A4M MMI - Anti-Aging Medical News - Spring 2018 by Tarsus Medical

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Greetings, and a warm welcome from the team at A4M/ MMI. We are proud to be embarking on a new chapter of exploration and discovery with your continued support, as we direct our focus this spring to brain diseases and disorders: the most current and cutting-edge topics in the landscape of modern medicine. Not only are the social and financial costs of these diseases staggeringly severe, but they also continuously impact your patients and people you encounter each day. Because the diagnoses are multifaceted, nuanced, and complex, A4M/MMI serves as an organization through which you can receive the necessary resources, committed motivation, and a wealth of support from our ever-growing community across the globe. With the assistance of our expert faculty members and clinicians, coupled with our extensive educational offerings and live events, we know that we can continue our original mission: to redefine medicine.

Ronald Klatz, MD, DO President, A4M

Robert Goldman, MD, PhD, DO, FAASP Chairman, A4M

We believe that peer-to-peer connections, in conjunction with the latest clinical education, can spur social change— ultimately transforming care and enhancing patient outcomes. Just as spring represents rebirth and rejuvenation, this Spring Congress emphasizes the concept of ‘brain awakening:’ renewing your understanding of the complex world of the mind, and finding collaborative solutions together. As Leonardo da Vinci aptly stated: “Learning never exhausts the mind.” We thank you for your engagement and involvement. Our efforts are impossible without your support.

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A R T IC L E S

Table of Contents General Information

Product Announcements

Exhibit Hall Floorplan

Exhibitor Index

Exhibitor Listings

100

Myo-Inositol And D-Chiro-Inositol Supplementation Alleviates Insulin Resistance Syndromes By Addressing Essential Metabolic Needs By Christiana Paul, MS

Obesity and the Food Industry By Kimball Lundahl, MD

Effects Of A Medical Food Formula On Plasma Lipid Profile And Selected Clinical Biomarkers For Metabolic Syndrome By Lewis Chang, PhD, and Kirti Salunkhe, MD

Alzheimer’s Disease: The Gut-Brain Axis By Thomas Bayne, DC

Oral Immunoglobulin G (IgG) Therapies in Immune Dysfunction By Angela Lucterhand, DC

Bringing Screening Technology Inside the Medical Practice: A Potential Paradigm Shift Can Assist Physicians in Improving Clinical Outcomes and Enhancing PhysicianPatient Relationships By Christina Rahm-Cook, PhD

Understanding the “Big 4” Heavy Metals - Why Sample Type Matters and Some Results Can Be Misleading By Theodore Zava

Digital Health: Applications to Brain Diseases & Disorders By Sarenka Smith, Editorial Director, A4M | MMI

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• SPRING 2018

Show Regulations 1.

An official picture ID is required to pick up name badge.

2. Name badge must be worn at all times during show hours and official events. 3. No one under the age of 18 will be admitted into the Exhibit Hall. 4. This event is open to healthcare professionals and their invited guests only. 5. Photography is permitted in the Exhibit Hall only by press, with the prior permission of show management, and prior permission from the firm(s) whose booth(s) are being photographed. Videography in the Exhibit Hall (motion video, film, or digital) is permitted only at discretion and with advance permission of show management and the prior permission of individual(s) and/or firm being photographed. 6. Audio and video recording (tape or digital) of this event is expressly prohibited. 7. Unauthorized solicitation is prohibited. In addition, non-A4M and/or commercial literature of any kind may not be distributed near or at the event registration area and all event-related general public areas. 8. No medical procedures are permitted to take place in Exhibit Hall booths without prior permission of show management. 9. Show management reserves the right to expel any individual and/or company without recourse or refund at its sole discretion. 10. PHOTO RELEASE: Anyone in attendance at any A4M event may be subject to any photography or videography conducted during the event which may be used in any form for future media purposes. Please contact A4M with any concerns.

The American Academy of Anti-Aging Medicine (A4M.) All rights reserved. ISSN 1533-6700. AntiAging Medical News publishes materials in good faith and makes no claims or endorsements for products, services or procedures that appear in the publication. Opinions expressed in articles and advertisements are not necessarily those of Anti-Aging Medical News, its owners, affiliates, or its staff. The publisher is not liable for advertiser product claims or representations. Advertisers assume total responsibility for the contents of their advertisements. Under no circumstances is the content of Anti-Aging Medical News to be construed as medical advice. Always consult your personal physician prior to beginning a new therapy, or changing any current regimen.

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â&#x20AC;˘ SPRING 2018

Welcome

RECEPTION

Thursday, April 12th 5:00 pm - 6:30 pm

Exhibit Hall

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HOUR

Friday, April 13th 4:00 pm - 6:00 pm

Exhibit Hall FOOD DRINKS

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FUNCTIONAL TESTING EXPERTS

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THANK YOU SPONSORS! Your entry form can be found in your attendee bag.

Rules Of Draw Open To Registered Conference Delegates Only 1] The giveaway is not open to any exhibitors and their staff, suppliers or supplier affiliates to the 26th Annual Spring Congress. 2] Only one entry per person will be accepted. 3] This entry form must be completed fully and correctly, validated by each of the sponsors and their unique stamps in the logo square, signed and including your full name, City & State of residence for verification purposes. 4] You must be present at the time of the giveaway to win. 5] The prize is not transferable or redeemable for cash. 6] Impact duties, federal, state, and local taxes are the responsibility of the winner. 7] A W-9 tax form must be completed prior to prize collection. 8] The actual Rolex watch on display may differ from photograph. 9] Must be 18 years or older to WIN.

Professional Medical Education WORKSHOPS (NON-CME)

THURSDAY Sponsored by:

APRIL 12TH – 6:15PM

Tired of Being Tired? Presented by: Filomena Trindade, MD, MPH Location: Regency Ballroom 1

Your Patients, Your Practice: Succeed with BodyLogicMD

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Presented by: Andrew Heyman, MD and Jennifer Landa, MD Location: Regency Atlantic 1

The ProLon Opportunity: Rapid Implementation of the Fasting Mimicking Diet as Core Therapeutic Opportunity to Your Integrative Health Practice

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The Clinical and Financial Benefits of the ProLon Program and What It Can do for Your Patients

CME

Presented by: James LaValle, RPh, CCN Location: Regency Ballroom 2

FRIDAY APRIL 13TH Breakfast | Lectures 6:45am - 8:00 am

The Neuroscience of Stress and Resilience Presented by: Jay Lombard, MD Location: Regency Ballroom 1

* This activity is supported by an educational grant from Standard Process

Professional Medical Education (NON-CME) WORKSHOPS

FRIDAY Connect the Dots - Lifestyle, Nutraceuticals, Hormone Optimization and Telomerase Activation with TA-65

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Presented by: Ron Rothenberg, MD of the California Healthspan Institute Location: Atlantic Ballroom 1 Sponsored by:

Learn About a New Game-Changing ED Treatment

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To Pee, or Not to Pee; That is the Question: An In-Depth Comparison of Urine, Serum and Saliva Testing

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Presented by: James LaValle, RPh, CCN Location: Regency Ballroom 1

Clinical Solutions: Translating Research into Products

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Presented by: Barry Ritz, PhD, Chief Scientific Officer, an expert in nutritional immunology Location: Regency Ballroom 2

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• SPRING 2018

Fellowship in Anti-Aging, Metabolic and Functional Medicine (FAAMFM) The Fellowship in Anti-Aging, Metabolic and Functional Medicine (FAAMFM) prepares practitioners to become leaders in a new form of medicine: one that is personalized, preventive, and predictive. Our Fellows learn a wellness-oriented approach to care, built upon the latest breakthroughs in scientific research across a diverse array of medical and healthcare disciplines. This program allows clinicians to continue caring for patients, while simultaneously learning the most current and relevant information related to the diagnosis, prevention, and treatment of disease.

Why the Fellowship is right for you: Our advanced Fellowship program provides an interactive educational experience through a modular training curriculum that includes hands-on training and active live participation. The Fellowship is designed to prepare professionals to effectively practice Anti-Aging, regenerative, and functional medicine: focusing on the patient holistically and comprehensively. The program is rooted in a systems-biology approach, and emphasizes progressive and innovative learning. Modules are facilitated by world-renowned experts of functional medicine, all of whom utilize an interdisciplinary approach. The programâ&#x20AC;&#x2122;s final two courses consolidate and streamline knowledge by simplifying and distilling complex issues, and demonstrating how to implement effective patient care. Throughout the course of the Fellowship, oneon-one mentorship will be provided as needed. Join our community of thought leaders as we discuss shared experiences, ask and answer questions, and reshape the field of integrative healthcare. Educationally partnered with:

www.a4m.com | 561.997.0112

MODULE IV

Gastroenterology This module focuses on comprehensive metabolic, functional, and nutritional approaches to gastrointestinal dysfunction and disease. Physiology and pathophysiology, GI microbiome and dysbiosis, gut permeability, hormones, diet, inflammatory bowel disease, celiac disease and gluten sensitivity, the gut-immune-brain connection, irritable bowel syndrome, and other digestive and glandular disorders are highlighted.

MODULE V (NONâ&#x20AC;&#x201C;CME)

Clinical Intensives: How to Interpret Functional Medicine Labs

Fellowship in Anti-Aging, Metabolic and Functional Medicine

This review course examines patient case histories, covering a range of metabolic symptoms, disorders, and diseases that are highlighted in modules I-IV. This clinically intensive course provides the tools to prevent, detect, diagnose, treat, and manage a variety of patient conditions in the clinical setting. The ultimate goal is to provide comprehensive metabolic, functional, and nutritional approaches towards disease management, and enable clinicians to practice Anti-Aging Medicine confidently and effectively.

MODULE VI MODULE I

Endocrinology This module provides an overview of the functions and interrelationships of specific hormones in the body, including hormonal changes that manifest in aging men and women. Metabolic, functional, and nutritional approaches to managing hormone deficiencies and endocrine disorders, including diabetes and obesity, are also covered.

MODULE II

Cardiology This module assesses the causes, mechanisms, diagnoses, and management of cardiovascular and cardiometabolic diseases including CHD, CHF, hypertension, metabolic syndrome, dyslipidemia, atherosclerosis, and renal disease. Topics include cardiovascular pathophysiology and biology, inflammation, oxidation, hormones, adipokines, stress, nutrition and nutrigenomics, glycemic control, environmental factors and toxicology, infections, and risk factor testing.

Mitochondrial Restoration and Infections Loss of function in mitochondria, organelles chiefly responsible for cellular energy production, can result in symptoms that range from excessive fatigue to other manifestations of chronic disease. This module will review overall mitochondrial dysfunction and restoration, with specific focus on treatments for common age-related diseases including dementia, cardiovascular disease, fatigue syndromes, and other genetic conditions.

MODULE VII

Autoimmune Diseases This module focuses on inflammatory disorders, autoimmune diseases, allergies, cancer, and the gut-immune-brain connection. Cellular and molecular biology of immunity, the cellular stress response, oxidation, genetic damage, inflammation, etiology of disease including environmental and lifestyle factors, and the risk for cancer development are also reviewed. Clinical approaches to patient evaluations, testing, and disease management are provided.

MODULE III

MODULE VIII

This module reviews the most recent developments in the field of neurology, utilizing a metabolic approach to the prevention, management, and treatment of neurological disorders. The course will cover pathophysiology and the role of neurotransmitters, inflammatory and degenerative disorders, neurovascular diseases, psychological and psychiatric syndromes, the gut-immune-brain connection, and healthy brain function.

This module will review a range of current topics in modern integrative healthcare, including key concepts surrounding metabolism & weight loss, sports medicine, and integrative cancer therapies. Become well-versed in the most cutting-edge therapies and treatment modalities to treat complex disorders, while addressing the root causes and symptoms of chronic disease.

Neurology

Weight Management / Nutrition / Integrative Cancer Therapies

Advancing Education in Cardiometabolic Disease

As a rapidly expanding global epidemic surrounds cardiometabolic disease, clinicians are increasingly faced with an imminent threat, and a pressing need for the most current clinical education and research. With heart disease as the primary cause of death in the United States, there is an urgency to not only combat cardiovascular disease, but also assist patients while improving inadequacies in cardiovascular care.

CHAIRPERSONS

CHRISTIE M. BALLANTYNE, MD

Continuing its tradition of delivering the latest research and findings surrounding cardiometabolic care, the Cardiometabolic Health Congress (CMHC) represents a diverse educational platform that allows frontline clinicians to stay current with evolving science and innovations. Our team at CMHC is consistently dedicated to sparking ingenuity and fostering collaborations at both our live conferences and digital forums, as we provide unique programming and a synergistic learning environment to healthcare professionals from across the globe. Due to recent estimates that indicate over one third of the nationâ&#x20AC;&#x2122;s population has at least one cardiometabolic risk factor, CMHC offers a convenient and accessible opportunity for clinicians to network, engage, and internalize the latest developments in cardiometabolic health and care.

GEORGE L. BAKRIS, MD

WEIGHT MANAGEMENT AGE, RACE, SEX, GENETICS, FAMILY HISTORY DYSLIPIDEMIA

ROBERT H. ECKEL, MD

BEHAVIORAL, LIFESTYLE CHOICES HYPERTENSION CARDI0-RENAL SYNDROME HEART FAILURE PRIMARY AND SECONDARY CVD RISK

JAY S. SKYLER, MD

INSULIN RESISTANCE, PREDIABETES, DIABETES

www.cardiometabolichealth.org | (561) 771-6668

CMHC WEST May 4-5, 2018 | Back by popular demand, our CMHC West event has returned: Advancing Cardiometabolic Health from East to West. As hundreds of participants gather at the two-day conference, taking place in Las Vegas from May 4-5, 2018, an extensive agenda of cutting-edge keynote speakers and thought leaders, clinical educational sessions, and interactive lectures will collectively deliver the most recent clinical research in cardiometabolic health to attendees. As a proliferation of scientific information and evidence continues to emerge surrounding the

Wynn, Las Vegas, NV

multitude of ways in which cardiovascular health is tied to a host of diseases and disorders, CMHC is proud to present a carefully curated agenda that features world-renowned experts, and continue its longstanding tradition of providing the latest, most current data and clinical education in cardiometabolic health. Moreover, as global public health epidemics including obesity and diabetes become progressively critical and severe, CMHC West represents a forum in which primary care practitioners and professionals can simultaneously learn from expert faculty, as well as each other.

CMHC & the American Heart Association have collaborated on a

CMHC-AHA Cardio-Oncology Workshop: Exploring the Frontiers of Care

SU NDAY, MAY 6

CMHC BOSTON

October 24-27, 2018

Our 13th Annual conference in Boston, The Cardiometabolic Event of the Yearâ&#x201E;˘, takes place from October 24-27. This event addresses the most critical and acute issues in cardiometabolic care, with an impressive lineup of expert speakers and clinicians in the field. Our pre-conference "Women's Health Summit" Day explores the unique challenges faced by women in cardiometabolic care,

A Multidisciplinary Approach to Cardio-Oncology

Boston, MA while our General Session features keynote Carl Ronald Kahn, MD: a world-renowned physician and scientist known for his work with insulin receptors and insulin resistance in diabetes and obesity. Supplemental Professional Medical Education workshops are available, in addition to an Exhibit Hall featuring a Lifestyle Showcase with the latest therapeutic developments in cardiometabolic health.

www.cardiometabolichealth.org | (561) 771-6668

Myo-Inositol And D-Chiro-Inositol Supplementation Alleviates Insulin Resistance Syndromes By Addressing Essential Metabolic Needs

By Cristiana Paul, MS

Cristiana Paul holds a Masters in Nutrition Science from Cal Poly Pomona, California and has extensive experience in clinical practice and nutrition research. She is a contributor to formulations and integrative medicine protocols for Designs for Health. The following article is not endorsed and/or supported by The American Academy of Anti-Aging Medicine. The purposes of this publication do not imply endorsement and/or support of any author, company or theme related to this article.

Introduction

This article presents the scientific rationale and options for using combinations of myo-inositol (MI) & D-chiro-inositol (DCI) for any insulin resistance-related condition/disease, regardless of gender. MI and DCI supplements have been preferentially studied and shown to alleviate symptoms and underlying metabolic dysregulations that characterize polycystic ovarian syndrome (PCOS) and are believed to work by reducing insulin resistance (IR). Studies have also shown benefits of these nutraceuticals for alleviating metabolic syndrome (MetS) in menopausal women and reducing risk of gestational diabetes (GD). However, animal studies, one recent human study and the mechanisms of action of MI and DCI in insulin signaling compound the evidence to substantiate other uses of MI and/or DCI, which include men with IR-related syndromes, and nonpregnant women at any age. MI and/or DCI have been proven effective in various doses and ratios, but there is no consensus on the most effective dosing regimen. These studies have been discussed in various reviews, some of which promote a supplement with a MI:DCI ratio of 40:1 as “ideal” for normalizing body MI:DCI ratio. However, it is important to keep in mind that some of these papers declared commercial interest in such a formula,1,37,65,71,75 while other reviews found no proof that a 40:1 ratio is superior to other ratios.2,69,70 For example, MI/DCI ratios of 2.5:1,45 7:1,72,73 or 0.4:174 reduced IR and incidence of GD.

(i) Insulin resistance related syndromes

IR is a syndrome involving dysregulation of insulin and glucose metabolism implicated as a

ANTI-AGING MEDICAL NEWS

causative and/or aggravating factor in: MetS, type 2 diabetes (T2D), GD, PCOS, gout, inflammatory conditions, cancer and brain degenerative conditions. MetS has been defined by “resistance to insulin-stimulated glucose uptake occurring in approximately 25% of the population at large”39 and is associated with high risk for coronary heart disease and diabetes.40,41 Genetics play an important role in the risk of developing all these conditions/diseases, which may be modulated by lifestyle, diet, supplements (nutrients or herbal extracts) and/or pharmaceuticals.2,8-13

(ii) Inositol forms, dietary intake, endogenous production

Inositol occurs naturally as nine isomers in a variety of vegetarian and animal foods as well as in the human body. The MI and DCI isomers predominate and both have important functions in human physiology. MI occurs in foods in the following forms: (1) Phytic acid (myo-inositol hexaphosphate or IP6), a component of the insoluble fiber of the bran of grains, legumes, nuts and seeds. A portion of ingested IP6 is converted to MI or inositol phosphates (IP1IP5) by intestinal flora and in human physiology. (2) Phosphatidyl-myo-inositol, which is found in plant and animal-derived foods. DCI occurs in small amounts in foods such as buckwheat, soy, lentils, beans (especially carob) and wheat germ. DCI is derived from MI in human physiology (see Fig.1). Average food-derived MI intake is 900 mg/day, while that of DCI has not been determined. However, food or supplement-derived MI and DCI

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Myo-Inositol And D-Chiro-Inositol Supplementation Alleviates Insulin Resistance Syndromes By Addressing Essential Metabolic Needs

compete with glucose for gut absorption and intracellular uptake. Endogenous synthesis of MI from glucose has been estimated at 2-4 g/day, but it is impaired by high glucose levels.67

(iii) MI and DCI derivatives and their role in insulin signaling

MI and DCI are components and precursors of intracellular signaling mediators of insulin action for glucose disposal, as shown in Figure 1.1,2,6,15,16,17,18 For details on how MI and DCI mediators stimulate intracellular enzymes, see review by Paul C., Brady D. et. al.2 Supplementation with MI and/or DCI is believed to upregulate the production of MI and DCIderived mediators,6,18 thus partially alleviating some of the main metabolic dysregulations specific to IR, such as impaired glucose transport and its reduced cellular disposal.19,20

(iv) MI and/or DCI supplementation alleviates IR related syndromes (a) Summary of MI and/or DCI interventions for PCOS

We omit discussing interventions with MI and/or DCI for PCOS in this article, because we have covered it elsewhere.2 We highlight instead the novel use of MI and DCI for other IR-related syndromes in women, and also in men, a newly emerging research area.

(b) Summary of interventions with MI and DCI for metabolic syndrome

Supplementation with MI, or MI+DCI, has been proven to alleviate essential aspects of MetS in postmenopausal and pregnant women (see Table 1). The rationale for adding lipoic acid to MI interventions in these studies3,4,5,44,66 is likely based on its ability to reduce IR by about 20-30% on its own,46,47 and due to potential synergy with DCI-derived mediators of insulin action, because they both stimulate the pyruvate dehydrogenase enzyme.46

Supplementation with 4 g MI was shown to reduce the risk of developing GD in women with PCOS.48,49,50 D’Anna R et al. supplemented pregnant women with PCOS with 4 g MI and found that the incidence of GD in the MI group was 17.4% versus 54% in the control group.18 In another study, where MI + diet was used to treat GD, HOMA-IR was reduced by 50% versus 29% in the placebo + dietary intervention group.50

(d) I nter ventions with MI and DCI for men and women with T2D

A 2016 review by Paul C., Brady D. et. al.2 and a 2017 study68 summarize cellular, animal and human studies in support of using MI and/or DCI for T2D. One 2016 study investigated the effects of supplementing men and women with T2D (mean age 60.8) with the equivalent of 3300 mg MI + 84 mg DCI per day. After three months of treatment, fasting blood glucose decreased from 192.6 mg/dL to 160.9 mg/dL, and HbA1c from 8.6% to 7.7%.66 This is one of the studies that advocates for a supplemental MI:DCI ratio of 40:1 as “ideal,” yet this lacks supporting published scientific references. However, a higher dose of DCI (thus a lower MI:DCI ratio), as used in GD risk reduction studies,45,72-74 may have brought blood glucose levels closer to normal. This hypothesis is based on the significant involvement of DCI in glucose disposal and a study showing that supplementation with 1 g DCI was as effective as 4 g MI in reducing IR in PCOS patients.38

(e) Considerations for optimal dosing of MI and/or DCI in support of insulin sensitivity

Since MI to DCI conversion is likely impaired in most individuals with IR, it is important to always add DCI when supplementing with MI. Conversely, supplementing with DCI alone, although very effective, cannot fulfill roles that are unique to MI, and DCI does not convert to MI. MI doses of 2-4 g and DCI doses of 84-1200 mg were proven effective alone or

ANTI-AGING MEDICAL NEWS

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Myo-Inositol And D-Chiro-Inositol Supplementation Alleviates Insulin Resistance Syndromes By Addressing Essential Metabolic Needs

in combination for alleviating IR and the IRrelated metabolic dysregulations in PCOS, MetS, GD and T2D. Individuals with PCOS or T2D have been shown to have a significant DCI deficiency in various tissues (liver, muscle, kidney, blood) compared to normal individuals, so it is sensible to supplement them with DCI doses comparable to the ones proven effective in studies. Supplementation with doses higher than 300 mg DCI (without MI) were found to impair oocyte quality in PCOS women.64 It is not clear whether this threshold may have been increased if MI was supplemented at the same time. Current research does not substantiate the superiority of supplementing with MI+DCI in a particular ratio for PCOS or other IR-related syndromes. However, if commercial tests for blood and urine levels of MI and DCI become available, treatment with MI and DCI could be better tailored to individual needs. In order to maintain therapeutic plasma levels of inositol throughout the day, it is best to administer them BID and on an empty stomach, since they compete with glucose during gut absorption and intracellular uptake from the bloodstream.21,22,65

(f ) Rationale for combining inositols with metformin treatment Metformin stimulates the mobilization of

MI derivatives, thus enhancing insulin signaling.2 This may increase the demand for MI supplementation. Metformin treatment in combination with MI was shown to have synergistic and beneficial effects in a PCOS study3, as shown in Table 2. Studies are needed to investigate whether the addition of DCI to metformin treatment would also prove synergistic.

(v) Increased nutritional demand for MI and DCI may be caused by excess carbohydrate intake, excess urinary loss of MI and DCI, and/ or impaired conversion of MI to DCI. Genetics and certain metabolic states aggravate these factors.

Individuals with PCOS or T2D were found to have elevated urinary excretion of MI and DCI compared to normal controls.6,21,22 Excess urinary loss of MI and DCI may be due to

ANTI-AGING MEDICAL NEWS

genetics and/or elevated blood glucose, which outcompetes MI and DCI for re-absorption in the kidneys.22,67 Urinary losses of MI and DCI likely contribute and progressively worsen IR, while supplementation with MI + DCI mitigates this phenomenon.14,28 An epimerase enzyme converts MI to DCI and enzyme activity was observed to correlate inversely with the degree of insulin resistance in various tissues.6,7 For example, MI to DCI conversion is approximately 8% in normal muscle cells but may be reduced to as little as 1% in those with IR. Tissues such as the brain, heart and ovaries contain higher amounts of MI than other tissues, while liver, muscle and fat contain higher amounts of DCI, likely due to their glycogen storage ability. However, the overall body content of MI is much higher than DCI, while their ratio is tissue and metabolic state-dependent.1,14,21,28 Studies have found elevated MI/DCI ratios in plasma or urine of individuals with IR, and interestingly also in normal ones with diabetic relatives, pointing to the genetic component of these conditions. One study reported urinary MI/DCI ratios in normal controls of 2.5, versus 20.4 in type 2 diabetics, and 13.2 in normal individuals with diabetic relatives.32 Average plasma MI/DCI ratio was reported at 206 in a PCOS group versus 112 in the control group.21 The elevated MI/DCI ratios in these conditions are attributed to an impaired conversion of MI to DCI, due to reduced epimerase activity. This in turn may be caused by metabolic dysregulation or polymorphisms involved in IR.1,14 In fact, the urinary MI/DCI ratio has been proposed as an index of IR by many research groups.59-63 Epimerase activity downregulation associated with IR is often referred to as an “enzyme defect,” but may be viewed instead as the result of evolutionary adaptation. This polymorphism downregulates glucose utilization, likely to promote survival when food/glucose availability is low, but it is unfavorable when carbohydrate intake is higher than optimal and is also aggravated by excess body fat.8-14

Conclusion

MI and DCI are naturally occurring in human physiology, but they are often deficient in IR-related conditions. Supplementation with MI and DCI to satisfy the metabolic demand for them represents an exciting natural intervention that may be able to alleviate critical metabolic dysregulations characteristic of IR, thus improving IR-related conditions such as PCOS, gestational diabetes, metabolic syndrome and T2D, regardless of gender.

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Myo-Inositol And D-Chiro-Inositol Supplementation Alleviates Insulin Resistance Syndromes By Addressing Essential Metabolic Needs

Resources

1. Unfer V, Carlomagno G, Dante G, Facchinetti F. Effects of myo-inositol in women with PCOS: a systematic review of randomized controlled trials. Gynecol Endocrinol. 2012 Jul;28(7):50915. doi: 10.3109/09513590.2011.650660. Epub 2012 Feb 1. Review. PubMed PMID: 22296306. 2. Paul C, Laganà AS, Maniglio P, Triolo O, Brady DM. Inositol’s and other nutraceuticals’ synergistic actions counteract insulin resistance in polycystic ovarian syndrome and metabolic syndrome: state-of-the-art and future perspectives. Gynecol Endocrinol. 2016 Jun;32(6):431-8. doi:10.3109/09513590.2016.1144741. Epub 2016 Feb 29. PubMed PMID: 26927948. 3. Cappelli V, Di Sabatino A, Musacchio MC, De Leo V. [Evaluation of a new association between insulin-sensitizers and α-lipoic acid in obese women affected by PCOS]. Minerva Ginecol. 2013 Aug;65(4):425-33. Italian. PubMed PMID: 24051942. 4. Genazzani AD, Despini G. Effects of a Combination of Alpha Lipoic Acid and Myo-Inositol on Insulin Dynamics in Overweight/ Obese Patients with PCOS. Endocrinol Metab Synd 2014, 3:3, Sep 30, 2014 http://dx.doi.org/10.4172/2161-1017.1000140. 5. Cianci A, Panella M, Fichera M, Falduzzi C, Bartolo M, Caruso S. d-chiro-Inositol and alpha lipoic acid treatment of metabolic and menses disorders in women with PCOS. Gynecol Endocrinol. 2015 Apr 20:1-4. PubMed PMID: 25893270. 6. Larner J, Brautigan DL, Thorner MO. D-chiro-inositol glycans in insulin signaling and insulin resistance. Mol Med. 2010 NovDec;16(11-12):543-52. doi:10.2119/molmed.2010.00107. Epub 2010 Aug 27. Review. PubMed PMID: 20811656; PubMed Central PMCID: PMC2972396. 7. Heimark D, McAllister J, Larner J. Decreased myo-inositol to chiro-inositol (M/C) ratios and increased M/C epimerase activity in PCOS theca cells demonstrate increased insulin sensitivity compared to controls. Endocr J. 2014;61(2):111-7. Epub 2013 Nov 2. PubMed PMID: 24189751. 8. Holte J. Polycystic ovary syndrome and insulin resistance: thrifty genes struggling with over-feeding and sedentary life style? J Endocrinol Invest. 1998 Oct;21(9):589-601. Review. PubMed PMID: 9856413. 9. Franks S, Gharani N, Waterworth D, Batty S, White D, Williamson R, McCarthy M. The genetic basis of polycystic ovary syndrome. Hum Reprod. 1997 Dec;12(12):2641-8. Review. PubMed PMID: 9455828. 10. Escobar-Morreale HF, Luque-Ramírez M, San Millán JL. The molecular-genetic basis of functional hyperandrogenism and the polycystic ovary syndrome. Endocr Rev. 2005 Apr;26(2):251-82. Epub 2004 Nov 23. Review. PubMed PMID: 15561799. 11. Strauss JF 3rd, Dunaif A. Molecular mysteries of polycystic ovary syndrome. Mol Endocrinol. 1999 Jun;13(6):800-5. Review. PubMed PMID: 10379878. 12. 1: Carulli L, Rondinella S, Lombardini S, Canedi I, Loria P, Carulli N. Review article: diabetes, genetics and ethnicity. Aliment Pharmacol Ther. 2005 Nov;22 Suppl 2:16-9. Review. PubMed PMID: 16225465. 13. Ricart W, Fernández-Real JM. [Insulin resistance as a mechanism of adaptation during human evolution]. Endocrinol Nutr. 2010 Oct;57(8):381-90. doi:10.1016/j.endonu.2010.05.003. Epub 2010 Aug 1. Review. Spanish. PubMed PMID:20675202. 14. Tsatsoulis A, Mantzaris MD, Bellou S, Andrikoula M. Insulin resistance: an adaptive mechanism becomes maladaptive in the current environment – an evolutionary perspective. Metabolism. 2013 May;62(5):622-33. doi:10.1016/j.metabol.2012.11.004. Epub 2012 Dec 20. Review. PubMed PMID: 23260798. 15. Croze ML, Soulage CO. Potential role and therapeutic interests of myo-inositol in metabolic diseases. Biochimie. 2013 Oct;95(10):1811-27. doi:10.1016/j.biochi.2013.05.011. Epub 2013 Jun 10. Review. PubMed PMID: 23764390. 16. Larner J. D-chiro-inositol--its functional role in insulin action and its deficit in insulin resistance. Int J Exp Diabetes Res. 2002;3(1):47-60. PubMed PMID: 11900279; PubMed Central PMCID: PMC2478565. 17. Larner J. Inositol, glycogen, insulin, and six nobelists. J Biol Chem. 2013, Apr 26;288(17):12313-24. doi: 10.1074/jbc. X113.471177. Epub 2013 Mar 20. PubMedPMID: 23515311; PubMed Central PMCID: PMC3636915. 18. Larner J, Allan G, Kessler C, Reamer P, Gunn R, Huang LC. Phosphoinositol glycan derived mediators and insulin resistance. Prospects for diagnosis and therapy. J Basic Clin Physiol Pharmacol. 1998;9(2-4):127-37. PubMed PMID:10212830. 19. Shulman GI. Cellular mechanisms of insulin resistance. J Clin Invest. 2000 Jul;106(2):171-6. Review. PubMed PMID: 10903330. 20. Abdul-Ghani MA, DeFronzo RA. Pathogenesis of insulin resistance in skeletal muscle. J Biomed Biotechnol. 2010;2010:476279. doi: 10.1155/2010/476279. Epub 2010 Apr 26. Review. PubMed PMID: 20445742; PubMed Central PMCID: PMC2860140. 21. Baillargeon JP, Diamanti-Kandarakis E, Ostlund RE Jr, Apridonidze T, Iuorno, MJ, Nestler JE. Altered D-chiro-inositol urinary clearance in women with polycystic ovary syndrome. Diabetes Care. 2006 Feb;29(2):300-5. PubMed PMID:16443877. 22. Chang HH, Choong B, Phillips AR, Loomes KM. The diabetic rat kidney mediates inosituria and selective urinary partitioning of D-chiro-inositol. Exp Biol Med (Maywood). 2014 Jul 24. pii:1535370214543064. [Epub ahead of print] PubMed PMID:25060739. 23. Baillargeon JP, Iuorno MJ, Jakubowicz DJ, Apridonidze T, He N, Nestler JE. Metformin therapy increases insulin-stimulated release of D-chiro-inositol-containing inositolphosphoglycan mediator in women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2004 Jan;89(1):242-9. PubMed PMID: 14715857. 24: Saha L, Kaur S, Saha PK. Pharmacotherapy of polycystic ovary syndrome—an update. Fundam Clin Pharmacol. 2012 Feb;26(1):54-62. doi:10.1111/ j.1472-8206.2010.00916.x. Epub 2011 Jan 7. Review. PubMed PMID: 21210850. 25. Marshall K. Polycystic ovary syndrome: clinical considerations. Altern Med Rev. 2001 Jun;6(3):272-92. Review. PubMed PMID: 11410072. 26. R. Murray, Polycystic Ovary Syndrome, Obesity and Insulin Resistance:The New Female Triad. ADVANCE for Nurse Practitioners, 1-20, 8//2004. https://nurse-practitioners.advanceweb.com/common/editorial/ PrintFriendly.aspx?CC=38617

27. Minozzi M, Nordio M, Pajalich R. The Combined therapy myo-inositol plus D-Chiro-inositol, in a physiological ratio, reduces the cardiovascular risk by improving the lipid profile in PCOS patients. Eur Rev Med Pharmacol Sci. 2013 Feb;17(4):537-40. PubMed PMID: 23467955. 28. Dunaif A. Insulin resistance and the polycystic ovary syndrome: mechanism and implications for pathogenesis. Endocr Rev. 1997 Dec;18(6):774-800. Review. PubMed PMID: 9408743. 29. Galazis N, Galazi M, Atiomo W. D-Chiro-inositol and its significance in polycystic ovary syndrome: a systematic review. Gynecol Endocrinol. 2011 Apr;27(4):256-62. doi: 10.3109/09513590.2010.538099. Epub 2010 Dec 10. Review. PubMed PMID: 21142777. 30. Baillargeon JP, Iuorno MJ, Apridonidze T, Nestler JE. Uncoupling between insulin and release of a D-chiro-inositol-containing inositolphosphoglycan mediator of insulin action in obese women with polycystic ovary syndrome. Metab Syndr Relat Disord. 2010 Apr;8(2):127-36. doi: 10.1089/met.2009.0052. PubMed PMID: 20156067; PubMed Central PMCID: PMC3140116. 31. Nestler JE, Jakubowicz DJ, Iuorno MJ. Role of inositolphosphoglycan mediators of insulin action in the polycystic ovary syndrome. J Pediatr Endocrinol Metab.2000;13 Suppl 5:1295-8. Review. PubMed PMID: 11117673. 32. Cheang KI, Baillargeon JP, Essah PA, Ostlund RE Jr, Apridonize T, Islam L, Nestler JE. Insulin-stimulated release of D-chiro-inositol-containing inositolphosphoglycan mediator correlates with insulin sensitivity in women with polycystic ovary syndrome. Metabolism. 2008 Oct;57(10):1390-7. doi: 10.1016/j.metabol.2008.05.008. PubMed PMID: 18803944; PubMed Central PMCID: PMC2574418. 33. Ireland K, Child T. Polycystic ovary syndrome and the postmenopausal woman. J Br Menopause Soc. 2006 Dec;12(4):143-8. Review. PubMed PMID: 17178014. 34. Stárka L, Duskova M, Cermakova I, Vrbiková J, Hill M. Premature androgenic alopecia and insulin resistance. Male equivalent of polycystic ovary syndrome? Endocr Regul. 2005 Dec;39(4):12731.PMID:16552990. 35. Stárka L, Cermáková I, Dusková M, Hill M, Dolezal M, Polácek V. Hormonal profile of men with premature balding. Exp Clin Endocrinol Diabetes. 2004 Jan;112(1):24-8.PMID:14758568. 36. Genazzani AD, Santagni S, Rattighieri E, Chierchia E, Despini G, Marini G,Prati A, Simoncini T. Modulatory role of D-chiro-inositol (DCI) on LH and insulin secretion in obese PCOS patients. Gynecol Endocrinol. 2014 Jun;30(6):438-43. Doi: 10.3109/09513590.2014.897321. Epub 2014 Mar 7. PubMed PMID: 24601829. 37. Nordio M, Proietti E. The combined therapy with myo-inositol and D-chiro-inositol reduces the risk of metabolic disease in PCOS overweight patients compared to myo-inositol supplementation alone. Eur Rev Med Pharmacol Sci. 2012 May;16(5):575-81. PubMed PMID: 22774396. 38. Pizzo A, Laganà AS, Barbaro L. Comparison between effects of myo-inositol and D-chiro-inositol on ovarian function and metabolic factors in women with PCOS. Gynecol Endocrinol. 2014 Mar;30(3):205-8. doi: 10.3109/09513590.2013.860120. Epub 2013 Dec 19. PubMed PMID: 24351072. 39. Reaven GM, Syndrome X: 6 years later. J Intern Med Suppl. 1994;736:13-22. 40. Reaven GM. The metabolic syndrome: requiescat in pace. Clin Chem. 2005 Jun;51(6):931-8. Epub 2005 Mar 3. Review. PubMed PMID: 15746300. 41. Reaven GM. The metabolic syndrome: is this diagnosis necessary? Am J Clin Nutr. 2006 Jun;83(6):1237-47. Review. Erratum in: Am J Clin Nutr. 2006 Nov;84(5):1253. PubMed PMID: 16762930. 42. Giordano D, Corrado F, Santamaria A, Quattrone S, Pintaudi B, Di Benedetto A, Effects of myo-inositol supplementation in postmenopausal women with metabolic syndrome: a perspective, randomized, placebo-controlled study. Menopause. 2011 Jan;18(1):102-4. doi:10.1097/gme.0b013e3181e8e1b1. PubMed PMID: 20811299. 43. Santamaria A, Giordano D, Corrado F, Pintaudi B, Interdonato ML, Vieste GD,One-year effects of myo-inositol supplementation in postmenopausal women with metabolic syndrome. Climacteric. 2012 Oct;15(5):490-5. doi: 10.3109/13697137.2011.631063. Epub 2011 Dec 23. PubMed PMID: 22192068. 44. Capasso I, Esposito E, Maurea N, Montella M, Crispo A, De Laurentiis M, Combination of inositol and alpha lipoic acid in metabolic syndrome-affected women: a randomized placebo-controlled trial. Trials. 2013 Aug 28;14:273. doi: 10.1186/1745-6215-14-273. PubMed PMID: 23981814; PubMed Central PMCID: PMC3765513. 45. Malvasi A, Casciaro F, Minervini MM, Kosmas I, Mynbaev OA, Pacella E, Monti Condesnitt V, Creanza A, Di Renzo GC, Tinelli A. Myo-inositol, D-chiro-inositol, folic acid and manganese in second trimester of pregnancy: a preliminary investigation. Eur Rev Med Pharmacol Sci. 2014;18(2):270-4. PubMed PMID: 24488919. 46. Evans JL, Goldfine ID. Alpha-lipoic acid: a multifunctional antioxidant that improves insulin sensitivity in patients with type 2 diabetes. Diabetes Technol Ther. 2000 Autumn;2(3):401-13. Review. PubMed PMID: 11467343. 47. Ansar H, Mazloom Z, Kazemi F, Hejazi N. Effect of alpha-lipoic acid on blood glucose, insulin resistance and glutathione peroxidase of type 2 diabetic patients. Saudi Med J. 2011 Jun;32(6):5848. PubMed PMID: 21666939. 48. D’Anna R, Di Benedetto V, Rizzo P, Raffone E, Interdonato ML, Corrado F, Di Benedetto A. Myo-inositol may prevent gestational diabetes in PCOS women. Gynecol 2012 Jun;28(6):440-2. doi: 10.3109/09513590.2011.633665. Epub 2011 Nov 28. 49. D’Anna R, Scilipoti A, Giordano D, Caruso C, Cannata ML, Interdonato ML, Myo-Inositol supplementation and onset of gestational diabetes mellitus in pregnant women with a family history of type 2 diabetes: a prospective, randomized, placebo-controlled study. Diabetes Care. 2013 Apr;36(4):854-7. doi: 10.2337/dc12-1371. Epub 2013 Jan 22. PubMed PMID: 23340885;PubMed Central PMCID: PMC3609506. 50. Corrado F, D’Anna R, Di Vieste G, Giordano D, Pintaudi B, Santamaria A, Di Benedetto A. The effect of myoinositol supplementation on insulin resistance in patients with gestational diabetes. Diabet Med. 2011 Aug;28(8):972-5. doi: 10.1111/j.1464-5491.2011.03284.x. PubMed PMID: 21414183. 51. Fulghesu AM, Ciampelli M, Muzj G, Belosi C, Selvaggi L, Ayala GF, Lanzone A. N-acetyl-cysteine treatment improves insulin sensitivity in women with polycystic ovary syndrome. Fertil Steril. 2002

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Jun;77(6):1128-35. PubMed PMID: 12057717. 52. Pereira S, Shah A, Fantus IG, Joseph JW, Giacca A. Effect of N-acetyl-L-cysteine on insulin resistance caused by prolonged FFA elevation. J Endocrinol. 2015 Jan 21. pii: JOE-14-0676. [Epub ahead of print] PubMed PMID:25609734. 53. Nestler JE, Jakubowicz DJ, Reamer P, Gunn RD, Allan G. Ovulatory and metabolic effects of D-chiro-inositol in the polycystic ovary syndrome. N Engl J Med 1999;340: 1314–1320. 54.Iuorno MJ, Jakubowicz DJ, Baillargeon JP, Dillon P, Gunn RD, Allan G, Nestler JE. Effects of D-chiro-inositol in lean women with the polycystic ovary syndrome. Endocr Pract 2002;8:417–423. 55. Gerli S, Papaleo E, Ferrari A, Di Renzo GC. Randomized, double blind placebo-controlled trial: effects of myo-inositol on ovarian function and metabolic factors in women with PCOS. Eur Rev Med Pharmacol Sci. 2007 Sep-Oct;11(5):347-54. PubMed PMID: 18074942 56. Costantino D, Minozzi G, Minozzi E, Guaraldi C. Metabolic and hormonal effects of myo-inositol in women with polycystic ovary syndrome: a double-blind trial. Eur Rev Med Pharmacol Sci. 2009;13(2):105-110. 57. Laganà AS, Barbaro L, Pizzo A. Evaluation of ovarian function and metabolic factors in women affected by polycystic ovary syndrome after treatment withD-Chiro-Inositol. Arch Gynecol Obstet. 2014 Nov 22. [Epub ahead of print] PubMed PMID: 25416201. 58. Sacchinelli A, Venturella R, Lico D, Di Cello A, Lucia A, Rania E, Cirillo R, Zullo F. The Efficacy of Inositol and N-Acetyl Cysteine Administration (Ovaric HP) in Improving the Ovarian Function in Infertile Women with PCOS with or without Insulin Resistance. Obstet Gynecol Int. 2014;2014:141020. doi: 10.1155/2014/141020. Epub 2014 Apr 30. PubMed PMID: 24876842; PubMed Central PMCID: PMC4021745. 59. Hong JH, Jang HW, Kang YE, Lee JH, Kim KS, Kim HJ, Park KR, Ku BJ. Urinary chiro- and myo-inositol levels as a biological marker for type 2 diabetes mellitus. Dis Markers. 2012;33(4):1939. doi: 10.3233/DMA-2012-0925. PubMed PMID: 22960342; PubMed Central PMCID: PMC3810682. 60. Kim BH, Park JY, Jang JB, Moon DC. LC-MS/MS method for the quantification of myo- and chiro-inositol as the urinary biomarkers of insulin resistance in human urine. Biomed Chromatogr. 2012 Apr;26(4):429-33. doi: 10.1002/bmc.1682. Epub 2011 Aug 9. PubMed PMID: 21830227. 61. Villeneuve MC, Ostlund RE Jr, Baillargeon JP. Hyperinsulinemia is closely related to low urinary clearance of D-chiro-inositol in men with a wide range of insulin sensitivity. Metabolism. 2009 Jan;58(1):62-8. doi: 10.1016/j.metabol.2008.08.007. PubMed PMID: 19059532.62. Stull AJ, Thyfault JP, Haub MD, Ostlund RE Jr, Campbell WW. Relationships between urinary inositol excretions and whole-body glucose tolerance and skeletal muscle insulin receptor phosphorylation. Metabolism. 2008 Nov;57(11):1545-51.doi: 10.1016/j.metabol.2008.06.009. PubMed PMID: 18940392; PubMed Central PMCID: PMC3469253. 63. Larner J, Craig JW. Urinary myo-inositol-to-chiro-inositol ratios and insulin resistance. Diabetes Care. 1996 Jan;19(1):76-8. PubMed PMID: 8720541. 64. Isabella R, Raffone E. Does ovary need D-chiro-inositol? J Ovarian Res. 2012 May 15;5(1):14. PubMed PMID: 22587479; PubMed Central PMCID: PMC3447676. 65. Carlomagno GDe Grazia SUnfer, et al. Myo-inositol in a new pharmaceutical form: a step forward to a broader clinical use. Expert Opin Drug Deliv. 2012 Mar;9(3):267-71. doi: 10.1517/17425247.2012.662953. 66. Pintaudi B, Di Vieste G, Bonomo M. The Effectiveness of Myo-Inositol and D-Chiro Inositol Treatment in Type 2 Diabetes. Int J Endocrinol. 2016;2016:9132052. Epub 2016 Oct 11. PubMed PMID: 27807448; PubMed Central PMCID: PMC5078644. 67. Dinicola S, Minini M, Unfer V, Verna R, Cucina A, Bizzarri M. Nutritional and Acquired Deficiencies in Inositol Bioavailability. Correlations with Metabolic Disorders. Int J Mol Sci. 2017 Oct 20;18(10). pii: E2187. doi:10.3390/ijms18102187. Review. PubMed PMID: 29053604; PubMed Central PMCID:PMC5666868. 68. Özturan A, Arslan S, Kocaadam B, Elibol E, İmamoğlu İ, Karadağ MG. Effect of Inositol and its Derivatives on Diabetes: A Systematic Review. Crit Rev Food Sci Nutr. 2017 Oct 20:0. doi: 10.1080/10408398.2017.1392926. [Epub ahead of print] PubMed PMID: 29053004. 69. Kalra B, Kalra S, Sharma JB. The inositols and polycystic ovary syndrome. Indian J Endocrinol Metab 2016 Sep-Oct; 20(5):720-724. doi: 10.4103/2230-8210.189231. Review. PubMed Central PMCID: PMC5040057. 70. Sortino MA, Salomone S, Carruba MO, Drago F. Polycystic Ovary Syndrome: Insights into the Therapeutic Approach with Inositols. Front Pharmacol 2017 Jun 8;8:341. eCollection 2017. doi: 10.3389/ fphar.2017.00341. Review. PubMed PMID: 28642705 PubMed Central PMCID: PMC5463048. 71. Unfer V, Nestler JE, Kamenov ZA, Prapas N, Facchinetti F. Effects of Inositol(s) in Women with PCOS: A Systematic Review of Randomized Controlled Trials. Int J Endocrinol. 2016;2016:1849162. Epub 2016 Oct 23. Review. PubMed PMID: 27843451; PubMed Central PMCID: PMC5097808. 72. Dell’Edera D, Sarlo F, Allegretti A, Simone F, Lupo MG, Epifania AA. The influence of D-chiro-inositol and D-myo-inositol in pregnant women with glucose intolerance. Biomed Rep. 2017 Aug;7(2):169-172. doi: 10.3892/br.2017.939. Epub 2017 Jul 4. PubMed PMID: 28804631; PubMed Central PMCID: PMC5526159. 73. Dell’Edera D, Sarlo F, Allegretti A, Epifania AA, Simone F,

Lupo MG, Benedetto M, D’Apice MR, Capalbo A. Prevention of neural tube defects and maternal gestational diabetes through the inositol supplementation: preliminary results. Eur Rev Med Pharmacol Sci. 2017 Jul;21(14):3305-3311. PubMed PMID: 28770950. 74. Malvasi A, Kosmas I, Mynbaev OA, Sparic R, Gustapane S, Guido M, Tinelli A. Can trans resveratrol plus d-chiro-inositol and myo-inositol improve maternal metabolic profile in overweight pregnant patients? Clin Ter. 2017 JulAug;168(4):e240-e247. doi: 10.7417/T.2017.2013. PubMed PMID: 28703838. 75. Dinicola S, Chiu TT, Unfer V, Carlomagno G, Bizzarri M. The rationale of the myo-inositol and D-chiro-inositol combined treatment for polycystic ovary syndrome. J Clin Pharmacol. 2014 Oct;54(10):1079-92. doi: 10.1002/jcph.362. Epub 2014 Jul 18. Review. PubMed PMID: 25042908.

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Obesity has become an epidemic in the United States, with more than two-thirds of adults being overweight or obese,1 which totals 87 million obese people – 13% of the worldwide total – in a country with only 5% of the population.2 Being overweight increases the risk of developing chronic diseases,3 which in turn increases the aging process and decreases quality of life. Almost half of adult Americans report that they are trying to lose weight,3 but many who do lose weight eventually regain most of what they lost.4 Successfully maintained weight loss requires focus on not only the intake of food and drink and physical activity,1 but also emphasis on behavioral modification.5 Behavioral modification involves strategies to reinforce diet and exercise changes and can include becoming educated about food preparation, portion sizes, label reading, and self-monitoring. Another important factor in combating obesity is the type of food that is consumed. Many foods in the United States consist of processed and genetically modified (GM) ingredients. An estimated 75 percent of processed foods contain genetically modified ingredients, and 80 percent of food consumed in the U.S. is processed.6 Data from the Centers for Disease Control show that obesity rates began increasing dramatically in the early 1990s,7 which happens to be soon after GM crops were introduced into the food supply. Data shows that the trends of obesity between 2000 and 2008 and the prevalence of GM corn were similar.8 Today, roughly 300 million Americans regularly consume food containing genetically modified organisms (GMOs),9 and obesity rates continue to climb. Peer-reviewed studies have found harmful effects on the health of laboratory and livestock animals fed GM foods. Most of these studies show that they can

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cause toxic and allergenic effects as well as altered nutritional value. Regulations do not require longterm or multi-generational studies, which means it is not known if the changes commonly reported in short-term studies ever develop into serious disease. Common rodent trials are too short to show long-term effects in a human’s lifespan, such as weight gain, organ damage, or cancer. Despite the shortcomings in the regulatory trials, there have been statistically significant harmful effects most commonly observed in the liver and kidneys. These are major detoxifying organs: typically the first to show evidence of chronic disease.10 Because it is not required to label GMOs in food in that U.S., eating organic is the best way to know you are eating food that is GMO-free. A 2014 study shows that organic crops have higher concentrations of antioxidants and other nutrients. Many of these antioxidants have been shown to protect cells and reduce the risk of some cancers, cardiovascular disease, and Alzheimer’s disease.11 Organic food is made without synthetic fertilizers and pesticides, genetic engineering, radiation, or preservatives. To be certified USDA organic, the food has to contain at least 95 percent organic ingredients. Organic food has to be produced, processed, and inspected according to strict standards in order to be certified.12 Reducing or eliminating GMOs and changing to an organic diet may improve health in many areas including digestion, energy, weight loss, food allergies, anxiety and depression, and other chronic health conditions. A survey conducted by the Institute for Responsible Technology showed that 54.6% of people who switched to a non-GMO diet had improvements with weight or obesity. About 75% of those surveyed also switched to an organic diet, with 85.2% seeing positive results in their digestion.13 Although anecdotal, the possible benefits • SPRING 2018

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to this dietary change could make a major impact on obesity in the U.S. With obesity spiraling out of control, it is important to find solutions that improve the health of Americans. Education on diet and behavioral modification can make a big impact. The prevalence of obesity could decrease with the introduction of more organic foods and less genetically modified products. Access to a medical provider that will support this kind of lifestyle can help guide Americans in a healthy direction with certified organic foods, which can prevent disease associated with GMO foods.

Resources

1. Ng M, Fleming T, Robinson M, et al. Global, regional, and national prevalence of overweight and obesity in children and adults during 1980-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2014;384(9945):766-81. 2. Ogden C.L., Carroll, M. D., Kit, B.K., & Flegal K. M. Prevalence of child-hood and adult obesity in the United States, 2011-2012. Journal of the American Medical Association.2014;311(8):806-814. 3. Office of the Surgeon General (US). The Surgeon Generals Call To Action To Prevent and Decrease Overweight and Obesity. National Center for Biotechnology Information. https://www.ncbi. nlm.nih.gov/books/NBK44206/. Published January 1, 1970. 4. Kruger J, Michels Blanck H, Gillespie C. Dietary Practices, Din-

ing Out Behavior, and Physical Activity Correlates of Weight Loss Maintenance. Preventing Chronic Disease. 2008;5(1):A11. 5. NHLBI Obesity Education Initiative Expert Panel on the Identification, Evaluation, and Treatment of Obesity in Adults (US). Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults: The Evidence Report. Bethesda (MD): National Heart, Lung, and Blood Institute; 1998 Sep. Available from: https://www.ncbi.nlm.nih.gov/books/NBK2003/ 6. Wright C. GMOs Encourage Weight Gain and Obesity, Researchers Discover. Natural News. https://www.naturalnews.com/045247_ GMOs_weight_gain_obesity.html. Published May 22, 2014. 7. Obesity Trends Among U.S. Adults Between 1985 and 2010. https://www.cdc.gov/obesity/downloads/obesity_trends_2010. pdf. 8. besity epidemic. Nutrition Research and Practice. 2011;5(3):253259. doi:10.4162/nrp.2011.5.3.253. 9. Bawa AS, Anilakumar KR. Genetically modified foods: safety, risks and public concerns—a review. Journal of Food Science and Technology. 2013;50(6):1035-1046. doi:10.1007/s13197-012-0899-1. 10. Antoniou M, Robinson C, Fagan J. GMO myths and truths: an evidence-Based examination of the claims made for the safety and efficacy of genetically modified crops. Kolkata: Earthcare Books; 2012. 11. Barański M, Średnicka-Tober D, Volakakis N, et al. Higher antioxidant and lower cadmium concentrations and lower incidence of pesticide residues in organically grown crops: a systematic literature review and meta-analyses. British Journal of Nutrition. 2014;112(05):794-811. 12. Organic 101: What the USDA Organic Label Means. USDA. https:// www.usda.gov/media/blog/2012/03/22/organic-101-what-usda-organic-label-means. 13. Smith, JM. Survey Reports Improved Health After Avoiding Genetically Modified Foods. Int J Hum Nutr Funct Med. 2017. https:// responsibletechnology.org/irtnew/wp-content/uploads/2017/11/ Improved-Health-by-Avoiding-GMOs-by-Jeffrey-Smith.pdf

About the Author

For the last 30 years, Dr. Kimball Lundahl’s goal has been to prevent serious diseases and save lives. As the President of Healthy Habits, he has developed a complete business system, helping other doctors combat obesity and create successful practices.

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Effects Of A Medical Food Formula On Plasma Lipid Profile And Selected Clinical Biomarkers For Metabolic Syndrome

By Lewis Chang, PhD, and Kirti Salunkhe, MD - Metagenics Institute

Dr. Chang received his PhD in Nutritional Sciences from University of Washington and Dr. Salunkhe is head of Metagenics Institute.

Background

Dyslipidemia is a group of conditions marked by abnormal levels of blood lipids or lipoproteins, such as elevated total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and very-low-density lipoprotein cholesterol (VLDL-C), raised triglycerides (TGs), and reduced high-density lipoprotein cholesterol (HDL-C). According to the National Health and Nutrition Examination Survey (NHANES 20032006), 53% (105.3 million) of U.S. adults have lipid abnormalities.1

nic acid (ALA) at 1.6 g for men and 1.1 g for women, ensuring 25% to 35% of daily energy comes from dietary fat and <7% of overall daily energy from saturated fat, dietary cholesterol intake <200 mg/day, 10 g to 20 g/day of soluble fiber, and importantly, inclusion of sources of antioxidants and efficacious doses of plant sterols/stanols.2,6,8-11 A multi-site, prospective case series was conducted to measure changes in plasma atherogenic lipid profile and metabolic syndrome-related variables from baseline to 4 weeks after daily consumption of UMC in subjects with dyslipidemia. Changes in these variables between baseline and 8 weeks were evaluated in a subgroup of these participants.

Dyslipidemia is a prominent risk factor for atherosclerotic cardiovascular disease (CVD). Elevated LDL-C is a well-established risk factor.2 Among the LDL-C subclasses that differ in size and density, the small dense LDL-C is more prone to oxidative modification and thus particularly atherogenic.3,4 High TGs and low HDL-C are also independent predictors of CVD.5 Aspects of dyslipidemia are part of the established diagnostic criteria for metabolic syndrome (plasma TGs ≥ 150 mg/dL and HDL-C < 40 mg/dL in men or < 50 mg/dL in women) along with elevated waist circumference (WC), blood pressure (BP), and fasting plasma glucose level.6 If present, metabolic syndrome considerably increases the risk for CVD and type II diabetes (T2D) and should be managed appropriately.

Participants were overweight (BMI>25 kg/m2) men and women ages 24 y/o to 65 y/o with documented dyslipidemia; some also had metabolic syndrome based on the ATP III criteria. Individuals who were on lipid-lowering drugs or anticoagulant medications within 4 weeks prior to the study or with a history of major illness were excluded. The study was carried out in compliance with the Helsinki Declaration of 1975, and the study was approved by Quorum Independent Review Board (Seattle, WA). Informed written consent was obtained from all participants prior to enrollment in the study.

Lifestyle-based interventions are essential in management of lipid abnormalities and halting progression towards advanced cardiovascular and metabolic disease.6,7 A new medical food formula (acronym: UMC) was recently developed to reflect current recommendations from the National Cholesterol Education Program, the American Heart Association, and Academy of Nutrition and Dietetics for dietary management of dyslipidemia. These recommendations include a dietary source of plant-derived omega-3 fatty acids through daily intake of α-linole-

This open-label, case observation series was conducted at 3 clinic sites (Mississauga, Canada, Avon, CT, and Chicago, IL) under the guidance of the Functional Medicine Research Center® (Gig Harbor, WA). At baseline (Visit 1), participants were instructed to begin 2 servings daily of the UMC medical food incorporated into their meal pattern. Participants returned to the clinic at Week 4 (Visit 2) and a subgroup returning at Week 8 (Visit 3) for clinical evaluation and assessment for compliance and adverse events. Dietary intakes were tracked throughout the study on a weekly

ANTI-AGING MEDICAL NEWS

Methods/Design

• SPRING 2018

Effects Of A Medical Food Formula On Plasma Lipid Profile And Selected Clinical Biomarkers For Metabolic Syndrome

basis using a 3-day food diary (2 weekdays and 1 weekend day). Nutritional analysis of these dietary intakes was completed by a registered dietitian using the US Department of Agriculture (USDA) Supertracker (https://www.supertracker.usda.gov), and the nutritional composition of the UMC medical food was added. Fasting blood samples obtained at each clinic visit were analyzed for lipid profile. Particle size was measured in select subjects. Glucose and hsCRP were measured in all subjects, and additional markers, such as Lp-PLA2, were measured in select subjects. Paired t-tests were performed to assess differences in primary and secondary outcome measures from baseline to Week 4 and from baseline to Week 8. A 2-sided value of P<0.05 was considered statistically significant.

Results

risk score from high (160 mg/dL to 189 mg/ dL) to borderline high (130 mg/dL to 159 mg/ dL) during the 4-week intervention.2 On average, participants had a weight reduction of 1.5 ± 1.4 lbs. at 4 weeks. Spearman correlation analyses showed that changes in TC and LDL-C were not significantly correlated with body weight changes, reflective of the delivery of lipid lowering actives in the formula (rho=0.09, p=0.72 for TC; rho=-0.04, p=0.89 for LDL-C). Apolipoprotein B (apo B), the main protein in LDL-C aiding in the transport of LDL-C in the bloodstream and the uptake of cholesterol into cells, was measured in select participants. Apo B concentrations in plasma were significantly reduced, with an average of 8.2% reduction within 4 weeks (p=0.038) (Table 1). Non-HDL cholesterol (non-HDL-C), a strong marker of CVD risk,12 was significantly reduced within 4 weeks (Table 1), with an average reduction of 8.6% (p=0.041).

A total of 24 participants (17 women and 7 men) were enrolled from 3 study sites. Twenty-one subjects completed 4 weeks, and blood work is available for 19 subjects. A subgroup of 12 participants continued and completed the 8-week evaluation. No adverse events were reported.

Main findings at 4 weeks:

After 4 weeks, TC showed a statistically significant reduction from baseline (252.3 ± 41.5 mg/dL) to 4 weeks (235.1 ± 35.4 mg/dL; Figure 1)—an average 6.2% reduction leading to a clinical reclassification of risk score from high (≥ 240 mg/dL) to borderline high (200 mg/dL to 239 mg/dL).2 Spearman correlation analysis showed that change in TC levels at 4 weeks was significantly associated with baseline TC levels, indicating that subjects with higher baseline TC experienced greater reduction (rho=-0.54;

* Statistically significant. †

From ADA/ACC Consensus Report Treatment Goals.13

At 4 weeks, a statistically significant change was seen in WC and systolic BP (Table 2). HDL-C and glucose levels were comparable at baseline and at 4 weeks, and remained within the normal range throughout. There was a trend towards a decrease (by an average 3.3% reduction) in plasma TGs.

Figure 1. Significant changes in TC and LDL-C levels at 4 weeks compared with baseline (mean ± SD; n=19). p=0.017). * Statistically significant.

Similarly, LDL-C was significantly reduced from baseline (163.1 ± 34.4 mg/dL) to 4 weeks (147.9 ± 31.1 mg/dL; Figure 1), an average 8.5% reduction. Overall, the group reclassified LDL

* Statistically significant from baseline (p<0.05) as assessed by paired t-tests between time points. Sample size varied due to missing data. † From AHA/NHLBI Scientific Statement.6

ANTI-AGING MEDICAL NEWS

• SPRING 2018

Effects Of A Medical Food Formula On Plasma Lipid Profile And Selected Clinical Biomarkers For Metabolic Syndrome

Subgroup findings at 8 weeks:

After 4 weeks, 12 participants continued to consume UMC to visit 3 (8 weeks). Compared with baseline, a statistically significant reduction was seen in TC (-6.4%), LDL-C (-10.0%), and WC (-2.0%; Table 3). Spearman correlation analyses found that the magnitude of change in TC, LDL-C, and WC were not correlated with body weight change during the study (p>0.05). No further significant change was seen in SBP, HDL, TGs, or glucose from baseline to 8 weeks.

*Statistically significant from baseline as assessed by paired t-tests between time-points (p<0.05).

Summary

In this practice-based research study, patients with dyslipidemia across 3 independent clinical sites were placed on 2 servings of UMC medical food per day with minimal changes in other dietary habits across the whole subject cohort, and no prescribed change in the amount of physical activity. At the end of 4 weeks, significant changes were seen in the atherogenic lipid profile, with significant reduction in total and LDL-C and apo B. In select cases where particle size was measured, these were further indication of improvements in overall lipid profile risk. Improvements in metabolic syndrome-related variables were also seen, highlighting potential for broader support for cardiometabolic patients. In clinical practice, an additional emphasis on combining a medical food such as UMC with

ANTI-AGING MEDICAL NEWS

dietary and lifestyle recommendations can bring broad benefits. This combination can form the basis of a medical nutrition therapy program for longerterm management of cardiometabolic health for individual patients.

References

1. Toth PP, Potter D, Ming EE. Prevalence of lipid abnormalities in the United States: the National Health and Nutrition Examination Survey 2003-2006. Journal of clinical lipidology. 2012;6(4):325-330. 2. ATP III At-A-Glance: Quick Desk Reference. http://www.nhlbi.nih. gov/health-pro/guidelines/current/cholesterol-guidelines/quickdesk-reference-html. Accessed September 9, 2015. 3. Berneis K, Shames DM, Blanche PJ, La Belle M, Rizzo M, Krauss RM. Plasma clearance of human low-density lipoprotein in human apolipoprotein B transgenic mice is related to particle diameter. Metabolism: clinical and experimental. 2004;53(4):483-487. 4. Ohmura H, Mokuno H, Sawano M, et al. Lipid compositional differences of small, dense low-density lipoprotein particle influence its oxidative susceptibility: possible implication of increased risk of coronary artery disease in subjects with phenotype B. Metabolism: clinical and experimental. 2002;51(9):1081-1087. 5. Miller M. Dyslipidemia and cardiovascular risk: the importance of early prevention. QJM : monthly journal of the Association of Physicians. 2009;102(9):657-667. 6. American Heart A, National Heart L, Blood I, et al. Diagnosis and management of the metabolic syndrome. An American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Executive summary. Cardiology in review. 2005;13(6):322-327. 7. Ahmed SM, Clasen ME, Donnelly JE. Management of dyslipidemia in adults. Am Fam Physician. 1998;57(9):2192-2204, 2207-2198. 8. Your Guide to Lowering Cholesterol with Therapeutic Lifestyle Changes (TLC). In: Services DoHaH, ed. 9. Gylling H, Plat J, Turley S, et al. Plant sterols and plant stanols in the management of dyslipidaemia and prevention of cardiovascular disease. Atherosclerosis. 2014;232(2):346-360. 10. Disorders of Lipid Metabolism (DLM) Guideline (2011). http://www. andeal.org/topic.cfm?menu=5300&cat=4527. Accessed September 22, 2015. 11. EFSA NDA Panel (EFSA Panel on Dietetic Products, Nutrition and Allergies), 2008. Plant Sterols and Blood Cholesterol - Scientific substantiation of a health claim related to plant sterols and lower/ reduced blood cholesterol and reduced risk of (coronary) heart disease pursuant to Article 14 of Regulation (EC) No 1924/2006[1]. doi:10.2903/j.efsa.2008.781. The EFSA Journal. 2008;781:1-12. 12. Cui Y, Blumenthal RS, Flaws JA, et al. Non-high-density lipoprotein cholesterol level as a predictor of cardiovascular disease mortality. Archives of internal medicine. 2001;161(11):1413-1419. 13. Brunzell JD, Davidson M, Furberg CD, et al. Lipoprotein management in patients with cardiometabolic risk: consensus conference report from the American Diabetes Association and the American College of Cardiology Foundation. Journal of the American College of Cardiology. 2008;51(15):1512-1524.

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Alzheimerâ&#x20AC;&#x2122;s Disease: The Gut-Brain Axis

By Thomas Bayne, D.C. & President of Microbiome Labs

Alzheimerâ&#x20AC;&#x2122;s disease (AD) is a progressive form of dementia that destroys memories and other cognitive functions. This chronic neurodegenerative disease is the 6th leading cause of death in the US, affecting over 5 million Americans. Scientists believe that damage to the brain likely begins a decade or more before memory loss and other cognitive symptoms arise. During this preclinical stage of AD, abnormal deposits of proteins can form amyloid plaques and tangled fibers throughout the brain. Meanwhile, neurons begin to lose function and die. The initial damage appears to take place in the hippocampus, where memories are formed. However, as more neurons die, the damage continues to spread to other parts of the brain, and the brain tissue begins to shrink. While the underlying cause of AD is not fully understood, more and more research continues to highlight the important bi-directional connection between the gut microbiome and the brain. One such study, published September 2017 in the Frontiers in Immunology journal, found that proinflammatory lipopolysaccharide (LPS) from the human gastrointestinal tract was abundant in the neocortex and hippocampus of AD-affected brains. Lipopolysaccharide, or LPS, is a structural component of gram-negative bacterial cell membranes that reside in the human GI tract. It is important to note that a majority of the microbes in the digestive tract are gram negative bacteria, including clostridium sp., enterococcus sp., escherichia sp., and bacteroides sp. Trillions of commensal bacteria in the gastrointestinal tract contain LPS, and they are the primary source of this toxin in chronic, low-dose endotoxemia and low-grade inflammation. However, these gramnegative bacteria play an important role in the gut microbiome. The goal is not to eradicate them from the gut, but rather to keep LPS from reaching the intestinal mucosa. When these gram-negative bacteria die, they shed the LPS from their cell membrane, and it begins

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to float freely in the lumen of the intestine as a bacterial endotoxin. Inside the intestinal lumen, LPS is mostly harmless. However, if there is damage to the intestinal lining, then LPS can enter into the bloodstream, where it can trigger an innate immune response, resulting in sub-clinical, persistent, and low-grade inflammation. This condition is better known as metabolic endotoxemia. Metabolic endotoxemia (ME) is a condition that stems from intestinal dysbiosis and a breakdown of intestinal barrier function. Among non-communicable diseases, metabolic endotoxemia is the leading cause of morbidity and mortality worldwide. The findings of this ground-breaking study suggest that metabolic endotoxemia is an important contributor in inflammatory neurodegenerative diseases like AD. Interestingly, meals that are high in saturated fats and dense in calories seem to impact the condition more so than low fat, low-calorie meals. This increase in serum endotoxin concentration is followed by systemic inflammation that is marked by measurable increases in interleukin-6, interleukin-1-alpha, interferon-gamma, triglycerides, and post-prandial insulin. Chronic metabolic endotoxemia and the associated inflammation has been shown to have significant correlation to a variety of chronic diseases. To date, studies support a strong correlation between metabolic endotoxemia and the risk or onset of conditions such as cardiovascular disease, diabetes, obesity, hypogonadism, autoimmunity, and even mood disorders such as anxiety and depression. Fortunately, there are some basic lifestyle choices that can help reduce the risk and incidence of ME. Minimizing alcohol consumption, giving up smoking, expanding the diversity of dietary macronutrients, and reducing saturated fat intake can all have a drastic impact on ME. In addition to the above lifestyle modifications, there are some promising interventional targets that could help decrease ME, including: boosting secretory

â&#x20AC;˘ SPRING 2018

Alzheimer’s Disease: The Gut-Brain Axis

IgA levels, increasing mucin production, and modulating the microbiome. Secretory immunoglobulin A (sIgA) is the first line of defense against free LPS liberated in the lumen of the intestines. This liberated LPS can eventually make its way through the mucosa and the paracellular pathways in the intestinal epithelium, thereby causing ME. sIgA has the capability to bind and neutralize LPS in the lumen and mucosa itself. Thus, increasing sIgA production could have a meaningful impact on ME. Nutrients that have been shown to have a positive impact on the production and secretion of IgA are essential omega fatty acids, glutathione, glycine, glutamine, phosphatidylcholine, vitamin C, zinc and colostrum. Another promising intervention is increasing mucin production. The mucosa is a key barrier to the entry of luminal LPS into the basolateral layer. When the mucosa suffers from inadequate viscosity and production of mucin, it fails to perform its barrier function and allows for the migration of LPS. Increasing mucin production can help restrict the movement of LPS towards the intestinal epithelial. Nutrients that have been shown to support increased mucin production are L-threonine, L-serine, L-proline, and L-cysteine. Finally, spore-based probiotics hold great promise in modulating the microbiome and offer protection in conditions like ME. It is clear that dysbiosis drives ME; as a result, a healthy microbiome has the capability to protect the body from ME. The major issue with most probiotics is that they do not survive gastric passage to enter the small or large intestines intact or viable. There are, however, probiotic spores that have the capability to survive the harsh gastric passage and enter the intestines completely viable. To date, bacterial spores are the only strains that have been shown to treat metabolic endotoxemia. Probiotic spores in the product MegaSporeBiotic® were the subject of a university, double-blind, and placebo-controlled trial to evaluate the ability of the product to reduce or prevent metabolic endotoxemia induced by dietary challenge.

In addition to assessing changes in dietary endotoxemia, the researchers also measured how this probiotic altered transient changes in cardiovascular disease (CVD) risk factors, other novel disease risk biomarkers, and the immune system itself, following a high-fat challenge meal. Healthy volunteers were screened for the metabolic endotoxemia response to the challenge meal. If they showed the response, they were enrolled into the study and randomized into either the placebo group or treatment group. They consumed the placebo or treatment product for 30 days, with no other interventions or dietary/lifestyle changes. After the 30 days, they reported back to the lab for their “post-treatment” response and were given the challenge meal again. All the same blood work was run to access their levels of endotoxemia. The data showed a clear shift to a protective microbiome with just 30 days of supplementation of the spores. The post-test challenge in the treatment group showed a 45% reduction in endotoxemia, whereas the placebo group had progressively worsened. When compared to the placebo group, the treatment group demonstrated a 60% reduction in LPS levels after only 30 days of supplementation with probiotic spores. These findings suggest that the probiotic spores were able to strengthen the integrity of the intestinal lining to keep endotoxins like LPS out of the bloodstream. Furthermore, this study suggests that probiotic spores may be one of the most promising therapies available for metabolic endotoxemia and its associated neurological conditions.

References

Zhao Y, Cong L, Jaber V, Lukiw W. Microbiome-Derived Lipopolysaccharide Enriched in the Perinuclear Region of the Alzheimer’s Disease Brain. Front Immunol. 2017;8:1064. Boutagy NE, McMillan RP, Frisard MI, Hulver MW. Metabolic endotoxemia with obesity: Is it real and is it relevant? Biochimie. 2016;121:11-20. Sylvia KE, Demas GE. A gut reaction: Microbiome-brain-immune interactions modulate social and affective behaviors. Horm Behav. 2018;506X(17): 30431-2. McFarlin BK, Henning AL, Bowman EM, et al. Oral spore-based probiotic supplementation was associated with reduced incidence of post-prandial dietary endotoxin, triglycerides, and disease risk biomarkers. World J Gastrointest Pathophysiol. 2017;8(3):117-126.

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• SPRING 2018

To Pee, or Not to Pee: That Is the Question An In-Depth Comparison of Urine, Serum and Saliva Testing

Special Evening Engagement Regency Ballroom 1 Friday, April 13th t 6:15 PM Join Us for an Evening of Food, Wine and Education with James LaValle, RPh, CCN Physicians choose the way they assess patient hormones based on various reasons, including: t▼ Clinical Relevance

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Welcome to wonderful! Physicians Lab is the leader in delivering State-of-the-art Science and Superior Solutions to practices across the country. We are excited to show you just how easy and effective Urinary Hormone Assessment can be in expanding your knowledge about hormone replacement, hormone metabolism and certain risk factors that you may be missing out on by testing with serum or saliva. Knowledge is power—take this opportunity to gain the knowledge that can grow your practice and make you a leader in this exciting and rewarding field of medicine. Whether you’re just starting out, ready for expansion to a new level of hormone assessment or a seasoned practitioner, our educational resources, practice/patient solutions and science can expand your knowledge and show you what you’ve been missing! Visit us at Booth #117 to get your ticket and information about the other events hosted by Physicians Lab at the 2018 Spring Congress! PhysiciansLab.com t info@PhysiciansLab.com t 877-316-8686 © 2018 Physicians Lab, Inc. All Rights Reserved. A4M-PHYL-FP-AD-2018-02-28

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ORAL IMMUNOGLOBULIN G (IgG) THERAPIES IN IMMUNE DYSFUNCTION

By Angela Lucterhand, DC

Most clinicians in the field today will tell you the fastest-growing patient population and most difficult cases are rooted in immune dysfunction. Whether it be persistent infectious disease or conditions under the umbrella of autoimmunity, clinicians recognize the growing need for more treatment options for these patients. It’s estimated that 50 million Americans suffer from at least one autoimmune condition. The current healthcare model treats autoimmunity as a genetic disease that cannot be cured and uses immunosuppression for its management. However, science is unveiling natural, safe, effective ways, based on lifestyle changes, to help these patients restore immune tolerance. If you look at the predominant demographic in autoimmunity, more than 80% of autoimmune conditions occur in middle-aged women.(1) The dominance of autoimmunity in woman points to the hormonal interplay of the disease, but the age of onset is also an indicator that the immune system changes as these patients age. Changes in immune system function resulting from aging are known as immunosenescence.(2) This can be described as a loss of immune “reserve” and immune discretion. This means that while most measurable features of the immune system decline over time, some may actually increase, such as autoantibody production or inflammatory upregulation. These changes create increased susceptibility to infectious diseases, increased risk for cancer and several autoimmune diseases. Immune system changes can be tied clinically to three main categories of impact: GI barrier dysfunction and dysbiosis, deterioration of mitochondrial function and depletion of metabolic reserve, and uncontrolled inflammation. By targeting these categories, clinicians can de-

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velop a comprehensive approach to treatment. For purposes of this article, the use of immunoglobulin G (IgG) and its impact on barrier function and antigen binding, as well as downstream effects on reducing uncontrolled inflammation will be discussed.

GI Barrier Dysfunction

Breaches in the gut barrier function are one of the most potent immune challenges. Intestinal permeability (leaky gut) may permit unprocessed antigens, or even intact organisms from the gut lumen, entry to the lamina propria by passing between, rather than being processed through, GI epithelial cells. These unprocessed antigens trigger immune responses that can then increase susceptibility to autoimmune cross-reactivity. In fact, one of the leading theories for the genesis of autoimmune diseases is the immune exposure to unprocessed non-self-antigens that have breached the intestinal barrier.(3) The lack of physical barrier integrity and the presence of antigens creates the environmental trigger needed to elicit an immune response.

Increased Antigen Presentation

We can generalize these unprocessed antigens as anything with a pathogen-associated molecular pattern (PAMP). These molecular patterns are what human immune cells use pattern-recognition receptors (PRRs) to recognize general “patterns” that may signal the need for an immune response. The first PRRs identified were the tolllike receptors (TLRs). Today, there are at least 10 different human TLRs known to be expressed in immune cells that mediate the signaling response of pathogen encounters with the immune system. Each TLR recognizes different PAMPs expressed • SPRING 2018

Oral Immunoglobulin G (IgG) Therapies in Immune Dysfunction

on bacteria, viruses, mycobacteria, fungi and parasites. The majority of the TLRs are expressed on the cell surface (as transmembrane receptors) and recognize pathogen surface molecular patterns such as lipopolysaccharides (LPS), flagellin, glucans, structural proteins or lipoproteins. Upon recognition of a particular PAMP, TLRs trigger intracellular signaling pathways that direct a specific immune response, appropriate for the particular pathogen. When one or more PRRs recognize a pathogenic or dangerous molecular pattern, a cascade of intracellular signals is triggered. Consistent among these signals is an upregulation of inflammatory cytokines (usually by activating NF-kB and/or MAPK). The differential nature of the diverse PRR signals also helps inform the way innate immune cells (especially macrophages, monocytes and dendritic cells) condition the adaptive immune response. PRR signaling during antigen presentation helps naĂŻve T cells differentiate into Th1, Th2, Th17 or Treg cells; it may also influence the type of immunoglobulin class produced by B cells.(4) When a patient has increased intestinal permeability, the immune system is forced to scan and recognize excessive amounts of these molecular patterns found on pathogens, and the downstream effect can end up in a mechanism of antibodies and T-cells cross-reacting with tissues of the human host, called molecular mimicry. (5)

Uncontrolled Inflammation

Once the mucosal immune system of the gut is triggered to respond to a potential threat (regardless of the source), the inflammatory process will be engaged and may persist well after the original trigger is neutralized.(6) Prolonged or inappropriate inflammatory responses by the immune system can, in turn, lead to signals that promote further intestinal permeability, leading to chronic cycles of inflammation. These cycles are thought to be at the heart of inflammatory bowel diseases.(7) Therefore, it is imperative to consider all intestinal barrier issues as having an immune/inflammatory component, meaning therapies designed to improve intestinal barrier function should also include immune-supporting and anti-inflammatory components.

Immunoglobulin Supplementation for the Restoration of Immune Tolerance

The question then becomes: while addressing the increase in permeability, is there a way to limit the exposure to the antigens that upregulate inflammation resulting in tissue damage? Many binding studies have demonstrated serum-derived bovine IgG has binding capabilities to many of the PAMPs associated with human pathogens, including C.

difficile, Toxin A and B, E. coli, H. pylori, and lipopolysaccharides (LPS). (8,9,10) When orally ingested, the Fab region of these immunoglobulins withstands the digestive process and binds antigens within the lumen. (11) By binding these antigens in the lumen, complexes too large to penetrate the intestinal epithelium are created, allowing for the antigenic complex to exit following normal peristalsis. Binding and removal of antigens enables normal healing processes to occur in the gut epithelium and prevents excessive release of inflammatory cytokines such as IL-1, IL-18 and TNF. (12) Oral ingestion of IgG has some specific benefits when working strictly within the gut lumen without having access to the bloodstream. Consuming IgG from another mammal means that, naturally, the antibodies formed are pathogens that affect humans without any hyperimmunization. When the immunoglobulin reaches the lumen and binds these antigens, it creates complexes too large to cross the epithelial barrier, and this prevents any risk of immune interaction in the bloodstream. Lumen placement prevents immune interactions internally, binding of complement, and any inflammatory cytokine release. (13) In addition to passive immunity, oral use of serum-derived bovine immunoglobulins (SBI) has demonstrated clinically-relevant reconstitution of the duodenal CD4+ counts in HIV patients. A 2013 study focused on neutralizing bacterial antigens and reducing intestinal inflammation while restoring mucosal immunity in individuals with HIV enteropathy. Within eight weeks of administering 5g SBI daily, mucosal CD4+ lymphocyte densities increased by 51%. (14) This was the first study of its kind to show that duodenal lymphocyte populations could be reestablished in HIV populations. This is promising in the world of immune dysfunction and the use of IgG in patient treatments targeted at the gut-immune interface. The use of oral IgG with broad-spectrum binding capabilities should be considered in a comprehensive GI protocol for patients because of the passive immunity provided at the barrier. This prevents pathogen patterns from presenting to the immune system. Removing burden from the immune system while simultaneously addressing dysbiosis is the first step in allowing enterocyte healing to occur. Enterocyte healing is more efficient when tissue inflammation is not present. There are plenty of additional options that support both immune and GI barrier function such as glutamine, probiotics, anti-inflammatory and immunomodulatory herb or botanical extracts (e.g., curcumin, boswellia, Scutellaria baicalensis, propolis, etc., omega-3 fatty acids, and vitamin D).

ANTI-AGING MEDICAL NEWS

â&#x20AC;˘ SPRING 2018

Oral Immunoglobulin G (IgG) Therapies in Immune Dysfunction

For a properly functioning immune system, barrier function, mitochondrial function and inflammation must be addressed. The use of nutraceuticals in conjunction with lifestyle changes has a potential to be the standard of care for patients with immune-related dysfunction as a part of both prevention and intervention. 1. Fairweather D, Frisancho-Kiss S, Rose NR. Sex differences in autoimmune disease from a pathological perspective. Am J Pathol. 2008 Sep;173(3):600-9. 2. Ponnappan S, Ponnappan U. Aging and immune function: molecular mechanisms to interventions. Antioxid Redox Signal. 2011 Apr 15;14(8):1551-85. 3. Fasano A. Leaky gut and autoimmune diseases. Clin Rev Allergy Immunol. 2012 Feb;42(1):71-8. 4. Pone EJ, Xu Z, White CA, Zan H, Casali P. B cell TLRs and induction of immunoglobulin class-switch DNA recombination. Front Biosci (Landmark Ed). 2012 Jun 1;17:2594-615. 5. Wucherpfennig KW. Mechanisms for the induction of autoimmunity by infectious agents. J Clin Invest. 2001 Oct; 108(8):1097-104 6. Sánchez de Medina F, Romero-Calvo I, et al. Intestinal inflammation and mucosal barrier function. Inflamm Bowel Dis. 2014 Dec;20(12):2394-404. 7. Lee SH. Intestinal permeability regulation by tight junction: implication on inflammatory bowel diseases. Intest Res. 2015 Jan;13(1):11-8. 8. Henderson AL, Horgan A, Detzel CJ, Maas KJ, Weaver EM. Serum-Derived Bovine Immunoglobulin/Protein Isolate Binds and Neutralizes Clostridium Difficile Toxins A and B. Digestive Disease Week DDW, May 3-6, 2014, Chicago, IL. 9. Horgan A et al. Serum-derived Bovine Immunoglobulin/Protein Isolate Binds to Pathogen-Associated Molecular Patterns. Experimental Biology. April 26-30, 2014, San Diego, CA. 10. Tomita GM, Todhunter DA, Hogan JS, Smith KL. Antigenic crossreactivity and lipopolysaccharide neutralization properties of bovine immunoglobulin G. J Dairy Sci. 1995; 78(12):2745–52. 11. Bogstedt AK, Hammarstrom L, Robertson AK. Survival of immunoglobulins from different species through the gastrointestinal tract in healthy adult volunteers: implications for human therapy. Antimicrob Agents Chemother. 1997;41:2320. 12. Detzel CJ, Horgan A, Henderson AL, Petschow BW, Warner CD, Maas KJ, et al. Bovine immunoglobulin/protein isolate binds pro-inflammatory bacterial compounds and prevents immune activation in an intestinal co-culture model. PloS one. 2015;10(4):e0120278. 13. Bosi P, Casini L, Finamore A, Cremokolini C, Merialdi G, Trevisi P, Nobili F, Mengheri E. Spray-dried plasma improves growth performance and reduces inflammatory status of weaned pigs challenged with enterotoxigenic Escherichia coli K88. J Anim Sci. 2004;82:1764–72. 14. Asmuth et al. Oral serum-derived bovine immunoglobulin improves duodenal immune reconstitution and absorption function in patients with HIV enteropathy. AIDS. 2013; 27(14):2207-17.

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Angela Lucterhand, DC

Dr. Angela Lucterhand received her doctorate in chiropractic from Palmer College of Chiropractic in Davenport, Iowa. While there, she was a graduate teaching assistant for courses including Anatomy and Physiology, Histology, the Central Nervous System, and Spinal Anatomy. She received her Bachelor of Arts at Indiana University. Her interest in basic health care led her to become a Health Education Specialist with the Peace Corps, where she served in Mali, West Africa. Dr. Lucterhand loves teaching and was an adjunct professor for Anatomy and Physiology at Ivy Tech. Her passion in practice is addressing the root causes of disease and emphasizing the impact of lifestyle medicine. Dr. Lucterhand practices chiropractic and functional medicine in Elkhart, Indiana, and currently holds the position of Immune Foundations Brand Manager at the Lifestyle Matrix Resource Center.

• SPRING 2018

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BRINGING SCREENING TECHNOLOGY INSIDE THE MEDICAL PRACTICE:

A Potential Paradigm Shift Can Assist Physicians in Improving Clinical Outcomes and Enhancing Physician-Patient Relationships

By Christina Rahm-Cook, PhD The following article is not endorsed and/or supported by The American Academy of Anti-Aging Medicine. The purposes of this publication do not imply endorsement and/or support of any author, company or theme related to this article.

The State of Health Prevention in the U.S.

Health screening in the U.S. is a fragmented mosaic out of reach for large segments of the population with particular consequences for the most vulnerable, the aging. According to the Centers for Disease Control and Prevention (CDC), “Americans use preventive services at about half the recommended rate. … Chronic diseases, such as heart disease, cancer, and diabetes, are responsible for 7 of every 10 deaths among Americans each year and account for 75% of the nation’s health spending. These chronic diseases can be largely preventable through close partnership with your healthcare team, or can be detected through appropriate screenings, when treatment works best. …Preventing disease before it starts is critical to helping people live longer, healthier lives and keeping health care costs down. Preventive services can also help those with early stages of disease keep from getting sicker.” Given the massive room for improvement in this arena, it is clear to a growing number of practitioners that one of the major hurdles in addressing prevention is accessibility to early screening. Increasing patient access to earlier diagnoses would support the ability of physicians to improve delivery of time-sensitive quality care, while enhancing cost predictive modeling for medical practices. Expanded screening availability would also contribute additional data and analytics for developing improved population pathways critical for achieving more effective management of ACOs, at-risk models, and overall healthcare improvements.

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Where-and-When is an Essential New Focus

The National Institutes of Health (NIH) in a paper titled Benefits and risks of screening tests (PubMed Health - December 27, 2016) states, “Not all people have the same risk of a disease. For example, the risk of many diseases depends very much on age. Whether or not a screening test is worth having will greatly depend on the overall risk of getting the disease, and also on a person’s own specific risk. If only 20 out of 10,000 people have a certain undetected disease without any symptoms, it might not necessarily make sense to test all 10,000 people in order to find the 20 people with the disease. But if 500 out of 10,000 people who are older than 60 have the disease in question, it might make sense to screen all people over the age of 60. Large statistical surveys are needed to identify the groups of people with a higher risk of certain diseases.” An aging population is more likely to frequent their family physician’s office for a checkup or to get looked at for symptoms. At this first line of defense for healthcare, however, patients are rarely screened for risks until they report symptoms. Most physicians are forced to rely only on decades-old tools and outside lab tests when what they really need are in-office technologies useful for uncovering a host of underlying health issues best treated early. Technology companies like UNIsource Health are working to change the standard send-it-out paradigm by offering physicians an in-office early screening solution that places the issues of “Where” and “When” on equal footing with “What” and “Why.” In addressing the need for more favorable patient access to testing (see presentation to the International Anti-Aging Society by Dr. Christina

• SPRING 2018

Bringing Screening Technology Inside The Medical Practice: A Potential Paradigm Shift Can Assist Physicians in Improving Clinical Outcomes and Enhancing Physician-Patient Relationships

Rahm Cook), we made study recommendations on pathway development and report-carding algorithms formed from utilizations of the UNIsource in-office model. This presentation and further research of the data led to reports and white papers showing improvements of care based on this technology. UNIsource Health screening technology devices and turnkey operation solutions give today’s integrative-minded physicians new hands-on capabilities using electronic-aided diagnostic support and treatment. Screenings are covered by public and private insurance carriers. Patients arriving for an annual check up, for example, can be screened for 8 essential risk factors in an 8-minute non-invasive process managed by an expert administrator provided on-premise by UNIsource Health. The data and analytics, available immediately, offer physicians the ability to uncover pre-manifest factors and to extract early insights into the need for wellness actions. Although referrals to labs, specialists, or hospitals continue to be relevant at certain stages and for specific procedures, this paradigm shift provides first-line physicians with the add-on ability to offer patients a comprehensive status report of their state of health, preventive treatment or wellness consultations, as well as opportunities to address frequently-asked questions.

As a result, for a growing number of medical practices wellness is the strategy they are increasingly adopting as it cultivates and nourishes a patient-physician partnership. Like any well-run business, keeping customers loyal requires an effective strategy that, in turn, is well executed, cost-efficient and repeatedly builds the relationship with the provider. Similarly physicians who adopt a patient-centered model usually turn to an in-office system of care based on a three-pronged initiative:

Screen. Review. Engage.

1. Screen – Initiating a program of early screening to regularly “follow” the state of a patient’s health by bringing inside the practice the technology needed to facilitate an integrated wellness strategy. 2. Review – Assessing results and sharing the written data report with each patient can be used to produce a treatment and/or lifestyle plan in consultation together. 3. Engage – Staying on top of it by using email or a brief follow-up call to check in on patient progress shows that the practice is continuously engaged and really cares.

Clinical Functions and Factors Upgrading the Physician-Patient Relationship

The pressures of managing costs, billing, time, compliance and care demands may strain the resources of many medical practices, and, in certain cases, lead to more vulnerability and less patient engagement. Emergencies, unexpected delays, or scheduling considerations, usually out of the physician’s immediate control, can add to the stress by triggering patient complaints and anxieties. Anecdotal evidence from physicians offering early screening in-office indicates that this pattern of grievances can be stopped and reversed. When patients see themselves as mere consumers of healthcare, rather than partners in their own wellbeing, time priorities and frustrations can get in the way of a healthy relationship. On the other hand, most patients insist that only their physician knows them well enough to care for them properly. They consider a trusted relationship to be vitally important. Offering patients a significant role in the physician-patient relationship is the first step in forming a productive wellness partnership.

The availability of diagnostic-support technology in the U.S. today is limited primarily to large medical institutions and specialist practices creating a certain amount of distance between patient and process. Radiology, circulatory, invasive procedures, and blood tests form the foundational efforts for detecting risk, most often discovered at a stage requiring surgery or urgent treatment. Because the initiation of screening efforts is based largely on symptomatic discernment or feedback from patients, most screenings tend to focus on specific biological target areas, like heart, brain, IG, obstetrics, or the pursuit of potential pathologies associated with specific diseases or injuries deemed statistically relevant to a population segment. The latest versions of comprehensive early screening devices now available for in-office practices rely on the following FDA-approved measures: pulse oximetry, heart rate variability, body composition index, galvanic skin response and ankle brachial index. The technology supports the identification of underlying causes for diabetes, blood clots, heart attack, stroke, irregular heartbeat, angina, shortness of breath, swelling of the ankles, numbness or tingling of hands or feet, sweating

ANTI-AGING MEDICAL NEWS

• SPRING 2018

Bringing Screening Technology Inside The Medical Practice: A Potential Paradigm Shift Can Assist Physicians in Improving Clinical Outcomes and Enhancing Physician-Patient Relationships

abnormalities, headaches, elevated blood sugar, low libido, erectile dysfunction, sexual complications, urinary tract infections, urinary complications, digestive problems, increased hunger, blurred vision, dizziness and fatigue. The screenings examine for these 8 risk factors: 1. Autonomic Nervous System Dysfunction (ANSD) 2. Sudomotor Dysfunction (SudoD) 3. Endothelial Dysfunction (EndoD) 4. Insulin Resistance (IR) 5. Cardiac Autonomic Neuropathy 6. Cardio- Metabolic Risk 7. Small Fiber Neuropathy 8. Cardio-Vascular Disease (Via Photo-Plethysmography) As one example of the clinical effectiveness of such a screening system, a study published in the Journal for Diabetes Complications conducted a comparative spectral analysis using photoplethysmography (PTG) for measuring insulin resistance versus the hyperinsulinemic euglycemic clamp (HEC) technique. It concluded that the use of the PTG-TP marker measured from the PTG spectral analysis is a useful tool in screening and follow up of IR, especially in large-scale studies. This type of technology is ideally suited for preventative treatment plans and managing risks recognized by Medicare- and Medicaid-recognized Meaningful Use Program.

Conclusion

The adoption of a “where-and-when accessibility” model for early screening technology can transform front-line physician practices. Physicians considering the use of early screening and wellness analytics in their practice are in position to create or improve their goodwill partnership with patients. This paradigm shift can have a dramatic effect on outcomes, incomes and the efficient operation of the practice. By having measurement data and analytical reports available immediately in support of preemptive insights, physicians can have increased opportunities to address impending deterioration or further debilitation in patients who would otherwise fail to be diagnosed in a timely manner. In many early screening cases, sharing the screening information with patients could inspire mindfulness and motivate patients to participate in nutritional and healthy lifestyle transformation programs.

Sources

Preventive Health Care https://www.cdc.gov/healthcommunication/toolstemplates/ entertainmented/tips/PreventiveHealth.html Benefits and risks of screening tests https://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0072602/ De Souza, A L, et al, Assessment of insulin sensitivity by the hyperinsulinemic euglycemic clamp: Comparison with the spectral analysis of photoplethysmography. Journal of Diabetes Complications, January 2017, Volume 31, Issue 1, Pages 128–133 http://www.jdcjournal.com/article/S1056-8727(16)30731-0/fulltext

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UNDERSTANDING THE “BIG 4” HEAVY METALS – WHY SAMPLE TYPE MATTERS AND SOME RESULTS CAN BE MISLEADING

By Theodore Zava The following article is not endorsed and/or supported by The American Academy of Anti-Aging Medicine. The purposes of this publication do not imply endorsement and/or support of any author, company or theme related to this article.

Introduction

Every two years the Agency for Toxic Substances and Disease Registry (ATSDR) publishes its Substance Priority List (SPL) which documents the greatest dangers to human health due to toxicity and potential for human exposure[1]. Since the SPL was first published in 1991, four of the top 10 most toxic substances have been heavy metals, namely arsenic (#1), lead (#2), mercury (#3), and cadmium (#6 or 7). For this reason, they are collectively referred to as the “Big 4” heavy metals. Even though they are widely accepted as dangerous, some aspects of heavy metal toxicity can cause confusion; for example, routes of exposure, length of retention in the body, excretion routes, and what laboratory test results mean. The following information has been compiled to shed light on each of the Big 4 heavy metals and explain what can be interpreted from laboratory testing.

Arsenic

Overview Arsenic exists in inorganic and organic forms, the former being highly toxic compared to the latter. The WHO and EPA have set a maximum allowable level of arsenic in drinking water to 10 µg/L, which is also the most common source of arsenic due to continuous exposure[2]. Even with these regulations, private wells may still contain high levels of arsenic. Additional exposure can come from foods such as fish, shellfish, rice, fruit, beer and wine, flour, corn and wheat[3]. Ocean fish and shellfish generally contain high levels of arsenic, but are able to convert toxic inorganic arsenic into the less toxic organic form[4]. Seaweeds are unable to convert inorganic to organic arsenic, with certain species such as hijiki containing very high levels[5]. Arsenic is known to disrupt over 200 enzymes in humans, and acts by inducing oxidative stress, altering DNA structure, suppressing and amplifying genes, and causing chromosomal abnormalities[6-7]. Inorganic arsenic and its metabolites can readily cross the human placenta, resulting in reduced fetal growth or even early termination of pregnancy due to increased oxidative stress and diminished nutrient transport to the fetus[8]. Chronic toxicity symptoms include cognitive deficits, fatigue, muscular weakness, anorexia, jaundice, nausea, vomiting, eczema, skin pigmentation, keratosis, scaling, brittle nails, white lines in nails, and localized subcutaneous edema[9]. There is evidence linking arsenic to cancers of the lung, prostate, bladder, and skin[10]. Long term arsenic exposure has also been linked to diabetes, hypertension, cardiovascular disease, vascular changes, neuropathy, memory loss, and hormonal regulation changes[11]. Arsenic can interfere with the thyroid’s ability to concentrate iodine, and can reduce selenium’s availability to be incorporated into selenoproteins by forming a tight complex between the two elements.

ANTI-AGING MEDICAL NEWS

• SPRING 2018

Understanding the “Big 4” Heavy Metals – Why Sample Type Matters and Some Results Can Be Misleading

The use of selenium supplementation to combat the toxic effects of arsenic exposure has been successful in humans[12-14]. Testing for Arsenic Exposure

Urinary arsenic is the best indicator of recent dietary intake, as 80% is excreted in urine after 3 days[15]. Normal urinary arsenic levels vary from 5-40 µg/day with acute toxicity possible at levels >100 µg/day[16]. Seafood, with its high concentrations of organic arsenic, can temporarily increase urinary arsenic levels for up to two days[17]. Serum and whole blood are poor indicators of recent dietary intake or body status for arsenic as it is cleared rapidly within a couple of hours[18]; they should only be used to detect very recent or extremely high levels of exposure[19].

Lead

Overview Lead is a non-essential toxic element that can affect all organs in the body, including the nervous, skeletal, urinary, cardiovascular, immune, gastrointestinal, and reproductive systems[20]. Documented as a probable human carcinogen, lead has been associated with cancers of the brain, kidney, stomach, lung, and meninges[21-22]. Lead’s toxic action is a result of its ability to mimic and replace other essential elements such as calcium, zinc, copper, magnesium, sodium, and iron[23-24]. The brain is the most sensitive organ to lead exposure due to damage to neurons and interference with neurotransmitters, specifically glutamate which is required for development and learning[25]. Symptoms related to short term lead exposure include abdominal pain, nausea, vomiting, diarrhea, constipation, and a metallic taste in the mouth[26]. Symptoms of long term exposure include memory loss, depression, abdominal pain, loss of coordination, numbness and tingling in extremities, sleep impairment, headaches, slurred speech, reproductive issues, and anemia[27]. High lead exposures have also been linked to delinquency, violence, and anti-social behavior[28]. Once lead is ingested (10% absorption) or inhaled (50% absorption), it binds to hemoglobin in red blood cells and is transported and deposited in different organs throughout the body[29-30]. Children and pregnant women absorb around 50% of ingested lead, making them more susceptible to lead toxicity[31]. Approximately 95% of lead that is absorbed is stored in the bones with a half-life of around 25 years[32]. Over the past three centuries, environmental levels of lead have increased 1000-fold as a result of human activities. The prime contributors to this increase are leaded gasoline (banned 1996), lead paint (banned 1978) and pipes (banned 1986), mining operations, and other industrial applications[33].

About one in three housing units in the U.S. still has lead-based paint hazards[34]. The amount of lead in soil and dust in cities is proportional to the historical traffic flow volumes during the time when lead was used in gasoline[35]. In the U.S., occupational exposure is the main cause of lead poisoning in adults while 14-20% of total lead exposure is attributed to drinking water[36]. Testing for Lead Exposure

Whole blood is the best indicator of lead status and the most commonly used sample for population and individual monitoring[37]. Around 95% of lead is bound to red blood cells with the rest complexed with intracellular proteins[37]. Lead’s half-life in the blood is around 40 days, about the same as that of a red blood cell[38]. Even after exposure has ceased, lead can be re-introduced into the bloodstream from bone, meaning that blood levels indicate both current and past exposure[39]. The Centers for Disease Control (CDC) considers blood lead to be elevated at 10 µg/dL for adults and 5 µg/dL for children[40]. Recent studies have shown that behavioral and neurological effects can occur at blood lead levels less than 5 µg/dL[41]. Lead in serum is only 1% of that found in whole blood[42]. Lead is excreted very slowly in urine, and urinary levels are only of interest for monitoring long term occupational exposure and chelation therapy[43].

Mercury

Overview Mercury is a non-essential toxic element that exists as inorganic, organic, and elemental species, each affecting the body differently. The half-life of mercury in the brain is estimated at 20 years, bound strongly to sulfur and selenium groups[44]. It is estimated that 50-75% of environmental mercury comes from human activity, the largest sources being coal-fired power plants, gold mines, metal production, and cement production[45]. Mercury’s toxicity is primarily through the creation of reactive oxygen species which burn down antioxidants such as glutathione, and reaction with selenium- containing enzymes involved in antioxidant actions and thyroid hormone formation[46]. Elemental Mercury There is little absorption of elemental mercury in the gut, but nearly 80% is absorbed by the lungs as a vapor[47]. Absorbed elemental mercury is oxidized to inorganic forms of mercury, but remains a vapor in the blood long enough for a significant amount to penetrate the blood-brain barrier[48]. Sources of elemental mercury include dental amalgams, lightbulbs, mines, industrial manufacturing, and thermometer production[49]. Dental amalgams, which are around 50% mercury, gas off between 2-28 µg elemental mercury per day[50].

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Understanding the “Big 4” Heavy Metals – Why Sample Type Matters and Some Results Can Be Misleading

Inorganic Mercury Inorganic mercury can reach most organs, but primarily accumulates in the kidneys where it does the most damage[51]. Many pharmaceutical and agricultural uses of inorganic mercury have been discontinued, but mercury chloride is still used as a pesticide and disinfectant[52]. Essentially all mercury in urine is inorganic, and comes from inorganic mercury exposure or exposure to organic/elemental mercury that has converted to inorganic[53]. Organic Mercury Methylmercury, the most common form of organic mercury, is believed to be 100 times more toxic than elemental or inorganic mercury[54]. Elemental and inorganic mercury is converted by microorganisms in water to organic mercury, which works its way up the food chain[55]. Fish at the top of the food chain (tuna, shark, swordfish) are known to have the highest tissue levels of mercury, with 95-97% present as organic mercury[56]. Nearly all methylmercury is absorbed by the gut[57]. Most of the toxic effects of methylmercury are on the central nervous system, although the immune system can be affected as well[58]. Testing for Mercury Exposure Urinary mercury is the best indicator of inorganic and elemental mercury exposure and long-term exposure/kidney burden[59-60]. Elimination of elemental mercury, which is converted to inorganic mercury in the body, is through urine and feces[61]. For each 10 amalgam surfaces, urine mercury levels will increase by about 1 µg/g creatinine[62].Even though only small amounts of organic mercury (methylmercury) are excreted in urine, it can show up as demethylated inorganic mercury. Whole blood is the best indicator of organic (methyl or ethyl) mercury exposure with 70-95% bound to hemoglobin in red blood cells and a half-life of around 50 days[63]. Serum should not be used for mercury analysis[64].

Cadmium

Overview Cadmium is a non-essential toxic element that mimics estrogen and possibly contributes to the development of lung, prostate, breast, endometrial, testicular, kidney, bladder, pancreatic, and gall bladder cancers[65-66]. Cadmium accumulates in the kidney causing tubular damage while preventing the re-absorption of nutritional elements[67]. Cadmium also damages the nervous and cardiovascular systems, liver, lungs, pancreas, bones, and reproductive organs[68]. Oxidative stress caused by cadmium can cause irregular gene expression, DNA damage, and cell death[69]. Unlike mercury, cadmium does not readily cross the blood brain

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barrier, so neurotoxic effects are more common in the peripheral than the central nervous system[70]. Cadmium bioaccumulates with a kidney half-life of 30+ years, meaning that at birth cadmium levels are low, but by age 30 the body burden may reach 30 mg[71]. Element interactions play a large role in preventing cadmium toxicity. Zinc has been shown to reduce cadmium absorption, compete with cadmium for enzyme binding sites, and induce synthesis of metallothionein, a metal binding protein that has a high affinity for heavy metals, in the liver and kidneys[72]. Proper iron intake is important because it can be displaced by cadmium from its binding sites and decrease cadmium absorption in the intestines[73]. It is believed that selenium can directly bind to cadmium, creating biologically inactive selenium-cadmium complexes[74]. The major sources of cadmium exposure are from vegetables, grains, and tobacco, all of which take up and accumulate cadmium from the soil[75]. Diet contributes to over 90% of cadmium exposure in non-smokers[76]. Vegans and vegetarians are particularly susceptible to cadmium because of their plant-based diets and increased likelihood of zinc or iron deficiency[77]. Absorption of dietary cadmium in the intestines is relatively low, only 3-5% being absorbed from a normal daily intake of 8-25 µg/ day[78]. In comparison, the lungs can absorb up to 50% of inhaled cadmium, which is why cadmium intake in smokers is double that of non-smokers[79]. Other sources of cadmium include seafood, organ meats, and root crops[80]. Human activities and products such as mining, smelting, waste disposal, fertilizer, pesticides, nickel-cadmium batteries, and vehicle exhaust all contribute to environmental and occupational cadmium exposure[81]. Testing for Cadmium Exposure Because cadmium is concentrated in the kidneys, urinary levels are the best indicator of cumulative long term cadmium exposure and kidney burden[82]. Only about 0.01-0.02% of the total body cadmium burden is excreted every day[83]. The Scientific Committee on Toxicity, Ecotoxicity and Environment reported that noticeable negative effects from cadmium exposure can be seen at levels as low as 0.5 µg/g creatinine[84]. The European Union has proposed that urinary cadmium levels should be below 0.66 µg/g creatinine, reflecting recent findings of adverse effects at low-level exposure[85]. A study with American and Belgian participants showed that each doubling of urinary cadmium levels resulted in a pooled estimate risk of 22% in total cancer incidence and 68% for lung cancer risk[86]. Whole blood cadmium levels represent recent (3-4 months) exposure[87]. Serum is a poor indicator of exposure because cadmium in the bloodstream binds to red blood cells, with erythrocyte concentrations 20 times higher than serum[88]

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Understanding the “Big 4” Heavy Metals – Why Sample Type Matters and Some Results Can Be Misleading

Chelation and Hair Testing

Chelation and hair testing are not covered in this review due to the complex nature of these testing methods. Chelation testing can be misleading if compared to non-chelated reference ranges, as all people are exposed to varying levels of toxic metals. Long term chelation therapy can potentially induce nutrient deficiencies as essential elements are chelated along with heavy metals, requiring a very cautious approach[89]. Hair testing is subject to contamination from shampoo, hair products, smoke, and the environment, while factors such as hair color, speed of growth, collection location, collection method, laboratory hair preparation, and lack of inter-laboratory standardization cause results to vary[90-92]. Patient Examples: 1. A patient eats mercury-contaminated fish. Testing would potentially show low urinary

REFERENCES [1] https://www.atsdr.cdc.gov/spl/ [2] USEPA. 2002. National primary drinking water regulations. Current drinking water regulations. U.S. Environmental Protection Agency. Office of Water. www.epa.gov/safewater/mcl.html mcls. [3] Xue J, Zartarian V, Wang SW, Liu SV, Georgopoulos P. Probabilistic Modeling of Dietary Arsenic Exposure and Dose and Evaluation with 2003-2004 NHANES Data. Environ Health Perspect. 2010;118(3):34550. [4] Rose M, Lewis J, Langford N, Baxter M, Origgi S, Barber M, MacBain H, Thomas K. Arsenic in seaweed--forms, concentration and dietary exposure. Food Chem Toxicol. 2007;45(7):1263-7. [5] Rose M, Lewis J, Langford N, Baxter M, Origgi S, Barber M, MacBain H, Thomas K. Arsenic in seaweed--forms, concentration and dietary exposure. Food Chem Toxicol. 2007;45(7):1263-7. [6] Kitchin KT. Recent advances in arsenic carcinogenesis: modes of action, animal model systems, and methylated arsenic metabolites. Toxicol Appl Pharmacol. 2001;172(3):249-61. [7] Abernathy CO, Liu YP, Longfellow D, Aposhian HV, Beck B, Fowler B, Goyer R, Menzer R, Rossman T, Thompson C, Waalkes M. Arsenic: health effects, mechanisms of actions, and research issues. Environ Health Perspect. 1999;107(7):593-7. [8] Vahter M. Health effects of early life exposure to arsenic. Basic Clin Pharmacol Toxicol. 2008;102(2):204-11. [9]Amster E, Tiwary A, Schenker MB. Case report: potential arsenic toxicosis secondary to herbal kelp supplement. Environ Health Perspect. 2007;115(4):606-8. [10] Smith AH, Hopenhayn-Rich C, Bates MN, Goeden HM, HertzPicciotto I, Duggan HM, Wood R, Kosnett MJ, Smith MT. Cancer risks from arsenic in drinking water. Environ Health Perspect. 1992;97:259-67. [11] Kapaj S, Peterson H, Liber K, Bhattacharya P. Human health effects from chronic arsenic poisoning--a review. J Environ Sci Health A Tox Hazard Subst Environ Eng. 2006;41(10):2399-428. [12] Momin A, Ali SK, Haque MM. Randomized placebo-controlled trial to evaluate the effectiveness of selenium in the treatment of arsenocosis patients. In: Applied research on arsenic in Bangladesh. Misbahuddin M (ed). Dhaka, World Health Organization (Bangladesh), Director General of Health services, Govt. of Bangladesh, 2007, pp

and serum mercury, while whole blood tests would be high for mercury. This is because a majority of the mercury in fish tissue is methylmercury which can only be detected in whole blood samples. 2. A patient continuously drinks water contaminated with arsenic from a well. Testing would potentially show low whole blood and serum arsenic and high urinary arsenic. This is because arsenic is cleared rapidly in blood but is excreted over multiple days in urine. 3. A patient ceased smoking cigarettes (high source of cadmium) 6 months ago, but was a habitual smoker for 20 years. Whole blood and serum would potentially show low cadmium levels while urine tests high for cadmium. This is because whole blood represents recent cadmium intake and serum is a poor indicator of cadmium burden, while urine indicates long term cadmium exposure.

17-30. [13] Yang L, Wang W, Hou S, Peterson PJ, Williams WP. Effects of selenium supplementation on arsenism: an intervention trial in inner Mongolia. Environ Geochem Health. 2002;24:359-74. [14] Verret WJ, Chen Y, Ahmed A, Islam T, Parvez F, Kibriya MG, Graziano JH, Ahsan H. A randomized, double-blind placebocontrolled trial evaluating the effects of vitamin E and selenium on arsenic-induced skin lesions in Bangladesh. J Occup Environ Med. 2005;47(10):1026-35. [15] Van Hulle M, Zhang C, Schotte B, et al. Identification of some arsenic species in human urine and blood after ingestion of Chinese seaweed Laminaria. J Anal At Spectrom. 2004;19:58-64. [16] Arnold HL, Odam RB, James WD. Disease of the skin Clinical Dermatology, 8th ed., Saunders W.B. Company, Philadelphia 1990, p. 121. [17] Freeman HC, Uthe JF, Fleming RB, Odense PH, Ackman RG, Landry G, Musial C. Clearance of arsenic ingested by man from arsenic contaminated fish. Bull Environ Contam Toxicol. 1979;22(12):224-9. [18] Baselt RC. Disposition of Toxic Drugs and Chemicals in Man. 7th ed. Foster City, CA: Biomedical Publications; 2004. [19] Mandal BK, Suzuki KT. Arsenic round the world: a review. Talanta. 2002;58:201-35. [20] ATSDR. 2007. Toxicological profile for lead. Atlanta, GA: US Department of Health and Human Services, Public Health Service, Agency for Toxic Substances and Disease Registry. p. 582. [21] IARC. 2010. Lead and lead compounds. In: Identifation of research needs to resolve the carcinogenicity of high-priority IARC carcinogens, IARC Technical Publication No 42. Lyon, France: International Agency for Research on Cancer. pp. 12–16. [22] Liao LM, Friesen MC, Xiang YB, Cai H, Koh DH, Ji BT, Yang G, Li HL, Locke SJ, Rothman N, Zheng W, Gao YT, Shu XO, Purdue MP. Occupational Lead Exposure and Associations with Selected Cancers: The Shanghai Men’s and Women’s Health Study Cohorts. Environ Health Perspect. 2016;124(1):97-103. [23] Pearson HA, Schonfeld DJ (2003). “Lead”. In Rudolph, C.D. Rudolph’s Pediatrics (21st ed.). McGraw-Hill Professional. [24] Goyer RA. Toxic and essential metal interactions. Annu Rev Nutr. 1997;17:37-50. [25] Cory-Slechta DA. Relationships between lead-induced learning impairments and changes in dopaminergic, cholinergic,

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Understanding the “Big 4” Heavy Metals – Why Sample Type Matters and Some Results Can Be Misleading

and glutamatergic neurotransmitter system functions. Annu Rev Pharmacol Toxicol. 1995;35:391-415. [26] Brunton LL, Goodman LS, Blumenthal D, Buxton I, Parker KL. ed. (2007). “Principles of toxicology”. Goodman and Gilman’s Manual of Pharmacology and Therapeutics. McGraw-Hill Professional. [27] Patrick L. Lead toxicity, a review of the literature. Part 1: Exposure, evaluation, and treatment. Altern Med Rev. 2006;11(1):2-22. [28] Hwang L. Environmental stressors and violence: lead and polychlorinated biphenyls. Rev Environ Health. 2007;22(4):313-28. [29] Sakai T. Biomarkers of lead exposure. Ind Health. 2000;38(2):12742. [30] American Academy of Pediatrics Committee on Environmental Health. Lead exposure in children: prevention, detection, and management. Pediatrics. 2005;116(4):1036-46. [31] Cleveland LM, Minter ML, Cobb KA, Scott AA, German VF. Lead hazards for pregnant women and children: part 1: immigrants and the poor shoulder most of the burden of lead exposure in this country. Part 1 of a two-part article details how exposure happens, whom it affects, and the harm it can do. Am J Nurs. 2008;108(10):40-9. [32] Barbosa F Jr, Tanus-Santos JE, Gerlach RF, Parsons PJ. A critical review of biomarkers used for monitoring human exposure to lead: advantages, limitations, and future needs. Environ Health Perspect. 2005;113(12):1669-74. [33] Registry AfTSaD (2007) Public Health Statement for Lead. CAS# 7439-92-1. US Department of Health and Human Services/Public Health Service, Atlanta. Available at: http://www.atsdr.cdc.gov/PHS/ PHS.asp?id=92&tid=22. [34] U.S. Department of Housing and Urban Development. American Healthy Homes Survey: lead and arsenic, 2011. Available at: http:// portal.hud.gov/hudportal/documents/huddoc?id=AHHS_REPORT.pdf [35] Mielke HW, Reagan PL. Soil is an important pathway of human lead exposure. Environ Health Perspect. 1998;106 Suppl 1:217-29. [36] Maas RP, Patch SC, Morgan DM, Pandolfo TJ. Reducing lead exposure from drinking water: recent history and current status. Public Health Rep. 2005;120(3):316-21. [37] Baselt RC. Disposition of Toxic Drugs and Chemicals in Man. 7th ed. Foster City, CA: Biomedical Publications; 2004. [38] American Academy of Pediatrics Committee on Environmental Health. Lead exposure in children: prevention, detection, and management. Pediatrics. 2005;116(4):1036-46. [39] Gulson BL, Mizon KJ, Korsch MJ, Howarth D, Phillips A, Hall J. Impact on blood lead in children and adults following relocation from their source of exposure and contribution of skeletal tissue to blood lead. Bull Environ Contam Toxicol. 1996;56(4):543-50. [40] Centers for Disease Control. Lead: Standard Surveillance Definitions and Classifications. Available at: https://www.cdc.gov/ nceh/lead/data/definitions.htm. [41] Health Canada. Second Report on Human Biomonitoring of Environmental Chemicals in Canada; Health Canada: Ottawa, ON, Canada, 2013. [42] Schütz A, Bergdahl IA, Ekholm A, Skerfving S. Measurement by ICP-MS of lead in plasma and whole blood of lead workers and controls. Occup Environ Med. 1996;53:736-40. [43] Barbosa F Jr, Tanus-Santos JE, Gerlach RF, Parsons PJ. A critical review of biomarkers used for monitoring human exposure to lead: advantages, limitations, and future needs. Environ Health Perspect. 2005;113:1669-74. [44] Friberg L, Mottet NK. Accumulation of methylmercury and inorganic mercury in the brain. Biol Trace Elem Res. 1989;21:201-6. [45] Pacyna EG, Pacyna JM, Steenhuisen F, Wilson S. Global anthropogenic mercury emission inventory for 2000. Atmos Environ. 2006;40(22):4048–4063. [46] Cuvin-Aralar ML, Furness RW. Mercury and selenium interaction: a review. Ecotoxicol Environ Saf. 1991;21(3):348-64. [47] WHO (World Health Organization). 2003. Elemental mercury and inorganic mercury compounds: Human health aspects. Concise International Chemical Assessment Document 50. [48] Research Triangle Institute; Agency for Toxic Substances and Disease Registry. Toxicological profile for mercury. Atlanta: US Department of Health and Human Services; 1999. [49] Mahaffey KR. Mercury exposure: medical and public health issues. Trans Am Clin Climatol Assoc. 2005;116:127-53; discussion 153-4. [50] Berglund A, Pohl L, Olsson S, Bergman M. Determination of the rate of release of intra-oral mercury vapor from amalgam. J Dent Res. 1988;67(9):1235-42. [51] CDC (Centers for Disease Control). 2009. Fourth National Report on Human Exposure to Environmental Chemicals. Department of Health and Human Services. [52] U.S. Environmental Protection Agency. Summary Review of Health Effects Associated with Mercuric Chloride: Health Issue Assessment. EPA/600/R-92/199. Office of Health and Environmental Assessment, Washington, DC. 1994. [53] Berglund M, Lind B, Björnberg KA, Palm B, Einarsson O, Vahter M. Inter-individual variations of human mercury exposure biomarkers: a cross-sectional assessment. Environ Health. 2005;4:20. [54] Eyl TB. Methyl mercury poisoning in fish and human beings. Clin Toxicol. 1971;4(2):291-6. [55] Bernhoft RA. Mercury toxicity and treatment: a review of the literature. J Environ Public Health. 2012;2012:460508. [56] Bloom NS. On the Chemical Form of Mercury in Edible Fish and Marine Invertebrate Tissue. Canadian Journal of Fisheries and Aquatic Sciences, 1992;49(5):1010-1017. [57] ATSDR (Agency for Toxic Substances and Disease Registry). 1999. Toxicological Profile for Mercury. U.S. Department of Health & Human Services. [58] Clarkson TW. The toxicology of mercury. Crit Rev Clin Lab Sci. 1997;34(4):369-403. [59] Clarkson TW, Magos L. The toxicology of mercury and its chemical compounds. Crit Rev Toxicol. 2006;36:609-62. [60] Holmes P, James KA, Levy LS. Is low-level environmental mercury exposure of concern to human health? Sci Total Environ. 2009;408:171-82.

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[61] ATSDR (Agency for Toxic Substances and Disease Registry). 1999. Toxicological Profile for Mercury. U.S. Department of Health & Human Services. [62] Kingman A, Albertini T, Brown LJ. Mercury concentrations in urine and whole blood associated with amalgam exposure in a US military population. J Dent Res. 1998;77(3):461-71. [63] Kershaw TG, Clarkson TW, Dhahir PH. The relationship between blood levels and dose of methylmercury in man. Arch Environ Health. 1980;35:28-36. [64] NCCLS. Control of Preanalytical Variation in Trace Element Determinations; Approved Guideline - 2nd edition. NCCLS document C38-A2. NCCLS, Wayne, PA, 2001. [65] Johnson MD, Kenney N, Stoica A, Hilakivi-Clarke L, Singh B, Chepko G, Clarke R, Sholler PF, Lirio AA, Foss C, Reiter R, Trock B, Paik S, Martin MB. Cadmium mimics the in vivo effects of estrogen in the uterus and mammary gland. Nat Med. 2003;9(8):1081-4. [66] Huff J, Lunn RM, Waalkes MP, Tomatis L, Infante PF. Cadmiuminduced cancers in animals and in humans. Int J Occup Environ Health. 2007;13(2):202-12. [67] Barbier O, Dauby A, Jacquillet G, Tauc M, Poujeol P, Cougnon M. Zinc and cadmium interactions in a renal cell line derived from rabbit proximal tubule. Nephron Physiol. 2005;99(3):p74-84. [68] Nordberg GF. Historical perspectives on cadmium toxicology. Toxicol Appl Pharmacol. 2009;238(3):192-200. doi: 10.1016/j. taap.2009.03.015. [69] Joseph P. Mechanisms of cadmium carcinogenesis. Toxicol Appl Pharmacol. 2009;238(3):272-9. [70] Chang LW. Toxico-neurology and neuropathology induced by metals. In: Chang LW ed. Toxicology of Metals. Boca Raton: CRC Press; 1996:511-535. [71] International Agency for Research on Cancer (1976) IARC. Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man (Cadmium, Nickel, Some Expoxides, Miscellaneous Industrial Chemicals, General Considerations on volatile Anaesthetics), ed 11. World Health Organization, pp 48–64 [72] Jihen el H, Fatima H, Nouha A, Baati T, Imed M, Abdelhamid K. Cadmium retention increase: a probable key mechanism of the protective effect of zinc on cadmium-induced toxicity in the kidney. Toxicol Lett. 2010;196(2):104-9. [73] Flanagan PR, McLellan JS, Haist J, Cherian G, Chamberlain MJ, Valberg LS. Increased dietary cadmium absorption in mice and human subjects with iron deficiency. Gastroenterology. 1978;74(5 Pt 1):841-6. [74] Ohta H, Seki Y, Yoshikawa H. Interactive effects of selenium on chronic cadmium toxicity in rats. ACES. 1995;8(1-2):97-104. [75] Alloway BJ, Jackson AP, Morgan H. The accumulation of cadmium by vegetables grown on soils contaminated from a variety of sources. Sci Total Environ. 1990;91:223-36. [76] CSTEE (Scientific Committee on Toxicity, Ecotoxicity and the Environment). 2004. Opinion on the Results of the Risk Assessment of: Cadmium Metal Human Health (CAS no.: 7440-43-9, EINECS no.: 231-152-8) Cadmium Oxide Human Health (CAS no.: 1306-190, EINECS no.: 215-146-2). Available at: http://ec.europa.eu/health/ ph_risk/committees/sct/documents/out220_en.pdf. [77] Krajcovicová-Kudládková M, Ursínyová M, Masánová V, Béderová A, Valachovicová M. Cadmium blood concentrations in relation to nutrition. Cent Eur J Public Health. 2006;14(3):126-9. [78] Satarug S, Garrett SH, Sens MA, Sens DA. Cadmium, environmental exposure, and health outcomes. Environ Health Perspect. 2010;118(2):182-90. [79] Friberg L. Cadmium. Annu Rev Public Health. 1983;4:367-73. [80] Järup L, Akesson A. Current status of cadmium as an environmental health problem. Toxicol Appl Pharmacol. 2009;238(3):201-8. [81] ATSDR. Toxicological profile for cadmium. 2008. Available at: http://www.atsdr.cdc.gov/toxprofiles/tp5.pdf. [82] Nordberg GF, Jin T, Kong Q, et al. Biological monitoring of cadmium exposure and renal effects in a population group residing in a polluted area in China. Sci Total Environ. 1997;199:111-4. [83] ATSDR (2008) Toxicological profile for cadmium. Agency for Toxic Substances and Disease Registry, Atlanta, GA [84] EC (European Commission). Scientific Committee on Toxicity, Ecotoxicity and the Environment (CSTEE). Opinion on the results of risk assessment of cadmium mental human health, cadmium oxide human health. Adopted by the CSTEE during the 41st plenary meeting of 8 January 2004. Available at: http://ec.europa.eu/health/ ph_risk/committees/sct/documents/out220_en.pdf. [85] Nawrot TS, Staessen JA, Roels HA, Munters E, Cuypers A, Richart T, Ruttens A, Smeets K, Clijsters H, Vangronsveld J. Cadmium exposure in the population: from health risks to strategies of prevention. Biometals. 2010;23(5):769-82. [86] Nawrot TS, Martens DS, Hara A, Plusquin M, Vangronsveld J, Roels HA, Staessen JA. Association of total cancer and lung cancer with environmental exposure to cadmium: the meta-analytical evidence. Cancer Causes Control. 2015;26(9):1281-8. [87] Järup L, Akesson A. Current status of cadmium as an environmental health problem. Toxicol Appl Pharmacol. 2009;238(3):201-8. [88] Friberg L, Piscator M, Nordberg GF, Kjellstrom T. Cadmium in the Environment. 2nd ed. Cleveland, OH: CRC Press; 1974. [89] Waters RS, Bryden NA, Patterson KY, Veillon C, Anderson RA. EDTA chelation effects on urinary losses of cadmium, calcium, chromium, cobalt, copper, lead, magnesium, and zinc. Biol Trace Elem Res. 2001;83(3):207-21. [90] Chojnacka K, Górecka H, Górecki H. The effect of age, sex, smoking habit and hair color on the composition of hair. Environ Toxicol Pharmacol. 2006;22(1):52-7. [91] Wołowiec P, Michalak I, Chojnacka K, Mikulewicz M. Hair analysis in health assessment. Clin Chim Acta. 2013;18;419:139-71. [92] Seidel S, Kreutzer R, Smith D, McNeel S, Gilliss D. Assessment of commercial laboratories performing hair mineral analysis. JAMA. 2001;285(1):67-72.

• SPRING 2018

DIGITAL HEALTH:

APPLICATIONS TO BRAIN DISEASES & DISORDERS

By Sarenka Smith Editorial Director, A4M | MMI

During a time in which healthcare services continue to increase, digital health technologies can provide more cost-effective solutions to both patients and providers. These devices have demonstrated enormous potential in improving the provision of healthcare, as the enormous social and financial costs of brain diseases and disorders continue to exact a toll of billions of dollars. The market of wearable medical technology is one of the most rapidly growing and advancing sectors in the global marketplace, now comprised of devices that have the potential to alter and enhance lifestyle, provide diagnostic and therapeutic support, and aid in injury prevention. With new evolving and transforming models in healthcare, these devices pave the way for effective alternatives to traditional ways that practitioners & providers have collected data, performed diagnostic tests, and interacted with patients.

ogies represent a burgeoning opportunity in healthcare; a 2014 report from Soreon Research linked the emergence of wearables to the beginning of a “deep transformation of the healthcare sector.” More recently, reviews of evidence and data have indicated that virtual reality (VR) holds potential for rehabilitation of Parkinson’s disease, the neurodegenerative disorder that has historically been managed by a combination of medication and

Now, popular widely-used and accessible consumer devices can potentially deliver molecular-level disease diagnosis and treatment. A smartwatch has the capabilities to collect all the data managed by intensive care; an ultrasound can be completed for a fraction of the price with a device that plugs into a smartphone. Hundreds of apps and startups have produced, and are continuing to deliver, massive amounts of data. With the advent and proliferation of these digital technologies, it is increasingly possible to make more effective and personalized healthcare the new standard. These devices, which once solely focused on one single measurement (i.e. the number of steps in a day), can now focus on a variety of bodily measurements: heart rate, blood pressure, breathing, etc. New miniaturized sensors, wireless communication protocols, portability and data transfer abilities, are only a small sampling of the market’s proliferation. Collectively, wireless and wearable medical technol-

ANTI-AGING MEDICAL NEWS

• SPRING 2018

Digital Health: Applications to Brain Diseases & Disorders

physiotherapy. Virtual reality technology has been proposed as a new and inventive rehabilitation tool, one that can potentially optimize motor learning and replicate real-life scenarios in order to improve functional activities: an immersive, interactive experience generated by a computer. One such study assessed the effect of VR training on gait and balance, in addition to an examination of the effects of VR on motor function, daily living activities, cognitive function, and quality of life. In comparison to physiotherapy, VR demonstrated an improvement in step and stride length and balance, by stimulating movement through computer-based games. Further studies revealed that VR exercise exhibited potential advantages over traditional exercise, as individuals were able to practice in a motivating and engaging environment. As Parkinson’s disease has significant adverse effects on quality of life and independence, VR interventions may lead to greater improvements than physiotherapy. The idea that technology can effectively curb and treat a disease that impacts millions of people globally in a host of negative and difficult ways is an innovative and exciting breakthrough, which will likely generate further findings and discoveries. Immersive VR has also been studied for its utilization in stress release and pain reduction for patients with chronic pain, with further applications to addiction and an alternative to opioids. Researchers theorize that by distracting the mind and flooding senses with a positive experience, immersive VR will assist in pain management. Dr. Brennan M. Spiegel and a research team at the Cedars-Sinai Medical Center have experimented with virtual reality for years, creating wearable biosensors, electronic health records, patient-provider portals, and other platforms. Dr. Spiegel has developed a biosensor that has the ability to monitor digestion sounds via computer attachment, while attached to the abdominal wall, and subsequently display results and statistics on an app. The device—AbStats—has been approved by the FDA.

ing a larger, randomized and controlled trial for measuring longitudinal outcomes; the interest in VR has grown, yet the main limitation has been the allotment of time resources and equipment availability. The solution, according to Spiegel, would be a kind of ‘VR-pharmacy,’ in which there is “evidence-based, well-characterized visualizations that clinicians can pull of the shelf and ‘prescribe’ to individual patients.” Another critical innovation in the sphere of digital technologies relates to addiction: due to the increasingly severe public health crisis, companies are now manufacturing new devices to replace addictive painkillers, and innovators are looking to technology for groundbreaking, inventive ways to tackle the increasingly critical opioid crisis—as statistics indicate that 140 people die each day from drug overdoses in the United States. A team of researchers at the Massachusetts Institute of Technology have founded Biobot Labs, merging a research collaboration between the departments of biological engineering and urban studies and planning. The ultimate goal was originally to design technology that “analyzes human waste flowing through the sewers at various points throughout the system,” and to test the wastewater systems for metabolized traces of various substances in order to isolate the places

The team has already treated hundreds of patients with VR therapy in an innovative pilot project, allowing subjects to experience VR worlds for up to twenty minutes through a Samsung Gear headset. Participants were given the option to travel to Iceland, swim with whales in the ocean, or participate in the creation of artwork in a studio. Spiegel relates positive data results, yet many patients—particularly those within the older population—are unwilling to try it, emphasizing the digital generational divide.

with the highest concentrations of opioid—or any drug—users. Cofounder and CEO of Biobot Labs Newsha Ghaeli has stated that the goal is to shift data collection away from overdose and death, and instead focus on overdose prevention and early detection.

Moreover, the research team’s experiment concerning pain reduction demonstrated a 24 percent decline in pain levels, among the patients who engaged in the virtual reality game that was offered. Spiegel and his colleagues are currently perform-

Newer clinical trials have demonstrated considerable success for a device known as a spinal cord stimulator, engineered to alleviate back pain. After implanting the experimental device

ANTI-AGING MEDICAL NEWS

• SPRING 2018

Digital Health: Applications to Brain Diseases & Disorders

under the skin at the spine base, the technology sends a mild electric current to the spinal cord’s nerve fibers. Scientists believe that the therapy, known as neuromodulation or neurostimulation, interrupts the pain signals that are carried from the nerves to the brain. While the idea was originally conceived in the 1960s, recent years have seen the technology expand and grow. Other less-invasive devices that can be used outside the body, and do not require surgery, stimulate the peripheral nerves: the network of nerves that connect the brain and spinal cord. Cleveland-based SPR Therapeutics, which received FDA clearance last year for its device, involves a simple nonsurgical procedure in which a tiny wire is placed under the skin—near the nerves—and connected externally to the stimulator, which can be worn anywhere on the body. As opioid use and abuse in the United States has skyrocketed, these new medical devices could offer drug-free alternatives for some patients. Michael Leong, a pain specialist at the Stanford University School of Medicine, states that the benefit of these devices is that they enable patients to take fewer or no pharmaceuticals. “People are afraid of opioids right now. There’s a stigma. Patients don’t want to be on opioids,” he says.

Valued at approximately $13.2 billion for the year of 2016, the industry of wearable technology is continuing to progress, as healthcare professionals and practitioners concentrate on the overwhelming need to monitor diseases and aging populations. Due to the advent of new wireless and Bluetooth technologies, a rapidly improving infrastructure, and a mounting patient familiarity with wireless devices, the technological advancements are being embraced by the healthcare industry. In order to engineer systems that facilitate the incorporation of wearable medical devices into patients’ and physicians’ daily routines, the marriage of medicine & IT advancements will continue to develop and strengthen. At A4M/MMI, one of our primary focuses is opening new frontiers of healthcare, as we continue to deliver information that helps transition from disease treatment to prevention, in addition to greater personalization of medical care.

Perhaps most importantly, digital devices have the potential to make an enormous positive impact and difference in the landscape of modern medicine. With the overall goal of improving and optimizing clinical outcomes, the digital health revolution is consistently and constantly growing.

ANTI-AGING MEDICAL NEWS

• SPRING 2018

Join the GAINSWave Team for Cocktails & Hors d'oeuvres Mix, mingle and discover how GAINSWave, a new gamechanging ED procedure, can be incorporated into your practice. This "out-of- the-box" business solution is designed to increase your revenue while optimizing the health of your patients. SPEAKERS

Mark White CEO GAINSWave

Zachary Bush, MD A4M Faculty Speaker GAINSWave Provider

WHEN

April 13, 2018 6:15 pm WHERE

A4M Conference Diplomat Resort & Spa, Hollywood, FL Atlantic Ballroom 2 RSVP: JoinGAINSWave.com/A4M2018

Visit Booth # 612

Call 855-383-5779

JoinGAINSWave.com

Product Announcements

ULTRA LIVER SUPPORT Booth #207

NEW Organic Acid Tests (OATs) Booth #312

3-Hour SIBO Breath Test Booth #307

Ultra Liver Support provides a unique combination of herbal and cruciferous ingredients to help support healthy liver function and detoxification. This formula contains broccoli sprout extract standardized to sulforaphanes and Wasabia japonica containing ITCs to support phase II activity in the liver and activation of Nrf2 for detoxification.

NEW to the DUTCH Complete™ and DUTCH Plus™, six organic acid tests (OATs), at no extra charge! This additional information will give practitioners a more comprehensive understanding into the hormone and adrenal picture, especially when it comes to commonly-reported symptoms such as fatigue, anxiety, insomnia, depression, motivation, sex drive, estrogen dominance, and stress. The OATs are now automatically added to all DUTCH Complete™ and DUTCH Plus™ results!

Genova Diagnostics now offers a 3-hour Small Intestinal Bacterial Overgrowth (SIBO) Profile, including novel clinical results interpretation, while continuing to offer clinicians an enhanced 2-hour SIBO panel. SIBO is a common clinical condition and can develop in a variety of patient populations. Some common conditions associated with SIBO include: IBS, Fibromyalgia, IBD, Rosacea, Celiac Disease, Parkinson’s disease, Diabetes and Obesity.

These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

Douglas Laboratories Ph: 800-245-4440 www.douglaslabs.com

Cortisol Awakening Response Booth #307 Genova Diagnostics announces the launch of salivary Cortisol Awakening Response (CAR) testing beginning in April. CAR reflects a person’s ability to cope with anticipated challenges and perception of control around chronic stress, providing insight into HPA axis resiliency. Symptoms of HPA axis dysfunction include: fatigue, insomnia, weight gain, depression, GI complaints, and chronic pain. Also available on: Adrenocortex Stress Profile, One Day Hormone Check, Rhythm Plus, Menopause Plus, Male Hormones Plus Genova Diagnostics Ph: 800-522-4762 www.gdx.net

Dutchtest by Precision Analytical, Inc. Ph: 503-687-2050 www.dutchtest.com

Genova Diagnostics Ph: 800-522-4762 www.gdx.net

MegaPreBiotic Booth #313

UltraFlora® Integrity Booth #501

*This statement has not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

An industry first, Precision Prebiotic. Conventional prebiotics could feed unfavorable bacteria equally as favorable bacteria, therefore making dysbiosis worse. As experts in Microbiome Health, Microbiome Labs has created a Precision Prebiotic that has been clinically shown to specifically feed favorable groups of commensals bacteria, thus supporting a healthy flora.

Metagenics Ph: 800-692-9400 www.metagenics.com

Microbiome Labs Ph: 904-940-2208 www.microbiomelabs.com

New UltraFlora® Integrity is the latest addition to the Metagenics UltraFlora® line of probiotics. Featuring 100 million CFUs of Lactobacillus salivarius UCC118, UltraFlora Integrity helps support intestinal immune health.*

ANTI-AGING MEDICAL NEWS

• SPRING 2018

Product Announcements

Micellized D3™ (1,200 IU Per Drop) Booth #722

Omax Cognitive Boost Booth #1016

SBI Protect Booth #413

Micellized D3™ is a natural, soy free, form of Vitamin D in a water-soluble micellized form. Micellization greatly increases the solubility, absorption and bioavailability of our vitamin D3 over oil or emulsified forms.* The micellization process produces tiny droplets (micelles) that are then formed into highly absorbable aggregate structures.*

Omax Cognitive Boost is a superior brain and cognition support product combining two pharmaceutical strength ingredients with over three decades of clinically validated results to support brain health. The breakthrough formula combines high-concentration Omega 3 DHA fatty acids and European sourced Alpha-GPC in a unique matrix that improves neurotransmission and memory, while helping to lower stress hormones that negatively impact brain health. The therapeutic formula supports a lifestyle change that can truly lead to a Better Brain for Life. Omax Health, Inc. Ph: 855-978-6615 ext. 100 www.omaxboost.com

SBI Protect is the only purified, dairy-free source of immunoglobulins (IgG) available as a dietary supplement. Serum-derived bovine immunoglobulins (SBI) provide the highest IgG concentration available for GI and immune challenges where allergens are a significant concern. Pure IgG helps to maintain a healthy intestinal immune system by binding a broad range of microbes and toxins within the gut lumen. SBI Protect is a targeted approach to resetting the immune system.

H2 Elite Booth #815

CytoQuel™ Booth #321

Turmeric Forte Booth #914

Quicksilver Scientific’s H₂ Elite tablets are a ground breaking new supplement for adding the benefits of high-dose Hydrogen to water and any non-carbonated beverage. As the tablet reacts millions of tiny Molecular Hydrogen bubbles infuse and saturate the liquid. Quicksilver Scientific’s H₂ Elite conveniently provides a high dose of the key active ingredient, Molecular Hydrogen, making it superior to other formulas. Our new high-dose H₂ Elite is safe to use in an open container.

Clinical research demonstrated significant pain reduction in just 2 weeks. Formulated to promote healthy cytokine activity, twenty patients completed an eight-week study at an independent research institution. The results from this open-label 8-week pilot study showed robust changes in a number of health-related parameters within two weeks that continued to improve over the course of the study. The senior researcher commented that the changes are "very tangible and very real".

MediHerb® Turmeric Forte provides a bioavailable form of curcumin by combining Turmeric rhizome with Fenugreek seed extract creating “free curcumin.” Several clinical studies have demonstrated the enhanced absorption and bioavailability of this curcumin-fenugreek extracted formulation compared to “unformulated” curcumin. MediHerb® has chosen specialized plant-sourced bioavailability technology that provides “free curcumin” helping you support your patients.

Quicksilver Scientific Ph: 303-531-0861 www.quicksilverscientific.com

Researched Nutritionals Ph: 800-755-3402 www.ResearchedNutritionals.com

Standard Process Inc. Ph: 800-558-8740 www.standardprocess.com

NuMedica Ph: 800-869-8100 www.numedica.com

ANTI-AGING MEDICAL NEWS

Ortho Molecular Products Ph: 800-332-2351 www.orthomolecularproducts.com

• SPRING 2018

Product Announcements

Walkabout Emu Oil Booth #120 Emu oil has long been used as a healing agent in Australian traditional cultures for the relief of symptoms of sunburn, eczema, pruritis, and urticaria. Contemporary uses of emu oil described in over 75 studies on Pub Med at the National Library of Medicine, document its use in cancer treatment (reducing the severity of colitis-associated colorectal cancer, mucositis from chemotherapy, and arthralgia in breast cancer treatment), in regenerative medicine, and in many other applications. Walkabout Health Products Ph: 715-305-2526 www.walkabouthealthproducts.com

IgA Food Intolerance Test Booth # 520 Dunwoody Labs now offers a non-invasive IgA Food Intolerance test using saliva. IgA antibodies, one of our five major antibodies, are found in mucous membranes and secretions, such as the lining of the gut, saliva, sweat, or tears. This is the body’s first defense against invading pathogens. Sometimes, IgA antibodies may form against specific foods when the body’s intestinal mucosa is damaged, as in the case of Crohn’s disease or colitis. This is known as Food Intolerance. Patients with suspected mucosal damage may benefit greatly from the removal of IgA-reactive foods, as well as patients with low IgG. Patients with high IgE antibodies should also consider IgA testing.

Essential Pro is an advanced oral delivery system of reduced glutathione utilizing the power of the new BioGlute Complex. Available exclusively to licensed healthcare professionals, Essential Pro is designed to increase the systemic bioavailability of glutathione using phosphatidylcholine-enriched liposomes. BioGlute Complex is a proprietary 1iposomal blend that combines reduced glutathione and specialized liposomes enriched with purified phosphatidylcholine.

Dunwoody Labs Ph: 678-736-6374 www.dunwoodylabs.com

Wellness Pharmacy Ph: 800-227-2627 www.essentialgsh.com

ANTI-AGING MEDICAL NEWS

• SPRING 2018

EssentialPro™ Liposomal glutathione capsules Booth #1205

IV THERAPY SYMPOSIUM October 19-20, 2018 | Dallas, TX

Martin Gallagher MD, DC, MS

Dorothy Merritt MD

Paul Anderson ND

Join us for an intensive symposium on IV Therapy. This symposium is designed for physicians, nurse practitioners, and other medical professionals seeking to develop their knowledge of intravenous nutritional therapies. The course will focus on the fundamental basics of the practice, while expanding upon the use of vitamins, minerals, amino acids, and other unique parenteral compounds. Clinicians will gain the ability to immediately and effectively implement various IV protocols into their practices.

Learning Objectives • Describe how to safely administer IV therapy and assess patient progress • Review diagnostic and evaluation testing requirements • Discuss compatible combinations of solutions and potential complications • Discuss vitamins, minerals, and amino acids, and learn how to create targeted IV therapies • Study chelation therapy and specifics on how to remove toxic heavy metals

561.997.0112 • www.a4m.com

BECOME BOARD CERTIFIED TODAY Run a successful medical practice as a leading Board Certified professional in your region Treat patients more effectively than traditional medical practitioners Demonstrate your committment to disease prevention

ABAARM

ABAAHP

The American Board of Anti-Aging /Regenerative Medicine (ABAARM) is a certification program for individuals with MD, DO, DPM and MBBS degrees.

The American Board of Anti-Aging Health Practitioners (ABAAHP) is a certification program for individuals with DC, PharmD, DDS, ND, RN, LPN, PA, MA, RPh, NP, PhD, and Acupuncturist degrees.

For More Information Call 561.997.0112 boards@a4m.com • www.a4m.com ANTI-AGING MEDICAL NEWS

• SPRING 2018

ANTI-AGING MEDICAL NEWS

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3555 South Ocean Drive, Hollywood FL 33019

April 12 - 14, 2018

Diplomat Hotel • Great Hall

Exhibit Floorplan

Exhibitor Index Acadian Diagnostic Laboratories 1007 Access Medical Lab 723 Accu Reference Medical Lab 122 Advanced Naturals 1108 Aerodiagnostics 1120 Ajinomoto North America, Inc. 1100 Allergan 908 Alletess Medical 425 Amen Clinics, Inc. 1218 American Biotech Labs 713 AnazaoHealth Corporation 617 APEX Biologix 015 Apex Energetics 213 APS Pharmacy 917 Argentyn 23 by Natural-Immunogenics 813 Aspen Laser Systems 1116 Asteria Health 319 AtCor Medical 525 Atlantic Biotech LLC 1123 Avoscience 1207 Bio-Botanical Research 417 Bio-Tech Pharmacal, Inc. 620 Bioclinic Naturals 1121 Biogenetix 524 BioMetrix 1202 BioProtein Technology 820 BioSensor Laboratories Inc. 825 Biosound Technologies 1125 BioStat Laboratories 1219 Biotics Research Corp. 324 Blue Horizon International 1203 BodyLogicMD 512 Boiron 523 Boston Heart Diagnostics 621 BrainMaster Technologies, Inc. 625 Calmoseptine, Inc. 1024 BioStat Laboratories 1219 Biotics Research Corp. 324 Blue Horizon International 1203 BodyLogicMD 512 Boiron 523 Boston Heart Diagnostics 621 BrainMaster Technologies, Inc. 625 Calmoseptine, Inc. 1024 Canbiola Inc. 101 Cardiometabolic Health Congress 027 Central Drugs Compounding Pharmacy 206 Cleveland HeartLab, Inc. 907 College Pharmacy 1107 Complete Medical Services 1025 Cosmofrance Inc. 909 CRE8 Pharmacy 421 Crystal Clear Digital Marketing 807 Cynosure, A Hologic Co. 1200 Cyrex Laboratories, LLC 221 DaVinci Laboratories 517

Designs for Health DIEM Labs LLC Doctor.com Doctor’s Data, Inc. Douglas Laboratories Dr. G’s Weight Loss & Wellness Dr.Fuji / ACIGI Dunwoody Labs DUTCH test by Precision Analytical eClinic.care Eclipse Aesthetics Erchonia Corporation Essential Formulations Evoke Neuroscience Folium BioSciences Fotona Fullscript Future Now Detox Gainswave Genomind Essential Formulations Evoke Neuroscience Folium BioSciences Fotona Fullscript Future Now Detox Gainswave Genomind Genomix Nutrition Genova Diagnostics Global Life Rejuvenation Go Wellness Great Plains Laboratory, Inc. Green Roads Wellness Hallandale Pharmacy Hawaiian Moon Healon Medical Health Wellness Industries Healthsnap Solutions Healthy Fusion Healthy Habits Hotze Elite Physicians ICA Health Ideal Protein of America In Body Induction Therapies, makers of Collagen PIN Innergy Development International Peptide Society InvigoMEDIA Isodiol KBMO Diagnostics KYOUI L-Nutra LeadingResponse Life Length LightStim

ANTI-AGING MEDICAL NEWS

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Liquivida Lounge Liveyon MasterPharm Compounding Pharmacy McGuff Compounding Pharmacy Services L-Nutra Procell Therapies LeadingResponse Life Length LightStim Liquivida Lounge Liveyon MasterPharm Compounding Pharmacy McGuff Compounding Pharmacy Services Med 7 Medical Wave Metabolic Code Metagenics MethylGenetic Nutrition Analysis Microbiome Labs Millennium Medical Tech. Mushroom Science My Practice Connect Nature-Throid New You MD Novus Optimum Lab, dba A Best Supplements NuMedica NuSkin Nutrafol Nutritional Frontiers Okyanos Omax Health, Inc. Ondamed OPKO Health, Inc. OrthoMolecular Products Oxy Health, LLC Pellecome, LLC pH Prescription, LLC Physician Compounding Alliance Physician Lab Inc. PhysioAge Systems Plasma Solutions, LLC Power2Practice Predictive Biotech Prestige Products Direct/ TRIADAER pH Prescription, LLC Physician Compounding Alliance Physician Lab Inc. PhysioAge Systems Plasma Solutions, LLC Power2Practice Predictive Biotech Prestige Products Direct/ TRIADAER Procell Therapies Professional Health Products Protocol For Life Balance PULS Cardiac Test

045 222 1003 521 407 050 1114 819 1113 045 222 1003 521 1001 1118 030 501 318 313 1008 418 821 325 103 616 722 100 317 1212 422 1016 601 1021 413 622 717 1023 419 117 1115 322 1015 113 924 1023 419 117 1115 322 1015 113 924 50 121 125 423

Pure Harmony Quicksilver Scientific Quincy Bioscience Quten Research Institute Refine USA Regenerative Tissue Science, LLC Regenomedix Researched Nutritionals RXQ Compounding, LLC Salveo Diagnostics, Inc. Sanesco International Inc. Sarcotropin Sciton Seca Select Lab Partners Selvas Healthcare Inc. South Beach Symposium Sovereign Laboratories, LLC Spectracell Standard Process Inc. Stellar Biomolecular Research Suneva Medical TA Science Tailor Made Compounding LLC Tesla Wellcare Inc. The Cardio Group THOR Photomedicine TruNiagen - Healthspan Research Stellar Biomolecular Research Suneva Medical TA Science Tailor Made Compounding LLC Tesla Wellcare Inc. The Cardio Group THOR Photomedicine TruNiagen - Healthspan Research UberLube UniSource University Compounding Pharmacy US Jaclean, Inc. Venus Concept Vital Reaction VitaminMed, LLC Vitelle Labs Walkabout Health Products, LLC Wavi Web to Med Wellness Pharmacy Wellness Works Wells Pharmacy Women’s International Pharmacy Xymogen Y Lift ZRT Laboratory ZYTO Corp

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Exhibitor Listings Absolute Pharmacy • Booth #104

16011 North Nebraska Avenue, Suite 105, Lutz, FL 33549 US Ph: 813-999-2700 • Fax: 813-999-2701 Email: info@absoluterx.com • Website: www.absoluterx.com Absolute Pharmacy is a first-in-class special compounding facility which is licensed nationwide. Our Sterile facility incorporates tomorrows regulatory standards with the “Absolute” highest quality custom drug production managed by the industries leading pharmacists. Complete with an in-house chemical analytic laboratory, each product is individually tested for potency, BUD, and stability developed by Harvard University chemists. As if that wasn’t enough, we really pride ourselves on our Customer Service and Account Management, which truly sets us apart from all the others.

Access Medical Labs • Booth #723 5151 Corporate Way, Jupiter, FL 33458 US Ph: 866-720-8386 • Fax: 866-610-2902 Email: info@accessmedlab.com • Website: www.accessmedlab.com Access is the nation’s PREMIER Anti-Aging and Wellness Laboratory. America’s largest private, CAP accredited lab, specializing in comprehensive hormone, cardiac & preventive health testing through blood, saliva and urine. Our new state of-the art instrumentation gives you precise insight on your patient’s overall health & wellbeing within 24hrs! Welcome to Access: The Nation’s Leader in Innovation and Laboratory Technology.

Advanced Naturals • Booth #1108 198 Alt 19 South, Palm Harbor, FL 34683 US Ph: 800-690-9988 • Fax: 727-474-1996 Email: support@advancednaturals.com • Website: www.advancednaturals.com Advanced Naturals is a digestive care company that provides natural supplements to practitioners and physicians for their patients. We are especially known for our guaranteed high potency, multiple strain, delayed release probiotics. Optimum health begins with a properly functioning digestive system. Because digestive care is our sole focus, we are able to concentrate entirely on providing the finest digestive care products available.

Aerodiagnostics • Booth #1120 1 Cranberry Hill, Suite 304, Lexington, MA 02421 US Ph: 1-617-608-3832 • Fax: 617-860-6617 Email: customerservice@aerodiagnostics.com • Website: www.aerodiagnostics.com At Aerodiagnostics we strive to provide accurate and timely information you and your family can depend on. We empathize with the challenges you face managing symptoms related to your gastrointestinal disorder(s). Our passion drives us to minimize your time in the process of diagnosis so together with your health care provider, you can resolve your symptoms quickly and accurately. Our mission is Advancing Healthcare into Human Care.

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Ajinomoto North America, Inc • Booth #1100 4105 Poole Road, Raleigh, NC 27610 US Ph: 877-227-2030 • Fax: 919-231-6233 Email: csr@ajiusa.com • Website: www.ajihealth.com Since 1909, Ajinomoto North America has been a global leader in the research, development, manufacturing, and sale of the highest quality amino acid-based products addressing many of today’s top health concerns. Our product portfolio includes well researched, scientifically substantiated dietary supplements including Capsiate Gold, Glysom, amino DEFENSE, and amino LIFE. For more information, please visit www.AjiHealth.com or call (877) 227-2030.

Alletess Medical Laboratory • Booth #425 14 Howard Street, Rockland, MA 02370 US Ph: 800-225-5404 • Fax: 800-225-5404 Email: info@alletess.us • Website: www.foodallergy.com Alletess Medical Laboratory is a world leader in allergy and immunology testing. For over 38 years we have provided excellent service to practitioners worldwide. Our quick turn-around time, transparent pricing and unrivaled customer service make us the best choice for your food sensitivity, allergy and immunology testing needs. We are well positioned to support you, your practice and your patients. Your patient, your voice, your choice...the first step...Alletess

ALLETESS INC.

American Biotech Labs • Booth #713 705 East 50 South, American Fork, UT 84003 US Ph: 801-756-1000 • Fax: 801-756-5454 Email: Sales@ablsilver.com • Website: www.ablsilver.com American Biotech Labs provides an extremely unique form of nano-silver that out-performs colloidal silvers and other silver technologies and is used in a wide variety of ways. ABL sells liquid immune system supplements, cosmetic gels, tooth gel products, hand/body lotions, skin creams, throat lozenges (NEW!) and FDA 510k cleared Wound Dressing Gels. The company continues to research, develop, and manufacture products with the end goal of blessing the lives of people worldwide.

AnazaoHealth Corporation • Booth #617 7465 West Sunset Road, Suite 200, Las Vegas, NV 89113 US Ph: 800-995-4363 • Fax: 800-238-8239 Email: customerservice@anazaohealth.com • Website: www.anazaohealth.com AnazaoHealth is a nationwide full-service compounding pharmacy. Our 503A pharmacy is located in Tampa, FL and our 503B FDA-Registered Outsourcing Facility is located in Las Vegas, NV. We specialize in aesthetics, age management, HRT, men and women’s health, mesotherapy, urology, vitamin injectables, weight loss, and more. Purity, Potency, and Quality define our preparations and is documented through our fulfillment process.

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Apex Energetics • Booth #213 16592 Hale Avenue, Irvine, CA 92606 US Ph: 800-736-4381 Email: tim@apexenergetics.com • Website: www.apexenergetics.com For over 25 years, Apex Energetics™ has served the healthcare community by sponsoring cutting-edge functional medicine education and offering an innovative portfolio of research-guided nutritional formulas. Our unique approach to nutrition involves capturing and integrating science and healthcare practitioner insights into successful performance-based health strategies for patients. At Apex Energetics, you and your patients are at the center of everything we do.TM

APS Pharmacy • Booth #917 34911 US HWY 19 North, 600, Palm Harbor , FL 34684 US Ph: 1-855-927-7633 • Fax: 727-330-7840 Email: newphysician@apsmeds.com • Website: www.apsmeds.com Physicians choose APS Pharmacy as their healthcare partner because of our commitment to quality compounding without compromise. The APS Pharmacy Team is the reliable healthcare partner that your practice and your patients deserve. We compound medications that are safe, reliable, and affordable.

Argentyn 23 by Natural Immunogenics • Booth #813 7504 Pennsylvania Avenue, Sarasota, FL 34232 US Ph: 888-328-8840 • Fax: 941-702-6101 Email: sales@n-icorp.com • Website: www.natural-immunogenics.com/ Made from the purest silver (99.999%) and pharmaceutical-grade water that meets USP or USP standards, Argentyn 23 Bio-Active Silver Hydrosol™ is composed of more than 98% bio-active silver ions and silver nanoclusters. With a consistent dispersion of particles as small as 0.8 nanometers, Argentyn 23 represents the ultimate refinement of the colloidal silver category and offers your patients unmatched safety*, efficacy* and purity in a professional formulation.

Asteria Health • Booth #319 7004 Champion Boulevard, Suite 100, Birmingham, AL 35242 US Ph: 855-771-0505 • Fax: 844-771-0505 Email: info@asteriahealth.com • Website: www.asteriahealth.com VISIT ASTERIA HEALTH AT BOOTH #319 TO WIN AN APPLE IPAD MINI! Asteria Health is a 503B Compounding Pharmacy in Birmingham, Alabama. As an FDA Registered Outsourcing Facility, Asteria Health is a growing company that is dedicated to making a difference in the lives of patients. At the center of this mission is an evolving line of quality-driven products such as bio-identical hormone replacement pellets, intravenous nutrition, and other health and wellness products.

AtCor Medical • Booth #525 One Pierce Place 225W, Itasca, IL 60143 US Ph: 630-228-8871 • Fax: 815-366-5953 Email: info@atcormedical.com • Website: www.atcormedical.com AtCor Medical develops SphygmoCor, the gold standard for arterial stiffness assessment. SphygmoCor provides a fast noninvasive measurement of arterial stiffness -- a proven early marker of hypertension and heart disease. Measure your arterial stiffness during the A4M World Congress at AtCor Medical booth 525.

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Exhibitor Listings

Avoscience • Booth #1207 PO Box 2867, Hayden, ID 83835 US Ph: 888-395-5102 • Fax: 208-902-2562 Email: info@avogenmedical.com • Website: www.avogenmedical.com Avoscience presents new, hormone-free Avogen Medical Intimate Capsules at A4M. These capsules provide a well tolerated, fast acting, lower cost alternative to hormone creams. Formulated with only two ingredients from a rainforest avocado, Avogen Medical Intimate Capsules and soon to be introduced Topical Drops that act on the appearance of sun damage are clinically proven resources for your practice.

Bio-Botanical Research • Booth #417 PO Box 2499, Aptos, CA 95001 US Ph: 800-775-4140 • Fax: 831-688-1733 Email: info@biocidin.com • Website: www.biocidin.com Biocidin®, our flagship product, has been found effective in research trials and in clinical practice for over 27 years. Bio-Botanical Research serves and helps to provide health care professionals with Broad-Spectrum botanical formulations, which address G.I. Dysbiosis, Lyme, Biofilms, and Systemic Immune Challenges. For more information go to: www.biocidin.com or call: 800.775.4140.

Bio-Tech Pharmacal, Inc. • Booth #620 PO Box 1927, Fayetteville, AR 72702 US Ph: 800-345-1199 • Fax: 479-443-5643 Email: customerservice@bio-tech-pharm.com • Website: www.biotechpharmacal.com Bio-Tech Pharmacal, Inc., established in 1984, is a cGMP registered / FDA registered nutraceuti-cal (dietary supplements) manufacturer specializing in innovative high quality hypo-allergenic preventative healthcare products, shipped to physicians, clinics, hospitals and pharmacies worldwide. Bio-Tech Pharmacal has over 100 research affiliations. Bio-Tech Pharmacal has intro-duced many innovative products, including D3-50,000 IU available in a water soluble delivery form. Some products are Halal / Kosher certified.

Biogenetix • Booth #524 4750 South Santa Fe Circle, Unit 3, Englewood, CO 80110 US Ph: 720-287-2155 • Fax: 720-287-2190 Email: support@biogenetix.com • Website: www.biogenetix.com We are proud to offer innovative, high-quality nutritional supplements that are manufactured with the highest standards of purity and safety. Biogenetix starts with a formula designed with sound research and carefully monitors every stage of production to deliver a finished product that lives up to the demands and needs of today’s health care practitioner.

BioMetrix • Booth #1202 6006 North Mesa Street, Suite 301, El Paso, TX 79912 US Ph: 915-307-3002 • Fax: 915-307-7524 Email: info@biometrixlife.com • Website: www.biometrixlife.com BioMetrix offers solutions for those individuals experiencing a decline in their quality of life due to the natural degeneration of hormone production, eating disorders, stress, and cardiovascular issues. We all get to a point in life where it seems as if a switch was flipped. We feel tired, we gain weight unexpectedly, and we just begin to feel different. If you are the person who has tried everything, but still can’t seem to get results, then BioMetrix was created for you! We help you to understand what your body is going through and tailor a program to get you feeling like yourself again.

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BioProtein Technology • Booth #820 14100 McCormick Drive, Tampa, FL 33626 US Ph: 800-280-2456 • Fax: 813-925-1066 Email: info@bioproteintech.com • Website: www.bioproteintech.com BioProtein Technology offers life-improving, all-natural products for patients of pharmacies, physicians and other healthcare practitioners. Our expansive range of products help with sleep quality, menopause symptoms, recovery support, weight loss, muscular endurance, improved nutrition, libido, anti-aging and more. We are a national manufacturer and distributor of supplements and nutraceuticals, specializing in bio-identical growth factors. BioProtein Technology is a vertically integrated company, overseeing the entire process of our product line.

Biosensor Laboratories, inc. • Booth #825 3F, 545 Bongchun-ro Gwanak-gu Seoul, KR11 08789 KR Ph: 822-534-5239 • Fax: 8225345238 Email: franz@biosensorlab.com • Website: www.franzskincare.com We, Biosensor laboratories, are cosmetic company that study the way to improve the skin condition and we produce and sell beauty products, based on our research. We have developed technology called TISSUE X, the way to deliver various nutrients through skin. We applied this tech in our products, Franz dual mask. This facial mask can increase the water content of skin by delivering hyaluronic acid into the skin. Try our products at booth #825

Biosound Technologies • Booth #1125 276 Plymouth Street, Safety Harbor,FL 34695 US Ph: 888-495-1946 • Fax: 727-400-6155 Email: sales@biosoundhealing.com • Website: www.biosoundhealing.com The Biosound Therapy System is a combination of biofeedback, music therapy, sound frequency massage, and meditation. During a session, patients experience full body low frequency vibrations, which enhance the relaxation response and reduce muscle tension and pain. Distinguish your practice and improve growth by becoming a provider of innovative healing therapy.

BioStat Laboratories • Booth #1219 9742 St. Vincent Avenue, Suite 200, Shreveport, LA 71105 US Ph: 318-789-3306 • Fax: 318-798-3386 Email: info@biostatlab.com • Website: www.biostatlab.com MORE THAN A SIMPLE TRANSACTIONAL LAB. A STRATEGIC PARTNER. Biostat Laboratories is Shreveport’s newest and most advanced CLIA certified clinical laboratory. We offer state-of-the-art testing platforms to assess a wide variety of clinical chemistry bio-markers and toxicology tests. Our technicians have many years of professional experience and represent a healthcare company that emphasizes accuracy, fast turn-around time and superior support services. Our ethos revolves around the knowledge that behind every specimen is a patient.

Biotics Research, Corporation • Booth #324 6801 Biotics Research Drive, Rosenberg, TX 77471 US Ph: 800-231-5777 • Fax: 800-231-5777 Email: biotics@bioticsresearch.com • Website: www.bioticsresearch.com Biotics Research Corporation was formed in 1975 and from day one the foundation has been “Innovation and Quality.” Our goals remain unchanged - innovative ideas, carefully researched concepts, and product development with advanced analytical and manufacturing techniques to develop and produce nutritional products of superior quality and effectiveness available exclusively to healthcare professionals.

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Exhibitor Listings

Blue Horizon International • Booth #1203 214 State Street, Suite 101, Hackensack, NJ 07601 US Ph: 212-206-7073 Email: kdoert@bluehorizoninternational.com • Website: www.bluehorizoninternational.com Blue Horizon International is a leader in regenerative medicine and stem cell technology. Home to BHI Rejuve, a program offering HRT and and anti-aging medicine as well as the Alpha Blu Skin Care line, BHI focuses on helping people look and feel their best. Our innovative treatment and research protocols are tailored to meet the needs of each individual and focus on providing optimal health and wellness for our patients.

BodyLogicMD • Booth #512 4850 T Rex Avenue, Suite 125, Boca Raton, FL 33431 US Ph: 561-972-9529 • Fax: 877-457-1564 Email: dastern@bodylogicmd.com • Website: www.bodylogicmd.com BodyLogicMD is the nation's largest and fastest growing network of the most highly-trained physicians specializing in integrative medicine and bioidentical hormone replacement therapy. Integrated with nutrition, cutting-edge therapies and comprehensive wellness strategies, BodyLogicMD's medically-supervised programs are for men and women suffering from hormonal imbalance and conditions of aging, such as menopause and andropause, and seeking to achieve and maintain optimal health throughout their lives.

Boiron • Booth #523 6 Campus Boulevard, Newtown Square, PA 19073 US Ph: 888-264-7668 • Fax: 610-325-7480 Email: info@boironusa.com • Website: www.boironusa.com Boiron, world leader in homeopathic medicines, is best known for Oscillococcinum®, a top-selling flu medicine, and its Arnicare® line of pain relievers. For more than 80 years, Boiron has been committed to funding scientific research and educating health care professionals on homeopathic medicines. As a pharmaceutical company, Boiron maintains the highest standards in manufacturing, complying with U.S. Food and Drug Administration regulations, the Homeo-pathic Pharmacopoeia of the United States and drug Good Manufacturing Practices.

Boston Heart Diagnostics • Booth #621 175 Crossing Boulevard, Suite 100, Framingham, MA 01702 US Ph: 508-877-8711 • Fax: 508-877-6305 Email: info@bostonheartdx.com • Website: www.bostonheartdiagnostics.com Boston Heart Diagnostics is transforming the treatment of cardiovascular disease by providing healthcare providers and their patients with novel, personalized diagnostics and integrated customized lifestyle programs that have the power to change the way clinicians and patients communicate about disease and improve heart health.

BrainMaster Technologies Inc. • Booth #625 195 Willis Street, Bedford, OH 44146 US Ph: 440-232-6000 • Fax: 440-232-7171 Email: sales@brainm.com • Website: www.brainmaster.com A single source manufacturer of neurofeedback medical devices, providing effective EEG brainwave monitoring, analysis, and training that may enable the prevention and/or reversing of cognitive decline, while encouraging mental fitness, memory improvement and self-improve-ment for your clientele.

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Calmoseptine, Inc • Booth #1024 16602 Burke Lane, Huntington Beach, CA 92647 US Ph: 714-840-3405 • Fax: 714-840-9810 Email: Info@Calmoseptine.com • Website: www.calmoseptine.com Calmoseptine® Inc. promotes Calmoseptine® Ointment for the prevention and treatment of skin irritations from moisture such as urinary and fecal incontinence. It is also effective for irritations from perspiration, wound drainage, fecal & vaginal fistulas and feeding tube site leakage. Calmoseptine® Ointment temporarily relieves discomfort and itching. Free samples at our booth!

Cardiometabolic Health Congress • Booth #027 1801 North Military Trail, Suite 200, Boca Raton, FL 33431 US Ph: 877-571-4700 • Fax: 866-218-9168 Email: info@cardiometabolichealth.org • Website: www.cardiometabolichealth.org The Cardiometabolic Health Congress (CMHC) is not only an annual conference or regional meeting. CMHC provides today’s health professionals with a focused point of access—designed to assist them in staying current with newly evolving scientific technologies. Cardiometabolichealth.org allows practitioners to learn about clinical advances, while receiving education in cardiometabolic disease prevention and treatment. Through its array of communications, CMHC provides an extensive educational platform, and delivers content to a broader audience of frontline clinicians: all of whom have a shared investment in cardiometabolic health.

Central Drugs Compounding Pharmacy • Booth #206 520 W La Habra Boulevard, La Habra, CA 90631 US Ph: 877-447-7077 • Fax: 562-694-3869 Email: marketing@centraldrugsrx.com • Website: www.centraldrugsrx.com “Central Drugs is an industry leader in the art and science of custom compounding, specializing in bioidentical hormone replacement therapy and sterile injectable medications. We offer the best in custom solutions through our state-of-the-art compounding laboratories across our pharmacy locations and outsourcing facility. With an expert team of 15 compounding pharmacists, we are dedicated to helping prescribers improve patient care and wellness across the country through our quality products, expert advice, and friendly customer service.”

Cleveland HeartLab • Booth #907 6701 Carnegie Avenue, Suite 500, Cleveland, OH 44103 US Ph: 866-358-9828 • Fax: 866-869-0148 Email: customersupport@clevelandheartlab.com • Website: www.clevelandheartlab.com Cleveland HeartLab is an established, premier inflammation testing laboratory. Our scientifically-proven, peer-reviewed multi-marker approach of adding inflammation-specific tests to traditional lipid testing provides additional insight into an individual's cardiovascular risk. Our approach measures risk across a spectrum, allowing for long-, mid-, and near-term assessment. Our testing is supported by over 100 peer-reviewed articles and we partner with leading academic and medical institutions to bring unique biomarker technologies to market.

College Pharmacy • Booth #1107 3505 Austin Bluffs Parkway, Suite101, Colorado Springs, CO 80918 US Ph: 800-888-9358 • Fax: 888-556-5893 Email: info@collegepharmacy.com • Website: www.collegepharmacy.com Knowledge Changes Everything : Quality. Innovation. Experience. Since 1974. Our compounding process, attention to detail, and quality of the compounding components continues to make our formulations exceptional. Our expertise includes: BHRT (Expanded Pellet Implant Selection), Specialty Injectables, IV Protocols, Chelation, Environmental Medicine, Addiction Medicine, and more. College Pharmacy’s state-of-the-art USP 795 & 797 compliant facility and ISO 8 compounding lab enables us to produce the highest quality sterile formulations

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Exhibitor Listings

Cosmofrance Inc • Booth #909 1444 Biscayne Boulevard, Suite 218, Miami, FL 33132 US Ph: 305-538-0110 • Fax: 305-675-2642 Email: contact@cosmofrance.net • Website: www.cosmofrance.net CosmoFrance inc. - established in 1997 in Miami FL - specializes in the manufacture and distribution of medical devices designed exclusively for non-surgical aesthetic procedures. DermaSculpt blunt-tipped microcannulas are revolutionizing dermal fillers injections. ezPRF is the Ultimate Blood Concentrate system. Other devices include Microneedling and PRF disposable kits.

CRE8 Pharmacy • Booth #421 3700 NW 126 Avenue, Coral Springs, FL 33065 US Ph: 754-529-8353 • Fax: 754-529-8294 Email: communications@cre8pharmacy.com • Website: www.cre8pharmacy.com CRE8 Pharmacy offers compounding services for personalized medicine and patient-specific prescriptions. We are a team, working at creating perfect formulations, dispensing orders reliably and resolving issues promptly. Our line of natural supplements, CRE8 Vitality Nutrition, is designed to support well-being and promote digestive health. Everything a patient needs is shipped in one simple order: - Sterile & non-sterile compounds/ - Nutritional supplementation/ - Generic & Brand medications. Welcome to the future of compounding pharmacy.

PHARMACY

CRYSTAL CLEAR DIGITAL MARKETING • Booth #807 5750 Major Boulevard, Suite 500, Orlando, FL 32819 US Ph: 407-793-9254 • Fax: 407-793-9254 Email: aneff@crystalcleardm.com • Website: www.crystalcleardm.com Crystal Clear is the industry leader in providing world-class software, marketing and consulting solutions for the modern medical aesthetic practice.

Cynosure, A Hologic Company • Booth #1200 5 Carlisle Road, Westford, MA 01886 US Ph: 978-256-4200 • Fax: 978-256-4200 Email: info@cynosure.com • Website: www.cynosure.com Cynosure, A Hologic Company is a leader in medical devices for aesthetic procedures and precise surgical applications. Its non-invasive and minimally invasive technologies enable plastic surgeons, dermatologists and other medical professionals to address skin revitalization, body contouring, fat removal, cellulite, scarring, tattoo removal, gynecologic health and other related applications. Cynosure also markets radiofrequency technologies for facial plastic and general surgery, gynecology, otolaryngology and other specialties. Products are sold under the Cynosure, Palomar, ConBio and Ellman brands.

Cyrex Laboratories • Booth #221 2602 South 24 Street, Phoenix, AZ 85034 US Ph: 657-303-3898 Email: michelle.c@cyrexlabs.com • Website: www.joincyrex.com Cyrex® is a clinical immunology laboratory specializing in functional immunology and autoimmunity. Cyrex offers multi-tissue antibody testing, and assessments of predictive antibodies to a variety of key antigens, for the early detection and monitoring of today’s complex autoimmune conditions. Through continuous collaboration with leading experts in medical research and clinical practice, Cyrex develops innovative arrays that address the cross-connections between the body’s immune, gastrointestinal and neurological systems.

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DaVinci Laboratories of Vermont • Booth #517 929 Harvest Lane, Williston, VT 05495 US Ph: 802-878-5508 • Fax: 802-878-0549 Email: bkanya@foodsciencecorp.com • Website: www.davincilabs.com For over 45 years, DaVinci® Laboratories has been a leader in nutritional research, product development and innovation from our home state of Vermont. Our dedication to higher integrity, and insistence on superior quality are a reflection of Vermont values. We are a family-owned and managed company and are always willing to assist you in any way possible on matters relating to nutrition. Every day, DaVinci® continues to set new standards for quality and product innovation so we can keep you as healthy and informed as possible.

Designs for Health • Booth #607 980 South Street, Suffield, CT 06078 US Ph: 860-623-6314 • Fax: 206-333-0408 Email: info@designsforhealth.com • Website: www.designsforhealth.com Our Company Since 1989, Designs for Health has been the health care professional’s trusted source for research-backed nutritional products of superior quality. By providing comprehensive support through our extensive product line, ongoing clinical education, and practice development programs, we are able to maximize the potential for successful health outcomes. Our wide array of added-value services not only set us apart, but indicate the depth of our commitment to you.

DIEM Labs, LLC • Booth #1019 221 Dino Drive, Suite A, Ann Arbor, MI 48103 US Ph: 1-800-971-3721 Email: jcurrie@diemlabsllc.com • Website: www.diemlabsllc.com DIEM Labs was founded upon the scientific development of novel products and a commitment to excellence in patient education. Our products range from medical foods with metabolic impact (Adiposano for modulation of WAT) to disease state nutritional support (Hepaxa for NAFLD management) and to the restoration of cell membrane function (Cerenx for stroke recovery). We are single source distribution with availability for direct product sales in your office (if desired). www.DIEMlabsllc.com | www.Adiposano. com | www.Cerenx.com | www.Hepaxa-USA.com | www.UmbrelluxDAO.com

Doctor's Data, Inc. • Booth #1214 3755 Illinois Avenue Street, Charles, IL 60174 US Ph: 630-377-8139 • Fax: 630-587-7860 Email: info@doctorsdata.com • Website: www.doctorsdata.com Doctor’s Data, Inc. has provided innovative specialty testing to healthcare practitioners around the world from our advanced, CLIA-licensed clinical laboratory since 1972. A specialist and pioneer in essential and toxic elemental testing, the laboratory provides a wide array of functional testing to aid in decision making and better patient outcomes. Choose DDI to help you assess and treat heavy metal burden, nutritional deficiencies, gastrointestinal function, hormone status, cardiovascular risk, liver and metabolic abnormalities, and more.

Doctor.com • Booth #913 85 5 Avenue, 7 Floor, New York, NY 10003 US Ph: 888-666-8135 • Fax: 212-203-6583 Email: conferences@corp.doctor.com • Website: www.doctor.com Doctor.com is the first platform purpose-built to help healthcare professionals build a thriving online presence and enhance their online reputation. Doctor.com’s industry-leading data management technology and its unique integrations with the most prominent directories and review sites have empowered over 20,000 practitioners to seamlessly enhance their online visibility, grow consumer trust, and ultimately attract more patients.

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Exhibitor Listings

Douglas Laboratories • Booth #207 112 Technology Drive, Pittsburgh, PA 15275 US Ph: 1-800-245-4440 • Fax: 888-245-4440 Email: dlcusservice@atrium-innovations.com • Website: www.douglaslabs.com Douglas Laboratories® researches, develops and manufactures science-based, healthy aging supplements and provides customized practice support. With a 60-year heritage of innovating and designing products to meet the needs of healthcare professionals, we push the potential of both clinical practices and patients to continually perform at their personal best. Douglas Laboratories is GMP and NSF International registered, and is approved to produce NSF Certified for Sport® products.†

Dr. G’s Weight Loss & Wellness • Booth #918 4380 Oakes Road, Suite 807, Davie, FL 33314 US Ph: 305-297-8586 Email: jason@drdsweightloss.com • Website: www.drgsweightloss.com Dr. G's Weight Loss & Wellness provides turnkey weight loss solutions for physicians practices wishing to add a unique and individualized weight loss program for their patients that will not only drive additional revenue but also add a much needed service for their patients.

Dr. Fuji / ACIGI • Booth #1201 4399 Ingot Street, Fremont, CA 94538 US Ph: 510-651-9088 • Fax: 510-651-6188 Email: marketing@drfuji.com • Website: www.fujichair.com Dr. Fuji Cyber-relax medical massage equipment, is the fruit of further evolution of intelligent pneumatic and mechanical milt-technology designed to partner with medical and health professionals in their clinical stress managements.

DR. FUJI

Dunwoody Labs • Booth #520 9 Dunwoody Park, Suite 121, Dunwoody, GA 30338 US Ph: 678-736-6374 • Fax: 770-674-1701 Email: info@dunwoodylabs.com • Website: www.dunwoodylabs.com Dunwoody Labs is an innovator of testing solutions that assist in the diagnosis and management of conditions commonly addressed by integrative medicine. Our unique profiles are designed to help practitioners address comprehensive approaches to patient care. We also offer educational programs to empower practitioners and patients

DUTCH test by Precision Analytical • Booth #312 3138 Northeast Rivergate Street, Suite 301C, McMinnville, OR 97128 US Ph: 503-687-2050 • Fax: 503-687-2052 Email: info@dutchtest.com • Website: www.dutchtest.com Precision Analytical is committed to improving wellness by providing important insight into hormones and their function. Precision's state-of-the-art innovation in testing uses the acronym DUTCH (Dried Urine Test for Comprehensive Hormones). The DUTCH Test™ quickly caught the attention of functional and integrative medicine influencers like Christiane Northrup, MD and Joseph Mercola, MD, and has become the world leader in hormone testing as their method is the most comprehensive informationally and offers the easiest sample collection.

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Erchonia Corporation • Booth #416 650 Atlantis Road, Melbourne, FL 32904 US Ph: 888-242-0571 • Fax: 888-242-0571 Email: Info@erchonia.com • Website: www.erchonia.com Erchonia is the global leader in low level laser healthcare applications. Over the last 16 years Erchonia has researched & developed with the world’s leading physicians to advance the science of lasers. Erchonia lasers are proven through rigorous Level (1) clinical trials to prove their efficacy.

Essential Formulas Incorporated • Booth #118 1861 Valley View Lane, Suite 180, Farmers Branch, TX 75234 US Ph: 972-255-3918 • Fax: 972-255-3918 Email: info@essentialformulas.com • Website: www.essentialformulas.com Essential Formulas Incorporated (EFI) was established in 2000 as the sole U.S. distributor of worldrenowned microbiologist Dr. Iichiroh Ohhira’s award-winning probiotic dietary supplements and skin care products; always an innovator EFI introduced REG’ACTIV® in 2015. These exceptional formulas contain ME-3, a probiotic catalyst that produces the “Master’” Oxidant Glutathione inside the body’s cells. A family-owned and operated business, EFI was founded on the philosophy of providing high-quality preventative, supportive and comprehensive pro-health products for the entire family.

Evoke Neuroscience • Booth #912 11 West 25 Street, 0th Floor, New York, NY 10010 US Ph: 917-261-6096 • Fax: 855-386-5387 Email: sales@evokeneuroscience.com • Website: www.evokeneuroscience.com Evoke Neuroscience was formed in 2009 with the mission to improve diagnosis and treatment of cognitive disorders with objective, clinically meaningful and easy-to-use products. Physicians use the eVox® System to assess brain health and aid in the diagnosis of memory loss and other cognitive disorders.

Fotona • Booth #716 2307 Springlake Road, Farmers Branch, TX 75234 US Ph: 972-598-9000 • Fax: 972-598-9094 Email: info@fotona.com • Website: www.fotona.com Fotona, celebrating over 50 years of laser expertise and leadership, was founded in 1964, just four years after the first laser was invented and has sold over 25,000 lasers around the world with distribution in over 60 countries. Fotona produces award-winning lasers in dentistry, aesthetics, dermatology, gynecology, and surgery. Advanced R&D combined with in-house manufacturing ensures industry-leading levels of quality, reliability, ease-of-use, and durability.

Fullscript • Booth #1018 245 Cooper Street, 6 Floor, Ottawa, ON K2P 0G2 CA Ph: 1-866-807-3828 Email: support@fullscript.com • Website: www.fullscript.com Fullscript is the leading platform for online supplement prescriptions. We provide effortless dispensing and fulfillment for over 20,000 practitioners, and over 450,000 patients across the U.S. and Canada. Fullscript's mission is to take the hassle out of integrative healthcare by making supplementation seamless and easy for practitioners and their patients. We're making strides on this mission with every new practitioner we bring on board.

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Exhibitor Listings

Future Now Detox • Booth #1119 4384 Purdy Lane, Palm Springs, FL 33406 US Ph: 855-933-6732 • Fax: 786-998-0712 Email: andrey@futurenowdetox.com • Website: www.futurenowdetox.com Future Now Detox pioneering NAD IV Brain Restoration Therapy in South Florida on inpatient and outpatient levels 24/7.

GAINSWave • Booth #612 20807 Biscayne Boulevard, Suite 100, Aventura, FL 33180 US Ph: 855-383-5779 • Fax: 844-843-3929 Email: team@joingainswave.com • Website: www.joingainswave.com GAINSWave is a premium brand name for Low-Intensity Extracorporeal Shockwave Therapy (Li-ESWT) used to optimize sexual performance. GAINSWave offers a turnkey business solution for progressive doctors looking to help their patients and increase revenue. GAINSWave has created the only provider network to use standardized protocols based on over 40 clinical studies that support the efficacy and safety of Li-ESWT. GAINSWave gives you a complete “business-in-a-box” solution with standardized medical protocols, medical training, marketing, sales and operational support and much more.

GAINSWave

Genomix Nutrition • Booth #719 13376 North Highway 183, Suite 125, Austin, TX 78750 US Ph: 844-258-5564 • Fax: 866-308-3425 Email: hq@genomixnutrition.com • Website: www.GenomixNutrition.com Genomix Nutrition offers a comprehensive Nutrigenomic Test, created by Kendal Stewart, MD, to validate your patient’s nutritional needs via DNA analysis. Our experts have designed a turn key solution to offer patients DNA testing through saliva swab analysis. Our report evaluates researched and validated single nucleotide polymorphisms (SNPs) that can affect metabolic functionality in: Methylation, Neurotransmitter, Mitochondria, Detoxification, Inflammatory Potential and health precautions. It also assists the practitioner in recommending more targeted nutritional support.

Genova • Booth #307 63 Zillicoa Street, Asheville, NC 28801 US Ph: 800-522-4762 • Fax: 828-252-9303 Email: info@gdx.net • Website: www.gdx.net Genova Diagnostics is a leading clinical laboratory applying systems-based testing approaches to the diagnosis, treatment and prevention of complex chronic disease. Genova specializes in clinical laboratory services with actionable information.

Global Life Rejuvenation • Booth #316 161 East Main Street, Denville, NJ 07834 US Ph: 973-627-1750 • Fax: 973-627-4158 Email: dglaab@globalliferejuvenation.com • Website: www.globalliferejuvenation.com Leader in Anti-Aging Medicine, medical weight loss, practice development and patient edu-cation. Creating a national physicians network. Marketing each location, educating patients and scheduling appointments, connecting doctors to patients and patients to state-of-the-art compounding pharmacies.

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Go Wellness • Booth #919 34 South 500 East, Suite 202, Salt Lake City, UT 84102 US Ph: 801-829-9227 Email: info@gowellness.com • Website: www.gowellness.com Go Wellness is on a mission to make Chronic Pain & Disease optional for 1 million by 2025. We are a passionate group of health practitioners, consultants, coaches and mentors that help healthcare entrepreneurs build their business and reach. We help these entrepreneurs achieve optimal clinical outcomes while improving their bottom line with the right business systems and marketing. We have programs to help clinics integrate systems for Acupuncture, Functional Medicine & Stem Cell Treatments to help more and more patients achieve their health goals.

Great Plains Laboratory, Inc. • Booth #1006 11813 West 77 Street, Lenexa, KS 66214 US Ph: 913-341-8949 • Fax: 913-341-8949 Email: sales@gpl4u.com • Website: www.greatplainslaboratory.com The Great Plains Laboratory, Inc. is a global leader in metabolic, environmental, and genetic testing for chronic illnesses and diseases. We provide easy access to the most reliable, comprehensive, and understandable scientific results, using the latest technology and proven techniques to maintain optimal health at all ages. All tests are designed to measure the contributing metabolic factors which cause symptoms of Alzheimers disease, chronic fatigue, fibromyalgia, migraines, multiple sclerosis, Parkinsons disease, rheumatoid arthritis, and more.

Green Roads Wellness • Booth #1224 5150 Southweast 48 Way, #610, Davie, FL 33314 US Ph: 844-747-3367 Email: info@greenroadswellness.com • Website: www.greenroadswellness.com Green Roads Wellness is a hemp products manufacturer specializing in high potency Cannabidiol (CBD) based formulations. Every product is formulated by our board-certified compound pharmacist, contains no THC, additives, or flavoring, and is sold exclusively through health professionals.

Hawaiian Moon • Booth #1013 321 South Missouri Avenue, Clearwater, FL 33756 US Ph: 727-466-1856 • Fax: 866-618-6480 Email: customerservice@hmaloe.com • Website: www.aloecream.biz Say Goodbye to Dry Skin with Hawaiian Moon Organic Aloe Cream! It is free of dyes, fragrance, parabens, sulfates, mineral oil?, and any other harsh chemicals, including petroleum. Our cream penetrates the skin up to 7 layers deep, and absorbs into the skin instantly.

Healeon Medical • Booth #925 1111 Rancho Conejo Boulevard, #204, Newbury Park, CA 91320 US Ph: 805-499-7482 • Fax: 805-435-1488 Email: sales@healeonmedical.com • Website: www.healeonmedical.com Healeon Medical provides innovative medical devices, clinical expertise and support for autologous pointof-care treatments and regenerative medicine. Healeon Medical’s technologies and techniques surpass the competition by offering simpler, quicker, safer solutions that isolate unparalleled cell counts to meet individual practice and patient needs, from the comfort of the clinician’s treatment room. Healeon is the exclusive distributor for Nouveaux Medical’s Almi branded products which offer the patient an all-natural solution to rejuvenation using their own tissues.

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Exhibitor Listings

HealthSnap, Inc. • Booth #323 1951 Northwest 7 Avenue, Suite 600, Miami, FL 33136 US Ph: 888-780-1872 Email: info@healthsnapsolutions.com • Website: www.healthsnapsolutions.com HealthSnap's platform helps proactive healthcare providers evaluate and interpret their patient's lifestyle health in one central and secure location. From a quick and non-invasive evaluation, healthcare providers can generate personalized lifestyle reports on the spot, with actionable insights powered by the latest research in exercise and nutritional science.

Healthy Fusion • Booth #1222 26711 Northwestern HWY, Suite 550, Southfield, MI 48033 US Ph: 248-204-6304 • Fax: 248-948-9904 Email: laura_snavely@healthyfusion.com • Website: www.healthyfusion.com Healthy Fusion supports the concepts of Functional Medicine. Our site allows providers to pair modern medications with the nutritional or herbal supplements that patients need to keep their bodies balanced and healthy throughout their course of treatment. Our database allows providers to search for a wide range of clinical conditions, medicinal therapies and corresponding lab work to ensure both modern and traditional treatments are improving patient health.

Healthy Habits Medical Business Consultants • Booth #212 26 S Baltic Place, #150, Meridian, ID 83642 US Ph: 877-581-4484 • Fax: 208-884-2067 Email: info@healthyhabitsmc.com • Website: www.healthyhabitsmc.com Tap into the biggest market in the U.S. 236 Million People are Obese/Overweight. With over 30 years of experience, Healthy Habits will teach you how to build a turn-key medical weight loss business to bring in new or help existing hormone patients. Along with our dual-frequency lipo light body contouring machine, our complete business system will dramatically increase your age-management practice. Our program has strong conversion rates to age-management services (Aesthetics, BHRT, IV Therapy, Functional Medicine, etc) and helps maintain a long-term patient base. Up to an 80% increase in patient volume!

Hotze Elite Physicians • Booth #712 20214 Braidwood Drive, #215, Katy, TX 77450 US Ph: 281-698-8698 • Fax: 281-579-2686 Email: WeHelpPhysiciansGrow@HotzeElite.com • Website: www.hotzeelite.com Do you want more time, more money and more freedom to enjoy your life? Hotze Elite Physicians will teach you to heal your patients, naturally and profitably, using Dr. Hotze’s proprietary business and medical protocols, delivered via on-demand virtual training or on-site training. If you’re feeling overworked, unfulfilled, and underpaid then “do a 180” in your practice and join the Wellness Revolution. For more information, visit www.hotzeelite.com or find us on Facebook and LinkedIn.

ICA Health • Booth #906 PO Box 26021, Tucson, AZ 85726 US Ph: 800-522-4762 • Fax: 520-395-9491 Email: ericka@icahealth.com • Website: www.icahealth.com Supplements and protocols designed by Dr. James L. Wilson for healthcare providers who want clinically effective results that address the source, not just symptoms, of stress, adrenal fatigue, blood sugar metabolism, digestive health and immune function.

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Ideal Protein of America • Booth #1220 3135 SR 580, Suite 5, Safety Harbor, FL 34695 US Ph: 866-314-4447 • Fax: 819-772-0416 Email: tradeshows@idealprotein.com • Website: www.idealprotein.com The Ideal Protein Weight Loss Protocol is medically designed and developed and is consistent with evidence-based guidelines, to help obese and overweight patients or clients achieve safe, long-term weight loss and maintain it. The Protocol helps to reverse the imbalance in insulin that occurs with the typical Western diet and that contributes to weight gain and metabolic syndrome. Physicians report that after successful completion of the Ideal Protein Weight Loss Protocol, patients experience significant improvement in metabolic parameters. Individualized, professional health coaching helps patients or clients learn proper nutrition and new eating habits

InBody • Booth #516 13850 Cerritos Corporate Drive, Suite C, Cerritos, CA 90703 US Ph: 323-932-6503 • Fax: 323-952-5009 Email: contact@inbody.com • Website: www.inbody.com Since 1996, InBody has made the most accurate and precise DSM-BIA devices. Used by professionals in the anti-aging, regenerative and functional medicine fields, InBody devices provide a holistic approach to preventing and treating disease. In less than 60 seconds, InBody Tests produce outputs like Visceral Fat Analysis, Percent Body Fat and BMR. These outputs can set more effective treatment plans, predict outcomes and accurately assess your clients' health status. To learn how an InBody can benefit your practice, visit www.InBody.com.

Induction Therapies, makers of Collagen PIN • Booth #623 3600 Chamberlain Lane, Louisville, KY 40241 US Ph: 877-746-4407 • Fax: 877-746-4407 Email: cathy@collagenpin.com • Website: www.inductiontherapies.com Induction Therapies™, makers of COLLAGEN P.I.N., the most advanced and powerful medical-grade, automated, percutaneous induction needling device available, and private label skincare, the result of years of research, expertise, and input from physicians seeking very specific formulations to address skincare concerns, resulting in more than 25 unique products that no other skincare company offers. Skin change is inevitable, but with Induction Therapies, skin change is beautiful.

Innergy Development • Booth #707

DEVELOPMENT

215 S Mountainlands Drive, Orem, UT 84058 US Ph: 385-445-3232 • Fax: 385-445-3232 Email: info@innergydev.com • Website: www.innergydev.com www.aoscan.com For more than 25 years we have developed health products and services that best serve the people. Innergy Development prides itself in manufacturing the best quality, most innovative non-invasive technologies available today. With minds like Albert Einstein, Nikola Tesla and Dr. Royal Rife something amazing was sure to develop and now we’re making it available to you!

International Peptide Society • Booth #119 4737 North Ocean Drive, #132, Fort Lauderdale, FL 33308 US Ph: 855-279-1695 Email: emily@peptidesociety.org • Website: www.peptidesociety.org IPS is a nonprofit organization founded by orthopedic surgeon Dr. William A. Seeds, MD and nationally recognized clinical pharmacist Jim LaValle, R.Ph., MS., CCN in late 2017 to better educate physicians who are new to peptides. The website houses a large repository of literature on peptides that only members can access. For each peptide, the literature includes the molecular formula, suggested dosage, an in-depth description of the peptide, clinical research studies with the full pdf at your fingertips, and much more.

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Exhibitor Listings

InvigoMEDIA • Booth #106 8105 Birch Bay Square Street, # 205, Blaine, WA 98230 US Ph: 604-371-0200 • Fax: 604-371-0200 Email: bob@invigomedia.com • Website: www.bobmangat.com We Walk Into 6, 7 & 8 Figure Clinics, Find and Plug “Leaks” Worth Hundreds of Thousands of Dollars, and Help Doctors Double Triple, or Even 10X Their Revenue Within 12 Months. We eliminate your STRESS of where your next patient is coming from. We Design “NEW PATIENT” Cash + Insurance lead generation campaigns that automatically reach and attract new leads day and night. We automate the process and train your staff on how to CONVERT new patients to raving fans, sell more services to existing ones, get current patients to refer more, cultivate positive reviews and create systems that automates tasks saving you thousands EVERY month.

Isodiol • Booth #801 2215 Auto Park Way, Escondido, CA 92029 US Ph: 855-979-6751 Email: info@isodiol.com • Website: www.isodiol.com Isodiol is the market leader in pharmaceutical grade phytochemical compounds and wellness products. Isodiol is the pioneer of many firsts for the cannabis industry including commercialization of 99%+ pure, bioactive pharmaceutical grade CBD and value added deliveries of the CBD such as micro-encapsulations and nanotechnology.

KBMO Diagnostics • Booth #320 4 Business Way, Hopedale, MA 01747 US Ph: 617-933-8130 • Fax: 267-219-6005 Email: jwhite@kbmodiagnostics.com • Website: www.kbmodiagnostics.com KBMO Diagnostics is a fully integrated medical diagnostics company. The company offers Food Sensitivity Testing that measures sensitivities to up to 132 different foods using the Food Inflammation Test (FIT) Test. The company continues to add new assays to their menu, including a Zonulin Test. KBMO Diagnostics produces easy-to-read and fully individualized color reports for each test. Patients can access reports and meal plans on a mobile phone app.

KYOUI • Booth #618 6787 West Tropicana Avenue, #274, Las Vegas, NV 89103 US Ph: 855-465-9684 • Fax: 855-465-9684 Email: info@kyoui.com • Website: www.kyoui.com Kyoui is a manufacturer of a unique patented device created to control and prevent periodontal disease that affects 75% of Americans leading to several systemic diseases such as stroke, cardiovascular disease, diabetes, etc. Our mission is to raise awareness about oral-systemic health link and our goal is to help people prevent and control periodontal disease for a better overall health.

LeadingResponse • Booth #1114 4805 Independence Parkway, Suite 250, Tampa, FL 33634 US Ph: 800-234-1807 • Fax: 813-889-4536 Email: john.mccloskey@leadingresponse.com • Website: www.leadingresponse.com/elective-medical Leading Response is the leader in direct marketing to Americans aged 50 and older. Elective medical practices can now benefit from our 20+ years experience and more than 500,000 face-to-face events marketed to this group that will attract more patients – ready to make a decision. Response occurs within days, not months of the execution of your LeadingResponse campaign.

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Life Length • Booth #819 3494 Progress Drive, Bensalem, PA 19020 US Ph: +34 917 37 12 98 • Fax: +(34) 91 310 1753 Email: info@lifelength.com • Website: www.lifelength.com Life Length is the world leader in providing telomere diagnostics and telomerase activity measurements for use in clinical and diagnostic medicine. Life Length has developed unique and proprietary technologies. Our robust, sensitive and reproducible tests can be combined with other analyses to provide a comprehensive picture of a patient’s health. Life Length’s TAT®, is the only test that measures critically short telomeres, for people wanting to optimize their health for the longest, healthiest possible lives.

LightStim • Booth #1113 16552 Von Karman Avenue, Irvine, CA 92606 US Ph: 949-502-4088 • Fax: 949-502-4090 Email: info@lightstim.com • Website: www.lightstim.com LightStim, used and recommend by Medical Doctors, Dermatologists, Plastic Surgeons and Skin Care Professionals for over 15 years is committed to changing the face of health and wellness through a holistic approach. LightStim MultiWave® Patented Technology brings proven, consistent and lasting results for the treatment of Anti-Aging, Acne and Pain.

MasterPharm Compounding Pharmacy • Booth #1003 115-06 Liberty Avenue, Richmond Hill NY 11419 US Ph: 866-630-5600 • Fax: 866-630-5700 Email: tmasta@masterpharm.com • Website: www.masterpharm.com MasterPharm is a full service PCAB Accredited compounding pharmacy. We offer the following therapies: ICI injectables, Pellet implantation and Platelet Rich Plasma. MasterPharm’s SOP’s exceeds all Federal USP/NF 797 standards as well as fully complies with all standards of The National Boards of Pharmacy (NABP). All intrathecal solutions are tested for potency, endotoxins, fungal growth and sterility. We operate two high tech ISO 5 clean rooms. We encourage site visits and welcome you to do so.

McGuff Compounding Pharmacy Services, Inc. • Booth #521 2921 West MacArthur Boulevard, Suite 142, Santa Ana, CA 92704 US Ph: 877-444-1133 • Fax: 877-444-1155 Email: pharmacyanswers@mcguff.com • Website: www.mcguffpharmacy.com McGuff Compounding Pharmacy Services provides a level of commitment and value that is unsurpassed. We are independently certified as ISO 9001:2008 compliant and accredited by the Pharmacy Compounding Accreditation Board (PCAB). We compound all dosage forms including sterile injections and deliver to all US states, territories and protectorates. Product quality and patient safety are our number one concern. Stop by the booth to find out more!

Metabolic Code • Booth #030 4850 T Rex Avenue, Suite 125, Boca Raton, FL 33431 US Ph: 561-237-1885 • Fax: 877-234-2879 Email: sales@metaboliccode.com • Website: www.metaboliccode.com The Metabolic Code is a proprietary approach to clinical assessment and treatment planning implemented as a component of all treatment programming where appropriate within medical, and non-medical services. Metabolic Code delivers evidence-based tools, delivered via the web, that support practitioners abilities to assess, interpret, and recommend proven integrative protocols to their patients which dramatically increasing their patients adherence and engagement levels resulting in patient centered care and higher levels of wellness.

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Exhibitor Listings

Metagenics • Booth #501 25 Enterprise, Suite 200, Aliso Viejo, CA 92656 US Ph: 800-692-9400 Email: Info.customerservice@metagenics.com • Website: www.metagenics.com Metagenics was founded on a revolutionary idea: Our genes do not predetermine our health potential, and through nutrition, we can impact how our genes express themselves. Embodied by our company motto?genetic potential through nutrition?this groundbreaking principle drives us to deliver high-quality, science-based nutritional supplements, medical foods, and lifestyle programs to support healthcare practitioners in their efforts to help patients achieve their health and wellness goals.

MethylGenetic Nutrition Analysis™ • Booth #318 15 Pleasure Road, Ephrata, PA 17522 US Ph: 717-466-5700 • Fax: 717-733-1756 Email: yvonnel@dnasupplementation.com • Website: www.dnasupplementation.com People are turning to genetic testing to help find answers to their health and need an experienced practitioner to help them. MethylGenetic Nutrition Analysis™ online software is the tool you need to easily guide you through this seemingly complex process. MGNA™ creates nutritional protocols, based upon one’s unique DNA, lab work, and presenting symptoms, giving you the ability to Assess, Analyze and Design Support™. This will take your practice into the future of care.

Microbiome Labs • Booth #313 101 East Town Place, Suite 210, St. Augustine, FL 32092 US Ph: 904-940-2208 • Fax: 904-940-2209 Email: info@gomegaspore.com • Website: www.microbiomelabs.co Microbiome Labs was originally established as Physicians Exclusive in 2013 as an organization focused on providing probiotic bacteriotherapy. In the past several years our business model has grown and so has public awareness for gut health issues. Microbiome Labs comes to you as an all inclusive resource center designed to address the needs of physicians and health care practitioners. Our goal is to provide integrative solutions and clinical research data to address indications that stem from digestive and immune health issues.

Millennium Medical Technologies • Booth #1008 6352 Corte Del Abeto, Suite A, Carlsbad, CA 92011 US Ph: 949-215-8560 • Fax: 949-215-8564 Email: info@mmt-us.com • Website: www.mmt-us.com Millennium Medical Technologies is an FDA registered manufacturer committed to providing comprehensive solutions and support for harvesting, isolation, and deployment of 361 compliant tissue and cells. We manufacture and distribute devices in liposuction and body shaping, adipose tissue collection, fat grafting, autologous cell isolation and processing as well as provide device development and clinical support services.

Mushroom Science • Booth #418 1025 Conger Street, Suite 6, Eugene, OR 97402 US Ph: 541-344-1396 Email: shannon@mushroomscience.com • Website: www.mushroomscience.com Mushroom Science has been providing high potency mushroom extracts through its practitioner brand JHS Natural Products for the past 2 decades. Mushroom extracts have historically been prepared as a tea/ decoction, also known as a hot water extract. The scientific literature has numerous human clinical trials on the dehydrated tea form, indicating the percent of actives. Mushroom Science ingredients are certified organic, tested for purity, and guarantee levels of active compounds on every bottle.

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MyPracticeConnect • Booth #821 2744 Summerdale Drive, Clearwater, FL 33761 US Ph: 727-754-3696 • Fax: 727-230-1437 Email: info@mypracticeconnect.com • Website: www.mypracticeconnect.com MyPracticeConnect™ is a cloud-based, mobile-friendly platform that acts as an electronic bridge between you and a network of compounding pharmacies. Our technology allows you to prescribe and track wellness meds without changing your EMR, and also comes pre-loaded with Nutrient IV protocols, patient and practice resources, and more. Whether you currently offer or want to start offering wellness solutions, we can help your practice thrive. We also offer hands-on, integrative physician training, including Peptide Therapy.

Novus Optimum Lab, dba: A Best Supplements • Booth #616 840 South Rancho Drive, #4-372, Las Vegas, NV 89016 US Ph: 702-405-7999 • Fax: 702-982-0480 Email: novusoptimum.sales@gmail.com • Website: www.novusoptimum.com NOVUS OPTIMUM LAB NEW PRODUCT : ARTERY CLEANSER™ BRAIN SHARPENER™, IQ-MAXIMIZER™, 4-STRESS™, THE ENERGIZER™, HERBAL HORMONE BALANCE™, 4-ENDOCRINE HEALTH™, APOPTOSIN™, VIRGIN-AGAIN™ - Libido Enhancer, PLEASURE EHNANCER™ - it is not VIAGRA but is ERECTILE ENHANCER™, OPTIMUM MAN™ - Anti-Aging for men & prostate health, PROLONG ECSTASY™ 4-WEIGHTLOSS™, ELASTEEN™, VITAMIN 4-HAIR™, BONE-HEALTH™, PAINLESS™, 4-HEALTHY JOINTS™, HERB- SULIN™ OPTIMUM ALL-INONE™, SLEEP EZZY™, BRAIN SHARPENER 4-KIDS™, 4-ACNE™, AGE-SPOTS CLEANSER™

NuMedica • Booth #722 9503 East 55 Place, Tulsa, OK 74145 US Ph: 800-869-8100 • Fax: 877-270-2005 Email: mail@numedica.com • Website: www.numedica.com NuMedica® is the leading brand of clinical nutrition in the professional market. We partner with healthcare professionals in helping patients achieve better health. Innovation at NuMedica® is founded on our commitment to quality, safety and performance. We rely on an network of innovators, industry opinion leaders, educators and university partners to research, develop and validate unique, breakthrough formulations. NuMedica is an NSF® GMP certified and FDA registered company. Learn more at www. numedica.com or call 800.869.8100.

Nutrafol • Booth #317 28 West 27 Street, 10 Floor, New York, NY 10001 US Ph: 646-362-1684 • Fax: 866-878-0671 Email: sales@nutrafol.com • Website: www.nutrafol.com New research proves that hair loss is not caused by one thing, but by an accumulation of causes including inflammation, stress hormones, DHT hormones, and oxidative stress. Leveraging the latest in biotechnology, Nutrafol's clinically-tested botanical ingredients are standardized to address all of these triggers, to strengthen hair, and to nourish thinning hair from within. Sold by over 700 physicians nationwide, our nutraceutical solution is designed to meet the specific needs for both men and women.

Nutritional Frontiers • Booth #1212

breaking through nutritional boundaries

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3191 Washington Pike Bridgeville, PA 15017 US Ph: 412-922-2566 • Fax: 412-282-4025 Email: info@nutritionalfrontiers.com • Website: www.nutritionalfrontiers.com Nutritional Frontiers brings you a combined 150+ years of experience in the wellness industry. We utilize over 40 researched, trademarked, and patented ingredients to maximize compliance and patient outcomes. We are the implementation experts and you receive solutions and assistance with Samples, Wellness Events, Customized Marketing, Inventory Management, Ordering Solutions, Private Labeling, Custom Formulations, and Special Requests. Our mission is to make the world healthy again, by providing natural solutions and educational programs for healthcare professional and their patients.

ANTI-AGING MEDICAL NEWS

• SPRING 2018

Exhibitor Listings

Okyanos • Booth #422 1497 Main Street, Suite 371. Dunedin, FL 34698 Ph: 281-768-4914 • Fax: 855-404-5012 Email: drpenn@okuanos.com • Website: www.okyanos.com Okyanos Center for Regenerative Medicine is a world-class treatment facility in Freeport, Bahamas providing outstanding clinical care using the latest stem cell applications & technologies for chronic cardiac, neurological, and orthopedic conditions. Using autologous, adipose-derived stem cells with oversight and guidance from leading researchers and clinicians, the Okyanos facility features a state-of-the art surgery center and cardiac cath lab. Built in accordance with the National Stem Cell Ethics Committee regulations, the facility offers integrity, transparency, and collaboration with patients and referring physicians.

OKYANOS

Center for Regenerative Medicine

Omax Heath - Omax3 • Booth #1016 50 West Bridge Street, New Hope, PA 18938 US Ph: 855-978-6615 • Fax: 267-247-5029 Email: lmh@omaxhealth.com • Website: www.omax3pro.com Omax Health is a science based, health and wellness company focused on developing premium quality nutraceuticals for healthcare professionals, including Omax3® Professional Strength Omega-3. Developed by scientists affiliated with Yale University, Omax3® is a pharmaceutical-grade fish oil supplement that is 93.9% concentrated, double molecularly distilled, tested by independent laboratories, and blister packed for freshness. With a patented 4:1 ratio of EPA to DHA, Omax3® has been developed specifically to fight inflammatory cytokines.

ONDAMED • Booth #601 5 Fairlawn Drive, Suite 200, Washingtonville, NY 10992 US Ph: 845-534-0456 • Fax: 845-534-0457 Email: support@ondamed.net • Website: www.ondamed.net The ONDAMED System is a unique treatment solution limitless in its use; wether your focus is chronic disease, injury recovery, performance enhancement, or prevention. A unique biofeedback method allows for detection of hidden stressed or dysfunctional areas on the body, raising the attentiveness to one's physiology, mental and emotional processes. Specialized applicators emit focused, pulsed electromagnetic fields to the discovered areas of hidden stress or dysfunction to attract local immune response and significantly improve metabolism functions.

a better way to make you better

OrthoMolecular Products • Booth #413 1991 Duncan Place, Woodstock, IL 60098 US Ph: 800-332-2351 • Fax: 800-476-4664 Email: contactus@ompimail.com • Website: www.orthomolecularproducts.com Ortho Molecular Products, Inc. has been manufacturing dietary supplements with unsurpassed efficacy for over 25 years. Deeply committed to their long-standing pledge to honor the doctor-patient relationship, Ortho Molecular Products believes evidence-based, lifestyle and nutri-tional therapies will transform the practice of medicine. To that end, Ortho Molecular Products is dedicated to creating innovative clinical models to help healthcare professionals implement lifestyle medicine into their clinical practice.

Oxy Health, LLC • Booth #622 10719 Norwalk Boulevard, Santa Fe Springs, CA 90670 US Ph: 562-906-8888 • Fax: 562-906-8885 Email: information@oxyhealth.com • Website: www.oxyhealth.com OxyHealth is the world’s leading provider of hyperbaric chambers. Presently, OxyHealth is the pioneer of the industry with over 12,000 chambers in use, more than all other providers combined. OxyHealth continues to remain at the forefront of superior performance, quality and cutting-edge design concepts that far exceed industry safety standards.

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Pellecome® LLC • Booth #717 111 Canfield Avenue, Suite A-1, Randolph, NJ 07869 US Ph: 888-773-9969 • Fax: 888-381-3828 Email: info@pellecome.com • Website: www.pellecome.com Pellecome® LLC is a company of scientists and clinicians that was established to provide safer, faster and more convenient delivery of Bio-Identical Hormone Replacement Therapy (BHRT). Pellecome® was created by a physician with a passion for helping his patients to achieve a balanced endocrine environment using measured hormone treatments to support their quest for better health. The passion was fueled by over 20 years of experience in BHRT and a long, established clinical practice.

Physician Compounding Alliance • Booth #419 3225 Templeton Gap Road, Colorado Springs, CO 80907 US Ph: 303-495-5525 • Fax: 303-495-5525 Email: leaj.pca@gmail.com • Website: www.physiciancompoundingalliance.com Add a new monthly income stream to your practice and greater convenience to your patients with PCA’s proven and unique turn key program. Please stop by PCA’s booth to learn how easy it is to add new income and value to your practice

Physicians Lab • Booth #117 4950 Communications Avenue, 250, Boca Raton, FL 33431 US Ph: 1-877-316-8686 • Fax: 877-536-4497 Email: info@physicianslab.com • Website: www.physicianslab.com Physicians Lab is the nation’s leading urinary hormone testing facility, delivering State-of-the-art Science with Superior Solutions. We deliver hormone assessment tools* to enhance your knowledge and leadership in the field of hormone therapy with ease and grow your practice. *Physicians Lab delivers accurate and reliable results, while providing the necessary tools, education and training to offer your patients convenient, affordable, error-free testing. We beat the competition in price and always deliver the fastest urinary hormone results. 1. Logo: “Jewel” + Color + Transparency

PhysioAge Systems • Booth #1115 15% 30% 55% 70% 85% 100%

30 Central Park South, 8A, New York, NY 10019 US Ph: 212-888-7074 • Fax: 212-888-7828 Email: jerry@physioage.com • Website: www.physioage.com How well are your patients aging? PhysioAge Systems is a web-based software platform that provides deeper insights into the status and function of your patients’ most important physiological systems. Our system relies on a unique combination of extensively-tested biomarkers that have been shown to highly correlate with age. Tracking physiological age over time provides a clear and detailed profile of a patient’s individual aging process and helps direct age-management interventions. Visit us in booth 1115!

Power2Practice • Booth #1015 2907 Butterfield Road, Suite 100, Oak Brook, IL 60523 US Ph: 800-590-7459 • Fax: 312-489-5532 Email: info@power2practice.com • Website: www.power2practice.com Power2Practice offers a comprehensive practice performance system, designed specifically for integrative and functional medicine providers, which allows you to more effectively run and optimize the business side of your practice. Our goal is to help you save time, increase staff productivity, boost patient engagement, and provide easy tools and metrics to increase your profits.

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Exhibitor Listings

Predictive Biotech, Inc. • Booth #113 2765 East Parleys Way, Suite 205, Salt Lake City, UT 84109 US Ph: 888-407-9761 • Fax: 801-487-2477 Email: info@predictivebiotech.com • Website: www.predictivebiotech.com Predictive Biotech, Inc., a Salt Lake City, UT life sciences company formed in 2015, is a leader in human cell and tissue products for use in regenerative medicine. A growing national network of clinics, health systems, researchers and physicians leverage Predictive’s four main placental-derived and Wharton’s Jelly umbilical cord-derived products. Predictive Biotech products are regulated by the FDA under 21 CFR part 1271 section 361 as minimally manipulated allografts intended for homologous use.

Prestige Products Direct/ TRIADAER • Booth #924 12440 Southwest 117 Court, Miami, FL 33186 US Ph: 305-234-8081 • Fax: 305-234-8053 Email: triadadirect@gmail.com • Website: www.triadear.com Triad Aer, an air purification system that combines three innovative technologies to reduce particles and microbes to create a healthier environment with minimal energy consumption.

Protocol For Life Balance • Booth #125 244 Knollwood Drive, Bloomingdale, IL 60108 US Ph: 877-776-8610 • Fax: 855-833-9012 Email: sales@protocolforlife.com • Website: www.protocolforlife.com Protocol for Life Balance is a well-researched, potent, and efficacious brand of high-quality dietary supplements and natural products sold exclusively through licensed healthcare practitioners. Protocol for Life Balance offers many unique formulas and products that come with a money -back guarantee if any patient is less than 100% satisfied. Our mission is simply to provide quality products that lead to healthy patients and satisfied physicians.

Quicksilver Scientific • Booth #815 1376 Miners Drive, Suite 103 Lafayette, CO 80301 US Ph: 303-531-0861 Email: support@quicksilverscientific.com • Website: www.quicksilverscientific.com Quicksilver Scientific is an industry leader in blood metals testing and the development and production of superior liposomal delivery systems. Quicksilver Scientific is the only company to offer advanced mercury speciation testing (the Mercury Tri-Test), which comprehensively assesses for the body burden of mercury. Quicksilver Scientific is dedicated to producing superior nutraceutical products tailored at supporting the human detoxification system for the optimization of health.

Quincy Bioscience • Booth #920 726 Heartland Trail, Suite 300, Madison, WI 53717 US Ph: 888-895-6463 • Fax: 608-237-2124 Email: mgaza@quincybioscience.com • Website: www.quincybioscience.com Quincy Bioscience developed Prevagen Professional, a first-in-class brain health support supplement. Only Prevagen contains the ingredient apoaequorin, originally discovered in jellyfish and shown to support mild memory problems associated with aging. In a computer assessed, double-blinded, placebo-controlled study, Prevagen showed the ability to improve aspects of cognitive function in participants with normal to very mild cognitive impairment, as determined by pre-trial screening over a 90 day period.

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Quten Research • Booth #1208 22 Audrey Place, Fairfield, NJ 07004 US Ph: 561 -445-4828 Email: kim.hassett@mkmkting.com • Website: www.qunol.com CoQ10 is a naturally occurring nutrient -like coenzyme that plays an important role in cellular energy production. CoQ10 is also a powerful antioxidant that can help protect cells from damage. Unfortunately, CoQ10 levels can drop due to age, stress and cholesterol-lowering statin drug therapy. Qunol CoQ10’s patented formulation is both water and fat-soluble and provides superior absorption. Supplementing with Qunol can help restore optimal levels of CoQ10 that the body needs to stay healthy.

Refine USA • Booth #721

REFINEUSA AESTHETIC TECHNOLOGIES

340 3 Avenue South, Jacksonville Beach, FL 32250 US Ph: 866-590-5533 • Fax: 888-842-0395 Email: support@refineusa.com • Website: www.refineusa.com Refine USA®, LLC located in Jacksonville, FL has been a market leader in manufacturing and distribution of premier aesthetic technologies for over a decade. We pride ourselves in designing and developing medical devices that meet the clinical and financial needs of aesthetic health care providers. The Rejuvapen® Micro-Pigmentation System, the Purespin PRP® System, and the Ontogeny C skincare line are just a few examples of our "market changing" technologies.

Regenerative Tissue Science, LLC • Booth #220

Regenerative Tissue Science, LLC. NATURAL BIOACTIVE PROTEINS A Subsidiary of ZyCal Bioceuticals Healthcare Company, Inc.

5 Executive Drive, Suite A, Toms River, NJ 08755 US Ph: 888-779-9225 • Fax: 888-373-0594 Email: marketing@zycalbio.com • Website: www.zycalbio.com Regenerative Tissue Science, LLC. (RTS) is a healthcare professional only company, focused on the stem cell and tissue regeneration through natural, bio-active proteins. RTS, is committed to the education and distribution of breakthrough products with proven scientific and clinical data, leading the way in natural, regenerative medicine with its flagship product Ostinol™ Advanced Bone and Cartilage Stimulating Proteins. RTS is a wholly owned subsidiary of ZyCal Bioceuticals Healthcare Company, Inc. the manufactures of Cyplexinol®- Nature’s BMP-Complex.

Researched Nutritionals • Booth #321 PO Box 224, Los Olivos, CA 93441 US Ph: 800-755-3402 • Fax: 805-693-1806 Email: customerservice@researchednutritionals.com • Website: www.researchednutritionals.com Physician-only line of clinically researched formulations: CytoQuel®-clinical research demonstrated statistically significant pain reduction in just 2 weeks; ATP Fuel®-mitochondrial product with published researched showing 31% fatigue reduction and 30% cognitive improvement; Tri-Fortify™– liposomal glutathione with published research demonstrating 28% increase in red blood cell (intracellular) glutathione in just two weeks; Transfer Factor Multi-Immune™ - demonstrating 620% increase in Natural Killer Cell function.

RXQ Compounding, LLC • Booth #720 2364 Blizzard Lane, Albany, OH 45710 US Ph: 866-280-0031 • Fax: 740-994-3887 Email: info@rxqcompounding.com • Website: www.rxqcompounding.com RXQ Compounding, LLC manufactures sterile and non-sterile medications including products that are on the FDA Short List. RXQ must comply with current good manufacturing practice (CGMP) guidelines and US Pharmacopeia Guidelines (USP) and is subject to risk based inspections by the FDA. Our products do not require a patient prescription and can be used for office use. We are required by the FDA to follow strict testing standards for sterility, potency, and endotoxins. Guarantee safety, availability, and compliance by making RXQ Compounding, LLC your FDA 503B Outsourcing Facility.

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Exhibitor Listings

Salveo Diagnostics, Inc. • Booth #921 4355 Innslake Drive, 225, Glen Allen, VA 23060 US Ph: 844-725-8365 • Fax: 844-725-8363 Email: info@salveodiagnostics.com • Website: www.salveodiagnostics.com Salveo Diagnostics is the premier chronic disease-focused laboratory, providing a unique and compelling program to help physicians and patients uncover the root cause of their chronic disease symptoms, enabling disease-specific therapies. Peer reviewed, evidence-based literature is used to develop a lab report with interpretative comments that guide physicians to appropriate therapies. Nutritional and lifestyle support is included to assist physicians in improving outcomes.

Sanesco International Inc. • Booth #124 1010 Merrimon Avenue, Asheville, NC 28804 US Ph: 866-670-5705 • Fax: 828-670-5805 Email: lesmond@sanescohealth.com • Website: www.sanescohealth.com For over a decade, Sanesco has been an industry leader in assessing, monitoring and correcting neurotransmitter and hormone imbalances. We believe in identifying the underlying root causes behind symptoms and conditions affecting HPA-T axis function. We offer licensed healthcare practitioners innovative, evidence-based solutions, including: non-invasive functional laboratory testing, personalized patient-centered reporting, and all-natural nutritional formulas. Our team's clinical expertise, on-staff clinician support, complimentary interpretations, education and hands-on training mean better results for practitioners and their patients.

South Beach Symposium • Booth #027 1801 North Military Trail, Suite 200, Boca Raton, FL 33431 US Ph: 904-309-6204 • Fax: 904-677-7843 Email: ecorrales@southbeachsymposium.org • Website: www.southbeachsymposium.org The South Beach Symposium (SBS) provides comprehensive education on the newest therapies, technologies, procedures and practice guidelines in medical dermatology, cosmetic dermatology and aesthetic medicine. The 2019 SBS will take place on February 7-10 in Miami Beach at the Loews Hotel and will offer 35 hours of CME credit through innovative methods such as live demonstrations of injectable and aesthetic devices. Visit the SBS booth and register for a $300 discount!

Sciton • Booth #1109 925 Commercial Street, Palo Alto, CA 94303 US Ph: 650-493-9155 Email: info@sciton.com • Website: www.sciton.com Sciton is committed to providing best-in-class laser and light solutions for medical professionals who want superior durability, performance and value. Sciton offers high-quality medical devices for laser-assisted lipolysis, fractional and full-coverage skin resurfacing, hair removal, phototherapy, wrinkle reduction, treatment of vascular and pigmented lesions, scar reduction, and acne.

Seca • Booth #1112 13601 Benson Avenue, Chino, CA 91710 US Ph: 800-542-7322 • Fax: 800-542-7322 Email: info.US@seca.com • Website: www.mbca.seca.com seca presents the first and only body composition analyzers designed for medical use and validated to the Four Compartment Model – the gold standard for fat mass calculation. Offering a non-invasive analysis that measures fat and fat-free mass, skeletal muscle mass, visceral adipose tissue, intra and extra-cellular water, all at a clinical level of precision. Enhance your HRT treatment and personalize your weight management and nutrition therapy programs with the seca medical Body Composition Analyzer.

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Select Laboratory Partners • Booth #1206 1100 Revolution Mill Drive, Suite 1, Greensboro, NC 27405 US Ph: 336-510-1120 • Fax: 336-387-8829 Email: bwaddington@slplabs.com • Website: www.slplabs.com With 40+ years of experience in the lab industry, and over 80 managed labs, Select Laboratory Partners has the most comprehensive managed in-practice clinical laboratory solution; offering state-of-the-art instruments, laboratory management software, reagents, supplies, and technical support. SLP is focused on improving lab efficiency and expanding the menu of tests and range of products offered to increase quality patient care. SLP is committed to providing excellence in management services, innovative solutions, and preventative health/wellness programs.

Sovereign Laboratories • Booth #816 2020 Contractors Road, Suite 5, Sedona, AZ 86336 US Ph: 928-202-4031 • Fax: 928-862-4039 Email: prosales@sovereignlaboratories.com • Website: www.colostrumtherapy.com Sovereign Laboratories is dedicated to developing natural products that provide the most efficacious solutions for optimal health, vitality, and aesthetics. Sovereign Laboratories’ signature product Colostrum-LD® is clinically proven to heal the G.I. lining; prevent infection and inflammation of the bowel; and increase bowel surface area for better nutritional absorption. Colostrum-LD® is considered the premier foundational supplement for optimal gut and immune health, and it was designed for successful aging no matter where one is on the spectrum of life.

Spectracell Laboratories • Booth #200 10401 Town Park Drive, Houston, TX 77072 US Ph: 800-227-5227 • Fax: 713-621-3234 Email: spec1@spectracell.com • Website: www.spectracell.com The SpectraCell Solution: SpectraCell Laboratories, the leader in functional nutritional test-ing, now offers comprehensive hormone testing and a cardiometabolic panel which includes a pre-diabetes risk score. Combined with our genetic test menu, SpectraCell offers the most integrative lab diagnostics for personalized medicine.

Standard Process • Booth #914 PO Box 904 Palmyra, WI 53156 US Ph: 800-558-8740 • Fax: 262-495-3069 Email: info@standardprocess.com • Website: www.standardprocess.com Since 1929, Standard Process® has been a visionary leader in whole food nutrient solutions. The company creates quality nutritional supplements based on the whole food philosophy of its founder, Dr. Royal Lee. Palmyra, Wisconsin-based Standard Process also offers Veterinary Formulas™ and is the exclusive U.S. Distributor of MediHerb® herbal supplements.

Stellar Biomolecular Research • Booth #522 An Der Welle 4, Frankfurt Am Main Frankfurt, DE05 60322 DE Ph: +49 69 7593 8412 • Fax: +49 69 7593 8200 Email: info@sbi-europe.com • Website: www.sbi-europe.com Stellar Biomolecular Research is a German scientific research company specializing in the emerging fields of integrative, regenerative and biological medicine. With the rapidly growing interest towards these specialized fields, the company also provides training and consulting services for its clients worldwide. The areas of consulting expertise include the commercialization strategies and management of integrated biological laboratory and biological medicine centers, as well as clinical and technical trainings on integrative, regenerative and biological medicine.

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Exhibitor Listings

Suneva Medical • Booth #1102 5870 Pacific Center Boulevard, San Diego, CA 92121 US Ph: (844-BELLAFILL • Fax: 858-550-9999 Email: info@sunevamedical.com • Website: www.sunevamedical.com Privately?held aesthetics company, Suneva Medical develops, manufactures and commercializes innovative products, including flagship brand, Bellafill®. Available in the U.S., Canada, Hong Kong, Korea and Mexico, Bellafill is the only dermal filler approved by the U.S. FDA for treating nasolabial folds and facial acne scars. For more information, visit www.sunevamedical.com.

TA Sciences® • Booth #401 420 Lexington Avenue, Suite 2900, New York City, NY 10170 US Ph: 888-360-8886 • Fax: 212-588-0058 Email: eric@tasciences.com • Website: www.tasciences.com T.A. Sciences® is the first healthcare company dedicated exclusively to creating research-based, clinically tested wellness products that help address cellular aging through the science of telomerase activation. TA-65® is a patented, all natural, plant-based compound which can help maintain or rebuild telomeres. It is currently available in TA-65MD® Nutritional Supplements, in 250 unit and 100 unit capsules, and TA65® for Skin which provides cosmetic benefits in all layers of the skin.

Tailor Made Compounding • Booth #513 200 Moore Drive, Nicholasville, KY 40515 US Ph: 859-887-0013 • Fax: 859-406-1242 Email: admin@tailormadehealth.com • Website: www.tailormadecompounding.com Tailor Made Compounding pharmacy has established itself as a leading compounding pharmacy specializing in tailor made medications and peptides, providing a high level of patient care to compliment physician’s therapies, and forming a holistic prescriber-pharmacy-patient interface. Located in Nicholasville, Kentucky we are able to provide you with all your compounding needs.

Tesla Wellcare Inc. • Booth #1101

Tesla Wellcare Inc

1530 Red Clover Lane, Hemet, CA 92545 US Ph: 909-539-3701 Email: curtis@teslawellcare.com • Website: www.teslawellcare.com We are a PEMF Treatment Machine Manufacturer With 15 plus years of build experience are brands are sold by our distributors world wide. I hope for your consideration to prove our superior quality and patient results.

THOR Photomedicine, Inc. • Booth #217 5021 Michael's Meadow Drive, Hampstead, MD 21074 US Ph: 877-723-4804 Email: valerie@thorlaser.com • Website: www.novothor.com THOR Photomedicine specializes in developing technologies for delivering PBM Therapy (formerly LLLT). Our hand-held LX2 and NovoTHOR Whole-Body Light Pod have become indispensable tools for over 3,000 customers in pioneering clinics and hospitals across 70 countries. We are the only PBM Therapy company with the appropriate FDA, CE, TGA, Health Canada and NATO clearances/approvals. Our dedication to R&D are what sets THOR Photomedicine apart from all other manufacturers. THORlaser.com | novothor.com

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UberLube • Booth #1106 2611 Hartzell Street, Evanston, IL 60201 US Ph: 888-391- 8082 • Fax: 800-590-6947 Email: info@uberlube.com • Website: www.uberlube.com Uberlube Luxury Lubricant Not harmful to healthy bacteria or pH levels Physician recommended, used in OB-GYN practices Cruelty free with no animal products and vegan friendly No gluten, no glycerin, no parabens, no scents and flavors Latex safe but not recommended for use with silicone Made in USA Uberlube for Sex: transfer sensation while reducing friction Uberlube for Sport: long lasting anti-chafe Uberlube for Style: finish hair with a perfect understated sheen

UNIsource Health • Booth #701 1894 E William Street, Suite 4 # 307, Carson City, NV 89701 US Ph: 805-660-0793 • Fax: 775-881-9300 Email: roberto@unisourcehealth.com • Website: www.unisourcehealth.com UNIsource Health offers the RM-3A Medical Device. It is a five time FDA cleared device which provides an innovative unique fast analytical screening system for risk factors pertaining to diabetes, cardiovascular disease, neuropathy and ANS dysfunction as well as other wellness and longevity markers. The non-invasive RM-3A and ABI devices are designed for in-practice early detection of risk variables offering up-tothe-minute data essential to whole-person analysis.

University Compounding Pharmacy • Booth #301 1875 Third Avenue, San Diego, CA 92101 US Ph: 619-683-2005 • Fax: 619-683-2008 Email: info@ucprx.com • Website: www.ucprx.com University Compounding Pharmacy specializes in the formulation of drugs that are not com-mercially available. Our pharmacists use state of the art technology with quality chemicals so that your finished medication meets the doctor’s exact specifications. We employ the highest standards in compounding, following nationally recognized United States Pharmacopoeia. In addition to the highest quality of compounds, UCP prides itself with providing the best physician and patient experience.

U. S. JACLEAN, INC. • Booth #1012 1816 West 135 Street, Gardena, CA 90249 US Ph: 310-538-2298 • Fax: 310-538-4521 Email: order@usjaclean.com • Website: www.daiwamassage.com Health and Wellness Massage Chair Company

Venus Concept • Booth #1216 255 Consumers Road, Suite 110, Toronto, ON M1J 2R4 CA Ph: 888-907-0115 • Fax: 855-907-0115 Email: events@venusconcept.com • Website: www.venusconcept.com Venus Concept is a global leader in the medical aesthetics device industry. We are present in 60 countries and offer cutting-edge devices that address the most in-demand aesthetic needs. Together with innovative technology, Venus Concept operates with a unique business model that offers the first and only subscription plan.

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Exhibitor Listings

VitaminMed, LLC • Booth #112 300 South Duncan Avenue, Suite 263, Clearwater, FL 33755 US Ph: 800-949-7875 • Fax: 800-259-8220 Email: manager@vitaminmed.com • Website: www.vitaminmed.com Wholesaler and Provider of Direct Shipping to Patients: High Quality Supplements, CBD Skin Care & Oil, and a Complete Weight Loss Program.

Vitelle Labs • Booth #216 120-8365 Ontario Street Vancouver, BC V5X3E8 CA Ph: 1-877-902-2332 • Fax: 604-279-5519 Email: info@VitelleLab.net • Website: www.VitelleLab.com Vitelle Labs is the manufacturing partner behind many of the most recognizable brands in the professional skincare market, their products are sold worldwide in clinical/medical esthetic practices. For over 20 years Vitelle has helped clients create unique, powerful boutique skin care brands that allow them to market proprietary skin and body care to their clientele. Vitelle Labs guides you through product and packaging selection; graphic design/label set up; training and post launch support.

Walkabout Health Products, LLC • Booth #120 343 South Central Avenue, Marshfield, WI 54449 US Ph: 715-305-2526 • Fax: 715-305-2526 Email: info@walkabouthealth.com • Website: www.walkabouthealthproducts.com Emu oil has long been used as healing agent in Australian traditional cultures for the relief of symptoms of sunburn, eczema, pruritis, and urticaria. Contemporary uses of emu oil described in over 75 studies on Pub Med at the National Library of Medicine, document its use in cancer treatment (reducing the severity of colitis-associated colorectal cancer, mucositis from chemotherapy, and arthralgia in breast cancer treatment), in regenerative medicine, and in many other applications. Emu oil healing properties are attributed to its unique composition.

Web to Med • Booth #107 6900 National Parkway, Suite 470, Schaumburg, IL 60173 US Ph: 866-999-8550 • Fax: 847-594-0780 Email: info@webtomed.com • Website: www.webtomed.com WebToMed™ helps healthcare practitioners reach qualified patients, generate more appoint-ments and grow their practices through innovate digital marketing solutions including search engine optimization, patient education, responsive website design, email marketing and social media marketing.

Wellness Pharmacy • Booth #1205 3401 Independence Drive, Suite 231, Birmingham, AL 35209 US Ph: 800-227-2627 • Fax: 800-369-0302 Email: bonnie@wellnesspharmacy.com • Website: www.wellnesspharmacy.com With 50 years of compounding experience, Wellness Pharmacy® is considered the industry leader in quality and customer service. Some of our specialties include chelation, bio-identical hormones, autism support, thyroid preparations, antifungals, pain gels and a large selection of preservative-free injectables. Wellness Pharmacy® is also the only pharmacy to successfully patent the preparation of injectable glutathione, guaranteeing that you are receiving one of the most stable and potent formulas available. PCAB Accredited ™ (800) 227-2627 www.wellnesspharmacy.com

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Wellness Works • Booth #822

9901 South Wilcrest Drive, Houston, TX 77099 US Ph: 800-331-2498 • Fax: 800-331-2498 Email: jpreckshot@wellnessworks.com • Website: www.wellnessworks.com WELLNESS WORKS COMPANY BACKGROUND - The mission of Wellness Works is to develop a profitable nutritional revenue stream in the independent practitioners practice. Wellness Works is not simply a professional quality “vitamin company”. Instead, Wellness Works seeks to create a customized proprietary nutritional brand in the practitioner’s marketplace and beyond. By marrying a professional quality product, with proprietary labeling and marketing and an online presence, practitioners can increase their presence in the world of professional nutritional supplementation.

Wells Pharmacy Network • Booth #412 1210 Southwest 33 Avenue, Ocala, FL 34474 US Ph: 800-622-4510 • Fax: 877-401-5653 Email: info@wellsrx.com • Website: www.wellsrx.com Wells Pharmacy Network is a compounding pharmacy operating as a 503A pharmacy in Florida and a FDA Registered 503B Outsourcing facility in Tennessee. Wells Pharmacy specializes in wellness, anti-aging, weight management, sexual wellness, thyroid/adrenal health and aesthetic dermatology preparations. Our comprehensive formulary encompasses an array of strengths and sizes of medications including Testosterone, hCG, Vitamin Injectables, Peptides and Sermorelin. Preparations come in many dosage forms such as creams, capsules, injectable, troches and sterile implantable pellets.

Women's International Pharmacy • Booth #1213 2 Marsh Court Madison, WI 53718 US Ph: 800-279-5708 • Fax: 800-279-8011 Email: info@womensinternational.com • Website: www.womensinternational.com Women’s International Pharmacy specializes in custom compounded bioidentical hormone prescriptions for men and women. Our pharmacy earned accreditation through the Pharmacy Compounding Accreditation Board (PCAB) by following stringent proficiency and quality assurance standards. Our pharmacists focus on meeting individual needs for licensed medical practitioners and their patients. Whether you are a practitioner or patient you can be assured Women’s International Pharmacy is here for you and we respect your freedom of informed personal choice.

XYMOGEN • Booth #901 6900 Kingspointe Parkway, Orlando, FL 32819 US Ph: 1-800-647-6100 • Fax: 407-445-0204 Email: info@xymogen.com • Website: www.xymogen.com XYMOGEN, a family-owned health sciences company headquartered in Orlando, Fla., has been providing high-quality dietary supplements to licensed healthcare practitioners for more than a quarter century. XYMOGEN's strength as a company has been reinforced for a tenth time, as it was recognized again in 2017 by Inc. magazine as one of the 5000 fastest-growing, best-run, most innovative and most inspiring private companies in America.

Y LIFT • Booth #613 61 East 66 Street, New York, NY 10065 US Ph: 212-861-7787 • Fax: 212-861-7787 Email: info@ylift.com • Website: www.ylift.com The Y LIFT® is a revolutionary non-surgical, minimally invasive facial contouring procedure based on "structural volumizing" yielding beautiful, natural, and instantaneous results. The Y LIFT® restores youthful facial contours by replenishing lost volume in specific anatomic layers and zones utilizing a specialized anatomically correct marking device, resulting in a dramatic rejuvenation of the face and upper neck. Y LIFT was founded and developed by Dr. Yan Trokel, a board certified surgeon specializing in facial aesthetics.

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Exhibitor Listings

ZRT Laboratory • Booth #507 8605 Southwest Creekside Place, Beaverton, OR 97008 US Ph: 866-600-1636 • Fax: 503-466-1636 Email: amslater@zrtlab.com • Website: www.zrtlab.com Since the beginning, ZRT has maintained a singular focus: helping people get and stay healthy. This people-first mindset means that while our results are complex, our tests are not. The education and support we provide helps practitioners understand how to use our results to improve patient health. And while our range of test methodologies and technologies has multiplied over the years, our commitment to end-user simplicity hasn’t wavered. With 20 years of experience and results from over eight million tests, ZRT Laboratory is a recognized leader in innovative, safe, and meaningful hormone and wellness testing.

ZYTO Corp • Booth #823 1172 West 700 North, Suite 300, Lindon, UT 84042 US Ph: 801-224-7199 • Fax: 888-286-3320 Email: sales@zyto.com • Website: www.zyto.com IMPROVING WELLNESS THROUGH BIOCOMMUNICATION ZYTO’s innovative decision support technology takes the guesswork out of choosing nutritional products and wellness options.

“Learning never exhausts the mind” - Leonardo da Vinci

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Tired of Being Tired? Be sure to attend the Genova Diagnostics A4M Workshop Join Dr. Filomena Trindade on April 12th when she presents:

Tired of Being Tired? An Update on the Cortisol Awakening Response (CAR) and Adrenal Dysfunction. This hour-long presentation will cover the following topics:

• • • •

Review of HPA Axis What is CAR and how is it related to HPA Axis? What do I do with an altered CAR? Question & Answer Session

Filomena Trindade, MD, MPH

is an international sought after speaker in functional medicine. She is a graduate of the fellowship in Anti-Aging, Regenerative and Functional Medicine and teaches in the Fellowship (a Master’s program through the University of South Florida) as well as for the Institute of Functional Medicine (IFM).

Where & When: Regency Ballroom 1 Thursday, April 12th (6:15PM)

ASHEVILLE • ATLANTA • LONDON 800.522.4762 • www.gdx.net

2018 Educational Schedule

SEPTEMBER 27-30 Gaylord Opryland Nashville, TN BHRT Symposium September 27-30, 2018 ABAARM/ABAAHP Exams September 27-30, 2018

MAY 4-6 Wynn Las Vegas Las Vegas, NV A4M Workshop - The Complex Patient: What To Do on Monday Morning May 4-6, 2018

OCTOBER 26-27 Sheraton Boston Hotel Boston, MA Workshop - Menâ&#x20AC;&#x2122;s Health October 26-27, 2018

Peptides Modules I/II September 27-30, 2018 Module IV: Gastroenterology September 28-30, 2018 Module VII: Autoimmune Diseases September 28-30, 2018 Module XVI- D/E: Advanced Cardiology September 28-30, 2018

DECEMBER 12-15 Venetian/Palazzo Resort Las Vegas, NV

AUGUST 10-12

World Congress December 13-15, 2018

Venetian/Palazzo Resort Las Vegas, NV

ABAARM/ABAAHP Written Exams December 12, 2018

Modules III: Neurology August 10-12, 2018 Module VIII: Weight, Nutrition & Integrative Cancer Therapies August 10-12, 2018 Pain Management Module August 10-12, 2018 Compounding Workshop (Non-CME) August 10-12, 2018

561.997.0112

www.a4m.com

OCTOBER 19-20 Westin Galleria Dallas Dallas, TX IV/Chelation Workshop October 19-20, 2018 Weight Management Workshop October 19-20, 2018 Pellet Therapy Workshop October 19-20, 2018 Module XV-A: Brain Health October 19-21, 2018

ABAARM Oral Exams December 13-15, 2018 Pre-Conference Workshops December 12, 2018 Peptides Module III/IV December 12-15, 2018 Module I: Endocrinology December 13-15, 2018 Module V: Clinical Intensives (non-CME) December 13-15, 2018 Aesthetics Module III December 13-15, 2018

DECEMBER 13-15

December 12 | Pre-Conference

VENETIAN/PALAZZO RESORT Las Vegas, NV

KEYNOTE PRESENTERS Pamela Wible, MD Physician Advocate

The 26th Annual World Congress, taking place from December 13-15, 2018, draws thousands of exhibitors and clinicians from across the globe, presenting world-renowned keynote presenters and speakers who will highlight the most innovative and cutting-edge practices and protocols in modern integrative healthcare. Attendees will have the opportunity to earn up to 26 CME/CRE credits, including preâ&#x20AC;&#x201C;conference workshops, while taking part in three days of advanced clinical education rooted in the most recent research and studies in modern healthcare.

www.a4m.com

Naveen Jain Philanthropist

WHY SHOULD YOU ATTEND _ Connect with Experts &

Thought Leaders

_ Discover Innovations that Impact Patient Care

_ Network with Peers _ Demo the Latest Technologies

(561) 997-0113