This was developed by the Institute for Functional Medicine. It provides a concise explanation of the new paradigm of medicine that focuses on underlying causes of disease and treatment from that level rather treating symptoms alone, the approach often taken by modern medicine. The presentation clearly differentiates between these approaches and discusses how they can be used in a complementary fashion to benefit patients. We included this presentation here because it explains how testing such as that provided by Metametrix is being used to identify underlying causes of health problems.

1. At the heart of medicine lies the individual and each patient’s unique story… At the heart of medicine lies the individual and each patient’s unique story…

4. In acute care, the patient’s story is squeezed down to the chief complaint and history of the present illness while the diagnosis increases in importance.

5. Example #1 Chief Complaint: Wheezing Diagnosis: Asthma Attack bronchodilators corticosteroids tightness in the chest sudden onset asthmatic history shortness of breath History of Present Illness

6. Example #2 Chief Complaint: Chest Pain Diagnosis: Heart Attack angioplasty thrombolytics sweating arm numbness shortness of breath History of Present Illness

8. Hypercholest- erolemia Statin Gastroesophageal Reflux Disease H2 blocker Depression SSRI Hypertension ACE inhibitor Migraines Triptan Osteoarthritis NSAID Irritable Bowel Syndrome Dicyclomine … the result is a focus on treating each symptom complex as a separate and distinct “disease” with a separate and distinct treatment.

9. Each individual diagnosis becomes a distinct entity unto itself. The patient’s whole story never has a chance to be heard and understood In context. Hypercholest- erolemia Statin Gastroesophageal Reflux Disease H2 blocker Depression SSRI Hypertension ACE inhibitor Migraines Triptan Osteoarthritis NSAID Irritable Bowel Syndrome Dicyclomine

10. It is apparent that – in its rush to diagnose – conventional medicine is focused on the branches and leaves of the tree, and not the trunk and roots. Cardiology Pulmonary Endocrinology Gastroenterology Neurology Organ System Diagnosis Urology/Nephrology Hepatology Allergy Signs and Symptoms Fundamental Clinical Imbalances Hormonal and Neurotransmitter Imbalances Redox Imbalance + Oxidative Stress + Mitochondropathy Detox/Biotransformation/Excretory Imbalance Immune Imbalance Inflammatory Imbalance Digestive/Absorptive and Microbiological Imbalance Structural Integrity Imbalance 1. Communication - Outside the cell - Inside the cell Mind and Spirit Genetic Predisposition Experiences, Attitudes, Beliefs Psycho-social Physical Exercise Trauma Diet, Nutrients, Air/Water Xenobiotics Micro-organisms Radiation Environmental Inputs 2. Bioenergetics/Energy Transformation 3. Replication/Repair/Maintenance/ Structural Integrity 4. Elimination of Waste 5. Protection/Defense 6. Transport/Circulation Fundamental Physiological Processes

11. Functional medicine should not be viewed as an alternative, but as a bridge to a more effective chronic-care model.

13. First, the full story must be understood within the context of antecedents, triggers, and mediators antecedents and triggers mediators To answer these questions requires a new perspective on the chronic-care model

14. Infectious micro- organisms Structural or physical damage Nutrient insufficiency Xenobiotics Disrupted light cycles —c ircadian dysrhythmias Radiation Emotional trauma Spiritual angst Nutrient excess Food toxicants (allergens, stimulants, etc,) Drug side effects Adiposity Toxic metals Aging Situational stress – fear, anxiety, worry Genetic pre- disposition (SNPs) Hyperglycemia Hypoglycemia Excessive exercise Excessive noise Dysbiosis The story is no longer just the CC and HPI, but is expanded to encompass all the patient’s history that may reveal the source(s) of symptoms.

15. Infectious micro- organisms Structural or physical damage Nutrient insufficiency Xenobiotics Radiation Emotional trauma Spiritual angst Nutrient excess Food toxicants (allergens, stimulants, etc,) Drug side effects Adiposity Toxic metals Psychological and Spiritual Equilibrium Hormone and Neurotransmitter Regulation Detoxification and Biotransformation Structural Integrity Immune Surveillance Digestion, Absorption, and Barrier Integrity Oxidative/Reductive Homeodynamics Inflammatory Process Aging Genetic pre- disposition (SNPs) Next, the patient’s story is filtered through these antecedents, triggers, and mediators, which leads to an understanding of where key imbalances may reside Disrupted light cycles —c ircadian dysrhythmias Hyperglycemia Hypoglycemia Excessive exercise Noise Situational stress – fear, anxiety, worry Dysbiosis The diagnosis remains useful, but is less important. These fundamental clinical imbalances are the underlying mechanisms of disease …

16. Exercise Acupuncture Manipulative Therapies Phytonutrients Minerals Vitamins Diet Yoga Drugs Surgery Counseling The expanded model permits the clinician to choose from an enlarged toolkit of therapies. Meditation

17. Let’s apply the functional medicine model to an apparently simple case… … a 37 year old female with a chief complaint of chronic headaches.

18. Diagnosis: Migraines Treatment: Triptan Chief Complaint: Headaches History of present illness We’ve already seen how she might be treated using the existing model.

19. But her case may not be as simple as it appears…

20. From a functional medicine perspective, the CC and HPI must be filtered through the relevant antecedents, triggers, and mediators. To understand the patient’s complete picture, past medical history, family history, diet, medications, and lifestyle all need to be viewed through this lens as well. Psychological and Spiritual Equilibrium Detoxification and Biotransformation Structural Integrity Immune Surveillance Inflammatory Process Hormone and Neurotransmitter Regulation Digestion, Absorption, and Barrier Integrity Oxidative/Reductive Homeodynamics

21. Psychological and Spiritual Equilibrium Detoxification and Biotransformation Structural Integrity Immune Surveillance Inflammatory Process A variety of potential antecedents, triggers, and mediators might be present in a woman with a chief complaint of chronic headaches: Hormone and Neurotransmitter Regulation Digestion, Absorption, and Barrier Integrity Oxidative/Reductive Homeodynamics

22. Psychological and Spiritual Equilibrium Hormone and Neurotransmitter Regulation Detoxification and Biotransformation Structural Integrity Immune Surveillance Digestion, Absorption, and Barrier Integrity Oxidative/Reductive Homeodynamics Inflammatory Process Food allergen Food Allergen Food allergen Circadian rhythm Situational stress Exposure to toxins Exposure to toxins Headaches triggered by food allergen Headaches triggered by menstrual cycle Headaches triggered by stress Headaches triggered by exposure to toxins MSG, aspartame, smoke, perfume Headaches triggered by changes in sleep Headaches triggered by fasting Estrogen dominance Circadian rhythm Hypoglycemia

23. Psychological and Spiritual Equilibrium Hormone and Neurotransmitter Regulation Detoxification and Biotransformation Structural Integrity Immune Surveillance Digestion, Absorption, and Barrier Integrity Oxidative/Reductive Homeodynamics Inflammatory Process Past medical history leads to additional clues: Food Allergen Food Allergen Food Allergen Estrogen dominance Circadian Rhythm Circadian Rhythm Situational Stress Hypoglycemia Exposure to toxins Exposure to toxins Past or recurrent infections Adiposity Surgeries Surgeries Surgeries Past or recurrent infections Past or recurrent infections Adiposity Adiposity Adiposity Adiposity Accidents or Injuries Emotional trauma Exposure to toxins Accidents, injuries Accidents, injuries Accidents, injuries Emotional trauma Emotional trauma Emotional trauma Exposure to toxins Exposure to toxins Exposure to toxins Exposure to toxins Chronic Disease Chronic disease Chronic disease Chronic antibiotic use Chronic antibiotic use —d ysbiosis Chronic antibiotic use Chronic antibiotic use

24. Psychological and Spiritual Equilibrium Hormone and Neurotransmitter Regulation Detoxification and Biotransformation Structural Integrity Immune Surveillance Digestion, Absorption, and Barrier Integrity Oxidative/Reductive Homeodynamics Inflammatory Process Estrogen dominance Circadian Rhythm Circadian Rhythm Situational Stress Hypoglycemia Exposure to toxins Exposure to toxins Surgeries Surgeries Past or recurrent infections Past or recurrent infections Adiposity Adiposity Adiposity Adiposity Accidents, injuries Accidents, injuries Accidents, injuries Emotional trauma Emotional trauma Emotional trauma Exposure to toxins Exposure to toxins Exposure to toxins Exposure to toxins Chronic disease Chronic disease Chronic antibiotic use —d ysbiosis Chronic antibiotic use Chronic antibiotic use Family history may indicate genetic predispositions: Food allergen Food allergen Food allergen Inflammatory conditions such as RA, UC, etc. Allergies Predisposition to inflammation

25. Psychological and Spiritual Equilibrium Hormone and Neurotransmitter Regulation Detoxification and Biotransformation Structural Integrity Immune Surveillance Digestion, Absorption, and Barrier Integrity Oxidative/Reductive Homeodynamics Inflammatory Process Estrogen dominance Circadian Rhythm Circadian Rhythm Situational Stress Hypoglycemia Exposure to toxins Exposure to toxins Surgeries Surgeries Past or recurrent infections Past or recurrent infections Adiposity Adiposity Adiposity Adiposity Accidents, injuries Accidents, injuries Accidents, injuries Emotional trauma Emotional trauma Emotional trauma Exposure to toxins Exposure to toxins Exposure to toxins Exposure to toxins Chronic disease Chronic disease Chronic antibiotic use —d ysbiosis Chronic antibiotic use Chronic antibiotic use Food allergen Food allergen Food allergen Predisposition to inflammation Dietary History Dietary insufficiencies…antioxidants, magnesium, fiber, EFAs, etc. Dietary excesses: saturated fat, simple sugars, caffeine, alcohol, etc. Nutrient insufficiencies—EFAs, etc. Nutrient insufficiencies – sulfur, amino acids, etc. Nutrient insufficiencies Nutrient insufficiencies – zinc, glutamine – leaky gut Nutrient insufficiencies antioxidants Nutrient insufficiencies Nutrient excess — alcohol Nutrient excess — caffeine Nutrient excess – simple sugars Nutrient excess —s aturated fat Dietary toxins…mercury, exogenous estrogens, etc. Dietary toxin — mercury Dietary toxin-mercury Dietary toxin — mercury Dietary toxins – exogenous estrogens Dietary toxin – mercury

26. Psychological and Spiritual Equilibrium Hormone and Neurotransmitter Regulation Detoxification and Biotransformation Structural Integrity Immune Surveillance Digestion, Absorption, and Barrier Integrity Oxidative/Reductive Homeodynamics Inflammatory Process Estrogen dominance Circadian Rhythm Circadian Rhythm Situational Stress Hypoglycemia Exposure to toxins Exposure to toxins Surgeries Surgeries Past or recurrent infections Past or recurrent infections Adiposity Adiposity Adiposity Adiposity Accidents, injuries Accidents, injuries Accidents, injuries Emotional trauma Emotional trauma Emotional trauma Exposure to toxins Exposure to toxins Exposure to toxins Exposure to toxins Chronic disease Chronic disease Chronic antibiotic use —d ysbiosis Chronic antibiotic use Chronic antibiotic use Food allergen Food allergen Food allergen Predisposition to inflammation Nutrient insufficiencies—EFAs, etc. Nutrient insufficiencies – sulfur, amino acids, etc. Nutrient insufficiencies Nutrient insufficiencies – zinc, glutamine – leaky gut Nutrient insufficiencies antioxidants Nutrient insufficiencies Nutrient excess — alcohol Nutrient excess — caffeine Nutrient excess – simple sugars Nutrient excess —s aturated fat Dietary toxin — mercury Dietary toxin-mercury Dietary toxin — mercury Dietary toxins – exogenous estrogens Dietary toxin – mercury Medication History Drug side effects Drug side effects-inhibit or promote Drug side effects Drug side effects Drug side effects

27. Psychological and Spiritual Equilibrium Hormone and Neurotransmitter Regulation Detoxification and Biotransformation Structural Integrity Immune Surveillance Digestion, Absorption, and Barrier Integrity Oxidative/Reductive Homeodynamics Inflammatory Process Estrogen dominance Circadian Rhythm Circadian Rhythm Situational Stress Hypoglycemia Exposure to toxins Surgeries Surgeries Past or recurrent infections Past or recurrent infections Adiposity Adiposity Adiposity Adiposity Accidents, injuries Accidents, injuries Accidents, injuries Emotional trauma Emotional trauma Emotional trauma Exposure to toxins Exposure to toxins Exposure to toxins Exposure to toxins Chronic disease Chronic disease Chronic antibiotic use —d ysbiosis Chronic antibiotic use Chronic antibiotic use Food allergen Food allergen Food allergen Predisposition to inflammation Nutrient insufficiencies—EFAs, etc. Nutrient insufficiencies – sulfur, amino acids, etc. Nutrient insufficiencies Nutrient insufficiencies – zinc, glutamine – leaky gut Nutrient insufficiencies antioxidants Nutrient insufficiencies Nutrient excess — alcohol Nutrient excess — caffeine Nutrient excess – simple sugars Nutrient excess —s aturated fat Dietary toxin — mercury Dietary toxin-mercury Dietary toxin — mercury Dietary toxins – exogenous estrogens Dietary toxin – mercury Drug side effects-inhibit or promote Drug side effects Drug side effects Drug side effects Hobbies Exercise Relationships Recreational Drugs Spirituality Lack of exercise Lack of exercise Lack of exercise Lack of exercise Lack of exercise Lack of exercise Spiritual angst Loneliness Loneliness Loneliness Spiritual angst Over or improper exercise Lifestyle Alcohol-leaky gut Inhibit or promote Exposure to toxins

28. Psychological and Spiritual Equilibrium Hormone and Neurotransmitter Regulation Detoxification and Biotransformation Structural Integrity Immune Surveillance Digestion, Absorption, and Barrier Integrity Oxidative/Reductive Homeodynamics Inflammatory Process A variety of potential laboratory assessments can then be useful in confirming key imbalances on which to focus. Cortisol, DHEA Glucose, insulin, HA1C TSH, Free T3, Free T4 Estrogen, Progesterone, Testosterone 2/16 ratio 8-OHdG Isoprostanes Reduced glutathione Lipid peroxides Gait Motion Analysis N-telopeptide Magnetic Resonance Imaging X-ray Bacterial Overgrowth Small Intestine Fecal Ova and Parasites Candida Antibodies Lactulose Mannitol IgG and IgG food allergy Chemical antibodies Salivary Secretory IgA Natural Killer Cell Cytotoxicity Activity High-sensitivity CRP RBC Fatty Acids Fecal Lactoferrin Fecal Calprotectin Urinary Serotonin, Dopamine Serum Amino Acids Homocysteine, folate, B12 RBC Fatty Acids Caffeine Clearance, Glucuronidation, Sulfation Hair toxic Elements Urinary Provocation/Challenge SNP Cyp P450

29. Psychological and Spiritual Equilibrium Hormone and Neurotransmitter Regulation Detoxification and Biotransformation Structural Integrity Immune Surveillance Digestion, Absorption, and Barrier Integrity Oxidative/Reductive Homeodynamics Inflammatory Process Food allergen Food allergen Specifically, what was this 37 year old female’s story? Headaches triggered by diet

30. Psychological and Spiritual Equilibrium Hormone and Neurotransmitter Regulation Detoxification and Biotransformation Structural Integrity Immune Surveillance Digestion, Absorption, and Barrier Integrity Oxidative/Reductive Homeodynamics Inflammatory Process Dysbiosis What are the clues in her past medical history? History of chronic sinusitis Food allergen Food allergen History of multiple antibiotics Drug side effects leaky gut Structural damage Gas and bloating Digestive enzyme/HCL insufficiency Inflammatory damage History of osteoarthritis of the knee

31. Psychological and Spiritual Equilibrium Hormone and Neurotransmitter Regulation Detoxification and Biotransformation Structural Integrity Immune Surveillance Digestion, Absorption, and Barrier Integrity Oxidative/Reductive Homeodynamics Inflammatory Process Dysbiosis Food allergen Food allergen Structural damage Digestive enzyme/HCL insufficiency Inflammatory damage Nutrient insufficiency – low EFAs, high AA Standard American Diet NSAIDS for OA Drug side effects – leaky gut What are the clues in her diet and medications?

32. Psychological and Spiritual Equilibrium Hormone and Neurotransmitter Regulation Detoxification and Biotransformation Structural Integrity Immune Surveillance Digestion, Absorption, and Barrier Integrity Oxidative/Reductive Homeodynamics Inflammatory Process Dysbiosis Food allergen Food allergen Structural damage Digestive enzyme/HCL insufficiency Inflammatory damage Nutrient insufficiency – low EFAs, high AA Drug side effects – leaky gut What are the clues in her family history? Ulcerative Colitis Eczema Inflammatory genetic predisposition

33. Psychological and Spiritual Equilibrium Hormone and Neurotransmitter Regulation Detoxification and Biotransformation Structural Integrity Immune Surveillance Digestion, Absorption, and Barrier Integrity Oxidative/Reductive Homeodynamics Inflammatory Process Dysbiosis Food allergen Food allergen Structural damage Digestive enzyme/HCL insufficiency Inflammatory damage Nutrient insufficiency – low EFAs, high AA Drug side effects – leaky gut Through critical thinking and pattern recognition, a therapeutic plan can be developed. In this case, the primary focus centers on three areas

34. Psychological and Spiritual Equilibrium Hormone and Neurotransmitter Regulation Detoxification and Biotransformation Structural Integrity Immune Surveillance Digestion, Absorption, and Barrier Integrity Oxidative/Reductive Homeodynamics Inflammatory Process Dysbiosis Food allergen Food allergen Structural damage Digestive enzyme/HCL insufficiency Inflammatory damage Nutrient insufficiency – low EFAs, high AA Drug side effects – leaky gut Laboratory analysis can be used to help confirm the prioritization Hs-CRP RBC fatty acids IgG/IgE food allergy Digestive stool analysis Ova and parasite Intestinal permeability

35. Psychological and Spiritual Equilibrium Hormone and Neurotransmitter Regulation Detoxification and Biotransformation Structural Integrity Immune Surveillance Digestion, Absorption, and Barrier Integrity Oxidative/Reductive Homeodynamics Inflammatory Process The prioritization of certain key clinical imbalances then leads to potential treatment options Dietary changes to lower arachidonic acid and the inflammatory cascade Omega-3 fatty acids to decrease inflammation Botanicals such as bromelain and curcumin to decrease inflammation Phytonutrients such as rutin and quercitin to decrease IP Pre and probiotics Decrease alcohol to decrease intestinal permeability Hydrochloric acid/digestive enzyme Food elimination diet

36. Functional medicine enlarges the chronic care model to encompass the full and unique story of the patient Finally it increases the range of potential treatment options It integrates underlying mechanisms of disease into the differential diagnosis paradigm

37. Exercise Acupuncture Manipulative Therapies Phytonutrients Minerals Vitamins Diet Yoga Drugs Surgery Counseling Meditation Psychological and Spiritual Equilibrium Hormone and Neurotransmitter Regulation Detoxification and Biotransformation Structural Integrity Immune Surveillance Digestion, Absorption, and Barrier Integrity Oxidative Reductive Homeodynamics Inflammatory Process Infectious micro- organisms Structural or physical damage Nutrient insufficiency Xenobiotics Radiation Emotional trauma Spiritual angst Nutrient excess Food toxicants (allergens, stimulants etc,) Drug side effects Adiposity Toxic metals Aging Genetic pre-disposition (SNPs) Disrupted light cycles – c ircadian dysrhythmias Hyperglycemia Hypoglycemia Excessive exercise Excessive noise Situational stress – fear, anxiety, worry Dysbiosis The functional medicine model recognizes and prioritizes the patient’s full, unique story and uses fundamental clinical imbalances as a key to treating complex, chronic illness

39. Cardiology Pulmonary Endocrinology Gastroenterology Neurology Organ System Diagnosis Urology/Nephrology Hepatology Allergy Signs and Symptoms Fundamental Clinical Imbalances Hormonal and Neurotransmitter Imbalances Redox Imbalance + Oxidative Stress + Mitochondropathy Detox/Biotransformation/Excretory Imbalance Immune Imbalance Inflammatory Imbalance Digestive/Absorptive and Microbiological Imbalance Structural Integrity Imbalance 1. Communication - Outside the cell - Inside the cell Mind and Spirit Genetic Predisposition Experiences, Attitudes, Beliefs Psycho-social Physical Exercise Trauma Diet, Nutrients, Air/Water Xenobiotics Micro-organisms Radiation Environmental Inputs 2. Bioenergetics/Energy Transformation 3. Replication/Repair/Maintenance/ Structural Integrity 4. Elimination of Waste 5. Protection/Defense 6. Transport/Circulation Fundamental Physiological Processes