PROBIOTIC SCIENCE & Innovation

pathways that fuel advances in beneficial bacteria
CONTENTS naturalproductsinsider.com
p.3
Probiotics’ Benefits Span Beyond the Gut Courtney Johnson explains that different probiotic strains target different areas of health, and brands much choose the right one for their formulations.
p.5
Vol. 7, No. 4 February 2017
Copyright © 2017 Informa Exhibitions LLC. All rights reserved. The publisher reserves the right to accept or reject any advertising or editorial material. Advertisers, and/or their agents, assume the responsibility for all content of published advertisements and assume responsibility for any claims against the publisher based on the advertisement. Editorial contributors assume responsibility for their published works and assume responsibility for any claims against the publisher based on the published work. Editorial content may not necessarily reflect the views of the publisher. Materials contained on this site may not be reproduced, modified, distributed, republished or hosted (either directly or by linking) without our prior written permission. You may not alter or remove any trademark, copyright or other notice from copies of content. You may, however, download material from the site (one machine readable copy and one print copy per page) for your personal, noncommercial use only. We reserve all rights in and title to all material downloaded. All items submitted to NATURAL PRODUCTS INSIDER become the sole property of Informa Exhibitions LLC.
SupplySide & Vitafoods Global Storefronts Directory
p.47
Use of Bacillus Probiotics to Promote Health and Wellbeing The genus of Bacillus offers beneficial activities that are synergistic with other probiotics, notes BIO-CAT Microbioals’ Chris Penet and Steve Lamb, Ph.D.
p.28
p.18
A Look at Probiotic Testing Tammy Blakemore, SORA Labs, details lab insights for probiotic testing.
p.31
p.23
Market Opportunities for Probiotics Supplements The strong U.S. market for probiotics is driven by specific demographics according to Monica Feldman, Nicholas Hall & Co.
p.34
Probiotics for IBS Sabinsa’s Anurag Pande describes how probiotic therapy can alleviate symptoms associated with Irritable bowel syndrome (IBS).
Probiotic New Dietary Ingredient Notifications Attorneys Ivan Wasserman and Amit Sharma, Amin Talati Uphadhye, look at challenges posed by the updated new dietary ingredient (NDI) draft guidance.
p.37
Leaders and Trends in Intellectual Property: Probiotics Probiotic patents and trademarks are on the rise, explains attorneys Andreas Baltatzis and Gideon Eckhouse, KramerAmado PC.
p.40
Fostering A Culture of Responsibility Andrea Wong, Ph.D., Council for Responsible Nutrition (CRN) explains key elements of new probiotic guidelines devloped by CRN and the International Probiotics Association (IPA).
p.25 p.44
p.46
Probiotic for Digestive Health Consulant Sudhir Ahluwalia dives into research that shows probiotics help numerous health conditions from rotavirus to gut inflammation and travelers’ diarrhea.
3 INSIDER Probiotic Ingredient Science Digital Magazine February 2017
Probiotic Powerhouses At the time of writing this viewpoint, Forbes is in the middle of a series on launching a probiotic product. Readers get a first-hand look at what a brand goes through during this process.
“Now, I just have to raise capital, figure out how to get a probiotic manufactured, create branding and packaging, get the retailers on board before they reset their probiotic category in eight months, figure out an online strategy and come up with a simple but effective way of making sure consumers understand the innovation. Plus about 80 other things,” the author, Afif Ghannoum, wrote in the second installment.
It’s an interesting series, but my guess is that most of the folks reading this know at least part of what Ghannoum is going through. The probiotic category is booming, as Monica Feldman from the Nicholas Hall Group notes on page 34 of this Digital Magazine. But it’s not an easy category to enter.
The science backing these beneficial microorganisms is solid, but that doesn’t automatically mean all probiotic products are backed by solid science. Different strains affect the body’s gut differently and thus, impart different healthy effects. Then, the issue of proper manufacturing must be addressed; these are living organisms after all, who often don’t survive processing, shelf life or stomach conditions. Once those are secured, a brand needs to ensure it’s following the proper regulations, which can be difficult when laws are interpreted differently by different stakeholders. It can be overwhelming.
INSIDER is here to help. This Digital Magazine will help probiotic product brands understand the emerging
science, the testing requirements, the market data and the regulatory landscape that make up the probiotic product category.
Forbes, as a consumer publication with a strong reputation, could have chosen any product to follow in its series. But it chose a probiotic product. Probably because the consumer interest is so high, along with the hurdles brands face. I’d take that as a sign that probiotic brands are on the right path to success.
As soon as this Digital Magazine posts to INSIDER, I’ll be sending the link to Ghannoum. I’d love to help another start up. Perhaps he’ll also be able to make it to Ingredient Marketplace this year, where many of the writers in the Digital Magazine will be speaking at Probiotic Marketplace, a day-and-a-half event on April 18 and 19. Probiotics Marketplace is produced with the International Probiotics Association (IPA), the premier underwriter is Nutraceutix, and additional support is provided by BIO-CAT, Sabinsa Corp., Unique Biotech and Viva 5 Corp.
Sandy Almendarez Editor in Chief (480) 281-6745 [email protected]
@sandyalmendarez
Viewpoint
Heat resistant
Shelf stable
Highly concentrated
No refrigeration required
OPTI-BIOME™ Bacillus subtilis MB40 is a naturally occurring, non-GMO probiotic that will withstand extreme temperatures and survive product preparation steps like extrusion and baking. Manufactured in a GMP certified US facility and proven safe by clinical study, OPTI-BIOME™ Bacillus subtilis MB40 can be incorporated to preserve your label claims without overformulation or refrigeration required.
Contact BIO-CAT Microbials to learn how OPTI-BIOME™ Bacillus subtilis MB40 can be cost-effectively included in a wide array of dietary supplements and food products.
877.959.7490 | www.bcmicrobials.com
No Limits.
Manufactured by
BIO-CAT Microbials is an affiliate of BIO-CAT, the industry leader in custom blending enzyme technology.
Viewpoint p.3 Digestion p.18 Table of Contents p.2IN THIS ISSUE
INSIDER's Take
Research shows different strains of probiotics can help with digestion, women’s health, immunity and sports nutrition.
Applications for probiotic delivery methods can vary from supplements to functional foods and beverages.
Manufacturers should consider formulation challenges from the survivability of a probiotic to the tableting process.
Ingredients
Probiotics’ Benefits Span Beyond the Gut by Courtney Johnson
Probiotics have exploded onto the market due to the wide range of health benefits they offer consumers, from supporting the digestive system internally to benefitting skin health outwardly. Knowing which strains target which areas of health can help companies market probiotic products. It is important to explore the research on different strains of probiotics since they affect different areas of health.
According to Global Market Insights Inc., the probiotic market size is predicted to exceed US$64 billion by 2023. Applications for probiotic delivery methods vary, but supplements and functional food and beverages are popular choices for consumers to achieve a healthy gut microbiome.
Probiotics are live microorganisms comprised of bacteria and yeast that live primarily in the gut. These microorganisms help regulate healthy bacteria. Popular strains of probiotics include Bifidobacterium and Lactobacillus, which can be found in the digestive, urinary and genital systems.
“Two of the most widely known and characterized bacterial strains are Bacillus coagulans (earlier known as Lactobacillus sporogenes) and Lactobacillus acidophilus,” said Shaheen Majeed, marketing director, Sabinsa. “These two strains are found in the digestive, urinary and genital systems naturally as well as in fermented foods, such as yogurt and dietary supplements.”
Probiotics are measured as colony forming units (CFUs), which determine how much of the bacteria can divide into colonies. Another standard for measuring probiotics is through viable, but non-culturable, cells (VBNCs). “At times, a probiotic ingredient can contain up to 50 percent VBNCs. The total count of viable probiotic cells equals CFUs plus VBNCs. Counting CFUs has been the standard measurement—but it does not count all efficacious cells. VBNCs are not measured via plating, which only detects cells that are ‘happy’ enough to form colonies in that specific media environment,” said Alexis Collins, director of scientific affairs, Pharmachem Laboratories Inc.
According to Global Market Insights Inc., the
probiotic market size is predicted to exceed
US$64 billion by 2023.
Cultivating Partnerships Cultivating Solutions
NEBRASKACULTURES.COM 877-377-4242
Probiotics is all we do. Our founder, acclaimed microbiologist Dr. Khem Shahani, performed forty years of groundbreaking research into the beneficial properties of probiotics that sparked a revolution in the health supplement industry and left a lasting legacy.
Visit us at Engredea, booth 456
World-class Scientific and Sales Support • Proprietary Stabilization Technology Proven Persistence through the GI Tract • A Body of Scientific Studies on our Flagship DDS-1 Strain of L. acidophilus and other Probiotic Cultures • Proven Durability
It’s a Strain to Find the Right Probiotic There are numerous amounts of strains targeting different areas of health, and
choosing the right strain can be dependent on the product’s intended health focus. Research shows various strains of probiotics help with immunity, women’s health, digestion, sports nutrition and skin health, and many of the strains support more than one area of health.
Probiotics play a major role in maintaining a healthy immune system. About 70 percent of the immune system is in the gut, so it’s no wonder probiotics have been shown to boost immune support. There are 10 times the amount of microbial cells in the intestine as there are cells in the entire body. Balancing those species of bacteria in the gut is crucial to controlling microbes that can cause disease. For a probiotic to be effective, it must be able to withstand the transit through the stomach to reach to the intestines.
Lactobacillus plantarum has been shown to have an effect on the immune system. A study concluded intake with the probiotic strains Lactobacillus plantarum and Lactobacillus paracasei reduced the risk of acquiring common cold infections.1 Bifidobacterium bifidum demonstrated an ability to modulate the immune system in the human body, and is found in the large intestine. Pharmachem’s Bifidobacterium breve BR03, alone and in combination with Lactobacillus salivarius LS01, was shown to help patients with asthma.2
Ganeden BC30 contains Bacillus coagulans, and research supports Bacillus coagulans to promote a healthy immune system by its ability to enhance immunological response to common viral respiratory tract infections.3 Bacillus coagulans is a lactic acid-forming bacterium that is dormant in its spore form, protected by an outer shell, but becomes active when it encounters perfect conditions of temperature, pH and moisture within the large intestine.
A study found Nebraska Cultures’ product ProDURA™, which contains Bacillus coagulans Unique IS-2, lowered total cholesterol and raised “good” cholesterol (high-density lipoprotein [LDL] cholesterol) by raising the HDL to low-density lipoprotein (LDL) ratio in people with high cholesterol.4
Unique Biotech offers Bacillus coagulans Unique IS2, which provided benefits to women who were administered antibiotics for the treatment of bacterial vaginosis, the most prevalent vaginal infection worldwide.5 The Lactobacillus genus is a group of bacteria belonging to the lactic acid bacteria group, defined by its ability to produce lactic acid. Lactobacillus plantarum has been shown to support women’s health by helping increase iron absorption, as women can struggle with maintaining adequate levels of iron in their bodies. A study found women who drank an iron-supplemented fruit drink that contained Probi’s Ferrosorb® containing Lactobacillus plantarum 299v helped increase iron absorption compared to a placebo group, who were administered
Ingredients
About 70% of the immune system
is in the gut, so it’s no wonder probiotics have been shown to boost
immune support.
Bulk Powder | Bulk Capsules, Tablets & Caplets | Fully Finished Bottled Product
Patented Improvements for Any Probiotic
• Protection from stomach acid
BIO - tract DELIVERS
Probiotic Ingredient Science Q&A
Probi USA Inc., dba Nutraceutix Niklas Bjärum, president, Probi USA Inc.
1. What are the top trends impacting the probiotics market in 2017? The main driver continues to be an overall focus on daily health and
well-being. Consumer awareness and the knowledge around probiotics and their vast health benefits will continue to grow. Probiotics offer a natural and convenient solution to include important health benefits in our daily food intake.
Also, the strong focus on product quality and scientific documentation of probiotic strains and their health benefits will continue to grow in importance. The real, perceived efficacy experienced by consumers of different product offerings will be an important differentiator for brand owners and suppliers in the market.
Expect to also see “for me” product offerings. The traditional gastro position will remain the base of the probiotic market, with an increasing need for effective and interesting consumer health solutions. As the market matures, consumer demand will be more diverse. Products targeting specific consumer groups—for example female health, sports and athletes, or children—will be offered in new exciting product formats, demanding robust strains and effective delivery technologies.
Finally, as the market for probiotics matures, products will be found in an increased number of sales channels—through mass market, pharmacy and multilevel marketing (MLM) to online shopping, sports/athletic stores, and even the convenience trade.
2. What should manufacturers do to help differentiate themselves in an increasingly competitive probiotics marketplace?
A strong focus on product quality and scientific documentation will be absolutely key for manufacturers and product developers.
Customer support also will be an important differentiator. At Probi, we believe growing with our customers and offering dedicated support in science, product development and marketing are important differentiators.
3. What unique value proposition does Probi offer? Probi is the only global top player in this market that focuses 100 percent on probiotics
and probiotic development. We are passionate about developing and delivering our probiotic products, all the way from research and development (R&D), through product development, to actually producing and packing ready-to-sell consumer products for global delivery.
We have premium offers in all market segments, ranging from products with comprehensive clinical dossiers showing health benefits on specific indications, to high- quality offerings in more general health positions.
Our robust strains sustain shelf life in consumer health care as well as different food formats. Probi/Nutraceutix is a true a “one stop shop” for any company wanting to improve their
success in probiotics!
an iron-supplemented fruit drink without Lactobacillus plantarum 299v, according to Niklas Larsson, research director, Probi.6 In conclusion, the study found intake of probiotics can increase iron absorption by approximately 50 percent from a fruit drink that was already high in iron bioavailability.
In terms of digestive health, Larsson noted a study found an oat beverage called Profermin containing Lactobacillus plantarum 299v helped patients with ulcerative colitis (UC).7 Other studies point to reduced symptoms of irritable bowel syndrome (IBS), including a study that found patients who took Lactobacillus plantarum for four weeks had greater relief from symptoms of IBS than the placebo group.8 Newer research found Lactobacillus plantarum helped improve symptoms of stress, including one study showing reduced symptoms of stress related to its effect on the gut-brain axis. It found patients who had oral supplementation with Lactobacillus plantarum had reduced cortisol levels in their saliva during induced stress.9
Research on probiotics for athletes or people who exercise revealed positive effects in reducing inflammation and improving post-workout recovery. A study involving 16 resistance-trained men had each participant consume probiotic capsules containing 5 billion live cells of Pharmachem’s Bifidobacterium breve BR03 and S. thermophilus FP4 each, and a different group received a placebo, prior to the performance (21 days) of a muscle-damaging exercise of the elbow flexors. The study found the group who took probiotics had reduced baseline inflammation and improved inflammatory response to exercise, suggesting probiotics may assist in recovery after exercise.10
Another strain of Lactobacillus, Lactobacillus acidophilus, has been shown to produce natural enzymes, for instance lactase, which helps with the digestion of milk,11 according to Michael Shahani, chief operations officer, Nebraska Cultures.
Beyond what probiotics can do internally, they also can provide outward benefits. Lactobacillus salivarius LS01 was found to help atopic dermatitis (AD), a common inflammatory skin disease characterized by eczema, in adults. After 16 weeks, 38 patients who were treated with Lactobacillus salivarius LS01 showed improvement of AD at the end of the treatment compared to the placebo group.12
Considering the numerous probiotic strains, it’s no easy task picking one to formulate with as they all offer benefits that can tackle prevention of diseases and help treat conditions. “Several probiotic-based foods, beverages and supplements contain bacteria
Ingredients
Research on probiotics for athletes revealed positive effects in reducing inflammation and improving post-workout recovery.
The Right Probiotic
are developing beyond traditional gut health—from
sports nutrition to allergies to healthy inflammatory
response, and more. At Pharmachem, we can guide you
in selecting a clinically substantiated strain for your
target market—and increase your product’s shelf life
and ability to survive the gastric system through our
exclusive Microbac™ microencapsulation technology.
We Make Ingredients Work!
and/or yeasts, but their health benefits are determined by the kind of microorganisms they contain (identified by their genus, species and strain level, as potential of different bacterial strains differs, even within the same species) and the sort of benefits they provide,” Majeed said.
Proper Delivery Methods of Probiotics Since probiotics are living organisms, proper handling and treatment of the organisms
is essential during the production process. Manufacturers should consider everything from the survivability of the probiotic to the tableting process.
“When choosing a method of delivering probiotics, manufacturers should be aware of the challenges that can negatively influence the integrity and effectiveness of the ingredients,” said Missy Lowery, senior marketing manager, Capsugel. “They need to be mindful of how to maintain the stability of probiotics and target delivery of the ingredients in the intestines where they work best.”
Cross contamination can also occur between strains during the production process, so manufacturers should be wary. “Because spore-forming Bacillus are naturally more hearty than Lactobacillus, an additional challenge facing manufacturers is that of cross contamination,” said Richard Kramer, microbiologist at BIO-CAT Microbials. “However, with proper cleaning and sterilization protocols, cross-contamination can be easily avoided.”
Stability of a probiotic can be a great challenge during the manufacturing process, since not all probiotics are room temperature stable, Majeed said. “Stability of probiotics is one of the greatest challenges faced by manufacturers while incorporating probiotics in any dosage form, as not all probiotics are room temperature stable, and many have limited stability which requires specific handling to stay viable. Hence, this issue has plagued the industry for years. Another point is calculating appropriate overages to ensure effective dosages in the end product.”
“The four elements that are detrimental to the stability of probiotic bacteria are moisture, heat, oxygen and light,” Shahani added. “In processing or using probiotics in functional foods, these four elements must be eliminated or at least reduced as much as possible. In addition, most lactic acid bacteria will slowly die off over time at room temperature, and even at refrigerated temperature, although at a much slower rate.”
Shahani noted some products claiming to have probiotics failed because the proper technology was not used to keep the bacteria alive, resulting in the bacteria dying before the expiration date of the product. He recommended keeping products as dry and as cool as possible, since there is no way yet to ensure stability.
In addition, it is imperative to consider the pressure and heat from the tableting process, as it is harsh and can compromise the stability of a probiotic, Lowery said. “Transportation and storage issues–such as length of time, temperature fluctuation, and exposure to moisture–can put probiotics in yogurt products and other packaging like sticks and sachets at risk for early activation.”
Ingredients
The four elements that are detrimental to the stability of probiotic
bacteria are
Probiotics can be acid-sensitive, so ensuring they transition through the stomach moisture and acid without early activation and degradation is key. Encapsulation helps preserve the bacteria as it offers more protection from moisture, as well as delaying release until the probiotics make their way through the intestines into the stomach, according to Lowery.
Lowery recommended vegetarian capsules as they are made from hydroxypropyl methylcellulose (HPMC), which delay and target release of solutions and offer moisture protection for probiotics. “Because HPMC is low in moisture content (4 to 6 percent moisture at 50 percent relative humidity compared to 12 to 14 percent for gelatin), the HPMC polymer can help shield ingredients from moisture in the package that can trigger premature activation before ingestion.”
There Are Great Opportunities for Further Research
Research on probiotics and the different strains can help manufacturers decide the proper formulation for their products, and new research is constantly being conducted. Interestingly, newer research is exploring the effects of probiotics on neurological health. “New research is now asking provocative questions involving neurological and mental health and even allergen sensitivities and how the microbiome impacts them,” Kramer said. “This, combined with the fact we are beginning to unravel how these organisms all work together, make this a very exciting time to be involved in anything related to probiotics.”
There is also still more research to be done on probiotics’ effects on sports nutrition, as Collins expressed belief that more benefits for athletes and fitness enthusiasts are still yet to be revealed from probiotics. “Specific areas of interest for the sports nutrition market are immune support, protein absorption enhancement and inflammation management.”
Sports nutrition isn’t the only category where there are still unknown mechanisms to probiotics, as there are other areas not yet known to science, according to Peter Agostino, vice president of product development, Viva5 Corp. “New applications for probiotics in human health are being discovered all the time,” Collins added. “When so much of the human body is composed of these bacteria, it makes sense that they will impact so many different aspects of health.”
Ingredients
Newer research is exploring the effects of probiotics on neurological health.

LQOLTXLGV LQIRRGV

š š”šššš”š

References:
1. Berggren A et al. “Randomised, double-blind and placebo-controlled study using new probiotic lactobacilli for strengthening the body immune defence against viral infections.” Eur J Nutr. 2011;50(3):203-210.
2. Drago et al. “Immunomodulatory Effects of Lactobacillus salivarius LS01 and Bifidobacterium breve BR03, Alone and in Combination, on Peripheral Blood Mononuclear Cells of Allergic Asthmatics.” Allergy Asthma Immunol Res. 2015 Jul;7(4):409-13.
3. Kimmel M et al. “A Controlled Clinical Trial to Evaluate the Effect of GanedenBC30 on Immunological Markers.” Methods and Findings in Experimental and Clinical Pharmacology. 2010;32(2):129-132.
4. Sudha R et al. “Effects of Supplementation of Probiotic Bacillus coagulans (ATCC PTA-11748) on Hypercholesterolemia Subjects: A Clinical Study.” International Journal of Probiotics and Prebiotics. May 2011;6(2):89-94.
5. Sudha R et al. “Clinical Study of Bacillus coagulans Unique IS2 (ATCC PTA-11748) in the Treatment of Patients with Bacterial Vaginosis.” Indian Journal of Microbiology. 2012;52(3):396-9.
6. Hoppe M et al.“Probiotic strain Lactobacillus plantarum 299v increases iron absorption from an iron-supplemented fruit drink: a double-isotope cross-over single-blind study in women of reproductive age.” Br J Nutr. 2015;114(8):1195-202.
7. Krag A et al. “Profermin is Efficacious in Patients with Active Ulcerative Colitis-A Randomized Controlled Trial.” Inflamm Bowel Dis. 2013;19(12):2584-92.
8. Ducrotté P, Sawant P, Jayanthi V. “Clinical trial: Lactobacillus plantarum 299v (DSM 9843) improves symptoms of irritable bowel syndrome.” World J Gastroenterol. 2012;18(30):4012-4018.
9. Andersson H et al. “Oral administration of Lactobacillus plantarum 299v reduces cortisol levels in human saliva during examination induced stress: A randomized, double-blind controlled trial.” International Journal of Microbiology. 2016. Article ID 8469018.
10. Jager R et al. “Probiotic Streptococcus thermophilus FP4 and Bifidobacterium breve BR03 Supplementation Attenuates Performance and Range-of-Motion Decrements Following Muscle Damaging Exercise.”Nutrients. 2016;8(10):642; DOI:10.3390/ nu810064.
11. Pakdaman et al. “The effects of the DDS-1 strain of lactobacillus on symptomatic relief for lactose intolerance - a randomized, double-blind, placebo-controlled, crossover clinical trial.” Nutrition Journal. 2016;15:56. DOI:10.1186/s12937-016-0172-y
12. Drago L et al. “Effects of Lactobacillus salivarius LS01 (DSM 22775) treatment on adult atopic dermatitis: a randomized placebo-controlled study.” Int J Immunopathol Pharmacol. 2011 Oct-Dec;24(4):1037-48.
IN THIS ISSUE Ingredients p.5 Sports Nutrition p.23 Table of Contents p.2
According to Robert Hutkins, professor of food science, University of Nebraska,
Lincoln, our gut microbiota contains tens of trillions of microorganisms from more than 1,000 different species having a cumulative genetic base of more than 3 million genes. He also stated that the gut microbiota could weigh up to 2 kg (4.4 pounds). The microorganisms are found in the stomach, and small and large intestines.
Everyone’s gut has a unique set of microbiota; less than 30 percent of the gut microbiota is common among humans. The microorganism composition keeps changing throughout the life of an individual. It is influenced by the food we eat and the environment we are exposed to. The microbiome composition in the aged person is different from that found in the youth.
At childbirth, the gut is microbiota free. As the child makes its way down and out of the birth canal, the first set of microorganisms acquired by the infant are from the mother’s vagina. Some claim caesarian birth infants who are not exposed to the mother’s vaginal microbiota could be more prone to ailments than those born vaginally.
The gut microorganism aids in digestion of food and helps protect the body from external infections. It assists the digestion process, helping release nutrition from the food and making it available to the body. A healthy and balanced gut microbiota is critical to a healthy gut and a healthy body.
Misbalances in the gut microbiota can lead to diarrhea, constipation, inflammatory bowel and other gut ailments. Even diabetes and allergies have been connected to the state of the gut microbiome, according to the International Scientific Association for Probiotics and Prebiotics (ISAPP).
Probiotics are a group of beneficial microorganisms found in the gut. The World Health Organization (WHO) said probiotics, when taken in adequate quantities, confer a health benefit to the host. They help maintain a healthy balance in the gut microbiota as well as assist in building the body’s immune system, according to a 2015 book, “The Good Gut” by Justin and Erica Sonnenburg.
Gut microbiota balance is affected by poor diet, infections, antibiotic treatments and other external factors. To restore this balance, physicians regularly recommend supplements containing live probiotic bacteria. The
Digestion
INSIDER's Take
Probiotics help create a healthier gut microorganism to aid digestion, immunity and general wellbeing.
Plenty of research shows probiotics help numerous health conditions from rotavirus to gut inflammation and travelers’ diarrhea.
Brands that offer probiotic products need to ensure manufacturing techniques don’t destroy the healthy bacteria.
Misbalances in the gut microbiota
can lead to diarrhea
and other gut ailments.
Vetting potential partners can be time-consuming and cumbersome— but it’s also vital. SupplySide & Vitafoods Global Storefronts simplifi es the process.
Visit supplysidestorefronts.com to begin simplifying your supplier selection process.
Each Storefront contains a wealth of information.
Choose from the tabs to access resources such as whitepapers, ingredient information, research and videos.
Do a keyword search for “Probiotics” and then select a company you’re interested in.
When you’re ready, click the “Request for Proposal” button to receive more information directly from the company.
CLICK HERE FOR A
most common probiotic bacteria belong to two genera—Lactobacillus and Bifidobacterium. Other genera included in this group are Enterococcus and Streptococcus, to name a few.
The protective role of probiotics in digestion is now well established. A 2012 meta- analysis of 74 studies, 84 trials and 10,351 patients showed probiotics are beneficial adjuncts in treatment and prevention of gastrointestinal (GI) diseases.1
Numerous studies conducted by scientists from across the world have shown probiotics to be beneficial in cases of acute diarrhea caused by pathogens such as Salmonella,2 and rotavirus in children.3 Those of us who travel internationally do often become victim to what is popularly called “travelers’ diarrhea.” Probiotics have been found helpful in providing relief in such cases.4 However, most studies have been conducted with probiotics in non-food form.
The role of probiotics in alleviating Helicobacteria pylori infection of the gut, common in developing countries,5 inflammation of the bowels and constipation are other digestive system ailments that have been studied. Initial results indicate probiotics are helpful in these cases, although conclusive evidence has not yet been secured.
The European Food Safety Authority (EFSA) has approved the use of a group of probiotic bacteria genera and species in yogurt cultures. Canadian, Italian and European regulators have accepted that probiotics help in maintaining a healthy gut.
EFSA recommends a level of 1 billion colony forming units (CFUs) per serving of probiotics in food. Clinical recommendation for those affected by digestive ailments is placed at 5 billion CFUs for children and 10 to 20 billion CFUs for adults.6 One to 2 billion CFUs per day is the recommended dose for healthy adults.
The non-strain specific species of permitted probiotics in Canada are Bifidobacterium (adolescentis, animalis, bifidum, breve and longum) and Lactobacillus (acidophilus, casei, fermentum, gasseri, johnsonii, paracasei, plantarum, rhamnosus and salivarius).
Different species and strains of probiotics as well as different ways of preparation can have varying impact on individuals. Some may feel bloated and even gassier after consuming a particular probiotic product.
Digestion
Different species and strains of probiotics as well as different ways of preparation can have varying impact on individuals.
Register today at
Learn From the Best at
Probiotics Marketplace April 18 9am-5:30pm April 19 9-11:00am Understanding the science and trends affecting the probiotics category is critical to making the most of the market opportunity. This day-and-a-half event will deliver insights on:
• Science and formulation considerations • Issues to consider for an effective go-to-market strategy • Market opportunities based off of consumer buying patterns and trends • Legal issues affecting the probiotics space • AND MORE
$99 Marketplace Pass includes:
2-Day Expo Hall Reverse Happy Hour And More
Take advantage of Early Registration Pricing—rates increase after March 3, 2017.
Separate registration is required.
Premier Underwriter Produced with
April 18-20 Expo Hall April 19-20 Orlando World Center Marriott
Dietary supplements, pharmaceutical products, medical foods, infant formula, fermented foods such as fresh yogurt, fermented milk, aged cheese, kimchi, craft beer, miso, fermented vegetables like sauerkraut or pickles, sourdough bread, etc., contain probiotic bacteria.
In some of these products, the bacteria are killed during processing. This happens in the process of baking or when the product is exposed to heat. In the case of aged cheese, bacteria die with time.
Probiotic bacteria are effective only when they are alive and consumed in adequate quantity. Consumers therefore need to look at the label of products at the time of purchase. It is best to consume the product within the indicated shelf life of the probiotic bacteria. The number of live CFUs in the product should also be consistent to the daily need of an individual.
Gut bacteria are passed out of the body daily in the stool. To benefit from probiotic bacteria, a daily serving must be consumed. A dose of 10 billion CFUs is often seen in probiotic supplements and pharmaceutical products.
Sudhir Ahluwalia is a business consultant. He has been management consulting head of Tata Consultancy
Services, an IT outsourcing company in Asia, business advisor to multiple companies, columnist and author of an
upcoming book on herbs, “Holy Herbs.” He has also been a member of the Indian Forest Service.
References
1. Meyre D et al. “Comment on: Valette et al. Melanocortin-4 receptor mutations and polymorphisms do not affect weight loss after bariatric surgery.” PLOS ONE 2012; 7(11):E48221. PLoS One. 2014 Mar 31;9(3):e93324. DOI: 10.1371/journal. pone.0093324.
2. Rokana N. “Modulation of intestinal barrier function to ameliorate Salmonella infection in mice by oral administration of fermented milks produced with Lactobacillus plantarum MTCC 5690 - a probiotic strain of Indian gut origin.” J Med Microbiol. 2016 Dec;65(12):1482-1493. DOI: 10.1099/jmm.0.000366.
3. Das S, Gupta P, Das R. “Efficacy and Safety of Saccharomyces boulardii in Acute Rotavirus Diarrhea: Double Blind Randomized Controlled Trial from a Developing Country.” J Trop Pediatr. 2016 Dec;62(6):464-470. Epub 2016 Jun 9.
4. Hilton E et al. “Efficacy of Lactobacillus GG as a Diarrheal Preventive in Travelers.” J Travel Med. 1997 Mar 1;4(1):41-43.
5. Hassan S, Šudomová M. “Probiotics as Dietary Supplements for Eradication of Helicobacter pylori Infection in Children: A Role Beyond Infection.” Children (Basel). 2016 Nov 10;3(4). pii: E27
6. Kligler B, Cohrssen A. “Probiotics.” Am Fam Physician. 2008 Nov 1;78(9):1073-8.
Digestion
Craft Beer Miso Pickles Sourdough Bread
IN THIS ISSUE Digestion p.18 Irritable Bowel Syndrome p.25 Table of Contents p.2
In the ever-evolving nutraceutical marketplace, consumers are constantly searching for the next great dietary supplement product. In turn, supplement industry insiders are constantly looking for ways to provide consumers with the next great product. While several supplement categories have experienced growth in recent years, there are few categories that have earned (and continue to earn) more attention than probiotics and sports nutrition.
The nutraceutical industry has started to explore—and embrace—the crossroads where probiotics and sports nutrition meet. Researchers and opportunity seekers have made it clear that probiotics may play a leading role in shaping the sports nutrition supplements of tomorrow. While there are dozens of different avenues being explored, certain opportunities have undeniable long-term potential.
Improving Performance by Boosting Immunity Research has shown that in the hours after intense exercise, the body will often
experience a physiological phenomenon known as the “window of immunosuppression.” As its name suggests, it’s during this window of suppressed immune activity that athletes are more susceptible to certain types of upper respiratory infections (URTIs) like the common cold (Nutr Rev. 2008 Jun;66(6):310-20).
Researchers examined the effects of a patented lactobacillus strain, Lactobacillus helveticus Lafti L10 (from Lallemand Human Health), when administered orally. (Appl Physiol Nutr Metab. 2016 Jul;41(7):782-9) During this 2016 study, researchers hypothesized that athletes who received doses of L. helveticus Lafti would be less prone to URTIs because gut health is linked, at least in part, to overall immune health. (Exerc Immunol Rev. 2011;17:6-63)
Researchers found the addition of oral probiotic supplements was not able to significantly affect or reduce the total number of URTIs that occurred. However, the addition of probiotics did have a significant effect on the intensity and duration of symptoms. Those who were administered probiotics experienced milder symptoms for a shorter time.
Studies like this one demonstrate the potential for probiotics and the human immune system to serve as defining factors for the next generation of sports nutrition products. Though indirect, supporting athletic performance and ability by means of the body’s ability to defend and heal itself could, at least in theory, help athletes avoid unwanted sickness or down time.
Sports Nutrition
INSIDER's Take
Research has shown probiotics help athletes decrease their risk of getting sick, even during times of suppressed immunity.
Other studies reveal probiotics’ ability to increase recovery from exercise and help maintain performance.
Use of probiotics in sports nutrition is in its infancy, but is projected to grow if brands focus on manufacturing efficacious products.
Improving Performance by Supporting Muscle Repair By means of a more direct approach, researchers have also explored links between
probiotics and the body’s ability to grow and repair muscle. In a 2016 study, researchers from Cleveland-based Ganeden wanted to study the effects (if any) of Ganeden BC30, also known as Bacillus coagulant GBI-30, 6086, on athletes who were supplementing their routines with casein-based protein. (PeerJ. 2016 Jul 21;4:e2276)
Over the course of two weeks, researchers administered 20 g of casein or 20 g of casein plus the probiotic (a 1 billion colony forming unit [CFU] dose) to the “recreationally trained” male participants. At the end of the crossover and diet-controlled supplementation period, researchers measured and analyzed athletic performance and muscle damage following a bout of “damaging” exercise.
What they found was that in the probiotic/protein group, there was a significant increase in recovery speed when compared to the protein control group at both the 24- and 72-hour marks. These perceived differences were confirmed by the increase in creatine kinase (CK) levels between the two groups (protein group: +266.8 percent, P=0.0002; probiotic/protein group: +137.7 percent, P=0.01).
The researchers were also able to record significant reduction in performance within the protein group (Wingate Peak Power; −39.8 watts, −5.3 percent, P=0.03) whereas participants in the probiotic/protein group maintained performance (+10.1 watts, +1.7 percent).
These studies (and others like it) have demonstrated clear links between certain aspects of athletic performance and the introduction of probiotic strains alongside traditional sports nutrition supplements.
The Road Ahead: Probiotics & Sports Nutrition The potential for probiotics to redefine the world of sports nutrition and supplementation
is there. Regardless of how many breakthroughs researchers can discover and validate, the industry needs to clear key hurdles from a manufacturing standpoint.
While the production and manufacturing of probiotics has come a long way, the production journey is not always a smooth one.
Along with constantly searching for better ways to enhance the shelf stability and bioavailability of probiotic organisms, issues relating to the actual cultivation of a specific strain (or strains) in the amounts necessary to complete a production run can prove both challenging and time consuming.
The nutraceutical industry will continue to push forward and unlock potential opportunities that exist for probiotics within the realm of sports nutrition. The speed at which these opportunities are unlocked is going to depend, almost entirely, on the ability to master the art of cultivating, storing and manufacturing probiotics.
Melissa DellaBartolomea is a content marketing specialist for NutraScience Labs. Based in Farmingdale, New
York, NutraScience Labs is dedicated to providing companies and brand owners with excellent customer service
and a full suite of dietary supplement manufacturing capabilities
Sports Nutrition
IN THIS ISSUE Sports Nutrition p.23 Bacillus Probiotics p.28 Table of Contents p.2
While using the word “probiotics” to describe beneficial bacteria that impart health benefits is relatively new, these bacteria themselves have been around for millennia—people recognized the health benefits of bacteria in fermented foods as far back as 6000 B.C. and possibly even earlier. Almost all major civilizations have a history of using beneficial bacteria in foods such as sour milk, kimchi, yogurt and sauerkraut.
Élie Metchnikoff, a Russian scientist, is often credited as the father of modern probiotics. His studies related to normalizing bowel movements and health by replacing the putrefactive bacteria with lactic acid, which created the foundation of probiotic use in the management of gut health. In his book “The Prolongation of Life: Optimistic Studies,” he noted the potential of lactic acid bacteria (LAB) in increasing the life cycle.
Today, probiotics have carved a space as functional foods and health supplements. The probiotic industry has achieved a 6-percent, five-year compound annual growth rate (CAGR), and is expected to reach US$36 billion globally in 2018, according to BCC Research. Sales growth in the last few years has paralleled our understanding on the human microbiome—the collection of microorganisms living in association with the human body—and the effect of probiotics on the microbiome.
The Human Microbiome Project was initiated in 2008 by the U.S. National Institutes of Health (NIH) to identify and characterize the microorganisms living in the human body, both those healthy and diseased. While the biomass of the bacterial cells residing in the human body may form only 1 to 3 percent of the mass of a human body, these cells can outnumber the human cells by 10 times. These cells play an important role in the maintenance of our health, and changes in the microbiome are often related to disease conditions.
Irritable Bowel Syndrome
INSIDER's Take
Probiotics can be used to maintain digestive health, and probiotic therapy may be optimal with specific bacteria.
Some bacteria can be formulated into food products to increase consumer compliance.
In a recent study, certain bacteria were found to help alleviate IBS patients’ symptoms.
Almost all major civilizations have a history of using beneficial bacteria in foods
Sour Milk Kimchi Yogurt Sauerkraut
Probiotics are used by people for a variety of reasons including maintaining a healthy gut, supplementing the gut microbiota with healthy bacteria, alleviating symptoms related to gastric disturbances such as traveler’s diarrhea, constipation, abdominal discomfort and other gut health-related conditions.
One of the most intriguing gut health conditions is irritable bowel syndrome (IBS), which affects millions around the world, in both developed and developing countries. It presents a gut condition, the causes of which are multifactorial in nature—alterations in gut motility, micro inflammation and visceral hypersensitivity, resulting in abdominal discomfort, bowel dismotility such as diarrhea, inflammation, latent or potential celiac disease and neurotransmitter imbalance. Some of these factors lend themselves to probiotic therapy to alleviate conditions related to IBS. However, the choice of species and strain must be carefully considered.
Although probiotics are often thought of as being equivalent, different species and different strains (even in the same species) may not have the same benefits. One of the important aspects of probiotic therapy is the survival of bacteria. Harsh conditions encountered during the formulation, long shelf storage and low pH in the stomach may all negatively affect the therapeutic benefit of a bacteria. Spore-forming lactic acid producing bacteria (SFLAB) overcome these hurdles and offer an alternative to provide probiotic therapy in a clinically effective dosage.
Spore-forming bacteria have brought a revolutionary change in probiotic delivery, allowing formulations such as soft chews, gummies and chewables to deliver adequate number of bacteria in the dietary supplements in forms that increase consumer compliance. Moreover, with FDA GRAS status, spore forming probiotics are now available to be formulated in a variety of food format products such as chocolates, protein shakes, dry yogurts, ice creams and confectionary items.
Probiotics Marketplace Anurag Pande, Ph.D., will be offering more information on the latest science in health categories including digestive support at Probiotics Marketplace, a day-and-a-half event on April 18 and 19 as part of Ingredient Marketplace in Orlando. Probiotics Marketplace is produced with the International Probiotics Association (IPA), the premier underwriter is Nutraceutix, and additional support is provided by BIO-CAT, Sabinsa Corp., Unique Biotech and Viva 5 Corp. For more information, visit marketplace.supplysideshow.com.
In a clinical setting, the spore forming Bacillus coagulans MTCC 5856 (as LactoSpore®, from Sabinsa) was used as an adjuvant to standard therapy in patients suffering from IBS type D. Probiotic dosage of 2 billion colony forming units (CFUs)/serving was administered once daily to IBS patients for 12 weeks in a randomized, double-blind, placebo-controlled clinical trial (Nutr J. 2016 Feb 27;15:21). Results showed improvement in clinical symptoms of bloating, vomiting, abdominal pain, diarrhea and stool frequency. The researchers concluded B. coagulans MTCC 5856 can be safely consumed by IBS patients to alleviate numerous symptoms and as a potential agent in management of diarrhea-predominant IBS.
The study is significant from the perspective of using a spore forming bacteria in management of IBS. Such bacteria, including B. coagulans MTCC 5856, provide a greater flexibility in choosing the delivery system, require lower overages with better survival rate both throughout manufacturing conditions as well as in the acidic condition in the gut. It also has a long shelf life at room temperature.
The success of B. coagulans MTCC 5856 has also provided a good case study for use of spore-forming bacteria in Canadian health supplements, where B. coagulans is not part of the probiotic monograph.
To introduce B. coagulans MTCC 5856 in the Canadian market as a Natural Health Product (NHP), human clinical safety studies were conducted to prove its safety, antibiotic resistance and stability. A four-week, double-blind, placebo-controlled, parallel study in 40 Canadian subjects was planned and designed in consultation with Health Canada (J Clin Toxicol. 2016;6(1)). The study results, along with a host of toxicity and viability studies, were submitted to Canada Health to support the use of this strain as a probiotic in Canada. Acceptance by Health Canada opened the doors to use of LactoSpore in Canadian health supplements. The clinical study on the IBS patients was also reviewed by Health Canada, resulting in B. coagulans MTCC 5856 being approved for use as a health supplement to relieve the abdominal pain associated with IBS, now allowing people suffering from IBS to use B. coagulans MTCC 5856 to manage gut health.
Anurag Pande, Ph.D., has been with Sabinsa’s sister company, Sami Labs, since 2004 in a research capacity,
and spent several years at Sabinsa Japan’s Tokyo office as senior technical manager. Today, Dr. Pande works
from Sabinsa’s corporate headquarters in East Windsor, New Jersey. Pande holds a doctorate in phytochemistry
from RML Awadh University, Faizabad, India, and has both a master’s and a bachelor’s from Lucknow University,
India. He is the author of several trade and peer reviewed publications. In his current capacity, Pande helps with
technical marketing, delivers talks on various health benefits, provides regulatory support of Sabinsa’s portfolio of
ingredients, as well as closely working with customers to help them develop new products and formulations.
The success of B. coagulans MTCC 5856 has provided a good case study for use of spore-forming bacteria in Canadian health supplements.
IN THIS ISSUE Irritable Bowel Syndrome p.25 Lab Insights p.31 Table of Contents p.2
Probiotics offerings and available information about beneficial bacteria change almost daily, making it difficult for manufacturers, formulators and consumers to keep up with the latest recommendations. It’s important for these parties to know which claims are scientifically validated and which strains are safe. Add understanding and interpreting the emerging rules from a regulatory perspective, and the category can be overwhelming. One can only wonder how consumers can make informed decisions. It
wasn’t all that long ago that the word “bacteria” was an omen of danger, illness or worse. Bacteria associated with foodborne illness, methicillin-resistant
Staphylococcus aureus (MRSA), Clostridium difficile (C. diff), cholera and so on, dominated the messaging to consumers from news sources. Those
“bad” bacteria still exist, but for the last 25 years or so, the concept of “good” bacteria has entered the consumer’s vocabulary. Discussions over coffee and in grocery store aisles are about introducing these “good bacteria” to their families and their daily regimen.
That dialogue started when consumers began to learn that the yogurt or cheese they had been consuming was beneficial to their
overall health, thanks largely to probiotic content. They then began to learn and understand that they could introduce even more of these good
bacteria by purchasing highly concentrated forms of probiotics in capsules. Media outlets began touting the health benefits, and initial studies began to build a scientific case that these good bacteria might impact their overall health and immunity.
The flow of information continues; data is constantly being developed and possibilities touted. However, the consumer now must also contend with other questions: Does my capsule actually contain the levels stated? Is one strain better than two? Two better than four? What strain produces benefits for my irritable bowel syndrome (IBS)? My immunity? Inflammation?
It is becoming increasingly obvious that many types of probiotics can address these issues, and research must continue to develop. The science addressing these questions must be validated, and clinical trials need to
Bacillus Probiotics
Use of Bacillus Probiotics to Promote Health and Wellbeing by Christopher Penet and Steve Lamb, Ph.D. INSIDER's Take
Manufacturers, formulators and consumers can have difficulty adapting to the vocabulary transition from “bad” to “good” bacteria and to the rapidly changing developments in the probiotic industry.
Consumers are educating themselves and introducing good bacteria into their daily regimens, with a preference for food products.
Clinical trials have shown Bacillus subtilis MB40 improves digestive health and has the potential to benefit other areas such as improving heart health.
Discussions over coffee and in grocery
store aisles are about introducing these
“good bacteria” to their families and their daily regimen.
address specific issues and follow protocols that result in clearly defined results. Research must continue to explore the strains that address various ailments.
The genus of bacteria known as Bacillus offers beneficial bacteria that is synergistic with the common strains of lactobacilli and bifidobacteria, and has a natural stability and a range of metabolites (including enzymes) that they produce. These properties make Bacillus a valuable addition to the toolbox of probiotics that can potentially address health issues. One strain of this genus, Bacillus subtilis MB40 (from BIO-CAT Microbials) has been shown in clinical trials to improve digestive health. It also holds promise in other areas such as heart health and pathogen reduction through competitive inhibition.
MB40 has been successfully tested in two clinical trials for safety, digestive health and improvement in overall wellbeing. In an unpublished trial of 29 individuals, no adverse effects were reported after 30 days of consuming MB40. Patients reported more than 70 initial digestive ailments when starting the trial, but those were reduced to fewer than 20 ailments after 30 days. In 21 of the 29 study subjects, decreases in serum triglycerides from initial readings to conclusion of the trial were measured. This indicated the potential for MB40 to aid in improving key factors in cardiac health.
In this trial, glucose levels were unchanged in any of the patients, suggesting the potential for MB40 to aid in controlled breakdown of carbohydrates and the reduction of blood glucose level spikes. MB40 also produced a wide variety of enzymes in vitro. The scope of enzymes produced may indicate MB40’s ability to aid in digestion for patients sensitive to certain food groups such as specific proteins or carbohydrates. The data from this trial is currently in process to be published in a peer-reviewed journal.
A second, larger ongoing clinical trial (100 individuals in a double-blind study) has assessed bloating as a primary endpoint coupled with nine secondary outcomes. This trial is scheduled to conclude in March 2017, but early results showed no adverse effects were reported, and all patients who completed the trial reported significant decreases in bloating, overall improvement in digestive health and decreases in symptoms.
Bacillus Probiotics
Probiotics Marketplace Chris Penet and Steve Lamb, Ph.D., will be offering more information on the latest science in health categories including digestive support at Probiotics Marketplace, a day-and-a-half event on April 18 and 19 as part of Ingredient Marketplace in Orlando. Probiotics Marketplace is produced with the International Probiotics Association (IPA), the premier underwriter is Nutraceutix, and additional support is provided by BIO-CAT, Sabinsa Corp., Unique Biotech and Viva 5 Corp. For more information, visit marketplace.supplysideshow.com.
TM
Future research will also focus on probiotic and enzyme combination in functional foods. Imagine pairing the best long distance runners (probiotics) that can compete with bad bacteria and produce metabolites that enhance health with the best sprinters (enzymes) that work to break down organic materials immediately in the digestive tract to provide nutrition to the body and feed the probiotics. And imagine a probiotic that can modulate triglycerides combined with a lipase enzyme that can break down dietary triglycerides so effectively that the triglyceride cannot be reformed in the blood system. These realities are being researched and will become part of the dialogue as to how health can be enhanced with probiotics in the future.
Chris Penet is vice president at BIO-CAT, where he oversees the strategic planning, research and
regulatory departments. Prior to BIO-CAT, he had a 20-year tenure with Genencor International (now
DuPont), holding several positions including global industry manager for the Food and Specialty
Enzymes business unit. Penet earned his master’s degree in food science from the University of
Georgia and holds several patents in enzyme applications. He serves on the Virginia Biotechnology
Association Board of Directors, the Strategic Planning Committee for the Enzyme Technical Association
and is a member of the Biotechnology Division of the Institute of Food Technologists.
Steve Lamb, Ph.D., earned his doctorate degree in microbial biochemistry from the University of
Wisconsin in 1974. For the past 40 years, he has worked in research and development for various
companies in the chemical, pharmaceutical and food industries. Lamb worked at Genencor International
(now DuPont) for more than 12 years, optimizing production processes for enzyme-producing microbes.
For the last seven years at BIO-CAT Microbials, he has worked to develop proprietary Bacillus-based
solutions for crop and animal agriculture, bio-remediation and waste treatment applications.
Bacillus Probiotics
IN THIS ISSUE Bacillus Probiotics p.28 Market Data p.34 Table of Contents p.2
Good bacteria in probiotics are defined by the World Health Organization (WHO) as “live microorganisms which when administered in adequate amounts, confer a health benefit on the host.” When testing live organisms, manufacturers must go beyond showing how many mg or the quantity included in the product. Measureable quantity comes from knowing the total viable count or colony forming units (CFUs) of the probiotic material. The health benefit comes from the live bacteria, so counting the CFUs is critical to determining the potency of the product.
In January 2017, the Council for Responsible Nutrition (CRN) and the International Probiotics Association (IPA) finalized “Best Practice Guidelines for Probiotics,” and presented a Citizen Petition to FDA to reword the 21CFR101, subpart C to require quantitative amounts of probiotics be listed in CFUs instead of mg weights.
Since the industry has officially decided CFUs will be the quantifier for potency, how do we then decide which test method is the best? Probiotic manufacturers have methods that are specific to their raw materials; the dairy industry has methods available from several sources, including the International Dairy Federation; and the Food Chemical Codex (FCC) recently added several probiotic monographs to their compendia, as well. But, most of these available testing methods are for single-strain raw materials and are complex pour plate methods, which could have 20 to 30 percent results variability in terms of repeatability and reproducibility. Having methods from compendia sources such as the FCC helps level the playing field where the same strain type can be compared regardless of the manufacturer.
Unfortunately, a blended strain product may not have one “ideal” testing method, and deciding on a method may be complicated. A good starting point is to review the individual strain methods and look for overlapping testing. Additionally, the testing lab may need to attempt several probiotic methods and perform method development before exact testing can be determined.
If determining the method wasn’t complicated enough, performing the testing presents challenges. All probiotic methods require specialized equipment, specific agars and broths to perform the testing. And, these methods require sterilized glassware with multiple dilutions and incubation time to get to a final countable area of 25 to 300 colonies per plate. Each specific method could have steps for heating using an ultrasonic bath or
Lab Insights
INSIDER's Take
Determining the correct assay to establish probiotic colony forming units (CFUs) is complicated and requires consideration of strain type(s).
The equipment that tests probiotics is specialized and requires detailed sterilization and possible care for freeze-dried products.
Probiotics can introduce an unwanted spread of bacteria to an environment, so labs need to take extra precaution to control contamination.
stomacher to break the spores of probiotics with spore forming bacteria. For other probiotic material, stomaching and rehydration steps may be needed for freeze-dried probiotics. It’s important to realize not every testing lab is set up for this type of specialized testing.
Another challenge is to control the microbiology lab environment. Typically, in a microbiology lab, the samples being tested have low plate counts. The air and environment remain clean and are monitored for contamination. When a lab decides to start testing probiotic material, this introduces a known contaminant to this clean environment. Even though probiotics are “good” bacteria, they could pollute a clean environment, and precautions must be taken to ensure other samples are not exposed to these high plate count bacteria. Since probiotics are designed to have high counts in the millions, or even billions, of CFU/g, proper sample handling, cleaning of all surfaces and using ultraviolet light or other air cleaning techniques after plating are important. The air quality must be kept at the highest standard to ensure a clean environment for other routine microbiology testing. Because of these challenges, working with probiotics in a separate section of the lab and at separate plating times is often required to avoid contamination of other samples in the lab.
Additional tests need to be considered for probiotic material, and the FCC monograph lists nucleic acid-based identification using polymerase chain reaction (PCR) or other genetic identification methods. It also lists other specific tests including standard microbiology panels and non-lactic acid bacteria. These standard microbiology tests include: Coliforms, E. coli, Listeria, Salmonella, Enterococci and Staph. It is important to note total plate counts (TPC) or aerobic plate counts (APC) and yeast and mold testing are not included in the FCC testing methods for probiotic material. These standard plate counts would show high growth due to the good bacteria that make up probiotics. Sometimes customers will inadvertently order APC, not realizing that products containing probiotics will always show counts on these types of general growth media.
As technology continues to advance, testing choices will evolve. Recent studies have been conducted on rapid count methods including flow cytometry. The Federation Internatioanle du Lait (FIL) and International Dairy Federation (IDF) worked on a joint study
Lab Insights
Even though probiotics are “good” bacteria, they could pollute a clean environment, and precautions must be taken to ensure other samples are not exposed.
using flow cytometry technology quantitative methods. This study demonstrated the large testing variability can be reduced, along with showing impressive precision and accuracy. This technology-based testing shortens the results reporting time by removing the incubation steps that the pour plate methods use. In the future, flow cytometry methods and other equipment-based methods may give alternative ways to quantify lactic acid bacteria and probiotics. In the meantime, before these equipment methods are realized, the industry will continue to use agars, media and large dilutions schemes to quantify the CFUs for probiotic potencies.
What does this mean for probiotic product testing? It means manufacturers must be careful which lab they choose to test their products. They need to research and ask the right questions when deciding who will be tasked with determining the quality of products. Choosing a lab that is accustomed to handling probiotic material and performing specialized testing can take the stress out of making sure a product meets the label claim today and in the future as alternate methods continue to evolve.
Tammy Blakemore is general manager at SORA Labs, a third-party dietary supplement testing lab that specializes
in enzyme testing.
IN THIS ISSUE Lab Insights p.31 New Dietary Ingredients p.37 Table of Contents p.2
Probiotics supplements remain a strong growth driver within the supplements industry in the United States and across the world. The retail market value of probiotics supplements sold in pharmacies and mass channels—excluding online, multilevel and the natural health shops—in the United States reached US$920 million MSP (manufacturer selling price) in 2015, up 17 percent from 2011, according to estimates from the database DB6 of Nicholas Hall Group of Companies. The United States held the largest share in value sales at 33 percent thanks to increased consumer awareness of probiotics and a highly visible presence at the points of sale at pharmacies and natural health food stores.
* Over-the-counter
Source: Nicholas Hall Group of Companies
The high degree of liberalization of the probiotic supplement market in the United States results in a fragmented marketplace where only a few top brands, such as Culturelle, ReNew Life, Align, Phillips Colon Health and Digestive Advantage, accounted for a combined value share of 33 percent in 2015. An intense competitive landscape promotes strong investment not only in the innovation of strains, but also in formulation, delivery forms and packaging that companies are using to stand apart from the competition.
Market Data
INSIDER's Take
The market for probiotic supplements is strong in the United States, up 17 percent in 2015 from 2011’s retail market.
New successful probiotic products focus on specific demographics, include other types of ingredients or use fun delivery systems.
At-home microbiome testing could be the next evolution that drives probiotic products as consumers focus on personalized nutrition.
2011 2012 2013 2014 2015
United States - Probiotics OTC* Sales 3,000
2,500
2,000
1,500
1,000
500
$ M
Innovation in the United States focuses on specific need by type of consumer considering age, gender, stage of life, lifestyle or medical condition. This segmentation creates new possibilities of revenue generation that benefits firms in a highly competitive environment. Pediatric probiotics, for example, has become a hot area of innovation as highlighted by launches since 2015 that claim to boost the immune system, or to promote digestive regularity in children. Moreover, novel delivery forms such as chewables, gummies and fizzy drinks are making it more palatable and fun for children— but also adults—to take their probiotic supplement.
Probiotic supplements marketed at women represent another area of market expansion that centers on the particular needs of feminine care using either a systemic or topical approach. For example, the combination of probiotics with cranberry extract is being touted as a good option to promote urinary health. Alternatively, skin care is becoming a sizzling area of interest as novel systemic probiotic options claim to help maintain healthy skin or, in any case, help treat conditions such as acne or eczema. Alternatively, more options in probiotics are coming to market that cater to the specific health needs of older adults, especially for digestive health and improved immunity.
Other interesting developments point to the launch of combinations with functional ingredients such as omega fatty acids to promote heart health, lactase to enhance digestion, vitamin B to promote energy, and vitamin C to boost immunity. In fact, new products are going even further in innovation with the launch of probiotic wellness options for the athlete, or as support for weight loss as a combination with green tea leaf.
Time-release probiotic supplements are gaining attention with their promise of sustained release during a specific period of time, including nighttime formulations that are popping up in the marketplace claiming to provide benefits of gut restoration while the person sleeps.
From the perspective of marketing and positioning, more firms are highlighting the number of colony forming units, or CFUs, on the packaging to show consumers the importance on the quantity of probiotics contained in the serving of a supplement. This is a key development to counteract the competition arising from packaged foods and beverages such as yogurt, kefir and kombucha that typically boast probiotic content, albeit at a much lower count when compared to probiotic supplements.
Market Data
Novel delivery forms are making it more palatable and fun for children—but also adults—to take their probiotic supplement.
Physician brands continue to gain momentum among consumers who seek the endorsement of the health care professional, especially given the conflicting information available by the media about the quality and proven health claims of supplements. Interestingly, physician brands are leaving their confined sales at the office to extend into other channels such as the internet via vendors such as Amazon or direct-to-consumer (DTC) online. In fact, DTC brands are challenging the traditional pattern of shopping for probiotics away from the pharmacy. Firms selling premium or exclusive probiotics, or those designing clever social media campaigns to reach out and sell to consumers have become successful in generating sales from an emergent generation of consumers highly connected to digital platforms for shopping.
Looking ahead, the advent of at-home microbiome testing is generating curiosity and disrupting the marketplace. uBiome, for example, offers DNA-sequenced microbiome screening to help consumers understand the status of their health as related to their lifestyle, other people, and time progression. Obviously, this development can open a door for the personalization of probiotic supplementation that can potentially generate another channel of revenue for firms. Projections from Nicholas Hall Group of Companies reveal probiotic supplements will reach a retail value of US$1.3 billion in 2020, up 44 percent from 2015.
Monica Feldman is the global director of client services at Nicholas Hall & Co. Her past 25 years of experience
include executive marketing positions and consulting work at leading multinational companies, consulting firms
and trade organizations. She has been a speaker at major consumer health events, and is regularly quoted in
leading trade press. Feldman is an active international advocate in business trade expansion for the life sciences
and wellness industries. She works with other thought leaders and members of academia to further opportunities
in consumer health. Monica holds a master’s of business administration in international marketing and finance
from DePaul University in Chicago and is a member of the Advisory Council at the Buck Institute for Research on Ageing.
Market Data
Probiotic Marketplace Monica Feldman will be offering more information on market opportunities, including examining consumer buying patterns and trends, at Probiotics Marketplace, a day-and-a-half event on April 18 and 19 as part of Ingredient Marketplace in Orlando. Probiotics Marketplace is produced with the International Probiotics Association (IPA), the premier underwriter is Nutraceutix, and additional support is provided by BIO-CAT, Sabinsa Corp., Unique Biotech and Viva 5 Corp. For more information, visit marketplace.supplysideshow.com.
IN THIS ISSUE Market Data p.34 Intellectual Property p.40 Table of Contents p.2
In August 2016, FDA released its revised draft guidance “Dietary Supplements: New Dietary Ingredient Notifications and Related Issues: Guidance for Industry.” The draft guidance is intended to help companies decide whether a substance is a new dietary ingredient (NDI), to outline the process for deciding if something requires a new dietary ingredient notification (NDIN), and to provide an overview of the procedures for submitting an NDIN.
While the draft guidance applies to all dietary ingredients, such as vitamins, minerals, botanicals, amino acids and more, some provisions are particularly important for probiotic ingredients. Understanding the document, including the best strategies to submitting NDINs if needed, will be key to business going forward.
The International Probiotics Association (IPA), a probiotic industry trade association, submitted comments to FDA on the draft guidance. IPA applauded FDA for proposals such as allowing “master files” and creating an official list a “grandfathered” ingredients. IPA offered to “provide FDA with a list of genera and species known to have a long, safe history of use in foods, and then establish criteria that would bring a strain belonging to these genera and species to be listed.”
However, IPA expressed concerns about parts of the draft guidance that would have particular ramifications, given the unique nature of probiotic ingredients.
Challenge: ‘Chemical Alteration’ Under the Dietary Supplement Health and Education Act of 1994 (DSHEA), an NDIN is
not needed for an NDI that is “present in the food supply” and that has not been “chemical altered.” The draft guidance provided examples of processes that FDA believes results in chemical alteration, including: “Using a fermentation medium different from the one used to make conventional foods in the food supply. Example: use of a defined commercial growth medium to produce a microorganism previously made by fermenting milk into dairy products like yogurt or cheese.’” As IPA noted in its comments, during the manufacturing process, several ingredients comprise the fermentation media to provide essential nutrients for propagation of the live microorganism and substituting one source
New Dietary Ingredients
Probiotic New Dietary Ingredient Notifications A ‘gut check’ full of challenges and opportunities
by Ivan Wasserman and Amit Sharma
INSIDER's Take
The updated new dietary ingredient draft guidance poses concerns for probiotic supplement brands due to the unique nature of beneficial bacteria.
The chemical alteration provision brings questions of fermentation, since a change in medium may not change the composition of the probiotic.
Notifying FDA is a complex process, but a quality, comprehensive submission is likely to be accepted by FDA, bringing competitive advantage.
of these ingredients with another does not chemically alter or change the genetic composition or identification of a probiotic strain. It simply provides the same “building blocks” of nutrients required for the cells to grow. Consider a change in diet; modifying a person’s diet does not render a change in genetic composition or identity of that person.
Challenge: Each Species a Separate Ingredient The draft guidance also said: “FDA considers each strain of a bacterial or yeast
species to be a separate ingredient.” That has been FDA’s longstanding position. IPA supports individually identifying each strain and evaluating its safety, as well as determining whether the notification requirement should be made at the strain level. However, once the identification and safety evaluations have been conducted, IPA’s position is that if the strain belongs to those genera and species that have long history of use—either in dietary supplements prior to DSHEA in the United States, or in foods, anywhere in the world at any time—they should be exempt from the notification requirement, unless genetically modified.
While those are only some of the concerns IPA has about the draft guidance, when the final guidance is released, the probiotic sector, like all sectors, will be affected. FDA can choose to regulate probiotics like they do all other dietary ingredients, which will likely lead to substantial regulatory hurdles (including the filing of repetitive NDINs by probiotic companies), or FDA may recognize the unique nature of probiotic ingredients and modify the guidance accordingly.
Opportunities The NDIN requirement is law. The draft guidance represents FDA’s attempt to inform
the industry on how it thinks the law should be interpreted. Regardless of the document being finalized, the law requires NDINs be submitted. Will FDA enforce more actions for not filing an NDIN? Only time will tell.
Probiotic Marketplace Ivan Wasserman will be offering more information on legal issues affecting the probiotics space, including new dietary ingredients (NDIs) and product claims at Probiotics Marketplace, a day-and-a-half event on April 18 and 19 as part of Ingredient Marketplace in Orlando. Probiotics Marketplace is produced with the International Probiotics Association (IPA), the premier underwriter is Nutraceutix, and additional support is provided by BIO-CAT, Sabinsa Corp., Viva5 Corp. and Unique Biotech. For more information, visit marketplace.supplysideshow.com.
TM
If a company determines an ingredient requires an NDIN, why not file one? While filing an NDIN that will not be rejected by FDA is easier said than done, it may not be as difficult as some believe. For those willing to go through the process, it may not only give a company peace of mind that it will not be subject to FDA enforcement, it could give it a competitive advantage.
Submitting an NDIN is an intensive process that requires the submission of all types of data. However, the draft guidelines provide a roadmap on what they should contain. While it is true a large percentage of NDINs are rejected by FDA (since DSHEA was passed, three out of every four NDINs have been objected to by FDA), a closer look shows many of them lacked essential information. High-quality, data-rich submissions certainly have a higher than average acceptance rate.
Filing an FDA-accepted NDIN for a probiotic ingredient can be a door opener. It can reassure potential customers about the safety and compliance of the ingredient and, therefore, its finished products. And even if FDA rejects the notification in the first round, it may highlight gaps in an ingredient’s safety dossier that ultimately will help protect the company once the gaps are filled.
Probiotics as dietary ingredients pose unique opportunities and challenges generally, so it is not surprising many of their NDI-related issues are complex. Carefully following FDA’s, IPA’s and other stakeholders’ statements and actions in this area will be critical to the probiotic industry’s future. Stay informed and get involved.
Ivan Wasserman is a partner in the Washington DC office of Amin Talati Upadhye LLP. Wasserman’s practice
covers health, wellness, beauty and other consumer products, and he represents companies of all sizes.
Frequently cited by the media as a legal authority, Wasserman advocates for clients subject to the jurisdictions
of FDA and FTC. He also regularly represents companies before the National Advertising Division (NAD) and the
Electronic Retailing Self-Regulation Program (ERSP). He has been included in Best Lawyers in America from
2007 to 2017.
With a background in both biology and chemistry, Amit Sharma advises on laws and related legal strategies for
companies in the food, beverage, supplement, drug and cosmetic industries. Sharma, as associate at Amin Talati
Upadhye, primarily helps clients with compliance and disputes before FDA, FTC, USDA, NAD and U.S. Customs.
Amit also reviews product labels and packaging for compliance and advises on claim substantiation for websites
and other advertising platforms such as social media, print, radio, television and Internet.
IN THIS ISSUE New Dietary Ingredients p.37 Self-Regulation p.44 Table of Contents p.2
Every day seems to bring exciting research about the important role of probiotics in human health. Consumers are seeking probiotics not only for digestive health, but also for improved immunity, women’s health, brain function, oral health and better skin.
Patent Filing Trends: Rapid Growth Patents protect inventions, and trademarks protect brands. Innovation in probiotics has dramatically increased in the past 20 years. As new
connections are made between probiotics and health and wellbeing, the rate of applications filed continues to increase, and has now reached more than 10,000 patent applications throughout the world. The increasing rate of filing shows inventions continue to be discovered.
The Leaders: Patent Applications Given the large number and wide range of applications for probiotics, including
supplements, food and beverage products, pharmaceuticals, nutraceuticals and cosmetics, a wide variety of companies are represented as leaders of application assignments. Moreover, a number of companies have established large portfolios indicating a dedication to research and development (R&D) of new innovations.
Intellectual Property
Leaders and Trends in Intellectual Property: Probiotics by Andreas Baltatzis and Gideon Eckhouse
INSIDER's Take
Probiotic patents and trademarks are on the rise, showing innovation as new products are increasing in the supplement market.
Globally, more than 10,000 patents cover inventions associated with probiotic innovation.
Since 2011, 600 probiotic supplement trademark applications and registrations have been filed compared to fewer than 300 registrations before 2011.
Applications Filed Per Year 1600
1400
1200
1000
800
600
400
200
0
Global Filing Trends: Probiotics Worldwide While most applications have been filed in the leading patent offices of the United
States, Europe and China, a great deal of interest in probiotic innovation flows throughout the world. Most applications have been published by the World Intellectual Property Organization (WIPO). WIPO administers the Patent Cooperation Treaty (PCT) system. The PCT system allows for a single patent application to be filed that applies to countries throughout the world. An applicant who files in their own country first must generally file globally (including a PCT) within one year of the earliest application.
Intellectual Property
Shaanxi Univ. of Sci. and Tech. Mars
Hu Anran Zhejiang Univ.
Jinshanmei Biotechnology Alimentary Health
Nanchang Univ. CHR Hansen
Nestec/Nestle
2000
1500
1000
500
New Brands: Trademark Applications in Probiotics Trademarks provide protection of brand names and logos for companies and individuals
who sell a product. Every trademark application and registration must list the goods and services with which the mark is used. This ensures that the scope of the trademark rights is limited to the products and services with which the brand is actually marketed.
Since 2011, 600 nutritional supplements trademark applications and registrations have been filed wi

PROBIOTIC SCIENCE & Innovation

Documents

Transcript of PROBIOTIC SCIENCE & Innovation