Immunology: Special Issue

OCTOBER 2016 SUPPLEMENT
SPECIAL ISSUE
Immunology
The Oral HealthAlzheimers Connection
Egg Introduction in
Food Allergy Mediation
Vitamin D Suppresses
Immune Reactions
Immune Processes
in Brain Health
Elderberry for Travel-Related

Respiratory Illness
The Root Cause

of Food Sensitivities
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Copyright 2016 by the Natural Medicine Journal. All rights reserved.
SPECIAL ISSUE IMMUNOLOGY

OCTOBER 2016 VOL 8, NO. 101 (SUPPL)
Contents
PEER-REVIEWED ARTICLE
6
Immunity Overview
Implications for Clinical Diagnosis and Management
ABSTRACTS & COMMENTARY
18
Benefits of Elderberry for Symptoms of Common Cold in Air Travelers
22
Treatment of IgE-mediated Food Allergies with Baked Egg Biscuits
24
Vitamin D Effective for Suppressing Immune Reactions
27
The Link Between Periodontitis and Alzheimers Disease

SPONSORED PODCAST
26
Getting to the Root Cause of Food Sensitivities

An Interview with Todd Born, ND
AUDIO INTERVIEW
30
Immune Processes and Brain Health

A Discussion with Heather Zwickey, PhD
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Contributors
ELEONORA NAYDIS, ND, LAc,
FABNO is a naturopathic physician, board certified in naturopathic
oncology, and a licensed acupuncturist
in the state of Washington. She holds
an undergraduate degree in chemEleonora Naydis,
istry from Florida International UniverND, LAC, FABNO
sity, and is a 2004 graduate of Bastyr
University with dual degrees in naturopathic medicine
and acupuncture. In addition to her private practice,
Naydis has worked as an attending physician at Bastyr
Integrative Oncology Research Center, as part of the
editing team for Natural Approach to Ophthalmology
and Otolaryngology, and has taught classes on health,
wellness, and natural medicine to university students
and general public. She currently sees patients for
complementary cancer care and for a variety of acute
and chronic health issues at her clinic in Woodinville,
Washington. For more information, you can visit her
website at www.treeofhealthmedicine.com.
HEATHER
PAULSON,
ND,
FABNO, is board certified in naturopathic oncology providing expert
cancer care while creating a plan that
restores health. Paulson is in private
practice at The Paulson Center for
Heather Paulson,
Integrative Healing, a center dedicated
ND, FABNO
to bringing comprehensive integrative
care to people with cancer. In addition to private practice, she loves teaching oncology at Southwest College
of Naturopathic Medicine and is currently cowriting
the Textbook of Naturopathic Oncology, which will be
published in 2017.
JACOB SCHOR, ND, FABNO, is a graduate of National College of Naturopathic

Medicine, Portland, Oregon, and now
practices in Denver, Colorado. He served
as president to the Colorado Association
of Naturopathic Physicians and is now on
Jacob Schor, ND,
the board of directors of both the Oncology
FABNO
Association of Naturopathic Physicians and
the American Association of Naturopathic Physicians. He
is recognized as a fellow by the American Board of Naturopathic Oncology. He serves on the editorial board for the
International Journal of Naturopathic Medicine, Naturopathic
Doctor News and Review (NDNR), and Integrative Medicine:
A Clinicians Journal. In 2008, he was awarded the Vis Award
by the American Association of Naturopathic Physicians. His
writing appears regularly in NDNR, the Townsend Letter,
and Natural Medicine Journal.
ERIC SECOR, ND, PhD, LAc, is the associate medical director of integrative medicine
for the Hartford Healthcare Cancer Institute,
Hartford Hospital and assistant professor of
medicine, University of Connecticut School
of Medicine. Secor helps oversee operaEric Secor, ND,
tions, clinical, education and research activiPhD, LAc
ties of the department, sees patients, and
conducts translational research on a variety of integrative
medicine modalities. His NIH funded F32 and K08 awards
were focused on immunology and natural products research.
MICHAEL TRAUB, ND, DHANP,
FABNO, has been practicing in Hawaii
since 1985. He is past-president of
the American Association of Naturopathic Physicians (AANP) and received
the AANPs Naturopathic Physician
Michael Traub, ND,
of the Year award in 2006. He is the
DHANP, FABNO
author of Essentials of Dermatological
Diagnosis and Integrative Therapeutics. His website is
www.michaeltraubnd.com.
42016 NATURAL MEDICINE JOURNAL. ALL RIGHTS RESERVED. NMJ, OCTOBER 2016 SUPPLEMENTVOL. 8, NO. 101 (SUPPL)
Copyright 2016 by the Natural Medicine Journal. All rights reserved.
EDITOR IN CHIEF
Tina Kaczor, ND, FABNO
MESSAGE FROM THE PUBLISHER
GUEST EDITOR
Eric Secor, ND, PhD, LAc
Impacting Immunity with

Integrative Medicine
ABSTRACTS &
COMMENTARY EDITOR
Jacob Schor, ND, FABNO
PUBLISHER
Karolyn A. Gazella
ASSOCIATE PUBLISHER
Kathi Magee
VP, CONTENT &
COMMUNICATIONS
Deirdre Shevlin Bell
DESIGN
Karen Sperry
PUBLISHED BY
IMPACT Health Media, Inc.
Boulder, Colorado
Natural Medicine Journal (ISSN
2157-6769) is published 14
times per year by IMPACT Health
Media, Inc. Copyright 2016 by
IMPACT Health Media, Inc. All
rights reserved. No part of this
publication may be reproduced
in whole or in part without written
permission from the publisher.
The statements and opinions in
the articles in this publication are
the responsibility of the authors;
IMPACT Health Media, Inc.
assumes no liability for any information published herein. Advertisements in this publication do not
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editors or authors of this publication. IMPACT Health Media, Inc. is
not liable for any injury or harm to
persons or property resulting from
statements made or products or
services referred to in the articles
or advertisements.
Thanks for reading this special issue of the Natural Medicine Journal. This issue
is devoted to the topic of immunologyan expansive and complex field of medicine. Our goal with this issue was not to publish an exhaustive resource on immunology; rather it was to provide an update on recent research in the field, as well as
unique perspectives on an integrative approach to immune system enhancement.
Immunity touches many aspects of medicine as integrative practitioners work to
shore up function in a diverse and expanding population.
In this issue, youll find an overview on immunology by naturopathic immunologist Eric Secor, ND, PhD, LAc, as well as an enlightening audio interview
with Natural Medicine Journal editorial board member, immunology researcher
Heather Zwickey, PhD. Our sponsored podcast features Todd Born, ND, talking
about integrative diagnosis and treatment of food sensitivities. From a research
perspective, our authors provide insight into several new studies involving egg
immunotherapy, elderberry, vitamin D, and the connection between periodontitis
and Alzheimers disease.
Wed like to thank the authors and reviewers who assisted with this special issue
and we hope you enjoy this glimpse into the fascinating and complex world of
immunology. Please share it with your colleagues!
In good health,
Karolyn A. Gazella
Publisher, Natural Medicine Journal
NMJ, OCTOBER 2016 SUPPLEMENTVOL. 8, NO. 101 2016 NATURAL MEDICINE JOURNAL. ALL RIGHTS RESERVED.
Immunity Overview
Implications for Clinical Diagnosis and Management
ABSTRACT
A healthy and intact immune response requires coordination between skin, mucosal barriers, and both the
innate and adaptive aspects of immune response. With
an overarching mandate of protection, the blueprints
of individual immune surveillance systems are inherited
through family history and fashioned through interactions
with the environment, including lifestyle choices and
chemical exposures. The goal of this article is to provide
an overview of the immune response and opportunities
for assessment, treatment, and management from an
integrative medical perspective.
INTRODUCTION
In biology immunity is the ability of an organism to resist
disease, either through the activities of specialized blood cells
or antibodies produced by them in response to natural exposure or inoculation (active immunity) or by the injection of
antiserum or the transfer of antibodies from a mother to her
baby via the placenta or breast milk (passive immunity).1
Our immune system must continually balance a state of readiness, having all the necessary biological responses prepared
to defend us from infection, disease, or invasion of organisms while simultaneously maintaining a state of tolerance or
trained immunity.2 Ideally, vigilance is tempered by tolerance
as the immune system needs to avoid mounting attacks on
self (ie, autoimmune diseases), reprogramming recognition
molecules (ie, cancers cells), and overreacting with exposure
to food and environmental antigens (ie, allergies and sensitivities).3,4 Clinical management includes an understanding
of the functional aspects of the immune system and development of treatment plans that include targeted therapies to
modulate immunity. Many of the treatment modalities help
support the pillars of our immune system, which include
barrier function as well as the innate and adaptive responses.
OVERVIEW OF IMMUNE SYSTEM
STRUCTURE AND FUNCTION
The immune system comprises a complex network of organs,
vessels, cells, and proteins. The skin and mucosal surfaces
create a mechanical and functional barrier5 to protect
Eric Secor, ND, PhD, LAc
against and eliminate environmental debris and foreign

invaders. For example, in the lungs mucus and the mucociliary escalator system work together with columnar epithelium to mechanically whisk microbes upward and outward.
Columnar epithelial cells also secrete cytokines and hostdefense molecules (human -defensins, lysozyme, lactoferrin, cathelicidin LL-37, and surfactant proteins A and
D) resulting in near-sterile airways when fully functional.6
Bodily secretions (eg, saliva, stomach acid, and tears) also
combine with biological reflexes such as coughing, sneezing,
vomiting, and diarrhea in an attempt to eliminate potentially dangerous organisms or irritants (antigens).
Additionally, prebiotics, probiotics,

and synbiotics may have the greatest health
effects when they are incorporated into
the diet early in life.
The bone marrow, thymus, and lymphocytes are the

primary lymph organs; secondary organs include the lymph
nodes, spleen, mucosal membranes, and the intestinal
gut-associated lymphoid tissue (GALT), which includes
the tonsils, Peyers patches, and immune aggregates of the
esophagus, stomach, and lamina propria. Together these
organs function and orchestrate the maturation of immune
cells and provide access to the non-immune privileged (eyes,
placenta, fetus, testes, and central nervous system) systemic
circulatory environment.7 In addition, normal human flora
(the microbiota)8 work synergistically with skin and mucosal
surfaces to maintain the functional barrier and create as
healthy an ecosystem as possible. Although the exact distribution, content, phenotype, and genotype of prebiotics
and probiotics have yet to be fully understood, it is clear
that significant disruption of the microbiota modulates gut,
brain, and immune function. For example, recent research
suggests that short-term restriction of short-chain fermentable carbohydrates (the low-fermentable oligosaccharides,
(continued on page 8)
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disaccharides, monosaccharides, and polyols [FODMAP]

diet),9 which directly impacts the microbiota, may be clinically useful. Additionally, prebiotics, probiotics, and synbiotics may have the greatest health effects when they are
incorporated into the diet early in life.10
Numerous integrative therapies,

dietary supplements, and botanicals (and
their extracts) are being investigated for
their ability to affect dendritic and Th cells,
their activation status, and their ability to
modulate the cytokines and
chemokines they produce.
CELLULAR COMPONENTS, INNATE AND

ADAPTIVE ARMS
All immune cells are derived from hematopoietic stem cells
found in the bone marrow. Stem cells give rise to both the
mature myeloid cells (red blood cells [RBCs], platelets,
neutrophils, eosinophils, basophils, and mast cells) and
lymphoid (natural killer [NK], B, and T) cells, key players
in the innate and adaptive immune responses. Although
traditionally these were distinct arms, many overlapping adaptive arm of the immune system is delayed (up to 5 days)
and intersecting functions of the humoral or cell-mediated and consists of critical antigen presenting cells (APCs), which
response are now being discovered.
orchestrate responses; T and B lymphocytes; plasma cells;
and the antigen-specific antibodies they produce. Dendritic
However, we can still define the role of each arm with
cells are considered the primary professional APCs in
some distinction. The innate immune system is fast-acting
addition to macrophages and nonprofessional APCs, such
(~0-15hrs) and composed of epithelial barriers, phagocytic
as B cells and epithelial cells.15,16 Antigen-presenting cells
granulocytes, dendritic, and NK cells as well as plasma
are responsible for antigen engulfment, uptake, processing,
proteins of the complement cascade (C1q, C2, C3, C3c,
and presentation to the adaptive cells through engagement
C4, and C4d). The overarching clinical symptoms of classic
with receptor cells such as the T cell receptor (TCR). Once
inflammation (calor, dolor, rubor, tumor)11 are indicative
of the innate response. The responding innate immune antigen-rich APCs engage T helper (Th) cells via their TCRs,
cells have the unique capacity to recognize and respond to the Th0 cells (precursors to all Th types) activate, prolifevolutionarily conserved patterns upon exposure to foreign erate, and expand within a skewed inflammatory milieu.
stimuli, therefore they act immediately. Pattern-recognition T helper 1 (Th1) cells produce interferon gamma (IFN-),
receptors (PRRs) embedded on macrophages and dendritic interleukin-2 (IL-2), and granulocyte-macrophage colonycells can detect or read patterns found in components of stimulating factor (GM-CSF) and modulate cell-mediated
bacterial and fungal cell walls and viral nucleic acids.12 These responses. Classically, Th2 cells produce IL-4, IL-5, IL-6,
PRRs include Toll-like and C-type lectin receptors. Pattern IL-9, IL-13, and IL-25 and drive the IgE-mediated antiparand antibody responses commonly seen
recognition receptors are reinforced by the complement asite, anti-allergy,
17,18
Regulatory T cells (Tregs) with a cell phenocascade. The complement cascade is a complex of proteins in clinic.
type of CD4+CD25+FoxP3+ produce IL-10 and transproduced by the liver and activated in plasma. The compleforming growth factor (TGF)- and are intimately involved
ment cascade modulates the systemic responses (inflammain chronic inflammation, scar formation, and the control
tion, anaphylaxis) and is now believed to bridge and inform
of other cell types. There are numerous other sub lineages
both innate and adaptive immunity.13,14
(Th17, Th22, Th9) being evaluated in the scientific literaWhen bacteria, viruses, or allergens (antigens collectively) ture that are generated by variations in the degree of antigen
evade innate responses, the adaptive system is engaged. The
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receptor engagement, the robustness of the secondary cytokine and chemokine signals, and the inflammatory cascade.
The ability of dendritic cells to orchestrate immune responses
makes them novel therapeutic targets in allergy, autoimmunity, and cancer.19,20
Numerous integrative therapies, dietary supplements, and
botanicals (and their extracts) are being investigated for
their ability to affect dendritic and Th cells, their activation status, and their ability to modulate the cytokines and
chemokines they produce. For example, previous work
in my laboratory in preclinical models has demonstrated
that the pineapple extract bromelain is a potent antiallergy and asthma therapy. Our group has demonstrated in
a mouse model that bromelain lessens immune response to
an antigenic stimulus.21 Specifically, bromelain ingestion
led to significant inhibition of allergic sensitization (egg
antigen) via direct modulation of dendritic cells (CD11c+)
as determined by reduced ovalbumin-specific IgE, antigenspecific CD8 T cells, and CD44 (a critical T cell receptor
involved in allergic immune response).22,23 Ongoing studies
will determine bromelains optimal dose in allergies and
asthma in humans. Other groups are also actively evaluating how dendritic cells can be affected by natural products24,25 such as vitamin D26,27 and probiotics,28 and what
clinical impact these findings will have. When possible all
treatment modalities should be evaluated in the context of
patient care and backed up with objective diagnostics and
laboratory measures.
distinct inheritance pattern (for example, through males

on the maternal side). In pediatric patients, the ROS may
indicate delayed growth, failure to thrive, malabsorption, or
developmental issues. In adults, common underlying symptoms may include frequent, recurrent colds and flus, less
common infections, iron-resistant anemias, severe eczema,
allergies, and hyper-IgE or allergic eosinophilic syndromes.
Collecting a detailed history (classic homeopathic interview) will reveal the cause much of the time. These are the
patients who present with textbook symptoms that will
lead directly to laboratory testing that confirms the diagnosis, such as anemia revealed by a complete blood count
(CBC)/iron panel. However, clinical presentations are often
not straightforward and labs are unremarkable. Recently
I had a patient present with a rash, mild irritable bowel
syndrome, difficulty concentrating, and fatigue. Although
my first thoughts were food-related allergy or atopy, all
allergy tests were negative; testing eventually revealed a
genetically altered uridine diphosphate glucuronosyltransferase enzyme (UGT1A1) and the subsequent diagnosis
of Gilberts syndrome. Therefore, a stepwise diagnostic
approach coupled with patient feedback throughout clinical interventions is warranted.
Table 1 outlines several options to consider when embarking

on a standard laboratory evaluation of inflammatory and
immune-mediated conditions. Even when immune dysregulation is not the chief complaint, several of these lab findings may be positive in patients who present with common
symptoms such as pain, fatigue, insomnia, depression,
anxiety, gastrointestinal complaints, and stress response. All
LABORATORY MEASUREMENT OF IMMUNE
labs in Table 1 can be ordered from any local or regional
SYSTEM AND INFLAMMATORY RESPONSE
Laboratory evaluation and determination of the degree Quest Diagnostics lab (or similar lab).
of immune system dysregulation and the contribution of For ease of use and clinical application, several options
inflammatory responses can be complex and overwhelming. for laboratory evaluation of common immune-mediated
A systematic approach based on the family and personal conditions are grouped from A (fundamental) through D
history (work and environmental exposure, sexual history, (more advanced). This is not meant to be an exhaustive
prescription and recreational drug use), review of symptoms list but will provide context and reminders as you proceed
(ROS), and physical exam findings is fundamental. Detailed with diagnosis and clinical management. Group A reprepersonal and family history may also reveal multiple chronic sents fundamental assessment beginning with a CBC to
immune-mediated conditions or conditions that follow a evaluate anemia. A helpful tool to remember when eval102016 NATURAL MEDICINE JOURNAL. ALL RIGHTS RESERVED. NMJ, OCTOBER 2016 SUPPLEMENTVOL. 8, NO. 101 (SUPPL)
uating CBC results (sometimes referred to as the rule of

3) is that hemoglobin equals approximately 3 times the
RBC count, and hematocrit equals approximately 3 times
hemoglobin. For example, using typical values for an otherwise healthy adult man, if the RBC count is 5 x 106/uL,
hemoglobin would be roughly 15 g/dL and hematocrit

roughly 45%. When reviewing the white blood cell (WBC)
count, consider both the total count and the differential
(percentage of each type of WBC), and platelets. Variation in WBCs and their subtypes (either too low or high)
TABLE 1. OPTIONS FOR LABORATORY EVALUATION OF IMMUNE MEDIATED CONDITIONS
Laboratory Testing
Group Associated Descriptors
Laboratory Testing
Group Associated Descriptors
CBC & Differential
Fundamental (RBC, WBC) immune

evaluation
Endomysial Antibody
Gluten-sensitive immune-mediated
enteropathies
Erythrocyte
Sedimentation Rate (ESR)
Marker of active inflammation (nonspecific)
Rheumatoid Factor (RF)

(IgA, IgG, IgM)
Early RA diagnosis and ongoing

management
C Reactive Protein (CRP,

hsCRP)
Marker of active inflammation (nonspecific)
ANA (Titer and Pattern)
Autoimmune/inflammatory screen
Zinc (RBC, plasma or

24hr)
General immune function & wound healing
Insulin-like Growth Factor

I (IGF-I)
Nutritional deficiency & growth hormone

& inflammation
Evaluate acute and chronic candida
General immune function, metabolic

disorders, Rx, ETOH
Candida Antibodies (IgG,

IgA, IgM)
Vitamin B6, Plasma
Dietary deficiency, liver metabolism, gut

immunity
Natural killer cells (NK

cells) Function
25-OH Vitamin D
Innate immune response, viral and cancer

cell clearance
Oxidative stress
Immune Cell
Function Testing
CoQ10
Evaluation of T cell-mediated activity &

immunity
DHEA, Pregnenalone
Hormone-associated stress response &

resiliency
Lymphocyte Subsets
CD4, CD8, numbers,% and ratio
Lymphocyte Proliferation
Panel
Cell-mediated immune responsiveness
Eosinophil Cationic
Protein (ECP)
Eosinophil-based allergic inflammation
Cortisol
Generalized stress response and resiliency
B12 & Folate
Poor diet, malabsorption, Rx, ETOH
Iron and Ferritin
Dietary, metabolic deficiency or excess
Lactoferrin
Surrogate marker leukocytes &

intestinal inflammation
IL-1B, IL-2, IL-6, TNFa
Cytokines vary in immune disease &

therapy
Prealbumin
Decreased in inflammation of the liver
Markers vary in immune-mediated disease
Protein, Total
Autoimmune hepatitis, inflammation
Complement (C1q, C2,

C3, C3c,C4, C4d)
Amino Acid Analysis
Proteins, neurotransmitters, hormone

precursors
Sjgrens Antibody
(SS-A, SS-B)
Autoimmune diseases
Hemoglobin A1c (with

MPG)
Diabetic and nondiabetic inflammation
14-3-3 eta Protein
Increase during joint inflammation
Adenosine Deaminase
Inflammation or infectious disease
Immune complex disease
Amylase & Lipase
Elevated in gatrointestinal, pancreatic

inflammation
Myeloperoxidase Ab
(MPO)
Immunoglobulins (IgG,
IgM and IgA)
Acute and chronic inflammation,

autoimmune diseases
Proteinase-3 Ab
Immune complex & bowel disease
Neurologic immune disorders
Celiac Disease (HLA

Typing)
Myelin Associated
Glycoprotein
Cryoglobulin Screen
Tissue Transglutaminase
(tTG-IgA, IgG)
Ganglioside Abs
(GD1a,GD1b,GM-1GQ1b)
Dx immune-mediated gluten intolerance

Gluten-sensitive immune-mediated
enteropathies
Table data represents standard laboratory test available through national labs such as Quest Diagnostics.
11
can indicate immune compromise (low total numbers, toward sugar regulation, and amylase and lipase abnormalilymphocytes, or neutrophils), allergic response (elevated ties may prompt a referral to a specialist in gastroenterology
eosinophils), autoimmune disorder, and cancer. The eryth- for further work-up.
rocyte sedimentation rate (ESR) and C-reactive protein
(CRP) levels provide evidence of an active inflammatory
process that may require further evaluation.29 Patients can
also be evaluated for nutrition-related immune status by TABLE 3. COMMON IGE-BASED ALLERGY TEST PROFILES
testing for levels of zinc, vitamin B6, 25-OH cholecalcifThree Panels to Diagnose IgE-Mediated Allergies
erol, coenzyme Q10, vitamin B12/methylmalonic acid
Food Allergy
Respiratory
(MMA), folate, iron, ferritin, and protein (total, albumin,
Clam, f207
Alternaria alternata, m6
and globulin) and ordering an amino acid analysis. Any of
Cod fish, f3
Aspergillus fumigatus, m3
these can be used in combination to determine if nutrient
Corn (Maize), f8
Bermuda grass (Cynodon dactylon), g2
absorption and/or metabolism are issues. Systemic stress or
Egg white, f1
Birch (Betula verrucosa), t3
resiliency can be determined with salivary or serum cortisol
Milk, f2
Cat dander, e1
(morning and evening) and hormone cascades such as
Peanut, f13
Cladosporium herbarum, m2
dehydroepiandrosterone (DHEA) and pregnenolone and
Scallop, f338
Cockroach, i6
their downstream products. The addition of hemoglobin
Sesame, f10
Common ragweed (Short; Ambrosia elatior), w1
A1c (with mean plasma glucose) will direct therapeutic goals
Shrimp, f24
Cottonwood (Populous deltoides), t14
TABLE 2. ALLERGY TESTING BY REGIONS
Designation
Geographic Regions
Region I
CT, MA, ME, NH, NJ, NY, PA, RI, VT
Region II
DC, DE, MD, NC, VA
Region III
Northern FL, GA, SC
Region IV
South of Orlando, FL
Region V
IN, KY, OH, TN, WV
Region VI
AL, AR, LA, MS
Region VII
MI, MN, WI
Region VIII
IA, IL, MO
Region IX
KS, ND, NE, SD
Region X
OK, TX
Region XI
AZ (Mtn), ID (Mtn), NM, CO, MT, UT, WY
Region XII
Southern AZ, SE CA Desert
Region XIII
Southern Coastal, CA
Region XIV
CA Central Valley
Region XV
Nevada, Southern Idaho
Region XVI
Central & Eastern WA & OR
Region XVII
NW CA, Western OR, WA
Region XVIII
Alaska
Region XIX
Puerto Rico
Soybean, f14
D. farinae, d2
Walnut, f256
D. pteronyssinus, d1
Wheat, f4
Dog dander, e5
Food/Environmental
Elm (Ulmus americana), t8
Alternaria alternata, m6
Maple (Box elder; Acer negindo), t1
Cat dander, e1
Maple leaf sycamore (London plane), t11
Cladosporium herbarum, m2
Mountain cedar (Juniperus sabinoides), t6
Cockroach, i6
Mugwort (Safebrush; Artemisia vulgaris), w6
Cod fish, f3
Mulberry, t70
D. farinae, d2
Oak (Quercus alba), t7
D. pteronyssinus, d1
Penicillium notatum, m1
Dog dander, e5
Rough pigweed (Amaranthus retroflexus), w14
Egg white, f1
Sheep sorrel (Rumex acetosella), w18
Milk, f2
Timothy grass (Phleum pratense), g6
Peanut, f13
Walnut (Juglans californica), t10
Shrimp, f24
White ash (Fraxinus americana), t15
Soybean, f14
Total IgE
Walnut, f256
Wheat, f4
Total IgE
Adapted from Quest ImmunoCAP.
d=dust mites (house), e=epidermal, f=food,g=grass, i=insect, m=mold, t=tree, w=weed
13
Altered immunoglobulins30 (Igs) may suggest broad compromise in immunity or autoimmunity, B cell production (all
Igs reduced), a specific cancer (eg, lymphoma, multiple
myeloma), or an autoimmune (eg, rheumatoid arthritis,
system lupus erythematosus) diagnosis. Labs that reveal an
increase or decrease in selective Igs may suggest an active
ongoing infection (IgM); gastrointestinal mucosal involvement (reduced IgA); chronic infection and immunocompromise (IgG increased); allergic, dermatitis, or parasitic
activity; or hyper IgE syndrome (increased IgE). Patients
who are responding to vaccination may see a 2- to 5-fold
increase in immunoglobulin response (4-8 weeks primary;
8-12 weeks memory), so determine if the CBC, WBC differential, or humoral response is altered due to vaccination.
Depending on the patients symptoms, further evaluation
and referral to an appropriate specialist for a more comprehensive immunological evaluation of immune dysregulation
may be warranted.29,30
Group B is directed toward immune-mediated gluten intolerance (celiac disease) and enteropathies as well as the initial
screen for autoimmunity (testing for antinuclear antibodies
[ANA]) and rheumatoid arthritis, metabolic inflammation (IGF-I) and concomitant immunologic response to
Candida. If there is indication of immune dysregulation
(low or high WBC subtypes), chronic unresolved infection,
inflammation, or frequent colds and flus, Group C will help
evaluate innate and adaptive arms of the immune response.
These tests may identify and enumerate additional lymphocyte cell subpopulations based on flow cytometry and identification of cell surface receptors (such as CD4 and CD8
T cells), or they may be functional tests performed on
isolated WBC subsets, which are cultured in vitro and challenged with a variety of antigenic and cellular stimuli. Tests
include evaluation of innate, NK cell function and proliferation panels as well as selected proteins of the complement (C1q, C2, C3, C3c, C4, C4d) cascade and cytokine
(IL-1B, IL-2, IL-6, tumor necrosis factor [TNF]) production. Based on test results you may decide to enhance innate
and or humoral immunity through lifestyle modification or
medicinally with dietary polysaccharides, larch arabinoga-
Diagnosing intolerances
and allergies can be difficult
because symptoms often overlap
or may be confused with
other conditions.
lactan, Ganoderma, Terminalia bellirica, Salacia chinensis,

Zingiber montanum, or Peltophorum pterocarpum.31-35
Group D provides a more detailed evaluation and diagnosis of selected autoimmune conditions such as Sjgrens
syndrome, arthritis (14-3-3 proteins), immune complex
disease (myeloperoxidase), or neurologic immune disorders
(myelin-associated glycoprotein antibody). Diagnosis of autoimmune conditions should be done in conjunction with an
immunologist and every effort put forth to work together for
the betterment of the patient.
TESTING ALLERGIES/INTOLERANCES
In addition to the standard metabolic labs described above,
patients presenting with conditions such as ongoing or
seasonal sinusitis, chronic recurrent rhinitis, postnasal drip,
sinus pressure, headaches, cough, allergic asthma, eczema,
dermatitis, and psoriasis, or elevation of WBCs, subsets of
eosinophils, and/or total IgE may benefit from an allergy and/
or sensitivity panel. As summarized in Table 2, some of these
panels vary based on the environmental allergens exposed by
region. For example, Connecticut is designated as Region I,
along with the rest of New England, New Jersey, New York,
and Pennsylvania. Therefore, consider this regional variation before ordering. In addition to the traditional IgE-based
allergy test profiles (Table 3), many laboratories now provide
IgG-based panels to evaluate sensitivity and intolerance in
addition to the anaphylactic or immediate type 1 IgE-driven
immune hypersensitivity responses.36
IMMUNO BENEFITS
IMMUNO BENEFITS IS AIMED AT PROVIDING IMMUNE SUPPORTIVE NUTRIENTS
BOTH ON A DAILY BASIS AS WELL AS DURING ACUTE IMMUNE STRESS.*
Because these ingredients support the immune systems ability to adapt and not simply
upregulate immune function, those with hyperactive immune responses may also incorporate
this formula, under a physicians supervision, into their daily regimen.*
WELLMUNE | 250 MG PER SERVING

The researched ingredients in Immuno Benefits include the yeast beta 1,3/ 1,6 glucan
derived from the cell wall of a proprietary strain. Wellmune is clinically proven ingredient to
support the functionality of the immune system. It has been studied for its effects on supporting
healthy respiratory tract function and immune response after physical stress, such as exercise.
This branded version of Beta glucan has also been found to play a support the balance of
Th1/Th2 (Kirmaz, Bayrak, Yilmaz, & Yuksel, 2005).
MONOLAURIN | 300 MG PER SERVING
Another ingredient in Immuno Benefits, Monolaurin, exhibits potent capabilities relative to

microbial balance in the body (Lieberman, Enig, & Preuss, 2006). Researchers have found that
Monolaurin can provide broad immune support (Lieberman, Enig, & Preuss, 2006), can support
the bodys ability to adapt appropriately when in the presence of many gram positive bacteria
(Peterson & Schlievert, 2006), and balance the presence of Candida albicans (Bergsson,
Arnfinnsson, Steingrimsson, & Thormar, 2001). Monolaurin achieves this at the cellular level by
incorporating itself into the cell membrane of gram-positive bacteria, supporting a healthy
level of replication (Tokarskyy & Marshall, 2008).
COLOSTRUM | 500 MG PER SERVING

YIELDING IMMUNOGLOBULINS (IgG) | 200 MG
Finally, Immuno Benefits contains colostrum. Colostrum supports immune system health
through its content of transfer factors, peptide and protein complexes, that directly support
immune capabilities.* Bovine colostrum also contains naturally occurring compounds, such as
lactoferrin and imunnoglobulin G, which our healthy cells continually recruit and utilize to
support the functionality of the immune system.* These compounds also provide support to the
immune system by working in the digestive system prior to foreign invaders even making it into
the blood (Cesarone MR, et al., 2007).
OUR NEW BENEFITS LINE

FORMULAS SO POWERFUL
YOU HAVE TO SEE TO BELIEVE
Contact Us | 800.325.1776 | www.davincilabs.com
Diagnosing intolerances and allergies can be difficult because

symptoms often overlap or may be confused with other conditions, such as gas, bloating, abdominal pain, diarrhea, constipation, heartburn, fatigue or loss of energy, headaches and
migraines, anxiety, depression, mood swings, poor concentration, and muscle/joint pain. According to the guidelines set
by the National Institute of Allergy and Infectious Diseases,37
food allergy arises from (and is reproduced by) a specific
immune response on exposure to a given food. However, an
intolerance may cause the same reproducible adverse reaction
but may not have an established underlying immune-mediated
mechanism. For example, someone who is truly allergic to
cows milk has an immune system response to milk protein
(casein or whey) and therefore has a food allergy. But someone
who has difficulty drinking milk due to an inability to digest
lactose in milk has food intolerance, which may be due to low
lactase production or any number of problems with the digestive system. Similarly, the diagnosis of celiac disease is based
on a multigenic immune-mediated enteropathy triggered by
dietary glutens, present in wheat, barley, and rye. With celiac
disease, human leukocyte antigen (HLA) typing is performed;
90% of celiac patients express the HLA-DQ2 molecules.
Gluten peptides presented by these HLA molecules induce
an abnormal mucosal immune response and tissue damage.38
CONCLUSION AND FUTURE DIRECTIONS

The immune system represents a complex network of
organs, tissues, and blood products whose role is to
balance a state of tolerance with swift and decisive action.
As integrative practitioners our focus is to promote lifestyle balance and immune optimization by minimizing
the impact of stressors and maximizing therapies that
positively modulate the immune response. Fundamental tools include a comprehensive understanding of
the immune system, its diagnosis, and its management;
proper application of healthy diets, food elimination,
and detoxification; exercise; dietary supplements; lifestyle
interventions such as stress reduction, sleep, meditation,
and energy therapies; and timely diagnosis and management of allergies, autoimmunity, cancer, and inflammatory processes. Communicating findings to both patients
and referring doctors can provide novel treatment options
for complex immune-mediated diseases that traditionally
rely on steroids, immunosuppressants, and chemotherapy
agents as first-line treatments. Keeping patients safe and
caregivers engaged will ultimately create an environment
in which integrative therapies can be used and given the
time they need to turn around the most complex immunemediated conditions.
TABLE 4. COMMON IGG-BASED ALLERGY TEST PROFILES
IgG Allergy Adult

Casein, f78
Cacao (chocolate), f93
Cod fish, f3
Coffee, f221
Maize/corn, f8
Egg white, f1
Peanut, f13
Soybean, f14
Tomato, f25
Wheat, f4
Yeast (bakers/brewers), f45
Food IgG Pediatric

Beef, f27
Casein, f78
Cod fish, f3
Maize/corn, f8
Egg white, f1
Orange, f33
Peanut, f13
Pork, f26
Soybean, f14
Wheat, f4
IgG Panel 1
Casein, f78
Maize/corn, f8
Egg white, f1
Wheat, f4
Yeast (bakers/brewers), f45
Cockroach, i6
Adapted from Quest ImmunoCAP. d=dust mites (house), e=epidermal, f=food,g=grass, i=insect, m=mold, t=tree, w=weed
IgG Panel 2
Apple, f49
Banana, f92
Beef, f27
Casein, f78
Chicken, f83
Maize/corn, f8
Egg white, f1
Orange, f33
Potato, f35
Soybean, f14
Tomato, f25
Wheat, f4
REFERENCES
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
Collins English Dictionary: Complete and Unabridged. 12th Edition. New York, NY:
HarperCollins; 2014.
Netea MG, Joosten LA, Latz E, et al. Trained immunity: a program of innate immune
memory in health and disease. Science. 2016;352(6284):aaf1098.
Kucuksezer UC, Ozdemir C, Akdis M, Akdis CA. Mechanisms of immune tolerance to
allergens in children. Korean J Pediatr. 2013;56(12):505-513.
Akdis M, Akdis CA. Mechanisms of allergen-specific immunotherapy: multiple
suppressor factors at work in immune tolerance to allergens. J Allergy Clin Immunol.
2014;133(3):621-631.
Juraki Toni R, Marinovi B. The role of impaired epidermal barrier function in atopic
dermatitis. Acta Dermatovenerol Croat. 2016;24(2):95-109.
Whitsett JA, Alenghat T. Respiratory epithelial cells orchestrate pulmonary innate immunity. Nat Immunol. 2014;16(1):27-35.
Ilan Y. Oral immune therapy: targeting the systemic immune system via the gut immune
system for the treatment of inflammatory bowel disease. Clin Transl Immunology.
2016;5(1):e60.
Belkaid Y, Hand T. Role of the microbiota in immunity and inflammation. Cell.
2014;157(1):121-141.
Staudacher HM, Whelan K. Altered gastrointestinal microbiota in irritable bowel
syndrome and its modification by diet: probiotics, prebiotics and the low FODMAP diet.
Proc Nutr Soc. 2016;75(3):306-318.
Frei R, Akdis M, OMahony L. Prebiotics, probiotics, synbiotics, and the immune system:
experimental data and clinical evidence. Curr Opin Gastroenterol. 2015;31(2):153-158.
Serhan CN, Ward PA, Gilro DW. Fundamentals of Inflammation. Yale J Biol Med.
2011;84(1):64-65.
Iwasaki A, Medzhitov R. Control of adaptive immunity by the innate immune system.
Nat Immunol. 2015; 16(4):343-353.
Mathern DR, Heeger PS. Molecules great and small: the complement system. Clin J
Am Soc Nephrol. 2015;10(9):1636-1650.
Thurman JM, Le Quintrec M. Targeting the complement cascade: novel treatments
coming down the pike. Kidney Int. 2016;90(4):746-752.
Rescigno M. Dendritic cell functions: Learning from microbial evasion strategies. Semin
Immunol. 2015;27(2):119-124.
Liu J, Cao X. Regulatory dendritic cells in autoimmunity: a comprehensive review. J
Autoimmun. 2015;63:1-12.
Maggi E. The TH1/TH2 paradigm in allergy. Immunotechnology. 1998;3(4):233-244.
Hirahara K, Nakayama T. CD4+ T-cell subsets in inflammatory diseases: beyond the
Th1/Th2 paradigm. Int Immunol. 2016;28(4):163-171.
Tang M, Diao J, Cattral MS. Molecular mechanisms involved in dendritic cell dysfunction in cancer [published online ahead of print August 5, 2016]. Cell Mol Life Sci.
Waisman A, Lukas D, Clausen BE, Yogev N. Dendritic cells as gatekeepers of tolerance
[published online ahead of print July 25, 2016]. Semin Immunopathol.
Secor ER, Carson WF, Cloutier MM, et al. Bromelain exerts anti-inflammatory effects
in an ovalbumin-induced murine model of allergic airway disease. Cell Immunol.
2005;237(1):68-75.
Secor ER, Singh A, Guernsey LA, et al. Bromelain treatment reduces CD25 expression
on activated CD4+ T cells in vitro. Int Immunopharmacol. 2009;9(3):340-346.
Secor ER, Szczepanek SM, Castater CA, et al. Bromelain inhibits allergic sensitization
and murine asthma via modulation of dendritic cells. Evid Based Complement Alternat
Med. 2013;2013:702196.
Lee C, Zhang Q, Kozlowski J, et al. Natural products and transforming growth factorbeta (TGF-) signaling in cancer development and progression. Curr Cancer Drug
Targets. 2013;13(5):500-505.
Qathama AL, Prieto JM. Natural products with therapeutic potential in melanoma
metastasis. Nat Prod Rep. 2015;32(8):1170-1182.
Barragan M, Good M, Kolls JK. Regulation of dendritic cell function by vitamin D. Nutrients. 2015;7(9):8127-8151.
Bscheider M, Butcher EC. Vitamin D immunoregulation through dendritic cells. Immunology. 2016;148(3):227-236.
You J, Dong H, Mann ER, Knight SC, Yaqoob P. Probiotic modulation of dendritic cell
function is influenced by ageing. Immunobiology. 2014;219(2):138-148.
29 Castro C, Gourley M. Diagnostic testing and interpretation of tests for autoimmunity.

J Allergy Clin Immunol. 2010;125(2 Suppl 2): S2380-S247.
30 Mouyis M, Leandro M. Abnormal antibodies: what do you do? Br J Hosp Med (Lond).
2014;75(10):568-572.
31 Lthje P, Brauner A. Novel strategies in the prevention and treatment of urinary tract
infections. Pathogens. 2016;5(1):E13.
32 Klaywong K, Khutrakul G, Choowongkomon K, et al. Screening for lead compounds
and herbal extracts with potential anti-influenza viral activity. Southeast Asian J Trop
Med Public Health. 2014;45(1):62-74.
33 Tan YF, Li HL, Lai WY, Zhang JQ. Crude dietary polysaccharide fraction isolated from
jackfruit enhances immune system activity in mice. J Med Food. 2013;16(7):663-668.
34 Wang CL, Pi CC, Kuo CW, Zhuang YJ, Khoo KH, Liu WH, Chen CJ. Polysaccharides
purified from the submerged culture of Ganoderma formosanum stimulate macrophage
activation and protect mice against Listeria monocytogenes infection. Biotechnol Lett.
2011;33(11):2271-2278.
35 Dion C, Chappuis E, Ripoll C. Does larch arabinogalactan enhance immune function?
A review of mechanistic and clinical trials. Nutr Metab (Lond). 2016;13:28.
36 Sicherer SH, Sampson HA. Food allergy: epidemiology, pathogenesis, diagnosis, and
treatment. J Allergy Clin Immunol. 2014;133(2):291-307.
37 Boyce JA, Assaad A, Burks AW, et al. Guidelines for the diagnosis and management of
food allergy in the United States: report of the NIAID-sponsored expert panel. J Allergy
Clin immunol. 2010;126(6 0):S1-58.
38 Bergseng E, Sidney J, Sette A, Sollid LM. Analysis of the binding of gluten T-cell
epitopes to various human leukocyte antigen class II molecules. Hum Immunol.
2008;69(2):94-100.
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ABSTRACT & COMMENTARY
Benefits of Elderberry for Symptoms

of Common Cold in Air Travelers
A randomized, placebo-controlled trial
REFERENCE
Tiralongo E, Wee SS, Lea RA. Elderberry supplementation reduces cold duration
and symptoms in air-travelers: a randomized, double-blind placebo-controlled clinical trial. Nutrients. 2016;8(4):182.
OBJECTIVE
To determine whether a standardized membrane-filtered elderberry extract (BerryPharma; Iprona, Italy) is effective in preventing symptoms of common colds during
long-haul air travel
DESIGN
Double-blind, placebo-controlled clinical trial

PARTICIPANTS
All participants were economy class air travelers on at least a 7-hour flight with less
than a 12-hour stopover and a minimum of a 4-day stay at their destinations. Three
hundred and twenty five adults were enrolled and 312 completed the trial. All participants were 18 years or older in good general health, with an average age of 50; 66%
were female. Fifty-four percent had received a vaccine more than 10 days before
starting the trial;.96% were nonsmokers; 70% had travel time of more than 16 hours;
82% traveled for holiday. Subjects were recruited from the Gold Coast region of
Australia and traveled between April 2013 and December 2014.
INTERVENTION
Study intervention was elderberry extract, each capsule containing 300 mg of elderberry extract [22% polyphenols (ie, quercetin and its glycosides, rutin); 15% anthocyanins (ie, cyanidin and pelargonidin glycosides), and 150 mg of rice flour]. Placebo
contained matched excipients and was identical in appearance.
Participants were randomized into 2 groups, to receive either study medication or
placebo, beginning with a priming dose of 2 capsules per day 10 days before air
travel (baseline; 10 days), followed by an overseas dose of 3 capsules per day taken
before departure (2 days) until 4 or 5 days after arrival (+4/5 days). A daily diary was
kept throughout the study period (from day 10 to days +4/5) to record cold symptoms as well as to note additional health issues and additional medications.
STUDY PARAMETERS ASSESSED
Participants completed a number of surveys during the study periodat baseline

(10 days), before travel (2 days), and after travel (+4/5 days). The Wisconsin Upper
Respiratory Symptom Survey (WURSS-21) was used to assess respiratory symptomrelated quality of life, the SF-12 assessed general quality of life, and the Perceived
Stress Scale (PSS) was used to measure participants perception of stress. Cold
diagnosis was assessed by measuring the Jackson Score.
PRIMARY OUTCOME MEASURES
Total number of cold episode days were measured for the 6 days prior to the end of
the study (days 2/1 to days +4/+5).
KEY FINDINGS
Twenty-nine of 312 participants (9%) suffered from a well-defined cold (12 on elderberry and 17 on placebo; nonsignificant difference: P=0.4). Collectively, the placebo
group had a longer duration of cold symptoms (117 d vs 57 d; P=0.02) and higher
symptoms scores (583 vs 247; P=0.05) compared to the elderberry group.
Michael Traub, ND, FABNO

PRACTICE IMPLICATIONS
Black elderberry (Sambucus nigra) extract
has been shown, in previous clinical studies
(including those discussed below), to lessen
duration and symptoms of both influenza
and the common cold. This trial aimed to
discover whether elderberry was effective at
preventing the common cold and reducing
its duration and symptoms, specifically in
the context of air travel.
Black elderberry extract has been shown
to inhibit human influenza A (H1N1)
infection in vitro by binding to H1N1
virions, thereby blocking the ability of the
viruses to infect host cells.1 The same study
showed elderberry to be effective against 10
strains of influenza virus and compared its
effectiveness favorably to the known antiinfluenza activities of oseltamivir (Tamiflu)
and amantadine.
In a double-blind, placebo-controlled,
randomized study, black elderberry extract
(Sambucol) reduced the duration of flu
symptoms by 3 to 4 days. In addition,
during the convalescent phase participants
blood serum showed a higher antibody
level to influenza virus in the Sambucol
group than in the control group.2
Another study assessed the effect of
Sambucol products on the healthy immune
systemnamely, their effects on cytokine
production. The production of inflammatory cytokines was tested using bloodderived monocytes from 12 healthy human
donors. Adherent monocytes were separated from peripheral blood lymphocytes
and incubated with different Sambucol
preparations (ie, Sambucol Elderberry
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Get to the Root Cause of Ill Health

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Sometimes, common foods, chemicals, and medications can overstress the immune system,
making it hard for the body to defend and repair as it should.
Prolonged assault by these hidden immune burdens can lead to chronic conditions like asthma,
diabetes, and many more.
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19
Extract, Sambucol Black Elderberry Syrup, Sambucol

Immune System, and Sambucol for Kids). Production of
inflammatory cytokines [interleukin (IL)-1 beta, tumor
necrosis factor (TNF)-alpha, IL-6, IL-8] was significantly
increased, mostly by the Sambucol Black Elderberry Extract
(from 2-fold to 45-fold), as compared to lipopolysaccharide
(LPS), a known monocyte activator (from 3.6-fold to 10.7fold). The most striking increase was noted in TNF-alpha
production (44.9-fold). The authors concluded that, in addition to its antiviral properties, Sambucol Elderberry Extract
and its formulations activate the healthy immune system by
increasing inflammatory cytokine production.3
factor in interpreting the results. As a group, the participants

with cold symptoms used 25 different conventional medications and 1 natural medicine. Some participants took 1
medication, others took up to 4.
The authors of this study previously published a similar trial

attempting to show Echinacea root extract to be effective
in reducing respiratory symptom score and the number of
participants affected by respiratory disease symptoms. The
results failed to achieve significance.5 Similarly, in the present
study, many of the outcome measures did not reach significance. Yet in both of these publications the authors repeatedly stretch the limits of statistical significance by reporting
Black elderberries are dark violet in color owing to their trends and marginal results rather than adhering to the
anthocyanins, which are considered to be the active constit- accepted standard of a P value < 0.05, giving the impression
uent of the fruit. The elimination of plasma anthocyanins that their studies are more conclusive than they actually are.
appears to follow first-order kinetics, and most anthocyanin
compounds are excreted in urine within 4 to 5 hours after Given the fact that I have lived in Hawaii for over 30 years and
ingestion. A study by Frank et al found the elimination travel frequently, every flight I take (other than to the other
half-life of total anthocyanins was slightly lower following Hawaiian islands) is at least 4.5 hours in duration (depending
consumption of 278 mg (1.85 h) than after the consump- on wind conditions). Whether I travel to the West Coast, East
tion of 1,852 mg (2.57 h). The urinary excretion rate of Coast, or Europe, I find the conditions uncomfortable and
intact anthocyanins was fast and appeared to be monoexpo- stressful and I routinely take an herbal formula containing
nential with high variability. The low dose-normalized area echinacea and elderberry to shore up my immune system. It
under the concentration curve (AUC) and the fraction of seems to work. However, we will need to wait for better highorally administered anthocyanins recovered unchanged in quality, well-powered studies to find out whether these herbal
extracts meet the standards of scientific proof for prophylaxis
urine indicate a low bioavailability of these compounds.4
and treatment of respiratory illness associated with air travel.
The product used in the current study under review consisted Meanwhile, I find the risk/benefit balance tips firmly in the
of 600-900 mg of elderberry extract containing 90-135 mg of direction of flu prophylaxis with elderberry extracts.
anthocyanins daily. This dose was far lower than the doses used
in the Zakay-Rones randomized study of Sambucol, which REFERENCES
used an extract containing approximately 1,900 mg anthocy- 1 Roschek B, Fink RC, McMichael MD, Li D, Alberte RS. Elderberry flavonoids bind to
and prevent H1N1 infection in vitro. Phytochemistry. 2009;70:1255-1261.
anins. Since most of the active ingredients are excreted within 2 Zakay-Rones
Z, Varsano N, Zlotnik M, et al. Inhibition of several strains of influenza
virus in vitro and reduction of symptoms by an elderberry extract (Sambucus nigra L.)
5 hours, it may be necessary to dose elderberry 4 or 5 times
during an outbreak of influenza B Panama. J Altern Complement Med. 1995;1(4):361daily to even begin to obtain a 24-hour anti-influenza action
369.
V, Halperin T, Kalickman I. The effect of Sambucol, a black elderberry-based,
from the plant. Whether this applies to the rhinoviruses and 3 Barak
natural product, on the production of human cytokines: I. Inflammatory cytokines. Eur
Cytokine Netw. 2001;12(2):290-296.
other viruses causing the common cold is unknown.
In both the elderberry and placebo groups, 50% of the
subjects who developed cold symptoms used co-medication
to relieve symptoms. This presents a significant confounding
4 Frank T, Janssen M, Netzet G, Christian B, Bitsch I, Netzel M. Absorption and excretion of elderberry (Sambucus nigra L.) anthocyanins in healthy humans. Methods Find
Exp Clin Pharmacol. 2007;29(8):525-533.
5 Tiralongo E, Lea RA, Wee SS, Hanna MM, Griffiths LR. Randomised, double-blind,
placebo-controlled trial of echinacea supplementation in air travelers. Evid Based
Complement Alternat Med. 2012;2012:417267.
with Glutalytic
*
GI
rt
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f
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fo
y!
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i
m
e fa
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Full spectrum non-GMO vegan enzyme

blend, including Glutalytic, lactase,
lipase, alpha-galactosidase, and amylase,
to assist breakdown of gluten, gliadin,
casein, whey, lactose, protein, fats, and
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other allergens, including salmon,
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*These statements have not been evaluated by the Food
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diagnose, treat, cure, or prevent any disease.
Treatment of IgE-mediated Food Allergies

with Baked Egg Biscuits
Updates on oral immunotherapy for food allergies
REFERENCE
Bravin K, Luyt D. Home-based oral immunotherapy with a baked

egg protocol. J Investig Allergol Clin Immunol. 2016;26(1):61-63.
STUDY OBJECTIVE
To develop a home-based oral immunotherapy with baked egg

and to find out if it is a safe, practical, and effective treatment for
children with egg allergies
DESIGN
Case series design

STUDY PROTOCOL
Immunotherapy protocol was designed in 5 stages, starting with

125 g of egg protein, increasing it daily over a period of 60 days
to a target maximum dose of 6.25 g of egg protein.
The first dose was administered in a hospital and the rest was
continued at home.
Baked egg biscuit recipe consisted of 4 ingredients: flour (40 g at
stages 1-4 and 80 g at stage 5); sugar (40 g); margarine (25 g at
stages 1-3, 15 g at stage 4, and none at stage 5); and egg (0.1
mL at stage 1, 0.5 mL at stage 2, 1.0 mL at stage 3, 10 mL at
stage 4, and 50 mL at stage 5). The amount of biscuit eaten was
gradually increased on a daily basis.
PARTICIPANTS
Fifteen children with IgE-mediated egg allergy; 9 boys and 6 girls

ranging from age 6 to 17, with median age of 11 years and 2
months. Inclusion criteria were age >5 years, persistent IgE-mediated egg allergy with a positive skin prick test (wheal>3 mm) to
egg white and egg yolk, and symptoms of allergic reaction to
baked egg in the previous 6 months or a positive open food challenge result.
Ability to tolerate whole boiled egg without adverse reactions

KEY FINDINGS
Eight children completed the whole program successfully, 4 children within the target of 60 days and 4 children between 80 and
270 days. Seven children did not complete the study; 2 could
not tolerate the first dose without symptoms and 5 achieved
partial tolerance at days 10 to 47, allowing them to include trace
amounts of egg in their diet. Adverse reactions were minor and
could be controlled by antihistamine medications.
LIMITATIONS
Study design and small number of participants
By Eleonora Naydis,
ND, LAc, FABNO
Food allergies are very common, and the prevalence is
growing globally. Up to 15 million Americans have food
allergies, including 1 in every 13 children under age 18.1
According to a 2013 study by the Centers for Disease
Control and Prevention, incidence of food allergies among
American children has increased.2 Other countries also are
experiencing more cases of food allergies.3
Kids at risk for food allergies are more likely to have parents
with allergic disorders, and the children themselves are
more likely to have related conditions, such as asthma and
other allergic reactions. Food allergies can actually trigger
many allergic disorders, such as food-induced anaphylaxis,
gastrointestinal (GI) food allergies (eg, eosinophilic GI
disorders), skin reactions (eg, urticaria, eczema), respiratory manifestations, and Heiners syndrome, a rare milkinduced pulmonary disease.4
Each year, food allergies in children are responsible for over
300,000 doctor visits5 and 200,000 emergency department
visits.6 They are the leading cause of anaphylaxis occurring
outside of a hospital setting. Current treatment guidelines
recommend identification and strict avoidance of allergenic
foods.4 However, diet and unintentional exposures to allergens have significant impact on the quality of life.7 Better
treatment options are needed, and the latest efforts have
been concentrated on oral immunotherapy (or OIT, which
was used in this study) and sublingual immunotherapy (or
SLIT, which employs liquid sublingual preparations of allergenic extracts).
Oral immunotherapy is a
great way to introduce allergens
in the form of food, as they are
encountered in real life.
The most common culprits that account for 90% of immunoglobulin (Ig) E-related food allergies are known as the big
8: milk, eggs, peanuts, tree nuts, wheat, soy, fish, and shellfish. About 18% of children dont outgrow egg allergies.4
Reaction to eggs is commonly triggered by the proteins in
egg whites, although egg yolk proteins can cause allergies
as well.
to food allergens.15,16 Encouraging our patients to eat unprocessed foods can help decrease inflammation, because there
is some association between food allergies and increased
intestinal permeability.17 Glutamine and curcumin,17 as well
as flavonoids,18 are helpful in maintenance of good GI function. The gut microbiome, which plays an important role
in the development of allergies,19 is another potential area
ofresearch.
Oral immunotherapy is a great way to introduce allergens in

the form of food, as they are encountered in real life. Cooking REFERENCES
processes (heating, acid, mixing) can change allergenicity of 1 Food Allergy Research and Education. Food Allergy Facts and Statistics for the U.S.
http://www.foodallergy.org/file/facts-stats.pdf. Accessed August 15, 2016.
the food proteins.8 Heating egg protein with wheat can form 2 Jackson
KD, Howie LD, Akinbami LJ. Trends in Allergic Conditions among Children:
United States, 1997-2011. Hyattsville, MD: National Center for Health Statistics; 2013.
a matrix with the wheat protein, which changes digestibility
SL, Pawankar R, Allen KJ, et al. A global survey of changing patterns of food
of the egg protein,9 making egg biscuits a good choice for 3 Prescott
allergy burden in children. World Allergy Organ J. 2013;6(1):21.
4 Boyce, JA, Assaad A, Burks AW, et al. Guidelines for the diagnosis and management of
thestudy.
Are we ready to apply oral immunotherapy to our clinical
practice? While it is a very promising approach to treat
egg allergies,10 as well as other food reactions,11,12 there are a
number of issues that make it difficult. Safety is a big factor
since the severity of a reaction cannot be predicted by past
responses, IgE level, or the size of the prick test wheal. The
most common known factor associated with severe reaction
is a concurrent diagnosis of asthma.4 Additionally, the search
for optimal doses and duration of treatment is ongoing,
and the ease of use outside of the research environment is
questionable. Nevertheless, it is very encouraging to see the
desensitization of allergic reactions in subjects participating
in studies. Oral immunotherapy seems to work faster but
has higher rates of systemic reactions. Sublingual immunotherapy reactions are more frequent but are typically milder
and confined to the oropharynx, therefore showing a better
safety profile at this time.13
Meanwhile, as providers we need to counsel our patients
regarding hidden sources of food allergens to prevent unintended exposures and remind them to check expiration dates
on their EpiPen prescriptions. We also want to consider
additional factors related to the development of allergies.
Interestingly, introduction of cooked egg earlier on, at 4 to
6 months of age, might protect against egg allergy.14 Vitamin
D deficiency is associated with increased risk of sensitization
food allergy in the United States. Report of the NIAID-Sponsored Expert Panel. J Allergy
Clin Immunol. 2010;126(6 Suppl):S1-58.
5 Branum AM, Lukacs SL. Food allergy among U.S. children: Trends in prevalence and
hospitalizations. Hyattsville, MD: National Center for Health Statistics; 2008.
6 Clark S, Espinola J, Rudders SA, Banerji A, Camargo CA. Frequency of US emergency
department visits for food-related acute allergic reactions. J Allergy Clin Immunol.
2011;127(3):682-683.
7 Sicherer SH, Noone SA, Munoz-Furlong A. The impact of childhood food allergy on
quality of life. Ann Allergy Asthma Immunol. 2001;87(6):461-464.
8 Verhoeckx KCM, Vissers YM, Baumert JL, et al. Food processing and allergenicity. Food
and Chemical Toxicol. 2015;80:223-240.
9 Netting M, Makrides M, Gold, M, Quinn P, Irmeli P. Heated allergens and induction of
tolerance in food allergic children. Nutrients. 2013;5(6):2028-2046.
10 Burks AW, Jones SM, Wood RA, et al. Oral immunotherapy for treatment of egg allergy
in children. N Engl J Med. 2012;367(3):233-243.
11 Sheikh A, Nurmatov U, Venderbosch I, Bischoff E. Oral immunotherapy for the treatment of peanut allergy: systematic review of six case series studies. Prim Care Respir J.
2012;21(1):41-49.
12 Keet CA, Frischmeyer-Guerrerio PA, Thyagarajan A, et al. The safety and efficacy of sublingual and oral immunotherapy for milk allergy. J Allergy Clin Immunol.
2012;129(2):448-455.
13 Narisety SD, Keet CA. Sublingual vs oral immunotherapy for food allergy: identifying the
right approach. Drugs. 2012;72(15):1977-1989.
14 Koplin JJ, Osborne NJ, Wake M, et al. Can early introduction of egg prevent egg allergy
in infants? A population-based study. J Allergy Clin Immunol.2010;126(4):807-813.
15 Beek JH, Shin YH, Chung IH, et al. The link between serum vitamin D level, sensitization to food allergens, and the severity of atopic dermatitis in infancy. J
Pediatr.2014;165(4):849-854.e1.
16 Sharief S, Jariwala S, Kumar J, Muntner P, Melamed ML. Vitamin D levels and food and
environmental allergies in the United States: results from the National Health and Nutrition Examination Survey 2005-2006.J Allergy Clin Immunol. 2011;127(5):1195-1202.
17 Rapin JR, Wiernsperger N. Possible links between intestinal permeability and
food processing: a potential therapeutic niche for glutamine. Clinics (Sao Paulo).
2010;65(6):635-643.
18 Suzuki T, Hara H. Role of flavonoids in intestinal tight junction regulation. J Nutr Biochem.
2011;22:401-408.
19 Riiser A. The human microbiome, asthma, and allergy. Allergy Asthma Clin Immunol.
2015;11:35.
NMJ, OCTOBER 2016 SUPPLEMENTVOL. 8, NO. 101 2016 NATURAL MEDICINE JOURNAL. ALL RIGHTS RESERVED. 23
Vitamin D Effective for Suppressing

Immune Reactions
Trial looks at vitamin D in patients at high risk of hypertension
Heather Paulson, ND, FABNO
REFERENCE
STUDY PARAMETERS ASSESSED
Konijeti GG, Arora P, Boylan MR, et al. Vitamin D supplementation modulates T cell-mediated immunity in humans: results
from a randomized control trial. J Clin Endocrinol Metab.
2016;101(2):533-538.
Activation of T cells was measured by estimating release of intracellular ATP in vitro using plant lectin phytohemagglutinin on whole
blood samples of participants. Measurements were taken at baseline and after 2 months of treatment with vitamin D.
STUDY OBJECTIVE
To determine whether oral supplementation with vitamin D3 affects

T cell activation in those with existing vitamin D deficiency
Whether ATP level changes were significantly different between

treatment groups
DESIGN
KEY FINDINGS
This was a single-center ancillary study within a study looking at

vitamin D therapy in individuals at high risk of hypertension. It was
a double-blind, multicenter, randomized controlled trial.
After 2 months of treatment, 25(OH)D levels significantly increased

by 5.77 ng/mL among those assigned low-dose vitamin D3 and
9.77 ng/mL among those assigned high-dose vitamin D3.
PARTICIPANTS
Participants (n=38) were derived from the Vitamin D Therapy in

Individuals at High Risk of Hypertension Study. The original study
included 534 men and women ages 18-50 years old with 25(OH)
D lower than 25 ng/mL and untreated prehypertension or stage
I hypertension. Participants were randomized to receive lowdose vitamin D (400 IU) or high-dose vitamin D (4,000 IU) daily
for 6months.
The current publication involved a subset of 38 randomly selected
men and women who had T-cell function in whole blood measured.
Among the cohort of 38 patients for whom T-cell function was
assessed, 20 participants were randomized to low-dose vitamin
D and 18 participants were randomized to high-dose vitamin D.
The median age was 45 years (interquartile range, 39-47 years); 9
were women (24%); 8 (21%) were white, 29 (76%) were black, and
1 (3%) was of other or unknown race. Patients were treated with
vitamin D for a mean of 117 days (SD: 52 days). Per protocol, both
groups were vitamin Ddeficient, with similarly low baseline 25(OH)
D levels (mean, 16.2 ng/mL; SD, 6.8 ng/mL).
Exclusion criteria included use of an antihypertensive medication
within the preceding 3 months; vitamin D supplementation (defined
as vitamin D found in a multivitamin or supplement) totaling 400
IU/d within the 3 months before enrollment; and known cardiovascular disease (defined as prior myocardial infarction, percutaneous transluminal coronary, angioplasty, coronary artery bypass,
or stroke).
Treatment with high-dose vitamin D significantly decreased intracellular CD4+ATP release (difference=95.5 ng/ml; interquartile
range [IQR], 219.5 to 105.8; P<.026). In contrast, treatment
with low-dose vitamin D3 did not significantly influence intracellular
CD4+ ATP release (difference=0.5 ng/mL; IQR, 69.2 to 148.5;
P=0.538). The difference in follow-up ATP levels at 2 months was
significantly different between the low- and high-dose vitamin D3
groups.
In a proportional odds model, treatment with high-dose vitamin
D3 was more likely to decrease ATP after antigen stimulation
compared to low-dose vitamin D3 (odds ratio [OR]: 3.43; 95%
confidence interval [CI]: 1.06-1.11).
Eleven of the 20 patients (45%) treated with high-dose vitamin D3
were considered responders with significant decreases in ATP
levels. Among those treated with high-dose vitamin D3, 63.5%
(7/16) of men, 25% (1/4) of women, 52.9% (9/17) of white, and
48.1% (8/17) of black participants were responders.
This study did not observe a significant difference in results
according to race. It did, however, find a significant difference
according to sex (P, interaction<0.02). Men were more likely to
have decreased ATP antigen stimulation compared to women.
Other exclusion criteria included history of ulcerative colitis,

Crohns disease, celiac disease, colostomy, pancreatic enzyme
deficiency, short bowel syndrome, gastric bypass, cystic fibrosis,
or dumpingsyndrome.
This study examined the function of CD4+T cells. As a
quick immunology reminder, the CD4+T cells have multiple
immune functions and include TH1, TH2, TH17, and T
regulator (Treg) cells. The diverse functions of T cells include
activation of the innate immune system, B lymphocytes, cytotoxic T cells, and nonimmune cells.1 In addition Tregs can
inhibit the action of other T cells, acting as a balance to the
inflammatory immune response. Unfortunately, this study
did not differentiate the subtypes of CD4+T cells. So it is
impossible to know which subsets of CD4+T cells were influenced by vitamin D3 supplementation.
In clinical practice we often

get the question, How long until my
vitamin D levels will increase? This
study confirms that in just 2 months of
therapy, significant changes were made
in serum vitamin D levels.
In clinical practice we often get the question, How long until

my vitamin D levels will increase? This study confirms that Vitamin D may also be used as a complement to drugs estabin just 2 months of therapy, significant changes were made in lished for overactive immune diseases. One study combining
serum vitamin D levels.
high-dose vitamin D with interferon -1b in patients with
multiple sclerosis showed an improvement in function and
In this study, vitamin D was associated with changes in cell- a reduction in relapse compared to patients treated with the
mediated immunity through reduction in activation (less drug alone.7
ATP produced). This reduction in activation was significantly different in the low-dose and high-dose groups, with The role of vitamin D3 supplementation on immune funcgreater suppression of activation in the high-dose group. This tion requires clinical trial outcomes to definitively determine
suggests that high doses may provide greater immune modu- if, and how much, oral vitamin D3 influences disease states.
lation than low doses.
Meanwhile, it can be considered not harmful to bring our
patients into the normal range of 25-hydroxycholicalciferol
This study is in keeping with animal studies that have demon- in an effort to optimize their health while clinical studies
strated vitamin Ds modulation of autoimmunity.2 Quelling continue to inform us.
overactive immune-mediated conditions may have far-reaching
clinical implications. The story, however, is complicated. REFERENCES
Vitamin D receptors (VDRs) are found on a variety of immune 1 Luckheeram RV, Zhou R, Verma AD, Xia B. CD4T cells: differentiation and functions.
Dev Immunol. 2012;2012:925135.
cells. These VDRs have high variability themselves, with many 2 Clin
Deluca HF, Cantorna MT. Vitamin D: its role and uses in immunology. FASEB J. 2001
Dec;15(14):2579-2585.
genotypes possible. There are also vitamin D binding proteins
3 Hewison M. An update on vitamin D and human immunity. Clin Endocrinol (Oxf).
(VDBPs) that influence the availability of vitamin D. In short,
2012;76(3):315-325.
KM, Fedorak RN, Madsen K, Kroeker KI. Vitamin D improves inflammatory
the interplay of vitamin D on immune function is complex, 4 Reich
bowel disease outcomes: Basic science and clinical review. World J Gastroenterol.
2014;20(17):4934-4947.
and confounding the data is the influence of VDRs, VDBPs,
5 Pappa HM, Mitchell PD, Jiang H, et al. Maintenance of optimal vitamin D status in
3
other nutrients (eg, calcium), and hormonal influences.
children and adolescents with inflammatory bowel disease: a randomized clinical trial
Evidence suggests that vitamin D provides an effective
therapy for cell-mediated immunity-based diseases such as
inflammatory bowel disease, but the ideal dosage continues
to be investigated.4-6
6
7
comparing two regimens. J Clin Endocrinol Metab. 2014;99(9):3408-3417.

Wingate KE, Jacobson K, Issenman R, et al. 25-Hydroxyvitamin D concentrations
in children with Crohns disease supplemented with either 2000 or 400 IU daily for 6
months: a randomized controlled study. J Pediatr. 2014;164(4):860-865.
Soilu-Hnninen M, Aivo J, Lindstrm BM, et al. A randomised, double blind, placebo
controlled trial with vitamin D3 as an add on treatment to interferon -1b in patients with
multiple sclerosis. J Neurol Neurosurg Psychiatry. 2012 May;83(5):565-571.
25
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In this podcast, naturopathic physician Todd Born, ND, addresses
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sensitivities and intolerances.
ABOUT THE EXPERT

TODD A. BORN, ND, is in private practice with
his wife, Lindsay Jones-Born, ND, at Born Naturopathic Associates, Inc., in Alameda, CA, where he
is co-owner and medical director. Born is product
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Borns clinical focus is using integrative medicine
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Periodontitis and
Alzheimers Disease
Improving dental hygiene may slow cognitive decline
REFERENCE
Ide M, Harris M, Stevens A, et al. Periodontitis and cognitive

decline in Alzheimers disease. PLoS One. 2016;11(3):e0151081.
DESIGN
Observational cohort study

PARTICIPANTS
Investigators recruited 60 nonsmoking adults with mild to

moderate dementia from referrals to community memory
assessment services in the United Kingdom. All participants
had a minimum of 10 teeth and had not been treated for periodontitis in the 6 months prior to the study. Fifty-two participants
completed the study.
OBJECTIVE
To observe any associations between periodontitis and dementia

severity, rate of cognitive decline, or chronic inflammation in
adults with mild to moderate Alzheimers disease.
OUTCOME MEASURES
Cognitive status of participants was tested using both the

Alzheimers Disease Assessment Scale (ADAS-cog) as the
primary cognitive outcome and the standardized Mini-Mental
State Examination (sMMSE) as a secondary cognitive outcome.
At baseline, venous blood was tested for C-reactive protein
(CRP), the pro-inflammatory cytokine tumor necrosis factor
(TNF) , the anti-inflammatory cytokine interleukin (IL)-10 and
immunoglobulin G (IgG) antibodies to P. gingivalis. Dental health
was assessed by a dental hygienist, blind to cognitive testing
outcomes, to determine the presence or absence of periodontitis following established Centers for Disease Control and
Prevention/American Academy of Periodontology (CDC/AAP)
case definitions. All assessments were performed at baseline
and repeated at 6 months.
KEY FINDINGS
The presence of periodontitis at baseline was not related to baseline cognitive state but was associated with a 6-fold increase in
the rate of cognitive decline (P=0.005). There was no correlation between carriers and noncarriers of apolipoprotein E (ApoE)
allele and baseline periodontitis or cognitive decline. Baseline
antibody levels to P gingivalis were not statistically associated
with cognitive outcomes. Periodontitis at baseline was associated with a relative increase in the pro-inflammatory state (CRP,
TNF-) and decrease in the anti-inflammatory state (IL10) over
the 6-month follow-up period. Periodontitis was associated with
an increase in cognitive decline in Alzheimers disease (AD),
independent of baseline cognitive state, which may be related
to systemic inflammation.
Jacob Schor, ND, FABNO
First, these data hold out the possibility that improving
dental hygiene might slow the rate of cognitive decline in
AD. Second, these data support a new theory that AD is in
part an immune response to infection.
Several earlier studies have reported that AD patients have
worse dental health than control subjects of similar ages and
that the worse the dementia, the worse the dental health.1,2
The obvious assumption was that this was due to poorer
self-care with advancing dementia (ie, people were forgetting to brush their teeth).3
This study did not find a clear relationship between the
dementia severity and periodontitis, but that may be
because patients with severe dementia were not included
in the cohort. This is the first study that correlates rates
of declining cognitive function with poor dental health.
Knowing that periodontitis was associated with faster
cognitive decline during this studys 6-month follow-up
period suggests that we should be far more proactive with
patients showing early signs of AD and insist on aggressive
dental care.
While we may look for other explanations for this association, the most obvious one, that periodontitis drives
Alzheimers disease progression, makes the most sense in
light of other recent research and the newer hypothesis
that suggests AD is an immune reaction to infection.
In May 2016, Science Translational Medicine published a
paper by Harvard researcher Deepak Kumar and colleagues
that suggested that the amyloid proteins that are the hallmark of AD normally serve an antimicrobial function,
protecting the brain against infection. Their theory is that
infections, in particular mild infections, combined with
increased permeability of the blood brain barrier (BBB),
elicit an over-response by the brains defensive mechanism that in its enthusiasm generates an overabundance
of amyloid plaque. Amyloid beta, the substance that
forms the plaque of Alzheimers disease, may in fact have
a purpose in the brain. It is a defense mechanism against
27
infection and is now described as primary effector molecules of innate immunity, antimicrobial peptides (AMPs),
also called host defense peptides.4
When a virus, fungus or bacteria slips across the BBB, the
brain generates amyloid material that surrounds and traps
the invader. The amyloid cocoons the interloper into a cage.
Even after the invader dies, the trap remains in place, forming
permanent plaque deposits in the brain. The Harvard team
has demonstrated this process occurring in vitro, to date. The
study currently under review lends support to this theory,
with its preliminary finding of an association between periodontitis and AD in humans.
These data support a new

theory that AD is in part
an immune response
to infection.
There are several other examples of chronic infections associated with AD. In September 2016, Shim et al reported
that elevated Epstein-Barr Virus (EBV) antibody levels
are associated with cognitive decline, and went so far as to
suggest EBV antibody levels might be used as a biomarker
for assessing rate of disease progression.5 Herpes simplex
virus-1 antibody titers also share a similar association with
cognitive impairment.6
A similar association has been seen with bacterial infections in numerous studies. A meta-analysis of 25 separate
studies, published in August 2016, found significant associations between both Chlamydia pneumoniae and spirochetal
bacteria with AD. Spirochetal infections were associated
with a 10-fold increased occurrence of AD (OR: 10.61;
95% CI: 3.38-33.29). A greater than 5-fold increase in risk
of AD was seen with Chlamydia infection (OR: 5.66; 95%
CI: 1.83-17.51).7
It may not be the type of infectious agent as much as the chronicity or persistence of the infection that provokes the AD triggering response in the brain. It may take continuous antigen
exposure to trigger the amyloid response.8
Another paper published in August 2016 expands this hypothesis, suggesting that the chain of events that leads to AD starts
in the gut with intestinal microbiota increasing intestinal
permeability and in turn increasing permeability of the BBB.
This in turn presents more antigenic material to the brain that
triggers the amyloid beta producing reaction.9
Noting the many studies that have associated herpes antibody levels with AD, Ruth Itzhaki, writing in August 2016
in the Journal of Alzheimers Disease, suggested we consider
the usage of antiviral treatment to slow or halt the progression of AD.10
Thus we could be fast entering a new era in how we view
Alzheimers disease, one in which we both understand the
underlying mechanisms and also have some simple interventions to offer our patients, starting with reminding them to
brush their teeth.
REFERENCES
1
Kamer AR, Morse DE, Holm-Pedersen P, Mortensen EL, Avlund K. Periodontal inflammation in relation to cognitive function in an older adult Danish population. J Alzheimers
Dis. 2012;28:613-624.
2 Martande SS, Pradeep AR, Singh SP, et al. Periodontal health condition in patients with
Alzheimers disease. Am J Alzheimers Dis Other Demen. 2014;29(6):498-502.
3 Syrjala AM, Ylostalo P, Ruoppi P, et al. Dementia and oral health among subjects aged 75
years or older. Gerodontology. 2012;29(1):36-42.
4 Kumar DK, Eimer WA, Tanzi RE, Moir RD. Alzheimers disease: the potential therapeutic role of the natural antibiotic amyloid- peptide. Neurodegener Dis Manag.
2016;6(5):345-348.
5 Shim SM, Cheon HS, Jo C, Koh YH, Song J, Jeon JP. Elevated Epstein-Barr Virus Antibody Level is Associated with Cognitive Decline in the Korean Elderly [published online
ahead of print September 2, 2016]. J Alzheimers Dis.
6 Mancuso R, Baglio F, Agostini S, et al. Relationship between herpes simplex virus-1specific antibody titers and cortical brain damage in Alzheimers disease and amnestic
mild cognitive impairment. Front Aging Neurosci. 2014;6:285.
7 Maheshwari P, Eslick GD. Bacterial infection increases the risk of Alzheimers disease:
an evidence-based assessment [published online ahead of print August 18, 2016]. J
Alzheimers Dis.
8 Licastro F, Porcellini E. Persistent infections, immune-senescence and Alzheimers
disease. Oncoscience. 2016;3(5-6):135-142.
9 Hu X, Wang T, Jin F. Alzheimers disease and gut microbiota [published online ahead of
print August 26, 2016]. Sci China Life Sci.
10 Itzhaki RF. Herpes and Alzheimers Disease: Subversion in the central nervous
system and how it might be halted [published online ahead of print August 1, 2016].
J Alzheimers Dis.
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AUDIO INTERVIEW
Immune Processes and Brain Health

An Interview with Heather Zwickey, PhD
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In this interview with Natural Medicine
Journals Editor-in-Chief, Tina Kaczor,
ND, FABNO, Zwickey explains how
immune processes can influence
brain healthincluding in Parkinsons,
Alzheimers, and depressive disorders. She discusses
nutrition, supplements, and the complicated ways gut
health and immunity interact with cognitive function.
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ABOUT THE EXPERT

HEATHER ZWICKEY, PhD, is dean
of research and graduate studies and

a professor of immunology at the
National College of Natural Medicine,
Portland, Oregon, as well as director of
Helfgott Research Institute. Currently,
she heads several pilot studies looking at the effects
of botanicals, hydrotherapy, energy medicine, and
diet on immunological parameters. Zwickey trained
at the National Jewish Medical and Research Center
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immunology and microbiology from the University
of Colorado Health Sciences Center and completed a
postdoctoral fellowship at Yale University.

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OCTOBER 2016 SUPPLEMENT

The Oral HealthAlzheimers Connection

Elderberry for Travel-Related

The Root Cause

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SPECIAL ISSUE IMMUNOLOGY

Benefits of Elderberry for Symptoms of Common Cold in Air Travelers

Treatment of IgE-mediated Food Allergies with Baked Egg Biscuits

Vitamin D Effective for Suppressing Immune Reactions

The Link Between Periodontitis and Alzheimers Disease

Getting to the Root Cause of Food Sensitivities

Immune Processes and Brain Health

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uating CBC results (sometimes referred to as the rule of

hemoglobin would be roughly 15 g/dL and hematocrit

TABLE 1. OPTIONS FOR LABORATORY EVALUATION OF IMMUNE MEDIATED CONDITIONS

Group Associated Descriptors

Group Associated Descriptors

CBC & Differential

Fundamental (RBC, WBC) immune

Marker of active inflammation (nonspecific)

Rheumatoid Factor (RF)

Early RA diagnosis and ongoing

C Reactive Protein (CRP,

Marker of active inflammation (nonspecific)

ANA (Titer and Pattern)

Zinc (RBC, plasma or

General immune function & wound healing

Insulin-like Growth Factor

Nutritional deficiency & growth hormone

General immune function, metabolic

Candida Antibodies (IgG,