Protect What Matters:

Supporting immune health from the inside

out with probiotics
Lori Lathrop Stern, PhD
The Science
Lynch and Pedersen 2016 N Engl J Med
Do We Need a RDA for Microbes?

With modern hygienic practices, we are

exposed to fewer & fewer microbes.

While this has reduced the risk of infectious

diseases, is this impacting our health and risk
of allergy and chronic diseases that are more
prevalent today?

A recent paper ponders if there should be a

recommended dietary allowance (RDA)
established for safe microbes, for example
• Fermented foods
• Probiotic foods or supplements

Hill 2018 The Biochemist

Sender et al 2016 PLoS Biol;
Perdigon et al 2001 Curr Issues
Intest Microbiol; Corr et al 2007
FEMS Immunol Med Microbiol
 Probiotics are a Way to Supplement the Microbiome

FAO/WHO defines probiotics as live microorganisms that

when administered in adequate amounts, confer a
health benefit on the host

Probiotics can help normalize and influence

a healthy and balanced microbiome
Probiotics
Background There are many clinically documented ways probiotics
can provide health benefits:
immune health, digestive, women’s health,
oral health, and weight management

Probiotics have been extensively studied for

immune health

Hill e al 2014; Hao et al 2015; King et al 2014; Lenoir-Wijnkoop et al 2019

Probiotics are Extensively Studied for Immune Health

Probiotics are the one of the most

studied immune ingredients
• More clinical trials for upper respiratory
tract illness have been conducted on
probiotics than vitamins C & D, zinc,
echinacea, elderberry and beta-glucans.*
• Two reputable reviews of clinical studies
(meta-analyses) reported probiotics
reduce the incidence and duration of
respiratory tract infections, number of
antibiotic courses and days absent from
work.
(Hao et al 2015, King et al 2014)
Public health and economic
impact have been modeled for
the US, Europe and Canada
• US model estimated health care payer
cost savings ranging from USD $4.6 -
$373 MM by averting 19 - 54.5 MM sick
days due to general probiotic use
• Absence from work decreased by
3.58 - 4.2 MM days
• Antibiotic prescriptions decreased by
1.39-2.16 MM courses
(Lenoir-Wijnkoop et al 2015, Lenoir-Wijnkoop 2016,
Lenoir-Wijnkoop 2019)

*Source - PubMed.gov search results for the number of upper

respiratory illness clinical trials for each ingredient, March 2020
 HOWARU® Protect Senior
Probiotic Benefits for Immune Function are Strain-Specific
To identify the strain, look for 3 names on the label
• Genus
• Species
Example: Bifidobacterium lactis Bl-04
• Strain
Bifidobacterium (genus) lactis (species) Bl-04 (strain)

Imagine you are looking for a dog to run the Iditarod. Would you choose

Canis lupus Husky - or - Canis lupus Chihuahua?

genus species strain genus species strain

8
HOWARU® Protect Senior

Human cells =
Intestinal cells
Immune cells

Immune
function
(local and systemic)

Gut
microbiota

Human
Intestinal Cells

Gut Microbes &

Probiotics Immune
Cells

9
The Science Behind
Howaru® Probiotics
 Immune Health
Importance
o With over 70% of the immune system
residing in the digestive tract, our gut is the
first line of defense against potentially
harmful pathogens and is closely related to
overall health.

o Our daily diet directly affects gut health and

therefore immune function.

o Accordingly the demand for dietary ways to

support immunity has only been growing.

o DuPont offers a full range of immune health

probiotic options perfected for every stage
of life.
 Protect Product Offering

HOWARU® HOWARU® HOWARU® HOWARU® HOWARU®

Protect Early Protect Kids Protect Adult Protect Senior Protect Sport
Life
Supports immune Helps keep children Helps maintain a Support the immune Helps physically
health of expectant healthy healthy respiratory health of seniors active adults stay
mothers and infants level healthy for optimal
sports performance

Active dose of 6 Billion CFU of Active dose of 10 Billion CFU of Active dose of 2 Billion CFU of Active dose of 5 Billion CFU Active dose of 10 Billion CFU of
Lactobacillus rhamnosus Lactobacillus acidophilus NCFM® Bifidobacterium lactis Bl-04® Bifidobacterium HN019™ Bifidobacterium lactis Bi-07® and
HN001™ and Bifidobacterium lactis Bi-07® Lactobacillus acidophilus NCFM®

12
 Protect Adult
• Clinically-documented, targeted probiotics specifically
formulated to help maintain natural immune defenses
• Research has also shown BI-04® to bolster healthy
respiratory function in adults
• Contains a unique proprietary** probiotic formulation

Contains 2B CFU | Bifidobacterium lactis Bl-04®

Benefits
• Promotes a healthy immune response
• Helps maintain healthy respiratory function
• Dr. Preferred Probiotic for Respiratory Health*

*2018 ProVoice Survey of 250 Board Certified Primary Care

Physicians. Claim cannot be used without a trademark licensing
agreement from DuPont
**Patent families WO 04/052462 and WO 12/168732
 Clinical benefits of HOWARU® Protect Adult
Key findings for
HOWARU® Protect Adult:
• Promotes a healthy immune response
• May help active adults stay healthy for longer

• Helps maintain healthy respiratory function

• Significantly less incidence of Upper Respiratory
Tract Illness episodes compared to placebo group

• Dose: 2 billion CFU/d

The study measured the effect of Bl-04® compared to placebo on healthy, active men and women over a five-month period.

• 465 healthy physically active adults participated in the study where upper respiratory tract illness (URTI) symptoms- sore throat, sneezing, stuffy or runny
nose - were monitored over a 5 month period during cold and flu season. Illness was defined as having  2 symptoms for 3 consecutive days.

• Results showed that the risk of experiencing a URTI episode was significantly less in the Bl-04 group compared to the placebo group by 27%.
• The participant group supplemented with Bl-04® also experienced a significant delay in the onset of URT illness episodes, with subjects remaining free of
upper respiratory tract illness for about 2.5-3.5 weeks longer than those in the placebo group.

• This study also included another probiotic combination that showed immune support, but not to the same extent as Bl-04.

West et al. Clinical Nutrition 2014 More scientific information on B lactis Bl-04 is available on HOWARU.com
 Clinical benefits of HOWARU® Protect Adult
Key findings for
HOWARU® Protect Adult:
• Promotes a healthy immune response
• May help active adults stay healthy for longer

• Helps maintain healthy respiratory function

• Significantly less incidence of Upper Respiratory
Tract Illness episodes compared to placebo group

• Dose: 2 billion CFU/d

The study investigated the effect of Bl-04® compared to placebo in healthy subjects given a a rhinovirus challenge infection

• 152 healthy adults participated in the clinical trial where Bl-04® was supplemented daily for 4 weeks after which rhinovirus was applied to the
nostrils of the volunteers to induce mild cold.

• Upper respiratory symptoms may be a sign of common cold that is typically caused by rhinovirus.

• The results showed that fewer of the participants in the Bl-04® supplementation group had detectable rhinovirus in the nose; plus there was less
rhinovirus in their nostrils over the 5 days following the infection compared to placebo.

• In addition, changes in the innate immune response were observed in the Bl-04® group compared to placebo group.

Turner et al. Beneficial Microbes 2017

 Protect Kids
• Clinically-documented probiotic solution developed to
support the health of children.
• A range of convenient ready-to-market formats and
concentrate or as a custom formulation suited to your
desired delivery format
• Patented probiotics* for their immune health properties
and shelf-stable stabilization technology

Contains 10B CFU | 5B Bifidobacterium lactis Bi-07™

and 5B Lactobacillus acidophilus NCFM®

Benefits
• Support of respiratory health with symptom duration shortened
from 6.5 to 3.5 days
• A decrease in incidences of respiratory symptoms
• A strong reduction in antibiotic use
• Reduced the number of sick days

*Patent families WO 04/052462 and WO 08/042101

 Clinical Benefits of HOWARU® Protect Kids
Key findings for
HOWARU® Protect Kids:

• Support of respiratory health with a

decrease in the incidence of respiratory
symptoms

• Symptom duration shortened from 6.5

to 3.5 days

• A reduction in antibiotic use

• Reduced number of days absent from
daycare
The study measured effect of Lactobacillus acidophilus NCFM® and Bifidobacterium lactis
Bi-07™ in healthy children over 6 months • Dose: 10 billion CFU/d (5 billion each
strain)
• The study was conducted during cold and flu season (November-May) and monitored the impact of Lactobacillus
acidophilus NCFM® and Bifidobacterium lactis Bi-07™ versus a placebo in healthy children aged 3-5 years old.

• Cold- and flu-like symptoms — namely fever, cough and runny nose — as well as the number of days absent from daycare
and antibiotic prescriptions were recorded.

• Each symptom was documented as to its frequency and duration, and questionnaires were reviewed for accuracy by
medical personnel. N=326

Leyer et al 2009 Pediatrics

 Protect Senior
• Designed to promote immune enhancement in
aging adults.
• Bifidobacterium lactis HN019™ is supported by
many successful clinical studies on the health of the
immune system in seniors.
• Regarded as a natural, safe, and efficacious way to
support a healthy aging population.

Contains 5B CFU | Bifidobacterium lactis HN019™

Benefits
• Promotes immune health in aging adults
• Shifts microbial balance in favor of a healthy gut
• Helps maintain regularity
 Protect Senior
HN019 may impact the immune system by increasing levels of
Bifidobacteria in the microbiota of elderly
Bifidobacteria Levels
Gut microbiota and immune function evolve
throughout life
• Immune function declines with age.
• Bifidobacteria levels also decline with age. High: 5 billion CFU/d
• Bifidobacteria have been shown to support the integrity Med: 1 billion CFU/d
of the intestinal barrier and function of the immune Low: 65 million CFU/d
system.
N = 80 healthy elderly
subjects

• In all HN019™ dose groups, bifidobacterium population increased

significantly during intervention when compared to pre-intervention
levels.
• Similarly lactobacilli population increased in high and medium dose
groups.
• No changes in placebo group.

Pinti et al 2016 Eur J Immunol; Arboleya et al 2016 Frontiers in Microbiol; Ahmed at al 2007 J Nutr Health & Aging
 HOWARU® Protect Senior
Age-related Changes to the Immune System Can
Lower Immune Function
There are two main types of immunity – innate and adaptive
• Innate immunity deals with the first signs of injury or infection and activates the adaptive system
• Adaptive immunity forms memory to fight an already encountered pathogen and is the basis of vaccination
• Phagocytosis and Natural Killer cell activity are part of the innate system and can be impaired with aging

Phagocytosis NK cell activity

Certain immune cells are capable of Immune cells called Natural Killer (NK)
eating bacteria and this function is called cells help to fight viral infections and
phagocytosis. this function is called NK cell activity.

Phagocytosis helps to: NK-cell activity helps to:

• Kill harmful pathogenic bacteria or • Kill virus infected cells

opportunistic pathogens like E. coli
• Restrict spreading of viral infection
• Maintain intestinal homeostasis

Study: Pinti et al 2016 Eur J Immunol

 Daily consumption of HOWARU® Protect Senior HN019™
improves immune cell function in healthy elderly adults

HN019™ phagocytic capacity HN019™ NK cell activity

Clinically documentation
o Meta-analysis of clinical
studies in healthy elderly
show that HN019™ is
associated with:
o Increasing phagocytic
capacity
o Improving NK-cell Total Total
activity

Dosage range across studies: 5x109 CFU/d to 3x1011 CFU/d

Supplementation period ranged from 3-6 weeks

Miller et al. 2017 Nutrients; Arunachalam et al. 2000 Eur J Clin Nutr; Chiang et al. 2000 Eur J Clin Nutr; Gill et al. 2001a Amer J Clin Nutr; and Gill et al. 2001b J Clin Immunol 21
The Howaru®
Probiotics Difference
 Why choose DuPont?
With over 100 years of Probiotic expertise, DuPont
is a leader in Probiotic Science

Clinically Studied High Functionality

• Broadest range of clinically-document • Industry leading potency
probiotics • Formatted with only the best probiotic strains
• Over 600 scientific publications on Probiotics • Product available in Finished Formats
• Safety Documentation

High Stability We are here for you

• Patent-protected stability technology
• Efficient fermentation and concentration
drying process
• Perfectly active probiotics in optimal form
delivered to consumers
• Unrivalled dietary supplement, food and beverage
formulation expertise
• Regulatory expertise and support to help you comply
with local requirements
• Marketing support and industry/end user insights to
help you successfully position your products
• World Class Supply Chain
 More Information Available on our Website

howaru.com
Protect What Matters:
Supporting immune health from the inside
out with probiotics

Lori Lathrop Stern, PhD RD LDN - DuPont

Matthew Oster – Euromonitor

April 28, 2020

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