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
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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posed by the updated new dietary ingredient (NDI) draft
guidance.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
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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.
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7 INSIDER Probiotic Ingredient Science Digital Magazine February
2017
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.
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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!
10 INSIDER Probiotic Ingredient Science Digital Magazine February
2017
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!
12 INSIDER Probiotic Ingredient Science Digital Magazine February
2017
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
14 INSIDER Probiotic Ingredient Science Digital Magazine February
2017
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.
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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.
18 INSIDER Probiotic Ingredient Science Digital Magazine February
2017
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.
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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
23 INSIDER Probiotic Ingredient Science Digital Magazine February
2017
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.
24 INSIDER Probiotic Ingredient Science Digital Magazine February
2017
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
25 INSIDER Probiotic Ingredient Science Digital Magazine February
2017
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
26 INSIDER Probiotic Ingredient Science Digital Magazine February
2017
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.
Irritable Bowel Syndrome
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.
27 INSIDER Probiotic Ingredient Science Digital Magazine February
2017
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.
Irritable Bowel Syndrome
The success of B. coagulans MTCC 5856 has provided a good case
study for use of spore-forming bacteria in Canadian health
supplements.
28 INSIDER Probiotic Ingredient Science Digital Magazine February
2017
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.
29 INSIDER Probiotic Ingredient Science Digital Magazine February
2017
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
30 INSIDER Probiotic Ingredient Science Digital Magazine February
2017
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
31 INSIDER Probiotic Ingredient Science Digital Magazine February
2017
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.
32 INSIDER Probiotic Ingredient Science Digital Magazine February
2017
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.
33 INSIDER Probiotic Ingredient Science Digital Magazine February
2017
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.
34 INSIDER Probiotic Ingredient Science Digital Magazine February
2017
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
35 INSIDER Probiotic Ingredient Science Digital Magazine February
2017
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.
36 INSIDER Probiotic Ingredient Science Digital Magazine February
2017
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.
37 INSIDER Probiotic Ingredient Science Digital Magazine February
2017
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.
38 INSIDER Probiotic Ingredient Science Digital Magazine February
2017
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.
New Dietary Ingredients
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
39 INSIDER Probiotic Ingredient Science Digital Magazine February
2017
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.
New Dietary Ingredients
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
42 INSIDER Probiotic Ingredient Science Digital Magazine February
2017
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