Textbook of Natural Medicine - 5th Edition

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To Dr. John Bastyr and all the natural healers of the past and future who
bring the “healing power of nature” to all the people of the world.
Dr. Bastyr, the namesake for Bastyr University, exemplified the ideal
physician/healer/teacher we endeavor to become in our
professional lives.
We pass on a few of his words of wisdom to all who strive to provide the
best of health care and healing: “Always touch your patients—let them
know you care,” and “Always read at least one research article or learn
a new remedy before you retire at night.”
CONTRIBUTORS
Kathy Abascal, BS, JD, RH(AHG) Warren M. Brown, ND Terry M. Elder, DC
Vashon, Washington Clinical Science Liaison Instructor
Medical Affairs Clinical Sciences
Yaser Abdelhamid, ND, LAc, MS, BS, BA Genova Diagnostics National University of Health Sciences
Licensed Acupuncturist Asheville, North Carolina Lombard, Illinois
Center for Integrative and Lifestyle
Medicine Michael J. Chapman, ND Geovanni Espinosa, ND, LAc, IFMCP,
Cleveland Clinic Medical Education Specialist CNS
Cleveland, Ohio Medical Affairs Faculty Clinical Assistant Professor
Genova Diagnostics NYU Langone Health, Urology
Zemphira Alavidze, PhD Asheville, North Carolina Educator
Institute for Functional Medicine
Lise Alschuler, ND Alan G. Christianson, NMD New York, New York
Professor of Clinical Medicine Assistant President and Executive
Director, and Fellowship in Integrative Integrative Health Ralph Esposito, ND, LAc
Medicine Scottsdale, Arizona Adjunct Faculty
Program of Integrative Medicine New York University
University of Arizona Anthony J. Cichoke Jr., BS, BS, MA, MA, New York, New York
Tucson, Arizona PhD, DC, DACBN
Portland, Oregon Susan Ann Gaylord, PhD
Sidney MacDonald Baker, MD Director, Program on Integrative Medicine
Independent Retirement Home George W. Cody, JD, MA Physical Medicine and Rehabilitation
Sag Harbor, New York Consulting Historian University of North Carolina (UNC)
Edmonds, Washington Chapel Hill, North Carolina
Stephen Barrie, ND, PhD Associate Professor
Senior Executive Kevin L. Conroy, ND Physical Medicine and Rehabilitation
Viome Owner UNC School of Medicine
Bellevue, Washington Private Practice Chapel Hill, North Carolina
Port Angeles Natural Health
David Barry, BS, BAppSci (Hons), DC, ND Port Angeles, West Virginia Alan Goldhamer, DC
Clinical Research Coordinator Director
Emeritus Research Peter J. D’Adamo, ND, MIFHI Residential Health Education Program
Camberwell, Victoria, Australia Professor Clinical Sciences TrueNorth Health Center
Senior Lecturer, Naturopathy University of Bridgeport College of Santa Rosa, California
Endeavour College of Natural Health Naturopathic Medicine Chairman of the Board
Melbourne, Victoria, Australia Coder/Developer Opus 23 & SWAMI Research/Education
TrueNorth Health Foundation
Peter W. Bennett, ND Jade Dandy, ND, MSiMR Santa Rosa, California
Clinic Director The Healing Hut Clinic
Patient Care Eagle, Idaho Andrea Gruszecki, ND
Meditrine Naturopathic Medical Clinic National University of Natural Science Support Specialist
Langley, British Columbia, Canada Medicine Meridian Valley Laboratory
Portland, Oregon Tukwilla, Washington
Bob G. Blasdel, PhD
Research Director Patricia M. Devers, DO Jason A. Hawrelak, ND, BNat(Hons), PhD
Vésale Pharma Medical Education Specialist Senior Lecturer in Complementary and
Noville-sur-Mehaigne, Belgium Department of Medical Affairs Alternative Medicines
Genova Diagnostics, Inc. College of Health & Medicine
Peter B. Bongiorno, ND, MSAc, LAc University of Tasmania
Co-Medical Director Jamie Doughty, BSc, ND Hobart, Tasmania, Australia
Naturopathic Medicine Medical Director Visiting Research Fellow
Inner Source Health Naturopathic Medicine Australian Research Centre for
New York, New York Tummy Temple Complementary and Integrative
Olympia, Washington Medicine
Rachelle S. Bradley, ND University of Technology Sydney
Private Practice William Eisner, BSc Sydney, New South Wales, Australia
Heartland Naturopathic Clinic Pediatrics/Cardiology
Omaha, Nebraska Duke University
Durham, North Carolina

vi
 CONTRIBUTORS vii

Bethany Montgomery Hays, MD Robert Kachko, ND, LAc Pina LoGiudice, ND, LAc
Assistant Clinical Professor Practitioner Co-Owner
Maine Medical Center Dept Ob/Gyn Naturopathic Medicine Innersource Natural Health and
Tufts University School of Medicine Inner Source Health Acupuncture, PC
Portland, Maine New York, New York Huntington, New York
Chief Executive Officer
Leah Hechtman, MSci (RHHG), TribeRx Robert Luby, MD
BHSc (Nat), ND New York, New York Executive Director of Medical
PhD Candidate Education
Department of Obstetrics, Gynaecology and Joseph Katzinger, ND Medical Education
Neonatology | Faculty of Medicine Science Director Institute for Functional Medicine
University of Sydney SaluGenecists Federal Way, Washington
Sydney, New South Wales, Australia Seattle, Washington
President Tennille Marx, ND, CFS
National Herbalists Association of Australia Parris M. Kidd, BSc, PhD Independent Researcher
Sydney, New South Wales, Australia Chief Science Officer and Director of Kenmore, Washington
Director and Clinician Quality
The Natural Health and Fertility Centre BrainMD Health Helen (Verhesen) Messier
Sydney, New South Wales, Australia Amen Clinics Founder & Chief Medical Officer
Costa Mesa, California Medical Intelligence Learning Labs, Inc.
Wendy Hodsdon, ND San Jose, California
Adjunct Faculty Richard J. Kitaeff, MA, ND,
Department of Graduate Studies Dip Ac, LAc Steven C. Milkis, ND
National University of Natural Medicine Doctor and Clinic Director Owner
Portland, Oregon New Health Medical Center Green Lake Natural Medicine
Adjunct Faculty Edmonds, Washington Seattle, Washington
Maryland University of Integrative Health Staff Acupuncturist
Laurel, Maryland Neurology Gaetano Morello, ND
Northwest Hospital Clinician, Complex Chronic Disease Program
Naomi Hoyle, MD Seattle, Washington BC Women’s Hospital
Eliava Phage Therapy Center Clinical Affiliate Faculty Vancouver, Canada
Phage Therapy Acupuncture and Oriental Medicine
Eliava Foundation Bastyr University Gerard E. Mullin, MD
Tbilisi, Georgia Seattle, Washington Associate Professor of Medicine
Gastroenterology and Hepatology
Corene Humphreys, ND, BHSc, Dip Med Cheryl Kos, ND Johns Hopkins School of Medicine
Herb, Dip Hom, QTA Developer Baltimore, Maryland
Director Content
Nutritional Medicine Personalized Medicine Lifestyle Stephen P. Myers, ND, BMed PhD
Institute Professor and Director NatMed Research
Mary James, ND Bainbridge Island, Washington Unit
Medical Editor Southern Cross University
Naturopathic Doctor News & Review Thomas A. Kruzel, MT, ND New South Wales, Australia
Scottsdale, Arizona Rockwood Natural Medicine Clinic
Expert Panel Member Scottsdale, Arizona Toshia R. Myers, BS, MA, MPhil, PhD
Women’s Health Network Research Director
Portland, Maine Sarah Kuhl, MD, PhD Research
Physician TrueNorth Health Foundation
Maeba Jonas, MDiv Medicine Santa Rosa, California
Ordained Minister VA Northern California
United Church of Christ Martinez, California Tara Nayak, ND
Naturopathic Physician
Wayne Jonas, MD Elizabeth Kutter, BS, PhD Philadelphia, Pennsylvania
Executive Director Faculty Emeritas
Samueli Integrative Health Programs Bacteriophage Lab Mark Harrison Nolting, ND, EAMP
H&S Ventures The Evergreen State College Senior Medical Director
Alexandria, Virginia Olympia, Washington Physical Medicine
TivityHealth
Michael Alexander Lane, MD Chandler, Arizona
Assistant Professor Medical Director
Department of Neurology Edmonds Wellness Clinic
Oregon Health and Sciences University Edmonds, Washington
Portland, Oregon
viii CONTRIBUTORS

John Nowicki, ND David Quig, PhD Michael Scott, ND, MSA

Medical Writer, Research Associate Vice President Doctor
Medical Research Team Scientific Support Private Practice
Integrative Medicine Advisors, LLC Doctor’s Data, Inc. UrbanHealthWorks
Seattle, Washington St. Charles, Illinois Boulder, Colorado

Brian Orr, BA, BS, ND John C. Reed, MD, MDiv Tracey Seipel, FANPA, ABC
Owner Founding VP and Fellow of the American Fellow of the Australian Naturopathic
Country Doc: Integrative Medical Specialty Academy of Medical Acupuncture Practitioners Association
Seattle, Washington Fellow of the Osteopathic Cranial Academy American Botanical Council
Diplomate of the American Board of Family Queensland, Australia
Kristaps Paddock, ND Medicine
Medical Director Diplomate of the American Board of William Shaw, PhD
Charm City Natural Health Integrative Medicine President
Baltimore, Maryland Founding Member, American Holistic Great Planes Laboratory
Medical Association Kansas City, Missouri
Cristiana I. Paul, MS Nutrition
Independent Research Consultant Ron Reichert, BA, ND Ann Shippy, MD
Nutritional Biochemistry Research Naturopathic Physician Functional Medicine Physician
Cristiana Paul Consulting North Vancouver, Canada Environmental Health Expert
Los Angeles, California Austin, Texas
Corey Resnick, ND
Nicole Pierce, ND President Barbara Siminovich-Blok, ND, LAc
Co-creator Integrative Health and Nutrition, Inc. Clinical Assistant Professor
The Vervain Collective Lake Oswego, Oregon Rusk Rehabilitation
Garden City, Idaho Member New York University Langone
Medical Advisory Board Medical Center
Lara Pizzorno, MAR, MA, LMT Integrative Therapeutics New York, New York
Senior Medical Writer and Editor Green Bay, Wisconsin Adjunct Professor
Writing and Editorial Staff Health Sciences
Integrative Medicine Advisors, LLC Sally J. Rockwell, PhD, CCN Touro College
Seattle, Washington Deceased New York, New York
Senior Medical Editor
SaluGenecists, Inc. Elaine Roe, MD Anna Sitkoff, BS, ND
Seattle, Washington Physician, Hall Health Center Herbalist
University of Washington Naturopathic Medicine
Terry Arden Pollock, BS, MS Seattle, Washington Bastyr University
Medical Education Specialist Seattle, Washington
Medical Affairs Robert A. Ronzio, PhD
Genova Diagnostics Executive Director Pamela Snider, ND
Asheville, North Carolina Research and Educational Services Executive and Senior Editor
Insight Learning Institute Foundations of Naturopathic Medicine
Dirk W. Powell, BS, ND Austin, Texas Project
Adjunct Professor Foundations of Naturopathic Medicine
Naturopathic Medicine Angela Sadlon, ND Institute
Bastyr University All Encompassing Healthcare Snoqualmie, Washington
Kent, Washington Centralia, Washington Associate Professor
College of Naturopathic Medicine
Lahnor Powell, ND, MPH Alexander G. Schauss, PhD National University of Natural Medicine
Medical Education Specialist Senior Director of Research Portland, Oregon
Department of Medical Affairs Natural and Medicinal Products Research Faculty
Genova Diagnostics AIBMR Life Sciences, Inc. School of Naturopathic Medicine
Duluth, Georgia Seattle, Washington Bastyr University
Research Associate Kenmore, Washington
Matt Pratt-Hyatt, PhD Bio5 Institute Co-Founder
Associate Lab Director University of Arizona Integrative Health Policy Consortium
The Great Plains Laboratory, Inc. Tucson, Arizona Conifer, Washington
Lenexa, Kansas Research Associate
Geosciences
University of Arizona
Tucson, Arizona
 CONTRIBUTORS ix

Virender Sodhi, MD (Ayurveda), ND Sherry Torkos, BSc, Phm, RPh Vijayshree Yadav, MD, MCR, FAAN
Founder Pharmacist and Author Associate Professor
Ayurvedic Naturopathic Medical Clinic Fort Erie, Ontario, Canada Neurology
Bellevue, Washington Oregon Health & Science University
Founder and Chief Executive Officer Jessica Tran, ND, MBA Portland, Oregon
Ayush Herbs Private Practice
Redmond, Washington Environmental Medicine Eric L. Yarnell, ND, RH(AHG)
Wellness Integrative Naturopathic Professor
Nick Soloway, LMT, DC, LAc Center, Inc. Botanical Medicine
Private Practice Irvine, California Bastyr University
Helena, Montana Kenmore, Washington
Michael Traub, ND, DHANP, FABNO Chief Medical Officer
Lindsey Stuart, MS, CNM Medical Director Northwest Naturopathic Urology
Certified Nurse Midwife Dermatology Seattle, Washington
Boulder, Colorado Lokahi Health Center
Kailua Kona, Hawaii Jared Zeff, ND
Cory Szybala, ND Clinical Professor of Graduate Medical Naturopathic Physician
Alumni Education Salmon Creek Clinic
Naturopathic Medicine Postgraduate Education Portland, Oregon
National University of Natural Medicine Bastyr University
Portland, Oregon Seattle, Washington Heather Zwickey, PhD
Professor
Mollie Parker Szybala, ND, MPH Roy Upton, RH School of Graduate Studies
Doctor President National University of Natural Medicine
Naturopathic Medicine American Herbal Pharmacopoeia Portland, Oregon
Sun Valley Natural Medicine Scotts Valley, California Adjunct Faculty
Ketchum, Idaho Neurology
Venessa Wahler, ND Oregon Health and Science University
Jade Teta, ND Lead ND Portland, Oregon
Owner/Founder/CEO Naturopathic Medicine Human Nutrition and Functional Medicine
Metabolic Effect Inc. Tummy Temple University of Western States
Greensboro/Winston-Salem, North Carolina Seattle, Washington Portland, Oregon

Keoni Teta, ND Edward C. Wallace, ND, DC

Owner Medical Education Specialist
The Naturopathic Health Clinic of North Medical Affairs
Carolina Genova Diagnostics
Greensboro/Winston-Salem, North Carolina Asheville, North Carolina

Brice Thompson, ND, MS Terry Willard, CIH, PhD

Postdoctoral Scholar Founder
Department of Pharmaceutics Wild Rose College of Natural Healing
University of Washington Calgary, Canada
Seattle, Washington
P R E FA C E

This fifth edition of the Textbook of Natural Medicine (which has facilitate utilization, the sections are now color coded, and we have
now been in publication since 1985) brings several new features and provided alphabetical tabs to help readers in searching for specific
changes to our structure and format. We are especially excited that we diseases. Closely related diseases have been placed in a single chap-
are in full color for the first time, including images and figures. These ter―for example, depression, dysthymia, manic phase, and seasonal
dramatically improve our ability to present, in a more understandable affective disorder are all located in the chapter on affective disorders
and visually interesting way, the key concepts of and insights into the chapter―so becoming familiar with these groupings is essential for
underlying causes of dysfunction and disease. We are also delighted finding specific diseases. There are now 14 appendices that provide
that with all the new chapters and graphics, Elsevier has moved us back additional resources for the clinician. We worked with authors to
to the two-volume format. To better fit the content into two logical make their writing more succinct and eliminate unnecessary content.
volumes, we changed the order (and some of the titles) of the sections. We also reduced the length of Section VI by removing duplication of
Syndromes and Special Topics moved to Section V because these fit content from Section V in the therapeutics portion of the chapters. We
better in Volume 2 with Section VI, Diseases. Pharmacology of Natural hope you will be as pleased with the latest edition as we are.
Medicines moved to Section IV because this fits better with Volume 1. Due to the substantial increase in pages this edition, to keep down
As usual, we offer many new chapters, and we think the new chapter costs we had to move all of the approximately 20,000 references to the
on sarcopenia is of particular importance. In addition to new chapters, online version.
some chapters have been renamed for better consistency, and some
Joseph E. Pizzorno
have been moved to sections that we felt were more appropriate. To
Michael T. Murray

x
 ACKNOWLED GMENTS

We would like to thank Inta Ozols, the original commissioning editor, our executive assistant Lavelle Brown
(who so effectively organized and managed all the authors and chapters), and the dedicated staff at Elsevier
(Kristin Wilhelm, Linda Woodard, Laurie Gower, Becky Leenhouts, Jeff Patterson, Julie Eddy, Clay Broeker,
Margaret Reid, Deanna Sorenson, and Allison Kieffer) for their excellent work in making this the best edi-
tion ever.

xi
 SECTION 1
Philosophy of Natural
­Medicine
One of the key features of the various schools of natural medicine that differentiates them from conventional medicine
is their strong philosophical foundation. The basic philosophical premise of naturopathic medicine, for example, is that
there is an inherent healing power in nature and in every human being. We believe that a primary role of the physician is to
“remove the blocks to cure” and enhance this innate healing power within his or her patients.
In many ways, this was the most difficult section of the textbook to write because, before this textbook, no comprehen-
sive history of the social, political, and philosophical development of naturopathic medicine had ever been written. Even in
the halcyon years of the 1920s and 1930s, the profession was never able to agree upon a concise philosophy. This situation
has now changed.
In this section, we provide well-documented chapters detailing the roots of American natural medicine. After a century
of maturation, the naturopathic profession has now widely agreed to a comprehensive definition, set of principles, and
system of case analysis that provide a systematic guide for the application of these concepts in a clinical setting.
The seven fundamental principles of naturopathic medicine are as follows:
The healing power of nature (vis medicatrix naturae)
First, do no harm (primum non nocere)
Find the cause (tolle causam)
Treat the whole person
Preventive medicine
Wellness
Doctor as teacher
These principles translate into the following questions the practitioner applies when analyzing a case:
• What is the first cause; what is contributing now?
• How is the body trying to heal itself?
• What is the minimum level of intervention needed to facilitate the self-healing process?
• What are the patient’s underlying functional weaknesses?
• What education does the patient need to understand why he or she is sick and how to become healthier?
• How does the patient’s physical disease relate to his or her psychological and spiritual health?
We have further expanded on the philosophical basis of naturopathic medicine by having these concepts addressed by
several authors whose backgrounds allow each of them a unique and, we believe, complementary insight into some of the
fundamental questions of the goals of health care. Although the dominant school of medicine has essentially ignored these
issues, we believe that the true physician cannot function without a sound philosophical basis to guide his or her actions.
Without more than a superficial understanding of health and disease, the physician is more likely to function as a tech-
nician, temporarily alleviating symptoms while allowing the real disease to progress past the point of recovery. The huge
and increasing burden of chronic disease in all age groups clearly validates the predictions of the founders of naturopathic
medicine that primarily treating symptoms, while not addressing causes, results in increased chronic disease.

1
 1
Functional Medicine: A 21st-Century Model
of Patient Care and Medical Education
Robert Luby, MD, and Leo Galland*, AB, MD

OUTLINE
What Is Functional Medicine?, 2 Triggers and the Provocation of Illness, 5
Principles, 2 Mediators and the Formation of Illness, 6
Lifestyle and Environmental Factors, 4 Constructing the Model, 6
Fundamental Physiological Processes, 4 Assessment, 6
Core Clinical Imbalances, 4 The Functional Medicine Matrix Model, 6
Antecedents, Triggers, and Mediators, 5 The Healing Partnership, 8
Antecedents and the Origins of Illness, 5 Integration of Care, 10

In this chapter, the basic principles, constructs, and methodology has not really produced an efficient method for identifying and assess-
of functional medicine are reviewed. It is not the purpose of this ing changes in basic physiological processes that produce symptoms of
chapter to recapitulate the range and depth of the science underlying increasing duration, intensity, and frequency, although it is known that
functional medicine; books and monographs covering that material such alterations in function often represent the first signs of conditions
in great detail are already available for the interested clinician and that, at a later stage, become pathophysiologically definable diseases. By
for use in health professional schools (see Bibliography at the end of broadening the use of functional to encompass this view, functional med-
the chapter). The purpose is to describe how functional medicine is icine becomes the science and art of detecting and reversing alterations
organized to deliver personalized systems medicine and is equipped in function that clearly move a patient toward chronic disease over the
to respond to the challenge of treating complex chronic disease more course of a lifetime.
effectively. One way to conceptualize where functional medicine falls in the
continuum of health and health care is to examine the functional
medicine “tree.” In its approach to complex chronic disease, func-
WHAT IS FUNCTIONAL MEDICINE? tional medicine encompasses the whole domain represented by the
Functional medicine encompasses a dynamic approach to assessing, graphic shown in Fig. 1.1, but it first addresses the patient’s core
preventing, and treating complex chronic disease. It helps clinicians clinical imbalances (found in the functional physiological organizing
of all disciplines identify and ameliorate dysfunctions in the phys- systems); the fundamental lifestyle factors that contribute to chronic
iology and biochemistry of the human body as a primary method disease; and the antecedents, triggers, and mediators that initiate and
of improving patient health. This model of practice emphasizes that maintain the disease state. Diagnosis, of course, is part of the func-
chronic disease is almost always preceded by a period of declining tional medicine model, but the emphasis is on understanding and
function in one or more of the body’s physiological organizing sys- improving the functional core of the human being as the starting
tems. Returning patients to health requires reversing (or substan- point for intervention.
tially improving) the specific dysfunctions that contributed to the Functional medicine clinicians focus on restoring balance and
disease state. Those dysfunctions are, for each of us, the result of improved function in the dysregulated systems by strengthening the
lifelong interactions among diet, environment, lifestyle choices, and fundamental physiological processes that underlie them and by adjust-
genetic predispositions. Each patient, therefore, represents a unique, ing the environmental and lifestyle inputs that nurture or impair them.
complex, and interwoven set of influences on intrinsic functional- This approach leads to therapies that focus on restoring health and
ity that, over time, set the stage for the development of disease or function, rather than simply controlling signs and symptoms.
the maintenance of health. To manage the complexity inherent in
this approach, functional medicine has adopted practical models for
PRINCIPLES
obtaining and evaluating clinical information that leads to individu-
alized patient-centered therapies. Seven basic principles characterize the functional medicine paradigm:
Historically, the word functional was used somewhat pejoratively • Acknowledging the biochemical individuality of each human being,
in medicine. It implied a disability associated with either a geriatric or based on the concepts of genetic and environmental uniqueness
psychiatric problem. The authors suggest, however, that this is a very • Incorporating a patient-centered rather than a disease-centered
limited definition of an extremely useful word. The medical profession approach to treatment

*Previous edition contributor

2
CHAPTER 1 Functional Medicine: A 21st-Century Model of Patient Care and Medical Education 3

The Functional Medicine Tree

Cardiology Pulmonary

Endocrinology Urology

Organ System
Diagnosis

Gastroenterology Hepatology

Neurology Immunology

Signs and
Symptoms

The Fundamental Organizing Systems and Core Clinical Imbalances

Assimilation Energy Transport
Digestion, Absorption, Microbiota/Gl, Energy regulation, Mitochondrial function Cardiovascular, Lymphatic systems
Respiration Biotransformation and Elimination Structural Integrity
Defence and Repair Toxicity, Detoxification From the subcellular membranes to
Immune system, Inflammatory Communication the musculoskeletal system
processes, Infection and microbiota Endocrine, Neurotransmitters, Immune
messengers, Cognition

Antecedents, Triggers, and Mediators

Mental, Emotional, Experiences,

Spiritual Influences
Genetic Predisposition Attitudes, Beliefs

Sleep & Relationships

Relaxation
Exercise & Stress
Movement
Nutrition

Personalizing Lifestyle and Environmental Factors

Version 2 © 2015 The Institute for Functional Medicine

Fig. 1.1 The continuum of health and health care: the functional medicine tree. (Courtesy the Institute for
Functional Medicine.)
4 SECTION 1 Philosophy of Natural Medicine

• Seeking a dynamic balance among the internal and external factors disease entities. Functional medicine requires that clinicians consider
in a patient’s body, mind, and spirit these in evaluating patients so that interventions can target the most
• Addressing the web-like interconnections of internal physiological fundamental level possible. These processes are as follows:
factors 1. Communication
• Identifying health as a positive vitality—not merely the absence of • Intracellular
disease—and emphasizing those factors that encourage a vigorous • Intercellular
physiology • Extracellular
• Promoting organ, cellular, and subcellular function as the 2. Bioenergetics/energy transformation
means of enhancing the health span, not just the life span, of 3. Assimilation
each patient 4. Structural integrity
• Staying abreast of emerging research—a science- and evidence-based 5. Biotransformation/elimination
approach 6. Defense and repair
7. Transport/circulation
These fundamental physiological processes are usually taught early
LIFESTYLE AND ENVIRONMENTAL FACTORS in health professions curricula, where they are appropriately presented
The building blocks of life, and the primary influences on them, are as the foundation of modern, scientific patient care. Unfortunately,
found at the base of the functional medicine tree graphic (see Fig. 1.1). subsequent training in the clinical sciences often fails to fully inte-
When we talk about influencing gene expression, we are interested in the grate knowledge of the functional mechanisms of disease with thera-
interaction between lifestyle and environment in the broadest sense and peutics and prevention, emphasizing organ system diagnosis instead.3
any genetic predispositions with which a person may have been born— Focusing predominantly on organ-system diagnosis without examin-
in a word, the epigenome. (Epigenetics is the study of how environmen- ing the underlying physiology that produced the patient’s signs, symp-
tal factors can affect gene expression without altering the actual DNA toms, and disease often leads to managing patient care by matching
sequence and how these changes can be inherited through generations.) diagnosis to pharmacology. The job of the health care provider then
Many environmental factors that affect gene expression are (or appear to becomes a technical exercise in finding the drug or procedure that best
be) a matter of choice (such as diet and exercise), others are very difficult fits the diagnosis (not necessarily the patient or the underlying phys-
for the individual patient to alter or escape (air and water quality, toxic iological dysfunction), leading to a significant curtailment of critical
exposures), and still others may be the result of unavoidable accidents thinking pathways: “Medicine, it seems, has little regard for a complete
(trauma, exposure to harmful microorganisms). Some factors that may description of how myriad pathways result in any clinical state.”4
appear modifiable are heavily influenced by the patient’s economic sta- Even more important, pharmacological treatments (and even nat-
tus—if you are poor, for example, it may be impossible to choose more ural remedies) are often prescribed without careful consideration of
nutritious food, decrease stress in the workplace and at home, or take the their physiological effects across all organ systems, physiological pro-
time to exercise and rest properly. Existing health status is also a pow- cesses, and genetic variations.5 This was notably exemplified by the
erful influence on the patient’s ability to alter environmental input. If cyclooxygenase-2 inhibitor drugs that were so wildly successful on
you have chronic pain, exercise may be extremely difficult; if you are their introduction, only to be subsequently withdrawn or substantially
depressed, self-activation is a major challenge. narrowed in use because of collateral damage.6,7
The influence of these lifestyle and environment factors on the
human organism is indisputable,1,2 and they are often powerful agents
CORE CLINICAL IMBALANCES
in the attempt to restore health. Neglecting to address them in favor
of merely writing a prescription—whether for pharmaceutical agents, The functional medicine approach to assessment, both before and after
nutraceuticals, or botanicals—means the cause of the underlying dys- diagnosis, charts a course using different navigational assumptions.
function may itself remain unaddressed and further able to contribute Every health condition instigates a quest for information centered on
to the genesis of other disease conditions. In general terms, the follow- understanding when and how the specific biological system(s) under
ing factors should be considered when working to reverse dysfunction examination became dysregulated and began manifesting dysfunction
or disease and restore health: and/or disease. Analyzing all the elements of the patient’s story, the
• Diet (type, quality, and quantity of food; food preparation; calories, signs and symptoms, and the laboratory assessment through a matrix
fats, proteins, carbohydrates) focused on functionality requires analytical thinking and a willing-
• Nutrients (both dietary and supplemental) ness on the part of the clinician to reflect deeply on the underlying
• Air and water biochemistry and physiology. The foundational principles of how the
• Microorganisms (and the general condition of the soil in which human organism functions—and how its systems communicate and
food is grown) interact—are essential to the process of linking ideas about multifacto-
• Physical exercise rial causation with the perceptible effects called disease or dysfunction.
• Trauma To assist clinicians in this process, functional medicine identified
• Psychosocial and spiritual factors, such as meaning and purpose, rela- and organized a set of core clinical imbalances that are linked to the
tionships, work, community, economic status, stress, and belief systems fundamental physiological processes (organizing systems). These serve
• Xenobiotics to marry the mechanisms of disease with the manifestations and diag-
• Radiation noses of disease. Many common underlying pathways of disease are
reflected in these clinical imbalances. The following list of imbalanced
systems and processes is not definitive, but some of the most common
FUNDAMENTAL PHYSIOLOGICAL PROCESSES examples are provided. We recommend that the organizing systems be
There are certain physiological processes that are necessary to life. considered in the order as shown in the following list:
These are the “upstream” processes that can go awry and create • Digestion
“downstream” dysfunctions that eventually become expressed as • Absorption
CHAPTER 1 Functional Medicine: A 21st-Century Model of Patient Care and Medical Education 5

One Condition – Many Imbalances

Inflammation Endocrine Genetics and epigenetics Diet and exercise Mood disorders

OBESITY

One Imbalance – Many Conditions

INFLAMMATION

Heart disease Depression Arthritis Cancer Diabetes

Fig. 1.2 Core clinical imbalances—multiple influences. (Courtesy the Institute for Functional Medicine.)

• Microbiome/gastrointestinal to acute or chronic illness. For a person who is ill, antecedents form
• Respiration the illness diathesis. From the perspective of prevention, they are risk
• Immune system factors. Knowledge of antecedents provides a rational structure for the
• Inflammatory processes organization of preventive medicine and public health.
• Infection and microbiome Medical genomics seeks to better understand disease by identify-
• Energy regulation ing the phenotypic expression of disease-related genes and their prod-
• Mitochondrial function ucts. The application of genomic science to clinical medicine requires
• Toxicity the integration of antecedents (genes and the factors controlling their
• Detoxification expression) with mediators (the downstream products of gene acti-
• Endocrine vation). Mediators, triggers, and antecedents are not only key bio-
• Neurotransmitter medical concepts; they are also important psychosocial concepts. In
• Immune messengers person-centered diagnosis, the mediators, triggers, and antecedents for
• Cognition each person’s illness form the focus of the clinical investigation.
• From the subcellular membranes
• To the musculoskeletal system Antecedents and the Origins of Illness
Using this construct, it becomes much clearer that one disease and/ Understanding the antecedents of illness helps the physician under-
or condition may have multiple causes (i.e., multiple clinical imbal- stand the unique characteristics of each patient as they relate to his or
ances), just as one fundamental imbalance may be at the root of many her current health status. Antecedents may be thought of as congeni-
seemingly disparate conditions (Fig. 1.2). tal or developmental. The most important congenital factor is gender:
The most important precept to remember about functional medi- women and men differ sharply in susceptibility to many disorders. The
cine is that restoring balance—in the patient’s lifestyle and/or environ- most important developmental factor is age; what ails children is rarely
ment and in the body’s fundamental physiological processes—is the the same as what ails the elderly. Beyond these obvious factors lies a
key to restoring health. diversity as complex as the genetic differences and separate life experi-
ences that distinguish one person from another.
ANTECEDENTS, TRIGGERS, AND MEDIATORS8 Triggers and the Provocation of Illness
What modern science has taught us about the genesis of disease can A trigger is anything that initiates an acute illness or the emergence of
be represented by three words: triggers, mediators, and antecedents. symptoms. The distinction between a trigger and a precipitating event
Triggers are discrete entities or events that provoke disease or its symp- is relative, not absolute; the distinction helps organize the patient’s
toms. Microbes are an example. The greatest scientific discovery of the story. As a general rule, triggers only provoke illness as long as the
19th century was the microbial etiology of the major epidemic diseases. person is exposed to them (or for a short while afterward), whereas a
Triggers are usually insufficient in and of themselves for disease forma- precipitating event initiates a change in health status that persists long
tion; however, host response is an essential component. after the exposure ends.
It is, therefore, the functional medicine practitioner’s job to know Common triggers include physical or psychic trauma, microbes,
not just the patient’s ailments or diagnoses but also the physical and drugs, allergens, foods (or even the act of eating or drinking), environ-
social environment in which illness occurs, the dietary habits of the mental toxins, temperature change, stressful life events, adverse social
person (present diet and preillness diet), his or her beliefs about the interactions, and powerful memories. For some conditions, the trig-
illness, the effect of illness on social and psychological function, factors ger is such an essential part of our concept of the disease that the two
that aggravate or ameliorate symptoms, and factors that predispose to cannot be separated; the disease is either named after the trigger (e.g.,
illness or facilitate recovery. This information is necessary for estab- strep throat) or the absence of the trigger negates the diagnosis (e.g.,
lishing a functional medicine treatment plan. concussion cannot occur without head trauma). For chronic ailments
Identifying the biochemical mediators that underlie host responses like asthma, arthritis, or migraine headaches, multiple interacting trig-
was the most productive field of biomedical research during the second gers may be present. All triggers, however, exert their effects through
half of the 20th century. Mediators, as the word implies, do not cause the activation of host-derived mediators. In closed-head trauma, for
disease. They are intermediaries that contribute to the manifestation example, activation of N-methyl-d-aspartic acid receptors, induction
and/or continuation of disease. Antecedents are factors that predispose of nitric oxide synthase, and liberation of free intraneuronal calcium
6 SECTION 1 Philosophy of Natural Medicine

BOX 1.1 Common Illness Mediators and expands upon demand, the amount and kind of data collected will
necessarily change in accordance with the patient’s situation and the
Biochemical Hormones clinician’s time and ability to piece together the underlying threads of
Neurotransmitters dysfunction.
Neuropeptides The conventional assessment process involving the chief complaint,
Cytokines history of present illness, and past medical history sections must be
Free radicals expanded (Fig. 1.3) to include a thorough investigation of antecedents,
Transcription factors triggers, and mediators and a systematic evaluation of any imbalances
within the fundamental organizing systems. Personalized medical care
Subatomic without this expanded investigation falls short.
Ions
Electrons The Functional Medicine Matrix Model
Electrical and magnetic fields Distilling the data from the expanded history, physical examina-
tion, and laboratory findings into a narrative storyline that includes
Cognitive/Emotional
antecedents, triggers, and mediators can be challenging. Key to devel-
Fear of pain or loss
oping a thorough narrative is organizing the story using the Functional
Feelings or personal beliefs about illness
Medicine Matrix Model form (Fig. 1.4).
Poor self-esteem, low perceived self-efficacy
The matrix form helps organize and prioritize information and also
Learned helplessness
clarifies the level of present understanding, thus illuminating where
Lack of relevant health information
further investigation is needed. For example:
Social/Cultural • Indicators of inflammation on the matrix might lead the clinician
Reinforcement for staying sick to request tests for specific inflammatory markers (such as highly
Behavioral conditioning sensitive C-reactive protein, interleukin levels, and/or homocyste-
Lack of resources because of social isolation or poverty ine).
The nature of the sick role and the doctor–patient relationship • Essential fatty acid levels, methylation pathway abnormalities, and
organic acid metabolites help determine the adequacy of dietary
and nutrient intakes.
• Markers of detoxification (glucuronidation and sulfation, cyto-
determine the late effects. Intravenous magnesium at the time of chrome P450 enzyme heterogeneity) can determine the functional
trauma attenuates the severity by altering the mediator response.9,10 capacity for molecular biotransformation.
Sensitivity to different triggers often varies among persons with similar • Neurotransmitters and their metabolites (vanilmandelate, homo-
ailments. A prime task of the functional practitioner is to help patients vanillate, 5-hydroxyindoleacetate, quinolinate) and hormone
identify important triggers for their ailments and develop strategies for cascades (gonadal and adrenal) have obvious utility in exploring
eliminating them or diminishing their virulence. messenger molecule balance.
• Computed tomographic scans, magnetic resonance imaging (MRI),
Mediators and the Formation of Illness or plain radiographs extend the view of the patient’s structural dys-
A mediator is anything that produces or perpetuates symptoms or functions. The use of bone scans, dual-energy x-ray absorptiome-
damages tissues of the body, including certain behaviors. Mediators try scans, or bone resorption markers11,12 can be useful in further
vary in form and substance. They may be biochemical (e.g., prosta- exploring the web-like interactions of the matrix.
noids and cytokines), ionic (e.g., hydrogen ions), social (e.g., rein- • Newer, useful technologies such as functional MRIs, single-photon
forcement for staying ill), psychological (e.g., fear), or cultural (e.g., emission computed tomography, and positron emission tomo-
beliefs about the nature of illness). A list of common mediators is pre- graphic scans offer a more comprehensive assessment of metabolic
sented in Box 1.1. Illness in any single person usually involves multiple function within organ systems.
interacting mediators. Biochemical, psychosocial, and cultural media- It is the process of completing a comprehensive history and physi-
tors interact continuously in the formation of illness. cal using the expanded functional medicine heuristic and then charting
these findings on the matrix that best directs the choice of diagnostic
CONSTRUCTING THE MODEL evaluations and successful treatment.
Therapies should be chosen for their potential effect on the most
Assessment significant imbalances of the particular patient. A completed matrix
Combining the principles, lifestyle and environment factors, funda- form facilitates review of common pathways, mechanisms, and
mental physiological processes, antecedents, triggers, mediators, and mediators of disease and helps clinicians select points of leverage for
core clinical imbalances demands a new architecture for gathering treatment strategies. However, even with the matrix as an aid to syn-
and sorting information for clinical practice—in effect, a new heuris- thesizing and prioritizing information, it can be very useful to consider
tic to serve the practice of functional medicine. (Heuristics are rules the effect of each variable at five different levels:
of thumb—ways of thinking or acting—that develop through exper- 1. Whole-body interventions: Because the human organism is a com-
imentation and enable more efficient and effective processing of data.) plex adaptive system, with countless points of access, interventions
This new model includes an explicit emphasis on principles and mech- at one level will affect points of activity in other areas as well. For
anisms that infuse meaning into the diagnosis and deepen the clini- example, improving the patient’s sleep beneficially influences the
cian’s understanding of the multivalent contributors to physiological immune response, melatonin levels, and T-cell lymphocyte lev-
dysfunction. Any methodology for constructing a coherent story and els and helps decrease oxidative stress. Exercise reduces stress,
an effective therapeutic plan in the context of complex chronic illness improves insulin sensitivity, and improves detoxification. Reduc-
must be flexible and adaptive. Like an accordion file that compresses ing stress (and/or improving stress management) reduces cortisol
CHAPTER 1 Functional Medicine: A 21st-Century Model of Patient Care and Medical Education 7

Chief Complaint (CC)

History of Present Illness (HPI)
Past Medical History (PMH)
– Explore antecedents, triggers, and mediators of CC, HPI, and PMH
Family Medical History
– Genetic predispositions?
Review of Organ Systems (ROS)
Medication and Supplement History
Dietary History
Social, Lifestyle, Exercise History
Physical Examination (PE)
Laboratory and Imaging Evaluations
Explore Core Clinical Imbalances:
Assimilation Imbalances
Digestion
Absorption
Microbiota/GI
Respiration
Defense and Repair Imbalances
Immune system
Inflammatory processes
Infection and microbiota
Energy Imbalances
Energy regulation
Mitochondrial function
Biotransformation and Elimination Imbalances
Toxicity
Detoxification
Communication Imbalances
Endocrine
Neurotransmitter
Immune messengers
Cognition
Structural Integrity Imbalances
From the subcellular membranes to the musculoskeletal system
Initial Assessment:
– Enter data on Matrix form; look for common themes
– Review underlying mechanisms of disease
– Recapitulate patient’s story
– Organ system-based diagnosis
– Functional medicine assessment: underlying mechanisms of disease; genetic and environmental
influences
Treatment Plan:
– Individualized
– Dietary, lifestyle, environmental
– Nutritional, botanical, psychosocial, energetic, spiritual
– May include pharmaceuticals and/or procedures
Fig. 1.3 Expanding the accordion file: the functional medicine assessment heuristic. (Courtesy the Institute
for Functional Medicine.)

levels, improves sleep, improves emotional well-being, and reduces vitamins, and cofactor minerals in the diet (or, if necessary, from
the risk of heart disease. Changing the diet has myriad effects on supplementation). An individual’s metabolic enzyme polymor-
health, from reducing inflammation to reversing coronary artery phisms can profoundly affect his or her nutrient requirements.
disease. For example, adding conjugated linoleic acid to the diet can alter
2. Organ-system interventions: These interventions are used more the peroxisome proliferator–activated receptor system, affect body
frequently in the acute presentation of illness. Examples include weight, and modulate the inflammatory response.13–15 However,
splinting; draining lesions; repairing lacerations; reducing frac- in a person who is diabetic or insulin resistant, adding conjugated
tures, pneumothoraxes, hernias, or obstructions; or removing a linoleic acid may induce hyperproinsulinemia, which is detrimen-
stone to reestablish whole-organ function. There are many inter- tal.16,17 Altering the types and proportions of carbohydrates in the
ventions that improve organ function. For example, bronchodila- diet may increase insulin sensitivity, reduce insulin secretion, and
tors improve air exchange, thereby decreasing hypoxia, reducing fundamentally alter metabolism in the insulin-resistant patient.
oxidative stress, and improving metabolic function and oxygen- Supporting liver detoxification pathways with supplemental gly-
ation in a patient with reactive airway disease. cine and N-acetylcysteine improves the endogenous production of
3. Metabolic or cellular interventions: Cellular health can be addressed adequate glutathione, an essential antioxidant in the central ner-
by ensuring the adequacy of macronutrients, essential amino acids, vous system and gastrointestinal tract.
8 SECTION 1 Philosophy of Natural Medicine

FUNCTIONAL MEDICINE MATRIX

Retelling the Physiology and Function: Organizing the Patient’s Clinical Imbalances
Patient’s Story

Antecedents Assimilation Defense & Repair

(e.g., Digestion, (e.g., Immune,
(Predisposing Factors— Absorption, Microbiota/GI, Inflammation,
Genetic/Environmental) Respiration) Infection/Microbiota)

Mental Emotional
e.g., cognitive e.g., emotional
Structural function, regulation, grief, Energy
Integrity perceptual sadness, anger, (e.g., Energy
Regulation,
Triggering Events (e.g., from Subcellular patterns etc.
Mitochondrial
(Activators) Membranes to
Function)
Musculoskeletal
Structure)

Spiritual
e.g., meaning &
purpose,
Communication relationship with Biotransformation
Mediators/Perpetuators something greater
(e.g., Endocrine, & Elimination
(Contributors) Neurotransmitters, Immune (e.g., Toxicity,
messengers) Detoxification)

Transport
(e.g., Cardiovascular, Lymphatic System)

Modifiable Personal Lifestyle Factors

Sleep & Relaxation Exercise & Movement Nutrition Stress Relationships

Name: Date: CC: © 2015 Institute for Functional Medicine

Version3

Fig. 1.4 The Functional Medicine Matrix Model. (Courtesy the Institute for Functional Medicine.)

4. Subcellular/mitochondrial interventions: There are many examples of and γ-linoleic acid.21 Adequate vitamin A allows the appropriate
nutrients that support mitochondrial function.18,19 Inadequate iron interaction of vitamin A–retinoic acid with more than 370 genes.23
intake causes oxidants to leak from mitochondria, damaging mito- Vitamin D in its most active form intercalates with a retinol protein
chondrial function and mitochondrial DNA. Making sure there is suf- and the DNA exon and modulates many aspects of metabolism,
ficient iron helps alleviate this problem. Inadequate zinc intake (found including cell division in both healthy and cancerous breast, colon,
in more than 10% of the U.S. population) causes oxidation and DNA prostate, and skin tissue.24 Vitamin D has key roles in controlling
damage in human cells.19 Ensuring the adequacy of antioxidants and inflammation, calcium homeostasis, bone metabolism, cardiovas-
cofactors for the at-risk individual must be considered in each part of cular and endocrine physiology, and healing.24
the matrix. Carnitine, for example, is required as a carrier for the trans- Experience using this model, along with improved pattern-recog-
port of fatty acids from the cytosol into the mitochondria, improving nition skills, will often lessen the need for extensive laboratory assess-
the efficiency of β-oxidation of fatty acids and resultant adenosine tri- ments. However, there will always be certain clinical conundrums
phosphate production. In patients who have lost significant weight, that simply cannot be assessed without objective data, and for most
carnitine undernutrition can result in fatty acids undergoing ω- patients, there may be an irreducible minimum of laboratory assess-
oxidation, a far less efficient form of metabolism.20 Patients with low ments required to accumulate information. For example, in the clinical
carnitine may also respond to riboflavin supplementation.20 workup of autism spectrum disorders in children, heavy-metal expo-
5. Subcellular/gene-expression interventions: Many compounds sure and toxicity may play an important role. The heavy-metal body
interact at the gene level to alter cellular response, thereby affecting burden cannot be sensibly assessed without laboratory studies. In most
health and healing. Any intervention that alters nuclear factor-κB initial workups, laboratory and imaging technologies can be reserved
entering the nucleus, binding to DNA, and activating genes that for those complex cases in which the initial interventions prove insuf-
encode inflammatory modulators, such as interleukin-6 (and thus ficient to the task of functional explication. When clinical acumen and
C-reactive protein), cyclooxygenase-2, interleukin-1, lipoxygenase, educated steps in both assessments and therapeutic trials do not yield
inducible nitric oxide synthase, tumor necrosis factor-α, or a num- expected improvement, laboratory testing often provides rewarding
ber of adhesion molecules, will affect many disease conditions.21,22 information. This is frequently the context for focused genomic testing.
There are many ways to alter the environmental triggers for nuclear
factor-κB, including lowering oxidative stress; altering emotional The Healing Partnership
stress; and consuming adequate phytonutrients, antioxidants, No discussion of the functional medicine model would be complete
alpha-lipoic acid, eicosapentaenoic acid, docosahexaenoic acid, without mention of the therapeutic relationship. Partnerships are