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Sixteen-year-old Female With Acute Abdominal Pain: A Case Report • Cannabidiol Oil for Decreasing Addictive Use of Marijuana: A Case Report • Presenters 2016—Bernard Fox, PhD: The Promise of Immunotherapy in Curing Cancer • Interview with Kara Fitzgerald, ND: Case Reports—Informing the Practice of Systems Medicine • Jeffrey Bland—When Is a Disease a Disease? • Editorial—The Kidney Dysfunction Epidemic, Part 1: Causes • Annual Author and Subject Indices

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December 2015/January 2016 • Vol. 14 No. 6

Integrative Medicine: A Clinician’s Journal www.imjournal.com

EDITORIALS 8

The Path Ahead—The Kidney Dysfunction Epidemic, Part 1: Causes Joseph Pizzorno, ND, Editor in Chief

Creating Synthesis—When Is a Disease a “Disease”? Jeffrey Bland, PhD, Associate Editor

BackTalk—Confessions of a Narcissist Bill Benda, MD, Associate Editor

COMMENTARY 18

Harvard Team Finds 43% Reduction in Use of Health Care Services via Mind-Body Intervention … plus more John Weeks

CASE REPORT 26

Sixteen-year-old Female With Acute Abdominal Pain: A Case Report Kara Fitzgerald, ND

Cannabidiol Oil for Decreasing Addictive Use of Marijuana: A Case Report Scott Shannon, MD; Janet Opila-Lehman, ND

PRESENTERS 2016 22

Bernard Fox, PhD: The Promise of Immunotherapy in Curing Cancer Interview by Craig Gustafson

VIEWPOINTS 36

Kara N. Fitzgerald, ND: Case Reports—Informing the Practice of Systems Medicine Interview by Craig Gustafson

EPTHECA 40

Author Index

Subject Index

Conference Calendar

Table of Contents

Integrative Medicine • Vol. 14, No. 6 • December 2015

December 2015/January 2016 • Vol. 14 No. 6

Integrative Medicine: A Clinician’s Journal www.imjournal.com

Editor in Chief Joseph Pizzorno, ND drpizzorno@innovisionhm.com IMCJ Associate Editors Sidney MacDonald Baker, MD

Jennifer C. Lovejoy, PhD, CNS

Autism Research Institute

Institute for Systems Biology

Bill Benda, MD, FAAEM

Senior Graduate Fellow, Program in Integrative Medicine, University of Arizona; St. Mary's Medical Center in West Palm Beach, FL

David S. Riley, MD

Academy of Integrative Health and Medicine; Integrative Medicine Institute; National College of Natural Medicine

Jeffrey Bland, PhD, FACN, FACB

Darcy Vavrek, ND, MS

Cofounder, Institute for Functional Medicine; Founder, Personalized Lifestyle Medicine Institute

University of Western States

Tori Hudson, ND

David Wickes, DC, FICC, Dipl ABCI

Medical Director, A Woman’s Time; Program Director, Institute of Women’s Health and Integrative Medicine; Research/Education Director, Vitanica

Canadian Memorial Chiropractic College

IMCJ Editorial Board Lise Alschuler, ND, FABNO ◆ Executive Director, TAP Integrative; Coprinciple, Thrivers; Clinician, Naturopathic Specialists Jeremy Appleton, ND ◆ Nature’s Way Brands

Douglas MacKay, ND ◆ Senior Vice President, Scientific & Regulatory Affairs, Council for Responsible Nutrition Antonio C. Martinez, II, JD ◆ Attorney at Law

Phillip Barr, MD ◆ Concierge Health Consultants

Robert Martinez, ND, DC, DABCO ◆ Private Practice, Kirkland, WA

Donald M. Blair, DDS, ND ◆ Bellevue, WA

David Matteson, MPH, MS, MPA, APR ◆ Early Edge Solutions, Nativis

O’Dane Brady, DC, MSc ◆ World Spine Care

Gerard E. Mullin, MD ◆ Division of Gastroenterology and Hepatology, Johns Hopkins Hospital Stephen P. Myers, ND, PhD, BMed, FACNEM ◆ Southern Cross University, Australia

Andrew W. Campbell, MD ◆ Editor in Chief, Alternative Therapies in Health and Medicine Alan R. Gaby, MD ◆ Concord, NH Steve Given, DAOM, LAc ◆ American College of Traditional Chinese Medicine Elizabeth A. Goldblatt, PhD, MPA/HA ◆ Academic Consortium of Complementary and Alternative Health Care (ACCAHC) Patrick Hanaway, MD ◆ Cleveland Clinic Mary L. Hardy, MD ◆ Stiles Integrative Oncology Program at UCLA; Wellness Works

Paula J. Nenn, MD, ABIHM, MRCP(UK) ◆ States of Jersey, Department of Medicine; University of Southampton David Perlmutter, MD, FACN, ABIHM ◆ Perlmutter Health Center Lara Pizzorno, MA (Div), MA (Lit), LMT ◆ Editor, Longevity Medicine Review; Integrative Medicine Advisors, LLC; Salugenecists, Inc Ronald G. Reichert, ND ◆ Boucher Institute of Naturopathic Medicine; Bioclinic Naturals Corey Resnick, ND ◆ Integrative Health & Nutrition; Integrative Therapeutics

Mark Hyman, MD ◆ Institute for Functional Medicine; The Center for Mind-Body Medicine; The UltraWellness Center Loren D. Israelsen, JD ◆ President, United Natural Products Alliance

Jacob Schor, ND, FABNO ◆ Denver Naturopathic Clinic; Fellow, American Board of Naturopathic Oncology; Associate Editor, The Natural Medicine Journal; Board Member and Past President, Oncology Association of Naturopathic Physicians Clyde B. Jensen, PhD ◆ University of Western States; Oregon Collaborative Vivek Shanbhag, ND, MD(Ayur) ◆ YogaAyurveda.org; Natural Medicine Clinic & for Integrative Medicine; Association of Health Sciences Colleges Academy; Adjunct Faculty, Bastyr University & MMI Ayurveda College and Universities Claire Johnson, DC, MSEd, DACBSP ◆ National University of Health Sciences Andrew David Shiller, MD ◆ Integrative Rehabilitation Medicine, Suffern, NY; The Valley Hospital, Ridgewood, NJ Herb Joiner-Bey, ND ◆ Barlean’s Organic Oils Pamela Snider, ND, PhND(Hon) ◆ Executive and Senior Editor, Foundations of Naturopathic Medicine Project; Associate Editor, National College of Natural Robert H. Lerman, MD, PhD ◆ Adjunct Associate Professor of Medicine, Boston Medicine; Adjunct Faculty, Bastyr University University School of Medicine DeAnn Liska, PhD ◆ Sr. Director Nutrition & Scientific Affairs, Biofortis Nutrition Nancy Sudak, MD, ABIHM ◆ Academy of Integrative Health & Medicine Research, a Merieux NutriSciences Company Chongyun Liu, OMD, LAc ◆ Bastyr University Kathie Madonna Swift, MS, RDN, LDN, FAND ◆ Saybrook University School of Mind Body Medicine; Dietitians in Integrative and Functional Medicine Rick Liva, ND, RPH ◆ Connecticut Center for Health; Vital Nutrients Melvyn R. Werbach, MD ◆ Tarzana, CA Michael R. Lyon, MD ◆ Diplomate of the American Board of Obesity Medicine; Adjunct Professor, University of British Columbia; Food, Nutrition and Health Research Director, Canadian Center for Functional Medicine; Medical Director, Medical Weight Management Centre

Jonathan V. Wright, MD ◆ Tahoma Clinic

Statement of Purpose

Integrative Medicine: A Clinician’s Journal® provides clinicians with peer-reviewed, scientifically accurate, practical information about the integration of conventional and natural medicine. Integrative Medicine: A Clinician’s Journal is indexed in CINAHL. The views expressed in this journal are those of the authors and not necessarily those of the publisher or its advertisers. Integrative Medicine: A Clinician’s Journal® (ISSN 1546-993X) is published 6 times per year (in February, April, June, August, October, and December) by InnoVision Professional Media, Copyright ©2015. Cover image used under license from Shutterstock.com, 2015 All rights reserved. No part of this publication may be reproduced in any medium or photocopied without written permission from the publisher. Individual subscriptions to Integrative Medicine: A Clinician’s Journal must be prepaid in US dollars only and are available for $85 for one year. To order or for subscription address changes, write, fax, or call: Integrative Medicine: A Clinician’s Journal, PO Box 11292, St. Paul, MN 55111 • Toll Free: (877) 904-7951 • Phone: ( 651) 251-9684

Integrative Medicine • Vol. 14, No. 6 • December 2015

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THE PATH AHEAD

The Kidney Dysfunction Epidemic, Part 1: Causes Joseph Pizzorno, ND, Editor in Chief

he kidney plays many important roles in maintaining health, ranging from activation of hormones to maintaining stable levels of key molecule in the blood to excretion of toxins. Most consider the kidneys second only to the liver in importance for toxin elimination. However, considering that 20% to 25% of cardiac output goes through these tiny organs, allowing them to filter the blood a remarkable 60 times per day, a case could be made that they are actually more important than the liver for toxin elimination. They rid the body of unwanted products of metabolism such as ammonia, urea, uric acid, creatinine, end products of hemoglobin metabolism, and hormone metabolites; toxins that have been made water soluble by phase 2 in the liver; and direct excretion of industrial toxins, such as heavy metals and a number of new-to-nature molecules. They also excrete nutrients or food constituents when consumed in excess, such as salt, vitamin C, B vitamins, and others. One of the big challenges for the kidneys is that although they are effective at removing many toxins from the blood, some are difficult to then excrete into the urine. This means they accumulate in the kidneys and as their concentration increases, they can cause disproportionate damage to the kidneys. Cadmium illustrates this problem well. Unfortunately, we are now exposed to such a high toxic load in the modern world that loss of function with aging—as can be seen in Figure 1—is considered “normal.” A 90-year-old has only one-third to one-half of the kidney Figure 1. Deterioration in Kidney Function With Aging1

Abbreviation: GFR, glomerular filtration rate. 8

Integrative Medicine • Vol. 14, No. 6 • December 2015

function of a 20-year-old. This means a significant decrease in ability to rid the body of many toxins and helps explain why almost everyone becomes sicker with aging. Once again, “normal” is not healthy. Because this is a huge topic, I am breaking my editorial into 2 parts: part 1, causes; and part 2, intervention. The latter will be published in volume 15, issue 1. Kidney Excretion of Toxins The kidney excretes toxins through essentially 3 mechanisms: (1) filtration through the glomeruli; (2) passive diffusion, typically from the distal tubules; and (3) active processes where the toxins are transported from the blood as well as into the urine. Note also in Figure 2: Some molecules are reabsorbed after being filtered by the glomeruli. This is a normal, controlled process by which the kidney maintains blood levels of key molecules within a narrow range. Basically, the glomeruli filter out of the blood almost all of the small- and medium-sized water-soluble molecules. Some are then reabsorbed, such as sodium, to ensure stable levels, blood volume, and other factors. In the proximal tubules are several active, energy-dependent processes such as organic anion transporters (OATs), organic anion transporting polypeptides (OATPs), organic cation transporters (OCTs), multidrug resistanceassociated protein (MRP), multidrug resistance protein (MDR), and multidrug and toxic compound extrusion (MATE) that transport specific toxins out of the blood and, hopefully, into the urine. Finally, there is passive diffusion of the more fat soluble toxins across the tubules into the urine. These later process are quite slow but may be important for some toxins. Several factors determine how well specific toxins are excreted by the kidneys. First, if the toxin is large or bound to protein, it does not pass through the glomeruli, so these have to be handled in other ways. Second, for toxins that are both water and fat soluble (the octanol/ water partition coefficient), as their fat soluble increases, they are more likely passively reabsorbed in the distal tubules back into the kidneys and, potentially, back into the blood. Third, the active toxin excretion pathways have limited capacity and can be easily saturated. This limitation is used sometimes to decrease the rate at which an expensive or difficult-to-obtain drug is excreted so higher blood levels can be attained at lower dosages. Finally, as the body uses adenosine triphosphate (ATP) Pizzorno—The Path Ahead

Figure 2. Kidney Excretion of Toxins Afferent arteriole

Efferent arteriole

Glomerular capillaries

1. Filtration 2. Reabsorption 3. Secretion 4. Excretion

Bowman’s capsule

Peritubular capillaries

Renal vein

Urinary excretion Excretion = Filtration - Reabsorption + Secretion

to actively pump out specific toxins, if the kidney’s mitochondria are not working well, these active processes do not work as well as needed. Worse, when the mitochondria are not working adequately, the kidneys also cannot protect their own tissue as high concentrations of toxins can that build up in the kidneys. How the Kidneys Are Damaged The kidney can be damaged by (1) poor blood flow, (2) mitochondrial dysfunction, (3) overload by high total level of toxins that may not be individually very toxic but become problematic when the total amount is high, (4) indirectly by toxins that cause general tissue damage, and (5) directly by toxins that are specifically harmful to the kidney tissues. These toxins can also come from within, such as from an unhealthy gut and externally from the many metals and chemicals in our industrialized world. Heavy Metals Cadmium, chromium, lead, mercury, platinum, and uranium are all nephrotoxic. Cadmium. Cadmium is a huge problem. With a worrisome half-life of more than 10 years, it is very difficult to excrete. Cadmium is especially a problem for the kidney, which holds 50% of the total body burden. Pizzorno—The Path Ahead

Once cadmium enters the body, much of it is bound to metallothioniens. These compounds are cleared through the glomeruli but are then reabsorbed by the tubules where they then become stuck. As the metallothioniens slowly degrade, highly toxic free cadmium is constantly released. Although it then passively migrates into the urine, it also causes oxidative stress to the tubules. The cadmium damage to the kidneys helps explain why it accounts for a surprising 20% of osteoporosis. The final stage in activation of vitamin D into its most active 1,25(OH)2D3 is in the kidneys. As the kidneys degenerate, they not only lose their ability to excrete toxins, but now are less able to perform their other functions. The main sources of cadmium are smoking and conventionally grown soybeans. Both are grown with high phosphate fertilizers that are contaminated with cadmium. Mercury. The kidneys have a high affinity for mercury. In fact, within a few hours of exposure, 50% of the mercury that gets into the blood ends up in the kidneys. Mercury damages both the glomeruli and the tubules. Much of the tissue damage appears due to poisoning of the kidney mitochondria so there is not enough ATP for the cells to protect themselves from the toxins they are excreting. The main sources of mercury are so-called “silver” fillings, which are actually 55% mercury and eating large fish. (See my editorials from February 20092 and April 20093.)

Persistent Organic Pollutants The persistent organic pollutants (POPs) are new-tonature molecules specifically designed for special purposes and to be difficult to break down. They range from herbicides and pesticides, to nonstick coatings, to fire retardants. Our patients are as contaminated with these chemicals as the environment. As they are typically mostly fat soluble they are particularly damaging to the kidneys. Research is still early on their long-term health effects as many have been created relatively recently. Many of these chemicals are classified as halogenated hydrocarbons and are so difficult to detoxify or excrete that they have half-lives measured in months to years. Following is a brief discussion of just a few of those with serious nephrotoxicity. Fluorinated Hydrocarbons. Tetrafluoroethylene and similar compounds are polymerized to produce polytetrafluoroethylene (PTFE) polymers, such as Teflon. This class of compounds is used as nonstick coatings on pots and pans; in clothing that is waterproof, but breathable; for stain prevention on carpet and upholstery; and for other purposes. Although these nonstick coatings are supposedly inert, the reality is quite different. When nonstick surfaces are heated to high temperatures on a stovetop, they emit toxic gases. Figure 3, work commissioned and reviewed by the Environmental Working Group, shows that within only Integrative Medicine • Vol. 14, No. 6 • December 2015

Figure 3. Nonstick Pan Coatings Release Toxic Gases When They Get Hot4 800 700

680°F: toxic gases released

Temperature (°F)

600 500 464°F: toxic particles released 400 300 200 100 0 0

1 2 3 4 Time from cold start (min)

Generic nonstick pan Teflon nonstick pan 2 minutes on a hot stove, the nonstick coatings start to release toxic gases. The lowest temperature at which this starts to occur is 392oF, a temperature commonly achieved in the typical kitchen.5 The temperature at which most oils start to smoke is high enough for the polymers to start breaking down. They damage the kidneys primarily by passive diffusion into the tubules, where they poison the mitochondria. This results in inadequate energy production so active excretion is impaired, increasing oxidative stress as the damaged mitochondria leak highly oxidative high-energy electrons and oxygen and, eventually, cell death resulting in progressive loss of kidney function.6 Other examples in this toxic class include perflurooctanoic acid (PFOA) and perflourooctanesulfonic (PFOS) acid. Glyphosate. The herbicide glyphosate appears to be a huge problem for the kidneys. It is heavily used in conventional agriculture and around the home under names such as Roundup. Epidemiological research has found a very strong correlation between glyphosate use and the kidney failure epidemic. Of course, association does not prove causation. Animal research shows that chronic exposure at very low dosages causes kidney damage. A 2-year study in rats’ drinking water with 0.1 PPB of glyphosate resulted in cellular kidney abnormalities. 10

Integrative Medicine • Vol. 14, No. 6 • December 2015

Researchers in Sri Lanka found that those who drink well water contaminated with glyphosate have a higher incidence of kidney failure in proportion to concentration starting at 0.7 PPB. Farmers spraying glyphosates in the fields have a 5.4-fold increased incidence.7 The European standard for water contamination is 0.1 PPB, whereas the US Environmental Protection Agency (EPA) standard is an inexplicable 700 PPB!8 Strangely, I was unable to find definitive current measures of the amount of glyphosate or its main metabolite, aminomethylphosphonic acid (AMPA), in US water supplies. It had to be current because the amount in use has increased rapidly the past 2 decades. The best I could find was a study commissioned by Moms Across America, published in 2014.9 This study lacks scientific rigor in that they tested only 21 drinking water samples with no apparent methodology for ensuring a representative distribution. Nonetheless, the results are alarming. Thirteen of the samples had glyphosate levels ranging from 85 to 330 PPB. Especially worrisome is that they found 76 to 166 PPB in all the breast milk samples they tested. Some researchers are speculating that glyphosates may also be a big part of the problem with genetically modified organism (GMO) foods. They are genetically modified specifically to be resistant to glyphosate. This means more is sprayed around them and, thus, into the food supply, water, and breast milk. Smoking As would be expected, smoking damages the kidneys. It is high in cadmium and nicotine constricts the blood vessels going into the kidneys, thus decreasing glomerular filtration. It also increases generation of reactive oxygen species and activation of fibrotic pathways in the kidneys. Nonsteroidal Anti-inflammatory Drugs This one is a bit of a surprise and quite serious. Most nonsteroidal anti-inflammatory drugs (NSAIDs) were initially available only by prescription and then became available over the counter when their patents ran out. Many of these now readily available drugs have long-term side effects that are not adequately appreciated by most people. Virtually all safety studies are short term, so many toxic effects are not detected during the research and development stages and are now showing up in population studies. Acetaminophen, aspirin, ibuprofen, naproxen, indomethacin, and COX-2 inhibitors have now all been shown to cause kidney damage when used chronically. Chronic consumption (>3 y) of single and combinations of NSAIDs are now known to cause typically irreversible analgesic nephropathy. Figure 4 summarizes the risks. As can be clearly seen, these classes of drugs greatly increase the risk of kidney failure. Please be clear, this is end-stage kidney failure we are looking at. Obviously, loss of kidney function is much more prevalent.

Pizzorno—The Path Ahead

Figure 4. Risk of Kidney Failure From Long-term Use of NSAIDs10

The good news is that even in patients with kidney failure, stopping the use of NSAIDs results in some recovery of function. As shown in Figure 5, after 6 months, those with the most damaged kidneys enjoy more than a doubling of kidney function. Toxins From the Gut Long-time subscribers will likely remember my editorial on the role of the gut in chronic disease. At the time, I had not adequately appreciated how hard endotoxins are on the kidneys. This is a bit of a chickenand-egg issue as damaged kidneys also have trouble clearing endotoxins. Figure 6 clearly demonstrates what happens to endotoxin levels as kidney function declines. Further supporting the concept that a toxic gut damages the kidney is the research showing a direct correlation between the level of indoles in the blood and loss of kidney function.13 A long-term prospective study also found a correlation between rate of death and indole levels in dialysis patients.14

Figure 5. Stopping NSAID Use Greatly Improves Function in Patients With Kidney Failure11

Follow-up time = 180 d

46.9

45.9

Figure 6. Endotoxins and the Kidneys12

27.1

25.6

fo re Aft er

Aft er

fo re

11.7

4 CKD stage

Abbreviations: eGFR, estimated glomerular filtration rate; CKD, chronic kidney disease.

Pizzorno—The Path Ahead

Endotoxin Levels (EU/mL)

23.9

50 45 40 35 30 25 20 15 10 5 0

fo re Aft er

Average eGFR

mL/min per 1.73 m2

Excessive Salt in the Diet Another big problem for the kidneys, and some researchers are suggesting may be an important contributing cause to their degeneration, is excessive salt consumption. The 2 to 6 excessive grams of salt the average person consumes every day appears to overload

eGFR

Abbreviation: eGFR, estimated glomerular filtration rate.

Integrative Medicine • Vol. 14, No. 6 • December 2015

Figure 7. The Dramatic Increase in Sodium and Decrease in Potassium Found in the Modern Diet Sodium

Potassium

3000 2000 1000 0

Developmental

Modern

the kidneys enough to impair their ability to eliminate other toxins, especially acidic metabolic waste products. In the millennia as we evolved as a species, salt was not readily available so we had developed effective mechanisms for retaining salt. As shown in Figure 7, we went from an evolutionary diet that had a Na/K ratio of 1:10, to one that is more than 3:1. Excessive Phosphates in the Diet The average American consumes far more phosphorus than the Recommended Dietary Allowance (RDA) of 700 mg/d for adults. As the amount of phosphorous added to prepared foods is under reported. See Lara Pizzorno’s article in issue 14.4 for a full discussion of this problem.15 It is difficult to be definitive, but it appears that a substantial portion of the population consumes more than the tolerable upper limit of 4000 mg/d. As clearly shown in Figure 8 (which underestimates actual phosphate consumption), the vast majority of the population consumes way more phosphorous than recommended. What is worse, though, is that at least 40% of Americans consume at least twice the recommended Figure 8. The Excessive Phosphorous Intake in the Typical Diet Increases All-cause Mortality16

daily allowance of phosphorous, a level known to as much as double all-cause mortality. Research has shown that excessive phosphorous consumption significantly disrupts hormonal regulation of phosphorus, calcium, and vitamin D, causing disordered mineral metabolism; osteoporosis; cardiovascular disease; and impaired kidney function.17 Anything that decreases blood flow to the kidneys results in decreased excretion of toxins. Excessive phosphates damage the tubules, increase fibrosis blocking the blood vessels, and decrease glomerular filtration rate. Getting rid of phosphates is a huge problem for the kidneys, with one of the early signs of kidney failure being increasing phosphate levels in the blood. The primary sources of “hidden” phosphates are additives used as processing aids, such as acid balancing (especially in carbonated beverage); leavening of bread; color and moisture retention; anticaking; and flavorings. Assessing total phosphate load is difficult as current databases underestimate the phosphorus content of processed foods by at least 25% to 30%.18 The primary sources of phosphates can be found in Lara’s article. Summary As I worked on this editorial, I was quite surprised to find that so much of our kidney’s normal function is being used up by everyday chemicals we eat, such as salt and phosphates, and commonly doctor- and self-prescribed NSAIDs. When environmental toxins such as cadmium, glyphosate, and halogenated hydrocarbons are added to the burden, the kidney function loss epidemic goes from inexplicable to predictable. Although, with the exception of workplace exposure, none of these toxic factors alone is the big problem, together they overwhelm and progressive damage the kidneys. I am coming to the conclusion that strengthening and protecting kidney function is one of the best antiaging strategies we can recommend to our patients. In the next issue, I will discuss ways of protecting the kidneys and actually increasing function even in “normal” people. In This Issue We start this issue with another interesting commentary by Associate Editor Jeff Bland, PhD. The concept of “disease” and how it has shaped the evolution of medical practice is a fascinating story. On the one hand, the standardization of disease, its diagnosis, and treatment played a substantial role in the efficacy of conventional medicine in many areas. On the other hand, the implicit standardization of humans to make this concept work is the root cause of many of the limitations of conventional medicine as well. I think John Weeks’ work compiling documentation of the cost-effectiveness of integrative medicine is very important. It was powerfully validated during a meeting I

Integrative Medicine • Vol. 14, No. 6 • December 2015

Pizzorno—The Path Ahead

had earlier today when an insurance broker asked me for documentation on why she should recommend integrative medicine to her corporate clients as a way of corralling spiraling health care costs. The potential of immunotherapy in the treatment of cancer has seemed a great idea for a long time. However, the implementation has been much more complex than expected. Managing Editor Craig Gustafson interviewed Bernard Fox, PhD, to help us better understand the challenges and successes. Dr Fox will be speaking at the annual conference of the Oncology Association of Naturopathic Physicians (OncANP) in Phoenix, Arizona, February 26 through 28, 2016. I am very excited that with the great leadership of David Riley, MD, we are now regularly publishing case reports—2 for this issue, a pace I hope we can maintain. All readers are invited to submit cases using the CARE guidelines he created (you can access these standards at http://www.imjournal.com). Kara Fitzgerald, ND, presents us an insightful intervention for a teenager with eosinophilic gastroenteritis. With concepts echoing Dr Bland’s commentary, Dr Fitzgerald’s case is a great example of diagnosing and treating the “disease” versus understanding the multiple functional disturbances that are the actual problem. Scott Shannon, MD; and Janet Opila-Lehman, ND, collaborate to provide us an intriguing way of helping patients addicted to marijuana. I find particularly intriguing the concept of anxiety reduction being an important driver of excessive marijuana use. Our clinician interview is with Kara N. Fitzgerald, ND. Craig Gustafson discusses with her the importance for clinicians of well-constructed case reports. Her recommendations on how busy clinicians can share their insights in this fashion and the templates she has created are extremely helpful and I am grateful for her sharing. As usual, Associate Editor Bill Benda, MD, finishes the issue with his, as usual, provocative BackTalk. All I can say is, “Are you sure, Bill?”

References

1. Frassetto LA, Morris RC Jr, Sebastian A. Effect of age on blood acid-base composition in adult humans: role of age-related renal functional decline. Am J Physiol. 1996;271(6/2 ):F1114-F1122. 2. Pizzorno J. Is mercury toxicity an epidemic? (Part I) Integr Med Clin J. 2009; 8(1):8-10 3. Pizzorno J. Is mercury toxicity an epidemic? (Part II). Integr Med Clin J. 2009; 8(2):8-12 4. No author listed. Canaries in the kitchen: Teflon toxicosis. Environmental Working Group Web site. http://www.ewg.org/research/canaries-kitchen. Published May 15, 2003. Accessed November 16, 2015. 5. Seidel WC, Scherer KV Jr, Cline D Jr, et al. Chemical, physical, and toxicological characterization of fumes produced by heating tetrafluoroethene homopolymer and its copolymers with hexafluoropropene and perfluoro(propyl vinyl ether). Chem Res Toxicol. 1996;4(2):229-236. 6. Groves CE, Lock EA, Schnellmann RG. Role of lipid peroxidation in renal proximal tubule cell death induced by haloalkene cysteine conjugates. Toxicol Appl Pharmacol. 1991;107(1):54-62 7. Jayasumana C, Paranagama P, Agampodi S, et al. Drinking well water and occupational exposure to herbicides is associated with chronic kidney disease, in Padavi-Sripura, Sri Lanka. Environ Health. January 2015;14:6 8. Environmental Protection Agency. Basic information about glyphosate in d r i n k i n g w a t e r. h t t p : / / w a t e r. e p a . g o v / d r i n k / c o n t a m i n a n t s / basicinformation/glyphosate.cfm#four. Updated February 9, 2014. Accessed November 18, 2015. 9. Honeycutt Z, Rowlands H. Glyphosate testing full report: Findings in American mothers’ breast milk, urine and water. Moms Across America Web site. http://www.momsacrossamerica.com/glyphosate_testing_results. Published April 7, 2014. Accessed November 18, 2015. 10. De Broe ME, Elseviers MM. Over-the-counter analgesic use. J Am Soc Nephrol. 2009;20(10):2098-2103. 11. Wei L, MacDonald TM, Jennings C, et al. Estimated GFR reporting is associated with decreased nonsteroidal anti-inflammatory drug prescribing and increased renal function. Kidney Int. 2013;84(1):174-178. 12. McIntyre CW1, Harrison LE, Eldehni MT, et al. Circulating endotoxemia: A novel factor in systemic inflammation and cardiovascular disease in chronic kidney disease. Clin J Am Soc Nephrol. 2011;6(1):133-141. 13. Lin CJ, Chen HH, Pan CF, et al. p-Cresylsulfate and indoxyl sulfate level at different stages of chronic kidney disease. J Clin Lab Anal. 2011;25(3):191-197. 14. Wu IW, Hsu KH, Hsu HJ, et al. Serum free p-cresyl sulfate levels predict cardiovascular and all-cause mortality in elderly hemodialysis patients—a prospective cohort study. Nephrol Dial Transplant. 2012;27(3):1169-1175. 15. Pizzorno L. Nothing boring about boron. Integr Med Clin J. 2015;14(4):35-48 16. Chang AR, Lazo M, Appel LJ, Gutiérrez OM, Grams ME. High dietary phosphorus intake is associated with all-cause mortality: Results from NHANES III. Am J Clin Nutr. 2014;99(2):320-327. 17. Pizzorno L. Canaries in the phosphate-toxicity coal mines. Integr Med Clin J. 2014;13(6):24-32 18. Calvo MS, Uribarri J. Contributions to total phosphorus intake: All sources considered. Semin Dial. 2013;26(1):54-61.

Joseph Pizzorno, ND, Editor in Chief drpizzorno@innovisionhm.com http://twitter.com/drpizzorno

Pizzorno—The Path Ahead

Integrative Medicine • Vol. 14, No. 6 • December 2015

CREATING SYNTHESIS

When Is a Disease a “Disease”? Jeffrey Bland, PhD, Associate Editor

Jeffrey Bland, PhD, is the president and founder of the Personalized Lifestyle Medicine Institute in Seattle, Washington. He has been an internationally recognized leader in nutrition medicine for more than 25 years. Dr Bland is the cofounder of the Institute for Functional Medicine (IFM) and is chairman emeritus of IFM’s Board of Directors. He is the author of the 2014 book The Disease Delusion: Conquering the Causes of Chronic Illness for a Healthier, Longer, and Happier Life.

ave you ever known anyone who you admired but found out later that there was much more to the person than you ever recognized? Such was my association with Dr Michael Burnhill, who was my colleague and friend from our first meeting in 1985 until his death at 72 years of age in 2000. I knew many things about Michael. He had graduated magna cum laude from Syracuse University in 1949 and received his medical degree in 1955. He was boardcertified in obstetrics and gynecology and had been a pioneer in women’s health. I also knew that Michael had an illustrious academic medical career at George Washington University Hospital and Johns Hopkins Hospital and School of Medicine, and that he had joined the staff at the Robert Wood Johnson Medical School and University Hospital as a professor of obstetrics and gynecology and senior attending physician from 1972 to 1999. What I didn’t know was that he and his father, Dr Charles Birnberg, had developed the popular early intrauterine device (IUD) known as the Birnberg Bow,1 and that he later became the vice president of medical affairs for the national Planned Parenthood Federation of America from 1995 to 2000; he was obviously a very strong advocate for women’s health issues and selfdeterminism. One of the many things I personally learned about from Michael during the years of our friendship was the historical way in which women’s health issues were often marginalized as “all in the mind” or a “functional disorder.” He was particularly concerned about the way that medicine treated pelvic pain in women where no overt pathology could be found as a psychosomatic issue that had no 14

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“organic” pathological explanation. His clinical experience told him that this was not true. When women came to him with a presentation of pelvic pain, he found that in many cases the pain could be attributed to chronic inflammation due to low-level bacterial or fungal infection. Using this concept as the etiology for pelvic pain syndromes, he successfully treated thousands of women with this presenting symptomatology in the course of his medical career by using probiotic and prebiotic therapy to improve mucosal immune function. My friendship with Michael coincided with my work on developing the concept of functional medicine as a systems biology approach to understanding the origin of chronic illness. Michael became more and more convinced that the solution to treating female pelvic pain of unknown origin was to understand the complex interrelationship among the patient’s microbiome, the systemic immune system, and the reproductive system. In essence, he believed that pelvic pain was a perfect example of a functional somatic disorder, the origin of which was rooted in a chronic disturbance of the urogenital immune system that was triggered by cross-infection from the gastrointestinal microbial community. He did not see unexplained urological pain syndromes as a “disease,” but rather as one of a group of functional somatic syndromes. So when should a condition be recognized as a “disease” and how does a “disease” differ from a functional somatic syndrome? The 9th edition of the International Classification of Diseases (ICD-9), established in 1975, listed 13 000 codes for diseases. The 10th edition, which was released in 2012, listed 68 000 codes for diseases. What does this mean in terms of our understanding of the term disease? How do we account for 55 000 additional codes for disease being provided in the ICD-10 if disease is discrete and well defined? I believe the answer relates to the lens though which we view human function. That is, the definition of a pathology changes when we move from descriptive symptomatology to a more quantitative series of diagnostic tools such as X-ray assessment, blood chemistry evaluation, electron microscope identified histopathology, nuclear magnetic resonance (NMR) spectral data, and immunohistochemistry. And to this list of assessment tools, we now need to add the full complement of omics analytics including genomics, transcriptomics, proteomics, metabolomics, and epigenomics. Bland—Creating Synthesis

Many of the new diseases listed in the ICD-10 were thought of as syndromes or conditions of unknown pathology in the ICD-9. As biomedical sciences have evolved, so has our understanding of the “organic” nature of many chronic conditions rooted in functional physiological disturbances that were previously considered “syndromes.” What information indicates a disturbance in function that justifies defining the condition as a “disease?” Where do we draw the line? There are clearly no hard and fast rules that guide us in determining where a functional somatic syndrome ends and a disease begins. But there is now strong evidence that stratification of different genotypes for major diseases such as heart disease, diabetes, autoimmune diseases, and cancer results in the identification of many variants of the disease that originate from different functional genomic expression patterns, and therefore respond to different therapies.2,3,4,5 From this new understanding comes a different definition of disease and an even greater blurring of the lines. There is recognition that there is a gradient of increasing pathology moving from early stage functional changes to functional somatic syndromes and then progressing onto a specific pathology that is called a “disease.” Functional Medicine, Functional Somatic Syndromes, and the Definition of “Disease” Let’s return to my story about Michael. He recognized that the presentation of pelvic pain of no known origin in his female patients was not simply because the condition was “all in the mind.” Rather, he surmised that the pain was resulting from disturbances in function within the urogenital tract that were not obvious through the traditional lens of pathology. Further, he recognized that these women suffered from a disturbance that involved multiple systems that cut across the disciplinary boundaries of medical specialties. Michael was most interested in the condition of vulvodynia, which he believed was a classic example of a “functional medicine” disorder. His experience identified the condition as a result of contamination of the vulvar area with both fungal and bacterial organisms that triggered the inflammatory immune response. His approach to treatment of this functional somatic syndrome was to use pre- and probiotics to restore lactic acid producing bacteria to the microbiome of the reproductive tract. In 2015 the identification of novel mechanisms involved in generating vulvodynia pain was published from work done at the Rochester School of Medicine and Dentistry.6 This work implicated a fibroblast-mediated proinflammatory response to the fungus Candida albicans as a major contributor to the induction of pain in women with vulvodynia. The findings of this clinical study on the origin of vulvodynia were supported by an earlier publication by a separate group of researchers. These results were from an animal model of the condition, which also demonstrated that vulvovaginal fungal infections Bland—Creating Synthesis

result in persistent pain.7 This etiology of the condition confirms Michael’s advocacy 25 years ago. He recognized that vulvodynia resulted from a functional imbalance of the mucosal microbiome, triggering immune system reactivity and their associated relationship to the gastrointestinal microbiome. It was not a “disease” but rather a result of a functional disturbance among several different physiological processes. Interstitial cystitis and chronic bladder pain as members of the disorders presenting with urogenital pain have also been defined as heterogeneous functional somatic syndromes with etiology related to disturbances in the systemic and mucosal immune systems. Supporting this systemic immune relationship to the etiology of these conditions is the recognition that both coronary heart disease and rheumatoid arthritis are inflammatory comorbidities associated with interstitial cystitis and chronic bladder pain.8 So we come back to the question I posed in the title of this article: When is a disease a “disease?” In any discussion of what constitutes a “functional somatic syndrome,” there is debate as to whether all of these syndromes that do not have a discrete pathology can be considered as derived from a singular cause or whether they derive from functional disturbances of multiple systems.9 In the medical literature, this debate has been defined as “lumpers” and “splitters.”10,11 Lumpers are those individuals who believe that functional somatic syndromes all arise from a singular psychogenic cause, whereas splitters believe that there are many different contributing features to functional somatic syndromes representing both organic and psychological factors. It is my belief that this debate is akin to the philosophical debate of “how many angels can exist on the head of a pin?” The 21st-century explanation of the etiology of functional somatic syndromes derives from the new concept of systems biology, which is focused on understanding the underlying disturbances that give rise to complex chronic illness. These disturbances arise from the interaction of the genes of the individual with their environment, lifestyle, diet, and activity patterns. The functional medicine approach to understanding the etiology of these functional somatic syndromes is to search for the underlying imbalances in core physiological processes that result in the presenting signs and symptoms. The differentiation between a “syndrome” and a “disease” is somewhat arbitrary under the functional medicine formalism and depends on the severity, intensity, and frequency of the presenting symptoms and how the diagnosis fits into the ICD-10 classification system. Basically, we need to move beyond even asking the question. The intellectual pursuit in defining whether a specific condition that a patient presents with is a disease or a functional somatic syndrome is not as important in improving patient outcome as defining the primary functional disturbance that results in their complex symptom profile. Integrative Medicine • Vol. 14, No. 6 • December 2015

CONGRATULATIONS! Dr. Heather Boon, BScPhm, PhD University of Toronto

A recent published review of functional somatic syndromes stated: The future classification of functional somatic syndromes should reflect the need for a balance between organic and psychological approaches. At present, patients with functional somatic syndromes are often dissatisfied with the care they receive, so training of medical students and doctors is mandatory to improve their skills regarding these conditions.12

Winner of the 2015 $250,000 Dr. Rogers Prize for Excellence in Complementary and Alternative Medicine DR. HEATHER BOON is Dean of the Leslie Dan Faculty of Pharmacy, University of Toronto. Her 25-year career was sparked by a recognition of the large number of Canadians using “alternative” medicine and how little research existed. She is a key player in the development of the Centre for Integrative Medicine, a joint venture between the University of Toronto and the Scarborough Hospital. She was

This need for improved understanding and approach to complex medical problems that fall between the cracks of a discrete “disease” and a transient, self-limiting set of symptoms represents the domain of a systems biology approach to functional somatic syndromes. As I look back at my 15-year friendship with Michael, I recognize that he knew instinctively that the concept of a “disease” was somewhat arbitrary, whereas identifying and treating the origin of the specific functional disturbances underlying the patient’s presenting signs and symptoms represented the key to a successful outcome.

a driving force behind the establishment of the IN-CAM network and the International Society for Complementary Medicine Research. She is a leader of the highest integrity and a champion of collaboration across disciplines. For more information on Dr. Boon’s achievements, please visit DrRogersPrize.org. The purpose of the Dr. Rogers Prize is to highlight the important contributions of Complementary and Alternative Medicine (CAM) to health care by recognizing and celebrating the pioneers who have made significant contributions to the field. The Dr. Rogers Prize was created in 2007 and is sponsored by the Lotte and John Hecht Memorial Foundation, Vancouver, BC.

20 15 16

1. Burnhill MS, Birnberg CH. Improving the results obtained with current intrauterine contraceptive devices. Fertil Steril. 1969;20(2):232-240. 2. Hazebroek MR, Moors S, Dennert R, van den Wijngaard A, Krapels I, et al. Prognostic relevance of gene-enviornment interactions in patients with dilated cardiomyopathy: Applying the MOGE(S) classification. J Am Coll Cardiol. 2015;66(12):1313-1323. 3. Dorajoo R, Liu J, Boehm BO. Genetics of type 2 diabetes and clinical utility. Genes (Basel). 2015;6(2):372-384. 4. Castro-Santos P, Laborde CM, Diaz-Pena R. Genomics, proteomics and metabolomics: their emerging roles in the discovery and validation of rheumatoid arthritis biomarkers. Clin Exp Rheumatol. 2015;33(2):279-286. 5. Sudmant PH, Mallick S, Nelson BJ, Hormozdiari F, Krumm N, et al. Global diversity, population stratification, and selection of human copy-number variation. Science. 2015;349(6253):aab3761. 6. Falsetta ML, Foster DC, Woeller CE, Pollock SJ, Bonha AD, et al. Identification of novel mechanisms involved in generating localized vulvodynia pain. Am J Obstet Gynecol. 2015;213(1):1-12. 7. Farmer MA, Tylor AM, Bailey AL, Tuttle AH, MacIntyre LC, et al. Repeated vulvovaginal fungal infections cause persistent pain in a mouse model of vulvodynia. Sci Transl Med. 2011;3(101):101ra91. 8. Keller JJ, Chen YK, Lin HC. Comorbidities of bladder pain syndrome/ interstitial cystitis: A population-based study. BJU Int. 2012;110(11 Pt C):E903-E909. 9. Ushiroyama T. Features and clinical management of functional somatic syndromes in gynecology. Nihon Rinsho. 2009;67(9):1721-1725. 10. Lacourt T, Houtveen J, van Doornen L. “Functional somatic syndromes, one or many?” An answer by cluster analysis. J Psychosom Res. 2010;68(5):455-459. 11. White PD. Chronic fatigue syndrome: Is it one discrete syndrome or many? Implications for the “one vs. many” functional somatic syndromes debate. J Psychosom Res. 2010;68(5):455-459. 12. Rabhi M, Ennibi K, Chaari J, Toloune F. Functional somatic syndromes. Rev Med Interne. 2010;31(1):17-22.

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Integrative Medicine • Vol. 14, No. 6 • December 2015

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References

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Bland—Creating Synthesis

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COMMENTARY

Harvard Team Finds 43% Reduction in Use of Health Care Services via Mind-Body Intervention … plus more John Weeks

This column is offered in collaboration with The Integrator Blog News & Reports (http://theintegratorblog.com), a leadership-oriented news, networking, and organizing journal for the integrative medicine community. For more information on these and other stories, enter keywords from the articles in the site’s search function.

Harvard Team Finds 43% Reduction in Use of Health Care Services via Mind-Body Intervention The understated title of the open access article at PLoS from a Harvard University–Benson-Henry Institute mind-body team is “Relaxation Response and Resiliency Training and Its Effect on Healthcare Resource Utilization.”1 The team examined service use of more than 4000 patients in the Relaxation Response Resiliency Program (3RP) and compared them with an usual care cohort. The findings: “At one year, total utilization for the intervention group decreased by 43%, clinical encounters decreased by 41.9%, imaging by 50.3%, lab encounters by 43.5%, and procedures by 21.4%.” Measured by dollar, reduction was estimated as “on the order of $2360/patient/year.” The authors note that “this reduction is on the order of that found by through other groups” in “other similar time-limited interventions.” They note that “mind-body medicine interventions are inexpensive relative to the cost of an emergency room visit, a hospitalization or even other complementary and alternative medicine (CAM) therapies.” The intervention group was slightly more female, Jewish or Asian versus Christian or black, better off economically, and less likely to include veterans. Comment: The work at what is now Benson-Henry began more than 40 years ago when Herbert Benson, MD, sidestepped the cultural-political challenges of “meditation” among Christian fundamentalists and began re-exploring what he generically called the “relaxation response.” I had a chance to collaborate in the late 1990s with one of Benson’s early partners, Eileen Stuart, RN, PhD, his coauthor on The Wellness Book. She once shared with me her experience of presenting at a major national cardiology meeting on the very positive clinical outcomes for the group-delivered program she had a lead in developing around Benson’s relaxation response research. A couple of audience members came to the stage with questions and interest when she finished her presentation. “If the positive outcomes we achieved had come through a drug,” Stuart told me, “the audience would have been swarming me.” Imagine if a drug or high-tech gadget were associated with a 43% decline in service utilization. Headlines would 18

Integrative Medicine • Vol. 14, No. 6 • December 2015

trumpet that the way out of the woods for the health care crisis had been discovered! “Miracle drug shows way to the Promised Land!” Instead, this report of an ancient practice from traditions across the globe, refashioned in a notable medical school, quietly drifted into the atmosphere. Fact is, the therapeutic option is hard, literally, to grasp. It doesn’t fit too well in the treatment rooms and practice schedules of most clinicians (including those integrative), in the organization of medical delivery, the balance sheets of hospitals, or the profit-taking of dominant stakeholders. This study needs the oomph that songwriter Joni Mitchell once called “star-maker machinery.” Let’s tend to our own garden. How many integrative practices respect this finding? How many integrative health educators focus on these approaches at the level the 43% reduction warrants? How can the integrative health community show leadership? Miracle of meditation shows way out of the health care cost crisis! RAND Report Engages Critical Issue: Complementary and Alternative Medicine—Modalities or Professions? Is a chiropractor a modality? Should his or her value to health care be reduced to the procedure of spinal manipulation? Should a licensed practitioner of acupuncture and Oriental medicine be viewed as a tool to stick needles in people? Or is the health of the public in the United States better served to utilize these practitioners for the breadth of their ability to evaluate and manage (E&M); to provide multiple procedures; and to counsel on stress, diets, and movement? These are among the questions engaged by researchers at the RAND Corporation in their new report Complementary and Alternative Medicine: Professions or Modalities?2 RAND’s veteran coauthor team of Patricia Herman, ND, PhD, and Ian Coulter, PhD, subtitled their work, “Policy Implications for Coverage, Licensure, Scope of Practice, Institutional Privileges, and Research.” The report was developed with the advice of 2 expert panels: one of licensed professionals, and the other of insurers and other stakeholders close to policy. A chief recommendation from the latter group is that any effort for broader recognition should not be framed as a demand from the profession for recognition. Rather, the patient and the values of the triple aim (enhance patient experience, lower per-capita cost, better population health) should be at the center of any such campaign. Other recommendations: (1) Employers are important stakeholders in upgrading Weeks—Industry Insights

ShortTakes u A sweeping policy report entitled “A Call to Action on Integrative Health and Medicine Policy—Advancing the Legacy of US Senator Tom Harkin” has been published by a multidisciplinary set of consortia.3 The report looks back on advances since the 2010 Affordable Care Act and the new directions toward community health. u Traditional medicine has been big news amid the report and controversy surrounding the award of the Nobel Prize in Medicine to Tu Youyou, who credited her discovery to an ancient traditional Chinese medicine text.4 u Botanical sales were up in the United States for the sixth straight year to $6.8 billion in 2014.5 u Separate studies in Germany and France on the economic effect of using homeopathy in their national health systems found opposite outcomes: (1) savings and a suggested public health value in France and (2) substantial increase in costs from users of homeopathic services in Germany.6 u David O’Bryon, JD, the longtime executive director of the Association or Chiropractic Colleges, is the new chair of the Academic Consortium for Complementary and Alternative Health Care.7 u In a rare 7-digit bequest to an academic program in the integrative health space not led by a medical doctor, the Thomas Blount Trust granted $1 million to YoSan University, an acupuncture institution in the Los Angeles area.8 u The American Association Naturopathic Physicians (AANP) has initiated a letter writing campaign to open the Veterans Health Administration to naturopathic physicians.9 u Heather Boon, PhD, was the recipient of the $250 000 Dr Rogers Prize awarded biennially to a

the value of these providers; (2) a great deal of education and health literacy of all parties remains key; and (3) “CAM professions need to work together.” Beyond this more general strategic guidance, the authors include a 1.5-page summary of formal restrictive policies: “Federal and State Laws and Regulations Limit the Inclusion of CAM in Health Systems.” The report was funded through a grant from the NCMIC Foundation. Comment: Since the dialogue about integrating these practitioners began, the medical industry has done its best to turn these human beings into drugs. The classic example is the treatment of chiropractors under Medicare. They are not paid for E&M, only to crack backs. An acupuncturist in San Francisco who I interviewed in the late 1990s captured this payment-induced narrowing of value well. She was considering her first insurance payment in an otherwise cash practice. On finding that she’d only Weeks—Industry Insights

Canadian leader in complementary and alternative medicine. Boon cofounded the IN-CAM Canadian organization of researchers in the field and is also the immediate past president of the International Society for Complementary Medicine Research. Presently dean of the pharmacy program at the University of Toronto, Boon is a globally recognized whole-systems research leader in integrative health, despite her pharmacy background. u The State of Oregon is pushing a nonpharma approach to back pain in its Medicaid program with expanded coverage of acupuncture, massage, and chiropractic.10 u The government of India beat Colgate–Palmolive and the UK pharmaceutical firm Pangaea Laboratories on separate intellectual properties cases related to traditional medicines.11 u The Cleveland Indians are the first baseball team to hire an acupuncturist, Jamie Starkey, LAc, who practices in the integrative medicine program at the Cleveland Clinic.12 u A historic research pilot between a naturopathic medical school the Canadian College of Naturopathic Medicine and Rwandan researchers has found selenium can be valuable against the advance of AIDS. Don Warren, ND, led the project.13 u A professional jokingly considered the “Godfather” in the chiropractic profession, Lou Sportelli, DC, has left his position as president of the NCMIC Group, the chiropractic and naturopathic malpractice insurance provider. He was become president of the NCMIC Foundation. NCMIC, and the foundation, have been major funders of strategic initiatives in chiropractic and integrative health.14

be paid a reduced fee for needling and nothing for any E&M, she told me that if she joined the insurance network that she certainly would no longer give patients the time, care, hand-holding, and counsel that she had historically. The logic was simple: The insurer wasn’t paying for that. Although not the first evidence that insurance can dehumanize and diminish, the denial of humanity of the practitioner in this structure also effectively discounts the humanity of the patient. The patient becomes the passive object of an active object, the tool of payment who sticks the needles. Fear-based and procedure-based, rather than patient-based, this business model expects the least and, by-golly, gets what it pays for. This focus of this report from the Herman-Coulter RAND team on the modality/profession issue is quite timely. The medical industry is stumbling toward what it likes to call a “values-based” approach (AKA, the triple aim). The reduction of “CAM” practitioners—who Integrative Medicine • Vol. 14, No. 6 • December 2015

ironically see themselves as whole-person and holistically focused—to mere tools came from the procedure production, fee-for-service era. It’s time for a thorough reconsideration of how to use these practitioners optimal health creation. The RAND report is a great jumping off point for a new era in integration. Ever Wonder About Those NIH-Funded Trials That Seemed to Dismiss Botanicals? Research on botanicals at the National Center for Complementary and Alternative Medicine (NCCIH) has been controversial since the agency was founded in 1998. Recently, the industry-backed American Botanical Council published an open-access gutsy article in HerbalGram by Don Hopp, PhD, NCCIH’s botanicals lead. His article, “Past and Future Research at National Center for Complementary and Integrative Health (NCCIH) with Respect to Botanicals,” began with a chart of 16 major NCCIH-backed controlled trials on leading herbs for major conditions.15 Hopp shared that the NCCIH has abandoned looking at herbs as useful against diseases and instead is favoring basic research on the complexity and on interactions. Following an invitation from the Integrator Blog News and Reports, 12 integrative health and medicine leaders responded to a call for perspectives.16 The discussants, mainly naturopathic educators and registered herbalists, credited Hopp for the myriad mistakes in dosing and botanical materials used that plagued the major trials. Many commended the agency for beginning to look at how individuals are using the agents as a means of staying healthy. One, James Snow, RH(AHG), an acting dean at Maryland University of Integrative Health, allowed that “the results [even with methods issues] should give pause to anyone looking for simple answers on the shelf at the natural food store.” A significant subgroup, including Snow, expressed intrigue with Hopp’s description of proposed research relative to the complexity of these plants, linking this with their own views that any herb-for-drug substitution scheme misappropriates how botanicals are typically used in practice. Most called for research that better reflects the way herbs are used by clinicians. One, Michael Levin, an industry consultant, strongly pushed for more substitution schemes, asserting that billions could potentially be saved. Comment: The forum provided a great look at multiple perspectives from the field, rather than from the inner sanctum. For these recommendations to gain traction, the challenge in the current NCCIH is that it appears that only 1 of the 18-member advisory council, naturopathic Jane Guiltinan, ND, has an education and clinical practice that makes use of herbs. I wonder, given the depth of the issues with the 16 trials, if NCCIH’s abandonment of herbs against diseases—even if clinically used not to attack the disease but fortify the host—are not a case of garbage in, garbage out. Dismissing botanicals for disease treatment 20

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kills exploration of potential costs savings, such as Levin recommends, from herbs in whole person practice-fordrug substitutions. Consider the opportunity costs related to potential financial savings and limitations of adverse events from conventional pharma. Consider the importance of mindfulness in health care utilization noted in the first article in this column. Might it be that comparing whole person, botanically-involved clinical practices to drug focused conventional practices for individuals with a specific disease also yield reductions in service utilization? We already know that holistic treatment shows well in patient experience. We may be choose to not explore practices that hit solidly on 2 parts of the triple aim—as referenced in the segment on the RAND study—patient experience and lowered costs. Are we ready to dismiss those possible contributions related to botanicals? Is the NCCIH’s choice to not explore botanicals in whole practices denying the “CAM” practitioners who use them a chance to make the case that the RAND study suggests is the key to the kingdom of greater respect, cultural authority, and utilization? References

1. Stahl JE, Dossett ML, LaJoie AS, et al. Relaxation response and resiliency training and its effect on healthcare resource utilization. PLoS ONE. 2015;10(10):1-14. 2. Herman PM, Coulter ID. Policy implications for coverage, licensure, scope of practice, institutional privileges, and research. Rand Corporation Web site. http://www.rand.org/pubs/research_reports/RR1258.html. Accessed November 18, 2015. 3. Integrative Health Policy Consortium. The 2014 symposium report. http:// www.ihpc.org/wp-content/uploads/HarkinSymposiumRpt_2014.pdf. Published September 2014. Accessed November 18 2015. 4. Weeks J. Nobel Prize based on a traditional Chinese medicine text: Themes from the robust media coverage. The Integrator Blog. http:// theintegratorblog.com/index.php?option=com_content&task=view&id=988 &Itemid=189. Published October 9, 2015. Accessed November 18, 2015. 5. Nutraceuticals World. Herbal dietary supplement sales in U.S. rise 6.8% in 2014. http://www.nutraceuticalsworld.com/contents/view_breakingnews/2015-09-10/herbal-dietary-supplement-sales-in-us-rise-68-in-2014/. Published September 10, 2015. Accessed November 18, 2015. 6. Weeks J. French-German mixed results on homeopathy costs, plus role(s) in cancer and public health. Glob Adv Health Med. http://www.gahmj.com/ page/French-German-Mixed-Results-on-Homeopathy-Costs-Plus-Roles-inCancer-and-Public-Health. Published August 19, 2015. Accessed November 18, 2015. 7. Clugston RM, Menard M. ACCAHC Collaborator. http://myemail. constantcontact.com/ACCAHC-Collaborator--62--Transitions--Updates-and-more-.html?soid=1109272039378&aid=edb_SgQz_TY. Accessed November 18, 2015. 8. No author listed. Yo San University receives its largest charitable gift. Santa Monica Mirror Web site. http://www.smmirror.com/articles/News/Yo-SanUniversity-Receives-Its-Largest-Charitable-Gift/44217. Published September 23, 2015. Accessed November 18, 2015. 9. American Association of Naturopathic Physicians. Legislative action center. http://www.congressweb.com/aanp/23. Accessed November 18, 2015. 10. The Lund Report. Oregon changing how it deals with back pain. https:// www.thelundreport.org/content/pills-pins-oregon-changing-how-it-dealsback-pain. Accessed November 18, 2015. 11. Weeks J. India beats Colgate-Palmolive and UK pharma firm in separate intellectual property cases. Glob Adv Health Med. http://www.gahmj.com/ page/India-Beats-Colgate-Palmolive-and-UK-Pharma-Firm-in-SeparateIntellectual-Property-Cases. Published August 15, 2015. Accessed November 18, 2015. 12. Gupta S. Baseball’s oldest player reveals his secret – acupuncture. Everday Health Web site. http://www.everydayhealth.com/news/baseballs-oldestplayer-reveals-his-secret-acupuncture/. Updated November 26, 2014. Accessed November 18, 2015.

Weeks—Industry Insights

13. Newswire. Canada-Rwanda study concludes daily selenium supplementation can delay progression of infection in HIV+ patients. http://www.newswire.ca/ news-releases/canada-rwanda-study-concludes-dailyselenium-supplementation-can-delay-progression-ofinfection-in-hiv-patients-522425091.html. Published August 19, 2015. Accessed November 18, 2015. 14. Weeks J. Integrative medicine, complementary and alternative health and medicine round-up #96: October 2015. The Integrator Blog. http://theintegratorblog. com/index.php?option=com_content&task=view&id= 989&Itemid=189. Published October 12, 2015. Accessed November 18, 2015. 15. American Botanical Council. Herbalgram. http://cms. herbalgram.org/herbalgram/issue107/hg107-featnccih.html. Accessed November 18, 2015. 16. Weeks J. Twelve integrator voices on a theme: NCCIHâ€™s past and future plans for research on botanicals. The Integrator Blog. http://theintegratorblog.com/index. php?option=com_content&task=view&id=987&Item id=189. Published October 17, 2015. Accessed November 18, 2015.

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PRESENTERS 2016

Bernard Fox, PhD: The Promise of Immunotherapy in Curing Cancer Interview by Craig Gustafson Facilitated by the Oncology Association of Naturopathic Physicians (OncANP) annual conference in Phoenix, Arizona, February 26–28, 2016.

Bernard Fox, PhD, will speak at the Oncology Association of Naturopathic Physicians (OncANP) annual conference in Phoenix, Arizona, February 26–28, 2016. He is chief of the Laboratory of Molecular and Tumor Immunology at the Robert W. Franz Cancer Research Center in the Earle A. Chiles Research Institute at Providence Cancer Center, UbiVac, and an associate professor of molecular microbiology and immunology in the School of Medicine at Oregon Health and Science University. Dr Fox was part of the team that performed the first-inhuman studies of genetically modified cells (National Cancer Institute) and was an investigator on the first clinical trial to genetically modify tumors in patients (University of Michigan), the first gene therapy trial for HIV/AIDS (University of Michigan) and the first trial of gene-modified tumor vaccines in Oregon. Dr Fox helped develop the tumor immunology training programs between the Earle A. Chiles Research Institute and both Xi’an Jiaotong University in Xi’an, China, and the Ludwig-Maximilians-University in Munich, Germany. A principal goal of these programs is to train scientists and physicians to translate preclinical studies into clinical trials. His research efforts are divided between preclinical animal models and the development, performance, and monitoring of immunotherapy trials for patients with cancer. His research efforts have been supported by the National Cancer Institute/National Institutes of Health, the Department of Defense, biotechnology and pharmaceutical companies, and philanthropic sources. Integrative Medicine: A Clinician’s Journal (IMCJ): At the Oncology Association of Naturopathic Physicians, or OncANP, conference in February, you will be speaking about cancer immunotherapy. How do immunotherapy treatments work against cancer cells? Dr Fox: We should start with the following concept: We think that everybody develops cancer over their lifetime, and probably many times. Those who do not have evidence of cancer have an immune system that has managed to eliminate it. It is only when the cancer figures out ways to 22

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evade the immune system—developing stealth mechanisms that can allow it to escape detection or by exploiting defects that reduce the capabilities of patients’ immune systems—that we see cancer growing out. The idea of cancer immunotherapy is to either educate or boost the immune system so that it can eliminate cancer. Recently there have been FDA approvals for a series of agents that can boost the immune response and are increasing survival for patients with cancer. IMCJ: Are specific escape routes targeted, or is the therapy more of a general strengthening or reinforcement of the immune system? Dr Fox: The drugs that have been approved recently have focused on taking the brakes off of the immune system. They are called checkpoint inhibitors. The first is normally used by the body to turn off its own immune cells. It is called CTLA-4, or cytotoxic T-lymphocyte-associated protein 4, and it is a molecule found on the surface of activated T cells. When immune cells express CTLA-4 instead of being “boosted” by other immune signals, termed costimulatory signals, the T cells are shut off, effectively putting the brakes on the T cells. So by giving an antibody that binds to CTLA-4—that inhibitor that negatively regulates T cells—the T cells no longer have that braking system and they can fight the cancer continuously. That antibody is anti-CTLA-4. The drug name for it is ipilimumab, or Yervoy, and it is one of the drugs that has been approved. Another molecule that gets upregulated when T cells are activated to respond to cancer is called PD-1, or programmed death 1. So PD-1, you can imagine, is not a good thing to have on your surface. It is programming you for death or turning you down or shutting you off—maybe transiently or maybe permanently. So when you have a blocking antibody against PD-1, you can take out that negative signal, effectively taking the brakes of off the immune T cells. The reason that this is so important is that many types of tumor cells can express the ligand for PD-1, which is programmed death ligand 1, or PD-L1. Tumor Presenters 2016—Fox

cells can upregulate this ligand, so that when the activated killer cells come in to kill the tumor with PD-1 on their surface, the tumor’s PD-L1 combines with the PD-1 to trigger those T cells and shut them off. By taking that inhibitory signal away—by administering an antibody against PD-1 that blocks the death signal, you can maintain the activated T cells and they can continue their killing mechanisms. Another facet is that tumor cells have also figured out ways, if they do not express PD-L1, to induce other immune cells to express PD-L1, essentially making a barrier of immune cells that protects the cancer. It is pretty fascinating. These are recent findings that are providing insights into why patients either respond or progress on immunotherapy. Additionally, new technology which gives us ways to evaluate multiple markers on cells, is providing incredible insight into what is going on in the patient’s tumor, leading to ways to tailor therapy in the future so that patients can have more effective therapy. IMCJ: Is this leading in the direction of individualized medicine? Dr Fox: It is individualized in terms that we can tailor therapy, for example, administer anti-PD-1 to patients with tumors that contain PD-L1+ cells, but it is not individualized in the sense that you have to make a product just for that patient. However, using biopsies to determine which drug, or combination of drugs, a patient should receive, is coming. The FDA has already approved a companion biomarker test for PD-L1 expression. It enriches for patients who are likely to respond to treatment with anti-PD-1. This is just a start, but it is getting there. I saw a paper this weekend, on a disease called diffuse large B-cell lymphoma, from a Japanese group that looked at more than 1000 patients and were able to separate and identify a new cohort of these B-cell lymphomas that express the PD-L1 molecule. It is a very small percentage. I do not remember the numbers offhand. I think it was 10% or 15%. For those 10% or 15%, since the cancer expresses PD-L1, you would want to try to do a clinical trial treating those patients with an antibody that would eliminate the negative effect of that PD-L1 molecule. You would imagine, that may be why those patients do so badly, is because the cancer figured out ways to turn off the killer cells so it can continue to grow uncontrolled. IMCJ: What are the advantages for immunotherapy for patients, as opposed to treatments that are more often used in oncology? Dr Fox: I will give you an example. Hodgkin’s lymphoma is a disease that can be treated effectively in a number of patients through bone-marrow transplant or stem-cell transplant. I think everybody reading this knows that in a Presenters 2016—Fox

stem-cell transplant, you do lethal doses of chemotherapy and, in many cases, radiation. You come back and rescue the patient by giving them a stem-cell transplant. This is a risky procedure but it can cure people of their disease. The data are still early, but it looks like Hodgkin’s lymphoma patients who have failed bone-marrow transplant are having an 80% response rate to treatment with anti-PD-1. This is amazing. Here you have a drug, so I do not want to minimize the fact that it has some very serious toxicities that can lead to death. For example, you can have really bad diarrhea, pneumonitis, or hypophysitis, and you can be taking a pill for the rest of your life. But this is different than being taken to the edge of death, through the elimination of your whole immune system and repopulating it with a bone marrow transplant. In this case, immunotherapy is giving an IV every 2 or 3 weeks and many people do not have serious side effects. That is where we think the field is going. As someone who has been in immunotherapy for more than 25 years, I see this moving to where we will eliminate the use of chemotherapy in many histologies. You will certainly want to use surgery to cut out whatever you can. Radiation will be used for some diseases, but I think we are going to get to the point where we can figure out what goes on and understand how cancer evades the immune system. We will then be able to take those escape mechanisms away and we will be able to eliminate those cancers. That view is not shared by a lot of people, but there were very few people that thought immunotherapy would be used for 60% of cancers, and that the biggest blockbuster drug of all time in oncology (at least until the next new immunotherapy arrives) would be anti-PD-1. It is clear—it is working across a majority of cancer histologies. Positive results from immunotherapy trials is shaking up the field in such a way that I think it is not unreasonable to think about a world where chemotherapy is rarely used. I think Hodgkin’s lymphoma is going to become the poster child for that concept of being able to eliminate chemotherapy. IMCJ: How is immunotherapy faring as far as remission and recurrence rates are concerned? Can these downstream observations be measured yet? Dr Fox: For the new drugs that we are talking about, it is way too early to know how that is going to work out. For immunotherapy in general, I would have you look at interleukin 2, or IL-2, which is a drug, a hormone of the immune system, a cytokine, and a T-cell growth factor. It has no effect directly on cancer cells, because they do not have the IL-2 receptor. The drug works by boosting the immune cells and can lead to complete remissions in a small percentage of patients with melanoma and renal cancer. That can be in the 5% to 10% range. For those who obtain a complete response, complete response is maintained in 70% to 90% of patients at 20 years. Integrative Medicine • Vol. 14, No. 6 • December 2015

We have data from 1 group that showed 90% at 20 years. Another group showed about 70% at 20 years. There is actually a woman with metastatic melanoma who was treated at the National Cancer Institute in 1984 who had a complete response and who is now out 30 years. This is a patient with melanoma that had failed treatment with many other therapies and was cured by immunotherapy. This is a great thing about the immune system, it can provide life-long immunity. Once you have had measles it does not come back. Once you have had mumps, you are protected—unless your immune system is knocked out— and it can provide lifelong immunity. The Society for Immunotherapy of Cancer has a t-shirt that says, “Cure. Yeah, we said it.” We think that if you can obtain complete responses with immunotherapy, it will lead to lifelong cures for patients. That is very different from small molecules for targeted therapy that can have complete remission rates of maybe 9 to 12 months in many diseases before the tumor evades—with the exception of chronic myeloid leukemia, where there can appear to be very longterm durable remission. However, the studies with these new immunotherapies in patients with solid cancers are not getting all of the patients into a complete response. For patients who have a partial response, we expect that the cancer cells that remain are going to find ways to evade the immune system. Some, including myself, think patients have a partial response because the immune system has not been educated to see enough of the variant cancer cells present in the tumor. To overcome this, we may need to induce broad immunity against 10s or 100s of targets expressed by the cancer. So, the future for our field is going to be in figuring out how to broaden a patient’s anticancer immune response to prevent the tumor cells from escaping—from turning off this gene or that gene that the immune system sees, so that tumor cells can not evade. We expect that the cancer cells will not be able to eliminate all those proteins, or it will cease to be a cancer cell. From my perspective, inducing broad anticancer immunity is one of the major goals for the next decade. IMCJ: What challenges are you encountering in cancer immunotherapy? Dr Fox: We are not getting all those patients into complete remission, but some of the patients with partial remissions are having stability for a very long period of time, 4 to 5 years. However, I am concerned, because cancer is a very tough adversary. It can evolve. It continues to evolve. If you have not eliminated all of the tumor cells, they’re going to continue to evolve. One of my concerns is that we may be breeding tumors that will learn to escape the immune system in some other way. That is why we need to be pushing for the complete response—getting complete response rates that are very high. 24

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For lung cancer, the study, which contributed to the approval of anti-PD-1 in lung cancer, has seen a doubling of response rates over chemotherapy. That is a great start, looking at only 1 agent—and that agent is only targeting 1 escape mechanism (PD-1). But again, while response rates are relatively high, many of these patients are not having a complete response and remain at risk of having their cancer progress. What we have been talking about are antibodies that are checkpoint inhibitors, However, there are other ways that we can boost the immune system: by giving costimulation or by directing the immune system to see the cancer better by employing cancer vaccines. We think the reason that checkpoint inhibitors do not work in some patients is because the patient receiving the checkpoint inhibitor does not have their immune system turned on so that it is able to recognize their tumor. While it is not perfect it is working in nonsmall cell lung cancer. It is also working in triplenegative breast cancer and is having an effect on gastric cancer, renal cancer, and bladder cancer. I believe antiPD-1 is currently active in approximately 12 different histologies. That is just by itself. As soon as these drugs were approved, partnerships started combining these immunotherapies with other things like chemotherapy or small molecules. That is where a big part of this field is going. There are as many as 200 trials going on in the United States, alone, using immunotherapies—anti-PD-1, in particular—for many different histologies. IMCJ: Is cancer immunotherapy giving us insight into which cancers are more treatable? Dr Fox: There is a paper in Nature Reviews Cancer by Wolf Fridman, MD, PhD,1 that reviewed more than 100 papers. This is now more than 3 years old. It looks at cancers and looks at how many different cancers show evidence that when you look at the patient’s biopsy, if there are immune cells present—certain types of immune cells—then those patients do better, regardless of the therapy. It is the prognostic biomarker for success. While this is well known in colon cancer, it is also true in 18 of the 20 malignancies that Dr Fridman looked at. This tells us 2 things: First, in all these cancers, we think that the immune system is really important. But, it also tells us that in cancer cases, where we catch them early and do not do anything for those patients, for instance stage I or II colon cancer, it turns out that patients with no immune cells present in their resected tumor have a high likelihood that their cancer is going to come back. Currently most centers do not offer treatment to these patients as the vast majority will do well and the 5-year survival rate is greater than 90%. However, if you could identify the patients who will progress in the next 2 years, you could offer them a clinical trial. One option might be a cancer vaccine that might prevent recurrence. Presenters 2016—Fox

IMCJ: What are the newest directions being explored? Dr Fox: The latest thing is probably the chimeric antigen receptor T cells. In this case you engineer immune cells with a receptor that can bind cancer cells. When these engineered immune cells bind a cancer cell, this new receptor turns on the killing mechanisms of the immune cell and the cancer can be destroyed This approach is working incredibly well in leukemias, lymphomas, and liquid tumors. They have not yet worked well in solid tumors, though. However, it is likely that they eventually will work well because there are a lot of really smart people putting in a lot of energy, and now they have financial resources to support the required research. Another strategy to direct immune cells to the cancer without having to genetically engineer a patients immune cells are called biospecific antibodies. These are small molecules that have at least 2 ends to them. One end binds to the immune cells, the other end binds to the cancer. That way they can redirect the T cells without having to engineer them. This is a very exciting area of clinical research. An area that I am also working on is cancer vaccines that can broaden the immune response against more targets expressed by cancer. IMCJ: Is immunotherapy poised to become a mainstream tool in the oncologist’s toolbox, or is it still at a point where access is restricted to those participating in a clinical trial? Dr Fox: Now that it has been approved for second-line treatment of the number 1 cancer, which is lung cancer, I think it is going to become a more common tool of the oncologist. In the next 2 to 3 years, you are going to see many more approvals. Probably in the next 6 months, we are going to see approvals. That is going to really broaden the application of these new agents. A current challenge for the field is to educate physicians and educate patients as to what the side effects are, how to give these drugs safely, and what to watch for. It is very different from the approach oncologists are used to when prescribing chemotherapy. For example, when somebody has diarrhea, you do not give them antibiotics, you give them steroids. We have got to educate people to do those sorts of things, because if you don’t, it can lead to ulcerations or other situations where patients will die. There is still a long way to go to get the general oncologist to become comfortable with this. Having said that, the American Society for Clinical Oncology’s meeting—the largest meeting in the world of medical oncology—this past year had significant time dedicated to immunotherapy oncology. It was in many of the major sessions and symposia. So, docs who are going to this meeting are learning about immunotherapy pretty rapidly, and that’s going to be the major way to get the information out. Then there are societies like the Society for the Immunotherapy of Cancer, which puts on a program Presenters 2016—Fox

called Advances in Cancer Immunotherapy day courses to help educate oncologists on to how to administer these drugs and what to look for. IMCJ: What more will you cover for attendees at the OncANP conference in February? Dr Fox: I think one of the big holes for the future of cancer immunotherapy is that our response rates, while they are great and they are going up, they are not perfect. There is all this wonderful news about these response rates. But, the response rate is still less than 30%. We can pick patients who have immune systems that are amazing and get it up to 40%, but that still means 60% of patients are not being helped. What are the next steps? What do we need to do so everybody can benefit from this? I don’t think that it is unreasonable to be thinking about increasing response rates to greater than 90%. I just came from The Society for Immunotherapy of Cancer annual meeting, and one of the big questions came from a think tank called the Cancer Immunotherapy Trials Network. They were talking about what our next steps will be. Almost universally, we think it is going to be vaccines, because many of us do not think chemotherapy and/or radiation alone are going to turn on the immune system in most patients. We need to find ways to educate the immune system to see cancer. From my perspective, that is going to require vaccines. There are many different strategies. All of them need to be tested, because nobody can figure out what is going to work until you test it. The immune system and the body are very complex. I am tending to bet more on the broader approach of looking at turning on immunity against as many things as possible. This idea that the tumor continues to evolve and escape immune detection, unless you can bombard it with immune cells against all kinds of components, means that you are not going to be successful. The solution is not just turning on the T cells, but turning on the other arms of the immune system, as well. I think you loose a lot if you just try to target T cells, or turning on the B cells so they can make antibodies against these tumors. We are looking at strategies to turn on the natural killer cells and other approaches to go after the cancer, too. We think that a vaccine strategy that uses other immunotherapeutics in combination to turn on all arms of the immune system is where the future is going to be for patients. That way, we hope we can get to a 100% cure rate, which of course, is what everybody wants. It has been hard to even imagine that—even just a few years ago—but it is coming.

Reference

1. Fridman WH. The immune contexture in human tumours: Impact on clinical outcome. Nat Rev Cancer. April 2012;12:298-306.

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CASE REPORT

Sixteen-year-old Female With Acute Abdominal Pain: A Case Report Kara Fitzgerald, ND

Abstract A 16-y-old girl presented with abdominal pain in the lower right quadrant, ranging in intensity from 2 to 10 on a visual analog scale (VAS) that prevented her from attending school. The pain was not associated with reflux, a fever, or blood in her stools. Eosinophilic esophagitis (EE) had been previously diagnosed, but treatment with a proton pump inhibitor (PPI) was not successful. The patient’s medical history was significant for allergies to fruit; trees, including birch; weeds; and pollen. She had also suffered an anaphylactic reaction to a raw apple. The treatment approach commonly used for EE is suppression of inflammation with steroid

Kara Fitzgerald, ND, is in private practice in Sandy Hook, Connecticut. Corresponding author: Kara Fitzgerald, ND E-mail address: kf@drkarafitzgerald.com

osinophilic esophagitis (EE) was first characterized in 1993 as an allergic inflammatory condition that is biased toward type 2 helper T (Th2) cells. It presents most commonly with heartburn, epigastric pain, dysphagia, and nausea and vomiting. Laboratory findings commonly identify eosinophilia concurrently with elevated total immunoglobulin E (IgE). More than 50% of those suffering from EE also have a history of atopic and allergic disease, particularly food allergies; however, airborne allergens have also been identified as triggers for EE. EE does not generally respond to antireflux therapy. Diagnosis is difficult, but key signs and symptoms are a lack of a favorable response to acid-blocking therapy and a history of allergic disease. Diagnosis can be confirmed with an esophageal biopsy, identifying 26

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therapy with short-term removal of offending foods. However, an attempt to reduce allergic bias and inflammation and treat intestinal permeability is not a part of the standard approach and may explain the high rate of relapse with the condition. Treatment included an elimination diet paired with a supplement regimen designed to reduce inflammation, support healing of the gut and reduce type 2 helper T (Th2) bias of her allergic response. As a result of treatment, the patient’s severe pain episodes abated and she was thereafter able to resume attendance at school.

eosinophil infiltration. Interventions include use of steroids and avoidance of trigger foods. A high degree of relapse exists with the condition because of poor dietary compliance.1-3 Eosinophilic gastroenteritis (EG) is considered relatively rare and often is misdiagnosed, although it is rising in incidence. The most common complaint of patients is nonspecific abdominal pain. Diagnosis involves a positive identification of eosinophil infiltration of mucosa—which is most common—or of the muscularis or serosal layers of the stomach and/or intestinal tract, with eosinophilia and elevated IgE on laboratory evaluation. EG is also strongly associated with atopic and allergic disease, particularly food allergies. EE patients often present with polysensitization, including allergies not only to multiple foods but also environmental allergies. Further, an increased incidence of EE onset occurs during allergy season.4 In 2013, van Rhijn et al5 showed that food sensitizations in EE patients are mainly caused by cross-reactivity to food allergens after primary birch-pollen sensitization, which appeared to be the case with the patient in the current case study. In addition, a small study conducted in 2014 identifying the presence of immunoglobulin G4 (IgG4) Fitzgerald—Acute Abdominal Pain

food-immune complexes deposited at the site of esophageal inflammation and in the serum of adult EE patients suggests a pathogenic role.6 The treatment approach commonly used for EE or EG is suppression of inflammation with steroid therapy with short-term removal of offending foods. However, an attempt to reduce allergic bias and inflammation, balance the gastrointestinal (GI) microbiome, and treat intestinal permeability is not a part of the standard approach and may explain the high rate of relapse with the condition. In theory, if a treatment restores the intestinal mucosa and reduces allergic bias, certain foods can at some point be reintroduced and tolerated. It makes mechanistic sense that successful desensitization to environmental allergens using immunotherapy would also reduce food crossreactions. Therefore, treatment should take this into account with the goal being to remove all offending foods during early treatment, with the expectation that careful challenge and reintroduction of nonanaphylactic foods may be attempted later in treatment, after underlying immune imbalances have been favorably augmented. Presenting Concerns The patient was 16 years old when she presented to the author’s clinic with constant pain in the right lower quadrant of her abdomen, which ranged from 2 to 10 on a visual analog scale (VAS) for pain, where 0 = no pain and 10 = worst possible pain. She had had 3 previous episodes, with pain ranging from 8-10/10; none of those episodes were associated with reflux, a fever, or blood in her stools. The patient was unable to attend school because of the pain and was feeling depressed and anxious given the lack of successful treatment. Clinical Findings History The first of the episodes had taken place 6 weeks before her first visit to the author’s clinic and had followed

a large meal, which was associated with vomiting and diarrhea. The pain woke her from sleep and was 10/10. She was taken to her local hospital’s emergency department, where an abdominal computed tomography (CT) scan showed no radiographic evidence of appendicitis but did show some gastric thickening. Laboratory studies showed an elevated white blood cell count (18.0) and an increased sedimentation rate. Ibuprofen offered some pain relief, and she was referred to a gastroenterologist. He performed an endoscopy and colonoscopy, diagnosed EE, and prescribed a proton pump inhibitor (PPI). The PPI provided no relief. The patient also noted that menstrual cramping precipitated a pain attack; however, a gynecological examination was unremarkable, and the gynecologist believed that the pain was likely to be of GI origin. The patient’s medical history was significant for allergies to fruit; trees, including Birch; weeds; and pollen. Two to 3 years prior to her visit to the clinic, she had experienced an anaphylactic reaction while eating a raw apple, but she did not have the same reaction to cooked apples. She then developed a similar reaction to most fruit, including bananas and melons but not berries and grapes. As for other food sensitivities, she reported that wheat and tomato were the primary foods that triggered symptoms, and both of those foods have been associated with EE.7 The patient’s family members also suffered from severe allergies and atopic disease. In a review of her systems, the patient reported ongoing constipation and flatulence. Her medications included cetirizine hydrochloride, ibuprofen, and an EpiPEN. She had no history of excessive antibiotic or steroid use. The patient was a picky eater, drank an occasional soda, loved pizza, and primarily ate a standard American diet (SAD). She did not drink coffee (Table 1).

Table 1. Timeline Family History

Mother, siblings: seasonal environmental allergies, food allergies, atopic disease.

Childhood

Seasonal environmental allergies; Rx: cetirizine.

Early Teens

Anaphylaxis to fruits: bananas, melons, apples. Rx: EpiPEN.

16 y

Abdominal pain diagnosed as eosinophilic esophagitis. Onset of EE coincided with birch-tree allergy season; unable to attend school for 6 wk; Rx: ibuprofen.

16 y

Prescribed elimination diet based on IgE ELISA testing and known fruit allergens; also prescribed probiotics, intestinal permeability combination formula, EPA/DHA, and vitamin D; pain reported as significantly reduced after start of plan; returned to school.

Abbreviations: EE, eosinophilic esophagitis; IgE, immunoglobulin E; ELISA, enzyme-linked immunosorbent assay; EPA, eicosapentaenoic acid; DHA, docosahexaenoic acid.

Fitzgerald—Acute Abdominal Pain

Integrative Medicine • Vol. 14, No. 6 • December 2015

Physical Exam The patient experienced pain when the right lower quadrant of her abdomen was palpated, although she had no rebound tenderness or guarding. She also experienced pain during a straight leg raise (SLR) exam for her right leg. She had keratosis pilaris on the posterior aspect of her upper arms, and she had mild macroglossia. Diagnostic Focus and Assessment Laboratory Tests The initial laboratory evaluations focused on GI and immune function, including deficiencies commonly associated with immune dysfunction, such as deficiencies in vitamin D, zinc, and magnesium. At the patient’s first visit, the author ordered the following tests: (1) a complete blood count (CBC), with a manual differential (5.6 [4.0-10.0]); (2) celiac profile (immunoglobulin A [IgA] total, antigliadin antibody, and tissue transglutaminase) (negative); (3) sedimentation rate (ESR) (normal); (4) C-reactive protein (CRP) (normal); (5) urinary analysis (UA) (normal); (6) complete metabolic panel (CMP) (normal); (7) vitamin D; (8) red blood count (RBC) essential elements; (9) ferritin; (10) microbiota imbalance (ie, a GI function stool test [GIfX]); and (11) food allergy and sensitivity panels for IgE (positive for wheat, rye, corn, rice, tomato, oat, orange, strawberry, apple, peach, grape, melon) and IgG4. The patient did not complete all of the lab work, including IgG4 food sensitivities panel, vitamin D, ferritin, RBC essential elements, and the stool test. Based on the examination and testing, the author diagnosed (1) EE, (2) constipation, (3) atopic disease, (4) food and environmental allergies, (5) premenstrual syndrome, (6) intestinal permeability, and (7) possibly EG. Therapeutic Focus and Outcomes The approach in the patient’s case was straightforward. She needed to (1) eliminate foods associated with her IgE food allergies, which are known triggers and mediators of EE/gastroenteritis, and (2) reduce her Th2 allergic bias and inflammatory response by treating her intestinal permeability and balancing her GI microbiota using probiotics, vitamin D, glutamine, zinc carnosine, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and an elimination diet.8-12 The author suggested the following regimen for the patient: (1) an elimination diet based on the laboratory results for IgE and known allergens; (2) 2.5 mL per day of a probiotic powder at 200-billion colony forming units (CFUs), mixed in juice or water; (3) a mixture of glutamine, zinc carnosine, slippery elm, and deglycyrrhizinated licorice (DGL), as directed, with the ability to mix it with juice or water; (4) 2 capsules once per day of EPA/DHA 360/250; and (5) 2 drops daily of vitamin D, at 2000 IU per drop.

Integrative Medicine • Vol. 14, No. 6 • December 2015

Follow-up and Outcomes At the patient’s 2-month follow-up, she had returned to school; seen improvement in her symptoms when she avoided antigenic foods, especially the wheat and tomatoes in pizza; found probiotics to be helpful with pain and constipation; and had no severe pain episodes. She continued, however, to experience sporadic pain, admitting that she was not perfect in following her diet. Discussion In the current case study, the patient was diagnosed with EE, although she did not present with heartburn, which is the main symptom associated with the condition. Her chief complaint was pain in the right lower quadrant of her abdomen. Endoscopy demonstrated eosinophilic infiltration of the esophagus but apparently not of the stomach or small intestine. The patient’s abdominal CT scan identified the gastric thickening that has been associated with eosinophilic gastritis. The patient also had peripheral eosinophilia and a number of IgE food allergies, the identification of which was based on an enzymelinked immunosorbent assay (ELISA). Although the author did not request a second endoscopy, her suspicion was that the patient may have had eosinophilic infiltration of both the esophagus and stomach or small intestines. The latter diagnosis is difficult to make, given the patchy distribution of eosinophils. EE and EG can present together.13 The patient had a strong personal and family history of atopic and allergic disease, including a recent-onset anaphylaxis to a number of fruits, including raw apples. She also had significant environmental allergies, including to birch pollen, weeds, and grasses. Thus, her heightened state of allergic inflammation increased her risk for development of EE or EG. Her fruit allergy and apple anaphylaxis specifically suggested cross-reactivity to an environmental allergen. Up to 70% of those individuals with a birch allergy have a cross-reaction to fruits, most commonly apples and other stone fruits (ie, fruits with a large, hard seed).8,14,15 The patient had experienced anaphylaxis to raw apples but could tolerate them when they were cooked. That fact shows that an antigenic peptide was no longer a problem for her when it was altered by cooking. Termed conformational epitopes, reaction to heat-labile peptides can be outgrown. Insufficient stomach acid, as is encountered with acid-blocking therapy, can contribute to this type of IgE food allergy, however, and may explain why the incidence of anaphylaxis is on the rise in adults.18 Tolerance to cooked apples and other cooked, cross-reactive fruits in a birch-allergic individual also suggests that the antigenic proteins are both of the PR-10 family.19 Other protein families shown to be associated with EE include profilins and lipid transfer proteins.20 Fitzgerald—Acute Abdominal Pain

Conclusions Probably the most important thing to remember when working with teenagers is that the plan must be straightforward, and the teen must be in agreement with the approach. Although the author can think of a number of laboratory evaluations and treatment interventions that may have resulted in a fuller resolution, the patient was not willing to adhere to the entire plan. Without the patient’s cooperation, nothing can be accomplished. In hindsight, the author could have opted for collection of a blood-spot specimen for IgG4 food testing and dysbiosis markers for urinary organic acids, as the ease of collection for both of these tests may have improved compliance. Further, research identifying the presence of IgG4 food-immune complexes deposited at the site of inflammation and in the serum of adult EE patients suggests that the IgG4 blood spot test may have been useful in identifying primary trigger foods. With the laboratory data and clinical history that the author did have, a sound and largely successful treatment plan was designed.

18. Untersmayr E, Bakos N, Scholl I, et al. Anti-ulcer drugs promote IgE formation toward dietar y antigens in adult patients. Faseb J. 2005;19(6):656-658. 19. Popescu FD. Cross-reactivity between aeroallergens and food allergens. World J Methodol. 2015;5(2):31-50. 20. Simon D, Straumann A, Dahinden C, Simon HU. Frequent sensitization to Candida albicans and profilins in adult eosinophilic esophagitis. Allergy. 2013;68(7):945-948.

Author Disclosure Statement

The author has no conflicts of interest to declare.

References

1. Anton Remirez J, Escudero R, Caceres O, Fernandez-Benitez M. Eosinophilic esophagitis. Allergol Immunopathol (Madr). 2006;34(2):79-81. 2. Katzka DA. Eosinophilic esophagitis. Curr Opin Gastroenterol. 2006;22(4):429-432. 3. Noel RJ, Putnam PE, Rothenberg ME. Eosinophilic esophagitis. N Engl J Med. 2004;351(9):940-941. 4. Wechsler JB, Bryce PJ. Allergic mechanisms in eosinophilic esophagitis. Gastroenterology clinics of North America. Jun 2014;43(2):281-296. 5. van Rhijn BD, van Ree R, Versteeg SA, et al. Birch pollen sensitization with cross-reactivity to food allergens predominates in adults with eosinophilic esophagitis. Allergy. Nov 2013;68(11):1475-1481. 6. Clayton F, Fang JC, Gleich GJ, et al. Eosinophilic esophagitis in adults is associated with IgG4 and not mediated by IgE. Gastroenterology. 2014;147(3):602-609. 7. Roy-Ghanta S, Larosa DF, Katzka DA. Atopic characteristics of adult patients with eosinophilic esophagitis. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. May 2008;6(5):531-535 8. Perrier C, Corthesy B. Gut permeability and food allergies. Clin Exp Allergy.2011;41(1):20-28. 9. Vassallo MF, Camargo CA, Jr. Potential mechanisms for the hypothesized link between sunshine, vitamin D, and food allergy in children. J Allergy Clin Immunol.2010;126(2):217-222. 10. Wang B, Wu G, Zhou Z, et al. Glutamine and intestinal barrier function. Amino Acids. 2015;47(10):2143-2154. 11. Miyata J, Arita M. Role of omega-3 fatty acids and their metabolites in asthma and allergic diseases. Allergol Int. 2015;64(1):27-34. 12. Mahmood A, FitzGerald AJ, Marchbank T, et al. Zinc carnosine, a health food supplement that stabilises small bowel integrity and stimulates gut repair processes. Gut.2007;56(2):168-175. 13. GI Motility Online: Part 1: Oral Cavity, Pharynx and Esophagus. 2006; http://www.nature.com/gimo/about/index.html. Accessed 3/10/2012, 2012. 14. Kinaciyan T, Jahn-Schmid B, Radakovics A, et al. Successful sublingual immunotherapy with birch pollen has limited effects on concomitant food allergy to apple and the immune response to the Bet v 1 homolog Mal d 1. J Allergy Clin Immunol.2007;119(4):937-943. 15. Bolhaar ST, Tiemessen MM, Zuidmeer L, et al. Efficacy of birch-pollen immunotherapy on cross-reactive food allergy confirmed by skin tests and double-blind food challenges. Clin Exp Allergy. 2004;34(5):761-769. 16. Moneret-Vautrin DA, Morisset M. Adult food allergy. Curr Allergy Asthma Rep. Jan 2005;5(1):80-85. 17. Scientific T. ImmunoCAP Allergens. 2011; www.immunocapinvitrosight. com. Accessed 3/10/2012, 2012.

Fitzgerald—Acute Abdominal Pain

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CASE REPORT

Cannabidiol Oil for Decreasing Addictive Use of Marijuana: A Case Report Scott Shannon, MD; Janet Opila-Lehman, ND

Abstract This case study illustrates the use of cannabidiol (CBD) oil to decrease the addictive use of marijuana and provide anxiolytic and sleep benefits. Addiction to marijuana is a chronic, relapsing disorder, which is becoming a prevalent condition in the United States. The most abundant compound in the marijuana, which is called tetrahydrocannabinol (THC), has been widely studied and known for its psychoactive properties. The second most abundant component—CBD—has been suggested to have the medicinal effects of decreasing anxiety, improving sleep, and other neuro-protective effects. The mechanism of action for CBD has been suggested to be antagonistic to the psychoactive properties of THC in many locations within the central nervous system. Such action raises the issue of whether it might be beneficial to

Scott Shannon, MD, is a psychiatrist; and Janet OpilaLehman, ND, is a naturopathic physician. Both are in private practice at the Wholeness Center in Fort Collins, Colorado. Corresponding author: Scott Shannon, MD E-mail address: scott@wholeness.com

annabidiol (CBD) oil is a naturally occurring constituent of industrial hemp and marijuana collectively called cannabis. CBD oil is one of at least 85 cannabinoid compounds found in cannabis and is popular for its medicinal benefits. After tetrahydrocannabinol (THC), which is the most abundant compound in cannabis, CBD is the second most abundant. Other names for CBD oil include CBD-rich hemp oil, hemp-derived CBD oil, or CBD-rich cannabis oil. CBD is generally considered to be safe and has been used medicinally for decades. The suggested medicinal effects of CBD include decreasing anxiety, improving sleep, and providing other neuroprotective effects. Shannon—Cannabidiol Oil

use CBD in isolation to facilitate withdrawal of marijuana use. The specific use of CBD for marijuana reduction has not been widely studied. The patient was a 27-y-old male who presented with a long-standing diagnosis of bipolar disorder and a daily addiction to marijuana use. In the described intervention, the only change made to the patient’s treatment was the addition of CBD oil with the dosage gradually decreasing from 24 to 18 mg. With use of the CBD oil, the patient reported being less anxious, as well as settling into a regular pattern of sleep. He also indicated that he had not used any marijuana since starting the CBD oil. With the decrease in the dosage to 18 mg, the patient was able to maintain his nonuse of marijuana.

THC is a cannabinoid and is the component that induces the euphoric psychoactive effect. Various cannabis plants can have different amounts of CBD and THC depending on the strain, and, thus, can provide different recreational or medicinal effects. The cannabinoid profile of industrial hemp or medical marijuana is ideal for people looking for the medical benefits of CBD without the high of the THC. The mechanism of action for CDB has been suggested to be antagonistic to the psychoactive properties of THC in many locations within the central nervous system, thus helping to attenuate the psychoactive behaviors of THC.1,2 The mechanism of action of CBD is multifold.3,4,5 Two cannabinoid receptors are known to exist in the human body: CB1 and CB2 receptors. The CB1 receptors are located mainly in the brain and modulate neurotransmitter release in a manner that (1) prevents excessive neuronal activity, thus calming and decreasing anxiety; (2) reduces pain; (3) decreases inflammation; (4) regulates movement and posture control; and (5) controls sensory perception, memory, and cognitive function.4 Integrative Medicine • Vol. 14, No. 6 • December 2015

Anandamide, an endogenous ligand that occurs naturally within our bodies, binds to the CB1 receptors through the G-protein coupling system. CBD has an indirect effect on the CB1 receptors by stopping the enzymatic breakdown of anandamide, allowing it to stay in the system longer and to provide its medical benefits.6 CBD has a mild effect on the CB2 receptors, which are located in the periphery of the lymphoid tissue. The CBD helps to mediate the release of cytokines from the immune cells in a manner that helps to reduce inflammation and pain.4 Other mechanisms of action of CBD include stimulation of vanilloid pain receptors, such as the transient receptor potential cation channel subfamily V member 1 (TRPV-1) receptor, which are known to mediate pain perception, inflammation, and body temperature.7 CBD may also exert its antianxiety effects by activating adenosine receptors that play a significant role in cardiovascular function, causing a broad anti-inflammatory effect throughout the body.7 At high concentrations, CBD directly activates the 5-HT1A serotonin receptor, thereby conferring an antidepressant effect.8 CBD has been found to be an antagonist at a potentially new third cannabinoid receptor (ie, G proteincoupled receptor 55, or GPR55), which resides in the caudate nucleus and putamen and can contribute to osteoporosis when stimulated.9 Since the 1940s, a considerable number of published articles have addressed the chemistry, biochemistry, pharmacology, and clinical effects of CBD.10 The last decade has shown a notable increase in the scientific literature on CBD, owing to its identification as being beneficial in reducing nausea and vomiting, combating psychotic disorders, decreasing inflammation, lessening anxiety, reducing depression, improving sleep, and increasing a sense of well-being.11,12,13,14 Findings presented at the 2015 International Cannabinoid Research Society at their 25th Annual Symposium in Nova Scotia, Canada, reported that use of CBD was beneficial for treatment of liver fibrosis and inflammation, metabolic syndrome, overweight and obesity, anorexia/cachexia syndrome, and osteoarthritic and other musculoskeletal conditions.15 Although studies have demonstrated the calming, anti-inflammatory, and relaxing effects of CBD, clinical data demonstrating the use of CBD to obtain help in marijuana withdrawal is minimal. One prior case study by Crippa et al16 documented the positive effects of using CBD for the treatment of marijuana withdrawal. The current case study offers further evidence that CBD is effective as a safe method of transitioning off marijuana without unwanted side effects. Presenting Concerns The patient was a 27-year-old male who presented with a long-standing diagnosis of bipolar disorder and a daily addiction to marijuana. His presenting concerns included erratic behaviors, anxiety, inconsistent sleep 32

Integrative Medicine • Vol. 14, No. 6 • December 2015

patterns, and irritability. He currently lives with his parents, works as a self-employed driver, and teaches chess to children. Informed consent was received from the patient. Clinical Findings The patient’s history included hospitalizations as a teenager for bipolar episodes. He came to the author’s clinic, Wholeness Center in Fort Collins, Colorado, in 2011 and was evaluated by a psychiatrist and naturopathic physician. The patient’s treatments for his bipolar disorder included pharmacological medications (Table 1). Evaluations included (1) a basic, complete blood count; (2) a nutritional evaluation; (3) a comprehensive metabolic panel; (4) a lipid panel; (5) a measurement of methylene tetrahydrofolate reductase (MTHFR); (6) a celiac panel; (7) a measurement of thyroid function; (8) a measurement of iron levels; and (9) a quantitative electroencephalogram (qEEG). Dietary recommendations were then implemented as was a regimen of nutritional supplements. The patient also received neurofeedback sessions and bodywork. Prior to the period of the case study, he had been stable for a number of years. In time, the patient’s marijuana habit progressed to addiction. In May 2015, it was recommended that he begin taking CBD as a way of transitioning off the daily marijuana use and stabilizing his erratic moods. Diagnostic Focus and Assessment Clinical observations of the patient’s erratic behaviors, mood swings, and disorientation, together with the patient’s self-report of daily marijuana use, reinforced the diagnoses of bipolar disorder and addiction. He was administered the Pittsburgh Sleep Quality Index (PSQI)17 and the Hamilton Anxiety Rating Scale (HAM-A)18 prior to initiation of the CBD oil. Theraputic Focus, Assessment, and Follow-up The only addition that the author made to the patient’s treatment regime was the CBD oil. At the same time, the patient’s other supplement therapy was discontinued to simplify treatment, as no clear benefit was demonstrated. The initial regimen was 24 mg of the CBD oil, with 6 sprays PRN during the day and 2 sprays QHS. The dosage was gradually decreased from 24 to 18 mg, with the patient using no sprays during the day and 6 sprays at bedtime. The patient was seen for monthly appointments, including readministration of the PSQI and the HAM-A to evaluate the effectiveness and proper dosing of the CBD oil. CannaVest Company (Las Vegas. NV, USA), which had no involvement in the case study or distribution of the product, provided the CBD oil that was administered to the patient.

Shannon—Cannabidiol Oil

Integrative Medicine • Vol. 14, No. 6 • December 2015

05/08/2014

03/27/2014

02/21/2014

11/201106/2012 08/201210/2012 10/22/2013

Date 06/20/2011

Contemplation of quitting THC; realization of connection with mood changes; concern of family about mood changes; limited social contact; works with Legos.

Citalopram: 20 mg Marijuana use: 1-2 joints /night + pot brownies; admitLamotrigine: 150 mg ted addiction to THC DEN: 3 caps TID Niacin: 2 caps BID O-3: 1 cap/d CoQ10: 150 mg/d Inositol: 2 scoops AM & PM Probiotic: 1 cap/d Meriva: 1 cap/d Citalopram: 20 mg Regular marijuana use Lamotrigine: 150 mg DEN: 3 caps TID Niacin: 2 caps BID O-3: 1 cap/d CoQ10: 150 mg/d Probiotic: 1 cap/d

Marijuana use daily

Marijuana use

No periods of mania/depression; 2 jobs. Erratic moods with resumption of THC; stressed family with patient’s deterioration when using THC. Mood withdrawn and erratic; passiveaggressive behaviors. Citalopram: 20 mg

Marijuana use

9 bodywork sessions.

Supplements Regular marijuana use

Marijuana use

Medications

Presentation Initial psychological evaluation; diagnosis of bipolar disorder and depression, with difficulty processing information; buzzing in head and some disorientation; 2 manic periods in previous 10 mo, exacerbated by substance abuse; history of hospitalizations; micromanagement of life by mother. 49 neurofeedback sessions.

Table 1. Patient’s Timeline, 2011-2015

Cannabidiol Oil

Integrative Medicine • Vol. 14, No. 6 • December 2015

Shannon—Cannabidiol Oil

Anxious, erratic moods; sensitive to gluten but no restriction; consumption of a lot of junk food; jobs teaching kids chess, making deliveries. Overall improved quality of sleep; slightly less anxious.

05/04/2015

Overall good sleep and no anxiety.

08/03/2015

No marijuana No supplements

0 sprays PRN during day; 6 sprays QHS

3-4 sprays PRN during day; 6 sprays QHS 2 sprays PRN during day; 4 sprays QHS

6 sprays PRN during day; 2 sprays QHS

Cannabidiol Oil

Abbreviations: THC, tetrahydrocannabinol; DEN, daily essential nutrients; cap(s), capsule(s); TID, 3 ×/d; BID, 2 ×/d; THC, tetrahydrocannabinol; PRN, when necessary; QHS, every bedtime.

Citalopram: 20 mg No marijuana Lamotrigine: 150 mg No supplements Deplin: 15 mg

Citalopram: 20 mg Lamotrigine: 150 mg Deplin: 15 mg Citalopram: 20 mg Overall doing well; better sleep; anxiety under control; new job as Uber Lamotrigine: 150 mg driver. Deplin: 15 mg

06/04/2015

07/02/2015

Marijuana use daily DEN: 3 caps TID Niacin: 2 caps BID O-3: 1 cap/d CoQ10: 150 mg/d

Supplements Marijuana use 1 ×/wk DEN: 3 caps TID Niacin: 2 caps BID O-3: 1 cap/d CoQ10: 150 mg/d

Citalopram: 20 mg No marijuana Lamotrigine: 150 mg No supplements Deplin: 15 mg

Citalopram: 20 mg Continuous destabilization; no Lamotrigine: 150 mg evidence of psychosis; difficulty with abuse of marijuana; jobs teaching chess Deplin: 15 mg to kids and catering.

04/24/2015

Medications Citalopram: 20 mg Lamotrigine: 150 mg Deplin: 15 mg

Presentation Less labile; mildly tired; no psychosis; continued marijuana use; less tension at home, with father home more often.

Date 07/10/2014

Table 1. (continued)

Outcome Measures Pittsburgh Sleep Quality Index. The PSQI is a standardized and validated self-report instrument that measures sleep quality over the prior month. Low scores indicate better sleep. A score under 5 means that you have no sleep concerns. 5 to 10 is fair quality sleep. Hamilton Anxiety Rating Scale. The HAM-A scale is a standardized and validated measure of anxiety in an adult population that has been in active use for decades. A score of 17 or less indicates mild anxiety in terms of severity. A score from 18 to 24 demonstrates mild to moderate anxiety severity. Last, a score of 25 to 30 indicates moderate to severe anxiety. Results Using the CBD oil, the patient was able to maintain nonuse of marijuana. With a subsequent, gradual decrease in anxiety, the patient was able to maintain a regular sleeping schedule (Table 2). He was able to get a more secure job as a self-employed driver, and he continued to teach chess to children. He also became more interactive with his family and friends. Discussion The current case study found that CBD oil can be an effective compound to use for transitioning an individual off addictive use of marijuana. The fact that no changes were made in the patient’s medication schedule, diet, or lifestyle gives credence to the idea that the results were the actual effects of the CBD oil. A possible weakness of the study is the fact that the patient’s total nonuse of marijuana was self-reported, and the reliability of his reporting could be suspect. However, the patient made significant gains in taking responsible actions and presented fewer erratic and disorganized behaviors. A systematic review of the literature previously had examined 14 studies on the use of CBD oil to modulate various neuronal circuits involved in drug addiction.19 That review suggested that CBD “may have therapeutic properties on opioid, cocaine, and psychostimulant addictions … and may be beneficial in cannabis addiction in humans.” The current case study seems to support that review’s conclusions. One reported consequence of the cessation of daily marijuana use is a withdrawal syndrome that is characterized by irritability, anxiety, marijuana craving, decreased quality and quantity of sleep, and reduced food intake.16,20 The use of the CBD oil in transitioning the current patient off the marijuana allowed him to avoid experiencing those side effects, as was demonstrated by his behavior and scores on the PSQI and HAM-A screening tools. Patient Perspective The patient reported being less anxious and sleeping better since taking the CBD oil. He reported not using any marijuana since starting the CBD and was proud of his Shannon—Cannabidiol Oil

Table 2. Patient Sleep Date PSQI HAM-A 05/4/2015 7 16 06/4/2015 8 8 07/2/2015 7 6 08/3/2015 7 5 09/10/2015 8 4 Abbreviations: PSQI, Pittsburgh Sleep Quality Index; HAM-A, Hamilton Anxiety Rating Scale. accomplishment of getting a job as a self-employed driver and continuing with teaching chess to children. Author Disclosure Statement

The author participated in no competing interests that would have affected the results of the case study. No financial support was provided by CannaVest at any time.

References

1. Karniol IG, Shirakawa I, Kasinski N, Pfeferman A, Carlinie EA. Cannabidiol interferes with the effects of delta 9-tetrahydrocannabinol in man. Eur J Pharmacol. 1974;28(1):172-177. 2. Dalton WS, Martz R, Lemberger L, Rodda BE, Forney RG. Influence of cannabidiol on delta 9-tetrahydrocannabinol effects. Clin Pharmacol Ther. 1976;19(3):300-309. 3. Campos AC, Moreira FA, Gomes FV, DelBel EA, Guimaraes FS. Multiple mechanism involved in the large-spectrum therapeutic potential of c annabidiol in psychi at r ic dis orders. Phil Trans R S oc B . 2012;367(1607):3364-3378. 4. GW Pharmaceuticals. Research papers. http://www.gwpharm.com/ publications-1.aspx. Published 2014. Accessed December 15, 2015. 5. McPartland JM, Guy G. The evolution of Cannabis and coevolution with the cannabinoid receptor: A hypothesis. In: Guy G, Robson R, Strong K, Whittle B, eds. The Medicinal Use of Cannabis. London, United Kingdom: Royal Society of Pharmacists; 2004:71-102. 6. Leweke FM, Piomelli D, Pahlisch F, Muhi D, Gerth CW, Hoyer C, Klosterkotter J, Hellmich M, Koethe D. Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia. Transl Psychiatry. 2012;20(2):e94. 7. Lee MA. How CBD works. Project CBD Web site. https://www.projectcbd. org. Accessed November 20, 2015. 8. Crippa JA, Derenusson GN, Ferrari TB, et al. Neural basis of anxiolytic effects of cannabidiol (CBD) in generalized social anxiety disorder: A preliminary report. J Psychopharmacol. 2011;25(1):121-130. 9. Ross RA. Modulation of human neutrophil migration by endocannabinoids and phytocannabinoids: Evidence for a site distinct from CB1 and CB2. Mol Pharmacol. 2008;73(2):1-10. 10. Zhornitsky S, Potvin S. Cannabidiol in humans: The quest for therapeutic targets. Pharmaceuticals. 2012;5(5):529-552. 11. Zuardi AW. Cannabidiol: From an inactive cannabinoid to a drug with wide spectrum of action. Rev Bras Psiquiatr. 2008;30(3):271-280. 12. Burstein S. Cannabidiol (CBD) and its analogs: A review of their effects on inflammation. Bioorg Med Chem. 2015;23(7):1377-1385. 13. Fernández-Ruiz J, Sagredo O, Pazos MR, et al. Cannabidiol for neurodegenerative disorders: Important new clinical applications for this phytocannabinoid. Br J Clin Pharmacol. 2013;75(2):323-333. 14. Zuardi AW, Crippa JA, Hallak JE, Moreira FA, Guimarães FS. Cannabidiol a Cannabis sativa constituent as an antipsychotic drug. Braz J Med Biol Res. 2006;39(4):421-429. 15. International Cannabinoid Research Society. Program for 25th annual symposium. http://www.icrs.co/SYMPOSIUM.2015/ICRS2015.Programme. pdf. Published June-July 2015. Accessed December 15, 2015. 16. Crippa JA, Hallak JE, Machado-de-Sousa JP, Queiroz RH, Bergamaschi M, Chagas MH, Zuardi AW. Cannabidiol for the treatment of cannabis withdrawal syndrome: A case report. J Clin Pharm Ther. 2013;28(2):162-164. 17. University of Pittsburgh. University of Pittsburgh Sleep Medicine Institute Pittsburgh Sleep Quality Index (PSQI). http://www.sleep.pitt.edu/content. Accessed November 20, 2015. 18. Hamilton M. The assessment of anxiety states by rating. Br J Med Psychol. 1959;32(1):50-55. 19. Prud’home M, Cata R, Jutras-Aswad D. Cannabidiol as an intervention for addictive behaviors: A systematic review of the evidence. Res Treat. May 2015;9:33-38. 20. Haney M. The marijuana withdrawal syndrome: Diagnosis and treatment. Curr Psychiatry Rep. 2005;7(5):360-366.

Integrative Medicine • Vol. 14, No. 6 • December 2015

VIEWPOINTS

Kara N. Fitzgerald, ND: Case Reports—Informing the Practice of Systems Medicine Interview by Craig Gustafson

Kara N. Fitzgerald, ND, received her doctorate of naturopathic medicine from the National College of Natural Medicine in Portland, Oregon. She completed the first Council on Naturopathic Medical Education (CNME)-accredited postdoctorate position in nutritional biochemistry and laboratory science at Metametrix (now Genova) Clinical Laboratory under the direction of Richard Lord, PhD. Her residency was completed at Progressive Medical Center, a large, integrative medical practice in Atlanta, Georgia. Dr Fitzgerald is lead author and editor of Case Studies in Integrative and Functional Medicine, a contributing author to Laboratory Evaluations for Integrative and Functional Medicine, and the Institute for Functional Medicine’s (IFM’s) updated Textbook for Functional Medicine. She has been published in numerous peer-reviewed journals. Dr Fitzgerald is on faculty at the IFM, and she is an IFM-certified practitioner. She was formerly on faculty at the University of Bridgeport in the School of Human Nutrition and the School of Naturopathic Medicine in Bridgeport, Connecticut. She is a clinician researcher for the Institute for Therapeutic Discovery. Dr Fitzgerald regularly lectures internationally for several organizations and is in private practice in Sandy Hook, Connecticut. Integrative Medicine: A Clinician’s Journal (IMCJ): As a clinician, what do you take from reading case reports? Dr Fitzgerald: I think most clinicians enjoy sitting next to another clinician and observing what they’re doing—how they are taking a history, what kind of laboratory data they’re ordering, the various interventions. It can be validating. It can be expanding to my own practice. I think reading—or listening to case reports if they’re presented live—is an extremely useful practice for us to expand our own horizons and evolve our own practice. The other piece that I want to add is something that David Jones has repeatedly pointed out and that I have really taken to heart: reporting failures and dialoguing about what we observe that doesn’t work. I have attempted to do that on my blog, and I also do a lot of dialoguing with my colleagues—what we have seen to be efficacious and what we haven’t. I think both experiences are profoundly important. 36

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IMCJ: That is good insight. Dr Fitzgerald: Yes. In fact, arguably, we probably learn more from failures—or at least just as much. IMCJ: There is a tendency to dismiss case reports as having less merit because there is no control for comparison. The sample size is 1, so it will not have any statistical power and, therefore, it is purely anecdotal. So, then, what really is the use? Could you respond to that? Dr Fitzgerald: Of course. That argument has been lodged against case reports since time immemorial. That is why they tend to take up a whole lot less space in journals and that is a disappointment. Case reports are the first step in forming the hypothesis that will become testable at some point. In fact, that is what has always been argued as the case report benefit. These reports will form the questions that we’ll later test. We are seeing what is happening, we are seeing what is working, and we are seeing what is not working. In the advent of systems medicine, as we move into the world of big data, I think of it as “the meek shall inherit the earth.” The case report is really going to, I think, gain much more attraction when we have thousands—even millions—of N-of-1 data points from wearable medical devices, history, and comprehensive laboratory data—including Omics— streamed to the cloud. Once those numbers are crunched, we are going to see meaningful trends. Arguably, that is an offspring of the case report. Systems medicine is going to transform health care and the research model as we know it. IMCJ: So you are anticipating that the cloud will provide virtually limitless data that can be interpreted through meta-analysis of N-of-1 cases? Dr Fitzgerald: We will be able to have great power behind those kinds of data collections, observe trends, and do it in real time—but not in a laboratory or an isolated environment. Many variables are happening all at once and that level of complexity is where we are headed. A precursor to that level of complexity is the case report, a comprehensive case report.

Fitzgerald—Viewpoints

IMCJ: Could it also be said that an important function of case reports is codifying the experience of clinicians? Might they provide a role in passing knowledge from generation to generation of clinician? There are so many really terrific clinicians who have had phenomenal success, but they may not have taken the time to document all their successes in a way that can be passed on and replicated by other clinicians down the line. Wouldn’t case reports represent a fantastic way for those experienced clinicians to sum up their career experience and pass that body of knowledge along? Dr Fitzgerald: Of course. That is a huge point and that really brings up the need for us to have support in codifying our knowledge. It is true that the best clinicians are in the trenches, seeing patients and getting them better. How can we best capture what it is that they are doing? I think about my own enjoyment of reading the very early literature, when the nutrition physical exam was so widely used—what they were seeing and some of the techniques that they were using, before antibiotics, without the pharmacopoeia that we have today. Some of them were what we would consider natural interventions. Observation was paramount because the laboratory was not as routinely used or available and interventions were arguably more creative. So capturing as much as we can is really important. I think as technology improves, those tools will be more readily available. Or conversely, we hire an army of medical writers to go to the offices of superb clinicians like Sidney Baker, MD, and capture what it is they’re doing! IMCJ: How might case reports better reflect the values of the integrative movement in emphasizing personalization in the art of healing? Dr Fitzgerald: In the case report, we can capture the nuances of the healing process and the interaction of clinician and patient. As I was thinking about this question, a case1 came to mind that I published in Case Studies in Integrative and Functional Medicine.2 It was actually one of the first patients I saw during my residency in Atlanta, Georgia, and she had rheumatoid arthritis. Her triggering event was exposure to mold. When they moved out of the affected home, she went into remission; there was no issue. The second triggering event was the loss of an aunt, who was a very close family member, which caused her arthritis to flare. That is when I started to work with her. She was unable to tolerate medications, but through the functional medicine approach, she went back into remission. She later had another flare after the loss of her father, and then again after being exposed to a minute amount of casein in the form of sodium caseinate, which was the preservative in a supplement that I had prescribed her. Fitzgerald—Viewpoints

All of these various triggers I captured in the case report were so incredibly important to her course of rheumatoid arthritis and what we did to address these things. Mind-body medicine, as you can imagine, became an important piece, with her emotional upheaval being such a trigger, but it is also useful for other clinicians to observe the variety of triggering events in this one particular case and pay attention to it in their own patient population. IMCJ: So then can an argument be made for case reports to be more valuable or more appropriate for integrative practice just because the double-blind, placebo-controlled study is designed to investigate patent pharmaceuticals, which by definition are substances that do not otherwise appear in the human body? Dr Fitzgerald: Because the case report allows for many data points, we can really capture the complexity in all its glory and track outcomes—with observation, with the patient report, and with laboratory data. It just allows for a much more nuanced investigation. It makes me think of a friend of mine, who is a medical writer and is currently writing a paper on interventions for attention-deficit/ hyperactivity disorder, or ADHD. She said that she was so disappointed in what she was finding in the literature, because everything was really turning out to have just minimal effects, if any. There was nothing really significant in the literature to demonstrate the efficacy of our approach, right? You probably know, and I certainly know being a clinician, that we have a pretty good track record of treating ADHD. In fact, there is a case report published in the book—a patient of Mark Hyman, MD—that really had lovely outcome.3 You can see the level of complexity to Mark’s approach. He is practicing systems medicine: diet is changed, environment is changed, lifestyle is changed, nutraceuticals are prescribed, and detoxification is used in the course of their months of work together. This simply isn’t available to a double-blind, placebo-controlled trial. IMCJ: What then do you look for in a well-constructed case study? Dr Fitzgerald: I want to read a good, robust history: past history and family history. I would like to see a decent laboratory-data baseline and follow-ups as indicated. I like to see the clinical reasoning behind the interventions used and what kind of outcome they were expecting with those interventions. There is hypothesis forming and testing in medicine all the time. It is nice that a lot of the interventions that we are using are really relatively safe and we can do this careful and informed trial and error. Certainly, hearing good outcome documentation— ideally in the patient’s own words—is valuable. The other piece is a robust, evidenced-informed discussion around what happened and why. Integrative Medicine • Vol. 14, No. 6 • December 2015

IMCJ: Is there a structure to the case report that you find is more helpful? Dr Fitzgerald: I like what David Riley has done with creating the CARE guidelines. Having a template to support moving through all of these various points that I have made is essential. IMCJ: Obviously, you have been quite active in contributing case studies to the body of literature. What advice would you give to clinicians for setting up their practice to support production of case reports? Dr Fitzgerald: It is a lot of work, so I do a few things to assist in data capture. First of all, I am a pretty copious charter. You want the details—whether you use them or not—when you’re writing a case report. I actually type into my chart—I use a Microsoft Word document chart template that I created to meet my needs—at the same time I am talking to my patient. I have become a fast typist and I can look at my patient and talk I am pretty consistent with getting baseline and follow-up labs, I place key findings into my chart where they are readily accessible. The structure of my chart allows for a good functional investigation. In the subjective section, I have areas for documenting a timeline. I have a discussion section where I can include big picture thoughts I’ve got regarding a case, as well as outlining any antecedents, triggers, and mediating factors I’ve identified. My assessment is structured as the Functional Medicine Matrix with an area for ICD-10 coding. The plans are a separate document I share with the patient. Patient’s goals for treatment are on the top of the plan and in the chart. In my policy forms, I ask patients if they are okay with me publishing their anonymous, HIPAA-compliant health data. Right at the start of our work, I find out whether or not I can write about their case. Another big thing that I do in clinical practice is taking physical exam photographs. I take a primarily nutritional physical exam and track changes to skin and changes to nails, and I am also interested in tongue diagnosis, which can be quite useful. I’ll use the observations and photographs when I am constructing cases, but, obviously, the primary use is to track patient outcomes. Patients are always interested in these findings. IMCJ: What resources might you recommend for clinicians who would like to begin producing case studies? Dr Fitzgerald: David Riley’s CARE guidelines are available at http://www.care-guidelines.org. I would certainly download those and look at them. I would turn to the literature and look at case reports there. I generated the template we used for Case Studies in Integrative and Functional Medicine. It was a huge job. It was an enormous labor of love writing that book and coming up with an appropriate template, which David evolved so beautifully in his work. 38

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I don’t know that electronic medical records, or EMRs, are quite where they need to be yet for us, but I expect to use an EMR when a good one comes down the pike. Capturing electronically is a little bit easier for writing a case rather than paper charting, but paper charting is okay, too. A lot of the big cases in the case book were in paper.2 The Institute for Functional Medicine, or IFM, is developing tools and those will continue to evolve. Part of the IFM certification process includes the requirement to generate a case. Anybody going through that process is going to learn how to generate a case study. IMCJ: Has your experience with preparing case studies affected how you interpret medical literature? Dr Fitzgerald: I would say that it has—not just my experience generating cases, but my experience as a clinician. You always have to interpret the literature realistically. What they find in this very controlled environment does not necessarily extrapolate to real life, and so that needs to be taken into consideration. I think all clinicians do that, consciously or not. I, like most integrative clinicians, enjoy reading and gain value from research. It informs my practice always—all the time. I may tweak and make alterations based on what I am reading. Once upon a time, I was in a lab and I was only seeing patients 1 day a week. I was just steeped, entirely immersed in the ivory tower. It was a wonderful time. I wouldn’t trade it for the world, but the realities of enacting what you read in the literature in clinical practice with a human being sitting in front of you are entirely different. We cannot do 1 intervention trial at a time with our patients. We are always practicing with multiple interventions. IMCJ: Not to mention the issue of patient compliance. Dr Fitzgerald: Absolutely. What is realistic? Here are 23 great supplements for you to prescribe this individual. What can you actually do? Is it cost effective? Is it too time consuming? Are they tolerated? Will they achieve the expected outcome? IMCJ: Does the fact that you have authored so many case reports change the way that you read a study? Does it inform your interpretation of what is realistic or what authors might be spinning in their presentation to make their results look a little stronger? Dr Fitzgerald: Oh, absolutely. Pay attention to the methods, the results. The study design … does it make sense? If you’re familiar with the compound(s) being used, are the dosages and forms appropriate? What kind of placebo is being used? Who’s running the study: Any conflicts of interest? Read the discussion section, my favorite part. Does the proposed mechanism(s) of action make sense? Who are they citing as references: Are they human, animal, in vitro studies? Fitzgerald—Viewpoints

I am particularly skeptical with regard to the metaanalysis. Data can so readily be cherry picked. We see this in fish oil studies. A lot of those negative trials just don’t make sense to me when you look at study design, study population, and dosages used. Studies looking at nutrition are notoriously problematic, be it due to the limitations of dietary recall (the cloud will help here) or when the study is limited to looking at broad macronutrient groups like proteins, fats, and carbohydrates. IMCJ: What role might case reports play in establishing your legacy as a clinician? Dr Fitzgerald: As a functional medicine clinician, my mission statement is to help change the global diseasecentered medical paradigm. I want to truly change the disease trajectory that we are on, and so I think that any role I can play—that “we,” the collective “we”—can play in demonstrating, over and over again, the evidence for our approach and informing future directions of research and clinical practice is important as our legacy. IMCJ: Any last thoughts before we close?

hemangiomas and how they inadvertently discovered that propranolol cleared them. The story describes how they were treating kids with supraventricular tachycardia with propranolol and happened to observe that for those children with hemangioma, the condition resolved. He has used that anecdote on a number of occasions because it changed standard of care with regard to treating infantile hemangiomas. That is a really nice way to articulate the utility of the case report for changing the direction of treatment. I speak, though, for functional medicine clinicians. Really, what we are doing is practicing systems medicine. We are showing that the systems approach is essential to good patient care—particularly for complex chronic disease that we all face in our practices. The case report is essential for demonstrating the utility for that approach. References

1. Fitzgerald K. Fifty-three-year-old female with rheumatoid arthritis and osteoporosis. In: Fitzgerald KN, Bralley JA, eds. Case Studies in Integrative and Functional Medicine. Duluth, Georgia: Metametrix; 2011:26-46. 2. Fitzgerald KN, Bralley JA. Case Studies in Integrative and Functional Medicine. Duluth, Georgia: Metametrix; 2011. 3. Hyman M. Twelve-year-old male with attention deficit hyperactivity disorder. In: Fitzgerald KN, Brailley JA, eds. Case Studies in Integrative and Functional Medicine. Duluth, Georgia: Metametrix; 2011:70-84.

Dr Fitzgerald: When he is articulating the importance of case studies, David Riley always talks about infantile

Fitzgerald—Viewpoints

Integrative Medicine • Vol. 14, No. 6 • December 2015

VOLUME 14 2015 INDEX

AUTHOR INDEX A Anderson B. The effect of dietary change in a patient with ichthyosis vulgaris: A case report. 2015;14(3):55-58.

F Fitzgerald K. Sixteen-year-old female with acute abdominal pain: A case report. 2015;14(6):26-29.

B Belmont JM (see Esparham AE et al) 2015;14(2):40-53. Benda B. BackTalk—Fear of flying. 2015;14(1):64. Benda B. BackTalk—Ginseng and jet engines. 2015;14(2):64. Benda B. BackTalk—A pirate looks at 60. 2015;14(3):68. Benda B. BackTalk—No satisfaction. 2015;14(4):68. Benda B. BackTalk—Quit your bellyaching. 2015;14(5):88. Benda B. BackTalk—Confessions of a narcissist. 2015;14(6):64. Bland J. Creating Synthesis—Functional medicine: An operating system for integrative medicine. 2015;14(5):18-20. Bland J. Creating Synthesis—When is a disease a “disease?” 2015;14(6):14-16. Boisvert JA, Harrell WA. Integrative treatment of pediatric obesity: Psychological and spiritual considerations. 2015;14(1):40-47. Bull MJ, Plummer NT. Part 2: Treatments for chronic gastrointestinal disease and gut dysbiosis. 2015;14(1):25-33.

G Greenberg B (see Mills PJ et al) 2015;14(1):51. Gustafson C. Jeffrey Bland, PhD, and Patrick Hanaway, MD: Taking the omics revolution to the street. 2015;14(1):20-23. Gustafson C. Gerald Krystal, PhD: The effects of protein and carbohydrates on cancer. 2015;14(1):52-58. Gustafson C. Stuart Tomc, cannabinoid educator: Staying in step with the state of research. 2015;14(2):18-21. Gustafson C. Nancy Sudak, MD: On unifying the voices of integrative practice. 2015;14(2):54-58. Gustafson C. Kevin Spelman, PhD—Keeping it together: The other compounds in cannabis and the benefits of whole-herb use. 2015;14(3):18-22. Gustafson C. Denis Wilson, MD: Low body temperature as an indicator for poor expression of thyroid hormone. 2015;14(3):24-28. Gustafson C. Michael Smith, MD: Treat the underlying causes of weight gain to facilitate successful weight loss; part 1. 2015;14(3):60-61. Gustafson C. Andrew Campbell, MD: Mechanisms of the gut–brain axis. 2015;14(4):20-21. Gustafson C. Michael Smith, MD: Treat the underlying causes of weight gain to facilitate successful weight loss; part 3. 2015;14(4):50-52. Gustafson C. Mark Blumenthal: Quality and efficacy of herbal medicines. 2015;14(4):54-59. Gustafson C. Dale E. Bredesen, MD: Reversing cognitive decline. 2015;14(5):26-29. Gustafson C. Barbara Dossey, PhD, RN: Developing a healing approach in nursing. 2015;14(5):72-77. Gustafson C. Bernard Fox, PhD: The promise of immunotherapy in curing cancer. 2015;14(6):22-25. Gustafson C. Kara N. Fitzgerald, ND: Case reports— Informing the practice of systems medicine. 2015;14(6):36-39.

C Carson CA. Tart cherry juice as a treatment for peripheral neuropathy. 2015;14(1):48-49. Chang JL (see Lerman RH et al) 2015;14(5):52-61. Chinh K (see Mills PJ et al) 2015;14(1):51. Chopra D (see Mills PJ et al) 2015;14(1):51. D Desai A (see Lerman RH et al) 2015;14(5):52-61. Drisko JA (see Esparham AE et al) 2015;14(2):40-53. E Esparham AE, Smith T, Belmont JM, Haden M, Wagner LE, Evans R, Drisko JA. Nutritional and metabolic biomarkers in autism spectrum disorders: An exploratory study. 2015;14(2):40-53. Evans R (see Esparham AE et al) 2015;14(2):40-53.

Integrative Medicine • Vol. 14, No. 6 • December 2015

H Haden M (see Esparham AE et al) 2015;14(2):40-53. Harrell WA (see Boisvert JA et al) 2015;14(1):40-47. Author Index

I Isaacs LL. Research battles: Survival tips from a veteran. 2015;14(5):30-32. J Jensen CB. The continuum of health professions. 2015;14(3):48-53. Jensen CB. The health professions’ continuum cleft. 2015;14(4):30-33. K Kesten D, Scherwitz L. Whole-person integrative eating: A program for treating overeating, overweight, and obesity. 2015;14(5):42-50. Konda V (see Lerman RH et al) 2015;14(5):52-61. L Lerman RH, Chang JL, Konda V, Desai A, Montalto M. Nutritional approach for relief of joint discomfort: A 12-week, open-case series and illustrative case report. 2015;14(5):52-61. Lobay D. Rauwolfia in the treatment of hypertension. 2015;14(3):40-46. Lopez HL, Ziegenfuss TN, Park J. Evaluation of the effects of BioCell collagen, a novel cartilage extract, on connective tissue support and functional recovery from exercise. 2015;14(3):30-38. Lucius K, Trukova K. Integrative therapies and cardiovascular disease in the breast cancer population: A review, part 1. 2015;14(4):22-29. Lucius K, Trukova K. Integrative therapies and cardiovascular disease in the breast cancer population: A review, part 2. 2015;14(5):33-40. Lunde O (see Mills PJ et al) 2015;14(1):51. M Maresz K. Proper calcium use: Vitamin K2 as a promoter of bone and cardiovascular health. 2015;14(1):34-39. Mills PJ, Wilson K, Punga MA, Chinh K, Pruitt C, Greenberg B, Lunde O, Wood A, Redwine L, Chopra D. The role of gratitude in well-being in asymptomatic heart failure patients. 2015;14(1):51. Montalto M (see Lerman RH et al) 2015;14(5):52-61. N Narayanan P (see Seppälä E et al) 2015;14(1):50. O Opila-Lehman J (see Shannon S et al) 2015;14(6):31-35. P Park J (see Lopez HL et al) 2015;14(3):30-38. Pizzorno L. Nothing boring about boron. 2015;14(4):35-48. Pizzorno L. Personalized Lifestyle Medicine Institute, October 2014: A seminal moment in the 21st century’s transformation of health care. 2015;14(5):64-71. Author Index

Pizzorno J. The Path Ahead—Acidosis: An old idea validated by new research. 2015;14(1):8-12. Pizzorno J. The Path Ahead—Issue 75! 2015;14(2):8-13. Pizzorno J. The Path Ahead—Hard to be healthy in North America. 2015;14(3):8-13. Pizzorno J. The Path Ahead—Is challenge testing valid for assessing body metal burden? 2015;14(4):8-14. Pizzorno J. The Path Ahead—Conventional laboratory tests to assess toxin burden. 2015;14(5):8-16. Pizzorno J. The Path Ahead—The kidney dysfunction epidemic, part 1: Causes. 2015;14(6):8-13. Plummer NT (see Bull MJ et al) 2015;14(1):25-33. Pruitt C (see Mills PJ et al) 2015;14(1):51. Punga MA (see Mills PJ et al) 2015;14(1):51. R Redwine L (see Mills PJ et al) 2015;14(1):51. Riley DS. Case reports, clinical practice guidelines, and evidence. 2015;14(5):78. S Saling JR (see Zdilla MJ et al) 2015;14(2):34-38. Scaffidi J (see Spinks K et al) 2015;14(2):23-32. Scherwitz L (see Kesten D et al) 2015;14(5):42-50. Seppälä E, Narayanan P. Breathing-based meditation decreases posttraumatic stress disorder symptoms in US military veterans: A randomized, controlled longitudinal study. 2015;14(1):50. Shannon S, Opila-Lehman J. Cannabidiol oil for decreasing addictive use of marijuana: A case report. 2015;14(6):31-35. Smith T (see Esparham AE et al) 2015;14(2):40-53. Spinks K, Walker M, Scaffidi J. Clinical assessment of lowdose osteoinductive protein as a stand-alone regimen in self-reported osteoarthritis. 2015;14(2):23-32. Starkey LD (see Zdilla MJ et al) 2015;14(2):34-38. T Trukova K (see Lucius K et al) 2015;14(4):22-29. Trukova K (see Lucius K et al) 2015;14(5):33-40. W Wagner LE (see Esparham AE et al) 2015;14(2):40-53. Walker M (see Spinks K et al) 2015;14(2):23-32. Weeks J. Industry Insights—End of a (lucky) era for integrative health policy: Republican wins sweep key integrative leaders from powerful committee chairs. 2015;14(1):16-18. Weeks J. Industry Insights—The Joint Commission moves integrative approach ahead of pharmaceuticals for pain management. 2015;14(2):14-16. Weeks J. Industry Insights—Going, going, nearly gone: Licensed “CAM” practitioners disappearing from the National Institutes of Health NCCIH advisory council. 2015;14(3):14-16.

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Weeks J. Industry Insights—Casey Health Institute: Integrative center marches into PCMH and ACO worlds … plus more. 2015;14(4):16-19. Weeks J. Industry Insights—The blue zone intersection: What role for integrative health in community health? 2015;14(5):22-24. Weeks J. Harvard team finds 43% reduction in use of health care services via mind-body intervention … plus more. 2015;14(6):18-21. Wilson K (see Mills PJ et al) 2015;14(1):51. Wood A (see Mills PJ et al) 2015;14(1):51. Woods JO. Dr Hal Alan Huggins, noted dental pioneer, passes away. 2015;14(1):14-15. Z Zdilla MJ, Starkey LD, Saling JR. A taste-intensity visual analog scale: An improved zinc taste-test protocol. 2015;14(2):34-38. Ziegenfuss TN (see Lopez HL et al) 2015;14(3):30-38.

CAM Practitioner: Where alternative meets mainstream. There are nearly 4 million articles in PubMed that respond to the search medical. But when you narrow it to complementary medicine the number of hits drops to just over 200,000. But even 200,000 are a lot of articles to sift through. CAM Practitioner is a new site to help target the most recent and most heavily researched topics within PubMed. CAM Practitioner is a valuable resource you can use to access leading research to guide your practice.

According to the National Institute of Health, more than 30 percent of adults and about 12 percent of children use health care approaches developed outside of mainstream Western, or conventional, medicine. A recent survey found that the use of dietary supplements is the most popular complementary health approach. The most frequently cited reasons for CAM use are general wellness, and pain management.

CAMPractitioner.com

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The Great Plains Laboratory, Inc.

VOLUME 14 2015 INDEX

SUBJECT INDEX

# 2,3-Dimercapto-1-propanesulfonic acid The Path Ahead—Is challenge testing valid for assessing body metal burden? Pizzorno J. 2015;14(4):8-14. 75th issue The Path Ahead—Issue 75! Pizzorno J. 2015;14(2):8-13. A AANP See American Association of Naturopathic Physicians Abstract Tart cherry juice as a treatment for peripheral neuropathy. Carson CA. 2015;14(1):48-49. Breathing-based meditation decreases posttraumatic stress disorder symptoms in US military veterans: A randomized, controlled longitudinal study. Seppälä E, Narayanan P. 2015;14(1):50. The role of gratitude in well-being in asymptomatic heart failure patients. Mills PJ, Wilson K, Punga MA, Chinh K, Pruitt C, Greenberg B, Lunde O, Wood A, Redwine L, Chopra D. 2015;14(1):51. Academic Consortium for Integrative Medicine and Health Industry Insights—Going, going, nearly gone: Licensed “CAM” practitioners disappearing from the National Institutes of Health NCCIH advisory council. Weeks J. 2015;14(3):14-16. Academy of Integrative Health and Medicine Nancy Sudak, MD: On unifying the voices of integrative practice. Gustafson C. 2015;14(2):54-58. Acidosis The Path Ahead—Acidosis: An old idea validated by new research. Pizzorno J. 2015;14(1):8-12. Acid load The Path Ahead—Acidosis: An old idea validated by new research. Pizzorno J. 2015;14(1):8-12. ACIMH See Academic Consortium for Integrative Medicine and Health Ageusia A taste-intensity visual analog scale: An improved zinc taste-test protocol. Zdilla MJ, Starkey LD, Saling JR. 2015;14(2):34-38. 44

Integrative Medicine • Vol. 14, No. 6 • December 2015

AIHM See Academy of Integrative Health and Medicine Allergic disease Sixteen-year-old female with acute abdominal pain: A case report. Fitzgerald K. 2015;14(6):26-29. Allergies Sixteen-year-old female with acute abdominal pain: A case report. Fitzgerald K. 2015;14(6):26-29. American Association of Naturopathic Physicians Stuart Tomc, cannabinoid educator: Staying in step with the state of research. Gustafson C. 2015;14(2):18-21. American Botanical Council Mark Blumenthal: Quality and efficacy of herbal medicines. Gustafson C. 2015;14(4):54-59. Antibiotics Part 2: Treatments for chronic gastrointestinal disease and gut dysbiosis. Bull MJ, Plummer NT. 2015;14(1):25-33. Anxiety Cannabidiol oil for decreasing addictive use of marijuana: A case report. Shannon S, Opila-Lehman J. 2015;14(6):31-35. Arthritis Nothing boring about boron. Pizzorno L. 2015;14(4):35-48. ASD See Autism spectrum disorder Autism Nutritional and metabolic biomarkers in autism spectrum disorders: An exploratory study. Esparham AE, Smith T, Belmont JM, Haden M, Wagner LE, Evans R, Drisko JA. 2015;14(2):40-53. Autism spectrum disorder Nutritional and metabolic biomarkers in autism spectrum disorders: An exploratory study. Esparham AE, Smith T, Belmont JM, Haden M, Wagner LE, Evans R, Drisko JA. 2015;14(2):40-53. B BackTalk BackTalk—Fear of flying. Benda B. 2015;14(1):64. BackTalk—Ginseng and jet engines. Benda B. 2015;14(2):64. BackTalk—A pirate looks at 60. Benda B. 2015;14(3):68. BackTalk—No satisfaction. Benda B. 2015;14(4):68. Subject Index

BackTalk—Quit your bellyaching. Benda B. 2015;14(5):88. BackTalk—Confessions of a narcissist. Benda B. 2015;14(6):64. Bland, Jeffrey Jeffrey Bland, PhD, and Patrick Hanaway, MD: Taking the omics revolution to the street. Gustafson C. 2015;14(1):20-23. BioCell collagen Evaluation of the effects of BioCell collagen, a novel cartilage extract, on connective tissue support and functional recovery from exercise. Lopez HL, Ziegenfuss TN, Park J. 2015;14(3):30-38. Biochemistry The Path Ahead—Acidosis: An old idea validated by new research. Pizzorno J. 2015;14(1):8-12. Biomarkers Evaluation of the effects of BioCell collagen, a novel cartilage extract, on connective tissue support and functional recovery from exercise. Lopez HL, Ziegenfuss TN, Park J. 2015;14(3):30-38. Blumenthal, Mark Mark Blumenthal: Quality and efficacy of herbal medicines. Gustafson C. 2015;14(4):54-59. BMP See Bone morphogenetic protein Breast cancer Nothing boring about boron. Pizzorno L. 2015;14(4):35-48. Integrative therapies and cardiovascular disease in the breast cancer population: A review, part 2. Lucius K, Trukova K. 2015;14(5):33-40. Body metal burden The Path Ahead—Is challenge testing valid for assessing body metal burden? Pizzorno J. 2015;14(4):8-14. Integrative therapies and cardiovascular disease in the breast cancer population: A review, part 1. Lucius K, Trukova K. 2015;14(4):22-29. Body temperature Denis Wilson, MD: Low body temperature as an indicator for poor expression of thyroid hormone. Gustafson C. 2015;14(3):24-28. Bone density Proper calcium use: Vitamin K2 as a promoter of bone and cardiovascular health. Maresz K. 2015;14(1):34-39. Bone morphogenetic protein Clinical assessment of low-dose osteoinductive protein as a stand-alone regimen in self-reported osteoarthritis. Spinks K, Walker M, Scaffidi J. 2015;14(2):23-32. Boron Nothing boring about boron. Pizzorno L. 2015;14(4):35-48. Botanical medicine Rauwolfia in the treatment of hypertension. Lobay D. 2015;14(3):40-46. Botanicals Industry Insights—The Joint Commission moves integrative approach ahead of pharmaceuticals for pain management. Weeks J. 2015;14(2):14-16. Subject Index

Bredesen, Dale E. Dale E. Bredesen, MD: Reversing cognitive decline. Gustafson C. 2015;14(5):26-29. C Calcium Proper calcium use: Vitamin K2 as a promoter of bone and cardiovascular health. Maresz K. 2015;14(1):34-39. Calcium supplements Proper calcium use: Vitamin K2 as a promoter of bone and cardiovascular health. Maresz K. 2015;14(1):34-39. Campbell, Andrew Andrew Campbell, MD: Mechanisms of the gut–brain axis. Gustafson C. 2015;14(4):20-21. Cancer The Path Ahead—Acidosis: An old idea validated by new research. Pizzorno J. 2015;14(1):8-12. Gerald Krystal, PhD: The effects of protein and carbohydrates on cancer. Gustafson C. 2015;14(1):52-58. Nothing boring about boron. Pizzorno L. 2015;14(4):35-48. Gustafson C. Bernard Fox, PhD: The promise of immunotherapy in curing cancer. 2015;14(6):22-25. Cannabidiol Kevin Spelman, PhD—Keeping it together: The other compounds in cannabis and the benefits of wholeherb use. Gustafson C. 2015;14(3):18-22. Cannabidiol oil for decreasing addictive use of marijuana: A case report. Shannon S, Opila-Lehman J. 2015;14(6):31-35. Cannabinoid Stuart Tomc, cannabinoid educator: Staying in step with the state of research. Gustafson C. 2015;14(2):18-21. Cannabidiol oil for decreasing addictive use of marijuana: A case report. Shannon S, Opila-Lehman J. 2015;14(6):31-35. Cannabis Kevin Spelman, PhD—Keeping it together: The other compounds in cannabis and the benefits of wholeherb use. Gustafson C. 2015;14(3):18-22. Cannabis sativa Cannabidiol oil for decreasing addictive use of marijuana: A case report. Shannon S, Opila-Lehman J. 2015;14(6):31-35. Carbohydrates Gerald Krystal, PhD: The effects of protein and carbohydrates on cancer. Gustafson C. 2015;14(1):52-58.

Cardiovascular Integrative therapies and cardiovascular disease in the breast cancer population: A Review, part 1. Lucius K, Trukova K. 2015;14(4):22-29. Integrative therapies and cardiovascular disease in the breast cancer population: A review, part 2. Lucius K, Trukova K. 2015;14(5):33-40. Cardiovascular health

Integrative Medicine • Vol. 14, No. 6 • December 2015

Proper calcium use: Vitamin K2 as a promoter of bone and cardiovascular health. Maresz K. 2015;14(1):34-39. CARE guidelines Case reports, clinical practice guidelines, and evidence. Riley DS. 2015;14(5):78. Cartilage Clinical assessment of low-dose osteoinductive protein as a stand-alone regimen in self-reported osteoarthritis. Spinks K, Walker M, Scaffidi J. 2015;14(2):23-32. Case control study Research battles: Survival tips from a veteran. Isaacs LL. 2015;14(5):30-32. Case report Nutritional approach for relief of joint discomfort: A 12-week, open-case series and illustrative case report. Lerman RH, Chang JL, Konda V, Desai A, Montalto M. 2015;14(5):52-61. Case reports, clinical practice guidelines, and evidence. Riley DS. 2015;14(5):78. Sixteen-year-old female with acute abdominal pain: A case report. Fitzgerald K. 2015;14(6):26-29. Cannabidiol oil for decreasing addictive use of marijuana: A case report. Shannon S, Opila-Lehman J. 2015;14(6):31-35. Kara N. Fitzgerald, ND: Case reports—Informing the practice of systems medicine. Gustafson C. 2015;14(6):36-39. Case study The effect of dietary change in a patient with ichthyosis vulgaris: A case report. Anderson B. 2015;14(3):55-58. Whole-person integrative eating: A program for treating overeating, overweight, and obesity. Kesten D, Scherwitz L. 2015;14(5):42-50. Casey Health Institute Industry Insights—Casey Health Institute: Integrative center marches into PCMH and ACO worlds … plus more. Weeks J. 2015;14(4):16-19. CBD See Cannabidiol Cervical cancer Nothing boring about boron. Pizzorno L. 2015;14(4):35-48. Challenge testing The Path Ahead—Is challenge testing valid for assessing body metal burden? Pizzorno J. 2015;14(4):8-14. Chiropractic The effect of dietary change in a patient with ichthyosis vulgaris: A case report. Anderson B. 2015;14(3):55-58. Chronic disease The Path Ahead—Hard to be healthy in North America. Pizzorno J. 2015;14(3):8-13. Clinical application Tart cherry juice as a treatment for peripheral neuropathy. Carson CA. 2015;14(1):48-49.

Integrative Medicine • Vol. 14, No. 6 • December 2015

Breathing-based meditation decreases posttraumatic stress disorder symptoms in US military veterans: A randomized, controlled longitudinal study. Seppälä E, Narayanan P. 2015;14(1):50. The role of gratitude in well-being in asymptomatic heart failure patients. Mills PJ, Wilson K, Punga MA, Chinh K, Pruitt C, Greenberg B, Lunde O, Wood A, Redwine L, Chopra D. 2015;14(1):51. Clinical practice The Path Ahead—Issue 75! Pizzorno J. 2015;14(2):8-13. Clinical practice guidelines Case reports, clinical practice guidelines, and evidence. Riley DS. 2015;14(5):78. Cognitive decline Dale E. Bredesen, MD: Reversing cognitive decline. Gustafson C. 2015;14(5):26-29. Commentary See also Industry Insights Research battles: Survival tips from a veteran. Isaacs LL. 2015;14(5):30-32. Personalized Lifestyle Medicine Institute, October 2014: A seminal moment in the 21st century’s transformation of health care. Pizzorno L. 2015;14(5):64-71. Community health Industry Insights—The blue zone intersection: What role for integrative health in community health? Weeks J. 2015;14(5):22-24. Complementary medicine Integrative therapies and cardiovascular disease in the breast cancer population: A review, part 1. Lucius K, Trukova K. 2015;14(4):22-29. Integrative therapies and cardiovascular disease in the breast cancer population: A review, part 2. Lucius K, Trukova K. 2015;14(5):33-40. Complementary therapies The effect of dietary change in a patient with ichthyosis vulgaris: A case report. Anderson B. 2015;14(3):55-58. Conference See Presenters 2015 Continuum cleft The continuum of health professions. Jensen CB. 2015;14(3):48-53. The health professions’ continuum cleft. Jensen CB. 2015;14(4):30-33. Conventional laboratory tests The Path Ahead—Conventional laboratory tests to assess toxin burden. Pizzorno J. 2015;14(5):8-16. CPG See Clinical practice guidelines Cross reactions Sixteen-year-old female with acute abdominal pain: A case report. Fitzgerald K. 2015;14(6):26-29. Creating Synthesis Creating Synthesis—Functional medicine: An operating system for integrative medicine. Bland J. 2015;14(5):18-20. Subject Index

Creating Synthesis—When is a disease a “disease”? Bland J. 2015;14(6):14-16. Cyplexinol Clinical assessment of low-dose osteoinductive protein as a stand-alone regimen in self-reported osteoarthritis. Spinks K, Walker M, Scaffidi J. 2015;14(2):23-32. D Degenerative joint disease Clinical assessment of low-dose osteoinductive protein as a stand-alone regimen in self-reported osteoarthritis. Spinks K, Walker M, Scaffidi J. 2015;14(2):23-32. Dental implants Dr Hal Alan Huggins, noted dental pioneer, passes away. Woods JO. 2015;14(1):14-15. Dentistry Dr Hal Alan Huggins, noted dental pioneer, passes away. Woods JO. 2015;14(1):14-15. Depression Rauwolfia in the treatment of hypertension. Lobay D. 2015;14(3):40-46. Diabetes The Path Ahead—Hard to be healthy in North America. Pizzorno J. 2015;14(3):8-13. Diet The Path Ahead—Acidosis: An old idea validated by new research. Pizzorno J. 2015;14(1):8-12. Proper calcium use: Vitamin K2 as a promoter of bone and cardiovascular health. Maresz K. 2015;14(1):34-39. Gerald Krystal, PhD: The effects of protein and carbohydrates on cancer. Gustafson C. 2015;14(1):52-58. Michael Smith, MD: Treat the underlying causes of weight gain to facilitate successful weight loss; part 3. Gustafson C. 2015;14(4):50-52. Dietary supplements The effect of dietary change in a patient with ichthyosis vulgaris: A case report. Anderson B. 2015;14(3):55-58. Diet therapy The effect of dietary change in a patient with ichthyosis vulgaris: A case report. Anderson B. 2015;14(3):55-58. Dimercaptosuccinic acid The Path Ahead—Is challenge testing valid for assessing body metal burden? Pizzorno J. 2015;14(4):8-14. Disease The Path Ahead—Acidosis: An old idea validated by new research. Pizzorno J. 2015;14(1):8-12. Creating Synthesis—When is a disease a “disease”? Bland J. 2015;14(6):14-16. DJD See Degenerative joint disease DMPS See 2,3-Dimercapto-1-propanesulfonic acid DMSA See Dimercaptosuccinic acid

Subject Index

Dossey, Barbara Barbara Dossey, PhD, RN: Developing a healing approach in nursing. Gustafson C. 2015;14(5):72-77. Dysfunction The Path Ahead—The kidney dysfunction epidemic, part 1: Causes. Pizzorno J. 2015;14(6):8-13. Dysgeusia A taste-intensity visual analog scale: An improved zinc taste-test protocol. Zdilla MJ, Starkey LD, Saling JR. 2015;14(2):34-38. E EBM See Evidence-based medicine Ebola BackTalk—Fear of flying. Benda B. 2015;14(1):64. Echinacea Kevin Spelman, PhD—Keeping it together: The other compounds in cannabis and the benefits of wholeherb use. Gustafson C. 2015;14(3):18-22. Editorial See also BackTalk, Creating Synthesis, and The Path Ahead Case reports, clinical practice guidelines, and evidence. Riley DS. 2015;14(5):78. Environmental medicine The Path Ahead—Is challenge testing valid for assessing body metal burden? Pizzorno J. 2015;14(4):8-14. Eosinophilic esophagitis Sixteen-year-old female with acute abdominal pain: A case report. Fitzgerald K. 2015;14(6):26-29. Epidemic BackTalk—Fear of flying. Benda B. 2015;14(1):64. Estrogen Nothing boring about boron. Pizzorno L. 2015;14(4):35-48. Evidence-based medicine Case reports, clinical practice guidelines, and evidence. Riley DS. 2015;14(5):78. Exercise Michael Smith, MD: Treat the underlying causes of weight gain to facilitate successful weight loss; part 3. Gustafson C. 2015;14(4):50-52. Exercise-induced muscle damage Evaluation of the effects of BioCell collagen, a novel cartilage extract, on connective tissue support and functional recovery from exercise. Lopez HL, Ziegenfuss TN, Park J. 2015;14(3):30-38. F Fatigue Cannabidiol oil for decreasing addictive use of marijuana: A case report. Shannon S, Opila-Lehman J. 2015;14(6):31-35. Fear BackTalk—Fear of flying. Benda B. 2015;14(1):64.

Integrative Medicine • Vol. 14, No. 6 • December 2015

Fecal microbiota transplantation Part 2: Treatments for chronic gastrointestinal disease and gut dysbiosis. Bull MJ, Plummer NT. 2015;14(1):25-33. Fitzgerald, Kara Kara N. Fitzgerald, ND: Case reports—Informing the practice of systems medicine. Gustafson C. 2015;14(6):36-39. FMT See Fecal microbiota transplantation Functional medicine Jeffrey Bland, PhD, and Patrick Hanaway, MD: Taking the omics revolution to the street. Gustafson C. 2015;14(1):20-23. Creating Synthesis—Functional medicine: An operating system for integrative medicine. Bland J. 2015;14(5):18-20. G Gastrointestinal disease Part 2: Treatments for chronic gastrointestinal disease and gut dysbiosis. Bull MJ, Plummer NT. 2015;14(1):25-33. Genomics Jeffrey Bland, PhD, and Patrick Hanaway, MD: Taking the omics revolution to the street. Gustafson C. 2015;14(1):20-23. Glutathione Nutritional and metabolic biomarkers in autism spectrum disorders: An exploratory study. Esparham AE, Smith T, Belmont JM, Haden M, Wagner LE, Evans R, Drisko JA. 2015;14(2):40-53. Glutathione peroxidase Nothing boring about boron. Pizzorno L. 2015;14(4):35-48. Gonzales, Nicholas Research battles: Survival tips from a veteran. Isaacs LL. 2015;14(5):30-32. Gratitude The role of gratitude in well-being in asymptomatic heart failure patients. Mills PJ, Wilson K, Punga MA, Chinh K, Pruitt C, Greenberg B, Lunde O, Wood A, Redwine L, Chopra D. 2015;14(1):51. Gut-Brain connection Andrew Campbell, MD: Mechanisms of the gut–brain axis. Gustafson C. 2015;14(4):20-21. Gut-Brain Relationship Conference Andrew Campbell, MD: Mechanisms of the gut–brain axis. Gustafson C. 2015;14(4):20-21. Gut dysbiosis Part 2: Treatments for chronic gastrointestinal disease and gut dysbiosis. Bull MJ, Plummer NT. 2015;14(1):25-33. Gut health Part 2: Treatments for chronic gastrointestinal disease and gut dysbiosis. Bull MJ, Plummer NT. 2015;14(1):25-33.

Jeffrey Bland, PhD, and Patrick Hanaway, MD: Taking the omics revolution to the street. Gustafson C. 2015;14(1):20-23. Healing approach Barbara Dossey, PhD, RN: Developing a healing approach in nursing. Gustafson C. 2015;14(5):72-77. Health care Industry Insights—End of a (lucky) era for integrative health policy: Republican wins sweep key integrative leaders from powerful committee chairs. Weeks J. 2015;14(1):16-18. Nancy Sudak, MD: On unifying the voices of integrative practice. Gustafson C. 2015;14(2):54-58. BackTalk—Ginseng and jet engines. Benda B. 2015;14(2):64. Industry Insights—Casey Health Institute: Integrative center marches into PCMH and ACO worlds … plus more. Weeks J. 2015;14(4):16-19. Health professions continuum The continuum of health professions. Jensen CB. 2015;14(3):48-53. The health professions’ continuum cleft. Jensen CB. 2015;14(4):30-33. Health promotion Integrative treatment of pediatric obesity: Psychological and spiritual considerations. Boisvert JA, Harrell WA. 2015;14(1):40-47. Heart disease Proper calcium use: Vitamin K2 as a promoter of bone and cardiovascular health. Maresz K. 2015;14(1):34-39. Heart failure The role of gratitude in well-being in asymptomatic heart failure patients. Mills PJ, Wilson K, Punga MA, Chinh K, Pruitt C, Greenberg B, Lunde O, Wood A, Redwine L, Chopra D. 2015;14(1):51. Herbal medicine Mark Blumenthal: Quality and efficacy of herbal medicines. Gustafson C. 2015;14(4):54-59. High-sensitivity C-reactive protein Nothing boring about boron. Pizzorno L. 2015;14(4):35-48. Holistic nursing Barbara Dossey, PhD, RN: Developing a healing approach in nursing. Gustafson C. 2015;14(5):72-77. Holistic treatment Integrative treatment of pediatric obesity: Psychological and spiritual considerations. Boisvert JA, Harrell WA. 2015;14(1):40-47. hs-CRP See High-sensitivity C-reactive protein Huggins, Hal Alan Dr Hal Alan Huggins, noted dental pioneer, passes away. Woods JO. 2015;14(1):14-15.

H Hanaway, Patrick

Integrative Medicine • Vol. 14, No. 6 • December 2015

Subject Index

Humulus lupulus L. Nutritional approach for relief of joint discomfort: A 12-week, open-case series and illustrative case report. Lerman RH, Chang JL, Konda V, Desai A, Montalto M. 2015;14(5):52-61. Hydrolyzed chicken sternal cartilage extract Evaluation of the effects of BioCell collagen, a novel cartilage extract, on connective tissue support and functional recovery from exercise. Lopez HL, Ziegenfuss TN, Park J. 2015;14(3):30-38. Nutritional approach for relief of joint discomfort: A 12-week, open-case series and illustrative case report. Lerman RH, Chang JL, Konda V, Desai A, Montalto M. 2015;14(5):52-61. Hydrolyzed collagen type 2 Evaluation of the effects of BioCell collagen, a novel cartilage extract, on connective tissue support and functional recovery from exercise. Lopez HL, Ziegenfuss TN, Park J. 2015;14(3):30-38. Hypertension Rauwolfia in the treatment of hypertension. Lobay D. 2015;14(3):40-46. Hypogeusia A taste-intensity visual analog scale: An improved zinc taste-test protocol. Zdilla MJ, Starkey LD, Saling JR. 2015;14(2):34-38. I IBS See Irritable bowel syndrome Ichthyosis The effect of dietary change in a patient with ichthyosis vulgaris: A case report. Anderson B. 2015;14(3):55-58. IFM See Institute for Functional Medicine Immune health Immunotherapy Gustafson C. Bernard Fox, PhD: The promise of immunotherapy in curing cancer. 2015;14(6):22-25. Part 2: Treatments for chronic gastrointestinal disease and gut dysbiosis. Bull MJ, Plummer NT. 2015;14(1):25-33. Industry Insights Industry Insights—End of a (lucky) era for integrative health policy: Republican wins sweep key integrative leaders from powerful committee chairs. Weeks J. 2015;14(1):16-18. Industry Insights—The Joint Commission moves integrative approach ahead of pharmaceuticals for pain management. Weeks J. 2015;14(2):14-16. Industry Insights—Going, going, nearly gone: Licensed “CAM” practitioners disappearing from the National Institutes of Health NCCIH advisory council. Weeks J. 2015;14(3):14-16. Industry Insights—Casey Health Institute: Integrative center marches into PCMH and ACO worlds … plus more. Weeks J. 2015;14(4):16-19. Subject Index

Industry Insights—The blue zone intersection: What role for integrative health in community health? Weeks J. 2015;14(5):22-24. Industry Insights—Harvard team finds 43% reduction in use of health care services via mind-body intervention … plus more. Weeks J. 2015;14(6):18-21. Infectious disease BackTalk—Fear of flying. Benda B. 2015;14(1):64. Inflammation Gerald Krystal, PhD: The effects of protein and carbohydrates on cancer. Gustafson C. 2015;14(1):52-58. Tart cherry juice as a treatment for peripheral neuropathy. Carson CA. 2015;14(1):48-49. Inflammatory bowel disease Part 2: Treatments for chronic gastrointestinal disease and gut dysbiosis. Bull MJ, Plummer NT. 2015;14(1):25-33. In memoriam Dr Hal Alan Huggins, noted dental pioneer, passes away. Woods JO. 2015;14(1):14-15. Insomnia Cannabidiol oil for decreasing addictive use of marijuana: A case report. Shannon S, Opila-Lehman J. 2015;14(6):31-35. Institute for Functional Medicine Jeffrey Bland, PhD, and Patrick Hanaway, MD: Taking the omics revolution to the street. Gustafson C. 2015;14(1):20-23. Insurance BackTalk—Ginseng and jet engines. Benda B. 2015;14(2):64. Integrative health Industry Insights—The blue zone intersection: What role for integrative health in community health? Weeks J. 2015;14(5):22-24. Integrative Health Policy Consortium Industry Insights—Casey Health Institute: Integrative center marches into PCMH and ACO worlds … plus more. Weeks J. 2015;14(4):16-19. Integrative medicine The Path Ahead—Issue 75! Pizzorno J. 2015;14(2):8-13. Industry Insights—End of a (lucky) era for integrative health policy: Republican wins sweep key integrative leaders from powerful committee chairs. Weeks J. 2015;14(1):16-18. Integrative treatment of pediatric obesity: Psychological and spiritual considerations. Boisvert JA, Harrell WA. 2015;14(1):40-47. Tart cherry juice as a treatment for peripheral neuropathy. Carson CA. 2015;14(1):48-49. Breathing-based meditation decreases posttraumatic stress disorder symptoms in US military veterans: A randomized, controlled longitudinal study. Seppälä E, Narayanan P. 2015;14(1):50. Industry Insights—The Joint Commission moves integrative approach ahead of pharmaceuticals for pain management. Weeks J. 2015;14(2):14-16. Integrative Medicine • Vol. 14, No. 6 • December 2015

Nancy Sudak, MD: On unifying the voices of integrative practice. Gustafson C. 2015;14(2):54-58. Industry Insights—Going, going, nearly gone: Licensed “CAM” practitioners disappearing from the National Institutes of Health NCCIH advisory council. Weeks J. 2015;14(3):14-16. Industry Insights—Casey Health Institute: Integrative center marches into PCMH and ACO worlds … plus more. Weeks J. 2015;14(4):16-19. Integrative therapies and cardiovascular disease in the breast cancer population: A review, part 1. Lucius K, Trukova K. 2015;14(4):22-29. Creating Synthesis—Functional medicine: An operating system for integrative medicine. Bland J. 2015;14(5):18-20. Integrative therapies and cardiovascular disease in the breast cancer population: A review, part 2. Lucius K, Trukova K. 2015;14(5):33-40. Integrative oncology Integrative therapies and cardiovascular disease in the breast cancer population: A review, part 1. Lucius K, Trukova K. 2015;14(4):22-29. Integrative therapies and cardiovascular disease in the breast cancer population: A review, part 2. Lucius K, Trukova K. 2015;14(5):33-40. Interview See Viewpoints and Presenters 2015/2016 Intestinal permeability Sixteen-year-old female with acute abdominal pain: A case report. Fitzgerald K. 2015;14(6):26-29. Irritable bowel syndrome Part 2: Treatments for chronic gastrointestinal disease and gut dysbiosis. Bull MJ, Plummer NT. 2015;14(1):25-33. Isaacs, Linda Research battles: Survival tips from a veteran. Isaacs LL. 2015;14(5):30-32. J Joint Commission Industry Insights—The Joint Commission moves integrative approach ahead of pharmaceuticals for pain management. Weeks J. 2015;14(2):14-16. Joint pain Tart cherry juice as a treatment for peripheral neuropathy. Carson CA. 2015;14(1):48-49. K Kidney The Path Ahead—The kidney dysfunction epidemic, part 1: Causes. Pizzorno J. 2015;14(6):8-13. Krystal, Gerald Gerald Krystal, PhD: The effects of protein and carbohydrates on cancer. Gustafson C. 2015;14(1):52-58.

Integrative Medicine • Vol. 14, No. 6 • December 2015

L Life Extension Michael Smith, MD: Treat the underlying causes of weight gain to facilitate successful weight loss; part 3. Gustafson C. 2015;14(4):50-52. Lifestyle trial design Research battles: Survival tips from a veteran. Isaacs LL. 2015;14(5):30-32. Ligament Evaluation of the effects of BioCell collagen, a novel cartilage extract, on connective tissue support and functional recovery from exercise. Lopez HL, Ziegenfuss TN, Park J. 2015;14(3):30-38. Lung cancer Nothing boring about boron. Pizzorno L. 2015;14(4):35-48. M Magnesium Nothing boring about boron. Pizzorno L. 2015;14(4):35-48. Marijuana Cannabidiol oil for decreasing addictive use of marijuana: A case report. Shannon S, Opila-Lehman J. 2015;14(6):31-35. Massage Industry Insights—The Joint Commission moves integrative approach ahead of pharmaceuticals for pain management. Weeks J. 2015;14(2):14-16. Medical marijuana Kevin Spelman, PhD—Keeping it together: The other compounds in cannabis and the benefits of wholeherb use. Gustafson C. 2015;14(3):18-22. Medical philosophy The Path Ahead—Issue 75! Pizzorno J. 2015;14(2):8-13. Meditation Breathing-based meditation decreases posttraumatic stress disorder symptoms in US military veterans: A randomized, controlled longitudinal study. Seppälä E, Narayanan P. 2015;14(1):50. Metabolic biomarkers Nutritional and metabolic biomarkers in autism spectrum disorders: An exploratory study. Esparham AE, Smith T, Belmont JM, Haden M, Wagner LE, Evans R, Drisko JA. 2015;14(2):40-53. Mercury Dr Hal Alan Huggins, noted dental pioneer, passes away. Woods JO. 2015;14(1):14-15. Metabolic syndrome The Path Ahead—Acidosis: An old idea validated by new research. Pizzorno J. 2015;14(1):8-12. Metabolism Denis Wilson, MD: Low body temperature as an indicator for poor expression of thyroid hormone. Gustafson C. 2015;14(3):24-28. The Path Ahead—Acidosis: An old idea validated by new research. Pizzorno J. 2015;14(1):8-12.

Subject Index

Methylation Nutritional and metabolic biomarkers in autism spectrum disorders: An exploratory study. Esparham AE, Smith T, Belmont JM, Haden M, Wagner LE, Evans R, Drisko JA. 2015;14(2):40-53. Microbiome Andrew Campbell, MD: Mechanisms of the gut–brain axis. Gustafson C. 2015;14(4):20-21. Sixteen-year-old female with acute abdominal pain: A case report. Fitzgerald K. 2015;14(6):26-29. Microbiota Part 2: Treatments for chronic gastrointestinal disease and gut dysbiosis. Bull MJ, Plummer NT. 2015;14(1):25-33. Mitochondrial dysfunction Nutritional and metabolic biomarkers in autism spectrum disorders: An exploratory study. Esparham AE, Smith T, Belmont JM, Haden M, Wagner LE, Evans R, Drisko JA. 2015;14(2):40-53. Multiple lymphoma Nothing boring about boron. Pizzorno L. 2015;14(4):35-48. Muscle connective tissue Evaluation of the effects of BioCell collagen, a novel cartilage extract, on connective tissue support and functional recovery from exercise. Lopez HL, Ziegenfuss TN, Park J. 2015;14(3):30-38. Muscle recovery Evaluation of the effects of BioCell collagen, a novel cartilage extract, on connective tissue support and functional recovery from exercise. Lopez HL, Ziegenfuss TN, Park J. 2015;14(3):30-38. N NACCIH See National Advisory Council for Complementary and Integrative Health NAD+ See Nicotinamide adenine dinucleotide National Advisory Council for Complementary and Integrative Health Industry Insights—Going, going, nearly gone: Licensed “CAM” practitioners disappearing from the National Institutes of Health NCCIH advisory council. Weeks J. 2015;14(3):14-16. National Center for Complementary and Alternative Medicine Industry Insights—End of a (lucky) era for integrative health policy: Republican wins sweep key integrative leaders from powerful committee chairs. Weeks J. 2015;14(1):16-18. National Institutes of Health Industry Insights—End of a (lucky) era for integrative health policy: Republican wins sweep key integrative leaders from powerful committee chairs. Weeks J. 2015;14(1):16-18.

Subject Index

Natural products Industry Insights—The Joint Commission moves integrative approach ahead of pharmaceuticals for pain management. Weeks J. 2015;14(2):14-16. NCCAM See National Center for Complementary and Alternative Medicine News See Industry Insights Nicotinamide adenine dinucleotide Nothing boring about boron. Pizzorno L. 2015;14(4):35-48. NIH See National Institutes of Health Non-Hodgkin’s lymphoma Nothing boring about boron. Pizzorno L. 2015;14(4):35-48. Nonpharmacologic pain treatment Industry Insights—The Joint Commission moves integrative approach ahead of pharmaceuticals for pain management. Weeks J. 2015;14(2):14-16. NorthWest Herb Symposium Kevin Spelman, PhD—Keeping it together: The other compounds in cannabis and the benefits of wholeherb use. Gustafson C. 2015;14(3):18-22. Nurse coaching Barbara Dossey, PhD, RN: Developing a healing approach in nursing. Gustafson C. 2015;14(5):72-77. Nutrient status Nutritional and metabolic biomarkers in autism spectrum disorders: An exploratory study. Esparham AE, Smith T, Belmont JM, Haden M, Wagner LE, Evans R, Drisko JA. 2015;14(2):40-53. Nutrition Gerald Krystal, PhD: The effects of protein and carbohydrates on cancer. Gustafson C. 2015;14(1):52-58. The Path Ahead—Issue 75! Pizzorno J. 2015;14(2):8-13. Stuart Tomc, cannabinoid educator: Staying in step with the state of research. Gustafson C. 2015;14(2):18-21. The Path Ahead—Hard to be healthy in North America. Pizzorno J. 2015;14(3):8-13. Michael Smith, MD: Treat the underlying causes of weight gain to facilitate successful weight loss; part 3. Gustafson C. 2015;14(4):50-52. Whole-person integrative eating: A program for treating overeating, overweight, and obesity. Kesten D, Scherwitz L. 2015;14(5):42-50. Nutritional deficiency Nutritional and metabolic biomarkers in autism spectrum disorders: An exploratory study. Esparham AE, Smith T, Belmont JM, Haden M, Wagner LE, Evans R, Drisko JA. 2015;14(2):40-53. O Obesity The Path Ahead—Hard to be healthy in North America. Pizzorno J. 2015;14(3):8-13.

Integrative Medicine • Vol. 14, No. 6 • December 2015

Michael Smith, MD: Treat the underlying causes of weight gain to facilitate successful weight loss; part 1. Gustafson C. 2015;14(3):60-61. Whole-person integrative eating: A program for treating overeating, overweight, and obesity. Kesten D, Scherwitz L. 2015;14(5):42-50. Obituary Dr Hal Alan Huggins, noted dental pioneer, passes away. Woods JO. 2015;14(1):14-15. Omics revolution Jeffrey Bland, PhD, and Patrick Hanaway, MD: Taking the omics revolution to the street. Gustafson C. 2015;14(1):20-23. Opinion See BackTalk, Industry Insights, and Path Ahead Oral tolerance Nutritional approach for relief of joint discomfort: A 12-week, open-case series and illustrative case report. Lerman RH, Chang JL, Konda V, Desai A, Montalto M. 2015;14(5):52-61. Organic foods The Path Ahead—Hard to be healthy in North America. Pizzorno J. 2015;14(3):8-13. Original research Clinical assessment of low-dose osteoinductive protein as a stand-alone regimen in self-reported osteoarthritis. Spinks K, Walker M, Scaffidi J. 2015;14(2):23-32. A taste-intensity visual analog scale: An improved zinc taste-test protocol. Zdilla MJ, Starkey LD, Saling JR. 2015;14(2):34-38. Osteoarthritis Clinical assessment of low-dose osteoinductive protein as a stand-alone regimen in self-reported osteoarthritis. Spinks K, Walker M, Scaffidi J. 2015;14(2):23-32. Nothing boring about boron. Pizzorno L. 2015;14(4):35-48. Nutritional approach for relief of joint discomfort: A 12-week, open-case series and illustrative case report. Lerman RH, Chang JL, Konda V, Desai A, Montalto M. 2015;14(5):52-61. Osteopenia Nothing boring about boron. Pizzorno L. 2015;14(4):35-48. Osteoporosis Proper calcium use: Vitamin K2 as a promoter of bone and cardiovascular health. Maresz K. 2015;14(1):34-39. Nothing boring about boron. Pizzorno L. 2015;14(4):35-48. Oxidative stress Nutritional and metabolic biomarkers in autism spectrum disorders: An exploratory study. Esparham AE, Smith T, Belmont JM, Haden M, Wagner LE, Evans R, Drisko JA. 2015;14(2):40-53. P Pain management Industry Insights—The Joint Commission moves integrative approach ahead of pharmaceuticals for pain management. Weeks J. 2015;14(2):14-16. 52

Integrative Medicine • Vol. 14, No. 6 • December 2015

Path Ahead, The The Path Ahead—Conventional laboratory tests to assess toxin burden. Pizzorno J. 2015;14(5):8-16. The Path Ahead—Acidosis: An old idea validated by new research. Pizzorno J. 2015;14(1):8-12. The Path Ahead—Issue 75! Pizzorno J. 2015;14(2):8-13. The Path Ahead—Hard to be healthy in North America. Pizzorno J. 2015;14(3):8-13. The Path Ahead—Is challenge testing valid for assessing body metal burden? Pizzorno J. 2015;14(4):8-14. The Path Ahead—The kidney dysfunction epidemic, part 1: Causes. Pizzorno J. 2015;14(6):8-13. Pediatric health Integrative treatment of pediatric obesity: Psychological and spiritual considerations. Boisvert JA, Harrell WA. 2015;14(1):40-47. Pediatric obesity Integrative treatment of pediatric obesity: Psychological and spiritual considerations. Boisvert JA, Harrell WA. 2015;14(1):40-47. Peripheral neuropathy Tart cherry juice as a treatment for peripheral neuropathy. Carson CA. 2015;14(1):48-49. Personalized Lifestyle Medicine Institute Personalized Lifestyle Medicine Institute, October 2014: A seminal moment in the 21st century’s transformation of health care. Pizzorno L. 2015;14(5):64-71. Pharmacology Rauwolfia in the treatment of hypertension. Lobay D. 2015;14(3):40-46. Phytomedicine Mark Blumenthal: Quality and efficacy of herbal medicines. Gustafson C. 2015;14(4):54-59. Pillars Michael Smith, MD: Treat the underlying causes of weight gain to facilitate successful weight loss; part 1. Gustafson C. 2015;14(3):60-61. Pilot study Nutritional and metabolic biomarkers in autism spectrum disorders: An exploratory study. Esparham AE, Smith T, Belmont JM, Haden M, Wagner LE, Evans R, Drisko JA. 2015;14(2):40-53. Evaluation of the effects of BioCell collagen, a novel cartilage extract, on connective tissue support and functional recovery from exercise. Lopez HL, Ziegenfuss TN, Park J. 2015;14(3):30-38. Michael Smith, MD: Treat the underlying causes of weight gain to facilitate successful weight loss; part 3. Gustafson C. 2015;14(4):50-52. PLMI See Personalized Lifestyle Medicine Institute Policy See also Industry Insights The Path Ahead—Issue 75! Pizzorno J. 2015;14(2):8-13.

Subject Index

Politics Industry Insights—End of a (lucky) era for integrative health policy: Republican wins sweep key integrative leaders from powerful committee chairs. Weeks J. 2015;14(1):16-18. Posttraumatic stress disorder Breathing-based meditation decreases posttraumatic stress disorder symptoms in US military veterans: A randomized, controlled longitudinal study. Seppälä E, Narayanan P. 2015;14(1):50. Prebiotics Part 2: Treatments for chronic gastrointestinal disease and gut dysbiosis. Bull MJ, Plummer NT. 2015;14(1):25-33. Presenters 2015/2016 Jeffrey Bland, PhD, and Patrick Hanaway, MD: Taking the omics revolution to the street. Gustafson C. 2015;14(1):20-23. Stuart Tomc, cannabinoid educator: Staying in step with the state of research. Gustafson C. 2015;14(2):18-21. Kevin Spelman, PhD—Keeping it together: The other compounds in cannabis and the benefits of wholeherb use. Gustafson C. 2015;14(3):18-22. Denis Wilson, MD: Low body temperature as an indicator for poor expression of thyroid hormone. Gustafson C. 2015;14(3):24-28. Michael Smith, MD: Treat the underlying causes of weight gain to facilitate successful weight loss; part 1. Gustafson C. 2015;14(3):60-61. Andrew Campbell, MD: Mechanisms of the gut–brain axis. Gustafson C. 2015;14(4):20-21. Dale E. Bredesen, MD: Reversing cognitive decline. Gustafson C. 2015;14(5):26-29. Probiotics Part 2: Treatments for chronic gastrointestinal disease and gut dysbiosis. Bull MJ, Plummer NT. 2015;14(1):25-33. Professional cysts The continuum of health professions. Jensen CB. 2015;14(3):48-53. The health professions’ continuum cleft. Jensen CB. 2015;14(4):30-33. Professional silos The continuum of health professions. Jensen CB. 2015;14(3):48-53. The health professions’ continuum cleft. Jensen CB. 2015;14(4):30-33. Prostate cancer Nothing boring about boron. Pizzorno L. 2015;14(4):35-48. Protein Gerald Krystal, PhD: The effects of protein and carbohydrates on cancer. Gustafson C. 2015;14(1):52-58. Psychometric test A taste-intensity visual analog scale: An improved zinc taste-test protocol. Zdilla MJ, Starkey LD, Saling JR. 2015;14(2):34-38. Psychotherapy Integrative treatment of pediatric obesity: Psychological and spiritual considerations. Boisvert JA, Harrell WA. 2015;14(1):40-47. Subject Index

PTSD See Posttraumatic stress disorder Public policy Stuart Tomc, cannabinoid educator: Staying in step with the state of research. Gustafson C. 2015;14(2):18-21. R Rauwolfia Rauwolfia in the treatment of hypertension. Lobay D. 2015;14(3):40-46. Reimbursement BackTalk—Ginseng and jet engines. Benda B. 2015;14(2):64. Research The Path Ahead—Acidosis: An old idea validated by new research. Pizzorno J. 2015;14(1):8-12. Stuart Tomc, cannabinoid educator: Staying in step with the state of research. Gustafson C. 2015;14(2):18-21. Kevin Spelman, PhD—Keeping it together: The other compounds in cannabis and the benefits of wholeherb use. Gustafson C. 2015;14(3):18-22. The Path Ahead—Is challenge testing valid for assessing body metal burden? Pizzorno J. 2015;14(4):8-14. Restorative Medicine Conference Denis Wilson, MD: Low body temperature as an indicator for poor expression of thyroid hormone. Gustafson C. 2015;14(3):24-28. Review article Part 2: Treatments for chronic gastrointestinal disease and gut dysbiosis. Bull MJ, Plummer NT. 2015;14(1):25-33. Proper calcium use: Vitamin K2 as a promoter of bone and cardiovascular health. Maresz K. 2015;14(1):34-39. Integrative treatment of pediatric obesity: Psychological and spiritual considerations. Boisvert JA, Harrell WA. 2015;14(1):40-47. Rauwolfia in the treatment of hypertension. Lobay D. 2015;14(3):40-46. The continuum of health professions. Jensen CB. 2015;14(3):48-53. Integrative therapies and cardiovascular disease in the breast cancer population: A review, part 1. Lucius K, Trukova K. 2015;14(4):22-29. The health professions’ continuum cleft. Jensen CB. 2015;14(4):30-33. Nothing boring about boron. Pizzorno L. 2015;14(4):35-48. Integrative therapies and cardiovascular disease in the breast cancer population: A review, part 2. Lucius K, Trukova K. 2015;14(5):33-40. Rheumatoid arthritis Nutritional approach for relief of joint discomfort: A 12-week, open-case series and illustrative case report. Lerman RH, Chang JL, Konda V, Desai A, Montalto M. 2015;14(5):52-61.

Integrative Medicine • Vol. 14, No. 6 • December 2015

S SAMe Nothing boring about boron. Pizzorno L. 2015;14(4):35-48. Satisfaction BackTalk—No satisfaction. Benda B. 2015;14(4):68. Scientific application Tart cherry juice as a treatment for peripheral neuropathy. Carson CA. 2015;14(1):48-49. Breathing-based meditation decreases posttraumatic stress disorder symptoms in US military veterans: A randomized, controlled longitudinal study. Seppälä E, Narayanan P. 2015;14(1):50. The role of gratitude in well-being in asymptomatic heart failure patients. Mills PJ, Wilson K, Punga MA, Chinh K, Pruitt C, Greenberg B, Lunde O, Wood A, Redwine L, Chopra D. 2015;14(1):51. Scripps Research Institute Tart cherry juice as a treatment for peripheral neuropathy. Carson CA. 2015;14(1):48-49. Breathing-based meditation decreases posttraumatic stress disorder symptoms in US military veterans: A randomized, controlled longitudinal study. Seppälä E, Narayanan P. 2015;14(1):50. The role of gratitude in well-being in asymptomatic heart failure patients. Mills PJ, Wilson K, Punga MA, Chinh K, Pruitt C, Greenberg B, Lunde O, Wood A, Redwine L, Chopra D. 2015;14(1):51. Side effects Rauwolfia in the treatment of hypertension. Lobay D. 2015;14(3):40-46. Smith, Michael Michael Smith, MD: Treat the underlying causes of weight gain to facilitate successful weight loss; part 1. Gustafson C. 2015;14(3):60-61. Michael Smith, MD: Treat the underlying causes of weight gain to facilitate successful weight loss; part 3. Gustafson C. 2015;14(4):50-52. SOD See Superoxide dismutase Spelman, Kevin Kevin Spelman, PhD—Keeping it together: The other compounds in cannabis and the benefits of wholeherb use. Gustafson C. 2015;14(3):18-22. Spirituality Integrative treatment of pediatric obesity: Psychological and spiritual considerations. Boisvert JA, Harrell WA. 2015;14(1):40-47. The role of gratitude in well-being in asymptomatic heart failure patients. Mills PJ, Wilson K, Punga MA, Chinh K, Pruitt C, Greenberg B, Lunde O, Wood A, Redwine L, Chopra D. 2015;14(1):51. Stress Cannabidiol oil for decreasing addictive use of marijuana: A case report. Shannon S, Opila-Lehman J. 2015;14(6):31-35.

Integrative Medicine • Vol. 14, No. 6 • December 2015

Sudak, Nancy Nancy Sudak, MD: On unifying the voices of integrative practice. Gustafson C. 2015;14(2):54-58. Sudarshan kriya Breathing-based meditation decreases posttraumatic stress disorder symptoms in US military veterans: A randomized, controlled longitudinal study. Seppälä E, Narayanan P. 2015;14(1):50. Superoxide dismutase Nothing boring about boron. Pizzorno L. 2015;14(4):35-48. Supplement pyramid Michael Smith, MD: Treat the underlying causes of weight gain to facilitate successful weight loss; part 1. Gustafson C. 2015;14(3):60-61. Michael Smith, MD: Treat the underlying causes of weight gain to facilitate successful weight loss; part 3. Gustafson C. 2015;14(4):50-52. Supplements Gerald Krystal, PhD: The effects of protein and carbohydrates on cancer. Gustafson C. 2015;14(1):52-58. Synbiotics Part 2: Treatments for chronic gastrointestinal disease and gut dysbiosis. Bull MJ, Plummer NT. 2015;14(1):25-33. Systems medicine Kara N. Fitzgerald, ND: Case reports—Informing the practice of systems medicine. Gustafson C. 2015;14(6):36-39. T T3

See Triiodothyronine Tart cherry juice Tart cherry juice as a treatment for peripheral neuropathy. Carson CA. 2015;14(1):48-49. Tendon Evaluation of the effects of BioCell collagen, a novel cartilage extract, on connective tissue support and functional recovery from exercise. Lopez HL, Ziegenfuss TN, Park J. 2015;14(3):30-38. Testosterone Nothing boring about boron. Pizzorno L. 2015;14(4):35-48. Tetrahydrocannabinol Stuart Tomc, cannabinoid educator: Staying in step with the state of research. Gustafson C. 2015;14(2):18-21. Kevin Spelman, PhD—Keeping it together: The other compounds in cannabis and the benefits of wholeherb use. Gustafson C. 2015;14(3):18-22. Cannabidiol oil for decreasing addictive use of marijuana: A case report. Shannon S, Opila-Lehman J. 2015;14(6):31-35. Tetrahydro iso-α acids Nutritional approach for relief of joint discomfort: A 12-week, open-case series and illustrative case report. Lerman RH, Chang JL, Konda V, Desai A, Montalto M. 2015;14(5):52-61.

Subject Index

THC See Tetrahydrocannabinol THIAA See Tetrahydro iso-α acids Thyroid Denis Wilson, MD: Low body temperature as an indicator for poor expression of thyroid hormone. Gustafson C. 2015;14(3):24-28. Tiredness Cannabidiol oil for decreasing addictive use of marijuana: A case report. Shannon S, Opila-Lehman J. 2015;14(6):31-35. TNF-α See Tumor necrosis factor α Tomc, Stuart Stuart Tomc, cannabinoid educator: Staying in step with the state of research. Gustafson C. 2015;14(2):18-21. Toxic burden The Path Ahead—Conventional laboratory tests to assess toxin burden. Pizzorno J. 2015;14(5):8-16. Toxicity The Path Ahead—Is challenge testing valid for assessing body metal burden? Pizzorno J. 2015;14(4):8-14. Toxins The Path Ahead—Issue 75! Pizzorno J. 2015;14(2):8-13. The Path Ahead—Hard to be healthy in North America. Pizzorno J. 2015;14(3):8-13. The Path Ahead—Is challenge testing valid for assessing body metal burden? Pizzorno J. 2015;14(4):8-14. Andrew Campbell, MD: Mechanisms of the gut–brain axis. Gustafson C. 2015;14(4):20-21. Transitions BackTalk—A pirate looks at 60. Benda B. 2015;14(3):68. Trial design advice Research battles: Survival tips from a veteran. Isaacs LL. 2015;14(5):30-32. Triiodothyronine Denis Wilson, MD: Low body temperature as an indicator for poor expression of thyroid hormone. Gustafson C. 2015;14(3):24-28. Tumor necrosis factor α Nothing boring about boron. Pizzorno L. 2015;14(4):35-48. V Veterans Breathing-based meditation decreases posttraumatic stress disorder symptoms in US military veterans: A randomized, controlled longitudinal study. Seppälä E, Narayanan P. 2015;14(1):50. Veterans Health Administration Industry Insights—End of a (lucky) era for integrative health policy: Republican wins sweep key integrative leaders from powerful committee chairs. Weeks J. 2015;14(1):16-18. VHA See Veterans Health Administration Subject Index

Viewpoints Gerald Krystal, PhD: The effects of protein and carbohydrates on cancer. Gustafson C. 2015;14(1):52-58. Nancy Sudak, MD: On unifying the voices of integrative practice. Gustafson C. 2015;14(2):54-58. Michael Smith, MD: Treat the underlying causes of weight gain to facilitate successful weight loss; part 1. Gustafson C. 2015;14(3):60-61. Michael Smith, MD: Treat the underlying causes of weight gain to facilitate successful weight loss; part 3. Gustafson C. 2015;14(4):50-52. Mark Blumenthal: Quality and efficacy of herbal medicines. Gustafson C. 2015;14(4):54-59. Barbara Dossey, PhD, RN: Developing a healing approach in nursing. Gustafson C. 2015;14(5):72-77. Kara N. Fitzgerald, ND: Case reports—Informing the practice of systems medicine. Gustafson C. 2015;14(6):36-39. Vitamin D Nothing boring about boron. Pizzorno L. 2015;14(4):35-48. Vitamin K Proper calcium use: Vitamin K2 as a promoter of bone and cardiovascular health. Maresz K. 2015;14(1):34-39. Vitamin K2 Proper calcium use: Vitamin K2 as a promoter of bone and cardiovascular health. Maresz K. 2015;14(1):34-39. W Weight loss Michael Smith, MD: Treat the underlying causes of weight gain to facilitate successful weight loss; part 1. Gustafson C. 2015;14(3):60-61. Michael Smith, MD: Treat the underlying causes of weight gain to facilitate successful weight loss; part 3. Gustafson C. 2015;14(4):50-52. Weight management Michael Smith, MD: Treat the underlying causes of weight gain to facilitate successful weight loss; part 1. Gustafson C. 2015;14(3):60-61. Michael Smith, MD: Treat the underlying causes of weight gain to facilitate successful weight loss; part 3. Gustafson C. 2015;14(4):50-52. Wilson, Denis Denis Wilson, MD: Low body temperature as an indicator for poor expression of thyroid hormone. Gustafson C. 2015;14(3):24-28. Y Yoga Breathing-based meditation decreases posttraumatic stress disorder symptoms in US military veterans: A randomized, controlled longitudinal study. Seppälä E, Narayanan P. 2015;14(1):50.

Integrative Medicine • Vol. 14, No. 6 • December 2015

Z Zinc deficiency A taste-intensity visual analog scale: An improved zinc taste-test protocol. Zdilla MJ, Starkey LD, Saling JR. 2015;14(2):34-38. Zinc sulfate A taste-intensity visual analog scale: An improved zinc taste-test protocol. Zdilla MJ, Starkey LD, Saling JR. 2015;14(2):34-38.

Integrative Medicine â€˘ Vol. 14, No. 6 â€˘ December 2015

Subject Index

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CONFERENCE CALENDAR Labrix Advanced Workshop January 16-17, 2016—Platinum Hotel & Spa, Las Vegas, Nevada Labrix advanced training weekend offers an intimate and in-depth intensive on hormone balancing, the complex relationship between sex hormones, adrenal hormones and neurotransmitters, and the complicated symptom pictures that can result from these imbalances. This training is designed for the hormone-savvy practitioner, who is looking to elevate his or her practice through deeper understanding and additional clinical insight. Topics presented for discussion cover the gamut of clinical presentations and will be heavily case oriented. Also included are clinical pearls and pitfalls, gleaned from the decades of combined clinical experience of Labrix cofounders Jay Mead, MD, and Erin Lommen, ND, along with additional perspective offered from expert guest speakers and Labrix clinical staff. For more information, please visit https://www.labrix.com/law/. 13th Annual Natural Supplements: An Evidence-Based Update January 28-31, 2016—Paradise Point Resort, San Diego, California This interactive educational event is a must-attend for anyone wanting to acquire a wide-range of knowledge and expertise for addressing and managing dietary supplement use. Please visit http://www.scripps.org/NaturalSupplements for more information, Functional Medicine Advanced Practice Modules (APMs) February 4-6, 2016—Loews Atlanta Hotel, Atlanta, Georgia “Cardiometabolic—Transforming the Assessment, Prevention, and Management of Chronic Metabolic and Cardiovascular Disorders.” The module will help clinicians understand the physiology underlying cardiometabolic syndrome and cardiovascular disease, new approaches to effective assessments and treatments, and how to integrate these lifesaving tools into practice. For more information, please visit https://www.functionalmedicine.org/. IVC & Cancer Symposium February 5-6, 2016—La Concha Resort, San Juan, Puerto Rico The Riordan Clinic IVC Academy is packed with 2 days of lectures, conversations, and camaraderie with other medical professionals who use high-dose vitamin C in their practices. On Friday there will be multiple speakers laying out the history and steps behind the proper use of Riordan IVC protocols. The academy lectures will serve as an excellent opportunity for IVC practitioners to become more involved with IVC therapy and adjunct therapies, and they will expound new approaches to treating cancer. Lectures continue into Saturday and will conclude the event with the Riordan IVC Certification Test. For more information, please visit https//IVCandCancer.org/. Functional Medicine Advanced Practice Modules (APMs) February 7-9, 2016—Loews Atlanta Hotel, Atlanta, Georgia “Immune—The Many faces of Immune Dysregulation and Chronic Inflammation: Chronic Infections, Atopy, and Autoimmune Disorders.” This course will focus on chronic inflammation, systemic influences on the immune system, and the consequent dysfunction that may ensue. The Immune APM will supply you with an in-depth understanding of underlying

Conference Calendar

immune mechanisms and enable you to develop effective interventions even in the absence of a conventional. For more information, please visit https://www.functionalmedicine.org/. Integrative Healthcare Symposium February 25-27, 2016—New York Hilton Midtown, New York, New York Integrative Healthcare Symposium brings together multidisciplinary health care professionals dedicated to improving patient care and defining the future of integrative health care. Visit http://www.ihsymposium.com/annual-conference for more information. Environmental Health Symposium Annual Conference “The Elephant in the Waiting Room” March 4-6, 2016—Hilton Resort & Spa San Diego, California EHS is committed to properly educating health care providers in the diagnosis and treatment of environmentally induced illnesses. Learn more about the 126 environmental toxicants that have been found in virtually ALL US residents and how they are linked to acute and chronic disease. Learn about mold contamination and related illness that may affect up to 50% of the homes in the United States that have water damage. Equip yourself with the necessary tools to properly identify the patients that present to you with illness due to these compounds. Learn the clinical presentations of these toxins and toxicants from the experts in the field of environmental medicine. Attend EHS and join the growing community of health care providers committed to offering answers to the increasing number of patients with conditions related to environmental exposures. For more information, visit http://environmentalhealthsymposium.com or call (855) 347-4477. Environmental Health Symposium Mold Summit Friday Mach 4, 2016—Hilton Resort & Spa San Diego, California This 1-day intensive education for health care providers in moldrelated illness will focus on disease conditions related to mold exposure as well as cutting-edge therapies for mold-related illness. We will also have leaders in the field address the current standards of practice and science of remediation for molddamaged buildings. For more information, call (855) 347-4477 or visit http://environmentalhealthsymposium.com/. Applying Functional Medicine in Clinical Practice (AFMCP) March 14-18, 2016—JW Marriott Desert Ridge, Phoenix, Arizona AFMCP teaches health care practitioners to more effectively integrate science, research, and clinical insights to treat and prevent disease and maintain health. Established and emerging diagnostics, therapeutics, and prevention strategies are extensively covered. AFMCP integrates these approaches through the Functional Medicine Matrix Model (an innovative and practical assessment tool) and the emphasis on a therapeutic partnership between patient and practitioner. AFMCP is a well-orchestrated, comprehensive, patient-centered education program that helps you deepen your clinical understanding and practical application of the Functional Medicine Matrix Model. For more information, please visit https://www.functionalmedicine.org/.

Integrative Medicine • Vol. 14, No. 6 • December 2015

AAEM 2016 Spring Meeting March 31-April 3, 2016—Marriott Dallas/Ft Worth Airport Hotel, Dallas, Texas The emphasis of this meeting will be on equipping MDs, DOs, NDs, FNPs, and PAs to practice medicine for those with environmentally-induced illness, with practical, yet simple, suggestions to increase your success and greatly increase the number of patients who will be singing your praises. Come with an open mind. Join in the brainstorming and hear about some ideas you never considered from doctors who have applied some basic principles that work and seem to have been forgotten. Find some of the most creative doctors in medicine and let them share exactly how they have developed larger practices, incomes, and, more important, happier, healthier patients. For more information, please visit http://www.aaemconference.com/spring/. 1-day Bioidentical Hormone Replacement Therapy Seminar April 2, 2016—The Rancho Bernardo Inn, San Diego, California If you are looking to break into this exciting field of hormone therapy, or reinforce your knowledge and learn the latest in evidence-based bioidentical hormone replacement therapy, then this seminar is for you. Whatever your level of expertise in BIHRT, this event will immediately provide you usable clinical skills for your practice. For more information, please visit http://advancedmedacademy.com or call (888) 747-8247. Merging Medicine XVIII Conference—Naturopathic Primary Care Update April 9-10, 2016—Marina del Rey Marriott Hotel, Los Angeles, California Join the California Naturopathic Doctors Association for their Merging Medicine XVIII Conference. For more information, please visit https://www.calnd.org or call (310) 670-8100. 14th Annual IOICP Conference—Best Answers for Cancer April 11-16, 2016—Town & Country Resort, San Diego, California Join the International Integrative Oncology Conference for their 14th annual conference. Speakers and attendees collaborate to provide tools that can be implemented in clinics immediately. The conference will include 3 FULL days of presentations with more than 22 speakers. For more information, please visit http://www.bestanswerforcancer.org/. The Institute for Functional Medicine 2016 Annual Conference May 12-14, 2016—Grand Hyatt, San Diego, California Save the date for the Institute for Functional Medicine annual meeting and conference. For more information, please visit https://www.functionalmedicine.org/. International Research Congress Integrative Medicine and Health 2016 May 17-20, 2016—Green Valley Ranch, Las Vegas, Nevada Join the International Congress on Integrative Medicine and Health for its “Bridging Research, Clinical Care, Education, and Policy” conference. The Congress is convened by the Consortium of Academic Health Centers for Integrative Medicine, a group of 61 esteemed academic health centers and affiliated institutions. For more information, visit http://www.icimh.org/.

Integrative Medicine • Vol. 14, No. 6 • December 2015

3rd ICNM Congress on Naturopathy July 1-3, 2016—Barcelona, Spain The 3rd International Congress on Naturopathic Medicine is the premier International Congress for the most influential and inspiring naturopathic medicine practitioners and health care professionals who are dedicated to improving patient care. You have the opportunity to network with the finest naturopaths from more than 50 countries and update your knowledge and skills learning from more than 40 internationally recognized researchers and clinicians. For more information, visit http://www.icnmnaturopathy.eu/. Functional Medicine Advanced Practice Modules (APMs) July 15-17, 2016—Gaylord Hotel, National Harbor, Maryland “Hormone—Re-establishing Hormonal Balance in the Hypothalamic, Pituitary, Adrenal, Thyroid, and Gonadal Axis.” This Functional Medicine Advanced Practice Module will clarify exactly how to approach hormonal dysregulation, with discussions on the most important evaluations to make and integrative treatment approaches to apply. We will help you analyze the controversies and provide you with tools that you can use immediately in your practice. Our expert faculty team will supply you with the foundational background, insight, and in-depth clinical thinking to confidently assess and treat patients who present with hormonal dysfunction. This program will provide a unique, experiential, case-based, clinically practical experience from which you will acquire the tools you need to apply a comprehensive functional medicine approach to hormone dysfunction in your patients. For more information, please visit https://www.functionalmedicine.org/. Functional Medicine Advanced Practice Modules (APMs) July 15-17, 2016—Gaylord Hotel, National Harbor, Maryland “Energy—Illuminating the Energy Spectrum: Evidence and Emerging Clinical Solutions for Managing Pain, Fatigue, and Cognitive Dysfunction.” This Advanced Practice Module will investigate the science of mitochondrial function and dysfunction, the impact of oxidative stress, as well as nutritional and lifestyle influences on both health and disease. Clinicians will learn how to regenerate compromised mitochondrial function and how to address the varied underlying causes of fatigue, depression, headache, and neurodegenerative disorders such as Alzheimer’s and Parkinson’s diseases. Evidence-based modalities to address pain will be introduced, and the profound potential of the healing partnership will be both explored and experienced. For more information, please visit https://www.functionalmedicine.org/. 14th Annual International Restorative Medicine Conference September 16-18, 2016—Sonesta Resort, Hilton Head Island, South Carolina The 14th Annual International Restorative Medicine Conference is an extraordinary opportunity to hear expert speaker’s present emerging research and up-to-date protocols that empower you to effectively treat your patients. The annual conference consistently lives up to its reputation for providing innovative educational opportunities for practitioners. For more information, please visit http://restorativemedicine.org/aarm2016/.

Conference Calendar

Applying Functional Medicine in Clinical Practice (AFMCP) September 19-23, 2016—Marriott Baltimore Waterfront, Baltimore, Maryland AFMCP teaches health care practitioners to more effectively integrate science, research, and clinical insights to treat and prevent disease and maintain health. Established and emerging diagnostics, therapeutics, and prevention strategies are extensively covered. AFMCP integrates these approaches through the Functional Medicine Matrix Model (an innovative and practical assessment tool) and the emphasis on a therapeutic partnership between patient and practitioner. AFMCP is a well-orchestrated, comprehensive, patientcentered education program that helps you deepen your clinical understanding and practical application of the Functional Medicine Matrix Model. For more information, please visit https://www.functionalmedicine.org/. AAEM 2016 Annual Meeting October 6-9, 2016—Marriott San Diego La Jolla, La Jolla, California The goal of this conference is to present current data regarding mitochondria as a therapeutic target in many disease states. The information presented will better train primary care clinicians with the knowledge and skills needed to help prevent chronic disease in their patients, as well as identifying mitochondrial dysfunction and formulating a more comprehensive and effective approach to managing and even eliminating many modern complex chronic disease states. For more information, please visit http://aaemconference.com/fall/.

Functional Medicine Advanced Practice Modules (APMs) October 28-30, 2016—Hyatt Regency, Chicago, Illinois “Detox—Understanding Biotransformation and Recognizing Toxicity: Evaluation and Treatment in the Functional Medicine Model.” There is persuasive evidence that even low-level toxic exposures contribute to the development of a variety of chronic health conditions, including fatigue, endocrine disruption, and chronic degenerative diseases such as Parkinson’s. Given the ubiquitous nature of chemicals in the environment, it is likely that the single exposure model of toxicology is more the exception than the rule. It is therefore critical for clinicians to learn how to assess both exposures and total toxic load to appropriately assess and address each individual’s toxicological situation. Our expert faculty team will review the foundational biochemistry and genetics of biotransformation pathways, connect organ system dysfunctions to potential toxic exposures, and detail the available laboratory evaluations useful in working up a toxin-exposed patient. Once these important clinical connections are made, the team will detail specific treatment approaches. This program also uses a case-based, integrated approach to deliver effectively the tools necessary for clinicians to diagnose and treat the toxic component of their patients’ total health pictures. For more information, please visit https://www.functionalmedicine.org/.

IVC & Cancer Symposium October 13-15, 2016—Hotel at Old Town, Wichita, Kansas Biannually Riordan Clinic IVC Academy holds an IVC and Cancer Symposium in Wichita that offers doctors from around the world the opportunity to visit our facilities, learn more about high-dose IV vitamin C (IVC), listen to leading doctors in functional medicine, and learn how to use IVC in their offices. For more information, please visit https://riordanclinic.org/riordan-ivc-academy-symposium/. Functional Medicine Advanced Practice Modules (APMs) October 28-30, 2016—Hyatt Regency, Chicago, Illinois “GI—Restoring Gastrointestinal Equilibrium: Practical Applications for Understanding, Assessing, and Treating Gut Dysfunction.” This Advanced Practice Module takes a wholesystems approach to evaluating and treating not only local gastrointestinal disease, but many systemic diseases that are linked to GI dysfunction. This course will supply you with the foundational background, insight, and in-depth clinical thinking to confidently work up and treat patients who may present with conditions, signs, and symptoms indicative of gastrointestinal dysfunction. We will discuss in detail the important laboratory evaluations to be considered, the appropriate clinical connections that must be made, and the treatment approaches that should be used. For more information, please visit https://www.functionalmedicine.org/.

Integrative Medicine • Vol. 14, No. 6 • December 2015

Conference Calendar

Job Listings

Family & Integrative Medicine—Full-time Core Faculty Position in Lewiston, Maine: Practice, teach, and live in the beautiful state of Maine. Central Maine Medical Center Family Medicine Residency is looking for a full-time, board-certified family physician to join its dynamic team and fill a faculty position specializing in integrative medicine. Applicants must be interested in a community-based practice serving a rural and underserved population, as well as enthusiastic about teaching integrative and family medicine to residents and students. Clinical setting includes busy outpatient community clinic adjacent to a large trauma hospital; many procedures; and community involvement. Outpatient required; inpatient and maternity care preferred, but not required (dedicated OB on site). Integrative medicine fellowship training or equivalent experience a plus. • • • • • • •

Dynamic 7-7-7 residency program with rural track Dually accredited Wilderness Medicine Selective Integrative Medicine Curriculum Osteopathic Manipulative Medicine Strong institutional support Hospital Medicine and Sports Medicine Fellowships

Competitive salary and highly qualified, friendly colleagues. Please forward your CV to Julia Lauver, Central Maine Medical Center Physician Recruitment, 300 Main Street, Lewiston, ME, 04240; call (800) 445-7431; fax (207) 755-5854; or e-mail LauverJu@cmhc.org. Not a J1 opportunity. Complementary and Integrative Medicine Medical Director—Austin, Texas: Seton Healthcare Family is seeking a board-certified family medicine or internal medicine physician, trained in complementary and integrative medicine to provide medical leadership and clinical services for a new integrative and complementary medicine center. Candidate should be a highly skilled physician, preferably in primary care, who seeks to incorporate a holistic, patient-centered team approach. The medical director for integrative medicine reports to the CEO/president of the clinical enterprise and is responsible for overseeing clinical standards, program growth and development, trainee exposure and education, research projects, quality of care, service excellence to patients, and professionalism by all staff and trainees as well as institutional goals set by the standards and mission of the Seton Healthcare Family. Seton Healthcare Family is the leading provider of healthcare services in Central Texas, serving an 11-county population of 1.9 million. The organization operates 5 major medical centers, including the region's only Level I Trauma Centers for adult and pediatrics and dedicated children's hospital, 2 community hospitals, 3 rural hospitals, an inpatient mental health hospital, and 3 primary care clinics for the uninsured. The Seton Healthcare Family is an Equal Opportunity/Affirmative Action/Equal Access Employer. Hiring is contingent upon obtaining medical licensure in the state of Texas. Interested applicants should submit a letter of interest and curriculum vitae to Carrie Schumacher/Physician Recruitment at CSchumacher@seton.org

Conference Calendar

Integrative Medicine • Vol. 14, No. 6 • December 2015

BACKTALK

Confessions of a Narcissist Bill Benda, MD, Associate Editor

had an interesting online conversation with my old friend, Bill Manahan, a few weeks ago. For those of you in Siberia who may not have heard of him, Bill has been as instrumental as any human in the birth and nurturing of the integrative movement, in a founding father sort of way. The thing is, you will not see his name and picture touting a latest book or new line of supplements, (although “Bill’s Botanicals” has a nice ring to it), because Dr Manahan is perhaps the least ego-driven individual within our field. In fact, in my experience, he has never uttered a negative word about anyone, a nice counterpoint to this bimonthly column. Anyway, during our “talk,” he asked a question that has been sticking in my mind ever since: “Are the holistic doctors and others becoming as self-centered as those in the regular medical system?” After pondering this query for the past couple of months, my conclusion is “no,” we aren’t becoming like our allopathic brethren from an ego standpoint—because we are and have always been as ego driven as anyone out there. For goodness’ sake, we all came up through one or another orthodox system, having gone through education and training in some standardized way. And we all choose how we practice based on the needs of our individualized egos. I am a perfect case in point. I wish I could say I left my Big Sur home in 1998 for the University of Arizona’s Program in Integrative Medicine for altruistic reasons, but the fact is I did it for me—to escape the pummeling of the emergency room, to learn something new besides the latest drug profile or ACLS standards, and to see my name in print (1 of 3 isn’t bad). I believe we all make such decisions for ourselves first and not for any lofty aspiration, such as saving the world. We do it to save ourselves. Which is as it should be. We cannot help anyone else, really, unless we are healthy from an ego perspective. Physician, first heal thyself, and then love thy neighbor. But Dr Manahan’s question was more about narcissism than simple human nature, and I will confess that while in Arizona, I became caught up in that particular whirlpool for a number of years, given the country’s sudden interest in Andy Weil’s new endeavor, until reality brought me down to Earth, hard. And on my way up, and back down,

Integrative Medicine • Vol. 14, No. 6 • December 2015

I saw many like myself, wide-eyed narcissi at book signings and television interviews surrendering to the sweet lure of self-importance. It is human nature, and we all succumb from time to time. The problem arises when such internal beliefs become external ideology. We have seen this happen within various religions throughout history (think crusades and inquisitions), and I see health care and its representative professions in the same light. You see, from a gestalt perspective, health care and spirituality have kindred goals—Jesus, Muhammad, the Buddha (who weren't Christian, Muslim, or Buddhist, by the way), and all prophets have instructed us that caring for our fellow human, specifically those unable to care for themselves, is our prime devotional duty. It is only when man-made religions, and health care professions, claim themselves “The One True” that trouble arises. It simply is not within the human condition to understand either a perfect God or a perfect way to care for another. But imperfect and limited as we may be, we must still choose some foundational principles from which to practice. Some choose pharmaceuticals and surgery. Some choose botanicals and nutrition. Some needles and homeopathic remedies. And it is in this choice that narcissism often finds fertile ground, and as we begin to believe our particular way superior, we begin to denigrate other paths. My conventional profession has done it to others throughout the 20th century, which in turn have been taking their revenge. As a matter of fact, MD bashing would be a prime event in the Integrative Olympics. Which brings me back to myself (narcissist that I am), and Dr Manahan’s question. I wandered into integrative medicine because I was seeking a new doctrine from which to practice, one that would fulfill the needs of my patients but especially my own. And, yes, I did for a time get lost in the belief that I was an important part of a new ideology, until the aforementioned reality stepped in. And I learned that the real danger of ego is not falling in love with our face on a magazine cover, or convention brochure, or pool of water, but in the belief that our way is the best way. Because it’s not. Benda—BackTalk

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