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Leaky gut info
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2015 Online Review Course
Important Schematics and Anchor Slides
Biotransformation&Elimination(e.g.,Toxicity,Detoxification)
Energy(e.g.,EnergyRegulation,MitochondrialFunction)
Communication(e.g.,Endocrine,Neurotransmitters,
Immunemessengers)
Defense&Repair(e.g.,Immune,Inflammation,
Infection/Microbiota)
StructuralIntegrity(e.g.,fromSubcellularMembranesto
MusculoskeletalStructure)
Assimilation(e.g.,Digestion,Absorption,Microbiota/GI,Respiration)
Antecedents(PredisposingFactorsGenetic/Environmental)
TriggeringEvents(Activators)
Exercise&Movement
PersonalizingLifestyleFactorsNutrition&Hydration
PhysiologyandFunction:OrganizingthePatientsClinicalImbalances
Mediators/Perpetuators(Contributors)
Spiritual
e.g.,meaning&purpose,relationshipwithsomething
greater
e.g., cognitivefunction,perceptualpatterns
e.g., emotionalregulation,grief,
sadness,anger,etc.
Sleep&Relaxation
Name:____________________________Date:___________CC:_____________________________________ Copyright2011InstituteforFunctionalMedicine
Stress&Resilience Relationships&Networks
Transport(e.g.,Cardiovascular,LymphaticSystem)
RetellingthePatientsStory
2012 The Institute for Functional Medicine2013 The Institute for Functional Medicine
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CurrentConcerns
Antecedents
TriggersorTriggeringEvents
Signs,SymptomsorDiseasesReported
P
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Birth
2012 The Institute for Functional Medicine2013 The Institute for Functional Medicine2013 The Institute for Functional Medicine
Functional MedicineOperating System
2012 The Institute for Functional Medicine2013 The Institute for Functional Medicine2013 The Institute for Functional Medicine
OO TT TTGG
Gather Oneself & InformationOrganize on Timeline & MatrixTell the Patients StoryOrder of your PrioritiesInitiate Assessment and CareTrack Progress
OO II
2014 The Institute for 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
ClinicalExpertise
EvidenceBasedClinicalPractice
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
Patient Centered Care
Organizing the C
linical Imbalances
2014 The Institute for Functional Medicine
Key functional roles of the Gut:
Digestion/AbsorptionIntestinal PermeabilityGut Microbiota/DysbiosisInflammation/ImmuneNervous 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 Repairof 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
AlteredIntestinal
Permeability
Poor Dietary Choices
Stress & Emotions
Infection
Lectins
Systemic Disease
Toxic Exposure
Food Allergy
Malnutrition
Dysbiosis
Toxic Overload
Elevated TotalToxic & AntigenicBurden
Low Stomach Acid
Systemic Disease
Pathophysiology
2014 The Institute for Functional Medicine
Triggers:nutrientinsufficiency,medication,dysbiosis,parasite,foodreaction,surgery,etc
Portalandsystemicoverload
Bacterial/yeast/protozoa/toxintranslocation
DistantSignsandSymptoms:Systemicillness
DisturbanceofGIflora
Increasedmucosalpermeability
Foodproteintranslocation
Immunologicallymediatedreactions(andperpetuation)
DisruptionofEpithelialTightJunctionsAndMucosalBarrier
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
MechanismsofImmuneandNonImmuneMediatedReactionstoFood
Immunemediated NonImmunemediated(Intolerance)
IgEmediatedreactions
Otherimmunereactions
Toxic(occurringin
anyindividual)
Nontoxic(individualsusceptibility)
Latephase
IgAmediated
Tcellmediated
IgG,Immunecomplexes
Enzymatic(e.g.lactoseintolerance)
Pharmacologic(e.g.vasoactiveamines)
Other(e.g.additiveintolerance
ImmediatePhase
2014 The Institute for Functional Medicine
Gut Permeability and Food Allergies
Clinical & Experimental AllergyVolume 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. IgGIgE IgG
ALLERGY SENSITIVITYOnset 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 Lifelong Months After EliminationAntibody
2014 The Institute for Functional Medicine
The Celiac Iceberg
The celiac iceberg represents all persons genetically susceptible to celiac disease because of a positive celiac-associated 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
Clinical & Experimental Allergy, 2011 (41) 2028.
1
4
32
56
7
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
Prevent infections(systemic and GI)
Regulate local and systemicimmune function
Metabolic pathway nutrients: glycemic control, cholesterol, amino acids
Enhance nutrient utilization
Regulate bowel motility
Regulate appetite(leptin, ghrelin)
Regulate inflammation(local and systemic)
Prevent neoplastic changes
Support mucosalbarrier
Probiotics and Prebiotics: Exploring the Mutually Beneficial Effects of Bacteria and
their Substrates in the Human Host
Prebiotics andProbiotics
2014 The Institute for Functional Medicine
Cancer
Arthritis
AtherosclerosisAlzheimers
Colitis
Psoriasis
Infection
Diabetes
Chronic inflammation plays a role in MOST disease conditions
Eczema
Inflammation
2014 The Institute for Functional Medicine
NFB bindstoDNAleading
activationof..
Leukotrienes Prostaglandins
NFB Activated
InflammatoryTrigger
CyclooxygenaseLipoxygenase
TNF,IL1,IL6
BiologicsRituximabEtanercept,
Etc.
2014 The Institute for Functional Medicine
TissueFactorPAI1
ICAMS,VCAMsSelectin,MIP
iNOS
NFB bindstoDNAleading
totranslationalactivationof..
CyclooxygenaseLipoxygenase
TNF,IL1,IL6OxidativeStress
DietaryComponentsVitamins,Minerals,EssentialFattyAcids,
nonessentialnutrients,Phytochemicals
PPARs NRf2
2014 The Institute for Functional Medicine
2014 The Institute for Functional Medicine
The Inflammatory Process: A Physiologic Algorithm
Antecedents:
Inflammatory Response (itis)
2014 The Institute for Functional Medicine
TriggersStressToxinsFood
InfectionsNutrient Insufficiencies
ThyroidHashimotosThyroiditisGraves Disease
SkinEczemaPsoriasisSclerodermaVitiligo
GI TractCeliacCrohn's DiseaseUlceratic Colitis
NervesPeripheral NeuropathyDiabetic Neuropathy
LungsAsthmaWegnersGranulomatosis
BloodLeukemiaLupusHemolyticDysglycemia
MusclesFibromyalgiaMuscular Dystrophy
BonesRheumatoid ArthritisAnkylosing SpondylitisPolymyalgia Rheumatica
BrainMultiple SclerosisAutismGuillain-Barre SyndromePsychological
2014 The Institute for Functional Medicine
Leaky Barriers: A Common Antecedent for Chronic Inflammatory Disease
2014 The Institute for Functional Medicine
Spectrum of virulence
poliomyelitis in a child0.1-1% of infections are clinically apparent
rubella50% of infections are clinically apparent
rabies100% of infections are clinically apparent
Asymptomatic Infections: The Iceberg Concept
asymptomatic Carrier/health
classical clinical disease
less acute/obviousdisease
Acute infections = obvious infections
Dysbiotic infections = chronic immune activation
Most people probably have some dysbiosis, but many tolerate it
for better or for worse.
2014 The Institute for Functional Medicine
2014 The Institute for Functional Medicine
CysteinylLeukotrienes
Cyclooxygenases(COX1,COX2)
Lipoxygenase
HPETE(hydroxyperoxyeicosatetraenoicacid)
LeukotrieneA4
LeukotrieneC4
LeukotrieneD4
LeukotrieneE4Prostacylcin(PGI2)
Thromboxane(TXA2)
Thromboxane(TXA2)
PGD2
PGE2
PGF2
LTB4
H2O
6ketoPGF1
(endothelium) (platelets)
Glutamicacid
Arachidonic Acid CascadeArachidonicacid(AA)
20:4n6
ProstaglandinH2 (PGH2)
Prostacyclinsynthase
Thromboxanesynthase
PGDSynthase
PGESynthase
GlutathioneStransferase
LipoxinsF2Isoprostanes
2014 The Institute for Functional Medicine
Baselinenutritionaldeficiency
Increasedbaseline
oxidativestressImpaired
immunefunctionImpairedmucosaldefenses
Increasedsusceptibilityto
infection
Exacerbationofnutritiondeficiencies,
tissuedepletion
Facilitatedviralmutation
Directmucosaldamage
Exacerbationofoxidativestress
Anorexia,reducedfoodintake,and
increasedmetabolicandrepairneeds
Increasedfrequency,severity,anddurationof
infection
Facilitatedviral
replication
2014 The Institute for Functional Medicine
Production
Sensitivity
Transport
Detoxification
Production/synthesis and secretion of the hormone
Transport/conversion/distribution/ interaction with other hormones
Cellular sensitivity to the hormone signal
Detoxification/excretion of the hormone
2014 The Institute for Functional Medicine
2014 The Institute for Functional Medicine
DHEASulfateSO4
O
DiHydroTestosterone
OH
O
CH3
CH3
17 hydroxysteroiddehydrogenase Aromatase
11 hydroxysteroiddehydrogenase1&2 Cytochrome3A4
CytochromeP450scc 18hydroxydehydrogenase 17hydroxylase Cytochrome1A1
18hydroxylase 21hydroxylase 11 hydroxylase Cytochrome1B1
17,20lyase 3 hydroxysteroiddehydrogenase,
Isomerase
CatecholOMethylTransferase(COMT)
Sulfatase(SO4)Sulfotransferase(+SO4)5 reductase
EstroneSulfate
16Hydroxyestrone
O
HO
OH
2HydroxyestroneHO
HO
O
4HydroxyestroneHO
HO
O
2MethoxyestroneHO
H3CO
O
4MethoxyestroneHO
OCH3
O
Estriol
OH
HO
OH
Cholesterol
PregnenoloneHO
O
Progesterone
O
O
11deoxycorticosterone
OOH
O
Corticosterone
HOO
OH
O
18OHcorticosterone
HOHO
O
OOH
Aldosterone
OHOHO
O
O
17OHpregnenoloneHO
OHO
17OHprogesteroneO
OHO
11deoxycortisol
OHO
OH
O
Cortisol
HO OHO
OH
O
Cortisone
OH
OHO
O
O
DHEAHO
O OH
SO4
Androstenedione
O
O
Testosterone
OH
OEstradiol
HO
OH
EstroneHO
O
Ster id genic Pathways
2014 The Institute for Functional Medicine
HO
Cholesterol
Pregnenolone
O
HO
Progesterone
O
O
11-deoxycorticosterone
OOH
O
Corticosterone
HO OOH
O
18-OH-corticosterone
HOHO
O
OOH
Aldosterone
OHO OOH
O
17-OH-pregnenoloneHO
OHO
17-OH-progesteroneO
OHO
11-deoxycortisol
OHO
OH
O
Cortisol
OHO
OH
O
OHO
OH
OCortisone
DHEAHO
O
Androstenedione
O
O
Testosterone
OH
OEstradiol
HO
OH
EstroneHO
O
Cortisol Steal
2014 The Institute for Functional Medicine
Primary Effects
(cellular events regulated by primary mediators)
A
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P
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M
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s
a
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d
E
f
f
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Secondary Outcomes
(waist-hip ratio, blood pressure, cholesterol, glucose)
Tertiary Outcomes
(cardiovascular disease, severe cognitive decline, diabetes, hypertension, cancer)
A
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L
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(insulin, immune capacity, glucose tolerance)
Repeated Hits Prolonged Response Inadequate Response
Stress RecoveryRe
s
p
o
n
s
e
Lack of Adaptation
2014 The Institute for Functional Medicine
FactorsthatAffectThyroidFunction
Factorsthatcontributetoproperproductionofthyroidhormones Nutrients:iron,iodine,
tyrosine,zinc,seleniumvitaminE,B2,B3,B6,C,D
Factorsthatinhibitproperproductionofthyroidhormones Stress Infection,trauma,radiation,
medications Fluoride(antagonisttoiodine) Toxins:pesticides,mercury,
cadmium,lead Autoimmunedisease:Celiac
FactorsthatincreaseconversionofT4toT3 Selenium Zinc
Factorsthatimprovecellularsensitivitytothyroidhormones VitaminA Exercise ZincCell
FactorsthatincreaseconversionofT4toRT3 Stress Trauma Lowcaloriediet Inflammation
(cytokines,etc.) Toxins Infections Liver/kidney
dysfunction Certainmedications
T3RT3T3andRT3competeforbindingsites
Nucleus/Mitochondria
T4
2014 The Institute for Functional Medicine
T4
T3 RT3
D35-deiodinase
(Se Independent)
D1 (and D2)5-deiodinase
(Se Dependent)
T2 (inactive)
D35-deiodinase
(Se Independent)
D1 5-deiodinase
(Se Dependent)
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
Stress signal to thecerebral cortex
Visceralbrain
NeurohypothalamusACh
Acute stress
Adrenalmedulla
Sympatheticnervoussystem Epinephrine
release
Chronicstress
Endocrinehypothalamus
CRH Anteriorpituitary
CRHPOMC
-Lipotropin
ACTH
-Endorphin
Adrenalcortex
Cortisolrelease
PNMTinduction
Neuroendocrine Pathways Associated with the Stress Response
Corticotrophinvia Gs
Estrogen Production/Metabolism(the estrogen factory in the breast)
DHEA Androstenediol
Androstenedione Testosterone
AromArom
Estrone Estradiol
STSSULT STSSULT
E1SE2S
DHEAS AdiolS
17HSD1
17HSD2
17HSD5
STS STS
3HSDisomerase
17HSD
17HSD2
17HSD6,2
3HSDisomerase
17HSD217HSD1
2014 The Institute for Functional Medicine
Macronutrients ATP
ATPPool
ProteinFat Carbs
oxidationTCACycle
ETC
2014 The Institute for Functional Medicine
2014 The Institute for Functional Medicine
LipoicAcid
Magnesium
2014 The Institute for Functional Medicine
2014 The Institute for Functional Medicine
Oxidative Stress Exposure to Medications Exposure to Heavy Metals Exposure to Chemicals Exposure to PCBs Exposure to Pesticides
Causes of 2o Mitochondrial Dysfunction
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
reductase2. Dietary Anti-Oxidants
Vitamin C for aqueous compartmentsVitamin E for lipid compartmentsCarotenoids, flavonoids, etc.
3. Endogenous Anti-Oxidant MoleculesGlutathione, cysteine, CoQ10, lipoic acid, uric acid, cholesterol.
2014 The Institute for Functional Medicine
Regulation of Cognitive Function
NeurogenesisNeuroprotection
Synaptic Plasiticity
Sedentary LifestyleDiabetes, ObesityHigh cholesterol
Exercise
Adaptive Cellular Stress
ResponsesBDNFIGFsHSPsUCPs
MnSODHO-1
Oxidative StressInflammation
Impaired Synaptic PlasticityImpaired Neurognesis
Neurodegeneration
Cognitive ImpairmentDisease Progression
Cognitive ImpairmentDisease Progression
Adapted from: Stranahan and Mattson, 2011
Caloric Restriction
Mild Oxidative Stress
PGC-1
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Caloric restriction Physical exercise
DHAMental exercise
BDNF
2014 The Institute for Functional Medicine
2014 The Institute for Functional Medicine
Treatment:
Get adequate nutrition Stay cool and hydrate Prevent infections Supplements:
CoQ-10 Omega-3 Fatty Acids
Exercise (physical & mental) Avoid toxins
a TO DO list to support your mitochondrial function
2014 The Institute for Functional Medicine
AnthropometricsScreening 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
2014 The Institute for Functional Medicine
Body SDefining Body Composition
Pattern Recognition
overfatOVER VAT
overfatOVER VAT
overfatOVER SAT
overfatOVER SAT
OVER WeightOVER Weight
GynoidObesityGynoidObesity
AndroidObesityAndroidObesity
2014 The Institute for Functional Medicine
NO
NO
Increased WC?
Possible High Muscle
Mass or Athlete
NO
Increased BIA Fat%?
YES
Abnormal High BMI?
YES
Dx:OverFatYESYES
NO
Gut/Detox/HPATG dysfunctions?
Assessing Body Composition
YES
NO YES
IdealSkinny Fat or Metabolically
Obese
NO
Increased WHR?
TLCNx/ Rx
Increased WC or WHR?
YES
Increased BIA Fat%?
NO
Increased WHR?
Increased BIA Fat%?
Metabolically Obese
(OverVAT)
YESNO
Gynoid Obesity/overSAT
Gynoid Obesity/overSAT
Possible High Muscle Mass
or Large Skeletal Frame
Increased BIA Fat%?
Dx:Overweight/Obese
Android Obesity(OverVAT)
MetSyn?
Dx:OverVAT
YES
YES
2014 The Institute for Functional Medicine
2014 The Institute for Functional Medicine
Role of ROS on Hypertension and Hyperlipidemia and Atherosclerosis
A-II
AT1 Receptor
NAD(P)H Oxidase
CytokinesGrowth Factors
O2 (Superoxide Anion)Ox LDL Inactivates NO
Upregulates
LOX-1Endothelial
Receptor for Ox LDLHypertension
Foam CellsFatty Streaks
HypertrophyProliferationED
Atherosclerosis
2014 The Institute for Functional Medicine
InsulinResistance
Chronic Stress
Genetic propensity
Elevated Fasting and PP
Insulin & Glucose
Visceral Adiposity
Lack of ExerciseSmoking
High Glycemic Diet
Inflammation
Antecedents, Triggers and MediatorsAntecedents, Triggers and Mediators
Sleep
2014 The Institute for Functional Medicine
Treatments that Change Risk Differentially
statins
statin + ezetimibe
low fat diet
Lipid-RichDISORDERS
omega 3 fatty acids fibrates niacin exercise low glycemic impact diet
Triglyceride-RichDISORDERS
METABOLICCARDIOCOMPREHENSIVE RISK REDUCTION
2014 The Institute for Functional Medicine
The Road to Diabetes: Insulin Resistance and Hyperinsulinemia
Overproductionof FFAs
by adipose cells
Glucose toxicity leading to further impaired insulin secretion
Inability to suppress hepatic glucose
production
Stimulates gluconeogenesisIncreases muscle insulin resistance
Impairs insulin secretion
Increased muscle cellresistance toinsulin action
Elevated serumglucose
Elevated serumglucose Elevated serum glucose
2014 The Institute for Functional Medicine
Type 2 Diabetes
Hypertension
Dyslipidemia
Cardiovascular Disease
Osteoporosis
Obesity
PCOSNASH
Cognitive Decline / Alzheimer's Disease
Sarcopenia
Erectile Dysfunction
Sleep Apnea
Clinical Consequences of CardioMetSynClinical Consequences of CardioMetSyn
CardioMetSynCardioMetSyn
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2014 The Institute for Functional Medicine
Communicate this
2014 The Institute for Functional Medicine
Inflammatory elements Inconsistent behaviors Imbalanced fats High glycemic impact
Standard American Diet
Healthy foods Phytonutrient dense Balanced diet
Core Food Plan Foods tailored to a
clinical condition Detox and Cleansing Elimination/Allergies CARDIOMETABOLIC
Modified Therapeutic Intervention
Clinical Use of Food as Medicine
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Basic Toxicology
Exposure
Assimilation
Retention
Toxicity
2014 The Institute for Functional MedicineFrom. Larry Needham, PhD: CDC NCEH Presentation (2004)
2014 The Institute for Functional Medicine
Periodontal Disease
Root Canals Mercury Amalgams
Mixed Metal/Base Metal
Crowns
Orthodontic Appliances
Dental Implants
Genetics Epigenetics Lifestyle Quality of Care
InflammationOxidative
StressImmune
Dysregulation
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TOTAL TOXIC LOADequals
Total Toxic Exposure minus
Ability to Detoxify and
Excrete Toxins
2014 The Institute for Functional Medicine
KnownEffects
The Limits of Certainty and Under-recognition of Toxic Threats
THE UNKNOWN
UNKNOWN
WHATWEKNOW
WHATWEDONTKNOW
Long latency effects
2014 The Institute for Functional Medicine
Thereiswidevariationinindividualsensitivitytotoxicantexposure.Thismeansthatinalargepopulationwithwidespreadexposures,evenwhenthedosageisacceptableonaverage,manypeoplewillstillbehurt.Asignificantmarginofsafetyisrequiredtopreventsuchinjuries.From:InHarmsWay:ToxicThreatstoChildDevelopment.GreaterBostonPSR
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heavymetals(Pb,Hg,As,Cd)
polycyclicaromatichydrocarbons
(PAH)
phthalates(i.e.plasticizers)
phenols(BPA,triclosan)
organochloride(OC)pesticides
organophosphate(OP)pesticides
polychlorinateddibenzodioxins
(PCDDs)&furans (PCDFs)
polychlorinatedbiphenyls(PCBs)
polybrominateddiphenyl ethers
(PBDEs)
polyfluorinatedcompounds(PFCs)
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Pattern Recognition
Undernourished
Reduce Exposures
Ensure a Safe Detox
2014 The Institute for Functional MedicineLiska;ExploreMarch2006,Vol 2,No2,pg125
2014 The Institute for Functional Medicine
Types of Reactions
Phase ICytochromeP450enzymes:
OxidationReductionHydrolysis
Parent Compound
Water-Soluble
Compound
Phase IIGlucuronosyl TransferaseSulfotransferasesAminoAcidConjugationGlutathioneConjugationAcetylation
ActivatedIntermediate
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The Role of Nutritional Factors in Liver Detoxification
FreeRadicals
Toxins Conjugated MetabolitesToxic
IntermediatesPhase I Phase II
Phase INutritional Support
AntioxidantsVitamin & Mineral Cofactors
Phase IINutritional Support
Conjugating AgentsVitamin & Mineral Cofactors
XenobioticsEndotoxins
Non-Polar, Lipophilic Poorly Excreted
Cytochrome P-450Mixed Oxidase System
Secondary Tissue Damage
EnzymaticConjugation
Less ToxicPolar
Water-solubleReadily Excreted
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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)
Phase I Reactions
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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
Phase ICYP P450
Phase IIConjugation
Damage to DNA, RNA, Proteins
Reactive Intermediate
Non-Polar Xenobiotic
InertWater-Soluble
Metabolite
2014 The Institute for Functional Medicine
PhysicalExam&ConventionalLabs
Intake&MedicalHistory
KeyQuestionnaires
KnownToxicExposures:Occupational,Lifestyle,Residential,Medical?
ToxicitySigns/Symptoms?NutritionalDeficiencies?Detox&Elim.Capacity?
ToxicDamage
Nutritional&
Assimilation
BodyBurden
EnvironmentalExposures PatientSensitivityLevel
MSQTEQ
ReviewofFindings&InterventionProgram
FUNCTIONALLABTESTS(ifindicated)
GeneticSusceptibility
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Physical Exam & Conventional Labs
Intake & Medical History
Key Questionnaires
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
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
Environmental Exposures Patient Sensitivity Level
MSQTEQ
2014 The Institute for Functional Medicine
Food Plays a Role in All Phases of Detoxification
ToxinsIn
PhaseISupport
PhaseIProtection
PhaseIISupport
ToxinsOut
FOOD
2014 The Institute for Functional Medicine
Phase I Nutrients and Food Sources on the Detox Food Plan
ToxinsIn
PhaseISupport
PhaseIProtection
PhaseIISupport
ToxinsOut
Nutrient FoodSourcesRiboflavin(vitaminB2) Soybeans,spinach,tempeh,crimini mushrooms,eggs,asparagus,almonds,
turkeyNiacin(vitaminB3) Tuna,chicken,turkey,salmon,lamb,beef,sardines,brownricePyridoxine(vitaminB6) Tuna,turkey,beef,chicken,salmon,sweetpotato,potato,sunflowerseeds,
spinach,bananaFolicacid Lentils,pintobeans,garbanzobeans,blackbeans,navybeans,turnip
greens,broccoliVitaminB12 Choosemethylcobalamin forsupplementalsource,sardines,salmon,tuna,
cod,lambbeefGlutathione Undenatured wheyprotein,asparagus,curcumin,broccoli,avocado,
spinach,garlic,foodshighinvitaminC(e.g.,citrusfruits)andselenium(e.g.,Brazilnuts)
Branchedchainaminoacids
Wheyprotein,chicken,fish,eggs
Flavonoids Virtuallyallplantfoods,includingapples,apricots,blueberries,pears,raspberries,strawberries,blackbeans,cabbage,onions,parsley,pintobeans,andtomatoes
Phospholipids Soy,sunflowerseeds,eggs
2014 The Institute for Functional Medicine
Antioxidant Nutrients and Phytonutrients that Protect Against Overproduction of Phase I Metabolites
Nutrient FoodSourcesCarotenes(vitaminA) Essentiallyallred,orange,yellow,andgreenplantfoodsAscorbicacid(vitaminC) AllwillbehigherinvitaminCifuncooked:Bellpeppers,papaya,citrusfruits,broccoli,
Brusselssprouts,strawberries,kiwiTocopherols (vitaminE) Sunflowerseeds,almonds,spinach,Swisschard,avocado,turnipgreens,asparagus,
mustardgreensSelenium Brazilnuts,tuna,sardines,salmon,turkey,cod,chicken,lamb,beefCopper Sesameseeds,cashews,soybeans,mushrooms(shiitake),sunflowerseeds,tempeh,
garbanzobeans,lentils,walnuts,limabeansZinc Beef,lamb,sesameseeds,pumpkinseeds,lentils,garbanzobeans,cashews,quinoa,
turkeyManganese Cloves,(glutenfree)oats,brownrice,garbanzobeans,spinach,pineapple,pumpkin
seeds,tempeh,soybeansCoenzymeQ10 Meat,poultry,fishThiols Chives,daikonradishes,garlic,leeks,onions,scallions,shallotsFlavonoids Virtuallyallplantfoods,includingapples,apricots,blueberries,pears,raspberries,
strawberries,blackbeans,cabbage,onions,parsley,pintobeans,andtomatoesSilymarin Milkthistle(herb),artichokesPycnogenol Smallamountsinthepeels,skins,orseedsofgrapes,blueberries,cherries,andplums
ToxinsIn
PhaseISupport
PhaseIProtection
PhaseIISupport
ToxinsOut
2014 The Institute for Functional Medicine
Nutrients for Phase II Conjugation Pathways
Nutrient FoodSources
Glycine Beef,chicken,lamb
Taurine Fish,meat
Glutamine Beef,chicken,fish,eggs,cabbage,beets,beans,spinach,andparsley
Nacetylcysteine Mosthighproteinfoods(e.g.,chicken),garlic,cruciferousvegetables
Cysteine Beef,chicken,lamb,fish
Methionine Eggwhite/wholeegg,sesameseeds,Brazilnuts,soyprotein,chicken,tuna,beef,chickpea,almonds,pintobeans,lentils,brownrice
ToxinsIn
PhaseISupport
PhaseIProtection
PhaseIISupport
ToxinsOut
2014 The Institute for Functional Medicine
Sequencing a Detox Program
REMOVE DetoxFoods
PotentialTherapeuticInterventions
Nutraceuticals&BotanicalsMedical/FunctionalFoodLiquidFastingChelationTherapyHydrotherapyHomeopathicDrainage
1 2 3Reduce Toxin ExposureInclude Dietary Changes
ReduceorRemoveAlcohol&CaffeineArtificialSweetenersFats&SugarHighAllergenFoodsEnvironmentalToxicantsToxicHabitsStressors
MayIncludeVegetablesCitrusProteinGoodOilsFiberWaterHerb
4 Maintenance Therapeutic Interventions & Monitoring TherapyTherapeuticIntervention Maintenance
MayIncludeMVM/EFAsBowelSupportKidneySupportLiverSupport
2014 The Institute for Functional Medicine
Methylation: Interconnections with Folate
Folate CycleMethionine Cycle
Transsulfuration
NeurotransmitterUrea Cancers
ASCVD
Adverse DrugEnvironmental
Reactions
DepressionAnxietySchizophrenia
PeriphVascdiseaseAsthma
neuropathies
DementiasCNS PathologiesAutism Spectrum
2014 The Institute for Functional Medicine
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