Alternative Therapies in Health and Medicine

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A PEER-REVIEWED JOURNAL • NOVEMBER/DECEMBER 2015 • VOL. 21, NO. 6 • $14.95 The Integrative Health and Wellness Program: Development and Use of a Complementary and Alternative Medicine Clinic for Veterans • Improvement in Vision Parameters for Participants Treated With Alternative Therapies in a 3-day Program • Brain-derived Neurotrophic Factor Signaling Pathway: Modulation by Acupuncture in Telomerase Knockout Mice • Compound Formulas of Traditional Chinese Medicine for the Common Cold: Systematic Review of Randomized, Placebo-controlled Trials • Editorial—Inflammation: The Root of Our Chronic Diseases • 2015 Author and Subject Indices

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NOVEMBER/DECEMBER 2015, VOL. 21, NO. 6

TABLE OF CONTENTS

EDITORIAL 8

Inflammation: The Root of Our Chronic Diseases Andrew W. Campbell, MD

Original Research 12

The Integrative Health and Wellness Program: Development and Use of a Complementary and Alternative Medicine Clinic for Veterans Amanda Hull, PhD; Stephanie Brooks Holliday, PhD; Christine Eickhoff, MS; Melane Rose-Boyce, MSW; Patrick Sullivan, MS; Matthew Reinhard, PsyD

22

Improvement in Vision Parameters for Participants Treated With Alternative Therapies in a 3-day Program Edward C. Kondrot, MD, MD(H), CCH, DHt

36

Brain-derived Neurotrophic Factor Signaling Pathway: Modulation by Acupuncture in Telomerase Knockout Mice Dong Lin, MD, PhD; Qiang Wu, MD; Xiaoyang Lin, MS; Cesar V. Borlongan, PhD; Zhi-Xu He, MD; Jun Tan, PhD; Chuanhai Cao, PhD; Shu-Feng Zhou, MD, PhD

review article 48

Compound Formulas of Traditional Chinese Medicine for the Common Cold: Systematic Review of Randomized, Placebo-controlled Trials Guanhong Li, MD; Linli Cai, MS; Hongli Jiang, MD; Shoujin Dong, MD; Tao Fan, MD; Wei Liu, MD; Li Xie, MD; Bing Mao, MS

departments

x Table of Contents

10

Patient Handout: Inflammation

58

Author Index

62

Subject Index

74

Conference Calendar

ALTERNATIVE THERAPIES, NOV/DEC 2015 VOL. 21 NO. 6 3

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editor in chief Andrew W. Campbell, MD CONTRIBUTING EDITORS

Michael Balick, PhD • Mark Hyman, MD • Jeffrey Bland, PhD, FACN, FACB • Roberta Lee, MD • Tieraona Low Dog, MD Editorial Board Sidney MacDonald Baker, MD ◆ Autism Research Institute

Rollin McCraty, PhD ◆ Institute of HeartMath

Brent A. Bauer, MD ◆ Mayo Clinic

Pamela Miles, Reiki Master ◆ New York, NY

Mark Blumenthal ◆ American Botanical Council

Daniel A. Monti, MD ◆ Thomas Jefferson University

Kelly Brogan, MD, ABIHM ◆ George Washington University

Gerard Mullin, MD ◆ Johns Hopkins University

Ian Coulter, PhD ◆ RAND/Samueli Chair in Integrative Medicine

John Neely, MD ◆ Pennsylvania State University

Jeffrey Dach, MD ◆ TrueMedMD, Davie, Florida

Paula J. Nenn, MD, ABIHM ◆ Optimal Health and Prevention Research Foundation Garth L. Nicolson, PhD ◆ The Institute for Molecular Medicine

James Dillard, MD, DC, LAc ◆ Integrative Pain Medicine Gloria F. Donnelly, PhD, RN, FAAN ◆ Drexel University

Joel S. Edman, DSc, FACN, CNS ◆ Thomas Jefferson University

Xie Ning, PhD ◆ Heilongjiang University of Traditional Chinese Medicine Thomas O’Bryan, DC, CCN, DACBN ◆ Institute for Functional Medicine, National Univ. of Health Sciences Dean Ornish, MD ◆ Preventive Medicine Research Institute

Karen Erickson, DC ◆ New York Chiropractic College

Nicole Pietschmann, PhD ◆ Cell Science Systems GmbH–Alcat Europe

Andrea Girman, MD, MPH ◆ Genova Diagnostics

Joseph E. Pizzorno, ND ◆ Seattle, WA

Ajay Goel, PhD ◆ Baylor Research Institute Garry F. Gordon, MD, DO ◆ Gordon Research Institute

Lawrence A. Plumlee, MD ◆ Chemical Sensitivity Disorders Association William J. Rea, MD ◆ Environmental Health Center – Dallas

Yuxin He, LAc, PhD ◆ Academy of Oriental Medicine at Austin

Sandeep Saluja, MD ◆ Saran Ashram Hospital, Dayalbagh

Elise Hewitt, DC ◆ Portland, OR

Eric R. Secor Jr, PhD, ND, MPH, MS, LAc ◆ Helen & Harry Gray Cancer Center, Hartford Hospital Stephen T. Sinatra, MD, FACC, FACN, CNS ◆ University of Connecticut School of Medicine Martha Stark, MD ◆ Harvard Medical School, Massachusetts Mental Health Center Alex Vasquez, DC, ND, DO ◆ University of Texas

Jeanne Drisko, MD ◆ University of Kansas

Alfred Johnson, DO ◆ Johnson Medical Associates Ellen Kamhi, PhD, RN, AHG, AHN-BC ◆ Stony Brook University Anup Kanodia, MD, MPH ◆ Ohio State University

Datis Kharrazian, DC, DHSc, MS, MNeuroSci ◆ Bastyr University of Aristo Vojdani, PhD, MSc, CLS ◆ Immunosciences Lab, Inc California; Institute for Functional Medicine Günver Kienle, DrMed ◆ Institute for Applied Epistemology Roeland van Wijk, PhD ◆ International Institute of Biophysics Lori, Knutson, RN, BSN, HN-BC ◆ Allina Hospitals & Clinics James B. Lago, EMT, DDS, BA ◆ Chicago Dental Health Erqiang Li, PhD ◆ East West College of Natural Medicine Susan Luck, MS, RN ◆ University of Miami Cuauhtemoc Hernandez Maya, MD ◆ Tao Healing Arts Center

James M. Whedon, DC, MS ◆ Southern California University of Health Sciences Shi Xian, MD, PhD ◆ General Hospital of the Chinese People’s Liberation Army Arthur Yin Fan, CMD, PhD, LAc ◆ McLean Center for Complementary and Alternative Medicine Qinhong Zhang, MD, PhD ◆ Stanford University Shun Zhongren, PhD ◆ Heilongjiang University of Traditional Chinese Medicine

Managing Editor, CRAIG GUSTAFSON • Creative Director, RANDY PALMER • Associate Editor, MICHAEL MILLER Editorial Assistant, CARALIN WALSH • Science Editor, PEGGY WRIGHT • E-mail: ATHM@innovisionhm.com Web: http://www.alternative-therapies.com

6 ALTERNATIVE THERAPIES, NOV/DEC 2015 VOL. 21 NO. 6

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EDITORIAL

Inflammation: The Root of Our Chronic Diseases

I

t takes time—sometimes decades, sometimes hundreds of years—for our bodies to adapt to a new environment.

In the past 60 or so years, we have added tens of thousands of new environmental factors, including chemicals, human-made substances, foods, liquids, and others. The onslaught defies the possibility of adaptation.

For example, the 80 000 chemicals that are used commercially throughout the United States were discovered within the last several decades; they did not exist before. The US Environmental Protection Agency (EPA) estimates that emissions from industrial plants and facilities will easily reach 2.5 billion pounds annually, making it very likely that every person in this country is exposed. The Integrated Information System of the EPA is the where all data are kept regarding toxicities reached by scientific consensus.

However, the list is woefully short—only 550 chemicals. One can only wonder why the other 79 450 chemicals are not currently on this list—an indication of the very serious gap in the knowledge necessary for calculation and evaluation of risks associated with exposures to these chemicals. Yet even the few chemicals included by the EPA are mainly occupationally oriented.1 Our immune system is responsible for protecting us from this environment, attacking all pathogens and xenobiotics, while ignoring all the cells of our own bodies—all 100 trillion of them. This is done in a highly complex and choreographed manner. However, the incessant daily onslaught of stress, of environmental factors in the air we breathe, in the foods and beverages we consume, and in what is absorbed by the 3 trillion pores on the average human body has brought us to the edge of the immune system’s capacity. As a result, we now have to contend with many more chronic diseases than ever before. The root cause of these new scourges of humankind is inflammation: chronic, often silent, but persistent. When inflammation continues in a low-grade state, it is a known factor in numerous age-related chronic conditions and causes a wide range of chronic health problems, including metabolic syndrome (MetS), type 2 diabetes, nonalcoholic fatty liver disease (NAFLD), cancer, cardiovascular disease (CVD), and others.

8 ALTERNATIVE THERAPIES, NOV/DEC 2015 VOL. 21 NO. 6

The immune system is essentially divided into 2 parts: the innate immune system with which we are born, and the adaptive immune system—also known as the antibody mediated immune system—that we develop. Put in a very simple manner, the cells of the innate system are the first to go into action and respond to pathogens, whereas the adaptive immune system confers long-lasting protective immunity. Inflammation is one of the main elements of the innate immune system and is triggered as a local response to cellular injury: It is led by neutrophils.

Neutrophils are the most common type of leukocytes and are highly motile, allowing them to quickly congregate at the site of injury or infection. Following this we have the release of chemicals, bradykinin, leukotrienes, prostaglandins, and others, which sensitize pain receptors and attract more neutrophils. The average person produces 100 billion neutrophils per day, with the bone marrow keeping mature neutrophils in reserve in case of an infection. If it occurs, 10 times more neutrophils will be released into the circulation. These neutrophils have 3 methods by which they attack microorganisms and other substances: phagocytosis, degranulation with the release of reactive oxygen species—also known as a respiratory burst—and the production of neutrophil extracellular traps (NETs). Under a microscope, these look like a spider web or a net, trapping pathogens in them. This inflammatory response is well known and is characterized by increased blood flow, capillary dilatation, leukocyte infiltration, and the production of chemical mediators, which initiate the elimination of toxic agents and start the repair process of damaged tissues.2 The resolution of inflammation is an active process with cytokines and other anti-inflammatory mediators; it is not only a switch that turns off proinflammatory pathways. It involves cytokines and other chemical mediators.3,4 Inflammation can be either a friend or a foe: It is an essential part of our innate immune response, or it can be a chronic low-grade inflammatory condition. This latter part is what is at the root cause of type 2 diabetes mellitus, CVDs, MetS, NAFLD, and others.5,6 Campbell—Inflammation

We have known for more than 20 years that inflammation plays an important role in the pathophysiology of CVD. When arteries are damaged, inflammation is triggered and leukocytes infiltrate the area and release inflammatory mediators. Cytokines and chemokines promulgate atherosclerosis by formation of lipid-laden foam cell formation; they initiate the proliferation of smooth muscle cells; they increase the formation of chemokines, which stimulate further leukocyte mobilization; and they stimulate plaque instability and potential rupture.7 NAFLD is the most common liver disease in Western countries, and inflammation plays a direct role in its development. The National Health and Nutrition Examination Survey (NHANES) recently showed a 30% prevalence of NAFLD in the United States between 2011 and 2012. NAFLD is associated with insulin resistance, diabetes, obesity, dyslipidemia, and MetS. A study in the World Journal of Gastroenterology showed a link between NAFLD and soft drink consumption, mainly due to the artificial sweeteners used in these beverages. This disease ranges from benign steatosis to cirrhosis. In a simplified way, NAFLD starts with increased levels of fatty acids in hepatocytes with triacylglycerol (TAG) synthesis and decreased fatty acid oxidation. This results in a pro-oxidative and proinflammatory condition, which if unabated can result in fibrosis and cirrhosis. Hepatic inflammation is mediated by Kupffer cells, the local leukocytes.8-10 At a recent conference titled “The Gut–Brain Relationship Conference” sponsored by InnoVision Professional Media, a number of outstanding speakers discussed the latest findings of how the microbiota plays an essential role in our health, including the intimate and essential connection with our central nervous system (CNS). One aspect of the microbiota is the effect on the immune system and keeping gut permeability intact. Lipopolysaccharides are found on the outer membrane of Gram-negative bacteria and are an important inflammatory stimulant in the gut. However, in the elderly, there are more Gram-negative bacteria in the colon, thereby giving rise to increased gut permeability due to inflammation. Inflammation in the gut leads to a leaky gut, which then affects the CNS. The inflammatory response in our brain includes fever and behavioral and metabolic changes, which include fatigue, depression, problems with cognitive function, and others. The principal players are the microglia, the macrophages of the CNS, which induce interleukin (IL) 1β, tumor necrosis factor α, and PGE2, all proinflammatory mediators.11 In a recent prospective clinical study, patients with Alzheimer’s disease were followed for 6 months. They were tested for circulating cytokine levels, episodes of microbial infections, and cognitive function.

These patients had elevated levels of TNF-α at baseline: Any microbial infection showed a 4-fold decline in cognitive function. Alzheimer’s disease patients also demonstrate apathy, agitation, anxiety and depression, along with elevated serum levels of TNF-α and IL-6, but, interesting, not C-reactive protein.12,13 Campbell—Inflammation

Gut microbiota play an important role in autoimmunity, including type 1 diabetes mellitus, celiac disease, rheumatoid arthritis, and others. The incidence of autoimmune disorders has risen dramatically in the last several decades and affects 5% to 10% of the population. When a condition of gut permeability exists, antigens may be produced that mimic normal human proteins and trigger the abnormal production of autoantibodies.12 Our bodies were not made for this daily onslaught of toxins, infectious agents, and stress. These kinds of demands require much support to maintain the immune system’s resilience. Our rapid, go-go, stressful lifestyle has shown what happens if we do not pay attention to what is in our environment: chronic inflammation leading to chronic diseases. All of us need to pay attention to what we breathe, eat, drink and absorb, and feel. If we do not, and if we do not help our patients do the same, for most of us the factors are skewed toward inflammation.

Andrew W. Campbell, MD Editor in Chief REFERENCES 1. Environmental Protection Agency. http://www.epa.gov. Accessed November 5, 2015.

2. Calder PC, Ahluwalia N, Albers R, et al. A consideration of biomarkers to be used for evaluation of inflammation in human nutritional studies. Br J Nutr.

2013;109(Suppl 1):S1-S34.

3. Ortega-Gomez A, Perretti M, Soehnlein O. Resolution of inflammation: An integrated view. EMBO Mol Med. 2013;5(5):661-674.

4. Serhan CN, Chiang N, Dyke TEV. Resolving inflammation: Dual antiinflammatory and pro-resolution lipid mediators. Nat Rev Immunol.

2008;8(5):349-361.

5. Hotamisligil GS. Inflammation and metabolic disorders. Nature.

2006;444:860-867.

6. Libby P. Inflammation in atherosclerosis. Nature. 2002;420:868-874.

7. Minihane AM, Vinoy S, Russell WR, et al. Low-grade inflammation, diet composition and health: Current research evidence and its translation. Brit J Nutr. 2015;114(7):999-1012.

8. Rinella ME. Nonalcoholic fatty liver disease: A systematic review. JAMA. 2015;313(22):2263-2273.

9. Ruhl CE, Everhart JE. Fatty liver indices in the multiethnic United States National Health and Nutrition Examination Survey. Aliment Pharmacol Therapeut. 2015;41(1):65-76.

10. Nseir W, Nassar F, Assy N. Soft drinks consumption and nonalcoholic fatty liver disease. World J Gastroent. 2010;16(21):2579-2588.

11. Dantzer R, Kelley KW. Twenty years of research on cytokine-induced sickness behavior. Brain Behav Immun. 2007;21(2):153-160.

12. Hennessy AA, Barrett E, Ross RP, et al. The production of conjugated alphalinolenic, gamma-linolenic and stearidonic acids by strains of bifidobacteria and propionibacteria. Lipids. 2012;47(3):313-327.

13. Holmes C, Cunningham C, Zotova E, et al. Proinflammatory cytokines, sickness behavior, and Alzheimer disease. Neurology 2011;77(3):212-218.

14. Campbell AW. Autoimmunity and the gut. Autoimmune Dis. 2014;2014:152428.

ALTERNATIVE THERAPIES, NOV/DEC 2015 VOL. 21 NO. 6 9

Patient Handout: Inflammation

Why is inflammation so important? How does it affect me?

Inflammation is your body’s response to invasions: bacteria, viruses, foreign substances, chemicals, and others. It is a normal immune response. But when you are frequently exposed to large amounts of foreign materials—for example, chemicals and other synthetic substances—low-grade inflammation can become chronic.

What are the symptoms of inflammation?

The classic symptoms of inflammation are redness, swelling, and pain. For example, if you get a splinter in your finger, you will have all these symptoms—plus, you will not want to use your finger because of pain. Once you take away the splinter, or the cause of inflammation, everything returns to normal. When you are regularly exposed to chemicals and other foreign substances, you develop low-grade chronic inflammation.

Where do these chemicals come from?

A large quantity of these chemicals is consumed in food. Pesticides, preservatives, artificial colorings and flavorings, artificial sweeteners, and plastic containers made with bisphenol A (BPA) are only some of the pollutants and additives that we consume. These can cause inflammation that, in turn, can trigger what is known as “leaky gut syndrome.” We also have 3 trillion pores on our bodies that can absorb chemicals in the air: small particulate matter from diesel engines, chemicals from deodorizers, formaldehyde from synthetic carpeting, or a variety of airborne sprays used in the home or workplace. We also take these into our lungs with every breath.

What are the dangers of chronic low-grade inflammation?

Chronic low-grade inflammation is known to cause diabetes; cardiovascular diseases, such as stroke and heart attacks; metabolic syndrome; liver disease; cancer; and others.

What can I do to avoid chronic low-grade inflammation?

You can start by following the Mediterranean diet and eating whole foods. Artificial scents, although pleasant, are made with chemicals; natural materials are better than synthetic ones. Eat organically as much as possible, drink from glass containers, use organic cleaning materials, avoid areas with heavy truck traffic, and take walks in state or federal natural parks, as pesticides are not used on those lands.

Your integrative doctor can best help you and give you personalized advice on what is the best course for you to follow.

10 ALTERNATIVE THERAPIES, NOV/DEC 2015 VOL. 21 NO. 6

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ORIGINAL RESEARCH

The Integrative Health and Wellness Program: Development and Use of a Complementary and Alternative Medicine Clinic for Veterans Amanda Hull, PhD; Stephanie Brooks Holliday, PhD; Christine Eickhoff, MS; Melane Rose-Boyce, MSW; Patrick Sullivan, MS; Matthew Reinhard, PsyD

ABSTRACT Context • A movement exists within the Veterans Health Administration (VHA) toward incorporating complementary and alternative medicine (CAM) as an integrative complement to care for veterans. The Integrative Health and Wellness (IHW) Program is a comprehensive CAM clinic offering services such as integrative restoration (iRest) yoga nidra, individual acupuncture, group auricular acupuncture, chair yoga, qigong, and integrative health education.

Objectives • The current study intended to detail the development of the CAM program, its use, and the characteristics of the program’s participants.

Design • Using a prospective cohort design, this pilot study tracked service use and aspects of physical and mental health for veterans enrolled in the program.

Participants • During the first year, the IHW Program received 740 consults from hospital clinics; 325 veterans enrolled in the program; and 226 veterans consented to participate in the pilot study.

Amanda Hull, PhD, is the Integrative Health and Wellness Program director and acting director of patient-centered care; Stephanie Brooks Holliday, PhD, is a postdoctoral fellow; Christine Eickhoff, MS, is a program support assistant; Melane Rose-Boyce, MSW, is a Wellness Specialist.

Patrick Sullivan, MS, is a program specialist; and Matthew Reinhard, PsyD, is the director. All are located at the War Related Illness and Injury Study Center at the Washington DC VA Medical Center.

Corresponding author: Amanda Hull, PhD E-mail address: amanda.hull2@va.gov

12 ALTERNATIVE THERAPIES, NOV/DEC 2015 VOL. 21 NO. 6

Outcome Measures • Outcome measures included data from self-report questionnaires and electronic medical records.

Results • Veterans enrolled in the program reported clinically significant depression, stress, insomnia, and painrelated interference in daily activities and deficits in healthrelated quality of life. Regarding use of the program services, individual acupuncture showed the greatest participation by veterans, followed by group auricular acupuncture and iRest yoga nidra. Of the 226 veterans who enrolled in the program and consented to participate in this study, 165 (73.01%) participated in >1 services in the first year of programming. Broadly speaking, enrollment in services appeared to be associated with gender and service branch but not with age or symptom severity.

Conclusions • Results have assisted with a strategic planning process for the IHW Program and have implications for expansion of CAM services within the VHA. (Altern Ther Health Med. 2015;21(6):12-21.)

M

ental health disorders, chronic disease, and chronic multisymptom illness (CMI) are unfortunately too common among veterans.1-6 Research has shown that veterans have a high rate of complex symptomatology involving physical, cognitive, psychological, and behavioral disturbances, including pain patterns that are difficult to diagnose, irritable bowel syndrome, chronic fatigue, anxiety, depression, sleep disturbances, and neurocognitive dysfunction.7-13 Standard medical models often target isolated disease states, such as infection, headaches, or insomnia, and at times they may miss the more complex, multisystem dysfunction that has been documented in the veteran population. In contrast, complementary and alternative medicine (CAM) interventions are often broad spectrum treatments designed to target multiple biological systems simultaneously and, thus, may be well suited for complex chronic illnesses, particularly when compared with traditional medical models.

Hull—IHW Program for Veterans

The emerging literature indicates that CAM approaches, such as meditation and acupuncture, augment standard medical treatments to enhance positive outcomes for patients with chronic disease, mental health disorders, and CMI.14-18 In fact, recent research has provided preliminary support for the effectiveness of acupuncture in treating veterans with chronic pain,19-21 posttraumatic stress disorder (PTSD),22 and substance abuse.23 In addition, initial research has shown promise for the use of yoga and meditation-based interventions in treating veterans with chronic pain24-25 and mental health disorders, including PTSD, anxiety, and depression.26-31 A 2011 survey conducted by the Healthcare Analysis and Information Group indicated that 125 of the Veterans Health Administration (VHA) facilities (82%) have provided CAM services and/or have referred patients to CAM service providers. Of those, 80% cited patient preference as the reason for offering CAM modalities, suggesting that interest has increased in incorporating CAM modalities as a complement to care within the VHA.32 In addition, the VHA Office of Patient Centered Care and Cultural Transformation has been leading an initiative to promote an integrative, personalized, and patient-driven approach to veteran health care and as part of that new approach, it has been particularly supportive of CAM services for veterans.

The War Related Illness and Injury Study Center in Washington, DC (WRIISC-DC) has been a leader in the integrative and patient-centered care movement within the VHA and has provided CAM modalities, including acupuncture and integrative restoration (iRest) yoga nidra, to veterans since 2007. Preliminary data from program evaluation have indicated that the vast majority of veterans who received acupuncture and yoga nidra were satisfied with care quality, noticed symptom improvement, and would recommend acupuncture and yoga nidra to other veterans.33 These data support the acceptability of CAM interventions for veterans at the Washington DC VA Medical Center (DCVAMC) and afford preliminary evidence for the feasibility of providing CAM services for symptom improvement among veterans.33 The initial data from program evaluation were a catalyst for the development of the WRIISC-DC Integrative Health and Wellness (IHW) Program. Initiated August 1, 2012, the IHW Program was designed and implemented to provide multiple CAM modalities to veterans in a comprehensive clinic setting. Treatment modalities offered in the IHW Program include iRest yoga nidra, individual acupuncture, group auricular acupuncture, chair yoga, qigong, and an integrative health education group. The program serves veterans hospital wide and receives ongoing referrals, without solicitation, from multiple services. Providers across the hospital can refer any veteran, including a veteran of any age, war era, or diagnosis, who is interested in integrative health services through the IHW Program. After a request for a consult (referral) is placed in the veteran’s electronic medical record, the veteran is contacted to schedule an appointment for an Hull—IHW Program for Veterans

orientation session. During this group orientation session, the group’s facilitator provides an overview of the program’s services, and the veteran is given a class schedule. After attending orientation, the veteran can use the majority of IHW services on a first-come, first-serve, drop-in basis. For the handful of groups that are time limited, the veteran must express an interest during orientation and then is subsequently called when the next group starts. During the first year, more than 700 consults occurred to the IHW Program from hospital clinics; 325 veterans enrolled in the program, and 226 veterans (69.5%) consented to participate in the pilot study that would assess patients’ outcomes.

STRUCTURE AND SERVICES Consult Service The IHW Program is a consult service at the DCVAMC, meaning—as indicated earlier—that a Veterans Affairs (VA) provider must place a consult in the electronic medical records (CPRS) for the veteran to participate.

Orientation Session All veterans are required to attend a 1-hour orientation session for the IHW Program. The orientation is offered once per week and provides in-depth information about the IHW Program to referred veterans. The first 30 minutes is dedicated to veteran education regarding the IHW Program services, including iRest yoga nidra, gentle yoga, individual acupuncture, group auricular acupuncture, qigong, and the integrative health education group. During the second half of the session, the research portion of the IHW Program and the informed consent process are reviewed, and veterans complete clinical questionnaires.

IHW Program Services As noted, during the first year of implementation, the IHW Program offered 6 primary services: iRest yoga nidra, individual and group auricular acupuncture, integrative health education, qigong, and gentle yoga. The program developed organically, in response to patients’ demands, providers’ specialties, and the evidence base for these services.

Integrative health services were first offered in 2007, when interested providers initiated the provision of group and individual acupuncture as well as iRest yoga nidra. As demand for the services continued to grow, the IHW Program was established in 2012 to provide integrative health services in a cohesive clinic setting. In addition, in response to a need expressed by providers in the hospital, the integrative health education group was added at the inception of the IHW Program. More recently, chair yoga and qigong were added in response to patients’ requests and providers’ interests. The evidence base for these services was also an important consideration, described in further detail later. iRest Yoga Nidra This type of yoga nidra is a form of guided mindfulness meditation that induces deep relaxation through a multifaceted approach that includes breathing, body sensing, guided imagery, ALTERNATIVE THERAPIES, NOV/DEC 2015 VOL. 21 NO. 6 13

and progressive relaxation techniques. As reported in various meta-analytic and systematic reviews, mindfulness-based approaches can lead to improvements in multiple physical and mental health problems simultaneously.16-17,34-36 Recent studies have suggested that the techniques (1) may improve chronic pain, fibromyalgia, and fatigue37-39; (2) reduce symptoms of depression,40-41 anxiety,42-43 PTSD,45-46 and substance abuse14, 47; (3) enhance one’s ability to cope with physical health problems17,48-49; and (4) improve self-reported quality of life.50 Several benefits exist for these interventions; they are low-cost and sustainable,43 do not have the side effects of traditional medical treatments, and can have lasting beneficial effects on participants.38,40,50 The flexibility and low risk for harm of these practices also make it possible to offer this intervention to people with a variety of needs and vulnerabilities.

Acupuncture Acupuncture originated in China more than 2500 years ago and is one of the oldest, most frequently used medical procedures in the world.51 Acupuncturists employ very fine gauge, sterile, stainless steel needles, which are placed at defined anatomical points beneath the skin’s surface, which are chosen to restore balance and regulation in the energetic systems of the body.52 The National Institutes of Health (NIH) advisory board reviewed the acupuncture literature in 1997 and issued a consensus statement concluding that acupuncture demonstrated promising results as an adjunct therapy for many chronic health symptoms.53 A growing body of research has shown that acupuncture can improve many physical and mental symptoms including nausea, headaches, musculoskeletal pain, fibromyalgia, insomnia, depression, PTSD, and addiction.22,53-60 The IHW Program services include both group auricular acupuncture and individual full-body acupuncture.

Integrative Health Education Group The Integrative Health Education Group was designed to provide integrative health education to veterans with chronic medical conditions. Topics addressed during these sessions include relaxation, nutritional psychology, cognitive health, healthy sleep habits, behavioral pain and fatigue management, and coping with chronic illness. The group meets for 1 hour per week, totaling 8 sessions.

Qigong Qigong is an exercise that uses breathing, posture, and movement together with focused awareness and attention to stimulate the sensations of qi (energy) in the body. With its roots in traditional Chinese medicine and martial arts, qigong is traditionally used for exercise, healing, and meditation. Because it is low impact and can be done lying, sitting, or standing, qigong is accessible to individuals with disabilities, older adults, and people recovering from injuries.

Research indicates qigong may have a positive effect on bone health, cardiopulmonary fitness, physical function, balance and prevention of falls, and psychological factors, including anxiety and depression.61-62 14 ALTERNATIVE THERAPIES, NOV/DEC 2015 VOL. 21 NO. 6

Gentle Yoga Yoga combines movement and postures, clear mental focus, and breathing techniques. Its aims include to (1) help people experience an increased sense of well-being and relaxation, (2) improve general physical health, and (3) facilitate flexibility and muscle strength. Gentle yoga is a form of yoga that is practiced sitting in a chair or standing using a chair for support. Research has suggested that yoga can assist in positively managing pain, insomnia, anxiety, and depression and in increasing flexibility and balance.63-64 CURRENT STUDY The purpose of this article is to describe (1) the overall characteristics of veterans who enrolled in the IHW Program, including demographic characteristics and self-reported physical and mental health symptoms; (2) broad trends in the use of the IHW Program services since its inception; and (3) factors associated with use of services.

MATERIALS AND METHODS Research Protocol The IHW Program was developed in conjunction with a research protocol designed to assess outcomes associated with program enrollment and to assist in further targeted program development. The research protocol was approved by the institutional review board and the research and development committee of the DCVAMC. Note that a previous study using intermediate portions of the currently included data (eg, with a briefer outcome period) focused specifically on the role of the Gulf War veteran status as it related to participation in the program.65 Research Aims The primary goal of the pilot study was to evaluate patient satisfaction with the IHW Program and the physical and mental health outcomes among veterans enrolled in it.

The secondary goals were to use the results to help direct future research (eg, randomized, controlled trials [RCTs]) for CAM interventions and future grant applications and to determine whether the program enhanced health service delivery of CAM modalities.

Research Design A prospective cohort study was used to evaluate whether veterans enrolled in the IHW Program reported satisfaction with the program services and experienced improved physical and mental health. Outcome measures included self-report questionnaires (Table 1), a study-specific patient satisfaction survey, a study-specific demographics survey, and medical data from CPRS. Questionnaires were filled out at baseline (ie, the orientation session) and at 6 assessment points (ie, at 4 wk, 8 wk, 12 wk, 6 mo, 9 mo, and 12 mo from baseline).

Notably, outcome data continue to be collected, although any additional data are beyond the scope of this article; thus, the present study provides an initial analysis of baseline symptoms and the factors associated with program enrollment.

Hull—IHW Program for Veterans

Table 1. Schedule of the Study Assessments

Baselinea

Assessments/ Follow-upb

Demographics Demographic Questionnaire

X

Physical and Mental Health Functioning MYMOP-2

X

X

SF-36

X

X

PSS

X

X

BDI-2

X

X

Pain Disability Questionnaire

X

X

Defense/Veteran Pain Rating Scales

X

X

X

X

Pain

Sleep Disturbance Insomnia Severity Index Veteran Satisfaction IHW Satisfaction Questionnaire

X

Abbreviations: MYMOP-2, Measure Yourself Medical Outcome Profile-2; SF-36, Medical Outcomes Study Short Form-36; PSS, Perceived Stress Scale; BDI-2, Beck Depression Inventory-2. a

At the orientation session.

At 4, 8, and 12 wk and 6, 9, and 12 mo from baseline.

b

Participants Participants included patients of the DCVAMC who were referred to the IHW Program by a VA provider and who were willing and able to provide informed consent to participate in the study. Eligibility criteria included (1) being ≥18 years of age and (2) having US veteran status. Exclusion criteria included (1) current involvement in meditation or acupuncture, (2) prior involvement in meditation or acupuncture treatments (involvement ≥1 month before enrollment was acceptable),63 and (3) self-reported pregnancy.

Outcome Measures As part of the current study, veterans completed several self-report measures of physical health, mental health, wellbeing, and program satisfaction. As previously mentioned, outcome measures continue to be collected and are beyond the scope of this current article; thus, only data from questionnaires that were administered at baseline were included in the present analyses.

Hull—IHW Program for Veterans

Measure Yourself Medical Outcome Profile-2.66 The Measure Yourself Medical Outcome Profile-2 (MYMOP-2) is a patient-generated, individualized questionnaire structured to measure the medical outcomes that the patients themselves consider to be most important. Patients identify 1 or 2 symptoms for which they are seeking assistance and that they consider to be the most critical. They also identify an activity of daily living that is limited or impeded by the symptoms.

These choices are recorded in a patient’s own words, and the patient then rates the severity of the symptoms for the week prior to the survey on a 6-point, Likert-type scale. On followup questionnaires, the wording of the items previously chosen by the patient is identical, which allows evaluation of changes from baseline. This questionnaire is sensitive to clinical changes with time and has strong convergent validity with other measures of health-related functioning.58,66 Medical Outcomes Study Short Form-36.67 Healthrelated functioning was assessed using the Medical Outcome Study Short Form-36 (SF-36), which is a self-report questionnaire that measures health-related functioning.

The SF-36 is a 36-question health survey and provides scores for an 8-subscale profile of functional health and well-being, psychometrically based summary measures on physical and mental health, and a preference-based health utility index. It is a generic measure, as opposed to one that targets a specific age, disease, or treatment group.

Accordingly, the SF-36 has proven useful in surveys of general and specific populations, comparing the relative burden of diseases and differentiating the health benefits produced by a wide range of treatments.67,68 Insomnia Severity Index.69 The Insomnia Severity Index (ISI) is designed to determine sleep quality during the month prior to the survey. It is reliable and valid and has 7 items that use a 5-point, Likert-style scale. Scores can range from 0 to 28, with a cutoff score of 10 suggesting the presence of clinical insomnia. This measure has strong psychometric properties, including high internal consistency—α = .91 for clinical populations and α = .90 for community populations— and good sensitivity and specificity in the detection of insomnia in a community population (score ≥ 10).70 Defense and Veteran Pain Rating Scales.71 This measure is designed to measure current pain intensity. This 2-part pain scale has been validated at Walter Reed Hospital on 300 active duty patients and is now undergoing vetting on 600 veterans at the Portland, Oregon, and the Atlanta.

Georgia, VA centers. The first part of this measure provides descriptors of pain and associated facial expressions on a 10-point scale. The second part has 4 questions, which ask how pain has affected activity, sleep, mood, and stress during the 24 hours prior to completing the questionnaire.

Pain Disability Questionnaire.72 The Pain Disability Questionnaire (PDQ) is a 15-item scale assessing selfreported functional difficulties associated with pain. Each item is rated on a 10-point, Likert-type scale. The measure has robust test-retest reliability coefficients that range from 0.94 to 0.98 and a robust Cronbach’s α FRHI¿FLHQW 72 ALTERNATIVE THERAPIES, NOV/DEC 2015 VOL. 21 NO. 6 15

Perceived Stress Scale.73 The Perceived Stress Scale (PSS) is designed to measure subjective distress. The PSS is a well-validated, 10-item scale that measures the degree to which situations in an individual’s life during the month prior to the survey are appraised as unpredictable, uncontrollable, and overwhelming. It posits that people appraise potentially threatening or challenging events in relation to their available coping resources. A higher score indicates a greater degree of perceived stress. Participation in meditation-based interventions has been associated with significant declines in PSS scores.74 Beck Depression Inventory-2.75 Depressive symptoms were assessed using the Beck Depression Inventory-2 (BDI-II), which is a brief, self-report measure of current depressive symptoms that is consistent with Diagnostic and Statistical Manual of Mental Disorders IV diagnostic criteria for major depressive disorders. This measure is commonly used for both research and clinical purposes, and it is estimated to take approximately 5 to 10 minutes to complete. Internal consistency reliability for the BDI-II in medical and psychiatric samples has been strong (≥0.88), and the BDI-II has good test-retest reliability (0.73–0.96). In addition, the BDI-II has strong convergent validity with other measures of depression.76 IHW Program Demographics Questionnaire. This questionnaire is an IHW study-specific questionnaire that assesses descriptive information on participants, such as (1) basic demographic characteristics (eg, age, race, ethnicity, educational level, income, and marital status); (2) militaryrelated characteristics (eg, branch of service, length of service, service connection, and theaters of deployment); and (3) prior CAM treatments.

Additional Electronic Medical Data. In addition to the previously mentioned measures, limited data were garnered from the participants’ medical records in CPRS to (1) confirm demographic variables such as gender, age, race, and ethnicity; (2) track and record number and types of appointments in the IHW Program; and (3) track health care use of veterans enrolled in the program, including total days of outpatient visits, primary care visits, mental health visits, and emergency room visits as well as total inpatient days, hospitalization discharges, and hospitalization days.

Data Analysis Descriptive statistics were calculated to examine the overall demographic characteristics, presenting concerns, and enrollment in services for the currently examined sample of patients. To assess variables associated with service use, Ȥ2, correlational, and 1-way analyses of variance (ANOVAs) were conducted.

RESULTS Referrals A total of 740 consults were received during the first year of the IHW Program. Referrals were received from more than 13 hospital-wide services (Table 2). Referrals were 16 ALTERNATIVE THERAPIES, NOV/DEC 2015 VOL. 21 NO. 6

Table 2. Referral Sources by Department and Provider Type Number of Referrals

Referral Source Department Psychology

216

Neurology/Pain Clinic

187

Primary Care

185

Women’s Clinic/Gynecology

37

Community-based Outpatient Clinic

15

Geriatric

14

Hematology

5

a

64

Other

723b

Total Provider Type Nonpsychiatrist Physician

299

Clinical Psychologist

186

Social Worker

59

Nurse Practitioner

50

Medical Student/Other Trainee

20

Physician Assistant

14

Psychiatrist

11

Speech Pathologist

2

Exercise Physiologist

1

Unknown Provider Type

98

Total

740

a

Includes social work, polytrauma, rehabilitation, ear/nose/ throat, oncology, orthopedic surgery, and walk-in. b Information regarding the referral source was available only for a subset of referrals. primarily made by nonpsychiatric physicians (40.41%) and clinical psychologists (25.14%), although providers from a variety of backgrounds made referrals to the program.

As part of the referral process, DCVAMC providers also had the opportunity to recommend a particular CAM modality or intervention. Individual acupuncture was the most commonly recommended service (n = 174), followed by iRest yoga nidra (n = 106), group auricular acupuncture (n = 98), and the integrative health education class (n = 44). Of note, qigong and gentle yoga services were added to the IHW Program in the final month of the first year and may not be reflected in the referral recommendations for that reason.

Notably, after attending orientation, each veteran chose the services that best fit his/her needs; thus, service choice was patient centered and patient driven. Of the referred veterans, 325 individuals enrolled in the program, of whom 226 (69.53%) consented to participate in the pilot study.

Hull—IHW Program for Veterans

Table 4. Average Baseline Symptoms for Veterans Enrolled in Program

Table 3. Demographic Characteristics Characteristic Age, mean (SD)

% (n) Self-report Questionnaires

49.52 (13.16)

Gender Male

70.35% (159)

Female

29.65% (67) 29.20% (66)

African American

56.64% (128)

Other

14.16% (32) 7.52% (17)

Symptom 1

222

4.77 (0.98)

1-6

Symptom 2

210

4.5 (1.07)

1-6

Mental Component Score

226 38.53a (11.44) 10.93-70.51

Physical Component Score

226

33.55a (9.65)

14.47-58.19

ISI

216

18.62 (7.01)

0-28

Non-Hispanic

69.47% (157)

BDI-2

207 24.27 (13.52)

0-58

Unknown

23.01% (52)

PSS

218

22.83 (7.48)

1-40

DVPRS

215

6.47 (2.27)

PDQ

209 88.61 (33.57)

Education High School/GED Exam

23.89% (54)

Technical/Trade School

11.50% (26)

Associate’s Degree

8.41% (19)

Bachelor’s Degree

30.09% (68)

Master’s Degree

14.16% (32)

Doctorate

3.54% (8)

Unknown

8.41% (19)

Air Force

17.70% (40)

Army

55.75% (126)

Navy

11.95% (27)

Marines

11.95% (27)

Coast Guard

0.44% (1)

Unknown

2.21% (5)

War Eraa Korea

10.18% (23)

Vietnam

15.04% (34)

Desert Shield/Desert Storm

18.58% (42)

OEF/OIF/OND

30.53% (69)

Other

9.73% (22)

Abbreviations: SD, standard deviation; GED, general education development exam; OEF, Operation Enduring Freedom; OIF, Operation Iraqi Freedom; OND, Operation New Dawn.

Note that the categories were not mutually exclusive, and complete data were not available for all participants.

Hull—IHW Program for Veterans

0-10 0-149

Abbreviations: SD, standard deviations; MYMOP-2, Measure Yourself Medical Outcome Profile-2; SF-36, Medical Outcomes Study Short-Form-36; ISI, Insomnia Severity Index; BDI-2, Beck Depression Inventory-2; PSS, Perceived Stress Scale; DVPRS, Defense/Veterans Pain Rating Scale; PDQ, Pain Disability Questionnaire. a

Branch of Service

a

Range

SF-36

Ethnicity Hispanic

Mean (SD)

MYMOP-2

Race White

n

t scores.

Participants The mean age of participants was 49.52 (SD = 13.16, n = 218), though ages ranged from 23 years to 86 years. See Table 3 for complete demographic information. All veterans enrolled in the program identified a pain or mental health– related issue as their primary symptom of concern on the MYMOP-2. The mean severity of the primary symptom was 4.77—SD = 0.98, range = 1-6, n = 222—and the mean severity of the secondary symptom was 4.50—SD = 1.07, range = 1-6, n = 210. In addition, participants in the sample reported moderate depressive symptoms (BDI-II), clinically significant stress symptoms (PSS), severe pain-related interference (DVPRS, PDQ), clinically significant insomnia (ISI), and clinically significant physical and mental health concerns (SF-36). See Table 4 for complete data on symptom severity.

Enrollment in Services Of the 226 veterans who enrolled in the program and consented during the orientation to participate in research, 165 (73.01%) participated in at least 1 service during the first year, with a mean of 7.08 (SD = 8.93) sessions attended.

Although veterans were referred to the IHW Program through a request for a consult from a VA provider, veterans were able to choose the services that best fit their needs during the program’s orientation, and all service options ALTERNATIVE THERAPIES, NOV/DEC 2015 VOL. 21 NO. 6 17

were available for each veteran. Substantial variability occurred in the number of sessions attended, ranging from 1 to 55 sessions. With respect to use of specific services, acupuncture was most commonly attended, with 54.42% of veterans attending at least 1 session of group auricular acupuncture and 34.51% attending at least 1 session of individual acupuncture. Approximately one-fourth of enrolled veterans attended iRest yoga nidra (26.99%), and 3.54% attended integrative health education groups. As indicated, gentle yoga and qigong services were added in the last month of the first year of programming; 3 veterans attended gentle yoga during that time (1.33%), and 6 attended qigong (2.65%).

The mean number of sessions attended for each specific service was examined for the 165 veterans who attended at least 1 service during the first year of services (Table 5).

Repeated measures t tests indicated that veterans attended significantly more sessions of individual acupuncture (t164 = 2.27, P = .02) and group auricular acupuncture (t164 = 4.56, P < .01) than iRest yoga nidra, although no difference existed in the number of sessions of group and individual acupuncture attended (t164 = -0.68, P = .50).

Factors Associated With Service Use Analyses were conducted to explore the characteristics of enrolled veterans who participated in at least 1 service (service users) and those who did not (nonusers). Independent measures t tests revealed no significant difference between the 2 groups with respect to age—t216 = -1.30, P = .20. A Ȥ2 test revealed that a larger proportion of women were service users (82.09%) than men (69.18%), χ2 = 3.99, P = .046.

Due to the small number of individuals in certain race and service-branch categories, χ2 analyses could not be conducted reliably. However, a comparison of category proportions suggested no significant differences in racial composition between service users and nonusers. With respect to branch of service, a comparison of category proportions suggested a significant difference in the proportion of service users who were Marines (9.26%) versus nonusers who were Marines (20.34%).

No significant differences existed between service users and nonusers with respect to severity of primary presenting symptom—t220 = -0.42, P = .68—or severity of secondary presenting symptom—t208 = -0.65, P = .52. Similarly, no significant differences existed between the 2 groups with respect to depressive symptoms: BDI—t205 = 0.98, P = .33; insomnia: ISI—t214 = 0.11, P = .91; pain severity: DVPRS— t213 = 0.87, P = .39; pain disability: PDQ—t207 = 0.08, P = .94; or perceived stress: PSS—t216 = 0.67, P = .50.

Correlational and χ2 analyses were conducted to identify factors associated with the number of sessions attended for the 165 service users. Results of Pearson correlation analyses indicated that age was correlated with service use—r = 0.21, P < .01. A 1-way ANOVA revealed no relationship between service branch and number of sessions attended— F3,157 = 1.96, P = .12. Note that that the analysis excluded the 18 ALTERNATIVE THERAPIES, NOV/DEC 2015 VOL. 21 NO. 6

Table 5. Average Service Use for Veterans Participating in Programming (n =165) Number of Sessions Attended Service

M (SD)

Range

iRest Yoga Nidra

1.58 (3.89)

0-22

Group Auricular Acupuncture

2.82 (4.56)

0-25

Individual Acupuncture

2.51 (3.79)

0-19

Integrative Health Classes

0.07 (0.33)

0-3

0.04 (0.32)

0-3

0.06 (0.34)

0-3

a

Gentle Yoga a

Qigong

Abbreviations: M, mean; SD, standard deviation; iRest, integrative restoration. a

Offered for 1 mo only during study period.

single individual who reported Coast Guard service to ensure a sufficient number of participants per category.

Similarly, no significant effect existed for race—F2,162 = 0.24, P =.79—or gender—F1,163 = 0.71, P = .40.

Regarding the relationship between symptom severity and service use, no significant correlation existed between severity of primary and secondary symptoms as rated by the MYMOP-2 and service use, r = -0.05 (P = .51) and r = -0.06 (P = .47), respectively. Similarly, no other self-report measures were significantly associated with service use: (1) BDI-II— r = 0.03, P = .71; (2) ISI—r = -0.002, P = .98; (3) PDQ— r = -0.03, P = .70; (4) DVPRS—r = 0.01, P = .90; and (5) PSS—r = 0.04, P = .61.

DISCUSSION It is clear from the results of the current preliminary study that the IHW Program serves a diverse group of veterans. Although all of the veterans enrolled in the study reported pain or mental health symptoms as their most salient symptoms of concern, the nature of these problems varied widely. Veterans enrolled in the IHW Program reported clinically significant depression, stress, insomnia, pain, and general physical and mental health symptoms on baseline measures.

With respect to use of services, these early results have suggested that individual and group acupuncture particularly have been sought by veterans in the IHW Program, although iRest yoga nidra sessions have also been well attended.

Although fewer veterans have attended the integrative health education classes, anecdotal reports by providers have indicated that those who have participated in the classes commonly have requested an advanced group that would build on the material covered in the first group. These requests have led to the development of additional educational groups, including a nutritional psychology group that provides veterans with education on the basic science of how Hull—IHW Program for Veterans

nutrients affect mood and behavior. In addition, although qigong and gentle yoga services were added only at the end of the first year of programming, initial data have suggested that veterans are already demonstrating interest and enrolling in these services.

Of the 226 veterans who enrolled in the program and consented to participate in research during the first year of the program, 165 attended at least 1 session of a service during the study period. The results have suggested that service users did not differ substantially from nonusers, although a higher proportion of females used services, and Marines were less well represented among service users.

With respect to demographic factors associated with the number of sessions attended by service users, only age appeared to have an effect, in that older individuals attended more services. Symptom severity was not associated with a specific pattern of service use. In general, the current results have provided further support for the inference that IHW Program services are appealing to a broad cross-section of veterans.

Notably, the IHW Program has been well received by the DCVAMC. Referrals continue to be received from a broad range of clinics, and recent clinical data from 2013 have indicated that the IHW Program has served 509 unique patients with a total of 3796 encounters.

Limitations One limitation of the present study is that data reflect the outcomes of veterans who were specifically referred to the CAM program and then elected to participate. It is likely that veterans enrolled in the current study expressed interest in CAM services, or their providers actively encouraged the veterans to pursue those services. As a result, it is possible that this group of veterans differs systematically in some way from the larger population of veterans served at the hospital and that improvements in symptoms that are observed during participation will be due in part to these factors.

Further exploration of these factors and the effectiveness of the IHW Program should be conducted using an RCT.

DCVAMC is one of the VHA Centers of Innovation for patient-centered care. In this spirit, the IHW Program has been envisioned as a model for patient-centered, integrative health programming that can serve as a template to create similar services across the VA system in the future.

The IHW Program is also in the process of collecting outcome data related to (1) mental health (eg, depression and anxiety); (2) physical health (eg, sleep and pain); and (3) overall well-being, and the program plans to explore to what extent program participation is associated with improvements along each of those axes. It is the research teamâ&#x20AC;&#x2122;s hope to share the aspects of the program that are most associated with positive outcomes for veterans and to use the information to develop programming and outreach efforts further, both at the DCVAMC and across the broader VA network.

The current study also has provided the foundation for future research into the use of CAM interventions with veterans. For instance, it would be interesting to examine the effectiveness of the IHW Program in a more systematic manner (eg, with an RCT). However, a significant barrier in CAM research is that CAM interventions are patient centered and, therefore, application and use of the same CAM modality can vary widely depending on the patient. Thus, researching specific protocols (eg, specific acupuncture points for pain) potentially removes the patient-centered quality of the intervention and, thereby, eliminates an aspect of the intervention that may be having a positive effect on patient outcomes. Developing forms of research on comparative effectiveness other than RCTs would be helpful in validating CAM interventions while preserving the patient-centered quality of the interventions that is integral to this form of treatment.

ACKNOWLEDGEMENTS The research team would like to acknowledge the integrative health providers in the IHW Program, including Alaine Duncan, Jeanette Akhter, Mike Basdavanos, and Karen Soltes. In addition, the team would like to acknowledge Kaya Sossin and Michael Peterson, volunteers who assisted with data collection, and Lauren Roselli, for administratively supporting the IHW Program.

REFERENCES

Future Directions Building on the study data to date and as a result of a strategic planning process, the IHW Program is increasing its services for veterans along a series of specialized, holistic program tracks, including the energetic body, mind and emotions, nutrition, spiritual life, education and events, and research. Increased services include mindfulness-based stress reduction, mindfulness workshops, a nutritional psychology group, tâ&#x20AC;&#x2122;ai chi, and massage. In addition, in the current year, the program will bring an integrative medicine physician and fellow on staff to coordinate and further develop specialized treatment plans for individual veterans.

All veterans participating in these program tracks will have the opportunity to participate in the ongoing research protocol. Additional study data will be used to further refine program offerings and the needs of enrolled veterans. The Hullâ&#x20AC;&#x201D;IHW Program for Veterans

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34. Crawford C, Wallerstedt DB, Khorsan R, Clausen SS, Jonas WB, Walter JA. A systematic review of biopsychosocial training programs for the self-management of emotional stress: potential applications for the military. Evid Based Complement Alternat Med. 2013;2013:747694.

35. Buffart LM, van Uffelen JG, Riphagen II, et al. Physical and psychosocial benefits of yoga in cancer patients and survivors, a systematic review and meta-analysis of randomized controlled trials. BMC Cancer. November 2012;12:559.

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38. Kwekkeboom KL, Cherwin CH, Lee JW, Wanta B. Mind-body treatments for the pain-fatigue-sleep disturbance symptom cluster in persons with cancer. J Pain Symptom Manage. 2010;39(1):126-138.

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48. Carlson LE, Speca M, Faris P, Patel KD. One year pre-post intervention follow-up of psychological, immune, endocrine and blood pressure outcomes of mindfulness-based stress reduction (MBSR) in breast and prostate cancer outpatients. Brain Behav Immun. 2007;21(8):1038-1049.

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51. Zhao CH, Stillman MJ, Rozen TD. Traditional and evidence-based acupuncture in headache management: theory, mechanism, and practice. Headache.

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53. Chan YY, Lo WY, Li TC, et al. Clinical efficacy of acupuncture as an adjunct to methadone treatment services for heroin addicts: a randomized controlled trial.

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ORIGINAL RESEARCH

Improvement in Vision Parameters for Participants Treated With Alternative Therapies in a 3-day Program Edward C. Kondrot, MD, MD(H), CCH, DHt

ABSTRACT Context • Eye conditions that are considered progressive and degenerative and for which the causation is generally poorly understood or not understood within conventional medicine can respond to natural therapeutic interventions that result in arrest and/or improvement of morbidity, with enhanced functional results. Because many of the treated conditions are age related, a delay of disease progression for 5 or even 10 y can mean an additional decade of independence for seniors. The 11 included ocular conditions are ordinarily considered incurable by any method except surgery and, even with surgery, the outcomes can be variable and/or transient.

Objective • The research intended to demonstrate the effectiveness of alternative modalities—intravenous (IV) nutrition, oxidative therapy, microcurrent stimulation, and syntonic light therapy—in improving vision in chronic eye conditions, even when administered for a short period.

Design • The study was a retrospective, open-label, singlegroup design. All participants in the 3-d conference during the period covered were selected.

Setting • The setting was ophthalmologist Edward Kondrot’s Healing the Eye and Wellness Center near Tampa, FL, USA. Participants • The participants in this study were all patients attending 1 of 11 CAM treatment events at the author’s center within 2 y. Each session lasted 3 d and the number of participants in each session ranged from 5-15 (mean = 13). The cohort numbered 152 patients who were diagnosed with ≥1 of 11 types of eye disease. Seventy-eight percent of the patients had either age-related macular degeneration (ARMD) or glaucoma, which, taken together, are the leading cause of blindness in persons >65 y.

Intervention • Each of 4 alternative modalities was provided at least once to each participant: (1) IV nutrition, (2) oxidative therapy, (3) microcurrent stimulation, and (4) syntonic light therapy. On the first day, a detailed treatment plan for each participant was developed. Each

22 ALTERNATIVE THERAPIES, NOV/DEC 2015 VOL. 21 NO. 6

day consisted of 2 therapeutic eye programs, a stress reduction program, and a detoxification program. Also included were daily lectures and instructions on the methods and use of the equipment.

Outcome Measures • To measure outcomes, changes from baseline were documented through comparison with postprogram results. Pre- and postprogram testing included the following measures: (1) Early Treatment Diabetic Retinopathy Study (ETDRS) eye chart; (2) Lighthouse Letter Contrast Sensitivity test; (3) campimetry; (4) pursuits, saccade, and fixation tests; (5) pupillary examination; (6) external examination; (7) examination of the anterior segment; (8) intraocularpressure test; and (9) dilated examination. Additional tests, if necessary, included (1) ocular coherence tomography, (2) infrared thermography, (3) 6-hour urine collection for heavy-metal toxicity, and (4) nocturnal oximetry.

Results • All participants remained in the study for the duration of the program. Following the administration of the protocol, significant improvement in acuity, contrast, and visual field resulted in the majority of participants.

None of the interventions was toxic or painful, and all likely contributed to an improved, overall health status for participants.

Conclusions • These treatment protocols should be considered part of a treatment program for all ocular disease processes. Eye health needs to be repositioned within an assessment of general health with the understanding that, with the exception of congenital disorders or accidents, vision decline represents a general diminishment in overall health and results directly from toxicity from both external sources such as air and water, and the internal accumulation of toxic metals; poor nutrition; and other life exposures and habits. Long-term follow-up studies are now in process. (Altern Ther Health Med. 2015;21(6):22-35.)

Kondrot—Vision Parameters and Alternative Therapies

Edward C. Kondrot, MD, MD(H), CCH, DHt, is the clinic director of integrative medicine at the American Medical College of Homeopathy in Phoenix, Arizona.

Corresponding author: Edward C. Kondrot, MD, MD(H), CCH, DHt E-mail address: info@healingtheeye.com

E

ye conditions that are considered progressive and degenerative and for which the causation is generally poorly understood or not understood at all can respond to natural therapeutic interventions that result in arrest and/or improvement of morbidity, with enhanced functional results.1 Because many of the treated conditions are age related, a delay of disease progression for 5 or even 10 years can mean an additional decade of independence for seniors.

The conditions are (1) age-related macular degeneration (ARMD), the dry type; (2) glaucoma; (3) ARMD, the wet type; (4) macular hole, wrinkling, pucker; (5) Stargardt’s disease; (6) cataracts; (7) ischemic optic nerve disease; (8) retinitis pigmentosa (RP); (9) diabetic retinopathy; (10) histoplasmosis scarring; and (11) cone dystrophy.

ARMD, Dry Type. ARMD dry is the most common cause of irreversible blindness in people older than 65 years.

It is a slow, progressive disease that affects the central area of the retina called the macula. This is the location in the retina responsible for central vision and the most detail. The dry or areolar type consists of degeneration of the retinal pigment cells, resulting in drusen—a small wart-like growth—and hyper- and hypopigmented areas in the retina, with loss of rods and cones and generalized atrophy. The exact cause of ARMD is not known,2 but the earliest changes occur in the choroid—the vascular layer of the eye—and in the pigmented retinal epithelium. These changes begin as a thickening of Bruch’s membrane, which is the layer of the choroid next to the retina. These thickened areas become raised and have the appearance of warts. These changes produce loss of pigment and cell death of the functioning layers of the retina. The condition eventually leads to fluid accumulation, hemorrhage, and scar tissue.

Loss of central vision occurs, but this rarely produces total blindness because the peripheral vision is preserved.

The disease commonly occurs in individuals older than 65 years, but several hereditary conditions can lead to this disorder at a much earlier age. Patients usually complain of blurred vision and difficulty with close work. They can also develop wavy lines and distortion of linear targets. They experience a loss of color sense and the development of scotomas, small areas of blindness.

Glaucoma. This disease occurs when the optic nerve of the eye begins to lose its function. The optic nerve is the transmitter of visual images from the eye to the brain. In the early stages, damage of the nerve results in loss of peripheral vision; in later stages, blindness can result. Abnormality in the circulation of the optic nerve appears to be the reason for damage to the optic nerve. Elevated intraocular pressure is

Kondrot—Vision Parameters and Alternative Therapies

believed to be the main contributing factor, although some patients with glaucoma have low or normal intraocular pressure. Other factors that make the nerve more susceptible to damage are arteriosclerosis and diabetes mellitus.

ARMD, Wet Type. The wet or exudative type of macular degeneration presents as vascular leakage with exudates and a detachment of the retina with loss of vision. A small percentage of the cases can be treated successfully with the argon laser.

Macular Hole, Wrinkling, Pucker. A macular hole is a small break in the macula, located in the center of the eye’s light-sensitive retina. A macular hole can cause blurred and distorted central vision. Macular holes are related to aging and usually occur in people older than 60 years. The size of the hole and its location on the retina determine how much it will affect a person’s vision. When a stage III macular hole develops, most central and detailed vision can be lost. If left untreated, a macular hole can lead to a detached retina, a sight-threatening condition.

Stargardt’s Disease. This disease is an inherited form of juvenile macular degeneration that causes progressive vision loss, usually to the point of legal blindness. The progression usually starts between the ages of 6 years and 12 years, and it plateaus shortly after rapid reduction in visual acuity. Several genes are associated with the disorder. Symptoms typically develop by 20 years of age and include wavy vision, blind spots, blurriness, impaired color vision, and difficulty adapting to dim lighting.

Cataracts. Cataracts are due to clouding, hardness, and loss of elasticity that occur in the human lens. Cataracts are associated with general arteriosclerotic changes, diabetes, sun exposure, trauma, and poor nutrition. More than 50% of people older than 60 years will develop cataracts. With age, changes in the protein of the lens develop. Oxidative reactions develop, which form abnormal disulfide and other covalent linkages. This change causes the lens fibers to lose their transparency. Ionizing radiation has a very high, cataractproducing effect, and the lens is its most sensitive target within the adult eye. Its damage is dose related and cumulative. The sources of electromagnetic radiation energy most important in damage to the lens are ionizing radiation— X-rays, gamma rays and neutrons, emission of infrared or ultraviolet rays from various hot bodies, and microwaves.

Copper, iron, and mercury poisoning can lead to the development of cataracts.

Ischemic Optic Nerve. The optic nerve is made up of 1 million, tiny, delicate nerve fibers that are like wires. Many blood vessels nourish the optic nerve with oxygen and nutrition. Vision actually takes place in the brain when the messages from the eye travel to the brain along the optic nerve; however, the nerve must be healthy to transmit these messages. Ischemic optic-nerve conditions occur due to damage to the optic nerve from insufficient blood supply.

Retinitis Pigmentosa. RP is an inherited, degenerative eye disease that causes severe vision impairment and often blindness. The progress of RP is not consistent. Some people exhibit symptoms from infancy; others may not notice ALTERNATIVE THERAPIES, NOV/DEC 2015 VOL. 21 NO. 6 23

symptoms until later in life. A form of retinal dystrophy, RP is caused by abnormalities of the photoreceptors (rods and cones) or the retinal pigment epithelium (RPE) of the retina, leading to progressive sight loss. Affected individuals may experience defective light-to-dark and dark-to-light adaptation (ie, night blindness) as the result of the degeneration of the peripheral visual field. Sometimes, central vision is lost first, causing the person to look sidelong at objects.

Diabetic Retinopathy. Diabetic retinopathy is damage to the retina caused by complications of diabetes, which can eventually lead to blindness. It is an ocular manifestation of diabetes, a systemic disease. The condition affects up to 80% of all patients who have had diabetes for 10 years or longer.

Histoplasmosis Scarring. Scientists believe that Histoplasma capsulatum (ie, spores spread from the lungs to the eye) lodge in the choroid, a layer of blood vessels that provides blood and nutrients to the retina. The condition develops when fragile, abnormal blood vessels grow underneath the retina. These abnormal blood vessels form a lesion known as choroidal neovascularization. If left untreated, the lesion can turn into scar tissue and replace the normal retinal tissue in the macula. The macula is the central part of the retina that provides the sharp, central vision.

When this scar tissue forms, visual messages from the retina to the brain are affected, and vision loss results.

Cone Dystrophy. Cone dystrophy is an inherited ocular disorder characterized by the loss of cone cells, the photoreceptors responsible for both central and color vision.

The most common symptoms of cone dystrophy are vision loss, with the age of onset ranging from the late teens to the 60s; sensitivity to bright lights; and poor color vision.

Therefore, patients see more at dusk. Visual acuity usually deteriorates gradually, but it can deteriorate rapidly. Color vision testing reveals many errors on both red-green and blue-yellow plates.

The eye diseases addressed here are often not responsive to traditional treatments, and some patients wish to avoid surgery or the side effects of medication.

METHODS Participants Patients applied to the program based on their interest in participating in a 3-day Healing the Eye program that was conducted at the investigator’s retreat setting, The Healing the Eye Wellness Center (near Tampa, FL, USA). The Wellness Center is a fully functioning, organic ranch with a garden and farm animals. The center encourages exercise, and the facilities include a basketball court, swimming pool, hot tub, weight room, and infrared sauna, together with many miles of sandy road for jogging. On-site, hotel-like accommodations are provided together with organic meals that are prepared on site.

Each participant forwarded tests and diagnostic information prior to being accepted into the program, and those results were verified at the start of the program. The 24 ALTERNATIVE THERAPIES, NOV/DEC 2015 VOL. 21 NO. 6

cost of the program was $3000 for the 3-day treatment program, excluding travel expenses. There are additional charges for home use of a Microcurrent machine, postprogram ($2250), and for follow-up care for 1 year.

A small number of participants were the investigator’s patients; others were referred by physicians or were selfreferred. At the time of the study, the 3-day programs had been conducted for more than 10 years, with the curriculum evolving to keep pace with research and the results of the investigator’s studies.

The study’s participants were selected to participate as paying participants in the 3-day program after meeting the following criteria: (1) they had eye disease that had not been responsive to traditional treatments or (2) they wished to avoid surgery or the side effects of medication. All participants signed detailed informed consent forms.

Participants ranged in age from 15 to 95 years; 52% were female, and 48% were male. Forty-six percent resided in California, Arizona, and Florida, with the remaining coming from 11 additional states. One participant lived in Mexico.

Procedures The study used a 3-day intervention protocol. On the first day of the program, the center obtained the following information for creation of a detailed treatment plan for each participant to allow the person to regain vision.

Detailed Eye History. This provided information related to the underlying cause of the eye problem.

Medical History. This provided information about other physical problems that potentially had contributed to the eye disease.

List of Medications. This was a list of a participant’s current medications; every medicine potentially can be toxic to the eye.

Dietary History. Nutritional education is an integral component of the program. Each participant receives a zinc taste test. This simple, 2-minute test measures the intracellular levels of zinc. Zinc is a key nutrient, not only for the eye but also for every enzymatic function in the body. A deficiency of zinc is a red flag that other nutritional deficiencies exist.

Only organic food that was not genetically modified (ie, non-GMO food) was served during the 3-day program, with much of it being raw. Following the program, participants were encouraged to continue a 70/30 diet, with 70% of food to be organic and consumed raw, and the other 30% also to be organic but allowed to be cooked.

Evaluation of Life Stressors. This information allowed the center to develop a program to reduce those stressors.

Investigation of Heavy-metal Exposure. Heavy-metal toxicity contributes to all degenerative eye diseases.

Zyto Energetic Analysis. This test is used to measure fluctuations in electrical conductivity of the skin. Fluctuations in electrical conductivity were measured during treatments, such as when the microcurrent and light therapy were applied. The responses helped determine participants’ physical preferences regarding the interventions being Kondrot—Vision Parameters and Alternative Therapies

considered and acted as guides in specification of treatment protocols.

Each day consisted of 2 therapeutic eye programs: (1) a stress reduction program and (2) a detoxification program. Also included were daily lectures and instructions on the methods and use of the equipment. The lecture schedule included the following information: Day 1. Provided information about diet, nutrition, hydration, and creation of balance in the autonomic nervous system. A balanced autonomic nervous system has been shown to contribute to reduced symptomatology in eye disease.3 Day 2. Homeopathy and microcurrent therapy were initiated. Homeopathic remedies were prescribed for but not taken by participants until after the 3-day workshop. It is the author’s intention to report on the effectiveness of homeopathic treatment for chronic eye conditions in a future publication.

Day 3. Provided instruction on light therapy and eye exercises.

Outcome Measures To measure outcomes, changes from baseline were documented through comparison with postprogram results.

Pre- and postprogram testing included: Early Treatment Diabetic Retinopathy Study Eye Chart. The Early Treatment Diabetic Retinopathy Study (ETDRS) eye chart is a test that measures acuity and has been accepted and approved in studies sponsored by the National Eye Institute and the US Food and Drug Administration (FDA). Each line on the chart has 5 letters, and the chart has a total of 14 lines or 70 letters.

Lighthouse Letter Contrast Sensitivity Test. This test measures the ability to see letters of increasingly lighter contrast. Failure to perceive lighter contrast is related to toxicity and heavy-metal poisoning.

Campimetry. Campimetry is one way to test the visual field systematically. It is used for testing central fields for white, blue, green, and red and also is used in syntonics to assess subtle changes in awareness and visual fields. This test measures the ability to perceive motion.

Pursuits, Saccade, and Fixation Tests. These tests measure basic visual functions that are essential to good vision. They relate to the eye’s ability to follow movement, to change focal point, and to fixate on an object of interest.

Pupillary Examination. The pupil reflects the autonomic nervous system, and subtle imbalances in this system can be detected through examination.

External Examination. This test requires a careful examination of the outer structure of the eye, including the lids, cornea, conjunctiva, and tear film. The outer layer protects the delicate inner parts of the eye, and the tear film lubricates the cornea and supplies nutrients and oxygen.

Examination of the Anterior Segment. This area is inspected for signs of inflammation and toxicity. The lens, or the part of the eye that focuses light into the eye, is inspected for signs of cataracts and toxicity.

Kondrot—Vision Parameters and Alternative Therapies

Intraocular-pressure Test. This test is important in detection of glaucoma. Participants’ pressures were monitored throughout the 3-day program.

Dilated Examination. The inside of the eye is the only place in the body where blood vessels and neurological tissue can be examined without surgery. The vasculature, retina, macula, and optic nerve were examined for disease.

Specialized Testing Available During the 3-day Program. Depending on a participant’s condition and the results of the above testing, the following tests were also available during the 3-day program: Ocular Coherence Tomography. This sophisticated test measures a cross-section of the retina under high magnification. It offers the opportunity to examine all 10 layers of the retina to locate the areas of disease precisely.

Infrared Thermography. This test measures temperature differences on the surface of the face. It is a very accurate test for detection of abnormalities of the orbits, sinuses, and teeth that might be contributing to eye problems.

While not specific to measuring vision or eye pathology, the following 2 tests are included as a way of measuring possible contributing factors to the participants’ eye condition.

Six-hour Urine Collection to Test For Heavy-Metal Toxicity. This test is the gold standard to determine the levels of toxic minerals stored in tissue. At the end of the 3-day program, patients were given the test kit and were requested to complete it at home and send the samples to the lab for results. The investigator then discussed the findings during a follow-up telephone evaluation that occurred 1 month after the 3-day session. Almost all participants tested positive for heavy-metal toxicity and were advised to undergo chelation therapy after the workshop.

Nocturnal Oximetry. This test measures oxygen saturation at night. Many patients, because of obstructive airway disease (sleep apnea), have low levels of oxygen at night, which can contribute to the development of eye disease, and if not treated, can affect the success of eye treatments.

Interventions The intervention in the 3-day program began with treatments that balanced the autonomic nervous system and neuroendocrine functions and activities to reduce stress.

Emphasis was placed on developing a customized program for each participant’s eye problem. This program was recalibrated for each participant during the 3 days, depending on outcomes and response to treatment from measurements taken intermittently.

The 4 alternative modalities were provided at least once to each participant: (1) intravenous (IV) nutrition, (2) oxidative therapy, (3) microcurrent stimulation, and (4) syntonic light therapy.

IV Nutrition—Myer’s Cocktail. This specialized intravenous vitamin mixture was designed to provide key vitamins and minerals to support the eye and visual function.4,5,6 ALTERNATIVE THERAPIES, NOV/DEC 2015 VOL. 21 NO. 6 25

It was suggested that all patients receive this mixture, particularly if they were deficient in zinc. It also was suggested that all patients in the program receive a Myer’s cocktail once per month at their home locations until nutritional levels were at an optimum level. The cocktail that the Wellness Center offers is tailored to provide nutrients known to be supportive of good vision: (1) ascorbic acid, 500 mg/mL, 12 cc; (2) pyridoxine, 100 mg/mL, 2 cc; (3) hydroxocobalamin 1000, μg/mL, 1 cc; (4) B complex 100, 1 cc; (5) calcium gluconate 10%, 1 cc; (6) dexpanthenol, 250 mg/mL, 1 cc; (7) magnesium chloride, 200 mg/mL, 1 cc; (8) multitrace-5 concentrate, 1 cc; (9) selenium, 40 μg/mL, 5 cc; (10) taurine, 50 mg/mL, 2 cc; (11) zinc, 1 mg/mL, 5 cc; (12) lidocaine 2%, 5 cc; (13) sterile water, 200 cc; and (14) folic acid, 1 mg.

Oxidative Therapy. Oxidative therapies such as ozone therapy, ultraviolet blood irradiation therapy, and intravenous hydrogen peroxide therapy can be beneficial for treating a wide range of conditions ranging from viral and fungal infections to joint pain and arthritis.7 Oxidative therapies work by stimulating the immune system, enhancing mitochondrial processes, and facilitating healing with virtually no side effects. Some researchers believe that this therapy can be very helpful in the treatment of macular degeneration and glaucoma and other eye disorders.8. Typically 20 to 40 treatments are necessary, although benefits can be experienced after 1 or 2 treatments. Each patient receives a minimum of 2 oxidative IV therapies during the program. Several oxidative modalities can be done in the home and participants were trained to continue them after the 3-day session and given the equipment needed to do so. Ozone therapy is a type of oxidative therapy breakthrough treatment that is able to detoxify as it heals. It uses highly reactive oxygen gas, which stimulates regeneration and healing. It is used to treat a wide range of chronic conditions, including macular degeneration.9 The program offered ozone therapy in several ways: (1) intravenously, called auto hemotherapy, where a small amount of blood is mixed with the ozone and then injected into the body; and (2) as eye drops, to help stimulate the healing of the eye. Hydrogen peroxide therapy was also provided to some participants in the program. This type of oxidative therapy is given directly into the blood stream through a slow IV drip and has the same beneficial results as other types of oxidative therapies Microcurrent Stimulation Therapy. Microcurrent stimulation (MCS) therapy is a well-established therapy that improves blood flow, stimulates cellular activity, reduces scar tissue and inflammation, and helps balance the autonomic nervous system.10 It was delivered to the eye via a specially designed glove that is used to stimulate the periorbital tissues. This device is the result of design refinement in the course of several years. The current is calibrated to respond specifically to the involved tissues and the condition being treated. The mechanism of action is believed to be 3 fold: improving blood flow, stimulating cellular activity, and reducing inflammation and scar tissue.

Patients with glaucoma have a compromised optic nerve. Elevations in pressure can cause the blood flow to the 26 ALTERNATIVE THERAPIES, NOV/DEC 2015 VOL. 21 NO. 6

optic nerve to be reduced, resulting in damage to the nerve and loss of vision. Research evidence suggests that microcurrent has a protective effect on the optic nerve.11 MCS can be beneficial to patients with glaucoma because it helps increase blood flow and stimulates cellular activity, and now evidence suggests a neuroprotective effect. MCS can lower the intraocular pressure, which is observed in patients after MCS treatment.12 MCS is very effective in treating most eye diseases, including macular degeneration, glaucoma, cataracts, inflammation, and dry eyes. The flow of current from cell to cell and within cells promotes repair and regeneration of tissues.13,14 All patients who participated in the 3-day workshop were provided microcurrent devices, calibrated to their specific eye diseases, and were instructed to use them at home to continue vision improvement.

Syntonic Light Therapy. Syntonics, or optometric phototherapy, is the branch of ocular science dealing with the application of selected light frequencies through the eyes. It has been used clinically for more than 70 years in the field of optometry with continued success in the treatment of visual dysfunctions, including strabismus (eye turns), amblyopia (lazy eye), focusing and convergence problems, learning disorders, and the after-effects of stress and trauma.15 In recent years, syntonics has been shown to be effective in the treatment of brain injuries and emotional disorders. A specific wavelength of light is selected for each person to help rebalance their particular imbalance. Research is ongoing, but data indicate certain frequencies of blue-green light can improve the vision in patients with macular degeneration and certain frequencies of green light can lower the pressures in patients with glaucoma.16 Each color can have a myriad of frequencies, and the task is to identify the frequency that best resonates with the eye, stimulates retinal function, and balances the autonomic nervous system. Each participant received 2 light-therapy treatments per day.

RESULTS Table 1 shows the number of patients affected by each of the 11 eye diseases as well as the total number of eyes affected. Some patients had disease in only 1 eye, and some patients had more than 1 disease.

Sixty-nine percent of the study’s participants had improvement of at least 1 line (ie, 5 letters) in acuity, and 36% had improvement of at least 1 line in contrast (Table 2; Figures 1, 2, and 3). One line of improvement is a significant change that is noticeable to patients and improves their levels of daily functioning. Typically when a spectacle measurement improves the acuity by 1 line, a patient will be advised to get a new pair of glasses. Most ophthalmic studies agree that a 5-letter or 1-line improvement is very significant and that a mechanism that produces this visual change deserves more research.

Kondrot—Vision Parameters and Alternative Therapies

Figure 1. Summary results for acuity improvement.

Eye Disease

Number of Patients

Number of Eyesa

ARMD-Dry

70

140

Glaucoma

29

58

ARMD-Wet

20

40

Macular hole, macular wrinkling, pucker

9

10

Stargardt’s disease

3

6

Cataracts

6

10

Ischemic optic nerve disease

4

6

Retinitis pigmentosa

4

8

Diabetic retinopathy

3

6

Histoplasmosis scarring

3

4

Cone dystrophy

1

2

152

290

160 140 120 100 80 60 40 20 0

Abbreviation: ARMD, age-related macular degeneration. a

Some patients had disease in only 1 eye; some patients had >1 disease.

160 140 120 100 80 60 40 20 0

Table 2. Summary Results of All 152 Patients or 290 Eyes Treated %

≥2 lines (10 letters)

43

15%

>1 line (5 letters)

158

54%

>1-4 letters

66

23%

No change

23

8%

Number of Eyesa

%

>5 letters

104

36%

>1-4 letters

151

52%

No change

35

12%

Number of Eyesa

%

Marked

165

57%

Moderate

75

26%

Minimal

19

6%

No change

31

11%

Contrast Improvement

Visual Field Expansion

66

43

23

2 lines 1 line (10 letters) (5 letters)

1-4 letters

No change

151 104 19 ≥5 letters

1-4 letters

No change

Figure 3. Summary results for visual field expansion.

Eyes

Number of Eyesa

Acuity Improvement

158

Figure 2. Summary results for contrast improvement.

Eyes

Total

Eyes

Table 1. Ocular Conditions, Number of Patients, and Number of Eyes

180 160 140 120 100 80 60 40 20 0

165 75 19 Marked

31

Moderate Minimal No change

a

Some patients had disease in only 1 eye; some patients had more than 1 disease.

Kondrot—Vision Parameters and Alternative Therapies

ALTERNATIVE THERAPIES, NOV/DEC 2015 VOL. 21 NO. 6 27

ARMD, DRY TYPE Table 3. Results: ARMD Drya,b

60

Number of Eyes

>2 lines

22

1-2 lines

53

<1 line

50

No change

15

40 Eyes

Acuity Improvement

Figure 4. ARMD dry: results for acuity improvement.

20

Number of Eyes

>6 letters

35

3-5 letters

38

1-2 letters

54

No change

13

0

76

Moderate

41

No change or minimal

1-2 lines

≥3 lines

Figure 5. ARMD dry: results for contrast improvement.

60 40

Number of Eyes

Marked

<1 line

Abbreviation: ARMD, age-related macular degeneration.

Eyes

Visual Field Expansion

22

15 No change

Contrast Improvement

53

50

50 38

20

35

13 0

23

No change

<1 line

1-2 lines

≥3 lines

Abbreviation: ARMD, age-related macular degeneration.

Abbreviation: ARMD, age-related macular degeneration. a

n = 70 patients, 140 eyes. b The average improvement of acuity was 5.5 letters and the average improvement of contrast was 3.8 letters.

Figure 6. ARMD dry: results for visual field expansion.

80

Eyes

60 40

76 41

20

23

0 Marked

Moderate

No change or minimal

Abbreviation: ARMD, age-related macular degeneration.

28 ALTERNATIVE THERAPIES, NOV/DEC 2015 VOL. 21 NO. 6

Kondrot—Vision Parameters and Alternative Therapies

GLAUCOMA Table 4. Results: Glaucomaa,b Acuity Improvement

Figure 7. Glaucoma: results for acuity improvement.

30

Number of Eyes

25

10

20

1-2 lines

26

15

Eyes

≥2 lines

<1 line

16

5

No change

6

0

>6 letters

17

3-5 letters

14

1-2 letters

17

No change

Visual Field Expansion:

10

37

Moderate

14

No change or minimal

7

Pressure Lowering

18 16 14 12 10 8 6 4 2 0

Number of Eyes

>5 mm Hg

13

1-5 mm Hg

27

No change

11c

Increase in pressure

7c

<1 line

No change

17

17

14

10

Figure 9. Glaucoma: results for visual field expansion.

40 35 30 25 20 15 10 5 0

37 14 Marked

7

Moderate

No change or minimal

Figure 10. Glaucoma: results for pressure lowered.

30

a

25 20 Eyes

n = 29 patients, 58 eyes. b The average change in acuity was 6 letters; the average change in contrast was 3.6 letters; and the average drop in pressure was 4.8 mm Hg. c The majority of these patients stopped their eye drops; therefore, the pressure elevation or lack of response could be due to stopping medication.

1-2 lines

> 6 letters 3-5 letters 1-2 letters No change

Number of Eyes

Marked

6

Figure 8. Glaucoma: results for contrast improvement.

Eyes

Number of Eyes

16 10 ≥2 lines

Eyes

Contrast Improvement

26

10

15 10 5

27 13

16

7

0 >5 mm Hg 1-5 mm Hg No lowering lowering change

Kondrot—Vision Parameters and Alternative Therapies

Increase in pressure

ALTERNATIVE THERAPIES, NOV/DEC 2015 VOL. 21 NO. 6 29

ARMD, WET TYPE Table 5. Results: ARMD Weta,b Number of Eyes

≥2 lines

8

1-2 lines

11

<1 line

20

No change

1

Eyes

Acuity Improvement

Figure 11. ARMD wet: results for acuity improvement.

20 18 16 14 12 10 8 6 4 2 0

17 8

1 ≥2 lines

Number of Eyes

>6 letters

11

3-5 letters

9

1-2 letters

13

No change

7

Visual Field Expansion

Number of Eyes

Marked

26

Moderate

8

No change or minimal

6

1-2 lines

<1 line

No change

Abbreviation: ARMD, age-related macular degeneration.

Figure 12. ARMD wet: results for contrast improvement.

Eyes

Contrast Improvement

11

14 12 10 8 6 4 2 0

11

>6 letters

13 9

7

2-5 letters

1-2 letters

No change

Abbreviation: ARMD, age-related macular degeneration.

Abbreviation: ARMD, age-related macular degeneration. a

Figure 13. ARMD wet: results for visual field expansion.

Eyes

n = 20 patients, 40 eyes. b The average improvement of acuity was 6.4 letters, and the average improvement of contrast was 5.0 letters.

30 25 20 15 10 5 0

26 8 Marked

Moderate

6 No change or minimal

Abbreviation: ARMD, age-related macular degeneration.

30 ALTERNATIVE THERAPIES, NOV/DEC 2015 VOL. 21 NO. 6

Kondrot—Vision Parameters and Alternative Therapies

MACULAR HOLE, WRINKLING, PUCKER Table 6. Results: Macular Hole, Wrinkling, Puckera

Figure 14. Macular hole, wrinkling, pucker: results for visual field expansion.

Acuity Improvement Average acuity change Range

Number of Letters 4.3 0-11

Contrast Improvement Average contrast change Range

Number of Letters 2.5 0-8

4

Number of Eyes 3 4 3

2

Eyes

Visual Field Expansion Marked Moderate Minimal a n = 9 patients, 10 eyes.

3 4 3

3 1 0 Marked

Moderate

Minimal

STARGARDT’S DISEASE

Acuity Improvement Average acuity change Range

Number of Letters 6.6 2-13

Contrast Improvement Average contrast change Range

Number of Letters 3.67 0-10

Visual Field Expansion Marked

Figure 15. Stargardt’s disease results for visual field expansion.

6 5 4 Eyes

Table 7. Results: Stargardt’s Diseasea

3

6

2 1

Number of Eyes 6

0

0

0 Marked

Moderate

Minimal

a

n = 3 patients, 6 eyes.

CATARACTS Table 8. Results: Cataractsa Acuity Improvement Average acuity change Range

Number of Letters 5.75 0-16

Contrast Improvement Average contrast change Range

Number of Letters 2.3 0-6

Visual Field Expansion Marked Moderate None to slight

Number of Eyes 7 1 2

Eyes

Figure 16. Cataract: results for visual field expansion.

7 6 5 4 3 2 1 0

7

4 Marked

Moderate

2 None to slight

a

n = 6 patients, 10 eyes.

Kondrot—Vision Parameters and Alternative Therapies

ALTERNATIVE THERAPIES, NOV/DEC 2015 VOL. 21 NO. 6 31

ISCHEMIC OPTIC NERVE Table 9. Results: Ischemic Optic Neuropathya

Figure 17. Ischemic optic neuropathy: results for visual field expansion.

Number of Letters 5.75 0-15

Contrast Improvement Average contrast change Range

Number of Letters 3.75 0-6

Visual Field Expansion Marked Moderate

3.0 2.5 2.0 Eyes

Acuity Improvement Average acuity change Range

3

3

1.5 1.0 0.5

Number of Eyes 3 3

0

0 Marked

Moderate

Minimal

a

n = 4 patients, 6 eyes.

RETINITIS PIGMENTOSA

Table 10. Results: Retinitis Pigmentosaa

Figure 18. Retinitis pigmentosa: results for visual field expansion.

Number of Letters 15.3 0-68

Contrast Improvement Average contrast change Range

Number of Letters 3.1 0-8

Visual Fields Expansion Marked Moderate Able to see color, previously unable No change

4 3 Eyes

Acuity Improvement Average acuity change Range

Number of Eyes 4 2 1

4

2

2

1

1

1

0 Marked

1

a

n = 4 patients, 8 eyes.

Moderate Able to see color, previously unable

No change

DIABETIC RETINOPATHY

Acuity Improvement Average acuity change Range

Number of Letters 7.8 3-17

Contrast Improvement Average contrast change Range

Number of Letters 5.5 2-11

Visual Field Expansion Marked Moderate

Number of Eyes 4 2

Figure 19. Diabetic retinopathy: results for visual field expansion.

4 3 Eyes

Table 11. Results: Diabetic Retinopathya

2

4 2

1

0 0 Marked

Moderate

Minimal

a

n = 3 patients, 6 eyes.

32 ALTERNATIVE THERAPIES, NOV/DEC 2015 VOL. 21 NO. 6

Kondrotâ&#x20AC;&#x201D;Vision Parameters and Alternative Therapies

HISTOPLASMOSIS SCARRING: THE CONDITION Table 12. Results: Histoplasmosis Retinal Scarringa Acuity Improvement Average acuity change Range

Number of Letters 4 2-11

Contrast Improvement Average contrast change Range

Number of Letters 7.3 3-12

Visual field expansion Marked Reduction in blind spots

Number of Eyes 4 2

a

n = 3 patients, 4 eyes.

CONE DYSTROPHY: THE CONDITION

Table 13. Results: Cone Dystrophya Acuity Improvement Average acuity change Range

Number of Letters 5 4-6

Contrast Improvement Average contrast change Range

Number of Letters 1 0-2

Visual field expansion Moderate

Number of Eyes 2

a

n = 1 patient, 2 eyes.

DISCUSSION Very little research has been done to date that has attempted to reverse chronic eye disease. One study involved 3 patients with Stargardt’s macular dystrophy and 1 patient with dry ARMD, who received stem-cell transplants. According to published results in Lancet on January 24, 2012, ... it is encouraging that during the observation period neither patient lost vision. Best-corrected visual acuity improved from hand motions to 20/800 (and improved from 0 to 5 letters on the Early Treatment Diabetic Retinopathy Study’s [ETDRS’] visual acuity chart) in the eye of the patient with Stargardt’s macular dystrophy, and vision also seemed to improve in the patient with dry age-related macular degeneration.

In that study, 5 letters of improvement was considered significant, but the cost of the treatment as well as its risks far exceeded those of the multifactorial intervention using natural therapies in the current 3-day program.

Kondrot—Vision Parameters and Alternative Therapies

Of the current study’s participants, 69% had improvement of at least 1 line (ie, 5 letters) in acuity, and 36% had improvement of at least 1 line in contrast (Table 2; Figures 1, 2, and 3). The treatment modalities used were statistically beneficial to all groups treated—improving acuity, contrast, and visual fields. All treatment modalities are beneficial individually and have absolutely no associated pain or discomfort, toxicity, or side effects. This is in significant contrast to conventional medicine’s treatments that are either invasive (surgery) or toxic (pharmaceuticals) and produce only short-term remediation without addressing any of the underlying causative factors that produce eye disease. The treatments used produced the results due to the possible mechanisms of (1) improvement of blood flow, (2) reduction in inflammation, (3) stimulation of cellular activity, and/or (4) stimulation of stem cell activity and regeneration. All of these processes are known to be conducive to tissue, organ, and system health.

Further, to fully grasp the significance of these results, it is important to highlight the limitations and toxicity involved in conventional treatments for macular degeneration, glaucoma, and cataracts.

ARMD is a progressive eye disease that is becoming more and more prevalent in the world. There are more than 2 million new cases per year in the United States and Canada.

Currently, more than 30 million people have the condition.

There are 600 new cases of wet macular degeneration every day, making it a significant problem. Ten thousand people turn 65 years old every day in North America. This is the highest risk group for eye conditions that lead to blindness due to age as well as due to early life exposure to heavy metals, prior to the banning of leaded gas and certain toxic pesticides.

Conventional pharmaceutical and surgical treatment of both glaucoma and macular degeneration are fraught with limitations and toxic side effects that make the acceptance of natural, overall health-improving strategies, such as those discussed in this article, even more compelling. None of the methods used in the 3-day program has any toxic side effects.

Eye specialists have long been aware of the pathological changes that can result from the treatment of wet macular degeneration with anti-VEGF (vascular endothelial growth factor) injections. Endophthalmitis, which is severe infection that usually leads to blindness, can occur, as can a retinal detachment. Glaucoma as well as cataracts can develop.

However, there are even more disturbing findings. A recent national study designed to compare the relative effectiveness of 2 frequently prescribed anti-VEGF medications to treat wet macular degeneration had some alarming results when it determined that, for more than 18% of those receiving the anti-VEGF treatment, the treatment itself was found to produce retinal geographic atrophy (GA), which is a more severe form of macular degeneration involving retinal cell death. The team of researchers led by Juan E. Grunwald, MD, of the University of Pennsylvania, has published a study of 1024 patients whose color fundus photos or fluorescein angiograms showed no visible signs of GA at enrollment.

ALTERNATIVE THERAPIES, NOV/DEC 2015 VOL. 21 NO. 6 33

After two years, the researchers found that GA had developed in 187 patients, or 18.3% of the cohort being studied. They concluded that “anti-VEGF therapy may have a role in the development of GA.”17 The pharmaceutical agents used to control glaucoma can be expected to produce several side effects depending on the type of agent used: (1) Prostaglandin analogs: possible changes in eye color and eyelid skin, stinging, blurred vision, eye redness, itching, burning.

(2) β-Blockers: low blood pressure, reduced pulse rate, fatigue, shortness of breath; rarely: reduced libido, depression.

(3) α-Agonists: burning or stinging, fatigue, headache, drowsiness, dry mouth and nose, relatively higher likelihood of allergic reaction.

(4) Carbonic anhydrase inhibitors: in eye drop form: stinging, burning, eye discomfort; in pill form: tingling hands and feet, stomach upset, memory problems, depression, frequent urination.

Some products use combined formulas and side effects of combined medications may include any of the side effects of the drug types they contain.18 Further, The development of systemic side effects is due to the medications [being] placed in the eye and absorbed into the conjunctival blood vessels on the eye’s surface. A certain percentage of the active ingredient of the medication, though small, will enter the bloodstream and may adversely affect functions such as heart rate and breathing. Likewise, some types of eye drops may worsen certain existing medical conditions such as asthma. Some glaucoma drugs also can interact with other common medications such as digitalis, prescribed for heart conditions.19

Cataract surgery, the long standing and most common— indeed the only—conventional treatment for cataracts is not without problems. Cataract surgery may increase the risk of macular degeneration, although at this time the studies linking macular degeneration and cataract surgery are conflicting. The Beaver Dam eye study found as high as a 3-fold increase in macular degeneration after cataract surgery. A study in the Journal of Ophthalmology showed no clear effect but advised caution.20 There are several reasons that may cause the development of ARMD after cataract surgery. The surgical procedure itself produces shock to the eye, which may result in inflammation.

The pharmaceutical drops used after surgery are toxic to the eye. The aging process of the eye is accelerated due to loss of the human lens, known to protect against ultraviolet light.

The last and most interesting is the suppressive effect of cataract surgery. Suppression is a homeopathic law that states that the human body has intelligence, and that symptoms and disease develop to achieve a homeostasis or balance in the body. If the underlying cause of disease is not treated, a more serious disease will develop. A cataract is a symptom of 34 ALTERNATIVE THERAPIES, NOV/DEC 2015 VOL. 21 NO. 6

an underlying disease. Surgery does not treat the underlying cause. The result is a more serious disease (ie, macular degeneration).

The 5-year results of the Beaver Dam eye study identified persons with and without a history of cataract extraction at a baseline examination and reexamined them for ARMD at 5 and 10 years. They found an association between cataract surgery and the 5-year incidence of late ARMD: These data strongly support the past findings of an association of cataract surgery with late A[R]MD independent of other risk factors, including high-risk genetic status, and suggest the importance of considering these findings when counseling patients regarding cataract surgery. These findings should provide further impetus for the search for measures to prevent or delay the development of age-related cataract.21

Vitamin C deficiency may be a cause of cataracts, leading to a form of focal scurvy in the eye. It has long been believed that a vitamin C deficiency in one area or tissue of the body means there is a comparable vitamin C deficiency everywhere else. Nothing could be further from the truth. When a cataract develops, the levels of ascorbic acid decease in the aqueous humor that surrounds and bathes the lens with nutrients and oxygen.22 Might high dosages of vitamin C might reverse cataracts? If so, this approach would be preferred to surgery in that it would correct the underlying conditions rather than only the manifestation of the deficiency.

Despite public health efforts to cut lead in gasoline, paint, and other sources in the environment, lead exposure continues to pose a significant problem, wrote researcher Debra A. Schaumberg, ScD, MPH,23 with the preventive medicine division at Brigham and Women’s Hospital in Boston.

In fact, “Most adults continue to have substantial body burdens of lead,” she wrote in her report.23 More than 90% of the total body burden of lead is accumulated in the bones, where it is stored. Much evidence has indicated that accumulated lead exposure increases the risk of several chronic disorders, including hypertension and mental decline. Studies have also shown that lead exposure could cause age-related cataracts, the leading cause of blindness and visual impairment worldwide, wrote Schaumberg.

Schaumberg’s study23 involved 642 men—all approximately 69 years old—who had leg bone measurements indicating lead exposure. Researchers also looked at the men’s medical records for information on eye cataracts. Men with the highest levels of lead in their bones had more than a 2.5-fold increased risk of cataracts compared with men with the lowest lead levels.

Lead exposure can damage eye cells in a variety of ways, leading to protein buildup on the lens and interfering with calcium absorption, which keeps the lens clear. Lead has even been found in cataracts removed from eyes. Based on the researchers’ estimates, 42% of cases of cataracts in the study were attributed to lead exposure. 23 Many of the treatment protocols used in this study can be implemented by general medical practitioners who have a Kondrot—Vision Parameters and Alternative Therapies

preventive and functional approach to understanding health and disease. With the expected increase in age-related vision loss due to both macular degeneration and glaucoma, a national movement to arrest or remediate these conditions at early stages can prevent millions in the aging population from disability or blindness, and it can bring the associated social and economic benefits to society. Data are being collected to study the long-term use of these modalities.

CONCLUSIONS These treatment protocols should be considered part of a treatment program for all ocular disease process. Eye health needs to be repositioned within an assessment of general health with the understanding that, with the exception of congenital disorders or accidents, vision decline represents a general diminishment in overall health and results directly from toxicity from both external sources such as air and water, and the internal accumulation of toxic metals; poor nutrition; and other life exposures and habits. The metabolism of the eye is such that this organ is very likely the first part of the body to signal overall health problems. Once this is accepted, a protocol for integrating eye health assessment can become part of an overall health evaluation rather than compartmentalized to specialists, and preventive strategies can be introduced at a time when they will be most effective.

In this article, I demonstrated that certain natural interventions given in a short period can reverse eye disease and improve vision. A long-term study is needed to compare a group with these interventions to a matched group with no interventions.

AUTHOR DISCLOSURE STATEMENT The author received no external funding for this study. Patients had the option to purchase a microcurrent machine, light-therapy equipment, and/or an ozone generator after the program, but the researcher has no financial interest in the manufacturing or distribution of the equipment. The purchase option was offered as a convenience to participants.

REFERENCES 1. Kondrot EC. Healing the Eye the Natural Way: Alternative Medicine and Macular Degeneration. Carson City, NV: Nutritional Research Press; 2001.

2. Goldberg J, Flowerdew G, Smith E, Brody JA, Tso MO. Factors associated with age-related macular degeneration: an analysis of data from the first National Health and Nutrition Examination Survey. Am J Epidemiol. 1988;128(4):700-710.

3. Kryzhanovskiĭ GN, Lipovetskaia EM, Kopp OP. Role of the sympathetic nervous system in the pathogenesis of experimental glaucoma [in Russian]. Biull Eksp Biol Med. 1980;89(5):535-538.

4. Paul EL Jr. The treatment of retinal diseases with micro current stimulation and nutritional supplementation. Paper presented at: International Society for LowVision Research and Rehabilitation (ISSLRR) Low Vision Congress; 2002; Goteborg, Sweden.

5. Michael LD, Allen MJ. Nutritional supplementation, electrical stimulation and age related macular degeneration. J Orthomol Med. 1993;8(3):168-171.

6. Kondrot EC. Ten Essentials to Save Your Sight. Charleston, SC: Advantage; 2012.

7. Bocci VA. Scientific and medical aspects of ozone therapy: state of the art. Arch Med Res. 2006;37(4):425-435.

8. Nguyen QD, Shah SM, Van Anden E, Sung JU, Vitale S, Campochiaro PA. Supplemental oxygen improves diabetic macular edema: a pilot study. Invest Ophthalmol Vis Sci. 2004;45(2):617-624.

9. Riva Sanseverino E, Meduri RA, Pizzino A, Prantera M, Martini E. Effects of oxygen-ozone therapy on age-related degenerative retinal maculopathy.

Panminerva Med. 1990;32(2):77-84.

10. Cheng N, Van Hoof H, Bockx E, et al. The effects of electrical currents on ATP generation, protein synthesis, and membrane transport of rat skin. Clin Orthop Relat Res. 1982;(171):264-272.

Kondrot—Vision Parameters and Alternative Therapies

11. Chan HH, Leung MC, So KF. Electroacupuncture provides a new approach to neuroprotection in rats with induced glaucoma. J Altern Complement Med. 2005;11(2):315-322.

12. Chu TC, Potter DE. Ocular hypotension induced by electroacupuncture. J Ocul Pharmacol Ther. 2002;18(4):293-305.

13. Kondrot EC. Initial results of microcurrent stimulation in the treatment of agerelated macular degeneration. Townsend Lett Doct Patients. 2002;(231):65-67.

14. Kondrot EC. Microcurrent Stimulation: Miracle Eye Cure? Carson City, NV: Nutritional Research Press; 2001.

15. Gottlieb RL, Wallace LB. Syntonic phototherapy. Photomed Laser Surg.

2010;28(4):449-452.

16. Zaretskaya RB. Intraocular pressure of normal and glaucomatous eyes as affected by accessory light stimuli. Am J Ophthalmol. 1948;31(6):721-727.

17. Grunwald JE, Pistilli M, Ying GS, Maguire MG, et al. Comparison of Agerelated Macular Degeneration Treatments Trials. Ophthalmology. 2015 Apr; 122(4):809-816.

18. Glaucoma Research Foundation. Glaucoma medications and their side effects. http://glaucoma.org/treatment/glaucoma-medications-and-their-side-effects. php. Updated July 31, 2013. Accessed June 10, 2015.

19. Haddrill M. Glaucoma treatment: eye drops and other medications. All About Vision Web site. http://www.allaboutvision.com/conditions/glaucoma-3treatment.htm. Updated February 2015. Accessed June 10, 2015.

20. Blair CJ, Ferguson J, Jr. Exacerbation of senile macular degeneration following cataract extraction. Am J Ophthalmol. 1979;87(1):77-83.

21. Klein BE, Howard KP, Lee KE, et al. The relationship of cataract and cataract extraction to age-related macular degeneration: the Beaver Dam Eye Study.

Ophthalmology. 2012;119(8):1628-1633.

22. Levy T. Curing the Incurable: Vitamin C, Infectious Diseases, and Toxins.

Philadelphia, PA: Xlibris Corp; 2002.

23. Schaumberg DA, Mendes F, Balaram M, Dana MR, Sparrow D, Hu H. Accumulated lead exposure and risk of age-related cataract in men. JAMA. 2004;292(22):2750-2754.

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ALTERNATIVE THERAPIES, NOV/DEC 2015 VOL. 21 NO. 6 35

ORIGINAL RESEARCH

Brain-derived Neurotrophic Factor Signaling Pathway: Modulation by Acupuncture in Telomerase Knockout Mice Dong Lin, MD, PhD; Qiang Wu, MD; Xiaoyang Lin, MS; Cesar V. Borlongan, PhD; Zhi-Xu He, MD; Jun Tan, PhD; Chuanhai Cao, PhD; Shu-Feng Zhou, MD, PhD

ABSTRACT Context • Telomerase is a critical enzyme that is involved in aging and cancer and that is thought to be a part of multiple neurological diseases.

Objective • To investigate the telomerase response in the brain to acupuncture, the study examined the levels of expression of brain-derived neurotrophic factor (BDNF) and its downstream signaling molecules, including tyrosine kinase receptor Β (TrkB), p75 neurotrophin receptor (p75NTR), protein kinase B (Akt), extracellular signal-regulated protein kinase (ERK1/2), and nuclear factor κΒ (NF-κΒ).

Design • Both telomerase-deficient (Terc-/-) mice (Terc-/- group) and normal, wild-type (WT) mice (WT group) were randomly assigned to 1 of 3 subgroups, 1 receiving acupuncture (acupuncture subgroup), 1 receiving sham acupuncture therapy (sham subgroup), and 1 receiving no treatment (control subgroup).

Setting • The study occurred at the University of South Florida Health Byrd Alzheimer’s Institute (Tampa, FL, USA).

Intervention • The 2 acupuncture subgroups received acupuncture at the stomach 36 (ST-36) position for 30 min/d for 4 d. For the 2 sham groups, the sham point

Dong Lin, MD, PhD, is an associate professor in the College of Acupuncture, Fujian University of Traditional Chinese Medicine (FUTCM), in Fuzhou, Fujian, China, and is an associate professor in the Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida (USF), in Tampa, Florida. Qiang Wu, MD, is a professor in the College of Acupuncture at FUTCM. Xiaoyang Lin, MS, is a research associate in the Department of Pharmaceutical Sciences, College of Pharmacy, at USF. Shu-Feng Zhou, MD, PhD, is chairman of the Department of Pharmaceutical Sciences, College of Pharmacy, at USF. Cesar V. Borlongan, PhD, is a professor in the Department of Neurosurgery and Brain Repair in the Morsani College of Medicine, at USF. Zhi-Xu He, MD, is a professor in the Guizhou Provincial Key Laboratory for Regenerative Medicine, Stem Cell and 36 ALTERNATIVE THERAPIES, NOV/DEC 2015 VOL. 21 NO. 6

was set at a location approximately 3 mm to the lateral side of the tail on the gluteus muscle following the same schedule.

Outcome Measures • After 4 d, the mice were sacrificed, and the brain tissues were collected. The protein levels in the hippocampus and dentate gyrus (DG) of each mouse were determined by western blotting and immunostaining assays.

Results • The Terc-/- group showed downregulated hippocampal BDNF expression compared with the WT mice. Acupuncture at ST-36 for 4 d upregulated BDNF, TrkB, p75NTR, Akt, and ERK1/2 in the DG and hippocampus of the telomerase-deficient mice, but that result was not seen in the WT mice with normally functioning telomerase.

Conclusions • The use of acupuncture in pathologies associated with telomerase deficiencies, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD), may provide some benefit in terms of eliciting better clinical responses. The research team believes that result occurs through the activation of BDNF and its downstream signaling pathways in populations of patients who exhibit low telomerase activity. (Altern Ther Health Med. 2015;21(6):36-46.)

Tissue Engineering Research Center, and at the Sino-US Joint Laboratory for Medical Sciences, Guiyang Medical University, in Guiyang, Guizhou, China. Jun Tan, PhD, is a professor in the Department of Psychiatry and Behavioral Neurosciences, Silver Child Development Center, Rashid Laboratory for Developmental Neurobiology, at the Morsani College of Medicine, at USF. Chuanhai Cao, PhD, is an assistant professor in the Department of Pharmaceutical Sciences, College of Pharmacy, and assistant professor at USF-Health Byrd Alzheimer’s Institute, at USF.

Corresponding author: Shu-Feng Zhou, MD, PhD E-mail address: szhou@health.usf.edu

Lin—BDNF Modulation by Acupuncture

A

cupuncture functions by inserting needles at specific points around the body, known as acupoints. Each specific acupoint conveys functional specificity when stimulated.1,2 Recent clinical studies have shown therapeutic benefits for both manual acupuncture and electroacupuncture (EA) in the central nervous system (CNS).3,4 It is thought that acupuncture carries out its function through the facilitation of homeostasis.5,6 The acupuncture point used in the current study was the stomach 36 (ST-36) acupoint, also known as the zusanli point, which is located directly below the knee on the anterior tibialis muscle. The ST-36 acupoint has been shown to have several effects on the CNS, such as improving cerebral blood flow via nitric oxide7 while decreasing sympathetic nerve activity and arterial pressure,8 as well as providing analgesic activity9 through an increase in endogenous opiates.10 In recent years, acupuncture has been used as a form of alternative treatment for various neurologic disorders, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and stroke.11,12 Use of the treatment is based on findings that acupuncture can facilitate neurogenesis and promote neuron survival and proliferation in those disease states.13 The hippocampus is known to be the seat of and to play a central role in memory and learning, both of which are deficient in many neurodegenerative pathologies. Animal studies have shown that acupuncture can improve the symptoms of hippocampus-related neuropathologies, and it is thought that the action is accomplished through neuroprotection and induction of neuron proliferation and stem-cell differentiation.14-16 The hippocampus has been found to have a rapid cell turnover and continues to generate neurons in the adult brain.17 Neurogenesis in the adult brain appears to be mainly restricted to the dentate gyrus (DG) and the subventricular zone (SVZ) of the hippocampus.18 Animal studies have shown that neuronal differentiation and cell proliferation in the DG and/or SVZ are significantly augmented by acupuncture treatment.19,20 Moreover, several recent studies have proposed that acupuncture exerts its therapeutic effects via regulation of various signaling pathways. However, only a few studies implicate neurotrophins, such as brain-derived neurotrophic factor (BDNF) or glial cell line–derived neurotrophic factor (GDNF), in the role of acupuncture-induced neuroprotection.

BDNF is a neurotrophin that regulates the growth, renewal, survival, and upkeep of neurons, playing many roles in the function of the CNS.21 The most recent data on the correlation between neurotrophins and acupuncture have shown that EA may relieve certain neuropathological disorders by modulating BDNF and its signaling pathway.

The beneficial effects of acupuncture have been associated with the release of neuropeptides from nerve endings and the modulation of the expression of neurotrophins.22,23 Telomerase is an enzyme that maintains the proper lengths of chromosome ends, also known as telomeres, during successive cell divisions. For some time, telomere Lin—BDNF Modulation by Acupuncture

length has been thought to be related to aging,24-26 and its action is thought to be related to the activity of the telomerase enzyme.27-30 Telomerase deficiencies and shortened telomeres have also been associated with aging-related neurological diseases, such as AD31-33 and PD.34,35 It is believed that the increases in oxidative stress and inflammation during those disease states in turn may cause increases in telomerase deficiencies and in telomere shortening.36,37 The enzyme is expressed at high levels in neural precursor cells in the developing brain and is essential for preserving the characteristics of stem cells and progenitor cells. Overall, telomerase activity plays an important role in regulating brain function.38 Studies have shown that telomerase is regulated by neurotrophins and other proteins in neuronal cells, including BDNF, secreted amyloid precursor protein (sAPP), and insulin-like growth factor (IGF).39,40 It has been reported that telomere shortening can reduce adult DG neurogenesis and impair the maintenance of postmitotic neurons in aged telomerase-deficient (Terc-/-) mice.41,42 BDNF significantly increases telomerase activity via activation of phosphatidylinositol-3 kinase and mitogenactivated protein kinases (MAPK/ERK1/2) in hippocampal neurons.39,43 Acupuncture has been demonstrated to have neuroprotective effects and to promote the expression of BDNF and other neurotrophins in PD, depression, and stroke.44,45 Those diseases are all age related, with patient populations lacking telomerase activity. Given the important role of BDNF in neuron survival, especially in patients lacking telomerase activity, the current research team decided to investigate whether acupuncture could regulate the expression of BDNF and its downstream signaling molecules in Terc-/- mice, in comparison with normal, wild-type (WT) mice. The team believed that the upregulation of BDNF could have neuroprotective effects and wanted to examine that benefit based on the known relationship between BDNF and telomerase activity in a telomerase Terc-/- mouse model.

The team believed it to be possible that acupuncture treatments could prove beneficial in a clinical setting when administered to patients with low telomerase activity.

METHODS Animals The mice deficient for TERC genes were generated by inbreed crossing of heterozygous knockout mice that were backcrossed to naïve C57BL/6J mice for more than 4 generations. That process was performed to ensure that the mice would show the phenotypic problem after 4 generations.

Two strains of 4- to 5-month-old adult mice were used for the current study (ie, WT mice [n = 9] and Terc-/- mice [n = 9], with 3 mice each in 3 subgroups).

The mice were housed in a specifically pathogen-free facility. The mice were given ad libitum access to water and food and were maintained on a 12-hour light/dark cycle. The animal use was approved by the ethics committee of the University of South Florida (Tampa, FL, USA). The sample size for each ALTERNATIVE THERAPIES, NOV/DEC 2015 VOL. 21 NO. 6 37

Figure 1. Experimental design, grouping, and acupuncture procedure. Figure 1A shows the mice in both the WT group and the Terc-/- group were randomly assigned to 1 of 3 treatment subgroups per group (n = 3 per subgroup): (1) controls with no treatment, (2) mice receiving acupuncture on the ST-36 acupoint, or (3) mice receiving a sham operation. Figure 1B shows the acupuncture and sham procedures for the WT and Terc-/- groups. The mice received a 30-min session of acupuncture or sham acupuncture for 4 consecutive days. Then the brain tissues were collected, and the levels of BDNF, TrkB, ERK1/2, and p75NTR in the hippocampus and DG were analyzed using the immunehistostaining and western blotting methods.

A

Genotyping test

Terc-/- mice

WT mice

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Western blotting assay

Abbreviations: WT, wild type; Terc-/-, telomerase deficient; ST-36, stomach 36; BDNF, brain-derived neurotrophic factor; TrkB, tyrosine kinase receptor B; ERK1/2, extracellular signal-regulated protein kinase; p75NTR, p75 neurotrophin receptor; DG, dentate gyrus. group was small due to difficulty in breeding the mice. In crossbreeding the mice within homozygous, the Terc-/- mice were no longer able to breed after 3 generations, and that issue limited the number of homozygous Terc-/- mice available for study.

Procedures Reagents and Chemicals. Monoclonal antibodies against protein kinase Β (Akt), extracellular signal-regulated protein kinase (ERK1/2), and p75 neurotrophin receptor (p75NTR) were purchased from Cell Signaling Technology (Danvers, MA, USA). The antibody to BDNF was obtained from Thermo Fisher Scientific (Waltham, MA, USA). The antibody to tyrosine kinase receptor Β (TrkΒ) was purchased from BD Bioscience (San Jose, CA, USA). Anti-β-actin antibody was purchased from Santa Cruz Biotechnology (Dallas, TX, USA). In addition, a 0.45-μm, polyvinylidene fluoride (PVDF) membrane was obtained from Invitrogen (Carlsbad, CA, USA).

Genotyping Using Polymerase Chain Reaction. The mice in both the WT group and the Terc-/- group were purchased from Jackson Laboratory (Bar Harbor, ME, USA). The mice were genotyped to confirm the genetic modifications. The genomic deoxyribonucleic acid (DNA) from leukocytes was used for the polymerase chain reaction (PCR) amplification.

38 ALTERNATIVE THERAPIES, NOV/DEC 2015 VOL. 21 NO. 6

Intervention The mice in both the WT group and the Terc-/- group were randomly assigned to 1 of 3 subgroups, 3 mice to each subgroup per group (Figure 1): (1) the control subgroup, (2) an intervention (acupuncture) subgroup that received acupuncture at the acupoint ST-36, and (3) an intervention group (sham subgroup) that received a sham operation at a sham point that was set at a location approximately 3 mm to the lateral side of the tail on the gluteus muscle.

ST-36 is reported to regulate brain function and modulate neuron proliferation and differentiation of progenitor cells in animals.46 ST-36 is located between the tibia and fibula, lateral to the distal end of the cranial tuberosity of the tibia. The transpositional method was used to determine the location of ST-36 in the mice as previously reported by Yin et al.47 In the acupuncture and sham groups, the animals were immobilized by gentle plastic restraints to minimize stress.

A small acupuncture needle (0.30 mm × 13 mm) from Suzhou Hua Tuo Medical Instrument Co (Suzhou, China) was used. Acupuncture at ST-36 and the sham procedure were performed by a licensed acupuncturist by inserting a pair of stainless steel pins to a depth of 1.5 mm into ST-36 in the mice.

Lin—BDNF Modulation by Acupuncture

In the practice of acupuncture, the needle is slowly rotated every 5 minutes for a total of 30 minutes per day, and the procedure generally occurs for 4 consecutive days. The current research team also chose the period of 4 days to study the immediate effects of the acupuncture treatment on the selected biochemical pathways. In other studies, the researchers were unable to find changes in levels of BDNF expression after acupuncture treatment for a 5-day period,48 but in the current study, the mice were treated for only 4 days. In choosing a shorter treatment time, the authors were able to study the immediate and short-term changes BDNF might have on the system.

After the 4 days, the mice were sacrificed, and the brain tissues were collected after intracardial perfusion with saline.

The brain samples were halved for each of the subjects and one-half was separated out for protein preparation, and the rest of the sample was fixed with 4% paraformaldehyde for further analysis.

Outcome Measures Western Blotting Analysis. The levels of BDNF, Akt, and ERK1/2 of in the brain tissues of the mice were detected using a western blotting assay, as described by Lai et al.49 Briefly, the brain samples were homogenized in protein lysis buffer (RIPA), and equal amounts of protein (40 μg) were subjected to the 10% sodium dodecyl sulfate (SDS)-polyacrylamide gel for protein separation. The resolved proteins were transferred electrophoretically onto a 0.45-μm, PVDF membrane, and immunoblotting was performed using antibodies against BDNF (1:1000), Akt (1:1000), and ERK1/2 (1:10 000). β-Actin was used as the internal control (1:100 000). The experiment was performed in triplicate.

Immunohistochemical Analysis. The levels of BDNF, TrkΒ, ERK1/2, and p75NTR in the mouse-brain tissues were determined using immunohistochemistry, as described previously by Luo et al.50 Briefly, mouse brains were collected and fixed overnight in freshly prepared 4% paraformaldehyde in phosphate-buffered saline (PBS). The brain samples were sliced sagittally into 25-μm sections, permeabilized with 0.2% lysine, 1% Triton X-100 in PBS solution, and incubated with an appropriate primary antibody—BDNF, 1:6000; TrkB, 1:3000; p75NTR, 1:3000; and ERK1/2, 1:4000.

Sections were washed in PBS and incubated with a corresponding biotinylated secondary antibody. Finally, sections were stained using 0.05% diaminobenzidine and 0.03% H2O2. The tissue sections were mounted onto slides, dehydrated, and coverslipped. Images of the stained sections were obtained using a Zeiss Mirax-scan 150 microscope (Carl Zeiss Microscopy GmbH, Jena, Germany) and Image Analysis software v1.0 (NIH, Bethesda, MD, USA). The areas of positive stains in each hippocampal and cortex section were analyzed.

Statistical Analysis Data are expressed as the mean ± SD. When analyzing groupings between the 2 strains of mice, the research team Lin—BDNF Modulation by Acupuncture

used a 2-group t test, and multiple-group studies among 1 strain of mice were analyzed with 1-way analysis of variance (ANOVA), followed by the Tukey HSD post hoc test using Prism 6.0 (GraphPad Software, San Diego, CA, USA).

The level of statistical significance was deemed to be P < .05.

RESULTS BDNF Expression BDNF was downregulated in the Terc-/- group and was not affected in the hippocampus by acupuncture. The research team observed that the expression level of BDNF in the hippocampus of Terc-/- mice in all subgroups, as determined by western blotting analysis, was significantly decreased compared with the WT mice in all subgroups (P < .001). The hippocampal BDNF levels in the Terc-/- group were 2.2-fold lower than those in the WT group. In the initial assessment of the hippocampi in all of the WT and Terc-/- mice, both the acupuncture therapy at ST-36 and the sham acupuncture, when performed for 4 days, did not change the hippocampal expression level of BDNF (Figure 2).

Acupuncture and BDNF Acupuncture at ST-36 upregulated the BDNF in the DG of the Terc-/- group but not in that of the WT group. Due to the functional importance of DG, the research team looked closer at that area of the hippocampus in both the WT and the Terc-/- mice to study the BDNF levels in it, using immunohistochemistry.

In the DG, BDNF-immunoreactive cells were located at the subgranular zone of the mouse brains. In the WT group, the BDNF level in the DG, as indicated by the percentage for the BDNF-positive area (4.03%), was significantly higher than that in the Terc-/- group (0.30%)—approximately 13-fold higher (0.30% vs 4.03%; P < .05). See Figure 3.

In investigating whether acupuncture modulated BDNF expression in the DG of the WT and Terc-/- mice, the research team found that receipt of acupuncture at ST-36 for 4 days resulted in a significantly increased expression of BDNF in DG for the Terc-/- mice in the acupuncture subgroup, when compared with the control subgroup, P < .05 (Figure 3).

However, statistical significance was not achieved when comparing the ST-36 and the sham groups, but the acupuncture performed for 4 days was found to increase BDNF levels by 144% in the acupuncture subgroup of the Terc-/- mice, P < .05 (Figure 3).

Acupuncture and TrkB and p75NTR Acupuncture at ST-36 upregulated both TrkB and p75NTR in the DG of the Terc-/- group but not in that of the WT group. Because BDNF exerts it biological effects via binding to the high-affinity TrkB and the low-affinity p75NTR,51 the research team next examined the expression levels of TrkB and p75NTR in the DG in the Terc-/- and WT mice, with and without acupuncture therapy. In the WT and Terc-/- mice, the basal levels of TrkB and p75NTR in the DG of the control groups were comparable.

ALTERNATIVE THERAPIES, NOV/DEC 2015 VOL. 21 NO. 6 39

Figure 2. Representative blots of BDNF in the hippocampus of WT and Terc-/- mice. Figure 2A shows the BDNF in each of the 3 mice in each subgroup in the 2 groups, which was determined using western blotting analysis. β-Actin was used as the internal control. Figure 2B compares the BDNF levels in the same subgroups for the 2 types of mice. Data are the mean ± SD. The data were analyzed using a 2-group t test.

A Control Acupoint Sham 1 WT mice

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Abbreviations: BDNF, brain-derived neurotrophic factor; WT, wild type; Terc-/-, telomerase deficient; SD, standard deviation.

0.0 Control

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P < .001, WT vs Terc-/- mice.

Level of BDNF (area %)

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Figure 3. Representative immunohistochemistry images for BDNF determination in the DG of WT and Terc-/- mice that were treated with acupuncture or sham acupuncture (n = 3 per subgroup). BDNF-positive cells were counted in the DG, and the data are shown as the area %. The 2 control subgroups received no treatment. In Figure 3A, the inserted images in each photo represent the amplified area that was analyzed for BDNF level. In Figure 3B, the bar graph represents the BDNF level determined as the area % in both strains of mice. Data are the mean ± SD. For multiple-genotype group comparisons, the research team used a 2-group t test.

For single-genotype group comparisons, data were analyzed using 1-way ANOVA followed by Turkey’s test of multiple comparisons.

A B Terc-/- mice WT mice 15 a a

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Ac up oi nt

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Ac up oi nt Co nt ro l

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Abbreviations: BDNF, brain-derived neurotrophic factor; DG, dentate gyrus; WT, wild type; Terc-/-, telomerase deficient; SD, standard deviation; ANOVA, analysis of variance. a

P < .05, WT vs Terc-/- mice.

40 ALTERNATIVE THERAPIES, NOV/DEC 2015 VOL. 21 NO. 6

Lin—BDNF Modulation by Acupuncture

Figure 4. Immunohistochemical staining for TrkΒ- and p75NTR-positive cells in the DG of the WT and Terc-/- mice (n = 3 per subgroup). TrkΒ- or p75NTR-positive cells were counted in the DG. The 2 control subgroups received no treatment. In Figure 4A, the inserted images in each photo represent the amplified area analyzed for TrkB and p75NTR level.

In Figure 4B, the bar graphs represent the levels of TrkΒ and p75NTR determined as the area % in both strains of mice. Data are the mean ± SD. For multiple-genotype group comparisons, the research team used a 2-group t test. For single-genotype group comparisons, data were analyzed using 1-way ANOVA followed by Turkey’s test of multiple comparisons.

A

TrkB Terc-/- mice

WT mice

WT mice

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p75NTR

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60 40 20

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0

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a

Sh am

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100

Co nt ro l

Level of p75NTR (area %)

15 Level of TrkB (area %)

a a

Terc-/- mice

Abbreviations: TrkB, tyrosine kinase receptor B; p75NTR, p75 neurotrophin receptor; DG, dentate gyrus; WT, wild type; Terc-/-, telomerase deficient; SD, standard deviation; ANOVA, analysis of variance. a

P < .05, WT vs Terc-/- mice.

Lin—BDNF Modulation by Acupuncture

ALTERNATIVE THERAPIES, NOV/DEC 2015 VOL. 21 NO. 6 41

In the Terc-/- group, acupuncture at ST-36 for 4 days significantly increased TrkB and p75NTR levels in the DG compared with those of the control mice (Figure 4), and the Terc-/- mice receiving sham acupuncture showed no changes in the levels of either neuroreceptor. Both acupuncture and sham acupuncture had no significant effect on the levels of TrkB and p75NTR in the DG of the WT mice (Figure 4).

Acupuncture and ERK1/2 and Akt Acupuncture at ST-36 upregulated ERK1/2 in the DG of the Terc-/- group and showed minimal or mixed results in the hippocampus. BDNF binds to its receptor, TrkB, and consequently activates the ERK1/2 and phosphoinositide 3-kinase and protein kinase B (PI3K/Akt) pathways.51,52 Therefore, the research team determined the levels of ERK1/2 and Akt using immunostaining (Figure 5A) and western blotting assays (Figure 5C) in the DG of the WT and Terc-/mice, with and without acupuncture. In the Terc-/- group, acupuncture at ST-36 for 4 days significantly increased the expression level of ERK1/2, as determined by immunohistochemistry, when compared with the control and sham groups, P < .05 and P < .01, respectively. However, neither acupuncture nor sham therapy significantly altered the level of ERK1/2 in the DG of the WT mice (Figure 5A and Figure 5B).

The research team also measured the hippocampal levels of Akt and ERK1/2 in the WT and Terc-/- mice, with and without acupuncture treatment. In the Terc-/- group, a significant difference existed in the level of Akt between the acupuncture and sham subgroups when compared with the 2 respective subgroups for the WT group (Figure 5C and Figure 5D). In WT mice, the sham and normal acupuncture treatments decreased the hippocampal expression of Akt compared with the control subgroup. With regard to hippocampal ERK1/2 expression in the Terc-/- group, the sham treatment increased the level compared with the control subgroup, but the acupuncture subgroup showed a significant increase, 25% to 38%, over the control subgroup.

Acupuncture and NF-κB The research team observed acupuncture therapy at ST-36 for 4 days did not significantly alter hippocampal levels of NF-κΒ in either the Terc-/- or the WT mice (Figure 6).

DISCUSSION In the current study, the research team observed the hippocampal expression of BDNF was significantly decreased in Terc-/- group compared with the WT group. The result may indicate that the basal expression of BDNF in the hippocampus may have a close relationship with the telomerase enzyme.

Previous studies that have supported that finding have found that adult Terc-/- mice had a remarkable reduction in neurogenesis of the SVZ, and telomerase shortening disrupted neural stem-cell proliferation, neuronal differentiation, and neurogenesis. 42,53 Another study by Fu et al39 had demonstrated telomerase mediates effects promoting the cell survival of 42 ALTERNATIVE THERAPIES, NOV/DEC 2015 VOL. 21 NO. 6

BDNF and sAPP in developing hippocampal neurons.

Currently, the exact mechanism is unknown as to how telomerase is related to BDNF expression.

On its initial examination of hippocampal and DG expression levels of BDNF, the current research team found significantly higher levels of BDNF in the WT mice in all subgroups compared to the Terc-/- mice in all subgroups (Figure 2). When the team examined results for the mice treated with acupuncture for 4 days, it found significant increases in the BDNF levels in the DG of the Terc-/- mice but not in that of the WT mice (Figure 3). However, those changes did not occur in the hippocampus of the mice.

It appears the Terc-/- mice are more sensitive to acupuncture therapy compared with WT mice with regard to BDNF reregulation in the DG. The results of the current study, although limited, also may suggest that acupuncture and its effects may be beneficial in telomerase-deficient genotypes and pathologies. Where a genotype, or in the case of pathology, where a certain disease causes an individual to have less-efficient telomerase, that situation may make the person more receptive in terms of the effects of acupuncture treatment on BDNF-expression levels.

A number of previous studies have shown acupuncture significantly induced the production of BDNF and other neurotrophins in the hippocampus and DG in diseased animal models.54-57 The research team reasons that acupuncture may not have induced BDNF expression in the hippocampus in the current study as compared with those previous studies due to discrepancies between their protocols. The lack of correspondence may be due to differences in (1) the studied animal species, with the current study using mice and the other studies using rats, cats, or other animal models; (2) the age of the animals, with the mice in the current study being relatively young at 4 to 5 months old; (3) the acupuncture therapy regimens (ie, the specific acupoint, duration, and procedure); and (4) the status of disease progression at the time of the acupuncture treatment. It has not been uncommon in studies to find no change in the expression levels of BDNF.48 The research team also believes that the Terc-/- mice used in the current study were more sensitive to the acupuncture treatment than were the WT mice.

To check whether acupuncture-induced upregulation of BDNF in Terc-/- mice affected the expression of its downstream signaling molecules, the current research team further determined the expression levels of TrkB, p75NTR, Akt, ERK1/2, and NF-κB in the DG and hippocampi of Terc-/mice in comparison with those of their WT counterparts.

The current study has demonstrated that acupuncture at ST-36 for 4 days significantly increased the expression of both TrkB and p75NTR in the DG of Terc-/- mice but not that of WT mice (Figure 4). An explanation of that difference may be that the prior study examined only the level of BDNF, an upstream molecule of these signaling molecules that are involved in a number of different pathways.

In the current study, the team found a significant decrease in the level of BDNF expression between the WT Lin—BDNF Modulation by Acupuncture

Figure 5. Immunohistochemistry and western blot analysis of ERK1/2 and Akt in the DG of the WT and Terc-/- mice (n = 3 per subgroup). ERK1/2-positive cells were counted in the DG (Figure 5A). The 2 control subgroups received no treatment. The inserted images in each photo represent the amplified area analyzed for ERK1/2 level. Figure 5B represents the level of ERK1/2 determined as the area % in both strains of mice. Figure 5C shows the ERK1/2 and Akt in each of the 3 mice in each subgroup, which was determined using western blotting analysis. The bar graphs in Figure 5D represent the levels of ERK1/2 and Akt in the DG from for the mice treated with acupuncture and sham acupuncture in both strains. Data are the mean ± SD. For multiple-genotype group comparisons, the research team used a 2-group t test. For single-genotype group comparisons, data were analyzed using 1-way ANOVA followed by Turkey’s test of multiple comparisons.

Terc-/- mice

WT mice

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Akt ERK1/2 β-Actin Akt ERK1/2 β-Actin

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a

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a

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b

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Abbreviations: ERK1/2, extracellular signal-regulated protein kinase; Akt, protein kinase B; DG, dentate gyrus; WT, wild type; Terc-/-, telomerase deficient; SD, standard deviation; ANOVA, analysis of variance. a

P < .05, WT vs Terc-/- mice.

P < .01, WT vs Terc-/- mice.

b

Lin—BDNF Modulation by Acupuncture

ALTERNATIVE THERAPIES, NOV/DEC 2015 VOL. 21 NO. 6 43

Figure 6. Effect of acupuncture at ST-36 on the expression level of NF-κΒ in the hippocampi of WT and Terc-/- mice (n = 3 each subgroup). Mice were treated with acupuncture at ST-36 or with sham acupuncture for 4 days and then sacrificed.

The hippocampal level of NF-κΒ was determined using a western blotting assay (Figure 6A). Figure 6B shows the NF-κΒ levels in the subgroups for the 2 types of mice. Data are the mean ± SD of 3 mice.

B

2

3

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3 65 kDa 45 kDa 65 kDa 45 kDa

NF-κΒ β-Actin NF-κΒ β-Actin

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0.8 Relative Level of NF-κΒ

A

WT mice

Abbreviations: ST-36, stomach 36; NF-κΒ, nuclear factor κΒ; WT, wild type; Terc-/-, telomerase deficient; SD, standard deviation.

Figure 7. Proposed mechanism for the effect of acupuncture on the BDNF/TrkB/p75NTR signal pathway in WT and Terc-/- mice. In the current study, the research team observed acupuncture increased the expression of BDNF, TrkB, Akt, ERK1/2, and p75NTR in the DG, suggesting acupuncture on the ST-36 acupoint can activate the PI3K/Akt and MEK/ERK1/2 signaling pathways via TrkB upregulation. The latter is a high-affinity catalytic receptor for several neurotrophins that induce the activation of downstream, survival signaling pathways of neurons. That action ultimately leads to neuron survival and promotes neurogenesis.

ST-36 acupoint

BDNF BDNF

TrkB

p75NTR Neuroprotection

NF-κΒ

Akt

ERK1/2

Neuron survival

e bran m e ear m

l Nuc

Gene transcription

Abbreviations: BDNF, brain-derived neurotrophic factor; TrkB, tyrosine kinase receptor B; p75NTR, p75 neurotrophin receptor; WT, wild type; Terc-/-, telomerase deficient; Akt, protein kinase B; ERK1/2, extracellular signal-regulated protein kinase; DG, dentate gyrus; ST-36, stomach 36; PI3K/Akt, phosphoinositide 3-kinase/protein kinase B; NF-κΒ, nuclear factor κΒ.

44 ALTERNATIVE THERAPIES, NOV/DEC 2015 VOL. 21 NO. 6

Lin—BDNF Modulation by Acupuncture

control and the Terc-/- control groups; however, those results were not replicated in the downstream signaling molecules.

Although BDNF significantly decreased in the Terc-/- mice, this significance was not seen to be the case with the ERK1/2 and Akt pathways. That result may be due to other higherlevel factors influencing those molecules.

The current research team also notes the slight decreases in BDNF in the current study could still have affected the overall chain of events for the signaling pathway, because a small change at the top of a pathway may have larger effects toward the bottom. The team also found the sensitivity of the molecules to BDNF was increased in the acupuncture subgroup of the Terc-/- group, which is shown in Figure 4 and Figure 5. As BDNF increased in the Terc-/- mice, the research team found a corresponding increase in the signaling molecules after acupuncture treatment.

In terms of the signaling pathways, on binding of BDNF to TrkB and p75NTR, the downstream signaling pathway is activated.51 An example of that pathway is shown in Figure 7.

To date, no reports have appeared in the literature on the effect of acupuncture therapy on brain expression of TrkB and p75NTR. One study by Manni et al58 has revealed EA did not modulate the ovary expression of p75NTR in rats with steroidinduced polycystic ovaries. The mechanisms for the upregulation of both TrkB and p75NTR by acupuncture in Terc-/- mice are unknown but may be associated with the upregulated BDNF and other pathways.

The current research team observed acupuncture at ST-36 for 4 days also upregulated the level of ERK1/2 in the DG of the Terc-/- mice but not in that of the WT mice. Several previous studies have shown that acupuncture therapy can induce ERK1/2 and modulate its phosphorylation in animal models.59-63 The present study has demonstrated that the upregulation of ERK1/2 in the DG of mice by acupuncture is genotype dependent (ie, dependent on a genotype or pathology with telomerase deficiencies).

In the current study, the research team also found acupuncture at ST-36 for 4 days significantly increased hippocampal Akt levels in the acupuncture subgroup compared with those of the sham subgroup in Terc-/- mice.

Several previous animal studies have revealed acupuncture can elicit neuroprotective effects via modulation of the PI3K/Akt pathway.64-66 It is known that telomerase can regulate Akt, but it is unknown how acupuncture can upregulate Akt in telomerase-deficient mice. In the literature, no reports exist on the effects of telomerase on the expression of ERK1/2.

In the current study, acupuncture did not alter hippocampal expression of NF-κB in either Terc-/- or WT mice (Figure 6). It appears the NF-κB pathways may play a less important role in acupuncture-induced neuroprotection.

It is worth mentioning the current study’s results show consistency among all parameters (BDNF, TrkB, and p75NTR) measured throughout the whole study, even though it had only a small sample size of 3 mice in each subgroup. The consistent results highlight the importance of telomerase in neuronal function and its relationship with acupuncture Lin—BDNF Modulation by Acupuncture

stimulation. With further experimentation, the current research team hopes to uncover that relationship further. The team hopes that its results will initiate more interest in studying the function of acupuncture and expanding the findings that the current study has made, and, thereby, lead to a nonpharmacological treatment for neurological disease.

CONCLUSIONS The Terc-/- mice in all subgroups had downregulated hippocampal BDNF expression compared with that of the WT mice in all subgroups. Acupuncture at ST-36 for 4 days upregulated BDNF, TrkB, p75NTR, Akt, and ERK1/2 in the DG of the Terc-/- group but not that of the WT group. In the current study, acupuncture therapy did not significantly change the levels of hippocampal NF-κB in either the WT or Terc-/- strains of mice.

Given the critical role of BDNF and the sensitivity of its signaling molecules in terms of neuroprotection and neuron survival, acupuncture-induced activation of BDNF in mice may be influenced by the genotype. Based on the increase in BDNF levels in the current study, genotypes displaying absent or reduced telomerase activity, such as the the Terc-/mice, may benefit more from acupuncture treatment than those with normal telomerase activity. Patients with neurological disease states, showing increased levels of telomerase deficiencies due to oxidative stress and inflammation, may display a better clinical response and overall may be more sensitive to the changes that acupuncture can provoke.

ACKNOWLEDGEMENTS The work discussed in the current article was supported by the National Natural Science Foundation of China (grant No. 81273672); the Fujian Province Health Planning Commission project of China in the training of young talents in 2014 (2014-ZQN-JC-28); and the startup fund from the College of Pharmacy, University of South Florida, Tampa, FL, USA. The authors also thank Kyle Sutherland for his contributions in the preparation of the manuscript.

AUTHOR DISCLOSURE STATEMENT The authors declare that they have no competing financial interests.

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REVIEW ARTICLE

Compound Formulas of Traditional Chinese Medicine for the Common Cold: Systematic Review of Randomized, Placebo-controlled Trials Guanhong Li, MD; Linli Cai, MS; Hongli Jiang, MD; Shoujin Dong, MD; Tao Fan, MD; Wei Liu, MD; Li Xie, MD; Bing Mao, MS

ABSTRACT Context • The common cold is one of the most frequent acute illnesses of the respiratory tract, affecting all age groups. The compound formulas of traditional Chinese medicine (TCM) are frequently used to treat the common cold in China and other parts of the world. Until now, however, the efficacy and safety of compound formulas of TCM for the common cold, studied in comparison with placebos, have not been systematically reviewed.

Objectives • This literature review intended to assess existing evidence of the effectiveness and safety of compound formulas of TCM for the common cold.

Design • Randomized, controlled trials (RCTs) comparing compound formulas of TCM with placebos in treating the common cold were included, regardless of publication status. The research team searched the Cochrane Library, PubMed, Embase, the Chinese Biomedical Literature Database, the Chinese Scientific and Technological Periodical Database, the Chinese National Knowledge Infrastructure and the Wangfang Database from their inceptions to December 2013. The team also searched Web sites listing ongoing trials and contacted experts in the field and relevant pharmaceutical companies to locate unpublished materials.

Outcome Measures • Two review authors independently extracted data and assessed the methodological quality of included studies, using the Cochrane risk of bias tool.

Guanhong Li, MD; Linli Cai, MS; Hongli Jiang, MD; Shoujin Dong, MD; and Wei Liu, MD, are graduate students in the Department of Integrated Traditional Chinese and Western Medicine at West China Hospital, West China Medical School, Sichuan University, in Chengdu, China. Tao Fan, MD, is an attending doctor in the Department of Integrated Traditional Chinese and Western Medicine at West China Hospital, West China Medical School, Sichuan University, in Chengdu, China. Li Xie, MD, is an assistant professor in the Third Department of Internal Medicine, Sichuan Second Hospital of TCM, in Chengdu. Bing Mao, MS, is professor in the Department of Integrated Traditional 48 ALTERNATIVE THERAPIES, NOV/DEC 2015 VOL. 21 NO. 6

Main Results • A total of 6 randomized, double-blind, placebo-controlled trials involving 1502 participants were included. Most trials had a low risk of bias. Five were conducted in mainland China and 1 in Hong Kong; 5 were multicenter clinical trials and 1 was a single-center trial; 4 were published in Chinese and 2 were published in English.

Compound formulas of TCM were superior to placebos in reducing disease symptoms, inducing recovery from a TCM syndrome, and increasing quality of life. In addition, the formulas were superior in shortening the duration of the main symptoms, the amount of time for a decline in temperature of at least 0.5°C to occur, and the duration of any fever. The team did not perform a summary meta-analysis due to clinical heterogeneity. No serious adverse event (AE) occurred in either the treatment or the control groups.

Conclusions • This systematic review indicated that compound formulas of TCM, compared with placebo, can provide benefits to patients with the common cold, with no serious side effects having been identified in the included trials. However, due to the small number of included studies and of participants and the unclear risk of some biases in the included studies, more high-quality, large-scale RCTs are still warranted to clarify fully the effectiveness and safety of compound formulas of TCM in treating the common cold. (Altern Ther Health Med. 2015;21(6):48-57.)

Chinese and Western Medicine at West China Hospital, West China Medical School, Sichuan University, in Chengdu, China.

Corresponding author: Bing Mao, MS E-mail address: maobing@medmail.com.cn

T

he common cold is an upper respiratory tract infection (URTI) and is one of the most common diseases, occurring in all ages. According to the US National Center for Health Statistics, 62 million cases of this mild Li—TCM for Common Cold

URTI occur each year.1 It is almost always a viral illness; although rhinoviruses cause 30% to 50% of colds throughout the year and 80% of colds during the peak season, up to 200 other viruses have been implicated.2 On average, colds affect adults 2 to 4 times per year.3 The common cold presents acute symptoms, such as cough, runny nose, sneezing, sore throat, hoarse voice, fever, chill, muscle pain, and headache. Despite being benign in nature, such symptoms can last for several days and cause 40% of all days of missed work.4 Moreover, various complications may occur with a cold, including suppurative pharyngitis, sinusitis, otitis media, bronchitis, exacerbations of asthma, chronic obstructive pulmonary disease, and acute progression or deterioration of underlying respiratory diseases. The probability of complications increases in the elderly and in patients with chronic heart, lung, kidney, or cerebral diseases or with a compromised immunity. The high incidence and clinical presentation represent a substantial economic burden, due to work absences, visits to physicians, and over-the-counter drug consumption.5 Despite the heavy burden that the common cold presents, no effective etiological treatment and few preventive strategies have been proven. Nonsteroidal, anti-inflammatory drugs (NSAIDs) may reduce pain and fever but not the overall duration or severity of a cold,6 and antiviral drugs, such as oseltamivir, only reduce symptom duration by 0.55 days in otherwise healthy adults.7 Because the common cold is usually caused by respiratory viruses, no role exists for antibiotics in treatment of the common cold. Although vaccination of healthy adults prevents influenza, it reduces the incidence of acute respiratory infections by only 16% and of work absenteeism by only 0.13 days.8 Therefore, it is imperative to develop more effective and safe drugs for patients with colds. Traditional Chinese medicine (TCM), a holistic system of medicine that is more than 2000 years old, has been used both for extensive treatment and for prevention of disease, including for the common cold. Several generations of TCM practitioners have developed several compound formulas for treating the common cold, which are prepared in various forms, such as tablets, pills, powders, capsules, and oral liquids. The Chinese Pharmacopeia 20109 documents 56 compound formulas of TCM for the common cold.10 After the outbreak of severe acute respiratory syndrome in late 2002, TCM has attracted more attention from researchers who endeavor to search for effective antiviral agents. TCM may be a good candidate, with special characteristics as an antivirus therapy.11 The treatment of the common cold in TCM is based on syndrome differentiation. According to TCM theories, the common cold is generally considered to be an exterior syndrome, which can be divided further into 3 types (ie, wind-cold, wind-heat, and summer-heat dampness). The exterior syndrome in the common cold is due to invasion by external pathogenic factors of the 3 types. Sometimes the common cold can occur in patients who suffer from other syndromes. For instance, if a patient with qi deficiency is Liâ&#x20AC;&#x201D;TCM for Common Cold

exposed to wind cold, the syndrome is regarded as a qi-deficiency syndrome, complicated by an exterior wind-cold syndrome.

For the past 2 decades, randomized, double-blind, placebo-controlled, clinical trials have been considered the general standard in clinical research on therapeutic interventions.12 Most previous studies on TCM have focused on individual herbs, which is inconsistent with TCM principles, as pointed out by the World Health Organization.13 For the past few years, an increasing number of randomized, controlled trials (RCTs) of compound formulas of TCM have been designed and implemented.14 Zhang et al15 and Wu et al16 both conducted systematic reviews on studies that focused on the use of TCM to treat the common cold, as compared with Western medicine, and concluded that TCM could accelerate the onset time of lowered body temperature and improve the symptoms of the common cold, without any significant adverse reactions. Chen et al17 performed a systematic review on Chinese patent medicines (CPMs) for the common cold and concluded that some CPMs have shown a potential positive effect on the common cold in terms of the cure rate. Up to now, however, no systematic review has been conducted to investigate the efficacy and safety of compound formulas of TCM, as compared with placebo, in the treatment of the common cold. Thus, the aim of the current systematic review was to provide evidence on the benefits and harms of compound formulas of TCM for the common cold, compared with placebo.

METHODS Research Protocol All procedures were performed according to a predefined protocol, which included the searched databases, a detailed research question, search strategies, and eligibility criteria.

According to the PICO (P, participants/patients; I, intervention; C, comparisons; O, outcomes) approach, a detailed research question consists of a study design, patientsâ&#x20AC;&#x2122; characteristics, interventions, comparisons, and outcomes.

Search Strategy The research team searched for RCTs in the following electronic databases: the Cochrane library, PubMed, Embase, the Chinese Biomedical Literature Database, the Chinese Scientific and Technological Periodical Database, the Chinese National Knowledge Infrastructure, and the Wanfang Database, from their inceptions to December 2013. The team searched for ongoing, registered, clinical trials on the Web sites of the Chinese Clinical Trial Registry18 and the International Clinical Trials Registry by the US National Institutes of Health (NIH).19 Searches for relevant conference proceedings in the China Important Conference Papers Database and for unpublished literature (eg, pharmaceutical companiesâ&#x20AC;&#x2122; unpublished studies) were also performed.

Meanwhile, the team also searched the reference lists of reviewed articles and identified RCTs from any possible titles that matched the inclusion criteria and contacted experts in the field. The following search terms were used individually ALTERNATIVE THERAPIES, NOV/DEC 2015 VOL. 21 NO. 6 49

or in combination: common cold, cold, acute URI, Chinese herbal medicine, TCM, Chinese herb, herb, herb medicine, clinical trial, RCT, and placebo. The team restricted the language to English and Chinese. Only data available in full text were reviewed.

Inclusion Criteria Types of Studies. Only RCTs of compound formulas of TCM for the common cold were included. If a trial did not report the outcomes for which the team was looking, its members contacted the trial’s authors to ask for additional information; the trials were excluded if this information was not obtained.

Types of Participants. Studies of patients with the common cold were eligible if participants (1) were at least 18 years old; (2) had a diagnosis of the common cold from a respiratory expert according to relevant criteria; (3) were within 96 hours of onset of at least 1 symptom of the common cold, such as fever, cough, running nose, nasal obstruction, sore throat, or sneezing; and (4) were able to understand and sign written informed consent. Studies were excluded if the participants (1) suffered from acute viral pharyngitis or laryngitis, acute conjunctivitis, acute tonsillitis, etc; (2) had taken any medication for relief of symptoms before evaluation for entry into the study; (3) were on an analgesic or anti-inflammatory regimen requiring treatment with analgesics, NSAIDs, or steroids; (4) were pregnant or nursing or a woman of childbearing potential who was not practicing adequate contraception; (5) had a history of cancer, liver disease, diabetes mellitus, immunodeficiency, asthma, allergic rhinitis, cystic fibrosis, chronic bronchopulmonary diseases, drug or alcohol abuse, or allergy to food additives or the study’s medications; or (6) were participating or had participated in another drug’s clinical trial within the 3 months prior to the current study.

Types of Interventions. Studies comparing compound formulas of TCM with placebos were included. Any form of administration of compound formulas of TCM, such as a decoction, capsule, tablet, pill, or powder was eligible for inclusion. Studies were excluded when Chinese herbs or other TCM therapies were used in the control group.

Types of Outcome Measures. The primary outcome measures included reduction in disease symptoms and the extent of recovery from the TCM syndrome. The secondary outcome measures included the duration of the main symptoms, the amount of time for a decline in temperature of at least 0.5°C and the duration of any fever, and a measure of health-related quality of life. The 2 primary outcome measures were assessed according to the Guiding Principle of Clinical Research on New Drugs of Traditional Chinese Medicine (Trial Implementation),20 using a scale of 4 levels (ie, totally recovered, markedly effective, effective, and ineffective).

The criteria for reduction in disease symptoms included (1) totally recovered—normalization of body temperature and disappearance of all cold symptoms after 3 days of treatment; (2) markedly effective—normalization of body 50 ALTERNATIVE THERAPIES, NOV/DEC 2015 VOL. 21 NO. 6

temperature and disappearance of most cold symptoms after 3 days of treatment; (3) effective—a decrease in body temperature and disappearance of some cold symptoms after 3 days of treatment; (4) ineffective—no decrease or an increase in body temperature, without any improvement of the cold symptoms after 3 days of treatment.

The criteria for recovery from the TCM syndrome included (1) totally recovered—disappearance of the clinical symptoms and signs and reduction in the TCM-syndrome score of more than 95%; (2) markedly effective—significant improvement in the clinical symptoms and signs and reduction in the TCM-syndrome score of more than 70% but less than 95%; (3) effective—improvement in the clinical symptoms and signs and reduction in the TCM-syndrome score of more than 30% but less than 70%; and (4) ineffective— no improvement in or even aggravation of the clinical symptoms and signs and reduction in the TCM-syndrome score of less than 30%. Any adverse events (AEs) resulting from the treatment were also recorded (ie, mortality, lifethreatening events, toxic responses, anaphylaxis, and events resulting in the discontinuation of treatment).

Study Selection and Data Extraction Two investigators independently selected studies for inclusion by scanning the titles, abstract sections, and keywords of each study retrieved and the full-text articles if necessary. The agreement between review authors for inclusion of studies was recorded.

To avoid bias in the data extraction process, data were extracted independently by 2 investigators, one of whom had been involved in the selection of the studies. The extracted data included (1) name of the first author, (2) title of the study, (3) year of its publication, (4) sample size, (5) mean age of participants, (6) the male-female ratio, (7) methodological information, (8) the name of the compound formulas of TCM, (9) outcomes, (10) ethical approval, (11) withdrawals and dropouts, and (12) AEs for each study. Each entry was doublechecked by both reviewers. Disagreement was resolved by discussion and, if necessary, consensus was reached through the evaluation of the study by a third author.

Assessment of Trial Quality Risk of bias was independently assessed by 2 of the review’s investigators, according to the Cochrane risk of bias tool, with consideration of the following aspects: (1) random sequence generation, (2) allocation concealment, (3) blinding of participants and personnel, (4) blinding of outcome assessments, (5) presence of incomplete outcome data, (6) selective reporting, and (7) other biases.21 The quality of all the included trials was evaluated, with the risk of bias being low, unclear, or high according to whether the study met the above criteria. A risk-of-bias graph was made using the Revman 5.2 software (Cochrane Collaboration, Copenhagen, Denmark).

Discrepancies were resolved by discussion between reviewers. If required, a third investigator was consulted. To avoid selection bias, no study was rejected because of the quality criteria.

Li—TCM for Common Cold

Figure 1. Flow diagram showing the stages of the identification of studies for the systematic review.

Literature search: (1) Database: Cochrane Library; PubMed; Embase; ChiCTR; CBM, CNKI, VIP, WANFANG; clinicaltrials.gov, other (2) Limits: English and Chinese language articles only Records identified through database searching: (1) Cochrane Library: 3; PubMed: 19; Embase: 20; clinicaltrials.gov: 4; CBM: 1; CNKI: 15; VIP: 11; WANFANG: 17; clinicaltrials.gov: 5, other: 2 (2) English: 46; Chinese: 51; total: 97

Records after duplicated removed through title review: English: 42, Chinese: 40, total: 82

Studies included in the systematic review: 6

In both Cochrane Library and PubMed: 2 In both PubMed and Embase: 1 In both PubMed and clinicaltrials.gov: 1 In all CNKI, VIP, and WANFANG: 1 In both CNKI and VIP: 1 In both CNKI and WANFANG: 2 In both VIP and WANFANG: 6 Articles excluded with reason: Not relevant to our review: 57 Reviews: 3 Single herb: 4 Children: 3 Duplicate articles: 1 Taking Western medicine in both treatment and control group: 1 No outcome: 7

Abbreviations: CBM, Chinese Biomedical Literature Database; CNKI, Chinese National Knowledge Infrastructure; VIP, Chinese Scientific and Technological Periodical Database; WANFANG, Wanfang Database; ChiCTR, Chinese Clinical Trial Register.

Data Analysis Data were summarized using relative risk, with 95% confidence intervals (CIs) for binary outcomes, or mean difference with 95% CI for continuous outcomes.

The Revman 5.2 software was used for data analyses. Metaanalysis was used if the trials had a good homogeneity for the studyâ&#x20AC;&#x2122;s design, participants, interventions, and outcome measures, which was assessed by examining I2, a quantity that describes approximately the proportion of variation in point estimates due to heterogeneity rather than sampling error.

If at least 10 trials were available for a meta-analysis, the research team planned to assess the likelihood of publication bias by constructing funnel plots. The I2 is a form of statistics that quantifies inconsistency, and the I2 test was applied to identify heterogeneity as well. The I2 can range from 0% to 100%, and values between 0% and 40% are interpreted as unimportant heterogeneity, up to 60% as moderate heterogeneity, and more than 60% as considerable heterogeneity. If the review was able to identify a sufficient number of RCTs, the current research team planned to perform sensitivity analyses to explore the influence of trial quality on effect estimates. An attempt for meta-analysis was not made due to the existing, significant clinical heterogeneity among the original trials.

Liâ&#x20AC;&#x201D;TCM for Common Cold

RESULTS The Search Figure 1 shows the process for study selection and reasons for exclusion. In the initial search of the 7 databases and other resources, a total of 97 potentially eligible citations were identified, of which 15 duplicates and 7 articles without outcomes were excluded. Based on title and abstract, 57 articles were excluded because they were not relevant to the topic, and another 10 articles were excluded for the following reasons: (1) 3 were review articles, (2) 3 were studies about children, and (3) 4 were studies on a single herb. After careful examination of the retrieved articles, the research team found that 2 articles24,28 described the same study; therefore, the research team considered them to be 1 study, represented by Wong et al.24 Another study29 was also excluded because participants in both the treatment and the control groups took Western medicine during the trial. Finally, a total of 6 RCTs22-27 that satisfied the eligibility criteria were included. All of the included studies compared compound formulas of TCM with placebos.

Characteristics of Included Studies The main characteristics of the included studies are listed in Tables 1 and 2. All of the 6 identified studies, involving a total of 1502 patients with the common cold, were conducted in China: 5 in mainland China and 1 in ALTERNATIVE THERAPIES, NOV/DEC 2015 VOL. 21 NO. 6 51

Table 1. Patient Characteristics for the Included Studies

Study

Source of No. of No. of Males/ Participants Participants Females

Age (y) (Mean ± SD)

Common Cold Informed Ethical Sample Size Similarity at Onset (h) Consent Approval Calculation Baseline

SACMS22 (2009)

Unclear

T: 116 C: 59

T: 49/67 C: 20/39

T: 38.38 ± 14.38 C: 38.42 ± 12.41

T: 12.22 ± 5.27 C: 10.00 ± 8.12

Yes

Yes

Yes

Similar

GSPCL23 (2010)

Unclear

T: 119 C: 59

T: 42/77 C: 21/38

T: 33.33 ± 13.69 C: 33.14 ± 13.97

T: 17.53 ± 8.54 C: 16.00 ± 9.75

Yes

Yes

Yes

Similar

Wong et al24 (2012)

Outpatients

T1: 82 T2: 82 C1: 80 C2: 83

T1: 40/42 T2: 44/38 C1: 35/45 C2: 40/43

T1: 44.4 ± 11.7 T2: 44.3 ± 10.4 C1: 42.0 ± 11.5 C2: 44.3 ± 11.5

≤48

Yes

No

Yes

Similar

Chang et al25 (2012)

Unclear

T: 231 C: 115

T: 147/84 C: 75/45

T: 35.98 ± 12.45 C: 35.64 ± 12.14

≤48

Yes

Yes

Yes

Similar

Zhou26 (2013)

Unclear

T: 160 C: 79

T: 65/95 C: 30/49

T: 41.20 ± 14.25 C: 39.67 ± 14.82

≤36

Yes

Yes

Yes

Similar

Shao27 (2013)

Unclear

T: 118 C: 119

T: 41/77 C: 46/73

T: 33.60 ± 13.13 C: 33.22 ± 12.09

≤96

Yes

Yes

Yes

Similar

Abbreviations: SACMS, Sichuan Academy of Chinese Medicine Sciences (unpublished data); GSPCL, Guilin Sanjin Pharmaceutical Co, Ltd (unpublished data); SD, standard deviation; T, treatment group; C, control group; T1, wind-coldsyndrome treatment group; T2, wind-heat-syndrome treatment group; C1, wind-cold-syndrome control group; C2, windheat-syndrome control group.

Table 2. Other Detailed Characteristics of the Included Studies Methods of Random Process

Intervention (T)

Control (C)

SACMS22 (2009)

Randomized, Computer- Qi deficiency QiXiangYiQi double-blind, generated syndrome JieDu controlled randomization granule trial list

Placebo

GSPCL23 (2010)

Randomized, Computerdouble-blind, generated controlled randomization trial list

Wind-heat syndrome

FuFangKang BingDu granule

Placebo

Wong et al24 (2012)

Randomized, Computerdouble-blind, generated controlled randomization trial list

Wind-cold syndrome and wind-heat syndrome

T1: JingFang BaiDu san granule, T2: YinQiaoSan granule

Placebo

Chang et Randomized, Computergenerated al25 (2012) double-blind, controlled randomization trial list

Wind-cold syndrome

ShiCha capsule

Placebo

Study

Study Design

TCM Syndrome

Zhou26 (2013)

Randomized, ComputerSuperficies double-blind, generated cold and controlled randomization interior heat trial list syndrome

QingJieKang Gan grain

Placebo

Shao27 (2013)

Randomized, Computerdouble-blind, generated controlled randomization trial list

JinChaiKang BingDu capsule

Placebo

Wind-heat syndrome

Treatment Outcome Duration Measuresa 3d

5d

1, 2, 4

1, 2, 3, 4

Until all symptoms resolved or up to a maximum of 10 d

3, 5

3d

3

3d

3d

2, 3, 4

1, 2, 3

P

Adverse Events

P1 < .05 P2 < .05 P4 < .05

No

P1 < .05 P2 < .05 P3 < .05 P4 < .05

T: 1

P3 < .05 P5 < .05

T1: 9 T2: 16 C1: 8 C2: 16

P3 < .05

T: 2 C: 2

Withdrawals and Dropouts ITT T: 4

Yes

C: 1

T: 4

Yes

C: 7

P2 < .05 P3 < .05 P4 < 05

T: 2 C: 3

P1 < .05 P2 < .05 P3 < .05

No

T: 9

Yes

C: 7

T: 14

Yes

C: 12

T: 9

Yes

C: 8

T: 13

Yes

C: 19

Abbreviations: SACMS, Sichuan Academy of Chinese Medicine Sciences (unpublished data); TCM, traditional Chinese medicine; T, treatment group; C, control group; ITT, intention to treat; GSPCL, Guilin Sanjin Pharmaceutical Co, Ltd (unpublished data). a

Outcome Measures: 1, reduction in disease symptoms; 2, the extent of recovery from TCM syndrome; 3, duration of main symptoms; 4, amount of time for a decline in temperature of at least 0.5°C and duration of fever; 5, health-related quality of life.

52 ALTERNATIVE THERAPIES, NOV/DEC 2015 VOL. 21 NO. 6

Li—TCM for Common Cold

Table 3. Assessment of Risk of Bias in the Included Studies Selection Bias

Study

Random Sequence Allocation Generation Concealment

Performance Bias Detection Bias

Attrition Bias

Reporting Bias

Other Biases

Blinding of Participants and Personnel

Blinding of Outcome Assessment

Incomplete Outcome Data Addressed

Free of Selective Outcome Reporting

Free of Other Sources of Bias

SACMS22 (2009)

Low risk

Low risk

Low risk

Low risk

Low risk

Unclear

Unclear

Company et al23 (2010)

Low risk

Low risk

Low risk

Low risk

Low risk

Unclear

Unclear

24

Wong et al (2012)

Low risk

Low risk

Low risk

Unclear

Low risk

Unclear

Unclear

Chang et al25 (2012)

Low risk

Low risk

Low risk

Low risk

Low risk

Unclear

Unclear

Zhou26 (2013)

Low risk

Low risk

Low risk

Low risk

Low risk

Unclear

Unclear

Shao27 (2013)

Low risk

Low risk

Low risk

Unclear

Low risk

Unclear

Unclear

Abbreviations: SACMS, Sichuan Academy of Chinese Medicine Sciences (unpublished data); GSPCL, Guilin Sanjin Pharmaceutical Co, Ltd (unpublished data).

Hong Kong. Two unpublished RCTs were located, and the other 4 RCTs were published between 2012 and 2013, of which 2 were in scientific journals, 1 was a master’s thesis, and 1 was a doctoral thesis. Five were multicenter clinical trials, and 1 was a single-center trial. The number of participants included in each study ranged from 175 to 346, with an average of 250 per trial. Four of the included studies were written in Chinese and the other 2 in English.

Three of the 6 studies23,25,26 were dose-escalation trials— high dose, low dose and placebo—and the research team pooled the data from the high-dose and low-dose groups.

One study22 randomly selected patients in a 2:1 ratio into the treatment and control groups. The wind-heat syndrome was included in 3 trials23-25; the wind-cold syndrome was included in 2 trials.24,25 The qi deficiency syndrome was included in only 1 trial,22 and the superficies cold-and-interior-heat syndrome was also included in only 1 trial.26 A total of 7 different compound formulas of TCM— QiXiangYiQiJieDu granules, FuFangKangBingDu granules, JingFangBaiDuSan capsules, YinQiaoSan capsules, ShiCha capsules, QingJieKangGan granules, and JinChaiKangBingDu capsules—were investigated. Participants in 1 study24 were classified into 2 intervention groups and randomly assigned to receive 1 of 2 TCM formulas—JingFangBaiDuSan capsules or YinQiaoSan capsules; the study also included a placebo group.

The total treatment duration ranged from 3 to 10 days.

The reported outcome measures included (1) reduction of disease symptoms, (2) extent of recovery from the TCM syndrome, (3) duration of main symptoms, (4) amount of time to temperature decline of at least 0.5°C and duration of fever, and (5) health-related quality of life. All the 6 trials reported information on AEs; AEs occurred in 4 trials.

in all 6 studies; a randomization table matching patients’ recruitment number to the medication number was generated by block randomization in a computer. All of the 6 studies provided descriptions of blinding methods.

After registered TCM practitioners assessed the potential participants to confirm that their symptoms satisfied the TCM diagnosis of the common cold and performed further syndrome differentiation, the eligible patients were randomly assigned to treatment or control groups, and all individuals involved were unaware of treatment assignment. At the same time, all 6 studies reported the quality standard of the medicines’ preparations. The compound formulas of TCM and placebo were supplied by a pharmaceutical company using modern extraction and concentration technologies, according to the Good Manufacturing Practice (GMP) standards. The placebos were indistinguishable from the compound formulas of TCM in form, color, taste, size, and packaging. Thus, the practice of random sequence generation, allocation concealment, and blinding of participants and personnel were adequate for all 6 studies at a low risk of bias.

All studies provided data on withdrawals, but only 2 studies24,25 described the reasons. All studies described intention-to-treat analyses or the method of assessing compliance.

No study mentioned a previous published protocol.

Thus, selective outcome reporting was an uncertain risk of bias. Assessment of other sources of bias included early stopping for benefit and baseline imbalance. The baseline characteristics of the treatment and control groups in the included studies were comparable. All the studies described a precalculated sample size, but information on early stopping was insufficient. Informed consent was obtained in all studies. Detailed information is shown in Tables 2 and 3.

Quality Assessment of Included Studies All of the 6 included studies were designed as randomized, double-blind, placebo-controlled trials. The risk of bias for the 6 studies was evaluated using the Cochrane Collaboration’s tool for assessing risk of bias.21 In general, most studies had a low risk of bias. All the studies used appropriate randomization methods (ie, a computer-generated randomization list).

Appropriate allocation-concealment methods were reported

Outcome Measures of Included Studies Reduction in Disease Symptoms. Three studies22,23,27 selected reduction in disease symptoms as an outcome measure. All 3 trials demonstrated better effects for the compound formulas of TCM compared with placebos. The rates of the 4 levels of reduction in disease symptoms—totally recovered, markedly effective, effective, and ineffective—in the treatment and control groups are shown in Table 4.

Li—TCM for Common Cold

ALTERNATIVE THERAPIES, NOV/DEC 2015 VOL. 21 NO. 6 53

Figure 2. Figure 2A is a risk-of-bias graph; it reviews the authors’ judgments about each risk-of-bias item presented, as percentages, across all included studies. Figure 2B is a risk-of-bias summary; it reviews the authors’ judgments about each risk-of-bias item for each included study.

2A

Random sequence generation (selection bias) Allocation concealment (selection bias) Blinding of participants and personnel (performance bias) Blinding of outcome assessments (detection bias) Incomplete outcome data (attrition bias) Selective reporting (reporting bias) Other bias 0% Low risk of bias

25%

Unclear risk of bias

54 ALTERNATIVE THERAPIES, NOV/DEC 2015 VOL. 21 NO. 6

100%

High risk of bias

Random sequence generation (selection bias)

Allocation concealment (selection bias)

Blinding of participants and personnel (performance bias)

Blinding of outcome assessments (detection bias)

Incomplete outcome data (attrition bias)

Selective reporting (reporting bias)

Other bias

2B The Extent of Recovery From TCM Syndrome. The extent of recovery from the TCM syndrome was investigated in 4 studies.22,23,26,27 The obvious effective rate was significantly higher in the treatment group compared with the control group in all 4 studies. The rates of the 4 levels of recovery from TCM syndrome—totally recovered, markedly effective, effective, and ineffective—in the treatment and control groups are shown in Table 5.

Duration of Main Symptoms. Five23-27 of the 6 RCTs provided data on the duration of main symptoms (eg, aversion to cold, nasal discharge, arthralgia of extremities, stuffy nose, sneezing, fatigue, fever, and weakness). In general, shorter symptom duration in the treatment group was found in 4 studies23,25-27; however, it should be pointed out that inconsistent findings were reported in the 4 RCTs in terms of the duration of fever. Two studies23,25 revealed significant differences between the treatment and control groups, but the other 2 studies26,27 did not observe any differences between groups. One study24 showed that no statistically significant difference existed in either wind-coldor wind-heat-syndrome patients between the treatment and placebo groups in terms of the disappearance of individual symptoms or complete resolution of overall symptoms.

The Amount of Time for a Decline in Temperature of at Least 0.5°C and Duration of Fever. This outcome was reported in 3 studies.22,23,26 Results revealed that the median times to temperature decline of at least 0.5°C and durations of fever were significantly shorter in the treatment groups than that in the control groups (log-rank test, P < .05) in 2 studies,22,23 whereas no difference was noted in the other study.26 Health-related Quality of Life. The common cold may affect patients’ quality of life. The Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) was used as an instrument to assess quality of life in 1 study.24 After adjustment for the baseline value, JingFangBaiDuSan significantly improved the general health score on the SF-36 for participants in the wind-cold-syndrome intervention group compared with the related placebo

75%

50%

(2009)

+

+

+

+

+

?

?

Chang et al (2012)

+

+

+

+

+

?

?

SACMS22 25

(2010)

+

+

+

+

+

?

?

27

Shao (2013)

+

+

+

?

+

?

?

24

+

+

+

?

+

?

?

26

+

+

+

+

+

?

?

23

GSPCL

Wong et al (2012) Zhou (2013)

Abbreviations: SACMS, Sichuan Academy of Chinese Medicine Sciences (unpublished data); GSPCL, Guilin Sanjin Pharmaceutical Co, Ltd (unpublished data). group, expressed as mean (standard deviation): 44.9 (19.6) versus 53.6 (19.1), respectively (P < .05). No statistically significant difference was found in other aspects of the SF-36 in either wind-cold-syndrome or wind-heatsyndrome patients.

Li—TCM for Common Cold

Table 4. Reduction in Disease Symptoms

Study (2009) (2010) Shao27 (2013) 22

SACMS

GSPCL23

Totally Markedly Recovered Effective (T vs C ) (T vs C ) 45.69% vs 22.03% 27.59% vs 25.42% 53.78% vs 13.56% 39.49% vs 27.12% 34.7% vs 15.1% 45.8% vs 36.9%

Effective (T vs C ) 18.97% vs 16.95% 6.7% vs 49.15% 14.4% vs 24.3%

Ineffective (T vs C ) 7.76% vs 35.59% 0% vs 10.17% 5.1% vs 23.5%

P .000 .000 <.05

Abbreviations: SACMS, Sichuan Academy of Chinese Medicine Sciences (unpublished data); T, treatment group; C, control group; GSPCL, Guilin Sanjin Pharmaceutical Co, Ltd (unpublished data).

Table 5. Extent of Recovery From the TCM Syndrome

Study 22 SACMS (2009) GSPCL23 (2010) Zhou26 (2013) Shao27 (2013)

Totally Recovered (T vs C ) 45.69% vs 22.03% 55.5% vs 15.25% 11.88% vs 1.27% 33.1% vs 13.4%

Markedly Dffective (T vs C ) 25% vs 33.9% 31.1% vs 15.25% 33.75% vs 16.46% 38.1% vs 27.7%

Effective (T vs C ) 18.97% vs 18.64% 10.1% vs 32.2% 44.38% vs 43.04% 23.7% vs 33.6%

Ineffective (T vs C ) 10.34% vs 25.42% 4.2% vs 37.29% 10% vs 39.24% 5.1 % vs 25.2%

P .0019 .0000 <.05 <.05

Abbreviations: SACMS, Sichuan Academy of Chinese Medicine Sciences (unpublished data); TCM, traditional Chinese medicine; T, treatment group; C, control group; GSPCL, Guilin Sanjin Pharmaceutical Co, Ltd (unpublished data).

Adverse Events. A total of 4 RCTs23-26 reported AEs during the treatment period. One study23 stated that 1 patient in the treatment group had experienced AEs, and a second26 reported that 2 patients in the treatment group and 3 patients in the control group suffered AEs. Neither of the 2 studies, however, described the specific AEs. The third study25 found that 2 patients in the treatment group and 2 in the control group had experienced mild upperabdominal discomfort, accompanied by nausea and vomiting. When the dose of the test drugs was reduced, those symptoms gradually eased in all 4 participants. For wind-cold-syndrome patients, the fourth study24 reported that 8 patients in the treatment group (11%) and 9 in the control group (11.3%) had at least 1 AE during the treatment period (eg, stomach gas, stomachache, vomiting, diarrhea, thirsty, sweating, loss of appetite, or insomnia).

For wind-heat-syndrome patients, the same study found that 16 patients in the treatment group (20.5%) and 16 in the control group (20%) had at least 1 AE such as found in the wind-cold-syndrome group. The remaining 2 of the 6 RCTs reported that no AE was observed.

Funnel Plot. Because the number of the included studies was fewer than 10, the research team did not conduct funnel plots.

DISCUSSION The common cold is generally mild and may go away on its own. To be clinically useful, simple, safe, and cost Liâ&#x20AC;&#x201D;TCM for Common Cold

effective, first-line therapies to treat multiple symptoms need to be available to patients with the disorder. To date, however, no validated strategies have been developed for the treatment of the common cold, and current therapies merely focus on symptom relief. The effects of some Western medicines, such as NSAIDS, antiviral drug, and vaccinations, are considered limited.

In China and other parts of the world, dissatisfaction with treatments offered by Western medicine has led many patients to turn to TCM for treating the common cold, but the quality of reported studies is of great concern when examining TCM therapies for safety.30 TCM stresses differentiation of symptoms and signs; it considers the human being to be an organic entirety and indicates that treatment should emphasize the entirety. To produce synergistic effects, TCM practitioners usually use a substantial number of herbs to treat various conditions, including the common cold, and this practice can overcome the shortcomings of Western medicine.

To promote the modernization of TCM and accelerate the pace of TCM development with international standards, the field must implement some important measures: (1) give full play to the advantages of Chinese medicine; (2) vigorously promote the use of anticold, proprietary Chinese medicines; (3) vigorously carry out research and development as well as production of anticold pharmaceutical preparations, and (4) strive to develop the production of more medicines that are even more efficacious than Western medicine.

ALTERNATIVE THERAPIES, NOV/DEC 2015 VOL. 21 NO. 6 55

It is recognized that randomization, blinding, and establishment of a control group are 3 principles of clinicalresearch design. However, patients receiving placebo may seek other treatments, especially if an established effective treatment is available, and this practice may lead to biased results.

Thus, in placebo-controlled studies, randomization and blinding play more important roles in reducing biases.31 Meanwhile, a placebo-controlled setting could eliminate the effect of the disease’s natural progression, identify the real adverse reactions caused by the test drug, and directly measure the difference between the test drug and placebo.32 In the current review, all of the included studies used a placebo as a control intervention, and most studies reported the essential information listed above, especially the method of sequence generation, the process of allocation concealment, the approach to implementation of randomization, an evaluation of blinding, a flow diagram, an estimation of sample size, and clear definition of outcome measures. All trials also stated that the placebo was designed to be identical in appearance, color, and taste to the test drug.

Given that the common cold is a self-limiting disease, it is scientifically sound and ethical to use a placebo-controlled trial design to explore the clinical efficacy of interventions for it. Several placebo-controlled, randomized trials assessing medicinal herbs, single or extract, in the treatment of colds have been published by foreign investigators.33-35 In addition, to clarify the efficacy of compound formulas of TCM for the common cold in a more scientific and standardized manner, the current research group took the lead in China to carry out a multicenter, randomized, double-blind, placebocontrolled trial on compound formulas of TCM in the treatment of the common cold,25 which was included in this systematic review.

In China, a general perception exists that it is safe to use herbal medicines for various conditions. However, with increasing reports of liver or renal toxicity and other AEs associated with Chinese medicinal herbs,36 the safety issue has become a growing concern. Mao et al37 have collected large amounts of data on anticold medicines and reported the common adverse reactions, which were mainly located in the central nervous system, urinary system, blood system, cardiovascular system, digestive system, skin, ear, nose, and throat. Almost all of these adverse reactions were caused by Western medicine, whereas the adverse reactions associated with Chinese medicine were far fewer than those of Western medicine. Their review found that the compound formulas of TCM had relatively few adverse reactions, with a favorable safety profile. Four of the 6 RCTs included in the current review reported AEs during the scheduled treatment period, and all of these events gradually disappeared after proper treatment; the other 2 studies reported that no AE was observed.

The theoretical basis of TCM is syndrome differentiation and treatment based on a holistic concept. Patients experiencing the same disease may manifest different TCM syndromes and, thus, may receive different treatments.38 At 56 ALTERNATIVE THERAPIES, NOV/DEC 2015 VOL. 21 NO. 6

present, it is believed by many clinicians that it is optimal to combine the concept of disease, as defined by Western medicine, with that of syndrome, as defined by TCM, in the diagnosis and treatment of diseases.39 In TCM,40 the common cold, commonly called invasion by wind, is a disease that is due to the imbalance of lung defenses that resulted from an attack of pathogenic wind or epidemic pathogenic factors. The syndrome types of this disorder mainly include wind-cold, wind-heat, summer-heat dampness, qi-deficiency, and yin-deficiency syndromes. The current review found that all 6 of the included RCTs recorded TCM syndromes (100%); 5 recorded syndrome’s indicators and criteria (83%), reflecting the disease and syndrome. The current research group is looking forward to more research on the manifestation of disease and syndrome to promote medical research in Chinese medicine research, using international standards.

The current research team acknowledges that the current review had a few limitations. First, only English- or Chineselanguage articles were included. The influence of the language of publication on reporting quality is unknown because TCM is also frequently used in other countries, such as Japan and Korea.

Second, despite a comprehensive literature search, only 6 studies met the inclusion criteria and only 7 compound formulas of TCM were assessed. Therefore, the team’s findings may not be generalized to other compound formulas of TCM for the common cold. Third, in TCM, disease is seen as the outcome of the struggle between a body’s resistance and pathogenic factors.

Certain factors and conditions, including time—seasonal and climatic conditions; place—geographical location and environment; and personal characteristics—living habits, age, gender, and body constitution, are also taken into consideration in the treatment of a disease. That principle is an important therapeutic one, guiding TCM clinical practice. The formulation and dosage of medicinal herbs in the formulas included in this study were standardized, which might not fully reflect the realworld practice of TCM practitioners, who often alter the formula by removing or adding specific herbs according to the time, place, and constitution of the patient’s body. In addition, the manufacturers providing the TCM therapies had assured the researchers from the reviewed studies that the quality and dosage of the herbs were up to the GMP standard. However, the current research team could not be certain that they had the same effectiveness as the traditional decoctions made from raw herbs. Fourth, although the common cold is a self-limiting disease, numerous factors, including age; underlying diseases of the heart, liver, kidney, blood system; or compromised immunity may have affected recovery times. Only Wong et al24 reported that the resolution of the common cold’s symptoms was significantly associated with age, with not having taken Western medication at baseline, with the daily total symptoms score at baseline, and with the proportion of days that a patient had taken Western medication during the period from baseline to recovery. That study reported that the older the patients, the more serious was the patient’s illness at baseline. It also reported that the higher the proportion of days that the patient had been taking Western medications, the slower was the patient’s Li—TCM for Common Cold

recovery. Finally, TCM signs are difficult to quantify because they are subjective outcomes and can easily be affected by investigators to some extent. TCM researchers and physicians should decide on an objective and persuasive method of measuring TCM signs.

CONCLUSIONS In conclusion, the effects of compound formulas of TCM for the common cold were investigated in the current systematic review, and the research team concluded that such formulas provide more benefits for patients with the common cold, compared with placebo, without any serious adverse reactions being identified. Encouraging evidence exists that suggests that compound formulas of TCM may be safe and effective treatment options for patients with colds. However, the numbers of included studies and participants were small in the current review; only 7 compound formulas of TCM were included, and some of the biases of the included studies were unclear, such as reporting bias. TCM benefits need to be confirmed further through large-scale, high-quality, prospective trials involving more compound formulas of TCM. AUTHOR DISCLOSURE STATEMENT The research team declares that no conflicts of interest existed regarding the publication of this article.

ACKNOWLEDGEMENTS No grants or funding were provided for the performance of this study. The project was initiated and designed by Bing Mao, who was also responsible for coordinating and supervising in the current review. Guanhong Li, Linli Cai, Hongli Jiang, Shoujin Dong, Tao Fan, Wei Liu, and Li Xie were involved in the performance and development of the review. Guanhong Li and Linli Cai contributed equally to the study. All authors have read and approved the final manuscript. The research team also thanks the anonymous referees for their helpful comments and advice, which greatly improved the quality of the review.

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ALTERNATIVE THERAPIES, NOV/DEC 2015 VOL. 21 NO. 6 57

Volume 21 2015 index

AUTHOR INDEX A Ada AM, Yavuz F. Treatment of a medial collateral ligament sprain using prolotherapy: A case study. 2015;21(4):68-71.

Agolli G (see Clarke DP et al) 2015;21(1):16-27.

Akcakaya A (see Kızıltan HŞ et al) 2015;21(2):24-29.

Akcakaya A (see Kiziltan HS et al) 2015;21(Suppl 2):68-72.

Akhavi Mirab-bashii A (see Malekzadeh G et al) 2015;21(2):42-47.

Akhtar N (see Asif HM et al) 2015;21(Suppl 2):33-39.

Anastasiadou E (see Dimas K et al) 2015;21(Suppl 2):46-54.

Araújo FM (see Teixeira-Machado L et al) 2015;21(1):8-14.

Arnedt JT (see Wyatt GK et al) 2015;21(4):18-23.

Arslan A (see Meral I et al) 2015;21(5):24-29.

Arslan H (see Meral I et al) 2015;21(5):24-29.

Asif HM, Zaidi SF, Sugiyama T, Akhtar N, Usmanghani K. Phytomedicine-based and quadruple therapies in Helicobacter pylori infection: A comparative, randomized trial. 2015;21(Suppl 2):33-39.

Awdish R, Small B, Cajigas H. Development of a modified yoga program for pulmonary hypertension: A case series. 2015;21(2):48-52.

Aydin T (see Kızıltan HŞ et al) 2015;21(2):24-29.

Aydin T (see Kiziltan HS et al) 2015;21(Suppl 2):68-72.

B Baggerly LL. Vitamin D: Dosages to optimize serum levels. 2015;21(3):14-15.

Bailey JN (see Catalino MP et al) 2015;21(3):26-35.

Bains GS, Berk LS, Lohman E, Daher N, Petrofsky J, Schwab E, Deshpande P. Humors effect on short-term memory in healthy and diabetic older adults. 2015;21(3):16-25.

Bayir AG (see Kızıltan HŞ et al) 2015;21(2):24-29.

Berk LS (see Bains GS et al) 2015;21(3):16-25.

Borlongan CV (see Lin D et al) 2015;21(6):36-46.

Botchey SA, Ouyang J, Vivekanantham S. Global water fluoridation: What is holding us back? 2015;21(3):46-52.

Bowden J, Sinatra D, Sinatra S. A statin for all diabetics? Not so fast ... .

2015;21(5):12-15.

Braun KL (see Hwang PW et al) 2015;21(5):64-70.

Breder KP (see Rice AD et al) 2015;21(3):36-44.

Brogan K. Nicholas Gonzalez, MD (1947-2015). 2015;21(5):8-10.

Brogan K. Psychobiology of vaccination effects: Bidirectional relevance of depression. 2015;21(Suppl 3):18-26.

Burdette C (see Clarke DP et al) 2015;21(1):16-27.

Burnett K. Aristo Vojdani, PhD: Environmental factors and autoimmune disease. 2015;21(Suppl 1):80-86.

C Cai G (see Li J et al) 2015;21(4):26-34.

Cai L (see Li G et al) 2015;21(6):48-57.

Cao C (see Lin D et al) 2015;21(6):36-46.

Cajigas H (see Awdish R et al) 2015;21(2):48-52.

Campbell AW. The gut, intestinal permeability, and autoimmunity.

2015;21(1):6-7.

Campbell AW. Food immune reactivities. 2015;21(Suppl 1):6-7.

Campbell AW. Our other vital organ. 2015;21(2):8-10.

Campbell AW. Vitamin C: It isn’t just for cancer anymore. 2015;21(3):8-10.

Campbell AW. Vaccines: Both sides of the same coin. 2015;21(4):8-10.

Campbell AW. Nutrition. 2015;21(Suppl 2):10-11.

Campbell AW. The gut-brain relationship. 2015;21(Suppl 3):8.

Campbell AW. Inflammation: The root of our chronic diseases.

2015;21(6):8-9.

58 ALTERNATIVE THERAPIES, NOV/DEC 2015 VOL. 21 NO. 6

Catalino MP, Durón RM, Bailey JN, Holden KR. The influence of traditional and complementary and alternative medicine on medication adherence in Honduras. 2015;21(3):26-35. Çelebioğlu A, Küçükoğlu S, Odabaşoğlu E. Turkish nurses’ use of nonpharmacological methods for relieving children’s postoperative pain.

2015;21(5):30-35.

Cherubini K (see de Freitas Cuba L et al) 2015;21(2):36-41.

Chesla S (see Clarke DP et al) 2015;21(1):16-27.

Chen R (see Li J et al) 2015;21(4):26-34.

Chen S (see Wang B et al) 2015;21(1):36-44.

Clarke DP, Burdette C, Agolli G, Dorval B, Gaston AM, Chesla S. The relevance of using the C3d/immunoglobulin G test in clinical intervention. 2015;21(1):16-27.

Cline JC. Nutritional aspects of detoxification in clinical practice.

2015;21(3):54-62.

Coban G (see Kiziltan HS et al) 2015;21(Suppl 2):68-72.

Cunha FA (see Teixeira-Machado L et al) 2015;21(1):8-14.

D Dach J. Gut-Brain: major depressive disorder, hypothalamic dysfunction, and high calcium score associated with leaky gut. 2015;21(Suppl 3):10-15.

Daher N (see Bains GS et al) 2015;21(3):16-25.

Dai ZK (see Huang YM et al) 2015;21(4):54-67.

Dashti-Rahmatabadi MH (see Malekzadeh G et al) 2015;21(2):42-47. de Abreu LC (see do Amaral JA et al) 2015;21(5):16-23. de Abreu LC (see Milan RC et al) 2015;21(5):37-43. de Figueiredo MA (see de Freitas Cuba L et al) 2015;21(2):36-41. de Freitas Cuba L, Salum FG, Cherubini K, de Figueiredo MA. Antioxidant agents: A future alternative approach in the prevention and treatment of radiation-induced oral mucositis? 2015;21(2):36-41.

DeSantana J (see Teixeira-Machado L et al) 2015;21(1):8-14.

Deshpande P (see Bains GS et al) 2015;21(3):16-25.

Detweiler MB, Self JA, Lane S, Spencer L, Lutgens B, Kim DY, Halling MH, Rudder TC, Lehmann LP. Horticultural therapy: A pilot study on modulating cortisol levels and indices of substance craving, posttraumatic stress disorder, depression, and quality of life in veterans.

2015;21(4):36-41.

Dimas K, Tsimplouli C, Houchen C, Pantazis P, Sakellaridis N, Tsangaris GT, Anastasiadou E, Ramanujam RP. An ethanol extract of Hawaiian turmeric: Extensive in vitro anticancer activity against human colon cancer cells. 2015;21(Suppl 2):46-54.

DiNicolantonio JJ (see McCarty MF et al) 2015;21(Suppl 2):40-45. do Amaral JA, Guida HL, Vanderlei FM, Garner DM, de Abreu LC, Valenti VE. The effects of musical auditory stimulation of different intensities on geometric indices of heart rate variability. 2015;21(5):16-23.

Dong S (see Li G et al) 2015;21(6):48-57.

Dorval B (see Clarke DP et al) 2015;21(1):16-27.

Du N (see Wang Z et al) 2015;21(Suppl 2):12-21.

DuBroff R, Lad V, Murray-Krezan C. A prospective trial of ayurveda for coronary heart disease: A pilot study. 2015;21(5):52-62.

DuBroff R (see DuBroff R et al) 2015;21(5):52-62.

Durón RM (see Catalino MP et al) 2015;21(3):26-35.

E Eickhoff C (see Hull A et al) 2015;21(6):12-21.

Eris AH (see Kızıltan HŞ et al) 2015;21(2):24-29.

Eris AH (see Kiziltan HS et al) 2015;21(Suppl 2):68-72.

Author Index

Evans JM. A broader conclusion to a well-conceived study: Must it be massage before reproductive technology? 2015;21(2):23.

J Jiang H (see Li G et al) 2015;21(6):48-57.

F Faith J, Thorburn S, Tippens KM. Examining the association between patient-centered communication and provider avoidance, CAM use, and CAM-use disclosure. 2015;21(2):30-35.

Fan F (see Li G et al) 2015;21(6):48-57.

Frambes DA (see Wyatt GK et al) 2015;21(4):18-23.

K Karatoprak C (see Kızıltan HŞ et al) 2015;21(2):24-29.

Kharrazian D. Traumatic brain injury and the effect on the brain-gut axis.

2015;21(Suppl 3):28-32.

Kim DJ, Lee J, Kim MR, Ha IH. Guillain-Barré syndrome mistaken for a common spinal disorder: A case report. 2015;21(3):64-67.

Kim DY (see Detweiler MB et al) 2015;21(4):36-41.

Kim MR (see Kim DJ et al) 2015;21(3):64-67.

King Iii R (see Rice AD et al) 2015;21(3):36-44.

Kilic G (see Kiziltan HS et al) 2015;21(Suppl 2):68-72.

Kızıltan HŞ, Bayir AG, Yucesan G, Eris AH, İdin K, Karatoprak C, Aydin T, Akcakaya A, Mayadagli A. Medical ozone and radiotherapy in a peritoneal, Erlich-ascites, tumor-cell model. 2015;21(2):24-29.

Kızıltan HŞ, Gunes Bayir A, Taspinar O, Yucesan G, Tastekin D, Sonmez FC, Coban G, Kilic G, Eris AH, Aydin T, Akcakaya A, Mayadagli A. Radioprotectant and cytotoxic effects of spirulina in relapsed verrucous vulvar cancer: A case report. 2015;21(Suppl 2):68-72 Kondrot EC. Significant improvements in vision parameters for participants with eye disease using 4 alternative therapies.

2015;21(6):22-35.

Küçükoğlu S (see Çelebioğlu A et al) 2015;21(5):30-35.

G Garner DM (see do Amaral JA et al) 2015;21(5):16-23.

Garner DM (see Milan RC et al) 2015;21(5):37-43.

Gao G (see Qu L et al) 2015;21(5):44-51.

Gaston AM (see Clarke DP et al) 2015;21(1):16-27.

Gomes RL (see Milan RC et al) 2015;21(5):37-43.

Gonzáles I (see Niehues JR et al) 2015;21(5):73-80.

Gonzalez NJ, Isaacs LL. Statistics: Why meaningful statistics cannot be generated from a private practice. 2015;21(2):11-15.

Guida HL (see do Amaral JA et al) 2015;21(5):16-23.

Guida HL (see Milan RC et al) 2015;21(5):37-43.

Gunes Bayir A (see Kiziltan HS et al) 2015;21(Suppl 2):68-72.

Gustafson C. Paul G. Harch, MD: The genetically modulated healing effects of hyperbaric oxygen therapy. 2015;21(1):46-55.

Gustafson C. James Forsythe, MD, HMD: The success of integrative cancer therapy based on chemosensitivity testing and insulin potentiation therapy. 2015;21(2):54-59.

Gustafson C. Leslie Ray Matthews, MD: Enhanced surgical outcomes and boosted soft-tissue wellness from vitamin D supplementation.

2015;21(3):68-72.

Gustafson C. Michael Smith, MD: Treat the underlying causes of weight gain to facilitate successful weight loss, part 2: Examining the first 2 pillars of weight gain. 2015;21(4):72-75.

Gustafson C. Gerard E. Mullin, MD: The influence of the gut-brain axis on health. 2015;21(Suppl 2):73-76.

Gustafson C. Jon Kaiser, MD: Supporting mitochondrial health with nutrient therapy. 2015;21(Suppl 2):77-79.

Gustafson C. Michael Smith, MD: Treat the underlying causes of weight gain to facilitate successful weight loss. 2015;21(5):82-86.

Gustafson C. Tieraona Low Dog, MD: The many aspects of greening medicine. 2015;21(5):88-91.

H Ha IH (see Kim DJ et al) 2015;21(3):64-67.

Haas P (see Niehues JR et al) 2015;21(5):73-80.

Halling MH (see Detweiler MB et al) 2015;21(4):36-41.

Harris RE (see Wyatt GK et al) 2015;21(4):18-23.

Hassali MA, Nazir SU, Saleem F, Masood I. Literature review: Pharmacists’ interventions to improve control and management in type 2 diabetes mellitus. 2015;21(1):28-35.

He ZX (see Lin D et al) 2015;21(6):36-46.

Him A (see Meral I et al) 2015;21(5):24-29.

Holden KR (see Catalino MP et al) 2015;21(3):26-35.

Holliday SB (see Hull A et al) 2015;21(6):12-21.

Houchen C (see Dimas K et al) 2015;21(Suppl 2):46-54.

Howarth GS (see Musa NS et al) 2015;21(Suppl 2):22-31.

Huang YM, Xu JH, Ling W, Li Y, Zhang XX, Dai ZK, Sui Y, Zhao HL. Efficacy of the wen dan decoction, a Chinese herbal formula, for metabolic syndrome. 2015;21(4):54-67.

Hull A, Holliday SB, Eickhoff C, Rose-Boyce M, Sullivan P, Reinhard M. The Integrative Health and Wellness (IHW) program: Development and use of a complementary and alternative medicine clinic for veterans. 2015;21(6):12-21.

Hwang PW, Braun KL. The effectiveness of dance interventions to improve older adults’ health: A systematic literature review.

2015;21(5):64-70.

I İdin K (see Kızıltan HŞ et al) 2015;21(2):24-29.

Isaacs LL (see Gonzalez NJ et al) 2015;21(2):11-15.

Author Index

L Lad V (see DuBroff R et al) 2015;21(5):52-62.

Lane S (see Detweiler MB et al) 2015;21(4):36-41.

Lee J (see Kim DJ et al) 2015;21(3):64-67.

Lehmann LP (see Detweiler MB et al) 2015;21(4):36-41.

Lemos RR (see Niehues JR et al) 2015;21(5):73-80.

Li C (see Qu L et al) 2015;21(5):44-51.

Li D (see Wang B et al) 2015;21(1):36-44.

Li G, Cai L, Jiang H, Dong S, Fan F, Liu W, Xie L, Mao B. Compound formulas of traditional Chinese medicine for the common cold: Systematic review of randomized, placebo-controlled trials.

2015;21(6):48-57.

Li J, Chen R, Cai G. Targeting NF-κΒ and TNF-α activation by electroacupuncture to suppress collagen-induced rheumatoid arthritis in model rats. 2015;21(4):26-34.

Li L (see Wang Z et al) 2015;21(Suppl 2):12-21.

Li M (see Wang B et al) 2015;21(1):36-44.

Li Y (see Huang YM et al) 2015;21(4):54-67.

Lin D, Wu Q, Lin X, Borlongan CV, He ZX, Tan K, Cao C, Zhou SF. Brain-derived neurotrophic factor (BDNF) signaling pathway modulation by acupuncture in telomerase knockout mice.

2015;21(6):36-46.

Lin X (see Lin D et al) 2015;21(6):36-46.

Ling W (see Huang YM et al) 2015;21(4):54-67.

Liu W (see Li G et al) 2015;21(6):48-57.

Lohman E (see Bains GS et al) 2015;21(3):16-25.

Lutgens B (see Detweiler MB et al) 2015;21(4):36-41.

Lv P (see Wang B et al) 2015;21(1):36-44.

M Mao B (see Li G et al) 2015;21(6):48-57.

Malekzadeh G, Dashti-Rahmatabadi MH, Zanbagh S, Akhavi Mirabbashii A. Mumijo attenuates chemically induced inflammatory pain in mice. 2015;21(2):42-47.

Masood I (see Hassali MA et al) 2015;21(1):28-35.

Mayadagli A (see Kızıltan HŞ et al) 2015;21(2):24-29.

Mayadagli A (see Kiziltan HS et al) 2015;21(Suppl 2):68-72.

McCarty MF. Preclinical studies suggest complex nutraceutical strategies may have potential for preventing and managing sepsis. 2015;21(Suppl 2):56-67.

McCarty MF, O’Keefe JH, DiNicolantonio JJ. Red yeast rice plus berberine: Practical strategy for promoting vascular and metabolic health. 2015;21(Suppl 2):40-45.

Melo (see Teixeira-Machado L et al) 2015;21(1):8-14.

Menezes M (see Teixeira-Machado L et al) 2015;21(1):8-14.

ALTERNATIVE THERAPIES, NOV/DEC 2015 VOL. 21 NO. 6 59

Menezes T (see Teixeira-Machado L et al) 2015;21(1):8-14.

Meral I, Arslan A, Him A, Arslan H. Smoking-related alterations in serum levels of thyroid hormones and insulin in female and male students. 2015;21(5):24-29.

Milan RC, Plassa BO, Guida HL, de Abreu LC, Gomes RL, Garner DM, Valenti VE. Oral contraceptives attenuate cardiac autonomic responses to musical auditory stimulation: Pilot study. 2015;21(5):37-43.

Murphy SL (see Wyatt GK et al) 2015;21(4):18-23.

Murray-Krezan C (see DuBroff R et al) 2015;21(5):52-62.

Murtinger M (see Okhowat J et al) 2015;21(2):16-22.

Musa NS, Howarth GS, Tran CD. Zinc supplementation alone is effective for partial amelioration of methotrexate-induced intestinal damage.

2015;21(Suppl 2):22-31.

N Nazir SU (see Hassali MA et al) 2015;21(1):28-35.

Niehues JR, Gonzáles I, Lemos RR, Haas P. Pilates method for lung function and functional capacity in obese adults. 2015;21(5):73-80.

O Odabaşoğlu E (see Çelebioğlu A et al) 2015;21(5):30-35.

O’Keefe JH (see McCarty MF et al) 2015;21(Suppl 2):40-45.

Okhowat J, Murtinger M, Schuff M, Wogatzky J, Spitzer D, Vanderzwalmen P, Wirleitner B, Zech NH. Massage therapy improves in vitro fertilization outcome in patients undergoing blastocyst transfer in a cryo-cycle. 2015;21(2):16-22.

Ouyang J (see Botchey SA et al) 2015;21(3):46-52.

P Pan Y (see Rea WJ et al) 2015;21(4):12-17.

Pantazis P (see Dimas K et al) 2015;21(Suppl 2):46-54.

Patterson K (see Rice AD et al) 2015;21(3):36-44.

Petrofsky J (see Bains GS et al) 2015;21(3):16-25.

Pietschmann N. Food intolerance: Immune activation through dietassociated stimuli in chronic disease. 2015;21(4):42-52.

Plassa BO (see Milan RC et al) 2015;21(5):37-43.

Puri S (see Sharma S et al) 2015;21 (Suppl 3):34-42.

Q Qu L, Ye Y, Li C, Gao G. Effect of electroacupuncture on transcutaneous oxygen partial pressure during hyperbaric oxygen therapy in healthy individuals. 2015;21(5):44-51.

R Ramanujam RP (see Dimas K et al) 2015;21(Suppl 2):46-54.

Rea WJ, Restrepo C, Pan Y. Terpenes and terpenoids in chemical sensitivity. 2015;21(4):12-17.

Reed ED (see Rice AD et al) 2015;21(3):36-44.

Reinhard M (see Hull A et al) 2015;21(6):12-21.

Restrepo C (see Rea WJ et al) 2015;21(4):12-17.

Rice AD, Patterson K, Wakefield LB, Reed ED, Breder KP, Wurn BF, King Iii R, Wurn LJ. Ten-year retrospective study on the efficacy of a manual physical therapy to treat female infertility. 2015;21(3):36-44.

Rose-Boyce M (see Hull A et al) 2015;21(6):12-21.

Rudder TC (see Detweiler MB et al) 2015;21(4):36-41.

S Saleem F (see Hassali MA et al) 2015;21(1):28-35.

Salum FG (see de Freitas Cuba L et al) 2015;21(2):36-41.

Sakellaridis N (see Dimas K et al) 2015;21(Suppl 2):46-54.

Schuff M (see Okhowat J et al) 2015;21(2):16-22.

Schwab E (see Bains GS et al) 2015;21(3):16-25.

Self JA (see Detweiler MB et al) 2015;21(4):36-41.

Sharma S, Puri S. Prebiotics and lipid metabolism: A review. 2015;21 (Suppl 3):34-42.

Sinatra D (see Bowden J et al) 2015;21(5):12-15.

Sinatra S (see Bowden J et al) 2015;21(5):12-15.

Small B (see Awdish R et al) 2015;21(2):48-52.

Sonmez FC (see Kiziltan HS et al) 2015;21(Suppl 2):68-72.

Spencer L (see Detweiler MB et al) 2015;21(4):36-41.

60 ALTERNATIVE THERAPIES, NOV/DEC 2015 VOL. 21 NO. 6

Spitzer D (see Okhowat J et al) 2015;21(2):16-22.

Stone JA. Why does treatment fidelity matter? 2015;21(4):24-25.

Sugiyama T (see Asif HM et al) 2015;21(Suppl 2):33-39.

Sui Y (see Huang YM et al) 2015;21(4):54-67.

Sullivan P (see Hull A et al) 2015;21(6):12-21.

T Tan K (see Lin D et al) 2015;21(6):36-46.

Taspinar O (see Kiziltan HS et al) 2015;21(Suppl 2):68-72.

Tastekin D (see Kiziltan HS et al) 2015;21(Suppl 2):68-72.

Teixeira-Machado L, Araújo FM, Cunha FA, Menezes M, Menezes T, Melo DeSantana J. Feldenkrais method-based exercise improves quality of life in individuals with Parkinson’s disease: A controlled, randomized clinical trial. 2015;21(1):8-14.

Thorburn S (see Faith J et al) 2015;21(2):30-35.

Ti G (see Wang B et al) 2015;21(1):36-44.

Tippens KM (see Faith J et al) 2015;21(2):30-35.

Tran CD (see Musa NS et al) 2015;21(Suppl 2):22-31.

Tsangaris GT (see Dimas K et al) 2015;21(Suppl 2):46-54.

Tsimplouli C (see Dimas K et al) 2015;21(Suppl 2):46-54.

U Usmanghani K (see Asif HM et al) 2015;21(Suppl 2):33-39.

V Valenti VE (see do Amaral JA et al) 2015;21(5):16-23.

Valenti VE (see Milan RC et al) 2015;21(5):37-43.

Vanderlei FM (see do Amaral JA et al) 2015;21(5):16-23.

Vanderzwalmen P (see Okhowat J et al) 2015;21(2):16-22.

Vivekanantham S (see Botchey SA et al) 2015;21(3):46-52.

Vojdani A. The evolution of food immune reactivity testing: Why immunoglobulin G or immunoglobulin A antibody for food may not be reproducible from one lab to another. 2015;21(Suppl 1):8-22.

Vojdani A. Oral tolerance and its relationship to food immunoreactivities.

2015;21(Suppl 1):23-32.

Vojdani A. Molecular mimicry as a mechanism for food immune reactivities and autoimmunity. 2015;21(Suppl 1):34-45.

Vojdani A. Lectins, agglutinins, and their roles in autoimmune reactivities.

2015;21(Suppl 1):46-51.

Vojdani A. Immune reactivities to peanut proteins, agglutinins, and oleosins. 2015;21(Suppl 1):73-79.

Vojdani A, Vojdani C. Immune reactivity to food coloring. 2015;21(Suppl 1):52-62.

Vojdani A, Vojdani C. Immune reactivities against gums. 2015;21(Suppl 1):64-72.

Vojdani C (see Vojdani A et al) 2015;21(Suppl 1):52-62.

Vojdani C (see Vojdani A et al) 2015;21(Suppl 1):64-72.

W Wakefield LB (see Rice AD et al) 2015;21(3):36-44.

Wang B, Chen S, Yan X, Li M, Li D, Lv P, Ti G. The therapeutic effect and possible harm of puerarin for treatment of stage III diabetic nephropathy: A meta-analysis. 2015;21(1):36-44.

Wang K (see Wang Z et al) 2015;21(Suppl 2):12-21.

Wang Z, Zhang Z, Du N, Wang K, Li L. Hepatoprotective effects of grape seed procyanidin B2 in rats with carbon tetrachloride-induced hepatic fibrosis. 2015;21(Suppl 2):12-21.

Wirleitner B (see Okhowat J et al) 2015;21(2):16-22.

Wogatzky J (see Okhowat J et al) 2015;21(2):16-22.

Wu Q (see Lin D et al) 2015;21(6):36-46.

Wurn BF (see Rice AD et al) 2015;21(3):36-44.

Wurn LJ (see Rice AD et al) 2015;21(3):36-44.

Wyatt GK, Frambes DA, Harris RE, Arnedt JT, Murphy SL, Zick SM. Self-administered acupressure for persistent cancer-related fatigue: Fidelity considerations. 2015;21(4):18-23.

X Xie L (see Li G et al) 2015;21(6):48-57.

Xu JH (see Huang YM et al) 2015;21(4):54-67.

Author Index

Y Yan X (see Wang B et al) 2015;21(1):36-44.

Yavuz F (see Ada AM et al) 2015;21(4):68-71.

Ye Y (see Qu L et al) 2015;21(5):44-51.

Yucesan G (see Kızıltan HŞ et al) 2015;21(2):24-29.

Yucesan G (see Kiziltan HS et al) 2015;21(Suppl 2):68-72.

Z Zaidi SF (see Asif HM et al) 2015;21(Suppl 2):33-39.

Zanbagh S (see Malekzadeh G et al) 2015;21(2):42-47.

Zech NH (see Okhowat J et al) 2015;21(2):16-22.

Zhang XX (see Huang YM et al) 2015;21(4):54-67.

Zhang Z (see Wang Z et al) 2015;21(Suppl 2):12-21.

Zhao HL (see Huang YM et al) 2015;21(4):54-67.

Zhou SF (see Lin D et al) 2015;21(6):36-46.

Zick SM (see Wyatt GK et al) 2015;21(4):18-23.

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

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 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 Author Index

DrRogersPrize.org

Volume 21. 2015 index

SUBJECT INDEX A Abdominal muscles Pilates method for lung function and functional capacity in obese adults.

Niehues JR, Gonzáles I, Lemos RR, Haas P. 2015;21(5):73-80.

Acupressure Self-administered acupressure for persistent cancer-related fatigue: Fidelity considerations. Wyatt GK, Frambes DA, Harris RE, Arnedt JT, Murphy SL, Zick SM. 2015;21(4):18-23.

Acupuncture The Integrative Health and Wellness (IHW) program: Development and use of a complementary and alternative medicine clinic for veterans.

Hull A, Holliday SB, Eickhoff C, Rose-Boyce M, Sullivan P, Reinhard M. 2015;21(6):12-21.

Brain-derived neurotrophic factor (BDNF) signaling pathway modulation by acupuncture in telomerase knockout mice. Lin D, Wu Q, Lin X, Borlongan CV, He ZX, Tan K, Cao C, Zhou SF. 2015;21(6):36-46.

Agglutinins Lectins, agglutinins, and their roles in autoimmune reactivities. Vojdani A. 2015;21(Suppl 1):46-51.

Immune reactivities to peanut proteins, agglutinins, and oleosins. Vojdani A. 2015;21(Suppl 1):73-79.

ALCAT test Food intolerance: Immune activation through diet-associated stimuli in chronic disease. Pietschmann N. 2015;21(4):42-52.

Alternative therapies Significant improvements in vision parameters for participants with eye disease using 4 alternative therapies. Kondrot EC. 2015;21(6):22-35.

Andullation therapy Massage therapy improves in vitro fertilization outcome in patients undergoing blastocyst transfer in a cryo-cycle. Okhowat J, Murtinger M, Schuff M, Wogatzky J, Spitzer D, Vanderzwalmen P, Wirleitner B, Zech NH. 2015;21(2):16-22.

Antigen The relevance of using the C3d/immunoglobulin G test in clinical intervention. Clarke DP, Burdette C, Agolli G, Dorval B, Gaston AM, Chesla S. 2015;21(1):16-27.

Antioxidant Vitamin C: It isn’t just for cancer anymore. Campbell AW. 2015;21(3):8-10.

Antitumor effect Medical ozone and radiotherapy in a peritoneal, Erlich-ascites, tumor-cell model. Kızıltan HŞ, Bayir AG, Yucesan G, Eris AH, İdin K, Karatoprak C, Aydin T, Akcakaya A, Mayadagli A. 2015;21(2):24-29.

Arterial function A prospective trial of ayurveda for coronary heart disease: A pilot study.

DuBroff R, Lad V, Murray-Krezan C. 2015;21(5):52-62.

Arthritis Targeting NF-κΒ and TNF-α activation by electroacupuncture to suppress collagen-induced rheumatoid arthritis in model rats. Li J, Chen R, Cai G. 2015;21(4):26-34.

Auditory stimulation The effects of musical auditory stimulation of different intensities on geometric indices of heart rate variability. do Amaral JA, Guida HL, Vanderlei FM, Garner DM, de Abreu LC, Valenti VE. 2015;21(5):16-23.

Autoimmune reactivity Lectins, agglutinins, and their roles in autoimmune reactivities. Vojdani A. 2015;21(Suppl 1):46-51.

62 ALTERNATIVE THERAPIES, NOV/DEC 2015 VOL. 21 NO. 6

Autoimmunity The gut, intestinal permeability, and autoimmunity. Campbell AW. 2015 Jan-Feb;21(1):6-7 Molecular mimicry as a mechanism for food immune reactivities and autoimmunity. Vojdani A. 2015;21(Suppl 1):34-45.

Psychobiology of vaccination effects: Bidirectional relevance of depression.

Brogan K. 2015;21(Suppl 3):18-26.

Autonomic nervous system The effects of musical auditory stimulation of different intensities on geometric indices of heart rate variability. do Amaral JA, Guida HL, Vanderlei FM, Garner DM, de Abreu LC, Valenti VE. 2015;21(5):16-23.

Ayurveda A prospective trial of ayurveda for coronary heart disease: A pilot study.

DuBroff R, Lad V, Murray-Krezan C. 2015;21(5):52-62.

B Berberine Red yeast rice plus berberine: Practical strategy for promoting vascular and metabolic health. McCarty MF, O’Keefe JH, DiNicolantonio JJ. 2015;21(Suppl 2):40-45.

Preclinical studies suggest complex nutraceutical strategies may have potential for preventing and managing sepsis. McCarty MF. 2015;21(Suppl 2):56-67.

Biliverdin Preclinical studies suggest complex nutraceutical strategies may have potential for preventing and managing sepsis. McCarty MF. 2015;21(Suppl 2):56-67.

Biochemical individuality Psychobiology of vaccination effects: Bidirectional relevance of depression.

Brogan K. 2015;21(Suppl 3):18-26.

Blastocyst transfer A broader conclusion to a well-conceived study: Must it be massage before reproductive technology? Evans JM. 2015;21(2):23.

BMI See Body mass index Body mass index Literature review: Pharmacists’ interventions to improve control and management in type 2 diabetes mellitus. Hassali MA, Nazir SU, Saleem F, Masood I. 2015;21(1):28-35.

Brain-derived neurotrophic factor Brain-derived neurotrophic factor (BDNF) signaling pathway modulation by acupuncture in telomerase knockout mice. Lin D, Wu Q, Lin X, Borlongan CV, He ZX, Tan K, Cao C, Zhou SF. 2015;21(6):36-46.

Brain injury Traumatic brain injury and the effect on the brain-gut axis. Kharrazian D. 2015;21(Suppl 3):28-32.

C CAM See Complementary and alternative medicine CAM-use disclosure Examining the association between patient-centered communication and provider avoidance, CAM use, and CAM-use disclosure. Faith J, Thorburn S, Tippens KM. 2015;21(2):30-35.

Subject Index

Cancer James Forsythe, MD, HMD: The success of integrative cancer therapy based on chemosensitivity testing and insulin potentiation therapy. Gustafson C. 2015;21(2):54-59.

Self-administered acupressure for persistent cancer-related fatigue: Fidelity considerations. Wyatt GK, Frambes DA, Harris RE, Arnedt JT, Murphy SL, Zick SM. 2015;21(4):18-23.

Carbon tetrachloride Hepatoprotective effects of grape seed procyanidin B2 in rats with carbon tetrachloride-induced hepatic fibrosis. Wang Z, Zhang Z, Du N, Wang K, Li L. 2015;21(Suppl 2):12-21.

Cardiac Oral contraceptives attenuate cardiac autonomic responses to musical auditory stimulation: Pilot study. Milan RC, Plassa BO, Guida HL, de Abreu LC, Gomes RL, Garner DM, Valenti VE. 2015;21(5):37-43.

Cardiovascular system The effects of musical auditory stimulation of different intensities on geometric indices of heart rate variability. do Amaral JA, Guida HL, Vanderlei FM, Garner DM, de Abreu LC, Valenti VE. 2015;21(5):16-23.

Case report Radioprotectant and cytotoxic effects of spirulina in relapsed verrucous vulvar cancer: A case report. Kiziltan HS, Gunes Bayir A, Taspinar O, Yucesan G, Tastekin D, Sonmez FC, Coban G, Kilic G, Eris AH, Aydin T, Akcakaya A, Mayadagli A. 2015;21(Suppl 2):68-72.

Guillain-Barré syndrome mistaken for a common spinal disorder: A case report. Kim DJ, Lee J, Kim MR, Ha IH. 2015;21(3):64-67.

Case study Treatment of a medial collateral ligament sprain using prolotherapy: A case study. Ada AM, Yavuz F. 2015;21(4):68-71.

CHD See Coronary heart disease Chemical sensitivity Terpenes and terpenoids in chemical sensitivity. Rea WJ, Restrepo C, Pan Y. 2015;21(4):12-17.

Chemosensitivity James Forsythe, MD, HMD: The success of integrative cancer therapy based on chemosensitivity testing and insulin potentiation therapy. Gustafson C. 2015;21(2):54-59.

Chemotherapy Zinc supplementation alone is effective for partial amelioration of methotrexate-induced intestinal damage. Musa NS, Howarth GS, Tran CD. 2015;21(Suppl 2):22-31.

Children Turkish nurses’ use of nonpharmacological methods for relieving children’s postoperative pain. Çelebioğlu A, Küçükoğlu S, Odabaşoğlu E. 2015;21(5):30-35.

Cholesterol A prospective trial of ayurveda for coronary heart disease: A pilot study.

DuBroff R, Lad V, Murray-Krezan C. 2015;21(5):52-62.

Cholesterol lowering Prebiotics and lipid metabolism: A review. Sharma S, Puri S. 2015;21 (Suppl 3):34-42.

Chronic pain Mumijo attenuates chemically induced inflammatory pain in mice.

Malekzadeh G, DashtiRahmatabadi MH, Zanbagh S, Akhavi Mirab-bashii A. 2015;21(2):42-47.

Colon cancer An ethanol extract of Hawaiian turmeric: Extensive in vitro anticancer activity against human colon cancer cells. Dimas K, Tsimplouli C, Houchen C, Pantazis P, Sakellaridis N, Tsangaris GT, Anastasiadou E, Ramanujam RP. 2015;21(Suppl 2):46-54.

Commentary See Perspectives Common cold Compound formulas of traditional Chinese medicine for the common cold: Systematic review of randomized, placebo-controlled trials. Li G, Cai L, Jiang H, Dong S, Fan F, Liu W, Xie L, Mao B. 2015;21(6):48-57.

Subject Index

Complement The relevance of using the C3d/immunoglobulin G test in clinical intervention. Clarke DP, Burdette C, Agolli G, Dorval B, Gaston AM, Chesla S. 2015;21(1):16-27.

Complementary and alternative medicine Examining the association between patient-centered communication and provider avoidance, CAM use, and CAM-use disclosure. Faith J, Thorburn S, Tippens KM. 2015;21(2):30-35.

The influence of traditional and complementary and alternative medicine on medication adherence in Honduras. Catalino MP, Durón RM, Bailey JN, Holden KR. 2015;21(3):26-35.

Why does treatment fidelity matter? Stone JA. 2015;21(4):24-25.

The Integrative Health and Wellness (IHW) program: Development and use of a complementary and alternative medicine clinic for veterans.

Hull A, Holliday SB, Eickhoff C, Rose-Boyce M, Sullivan P, Reinhard M. 2015;21(6):12-21.

Compound formula Compound formulas of traditional Chinese medicine for the common cold: Systematic review of randomized, placebo-controlled trials. Li G, Cai L, Jiang H, Dong S, Fan F, Liu W, Xie L, Mao B. 2015;21(6):48-57.

Conversations Paul G. Harch, MD: The genetically modulated healing effects of hyperbaric oxygen therapy. Gustafson C. 2015;21(1):46-55.

Aristo Vojdani, PhD: Environmental factors and autoimmune disease.

Burnett K. 2015;21(Suppl 1):80-86.

James Forsythe, MD, HMD: The success of integrative cancer therapy based on chemosensitivity testing and insulin potentiation therapy. Gustafson C. 2015;21(2):54-59.

Leslie Ray Matthews, MD: Enhanced surgical outcomes and boosted softtissue wellness from vitamin D supplementation. Gustafson C. 2015;21(3):68-72.

Michael Smith, MD: Treat the underlying causes of weight gain to facilitate successful weight loss, part 2: Examining the first 2 pillars of weight gain. Gustafson C. 2015;21(4):72-75.

Gerard E. Mullin, MD: The influence of the gut-brain axis on health.

Gustafson C. 2015;21(Suppl 2):73-76.

Jon Kaiser, MD: Supporting mitochondrial health with nutrient therapy.

Gustafson C. 2015;21(Suppl 2):77-79.

Michael Smith, MD: Treat the underlying causes of weight gain to facilitate successful weight loss. Gustafson C. 2015;21(5):82-86.

Tieraona Low Dog, MD: The many aspects of greening medicine. Gustafson C. 2015;21(5):88-91.

Coronary heart disease Prebiotics and lipid metabolism: A review. Sharma S, Puri S. 2015;21 (Suppl 3):34-42.

A prospective trial of ayurveda for coronary heart disease: A pilot study.

DuBroff R, Lad V, Murray-Krezan C. 2015;21(5):52-62.

Cortisol Horticultural therapy: A pilot study on modulating cortisol levels and indices of substance craving, posttraumatic stress disorder, depression, and quality of life in veterans. Detweiler MB, Self JA, Lane S, Spencer L, Lutgens B, Kim DY, Halling MH, Rudder TC, Lehmann LP. 2015;21(4):36-41.

Cryo-cycle A broader conclusion to a well-conceived study: Must it be massage before reproductive technology? Evans JM. 2015;21(2):23.

Curcuma longa An ethanol extract of Hawaiian turmeric: Extensive in vitro anticancer activity against human colon cancer cells. Dimas K, Tsimplouli C, Houchen C, Pantazis P, Sakellaridis N, Tsangaris GT, Anastasiadou E, Ramanujam RP. 2015;21(Suppl 2):46-54.

D Dance The effectiveness of dance interventions to improve older adults’ health: A systematic literature review. Hwang PW, Braun KL. 2015;21(5):64-70.

Delayed hypersensitivity reaction The relevance of using the C3d/immunoglobulin G test in clinical intervention. Clarke DP, Burdette C, Agolli G, Dorval B, Gaston AM, Chesla S. 2015;21(1):16-27.

ALTERNATIVE THERAPIES, NOV/DEC 2015 VOL. 21 NO. 6 63

Dentate gyrus Brain-derived neurotrophic factor (BDNF) signaling pathway modulation by acupuncture in telomerase knockout mice. Lin D, Wu Q, Lin X, Borlongan CV, He ZX, Tan K, Cao C, Zhou SF. 2015;21(6):36-46.

Depression Psychobiology of vaccination effects: Bidirectional relevance of depression.

Brogan K. 2015;21(Suppl 3):18-26.

Horticultural therapy: A pilot study on modulating cortisol levels and indices of substance craving, posttraumatic stress disorder, depression, and quality of life in veterans. Detweiler MB, Self JA, Lane S, Spencer L, Lutgens B, Kim DY, Halling MH, Rudder TC, Lehmann LP. 2015;21(4):36-41.

Detoxification Nutritional aspects of detoxification in clinical practice. Cline JC. 2015;21(3):54-62.

Diabetes The therapeutic effect and possible harm of puerarin for treatment of stage III diabetic nephropathy: A meta-analysis. Wang B, Chen S, Yan X, Li M, Li D, Lv P, Ti G. 2015;21(1):36-44.

Humors effect on short-term memory in healthy and diabetic older adults.

Bains GS, Berk LS, Lohman E, Daher N, Petrofsky J, Schwab E, Deshpande P. 2015;21(3):16-25.

A statin for all diabetics? Not so fast ... Bowden J, Sinatra D, Sinatra S. 2015;21(5):12-15.

Diabetes mellitus Literature review: Pharmacists’ interventions to improve control and management in type 2 diabetes mellitus. Hassali MA, Nazir SU, Saleem F, Masood I. 2015;21(1):28-35.

Diabetic Humors effect on short-term memory in healthy and diabetic older adults.

Bains GS, Berk LS, Lohman E, Daher N, Petrofsky J, Schwab E, Deshpande P. 2015;21(3):16-25.

Diet Food intolerance: Immune activation through diet-associated stimuli in chronic disease. Pietschmann N. 2015;21(4):42-52.

E Ebola Preclinical studies suggest complex nutraceutical strategies may have potential for preventing and managing sepsis. McCarty MF. 2015;21(Suppl 2):56-67.

Editorial The gut, intestinal permeability, and autoimmunity. Campbell AW. 2015 Jan-Feb;21(1):6-7 Food immune reactivities. Campbell AW. 2015;21(Suppl 1):6-7.

Our other vital organ. Campbell AW. 2015;21(2):8-10.

Nutrition. Campbell AW. 2015;21(Suppl 2):10-11.

Vitamin C: It isn’t just for cancer anymore. Campbell AW. 2015;21(3):8-10.

The gut-brain relationship. Campbell AW. 2015;21(Suppl 3):8.

Vaccines: Both sides of the same coin. Campbell AW. 2015;21(4):8-10.

Inflammation: The root of our chronic diseases. Campbell AW. 2015;21(6):8-9.

Ehrlich ascites carcinoma cells Medical ozone and radiotherapy in a peritoneal, Erlich-ascites, tumor-cell model. Kızıltan HŞ, Bayir AG, Yucesan G, Eris AH, İdin K, Karatoprak C, Aydin T, Akcakaya A, Mayadagli A. 2015;21(2):24-29.

Electroacupuncture Targeting NF-κΒ and TNF-α activation by electroacupuncture to suppress collagen-induced rheumatoid arthritis in model rats. Li J, Chen R, Cai G. 2015;21(4):26-34.

Effect of electroacupuncture on transcutaneous oxygen partial pressure during hyperbaric oxygen therapy in healthy individuals. Qu L, Ye Y, Li C, Gao G. 2015;21(5):44-51.

Embryo transfer Massage therapy improves in vitro fertilization outcome in patients undergoing blastocyst transfer in a cryo-cycle. Okhowat J, Murtinger M, Schuff M, Wogatzky J, Spitzer D, Vanderzwalmen P, Wirleitner B, Zech NH. 2015;21(2):16-22.

64 ALTERNATIVE THERAPIES, NOV/DEC 2015 VOL. 21 NO. 6

Exercise Feldenkrais method-based exercise improves quality of life in individuals with Parkinson’s disease: A controlled, randomized clinical trial.

Teixeira-Machado L, Araújo FM, Cunha FA, Menezes M, Menezes T, Melo DeSantana J. 2015;21(1):8-14.

Extract An ethanol extract of Hawaiian turmeric: Extensive in vitro anticancer activity against human colon cancer cells. Dimas K, Tsimplouli C, Houchen C, Pantazis P, Sakellaridis N, Tsangaris GT, Anastasiadou E, Ramanujam RP. 2015;21(Suppl 2):46-54.

F Fatigue Self-administered acupressure for persistent cancer-related fatigue: Fidelity considerations. Wyatt GK, Frambes DA, Harris RE, Arnedt JT, Murphy SL, Zick SM. 2015;21(4):18-23.

Feldenkrais Feldenkrais method-based exercise improves quality of life in individuals with Parkinson’s disease: A controlled, randomized clinical trial.

Teixeira-Machado L, Araújo FM, Cunha FA, Menezes M, Menezes T, Melo DeSantana J. 2015;21(1):8-14.

Female Ten-year retrospective study on the efficacy of a manual physical therapy to treat female infertility. Rice AD, Patterson K, Wakefield LB, Reed ED, Breder KP, Wurn BF, King Iii R, Wurn LJ. 2015;21(3):36-44.

Fertilization A broader conclusion to a well-conceived study: Must it be massage before reproductive technology? Evans JM. 2015;21(2):23.

Fluoridation Global water fluoridation: What is holding us back? Botchey SA, Ouyang J, Vivekanantham S. 2015;21(3):46-52.

Folic acid Preclinical studies suggest complex nutraceutical strategies may have potential for preventing and managing sepsis. McCarty MF. 2015;21(Suppl 2):56-67.

Food The evolution of food immune reactivity testing: Why immunoglobulin G or immunoglobulin A antibody for food may not be reproducible from one lab to another. Vojdani A. 2015;21(Suppl 1):8-22.

Oral tolerance and its relationship to food immunoreactivities. Vojdani A. 2015;21(Suppl 1):23-32.

Food coloring Immune reactivity to food coloring. Vojdani A, Vojdani C. 2015;21(Suppl 1):52-62.

Food immune reactivities Molecular mimicry as a mechanism for food immune reactivities and autoimmunity. Vojdani A. 2015;21(Suppl 1):34-45.

Food immunity Food immune reactivities. Campbell AW. 2015;21(Suppl 1):6-7.

Aristo Vojdani, PhD: Environmental factors and autoimmune disease.

Burnett K. 2015;21(Suppl 1):80-86.

Food intolerance Food intolerance: Immune activation through diet-associated stimuli in chronic disease. Pietschmann N. 2015;21(4):42-52.

Food sensitivity The relevance of using the C3d/immunoglobulin G test in clinical intervention. Clarke DP, Burdette C, Agolli G, Dorval B, Gaston AM, Chesla S. 2015;21(1):16-27.

Forsythe, James James Forsythe, MD, HMD: The success of integrative cancer therapy based on chemosensitivity testing and insulin potentiation therapy. Gustafson C. 2015;21(2):54-59.

G Genetics Paul G. Harch, MD: The genetically modulated healing effects of hyperbaric oxygen therapy. Gustafson C. 2015;21(1):46-55.

Subject Index

Joint Providership

MARCH 3-6, 2016 â&#x20AC;˘ SAN FRANCISCO, CA This course includes a hard copy and electronic version of a

400+ PAGE SYLLABUS of scientific medical evidence for reference

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Glycine Preclinical studies suggest complex nutraceutical strategies may have potential for preventing and managing sepsis. McCarty MF. 2015;21(Suppl 2):56-67.

Gonzalez, Nicholas Nicholas Gonzalez, MD (1947-2015). Brogan K. 2015;21(5):8-10.

Grade seed Hepatoprotective effects of grape seed procyanidin B2 in rats with carbon tetrachloride-induced hepatic fibrosis. Wang Z, Zhang Z, Du N, Wang K, Li L. 2015;21(Suppl 2):12-21.

Guillain–Barré syndrome Guillain-Barré syndrome mistaken for a common spinal disorder: A case report. Kim DJ, Lee J, Kim MR, Ha IH. 2015;21(3):64-67.

Gut The gut, intestinal permeability, and autoimmunity. Campbell AW. 2015 Jan-Feb;21(1):6-7 Gut-brain axis Traumatic brain injury and the effect on the brain-gut axis. Kharrazian D. 2015;21(Suppl 3):28-32.

Gut-brain relationship The gut-brain relationship. Campbell AW. 2015;21(Suppl 3):8.

Gut-Brain: major depressive disorder, hypothalamic dysfunction, and high calcium score associated with leaky gut. Dach J. 2015;21(Suppl 3):10-15.

H Harch, Paul Paul G. Harch, MD: The genetically modulated healing effects of hyperbaric oxygen therapy. Gustafson C. 2015;21(1):46-55 HbA1c Literature review: Pharmacists’ interventions to improve control and management in type 2 diabetes mellitus. Hassali MA, Nazir SU, Saleem F, Masood I. 2015;21(1):28-35.

Head and neck cancer Antioxidant agents: A future alternative approach in the prevention and treatment of radiation-induced oral mucositis? de Freitas Cuba L, Salum FG, Cherubini K, de Figueiredo MA. 2015;21(2):36-41.

Health care-provider avoidance Examining the association between patient-centered communication and provider avoidance, CAM use, and CAM-use disclosure. Faith J, Thorburn S, Tippens KM. 2015;21(2):30-35.

Hearing The effects of musical auditory stimulation of different intensities on geometric indices of heart rate variability. do Amaral JA, Guida HL, Vanderlei FM, Garner DM, de Abreu LC, Valenti VE. 2015;21(5):16-23.

Helicobacter pylori Phytomedicine-based and quadruple therapies in Helicobacter pylori infection: A comparative, randomized trial. Asif HM, Zaidi SF, Sugiyama T, Akhtar N, Usmanghani K. 2015;21(Suppl 2):33-39.

Heme oxygenase 1 Preclinical studies suggest complex nutraceutical strategies may have potential for preventing and managing sepsis. McCarty MF. 2015;21(Suppl 2):56-67.

Hepatic fibrosis Hepatoprotective effects of grape seed procyanidin B2 in rats with carbon tetrachloride-induced hepatic fibrosis. Wang Z, Zhang Z, Du N, Wang K, Li L. 2015;21(Suppl 2):12-21.

Hepatoprotective effects Hepatoprotective effects of grape seed procyanidin B2 in rats with carbon tetrachloride-induced hepatic fibrosis. Wang Z, Zhang Z, Du N, Wang K, Li L. 2015;21(Suppl 2):12-21.

High calcium score Gut-Brain: major depressive disorder, hypothalamic dysfunction, and high calcium score associated with leaky gut. Dach J. 2015;21(Suppl 3):10-15.

Hippocampus Brain-derived neurotrophic factor (BDNF) signaling pathway modulation by acupuncture in telomerase knockout mice. Lin D, Wu Q, Lin X, Borlongan CV, He ZX, Tan K, Cao C, Zhou SF. 2015;21(6):36-46.

66 ALTERNATIVE THERAPIES, NOV/DEC 2015 VOL. 21 NO. 6

Honduras The influence of traditional and complementary and alternative medicine on medication adherence in Honduras. Catalino MP, Durón RM, Bailey JN, Holden KR. 2015;21(3):26-35.

Hormones Smoking-related alterations in serum levels of thyroid hormones and insulin in female and male students. Meral I, Arslan A, Him A, Arslan H. 2015;21(5):24-29.

Horticultural therapy Horticultural therapy: A pilot study on modulating cortisol levels and indices of substance craving, posttraumatic stress disorder, depression, and quality of life in veterans. Detweiler MB, Self JA, Lane S, Spencer L, Lutgens B, Kim DY, Halling MH, Rudder TC, Lehmann LP. 2015;21(4):36-41.

HPA axis See Hypothalamic–pituitary–adrenal axis Human An ethanol extract of Hawaiian turmeric: Extensive in vitro anticancer activity against human colon cancer cells. Dimas K, Tsimplouli C, Houchen C, Pantazis P, Sakellaridis N, Tsangaris GT, Anastasiadou E, Ramanujam RP. 2015;21(Suppl 2):46-54.

Humor Humors effect on short-term memory in healthy and diabetic older adults.

Bains GS, Berk LS, Lohman E, Daher N, Petrofsky J, Schwab E, Deshpande P. 2015;21(3):16-25.

Hyperbaric oxygenation Effect of electroacupuncture on transcutaneous oxygen partial pressure during hyperbaric oxygen therapy in healthy individuals. Qu L, Ye Y, Li C, Gao G. 2015;21(5):44-51.

Hyperbaric oxygen therapy Paul G. Harch, MD: The genetically modulated healing effects of hyperbaric oxygen therapy. Gustafson C. 2015;21(1):46-55.

Hypertension Development of a modified yoga program for pulmonary hypertension: A case series. Awdish R, Small B, Cajigas H. 2015;21(2):48-52.

A prospective trial of ayurveda for coronary heart disease: A pilot study.

DuBroff R, Lad V, Murray-Krezan C. 2015;21(5):52-62.

Hypothalamic dysfunction Gut-Brain: major depressive disorder, hypothalamic dysfunction, and high calcium score associated with leaky gut. Dach J. 2015;21(Suppl 3):10-15.

Hypothalamic–pituitary–adrenal axis Gerard E. Mullin, MD: The influence of the gut-brain axis on health.

Gustafson C. 2015;21(Suppl 2):73-76.

Psychobiology of vaccination effects: Bidirectional relevance of depression.

Brogan K. 2015;21(Suppl 3):18-26.

I Ig See Immunoglobulin IgA See Immunoglobulin A IgE See Immunoglobulin E IgG See Immunoglobulin G Immune reactivity Immune reactivity to food coloring. Vojdani A, Vojdani C. 2015;21(Suppl 1):52-62.

Immunoglobulin The relevance of using the C3d/immunoglobulin G test in clinical intervention. Clarke DP, Burdette C, Agolli G, Dorval B, Gaston AM, Chesla S. 2015;21(1):16-27.

Immunoglobulin A The evolution of food immune reactivity testing: Why immunoglobulin G or immunoglobulin A antibody for food may not be reproducible from one lab to another. Vojdani A. 2015;21(Suppl 1):8-22.

Lectins, agglutinins, and their roles in autoimmune reactivities. Vojdani A. 2015;21(Suppl 1):46-51.

Subject Index

Immunoglobulin E The evolution of food immune reactivity testing: Why immunoglobulin G or immunoglobulin A antibody for food may not be reproducible from one lab to another. Vojdani A. 2015;21(Suppl 1):8-22.

Immune reactivities to peanut proteins, agglutinins, and oleosins. Vojdani A. 2015;21(Suppl 1):73-79.

Immunoglobulin G The evolution of food immune reactivity testing: Why immunoglobulin G or immunoglobulin A antibody for food may not be reproducible from one lab to another. Vojdani A. 2015;21(Suppl 1):8-22.

Lectins, agglutinins, and their roles in autoimmune reactivities. Vojdani A. 2015;21(Suppl 1):46-51.

Immune reactivities to peanut proteins, agglutinins, and oleosins. Vojdani A. 2015;21(Suppl 1):73-79.

Immunoreactivities The evolution of food immune reactivity testing: Why immunoglobulin G or immunoglobulin A antibody for food may not be reproducible from one lab to another. Vojdani A. 2015;21(Suppl 1):8-22.

Infertility Ten-year retrospective study on the efficacy of a manual physical therapy to treat female infertility. Rice AD, Patterson K, Wakefield LB, Reed ED, Breder KP, Wurn BF, King Iii R, Wurn LJ. 2015;21(3):36-44.

Inflammasome Food intolerance: Immune activation through diet-associated stimuli in chronic disease. Pietschmann N. 2015;21(4):42-52.

Inflammation The relevance of using the C3d/immunoglobulin G test in clinical intervention. Clarke DP, Burdette C, Agolli G, Dorval B, Gaston AM, Chesla S. 2015;21(1):16-27.

Psychobiology of vaccination effects: Bidirectional relevance of depression.

Brogan K. 2015;21(Suppl 3):18-26.

Inflammation: The root of our chronic diseases. Campbell AW. 2015;21(6):8-9.

Informed consent Psychobiology of vaccination effects: Bidirectional relevance of depression.

Brogan K. 2015;21(Suppl 3):18-26.

Insulin Smoking-related alterations in serum levels of thyroid hormones and insulin in female and male students. Meral I, Arslan A, Him A, Arslan H. 2015;21(5):24-29.

Interview See Conversations Intestinal mucositis Zinc supplementation alone is effective for partial amelioration of methotrexate-induced intestinal damage. Musa NS, Howarth GS, Tran CD. 2015;21(Suppl 2):22-31.

Intestinal permeability The gut, intestinal permeability, and autoimmunity. Campbell AW. 2015 Jan-Feb;21(1):6-7 The relevance of using the C3d/immunoglobulin G test in clinical intervention. Clarke DP, Burdette C, Agolli G, Dorval B, Gaston AM, Chesla S. 2015;21(1):16-27.

In vitro A broader conclusion to a well-conceived study: Must it be massage before reproductive technology? Evans JM. 2015;21(2):23.

In vitro fertilization Massage therapy improves in vitro fertilization outcome in patients undergoing blastocyst transfer in a cryo-cycle. Okhowat J, Murtinger M, Schuff M, Wogatzky J, Spitzer D, Vanderzwalmen P, Wirleitner B, Zech NH. 2015;21(2):16-22.

Ionizing radiation Antioxidant agents: A future alternative approach in the prevention and treatment of radiation-induced oral mucositis? de Freitas Cuba L, Salum FG, Cherubini K, de Figueiredo MA. 2015;21(2):36-41.

IVF See In vitro fertilization

Subject Index

K Kaiser, Jon Jon Kaiser, MD: Supporting mitochondrial health with nutrient therapy.

Gustafson C. 2015;21(Suppl 2):77-79.

L LDL cholesterol See Low-density lipoprotein Leaky gut Gut-Brain: major depressive disorder, hypothalamic dysfunction, and high calcium score associated with leaky gut. Dach J. 2015;21(Suppl 3):10-15.

Lectins Lectins, agglutinins, and their roles in autoimmune reactivities. Vojdani A. 2015;21(Suppl 1):46-51.

Letter to the editor Vitamin D: Dosages to optimize serum levels. Baggerly LL. 2015;21(3):14-15.

Lipid profile Prebiotics and lipid metabolism: A review. Sharma S, Puri S. 2015;21 (Suppl 3):34-42.

Lipoic acid Preclinical studies suggest complex nutraceutical strategies may have potential for preventing and managing sepsis. McCarty MF. 2015;21(Suppl 2):56-67.

Literature review See Review article Low-density lipoprotein cholesterol Literature review: Pharmacists’ interventions to improve control and management in type 2 diabetes mellitus. Hassali MA, Nazir SU, Saleem F, Masood I. 2015;21(1):28-35.

Vitamin C: It isn’t just for cancer anymore. Campbell AW. 2015;21(3):8-10.

Low Dog, Tieraona Tieraona Low Dog, MD: The many aspects of greening medicine. Gustafson C. 2015;21(5):88-91.

M Major depressive disorder Gut-Brain: major depressive disorder, hypothalamic dysfunction, and high calcium score associated with leaky gut. Dach J. 2015;21(Suppl 3):10-15.

Manual physical therapy Ten-year retrospective study on the efficacy of a manual physical therapy to treat female infertility. Rice AD, Patterson K, Wakefield LB, Reed ED, Breder KP, Wurn BF, King Iii R, Wurn LJ. 2015;21(3):36-44.

Massage therapy A broader conclusion to a well-conceived study: Must it be massage before reproductive technology? Evans JM. 2015;21(2):23.

MCL See Medial collateral ligament Medial collateral ligament Treatment of a medial collateral ligament sprain using prolotherapy: A case study. Ada AM, Yavuz F. 2015;21(4):68-71.

Medical ozone therapy Medical ozone and radiotherapy in a peritoneal, Erlich-ascites, tumor-cell model. Kızıltan HŞ, Bayir AG, Yucesan G, Eris AH, İdin K, Karatoprak C, Aydin T, Akcakaya A, Mayadagli A. 2015;21(2):24-29.

Meditation The Integrative Health and Wellness (IHW) program: Development and use of a complementary and alternative medicine clinic for veterans.

Hull A, Holliday SB, Eickhoff C, Rose-Boyce M, Sullivan P, Reinhard M. 2015;21(6):12-21.

Meta-analysis The therapeutic effect and possible harm of puerarin for treatment of stage III diabetic nephropathy: A meta-analysis. Wang B, Chen S, Yan X, Li M, Li D, Lv P, Ti G. 2015;21(1):36-44.

Metabolic health Red yeast rice plus berberine: Practical strategy for promoting vascular and metabolic health. McCarty MF, O’Keefe JH, DiNicolantonio JJ. 2015;21(Suppl 2):40-45.

ALTERNATIVE THERAPIES, NOV/DEC 2015 VOL. 21 NO. 6 67

Metabolic syndrome Efficacy of the wen dan decoction, a Chinese herbal formula, for metabolic syndrome. Huang YM, Xu JH, Ling W, Li Y, Zhang XX, Dai ZK, Sui Y, Zhao HL. 2015;21(4):54-67.

Metformin Preclinical studies suggest complex nutraceutical strategies may have potential for preventing and managing sepsis. McCarty MF. 2015;21(Suppl 2):56-67.

Methotrexate Zinc supplementation alone is effective for partial amelioration of methotrexate-induced intestinal damage. Musa NS, Howarth GS, Tran CD. 2015;21(Suppl 2):22-31.

Metronidazole Radioprotectant and cytotoxic effects of spirulina in relapsed verrucous vulvar cancer: A case report. Kiziltan HS, Gunes Bayir A, Taspinar O, Yucesan G, Tastekin D, Sonmez FC, Coban G, Kilic G, Eris AH, Aydin T, Akcakaya A, Mayadagli A. 2015;21(Suppl 2):68-72.

Microalgae Radioprotectant and cytotoxic effects of spirulina in relapsed verrucous vulvar cancer: A case report. Kiziltan HS, Gunes Bayir A, Taspinar O, Yucesan G, Tastekin D, Sonmez FC, Coban G, Kilic G, Eris AH, Aydin T, Akcakaya A, Mayadagli A. 2015;21(Suppl 2):68-72.

Microbiome Our other vital organ. Campbell AW. 2015;21(2):8-10.

Gerard E. Mullin, MD: The influence of the gut-brain axis on health.

Gustafson C. 2015;21(Suppl 2):73-76.

Psychobiology of vaccination effects: Bidirectional relevance of depression.

Brogan K. 2015;21(Suppl 3):18-26.

Military The Integrative Health and Wellness (IHW) program: Development and use of a complementary and alternative medicine clinic for veterans.

Hull A, Holliday SB, Eickhoff C, Rose-Boyce M, Sullivan P, Reinhard M. 2015;21(6):12-21.

Mitochondrial health Jon Kaiser, MD: Supporting mitochondrial health with nutrient therapy.

Gustafson C. 2015;21(Suppl 2):77-79.

Molecular mimicry Molecular mimicry as a mechanism for food immune reactivities and autoimmunity. Vojdani A. 2015;21(Suppl 1):34-45.

Morphine sulfate Mumijo attenuates chemically induced inflammatory pain in mice.

Malekzadeh G, Dashti-Rahmatabadi MH, Zanbagh S, Akhavi Mirabbashii A. 2015;21(2):42-47.

Mullin, Gerard Gerard E. Mullin, MD: The influence of the gut-brain axis on health.

Gustafson C. 2015;21(Suppl 2):73-76.

Mumijo Mumijo attenuates chemically induced inflammatory pain in mice.

Malekzadeh G, Dashti-Rahmatabadi MH, Zanbagh S, Akhavi Mirabbashii A. 2015;21(2):42-47.

Muscular strengthening Pilates method for lung function and functional capacity in obese adults.

Niehues JR, Gonzáles I, Lemos RR, Haas P. 2015;21(5):73-80.

Music Oral contraceptives attenuate cardiac autonomic responses to musical auditory stimulation: Pilot study. Milan RC, Plassa BO, Guida HL, de Abreu LC, Gomes RL, Garner DM, Valenti VE. 2015;21(5):37-43.

N Nephropathy The therapeutic effect and possible harm of puerarin for treatment of stage III diabetic nephropathy: A meta-analysis. Wang B, Chen S, Yan X, Li M, Li D, Lv P, Ti G. 2015;21(1):36-44.

NF-κB Targeting NF-κΒ and TNF-α activation by electroacupuncture to suppress collagen-induced rheumatoid arthritis in model rats. Li J, Chen R, Cai G. 2015;21(4):26-34.

68 ALTERNATIVE THERAPIES, NOV/DEC 2015 VOL. 21 NO. 6

Nurse Turkish nurses’ use of nonpharmacological methods for relieving children’s postoperative pain. Çelebioğlu A, Küçükoğlu S, Odabaşoğlu E. 2015;21(5):30-35.

Nutrition Nutritional aspects of detoxification in clinical practice. Cline JC. 2015;21(3):54-62.

Nutrition. Campbell AW. 2015;21(Suppl 2):10-11.

Jon Kaiser, MD: Supporting mitochondrial health with nutrient therapy.

Gustafson C. 2015;21(Suppl 2):77-79.

O Older adults Humors effect on short-term memory in healthy and diabetic older adults.

Bains GS, Berk LS, Lohman E, Daher N, Petrofsky J, Schwab E, Deshpande P. 2015;21(3):16-25.

The effectiveness of dance interventions to improve older adults’ health: A systematic literature review. Hwang PW, Braun KL. 2015;21(5):64-70.

Oleosin Immune reactivities to peanut proteins, agglutinins, and oleosins. Vojdani A. 2015;21(Suppl 1):73-79.

Oral contraceptives Oral contraceptives attenuate cardiac autonomic responses to musical auditory stimulation: Pilot study. Milan RC, Plassa BO, Guida HL, de Abreu LC, Gomes RL, Garner DM, Valenti VE. 2015;21(5):37-43.

Oral mucositis Antioxidant agents: A future alternative approach in the prevention and treatment of radiation-induced oral mucositis? de Freitas Cuba L, Salum FG, Cherubini K, de Figueiredo MA. 2015;21(2):36-41.

Oral tolerance The evolution of food immune reactivity testing: Why immunoglobulin G or immunoglobulin A antibody for food may not be reproducible from one lab to another. Vojdani A. 2015;21(Suppl 1):8-22.

Oral tolerance and its relationship to food immunoreactivities. Vojdani A. 2015;21(Suppl 1):23-32.

Original research Feldenkrais method-based exercise improves quality of life in individuals with Parkinson’s disease: A controlled, randomized clinical trial.

Teixeira-Machado L, Araújo FM, Cunha FA, Menezes M, Menezes T, Melo DeSantana J. 2015;21(1):8-14.

The relevance of using the C3d/immunoglobulin G test in clinical intervention. Clarke DP, Burdette C, Agolli G, Dorval B, Gaston AM, Chesla S. 2015;21(1):16-27.

Immune reactivities against gums. Vojdani A, Vojdani C. 2015;21(Suppl 1):64-72.

Immune reactivities to peanut proteins, agglutinins, and oleosins. Vojdani A. 2015;21(Suppl 1):73-79.

Medical ozone and radiotherapy in a peritoneal, Erlich-ascites, tumor-cell model. Kızıltan HŞ, Bayir AG, Yucesan G, Eris AH, İdin K, Karatoprak C, Aydin T, Akcakaya A, Mayadagli A. 2015;21(2):24-29.

Examining the association between patient-centered communication and provider avoidance, CAM use, and CAM-use disclosure. Faith J, Thorburn S, Tippens KM. 015;21(2):30-35.

Hepatoprotective effects of grape seed procyanidin B2 in rats with carbon tetrachloride-induced hepatic fibrosis. Wang Z, Zhang Z, Du N, Wang K, Li L. 2015;21 (Suppl 2):12-21.

Zinc supplementation alone is effective for partial amelioration of methotrexate-induced intestinal damage. Musa NS, Howarth GS, Tran CD. 2015;21(Suppl 2):22-31.

Phytomedicine-based and quadruple therapies in Helicobacter pylori infection: A comparative, randomized trial. Asif HM, Zaidi SF, Sugiyama T, Akhtar N, Usmanghani K. 2015;21(Suppl 2):33-39.

Preclinical studies suggest complex nutraceutical strategies may have potential for preventing and managing sepsis. McCarty MF. 2015;21(Suppl 2):56-67.

Humors effect on short-term memory in healthy and diabetic older adults.

Bains GS, Berk LS, Lohman E, Daher N, Petrofsky J, Schwab E, Deshpande P. 2015;21(3):16-25.

Subject Index

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The influence of traditional and complementary and alternative medicine on medication adherence in Honduras. Catalino MP, Durón RM, Bailey JN, Holden KR. 2015;21(3):26-35.

Terpenes and terpenoids in chemical sensitivity. Rea WJ, Restrepo C, Pan Y. 2015;21(4):12-17.

Self-administered acupressure for persistent cancer-related fatigue: Fidelity considerations. Wyatt GK, Frambes DA, Harris RE, Arnedt JT, Murphy SL, Zick SM. 2015;21(4):18-23.

Targeting NF-κΒ and TNF-α activation by electroacupuncture to suppress collagen-induced rheumatoid arthritis in model rats. Li J, Li J, Chen R, Cai G. 2015;21(4):26-34.

The effects of musical auditory stimulation of different intensities on geometric indices of heart rate variability. do Amaral JA, Guida HL, Vanderlei FM, Garner DM, de Abreu LC, Valenti VE. 2015;21(5):16-23.

Smoking-related alterations in serum levels of thyroid hormones and insulin in female and male students. Meral I, Arslan A, Him A, Arslan H. 2015;21(5):24-29.

Turkish nurses’ use of nonpharmacological methods for relieving children’s postoperative pain. Çelebioğlu A, Küçükoğlu S, Odabaşoğlu E. 2015;21(5):30-35.

Oral contraceptives attenuate cardiac autonomic responses to musical auditory stimulation: Pilot study. Milan RC, Plassa BO, Guida HL, de Abreu LC, Gomes RL, Garner DM, Valenti VE. 2015;21(5):37-43.

The Integrative Health and Wellness (IHW) program: Development and use of a complementary and alternative medicine clinic for veterans.

Hull A, Holliday SB, Eickhoff C, Rose-Boyce M, Sullivan P, Reinhard M. 2015;21(6):12-21.

Significant improvements in vision parameters for participants with eye disease using 4 alternative therapies. Kondrot EC. 2015;21(6):22-35.

Brain-derived neurotrophic factor (BDNF) signalling pathway modulation by acupuncture in telomerase knockout mice. Lin D, Wu Q, Lin X, Borlongan CV, He ZX, Tan K, Cao C, Zhou SF. 2015;21(6):36-46.

P Parkinson’s disease Feldenkrais method-based exercise improves quality of life in individuals with Parkinson’s disease: A controlled, randomized clinical trial.

Teixeira-Machado L, Araújo FM, Cunha FA, Menezes M, Menezes T, Melo DeSantana J. 2015;21(1):8-14.

Patient-centered communication Examining the association between patient-centered communication and provider avoidance, CAM use, and CAM-use disclosure. Faith J, Thorburn S, Tippens KM. 2015;21(2):30-35 Patient-provider relationships Examining the association between patient-centered communication and provider avoidance, CAM use, and CAM-use disclosure. Faith J, Thorburn S, Tippens KM. 2015;21(2):30-35 Peanut protein Immune reactivities to peanut proteins, agglutinins, and oleosins. Vojdani A. 2015;21(Suppl 1):73-79.

Peritoneal carcinomatosis Medical ozone and radiotherapy in a peritoneal, Erlich-ascites, tumor-cell model. Kızıltan HŞ, Bayir AG, Yucesan G, Eris AH, İdin K, Karatoprak C, Aydin T, Akcakaya A, Mayadagli A. 2015;21(2):24-29.

Perspectives Statistics: Why meaningful statistics cannot be generated from a private practice. Gonzalez NJ, Isaacs LL. 2015;21(2):11-15.

A broader conclusion to a well-conceived study: Must it be massage before reproductive technology? Evans JM. 2015;21(2):23.

Why does treatment fidelity matter? Stone JA. 2015;21(4):24-25.

Gut-Brain: major depressive disorder, hypothalamic dysfunction, and high calcium score associated with leaky gut. Dach J. 2015;21(Suppl 3):10-15.

Nicholas Gonzalez, MD (1947-2015). Brogan K. 2015;21(5):8-10.

A statin for all diabetics? Not so fast ... Bowden J, Sinatra D, Sinatra S. 2015;21(5):12-15.

Pharmacist’s intervention Literature review: Pharmacists’ interventions to improve control and management in type 2 diabetes mellitus. Hassali MA, Nazir SU, Saleem F, Masood I. 2015;21(1):28-35.

70 ALTERNATIVE THERAPIES, NOV/DEC 2015 VOL. 21 NO. 6

Phycocyanobilin Preclinical studies suggest complex nutraceutical strategies may have potential for preventing and managing sepsis. McCarty MF. 2015;21(Suppl 2):56-67.

Phytomedicine Phytomedicine-based and quadruple therapies in Helicobacter pylori infection: A comparative, randomized trial. Asif HM, Zaidi SF, Sugiyama T, Akhtar N, Usmanghani K. 2015;21(Suppl 2):33-39.

Pilot study Horticultural therapy: A pilot study on modulating cortisol levels and indices of substance craving, posttraumatic stress disorder, depression, and quality of life in veterans. Detweiler MB, Self JA, Lane S, Spencer L, Lutgens B, Kim DY, Halling MH, Rudder TC, Lehmann LP. 2015;21(4):36-41.

Oral contraceptives attenuate cardiac autonomic responses to musical auditory stimulation: Pilot study. Milan RC, Plassa BO, Guida HL, de Abreu LC, Gomes RL, Garner DM, Valenti VE. 2015;21(5):37-43.

Effect of electroacupuncture on transcutaneous oxygen partial pressure during hyperbaric oxygen therapy in healthy individuals. Qu L, Ye Y, Li C, Gao G. 2015;21(5):44-51.

A prospective trial of ayurveda for coronary heart disease: A pilot study.

DuBroff R, Lad V, Murray-Krezan C. 2015;21(5):52-62.

The Integrative Health and Wellness (IHW) program: Development and use of a complementary and alternative medicine clinic for veterans.

Hull A, Holliday SB, Eickhoff C, Rose-Boyce M, Sullivan P, Reinhard M. 2015;21(6):12-21.

Postoperative pain management Turkish nurses’ use of nonpharmacological methods for relieving children’s postoperative pain. Çelebioğlu A, Küçükoğlu S, Odabaşoğlu E. 2015;21(5):30-35.

Posttraumatic stress disorder Horticultural therapy: A pilot study on modulating cortisol levels and indices of substance craving, posttraumatic stress disorder, depression, and quality of life in veterans. Detweiler MB, Self JA, Lane S, Spencer L, Lutgens B, Kim DY, Halling MH, Rudder TC, Lehmann LP. 2015;21(4):36-41.

Pregnancy rate Massage therapy improves in vitro fertilization outcome in patients undergoing blastocyst transfer in a cryo-cycle. Okhowat J, Murtinger M, Schuff M, Wogatzky J, Spitzer D, Vanderzwalmen P, Wirleitner B, Zech NH. 2015;21(2):16-22.

Probiotics Zinc supplementation alone is effective for partial amelioration of methotrexate-induced intestinal damage. Musa NS, Howarth GS, Tran CD. 2015;21(Suppl 2):22-31.

Prebiotics and lipid metabolism: A review. Sharma S, Puri S. 2015;21 (Suppl 3):34-42.

Procyanidin B2 Hepatoprotective effects of grape seed procyanidin B2 in rats with carbon tetrachloride-induced hepatic fibrosis. Wang Z, Zhang Z, Du N, Wang K, Li L. 2015;21(Suppl 2):12-21.

Prolotherapy Treatment of a medial collateral ligament sprain using prolotherapy: A case study. Ada AM, Yavuz F. 2015;21(4):68-71.

Psychiatry Psychobiology of vaccination effects: Bidirectional relevance of depression.

Brogan K. 2015;21(Suppl 3):18-26.

Psychological stress Massage therapy improves in vitro fertilization outcome in patients undergoing blastocyst transfer in a cryo-cycle. Okhowat J, Murtinger M, Schuff M, Wogatzky J, Spitzer D, Vanderzwalmen P, Wirleitner B, Zech NH. 2015;21(2):16-22.

PTSD See Posttraumatic stress disorder Puerarin The therapeutic effect and possible harm of puerarin for treatment of stage III diabetic nephropathy: A meta-analysis. Wang B, Chen S, Yan X, Li M, Li D, Lv P, Ti G. 2015;21(1):36-44.

Subject Index

Q QOL See Quality of life Quadruple therapies Phytomedicine-based and quadruple therapies in Helicobacter pylori infection: A comparative, randomized trial. Asif HM, Zaidi SF, Sugiyama T, Akhtar N, Usmanghani K. 2015;21(Suppl 2):33-39.

Quality of life Feldenkrais method-based exercise improves quality of life in individuals with Parkinson’s disease: A controlled, randomized clinical trial.

Teixeira-Machado L, Araújo FM, Cunha FA, Menezes M, Menezes T, Melo DeSantana J. 2015;21(1):8-14.

Horticultural therapy: A pilot study on modulating cortisol levels and indices of substance craving, posttraumatic stress disorder, depression, and quality of life in veterans. Detweiler MB, Self JA, Lane S, Spencer L, Lutgens B, Kim DY, Halling MH, Rudder TC, Lehmann LP. 2015;21(4):36-41.

R Radioprotectants Radioprotectant and cytotoxic effects of spirulina in relapsed verrucous vulvar cancer: A case report. Kiziltan HS, Gunes Bayir A, Taspinar O, Yucesan G, Tastekin D, Sonmez FC, Coban G, Kilic G, Eris AH, Aydin T, Akcakaya A, Mayadagli A. 2015;21(Suppl 2):68-72.

Radiotherapy Medical ozone and radiotherapy in a peritoneal, Erlich-ascites, tumor-cell model. Kızıltan HŞ, Bayir AG, Yucesan G, Eris AH, İdin K, Karatoprak C, Aydin T, Akcakaya A, Mayadagli A. 2015;21(2):24-29.

Reactivities Food immune reactivities. Campbell AW. 2015;21(Suppl 1):6-7.

Aristo Vojdani, PhD: Environmental factors and autoimmune disease.

Burnett K. 2015;21(Suppl 1):80-86.

Reactivity testing The evolution of food immune reactivity testing: Why immunoglobulin G or immunoglobulin A antibody for food may not be reproducible from one lab to another. Vojdani A. 2015;21(Suppl 1):8-22.

Red yeast rice Red yeast rice plus berberine: Practical strategy for promoting vascular and metabolic health. McCarty MF, O’Keefe JH, DiNicolantonio JJ. 2015;21(Suppl 2):40-45.

Renal function Efficacy of the wen dan decoction, a Chinese herbal formula, for metabolic syndrome. Huang YM, Xu JH, Ling W, Li Y, Zhang XX, Dai ZK, Sui Y, Zhao HL. 2015;21(4):54-67.

Respiratory function Pilates method for lung function and functional capacity in obese adults.

Niehues JR, Gonzáles I, Lemos RR, Haas P. 2015;21(5):73-80.

Retrospective study Ten-year retrospective study on the efficacy of a manual physical therapy to treat female infertility. Rice AD, Patterson K, Wakefield LB, Reed ED, Breder KP, Wurn BF, King Iii R, Wurn LJ. 2015;21(3):36-44.

Review article Literature review: Pharmacists’ interventions to improve control and management in type 2 diabetes mellitus. Hassali MA, Nazir SU, Saleem F, Masood I. 2015;21(1):28-35.

The therapeutic effect and possible harm of puerarin for treatment of stage III diabetic nephropathy: A meta-analysis. Wang B, Chen S, Yan X, Li M, Li D, Lv P, Ti G. 2015;21(1):36-44.

The evolution of food immune reactivity testing: Why immunoglobulin G or immunoglobulin A antibody for food may not be reproducible from one lab to another. Vojdani A. 2015;21(Suppl 1):8-22.

Oral tolerance and its relationship to food immunoreactivities. Vojdani A. 2015;21(Suppl 1):23-32.

Molecular mimicry as a mechanism for food immune reactivities and autoimmunity. Vojdani A. 2015;21(Suppl 1):34-45.

Lectins, agglutinins, and their roles in autoimmune reactivities. Vojdani A. 2015;21(Suppl 1):46-51.

Immune reactivity to food coloring. Vojdani A, Vojdani C. 2015;21(Suppl 1):52-62.

Subject Index

Antioxidant agents: A future alternative approach in the prevention and treatment of radiation-induced oral mucositis? de Freitas Cuba L, Salum FG, Cherubini K, de Figueiredo MA. 2015;21(2):36-41.

Mumijo attenuates chemically induced inflammatory pain in mice.

Malekzadeh G, Dashti-Rahmatabadi MH, Zanbagh S, Akhavi Mirabbashii A. 2015;21(2):42-47.

Red yeast rice plus berberine: Practical strategy for promoting vascular and metabolic health. McCarty MF, O’Keefe JH, DiNicolantonio JJ. 2015;21(Suppl 2):40-45.

An ethanol extract of Hawaiian turmeric: Extensive in vitro anticancer activity against human colon cancer cells. Dimas K, Tsimplouli C, Houchen C, Pantazis P, Sakellaridis N, Tsangaris GT, Anastasiadou E, Ramanujam RP. 2015;21(Suppl 2):46-54.

Global water fluoridation: What is holding us back? Botchey SA, Ouyang J, Vivekanantham S. 2015;21(3):46-52.

Nutritional aspects of detoxification in clinical practice. Cline JC. 2015;21(3):54-62.

Psychobiology of vaccination effects: Bidirectional relevance of depression.

Brogan K. 2015;21(Suppl 3):18-26.

Traumatic brain injury and the effect on the brain-gut axis. Kharrazian D. 2015;21(Suppl 3):28-32.

Prebiotics and lipid metabolism: A review. Sharma S, Puri S. 2015;21 (Suppl 3):34-42.

Food intolerance: Immune activation through diet-associated stimuli in chronic disease. Pietschmann N. 2015;21(4):42-52.

The effectiveness of dance interventions to improve older adults’ health: A systematic literature review. Hwang PW, Braun KL. 2015;21(5):64-70.

Pilates method for lung function and functional capacity in obese adults.

Niehues JR, Gonzáles I, Lemos RR, Haas P. 2015;21(5):73-80.

Compound formulas of traditional Chinese medicine for the common cold: Systematic review of randomized, placebo-controlled trials. Li G, Cai L, Jiang H, Dong S, Fan F, Liu W, Xie L, Mao B. 2015;21(6):48-57.

S Second-line radiotherapy Radioprotectant and cytotoxic effects of spirulina in relapsed verrucous vulvar cancer: A case report. Kiziltan HS, Gunes Bayir A, Taspinar O, Yucesan G, Tastekin D, Sonmez FC, Coban G, Kilic G, Eris AH, Aydin T, Akcakaya A, Mayadagli A. 2015;21(Suppl 2):68-72.

Sepsis Preclinical studies suggest complex nutraceutical strategies may have potential for preventing and managing sepsis. McCarty MF. 2015;21(Suppl 2):56-67.

Serum Smoking-related alterations in serum levels of thyroid hormones and insulin in female and male students. Meral I, Arslan A, Him A, Arslan H. 2015;21(5):24-29.

Short-term memory Humors effect on short-term memory in healthy and diabetic older adults.

Bains GS, Berk LS, Lohman E, Daher N, Petrofsky J, Schwab E, Deshpande P. 2015;21(3):16-25.

Smith, Michael Michael Smith, MD: Treat the underlying causes of weight gain to facilitate successful weight loss. Gustafson C. 2015;21(5):82-86.

Smoking Smoking-related alterations in serum levels of thyroid hormones and insulin in female and male students. Meral I, Arslan A, Him A, Arslan H. 2015;21(5):24-29.

Sodium diclofenac Mumijo attenuates chemically induced inflammatory pain in mice.

Malekzadeh G, Dashti-Rahmatabadi MH, Zanbagh S, Akhavi Mirabbashii A. 2015;21(2):42-47.

Spinal disorder Guillain-Barré syndrome mistaken for a common spinal disorder: A case report. Kim DJ, Lee J, Kim MR, Ha IH. 2015;21(3):64-67.

Spirulina Radioprotectant and cytotoxic effects of spirulina in relapsed verrucous vulvar cancer: A case report. Kiziltan HS, Gunes Bayir A, Taspinar O, Yucesan G, Tastekin D, Sonmez FC, Coban G, Kilic G, Eris AH, Aydin T, Akcakaya A, Mayadagli A. 2015;21(Suppl 2):68-72.

ALTERNATIVE THERAPIES, NOV/DEC 2015 VOL. 21 NO. 6 71

Sprain Treatment of a medial collateral ligament sprain using prolotherapy: A case study. Ada AM, Yavuz F. 2015;21(4):68-71.

Statins A statin for all diabetics? Not so fast ... Bowden J, Sinatra D, Sinatra S. 2015;21(5):12-15.

Students Smoking-related alterations in serum levels of thyroid hormones and insulin in female and male students. Meral I, Arslan A, Him A, Arslan H. 2015;21(5):24-29.

Tumor spheroids An ethanol extract of Hawaiian turmeric: Extensive in vitro anticancer activity against human colon cancer cells. Dimas K, Tsimplouli C, Houchen C, Pantazis P, Sakellaridis N, Tsangaris GT, Anastasiadou E, Ramanujam RP. 2015;21(Suppl 2):46-54.

Turmeric An ethanol extract of Hawaiian turmeric: Extensive in vitro anticancer activity against human colon cancer cells. Dimas K, Tsimplouli C, Houchen C, Pantazis P, Sakellaridis N, Tsangaris GT, Anastasiadou E, Ramanujam RP. 2015;21(Suppl 2):46-54.

T TCM See Traditional Chinese medicine Telomerase Brain-derived neurotrophic factor (BDNF) signaling pathway modulation by acupuncture in telomerase knockout mice. Lin D, Wu Q, Lin X, Borlongan CV, He ZX, Tan K, Cao C, Zhou SF. 2015;21(6):36-46.

Telomerase-deficient mice Brain-derived neurotrophic factor (BDNF) signaling pathway modulation by acupuncture in telomerase knockout mice. Lin D, Wu Q, Lin X, Borlongan CV, He ZX, Tan K, Cao C, Zhou SF. 2015;21(6):36-46.

Terpenes Terpenes and terpenoids in chemical sensitivity. Rea WJ, Restrepo C, Pan Y. 2015;21(4):12-17.

Terpenoids Terpenes and terpenoids in chemical sensitivity. Rea WJ, Restrepo C, Pan Y. 2015;21(4):12-17.

Therapeutic use Effect of electroacupuncture on transcutaneous oxygen partial pressure during hyperbaric oxygen therapy in healthy individuals. Qu L, Ye Y, Li C, Gao G. 2015;21(5):44-51.

Thyroid Smoking-related alterations in serum levels of thyroid hormones and insulin in female and male students. Meral I, Arslan A, Him A, Arslan H. 2015;21(5):24-29.

TNF-α See Tumor necrosis factor α Traditional Chinese medicine Efficacy of the wen dan decoction, a Chinese herbal formula, for metabolic syndrome. Huang YM, Xu JH, Ling W, Li Y, Zhang XX, Dai ZK, Sui Y, Zhao HL. 2015;21(4):54-67.

Compound formulas of traditional Chinese medicine for the common cold: Systematic review of randomized, placebo-controlled trials. Li G, Cai L, Jiang H, Dong S, Fan F, Liu W, Xie L, Mao B. 2015;21(6):48-57.

Traditional medicine The influence of traditional and complementary and alternative medicine on medication adherence in Honduras. Catalino MP, Durón RM, Bailey JN, Holden KR. 2015;21(3):26-35.

Transcutaneous oximetry Effect of electroacupuncture on transcutaneous oxygen partial pressure during hyperbaric oxygen therapy in healthy individuals. Qu L, Ye Y, Li C, Gao G. 2015;21(5):44-51.

Treatment fidelity Why does treatment fidelity matter? Stone JA. 2015;21(4):24-25.

Tribute Nicholas Gonzalez, MD (1947-2015). Brogan K. 2015;21(5):8-10.

Tumor invasion An ethanol extract of Hawaiian turmeric: Extensive in vitro anticancer activity against human colon cancer cells. Dimas K, Tsimplouli C, Houchen C, Pantazis P, Sakellaridis N, Tsangaris GT, Anastasiadou E, Ramanujam RP. 2015;21(Suppl 2):46-54.

Tumor necrosis factor α Targeting NF-κΒ and TNF-α activation by electroacupuncture to suppress collagen-induced rheumatoid arthritis in model rats. Li J, Chen R, Cai G. 2015;21(4):26-34.

V Vaccination Psychobiology of vaccination effects: Bidirectional relevance of depression.

Brogan K. 2015;21(Suppl 3):18-26.

Vaccines Vaccines: Both sides of the same coin. Campbell AW. 2015;21(4):8-10.

Vascular health Red yeast rice plus berberine: Practical strategy for promoting vascular and metabolic health. McCarty MF, O’Keefe JH, DiNicolantonio JJ. 2015;21(Suppl 2):40-45.

Veterans Horticultural therapy: A pilot study on modulating cortisol levels and indices of substance craving, posttraumatic stress disorder, depression, and quality of life in veterans. Detweiler MB, Self JA, Lane S, Spencer L, Lutgens B, Kim DY, Halling MH, Rudder TC, Lehmann LP. 2015;21(4):36-41.

The Integrative Health and Wellness (IHW) program: Development and use of a complementary and alternative medicine clinic for veterans.

Hull A, Holliday SB, Eickhoff C, Rose-Boyce M, Sullivan P, Reinhard M. 2015;21(6):12-21.

Vision Significant improvements in vision parameters for participants with eye disease using 4 alternative therapies. Kondrot EC. 2015;21(6):22-35.

Vitamin C Vitamin C: It isn’t just for cancer anymore. Campbell AW. 2015;21(3):8-10.

Vitamin D Vitamin D: Dosages to optimize serum levels. Baggerly LL. 2015;21(3):14-15.

Leslie Ray Matthews, MD: Enhanced surgical outcomes and boosted softtissue wellness from vitamin D supplementation. Gustafson C. 2015;21(3):68-72.

Verrucous vulvar cancer Radioprotectant and cytotoxic effects of spirulina in relapsed verrucous vulvar cancer: A case report. Kiziltan HS, Gunes Bayir A, Taspinar O, Yucesan G, Tastekin D, Sonmez FC, Coban G, Kilic G, Eris AH, Aydin T, Akcakaya A, Mayadagli A. 2015;21(Suppl 2):68-72.

72 ALTERNATIVE THERAPIES, NOV/DEC 2015 VOL. 21 NO. 6

W Water Global water fluoridation: What is holding us back? Botchey SA, Ouyang J, Vivekanantham S. 2015;21(3):46-52.

Weight gain Michael Smith, MD: Treat the underlying causes of weight gain to facilitate successful weight loss, part 2: Examining the first 2 pillars of weight gain. Gustafson C. 2015;21(4):72-75.

Michael Smith, MD: Treat the underlying causes of weight gain to facilitate successful weight loss. Gustafson C. 2015;21(5):82-86.

Weight loss Michael Smith, MD: Treat the underlying causes of weight gain to facilitate successful weight loss, part 2: Examining the first 2 pillars of weight gain. Gustafson C. 2015;21(4):72-75.

Michael Smith, MD: Treat the underlying causes of weight gain to facilitate successful weight loss. Gustafson C. 2015;21(5):82-86.

Wen dan decoction Efficacy of the wen dan decoction, a Chinese herbal formula, for metabolic syndrome. Huang YM, Xu JH, Ling W, Li Y, Zhang XX, Dai ZK, Sui Y, Zhao HL. 2015;21(4):54-67.

Subject Index

Whole-body vibration dependent relaxation Massage therapy improves in vitro fertilization outcome in patients undergoing blastocyst transfer in a cryo-cycle. Okhowat J, Murtinger M, Schuff M, Wogatzky J, Spitzer D, Vanderzwalmen P, Wirleitner B, Zech NH. 2015;21(2):16-22.

Y Yoga Development of a modified yoga program for pulmonary hypertension: A case series. Awdish R, Small B, Cajigas H. 2015;21(2):48-52.

Z Zinc Zinc supplementation alone is effective for partial amelioration of methotrexate-induced intestinal damage. Musa NS, Howarth GS, Tran CD. 2015;21(Suppl 2):22-31.

Zonulin The relevance of using the C3d/immunoglobulin G test in clinical intervention. Clarke DP, Burdette C, Agolli G, Dorval B, Gaston AM, Chesla S. 2015;21(1):16-27.

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

CONFERENCE CALENDAR The Institute for Functional Medicine: Energy Regulation Advanced Practice Module November 6-8, 2015—Omni Hotel, Dallas, Texas “Illuminating the Energy Spectrum: Evidence and Emerging Clinical Solutions for Managing Pain, Fatigue, and Cognitive Dysfunction.” This program will help clinicians develop and refine their ability to assess and treat a variety of conditions involving energy regulation. We will investigate the science of mitochondrial function and dysfunction, as well as harness the power of intention and compassion within the therapeutic relationship. For more information, please visit https://www.functionalmedicine.org/Energy/.

The Institute for Functional Medicine Advanced Practice Module: GI November 6-8, 2015, Omni Hotel, Dallas, Texas “Restoring Gastrointestinal Equilibrium: Practical Applications for Understanding, Assessing, and Treating Gut 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 (GI) dysfunction.

For more information, please visit https://www.functionalmedicine.org/GI/.

Nutritional Interventions You Will Use Everyday November 7-8, 2015—SpringHill Suites by Marriot, Orlando, Florida Presented by Wally Schmitt, DC. To help take your interventions to the next level as you understand and integrate individualized nutritional protocols.

In this seminar you will acquire simple to use tools to increase compliance and provide successful patient outcomes. To register, contact Biotics Research at (800) 231-5777, or e-mail biotics@bioticsresearch.com/.

American College of Nutrition’s 56th Annual Conference: November 11-14, 2015—B Resort & Spa, Orlando, Florida Join the American College of Nutrition (ACN) for its 56th annual conference titled “Translational Nutrition: Optimizing Brain Health.” Join world renowned researchers and clinicians as we learn to translate nutrition science into practice.

This interactive educational event is a must-attend for anyone interested in the field of nutrition science. This year’s conference will focus on the impact of nutrition on the brain and cognitive health. For more information, please visit http://www.americancollegeofnutrition.org/conference or call (858) 652-5400.

AFNA Annual Functional Medicine Conference November 12-15, 2015—Georgia World Congress Center, Atlanta, Georgia The American Functional Medicine Association (AFMA) is an organization composed of scientists and health care practitioners from all specialties, ranging from physicians, pharmacists, naturopaths, and chiropractors to nurse practitioners, nurses, and physician assistants. AFMA is dedicated to the advancement of scientific knowledge to detect, prevent, and treat functional and aging related diseases. For more information, please visit http://www.AFMAssociation.com or call (855) 500-2362.

American College for Advancement in Medicine 2015 Annual Meeting November 12-15, 2015—Red Rock Resort, Las Vegas, Nevada Join ACAM for their annual conference titled “Integrative Medicine’s New Landscape: Practical Applications of New Technologies.” The world class faculty offer both practical and relevant applications practitioners can use today. With an all-new program format, the 2015 annual meeting format has changed to offer increased non-CME workshops and greater networking opportunities. For more information, please visit http://www.acam.org/ACAM2015/.

ICNITE Conference 2015: The Business of Better Medicine November 13-15, 2015—Omni La Costa Resort & Spa, San Diego, California Emerson Ecologics will host its first annual conference. The conference will provide integrative health care practitioners with the necessary business knowledge to develop a thriving and fulfilling practice. Workshops are designed to address key business challenges related to clinic operations, sales and marketing, and patient compliances, with a focus on providing

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valuable and actionable takeaways. For more information, please visit http://www.eeignite.com/.

Achieve Optimal Wellness with Detoxification November 14, 2015—Hilton Garden Inn Washington/Bethesda, Bethesda, Maryland Presented by Dr Abbas Qutab to more effectively help patients manage such conditions as chronic fatigue syndrome, fibromyalgia, polymyalgia, rheumatoid arthritis, degenerative joint disease, arthritis, and acute and chronic pain. Topics will include basic concepts of pain/inflammation, chronic disease disorders, understanding and restoring balance through detoxification, diagnostic strategies, and clinical protocols. To register, contact Biotics Research at (800) 231-5777, or e-mail biotics@bioticsresearch.com.

12th International Conference of the Society for Integrative Oncology November 14-16, 2015—Joseph B. Martin Conference Center, Boston, Massachusetts The first day will be a special joint program of the Society for Acupuncture Research, Fascia Research Society, and the Society for Integrative Oncology.

For more information, please visit http://www.integrativeonc.org/.

Nutrition Pro 2015: Medical Nutrition Therapy in Practice November 15, 2015—B Resort & Spa, Orlando, Florida Immediately following The American College of Nutrition Conference 56th annual conference join the Board for Certification of Nutrition Specialists for Nutrition Pro 2015. Discussion topics will include nutritional practices influencing trends in 2015, clinical nutrition management of inflammation, digestive health, and much. For more information, please visit http://www.cbns.org/.

Dr Roizen’s Preventive and Integrative Medicine Conference December 4-6, 2015—Encore Hotel, Las Vegas, Nevada Attend the Cleveland Clinic 12th Annual Dr Roizen’s Personalized, Preventive, and Integrative Medicine Conference. During the past decade, use of preventive and integrative medicines have greatly expanded along with the types of therapies, patient populations, and conditions treated.

This conference will focus on discussing the most recent data, analyzing its impact, and assessing its best use in clinical practice. For more information, please visit http://www.clevelandclinicmeded.com/live/.

A Different Look at Thyroid, Cholesterol, & Diabetes Using Blood Chemistry December 5, 2015—Hilton Garden Inn Pineville, Pineville, North Carolina Join William M. Kleber, DC to present on thyroid, cholesterol, and diabetes.

The seminar will include basic anatomy, physiology of the thyroid, thyroid function testing, and why basic throid testing is not good enough and leads to incorrect statistics. Cholesterol: Why you should not compete with the allopaths in lowering it and the benefits of fat-based metabolism. Leave the seminar connecting the dots between thyroid, cholesterol, diabetes, immune malfunction, and common clinical symptoms. To register, contact Biotics Research at (800) 231-5777, or e-mail bitoics@bioticsresearch.com.

Nutritional Interventions You Will use Everyday December 5-6, 2015—Sheraton Hartford Hotel at Bradley Airport, Windsor Locks, Connecticut Join Wally Schmitt, DC, to help take your interventions to the next level as you understand and integrate individualized nutritional protocols. In this seminar you will acquire simple to use tools to increase compliance and provide successful patient outcomes. Seminar topics include addressing colds, flu, and other infections, Nutrients that support immune function, lingering cough, insomnia, anxiety, hormone detoxification, and a special presentation of “Remedies Every Medicine Cabinet Should Contain.” To register, contact Biotics Research at (800) 231-5777, or e-mail bitoics@bioticsresearch.com.

Conference Calendar

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13th Annual Natural Supplements: An Evidence-Based Update A CONTINUING EDUCATION CONFERENCE FOR HEALTH CARE PROFESSIONALS

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.

Visit www.scripps.org/NaturalSupplements for conference updates!

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The American Academy of Anti-Aging Medicine (A4M) 23rd Annual Winter World Congress December 11-13, 2015—Venetian/Palazzo Hotel, Las Vegas, Nevada The American Academy of Anti-Aging Medicine (A4M) invites you to attend the 23rd Annual World Congress on Anti-Aging, Regenerative and Aesthetic Medicine. A4M is the largest Anti-Aging and Aesthetic event with more than 3000 health care practitioners, both domestic and international attendees. This event will include board certification exams, fellowship modules, general conference activities, and exhibition. For more information, visit http://www.a4m.com or call (888) 997-0112.

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. For more information, please visit http://www.scripps.org/NaturalSupplements/.

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 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/.

Conference Calendar

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. For more information, visit http://www.ihsymposium.com/annual-conference/.

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 mold-related 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 mold-damaged buildings. For more information, visit http://environmentalhealthsymposium.com or call (855) 347-4477.

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/.

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.

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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/.

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/.

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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/.

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, 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/.

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/.

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 whole-systems 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/.

Conference Calendar

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/.

Job Listing Complementary and Integrative Medicine Medical Director-Austin, TX 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.

Candidates 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 health care 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 on obtaining medical licensure in the state of Texas. Interested applicants should submit a letter of interest and curriculum vitae to: to Carrie Schumacher, physician recruitment, at CSchumacher@seton.org Conference Calendar

ALTERNATIVE THERAPIES, NOV/DEC 2015 VOL. 21 NO. 6 79

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