Nutrigenomics White Paper

White Paper
The Power of Nutrigenomics:

A Practical Guide for Application in the
Treatment of Chronic Illness
Advances in the understanding of genetics are changing the way
healthcare professionals think about disease causes and prevention. It's
now accepted that a person's state-of-health arises from the dynamic
interaction of environmental factors with his or her genetic uniqueness.
And, nutrition has emerged as a primary environmental factor that can
positively or negatively impact the extent to which a person will realize
his or her genetic potential.
Nutrition research in the past has focused on nutrient deficiencies and
impairment of health.1 But the Human Genome Project has led to the
concept of personalized medicine not only with drugs
(pharmocogenetics), but with nutritional modalities as well.1-4 Nutritional
genomicsor nutrigenomicsis the junction between health, diet, and
genomics.1 In other words, nutrigenomics is the effect that nutritive
substances and phytochemicals have on genetic expression within
human cells.
As a growing field of research, nutrigenomics is the recognition of the
ability to optimize nutrition for maintaining and extending a state of
optimal health.5 This growing field of research has demonstrated the
effects that nutrients and botanicals can have on modifying gene
expression, prompting the development of research-based
nutraceuticals, functional foods, and dietary approaches to address
disorders in genetically pre-disposed individals.2,3,5
The Future of Health CareHere Today

New developments in nutrigenomic research are predicted to offer
enormous potential for the development of dietary optimization
approaches.5 But you wont have to wait for therapies applying basic and
advanced nutrigenomic principals to benefit the health of your patients.
Theyre already here.
Clinically effective modalities
for applying nutrigenomics
are already in use in a variety
of healthcare practices.
Nutrigenomics in clinical practice entails using specified, defined

nutrients and nutritional programs to target genetic expression for
improved patient outcomes without serious adverse effects. These new,
patient-centered approaches to health care rely upon nutrition and other
modifiable lifestyle factors to help people achieve optimal genetic
expression.
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Table of Contents
The Nutrigenomics Matrix........... 3
3-Phase Plan for Implementing Nutrigenomics......... 4
Phase 1AChanging Primary Dietary Signals with TLC.. 6
Help for Implementing Dietary Signal Changes... 7
Cardiovascular & Insulin Resistance Conditions.........8
Inflammatory, Gastrointestinal, Autoimmune & Fatigue
Disorders............................................................................... 8
Hormone Imbalances & Cyclerelated Symptoms.. 9
Phase 1BChanging Primary Dietary Signals with Medical Foods..10
The SKRM Effect: Creating the Next Generation of Medical
Foods10
Metabolic Syndrome & Cardiovascular Disease....11
Inflammatory Bowel Disease (Autoimmune Support)... 13
Type 2 Diabetes.. 14
Chronic Fatigue Syndrome (Live Detoxification Support)15
Premenstrual Syndrome .. 16
Leaky Gut Syndrome . 17
Phase 2Modulating Kinase Signaling with SKRMs..18
Insulin SKRMs. 19
Inflammation & Autoimmune SKRMs.. 21
Future SKRMs........ 23
Phase 3Recommending Key Nutritional Support. 24
Cardiovascular Support. 24
Blood Sugar Metabolism Support 25
Liver Detoxification Support.. 25
Intestinal Support 26
Joint Inflammation Support... 27
Hormone Balance Support .. 27
Putting It All Together 29
Appendices
Applying Nutrigenomics for Children & Teens... 30
The Need for Therapeutic Lifestyle Changes 31
References.. 32
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The Nutrigenomics Matrix

The principles of
nutrigenomics can be applied
easily in any healthcare
practice.
This chart is provided for your reference as a summary of how

nutrigenomics can easily be put into practice for the health of your
patients. The combination of healthy dietary choices, medical foods,
SKRMs, and other targeted nutrients can be a revolutionary avenue of
support for those suffering from a number of chronic illnesses.
This is the power of nutrigenomics.
Conditions
Metabolic
Syndrome &
Cardiovascular
Disease (CVD)
Dietary
Signal
Modification
Medical Food Support
FirstLine
Therapy
UltraMeal PLUS 360

featuring SKRMs
UltraMeal
SKRMs
Key
Nutritional
Support
RIAA &
Acacia
CoQ10
EFAs
RIAA
Glucosamine
Chondroitin
MSM
RIAA &
Acacia
Cinnamon
Green Tea
Proteomic
research in
progress
Silymarin
Catechins
Artichoke
Leaf
Watercress
Ellagic Acid
UltraMeal PLUS
Inflammatory
Bowel Disease
(IBD)
FirstLine
Therapy
UltraInflamX PLUS
360 featuring SKRMs
UltraInflamX
Type 2
Diabetes
FirstLine
Therapy
UltraGlycemX PLUS
360
featuring SKRMs
Chronic
Fatigue
Syndrome
(liver
detoxification
support)
FirstLine
Therapy
UltraClear
Leaky Gut
Syndrome
FirstLine
Therapy
UltraClear SUSTAIN
Premenstrual
Syndrome
(PMS)
FirstLine
Therapy
Estrium
UltraClear PLUS
UltraClear Plus pH
Probiotics
Kudzu
Red Clover
Turmeric
Resveratrol
Stabilized I3C
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3-Phase Plan for Implementing

Nutrigenomics
You can easily tailor and prescribe a program for patients presenting
with a variety of common and chronic health conditions. A nutrigenomic
approach to wellness can include any or all of the following:
Adopt a simple, 3-phase plan

for applying nutrigenomics in
your practice.
1A. Dietary Signal Modification with TLC

Western diets, foods of convenience, and other unhealthy
dietary habits can muddle the signals sent to cells throughout
the body, fostering negative genetic (phenotypic) expression
that leads to premature aging and disease. What people eat,
therefore, may have a direct influence on how they feel. And
addressing those eating patterns allows your patients to
manage symptoms and even halt or reverse the progression of
their illnesses.
You can help them make informed decisions that impact their
health by offering therapeutic lifestyle changes (TLC). TLC can
provide food plans that incorporate nutrigenomic principles for a
broad population, then further customize these plans based on
patient response, individual concerns, and specific nutritional
needs.
1B. Dietary Signal Modification with Medical Foods
Medical foods offer an adjunct approach to dietary
recommendations to nutritionally manage specific conditions. A
medical food is formulated with macro- and micronutrients that
are recognized by scientific principles to support the dietary
management of a disease or condition, and is to be
administered under the supervision of a physician or licensed
healthcare practitioner.
Medical foods contain nutrients that typically cannot be acquired
through normal dietary measures. Some patients may require a
level of nutritional support that simply cannot be met by even a
food plan with the best intentions. Medical foods offer a
powerful tool, yet can be very simple to implement in your
practice.
2.
Selective Kinase Response Modulators (SKRMs)

Dietary signals are translated by enzymes known as kinases at
the cellular level, helping to direct genetic expression. Selective
kinase response modulatorsor SKRMsare nutritional
substances that can work to modulate kinase signaling back
into balance, helping to restore healthy signaling to genes,
favorably affect genetic expression, and reverse the effects of
chronic illness.
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Where an unhealthy diet makes the kinase signaling unclear,

SKRMs help increase the volume of the message for positive
genetic expression and preservation or restoration of health.
These research-based nutritional substances offer the newest
avenue for a natural approach to wellness that embodies the
ideals of nutrigenomics.
3.
Targeted Nutritional Support

Even the most comprehensive approach to wellness may
require additional nutritional support for maintaining health,
addressing specific symptoms, or customizing approaches for
patients with multiple health concerns.
Outlined here are just a few approaches of the hundreds of
possibilities for targeted nutritional applicationsfrom additional
support for joint protection and restoring healthy gut ecology to
maintaining healthy hormone balance and blood sugar levels.
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Phase 1A
Changing Primary Dietary Signals with TLC
Unhealthy diets are a leading

cause of chronic illness
fatalities.
The first step in a nutrigenomics intervention is changing primary dietary

signals. Foods contain nutrients serving as dietary signals that travel to
cells throughout the body, where they are translated by kinases. Healthy
food choices foster healthy signaling. Poor food choices, however, can
trigger a disorder of kinase signaling, resulting in poor genetic
expression and, ultimately, chronic illness.6,7 In fact, poor nutrition is one
of the three leading factors attributed to 70% to 90% of mortalities from
chronic illnesses in the U.S. alone.8
Prior to the commercialization of the Western diet, humans (over
centuries) developed a relationship with commonly eaten foods. Existing
in harmony with these foods meant dietary signals that were adequate to
maintain health. Changing the diet with commercialized foods and
introducing foreign substances creates a state of cellular stress where
messages can be distorted and negatively affect physiological function.6
But these negative dietary signals dont have to be a part of modern
living, nor do the long-term costs of premature aging and chronic
disease development.
Modifying Genetic Expression
Diet, Exercise
& Lifestyle
Direct
Nutrients &
Xenobiotics
Indirect
Metabolism
Signal Transduction
Gene Expression
Cell Phenotype
Figure 1. The nutrients (or lack thereof) and other foreign substances (xenobiotics) in
a diet can both directly and indirectly influence genetic expression, impacting health.
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How can you help modify your patients dietary signals? This can be
accomplished through therapeutic lifestyle changes (TLC). Scientific
evidence in support of TLC programs as a fundamental therapy for
chronic conditionsincluding cardiovascular disease (CVD), type 2
diabetes, and obesitycontinues to grow.7,9-21
TLCthe first step in
harnessing the power of
nutrigenomics.
An optimal TLC program should include recommendations for exercise

for a comprehensive approach. It should also provide the means and
flexibility for further personalization of condition-specific support with
nutrients that may not be possible to obtain through dietary measures
or difficult to obtain in therapeutic amounts. Medical foods (Phase 1B on
page 10) are designed to complement dietary approaches for the
nutritional management of specific conditions.
Help for Implementing Dietary Signal Changes
The responsibilities of a patient change in the management of chronic
disease. Because the patient takes on a caretaker role in the treatment
process, greater educational efforts are needed for successful
outcomes.22,23 Unfortunately, many practices are set up for acute
disease management rather than chronic illness care, and may not be
prepared to institute efforts such as lifestyle modification programs.23
FirstLine Therapy is an example of a TLC program that can help
healthcare practitioners teach their patients how to adopt dietary
changes that can positively affect kinase signaling to support genetic
expression, befitting a longer, healthier life.
The FirstLine Therapy food plans are based on a traditional
Mediterranean-style eating plan that has an overall low glycemic load
(for balancing blood sugar), low in arachidonic acids (anti-inflammatory),
and high in phytonutrients. Moreover, the foods have been screened for
a history of safe use and for unique molecules that have the ability to
modulate kinase signaling in a positive manner. These foods affect
signal transduction to help increase the clarity of messages sent to
kinases, creating a potential to combat chronic disease and restore
optimal wellness. A disordered physiology will respond to these new
signal conductors, reducing the burden of prior unhealthy eating habits.
For optimal support, these dietary changes may be customized
through tailored food plans and medical foodsto meet the specific
needs of patients, such as those with conditions related to insulin
resistance, cardiovascular disease, autoimmune disorders, inflammatory
conditions, fatigue syndromes, and hormone imbalances.
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Cardiovascular & Insulin Resistance Conditions

Many conventional dietary programs recommended by leading
health organizations are lowfat, high-carbohydrate diets designed to
lower elevated cholesterol levels. However, individuals on these
diets may eat high-glycemic-index foods that can cause spikes in
blood sugarincreasing hunger, decreasing satiety (feeling of
fullness), and fostering insulin resistance and a variety of related
health problems. Most importantly, these diets may not produce the
desired results.19
Dietary choices causing a high insulin response have been linked to
the development of metabolic syndrome, type 2 diabetes, and
cardiovascular disease (CVD).12,24-26 Research has demonstrated,
for example, that the Western dietalso referred to as the Standard
American Diet (SAD)modulates kinases and insulin signaling.27
Science-based recommendations include reducing consumption of
high-glycemic-index foods (e.g., simple sugars, processed and
snack foods) and/or replacing them with low-glycemic-index fruits,
vegetables, and whole grains.12,28-30 This also adds fiber for a lower
overall glycemic load (GL).26
A low-GL food plan promotes healthy blood sugar and energy levels
in your patients. Research also links insulin resistance to CVD risk
(as is the case in metabolic syndrome), making this an appropriate
eating plan for cardiovascular disease.13,19 Low-GL diets have also
been shown useful in conditions involving inflammation and
oxidative stress, reinforcing its application for CVD patients.21,31
Inflammatory, Gastrointestinal, Autoimmune & Fatigue Disorders

Diet may also represent a significant immune-modulating part of a
patients environmental exposure. An increasing body of research
suggests that chronic or recurring inflammatory disorders may be
reactions to substances that trigger an immune response from the
gastrointestinal (GI) tract. Dietary changes may have a noticeable
impact on modifying the underlying inflammatory signals that are
associated with autoimmune disorders. Scientific studies have
demonstrated the effectiveness of dietary therapies in alleviating the
symptoms and even in altering the progression of inflammatory and
autoimmune conditions.31-49
Research suggests that many common inflammatory and
gastrointestinal conditions are triggered by sensitivities or reactions
to certain foods and that removing these offending foods may
provide relief.32-49 Broad guidelines for eliminating common foods
that trigger inflammation can be customized as patients slowly
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challenge the reintroduction of foods to determine those that may

exacerbate symptoms.
A low-GL diet has also been shown to be beneficial in reducing
oxidative stressthe overproduction of damaging free radicals
associated with chronic fatigue syndrome and conditions such as
rheumatoid arthritis and inflammatory bowel disease (IBD).31 LowGL foods that are rich in antioxidantsberries, red grapes, garlic,
spinach, whole grainscan help restore the bodys balance of
antioxidants and combat harmful free radicals generated by
environmental toxins, inflammation, and unhealthy lifestyle habits.
While a modified elimination diet may provide an approach for longterm condition and symptom management, sometimes a more
aggressive, non-fasting dietary approach may be warranted. Some
symptoms of chronic fatigue syndrome, for example, may be
immediately relieved through a liver detoxification program featuring
a more aggressive elimination diet for a shorter term.
Hormone Imbalances & Cyclerelated Symptoms

In both men and women, unhealthy diets are one of the many
factors that influence the bodys ability to balance hormones.
Additionally, foods and beverages can include exogenous sources
of hormones that overload the bodys natural ability to detoxify and
excrete them.
Estrogen imbalance in women, for example, may manifest as
premenstrual syndrome, irregular menstrual cycles, fibrocystic
breast disease, endometriosis, or dysmenorrhea, as well as foster
symptoms that impact daily livinghot flashes, night sweats, anxiety
attacks, and mood fluctuations.
Targeted dietary changessuch as the inclusion of cruciferous
vegetables and adaptogenic phytoestrogens like soycan support
the bodys production, use, and excretion of various hormones,
particularly estrogen. These dietary changes can positively affect
the detoxification of circulating estrogens, thereby creating a positive
estrogenic influence on activities at the cellular level.50-55
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Phase 1B
Changing Primary Dietary Signals with
Medical Foods
Medical foods provide
powerful signaling nutrients
not found in typical diets.
Food plans and other lifestyle changes may only provide part of the
recommendations for changing dietary signals for optimal health
support. Medical foods, ever increasing in use, provide an ideal
complement to dietary changes to help modify kinase signaling for
patients presenting with a variety of conditions, such as those related to
dysglycemia and inflammation. Medical foods contain therapeutic levels
of nutrients that would be difficult, if not impossible, to achieve through
traditional dietary means to support specific conditions.
For almost two decades, Metagenics has been one of the few
companies to develop and manufacture medical foods. The genesis of
these medical foods was based on burgeoning research now known as
nutrigenomics. These medical foods are backed by numerous clinical
studies and extensive peer-reviewed scientific support.
For added assurance and developmental research purposes, these
medical foods undergo continual testing in a clinical setting at the
Functional Medicine Research CenterSM (FMRC), the clinical research
arm of Metagenics.
The SKRM Effect: Creating the Next Generation of Medical Foods
Medical foods containing

SKRMs offer a multidimensional approach to
wellness.
Medical Foods with the inclusion of SKRMs offer a multi-mechanistic

approach to offer even more opportunities for patient success. They
represent the latest in medical food development, incorporating
nutrigenomic research and technology for a new degree of health
support. (For more information on SKRM research, please see Phase
2Modulating Kinase Signaling with SKRMs on page 18.)
The following medical foods are intended to complement dietary
recommendations to offer nutritional support for the management of
specific conditions. Healthcare practitioners, however, are best qualified
to decide on a case-by-case basis when other patients may also

benefit from the nutrients provided by formulas designed to address:
Metabolic syndrome
Cardiovascular disease
Inflammatory bowel disease (autoimmune support)
Type 2 diabetes
Chronic fatigue syndrome (liver detoxification support)
Premenstrual syndrome (hormone balance)
Leaky gut syndrome
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Metabolic Syndrome & Cardiovascular Disease

UltraMeal PLUS 360 Medical Food is formulated with the addition
of SKRMsin the form of reduced iso-alpha acids (RIAA, from
hops) and acacia extractto complement the formulas nutritional
support for the management of conditions associated with
cardiovascular disease and metabolic syndrome. This advanced
formula:
o
o
o
Provides a proprietary soy protein and plant sterol blend that

contains 2 grams of plant sterols (including beta-sitosterol) and
15 grams of soy protein per serving. Foods containing at least
0.65 g per serving of plant sterol esters, eaten twice a day with
meals for a daily total intake of at least 1.3 g as part of a diet
low in saturated fat and cholesterol, may reduce the risk of heart
disease.
Provides 5-methyl-tetrahydrofolate (5-MTHF)a body-ready,
nature-identical folateto promote healthy homocysteine levels
for cardiovascular health.
Offers a low-glycemic-index meal option to encourage healthy
insulin and blood sugar levels.
Supplies high quality foundation nutrition for patients with CVD.
In individuals with metabolic syndrome and high cholesterol, this

advanced medical food formula and accompanying program has
been clinically shown to improve the following important
cardiovascular risk factors:56
o
o
o
o
Lower the apolipoprotein Bto-apolipoprotein A1 (apoB/ApoA1)

ratio
Reduce total cholesterol, LDL cholesterol, and triglyceride levels
Increase HDL (good) cholesterol levels
Lower homocysteine levels
(See Table 1 on the following page for clinical results.)

Also available without SKRMs as UltraMeal and UltraMeal PLUS.
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Greater Improvement in CV Health Markers
Medical Food with SKRMs Shows Greater Results

vs. Dietary Signal Modification & Exercise Alone
Measurement
Arm 1: UltraMeal PLUS

360 with Low-GL Diet
Plan & Exercise
Arm 2: Low-GL Diet

Plan & Exercise Only
Total Cholesterol
-36.74*
-16.33*
Triglycerides
-89.39*
-30.89
HDL-C
2.65*
1.06
LDL-C
-28.38*
-15.06*
TChol/HDL-C
-1.35*
-.61*
TG/HDL
-3.01*
-1.01
ApoA1
-4.00
-8.44
ApoB
-25.70*
-15.06*
-.12*
-.05*
ApoB/ApoA1
* These results are statistically significant.

Table 1. The summary of lab value changes from a 12-week, 2-arm study above
illustrates the additive affect of a medical food and SKRMs on markers of
cardiovascular health. Metabolic outcomes were improved more significantly with a
56
medical food and SKRMs than with a low-GL diet and exercise alone.
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Inflammatory Bowel Disease (Autoimmune Support)

UltraInflamX PLUS 360 Medical Food is formulated with SKRMs
in the form of reduced iso-alpha acids (RIAA, from hops)to
complement the formulas nutritional support for the management of
inflammatory bowel disease (IBD), such as Crohns disease or
ulcerative colitis. This unique medical food:
Provides a low-allergenic-potential protein base in the form of

rice protein concentrate.
Supplies L-glutamine, a valuable energy source for intestinal
mucosal cells.
Provides ginger and rosemary, which may help support healthy
eicosanoid and cytokine metabolism.
Supplies generous levels of turmeric extract, which has been
shown to inhibit the activity of a wide variety of enzymes,
cytokines, eicosanoids, and reactive species implicated in pain
and inflammation.
Offers an excellent source of antioxidants with a very high
oxygen radical absorbance capacity (ORAC) value.
Advantages of the addition of SKRMs include:
Shown to beneficially influence the function of kinases involved

in inflammatory processes.
Suggested by research to positively influence inflammationsignaling molecules such as NF-B, COX-2, and PGE2.
Also available without SKRMs as UltraInflamX Medical Food.
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Type 2 Diabetes
UltraGlycemX Medical Food is formulated to meet the specialized
nutritional needs of patients with type 2 diabetes, insulin resistance,
and hypoglycemia by providing a low-glycemic-index blend that
includes high amylose starch (a resistant starch), targeted plant
nutrients from green coffee beans and cinnamon, and heart-healthy
soy protein and barley ingredients. UltraGlycemX:
o
o
o
o
o
Supports healthy heart function by providing 15 grams of soy

protein per serving. Diets low in saturated fat and cholesterol
that include 25 grams of soy protein a day may reduce the risk
of heart disease.
Provides 11 grams of specialized dietary fibers per serving to
help maintain healthy blood glucose levels in type 2 diabetics.
Includes green coffee bean extract (containing chlorogenic acid)
and barley beta-glucans for support of healthy glucose, lipid,
and insulin metabolism.
Offers a low-glycemic-index meal option to encourage healthy
insulin and blood sugar levels.
Supplies resistant starch that resists digestion and is
metabolized much like dietary fiber, with positive implications for
glucose and insulin metabolism.
Provides beneficial levels of cinnamon, chromium, biotin, and
magnesium to promote healthy glucose uptake and insulin
function.
36% Average Decrease in 2-hr Postprandial Insulin
Insulin (IU/mL)
150
111
100
71.5
50
Before Program After 8 Weeks on

UltraGlycemX
Program
Figure 2. A preliminary, randomized, 2-arm clinical study of 37 insulin-resistant

patients showed a greater average decrease when supplementing with an
57
UltraGlycemX formula.
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Chronic Fatigue Syndrome (Liver Detoxification Support)

UltraClear Medical Food is formulated to provide readily
assimilable macronutrients (protein, carbohydrates, and fats) to help
address altered energetic function in patients with chronic fatigue
syndrome.
o
o
o
Further personalize an
approach by identifying those
patients with needs for
additional detoxification
support.
Designed for those patients who may benefit from specific

nutritional support for hepatic detoxification function.
Provides nutrients and antioxidants that support hepatic
detoxification processes.
Provides low-allergenic-potential protein in the form of rice
protein concentrate, which may be beneficial during times of
increased hepatic detoxification burden.
The rice protein concentrate has been prepared via a unique
process that reduces its already low allergenic potential.
UltraClear PLUS Medical Food

o
Provides the same low-allergenic-potential rice protein base and

macronutrients, but designed for those patients who may benefit
from specific nutritional support for Phase II hepatic
detoxification function with the addition of:
Glycine to support Phase II glycine conjugation
Magnesium sulfate and L-cysteine to support Phase II
sulfation
Also provides green tea catechins and mixed carotenoids to
protect against reactive species generated during hepatic
detoxification.
UltraClear Plus pH Medical Food

o
Provides the same low-allergenic-potential rice protein base and

macronutrients, but designed for those patients who may benefit
from specific nutritional support to promote alkalinization of
urine and Phase II hepatic detoxification function with the
addition of:
Potassium citrate to promote alkalinization of urine
Sesame (a source of sesamin) to help support Phase II
hepatic metabolism of lipids (including cholesterol) and
other substances
Glycine and taurine to support Phase II amino acid
conjugation
Magnesium sulfate to support Phase II sulfation
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Premenstrual Syndrome (PMS)

Estrium Medical Food is formulated to provide specialized
nutritional support for premenstrual syndrome by supplying flaxseed,
isoflavones, and targeted nutrients. This targeted formula:
o
o
o
o
Supports healthy estrogen metabolism and balance with

flaxseed and non-soy isoflavones (from kudzu).
Supplies generous levels of vitamin E, vitamin B6, calcium,
magnesium, and chromium to address particular concerns
associated with PMS.
Offers a low-glycemic-index meal option to help support healthy
energy and insulin metabolism.
Provides turmeric extract, which has been shown in research to
inhibit the activities of a wide variety of enzymes, cytokines,
eicosanoids, and reactive species implicated in pain and
inflammation.
59% Reduction in PMS Symptoms
SPAF Total Score
60
40
20
Before Program
After Estrium
Program
Figure 3. In a clinical study of 40 PMS patients following the Estrium program for two
menstrual cycles there was a significant improvement in symptoms as measured by
the Shortened Premenstrual Assessment Form (scores from 10 to 30 indicate
58
symptomatology in the last half of the cycle).
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Leaky Gut Syndrome

UltraClear SUSTAIN Medical Food is formulated to provide
specialized nutritional support, including L-glutamine and readily
assimilable, low-allergenic-potential macronutrients for patients with
leaky gut syndrome.
o
o
Provides L-glutamine, a valuable energy source for intestinal

mucosal cells.
Addresses dysbiosis associated with leaky gut syndrome by
providing inulin and fructooligosaccharides (FOS) to promote
the growth of healthy intestinal bacteria.
Provides prebiotic factors, which encourage the production of
short-chain fatty acids (SCFAs) that promote intestinal mucosal
health and a healthy intestinal environment.
The rice protein concentrate has been prepared via a unique
process that reduces its already low allergenic potential.
Medical Food Nutritional Profiles & Research

Nutritional information for the medical foods mentioned in this document
is available at www.metagenics.com. In addition to extensive
developmental research and clinical studies, these medical foods
undergo continual testing in a clinical setting at the Functional Medicine
Research Center.
Individual case management studies with medical foods are available for
viewing at www.metagenics.com in the resources section:
www.metagenics.com/science/case_studies.asp?sect=2
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Phase 2
Modulating Kinase Signaling with SKRMs
SKRMs provide another
nutritional modality to
modulate cellular signals.
Nutrigenomic research, such as that conducted by the MetaProteomics

Nutrigenomics Research Center, attempts to discover highly active
substances from food and other natural sources that can serve as potent
dietary signaling molecules to positively affect genetic expression.
Optimally, this yields the development of unique food ingredient extracts
from which individual bioactive molecules can be isolated and tested for
their ability to modify cellular function related to various disease
processes.
Many prevalent health issues have been found to have specific
underlying kinase signaling components. This is due to the ability of
kinases to translate dietary signals in a positive or negative manner to
influence health. For example, research has shown that impaired kinase
signaling can lead to impaired insulin response and hyperlipidemia
associated with type 2 diabetes.59
Kinases are enzymes that chemically modify other proteins and regulate
the majority of cellular pathwaysparticularly those involved in the
transmission of intracellular signals. These enzymes also help regulate
eicosanoids, cytokines, reactive oxygen species, and other mediators
that may negatively impact the body both locally and systemically.
Modifying Genetic Expression with SKRMS
Diet, Exercise
& Lifestyle
Direct
Nutrients &
Xenobiotics
Metabolism
Indirect
SKRMs
Signal Transduction
Gene Expression
Cell Phenotype
Figure 4. SKRMs positively affect kinase signaling for optimal genetic and phenotypic
expression for wellness. SKRMs are an ideal complement to positive dietary changes
for restoration of healthy kinase activities.
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As mentioned previously, SKRMs are nutritional substances that can

work to modulate kinase signaling back into balance. This balance helps
restore healthy signaling to genes for positive genetic expression and
reversal of illness.
Proprietary research has yielded the discovery of food-derived SKRMs
that specifically inhibit kinase-mediated processes associated with
insulin resistance and inflammation. SKRMs may offer therapeutic
advantages over dietary modifications alone.
Insulin SKRMs
Groundbreaking preliminary research suggests the identification of
SKRMs that have the ability to improve insulin sensitivity by modulating
specific kinase enzymes that serve as hubs for insulin-signaling
processes.
More than 200 natural substances and extracts were tested for their
influence on insulin responses and adipocyte (fat-storing) cells at the
MetaProteomics Nutrigenomics Research Center. A combination of
reduced iso-alpha acids (RIAA) derived from hops (Humulus lupulus)
and acacia extract (Acacia nilotica) was shown via in vitro testing to
inhibit inflammatory markers that influence insulin function.60
Research has implicated dysregulated inflammatory processes in the
development of insulin resistance, and several inflammation-induced
cytokines have been shown to be expressed during insulin resistance
and metabolic syndrome.61-63 Cytokinessuch as interleukin-1 beta (IL1), tumor necrosis factor alpha (TNF-), and interferon gamma (IFN)have been shown to play a role in cytokine-induced -cell
dysfunction in diabetes.64,65
In human clinical testing at the Functional Medicine Research Center,
supplementation of metabolic syndrome subjects with a combination of
RIAA and acacia led to greater reduction of 2 h pp insulin levels, as
compared to placebo. Furthermore, greater decreases of fasting insulin,
fasting and 2 h pp glucose, fasting triglyceride, and HOMA scores were
observed in subjects taking RIAA/acacia supplement versus subjects
taking placebo. These collective results indicate RIAA/acacia
supplementation might be useful in maintaining insulin homeostasis in
subjects with metabolic syndrome.60
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Insulin SKRM Research
Increased Insulin Sensitivity with SKRMs

1
0.78
HOMA
0.8
0.6
0.4
0.2
0
0.16
Placebo
RIAA/Acacia Blend
Figure 5. The Homeostasis Model Assessment (HOMA) estimates steady state beta
cell function and insulin sensitivity, and is a published measure of insulin resistance. A
significant decrease was observed for the RIAA/acacia group as compared to the
60
placebo group in an 8-week clinical trial.
Improvement in Triglycerides with SKRMs
Triglycerides
-5
-1.48
-15
-25
-35
-45
-55
-48.97
Placebo
RIAA/Acacia Blend
Figure 6. In the same blinded, placebo-controlled study of 91 patients, the

RIAA/acacia blend showed a greater improvement in triglyceride levels than
60
placebo.
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Inflammation & Autoimmune SKRMs

Chronic inflammation, nutritional deficiencies, and oxidative stress are
believed to be involved in the pathogenesis of autoimmune disorders.
Mounting scientific evidence indicates that inflammation is also intrinsic
to autoimmune conditions. In fact, during inflammation, an array of
cytokines, eicosanoids, reactive oxygen species, and other mediators
that can overwhelm and disrupt Th1/Th2 balance are released, which
can potentially damage body tissues.66-69
People with chronic inflammation often have excess proinflammatory
mediators. The present direction of research is the development of
therapeutic agents that modulate the immune system by targeting
specific cell types involved in the inflammatory response.
SKRMs in the form of reduced iso-alpha acids derived from hops
(Humulus lupulus) have been extensively tested for safety and
effectiveness and professionally recommended as a safer option for joint
relief for over 5 yearsoffering a high level of predicted cardiovascular,
gastric, renal, and liver safety.70-78
RIAA still offers an excellent SKRM approach to inflammatory and
autoimmune conditions. Recent nutrigenomics research, however, has
identified even more powerful SKRMs from hops. Like RIAA, these new
constituents, tetrahydro-iso-alpha acids (THIAA), offer a safer approach
to modulating the arachidonic acid cascade. THIAA have also been
extensively researched and testeddemonstrating the ability to
modulate specific kinases associated with activities underlying joint
tissue health and immune function, such as PGE2 and TNF-.
THIAA have been shown in scientific testing to provide even greater
targeted support with lower clinically effective dosing. In fact, in studies
at MetaProteomics, THIAA have been shown to modulate induced PGE2
production with two times greater effectiveness than RIAA, and to
modulate induced TNF- production with three times greater
effectiveness.
Additional Support for Autoimmune Conditions
Common nutritional deficiencies associated with abnormal autoimmune
response include inadequate vitamin D intake.79-81 The role of selenium
and zinc has also been the source of heightened interest because of the
role these nutrients play in metabolic processes involving joint tissues
and immune system function.82-86
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Inflammation & Autoimmune SKRM Research
PGE2 Inhibition with SKRMs

2500
Control
THIAA
RIAA
PGE2(pg/ml)
2000
1500
1000
500
0
2.5
5.0
Concentration (g/ml)
Figure 7. Cells were pre-incubated with THIAA or RIAA, followed by lipopolysaccharide (LPS)-induced stimulation of PGE2 production. The data show that
compared to the control and RIAA, THIAA inhibits PGE2 expression more effectively.
TNF- Inhibition with SKRMs
TNF-(pg/ml)
2500
Control
THIAA
2000
1500
1000
500
0
10.0
20.0
Concentration (g/ml)
Figure 8. Cells were pre-incubated with THIAA and then stimulated with LPS to induce
TNF- production. Results show that THIAA can lead to greater inhibition of TNF-
expression in a dose-dependent manner.
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Future SKRMs
Nutrigenomic research continues to focus on naturally derived
substances that act as SKRMs to beneficially influence health in other
areas, such as liver detoxification, bone resorption, and hormone
balance.
For more information on nutrigenomic research and the development of
innovative nutritional protocols, please visit:
www.metaproteomicslabs.com
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Phase 3
Recommending Key Nutritional Support
Targeted nutrients offer
another means of positive
dietary signaling.
The following nutrients may provide complementary support for certain

patients and offer a flexible and highly customizable nutrigenomic
approach to wellness.
Cardiovascular Support
Coenzyme Q10 (CoQ10 or ubiquinone) and essential fatty acids (omega3s) are both important for cardiovascular health. In addition to
complementing nutrigenomic therapies, they may also play key roles in
conventional therapies for CVD.
CoQ10CoQ10 plays an important role in the bodys energyproducing process. The bodys endogenous production of CoQ10
decreases with age and dietary availability and absorption of CoQ10
is rather limited, prompting the need for supplementation to correct a
deficiency.87-89 CoQ10 deficiency has been observed in patients with
a variety of cardiovascular conditionsand patients with more
advanced stages of CVD have been shown to possess lower levels
of CoQ10 than patients with milder forms of CVD.90-93
CoQ10 levels can be further impacted by drugs in conventional
therapies, such as statins that block its synthesis.94-96 Fortunately,
statin-induced CoQ10 deficiency can be prevented with supplemental
CoQ10 with no adverse impact on the cholesterol-lowering or antiinflammatory properties of statin drugs.96,97 Scientific studies have
also shown that CoQ10 may be recommended as preventive therapy
or as a safe and effective adjunct to conventional therapy for
CVD.87-92,97
Essential Fatty Acids (EFAs)Omega-3 fatty acids, such as those

found naturally in cold-water fish (including EPA and DHA), have
been examined in previous clinical and epidemiological research
that has shown they may: 98-105
o
o
o
o
o
Decrease the risk of fatal arrhythmias

Decrease triglyceride levels
Decrease growth rate of atherosclerotic plaque
Lower blood pressure (slightly)
Decrease the chance of stroke
Note: Clinical tests have also shown that people with diets rich in
EPA are less prone to inflammation in joints, intestines, lungs, and
skin.
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Blood Sugar Metabolism Support

Ever-growing research continues to show the newly discovered benefits
of green tea and cinnamon in complementing dietary approaches to
blood sugar management. Insulin resistance conditions can also induce
oxidative stress that can lead to vascular complications, such as
neuropathy.
CinnamonCinnamon has been shown to display insulin-enhancing

activity in vitro and shown in human clinical trials to positively
influence glucose levels.106-108 Extracts of cinnamon have also been
shown to activate insulin receptor kinase and inhibit
dephosphorylation of the insulin receptorleading to increased
insulin sensitivity.
Green Tea (EGCG)Green tea contains epigallocatechin gallate

(EGCG), a bioflavonoid shown to protect pancreatic islet cells and
enhance insulin sensitivity.109 Catechins from green tea also provide
strong antioxidant protection.110
Liver Detoxification Support

There are two primary phases in the detoxification process. In Phase I,
fat-soluble toxins are transformed into intermediate compounds that are
more reactive, but will bind more easily to non-toxic, water-soluble
molecules in Phase II. In Phase II, formation between the reactive
intermediates and water-soluble molecules make the entire compound
ready for excretion out of the body. Targeted nutrients can influence
detoxification activities in either phaseor sometimes both.
SilymarinThis active constituent of milk thistle (Silybum marianum)

is well-recognized for its beneficial effects on protecting the liver
from toxins and stimulating liver regeneration, as well as its
antioxidant properties. Preliminary research also indicates that it
may influence Phase I and Phase II enzymes, and therefore may be
called a bifunctional modulator.111,112
CatechinsThese strong antioxidants have the capacity to

scavenge most oxygen free radicals.110 Also derived from green tea
(Camilla sinensis, see above), catechins enhance the induction of
Phase II enzymesglutathione S-transferase and quinine
reductaseand inhibit the overinduction of specific cytochrome
P450 Phase I biotransformation enzymes.113,114
WatercressGlucosinolates found in watercress (Nasturtium

officinale) are precursors of phenythyl isothicynate (PEITC), which
effectively inhibits the overinduction of specific sytochrome P450
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enzymes and enhances Phase II glutathione S-transferase and

quinine reductase.115-117
Ellagic AcidNaturally found in pomegranate fruit (Punica

granatum), ellagic acid beneficially modulates Phase I
biotransformation and enhances Phase II glutathione S-transferase
and quinine reductase enzyme induction.118-120 Also scavenges
superoxide radicals and hydroxyl radicals, reducing hepatic
oxidative stress.120,121
Note: Catechins, watercress, and ellagic acid also influence genetic
expression of enzymes that control Phase II conjugation
reactions.113-120
Artichoke LeafExtracts from artichoke (Cynara scolymus) have a

long history of traditional use in promoting liver function. Research
suggests that several constituents of artichoke, including
chlorogenic acid and cynarin, have marked antioxidant and
hepatoprotective properties.122-124
Intestinal Support
Probiotic strains have specific characteristics that determine whether
they have the ability to benefit the intestinal environment. But not all
genera, species, and strains are suitable for all purposes. Following are
beneficial bacteria shown to adhere to the intestinal lining and support a
healthy balance of microflora.125-130
Lactobacillus acidophilus NCFMThis strain of human origin has

been proven safe and effective by more than 60 scientific studies
and almost 30 years of commercial use. It produces lactic acid,
hydrogen peroxide, and other natural substances while modulating
the activity of enzymessuch as -glucuronidase, nitroreductase,
and azoreductaseto positively influence the balance of intestinal
bacteria and support intestinal tissue health.125 Its also one of a
limited number of Lactobacillus species shown to adhere in the
intestines.131
BifidobacteriumThis major group of carbohydrate-metabolizing

bacteria in the intestines (including B. lactis) is 1000 times more
abundant than lactobacilli in healthy adults (and some researchers
believe more important as well).132 Bifidobacteria have proven
effectiveness as immunosupportive agents that enhance host
resistance, as well as produce strong acids (e.g., acetic, lactic) that
positively affect intestinal pH; thereby, playing a critical role in
modulating ammonia, phenol, steroidal, and other toxin levels to
maintain health and support intestinal microbial balance.125-127
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Note: Scientific identification of strains is not only an indicator of

predicted safety, but assures the means for providing optimal health
benefits.
Joint Inflammation Support
Many inflammatory and autoimmune conditions are characterized by
pain and motility concerns related to the joints. Glucosamine and
chondroitin sulfates, as well as MSM, offer widely accepted approaches
for maintaining healthy connective tissue and relieving pain associated
with concerns that affect a growing number of patients.
Glucosamine & ChondroitinThese nutrients are naturally found in

healthy tissue and work together in forming healthy joint matrix
cartilage and enhancing joint lubrication.133,134 They may also
promote the incorporation of sulfur into cartilage. Sulfur is necessary
for the synthesis of collagen and improves the moisture content of
cartilage, supporting its shock-absorbing ability.135 Supplementation
with glucosamine and chondroitin can help restore normal joint
motility and relieve pain.133,135-138 Continued use is required to
maintain benefits.
Methyl-Sulfonyl-Methane (MSM)This natural compound

complements glucosamine and chondroitin sulfates, and also
provides a highly biologically valuable source of sulfur. MSM has
been widely used to support joint health and relieve pain as an
effective natural analgesic and anti-inflammatory agent.139 A
randomized, placebo-controlled trial showed that MSM improved
symptoms of pain and physical function in patients with
osteoarthritis.140 Another randomized, double-blind, parallel,
placebo-controlled trial also showed that MSM significantly improved
the signs and symptoms of osteoarthritis. Furthermore, the
combination of glucosamine and MSM showed better efficacy in
reducing pain and swelling and in improving the functional ability of
joints than the individual agents.139
Hormone Balance Support

Phytoestrogens are plant compounds that have structural and functional
similarities to estrogen.55,141 Selective estrogen receptor modulators
(SERMsnot to be confused with SKRMs) are non-steroidal
compounds capable of binding to the estrogen receptors and influencing
their activities. Specifically, SERMs are noted as being both agonists (in
cases of low estrogen levels, such as with menopause) and antagonists
(in cases of high estrogen). Because they support a moderate level of
estrogen activity, upon binding to the estrogen receptors they inhibit
endogenous estrogen when too much is present, but can still support
estrogens important functions.142-144
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Kudzu & Red CloverProvide a varied profile of non-soy

isoflavones and isoflavone glycosidesincluding daidzein,
genistein, puerarin, and fromononetinthat bind to the estrogen
receptor and may act as weaker estrogens, resulting in an inhibition
of the estrogenic effect.50,144-146
TurmericCurcuminoids, the active component in turmeric

(Curcuma longa), induce glutathione production and glutathione-S
transferase activityhelping to protect tissues from reactive
estrogen metabolites.147 In combination with isoflavones, curcumin
shows in vitro evidence of reducing xenoestrogens-induced growth
in estrogen receptor-positive and negative cancer cells, thereby
promoting breast health.55,148
Resveratrol (from Polygonum cuspidatum)Classified as a SERM

based on its ability to bond to estrogen receptors and act as both an
estrogen agonist and antagonist. Resveratrol provides many other
benefits, including cardioprotective properties.149 Resveratrol has
been shown to promote healthy cytokine production by influencing
the cyclooxygenase and 5-lipoxygenase pathways. It is also
associated with reduced activity of nuclear factor kappaB (NF-B)
a transcription factor that may promote the expression of
undesirable genes. Resveratrol has potent antioxidant activity
(especially in lipids that are highly concentrated in brain tissue),
promotes healthy blood flow, and induces hepatic phase II
detoxification activity.
Stabilized Indole-3-Carbinole (I3C)This naturally occurring

compound found in cruciferous vegetables protects estrogensensitive tissues by promoting the formation of 2-hydroxyestrone,
diindolymethane (DIM), and other beneficial estrogen metabolites. It
supports the detoxification of estrogens, other steroid hormones,
and xenoestrogens by enhancing the activity of enzymes involved in
their metabolism and excretion. Research indicates great promise
as a natural hormone-balancing agent.150-157
Note: Natural-source I3C may be an important consideration when
recommending supplementation to patients.
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Putting It All Together

The Nutrigenomics Matrix (provided on page 3) gives you a top-line
overview of implementing nutrigenomics in your practice for a broad
range of patients. Determine the appropriate level of support for your
patients, as well as the components that complement the structure of
your practice.
For further assistance, the FirstLine Therapy program also provides
diagnostic tools and assistance in determining appropriate nutritional
support based on symptoms and in-office measurements. It also
provides helpful materials for educating and motivating patients, as well
as monitoring their progress.
As always, the Metagenics Technical Support team of professionals is
available to answer questions regarding products and clinically tested
nutritional protocols.
About Metagenics, Inc.

Metagenics is a life sciences company and leading developer and
manufacturer of professional grade, science-based medical foods and
nutraceuticals sold to healthcare practitioners worldwide. For more than
25 years, Metagenics has been a leader in quality, scientific discovery,
and innovation, with multiple proprietary formula patents and more than
400 research-based products to optimize health. The company is
headquartered in San Clemente, CA, with manufacturing and research
facilities located in Gig Harbor, WA, including the MetaProteomics
Nutrigenomics Research Center and the Functional Medicine Research
CenterSM for human clinical research. For more information, please visit
www.metagenics.com.
FirstLine Therapy is a registered trademark of Metagenics, Inc.
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APPENDIX A
Applying Nutrigenomics for Children & Teens
A nutrigenomic approach to wellness doesnt have to wait until
adulthood. With the rise of metabolic syndrome and other conditions in
children and teenagers, your younger patients may already be in need of
some beneficial signal modification. And you can help them now.
The following medical food programs offer targeted nutritional support
and complementary dietary programs to address the nutritional
management needs of children and teens. Customize these programs
with other nutrients to address specific needs.
Metabolic Syndrome
Ultracare First Start Medical Food is formulated to provide specialized
nutritional support for children and adolescents ages 6-18 with metabolic
syndrome, obesity, dyslipidemia, and insulin resistance by supplying a
low-glycemic-index blend of macro- and micronutrients, including
cinnamon, chromium, and heart-healthy soy protein and isoflavones.
This unique formula:
Addresses the protein needs of growing children and teenagers by
providing 6-12 grams of soy protein per serving.
Supplies cinnamon to help maintain healthy glucose and insulin
function.
Provides a good source of dairy-free calcium and magnesium to
support peak bone mass development.
Atopic Disorders
Ultracare for Kids Medical Food is formulated to provide specialized
nutritional support for children with food allergy-related symptoms and
atopic disorders by supplying readily assimilable, low-allergenic-potential
rice protein.
Low-allergenic-potential rice protein to complement restricted diets.
The rice protein has been prepared via a unique process that
reduces the already low-allergenic potential of rice protein.
Provides fructooligosaccharides (FOS) to promote the growth of
bifidobacteria, which may help encourage healthy, balanced
immune function in young children.
Supplies dairy-free calcium to support bone health and new bone
formation.
Provides high quality foundation nutrition for children up to 12 years
of age.
Comprehensive dietary recommendations and other lifestyle guidelines
are available for parents to help implement and monitor.
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APPENDIX B
The Need for Therapeutic Lifestyle Changes
A white paper discussion on the scientific basis for and effectiveness of
therapeutic lifestyle changes (TLC) programs has been prepared for
your reference. This paper is entitled The Chronic Disease Epidemic: A
Prescription of Primary Prevention and Profitability and is available
upon request at: www.metagenics.com/flt/whitepaper_request.asp
Also included are practical tips for evaluating a TLC program to fit the
needs of your practice.
Further information for patients and practitioners on the FirstLine
Therapy TLC program is also available at www.metagenics.com.
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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.
29.
30.
31.
32.
33.
34.
35.
36.
37.
38.
39.
40.
41.
Alffman L, Muller M. Nutrigenomics: from molecular nutrition to prevention of disease. J M Diet Assoc.
2006;106(4):569-576.
Subbiah MT. Nutrigenetics and nutraceuticals: the next wave riding on personalized medicine. Transl Res.
2007;149(2):55-61.
Mariman EC. Nutrigenomics and nutrigenetics: the omics revolution in nutritional science. Biotechnol Appl
Biochem. 2006;44(Pt 3):119-128.
Kaput J. Nutrigenomics2006 update. Clin Chem Lab Med. 2007;45(3):279-287.
Ferguson LR. Nutrigenomics: integrating genomic approaches into nutrition research, Mol Diag Ther.
2006;10(2):101-108.
Bland JS. What role has nutrition been playing in our health? The xenohormesis connection. 2007 [In press.]
Roberts CK, Barnard RJ. Effects of exercise and diet on chronic disease. J Appl Physiol. 2005;98:3-30.
Aldan SG, Greenlaw RL, Diehl HA, et al. The behavioral and clinical effects of therapeutic lifestyle changes
on middle-aged adults. Preventing Chronic Disease. 2006;3(1):1-16.
Ashley JM, St. Jeor ST, Schrage JP, et al. Weight control in the physicians office. Arch Intern Med
2001;161:1599-1604.
Woollard J, Burke V, Beilin LJ, et al. Effects of a general practice-based intervention on diet, body mass
index and blood lipids in patients at cardiovascular risk. J Cardiovasc Risk 2003;10(1):31-40.
Mattila R, Malmivaara A, Kastarinen M, et al. Effectiveness of multidisciplinary lifestyle intervention for
hypertension: a randomized controlled trial. J Hum Hypertens 2003;17(3):199-205.
Hu FB, Manson JE, Stampfer MJ, et al. Diet, lifestyle, and the risk of type 2 diabetes mellitus in women. N
Engl J Med 2001;345(11):790-97.
Case CC, Jones PH, Nelson K, et al. Impact of weight loss on the metabolic syndrome. Diabetes Obes
Metab 2002;4(6):407-14.
OReilly S, Doherty M. Lifestyle changes in the management of osteoarthritis. Best Pract Res Clin
Rheumatol 2001;15(4):559-68.
The North American Menopause Society. Management of osteoporosis in postmenopausal women: 2006
position statement of The North American Menopause Society. Menopause 2006;13(3):340-67.
Preuss HG, Bagchi D, Bagchi M. Protective effects of a novel niacin-bound chromium complex and a grape
seed proanthocyanidin extract on advancing age and various aspects of syndrome X. Ann N Y Acad Sci
2002;957:250-59.
Gordon NF, Salmon RD, Franklin BA, et al. Effectiveness of therapeutic lifestyle changes in patients with
hypertension, hyperlipidemia, and/or hyperglycemia. Am J Cardiol. 2004;94:1558-1561.
Aldana SG, Greenlaw RL, Diehl HA, et al. Effects of an intensive diet and physical activity modification
program on the health risks of adults. J Am Diet Assoc. 2005;105:371-381.
Wannamethee SG, Sharper AG, Whincup PH. Modifiable lifestyle factors and the metabolic syndrome in
older men: effects of lifestyle changes. J Am Geriatr Soc. 2006;54:1909-1914.
Tuomilehto J, Lindstrom J, Eriksson JG, et al. Prevention of type 2 diabetes mellitus by changes in lifestyle
among subjects with impaired glucose tolerance. N Engl J Med. 2201;344:1343-1350.
Esposito K, Marfella R, Ciotola M, et al. Effects of a Mediterranean-style diet on endothelial dysfunction and
markers of vascular inflammation in the metabolic syndrome: a randomized trial. JAMA. 2004;292(12):14401446.
Holman H. Chronic diseasethe need for a new clinical education. JAMA. 2004;292(9):1057-1059.
Casalino LP. Disease management and the organization of physician practice. JAMA. 2005; 293(4):485488.
Roche HM, Phillips C, Gibney MJ. The metabolic syndrome: the crossroads of diet and genetics. Proc Nutr
Soc. 2005;64:371-377.
Kendal CW, Augustin LS, Emam A, Josse AR, Saxena N, Jenkins DJ. The glycemic index: methodology and
use. Nestle Nutr Workshop Ser Clin Perform Programme. 2006;11:43-56.
Hyman, Mark. UltraMetabolism: The Simple Plan for Automatic Weight Loss. New York: Scribner, 2006.
Prada PO. Gottardello, Zecchin H, Lia Gaspaparetti A, et al. Western diet modulates insulin signaling, c-Jun
N-terminal kinase activity, and insulin receptor substrate-1 [ser307] phosphorylation in a tissue-specific
fashion. Endocrinology. 2005;146(3):1576-1587.
Pins JJ, Keenan JM. Dietary and nutraceutical options for managing the hypertriglyceridemic patient. Prog
Cardiovasc Nurs. 2006;21(2):89-93.
Deen D. Metabolic syndrome: time for action. Am Fam Physician. 2004;69(12):2875-882.
Deedwania PC, Volkova N. Current treatment options for the metabolic syndrome. Curr Treat Options
Cardiovasc Med. 2005;7(1):61-74.
Hu Y, Block G, Norkus EP, Morrow JD, Dietrich M, Hudes M. Relations of glycemic index and glycemic load
with plasma oxidative stress markers. Am J Clin Nutr. 2006;84(1):70-76.
Stamp LK, James MJ, Cleland LG. Diet and rheumatoid arthritis: a review of the literature. Semin Arthritis
Rheum 2005;35(2):77-94.
van de Laar, MA, van der Korst JK. Food intolerance in rheumatoid arthritis. I. A double blind, controlled trial
of the clinical effects of elimination of milk allergens and azo dyes. Ann Rheum Dis 1992;51(3):298-302.
Pena AS, Crusius JB. Food allergy, coeliac disease and chronic inflammatory bowel disease in man. Vet Q
1998;20 Suppl 3:S49-52.
Stark ME, Tremaine WJ. Maintenance of symptomatic remission in patients with Crohns disease. Mayo Clin
Proc 1993;68(12):1183-90.
Khan S, Orenstein SR. Eosinophilic gastroenteritis: epidemiology, diagnosis and management. Paediatr
Drugs 2002;4(9):563-70.
Ebo DG, Stevens WJ. IgE-mediated food allergyextensive review of the literature. Acta Clin Belg
2001;56(4):234-47.
Sullivan PB. Food allergy and food intolerance in childhood. Indian J Pediatr 199;66(1 Suppl):S37-45.
Caffarelli C, Cavagni G, Menzies IS, Bertolini P, Atherton DJ. Elimination diet and intestinal permeability in
atopic eczema: a preliminary study. Clin Exp Allergy 1993;23(1):28-31.
Atherton DJ. Role of diet in treating atopic eczema: elimination diets can be beneficial. BMJ
1988;277(6661):1458,1460.
Veien NK, Hattel T, Justesen O, Norholm A. Dietary restrictions in the treatment of adult patients with
eczema. Contact Dermatitis 1987;17(4):223-28.
___________________________________________________
Version 1.4
Page 32
42.
43.
44.
45.
46.
47.
48.
49.
50.
51.
52.
53.
54.
55.
56.
57.
58.
59.
60.
61.
62.
63.
64.
65.
66.
67.
68.
69.
70.
71.
72.
73.
74.
75.
76.
Fogg MI, Spegel JM. Management of food allergies. Expert Opin Pharmacother 2003;4(7):1025-1037.
Garcia-Careaga M Jr, Kerner JA Jr. Gastrointestinal manifestations of food allergies in pediatric patients.
Nutr Clin Pract 2005;20(5):526-35.
Veien NK, Hattel T, Justesen O, Norholm A. Oral challenge with food additives. Contact Dermatitis
1987;17(2)100-103.
Burr ML, Fehily AM, Stott NC, Merrett TG. Food-allergic asthma in general practice. Hum Nutr Appl Nutr
1985;39(5)349-355.
Atkinson W, Sheldon Tam Shaath N, Whorwell PJ. Food elimination based on IgG antibodies in irritable
bowel syndrome: a randomised controlled trial. Gut 2004;53(10):1459-1464.
Hafstrom I, Ringertz B, Spanberg A, et al. A vegan diet free of gluten improves the signs and symptoms of
rheumatoid arthritis: the effects on arthritis correlate with a reduction in antibodies to food allergens.
Rheumatology (Oxford) 2001;40(10):1175-1179.
Galli E, Cicconi R, Rossi P, Casati A, Brunetti E, Mancino G. Atopic dermatitis: molecular mechanisms,
clinical aspects and new therapeutic approaches. Curr Mol Med 2003;3(2):127-138.
Darlington LG, Ramsey NW. Review of dietary therapy for rheumatoid arthritis. Br J Rheumatol
1993;32(6):507-14.
Cassidy A. Potential tissue selectivity of dietary phytoestrogens and estrogens. Curr Opin Lipid. 1999:10:4752.
Keck AS, Finley JW. Cruciferous vegetables: cancer protective mechanisms of glucosinolate hydrolysis
products and selenium. Integr Cancer Ther. 2004;3(1):5-12.
Setchell KD. Soy isoflavonesbenefits and risks from natures selective estrogen receptor modulators
(SERMs). J Am Coll Nutr. 2001;20(5 Suppl):354S-362S.
Ganry O. Phytoestrogen and breast cancer prevention. Eur J Cancer Prev. 2002;11(6):519-522.
Xu X, Duncan AM, Wangen KE, Kurzer MS. Soy consumption alters endogenous estrogen metabolism in
premenopausal women. Cancer Epidemiol Biomarkers Prev. 200;9(8):781-786.
Cos P, DeBruyne T, Apers S, Vanden Burrghe D, Pieters L, Vlietinck AJ. Phytoestrogens: recent
developments. Planta Med. 2003;69:589-599.
Lerman RH, Bland JS, Darland G, Lamb JJ, Minich DM, Schiltz B, Trip ML. Supplementation with a novel
selective kinase response modulator (SKRM) nutraceutical and medical food significantly enhances the
benefits of a diet and exercise program in subjects with metabolic syndrome. Functional Medicine Research
Center, Gig Harbor, WA. [In preparation.]
Lukaczer D, Lerman R, Schiltz B, et al. A pilot trial comparing the effects of identical weight loss diet
programs with or without additional nutrient supplementation in subjects with insulin resistance and
hyperinsulinemia. Gig Harbor, WA: Functional Medicine Research Center; Research Report No. 105, 2000.
Lukaczer D, Liska DJ, Darland G, et al. Improvement in symptoms and estrogen metabolism in women with
premenstrual syndrome using a newly formulated medical food. Gig Harbor, WA: Functional Medicine
Research Center; Research Report No. 110, 2001.
Luo J, Sobkiw CL. Hirshman MF, Logsdon MN, et al. Loss of class IA PI3K signaling in muscle leads to
impaired muscle growth, insulin response, and hyperlipidemia. Cell Metab. 2006;3(5):355-366.
Lerman RH, Tripp ML, Bland JS. Double-blind, placebo-controlled trial examining the effects of RIAA/acacia
supplementation on insulin homeostasis. Functional Medicine Research Center, Gig Harbor, WA.
Yudkin JS, Stehouwer CD, Emeis JJ, Coppack SW. C-reactive protein in healthy subjects: associations with
obesity, insulin resistance, and endothelial dysfunction: a potential role for cytokines originating from
adipose tissue? Arterioscle Thromb Vasc Biol. 1999;19:972-978.
Mohamed-Ali V, Goodrick S, Rawesh A, et al. Subcutaneous adipose tissue releases interleukin-6, but not
tumor necrosis factor-, in vivo. Endocrinol Metab. 1997;82:4196-4200.
Lundgren CH, Brown SL, Nordt TK, Sobel BE, Fujii S. Elaboration of type-1 plasminogen activator inhibitor
from adipocytes. A potential pathogenetic link between obesity and cardiovascular disease. Circulation.
1996;93:106-110.
Heitmeier MR, Kelly CB, Ensor NJ, et al. Role of cyclooxygenase-2 in cytokine-induced -cell dysfunction
and damage by isolated rat and human islets. J Biol Chem. 2004;279:53145-53151.
McDaniel ML, Kwon G, Hill JR, Marshall CA, Corbett JA. Cytokines and nitric oxide in islet inflammation and
diabetes. Proc Soc Exp Biol Med. 1996;211:24-32.
Elenkov IJ, Iezzoni DG, Daly A, et al. Cytokine dysregulation, inflammation and well-being.
Neuroimmunomodulation. 2005;12(5):255-269.
Cook ME. Regulation of eicosanoid pathways: a pathway to health and development. Pakistan J Nut.
2002;1(2):103-105.
Kidd P. Th1/Th2 balance: the hypothesis, its limitations, and implications for health and disease. Altern Med
Rev. 2003;8(3):223-246.
Skapenko A, Leipe J, Lipsky PE, et al. The role of the T cell in autoimmune inflammation. Arthritis Res Ther.
2005;7(Suppl 2):S4-S14.
Liska D, Garland G,Tripp M. Proprietary Clinical Research Report. Gig Harbor,WA: Functional Medicine
Research Center; 2004.
Lukaczer D, Lerman RH, Darland G, et al. Effects of a reduced iso-alpha acids (RIAA), rosemary extract,
and oleanolic acid supplement on pain in subjects with osteoarthritis (OA), Proprietary Clinical Research
Report. Gig Harbor,WA: Functional Medicine Research Center;2004.
Tripp M, Darland G, Lerman RH, et al. Development of Meta050, a natural anti-inflammatory targeting
inhibition of cyclooxygenase gene induction instead of direct cyclooxygenase enzyme inhibition, resulting in
an anti-inflammatory with low-predicted GI toxicity. Presented at: Fed Am Soc Experimental Biol. 2003: April.
Lerman RH, Liska D, Tripp M, et al. Summary of effects of a reduced iso-alpha acids (RIAA), rosemary
extract, and oleanolic acid supplement on parameters of cardiovascular health. Proprietary Clinical
Research Report. Gig Harbor,WA: Functional Medicine Research Center;2004.
Lerman RH, Liska D, Tripp M, et al. Clinical trial evaluating the effect of Meta050 on parameters of platelet
function and blood coagulation. Proprietary Clinical Research Report. Gig Harbor,WA: Functional Medicine
Research Center;2004.
Tripp M, Babish J, Darland G, et al. Hop and modified hop extracts have potent in vitro anti-inflammatory
properties. Published Proceedings from 1st International Symposium on Humulus. Editors K.E. Hummer and
J.A. Henning. Acta Horiculturae. 668, ISHS 2005.
Babish JG, Howell T. Proprietary Research Report. San Clemente, CA: MetaProteomics, Inc. 2003.
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77.
78.
79.
80.
81.
82.
83.
84.
85.
86.
87.
88.
89.
90.
91.
92.
93.
94.
95.
96.
97.
98.
99.
100.
101.
102.
103.
104.
105.
106.
107.
108.
109.
110.
111.
112.
113.
114.
Lukaczer D, Lerman RH,Tripp M, et al. A randomized cross-over study to assess the effects of a proprietary
reduced iso-alpha acid (RIAA), rosemary extract, and oleanolic acid supplement on gastrointestinal integrity
using the fecal calprotectin assay. Proprietary Clinical Research Report. Gig Harbor, WA: Functional
Medicine Research Center;2004.
Yamamoto K, Wang J, Yamamoto S, et al. Suppression of cyclooxygenase-2 gene transcription by humulon
of beer hop extract studied with reference to glucocorticoid. FEBS Lett. 2000;465:103-06.
Cantorna MT, Zhu Y, Froicu M, et al. Vitamin D status, 1,25-dihydroxyvitamin D3, and the immune system.
Am J Clin Nutr. 2004;80(6 Suppl):1717S-1720S.
Peterlik M, Cross HS. Vitamin D and calcium deficits predispose for multiple chronic diseases. Eur J Clin
Invest. 2005;35(5):290-304.
Holick MF. The vitamin D epidemic and its health consequences. J Nutr. 2005;135(11):2739S-2748S.
Prabhu KS, Zamamiri-Davis F, Steward JB, et al. Selenium deficiency increases the expression of inducible
nitric oxide synthase in RAW 264.7 macophages: role of nuclear factor-B in up-regulation. Biochem J.
2002;366:203-209.
Tarp U. Selenium and the selenium-dependent glutathione peroxidase in rheumatoid arthritis. Dan Med Bull.
1994;41(3):264-274.
Zamamiri-Davis F, Lu Y, Thompson JT, et al. Nuclear factor-kappaB mediates over-expression of
cyclooxygenase-2 during activation of RAW 264.7 macrophages in selenium deficiency. Free Radic Biol
Med. 2002;32(9):890-897.
Rosenstein ED, Caldwell JR. Trace elements in the treatment of rheumatic conditions. Rheum Dis Clin North
Am. 1999;25(4):929-935.
Peretz A, Cantinieaux B, Neve J, et al. Effects of zinc supplementation on the phagocytic functions of
polymorphonuclears in patients with inflammatory rheumatic diseases. J Trace Elem Electrolytes Health Dis.
1994;8(3-4):189-194.
Bahagavan HN, Chopra RK. CoQ10: absorption, tissue uptake, metabolism and pharmacokinetics. Free
Radic Res. 2006;40(5):445-453.
Crane FL. Biochemical functions of coenzyme Q10. J Am Coll Nutr. 2001;20(6):591-598.
Wolters N, Hahn A. Plasma ubiquinone status and response to six-month supplementation combined with
multivitamins in healthy elderly womenresults of a randomized, double-blind, placebo-controlled study. Int
J Vitam Nutr Res. 2003;73(3):207-214.
Lu WL, Zhang Q, Lee SH, et al. Total coenzyme Q10 concentrations in Asian men following multiple oral 50mg doses administered as coenzyme Q10 sustained release tablets or regular tablets.
Biol Pharm Bull. 2003;26(1):52-55.
Singh RB, Niaz MA, Rastogi V, Rastogi SS. Coenzyme Q in cardiovascular disease. J Assoc Physicians
India. 1998;46(3):299-306.
Weant KA, Smith KM. The role of coenzyme Q20 in heart failure. Ann Pharmacother. 2005;39(9):1522-1526.
Mortensen SA. Perspectives on therapy of cardiovascular disease with coenzyme Q10 (ubiquinone). Clin
Investig. 1993;71(8 Suppl):S116-S123.
Folkers K, Langsjoen P, Willis R, Richardson P, Xia LJ, Ye CQ, Tamagawa H. Lovastatin decreases
coenzyme Q levels in humans. Proc Natl Acad Sci USA. 1990;87(22):8931-8934.
Passi S, Stancato A, Aleo E, Dmitrieva A, Littarru GP. Statins lower plasma and lymphocyte
ubiquinol/ubiquinone without affecting other antioxidants and PUFA. Biofactors. 2003;18(1-4):113-124.
Bargossi AM, Battino M, Gaddi A, Fiorella PL, Grossi G, Barozzi G, Di Giulio R, Descovich G, et al.
Exogenous CoQ10 preserves plasma ubiquinone levels in patients treated with 3-hydroxy-3-methylglutaryl
coenzyme A reductase inhibitors. Int J Clin Lab Res. 1994;24(3):171-176.
Langsjoen PH, Langsjoen AM. The clinical use of statins and the associated depletion of the essential cofactor coenzyme Q10: a review of the pertinent human and animal data. Biofactors. 2003;18(1-4)101-111.
Harris WS, Park Y, Isley WL. Cardiovascular disease and long-chain omega-3 fatty acids. Curr Opin Lipidol.
2003;14(1):9-14.
Carroll DN, Roth MT. Evidence of the cardioprotective effects of omega-3 fatty acids. Ann Pharmacother.
2002;36(12):1950-1956.
Schrepf, R. Clinical prevention of sudden cardiac death by n-3 polyunsaturated fatty acids and mechanism
of prevention of arrhythmias by n-3 fish oils. The Lancet 2004;363:1441-1442.
Biscione F, Totteri A, De Vita A, Lo Bianco F, Altamura G. Effect of omega-3 fatty acids on the prevention of
atrial arrhythmias. Ital Heart J Suppl. 2005;6(1):53-59.
Leaf A, Kang JX, Xiao YF, Billman GE. Clinical prevention of sudden cardiac death by n-3 polyunsaturated
fatty acids and mechanism of prevention of arrhythmias by n-3 fish oils. Circulation. 2003;107(21):26462652.
Mozaffarian D, Psaty BM, Rimm EB, et al. Fish intake and risk of incident atrial fibrillation. Circulation.
2004;110(4):368-373.
He K, Rimm EB, Merchant A, et al. Fish consumption and risk of stroke in men. JAMA. 2002;288(24):31303136.
Siscovick DS, Raghunathan TE, King I, et al. Dietary intake and cell membrane levels of long-chain n-3
polyunsaturated fatty acids and the risk of primary cardiac arrest. JAMA. 1995;274:1363-1367.
Khan A, Safdar M, Ali Khan MM, Khattak KN, Anderson RA. Cinnamon improves glucose and blood lipids of
people with type 2 diabetes. Diabetes Care. 2003;26(12):3215-3218.
Khan A, Bryden NA, Polanshy MM, Anderson RA. Insulin potentiating factor and chromium content of
selected foods and spices. Bio Trace Element Res. 1990;24:183-188.
Broadhurst CL, Polansky MM, Anderson RA. Insulin-like biological activity of culinary and medicinal plant
aqueous extracts in vitro. J Agric Food Chem. 2000;48:849-852.
Anderson RA, Polansky M. Tea enhances insulin activity. J Agric Food Chem. 2002;50:7182-7186.
Dreosti IE. Bioactive ingredients: antioxidants and polyphenols in tea. Nutr Rev. 1996;54:S51-S58.
Saller R, Meier R, Brignoli R. The use of silymarin in the treatment of liver diseases. Drugs.
2001;61(14):2035-2063.
Wellington K, Jarvis B. Silymarin: a review of its clinical properties in the management of hepatic disorders.
Bio Drugs. 2001;15(7):465-489.
Steel VE, Kelloff GJ, Balentine D, et al. Comparative chemopreventive mechanisms of green tea, black tea,
and selected polyphenol extracts measured by in vitro bioassays. Carcinogenesis. 200;21(1):63-67.
Ahmad N, Muktar H. Green tea polyphenols and cancer: biological mechanisms and practical implications.
Nutr Rev. 1999;57(3):78-83.
___________________________________________________
Version 1.4
Page 34
115.
116.
117.
118.
119.
120.
121.
122.
123.
124.
125.
126.
127.
128.
129.
130.
131.
132.
133.
134.
135.
136.
137.
138.
139.
140.
141.
142.
143.
144.
145.
146.
147.
148.
149.
150.
151.
152.
153.
Chen L, Mohr SN, Yang CS. Decrease of plasma and urinary oxidative metabolites of acetaminophen after
consumption of watercress by human volunteers. Clin Pharmacol Ther. 1996;60(6):651-660.
Rose P, Faulkner K, Williamson G, et al. 7-Methylsulfinylheptyl and 8-methylsulfinyloctyl isothiocyanates
from watercress are potent inducers of phase II enzymes. Carcinogenesis. 2000;21(11):1983-1988.
Hecht SS. Chemoprevention of cancer by isothiocyanates, modifiers of carcinogen metabolism. J Nutr.
1999;129(3 Suppl):768S-774S.
Barch DH, Rundhaugen LM, Pillay NS. Ellagic acid induces transcription to the rat glutathione S-transferaseYa gene. Carcinogensesis. 1995;16(3):665-668.
Ahn D, Putt D, Kresty L, et al. The effects of dietary ellagic acid on rat hepatic and esophageal mucosal
cytochromes P450 and phase II enzymes. Carcinogenesis. 1996;17(4):821-828.
Ahmed S, Rahman A, Saleem M, et al. Ellagic acid ameliorates nickel induced biochemical alterations:
diminution of oxidative stress. Hum Exp Toxicol. 1999;18(11):691-698.
Thresiamma KC, George J, Kuttan R. Protective effect of curcumin, ellagic acid and bixin on radiation
induced genotoxicity. J Exp Clin Cancer Res. 1998;17(4):431-434.
Gebhardt R. Antioxidative and protective properties of extracts from leaves of the artichoke (Cynara
scolymus L.) against hydroperoxide-induced oxidative stress in cultured rat hepatocytes. Toxicol Appl
Pharmacol. 1997;144(2):279-286.
Adzet T, Camarasa J, Laguna JC. Hepatoprotective activity of polyphenolic compounds from Cynara
scolymus against CCI4 toxicity in isolated rat hepatocytes. J Nat Prod. 1987;5(4):612-617.
Perez-Garcia F, Adzet T, Canigueral S. Activity of artichoke leaf extract on reactive oxygen species in
human leukocytes. Free Radic Res. 2000;333(5):661-665.
Isolauri E, Kirjavainen PV, Salminen S. Probiotics: a role in the treatment of intestinal infection and
inflammation? Gut. 2002:50(3 Suppl):11154-11159.
Gill HS, Rutherford KJ, Cross ML, et al. Enhancement of immunity in the elderly by dietary supplementation
with the probiotic Bifidobacterium lactis HN019. Am J Clin Nutr. 2001;74(6):833-839.
Wagner RD, Pierson C,Warner T, et al. Biotherapeutic effects of probiotic bacteria on candidiasis in
immunodeficient mice. Infect Immun. 1997;65(10):4165-4172.
Klaenhammer TR, Kullen MJ. Selection and design of probiotics. Int J Food Microbiol. 1999;50(1-2):45-57.
Tejada-Simon MV, Lee JH, Ustunol Z, et al. Ingestion of yogurt containing Lactobacillus acidophilus and
Bifidobacterium to potentiate immunoglobulin A responses to cholera toxin in mice. J Dairy Sci.
1999;82(4):649-660.
Mutai M, Tanaka R. Ecology of Bifidobacterium in the human intestinal flora. Bifidobacteria Microflora.
1987;6(2):33-41.
Kaplan H, Hutkins RW. Fermentation of fructooligosaccharides by lactic acid bacteria and bifidobacteria.
Appl Environ Microbiol. 2000;66(6):2682-2684.
Mitsuoka T. Intestinal flora and aging. Nutr Rev. 1992;50:438-444.
De Los Reyes GC, Koda RT, Lien EJ. Glucosamine and chondroitin sulfates in the treatment of
osteoarthritis: a survey. Prog Drug Res. 2000;55:81-103.
Giordano N, Nardi P, Senesi M, et al. The efficacy and safety of glucosamine sulfate in the treatment of
gonarthritis. Clin Ter. 1996;147:99-105.
Leffler CT, Philippi AF, Leffler SG, et al. Glucosamine, chondroitin, and manganese ascorbate for
degenerative joint disease of the knee or low back: a randomized, double- blind, placebo-controlled pilot
study. Mil Med. 1999;164(2):85-91.
Morreale P, Manopoulo R, Galati M, et al. Comparison of the anti-inflammatory efficacy of chondroitin sulfate
and diclofenac sodium in patients with knee osteoarthritis. J Rheumatol. 1996;23:1385-1391.
Uebelhart D,Thonar EJ, Delmas PD. Effects of oral chondroitin sulfate on the progression of knee
osteoarthritis: a pilot study. Osteoarthritis Cartilage. 1998;6(Suppl A):31-36.
McAlindon TE, LaValley MP, Gulin JP, et al. Glucosamine and chondroitin for treatment of osteoarthritis: a
systematic quality assessment and meta-analysis. JAMA. 2000;283(11):1469-1475.
Usha PR, Naidu MU. Randomised, double-blind parallel, placebo-controlled study of oral glucosamine,
methylsulfonylmethane and their combination in osteoarthritis. Clin Drug Investig. 2004;24(6):353-363.
Kim LS, Axelrod LJ, Howard P, Buratovich N, Waters RF. Efficacy of methylsulfonylmethane (MSM) in
osteoarthritis pain of the knee: a pilot clinical trial. Osteoarthritis Cartilage. 2006;14(3):286-294.
Gruber CJ, Tschugguel W, Schneeberger C, Huber JC. Production and action of estrogens. N Engl J M.
2002;346(5):340-351.
Setchell KDR. Soy isoflavonesbenefits and risks from natures selective estrogen receptor modulators
(SERMs). J Am Coll Nutr. 2001;20(5):354S-362S.
Nestel PJ, Pomeroy S, Kay S, et al. Isoflavones from red clover improve systemic arterial compliance but
not plasma lipids in menopausal women. J Clin Endocrinol Metab. 1999;84(3):895-898.
Kuiper GG, Lemmen JG, Carlsson BO, et al. Interaction of estrogenic chemicals and phytoestrogens with
estrogen receptor b. Endocrinology. 1998;139:4252-4563.
Kaufman PB, Duke JA, Brielmann H, et al. A comparative survey of leguminous plants as sources of the
isoflavones genistein and daidzein: implications for human nutrition and health. J Altern Complement Med.
1997;3(1):7-12.
Davis SR, Dalais FS, Simpson ER, et al. Phytoestrogens in health and disease. Recent Prog Horm Res.
1999;54:185-210.
Goud VK, Polasa K, Krishnaswamy K. Effect of turmeric on xenobiotic metabolising enzymes. Plant Foods
Hum Nutr. 1993;44(1):87-92.
Verma SP, Goldin BR, Lin PS. The inhibition of the estrogenic effects of pesticides and environmental
chemicals by curcumin and isoflavonoids. Environ Health Perspect. 1998;106(12):807-812.
Bowers JL,Tyulmenkov V, Jernigan SC, et al. Resveratrol acts as a mixed agonist/antagonist for estrogen
receptors and . Endocrinology. 2000;141(10):3657-3667.
Bell MC, Crowley-Nowick P, Bradlow HL, et al. Placebo-controlled trial of indole-3-carbinol in the treatment
of CIN. Gynecol Oncol. 2000;78:123129.
Michnovicz JJ. Increased estrogen 2-hydroxylation in obese women using oral indole-3-carbinol. Int J Obes
Relat Metab Disord. 1998;22(3):227-229.
Michnovicz JJ, Bradlow HL. Altered estrogen metabolism and excretion in humans following consumption of
indole-3-carbinol. Nutr Cancer. 1991;16:59-66.
McAlindon TE, Gulin J, Chen T, Klug T, Lahita R, Nuite M. Indole-3-carbinol in women with SLE: effect on
estrogen metabolism and disease activity. Lupus. 2001;10(11):779-783.
___________________________________________________
Version 1.4
Page 35
154.
155.
156.
157.
Taioli E, Bradlow HL, Garbers SV, et al. Role of estradiol metabolism and CYP1A1 polymorphisms in breast
cancer risk. Cancer Detect Prev. 1999;23(3):232-237.
Rosen CA, Woodson GE, Thompson JW, Hengesteg AP, Bradlow HL. Preliminary results of the use of
indole-3-carbinol for recurrent respiratory papillomatosis. Otolaryngol Head Neck Surg. 1998;118(6):810815.
Bradlow HL, Michnovicz JJ, Halper M, Miller DG, Wong GY, Osborne MP. Long-term responses of women
to indole-3-carbinol or a high fiber diet. Cancer Epidemiol Biomarkers Prev. 1994;3(7):591-595.
Michnovicz JJ, Adlercreutz H, Bradlow HL. Changes in levels of urinary estrogen metabolites after oral
indole-3-carbinol treatment in humans. J Natl Cancer Inst. 1997;89:718-723.
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The Power of Nutrigenomics:

The Future of Health CareHere Today

Nutrigenomics in clinical practice entails using specified, defined

2007 Metagenics, Inc.

2007 Metagenics, Inc.

The Nutrigenomics Matrix

This chart is provided for your reference as a summary of how

Medical Food Support

UltraMeal PLUS 360

2007 Metagenics, Inc.

3-Phase Plan for Implementing

Adopt a simple, 3-phase plan

1A. Dietary Signal Modification with TLC

Selective Kinase Response Modulators (SKRMs)

2007 Metagenics, Inc.

Where an unhealthy diet makes the kinase signaling unclear,

Targeted Nutritional Support

2007 Metagenics, Inc.

Unhealthy diets are a leading

The first step in a nutrigenomics intervention is changing primary dietary

2007 Metagenics, Inc.

An optimal TLC program should include recommendations for exercise

2007 Metagenics, Inc.

Cardiovascular & Insulin Resistance Conditions

Inflammatory, Gastrointestinal, Autoimmune & Fatigue Disorders

2007 Metagenics, Inc.

challenge the reintroduction of foods to determine those that may

Hormone Imbalances & Cyclerelated Symptoms

2007 Metagenics, Inc.

Medical foods containing

Medical Foods with the inclusion of SKRMs offer a multi-mechanistic

to decide on a case-by-case basis when other patients may also

2007 Metagenics, Inc.

Metabolic Syndrome & Cardiovascular Disease

Provides a proprietary soy protein and plant sterol blend that

In individuals with metabolic syndrome and high cholesterol, this

Lower the apolipoprotein Bto-apolipoprotein A1 (apoB/ApoA1)

(See Table 1 on the following page for clinical results.)

2007 Metagenics, Inc.

Greater Improvement in CV Health Markers

Medical Food with SKRMs Shows Greater Results

Arm 1: UltraMeal PLUS

Arm 2: Low-GL Diet

* These results are statistically significant.

2007 Metagenics, Inc.

Inflammatory Bowel Disease (Autoimmune Support)

Provides a low-allergenic-potential protein base in the form of

Advantages of the addition of SKRMs include:

Shown to beneficially influence the function of kinases involved

Also available without SKRMs as UltraInflamX Medical Food.

2007 Metagenics, Inc.

Supports healthy heart function by providing 15 grams of soy

36% Average Decrease in 2-hr Postprandial Insulin

Before Program After 8 Weeks on

Figure 2. A preliminary, randomized, 2-arm clinical study of 37 insulin-resistant

2007 Metagenics, Inc.

Chronic Fatigue Syndrome (Liver Detoxification Support)

Designed for those patients who may benefit from specific

UltraClear PLUS Medical Food

Provides the same low-allergenic-potential rice protein base and

UltraClear Plus pH Medical Food

Provides the same low-allergenic-potential rice protein base and

2007 Metagenics, Inc.