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2015 Online Review Course

Important Schematics and


Anchor Slides

RetellingthePatientsStory

PhysiologyandFunction:OrganizingthePatientsClinicalImbalances

Antecedents

Assimilation

Defense&Repair

(PredisposingFactors
Genetic/Environmental)

(e.g.,Digestion,Absorption,
Microbiota/GI,Respiration)

(e.g.,Immune,Inflammation,
Infection/Microbiota)

TriggeringEvents
(Activators)

StructuralIntegrity

Energy

(e.g.,fromSubcellularMembranesto
MusculoskeletalStructure)

e.g., cognitive
function,
perceptualpatterns

(e.g.,EnergyRegulation,
MitochondrialFunction)

e.g., emotional
regulation,grief,
sadness,anger,etc.

e.g., meaning&purpose,
relationshipwithsomething
greater

Mediators/Perpetuators
(Contributors)

Communication

Spiritual

(e.g.,Endocrine,Neurotransmitters,
Immunemessengers)

Transport

Biotransformation&Elimination
(e.g.,Toxicity,Detoxification)

(e.g.,Cardiovascular,LymphaticSystem)

PersonalizingLifestyleFactors
Sleep&Relaxation

Exercise&Movement

Nutrition&Hydration

Stress&Resilience

Name:____________________________Date:___________CC:_____________________________________

Relationships&Networks

Copyright2011InstituteforFunctionalMedicine

Antecedents

Prenatal

Preconception

TriggersorTriggeringEvents

Birth

Current
Concerns

Signs,SymptomsorDiseasesReported

2012
The
Institute
Functional
Medicine
2013
The
Institute
forfor
Functional
Medicine

Functional Medicine
Operating System

2012
The
Institute
Functional
Medicine
2013
The
Institute
forfor
Functional
Medicine

Gather Oneself & Information


Organize on Timeline & Matrix
Tell the Patients Story
Order of your Priorities
Initiate Assessment and Care
Track Progress
G

T
2012
The
Institute
Functional
Medicine
2013
The
Institute
forfor
Functional
Medicine

THE PRINCIPLES:
A SCIENCE BASED FIELD OF HEALTHCARE
Biochemical individuality based on genetic and
environmental uniqueness
Patient centered versus disease centered
Dynamic balance of internal and external factors
Web-like interconnections of physiological
factors
Health as a positive vitality not merely the
absence of disease
Promotion of organ reserve healthspan

2014 The Institute for Functional Medicine

Key differences between


Conventional and Functional Medicine
The Conventional Model
Differential diagnosis:
reductionism
Eliminating confounding
variables
Naming and blaming
Confirmatory laboratory
and imaging tests
Symptom suppression

The Functional Model


Etiologic and causative
evaluation: patterns and
connections
Including all variables
New lenses and cognitive
organization
Testing: causes and
mechanisms
Removing causes and
restoring normal function
2014 The Institute for Functional Medicine

Evidence
Based
Clinical
Practice

ClinicalExpertise

2014 The Institute for Functional Medicine

Definitions:
Antecedents, Triggers, and Mediators
Antecedents are factors, genetic or acquired, that
predispose individual to an illness or pattern
Triggers are factors that provoke the symptoms and
signs of illness
Mediators/mediation are factors, biochemical or
psychosocial, that contribute to pathological changes
and dysfunctional responses
2014 The Institute for Functional Medicine

Organizing the Clinical Imbalances

Patient
Centered Care

2014 The Institute for Functional Medicine

Key functional roles


of the Gut:
Digestion/Absorption
Intestinal Permeability
Gut Microbiota/Dysbiosis
Inflammation/Immune
Nervous System

2014 The Institute for Functional Medicine

The 5R Approach
What does this patient need to have Removed?
What does this patient need to have Replaced?
What does this patient need to support and/or to re-establish
a healthy balance of microflora; that is, does he/she require
pre- or probiotic Reinoculation?
What does this patient require to support healing and Repair
of the GI epithelial barrier and the biofilm?
What does this patient need to do to Rebalance their lifestyle;
that is, are there things to modify in their attitude, diet, and
lifestyle to promote a healthier way of living?
2014 The Institute for Functional Medicine

Pathophysiology
Poor Dietary Choices

Food Allergy

Stress & Emotions


Infection
Lectins

Altered
Intestinal
Permeability

Malnutrition
Elevated Total
Toxic & Antigenic
Burden

Systemic Disease
Dysbiosis
Low Stomach Acid
Toxic Exposure

Toxic Overload
Systemic Disease

2014 The Institute for Functional Medicine

Triggers:nutrientinsufficiency,medication,dysbiosis,
parasite,foodreaction,surgery,etc
DisturbanceofGIflora
DisruptionofEpithelialTightJunctions
AndMucosalBarrier

Increasedmucosalpermeability
Bacterial/yeast/protozoa
/toxintranslocation

Foodprotein
translocation

Portalandsystemicoverload
Immunologicallymediatedreactions(andperpetuation)
DistantSignsandSymptoms:Systemicillness

2014 The Institute for Functional Medicine

IFM Food Reaction Definitions


Food allergy: IgE-mediated type 1
hypersensitivity
Food sensitivity: IgG-mediated type 3 delayed
hypersensitivity
Food intolerance: Non-immunological reaction
to food (e.g. lactose intolerance)

2014 The Institute for Functional Medicine

MechanismsofImmuneandNonImmuneMediatedReactions
toFood
NonImmunemediated
(Intolerance)

Immunemediated

IgE
mediated
reactions

Immediat
ePhase

Late
phase

Other
immune
reactions

IgA
mediated

Tcell
mediated

Toxic
(occurringin
any
individual)

IgG,Immune
complexes

Enzymatic
(e.g.lactose
intolerance)

Nontoxic
(individual
susceptibility)

Pharmacologic
(e.g.vasoactive
amines)

Other(e.g.
additive
intolerance

2014 The Institute for Functional Medicine

Gut Permeability and Food Allergies

Clinical & Experimental Allergy


Volume 41, Issue 1, pages 20-28, 11 NOV 2010

2014 The Institute for Functional Medicine

Labs

2014 The Institute for Functional Medicine

Symptom Characteristics:
IgE vs. IgG
IgE
ALLERGY

IgG
SENSITIVITY

Onset

Rapid (minutes)

Delayed (hours)

Duration

Brief (hours)

Prolonged (days)

Mechanism

Mast Cell

Circulating Complexes

Quantity of Food

Tiny

Dose Dependent

Food

Any (uncommon)

Common Foods

Patient Awareness

Often

Rarely

Persistence of
Antibody

Lifelong

Months After Elimination

2014 The Institute for Functional Medicine

The Celiac Iceberg

The celiac iceberg represents all persons genetically


susceptible to celiac disease because of a positive celiacassociated antibody test. The majority of such persons have
latent celiac disease. The tip of the iceberg represents the
minority of persons who present with classic celiac disease.
2014 The Institute for Functional Medicine

7
6
Clinical & Experimental Allergy,
2011 (41) 2028.

5
2014 The Institute for Functional Medicine

Figure 3 | Proposed causes of dysbiosis of the microbiota. We propose that the composition of the
microbiota can shape a healthy immune response or predispose to disease.

Nature Reviews in Immunology Vol 9 May 2009 | 313

2014 The Institute for Functional Medicine

2014 The Institute for Functional Medicine

Probiotics and Prebiotics: Exploring the


Mutually Beneficial Effects of Bacteria and
their Substrates in the Human Host
Regulate local and systemic
immune function
Metabolic pathway
nutrients: glycemic control,
cholesterol, amino acids

Prevent infections
(systemic and GI)

Regulate
inflammation
(local and systemic)

Prebiotics and
Probiotics

Regulate appetite
(leptin, ghrelin)
Regulate bowel
motility

Support mucosal
barrier
Enhance nutrient
utilization

Prevent neoplastic
changes
2014 The Institute for Functional Medicine

Chronic inflammation plays a role


in MOST disease conditions

Alzheimers

Atherosclerosis

Diabetes

Infection

Cancer

Inflammation

Arthritis

Psoriasis
Eczema

Colitis
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Inflammatory
Trigger
Biologics
Rituximab
Etanercept,
Etc.

NFB Activated

NFB bindstoDNA
leading
activationof..
TNF,IL1,IL6

Lipoxygenase

Leukotrienes

Cyclooxygenase

Prostaglandins

2014 The Institute for Functional Medicine

DietaryComponents
Vitamins,Minerals,
EssentialFattyAcids,
nonessentialnutrients,
Phytochemicals

PPARs

NFB bindstoDNA
leading
totranslationalactivation
of..

NRf2

TNF,IL1,IL6

TissueFactor
PAI1

Lipoxygenase

Cyclooxygenase

Oxidative
Stress

ICAMS,VCAMs
Selectin,MIP

iNOS
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2014 The Institute for Functional Medicine

Antecedents:

The Inflammatory Process:


A Physiologic Algorithm

Inflammatory Response (itis)


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Triggers
Stress
Toxins
Food
Infections
Nutrient Insufficiencies

Thyroid

Hashimotos
Thyroiditis
Graves Disease

Brain

Multiple Sclerosis
Autism
Guillain-Barre Syndrome
Psychological

Blood

Leukemia
Lupus
Hemolytic
Dysglycemia

Bones

Rheumatoid Arthritis
Ankylosing Spondylitis
Polymyalgia Rheumatica

GI Tract

Muscles

Celiac
Crohn's Disease
Ulceratic Colitis

Fibromyalgia
Muscular Dystrophy

Nerves

Peripheral Neuropathy
Diabetic Neuropathy

Lungs

Asthma
Wegners
Granulomatosis

Skin

Eczema
Psoriasis
Scleroderma
Vitiligo

2014 The Institute for Functional Medicine

Leaky Barriers: A Common Antecedent


for Chronic Inflammatory Disease

2014 The Institute for Functional Medicine

Asymptomatic Infections:
The Iceberg Concept
poliomyelitis in a child
0.1-1% of infections are
clinically apparent
Acute infections = obvious infections

Dysbiotic infections = chronic


rubella
immune activation
50% of infections are
clinically apparent

Spectrum of
Most people probably have some
virulence
dysbiosis, but many tolerate it
for better or for worse.

classical
clinical
disease

less acute/obvious
disease

asymptomatic
Carrier/health

rabies
100% of infections
are clinically apparent
2014 The Institute for Functional Medicine

2014 The Institute for Functional Medicine

Arachidonic Acid Cascade


Arachidonicacid(AA)
20:4n6

F2Isoprostanes

Lipoxygenase

Cyclooxygenases
(COX1,COX2)

PGD2

H2O

PGE
Synthase

LTB4

PGE2

PGF2

HPETE(hydroxyperoxy
eicosatetraenoicacid)

ProstaglandinH2 (PGH2)

PGD
Synthase

Lipoxins

GlutathioneStransferase

Thromboxane
synthase
Prostacyclin
synthase

Prostacylcin(PGI2)

LeukotrieneA4

LeukotrieneC4

Cysteinyl
Leukotrienes

Thromboxane(TXA2)

(endothelium)

(platelets)

6ketoPGF1

Thromboxane(TXA2)

LeukotrieneD4

Glutamicacid

LeukotrieneE4

2014 The Institute for Functional Medicine

Baselinenutritional
deficiency

Increased
baseline
oxidativestress

Impaired
immunefunction

Facilitated
viral
replication
Facilitated
viralmutation

Exacerbationof
oxidativestress

Impaired
mucosal
defenses
Exacerbationof
nutritiondeficiencies,
tissuedepletion

Increased
susceptibilityto
infection

Increasedfrequency,
severity,anddurationof
infection

Directmucosal
damage
Anorexia,reduced
foodintake,and
increasedmetabolic
andrepairneeds

2014 The Institute for Functional Medicine

Production

Production/synthesis and secretion of the


hormone
Transport

Transport/conversion/distribution/ interaction
with other hormones
Sensitivity

Cellular sensitivity to the hormone signal


Detoxification

Detoxification/excretion of the hormone


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2014 The Institute for Functional Medicine

DHEASulfate

HO

Pregnenolone

O
OH

HO

17OHpregnenolone

17OHprogesterone

OH
O

OH
O
OH
O

11deoxycorticosterone

HO

OH
O
OH

HO

OH
O

HO

Estrone

OH

Cortisone

OH

OH
HO

Testosterone

HO

Estradiol

HO
HO

HO

HO

16Hydroxyestrone 2Hydroxyestrone 4Hydroxyestrone

CH3OH

OH

CH3

Estriol

DiHydroTestosterone

O
OH

HO

H3CO
HO

HO

OCH

3
2Methoxyestrone 4Methoxyestrone

17 hydroxysteroid
dehydrogenase

Aromatase

11 hydroxysteroid
dehydrogenase1&2

Cytochrome3A4

CytochromeP450scc

18hydroxy
dehydrogenase

17hydroxylase

Cytochrome1A1

18hydroxylase

21hydroxylase

11 hydroxylase

Cytochrome1B1

17,20lyase

3 hydroxysteroid
dehydrogenase,
Isomerase

Aldosterone

Cortisol

OH
O

18OHcorticosterone

Androstenedione

OH
O
OH

O
HO

EstroneSulfate

HO

Corticosterone

SO4

DHEA
O

11deoxycortisol

OH
O

HO

Progesterone

OH

O
OH
O

HO

Ster id genic
Pathways

SO4

Cholesterol

5 reductase

CatecholOMethyl
Sulfatase(SO4)
Transferase
Sulfotransferase(+SO4)
(COMT) 2014 The Institute for Functional Medicine

Cortisol Steal

Cholesterol

O
OH

HO

Pregnenolone

HO

HO

17-OH-pregnenolone

O
OH
O

Progesterone

17-OH-progesterone

O
OH
O

HO

Androstenedione

HO

Estrone

OH

Testosterone

OH

HO

Estradiol

OH
O
OH

Corticosterone
HO

HO

Cortisol

OH
O

OH
O
OH

18-OH-corticosterone
HO

11-deoxycortisol

11-deoxycorticosterone

DHEA
O

OH
O
OH

OH
O

HO

Cortisone

OH
O

Aldosterone
2014 The Institute for Functional Medicine

Response

Allostasis

Stress Recovery

Primary Effects

Long-Term
Activation of
Primary
Mediators and
Effects

(cellular events regulated by primary mediators)

Repeated Hits

Lack of Adaptation

Prolonged Response Inadequate Response

Allostatic
Load

Secondary Outcomes
(waist-hip ratio, blood pressure, cholesterol, glucose)
(insulin, immune capacity, glucose tolerance)
Tertiary Outcomes
(cardiovascular disease, severe cognitive decline,
diabetes, hypertension, cancer)
2014 The Institute for Functional Medicine

FactorsthatAffectThyroidFunction
Factorsthatcontributeto
properproductionofthyroid
hormones
Nutrients:iron,iodine,
tyrosine,zinc,selenium
vitaminE,B2,B3,B6,C,D

Factorsthatincrease
conversionofT4toRT3
Stress
Trauma
Lowcaloriediet
Inflammation
(cytokines,etc.)
Toxins
Infections
Liver/kidney
dysfunction
Certainmedications

Factorsthatinhibitproper
productionofthyroidhormones
Stress
Infection,trauma,radiation,
medications
Fluoride(antagonisttoiodine)
Toxins:pesticides,mercury,
cadmium,lead
Autoimmunedisease:Celiac

T4

Factorsthatincrease
conversionofT4toT3
Selenium
Zinc

RT3 T3

T3andRT3competeforbindingsites

Nucleus/
Mitochondria

Cell

Factorsthatimprovecellular
sensitivitytothyroidhormones
VitaminA
Exercise
Zinc
2014 The Institute for Functional Medicine

T4
D1 (and D2)
5-deiodinase

D3
5-deiodinase

(Se Dependent)

(Se Independent)

T3

RT3

D3
5-deiodinase

D1
5-deiodinase

(Se Independent)

(Se Dependent)

T2 (inactive)

T2 (inactive)

Peeters, RP et. al. Reduced Activation and Increased Inactivation of Thyroid Hormone in Tissues of
Critically Ill Patients J Clin Endocrinol Metab. 2005 Oct;90(10):5613-20.
2014 The Institute for Functional Medicine

Sympathetic
nervous
system

Stress signal to the


cerebral cortex

Adrenal
medulla

Neurohypothalamus

ACh
Visceral
brain

Anterior
pituitary

CRH

Endocrine
hypothalamus

Epinephrine
release
PNMT
induction
Acute
stress
Chronic
Adrenal stress
cortex

CRH
POMC

ACTH

Cortisol
release

Corticotrophin

via Gs

-Lipotropin

-Endorphin

Neuroendocrine Pathways Associated with


the Stress Response
2014 The Institute for Functional Medicine

Estrogen Production/Metabolism
(the estrogen factory in the breast)
17HSD

DHEA
3HSD
isomerase

Androstenediol
17HSD2

3HSD
isomerase

17HSD5

Androstenedione

Testosterone

17HSD6,2

AromArom
Estrone

17HSD1
17HSD2

STS

STSSULT

Estradiol
STSSULT

STS

E1SE2S
17HSD1
DHEAS
17HSD2

AdiolS

Macronutrients ATP

Protein

Fat

Carbs

oxidation
TCA Cycle
ETC

ATP Pool
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2014 The Institute for Functional Medicine

Lipoic
Acid

Magnesium

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2014 The Institute for Functional Medicine

Causes of 2o Mitochondrial
Dysfunction
Oxidative Stress

Exposure to Medications
Exposure to Heavy Metals
Exposure to Chemicals
Exposure to PCBs
Exposure to Pesticides

2014 The Institute for Functional Medicine

How Does Body Protect From ROS?


1. Enzymes
Catalase (Fe)
Superoxide dismutase-SOD (Zn, Cu, Mn)
Glutathione peroxidase (Se) and glutathione
reductase

2. Dietary Anti-Oxidants
Vitamin C for aqueous compartments
Vitamin E for lipid compartments
Carotenoids, flavonoids, etc.

3. Endogenous Anti-Oxidant Molecules


Glutathione, cysteine, CoQ10, lipoic acid, uric
acid, cholesterol.

2014 The Institute for Functional Medicine

Regulation of Cognitive Function


Exercise

Caloric Restriction
PGC-1

Mild Oxidative
Stress

Sedentary Lifestyle
Diabetes, Obesity
High cholesterol

Adaptive
Cellular Stress
Responses

Neurogenesis
Neuroprotection
Synaptic
Plasiticity

BDNF
IGFs
HSPs
UCPs
MnSOD
HO-1

Cognitive Impairment
Disease Progression
Adapted from: Stranahan and Mattson, 2011

Oxidative Stress
Inflammation
Impaired Synaptic Plasticity
Impaired Neurognesis
Neurodegeneration
Cognitive Impairment
Disease Progression
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Caloric restriction
Physical exercise
DHA
Mental exercise

BDNF

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2014 The Institute for Functional Medicine

Treatment:
a TO DO list to support your
mitochondrial function

Get adequate nutrition


Stay cool and hydrate
Prevent infections
Supplements:
CoQ-10
Omega-3 Fatty Acids
Exercise (physical & mental)
Avoid toxins
2014 The Institute for Functional Medicine

Anthropometrics
Screening Exam
Vitals
Blood Pressure
Height and Weight
Pulse Ox

Body Mass Index


Waist to Hip Ratio
Waist Circumference
Hip Circumference

Waist to Height Ratio


Bioelectrical Impedance Analysis
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Defining Body Composition


S
PatternBody
Recognition

Android
Obesity

Gynoid
Obesity

overfat
OVER VAT

overfat
OVER SAT

OVER
Weight
2014 The Institute for Functional Medicine

Assessing Body Composition


Dx:Overweight/Obese
YES

Abnormal
High BMI?

Increased
WC?

YES

NO

NO

Increased
WC or WHR?

Increased
WHR?

Increased
BIA Fat%?

YES

NO

YES

YES

Increased
WHR?

NO

NO

Dx:OverVAT

Dx:OverFat

YES

YES
Android Obesity
(OverVAT)

YES

NO

Metabolically GynoidPossible High


Increased
Increased
Obese
Obesity/Muscle Mass
BIA Fat%?
BIA Fat%? (OverVAT) overSAT or Large
Skeletal
Frame
NO
YES NO
YES
IdealSkinny Fat or Possible Gynoid
Metabolically High MuscleObesity/
Obese
Mass or overSAT
Athlete

Increased
BIA Fat%?

MetSyn?

TLC
Gut/Detox/HPATG
dysfunctions?

Nx/ Rx
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2014 The Institute for Functional Medicine

Role of ROS on Hypertension and


Hyperlipidemia and Atherosclerosis
A-II

AT1
Receptor

Upregulates

Cytokines
Growth
Factors

NAD(P)H
Oxidase

Ox LDL

O2

(Superoxide
Anion)

LOX-1
Endothelial
Receptor for Ox LDL

Inactivates NO
Hypertension
Hypertrophy
Proliferation
ED

Foam Cells
Fatty Streaks
Atherosclerosis

2014 The Institute for Functional Medicine

Antecedents, Triggers and Mediators


Inflammation

Genetic propensity

High Glycemic Diet

Chronic Stress

Visceral Adiposity
Smoking
Lack of Exercise

Insulin
Resistance

Sleep

Elevated
Fasting and PP
Insulin & Glucose
2014 The Institute for Functional Medicine

Treatments that Change


Risk Differentially
Lipid-Rich

Triglyceride-Rich

DISORDERS

DISORDERS

statins
statin + ezetimibe
low fat diet

CARDIO

omega 3 fatty acids


fibrates
niacin
exercise
low glycemic impact diet

METABOLIC

COMPREHENSIVE RISK REDUCTION


2014 The Institute for Functional Medicine

The Road to Diabetes: Insulin


Resistance and Hyperinsulinemia
Inability to suppress
hepatic glucose
production

Overproduction
of FFAs
by adipose cells

Increased muscle cell


resistance to
insulin action

Stimulates gluconeogenesis
Increases muscle insulin resistance
Impairs insulin secretion
Elevated serum
Elevated serum
glucose
glucose
Elevated serum glucose
Glucose toxicity leading to
further impaired insulin secretion
2014 The Institute for Functional Medicine

Clinical Consequences of CardioMetSyn


Cardiovascular
Disease

Type 2
Diabetes

Dyslipidemia

Sarcopenia

Hypertension

Sleep Apnea
Obesity

Erectile
Dysfunction

CardioMetSyn
PCOS

NASH
Osteoporosis

Cognitive Decline /
Alzheimer's Disease
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2014 The Institute for Functional Medicine

Communicate
this

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Clinical Use of Food as Medicine

Inflammatory elements
Inconsistent behaviors
Imbalanced fats
High glycemic impact

Standard
American Diet

Core Food
Plan
Healthy foods
Phytonutrient dense
Balanced diet

Foods tailored to a
clinical condition
Detox and Cleansing
Elimination/Allergies

CARDIOMETABOLIC
Modified Therapeutic
Intervention

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Basic Toxicology
Exposure
Assimilation

Retention

Toxicity
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From. Larry Needham, PhD: CDC NCEH Presentation (2004)

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Periodontal
Disease
Mixed Metal/
Base Metal
Crowns
Mercury
Amalgams

Root Canals

Genetics

Orthodontic
Appliances

Epigenetics

Immune
Dysregulation

Dental
Implants

Lifestyle

Quality of Care

Inflammation

Oxidative
Stress
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TOTAL TOXIC LOAD


equals

Total Toxic Exposure


minus

Ability to Detoxify
and
Excrete Toxins
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The Limits of Certainty and


Under-recognition of Toxic Threats
WHATWE
DONTKNOW

WHATWE
KNOW

Known
Effects

THE
UNKNOWN
UNKNOWN

Long latency effects

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Thereiswidevariation
inindividualsensitivityto
toxicantexposure.This
meansthatinalarge
populationwithwide
spreadexposures,even
whenthedosageis
acceptableonaverage,
manypeoplewillstillbe
hurt.Asignificantmargin
ofsafetyisrequiredto
preventsuchinjuries.
From:InHarmsWay:ToxicThreats
toChildDevelopment.
GreaterBostonPSR

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heavymetals
(Pb,Hg,As,Cd)

polycyclicaromatic
hydrocarbons
(PAH)

phthalates
(i.e.plasticizers)
phenols
(BPA,triclosan)

organochloride
(OC)pesticides

organophosphate
(OP)pesticides

polychlorinated
dibenzodioxins
(PCDDs)&
furans (PCDFs)

polychlorinated
biphenyls(PCBs)

polybrominated
diphenyl ethers
(PBDEs)

polyfluorinated
compounds(PFCs)

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Pattern Recognition
Undernourished
Reduce Exposures
Ensure a Safe Detox
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Liska;ExploreMarch2006,Vol 2,No2,pg125

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Types of Reactions
Parent
Compound

WaterSoluble
Compound

Activated
Intermediate

Phase I

Phase II

CytochromeP450enzymes:
Oxidation
Reduction
Hydrolysis

Glucuronosyl Transferase
Sulfotransferases
AminoAcidConjugation
GlutathioneConjugation
Acetylation
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The Role of Nutritional Factors in


Liver Detoxification
Phase I
Nutritional Support
Antioxidants
Vitamin & Mineral Cofactors

Phase II
Nutritional Support
Conjugating Agents
Vitamin & Mineral Cofactors

Free
Radicals

Toxins

Phase I

Toxic
Intermediates

Cytochrome P-450
Mixed Oxidase System
Xenobiotics
Endotoxins
Non-Polar, Lipophilic
Poorly Excreted

Phase II

Conjugated
Metabolites

Enzymatic
Conjugation
Secondary Tissue
Damage

Less Toxic
Polar
Water-soluble
Readily Excreted
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Phase I Reactions
Oxidation, reduction, or hydrolysis
Introduce or expose a functional group on
the parent compound
Rendering parent more polar
May activate inert compounds
(e.g. pro-drugs & pro-carcinogens)
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Phase II Reactions
Covalent linkage between parent compound
and a polar (water-soluble) moiety
Phase II Products are generally:
Metabolically Inactive
Prepared for elimination (via bile or urine)

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Imbalanced Detoxification

Non-Polar
Xenobiotic

Phase I

Phase II

CYP P450

Conjugation

Reactive
Intermediate

Damage to DNA,
RNA, Proteins

Inert
Water-Soluble
Metabolite

2014 The Institute for Functional Medicine

Intake&
MedicalHistory

Key
Questionnaires
TEQ

EnvironmentalExposures
KnownToxicExposures:
Occupational,Lifestyle,
Residential,Medical?
FUNCTIONAL
LABTESTS
(ifindicated)

Nutritional
&
Assimilation

PhysicalExam&
ConventionalLabs

MSQ

PatientSensitivityLevel
ToxicitySigns/Symptoms?
NutritionalDeficiencies?
Detox&Elim.Capacity?

Toxic
Damage

Body
Burden

Genetic
Susceptibility

ReviewofFindings&
InterventionProgram
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Intake &
Medical History

Key
Questionnaires
TEQ

Environmental Exposures
Known Toxic Exposures:
Obtain a Historical Implant
List of the Entire Body
what was used and how
did it work
Ask about periodontal
disease
Root Canals if present
3D cone beam evaluation
to screen for infection

Physical Exam &


Conventional Labs

MSQ

Patient Sensitivity Level


Oral soft and hard tissue exam:
Look for red, puffy swollen gums
around crowns; note any
mucosal lesions on cheeks and
tongue
Salivary pH ideal is 6.8+
Oral galvanism Ammeter is
best, chew strip of Aluminum foil
(1x 2) as alternative
Mercury chew test for patients
with Amalgams

2014 The Institute for Functional Medicine

Food Plays a Role in All Phases of


Detoxification
ToxinsIn

PhaseI
Support

ToxinsOut

FOOD
PhaseII
Support

PhaseI
Protection
2014 The Institute for Functional Medicine

ToxinsIn

Phase I Nutrients and Food


Sources on the Detox Food Plan
Nutrient
Riboflavin(vitaminB2)
Niacin(vitaminB3)
Pyridoxine(vitaminB6)
Folicacid
VitaminB12
Glutathione

Branchedchainamino
acids
Flavonoids

Phospholipids

ToxinsOut

PhaseII
Support

PhaseI
Support

PhaseI
Protection

FoodSources
Soybeans,spinach,tempeh,crimini mushrooms,eggs,asparagus,almonds,
turkey
Tuna,chicken,turkey,salmon,lamb,beef,sardines,brownrice
Tuna,turkey,beef,chicken,salmon,sweetpotato,potato,sunflowerseeds,
spinach,banana
Lentils,pintobeans,garbanzobeans,blackbeans,navybeans,turnip
greens,broccoli
Choosemethylcobalamin forsupplementalsource,sardines,salmon,tuna,
cod,lambbeef
Undenatured wheyprotein,asparagus,curcumin,broccoli,avocado,
spinach,garlic,foodshighinvitaminC(e.g.,citrusfruits)andselenium(e.g.,
Brazilnuts)
Wheyprotein,chicken,fish,eggs
Virtuallyallplantfoods,includingapples,apricots,blueberries,pears,
raspberries,strawberries,blackbeans,cabbage,onions,parsley,pinto
beans,andtomatoes
Soy,sunflowerseeds,eggs
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Antioxidant Nutrients and


Phytonutrients that Protect Against
Overproduction of Phase I Metabolites

ToxinsIn

ToxinsOut

PhaseII
Support

PhaseI
Support

PhaseI
Protection

Nutrient

FoodSources

Carotenes(vitaminA)
Ascorbicacid(vitaminC)

Essentiallyallred,orange,yellow,andgreenplantfoods
AllwillbehigherinvitaminCifuncooked:Bellpeppers,papaya,citrusfruits,broccoli,
Brusselssprouts,strawberries,kiwi
Sunflowerseeds,almonds,spinach,Swisschard,avocado,turnipgreens,asparagus,
mustardgreens
Brazilnuts,tuna,sardines,salmon,turkey,cod,chicken,lamb,beef
Sesameseeds,cashews,soybeans,mushrooms(shiitake),sunflowerseeds,tempeh,
garbanzobeans,lentils,walnuts,limabeans
Beef,lamb,sesameseeds,pumpkinseeds,lentils,garbanzobeans,cashews,quinoa,
turkey
Cloves,(glutenfree)oats,brownrice,garbanzobeans,spinach,pineapple,pumpkin
seeds,tempeh,soybeans
Meat,poultry,fish
Chives,daikonradishes,garlic,leeks,onions,scallions,shallots
Virtuallyallplantfoods,includingapples,apricots,blueberries,pears,raspberries,
strawberries,blackbeans,cabbage,onions,parsley,pintobeans,andtomatoes
Milkthistle(herb),artichokes
Smallamountsinthepeels,skins,orseedsofgrapes,blueberries,cherries,andplums

Tocopherols (vitaminE)
Selenium
Copper
Zinc
Manganese
CoenzymeQ10
Thiols
Flavonoids
Silymarin
Pycnogenol

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ToxinsIn

Nutrients for Phase II Conjugation


Pathways

PhaseI
Support

ToxinsOut

PhaseII
Support

PhaseI
Protection

Nutrient

FoodSources

Glycine

Beef,chicken,lamb

Taurine

Fish,meat

Glutamine

Beef,chicken,fish,eggs,cabbage,beets,beans,spinach,
andparsley
Mosthighproteinfoods(e.g.,chicken),garlic,cruciferous
vegetables
Beef,chicken,lamb,fish

Nacetylcysteine
Cysteine
Methionine

Eggwhite/wholeegg,sesameseeds,Brazilnuts,soy
protein,chicken,tuna,beef,chickpea,almonds,pinto
beans,lentils,brownrice

2014 The Institute for Functional Medicine

Sequencing a Detox Program


ReduceorRemove
Alcohol&Caffeine
ArtificialSweeteners
Fats&Sugar
HighAllergenFoods
EnvironmentalToxicants
ToxicHabits
Stressors

Toxin
1 Reduce
Exposure

REMOVE

MayInclude
Vegetables
Citrus
Protein
GoodOils
Fiber
Water
Herb

PotentialTherapeutic
Interventions
Nutraceuticals&Botanicals
Medical/FunctionalFood
LiquidFasting
ChelationTherapy
Hydrotherapy
HomeopathicDrainage

2 Include Dietary 3
Changes

DetoxFoods

Therapeutic Interventions
& Monitoring Therapy

TherapeuticIntervention

MayInclude
MVM/EFAs
BowelSupport
KidneySupport
LiverSupport

4 Maintenance
Maintenance

2014 The Institute for Functional Medicine

Methylation: Interconnections with Folate


Methionine Cycle
Folate Cycle
Neurotransmitter
Cancers

Urea
Periph
Vasc
disease
Asthma

ASCVD

Transsulfuration
Depression
Anxiety
Schizophrenia

Dementias
CNS Pathologies
Autism Spectrum

Adverse Drug
Environmental
Reactions

neuropathies
2014 The Institute for Functional Medicine

2014 The Institute for Functional Medicine