Probiotics, prebiotics and to a lesser degree, synbiotics, are finally starting to hit the radar screen in terms of recognition in the marketplace. Over the next several years more scientific documentation of health benefits and better communication to the consumer will provide a more solid platform from which these products can be expected to launch. Together and separately these ingredients serve as powerful tools in the prevention and treatment of certain conditions, in addition to providing regular maintenance of the gastrointestinal (GI) tract.

Probiotics: "A live microbial food supplement, which beneficially affects the host animal by improving its intestinal microbial balance…" Probiotic research R. Fuller, 1989

You know the saying, "Build a better mousetrap and the world will beat a path to your door"? You'd think that would be the case with probiotics, the "good" bacteria. Probiotics have the potential to improve health, they have been used for years in other cultures and they have a wealth of research behind them. Yet, apparently, no one knows how to tell the average American consumer about them. American society today is inundated with media messages about the need for antibiotics and antibacterial soaps, but no one is talking about the positive aspects of bacteria and how certain types can be beneficial for health.

For probiotics it is a matter of changing consumers' perceptions of bacteria. Consumers have been exposed to the ingredient mainly through yogurt consumption, but the term "probiotics" has yet to penetrate the American vernacular. Awareness is growing, however. According to The Hartman Group, Bellevue, WA, total sales of probiotics in 1999 were $67.2 million. Broken down further, health and natural food stores accounted for 38% of sales; direct sales accounted for 28% of sales; food, drug and mass accounted for 21% of sales; practitioners accounted for 5% of sales and "other" channels accounted for 8%.

Probiotic Trends And Issues
For probiotics the two main trends are developing more concrete scientific evidence and moving beyond established delivery forms. From a research perspective most experts agree that there is a trend moving toward conducting well-controlled clinical trials and determining how probiotic bacteria work in the human gut. Dr. Jon Vanderhoof, professor of pediatrics and director of pediatric gastroenterology at the University of Nebraska Medical Center and vice president-Nutrition & Health Sciences, ConAgra, Omaha, NE-manufacturer of the Culturelle™ probiotic supplement-said, "People are beginning to recognize the importance of doing good double blind placebo-controlled studies in various disease states or conditions in order to find out which probiotics work for what conditions." He continued, "The other trend goes toward legitimacy. There are enough studies that have been done that have lent legitimacy to the whole concept of probiotics and now a lot of the major players are becoming more interested in developing probiotic businesses. This trend is driving the category to a more ethical approach than what we have seen in the past."

Dr. Mary Ellen Sanders, consultant, Dairy and Food Culture Technologies, Littleton, CO, and research professor at Cal Poly State University, San Luis Obispo, CA, said companies are also becoming more strain savvy. "People are becoming much more aware of the importance of choosing appropriate strains that have good scientific documentation. In the past you would see a product saying 'contains acidophilus' or 'contains bifidus.' Now you are seeing people label products with specific strains, such as Stonyfield Farm's use of L. reuteri and three other strains, specifically for their probiotic benefit," she said. "Stonyfield is capitalizing on the fact that those people who developed the L. reuteri business and isolated it and studied it have a certain amount of strain-specific information on benefits. Companies are starting to realize that they not only need probiotics but they need specific strains at specific levels to yield a health benefit."

Research is also moving toward determining a more definite mechanism of action for probiotics, according to Silvano Arnoldo, sales manager-North America, Chr. Hansen, Milwaukee, WI, suppliers of the Probio-Tec® probiotic range. "There is a lot that we see probiotics do but we do not always understand the mechanism of action," he said, adding that scientists should also pay more attention to the selection criteria for probiotics. "Strains should be resistant to pH so they can survive passage through the stomach and be resistant to acid and bile. Also, probiotics should adhere to the intestinal epithelium and be able to inhibit pathogens. Lastly, it is desirable that probiotics possess activity regarding modulation of immune response."

There is also an increasing trend of combining strains to target specific health benefits. Dr. Jacques Goulet, scientific director, Institut Rosell, Montreal, Canada, suppliers of L b.acidophilus Rosell-52 and Lb. rhamnosus Rosell-11, commented, "From a scientific point of view we are noticing that a single strain won't do the best job in improving health. Scientists are suggesting that probiotic supplements be a mixture of four, five and even eight strains to get the most benefit. The probiotic strains in these blends, however, should also be compatible because not all probiotic strains are and, therefore, may not yield the most beneficial effect."

Scott Bush, commercial development manager, Rhodia Inc., Madison, WI, suppliers of the Flora-Fit™ probiotic range agreed, but urged caution. "We see an increased number of multi-strain probiotic blends being offered in yogurts and as dietary supplements. As many as 16 different probiotic strains are being offered in a single dietary supplement and on the yogurt side we see people requesting five or six strains per blend," he said. "But if you are delivering a specific number of probiotic bacteria per day, it doesn't necessarily mean that having more strains makes the product more efficacious. To some degree that seems to be more of a marketing issue."

On the delivery system front, Kalle Leporanta, business manager, LGG-Research and Development, Valio, Helsinki, Finland, supplier of the Lactobacillus rhamnosus GG (LGG) strain, said one of the trends includes finding novel delivery systems for probiotics. "Traditionally probiotics have been used in fermented milks and a few years ago daily dose drinks (i.e., Yakult) entered the European market," he said. "The latest applications are non-dairy fruit-based drinks and cheeses. Further, the use of probiotics in infant foods such as powdered infant milks and follow-on milks has begun."

Todd Norton, president, Sabinsa, Payson, UT, manufacturer of Lactospore®, said there is a lot of opportunity for new strains to come forth as well as new applications beyond yogurt, capsules or tablets. Additionally, he said, in other countries probiotics are being administered vaginally, moving probiotics away from the traditional delivery systems.

Conditions Targeted For Probiotics
Obviously, probiotic use is focused on the general category of gut health. Providing an overall perspective was Dr. S. K. Dash, president and founder of probiotic supplement manufacturer UAS Laboratories, Minnetonka, MN, who used an analogy to describe probiotic function. "When you think of probiotics, think of a green lawn. In the lawn you want to have only green grass and no weeds. As long as green grasses are present there is no chance for weeds to grow," he said. "Green grass is like the L. acidophilus in our gut, while the weeds are like e. coli and candida. But if the gut is maintained there is no chance for weeds to grow."

Within the category of gut health, however, there are many subconditions that can be impacted with probiotics. According to Dr. Sanders, current research indicates use of probiotics in protecting against diarrhea, colon cancer (animal studies only) and harmful microbe activities. Additionally, she said, they have been investigated in lactose digestion, immune system modulation, vaginal and urinary tract health, allergies, inflammatory disorders and hypertension. She qualified, "A long term impact on chronic disease and immune function on human health is still undetermined."

Discussing research in terms of lactose digestion and gut repopulation was Bill Haines, vice president of B2B marketing, Dairy Management Inc. (DMI), Rosemont, IL. "Gut health is about the only thing that has a lot of documented evidence behind it at this point, particularly when you talk about lactose digestion," said Mr. Haines. "The other gut health issue that has been in the forefront is gut repopulation following antibiotic therapy. Doctors have often advised patients to consume foods like acidophilus milk and yogurt after they have been on extended antibiotic therapy as a way to repopulate their gut with healthy organisms." As for other health benefits, Mr. Haines stated, "Some of the more exotic claims like cholesterol reduction and immune system stimulation or cancer prevention may have been shown in animal models but there is tremendous paucity of clinical evidence right now."

As an aside, with antibiotic overuse running rampant in the nation, a four-year media campaign will be launched in Colorado next year, aiming to coax patients away from antibiotics, according to a recent article in the Denver Post. Federal funds of $2 million will pay for advertisements on radio, television, bus stops, billboards and newspapers warning patients of the risks of overprescribing antibiotics.

Dr. Gregor Reid, director, Canadian Research and Development Centre for Probiotics, Lawson Health Research Institute, and professor of Microbiology and Immunology, University of Western Ontario, London, Ontario, Canada, agreed there is strong evidence for probiotics in preventing and treating diarrhea and lactose intolerance and added that preliminary studies he conducted also show strong evidence linking probiotics with the prevention of urogenital infections.

For LGG in particular, Valio's Mr. Leporanta discussed recent research. "Recent findings with LGG show that probiotics may have potential in the prevention of food allergies and possibly in the prevention of infections in general."

Consumer Awareness/Acceptance For Probiotics
On the consumer level, the reasons for taking probiotics do not always parallel what has been studied in clinical trials. The Hartman Group tracked the reasons consumers take probiotics and surprisingly some of the more scientifically backed indications fall lower in priority on consumers' lists. In a survey the top reasons for use were general health and wellness (49%) and digestive problems (31%), followed by a host of lesser concerns.

There is no question that consumer awareness for probiotics is low. Considering that fermented products are not commonplace in the U.S. market-coupled with the monumental task of communicating the concept of "good" bacteria in an all too sterile society-the U.S. environment is a challenging one.

Dr. Sanders said communicating the importance of specific levels of bacteria to health professionals and then to consumers will prove beneficial for this market in the long run. She used Dannon's fermented milk product, Actimel®, as an example. "I am excited that Dannon is providing specific levels of bacteria on their label because it provides important information to consumers as they learn the significance of specific levels from their health professionals," she said. "Consumers are used to the concept of dose and are aware they need to take a certain amount of something to receive a benefit. They wouldn't take one-tenth of an aspirin, for example, and expect an effect. Doctors and dietitians are going to enhance awareness of this eventually but right now consumers don't have enough information to know if the food product they are consuming really is going to do for them what it needs to."

Hindering consumer awareness is the fact that per capita consumption of culture products in the U.S. is very low, barely equaling that of a small country in Europe, according to Kasi Reddy, vice president, R&D and quality assurance at yogurt manufacturer Stonyfield Farm, Londonderry, NH. "Stonyfield's typical consumer, who is born and raised in the natural foods arena, is very educated and in fact, asks questions about products we haven't even developed yet. But this is not the norm," he said. "For the major players, probiotics and prebiotics are considered very underdeveloped areas and that is not because the research is not up to date but is more due to claims and what major companies' consumer research allows them to do."

Steve Allen, vice president, business development, Nestle USA, Glendale, CA, manufacturer of LC1™, also weighed in on the consumer awareness issue. "What is holding us back in the U.S. is that the consumer does not really have an explanation for probiotics because there is no vehicle or preexisting knowledge on which to build. In Europe, the notion that yogurt is good for you is well established," he said. "The other problem is that the benefits being touted for probiotics are too general and not specific like St. John's Wort for depression and echinacea for colds. To say probiotics provide immunity is too vague.

As an aside, Mr. Allen commented on the recent failure of LC1 in the U.S. "Nestle LC1 was too early for the U.S.; the benefits were too general and the price/value relationship wasn't there," he said. "LC1 needed a huge PR event for it to make a significant impact. It needed to be on 60 Minutes or 20/20 where you have someone like Barbara Walters interviewing a consumer of probiotics saying it saved her life."

Terri Butler, general manager-nutraceuticals, Nutraceutix, Redmond, WA, creator of the LiveBac® manufacturing system, said the lack of success of probiotics in the U.S. is due to education. "In the U.S. we have been taught that bacteria are bad for our health and the cause of disease," she said. "This is a hurdle we have to overcome education-wise. We need to teach people that they are full of trillions of bacteria themselves when they are in a healthy condition and that they need those healthful bacteria to stay that way."

Delivery And Dosage Issues
Defining dosage levels and maintaining viability in various delivery systems are the next challenges for manufacturers to overcome. Discussing the latter was Michael Shahani, director of operations, Nebraska Cultures, Lincoln, NE, supplier of the DDS-1™ strain. "All probiotics are adversely affected by four elements; light, heat, oxygen and moisture. Stability in probiotics is achieved by minimizing all four elements in all stages of probiotic processing," he said. "In addition, customers should be educated that even after purchasing, they should try to keep the products in a cool, dry place with minimal exposure to light and air."

Offering his perspective on delivery forms was Mr. Haines of DMI. "A lot of DMI's research is aimed to verify that probiotic function is enhanced if they are consumed in a food environment, particularly within a dairy product. Dairy products provide an ideal medium in which these organisms can grow," he said. "With supplements you have to question whether or not the probiotics will get into the intestine and maintain viability. Also, can probiotics be consumed by themselves or do they need to be consumed with something like a prebiotic that will stimulate their growth?"

Also weighing in on the food side of the equation was Dr. Sanders, who said, "With stability, most of the responsibility for appropriate formulation falls on the dietary supplement side because those are the companies stating that they have certain levels of bacteria in their products," she said. "Stability can become a problem especially when pill manufacturers are looking for a two-year, room temperature shelf life." She continued, "I think a probiotic product should mimic something similar to what the food industry does, which says when you buy a carton of milk, it is good through a certain date. Also, I think in terms of enhancing stability the fresh dairy product concept really fits in with keeping these probiotic bacteria alive."

Offering a supplement perspective was Institut Rosell's Dr. Goulet. "At issue is the protection of probiotics against stomach acidity and shelf stability. Everyone knows that the stress due to the acidity in the stomach is detrimental to probiotics and that 90-95% of probiotics are lost during the passage through the stomach. Improving the protection of probiotics using enteric coated capsules and microencapsulation will be a great improvement over existing products," he said. (See accompanying sidebar on Institut Rosell and Balchem.)

David Howard, president and CEO, Nutraceutix, cited other issues that can arise with supplements. "One of the problems lies with capsules because they can contain moisture and probiotics are freeze-dried. If you put a freeze-dried material with a moisture content of less than 3% into a capsule with a moisture content of 6-8% then the freeze-dried material will draw moisture out of the capsule, which will re-awaken the probiotic, causing it to eventually die within the capsule," he explained. "Our research has shown that with a tablet we can control the stability and viability for a longer period of time because we can keep the moisture content under control."

On the dosage front there is no published standard for the amount of bacteria that should be in a probiotic product, only ballpark figures ranging from 106 to 1010 bacteria per day, depending on the condition of the host. Fortunately, probiotics are generally safe and well tolerated by humans even at high dosages. Mr. Shahani of Nebraska Cultures offered, "Generally, 5-10 billion live bacteria per day is a sufficient dose to maintain healthy intestinal flora. Persons with severe problems may take more with the advice of a health practitioner. It is not possible to 'overdose' with probiotics, nor is taking a very high dose (20+ billion/day) of probiotics necessarily more beneficial."

Ms. Butler agreed there is tremendous variability on how much bacteria to deliver. "There is no real solid research on dosage yet. You hear a lot of people state very certainly that a particular dose is the amount you need and certain companies put capsules and tablets together aiming for pretty high doses like five to 10 billion organisms per dose. However, it is not clear whether that many is needed or not."

Dosage also depends on whether you are delivering probiotics in a supplement or in a food, according to ConAgra's Dr. Vanderhoof. "You can generally get colonization at a lower dosage in food than you can with a supplement. This is because when you eat the freeze-dried bacteria in a supplement, not all of the bacteria will survive and colonize so you need a lot more bacteria."

For The Future
Interesting, innovative things lie ahead in probiotics, according to industry experts. Dr. Sanders predicted, "We have the technology to do chromosome sequencing of probiotic bacteria. Different research groups around the world are targeting sequencing of several different probiotic strains. The type of information gained from this functional genomic analysis will greatly aid our ability to answer the many unanswered questions about how probiotics do what they do."

Dr. Vanderhoof also discussed futuristic possibilities. "In 10 or 20 years I think you will see people take these bacteria and splice them with particular genes." For example, he said, "You can take a bug that colonizes really well and splice a gene into it that makes a chemical that kills other bugs to make a 'super probiotic.'" However, he said, because of the fear of genetically modified organisms, it will be awhile before these products are acceptable.

Dr. Reid said a change in philosophy is needed in our society. "At present, we have a disease mind set, which leads to massive use of expensive drugs and huge medical health bills for the government, population and insurers," he said. "In my view, there are substantial business opportunities for companies willing to put scientific and clinical backing behind their products, so there is life after pharmaceuticals. These can be diagnostics, as well as preventive and treatment regimens. We now have good evidence to use probiotics, if only the powers that be (big business, FDA, etc.) allow it to happen. Lastly, we need to improve our manufacturing capabilities so that top quality probiotic products are the norm, not the exception."

Valio's Mr. Leporanta said the increasing interest in probiotics is good but can lead to problems. "Probiotic products have been and are one of the few dairy product categories that has been expanding. In many countries this has unfortunately led to 'inflation' of probiotics. Manufacturers are calling their products 'probiotic' even though there are no studies or any information on the specific health benefits of these products," he said. "Therefore in some countries consumer organizations and also food researchers have criticized the use of probiotics in general. In the future, scientifically backed probiotics like LGG, Yakult, LC1 and L. reuteri will most probably survive best on the market."

Prebiotics
Prebiotics:"Nondigestible food ingredients that benefically affect the host by selectively stimulating the growth and/or activity of beneficial microflora…" scientist M.B. Roberfroid, 1996

If probiotics are the better mousetrap, then prebiotics are the cheese. While relatively new on the scene in terms of health benefits, these products have potential as a catalyst in the gut and-while suffering from the same lack of awareness as probiotics-show potential for strong growth. From a functional perspective prebiotics have been present in food systems for several years but were not touted for any health benefits. Today industry interest has been piqued and more products are lining the shelves. The hurdle with prebiotics is also the need for more clinical evidence as to their health benefits.

Some of the typical prebiotics include fructooligosaccharides (FOS, BeFlora™); short chain fructooligosaccharides (scFOS™/NutraFlora®); inulin (Raftiline®, Frutafit®, Inuflora™); oligofructose (Raftilose®); other indigestible oligosaccharides; resistant starch (Hi-Maize™) and others such as Fibersol-2™ derived from natural corn starch, larch arabinogalactan AG derived from the Larch tree and Lacty® derived from lactitol, which is a hydrogenated lactose.

Prebiotic Trends And Issues
Prebiotics are ideal for companies that want to provide a function in food systems as well as health benefits. Bryan Tungland, vice president of scientific and regulatory affairs, Imperial Sensus, Sugarland, TX, supplier of Frutafit® inulin, recognized this trend. "The tendency for product developers is to examine the various prebiotic sources that are available and not only utilize those prebiotic sources for food delivery development but also try to manage systemic health by influencing local GI health."

Steve Young, technical consultant for Fibersol-2 supplier Matsutani America, Decatur, IL, said in comparison with probiotics, prebiotics are stealing the spotlight. "Probiotics are something people have talked about for years in the yogurt business but the weight of all the action seems to be on the prebiotic side."

There is a relative superiority in using prebiotics versus probiotics, said Dr. Aftab Ahmed, director of R&D and business development, Naturally Vitamins, a subsidiary of Marlyn Nutraceuticals, Phoenix, AZ, manufacturer of Inuflora. "It stands to reason that if you provide a food source to the intestinal bacteria that are already in their natural habitat, they will grow more robustly. In contrast, with probiotics, these organisms may be so weakened by the time they reach the intestine that only a few will actually be able to attach to the intestinal wall and multiply," he said. "People have to remember that the bacteria already attached to the intestinal wall are very fierce competitors that the new bacteria will have battle in order to take over their turf."

Koen Kummel, market development specialist, Purac America, Lincolnshire, IL, supplier of Lacty®, also described how prebiotics can be beneficial for health. "Probiotics produce short chain fatty acids (SCFAs), which will reduce pH. Reduction of pH will prevent growth of pathogens and increase the solubility of minerals in the colon, which will influence absorption (i.e. influence of lactitol and inulin on calcium absorption)," he said. "Prebiotics could have a role in the reduction of attachment of pathogens to the cell wall of the colonic cells."

On the other side of the coin was ConAgra's Dr. Vanderhoof, who said prebiotics can be helpful but there are concerns. "The good thing about prebiotics is that they are stable and can be put into almost any food product and they will cause the proliferation of certain kinds of bacteria. However, prebiotics do not have a strain specific effect," he said, "If you put FOS in food you might be able to change the ratio of bifidobacteria to e. coli but you will not be able to select out probiotic strains of bifidobacteria versus non-probiotic strains. There is no specific beneficial effect with prebiotics as opposed to probiotics. Therefore the opportunity to do magical things with bacteria are probably more on the probiotic side rather than prebiotic side."

Valio's Mr. Leporanta concurred. "Prebiotics are substances that promote the growth and effects of positive bacteria. But first one should know which are positive bacteria. The interaction of prebiotics to probiotics is not documented very well and there is a risk as the industry starts to label all fibers as 'prebiotics' despite the fact that not all are prebiotic to the bacterial strains that we would like to boost. For example, most 'prebiotics' are not prebiotic to LGG."

Prebiotics will gain headway as soon as FDA defines dietary fiber, said Susan Drake, R.D., technical sales manager, GTC Nutrition, Golden, CO, distributor of scFOS™/NutraFlora®. "I think you will start seeing more prebiotics in products with the impending definition of dietary fiber from FDA, which will hopefully allow companies to claim it as a source of fiber on the packaging," she said. "Within the next two years I would expect a decision to be made after which you will more than likely see an increase in prebiotics incorporated into food products."

Despite its newness and lack of clinical studies, the prebiotic trend has major players in the industry interested, according to Stonyfield's Mr. Reddy. "Inulin has already been discovered by several major manufacturers in the U.S. and is being used in foods such as yogurt, milk, cheese, soy milk, confections, nutrition bars and even baby cereal," he said. "An increasing number of people are taking giant leaps into this area because of inulin's capabilities in terms of calcium absorption and digestive health maintenance."

Prebiotic Research In Brief
Calcium absorption was one of the prebiotic research areas discussed by Mr. Tungland, who said inulin is the most researched dietary fiber from a clinical aspect. "It has centuries of research and is definitely the most studied from a prebiotic standpoint for health purposes." As to the issue of mineral absorption, particularly calcium and magnesium, he said, "There are a number of animal studies and four human clinicals right now that have shown that inulin oligosaccharides enhance calcium absorption in the proximal GI. In addition, there are recent studies as well as some in the late 1980s and early 1990s that showed fairly substantial magnesium absorption."

Stonyfield's Mr. Reddy offered, "All of the animal and human studies to date support calcium absorption rates ranging from 20-50%. In fact, Stonyfield is in the process of developing structure-function claims in relation to this."

Purac's Mr. Kummel also discussed mineral absorption. "Inulin is fermented by probiotics, whereby SCFAs are produced reducing pH in the colon. A pH decrease will increase solubility of calcium and other minerals," he explained. "Similar results of this activity were also found with Lacty in a study in Japan."

Ms. Drake suggested research dictates a wide range of capabilities for prebiotics. "Since FOS can act as a soluble dietary fiber there is some research suggesting that it may help with lipid reduction." As for mineral absorption, she said, there is preliminary data suggesting that FOS can enhance calcium absorption but the data is inconclusive in humans for long term use. For magnesium absorption, she said, FOS has been very beneficial in both humans and animals.

Most recently a double blind placebo controlled study using Orafti's Raftilose Synergy 1 (a combination of inulin and oligofructose) was conducted. Twenty-nine girls aged 11-14 participated in a study, which took place at the USDA/ARS Children's Nutrition Research Center at Baylor College of Medicine, Houston, TX. The girls consumed a calcium fortified diet during two three-week periods, with a two-week wash out period in between. They were given a daily calcium dose of 1500 mg, which is the recommended daily intake for their age category. Additionally, the girls were given either eight grams per day of Raftilose Synergy 1 or a placebo. At the end of each three-week period, calcium absorption and urinary calcium excretion were monitored. Results showed that in the placebo group, 32% of the consumed calcium was absorbed, while in the Raftilose Synergy 1 group, 38%-a 20% increase-of the consumed calcium was absorbed.

Dosage Dilemmas
Dosage issues abound primarily due to the fact that, as with probiotics, there is no set standard for the level of prebiotics needed to produce a health benefit. The dose, however, should be enough to positively stimulate the healthy microflora in the gut and cause these "good" bacteria to reproduce. Further, dose depends on the type of prebiotic used and to what levels clinical trials have indicated a health benefit. Discussing these issues was Dr. Mark Izzo, director of science and technology at Malvern, PA-based Orafti, which supplies inulin and oligofructose. "The dosages for particular prebiotics are dictated by what your clinical trials tell you. Our clinicals have told us that two to four grams of inulin is needed in order to yield a beneficial effect. The reason there are not set dosages for prebiotics across the board is because they are not all the same."

In terms of Matsutani's Fibersol-2, Mr. Young said, "Most of the work out of Japan shows that you can get the prebiotic benefits of Fibersol-2 by consuming as low as three and as high as 10 grams per serving. Three grams per serving is roughly 12-13% of the daily value of dietary fiber and 10 grams per serving represents about one-third of the daily value."

Mr. Kummel discussed the dosage of Purac's Lacty and the need for more regulation. "A 10 gram level of Lacty is where Purac's research dictated a prebiotic effect. But every product has a prebiotic effect if you use enough of it," he said. "I think when more and more companies look into this FDA will start to regulate because otherwise it will grow in the wrong direction."

Rodger Rohde, president, Triarco Industries, Wayne, NJ, supplier of BeFlora, said that one to three grams daily of FOS is needed for adults for regular daily maintenance. However, he said, children, those taking antibiotics or other prescription medications and those that are ill may need additional amounts.

GTC's Ms. Drake discussed some of the differences in prebiotics relative to dose. "When you use short chain fructooligosaccharides the minimum dosage recommended is a quarter teaspoon or one gram per day. That is enough for the bifidobacteria to reproduce by 500% within a month," she explained. "Some of the longer chain fructooligosaccharides or inulin products may require a dose of five to eight grams per day for the bifidobacteria to reproduce."

Prebiotic Awareness
Prebiotics rate pretty low on the awareness scale with consumers. However, marketers do not have to handle as steep a learning curve as with probiotics because most, if not all, prebiotic ingredients are generally recognized as safe (GRAS) and do not have as difficult a health message to convey. As with probiotics, prebiotics have more of a presence in the rest of the world as compared with the U.S.

Imperial Sensus' Mr. Tungland pointed out that prebiotics will become easier to market as gut health becomes an easier topic for consumers to digest. "There has been a lot of national media that has used TV time for talking about gut health. Also, if you look at grocery store counters you will see a lot of products that carry a message about detoxification, which is directly associated with gut health," he said. "With that association people are becoming much more attuned to prebiotic products and the need for better gut health and the old notion that people don't want to talk about gut health is changing."

Synbiotics
Synbiotics: "The combination of probiotics and prebiotics in a synbiotic has not been studied. This combination might improve the survival of the bacteria crossing the upper part of the gastrointestinal tract, thereby enhancing their effects in the large bowel. In addition, their effects might be additive or even synergistic…" Roberfroid, 2000

Synbiotics is not a well studied area as yet but preliminary research has scientists intrigued and hopeful. Most experts agree that there is a place for synbiotics as soon as the science catches up. Some companies-such as Stonyfield Farm with its Blends line of yogurts combining specific probiotic strains and inulin-have taken advantage of the relationship between prebiotics and probiotics. It remains to be seen if other companies will follow suit.

From Dr. Sanders' point of view, there is not a lot of scientific support to show a synergistic effect in terms of taking a probiotic matched with a prebiotic in the same product, compared to taking the two separately. "There might be one or two papers out there to suggest the benefit of synbiotics but I think that is going to be an interesting area of development," she said. "There are products on the market that are considered synbiotics and in Japan it is very common to see products combining both prebiotics and probiotics."

To Mr. Reddy of Stonyfield synbiotics are the answer. "Together I think prebiotics and probiotics make the perfect combination. Prebiotics ensure the survivability of some beneficial bacteria, specifically bifidus bacteria, with some reports pointing to other probiotic strains as well," he said. "Even from a common sense standpoint it is the perfect situation for both prebiotics and probiotics to co-exist. One is an ingredient component, which functionally helps the product composition as well as health and the other offers built-in therapeutic and prophylactic factors for synbiotic effects."

Most of the research on synbiotics is related to anti-tumor based studies and the ability to show stability and enhance growth of probiotics, according to Imperial Sensus' Mr. Tungland. "The main reason for using a synbiotic is because a true probiotic, without a prebiotic, is not very viable. To be able to enhance viability not only on the shelf but also in the colon allows for much greater attachment and growth rate of the healthy bacteria to minimize the growth of bad bacteria." Mr. Tungland continued, "Without a specific food source, i.e. the synbiotic relationship, you are left with a probiotic having greater propensity for oxygen intolerance, low pH intolerance and temperature intolerance and they have to compete against other bacteria that may compete more favorably if their true specific food source is not available."