April 20, 2010
Bacteria used to be a dirty word in the ingredient industry. No one wanted it to find its way into batches, and then delivered to consumers. Bacteria in products meant adulteration, sick consumers and potential fines from regulation agencies.
With probiotics, that has changed. Probiotics are defined by the World Health Organization (WHO) as Live organisms, which, when administered in adequate amounts, confer a health benefit to the host, while the International Scientific Association for Probiotics and Prebiotics (ISAPP) says a probiotic must: be alive when administered, have undergone controlled evaluation to document health benefits in the target host, be a taxonomically defined microbe or combination of microbes (genus, species and strain level), and be safe for its intended use.
In short, probiotics are bacteria that have been shown to help bolster health, and research has emerged showing health benefits ranging from gut to immune to skin. Probiotics are ingested and help maintain a critical flora balance between various groups of bacteria, such as lactobacilli, streptococci, lostridia, coliform and bacteriodes, in the intestine. This balance can be disrupted by stress, disease, antibiotics, unhealthy foods, lack of sleep and harmful environmental conditions.
In his book, The Consumers Guide to Probiotics, S.K. Dash, Ph.D., noted, Normally, populations of pathogenic flora are kept in balance by competition from good bacteria and because of symbiosis, which is the mutually interdependent relationship among the hundreds of microbial species. The problem is that our modern lifestyles have left many people with an imbalance of beneficial to pathogenic gut bacteria. The solution: replenishing and stabilizing levels of beneficial bacteria in the gastrointestinal tract.
Probiotics supplant pathogenic bacteria that cause various kinds of illnesses, said Michael Shahani, director of operations, Nebraska Cultures. They create enzymes to help with digestion. They create B vitamins and folic acid. They improve vaginal health in women, and fight fungal and yeast infections in everyone. They have been shown to help with skin conditions such as eczema and psoriasis. And there is new research showing that probiotics can favorably modify immune response.
Mike Bush, vice president of business development, Ganeden Biotech, said probiotics address a broad spectrum of health conditions ranging from immune, digestive and inflammatory benefits, and added, Research is being performed looking at conditions as diverse as obesity and metabolic syndrome to autism and oral health.
All these benefits are driving increased consumer usage. According to a survey by ConsumerLab.com of 6,012 consumers in February 2010, probiotics were used by 30.4 percent of respondents, up from 25 percent last year. One-third of women in the survey used a probiotic. Usage has translated into rising sales. Packaged Facts reported sales of probiotic/prebiotic foods and beverages topped $15 billion in 2008, a 13 percent increase over 2007, and projects the market for functional foods and beverages addressing digestive health will top $22 billion in 2013, a compound annual growth rate (CAGR) of 12 percent between 2004 and 2013.
The economy may also be a factor behind these increased sales. As a growing number of consumers seek to counter rising health care costs with preventive measures and non-prescription treatments for digestive problems, probiotics are going mainstream, said Mark Vieceli, director of sales, marketing and business development, Capsugel.
While many in the industry welcome these rising sales, awareness of probiotics is still on the rise. Most consumers are aware of probiotics from Activia commercials, said Mike Smith, vice president, Specialty Enzymes & Biochemicals Co. As a result, I think the typical consumer believes probiotics exist to make you regular. Groupe Danone (Dannon in the United States) even made up the name Bifidus Regularis. Its good marketing, but not very informative.
Isabelle Champié, human nutrition brand manager for Institut Rosell-Lallemand, added, According to recent surveys, probiotic awareness has soared in recent years mainly due to marketing and communication efforts of dairy/food companies, but it seems understanding of health benefits among the general public is still very low.
In a seminar at SupplySide West in November 2009, Greg Stephens, Natural Marketing Institute (NMI), said approximately 7 percent of Gen Xers, Boomers and Matures use probiotic supplements, but the Gen X demographic has the highest awareness of probiotics, at 52 percent. At the same time, 70 percent of consumers dont know any specific health benefits of probioticsunderscoring the point that awareness doesnt equal understanding.
Luis Echeverria, business development manager, Unique Biotech USA, said it simply, Consumers are definitely not aware of probiotics. He added, Only a small percentage of the population is actually aware of them and the ones who are aware actually do not know what the uses or real benefits of probiotics are.
This may not be for a lack of trying to understand, noted Frank Hodal, founder and CEO, Vidazorb. For the small number who do seek to add probiotic bacteria to their health regime, few know how to distinguish the good from the bad, the wheat from the chaff. Thats not the consumers fault by any means. Rather, its because it takes time to learn what there is to know about probiotic bacteria. It helps when the media, especially the industry media, makes a concerted effort to dig deep and report the science behind the facts.
This lack of awareness may also not be the fault of the industry, according to Tim Gamble, senior vice president of sales and marketing, Nutraceutix Inc. Consider what has happened with a number of other huge sellers like vitamin C or calcium, both available in a variety of different forms with, in some cases, different bioavailabilities and benefits. After many years of attempted differentiation by brands, the vast majority of consumers still just look for a bottle that states vitamin C or calcium, and probably pay more attention to price than any other factor. This is not necessarily good or bad, but does lead one to consider that the industry can often spend an inordinate amount of time trying to differentiate products in a fashion that accomplishes very little, at least in terms of broad market sales.
Part of the reason for consumer confusion may be the complexity and number of different probiotics in the market. Probiotics can be identified using genus and species, such as Lactobacillus acidophilus. However, they can further be differentiated with strain. Educating the consumers (and the marketing companies) about strains versus species is key to success in this area, said Brian Peeters, strategic sales manager, Chr. Hansen Inc. Probiotics which are identified by their strain designation (L. acidophilus LA-5, B. lactis BB-12, and L. casei 431) are usually documented strains, while those which are listed at only the species level (L. acidophilus, B. lactis, L. casei, etc.) usually do not have any documentation and are classified as generic or non-documented strains. He added, Some researchers, such as Dr. Gregor Reid, argue that probiotic products should not even be allowed to be called probiotics if the strains contained in the product are not documented. However, at this time, no regulatory agency is enforcing this.
That said, some product manufacturers dont see the benefit of adding a strain to their marketing, or even their products. Consumers will buy without it, so why bother? Slap the word probiotics on the box or bottle and people will buy it, but a word on the box doesnt mean youll be getting anything beneficial to your health, Hodal said.
In spite of, or maybe because of, this uphill battle, probiotic manufacturers are increasingly patenting their own strains to sell to product makers. In many cases, brand manufacturers themselves are looking to distinguish the benefits of their specific probiotic strain by branding them differently, said Grant Washington-Smith, business development manager, BLIS Technology Ltd. We are nowhere near the point where mainstream consumers are looking for a specific strain for a specific benefit. However, as more brand manufacturers publish more data about their strain, we will see more of that coming to pass. We are already starting to see some brands put a consumer-centric brand around their strain to help consumers understand these benefits.
These branded strains usually come with a slew of scientific studies. Washington-Smith noted BLIS Technologies BLIS K12 probiotic, an S. salivarius strain, has clinically demonstrated benefits for the mouth and throat. A German study found BLIS K12 may have the potential to control oral bacterial infections when the uptake is repeated frequently,1 and a New Zealand study found it may provide an effective strategy to reduce the severity of halitosis.2
As consumers become more aware of the probiotic benefits, they will start to choose probiotics by the strain and not just by the packaging claims, Bush said. As a way to help educate consumers about probiotics, Ganeden Biotech has branded our Bacillus coagulans GBI-30, 6086 strain under the brand name GanedenBC30®, and is spending money to educate consumers of the benefits of that ingredient over others. He noted Ganeden Biotech has a line of consumer products sold under the Digestive Advantage and Sustenex brands, with products focused on aiding in the symptoms of irritable bowel syndrome (IBS), lactose intolerance, gas and constipation. We have also performed, and continue to perform, studies relating to immunity, metabolic activity and other digestive areas.
Indeed, studies have shown GanedenBC30 probiotic may be a safe and effective therapeutic option for enhancing T-cell response to certain viral respiratory tract infections, which aids immune function.3 For digestion, GanedenBC30 may be a safe and effective option for the relief of abdominal pain and bloating for patients with IBS;4 was effective in improving the quality of life and reducing gastrointestinal (GI) symptoms in adults with post-prandial intestinal gas-related symptoms and no GI diagnoses;5 aids the digestion of lactose and fructose, which could be used to prevent occurrence of intestinal symptoms in individuals sensitive to these carbohydrates;6 and is safe and effective for reducing daily bowel movements in patients with diarrhea-predominant IBS.7 An additional pilot study suggested adjunctive treatment with GanedenBC30 in combination with pharmacological anti-arthritic medications appeared to be a safe and effective for patients suffering from rheumatoid arthritis (RA).8
GI health, women's urogenital health, immunity, children's health and oral health are some of the major categories Peeters said probiotics have been shown to address. A randomized, placebo-controlled cross-over study with 46 healthy females who took 1 billion colony forming units (CFU)/day BB-12®, 0.3 billion LA-5®, 50 billion S. thermophilus FK 303 and S. thermophilus FK 320 in fermented milk (all offered by Chr. Hansen) found significant increase in defecation frequency, significant increase in fecal quantity, improvement in fecal characteristics and improvement in fecal microbiota during probiotic intake compared to no intake.9 A different randomized, placebo-controlled, parallel study of 160 healthy Helicobacter pylori (H. pylori)-infected subjects, mean age of 47 years, found 5 billion CFU of BB-12® + LA-5® twice daily in yogurt reduced the risk of antibiotic side effects including diarrhea, improved eradication of H. pylori and restored depletion of Bifidobacterium after antibiotic treatment.10 H. pylori is the bacteria responsible for most ulcers and many cases of stomach inflammation (chronic gastritis).
For immune health, phagocytic activity significantly increased after intake of Chr. Hansens BB-12®, which shows it has an immune modulating effect.11 Fecal immunoglobulin A (IgA) and anti-poliovirus IgA increased significantly during BB-12 intake and peaked at day eight in healthy children aged 15 to 31 months.12 LGG® and L. casei 431® (from Chr. Hansen) enhanced the immune response after vaccination, while enhancing systemic protection against viruses by increasing virus neutralizing antibodies.13
Chr. Hansens probiotics also show childrens health benefits by alleviating symptoms of atopic eczema (BB-12® and LGG®),14 reducing the risk of diarrhea (BB-12® and TH-4®),15,16 and lowering frequency of colic and irritability (BB-12® + TH-4®).17
For women, its GR-1® + RC-14® combination helped maintain a healthy vaginal microbiota by increasing the number of beneficial Lactobacilli and lowered the risk of bacterial vaginosis,18 and decreased yeast and potential pathogenic bacteria while lowering the risk of yeast vaginitis.19 That same combination of Chr. Hansen probiotics also augmented the efficacy of antibiotics against yeast vaginitis20 and bacterial vaginosis.21
Institut Rosell-Lallemand also has a branded strain, Lactobacillus plantarum 299V (LP299V), aka, Lp299v. To study Lp299vs effects in patients with IBS, 40 patients were randomized to receive either LP299V in liquid suspension (20 patients) or placebo (20 patients) over a period of four weeks.22 All patients treated with LP299V reported resolution of their abdominal pain as compared to 11 patients from a placebo group (P = 0.0012). There was also a trend toward normalization of stools frequency in constipated patients in six out of 10 patients treated with LP299V compared with two out of 11 treated with placebo (P = 0.17). With regards to all IBS symptoms, an improvement was noted in 95 percent of patients in the LP299V group versus 15 percent of patients in the placebo group (P < 0.0001). Other studies found Lp299v decreased pain and flatulence in patients with IBS.23
Champié said Institut Rosell-Lallemand research is ongoing. One of our synbiotic formulas (ProbioKid) was recently involved in a clinical study in children and showed that it was effective in the prevention of common winter infections episode. However, this has not been published yet. She also noted, We dedicated our last scientific symposium to the interactions between the microflora and the brain-gut axis, the gut being often described as the second brain. Didier Desor, professor of behavioral and cognitive neurosciences at University Henri Poincaré in Nancy, France, presented an innovative study with ProbioStick® , a formulation containing the documented strains Lactobacillus Rosell-52 and Bifidobacterium Rosell-175 in a stick format and shown to provide a beneficial effect on the GI symptoms experienced by individuals affected by chronic stress.24 Using a mouse model validated with Diazepam, it was shown that ProbioStick was able to reduce signs of anxiety, displaying an anxiolytic-like effect. Such effect had not been previously described with probiotics.
Daniscos probiotics include: HOWARU Bifido® (Bifidobacterium lactis HN019), HOWARU® Rhamnosus (Lactobacillus rhamnosus HNOOI), HOWARU® Dophilus (Lactobacillus acidophilus NCFM), HOWARU® Protect (combination of Lactobacillus acidophilus NCFM® and Bifidobacterium lactis Bi-07) and HOWARU® Restore. Bifido enhanced natural immunity in healthy elderly subjects after six weeks of supplementation,25 and enhanced immune function of two different types of leukocytes.26 Dophilus can potentially prevent colon cancer development,27 was associated with decreased lactose intolerance symptoms compared with placebo,28 and induced some protection against candidiasis.29 Rhamnosus exhibited dose-dependent effects on the phagocytic defense system of mice, and stimulated specific gut mucosal immunity;30 as well as reduced the severity of E. coli infection by enhancing humoral and cellular immune responses.31 Protect reduced fever incidence, coughing, runny noses, and the duration and severity of cold and flu symptoms in children;32 and Restore promoted a more rapid return to pre-antibiotic baseline fecal bacterial microbiota in healthy subjects undergoing antibiotic therapy.33
Nebraska Cultures Inc. is currently sponsoring a study of Dr. Shahanis DDS-1 strain of L. acidophilus and its efficacy in humans. The study specifically seeks to determine whether healthy bacteria can survive an extended time in the human GI tract. The study will employ human trial subjects who ingest controlled amounts of specified bacteria strains, and who are then tested after an extended period of time to see what, if any, of the bacteria can still be detected. A study showing that our DDS-1 strain of Lactobacillus acidophilus actually does implant in the gut is the first and most critical step in showing that any other health benefits imparted by L. acidophilus DDS-1 can be proven, Shahani said. So far, the results of the study have shown to be very positive.
Gamble noted Nutraceutix produced a product for a small clinical study on the impact probiotic supplementation has on the healthy adult immune system, which he said is now peer-reviewed and published. Results were so positive that the product, Immunobiotix®, is now available on the market in the exact form studied, he said. More recently, Nutraceutix produced a variety of probiotic products that are being studied for their contributions to oral health. One key takeaway from all of this is that researchers, both commercial and academic, are realizing that conducting studies with probiotics in a commercially viable, consumer-ready form, particularly one that is proven and heightens potential outcomes, is a wise decision.
And, Echeverria added Unique Biotech USA is currently working on four studies on its strain Unique IS-2 (Bacillus Coagulans) for general GI support and immune support.
All of these new studies with specific, branded strains have spurred R&D efforts to add probiotics in a broader range of consumer products. Danisco has recently launched an offer on probiotics in refrigerated juices, and our applications specialists have been working extensively to gain specific expertise in process and formulations in this area, said Rob Slemmons, marketing communications, Danisco. By acquiring this real know-how, Danisco will support the manufacturers to create a probiotic juice adapted to their manufacturing environment.
For consumers, these new probiotic food products may take some getting used to. Most people attribute gut health probiotics with the delivery system such as yogurt or cultured foods, which is not many miles away from how we would have expected to take these products several years ago, Washington-Smith said. Where consumers are starting to be tested is when they see a dry breakfast cereal or a chocolate product with probiotics. Live organisms in something that is dry and chewable may still take a bit longer for consumers to wrap their minds around. Thats still a challenge for the industry, but its a matter of time and marketing.
Ingredient manufacturers would be wise to create probiotic ingredients that can fit into products consumers already use, according to Bush. We are seeing increasing interest in product categories that fit into existing habits of consumers, he said. Whether through shelf-stable bars and drink mixes to more indulgent products, consumers want flexibility in probiotic consumptions so that they are not tied to a single product type such as yogurt or supplements. As awareness of the importance of daily probiotic consumption, so has the demand for products that fit into the lifestyles of consumers.
These products include mainstream foods. The major trend right now is in the functional foods market by adding probiotics to foods in different applications like bakery, candies, drinks, etc., said Echeverria. For this reason, our company had decided to invest in stable probiotics segment as Unique IS-2 because all the new future food applications will need versatile and flexible strains that are heat, humidity, cold and handling resistant in order to reach consumer alive and still have a benefit.
Also addressing formulation challenges, Shanani noted, Probiotic use in foods has met with only limited success. Many systems cannot sustain live bacteria, and they die before reaching the consumer. However, probiotics in yogurt, ice cream, chilled beverages, chocolate and a few other applications, can work very well. Probiotic supplements in capsule or powder form are still the most effective.
Gamble said the majority of struggles/challenges facing this market are self-inflicted. We see probiotics, as a hot ingredient, being incorporated (usually unsuccessfully) by others into a variety of products and forms that are just not well-suited to being an effective delivery mechanism for probiotics. The resulting products, either gimmicky or unsound, or both, cast shadows on the real potential of well-manufactured, properly delivered probiotic dietary supplements.
Albert Dahbour, M.B.A., chief sales officer, Wakunaga of America Co. Ltd., said the majority of probiotic supplements have been shown by independent testing labs to be unstable or contain only a fraction of viable cells compared to label claims. As a result, manufacturers have had to label their probiotic products at time of manufacture or by weight of probiotic powder, which leaves much doubt about the viability and efficacy of beneficial bacteria in these products.
In fact, manufacturing plays a critical role in the viability of probiotics. Dash noted, The medium, the temperature and other associated factors influence the viability and identity of the microorganisms. If the probiotic supplements do not contain the same microorganisms with the same viability, they will not offer the same, consistent good results. Also, make sure that the probiotic culture has not itself been contaminated with other harmful bacteria during manufacturing process and packaging.
Mark Brudnak, Ph.D., senior executive vice president of technology, MAK Wood Inc. said he is seeing a more delivery systems that can handle these challenges. There are harsh conditions in the gastrointestinal tract, such as stomach acid, that have to be contended with, and there are various delivery systems designed to address this, such as our MAK Trek Bypass Delivery (MBT) system. MBT allows the probiotics to bypass the stomach acid and be delivered live to the intestines.
Some day, adding probiotics to food items may be a breeze for manufacturers, but doing so now, before making sure science supports health and label claims, could cause regulatory agencies to crack down in this market. Before you can start making health claims, the regulatory bodies want to see greater bodies of evidence, Washington-Smith said, noting European regulatory agencies currently require a greater level of scrutiny than the United States.
Champié added, Challenges for this market come mainly from the regulatory side. The industry has to face more stringent regulations that tend to be closer to drug regulations, but also request substantiations on healthy subjects, representing huge investments of time and resources for the industry.
It may be only a matter of time before FDA steps in against manufacturers whose products dont live up to claims. FDA has not any official position on probiotics, but they will have to refer to this topic very soon, Echeverria said. I think they will not allow any claims on particular conditions, but at least they will have to put some parameters on what can be done and said.
Bushed echoed Echeverria: Obviously, FDA is taking a very firm stance on claims, support and packaging, and the recent rash of warning letters should serve as fair warning to all companies making health claims. That said, we are not aware of any recent activity by the FDA as it pertains to probiotic claims, but we would not be surprised to see some in the future.
FDA enforcement can be a good thing, and may be necessary to protect the consumers, and help the probiotic market grow. I think we will see more enforcement from the FDA against probiotic products based on false claims, misleading consumers (e.g., promoting prebiotics as a probiotic, etc.) as well as poor-quality products, Dahbour said. If we can get the inferior probiotics off the shelf, it would be better for the probiotic market because probiotics can have good benefits for a range of digestive conditions, and consumers who benefit from probiotic products will show better compliance and long-term usage, allowing the category a greater opportunity to grow.
More credibility may help the market swell in the future, but some see this expansion as inevitable. With all the bacteria on the planet, you are always going to find new variants, Washington-Smith said. What it really comes down to is putting money behind a particular bacterium, getting all the safety data you need to get it GRAS approval, then all the appropriate clinical data to support health claims. There is no shortage of potential applications, its just a matter of funding to make sure all the right research is done and all the regulatory boxes are checked.
Added Brudnak, We are still very early into what is going to be a hyperbolic growth curve. As the concept that bacteria can be good for you becomes firmly entrenched in the mass mind-set, more questions will be asked by the general public. As they ask questions, their understanding will grow and they will realize the scope of probiotics is way beyond general digestive help. That will spur a proliferation of products addressing various health aspects into the mass market place.
References available on the next page.
Editors Note: INSIDERs Market Insight section is designed to give a broad overview of marketing and sales trends, and select hot ingredients, in a particular category. For more comprehensive information on related health conditions or ingredients, visit NaturalProductsINSIDER.com.
References for The Booming Probiotic Market"
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