japan, $3 billion in Europe and $300 million in the U.S., according to "Ten Key Trends in Food, Nutrition & Health 2007." Mr. Mellentin, the report author, says "consumer researchers and industry executives assert that the U.S. consumer wasn't interested in digestive health to the same extent as Europeans or Asians (despite the peculiar fact that America has the world's highest per capita consumption of laxatives)…Danone is now, with its Activia brand, showing just how wrong those market researchers were."
Previously launched in Europe, Danone(Dannon) Activia debuted in the U.S. in January last year, bringing with it a new approach to yogurt in the U.S. market. "The yogurt carried an overt, very explicitly communicated health message about digestion. Messages describe how consumers can relieve constipation, and help speed up intestinal transit time," according to Mr. Mellentin. Activia contains the probiotic culture Bifidus Regularis, which has been clinically proven to help regulate the digestive system in two weeks.
"There are several reasons why dairy foods are the preferred choice for getting probiotic bacteria," explained Michael Neuwirth, senior director of public relations, The Dannon Company, White Plains, NY. "Because dairy helps to buffer stomach acids, probiotics in dairy are more likely to survive the journey through the digestive system." Dairy forms are also ideal since short shelf life and refrigeration allows the living microorganisms to remain as active living cultures.
Mr. Neuwirth added that fermented dairy products like yogurt are also a source of calcium, riboflavin, vitamin B12, potassium and certain amino acids, all nutrients that are critical for good health. "In addition, during the fermentation of dairy foods, new products such as functional peptides are formed, which research shows may have beneficial effects," he said.
As competition heats up, several companies are working behind the scenes with a variety of new delivery methods/technologies to enhance the survival, viability and health benefits of probiotics, particularly in functional foods. As a result of these innovative technologies and strong formulations surrounding the viability of the probiotic bacteria throughout the industrial process and in non-refrigerated environments, non-dairy probiotic products are starting to give dairy products a run for their money. Probiotics can now be found in infant formulas, biscuits, oral care products, chocolate and fruit juices.
"Many probiotic producers have developed protective technologies, mainly based on microencapsulation of the dried live bacteria, providing them increased resistance to the temperature and pressure environments typical of many food processes. These technologies also protect them from acidity," said Institut Rosell's Ms. Delahaye. "Each different probiotic strain has a different stability profile, and for every new probiotic application, stability studies are key to guarantee the proper probiotic count to the customer."
With the rise in reduced sugar and sugar-free applications, Mr. O'Neil says many foods formulated with high intensity sweeteners could use the help of inulin and oligofructose to mask the "licorice" off-notes associated with them, particularly sucralose. In addition, he said, oligofructose enhances fruit/berry flavors in fruit preparations, while reduced sugar and sugar-free chocolate applications benefit from inulin due to its bulking effect.
Cereals and wellness bars are only two examples of new probiotic delivery forms that consumers can now benefit from. Last year, Kashi Co., La Jolla, CA, launched the shelf-stable Kashi Vive Probiotic Digestive Wellness Cereal. According to the company, Lactobacillus probiotics become live and active in the body and can thrive in the human intestine over an extended period of time, ultimately improving the balance of good and bad bacteria in the digestive system.
Attune Foods, San Francisco, CA, recently introduced Attune Yogurt & Granola Wellness Bars, which feature more than five times the beneficial probiotics found in yogurt. They contain three different, specially formulated Lafti probiotic strains (a range supplied by DSM Food Specialties, Inc.). Each Attune bar contains more than 10 billion probiotic bacteria, which are proven to survive in the digestive tract in an amount shown to provide optimal results. Attune wellness bars also include the prebiotic inulin.
The Viability Issue
With the existence of a wide variety of probiotic strains, any company wanting to formulate a probiotic product has many factors to consider. Gregory Miller, PhD, MACN, executive vice president, science and innovation, Dairy Management Inc. (DMI), Rosemont, IL, discussed some of these issues, including: What bacteria are going to be in the product? How many bacteria constitute an effective dose? How long must the probiotics remain viable to deliver the dose? And, perhaps most important of all, What claims or benefits will be associated with this product? Securing documentation of the bacteria's type, potency and purity, as well as any nutrition research published on that strain, is very important.
"Processing conditions offer additional considerations," said Dr. Miller. "How well will a certain strain tolerate acid, shear force and varying oxygen levels? Would additional ingredients enhance bacteria viability, suggesting a pre- and probiotic combination?"
As mentioned previously, the bacteria's ability to survive the stomach and bile acid is important. Not all strains can withstand the acid environment to the same extent, so it is important that each strain is tested for survival throughout the gastrointestinal tract.
"Studies have shown that unprotected probiotic forms can suffer significantly from exposure to stomach acids, losing as much as 99% of their viability before reaching optimal locations in the intestines," said Tim Gamble, vice president, sales and marketing, Nutraceutix, Inc., Redmond, WA. "Freeze dried probiotic organisms, like those in supplements, are activated when hydrated and, unless in a fertile environment, will quickly expire. As such, probiotic-containing foods, beverages and other high-moisture forms present some formidable challenges, primarily in terms of shelf-life and viability through time of consumption. Probiotic manufacturing expertise and novel delivery technologies are a must."
According to Nebraska Cultures' Mr. Shahani, probiotic bacteria are damaged by heat, moisture, light and exposure to air. "Minimizing these four factors are the key to keeping probiotic bacteria alive both during and after manufacturing," he said. "The required amount of probiotics must be present at the time you eat the product-not just when the product was manufactured."
According to GTC's Dr. Francis, the main challenge in working with synbiotics is the limited number of systems probiotics can be added to. "The probiotics industry is currently working to overcome this limitation by finding ways to maintain the stability of cultures in systems that are not traditionally known to contain probiotics," she said.
Recent Developments
With the success of Activia, The Dannon Company recently introduced a reduced-calorie version called Activia Light. The company also reformulated its Danimals kids products to include one of the most widely researched probiotic strains, Lactobacillus GG (LGG), which is a product of Valio, Helsinki, Finland. Most recently, the company launched DanActive, a probiotic dairy drink that "helps strengthen the body's defenses" through a proprietary culture called L. casei Immunitas. "It is too early to assess the public's reaction, but we are hopeful that DanActive will also be a significant success," said Mr. Neuwirth. According to the company, L. casei Immunitas has been clinically proven to work in the digestive track where 70% of a person's immune system is located.
Valio recently launched A+Express, a yogurt enriched with prebiotic galacto-oligosaccharides (GOS) for a better maintained digestive system. "GOS are a heterogeneous group of milk-derived carbohydrates that are able to enhance gut function by acting as soluble fiber in the colon," said Kaarle (Kalle) Leporanta, marketing manager, Valio. "Human clinical studies show that GOS improves regularity and increases the number of beneficial bifido-bacteria in the gut." In fact, Valio teamed up with healthcare professionals to develop A+ Express, two cups of which contain 8 grams of GOS-an optimal amount for everyday gut well-being, according to Mr. Leporanta.
In other developments, Valio and Chr. Hansen A/S recently agreed to strengthen their cooperation in the manufacturing and commercialization of LGG for food supplements. Chr. Hansen A/S will now directly handle processes related to manufacturing and selling LGG for the food supplement segment. As a result, Chr. Hansen A/S will also develop and sell food supplement products where LGG is combined with BB-12 or other Chr. Hansen probiotic strains.
Valio has also developed a method to produce a non-dairy fruit juice drink with probiotics. These products are successfully on the market in Finland, Estonia, Latvia and Lithuania. "Tine in Norway is also producing similar products under license from Valio," said Mr. Leporanta. "These products offer an opportunity to develop a totally new kind of drink category."
On the supplement side, P&G recently introduced Align, a new probiotic supplement containing Bifantis (Bifidobacterium infantis 35624), which was developed to appeal to a consumer that prefers to take a dietary probiotic supplement as a capsule once a day, every day.
In the January 2007 edition of Nature Medicine, researchers from Inserm (French National Institute of Health and Medical Research) and Danisco, Madison, WI, released the results of a study demonstrating for the first time that the oral administration of Lactobacillus acidophilus NCFM mediates analgesic functions in the gut equivalent to morphine effects. These results suggest that the microbiology of the intestinal tract influences visceral pain perception, and open new perspectives in the treatment of abdominal pain and IBS with this unique probiotic strain.
"When we put intestinal epithelial cells in contact with various lactic acid bacteria, Lactobacillus acidophilus NCFM induce a significant expression of µ opioid receptor (MOR) and receptors for cannabinoid (CB2) that exert an analgesic effect," said Dr. Pierre Desreumaux, head of the Department of Gastrointestinal Diseases and Nutrition at Lille Hospital, France, research director at Inserm and principal author of the study. "One could envision NCFM to be prescribed for intestinal functional disorders or co-administered with morphine to relieve serious gastrointestinal pathologies, therefore reducing the morphine doses and related side effects."
On the dairy front, DMI is funding research looking into the components of milk, which enhance the ability of probiotic organisms to survive and deliver their benefits. "We are trying to find out if dairy components or the dairy environment positively impact the bacteria," explained Dr. Klaenhammer. "What are the components in milk that appear to enhance bacteria's ability to survive and deliver those benefits? For instance, research by the Nestlé Research Center has already shown that lactose, or milk sugar, is the preferred food source for Bifidobacterium longum. There may be some noteworthy traits in lactobacilli that are turned on by lactose as well. This is interesting because human infants get lactose as they ingest milk and Bifidobacteria become one of the predominant bacteria present in the newborn gut."
Given the rapid development of the pre/probiotic market of late, many companies felt a need to gather under one umbrella to further research and educate the public. Recognizing this strong need, Institut Rosell aided in the launch of the International Probiotics Association (IPA) at the end of 2006. "Its mission is to provide a forum for the exchange of new clinical research and advances in product development, to establish scientific standards for probiotic products within the international marketplace, and to promote the health benefits of probiotics," said Ms. Delahaye. In November 2007, the IPA will hold its first Congress in Beverly Hills, CA.
A Lively Future
Experts agree that the pre/probiotics market has a strong future as the battle between good versus bad bacteria continues to rage on in the human body. While today's main areas for pre/probiotics are gut, female, immune and dental health, there will probably be an expansion of these areas in the future. "There is great potential for the prebiotic/probiotic market to grow in terms of awareness," saidGTC's Dr. Francis. "As consumers be-come more knowledgeable about the health benefits associated with pre/probiotics, demand for food, beverage and supplement products enriched with these ingredients will only increase."
Dannon's Mr. Neuwirth agreed. "We anticipate there will continue to be new product introductions, which will serve to increase public awareness of the benefits of probiotics. Additionally, we are hopeful that consumer awareness of the strain-specific benefits of probiotics will improve. This is key in order for consumers to differentiate among products based on the clinical research that supports a specific strain's claims."
The presence of synbiotics will also increase in many new foods and beverages. Dr. Jan Van Loo, senior manager, New Business Development and Information, Orafti Group, Tienen, Belgium, points out that there are already a number of products on the market with pre- and probiotics, including Symbi from Priegola in Spain, Muller Vitality in the U.K., Healthier Synbiotic Yogurt in Ireland and Bio+ from Yoplait in Ireland-all of which claim on pack the synbiotic effect. "Ninety-five percent of the products currently on sale are dairy products like yogurts and dairy drinks, which is largely due to the chilled environment requirement," said Dr. Van Loo, adding, "But there is still huge potential for product development, including the introduction of other chilled drinks such as fruit and vegetable juices, cheeses and chilled baby foods."
"We're seeing just the tip of the iceberg today in the development of probiotic products that provide a consumer benefit," said DMI's Dr. Miller. "Consumers have demonstrated their strong interest in functional foods focused on health benefits and a lot of industry leaders are looking at the available science and considering the possibilities. And based on what could eventually emerge in this area, I think the door is just starting to open."
