Anti-Aging Medical News | Spring 2019 by Tarsus Medical

Rooted in comprehensive and holistic health, the Fellowship in Anti-Aging, Metabolic and Functional Medicine (FAAMFM) develops forward-thinking practitioners to effectively practice a new form of medicine that is both personalized and preventive. Our fellows are equipped to lead at the forefront of the chronic health crisis with a firm focus on root causes and an extensive array of personalized approaches and strategies. Adaptively designed with you in mind, this fellowship allows practitioners to continue treating patients while gaining the most clinically current education needed to prevent, diagnose, and treat chronic diseases.

Dear Distinguished Colleagues,

! e m o c l e W

Our team is thrilled to welcome you to the 27th Annual Spring Congress. Since our inauguration in 1992, A4M/MMI has been committed to the mission of redefining medicine and we thank you for making this continued journey of exploration, discovery, and innovation possible.

For too long, the practice of traditional, allopathic medicine has championed the study and treatment of sickness over the promotion and maintenance of wellness. As chronic diseases become more prominent, anti-aging medicine has become increasingly important in the modern day healthcare system. With an emphasis on the treatment of root causes and patient-centered care, the field of anti-aging medicine is well-positioned to address many of the systemic issues that plague the traditional system. A4M and its members embody the original—but, today, often forgotten—model of comprehensive, holistic health and wellness. Through our online educational offerings, annual conferences, and strategic partnerships we continue to strive for a paradigm shift within healthcare. Through our programming seek to instigate changes that will enhance the overall quality of life, increase longevity, and reduce rates of chronic disease. This year, we have curated a program that highlights the ways in which practicing clinicians and thought-leaders are changing the field of modern medicine. Through the 27th Spring Congress, we will sustain our commitment to pushing boundaries: highlighting entrepreneurial opportunities in integrative medicine, inviting the useful applications of technology in healthcare, addressing the critical trend of physician burnout and its impact on mental health, and studying the most cutting-edge clinical breakthroughs in longevity. As one of the largest events in anti-aging medicine, this year’s Spring Congress is an invitation to all healthcare professions to join us in defining the future of healthcare. As we, together, embark on the path to new breakthroughs, we thank you for both your time and engagement and wish you a fruitful stay in Orlando.

Cordially,

A4M Management Team

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MEDICAL NEWS SPRING 2019 Issue

TABLE OF CONTENTS General Information . . . . 6

Exhibitor Index . . . . . . 94

Product Announcements .

Exhibitor Listings . . . . . 97

ARTICLES

Exhibit Hall Floormap . . . 93

Fasting: An Emerging Method For Weight Management By: Victoria Hahn, MS, RDN

Topical Delivery of Sex Steroid Hormones and Distribution in Different Body Fluids By: David T. Zava, PhD

DIM from Cruciferous Vegetables for Men’s Health By: Whitney Crouch, RDN, CLT

The Science Behind Vitamin E Tocotrienols By: Barrie Tan, PhD

What to Look for in a Regenerative Medicine Manufacturer By: Monica Vazquez, PhD; Jessica Sanchez, BS; Cheyenne Ziegler, BS; Erin Sairafe, MS; Ernesto Gutierrez, MD

The Human Microbiome-Genome Connection in Aging By: Aicacia Young, RDN

Mitochondria: More Than Just The Powerhouses of The Cell By: Kai Man Yuen, MSc

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14 20

30 38 50 73 85 5

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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A4M | MMI Planning Committee

Pamela W. Smith

Andrew Heyman

MD, MPH, MS

MD, MHSA, ABFM, ABIHM

Mark C. Houston MD, MS, MSc, FAARM, ABAARM

James LaValle RPh. CCN, MT, ND(trad)

Mark Rosenberg MD, FAARM, ABAARM

A4M Founders Ronald Klatz MD, DO Co-Founder

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Robert Goldman MD, PhD, DO, FAASP Co-Founder

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*The actual Rolex on display may differ from photograph.

DRAWING Saturday May 18th 4:00 PM EXHIBIT HALL

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FUNCTIONAL TESTING EXPERTS

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Rules Of Draw

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n You a h T ROLEX GIVEAWAY SPONSORS! Booth #635

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Your entry form can be found in your attendee bag.

Open To Registered Conference Delegates Only 1] The giveaway is not open to any exhibitors and their staff, suppliers or supplier affiliates to the 27th 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.

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PROFESSIONAL MEDICAL EDUCATION (Non-CME)

Thursday, May 16th - 6:15pm Make More. Work Less. Gain Support.

Sponsored by:

Presented by:

Jennifer Landa, MD—Chief Medical Officer of BodyLogicMD, Medical Director of BodyLogicMD of Orlando

Location:

Sun Ballroom C

Beyond Detox: Integrating Autophagy into Detoxification Protocols Presented by:

Christopher Shade, PhD

Location:

Sun Ballroom A

Fasting Mimicking Diet: A Timely Solution to Today’s Diet Conundrum Presented by:

James LaValle, RPh, CCN, ND(trad)

Location:

Sun Ballroom B

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Friday, May 17th - 6:15pm Clinical Application of the Methylation Pathway The Effects of 1-Carbon Metabolism on Chronic Disease Presented by:

Michael Chapman, ND

Location:

Sun Ballroom C

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The Untold Truths of the Stem Cell Industry Presented by:

Rafael Gonzalez Ph.D, Alan Gaveck, MD & Joe Case, President of Sales

Location:

Sun Ballroom B

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Panel Discussion with Industry Experts on Peptide Therapy

Panel Moderator: Jim Meehan, M.D.; James LaValle, R.Ph., CCN, ND(trad); Christopher Asandra, M.D.; Cecilia Lacayo, M.D. ; Frederick Brown, M.D. Location:

Sun Ballroom A

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Sponsored by:

PRODUCT THEATER in the Exhibit Hall

(Non-CME)

Friday, May 17th 12:00 PM

How to Attract Large Fee For Service Regenerative Medical Cases Through Public Seminars Presented by:

12:30 PM

5:30 PM

BETTER PROSPECTS. BETTER RESULTS.

Fact or Fiction: Results of Head-to-Head CBD Product and Serum Bioabsorption Study Presented by:

4:30 PM

John McCloskey

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Clifford Morris, PhD and Stacy Hinz, M.S.

Maintaining Resilience To Stress By Supporting Mitochondrial Health With NAD+ Presented by:

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Dr. Charles Brenner, Roy J. Carver, Chair and Head of Biochemistry; University of Iowa and discoverer of NR as a vitamin Sponsored by:

5 Celebrity Storytelling Secrets to Increase Your Impact, Influence, & Income Panel Moderator: Clint Arthur

Saturday, May 18th 12:00 PM

12:30 PM

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Regeneration Medicine Using Human Placenta Extract Injection Presented by:

Dr. Kim Dong Hwan (Specialist of Neuro Surgery/ Physician)

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Quantifying Endothelial Damage to Identify the Vulnerable Patient Presented by:

Dr. Douglas Harrington

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RECEPTIONS 12

COCKTAIL RECEPTION FRIDAY May 17th 4:00 pm - 6:00 pm Exhibit Hall

HAPPY HOUR SATURDAY May 18th 3:00 pm - 4:30 pm Exhibit Hall

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

ABAAHP - 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.

Fasting:

An Emerging Method For Weight Management By: Victoria Hahn, MS, RDN Bio: Victoria is a Registered Dietitian and Nutrition Science Liaison with a Master of Science in Nutrition, Healthspan, and Longevity from the University of Southern California. She also functions as an inpatient clinical dietitian and has a background in nutrition research covering a wide range of topics including nutritional sufficiency in specific populations and the ketogenic diet. She has a passion for research and evidence-based practice.

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.

ABSTRACT: Fasting has been shown to be a topic of growing

interest not only within the scientific field, but also with consumers. As this science becomes commercialized, we must sort out the evidence from the fiction to support the claims that surround fasting as a strategy for weight loss. Fasting can be broken up into three types: time restricted eating (TRE), intermittent fasting (IF), and prolonged or periodic fasting (PF). Each type of fasting appears to impact weight loss, but evidence suggests that PF is the optimal method for this. Ultimately, more evidence is needed to support fasting as a medical intervention with validated protocols to ensure that the fasts are done in a safe manner.

Introduction

1), and protein kinase A (PKA). It has been established that key regulators of these nutrient sensing pathways include glucose, amino acids, and the energy status within the cell.6 There are several distinct methods of fasting, including time restricted eating (TRE), intermittent fasting (IF), and prolonged or periodic fasting (PF) (See Table 1). These categories are separated by a difference in duration of fasting, as well as the physiological impact of each type. Due to these differences, it has been hypothesized that there is an optimal amount of time during which the body needs to be in the fasting mode in order to induce a more pronounced physiological impact.3,8 This brief review of fasting will try to tease out the rationale to support each type of

fast in the clinical setting as it pertains to weight loss. Fasting is an ancient practice that has its roots in religious practices, 1 and appears to be present universally among all cultures. The definition of fasting is “to abstain from food.”2 It has been cited Time Restricted Eating that fasting is now being used as a medical intervention in many Time restricted eating (TRE) gains its roots from circadian clinics for disease prevention and weight management.3,4 More so, rhythms; these are daily cycles of ~24 h that control a multitude of there has been a rise in the interest of fasting over the last few physiological and behavioral processes including, but not limited years and increase in consumer interest that has followed.5 With to, energy metabolism, gastrointestinal motility, and sleep-wake all this new information, it can be difficult for the clinician to cycles.9 TRE has been defined as a daily eating pattern that is find evidence-based information on this emerging topic, especially conducted over the span of usually ≤12h in which all nutrition given the inherent risk of over-fasting, or inducing starvation. is consumed within this timeframe; there is no regard to the One of the main benefits of fasting rests in the natural ability of Table 1: Types of Fasting the body to downregulate Type of Fast Definition Example the nutrient-sensing A daily pattern of eating, usually pathways (6) which can in 8-h Diet (8 hours of eating, conducted between 10-12h. The turn stimulate a protective Time Restricted Eating with the remaining 16h of rest of the day would be non-eating the day fasting) response that results in hours, or fasting. 3,6-8 stress resistance. Perhaps 5:2 Diet (5 days of normal A pattern of eating little to no nutrition intake with 2 days the most well-categorized Intermittent Fasting calorie intake conducted 2 to 3 of no calorie or low calorie nutrient sensing pathways times per week. intake per week) are the mechanistic target of A pattern of eating little to no calorie Periodic or rapamycin (mTOR), insulinintake conducted for 4 or more 5 day fasting mimicking diet Prolonged Fasting like growth factor 1 (IGFconsecutive days.

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Fasting: An Emerging Method For Weight Management composition of nutrition, rather, the focus is when food is consumed.10 The mechanism by which the circadian rhythm is regulated is complex.10-12 Briefly, the circadian rhythm is sustained by an organ specific process that is cell-autonomous, albeit the master oscillator is the suprachiasmatic nucleus (SCN) feedback loop in which specific transcription activators help to increase the production of the CRY and PER protein levels.10,12 The reason this is important is because both of these proteins, CRY and PER, interact with the nutrient sensing pathways, including TOR and AKT, as well as other pathways that are upregulated during fasting, such as AMPK and SIRT1.13-17 There is now evidence to support the postulation that TRE within a period of 8-12h without nutrient fluctuation may be utilized to help re-establish these diurnal patterns and potentially serve as a novel therapy for treating obesity as well as metabolic diseases.18-20 Human data are sparse in this emerging field. In a 16-week feasibility trial, eight overweight individuals were instructed to consume their entire daily caloric intake over the span of a self-selected 10-12h period to determine if this would lead to a reduction in body weight.21 They found that all subjects were not only able to reduce their eating duration, but also lost weight (average of 3.27 kg). Although the reduction in eating time also induced a decrease in estimated caloric intake, which may have contributed to the weight loss observed, there is new evidence to show that the benefits of TRE may be independent of weight loss in a specific population.22 It is also worth noting that different physiologies may require a different period of TRE, as seen with the obese population potentially benefitting from an 8h TRE period for weight loss.23 Although TRE has proven to be beneficial in a multitude of areas, more research is needed within this area to determine TRE’s overall effectiveness as a weight loss strategy.

Intermittent Fasting

Intermittent fasting (IF) goes by many definitions in the literature, but will be defined as very little (~25% energy restriction) to no calorie intake conducted 2-3 times per week; the majority of studies discussed in this section represent the 2-day non-contiguous restriction and 5-day feasting model. With IF, the upregulation of autophagy, stress resistance, and antioxidant activity, as well as extension of lifespan while decreasing cellular proliferation, have all been observed.3,24 Note that because of the reduction in the duration of fasting with IF, the fasting effects are less pronounced when compared to a PF.3 Somewhat surprisingly, it has also been found that IF may not impact lifespan at all, so more evidence with a standardized process is needed to support or refute these findings.25 IF has become more prevalent over the years as an alternative to caloric restriction; however, clinical trial results have been inconclusive and occasionally contradictory to popular belief.26-28 In a 1-year trial, 112 subjects who had a BMI between 30-45 kg/m2 followed a meal pattern where they were to restrict calories to 400/600 kcal (female/male)

for two non-consecutive days per week.29 After 1 year, the IF group had similar weight loss (8.0 kg in the IF group versus 9.0 kg, p = 0.6) and improvements in their cardiovascular risk factors in comparison to the continuous calorie restricted group. In a separate study, 107 premenopausal women with a BMI between 24-40 kg/m2 followed 2 days of 25% kcal restriction and 5 days of normal intake each week over 6 months.30 After 6 months, the women in the IF group had comparable weight loss, which was on average 6.4 kg in the IF group compared to 5.6 kg (p= 0.4). Comparable body fat reduction and cardiovascular risk marker reduction were also observed between the groups, but greater declines in fasting serum insulin and improvements in insulin sensitivity in comparison to the continuous calorie restricted group. There is evidence to show that the weight loss observed in these studies may be contingent on the spontaneous reduction of caloric intake on non-IF days, so it may be an overall behavior change that is enabling the potential weight loss to occur rather than the effects of fasting.31

Periodic Fasting

Periodic fasting (PF) can be described as an extension in duration and sequence of IF in that it is greater than 2-3 days, as well as consecutive days. PF can be categorized as consecutive days of fasting for 4 or more days. The mechanism of PF is a prolongation of IF because the fast is conducted for a longer period of time, enabling a more pronounced metabolic switch to occur which in turn causes glycogen reserve depletion to enable fat and ketone body catabolism.3 With this longer period of time (72h) in the fasting mode, it has been observed to promote a greater upregulation in the stress response gene HO-1 and antioxidant enzymes SOD2, Gpx1, and GSR.32,33 Moreover, there is evidence to show that a 72h fast in mice decreases key regulators of the nutrient sensing pathways, such as IGF-1 and glucose.34 As eluded to, there appears to be an ideal duration of time to be spent in the fasting mode in order to achieve the benefits of autophagy and multi-system regeneration.35 Due to the difficulty of PF and inherent risk of adverse events, a novel modality that mimics fasting with a diet has been elucidated.35 The diet is a five-day regimen low protein, moderately low carbohydrate, and moderately high fat diet that is also moderately restricted in calories. This diet that mimics PF was found to decrease IGF-1, reduce visceral fat mass, extend median lifespan, promote neurogenesis, enable hepatic regeneration, and increase hematopoietic and mesenchymal stem and progenitor cells in mice.35 Within this same article, a pilot clinical trial of 19 healthy individuals utilizing this 5-day PF mimicking diet found that after three consecutive cycles done once a month, participants lost an average of 3% of body weight and had no lean body mass loss. Additionally, anti-inflammatory effects, such as C-reactive protein reduction, were observed. The pilot trial was replicated in a larger clinical trial with 71 additional healthy individuals who experienced a reduction in body weight (2.6 kg on average), total body fat, trunk fat, waist circumference, IGF-1, and blood

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Fasting: An Emerging Method For Weight Management pressure without any lean body mass loss.36 Moreover, the effects on body weight, waist circumference, IGF-1, and blood pressure appeared

opinion in neurobiology. 2013;23(5):724-731. doi:10.1016/j.conb.2013.02.018. 13. Zheng X, Sehgal A. AKT and TOR Signaling Set the Pace of the Circadian Pacemaker. Current biology : CB. 2010;20(13):1203-1208. doi:10.1016/j.cub.2010.05.027.

to persist even 3.2 months after having discontinued the protocol.

14. Lamia KA, Sachdeva UM, DiTacchio L, et al. AMPK Regulates the Circadian Clock

Conclusion - Where do we go next?

15. Asher G, Gatfield D, Stratmann M, et al. SIRT1 regulates circadian clock gene

an emerging medical therapy. Novel interventions in order to induce

16. Nakahata Y, Kaluzova M, Grimaldi B, et al. The NAD+-Dependent Deacetylase SIRT1

that enable the body to fast, but for a brief period of time. Although

17. Nakahata Y, Sahar S, Astarita G, et al. Circadian control of the NAD+ salvage pathway by

For instance, while all types of fasting appear to yield some amount of

18. Chaix A, Zarrinpar A, Miu P, Panda S. Time-restricted feeding is a preventative and

overall decreased caloric intake, and the weight loss attributed to IF

19. Hatori M, Vollmers C, Zarrinpar A, et al. Time restricted feeding without reducing

PF appears to induce a significant amount of weight loss due to the

20. Melkani GC, Panda S. Time�restricted feeding for prevention and treatment of

may be the root etiology of the effectiveness of the weight lost. We are

21. Gill S, Panda S. A smartphone app reveals erratic diurnal eating patterns in humans that

PF regimens or regimens that mimic PF, may be the most advantageous

22. Sutton EF, Beyl R, Early KS, et al. Early Time-Restricted Feeding Improves Insulin

by Cryptochrome Phosphorylation and Degradation. Science (New York, NY). 2009;326(5951):437-440. doi:10.1126/science.1172156.

Fasting is a wide-ranging topic that spans from a religious practice to fasting have also been elucidated, as well as a variety of eating patterns each type of fasting may yield unique findings, there are similarities. weight loss, it appears the weight loss for TRE may be attributable to

may be comparable to continuous caloric restriction. On the other hand, sustained physiological changes of fasting for consecutive days, which now starting to obtain evidence that certain types of fasting, particularly

expression through PER2 deacetylation. Cell. 2008 Jul 25;134(2):317-28. doi: 10.1016/j. cell.2008.06.050. Modulates CLOCK-Mediated Chromatin Remodeling and Circadian Control. Cell. 2008;134(2):329-340. doi:10.1016/j.cell.2008.07.002. CLOCK-SIRT1. Science. 2009 May 1;324(5927):654-7. doi: 10.1126/science.1170803. Epub 2009 Mar 12. therapeutic intervention against diverse nutritional challenges. Cell metabolism. 2014;20(6):991-1005. doi:10.1016/j.cmet.2014.11.001. caloric intake prevents metabolic diseases in mice fed a high fat diet. Cell metabolism. 2012;15(6):848-860. doi:10.1016/j.cmet.2012.04.019. cardiometabolic disorders. The Journal of Physiology. 2017;595(12):3691-3700. doi:10.1113/JP273094. can be modulated for health benefits. Cell metabolism. 2015;22(5):789-798. doi:10.1016/j. cmet.2015.09.005.

for not only weight loss, but also for receiving the most benefits of

Sensitivity, Blood Pressure, and Oxidative Stress Even without Weight Loss in Men with

in clinic for any indication other than maintaining general wellness, it

23. Gabel K, Hoddy KK, Haggerty N, et al. Effects of 8-hour time restricted feeding on body

patients through their fasting regimens, no matter the type initiated.

24. Harvie MN, Howell T. Could Intermittent Energy Restriction and Intermittent Fasting Reduce

to further support or refute PF as an ideal strategy, as well as if there are

25. Goodrick CL, Ingram DK, Reynolds MA, Freeman JR, Cider N. Effects of intermittent

any type of fast. However, if any of these therapies are to be initiated

would be of the utmost importance for trained clinicians to guide their While early indications are encouraging, more evidence will be needed ideal ways to implement IF and TRE for weight loss.

Prediabetes. Cell Metab. 2018 Jun 5;27(6):1212-1221.e3. doi: 10.1016/j.cmet.2018.04.010. Epub 2018 May 10. weight and metabolic disease risk factors in obese adults: A pilot study. Nutrition and Healthy Aging. 2018;4(4):345-353. doi:10.3233/NHA-170036. Rates of Cancer in Obese, Overweight, and Normal-Weight Subjects? A Summary of Evidence. Advances in Nutrition. 2016;7(4):690-705. doi:10.3945/an.115.011767. feeding upon body weight and lifespan in inbred mice: interaction of genotype and age. Mech Ageing Dev. 1990 Jul;55(1):69-87. 26. Anton S, Leeuwenburgh C. Fasting or caloric restriction for Healthy Aging. Experimental gerontology. 2013;48(10):1003-1005. doi:10.1016/j.exger.2013.04.011.

Disclosures:

27. Collier R. Intermittent fasting: the science of going without. CMAJ : Canadian Medical

The author is affiliated with L-Nutra, Inc.

28. Anton SD, Moehl K, Donahoo WT, et al. Flipping the Metabolic Switch: Understanding

Association Journal. 2013;185(9):E363-E364. doi:10.1503/cmaj.109-4451. and Applying Health Benefits of Fasting. Obesity (Silver Spring, Md). 2018;26(2):254-268.

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2010;10:161-177. doi:10.1100/tsw.2010.8. 35. Brandhorst S, Choi IY, Wei M, et al. A periodic diet that mimics fasting promotes multi-

10. Longo VD, Panda S. Fasting, circadian rhythms, and time restricted feeding in healthy lifespan. Cell metabolism. 2016;23(6):1048-1059. doi:10.1016/j.cmet.2016.06.001. 11. Reddy AB, O’Neill JS. Healthy clocks, healthy body, healthy mind. Trends in Cell Biology. 2010;20(1):36-44. doi:10.1016/j.tcb.2009.10.005.

system regeneration, enhanced cognitive performance and healthspan. Cell metabolism. 2015;22(1):86-99. doi:10.1016/j.cmet.2015.05.012. 36. Wei M, Brandhorst S, Shelehchi M, et al. Fasting-mimicking diet and markers/risk factors for aging, diabetes, cancer, and cardiovascular disease. Sci Transl Med. 2017 Feb 15;9(377).

12. Hardin PE, Panda S. Circadian timekeeping and output mechanisms in animals. Current

29. Sundfør TM, Svendsen M, Tonstad S. Effect of intermittent versus continuous energy

pii: eaai8700. doi: 10.1126/scitranslmed.aai8700.

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Topical Delivery of Sex Steroid Hormones and Distribution in Different Body Fluids By: David T. Zava, PhD

Delivery of the bioidentical sex-steroid hormones estradiol (E2), progesterone (Pg), and testosterone (T) through the skin as a cream or gel (percutaneous or more commonly referred to as topical) has become a mainstay of bioidentical hormone replacement therapy (BHRT) for women and men. A plethora of FDA-approved pharmaceuticals, compounded, and even over-the-counter topical BHRT products are available. The popularity of these products lies not only in their ease of use, but in proven clinical efficacy (Basdevant, 1980; Egras AM, 2010; Prestwood KM, 2003; Leonetti HB, 2003; Bhasin S, 2010) in treating hormonal deficiencies mostly brought on by aging of the female (menopause) and male (andropause) reproductive systems. Over the past 30 or so years, higher FDA-approved topical BHRT dosing has dominated allopathic acceptance. However, these concepts are beginning to erode as more practitioners open their thinking to alternative views of much lower dosing as being optimal, based on clinical observations coupled with scientific discovery. It also is becoming more evident that while serum and urine testing work fine for detecting endogenously produced hormones, or hormones supplemented by nearly all other forms of delivery (e.g. transdermal patch, oral, vaginal, troche/sublingual, sc-injections and pellets) these body fluids grossly underestimate sex hormone delivery to capillary beds and, hence, tissues, relative to topical hormone delivery (Zava DT, 2014). Attempts to achieve physiological levels of E2, Pg, and T in serum with topical BHRT has met with little success, resulting in use of pharmacological dosing to raise serum levels to physiological ranges (Du JY, 2013, Zava DT, 2014). Despite the clear clinical efficacy of topical HRT with natural estrogens (mostly E2 and estriol-E3) and Pg in women and T in men, controversy still encircles the dose of hormone needed to achieve optimal clinical benefit. This controversy has arisen out of attempts to explain why topical BHRT results in very little increase in venipuncture serum or urine levels of the hormone delivered through the skin (Du JY, 2013; Zava DT, 2014; Oâ&#x20AC;&#x2122;Leary P, 2000) despite use of topical hormone doses that usually are more than 10 times higher than daily endogenous production of these hormones in women and men (see Table 1).

Expected Synthesis of Estradiol Progesterone (Pg) in Justification for the higher dosing(E2) of and both FDA-approved Table 1 Women and Testosterone (T) in Men vs. Median Serum Levels pharmaceutical and compounded products comes from

pharmacokinetic studies showing that pharmacological dosing is necessary to increase serum and urine levels of the dosed hormones to physiological levels. But, in fact, even with supra-high pharmacological BHRT dosing serum and urine levels of some of the sex-hormones rarely increase to even within low physiological ranges. This is most notable for Pg (Du JY, 2013, Zava DT, 2014; Burry KA, 1999), and less so for E2 and T (Basin S, 2010) which only increase to physiological levels in serum/plasma and urine with pharmacological dosing. Daily ovarian production of E2 during peak of the luteal phase of the menstrual cycle is about 100-300 ug (Williams, 2003). With this physiological ovarian production of E2 in serum and capillary blood, levels of E2 are quantitatively equivalent at about 80-200 pg/ml; saliva ranges from about 1.5-4 pg/ml (approximately 2% of serum/plasma levels), and urine levels range from about 0.8-2.0 ug/g Cr (see Tables 2-4). For postmenopausal women to achieve physiological ranges seen in mid-luteal phase of premenopausal women, topical E2 therapy only requires physiological dosing to achieve physiological levels in saliva and capillary whole blood (i.e. about 100-300 ug E2), but at least 10x higher dosing (1000-3000 ug = 1-3 mg) to achieve physiological levels in venipuncture serum/plasma and urine (Table 2). A similar distribution of Pg is seen during peak of the luteal phase of the menstrual cycle where daily Pg production by the ovaries is about 10-40 mg, and the Pg in serum and capillary blood are quantitatively equivalent at about 10-30 ng/ml, saliva about 100-300 pg/ml (approximately 1% of serum/

ANTI - AGING MEDICAL NEWS

â&#x20AC;˘ SPRING 2019

Topical Delivery of Sex Steroid Hormones and Distribution in Different Body Fluids

Table 2

Saliva, DBS, Serum, Urine with Topical Estradiol (E2)

plasma levels), and urine pregnanediol, a surrogate for Pg, about 500-2000 ug/g Cr (Table 3). To achieve premenopausal luteal physiological ranges in postmenopausal women with topical Pg therapy only requires physiological dosing when measuring saliva and capillary whole blood (i.e. about 10-50 mg topical Pg)(Du JY, 2013, Zava DT, 2014), but at least 10x higher dosing (100-300 mg topical progesterone) when measuring venipuncture serum/plasma. Urine pregnanediol increases very little with increasing doses of Pg (Oâ&#x20AC;&#x2122;Leary P, 2000).

Table 3

Saliva, DBS, Serum, Urine Progesterone (Pg) with Topical Progesterone Therapy

In men, topical T distributes into the same body fluids similar to topical E2 and Pg in women. In healthy young males, the testes produce about 5-7 mg of testosterone daily and the morning and testosterone levels range from about 500-1200 ng/dL in serum/plasma and capillary blood, 100250 pg/ml in saliva, and 1-4 ug/g Cr in urine (Table 4). To achieve physiological ranges of a healthy young male in the body fluids of hypogonadal men with topical T therapy only requires physiological dosing for saliva and capillary whole blood (i.e. about 5-10 mg topical T), but at least 10x higher dosing (50-200 mg topical T) for venipuncture serum/plasma or urine levels.

Table 4

Saliva, DBS, Serum, and Urine Testosterone (T) with Topical Testosterone Therapy

The lack of increase in serum and urine levels of topically delivered hormones at physiological dosing (i.e. 50-200 ug E2 and 10-30 mg Pg in women and 5-10 mg T in men)(Tables 2-4), has resulted in justification of dose escalation of FDAapproved and compounded products to amounts that are 10 to 20-fold higher (i.e. 500-5000 ug E2 and 100-300 mg Pg in women and 50-200 mg T in men) than levels of these hormones that are produced by the gonads of healthy young women and men over a 24 hr period (Table 1). Justification for these 10x pharmacological topical doses is based more on serum and urine levels than clinical response. Only a handful of studies have evaluated the clinical efficacy of lower physiological topical hormone dosing relative to the more allopathic acceptance of pharmacological dosing. However, some studies have clearly shown that more physiological dosing with topical E2 and progesterone are clinically effective for increasing bone mass (Prestwood KM, 2003) and protecting the breasts (Chang KJ, 1995) and endometrium (Leonetti HB, 2003) at physiological dosing of E2 and Pg applied topically. The advent of monitoring steroid hormones in body fluids that more closely reflect tissue levels of hormones, namely saliva and capillary whole blood derived from the fingertip (Dried Blood Spot-DBS), has serendipitously shed light on why such high pharmacological dosing is required to achieve even suboptimal physiological levels of hormones in serum and urine. More recent studies over the past 20 years has revealed that while salivary and capillary blood levels of endogenously produced steroids quantitatively parallel levels of parent hormones (E2, Pg, T) seen in serum and their metabolites in urine, these quantitative equivalencies no longer hold when these sex-steroid hormones are delivered percutaneously through the skin as gels or creams. Instead, salivary and capillary blood levels rise in a more linear fashion with dosing and achieve physiological levels in these body fluids at 10x lower physiological dosing (Tables 2-4); in stark contrast serum and urine levels increase very little at physiological doses. This has raised the interesting question of why salivary and capillary blood levels, which are equivalent to free serum levels with endogenously produced hormones, are so much higher (10-100 x) than levels seen in serum and urine when hormones are delivered topically through the skin. The obvious question arises as to which one of these categories of body fluids (serum and urine vs saliva and capillary whole blood) more closely reflect tissue levels of the hormone and the optimal dose that is needed for optimal physiological response. As a lab that tests all four of these body fluids, and is involved in many IRB-approved clinical research projects related to topical BHRT, we have had the opportunity to evaluate levels of endogenous steroids in women and men at different stages of life and supplementing with different hormone delivery systems (oral, occluded patch, topical, vaginal, subcutaneousinjections and pellets, troche, etc.) and doses at different time points following hormone application. From these tests and evaluation of symptom relief, or not, we have come to the conclusion that the bioavailable fractions of topically delivered hormones are not accurately quantified by testing serum or urine and that saliva and capillary whole blood levels of the

ANTI - AGING MEDICAL NEWS

â&#x20AC;˘ SPRING 2019

Topical Delivery of Sex Steroid Hormones and Distribution in Different Body Fluids

topically delivered sex-steroids more closely reflect tissue bioavailable levels of E2 and Pg in women, and T in men. In this mini-review I will dig deep into our database of more than 2 million women and men who have been tested for different hormones following hormone therapies over the past 20 years. I will focus only on our testing of topical (percutaneous) hormone delivery as a cream or gel as it relates to body fluid (saliva, capillary blood-DBS, venipuncture serum, and urine) distribution of estradiol and progesterone in postmenopausal women and testosterone in men over the age of 40 (mostly hypogonadal based on blood levels of T < 300 ng/dL). Tables 2 and 3 show the median levels of E2 and Pg in saliva, capillary blood (DBS), serum, and urine of postmenopausal women before and after increasing doses of topical E2 and Pg therapies. Table 4 shows the median levels of testosterone in these same body fluids in men over the age of 40 before and after increasing doses of topical testosterone. Insufficient information was available from our database for serum E2 and Pg (women) and T (men) with different topical doses of these hormones as we test much fewer serum and urine samples than saliva and finger-stick capillary blood (DBS),; therefore, we used reported median values from several well designed clinical studies that investigated different topical doses and reported serum/plasma levels of each hormone category (Prestwood KM 2003, Brennan JJ 2001, Basdevant A 1980). For reference to endogenous production of E2 and Pg in women, and T in men, approximate physiological amounts of these hormones at different stages of reproductive life are shown in Table 1. Data showing saliva, capillary blood-DBS, serum, and urine levels of E2 and Pg in postmenopausal women, and T in men, at increasing topical doses of each hormone are shown in Tables 2-4. As seen in Tables 2 and 3, physiological luteal levels of E2 and Pg are seen in saliva and capillary blood with physiological topical dosing of E2 (100-300 ug) and Pg (10-30 mg). E2 and Pg in saliva and DBS continue to increase in a somewhat linear fashion with increasing doses. In sharp contrast, the data clearly show that to achieve luteal premenopausal serum levels of estradiol (range 80-200 pg/ml) requires pharmacological dosing (1000-3000 ug) with topical E2, as reported by others (Prestwood KM 2003, Brennan JJ, 2001). Further, physiological luteal levels of Pg in serum and urine are not achieved even with pharmacological (100-300 mg) topical Pg dosing, as reported by others (Du, JY 2013). Dosing at this pharmacological range results in salivary and capillary blood levels of E2 and Pg that are 10-20 x higher than physiological range. As shown in Table 4, topical T in men follows the same pattern as seen with topical E2 and Pg in women in that the physiological levels of T found in young healthy males (Table 1) are seen in the saliva and capillary blood of older hypogonadal men (> 40 y/o) with topical T dosing in a physiological range (5-10 mg). Very little increase in serum and urine T occurs at a physiological topical dose. At least

10-20 x higher dosing (50-200 mg) is required to achieve even mid-physiological levels as reported by others (Bhasin S, 2005). Dosing at this pharmacological range results in salivary and capillary blood levels of T 10-20 x higher than physiological range. Results from Tables 2-4 clearly show that pharmacological topical dosing with E2 (1000-3000 ug) and Pg (100-300 mg) in women, and T (50-200 mg) in men are required to achieve near physiological mid-luteal levels of serum E2 seen in premenopausal women, and T in healthy young men. In sharp contrast, much lower physiological topical dosing (1020 x lower dosing than above for each hormone) is required to achieve optimal physiological levels of these hormones based on saliva and capillary blood levels of E2 and Pg in women, and T in men. These data suggest that at least for topical E2 and Pg in women, and topical T in men, serum and urine underestimate by at least 10-fold the amount of topically delivered hormone distributed to several tissues of the body (salivary gland and capillary beds of the finger tip). Similar results have been seen in tissues such as breast biopsies following physiological dosing with topical estradiol (1 mg) and progesterone (25 mg) (Chang KG, 1995) where mammary tissue levels of hormones increased 100-fold and progesterone suppressed estradiolstimulated mammary cell proliferation, but serum levels of E2 and Pg showed no significant change from patients treated only with placebo topical cream. These doses of E2 (1 mg) and Pg (25 mg) significantly raise salivary and DBS levels of E2 and Pg to physiological levels but have little impact on serum or urine levels of these hormones. Similar results have been reported for bone response to physiological (250 ug) levels of E2 (Prestwood KM, 2003) and Pg (30 mg) to protect the uterus from overstimulation by E2 (Leonetti HB, 2003). Based on our results above from tens of thousands of female and male patients who have used different doses of topical estradiol, progesterone, and testosterone and tested saliva, capillary blood, serum, and urine levels of these hormones it would appear that serum and urine are not appropriate body fluids to monitor topical hormone therapy but are fine for measuring endogenous hormones, or BHRT delivered by other methods. Saliva or capillary whole blood (DBS) testing provide a more accurate picture of topical doses needed to achieve physiological levels of these hormones in tissues, thus avoiding the potential for overdosing. Continued use of serum or urine for establishing dosing regimens of topically delivered hormones could potentially lead to excessive tissue exposure, suboptimal response, and eventual symptoms/ conditions of hormone excess as well as pseudo deficiency caused by tachyphylaxis (down-regulation of tissue receptors and lack of response due to excessive prolonged exposure). No doubt, more research is needed to clarify these issues regarding the optimal topical hormone dose necessary to achieve optimal physiological levels of and clinical response to estradiol and progesterone in women and testosterone in men.

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â&#x20AC;˘ SPRING 2019

Topical Delivery of Sex Steroid Hormones and Distribution in Different Body Fluids

References

Basdevant A and de Lignieres B. Treatment of menopause by topical administration of oestradiol. In: Percutaneous Absorption of Steroids, MauvaisJarvis P, Vickers, CFH., and Wepierre J, Eds., Academic Press (London), 1980; pp. 249-258.

Modena MG, Molinari R, Muia N Jr, Castelli A, Pala F, Rossi R. Double-blind randomized placebo-controlled study of transdermal estrogen replacement therapy on hypertensive postmenopausal women. Am J Hypertens. 1999;12:10008.

Bhasin S, et. al. J Clin Endocrinol Metab 90: 678-688, 2005. Older men are as responsive as young men to the anabolic effects of graded doses of testosterone on skeletal muscle

Oâ&#x20AC;&#x2122;Leary P, Feddema P, Chan K, Taranto M, Smith M, Evans S. Salivary, but not serum or urinary, levels of progesterone are elevated after topical application of progesterone cream to pre- and post-menopausal women. Clin Endocrinol 2000; 53: 615-620.

Brennan JJ, Lu Z, Whitman M, Stafiniak P, van der Hoop RG. Serum concentrations of 17beta-estradiol and estrone after multiple-dose administration of percutaneous estradiol gel in symptomatic menopausal women. Ther Drug Monit. 2001;23:134-8.

Place VA, Powers M, Darley PE, Schenkel L, Good WR. A double-blind comparative study of Estraderm and Premarin in the amelioration of postmenopausal symptoms. Am J Obstet Gynecol.1985;152:1092-9.

Burry KA, Patton PE, Hermsmeyer K. Percutaneous absorption of progesterone in postmenopausal women treated with transdermal estrogen. Am J Obstet Gynecol. 1999; 180:1504-11.

Prestwood KM, Kenny AM, Kleppinger A, Kulldorff M. Ultralow-dose micronized 17beta-estradiol and bone density and bone metabolism in older women: a randomized controlled trial. JAMA. 2003;290:1042-8.

Chang KU, Lee TT, Linares-Cruz G, Fournier S, de Lignieres B. Influence of percutaneous administration of estradiol and progesterone on human breast epithelial cell cycle in vivo. Fertil Steril 1995; 63: 785-791.

Prestwood KM, Kenny AM, Unson C, Kulldorff M. The effect of low dose micronized 17beta-estradiol on bone turnover, sex hormone levels, and side effects in older women: a randomized, double blind, placebo-controlled study. J Clin Endocrinol Metab. 2000;85:4462-9.

Chetkowski RJ, Meldrum DR, Steingold KA, Randle D, Lu JK, Eggena P, Hershman JM, Alkjaersig NK, Fletcher AP, Judd HL. Biologic effects of transdermal estradiol. N Engl J Med. 1986;314:1615-20.

Scott RT Jr, Ross B, Anderson C, Archer DF. Pharmacokinetics of percutaneous estradiol: a crossover study using a gel and a transdermal system in comparison with oral micronized estradiol. Obstet Gynecol. 1991;77:758-64.

De Lignieres B, Basdevant A, Thomas G, Thalabard JC, Mercier-Bodard C, Conard J, Guyene TT, Mairon N, Corvol P, Guy-Grand B, et al. Biological effects of estradiol-17 beta in postmenopausal women: oral versus percutaneous administration. J Clin Endocrinol Metab. 1986;62:536-41.

Stanczyk FZ, Shoupe D, Nunez V, Macias-Gonzales P, Vijod MA, Lobo RA. A randomized comparison of nonoral estradiol delivery in postmenopausal women. Am J Obstet Gynecol. 1988;159:1540-6.

Du JY, Sanchez P, Kim L, Azen CG, Zava DT, Stanczyk FZ. Percutaneous progesterone delivery via cream or gel application in postmenopausal women: a randomized cross-over study of progesterone levels in serum, whole blood, saliva, and capillary blood. Menopause. 2013;20:1169-75. Edelman A, Stouffer R, Zava DT, Jensen JT. A comparison of blood spot vs plasma analysis of gonadotropin and ovarian steroid hormone levels in reproductive-age women. Fertil Steril 2007; 88: 1404-1407. Egras AM, Umland EM. The role of transdermal estrogen sprays and estradiol topical emulsion in the management of menopause-associated vasomotor symptoms. Int J Gen Med. 2010;3:147-51. Leonetti HB, Wilson KJ, Anasti JN. Topical progesterone cream has an antiproliferative effect on estrogen-stimulated endometrium. Fertil Steril. 2003;79:221-2.

Strecker JR, Lauritzen C, Nebelung T, and Musch K. Climacteric symptoms, oestrogens and gonadotrophins in plasma and urine after application of oestradiol ointment on the abdominal skin of oophorectomized women. In Percutaneous Absorption of Steroids, Mauvais-Jarvis P, Vickers CFH., and Wepierre J, Eds., Academic Press (London), 1980. Williams Textbook of Endocrinology, Larsen PR, Kronenberg HM, Melmed S, and Polonsky KS, Eds., 10th Ed., Elsevier Health Services (Saunders), Philadelphia, 2003. Zava D. Testing with Different Body Fluids and the Results of the Hormone Delivery Rate. Anti-Aging Medical News, Amer. Academy of Anti-Aging Medicine, pp. 47-51, Fall 2013. Zava DT, Groves MN, Stanczyk FZ. Percutaneous absorption of progesterone. Maturitas. 2014 Feb;77(2):91-2.

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â&#x20AC;˘ SPRING 2019

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DIM from Cruciferous Vegetables for Men’s Health By: Whitney Crouch, RDN, CLT

Cruciferous vegetables belong to the Brassica genus of plants and include foods such as broccoli, arugula, Brussels sprouts, mustard and collard greens, cabbage, and watercress. Known for their cancer-fighting biological properties and support of the body’s natural detoxification system, these veggies contain sulfur-containing chemicals called glucosinolates, which are responsible for the vegetable’s pungent aroma and bitter flavor.1 During the digestion of cruciferous vegetables, glucosinolates are broken down to form biologically active compounds such as indoles, nitriles, thiocyanates, and isothiocyanates.2 One of these compounds, indole-3-carbinol (I3C), is then converted into 3,3’-diindolylmethane (DIM) in the stomach; both compounds are known for their health supportive characteristics.3 Studies investigating these unique nutritional bioactives, I3C and DIM, have found that I3C is unstable in the acidic stomach acid environment and is rapidly converted to DIM.4 To simplify the discussion, some of the observed effects of I3C will be assumed for DIM, except for any dose-specific references.4-6 I3C and DIM are best known for their use in cancer prevention applications and female hormone balance, with DIM regarded as a go-to support for reducing excess estrogens in the body.7-8 While it’s predominantly regarded as a women’s health ingredient, DIM is not a compound just for women.

A preclinical study in a mouse model found that a combination of DIM (10 mg/kg) and chloroquine (60 mg/kg), taken 3x/week, significantly decreased prostate cancer (PC-3) tumor growth in vivo after 3 and 4 weeks of treatment.10 The mouse prostate cancer model used was a unique one, as the researchers performed a xenograft (i.e., tissue graft from a donor of a different species from the recipient) of human prostate cancer cells A more active type of DIM, 4,4’-Br2DIM, given at the same dose (10 mg/kg, 3x/week) was found to significantly inhibit tumor growth after 4 weeks of treatment, making DIM a novel addition to prostate health plans and prostate cancer treatments.10 Translation: DIM paired with chloroquine for 3 to 4 weeks can slow prostate tumor progression.

Prostate cancer is the most common non-skin cancer in American men, with a lifetime risk for diagnosis of approximately 15.9%.9 It is estimated that 164,690 new cases were diagnosed, and 29,430 patients died from prostate cancer in 2018.9

Next, a clinical study used a nutritional grade, absorptionenhanced DIM (BR-DIM) given in 225 mg doses 2x/ day for a minimum of 14 days in 41 Caucasian (55%) and African American (40%) patients with localized prostate cancer.13 Baseline plasma DIM blood levels were assessed in patients, who were given BR-DIM for 14-72 days before undergoing a radical prostatectomy; blood DIM levels were re-tested immediately prior to surgery and during a follow-up to surgery within 24 months post-operation. Prostate tissue DIM was also measured at the time of surgery.

Nutrition represents a modifiable cancer risk factor that practitioners can and should leverage in their patients. Epidemiological evidence demonstrates that consumption of cruciferous foods has been associated with decreased prostate cancer incidence10 and risk.11 So, how much broccoli, you ask? Consuming ≥ 3 servings of cruciferous vegetables (as compared to < 1 serving/week) was associated with a 41% risk reduction in prostate cancer.11

Biologically significant levels of DIM concentrations were found in prostate tissue by day 14 of BR-DIM supplementation, with no incremental increases achieved with BR-DIM treatment of longer duration.13 Further, a reduction in PSA levels was observed in the majority (71%) of study participants.13 Lastly, BR-DIM had a significant, anti-androgenic impact on the nuclear translocation of the androgen receptor (i.e., exclusion from the nucleus) in 96%

DIM for Men Prostate cancer

Crucifer bioactives I3C and DIM have been studied for their anti-cancer pathophysiological properties. Mechanistically, it is thought that the anti-prostate cancer effects of I3C and DIM are driven by DIM’s inhibitory effects on androgenmediated pathways, meaning multiple testosterone-producing pathways are reduced through different mechanisms of DIM’s bioactivity.8 Furthermore, DIM imparts anti-cancer effects via its ability to reduce cell proliferation, provoke cell cycle arrest, induce cell death (apoptosis) and autophagy in human prostate cancer cells.12-13

ANTI - AGING MEDICAL NEWS

• SPRING 2019

DIM from Cruciferous Vegetables for Men’s Health

of patients; this receptor plays a key role in prostate tumor pathogenesis via testosterone binding.13 Translation: BRDIM treatment produced clinically relevant DIM levels in the prostate and reduced the effectiveness of androgen receptors to bind testosterone, which has potential chemopreventive implications for prostate cancer.

• DIM may support healthy testosterone-to-estrogen balance in males, which in turn can improve myriad symptoms and clinical manifestations of estrogen excess If you suspect estrogen excess or would like to learn more about DIM’s appropriateness for a specific prostate condition, consult with a qualified healthcare provider for hormone testing and personalized clinical recommendations.

Finally, a double-blind, randomized, placebo-controlled clinical trial examined the efficacy of a pharmaceutical DIMcontaining drug (900 mg/day DIM) in 21 patients with high-grade prostatic intraepithelial neoplasia (PIN), a major risk factor for development of prostate cancer.14 An interim analysis of data after 12 months of treatment demonstrated a significant reduction in the morphological index (based on histological examination of prostate biopsy specimens) in the treatment group as compared to placebo.14 Additional treatment group effects include an improvement in maximal urinary flow rate and a complete regression of PIN in 45% of patients. Translation: intermediate results from a DIM drug trial demonstrate significant clinical promise for patients with high-grade PIN.

Citations

Other male-centric hormonal applications

5. Weng JR et al. Indole-3-carbinol as a chemopreventive and anti-cancer agent. Cancer Lett. 2008;262:153–163.

In addition to its aforementioned role in hormone-related prostate cancer, DIM may support other areas of men’s health.

6. Grose KR et al. Oligomerization of indole-3-carbinol in aqueous acid. Chem Res Toxicol. 1992;5:188–193.

Obesity

A preclinical study in mice compared the effects of a highfat diet (HFD) vs. control diet within the context of DIM supplementation.15 In the mice fed the HFD, 50 mg DIM per kg body weight suppressed HFD-induced obesity; the group receiving the HFD alone gained weight and fat tissue, while the group receiving the HFD plus DIM did not gain weight nor adipose tissue, likening them to the control diet group.15 Furthermore, cellular analyses revealed that DIM significantly inhibited adipogenesis of pre-adipocyte cells.15 In other words, DIM has anti-obesity properties.

Estrogen-related effects

More often discussed in women’s health conversations, one well-known characteristic of DIM is its ability to reduce excess estrogen in the body and convert the more carcinogenic type of estrogens (16-hydroxy and 16-methoxy estrogens) into the “good estrogens” (2-hydroxy and 2-methoxy estrogens).16 But, men make estrogens too through the conversion of testosterone into estradiol via the aromatase enzyme. By DIM reducing excess estrogens in men (possibly caused by genetics, diet, or xenoestrogen exposure), there may also be a reduction in estrogen-excess symptoms like fatigue, erectile dysfunction, obesity, and estrogen-related cancers.15-16

Clinical Takeaways:

• DIM is not just an indole phytochemical that supports women’s health, but men’s health as well • DIM may be used as a preventative measure in men with certain risk factors for prostate cancer (e.g., PIN), and as an adjunct therapy during conventional treatment for certain types of prostate cancers

1. NIH. Cruciferous vegetables and cancer prevention. https://www.cancer.gov/about-cancer/ causes-prevention/risk/diet/cruciferous-vegetables-fact-sheet. Accessed December 18, 2018. 2. Hayes JD et al. The cancer chemopreventive actions of phytochemicals derived from glucosinolates. Eur J Nutr. 2008;47 Suppl 2:73-88. 3. Li Y et al. Recent progress on nutraceutical research in prostate cancer. Cancer Metastasis Rev. 2014;33(2-3):629-640. 4. Anderton MJ et al. Pharmacokinetics and tissue disposition of indole-3-carbinol and its acid condensation products after oral administration to mice. Clin Cancer Res. 2004;10:5233–5241.

7. Murillo G et al. Cruciferous vegetables and cancer prevention. Nutr Cancer. 2001;41(1-2):1728. 8. Wang TT et al. Broccoli-derived phytochemicals indole-3-carbinol and 3,3’-diindolylmethane exerts concentration-dependent pleiotropic effects on prostate cancer cells: comparison with other cancer preventive phytochemicals. Mol Carcinog. 2012;51(3):244-256. 9. Siegel RL et al. Cancer statistics, 2018. CA Cancer J Clin. 2018;68:7–30. 10. Kristal AR et al. Brassica vegetables and prostate cancer risk: a review of the epidemiological evidence. Nutr Cancer. 2002;42(1):1-9. 11. Cohen JH et al. Fruit and vegetable intakes and prostate cancer risk. J Natl Cancer Inst. 2000;92(1):61-68. 12. Draz H et al. Autophagy inhibition improves the chemotherapeutic efficacy of cruciferous vegetable-derived diindolylmethane in a murine prostate cancer xenograft model. Invest New Drugs. 2018;36(4):718-725. 13. Hwang C et al. Anti-androgenic activity of absorption-enhanced 3, 3’-diindolylmethane in prostatectomy patients. Am J Transl Res. 2016;8(1):166-176. 14. Paltsev M et al. First results of the double-blind randomized placebo-controlled multicenter clinical trial of DIM-based therapy designed as personalized approach to reverse prostatic intraepithelial neoplasia (PIN). EPMA J. 2016;7:5. 15. Yang H et al. 3,3’-Diindolylmethane suppresses high-fat diet-induced obesity through inhibiting adipogenesis of pre-adipocytes by targeting USP2 activity. Mol Nutr Food Res. 2017;61(10). 16. Wendlová J. Scientific medicine in integrative treatment of erectile dysfunction. J Integr Nephrol Androl. 2015;2:5-18 17. Wu F et al. Levels of estradiol and testosterone are altered in Chinese men with sexual dysfunction. Andrology. 2016;4(5):932-938.

Whitney Crouch, RDN, CLT

Whitney Crouch is a Registered Dietitian who received her undergraduate degree in Clinical Nutrition from the University of California, Davis. She has over 10 years of experience across multiple areas of dietetics, specializing in integrative and functional nutrition and food sensitivities. When she’s not writing about nutrition or educating others, she’s spending time with her husband and young son. She’s often found running around the bay near her home with the family’s dog or in the kitchen cooking up new ideas to help her picky eater expand his palate.

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• SPRING 2019

A Comprehensive Range of Practitioner-Grade Formulas to Support Hormone Health Hormones are involved in most basic processes within the body for both men and women. Hormones play a role in a variety of general and sex-specific functions, including mood, sexual libido, premenstrual syndrome (PMS), weight management, and energy levels. Metagenics builds upon this science to offer an extensive line of nutritional formulas that target specific support areas for men’s and women’s hormonal health.* • Axis Endo™ Specialized support for hormone metabolism in men and women* • EstroFactors® Features phytonutrients and BioResponse DIM® • Meta I 3 C® Designed to promote healthy estrogen metabolism and balance* • Testralin® Testosterone balance support*

Contact your Metagenics representative today to learn more, or visit Metagenics.com

*These statements have not been evaluated by the Food and Drug Administration. These products are not intended to diagnose, treat, cure, or prevent any disease. © 2018 Metagenics, Inc. All Rights Reserved.

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Friday, May 17th, 2019 6:15 pm Sun Ballroom C

Michael Chapman, ND Michael Chapman, ND is a licensed naturopathic physician who graduated from Bastyr University in Seattle, Washington in 2012. Dr. Chapman joined Genova Diagnostics, Inc. in 2015 as a medical educator. He is currently the Product Development Manager and a product line specialist for nutrition, hormones, and genomics at Genova. Over the last three years, he has delivered multiple presentations at American Academy of Anti-Aging Medicine and Institute for Functional Medicine events. Dr. Chapman has a passion for learning and helping others come to a greater understanding of the vast and dynamic processes that exist and interact within the human body.

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The Science Behind Vitamin E Tocotrienols By: Barrie Tan, PhD

Tocotrienols are novel components of the vitamin E family. The vitamin E family consists of two subgroups: tocotrienols (T3) and tocopherols (T). Tocotrienols are naturally derived from several sources, including rice bran, palm, and annatto. Numerous studies have uncovered the benefits and superior function of annatto-derived delta- and gamma-tocotrienols, including their role in cholesterol reduction and cardiovascular disease, influence on metabolic syndrome and diabetes, novel function for bone health, and support for eye and skin health. Additionally, the substantial potential for tocotrienols as adjuncts to conventional cancer therapies has been addressed in a previous paper.120

Structures of Tocotrienol, Tocopherol, and Isomers

History and Discovery of Tocotrienols

Alpha, beta, gamma, and delta are among the isomers of tocotrienol as well as tocopherol. The potency of cholesterol inhibition by these tocotrienol isomers is delta > gamma > alpha > beta. Tocopherols are inactive in lowering cholesterol.5

Although vitamin E (in the form of alpha-tocopherol) was discovered in the 1920s,1 it was not until the 1960s that tocotrienols were assessed to be part of the vitamin E family.2 Vitamin E is known as a “vitamin” because it is essential for reproduction, and has been dubbed the “birth vitamin.” Its antioxidant activity was discovered soon after (1930s).3 Tocotrienols from current sources (rice, palm and annatto) were first developed and brought to the dietary supplement market by Dr. Barrie Tan, inventor of numerous tocotrienol extraction processes from natural sources. These discoveries include tocotrienols from palm (1992), then rice (1998), and finally annatto (2002). The first ever tocopherol-free tocotrienol product derived from annatto seeds – DeltaGold® –became available around 2005. Annatto as a natural colorant was introduced into the US during the 17th century, and today it is used in the food industry worldwide. The “tocopherol-free” aspect of annatto tocotrienol is important, since research has shown alpha-tocopherol to interfere with tocotrienol functions and benefits. Contrary to annatto, both palm and rice contain a significant amount of alpha-tocopherol (25-50% of total vitamin E) (Figure 1). Annatto remains the first and only true source of naturederived vitamin E that supplies tocotrienol only.

Tocotrienol and tocopherol both have a chromanol nucleus, which is the site of antioxidant activities. Tocotrienol and tocopherol differ in the tail region of the molecule. Tocotrienol has a farnesylated tail, allowing it to downregulate 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase – an essential enzyme for cholesterol synthesis – whereas tocopherol has a longer phytyl tail without double bonds, disallowing a similar function. The downregulation of HMG-CoA reductase has been shown to decrease total and LDL cholesterol levels, and is considered a critical pathway that involves tocotrienol in the inhibition of several cancers.4

Desmethyl tocotrienol is a collective term for reduced methyl substituents on the vitamin E molecule, and primarily refers to delta- and gamma-tocotrienol. Desmethyl tocotrienols are more potent, especially in the absence of a methyl group at the C5 position on the chromanol ring system. Delta-tocotrienol is monomethylated at the C8 position of the chromanol ring system, making it the least substituted, and therefore the most potent isomer of the four tocotrienol compounds. The majority of vitamin E dietary supplements contain mostly tocopherols, of which alpha-tocopherol is the most common. Typically, only traces of tocotrienol are found, which is due to its scarcity in plants from which vitamin E is extracted. While tocopherols have high antioxidant value, they lack the ability to regulate aberrant cells (e.g., cancer), cholesterol synthesis (hypercholesterolemia) and triglyceride synthesis/ transport (hypertriglyceridemia). Large clinical studies on alpha-tocopherol benefits to treat cardiovascular or other diseases have been equivocal or without effect,6 and have shown alpha-tocopherol to possibly be harmful.7, 8

Tocotrienol Mechanism

The mechanism of tocotrienol’s hypolipidemic action involves

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The Science Behind Vitamin E Tocotrienols

Figure 1. Typical compositions of vitamin E in natural tocotrienol sources.

post-transcriptional suppression of HMG-CoA reductase via controlled degradation of the reductase protein.9, 10 Recently it has been reported that only gamma- and delta-tocotrienol stimulate the degradation of HMG-CoA reductase, and block processing of sterol regulatory element-binding protein (SREBP). Blocking SREBP processing has implications for triglyceride synthesis (and reduction), with importance in diabetes and prediabetes. Therefore, the mechanism for cholesterol reduction by tocotrienol shown 20 years ago was revalidated some 15 years later. This study came from the Brown and Goldstein research group that discovered the LDL cholesterol receptor, explaining how cholesterol is regulated. Brown and Goldstein were awarded the 1985 Nobel Prize for this work.11 These tocotrienol mechanisms of cholesterol and triglyceride synthesis – collectively controlling hyperlipidemia – have manifested into clinical significance for cardiovascular disease (CVD), such as hypercholesterolemia,12 chronic inflammation,13 atherosclerosis,14 and obesity and liver function associated with NAFLD.15 Other forms of vitamin E (all four tocopherols and alpha- and beta-tocotrienols) do not degrade, downregulate, nor block SREBP processing.10 Delta-tocotrienol was also found to have the greatest antioxidant properties among the tocotrienol isomers,16 which is due to the decreased methylation on the chromanol ring that allows the molecule to be more easily incorporated into cell membranes.17 A comparative in vitro study showed that gamma- and delta-tocotrienols were 4-fold more efficient as scavengers of peroxyl radicals than other tocotrienol isomers.18

Tocotrienol Mechanism

Tocopherols do not have the cholesterol-lowering ability that tocotrienols do.9 In fact, the opposite is true. Alpha-tocopherol has been repeatedly shown to attenuate or interfere with the cholesterol-lowering action of tocotrienols.19 Combinations effective in cholesterol-lowering consist of 15% (or less) alphatocopherol and 60% (or more) gamma- and delta-tocotrienol, whereas ineffective formulations consist of 20% (or more) alphatocopherol and 45% (or less) of gamma- and delta-tocotrienol. Substantiating these formulating guidelines are clinical studies in which supplements with high alpha-tocopherol content did not contribute to the lowering of cholesterol,20-22 whereas supplements containing low amounts of alpha-tocopherol and high amounts of gamma- and delta-tocotrienol led to a significant decrease in total and LDL cholesterol.13, 23-25

While tocotrienols are absorbed better than tocopherols, tocopherols have been shown to prevent absorption and organ/tissue delivery of tocotrienols. 26-30 To summarize, alpha-tocopherol is thought to interfere with tocotrienol benefits directly by: • Compromising cholesterol and triglyceride reduction19, 30, 31 • Lowering antioxidant capacity32

• Attenuating cancer cell inhibition33, 34

• Blocking absorption26-29

• Inducing tocotrienol catabolism35

• Preventing adipose and liver storage30 By itself, alpha-tocopherol may lead to other predicaments, potentially: • Causing the premature catabolism of prescription drugs36 • Interfering with chemotherapy drug action 34, 37, 38 • Increasing cholesterol and blood pressure19, 31, 39-41

• Increasing prostate cancer and glioblastoma risk in humans7, 42, 43 • Exacerbating stroke injury44 • Decreasing bone mass45

• Increasing LDL oxidation46

Tocotrienol Absorption and Bioavailability

As part of the vitamin E family, tocotrienols are fat-soluble, and are absorbed in a similar fashion as fats from food in the gut, aided by bile salts. These vitamin Es are mixed into large emulsified particles (1,000um) called chylomicrons that absorb through the gut. These particles that carry both tocopherols and tocotrienols travel in the lymph and blood. Along the way, the particles become smaller and denser, variously named VLDL (~65um), IDL (~45um), and LDL (~25um). The larger particles mainly contain tocotrienols. The IDL sheds the denser HDL (~10um) that enter the cells and organs, and the less dense LDL that stay in the blood and return to the liver. Therefore, lipoproteins are “fat shuttles” transporting cholesterol and lipid nutrients alike to organs including the liver. At this stage, the path of tocopherols and tocotrienols part way (this is a preferential picture, not an absolute one). Tocotrienols progressively deposit into cells as larger lipoproteins move to smaller ones. Alpha-tocopherol progressively remains in the LDL and returns to the liver or gets repackaged into LDL in the liver. Therefore, tocotrienols are particularly bioavailable, and have been shown to deposit in lipid-rich organs, including the brain, spleen, lung, kidney, and heart [27, 47], with particular preference in the adipose,

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skin, and heart [48] prior to hepatic circulation. Conversely, alpha-tocopherol is particularly bioavailable to the liver and blood [48] after hepatic circulation. An alpha-tocopherol transport protein (ATTP) exists and adds to the complexity. When vitamin E is returned to the liver (entero-hepatic circulation), ATTP preferentially repackages alpha-tocopherol into LDL without (or little) recognition of the other tocopherols and tocotrienols. Hence, the blood alpha-tocopherol level remains high (≥10-fold that of tocotrienol), providing the perception that alpha-tocopherol is more bioavailable. It means only that alpha-tocopherol is conserved in the blood, and not destructed in the liver. Since tocotrienols have been shown to be present in many organ tissues – and in some cases at levels comparable to alphatocopherol – tocotrienols are deported to cells and organs prior to entero-hepatic circulation, thereby not destructed in the liver. Tocotrienol’s rapid drop in the blood after ~4 hours (whereas alpha-tocopherol remains in the blood for longer) attests to the fast absorption of tocotrienols into organs rather than the presumption that tocotrienols are excreted. It is now generally accepted that all vitamin E molecules absorb through the intestines equally via triglyceride-rich chylomicrons (TRC) into the lymphatic blood system [49]. All tocotrienols are higher in TRC and HDL (particularly delta-tocotrienol) [50], allowing for rapid absorption while alpha-tocopherol retains preferentially in the LDL, the main task of which is to return to the liver. Two studies on DeltaGold® confirmed the bioavailability of tocopherol-free annatto tocotrienol [51, 52]. An openlabel randomized trial involved 125, 250, 500, 750, and 1000 mg/day dosage groups. Many pharmacokinetic parameters were studied in healthy subjects to ascertain that delta- and gamma-tocotrienol were absorbed. When taken with a meal, both tocotrienols were absorbed and are bioavailable. A trial is now underway to ascertain tocotrienol’s bioavailability in adipose tissue, considered the main depot for tocotrienol.

Tocotrienol’s Antioxidant Properties

Vitamin E is uniquely shaped to reside within cell membranes to protect against oxidation. Aside from protecting cell membranes (tocotrienols were shown to be ~50x more potent as an antioxidant compared to tocopherols54), tocotrienols also protect lipids such as omega-3s in softgel products and foods and beverages.55 The antioxidant efficiency of tocotrienols was evaluated as the ability of the compounds to inhibit lipid peroxidation and reactive oxygen species (ROS) production. Delta-tocotrienol was found to have the greatest antioxidant properties among the tocotrienol isomers,56 which is due to the decreased methylation of the chromanol ring that allows the molecule to be more easily incorporated into cell membranes.57 In lipid ORAC studies, delta- and gamma-tocotrienols had the highest antioxidant value of all vitamin E isomers at 5.5x and 3x the potency of alpha-tocopherol, respectively. Interestingly, delta- and gamma-tocopherol were also strong antioxidants.16 In vitamin E mixtures containing both tocotrienols and tocopherols, a higher concentration of alpha-tocopherol was associated with lower antioxidant activity.32

Regulation of Cholesterol Synthesis in Animal and Clinical Studies: Approximately one in every three adults in the US has high total cholesterol (240 mg/dL and above).59 Recently, animal studies supported the earliest studies first conducted by University of Wisconsin, Madison researchers in the early 1980s.60 Mechanisms of cholesterol reduction were elucidated then and confirmed today by University of Texas researchers.10 Animals whose diet was supplemented with gamma- and delta-tocotrienols showed the greatest decrease in cholesterol levels (32% total and 66% LDL cholesterol), whereas alphatocopherol had no effect on cholesterol-lowering. In this study, HDL/LDL cholesterol ratios were improved by 123-150% in chickens, which more closely reflect the lipogenic activity and cholesterol levels of humans.5

In a recent clinical trial, researchers tested the dose-dependent effects of annatto tocotrienols ranging from 125 – 750mg per day on hypercholesterolemic individuals.13 Results showed that after only 4 weeks, the optimum daily dose of 250mg decreased total cholesterol by 15%, LDL cholesterol by 18%, and triglycerides by 14%. Furthermore, cytokines associated with cardiovascular disease and their gene expression, including TNF-alpha, IL-2, IL-4, IL-6, and IL-8, were down-regulated 39-64%. Selected microRNAs that are typically down-regulated in hypercholesterolemic individuals were upregulated by tocotrienol treatment, suggesting a beneficial effect on these biomarkers. Anti-Inflammation: The traditional view of cardiovascular disease combines the clogging of arteries with elevated cholesterol. Surprisingly, however, half of the patients presenting with heart attacks have normal cholesterol levels. Today, it is well-known that inflammation is cholesterol’s aid in furthering cardiovascular disease progression, recruiting white blood cells to arterial walls, causing them to stick and initiate plaque buildup. Tocotrienols were shown to have potent anti-inflammatory properties. New research focused on the effect of tocotrienols in reducing inflammation in experimental mice.61 They demonstrated that alpha-, gammaand delta-tocotrienols strongly inhibited the inflammatory response using such markers as chymotrypsin, trypsin and tumor necrosis factor-a (TNF-a), with delta-tocotrienol being the most effective. The results of this study demonstrated that the use of tocotrienols can function as a powerful proteasome modulator, while increasing the immune system’s ability to fight inflammation. At the same time, tocotrienols induce a hormone that produces an anti-inflammatory steroid to block inflammation directly. One tocotrienol clinical study underscores the supplement’s impressive anti-inflammatory benefits.12 Among the most notable biomarkers to be affected by a 250mg tocotrienol dosage were C-reactive protein (CRP; a predictor for chronic inflammation), nitric oxide (NO), and malondialdehyde, with decreases of 40%, 40%, and 34%, respectively. Total antioxidant status, on the other hand, increased 22%. Several inflammatory cytokines and microRNAs were found to be modulated by tocotrienol treatment, suggesting more favorable outcomes in cardiovascular and aging diseases with supplement use.

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The Science Behind Vitamin E Tocotrienols

When combined with other anti-inflammatory ingredients, tocotrienols showed synergistic efficacy. Two clinical studies show that delta-tocotrienol in combination with antioxidant polyphenols curb inflammation and manage dyslipidemia.62, 63 One of the placebo-controlled studies was conducted in two groups of elderly subjects, one with normal levels and the other with elevated lipid levels. The product formulation was composed of delta-tocotrienol from annatto (as found in DeltaGold®), along with niacin and polyphenols. In both groups, supplementation led to a significant drop in CRP and γ-glutamyl-transferase (a predictor for non-fatal myocardial infarction and fatal coronary heart disease), while increasing total antioxidant status, a measure of the body’s capacity to counteract reactive oxygen species. In the hypercholesterolemic group, LDL cholesterol (20-28%) and triglycerides (11-18%) also dropped. C-reactive protein dropped in healthy elderly (21-29%) as well as hyperlipidemic elderly (31-48%), as did γ-glutamyl-transferase (14-20%). There were no adverse effects associated with the 6-week supplementation period. Tocotrienol and Monocyte-Endothelial Cell Adhesion and Platelet Aggregation: The adhering of “activated” cells in the blood to artery walls is undesirable. It is a stressed condition prompted by inflammation and an attempt to remove chemicals and particles out of circulation. This process of arterial adhesion is termed chemotaxis. Tocotrienol’s role is anti-chemotactic. Studies have shown that tocotrienols positively affect monocyte-endothelial cell adhesion and platelet aggregation. In other words, tocotrienols may prevent artery walls from getting narrower and clots from forming, important elements for cardiovascular health. One of the first steps of atherogenesis is fatty streak formation in arteries, which begins with the adherence of circulating monocytes to the endothelium. Tocotrienols have been shown to reduce cellular adhesion molecule expression and monocyte adherence.64, 65 In particular, delta-tocotrienol showed the most profound inhibitory effect on monocyte adherence compared to tocopherols and other tocotrienol isomers. Delta- and gamma-tocotrienol were 60x and 30x more potent than alpha-tocopherol, respectively.66 It has been suggested that this phenomenon occurs via inhibition of VCAM-1 expression by delta- tocotrienol.66 Essentially, delta-tocotrienol dramatically reduces the “Velcro-effect” of circulating monocytes on the arterial wall, a process known to initiate plaque formation.67 Elevated LDL is a risk factor for CVD, especially atherosclerosis. It is generally understood that it is oxidized LDL particles, not non-oxidized particles, that are atherogenic.68 In a clinical trial where all four tocotrienols were studied, delta-tocotrienol alone reduced oxidized LDL, a significant indicator to reduced atherosclerosis. Contrary to this, alpha-tocotrienol can potentially pro-oxidize LDL to oxidized LDL.46 Tocotrienol and Hypertension: Approximately 32% of American adults have hypertension, and 25% have prehypertension.69 Animal studies showed that tocotrienols lower blood pressure, reduce plasma and blood vessel lipid peroxides, and improve total antioxidant status.70 Gamma-tocotrienol was shown to reduce systolic blood pressure significantly, and

improved nitric oxide synthase activity, both of which play a critical role in the pathogenesis of essential hypertension. 71 In humans, tocotrienols have been shown to increase arterial compliance and reduce blood pressure.72, 73 Tocotrienol and Atheroma Formation: Before turning 35, two out of three Americans will have some degree of plaque buildup in their arteries.74 This may be variously termed coronary, carotid, or peripheral atherosclerosis and/or stenosis. The effects of tocotrienols on atheroma formation have been compared in vivo. Comparison studies on animals investigated the impact of tocotrienol supplementation vis-à-vis tocopherol or non-supplementation. Results to date indicate that animals on an atherogenic diet and given desmethyl tocotrienols had 60% lower plasma cholesterol than the control group, and the size of atherosclerotic lesions was reduced 10-fold. Alpha-tocopherol, on the other hand, had no effect.75 This finding was further corroborated in a similar independent study, where desmethyl tocotrienols inhibited atherosclerotic lesions in hyperlipidemic mice. Atherosclerotic lesion size in mice supplemented with desmethyl tocotrienols was decreased by 42%, whereas with alpha-tocopherol, lesion size was only decreased by 11%.76 Fully methylated tocotrienols and tocopherols – namely alpha- and beta-isomers – do not have the cardiovascular benefits characteristic of desmethyl tocotrienols. Later studies with advanced designs pinned this concept down even further. Tocotrienols, especially deltaand gamma-tocotrienols, significantly reduced plaque scores, plaque stabilization, and inflammation, three of the pillars responsible for overall atherosclerosis.77, 78 Tocotrienol and Carotid Arteriosclerosis: A 4-year study on patients taking a 240 mg/day dosage with carotid arteriosclerosis showed that tocotrienol-tocopherol supplementation caused regression of the disease. In 88% of patients that took the supplement, carotid artery stenosis was regressed or stabilized. Of the control group receiving a placebo, 60% deteriorated, and only 8% improved.79, 80 Interestingly, total cholesterol in the supplemented group decreased 14% and LDL cholesterol fell 21% in the fourth year of the study.14

Cardiovascular Benefits of Tocotrienols

According to the American Diabetes Association, 30 million Americans have diabetes, with an additional 85 million Americans diagnosed with prediabetes, representing more than one-third of all Americans. Furthermore, metabolic syndrome – defined by a cluster of distinct abnormal cardiovascular measurements – is on the rise and mirrors the US obesity pandemic, with two in three adults being overweight or obese.81 Some of the AHA and NIH defining hallmarks of metabolic syndrome include:82, 83 • Increased serum triglycerides (above 150mg/dL) • Elevated blood pressure (above 130/85mmHg)

• Elevated serum glucose (100mg/dL and higher)

• Decreased HDL (under 40mg/dL for males; under 50mg/ dL for females)

• Increased waist circumference (above 40in. for males;

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The Science Behind Vitamin E Tocotrienols

MetS Animal Studies: In one study, researchers gave rats a high-carb, high-fat diet to induce obesity with accompanying cardiac remodeling, insulin resistance, hypertension, and fatty liver.84 Animals then received oral alpha-tocopherol, alpha-, gamma-, or delta-tocotrienol at 85mg/kg/day, corresponding to a 60kg human dose of ~800mg/day. Results showed that, while all isomers reduced collagen deposition and inflammatory cell infiltrates in the heart, only delta- and gamma-tocotrienol improved cardiovascular function and systolic blood pressure. Delta-tocotrienol normalized eccentric hypertrophy shown by lower left ventricular internal diameter (during diastole), stroke volume and cardiac output. Furthermore, only delta-tocotrienol affected important markers of metabolic syndrome and diabetes by enhancing glucose metabolism and improving insulin sensitivity, while reducing lipids and abdominal adiposity. The mechanism of action appears to be reduction in organ inflammation, especially of the heart, liver, and abdominal fat. A similar study confirmed this anti-inflammatory mechanism in a high-fat-fed mouse model, which examined the effects of tocotrienol on obesity-related adipocyte hypertrophy, inflammation, and hepatic steatosis.85 The approximate human equivalent of tocotrienol given to the mice was 160-640mg/ day for 14 weeks, at which point improvements in glucose tolerance along with reduced hepatic steatosis and triglycerides were observed. In addition, adipocyte size and macrophage infiltration into the liver were reduced, with the result being an overall improved metabolic profile. Closely related research further added to this MetS construct using tocotrienols. One group separately looked at delta-T3 and gamma-T3, and these tocotrienols attenuated “nascent flames” – called inflammasomes – of macrophages that protected chronic metabolic diseases.86-88 The other research group looked at the impact of tocotrienols with alpha-tocopherol removed.30 They found that tocopherol-free rice bran tocotrienol had anti-lipidemic effects, simultaneously reducing cholesterol by 15% and triglycerides by 28%. Further, tocotrienol upregulated both carnitine palmitoyltransferase by 67% (responsible for triglyceride drop) and cytochrome P450 by 47% (responsible for cholesterol drop). When alpha-tocopherol was added to the tocotrienols, the coadministration abrogated the tocotrienols’ anti-lipidemic effects and decreased the presence of all tocotrienols in the liver by about 2.5-fold. Alpha-tocopherol on its own had almost no anti-lipidemic effects. MetS Clinical Studies: In several clinical studies with metabolic syndrome and diabetes patients, tocotrienol was shown to reduce the symptoms associated with the disease. Rice bran water solubles (270ppm of >90% tocotrienols) reduced hyperglycemia, glycosylated hemoglobin, and increased insulin levels, while rice bran fiber (30ppm of >90% tocotrienols) reduced hyperlipidemia in both type 1 and type 2 diabetics.89 In another large clinical study, vitamin E intake from diet was associated with reduced risk of type 2 diabetes.90 In patients with type 2 diabetes, progression of atherosclerosis is more rapid, and 80% of patients die of atherosclerotic events. In addition, LDL-lowering therapies normally prescribed for patients with diabetes have many side-effects, creating a need for alternative treatments. Tocotrienols, which have no known side-effects, were shown to decrease serum total lipids by 23%, total cholesterol by 30%, and LDL-cholesterol by

42% (from 179mg/dL to 104mg/dL) within 60 days in type 2 diabetics. 91 Clinical studies have shown that tocotrienols – when taken apart from alpha-tocopherol (due to interference issues25) – lower total cholesterol, LDL, and triglyceride levels between 15-20%. 13 Further, a daily dose of 250mg tocotrienols (without tocopherols) lowered C-reactive protein and other inflammatory markers between 35-60%.12 Combinations with other anti-inflammatory ingredients, such as quercetin, resveratrol, and B-vitamins can synergize with tocotrienols’ cardiometabolic benefits, as was shown in clinical trials.62, 63 However, in patients with MetS on tocopherol-tocotrienol mixtures, cardiometabolic benefits were not observed22 nor was the chemotaxis/platelet aggregation reduced.92 Non-Alcoholic Fatty Liver Disease (NAFLD): An ailment closely associated with obesity and MetS is NAFLD, which occurs when excess fat is stored in the liver. Based on findings by the National Institutes of Health, NAFLD affects 30-40% of US adults, and treatment is limited to diet and exercise. To examine the effects of tocotrienol on fatty liver disease, a 12week randomized, double-blind, placebo-controlled study was conducted with 71 NAFLD patients.15 Significant improvements in liver biomarkers indicative of hepatic stress reduction were evident after 12 weeks, with decreases of 15-16% in ALT and AST. Furthermore, significant decreases in triglycerides (11%), MDA (14%), and hs-CRP (18%) were indicative of reduced inflammation and are consistent with results of previous clinical trials conducted with DeltaGold® in hypercholesterolemic subjects. Notably, the fatty liver index (FLI) score decreased a significant 11%, suggesting intrahepatic fat reduction. During the 12-week treatment period, patients in the tocotrienolsupplemented group lost an average of 9.7 pounds.

Tocotrienol’s Protective Effect on Skin

Vitamin E, and in particular delta- and gamma-tocotrienol and tocotrienol-rich fractions (TRF), have been shown to be superior protectors against environmental stressors such as UV-irradiation of the skin.94 TRF have significantly higher potency than alpha-tocopherol, and are effective against protein oxidation and lipid peroxidation at low concentrations.95,96 Normally, UV-irradiation destroys the antioxidants in the skin, but prior application of TRF to mouse skin preserved the vitamin E.97 Also, the largest fraction of vitamin E was found in the subcutaneous layer of the skin, which shows that applied vitamin E penetrates rapidly through the skin,98 and therefore combats oxidative stress induced by UV or ozone.99 In addition, delta- and gamma-tocotrienol have been shown to reduce inflammation, 61, 100, 101 and are potent skin whitening agents via reduction of tyrosinase activity, while also blocking UV-induced melanogenesis.102-104 Delta-tocotrienol has the greatest sun protection factor (SPF) of the tocotrienol isomers at SPF 5.5.104 Methicillin-resistant Staphylococcus aureus (MRSA) is a bacterium responsible for several difficult-to-treat infections in humans, and also a common reason for skin and soft-tissue infections worldwide. This is a particular concern in hospice and hospital settings. For the first time, a study in animals showed that DeltaGold® tocotrienol can be an immunomodulator to help fend off infections and improve wound repair.105 In the prevention model, the MRSA-infected animals were

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The Science Behind Vitamin E Tocotrienols

administered tocotrienol, antibiotics, or tocotrienol plus antibiotics, and compared to infected controls (no treatment). Tocotrienol was given orally to animals eight days before wound infection and antibiotics were given intraperitoneally two days following infection. Other conditions were the same for all groups. The results showed that tocotrienol reduced bacterial load by a factor of 10, antibiotics by 1,000 times, and tocotrienols in combination with the antibiotic by 10,000. This suggests that, while antibiotics were effective as expected, tocotrienol potentiated the antibiotics’ bacterial kill by reducing bacterial load in animals. Responsible for potentiating the antibiotic properties, at least in part, was tocotrienol’s effect on natural killer cells. Although the number of natural killer cells remained unchanged throughout the treatments, their activity was dramatically improved in parallel to decreased bacterial load with a ranking order of: tocotrienol + antibiotics > antibiotics >> tocotrienol > control. In addition to being a potent immune adjuvant to antibiotics, tocotrienol had dramatic wound healing effects. Compared with antibiotics, which showed adverse effects in wound healing, tocotrienol was 2-6 times more effective in improving wound healing biomarkers, indicating efficacy in wound healing in the order of: tocotrienol > tocotrienol + antibiotics >> control > antibiotics. The authors of the study speculated that DeltaGold® could work to reduce bacterial load and improve wound healing due to a local protection and regenerative action because of its accumulation in the skin.

Eye Health

Vitamin E has long been regarded as a beneficial nutrient to support eye health. It was included in the original Age-Related Eye Disease Study (AREDS), as well as in AREDS2, which also examined addition of lutein, zeaxanthin, DHA and EPA. Vitamin E has since become a staple ingredient in the standard AREDS formula as well as other eye health formulations. While the AREDS study investigated only the alphatocopherol form of vitamin E, new studies suggest tocotrienol deserves a closer look. Tocotrienols may have application in improving eye conditions, especially those of angiogenic nature. In macular degeneration, central vision loss occurs due to abnormal neovascularization in the retina beneath the macula, and leaking blood vessels push up the retina. Similarly, diabetic retinopathy is caused by damage to blood vessels of the retina, and is the leading cause of adult blindness in the West. In both cases, angiogenesis – the aberrant growth of new blood vessels – is to blame. Recent studies found tocotrienol to be a superb anti-angiogenic agent, with delta-tocotrienol being the most potent in reducing angiogenesis dose-dependently.93, 107 The Glaucoma Research Foundation estimates that over 3 million Americans have glaucoma, a condition where patients present with raised intraocular pressure that may lead to permanent damage of the optic nerve and can cause blindness. Tocotrienols reduce scarring of the Tenon’s fibroblast that occurs during glaucoma filtration surgery.108 As a potent antioxidant, tocotrienol accumulates in the eye to

combat cataract development,109 one of the most common eye problems of the aging population. A Malaysian study tested the effect of tocotrienols from annatto (DeltaGold®) on cataract formation in galactosemic rats.110 In the study, topically applied tocotrienol at 0.01-0.05% delayed the onset and progression of cataract by reducing lenticular oxidative and nitrosative stress. In a follow-up study on diabetic rats, tocotrienols were applied topically via eye drops at a low concentration of 300ppm.111 Diabetic rats that did not receive tocotrienols quickly progressed to stage 3 and 4 cataracts, whereas for those receiving the tocotrienols progression was arrested. Notably, tocotrienol restored lens transparency to normal. The anti-cataract effect of tocotrienol may in part be attributed to the vitamin’s anti-inflammatory action and ability to reduce oxidative stress, while mitochondrial function was improved.

SUMMARY

Most studies published to date, especially in the last decade, point clearly to delta- and gamma-tocotrienol as the key isomers for vitamin E health benefits in reversing chronic conditions or aging maladies. This has been shown for reducing cholesterol and triglycerides, with implications for CVD9, 10, 107 and diabetes,5, 107, 118 and blood hypercoagulation/ chemotaxis, with implications for arteriosclerosis.14, 66, 76 These effects are in addition to tocotrienol’s known power as lipidsoluble antioxidant.56, 99 Compared to other major sources of tocotrienol, annatto has a distinct advantage in lowering lipids and enhancing cellular health without the interferences that would be expected from alpha-tocopherol. With all these positive reports, annatto tocotrienol is an excellent candidate for addressing chronic conditions, particularly those associated with aging. Deltatocotrienol is considered to be the 21st Century vitamin E.

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107. Miyazawa, T., et al., Antiangiogenic and anticancer potential of unsaturated vitamin E (tocotrienol). J Nutr Biochem, 2009. 20(2): p. 79-86. 108. Tappeiner, C., et al., Antifibrotic effects of tocotrienols on human Tenon’s fibroblasts. Graefes Arch Clin Exp Ophthalmol, 2009. 109. Tanito, M., et al., Distribution of tocopherols and tocotrienols to rat ocular tissues after topical ophthalmic administration. Lipids, 2004. 39(5): p. 469-74.

110. Abdul Nasir, N.A., et al., Effects of topically applied tocotrienol on cataractogenesis and lens redox status in galactosemic rats. Mol Vis, 2014. 20: p. 822-35.

111. Abdul Nasir, N.A., et al., Reduction of oxidative-nitrosative stress underlies anticataract effect of topically applied tocotrienol in streptozotocin-induced diabetic rats. PLoS One, 2017. 12(3): p. e0174542.

112. Rink, C., et al., Tocotrienol vitamin E protects against preclinical canine ischemic stroke by inducing arteriogenesis. J Cereb Blood Flow Metab, 2011. 31(11): p. 221830. 113. Kuhad, A. and K. Chopra, Attenuation of diabetic nephropathy by tocotrienol: involvement of NFkB signaling pathway. Life Sci, 2009. 84(9-10): p. 296-301.

114. Anderson, S.L., J. Qiu, and B.Y. Rubin, Tocotrienols induce IKBKAP expression: a possible therapy for familial dysautonomia. Biochem Biophys Res Commun, 2003. 306(1): p. 303-9.

115. Anderson, S.L. and B.Y. Rubin, Tocotrienols reverse IKAP and monoamine oxidase deficiencies in familial dysautonomia. Biochem Biophys Res Commun, 2005. 336(1): p. 154-6. 116. Nur Azlina, M.F., et al., Tocotrienol Attenuates Stress-Induced Gastric Lesions via Activation of Prostaglandin and Upregulation of COX-1 mRNA. Evid Based Complement Alternat Med, 2013. 2013: p. 804796.

117. Rodzian, M.N., et al., Pure tocotrienol concentrate protected rat gastric mucosa from acute stress-induced injury by a non-antioxidant mechanism. Pol J Pathol, 2013. 64(1): p. 52-8. 118. Zaiden, N., et al., Gamma delta tocotrienols reduce hepatic triglyceride synthesis and VLDL secretion. J Atheroscler Thromb, 2010. 17(10): p. 1019-32. 119. Sylvester, P.W. and S.J. Shah, Mechanisms mediating the antiproliferative and apoptotic effects of vitamin E in mammary cancer cells. Front Biosci, 2005. 10: p. 699-709.

120. Tan B and Trias A. Emerging Cancer Research in Vitamin E Tocotrienol. Anti-Aging Therapeutics, Ed, R Klatz & R. Goldman. Vol 15 Ch 20m 227-239.

90. Montonen, J., et al., Dietary antioxidant intake and risk of type 2 diabetes. Diabetes Care, 2004. 27(2): p. 362-6.

91. Baliarsingh, S., Z.H. Beg, and J. Ahmad, The therapeutic impacts of tocotrienols in type 2 diabetic patients with hyperlipidemia. Atherosclerosis, 2005. 182(2): p. 367-74. 92. Gan, Y.L., et al., Effect of palm-based tocotrienols and tocopherol mixture supplementation on platelet aggregation in subjects with metabolic syndrome: a randomised controlled trial. Sci Rep, 2017. 7(1): p. 11542.

93. Shibata, A., et al., delta-Tocotrienol suppresses VEGF induced angiogenesis whereas alpha-tocopherol does not. J Agric Food Chem, 2009. 57(18): p. 8696-704.

94. Traber, M.G., et al., Diet-derived and topically applied tocotrienols accumulate in skin and protect the tissue against ultraviolet light-induced oxidative stress. Asia Pac J Clin Nutr, 1997. 6(1): p. 63-67. 95. Kamat, J.P., et al., Tocotrienols from palm oil as effective inhibitors of protein oxidation and lipid peroxidation in rat liver microsomes. Mol Cell Biochem, 1997. 170(1-2): p. 131-7. 96. Mutalib, M.S.A., H. Khaza’ai, and K.W.J. Wahle, Palm-tocotrienol rich fraction (TRF) is a more effective inhibitor of LDL oxidation and endothelial cell lipid peroxidation than alpha-tocopherol in vitro. Food Res. Int., 2003(36): p. 405-413. 97. Weber, C., et al., Efficacy of topically applied tocopherols and tocotrienols in protection of murine skin from oxidative damage induced by UV-irradiation. Free Radic Biol Med, 1997. 22(5): p. 761-9.

98. Traber, M.G., et al., Penetration and distribution of alpha-tocopherol, alpha- or gamma-tocotrienols applied individually onto murine skin. Lipids, 1998. 33(1): p. 87-91. 99. Packer, L., S.U. Weber, and G. Rimbach, Molecular aspects of alpha-tocotrienol antioxidant action and cell signalling. J Nutr, 2001. 131(2): p. 369S-73S.

100. Qureshi, A.A., et al., delta-Tocotrienol and quercetin reduce serum levels of nitric oxide and lipid parameters in female chickens. Lipids Health Dis, 2011. 10: p. 39. 101. Yam, M.L., et al., Tocotrienols suppress proinflammatory markers and cyclooxygenase-2 expression in RAW264.7 macrophages. Lipids, 2009. 44(9): p. 787-97.

102. Michihara, A., et al., Delta-tocotrienol causes decrease of melanin content in mouse melanoma cells. J Health Sci, 2009. 55(2): p. 314-318.

103. Michihara, A., et al., Effect of delta-tocotrienol on melanin content and enzymes for melanin synthesis in mouse melanoma cells. Biol Pharm Bull. 33(9): p. 1471-6. 104. Yap, W.N., et al., Gamma- and delta-tocotrienols inhibit cutaneous melanosis (hallmark of melanoma) by suppressing constitutive and UV-induced tyrosinase

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WHAT TO LOOK FOR IN A REGENERATIVE MEDICINE MANUFACTURER Authors: Monica Vazquez, PhD; Jessica Sanchez, BS; Cheyenne Ziegler, BS; Erin Sairafe, MS; Ernesto Gutierrez, MD Contact: m.vazquez@liveyon.com (844) 548-3966

The use of regenerative medicine products is on the rise.

Where do the cells come from?

Stem cells are considered the next frontier in regenerative

• Products should be tested to ensure the absence of

The FDA has set standards for isolating and processing

This is a 14-day evaluation, testing for aerobic, anaerobic

medicine, with great potential for repair and regeneration.

microorganisms. Stringent standards are set by USP71. and fungal microorganisms, using two different culture

cells, but these guidelines are minimum standards.

media. Testing should be performed by an independent

Physicians should be aware of additional criteria to consider

third-party, CLIA-certified laboratory to avoid any bias.

--- to ensure that the safest, most consistent and efficacious products are used.

• The maternal donor must be tested for a variety of infectious agents. The donor’s blood should be collected within a day or two of the birth. Testing should be

Where do the cells come from?

performed by a CLIA-certified laboratory. Tests required

• Cord blood should come from healthy, full term births.

by the state of California are listed in Table 1.

There must be no risk to the mother or baby. Cord blood

can be collected from the umbilical cord and placenta, after the baby is safely delivered.

1: Cord blood donors must be tested for the following infectious diseases:

• The mothers who donate cord blood must give fully

informed, written consent. They should be unpaid, volunteer donors.

• Cells should be isolated from fresh (not frozen) cord blood and processed within specific timelines to assure

and 2

(Cytomegalovirus)

Hepatitis B

Nile Virus

human T cell lymphotropic virus)

consistent results.

• While embryonic and fetal stem cells have ethical

• The maternal donor must undergo extensive screening for health and behavioral risks, including travel to foreign

concerns, cord blood cells do not have these issues.

countries. This is to screen out possible exposure to Zika

• For regulatory and safety concerns, cord blood should be

virus, Creutzfeldt-Jakob disease, etc. Family health history

donated within the United States.

• Umbilical cord blood is a rich source of stem cells. While

must also be collected.

• The manufacturer must be registered with the FDA.

stem cells can be isolated from adult sources (bone marrow,

• The donated cord blood should be traceable from the

cells. In addition, adult stem cells have undergone a lifetime

and back again to the manufacturer. Information must be

fat, peripheral blood), there are fewer and less potent stem of DNA damage and have shortened telomeres.

ANTI - AGING MEDICAL NEWS

donor, to the cellular product manufacturer, to the recipient communicated using a HIPPA-compliant procedure.

• SPRING 2019

WHAT TO LOOK FOR IN A REGENERATIVE MEDICINE MANUFACTURER

• Equipment inside the clean room must be designed to

generate little or no air contamination. This means many

Processing Environment

common materials such as paper, pencils, and natural fibers

• Cells should be isolated in a clean room dedicated to the preparation of a single product.

• The clean room must be built, monitored and most

are excluded.

• There must be detailed protocols (“SOP” or “Standard

Operating Procedures”) for entry and exit from the clean

importantly maintained to ensure extremely low levels of

room, and for processing the cellular product.

particulates (dust, airborne organisms, vaporized particles, etc.). A routine environmental monitoring program must be in place.

• Entry and exit should be through an “air lock” or “air

Processing Environment • Each production lot should have step-by-step

documentation of the isolation process (i.e. batch record).

shower”. Personnel must wear clean room suits including:

Any deviations should be documented and investigated

full-body coveralls, face masks, booties and hoods.

before the release of the affected product. Quality Systems

must be implemented to prevent unreleased products

• Monitoring should include “dynamic readings” and “static

readings”. Dynamic readings take place while operations

from distribution.

It includes particulate counts and

• Cells must be isolated with a validated process to ensure

and on personnel. (Petri dishes serving as “settle plates” and

• Only experienced technicians who are well-trained in

are in progress.

measurements of microorganisms in the air, on surfaces, “touch plates” should be included). Static readings assess the quality of the air in the clean room, operating as the original building specifications.

• Air should be filtered and constantly recycled through

high-efficiency HEPA filters according to build standards,

a consistent product.

aseptic techniques should process and analyze cells.

• Quality control and quality assurance (QC/QA) standards must be in place.

• Clinical-grade equipment should be used instead of research-grade equipment. For example, instead of a

i.e. ISO 6 or 7. There should be a positive air flow, this

bench-top cell counter, a hospital-grade hematology

ensures that air can only flow out (and prevents entry of

analyzer should be used. The commonly used Trypan Blue

unfiltered air).

stain should not be used as it is not accurate or appropriate

for any product that contains any form of blood (i.e. tissue,

• Access to the clean room must be limited to personnel

that understand methods of use, gowning and work flow.

Personnel must test clean, according to built-in standards,

and blood related products).

• Ideally, processing should not include any raw materials

that are detrimental to the health of the cells. For example,

to work in the clean room.

density gradient medium (e.g. Ficoll, Lymphoprep) can be avoided through the use of alternative methods.

• A cleanroom should undergo weekly cleaning and disinfection by a dedicated contractor. Different cleaning agents should be used in cycles to avoid resistant

• The processing should be a “closed system” as much as possible. This means using sterile docking devices to

microorganisms.

connect tubing and transfer cells between blood bags and

• The clean room and all equipment, (e.g. biosafety cabinets)

should have routine inspections, calibrations and validation of their proper function.

• The clean room should be maintained at ISO 7 standards (at

minimum). The biological safety cabinets within the clean

other containers.

• Cell counts should include the percentage of live cells, a CBC, and differential count of WBC.

• No detectable RBC should be present, this prevents ABO incompatibility as a potential issue (figure 2).

room should be maintained at ISO 5 standards (at minimum).

• Cells should be frozen in a DMSO-free cryopreservative,

records of such at minimum one time per year.

• Processing should be routinely monitored, through

All equipment within this area should be calibrated with

to avoid potential allergic reactions.

ANTI - AGING MEDICAL NEWS

• SPRING 2019

WHAT TO LOOK FOR IN A REGENERATIVE MEDICINE MANUFACTURER

rigorous testing of manufactured lots of cells for postthaw viability, growth factor and cytokine content, and cell surface markers (flow cytometric analysis of CD markers. Figure 3 is an example of an evaluation of cytokine content by ELISA. All testing should be completed on final product that will be distributed for use.

SELECTED REFERENCES

9. Y. Y. Lipsitz, N.E. Yonatan, N.E. Timmins, P. W. Zandstra, Quality cell therapy manufacturing by design Nat Biotechnology 34, 393–400 (2016) 10. E. A. Rayment, D. J. Williams, Concise Review: Mind the Gap: Challenges in Characterizing and Quantifying Celland Tissue-Based Therapies for Clinical Translation Stem Cells, 996-1004 (2010)

Acknowledgements: Thanks to Drs. Rafael Gonzalez and Toai Nguyen for their insightful comments.

1. K. K. Ballen, E. Gluckman, H. E. Broxmeyer, Umbilical cord blood transplantation: the first 25 years and beyond. Blood 122, 491-498 (2013).

Author Biographies

2. S. Roura, J. M. Pujal, C. Galvez-Monton, A. Bayes-Genis, The role and potential of umbilical cord blood in an era of new therapies: a review. Stem Cell Res Ther 6, 123 (2015).

Monica Vazquez, PhD is a Regulatory Officer at Liveyon Labs. Her thesis work focused on the role of cytokines in hematology and Immunology.

3. P. Damien, D. S. Allan, Regenerative Therapy and Immune Modulation Using Umbilical Cord Blood-Derived Cells. Biol Blood Marrow Transplant 21, 1545-1554 (2015). 4. N. H. Riordan, K. Chan, A. M. Marleau, T. E. Ichim, Cord blood in regenerative medicine: do we need immune suppression? J Transl Med 5, 8 (2007). 5. C. Basford, N. Forraz, C. McGuckin, Optimized multiparametric immunophenotyping of umbilical cord blood cells by flow cytometry. Nat Protoc 5, 1337-1346 (2010). 6. E. D. Quinley, J Schwartz. Chapter 89. Quality and Regulatory Issues in Cellular Therapy. In: Transfusion Medicine and Hemostasis (Third edition), Elsevier. Edited by: B. H. Saz, D. H. Hillyer and M. R. Gil 2019 pages 543551 7. 21 C.F.R. §210 Current Good Manufacturing Practice In Manufacturing, Processing, Packing, Or Holding Of Drugs; General

8. 21 C.F.R. §211 Current Good Manufacturing Practice For Finished Pharmaceuticals

Cheyenne Ziegler is a Laboratory Technician with a BS in Biological Sciences and an Emphasis on Cell and Molecular Biology. She has 5+ years of laboratory experience. Jessica Sanchez, BS is a Laboratory Technician at Liveyon Labs. Ms. Sanchez has more than four years of experience producing regenerative cell products. Erin Sairafe, MS is Chief Regulatory and Compliance Officer at Liveyon Labs. She has over 15 years’ experience in laboratory, regulatory, quality, and compliance affairs. Ernesto Gutierrez, MD is the Chief Operating Officer at Liveyon Labs. Dr. Gutierrez has a 10+ year history of leading medical teams and researchers, developing innovative treatments for autoimmune disorders, as well as orthopedic and sports medicine conditions.

ANTI - AGING MEDICAL NEWS

• SPRING 2019

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ANTI - AGING MEDICAL NEWS

• SPRING 2019

PRODUCT ANNOUNCEMENTS

Annatto-E™ is a unique tocopherol-free, tocotrienols-only product, featuring tocotrienols sourced from the annatto tree, containing 100% tocotrienols. Commercial vitamin E supplements are typically rich in tocopherols and low or absent in tocotrienols; however, tocotrienol fractions have unique beneficial effects across a variety of tissues that make them desirable for supporting many aspects of health: - Cardiovascular health & a healthy lipid profile / - Antioxidant status / - A healthy inflammatory response / - Bone mass, skin and eye health / - Anti-proliferative effects

(Chocolate & Vanilla) Booth #104

Erchonia Corporation Ph: 866-551-7847 www.erchonia.com

PRODUCT ANNOUNCEMENTS

BPC-157

Booth #337

Booth #106 Integrative Peptides, founded in 2018 with one purpose: to offer peptide supplements that meet the highest standards of quality, safety, and value. Integrative Peptides continues to be the only company selling an authentic BPC-157 supplement. We are proud to have brought the price of BPC-157 down by an order of magnitude. We encourage our customers to ask any potential competitors two questions: how much does it cost, and does it contain actual BPC-157?

Integrative Peptides, LLC Ph: 888-699-4150 www.integrativepeptides.com

Curacen Essence is an anti-aging treatment. It represents extract of Human Placenta Extract (HPE) -a rich source which makes HPE highly valuable and sought after. Curacen Essence is taking advantage of a smaller molecular weight (<200 Dalton). JBP Has developed Curacen essence for specific applications. Smaller molecular weight is expected to help penetrate deep into the skin. JBP has also been investing and researching medical devices which have synergy with our various product lines: Ultra-thin Walled needle/ cannula, PDO thread and HA filler. And JBP successfully enlarged the needle ‘ s diameter allowing doctors to use thinner gauge needles for cosmetic treatment injections.

Japan Bio Products Co., Ltd Ph: 81368049643 jbpglobal.placenta.co.jp

NanoZeolite MD

Estrofactors®

Booth #804

Booth #517

MD Prescriptives’™ NanoZeolite MD™ is a water suspension of natural food-grade zeolite sourced from uncontaminated clinoptilolite clay. The primary bioactive ingredient found in NanoZeolite MD™ is a silicate mineral complex. Particle size ranges span the upper nanometer to lower micrometer size ranges, rendering the absorption powers of the “micronized” zeolite particles ‘extremely bioactive’. This enables cost-effective quick removal of noxious body loads containing harmful xenobiotics, heavy metals, radionuclides, exoprotein/endotoxins, and even

EstroFactors® - For women, there is a constant cycle of hormonal fluctuations that may play a role in day-to-day mood, energy, weight management, and other factors. Lifestyle choices may compound changes in hormones-impacting the balance that is important for overall health. That‘s why EstroFactors features key phytonutrients including bioavailable BioResponse DIM®, which may support the 2-hydroxy estrone pathway and promote healthy estrogen metabolism as well as help support breast comfort during normal estrogen cycles in women.*

accomplishes microbiota purification.

MD Prescriptives, LLC Ph: 877-963-7737 www.mdprescriptives.com

JBP Curacen Essence and JBP Nanoneedle

Metagenics

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

ANTI - AGING MEDICAL NEWS

• SPRING 2019

IvyGene Test Booth #1022 The IvyGene test is a highly accurate blood test that confirms cancer presence and gives measurable information about cancer. The IvyGene test utilizes advanced sequencing techniques to identify cancer presence at the time of testing.

Laboratory for Advanced Medicine Ph: 844-489-4363 www.ivygenelabs.com

MegaMycoBalance Booth #623 MegaMycoBalance is formulated with undecylenic acid and bee propolis to support healthy yeast and fungal balance in the body. Undecylenic acid is an organic fatty acid derived from castor bean oil that supports a healthy balance of yeast in the gut. Pathogenic and opportunistic yeasts, like Candida albicans, spread quickly through the intestines by creating tiny roots, or hyphae, that can become deeply embedded in the intestinal wall. This embedment of hyphae makes it very difficult to control yeast overgrowth in the body. MegaMycoBalance can help support a healthy yeast balance in the gut by targeting these roots.

Microbiome Labs

Ph: 904-940-2208 www.microbiomelabs.com/products/ megamycobalance/

ImmunoG Chocolate Delight

Vitamin D3 & K2 (MK7) Drops

InflammaCORE Booth #311

Booth #310

Booth #900 InflammaCORE is an advanced nutritional formula built to address immune challenges, maintain normal inflammatory balance and strengthen gastrointestinal barrier function.

NuMedica

Ortho Molecular Products

Ph: 800-869-8100 www.numedica.com/ImmunoG

Procedural Kit Booth #310 The procedural accessory kit is sterile and latex free containing all the supplies required to perform the pellet insertion procedure including drape, prep swabs, syringes, needles, and dressings. Contents: 1 - CSR Wrap, 1 - Plastic Posi-Grip Forceps, 1 - 24” x 18” Blue Drape w/4” Fen. & Adh. Strip, 1 - Transparent Dressing w/ID Label, 1 - .25” x 1.5” Tape Strips 6/CD, 2 4” x 4” Non-Woven Dressings, 2- 10cc Luer Lock Syringes, 1 - 18 Gauge x 1.5” Needle, 2 - 21 Gauge x 2” Needles, 1 - Lodopher PVP Swabstick, 1 - 1 oz. Medicine Cup, 2 - 2” x 2” Non-Woven Dressings, 2 - Alcohol Prep Pads

Pellecome LLC

Ph: 888-773-9969 www.pellecome.com

Vitamins D3 & K2 (MK7) liquid drops. Pharmaceutical quality, all natural, no artificial flavorings, non-GMO. No taste! Each bottle contains: D3 1,000 IU & K2 25 mcg. Supplements BHRT and assists in hormone stabilization*. Easy to use: 1 dropper-full every day. Can be added to your favorite meal or drink. Easy to carry, 30-day supply. Dose as recommended by physician.

Pellecome LLC

Ph: 800-332-2351

Ph: 888-773-9969 www.pellecome.com

www.orthomolecularproducts.com

PlusCBD Oil™ Total Plant Complex Softgels Booth #1018

P2P Patient Portal Booth #101 The P2P Patient Portal has a whole new

A quick and easy solution for an active lifestyle, PlusCBD Oil™ Total Plant Complex Softgels contain a complex matrix of phytocannabinoids and natural plant nutrients from agricultural hemp to keep the body balanced on the go.

look and feel that incorporates responsive technology; this means your patients can access the portal on all desktop, tablet and mobile devices. Plus, we’ve simplified navigation and enhanced our questionnaire, making it easier than ever

Made with our Total Plant Complex - No artificial dyes or fragrances - Non-GMO & Gluten Free - 100% Vegetarian

for patients to engage with your practice.

PlusCBD Oil™ by CV Sciences Ph: 855- PLUS-CBD (758-7223) www.pluscbdoil.com

ANTI - AGING MEDICAL NEWS

• SPRING 2019

PRODUCT ANNOUNCEMENTS

ImmunoG™Chocolate Delight is a natural bovine colostrum powder formula collected within 24 hours after birthing. This formula is a whole food providing IgG and colostrum polypeptides. It also supplies protein, immune factors, growth factors, vitamins and minerals to ensure health and vitality naturally.* Numerous scientific studies have shown that colostrum supports the human immune and cytokine systems.* This formula is carefully processed for maximum biological activity, colostrum polypeptides content (CPPs), and is antibiotic-free.*

Power2Practice

Ph: 800-590-7459 www.power2practice.com

PRODUCT ANNOUNCEMENTS

Premier Fermented Greens Capsules

PRO2 Booth #228

Booth #103 Premier Fermented Greens provides a highly bioavailable, fermented vegetarian prebiotic blend of the most exquisite greens that also includes LIVE PROBIOTICS! This extraordinary, gluten free, fermented plant blend features a prebiotic greens blend of: Fermented Organic Barley Grass, Fermented Organic Oat Grass, Fermented Organic Kale, Fermented Organic Chlorella plus a garden blend of 100% fermented vegetarian greens air-dried at a low temperature to deliver naturally occurring vitamins and minerals to promote the body’s natural alkalinity.

The PRO2 delivers 10,000 RPM of powerful, pain relieving, tension removing, revitalizing vibration therapy. The PRO2 is intended for various medical purposes such as relaxing muscles and relieving minor aches and pains quickly. • FDA Registered Class 1 Medical Device • 5 Built-in treatment surfaces, each creating a different effect • Uniquely suited for extremities –arms, wrists, hands, legs, ankles, feet • Balanced mechanism reduces vibration at handle • New 3-Year Limited Warranty

Premier Research Labs

Rapid Release Technologies

Ph: 800-325-7734 www.prlabs.com

Ph: 949-415-4778 www.rapidreleasetech.com

CBD Inhalation Pen Plus Broad Spectrum Terpenes 275mg/.5ml Booth #437 Remedio Laboratories is bringing pharmaceutical and medical device development expertise to address unmet patient and clinician needs for high quality cannabidiol. Our products are independently batch tested for purity, pesticides, heavy metals, microbials and residual solvents. Made for healthcare professionals, by healthcare professionals. CBD Inhalation Pen Plus Broad Spectrum Terpenes 275mg/.5ml delivers roughly 6mg of CBD per dose in an inconspicuous way. Our products are completely organic, THC/soy free, and vegan friendly.

Remedio Laboratories Ph: 310-560-0017 www.remediolabs.com

Neuro-Protect Px Booth #434

CBD Mist Plus Broad Spectrum Terpenes 550mg/10ml Booth #437 Remedio Laboratories is bringing pharmaceutical and medical device development expertise to address unmet patient and clinician needs for high quality cannabidiol. Our products are independently batch tested for purity, pesticides, heavy metals, microbials and residual solvents. Made for healthcare professionals, by healthcare professionals. CBD Mist Plus Broad Spectrum Terpenes 550mg/10ml delivers roughly 12mg of CBD per dose in a convenient sublingual spray. Our products are completely organic, THC/soy free, and vegan friendly.

Remedio Laboratories Ph: 310-560-0017 www.remediolabs.com

NeuroLab HPA-G Complete Profile

Neuro-Protect Px supports neuronal health and balances the neurotransmitters which have a positive effect on brain health, memory, and cognition. The Vermont-grown, certified organic lion’s mane mushroom provides terpenoids (hericenones and erinacines), which cross the blood-brain barrier. Lion’s mane provides neuroprotection by supporting the production of nerve growth factor (NGF) activity, which is responsible for healthy nerves and supports myelin sheath generation. The certified organic Cordyceps contains 25% beta glucan, and 2% cordycepin which supports healthy immune and acetylcholine activity.

NeuroLab launches its newest laboratory profile which tests for comprehensive neurotransmitter and hormone imbalances. Using a non-invasive, take-home collection kit, you can measure: 7 neurotransmitters (Serotonin, GABA, Dopamine, Glutamate, Norepinephrine, Epinephrine & PEA), 2 adrenal hormones (Cortisol & DHEA-s), and 5 sex hormones (Estrone, Estradiol, Estriol, Progesterone & Testosterone). Open a window into your patients’ neuroendocrine function and gain insight into their HPA axis function. Test is fully reimbursable by Medicare.

Restorative Formulations

Sanesco International, Inc.

Ph: 800-420-5801 www.restorative.com

ANTI - AGING MEDICAL NEWS

• SPRING 2019

Booth #836

Ph: 866-670-5705 www.sanescohealth.com

Hemp Oil Complex Booth #817

Suneva Medical HD PRP and PureGraft Booth #1017

Hemp Oil Complex™ is a unique formulation of ingredients, combined to provide a 3-in-1 benefit for the whole body – supporting the endocannabinoid system, inflammation response resolution pathways, and endogenous anti-oxidant pathways.

Ph: 800-558-8740 www.standardprocess.com

Suneva Medical

Ph: 888-278-3345 www.sunevamedical.com

ANTI - AGING MEDICAL NEWS

• SPRING 2019

PRODUCT ANNOUNCEMENTS

Standard Process Inc. Research UG

Privately-held regenerative aesthetics company, Suneva Medical, develops, manufactures and commercializes innovative products, including flagship brand, Bellafill®. Building out their regenerative aesthetics product portfolio in 2019, Suneva Medical added an innovative PRP technology and Puregraft, the most predictable fat graft in the market. For more information, visit www.sunevamedical.com.

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The Microbiome Labs three-layer system of total gut restoration was uniquely designed to support a healthy gut microbiome and intestinal barriers.

Donâ&#x20AC;&#x2122;t forget to stop by the Microbiome Labs booth at the upcoming 2019 A4M trade shows.

To learn more: Contact us at info@microbiomelabs.com or visit our website at www.microbiomelabs.com

The Human MicrobiomeGenome Connection in Aging By: Aicacia Young, RDN

According to the Human Microbiome Project (HMP) launched by the National Institute of Health, the human body contains roughly 25,000 human genes and over 3.3 million bacterial genes, outnumbering human genes 150 to 1. Not only are human genes outnumbered by bacteria, but human cells are also outnumbered – 10 trillion human cells versus 100 trillion bacterial cells. The HMP also reported that no two individuals have the exact same bacterial composition – not even twins. In fact, a twin study conducted in 2016 of 1,126 pairs of twins found that only 1.9-8.1% of the human microbiome is heritable.1 Another study investigating the microbiome-genome connection collected blood and stool samples from 1,046 Israeli adults from varying genetic populations. After analyzing the data, researchers concluded that host genetics only determined a very small fraction of the variability seen across various microbiomes. Instead, they found that the environment plays a much larger role in shaping the microbiome and influencing disease pathogenesis. Furthermore, they found that combining human genetic data with microbiome profiles significantly improved their ability to accurately predict human phenotypes, compared to using genetic data alone. For instance, after accounting for environmental and genetic factors, the gut microbiome contributed to 36% of the variation between HDL cholesterol levels and 25% of the variation in body mass indices (BMI).2 These findings suggest that the environment is the primary factor in shaping the human microbiome, which has been connected in the onset of many chronic diseases. While the human genome was once believed to be the dictator of human health, surmounting evidence suggests that the gut microbiome may have the power to influence human genetics.

contains roughly 150 million units of DNA, known as a base pair. In white blood cells, for example, the length of telomeres usually ranges from 8,000 base pairs in newborns to 3,000 base pairs in adults and as low as 1,500 in elderly people. With every cell division, the average cell loses 30 to 200 base pairs from its telomeres. At this rate, healthy cells can normally divide about 50 to 70 times before they become senescent or die. This shortening process is known as telomere attrition and is considered a biomarker of the aging process. Additionally, alterations in genetic coding can cause telomeres to become dysfunctional, causing them to die prematurely.3 Aging is a natural process that can be characterized by chronic inflammation and telomeric attrition. In fact, there are many indications that chronic inflammation can directly cause telomere dysfunction through the nuclear factor kappa-B (NF-κB) signaling pathway – a pathway associated with chronic inflammation.4 NF-κB has been shown to regulate telomerase expression – an enzyme that counteracts telomere shortening by adding bases to telomere ends.5-6 Additionally, reactive oxygen species (ROS) produced in response to inflammation appear to affect telomeric DNA, trigger DNA damage pathways, and ultimately lead to cellular senescence.7-8 Furthermore, ROS have been shown to contribute to the overexpression of NF-κB in chronic inflammatory states, creating a self-perpetuating feedback loop.9 Lastly, researchers have demonstrated that chronic low-grade inflammation in mice is directly associated with ROS-mediated telomeric DNA damage and that this dysfunction can be resolved by reducing systemic inflammation.4, 7, 10

Genetics and Aging Within the nucleus of a cell, genes are arranged along double helix structures of DNA called chromosomes. At the ends of these chromosomes are stretches of DNA known as telomeres, which protect genetic data, similar to the plastic tips on shoelaces. Without telomeres, genetic information would be scrambled and lost during cell division. Yet, as cells divide, telomeres grow shorter and shorter in length. When telomeres become too short, the cell can no longer divide, and it becomes inactive or “senescent”. An entire chromosome

ANTI - AGING MEDICAL NEWS

• SPRING 2019

The Human Microbiome-Genome Connection in Aging

The Microbiome and Inflammation Telomeres shorten with age, and this shortening is considered a sign of aging. Chronic inflammation is a major driver of telomere shortening, in part by inhibiting telomerase. As it turns out, a dysfunctional microbiome is a major cause of the type of inflammation that disrupts telomere function. Within the gut microbiome is an inflammatory endotoxin known as lipopolysaccharide, or LPS. This endotoxin is a major component of the outer cell membrane of gramnegative bacteria residing in the gut. In fact, the 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 in their cell membranes and release it into the intestinal lumen upon bacterial cell death. This process happens quite frequently, as many bacteria die off during a meal, but LPS remains harmless inside the intestinal lumen. However, if LPS reaches the brush border and enters circulation, it can then trigger low-grade inflammation by activating the NF-κB signaling pathway. Once inside the circulatory system, LPS can trigger innate immune activation and subsequent inflammation anywhere in the body, resulting in a condition known as metabolic endotoxemia. Metabolic endotoxemia (ME) is a condition characterized by increased serum endotoxin levels during the first five hours following a meal. High levels of these circulating endotoxins can activate the NF-κB signaling pathway and trigger the release of pro-inflammatory cytokines like interleukin-6 (IL-6), interleukin-1-beta (IL-1 β), tumor necrosis factoralpha (TNF-α), and interferon-gamma (IFNγ). Considering its ability to trigger inflammation, metabolic endotoxemia could very well be the primary driver of most chronic illnesses plaguing the Western world since it can be triggered by eating. Furthermore, the causes of ME do not appear to be genetic or congenital, but rather environmental.11 New research indicates that meals that are high in saturated fat appear to be more damaging to the gut than meals containing unsaturated fats.12 When commensal gut bacteria use saturated fatty acids to form their outer membranes, they produce a more toxic form of LPS. In fact, coconut oil appears to be the most potent stimulator of LPS toxicity in the gut. However, unsaturated fatty acids appear to produce a neutral form of LPS, and omega-3 fatty acids appear to protect the intestinal lining by reducing the amount of LPS released into circulation.13 In addition to environmental influences, low-grade inflammation from ME can also be regulated by the gut microbiome. The fundamental aspects of gut health are increased microbial diversity and intact physical structures. Enhanced microbial diversity can increase the production of anti-inflammatory metabolites like short-chain fatty acids (SCFAs), which are necessary to rebuild healthy intestinal barriers. The best way to increase microbial diversity in the gut is through the supplementation of spore-based probiotics and a precision prebiotic.14-15 The major issue with traditional probiotics is that they cannot survive digestion in order to

colonize in the intestines. However, probiotic spores have the natural ability to survive the harsh gastric system and enter the intestines completely viable. To date, bacterial spores are the only strains that have been shown to heal intestinal permeability and treat metabolic endotoxemia. Probiotic spores were investigated in a university, doubleblind, and placebo-controlled trial to evaluate the ability of the Bacillus spores to reduce serum levels of LPS after a challenge meal.16 The treatment group showed a 45% reduction in serum LPS levels, while the placebo group showed a 32% increase in serum LPS. Collectively, the findings of this study demonstrate a 60% decrease in metabolic endotoxemia and a significant reduction of triglycerides and systemic inflammatory markers IL-6, IL-8, MCP-1, IL-1β and IL-12 following a 30-day period of probiotic supplementation. Gut model studies also indicate that Bacillus spores can increase the production of SCFAs by 38% and encourage the growth of butyrate-producing bacteria like Faecalibacterium prausnitzii and Akkermansia muciniphila.17 Prebiotic fibers like fructo-oligosaccharides (FOS), galactooligosaccharides (GOS), and xylo-oligosaccharides (XOS) can also help to increase microbial diversity by increasing the abundance of F. prausnitzii and A. muciniphila. A 2017 study published in the Journal of Nutritional Sciences found that oral supplementation of FOS derived from kiwifruit increased the abundance of F. prausnitzii by 100% in 4 weeks, while another study found that it increased A. muciniphila by 8,000% in as little as 5 weeks.18-19 XOS and GOS have been shown to significantly increase the abundance of Bifidobacterium spp. In as little as 7 days.20-21 With the addition of Bacillus spores and non-digestible precision oligosaccharides, the gut microbiome can be reconditioned to produce SCFAs that fortify the intestinal mucosa and epithelium. The intestinal mucosa is the key barrier that prevents toxins from entering into the basolateral layer. The inner mucosal barrier contains a protein called MUC2 that gives this layer its thick, gel-like quality. When the mucosa suffers from inadequate production of MUC2 mucin and inadequate viscosity, it fails to perform its barrier function and thus allows for the migration of lipopolysaccharide and other toxins into circulation. Increasing MUC2 mucin production can help prevent toxins from migrating towards the intestinal epithelial and triggering self-perpetuating lowgrade inflammation. Butyrate is a SCFA that feeds enterocytes and acts as one of the most potent stimulators of MUC2 mucin production, but a healthy mucosal barrier needs more than an ample supply of butyrate. Healthy intestinal barriers also require the essential the amino acid building blocks: L-threonine, L-serine, L-proline, and L-cysteine. These four amino acids have been shown to drastically increase MUC2 production and stimulate mucin synthesis in the colon, resulting in a thicker and healthier mucosal barrier.22 In conclusion, aging is driven by telomeric dysfunction which is driven by inflammation. Supplementation with Bacillus spores and precision prebiotics can modulate the microbiome and increase diversity of keystone strains, thereby increasing the production of SCFAs and mucin, as well as other protective metabolites. At this point, the addition of key amino acids

ANTI - AGING MEDICAL NEWS

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The Human Microbiome-Genome Connection in Aging

will provide the building blocks that support the necessary production of mucin.

In this way, you can help your patients can age more gracefully by repairing the gut. The significance of an effective probiotic and prebiotic in anti-aging medicine cannot be overstated.

References 1. Goodrich JK, et al. Genetic determinants of the gut microbiome in UK twins. Cell Host & Microbe. 2016; 19(5):731-743. 2. Rothschild D, et al. Environment dominates over host genetics in shaping human gut microbiota. Nature. 2018; 555:210-215. 3. Kordinas V, et al. The Telomere/Telomerase System in Chronic Inflammatory Diseases. Cause or Effect? Genes (Basel). 2016;7(7):60. 4. Jurk D, et al. Chronic inflammation induces telomere dysfunction and accelerates aging in mice. Nat Commun. 2014;2:4172. 5. Zhang J, et al. Aging and the telomere connection: An intimate relationship with inflammation. Ageing Res Rev. 2016;25:55–69. 6. Ghosh AS. Telomeres and inflammation: Rap1 joins the ends? Cell Cycle. 2010;9:3834–3835. 7. Correia-Melo C, et al. Telomeres, oxidative stress, and inflammatory factors: partners in cellular senescence? Longev Healthspan. 2014;3:1-9. 8. Rai P. Oxidation in the nucleotide pool, the DNA damage response and cellular senescence: Defective bricks build a defective house. Mutat Res. 2010;703:71–81. 9. Sarkar D, et al. Molecular mechanisms of aging-associated inflammation. Cancer Lett. 2006;236:13–23. 10. Effros RB. Telomere/telomerase dynamics within the human immune system: Effect of chronic infection and stress. Exp Gerontol. 2011;46:135– 140. 11. Lira FS, et al. Endotoxin levels correlate positively with a sedentary lifestyle and negatively with highly trained subjects. Lipids in health and disease. 2010;9:82. 12. Rocha DM, et al. Saturated fatty acids trigger TLR4-mediated inflammatory response. Atherosclerosis. 2016;244:211-5.

13. Mani V, et al. Dietary oil composition differentially modulates intestinal endotoxin transport and post-prandial endotoxemia. Nutr Metab (Lond). 2013;10(1):6. 14. Hong HA, et al. The use of bacterial spore formers as probiotics. FEMS Microbiology Reviews. 2005;29:813–835. 15. Gua M, et al. Bacillus subtilis protects porcine intestinal barrier from deoxynivalenol via improved zonula occludens-1 expression. AsianAustralasian Journal of Animal Sciences. 2014;27(4): 580-586. 16. McFarlin BK, 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 Aug 15; 8(3): 117–126. 17. Possemiers S, et al. Evaluation of the Bacillus subtilis strain HU-58 in the SHIME technology platform. ProDigest Final Report. 2013: 1-40. 18. Blatchford P, et al. Consumption of kiwifruit capsules increases Faecalibacterium prausnitzii abundance in functionally constipated individuals: a randomized controlled human trial. J Nutr Sci. 2017; 6: e52. 19. Everard A, et al. Responses of Gut Microbiota and Glucose and Lipid Metabolism to Prebiotics in Genetic Obese and Diet-Induced LeptinResistant Mice. Diabetes. 2011 Nov; 60(11): 2775–2786. 20. Finegold SM, et al. Xylooligosaccharide increases bifidobacteria but not lactobacilli in human gut microbiota. Food Funct. 2014;5(3):436-45. 21. Depeint F, et al. Prebiotic evaluation of a novel galactooligosaccharide mixture produced by the enzymatic activity of Bifidobacterium bifidum NCIMB 41171, in healthy humans: a randomized, double-blind, crossover, placebo-controlled intervention study 1–3. Am J Clin Nutr. 2008;87(3):785-91. 22. Faure M, et al. Specific Amino Acids Increase Mucin Synthesis and Microbiota in Dextran Sulfate Sodium–Treated Rats. J Nutr. 2006;136(6):1558-64.

ANTI - AGING MEDICAL NEWS

• SPRING 2019

Purity, Potency, and Quality Define Our Products

Visi t To L Booth ear n M 117 ore

As a recognized compounding pharmacy leader, we are committed to providing high-quality preparations to improve your patients’ quality of life. AnazaoHealth® is a nationwide full-service compounding pharmacy, with both a 503A traditional pharmacy and a 503B FDA-Registered Outsourcing Facility. We provide patient-specific and office use products that are not commerically available for Aesthetics, Age Management, HRT, Men’s and Women’s Health, Mesotherapy, Urology, Vitamin Injectables, Weight Management, as well as products focused on Addiction Detoxification & Recovery, Mental Clarity and Acuity.

AnazaoHealth Presents the Following Products and Preparations: Patient-Specific Preparations: • • • •

B-Complex Injectable B-NAD Injectable B-NAD Sublingual Tablet GlucoVan™ Topical Metformin

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Ibutamoren (MK-677) Capsule PhytoTress™ Hair Care Solutions ResveraVan™ Topical Resveratrol Sublingual Tablets for Erectile Dysfunction

Office Use Products: • • • • • • •

L-Carnitine Injectable Methylcobalamin (Vitamin B12) Injectable Methionine / Inositol / Choline (M.I.C.) Injectable Methionine / Inositol / Choline / Cyanocobalamin (M.I.C. + Vitamin B12) Injectable Pellets (Estradiol, Testosterone, Testosterone/Anastrozole) Pyridoxine / Thiamine (Vitamin B6+ Vitamin B1) Injectable Testosterone Cypionate Injectable

For a complete list of product offerings contact an AnazaoHealth Sales Representative. Disclaimer: The headings and descriptions contained within this document are general headings describing formulas, productsand services offered by AnazaoHealth Corporation. These general headings are not intended and should not be interpreted to make recommendations or claims regarding the use, efficacy or safety of products, formulas, and/or services listed herein. Only a doctor or other appropriately licensed health care professional, as a learned intermediary, can determine if a formula, product or service described herein is appropriate for a patient. GlucoVan™, ResveraVan™, and PhytoTress™ are all trademarks of AnazaoHealth Corporation AnazaoHealth®, Anazao®, Create, Heal, Live.®, and the Compass are registered trademarks of AnazaoHealth Corporation, © 2019. AC102-030119 A4M Ad.indd 1

5710 Hoover Boulevard Tampa, Florida 33634 Tel: 800.995.4363 F: 800.985.4363 www.anazaohealth.com 3/1/2019 4:05:25 PM

*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.

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MITOCHONDRIA:

More Than Just The Powerhouses of The Cell By: Kai Man Yuen, MSc

Introduction Mitochondria are organelles that convert oxygen and nutrients into adenosine triphosphate (ATP) in a process known as oxidative phosphorylation1. Once unique to proteobacteria, mitochondria became incorporated into eukaryotic cells over time. This incredible evolutionary feat has positioned mitochondria as the main energy production sites, turning over approximately 65 kg ATP per day. However, free radicals produced as by-products of oxidative phosphorylation can cause mitochondrial dysfunction1,2. In recent decades, numerous studies have linked mitochondrial dysfunction to age-related diseases, prompting additional research to protect these “powerhouses” of the cell1,2.

Regulation of Processes By Mitochondria The genetic process of aging has intrigued scientists for many years. Multiple theories have been put forward, including Medawar’s mutation accumulation theory, Kirkwood’s disposable soma theory and the concept of antagonistic pleiotropy. These all center on the hypothesis that genes which regulate growth and fertility in early life may have antagonistic properties on older individuals, leading to senescence and therefore aging3. Central to these cellular processes are mitochondria and indeed, energy production has been demonstrated to decline as aging occurs3. As more research is being done to investigate the genetics of mitochondria, researchers are starting to realise that these organelles are not simply structures that produce energy, but they are also involved in a number of regulation processes (Figure 1)1,3. Mitochondrial stem cell function and mitophagy represent two such mitochondrial regulatory processes and will be highlighted here.

The decline of adult stem cells is hypothesized to contribute to aging and connections between mitochondria, stem cell function and maintenance have been investigated3,4. A recent study had demonstrated that the ratio of α-ketoglutarate and succinate, produced in the matrix of the mitochondria as intermediate metabolites of the tricarboxylic acid (TCA) cycle, was vital in preserving pluripotency of the stem cells4. The NADH/NAD+ ratio has also been linked to stem cell pluripotency and mitochondrial activity3. NADH is an electron transporters involved in the TCA cycle and studies have shown that the levels of NAD+ in tissues decline as people age, affecting ATP production1,3. To combat this, NAD+ supplementation has been the subject of intense research. The process is postulated to be mediated by the sirtuin (SIRT) family of NAD-dependent enzymes5. SIRT3 in particular regulates mitochondrial acetylome in a NADdependent manner and is found within hemopoietic stem cells3,6. An increased level of SIRT3 has been shown to improve the capacity of old stem cells to regenerate6.

Figure 1: Mitochondria and Aging. Mitochondria contribute to the aging process in many ways through different pathways. Research has shown that the pathways interlink and do not work independently from each other. Adapted from Sun et al., 20163.

ANTI - AGING MEDICAL NEWS

• SPRING 2019

Mitochondria:

More Than Just The Powerhouses of The Cell.

Autophagy of mitochondria (mitophagy) on the other hand occurs when the level of misfolded proteins (either from mitochondrial DNA mutations or proteolytic stress) exceeds the mitochondrial unfolded protein response3. The mitochondrial PTEN-induced kinase-1 (PINK1) can sense damage and communicates with Parkin, an E3 ligase7. This ultimately leads to the assembly of an autophagosome and the phagocytosis of damaged mitochondria. The average age of Parkinson’s disease onset is 60 years old but mutations in either PINK1 or Parkin in humans can lead to early onset of the disease due to compromised mitophagy. The defective mechanism results in the loss of dopaminergic neurons which regulate muscle movement and coordination7. Studies have shown that the family of mitochondrial deubiquitinating enzymes (DUBs) can counteract and reverse the effects of Parkin, thereby inhibiting defective mitophagy and potentially this debilitating disease8.

Dysfunctional Mitochondria As We Age Over the course of a lifespan, mitochondrial quality and activity decrease. Emerging evidence suggests a strong correlation between mitochondrial dysfunction and the development of a wide range of age-related diseases9. Mitochondria are one of the largest producers of reactive oxygen species (ROS) in the body. These are formed as a by-product of ATP production9,10. Naturally occurring antioxidants such as coenzyme Q10 (CoQ10) scavenge and neutralize the ROS, preventing their escape from the mitochondria and damage to other parts of the cell. Unregulated levels of ROS can lead to oxidative stress, resulting in compromised mitochondria integrity, function and regulation9. The overproduction can also cause mitochondrial DNA damage, degradation of lipids and proteins as well as neurodegenerative diseases eg. Parkinson’s and Alzheimer’s. The mitochondrial free radical theory of aging hypothesizes that mitochondrial DNA is damaged as a result of free radicals that are generated during the transport of electrons in complex I11. Besides the nucleus, the mitochondria are the only organelles in the cells that contain their own DNA and machinery to synthesize RNA and proteins1,11. Located in the inner membrane of the mitochondria, the mitochondrial respiratory chain comprising five complexes is made from over 80 proteins, of which 13 are encoded by mitochondrial DNA10. Complexes I and III are thought to be major sites of superoxide production causing damage to lipids, DNA and protein within these complexes10. If left unrepaired, defective complexes can lead to increased reduction of O2 to superoxide, causing a vicious cycle that eventually leads to apoptosis10,12. Oxidation along with nitration can modify proteins within the respiratory chain too, resulting in the inhibition of energy production10. Membrane permeability and structural integrity are very important to functioning mitochondria. Normally the outer membrane is more permeable than the inner membrane. Outer membrane permeability is conferred by the presence of channel-forming porin proteins. The inner membrane, where oxidative phosphorylation occurs, is only permeable to neutral small molecules10,13. As the site of ROS production is

near the inner mitochondrial membrane, lipid peroxidation of the phospholipids can occur10. This alters membrane fluidity, increases proton permeability of the inner membrane and restricts various transport and enzymes in both mitochondrial membranes13. Superoxide dismutase, catalase and low molecular weight antioxidants such as ubiquinol are efficient at scavenging ROS and preventing lipid peroxidation14. Unfortunately the system is not completely fool proof as ROS can also blunt the the antioxidant system10.

Mitochondrial-Targeted Antioxidants CoQ10 is a mitochondrial coenzyme that plays a vital role in the electron transport chain. It is an essential cofactor for ATP production and acts as a ROS scavenger. Since antioxidants decline as we age, CoQ10 supplementation has been proposed to help alleviate the effects of aging. Due to its low oral bioavailability, various structural modifications have been made to CoQ10 to improve distribution of this antioxidant to the ROS production site15,16. For instance, mitoquinol contains a triphenylphosphonium ion fused to a ubiquinone group (the active antioxidant component of CoQ10) through a lipophilic hydrocarbon chain. It was found that a 10-atom carbon chain enabled optimal absorption and interaction with the inner membrane of the mitochondria (Figure 2)17. Additional research suggests mitoquinol may have beneficial effects on the regulatory processes that mitochondria influence.

Figure 2 Comparison of mitoquinol and CoQ10. Mitoquinol (left) contains a triphenylphosphonium ion fused to a ubiquinone group through a lipophilic hydrocarbon group. Compared to CoQ10 (right), Mitoquinol only contains 10atom carbon chain. Images retrieved from MolView18,19.

According to a 2016 report by the World Health Organization (WHO), cardiovascular diseases (CVDs) represent the top 2 leading causes of global death. Age-related changes in vasculature caused by oxidative stress were postulated to be the main factors for the development of CVD18. A previous report had demonstrated that oral supplementation of mitoquinol restored endothelium-dependent dilation in murine models18. In 2018, Rossman et al. conducted the first randomized, double-blind, placebo-controlled clinical trial

ANTI - AGING MEDICAL NEWS

• SPRING 2019

Mitochondria:

More Than Just The Powerhouses of The Cell.

using mitoquinol in healthy middle-aged and older adults to identify its effects on the vasculature. mitoquinol was deemed safe and well-tolerated. Brachial artery flow mediated dilation (method to analyse endothelial function) was 42% higher in patients who were administered mitoquinol due to the inhibition of mitochondrial ROS20. In addition, oxidized LDL (a circulating biomarker for oxidative stress) and aortic stiffness were both lowered 6 weeks post-administration18. Mitoquinol has also been shown to inhibit E. coli lipopolysaccharide (LPS)-induced accumulation of triacylglycerol (TAG) and generation of lipid droplets (LD) in epithelial cells19. Bacterial LPS is an important pathogenassociated molecular pattern recognized by the immune system in the production of inflammatory response. Secondary effects of LPS include a metabolic shift in the accumulation of TAG in the form of LD due to the downregulation of genes for fatty acid oxidation21. TAG usually accumulates in tissues containing a high concentration of mitochonrdria, such as the kidney, the liver and the heart. LPS also decreases ATP production through increased ROS generation. Since LD and mitochondria are interconnected, impairment of mitochondria can lead to TAG storage and LD biogenesis. Fock et al. demonstrated a reduction in the generation of ROS in frog urinary blader epithelial cells after treatment with mitoquinol 19. This in turn prevented the accumulation of TAG and LD, restoring fatty acid oxidation in LPS-treated cells. Interestingly, the beneficial effects were abolished when a non-mitochondrial-targeted antioxidant was used. Separately, Park et al. had performed experiments on human skeletal muscle feed arteries (SMFAs) to investigate how mitoquinol can affect age-related endothelial dysfunction22. After treatment with mitoquinol, the vasodilator response of older patients to flow (an analytical method for assessing endothelial function) was restored to values closer to those typically observed in younger patients22. Likewise, mitoquinol reduced elevated O2- to normal levels22. Interestingly, restoration of vasodilation did not occur when a nitric oxide synthase blockade was used, suggesting a nitric oxide-mediated mechanism of action of mitoquinol. The observation that older patients had increased p-eNOS/NOS ratio further lends support to this theory22. Taken together, preliminary findings suggest mitochondrialtargeted antioxidants such as mitoquinol could be an effective treatment for inflammation, CVDs and other age-related diseases and disorders. Additional research is needed to address knowledge gaps and to determine the translatability of animal models for clinical development.

Conclusions As our knowledge of mitochondria expand, important links between their regulatory functions and age-related diseases have been identified. Not surprisingly, the majority of the top ten causes of global death have an association with mitochondrial dysfunction. As the average life expectancy continues to rise, it is imperative that we become proactive when it comes to mitochondrial health. Mitochondrialtargeted antioxidants have shown early success in neutralizing ROS and reducing symptoms in various disorders and

diseases. Agents such as mitoquinol carry the promise of becoming clinically relevant for treating mitochondrial dysfunction and slowing down the effects of aging.

References 1. Kim A. A Panoramic Overview of Mitochondria and Mitochondrial Redox Biology. Toxicol Res. 2014;30(4):221-234. doi:10.5487/TR.2014.30.4.221 2. Chen Y, Zhou Z, Min W. Mitochondria, Oxidative Stress and Innate Immunity. Front Physiol. 2018;9. doi:10.3389/fphys.2018.01487 3. un N, Youle RJ, Finkel T. The Mitochondrial Basis of Aging. Mol Cell. 2016;61(5):654666. doi:10.1016/j.molcel.2016.01.028 4. Carey BW, Finley LWS, Cross JR, Allis CD, Thompson CB. Intracellular α-ketoglutarate Maintains the Pluripotency of Embryonic Stem Cells. Nature. 2015;518(7539):413-416. doi:10.1038/nature13981 5. Mouchiroud L, Houtkooper RH, Moullan N, et al. The NAD(+)/Sirtuin Pathway Modulates Longevity through Activation of Mitochondrial UPR and FOXO Signaling. Cell. 2013;154(2):430-441. doi:10.1016/j.cell.2013.06.016 6. Stein LR, Imai S. Specific Ablation of Nampt in Adult Neural Stem Cells Recapitulates Their Functional Defects During Aging. EMBO J. 2014;33(12):1321-1340. doi:10.1002/ embj.201386917 7. Pickrell AM, Youle RJ. The Roles of PINK1, Parkin, and Mitochondrial Fidelity in Parkinson’s Disease. Neuron. 2015;85(2):257-273. doi:10.1016/j.neuron.2014.12.007 8. Bingol B, Tea JS, Phu L, et al. The Mitochondrial Deubiquitinase USP30 Opposes Parkin-mediated Mitophagy. Nature. 2014;510(7505):370-375. doi:10.1038/ nature13418 9. Cadenas E, Davies KJ. Mitochondrial Free Radical Generation, Oxidative Stress, and Aging. Free Radic Biol Med. 2000;29(3-4):222-230. 10. Guo C, Sun L, Chen X, Zhang D. Oxidative Stress, Mitochondrial Damage and Neurodegenerative Diseases. Neural Regen Res. 2013;8(21):2003-2014. doi:10.3969/j. issn.1673-5374.2013.21.009 11. Lagouge M, Larsson N-G. The Role of Mitochondrial DNA Mutations and Free Radicals in Disease and Ageing. J Intern Med. 2013;273(6):529-543. doi:10.1111/ joim.12055 12. Wang L, Duan Q, Wang T, et al. Mitochondrial Respiratory Chain Inhibitors Involved in ROS Production Induced by Acute High Concentrations of Iodide and the Effects of SOD as a Protective Factor. Oxidative Medicine and Cellular Longevity. doi:10.1155/2015/217670 13. Zorov DB, Juhaszova M, Sollott SJ. Mitochondrial Reactive Oxygen Species (ROS) and ROS-Induced ROS Release. Physiol Rev. 2014;94(3):909-950. doi:10.1152/ physrev.00026.2013 14. Patlevič P, Vašková J, Švorc P, Vaško L, Švorc P. Reactive Oxygen Species and Antioxidant Defense in Human Gastrointestinal Diseases. Integr Med Res. 2016;5(4):250-258. doi:10.1016/j.imr.2016.07.004 15. Zaki NM. Strategies For Oral Delivery and Mitochondrial Targeting of CoQ10. Drug Deliv. 2016;23(6):1868-1881. doi:10.3109/10717544.2014.993747 16. Kelso GF, Porteous CM, Coulter CV, et al. Selective Targeting of a Redox-active Ubiquinone to Mitochondria Within Cells: Antioxidant and Antiapoptotic Properties. J Biol Chem. 2001;276(7):4588-4596. doi:10.1074/jbc.M009093200 17. Murphy MP. Targeting Lipophilic Cations to Mitochondria. Biochim Biophys Acta. 2008;1777(7-8):1028-1031. doi:10.1016/j.bbabio.2008.03.029 18. Bergwerf H. Coq10. MolView. http://molview.org/. Accessed February 14, 2019. 19. Bergwerf H. MitoQ. MolView. http://molview.org/. Accessed February 14, 2019. 20. ossman MJ, Santos-Parker JR, Steward CAC, et al. Chronic Supplementation With a Mitochondrial Antioxidant (MitoQ) Improves Vascular Function in Healthy Older Adults. Hypertens Dallas Tex 1979. 2018;71(6):1056-1063. doi:10.1161/ HYPERTENSIONAHA.117.10787 21. Fock E, Bachteeva V, Lavrova E, Parnova R. Mitochondrial-Targeted Antioxidant MitoQ Prevents E. coli Lipopolysaccharide-Induced Accumulation of Triacylglycerol and Lipid Droplets Biogenesis in Epithelial Cells. Journal of Lipids. doi:10.1155/2018/5745790 22. Park S-Y, Kwon OS, Andtbacka RHI, et al. Age-related endothelial dysfunction in human skeletal muscle feed arteries: the role of free radicals derived from mitochondria in the vasculature. Acta Physiol Oxf Engl. 2018;222(1). doi:10.1111/ apha.12893

Bio: Kai Man Yuen achieved his MSc from the University of Auckland, researching the feasibility of a vaccine using Staphylococcal enterotoxin-like toxin X (SElX) to fight Staphylococcus aureus infection.

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Dental

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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.

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Liveyon LLC . . . . . . . . . . . . . . . . . . . . .

417

Masterthreads USA . . . . . . . . . . . . . . . . . 1015 MED 7 . . . . . . . . . . . . . . . . . . . . . . . 1034 Medical Wave LLC . . . . . . . . . . . . . . . . . . 334 Metagenics . . . . . . . . . . . . . . . . . . . . . . 517 Microbiome Labs . . . . . . . . . . . . . . . . . . . 623 MitoQ . . . . . . . . . . . . . . . . . . . . . . . .

422

Mushroom Science . . . . . . . . . . . . . . . . . . 904 My Practice Connect . . . . . . . . . . . . . . . . . 129 Nature-Throid . . . . . . . . . . . . . . . . . . . .

237

NewULife . . . . . . . . . . . . . . . . . . . . . . . 107 Nitric Oxide Innovations . . . . . . . . . . . . . . . 109 Novus Optimum . . . . . . . . . . . . . . . . . . . 218 NuMedica . . . . . . . . . . . . . . . . . . . . . .

900

NuSkin . . . . . . . . . . . . . . . . . . . . . . . . 100 Nutritional Fontiers . . . . . . . . . . . . . . . . .

913

Olympia Pharmaceuticals | Olympia Pharmacy . . .

801

Omax Health . . . . . . . . . . . . . . . . . . . . . 929 Ortho Molecular Products . . . . . . . . . . . . . . 311 OxyHealth LLC . . . . . . . . . . . . . . . . . . . . 317 Pellecome LLC . . . . . . . . . . . . . . . . . . . .

310

Pharmacy Solutions . . . . . . . . . . . . . . . . .

736

Physicians Lab, Inc. . . . . . . . . . . . . . . . . . . 500 PhysioAge . . . . . . . . . . . . . . . . . . . . . . 208 Plattr . . . . . . . . . . . . . . . . . . . . . . . . . 704 PlusCBD Oil by CV Sciences . . . . . . . . . . . . . 1018 Power2Practice . . . . . . . . . . . . . . . . . . . . 101 Predictive Biotech . . . . . . . . . . . . . . . . . .

528

Quest Diagnostics - Cleveland HeartLab CardioMetabolic Center of Excellence . . . . . . . . 235 Quicksilver Scientific . . . . . . . . . . . . . . . . . 711 Rapid Release Technology . . . . . . . . . . . . . .

228

Regenative Labs LLC . . . . . . . . . . . . . . . . . 811 RegenMedix LLC . . . . . . . . . . . . . . . . . . . 114 Remedio Laboratories, Inc. . . . . . . . . . . . . . . 437 Restorative Formulations . . . . . . . . . . . . . . . 434 RioRoadan Technologies . . . . . . . . . . . . . . . 301 Sanesco International, Inc. . . . . . . . . . . . . . . 836 Seca . . . . . . . . . . . . . . . . . . . . . . . . . 918 Slyngshot Health . . . . . . . . . . . . . . . . . . 1023 Sovereign Laboratories . . . . . . . . . . . . . . . . 322 SpectraCell Laboratories . . . . . . . . . . . . . . . 316 Standard Process . . . . . . . . . . . . . . . . . . . 817 Stellar Biomolecular Research . . . . . . . . . . . .

125

Suneva Medical . . . . . . . . . . . . . . . . . . . 1017 T.A. Sciences . . . . . . . . . . . . . . . . . . . . . 505 Tailor Made Compounding . . . . . . . . . . . . . . 605 Theragun . . . . . . . . . . . . . . . . . . . . . . . 901 Thermi, an Almirall Company . . . . . . . . . . . . 1021 THOR Photomedicine . . . . . . . . . . . . . . . . 1001 TruGen3 . . . . . . . . . . . . . . . . . . . . . . . 800 U.S Jaclean, Inc. . . . . . . . . . . . . . . . . 328 / 725 Üforia Sciences LLC . . . . . . . . . . . . . . . . . . 331 University Compounding Pharmacy . . . . . . . . .

617

Veritas Farms . . . . . . . . . . . . . . . . . . . . . 828 Vital Nutrients . . . . . . . . . . . . . . . . . . . 1019 Weave . . . . . . . . . . . . . . . . . . . . . . . . 935 Welife Naturals . . . . . . . . . . . . . . . . . . . . 843 Wells Pharmacy Network . . . . . . . . . . . . . . . 205 Women’s International Pharmacy . . . . . . . . . 1012 Xymogen . . . . . . . . . . . . . . . . . . . . . . . 202 Y Lift . . . . . . . . . . . . . . . . . . . . . . . . . 501 Yolanda Cintron DMD PA . . . . . . . . . . . . . .

435

ZRT Laboratory . . . . . . . . . . . . . . . . . . .

611

ZyCal Bioceutials Healthcare Co., Inc. . . . . . . . .

123

Premier Research Labs . . . . . . . . . . . . . . . . 103 Prestige Products Direct / TriadAer . . . . . . . . . . 919 Professional Health Products . . . . . . . . . . . . . 917 Protocol for Life Balance . . . . . . . . . . . . . . 1030

ANTI - AGING MEDICAL NEWS

• SPRING 2019

PANEL

A Cutting Edge Product to Offer Insight into Your Ability to Methylate

Genova’s Methylation Panel is an innovative genotypic and phenotypic assessment designed to offer insight into the biochemical methylation pathway. This profile directly measures levels of key amino acids and intermediate metabolites involved in methylation, homocysteine transsulfuration, and folate metabolism to help clinicians design more targeted and specific treatment strategies to optimize patient outcomes. Single nucleotide polymorphisms (SNPs) are also assessed to offer insight into genetic predispositions that affect enzymes within these pathways.

Learn more about our Methylation Panel at www.gdx.net

Visit our Booth in the exhibit area, or learn more at www.gdx.net or call 800.522.4762

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

EXHIBITOR LISTINGS A Digital Health Guide • Booth #122 1801 N Military Trail Suite 200, Boca Raton, FL 33431 US 561-997-0112 info@a4m.com ● www.a4m.com/digital-health-guide.html A Digital Health Guide serves as a tool for clinicians to ensure that all patients receive the necessary care information they require, with daily communication and instructions via email. Users can not only monitor patients in real-time, but also create consistent connections and follow-up: ensuring optimal care. From over 60 wellness programs & hundreds of exercises & recipes to calorie/food trackers & shared patient journals, this personalized service is where efficiency meets effectiveness in healthcare.

A&Z Pharmaceutical • Booth #130 350 Wireless Boulevard, Hauppauge, NY 11788 US 631-952-3802 ● 631-952-3900 Info@azpharmaceutical.com ● www.azpharmaceutical.com For over 20 years, A&Z Pharmaceutical, Inc. has been a leading developer, manufacturer and marketer of premium quality pharmaceutical and dietary supplements. Our product portfolio includes customer favorites, like our flagship brand, D-Cal®, a Calcium and Vitamin D supplement focusing on Bone Health, and a full line of Sports Nutrition products, MFIT SUPPS. Through advanced technology, extensive research, and sound business practices, we continue to earn the trust of consumers world-wide..

Absolute Pharmacy • Booth #910 16011 North Nebraska Avenue, Suite 103, Lutz, FL 33549 US 844-338-2200 ● 813-999-2701 sales@absoluterx.com ● www.absoluterx.com Absolute Pharmacy opened in 2014 with one purpose; to supply the highest quality compounded medications available with the shortest turnaround time in the industry. Four years later we are licensed in 48 states, average an under 24-hour processing time and have a formulary with over 100 medications. Contact a pharmacy representative today at (844)338-2200 to experience the Absolute difference and have Absolute Pharmacy meet all your Anti-Aging, Weight Loss and HRT needs.

AC Grace Company • Booth #723 PO Box 570, Big Sandy, TX 75755 US 903-636-4368 ● 903-636-4051 info@acgrace.com ● www.acgrace.com A.C. Grace Company provides a line of Vitamin E products for whole health support and specific condition needs. UNIQUE E® branded: Mixed Tocopherols Concentrate, Annatto Tocotrienols, Natural Moisturizing Cream, Derma Cream, Omega Krill Oil and Omega E+ (for cardiovascular support) formulated in collaboration with Dr. Mark Houston, along with AquaE® - a water-soluble E, and IronUP™ - a grape flavored product for children.

ANTI - AGING MEDICAL NEWS

• SPRING 2019

Access Medical Laboratories • Booth #823 5151 Corporate Way, Jupiter, FL 33458 US 866-720-8386 ● 866-610-2902 sales@accessmedlab.com ● www.accessmedlab.com Access is a nationwide CAP accredited Health & Wellness Laboratory. We specialize in hormone, cardiac & preventive medicine testing through blood, saliva and urine. Our new Heavy-Metal testing alongside our advanced diagnostic evaluations give you precise insight on your patient’s overall health within 24 hrs. Welcome to Access: The Nation’s Leader in Innovation and Laboratory-Technology.

ACCUNIQ • Booth #1024 4616 West Howard Lane, Suite 960, Austin, TX 78728 US 844-768-0815 ● 512-837-2011 sales@accuniqusa.com ● www.accuniqusa.com ACCUNIQ is a global supplier of the body composition analyzers and blood pressure monitoring systems known for accuracy and durability. The company has a long well-earned reputation for excellence in quality and innovation. The line includes our new BC-380 Body Composition Analyzer as well as BC-720 high-end model to health and fitness providers that help improve the diagnostic evaluation and treatment plans.

Acella Pharmaceuticals • Booth #1035 1880 McFarland Parkway, Suite 110, Alpharetta, GA 30005 USA Ph: 678-697-3065 Email: info@acellpharma.com • Website: acellapharma.com Acella Pharmaceuticals is a specialty pharmaceutical company located in Alpharetta, Ga. Our mission is to deliver quality products at affordable prices, including desiccated porcine thyroid extract therapy.

Advanced Naturals • Booth #737 198 Alt. 19 South, Palm Harbor, FL 34683 US 800-690-9988 ● 727-474-1996 ecassaras@advancednaturals.com ● www.advancednaturals.com Since 1999, Advanced Naturals has pioneered superior-quality supplements to empower people to elevate the quality of their lives through better digestive health. These include probiotics, fiber, digestive aids, enzymes, internal cleanses and Omega-3 fish oils. By focusing on innovation and proven science to create powerful and effective formulas, Advanced Naturals has become a trusted leader in providing natural health professionals with quality digestive wellness supplements for their patients.

Aerodiagnostics • Booth #905 561 Virginia Road, Suite 100, Concord, MA 01742 USA 617-608-3832 • 617-860-6617 kmagoon@aerodiagnostics.com ● www.aerodiagnostics.com Aerodiagnostics was founded on the principles of customer service and convenience. We offer convenient non-invasive hydrogen and methane breath collection kits that can be used in the comfort of your patients home or place of employment. Our goal is to provide you with highly accurate tests in a collection environment that is convenient.

Allergy Research Group • Booth #1016 2300 North Loop Road, Alameda, CA 94502 US 510-263-2000 ● 510-263-2100 info@allergyresearchgroup.com ● www.allergyresearchgroup.com Since 1979 Allergy Research Group®, founded by Stephen Levine Ph.D., continues to be a leader in the nutritional supplement industry. Dr. Levine heads product development; our intention being to provide healthcare practitioners and their patients with an impelling nutritional means for improving the quality of life through quality, innovative supplementation.

ANTI - AGING MEDICAL NEWS

• SPRING 2019

Alletess Medical Laboratory • Booth #429 14 Howard Street, Rockland, MA 02370 US 800-225-5404 ● 781-871-4426 alletess@foodallergy.com ● www.foodallergy.com Alletess Medical Laboratory has provided allergy and immunology testing services to healthcare practitioners worldwide since 1980. We offer food sensitivity testing, allergy testing for molds, inhalants, foods, as well as panels for autoimmune disorders. Our transparent pricing, unrivaled customer service, and quick turnaround time make us the best choice for your practice. Visit our booth for more information.

The first step... Alletess

Anazao Health Corporation • Booth #117 5710 Hoover Boulevard, Tampa, FL 33634 US 800-995-4363 ● 800-985-4363 customerservice@anazaohealth.com ● www.anazaohealth.com AnazaoHealth is a full-service nationwide compounding pharmacy, with both a 503A Traditional Pharmacy and a 503B FDA-Registered Outsourcing Facility. We provide patient-specific and office use preparations that are not commercially available for Aesthetics, Age Management, Addiction Detoxification & Recovery, HRT, Men’s and Women’s Health, Mental Clarity and Acuity, Mesotherapy, Urology, Vitamin Injectables, Weight Management and more.

APS Pharmacy • Booth #112 34911 US Highway 19 North, #600, Palm Harbor, FL 34684 US 727-787-4137 ● 844-955-5565 feedback@apsmeds.com ● www.apsmeds.com The APS Pharmacy Team’s mission is to support patients’ health with quality, customized medications that are safe, reliable, and affordable. Continuous quality improvements ensure that our customized medications and compounding methods meet USP sterility, nonsterile, and safe handling of hazardous drugs standards. Our philosophy is relentless focus on our patients; everything we do is to improve your patient’s experience.

Argentyn 23 by Natural-Immunogenics • Booth #428 7504 Pennsylvania Avenue, Sarasota, FL 34243 US 888-328-8840 ● 941-702-6101 aalesteam@n-incorp.com ● www.sovereignsilver.com Since 2001, Argentyn 23 has offered health care practitioners a strategic immune-enhancing alternative devoid of toxic side effects and contraindications. Made from the purest silver (99.999%) and pharmaceutical-grade water, Argentyn 23 Bio-Active Silver Hydrosol is composed of more than 98% positively-charged silver ions and nanoclusters. It is only packaged in nonreactive glass bottles at a verified concentration of 23 parts-per-million. Argentyn 23 represents the ultimate refinement of the colloidal silver category and offers your patients unmatched safety, efficacy and purity in a professional formulation.

Arise Bioscience • Booth #210 2300 Northwest Corp Boulevard, Suite 110, Boca Raton, FL 33431 US 866-407-1164 Info@AriseBioscience.com ● www.arisebioscience.com Arise Bioscience is an industry leader in the production and distribution of hemp derived health and wellness products. Through extensive research, product development, and innovative production capabilities, we are focused on advancing world’s perception of the hemp CBD industry though familiar brands people trust.

AtCor • Booth #837 184 Shuman Boulevard, Suite 515, Naperville, IL 60563 US 630-228-8871 ● 815-366-5953 info@atcormedical.com ● www.atcormedical.com SphygmoCor XCEL from AtCor facilitates individualization of blood pressure management in both wellness and disease. SphygmoCor central arterial pressure waveform analysis informs BP management via state-of-the-art brachial BP measurement and noninvasive central aortic BP waveform derivation, which provides measures of central pressure, arterial stiffness, and estimated arterial age. SphygmoCor helps physicians individualize care in the wellness setting, as well as for patients with hypertension, renal disease, diabetes and heart failure, among other diseases and conditions.

ANTI - AGING MEDICAL NEWS

• SPRING 2019

UNIQUE E®

Mixed Tocopherols Concentrate — High gamma-tocopherol fraction along with free-radical scavenging alpha-tocopherol, and beta and delta are contained in this pure E product.

UNIQUE E

Tocotrienol — Small, powerful softgels containing high delta-tocotrienol with gammatocotrienol.

UNIQUE D3® —

Vitamin D3 capsules supply a high-potency amount of naturally-derived vitamin D, called D3. This fat soluble vitamin occurs naturally in only a few foods, thus is often fortified in milk and other products.

UNIQUE OMEGA E+®

— Strategic formulation of omega-3

fatty acids with vitamin E as natural tocopherols plus tocotrienols, vitamin D, highly absorbable CoQ10’ natural lycopene, plus astaxanthin-rich carotenoids.

UNIQUE K2® — Vitamin K has long been recognized as an important fat-soluble vitamin essential for blood coagulation and normal bone mineralization. While most of the benefits of vitamin K were previously attributed to vitamin K1, recent research has identified important benefits for vitamin K2.

AQUA-E® — Formulated with TPGS, and micellized for enhanced absorption, this unique, patented, vitamin E contains natural tocopherols and tocotrienols in a water-soluble liquid.

UNIQUE DERMA® —

Developed for use in dermatological clinics, this topical cream contains vitamin E (tocopherols and tocotrienols), chondroitin, astaxanthin and many other beneficial ingredients.

IRON UP® — Liquid Iron Supplement was specifically formulated to supplement the levels of dietary iron for infants and children who do not receive adequate amounts in their diets. Contains only natural flavors and sweeteners, gluten and casein free. Bioavailable source of iron with great-tasting grape flavored liquid.

Berkeley Life Professional Nitric Oxide • Booth #924 PO Box 11347, 355 East Ohio Street, Suite 200, Chicago, IL 60611 US 773-750-7745 info@berkeleylifeprofessional.com ● www.berkeleylifeprofessional.com Berkeley Life Nitric Oxide provides patients with the dietary nitrate bio-equivalents found in a leafy green diet, essential for maintaining optimal nitric oxide levels in the body. Pairing this with a patented diagnostic test strip allows patients to get real time indications of their nitric oxide levels allowing them to make personalized diet or supplement changes. Nitric oxide has been proven to play a vital role in a healthy cardiovascular system.

Bio-Botanical Research, Inc. • Booth #701 PO Box 2499, Aptos, CA 95001 US 831-786-9711 ● 831-319-4782 info@biocidin.com ● www.biocidin.com Bio-Botanical Research Inc. provides healthcare professionals with broad-spectrum botanical formulations designed to assist those with GI dysbiosis, biofilms, oral, and systemic immune challenges. Biocidin® has been laboratory tested and clinically verified for effectiveness. Research and trials include multi-pathogen biofilms, Lyme, sIgA modulation, SIBO, GI pathogens, and periodontal health. Our products offer a valuable alternative to standard therapies by eliminating pathogens and reducing inflammation. We provide practitioners with free educational resources and personalized training. www.biocidin.com, 800.775.4140

BIO-BOTANICAL RESEARCH INC. Clinically Effective, Evidence Based Formulas

Biocidin.com

Bio-Tech Pharmacal, Inc. • Booth #329 PO Box 1927, Fayetteville, AR 72702 US 800-345-1199 customerservice@bio-tech-pharm.com ● www.biotechpharmacal.com Bio-Tech Pharmacal, Inc., provides premium nutrition at the cellular level. Bio-Tech was established in 1984, is a cGMP registered / FDA registered nutraceutical (dietary supplements) manufacturer specializing in innovative high quality hypoallergenic preventative healthcare products, shipped to physicians, clinics, hospitals and pharmacies worldwide. Bio-Tech Pharmacal has over 100 research affiliations including Mayo, Cleveland, Emory, Harvard, etc. Bio-Tech Pharmacal has introduced many innovative products including D350,000 IU available in a water soluble delivery form. Some products are Kosher/Halal certified.

Bioclinic Naturals • Booth #1005 #104-3686 Bonneville Place, Burnaby, BC V3N 4T6 CA 888-826-9625 ● 844-384-7503 customercare@assurednatural.com ● www.bioclinicnaturals.com Natural health pioneer, Dr. Joseph Pizzorno with fellow naturopathic physician and author, Dr. Michael T. Murray collaborated with Canada’s leading functional food manufacturer to develop the ultimate professional line -- Bioclinic Naturals. Bioclinic Naturals’ commitment is to quality; pure, potent, tested and trusted products. Made in Canada, GMP, TGA (Australia) and USP certified. Call 1.877.433.9860/www.bioclinicnaturals.com.

Biosound Technologies • Booth #1004 21955 US 19 North, Clearwater, FL 33765 US 888-495-1946 sales@biosoundhealing.com ● 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. Come visit us in booth 1004 for a Demonstration.

Biotics Research • Booth #805 6801 Biotics Research Drive, Rosenberg, TX 77471 US 800-231-5777 ● 281-344-0725 biotics@bioticsresearch.com ● www.bioticsreseach.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. 1-800-2315777 www.bioticsresearch.com

ANTI - AGING MEDICAL NEWS

• SPRING 2019

101

BodyLogicMD • Booth #705 4950 T-Rex Avenue, Boca Raton, FL 33431 US 561-425-9912 ● 977-457-1564 dastern@bodylogicmd.com ● www.joinbodylogicmd.com Founded in 2003, BodyLogicMD makes up the nation’s largest network of the most highly-trained practitioners specializing in integrative medicine and bioidentical hormone replacement therapy. BodyLogicMD’s medically supervised programs are for men and women seeking to achieve and maintain optimal health. BodyLogicMD network practitioners make nearly nine times more per hour than average conventional practitioners* and have been featured on Oprah.com, Fox News, and Dr. Oz, among other media outlets. *2018 U.S. Bureau of Labor Statistics

Boston Heart Diagnostics • Booth #735 175 Crossing Boulevard, Suite 100, Framingham, MA 01702 US 877-425-1252 customercare@bostonheartdx.com ● www.bostonheartdiagnostics.com Boston Heart Diagnostics is focused on the treatment and prevention of disease by offering novel diagnostics that drive a personalized approach to improve patient health.

BrainMaster Technologies, Inc. • Booth #216 195 Willis Street, Bedford, OH 44146 US 440-232-6000 ● 440-232-7171 billm@brainm.com ● www.brainmaster.com A single source manufacturer of QEEG and neurofeedback medical devices. We are proud to introduce the All New Freedom 24D, 20D, 10D Dry, Wireless EEG brainwave Headset. This headset is compatible with previous Brain Mapping, QEEG analysis, and training, that may enable the prevention and/or reversing of cognitive decline, while encouraging mental fitness, memory improvement and self-improvement for your clientele.

Calmoseptine, Inc. • Booth #430 16602 Burke Lane, Huntington Beach, CA 92647 US 714-840-3405 ● 714-840-9810 Info@Calmoseptine.com ● 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!

Canbiola, Inc. • Booth #113 960 South Broadway, Suite 120, Hicksville, NY 11801 US 516-595-3544 info@canbiola.com ● www.canbiola.com Canbiola aims to be the premier provider of the highest quality Hemp natural products on the market through sourcing the very best raw material and developing a variety of products we believe will improve people’s lives in a variety of areas. Canbiola develops its own line of proprietary products.

Candela Corporation • Booth #111 530 Boston Post Road, Wayland, MA 01778 US 949-716-6670 info@syneron-candela.com ● www.syneron-candela.com Candela is a leading aesthetic device company with an extensive product portfolio and expansive global footprint. The Company’s technology provides advanced solutions for a variety of medical-aesthetic applications, including wrinkle reduction, hair removal, tattoo removal, body contouring, and treatment of vascular and pigmented lesions, scars, acne, leg veins and cellulite.

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ANTI - AGING MEDICAL NEWS

• SPRING 2019

JOIN.BodyLogicMD.com BodyLogicMD Network Practitioners Make Nearly 9x More per Hour than Average Conventional Medicine Practitioners.* Make More. Work Less. Gain Support.

“

One of my favorite things about being part of BodyLogicMD is what we call our ‘brain trust.’ All of our practitioners are in constant contact supporting each other with answers to challenging clinical questions, sharing new research and being part of a community that truly functions as an extended family as well. —Dr. Jennifer Landa Chief Medical Officer, BodyLogicMD

”

Franchise Owner, BodyLogicMD of Orlando, FL

BodyLogicMD is a turn-key solution exclusively for top-level practitioners who are looking to maximize their practice revenue and personal time while gaining clinical support from a network of practitioners with over 15 diverse board certifications and specializations.

More Means More with BodyLogicMD... Revenue. Support. Time. ■■

Cash-Based Medicine

■■

Administrative Support

■■

Active and Passive Revenue

■■

Sales and Marketing Support

■■

Practitioner Brain Trust

■■

More Time for Personal Endeavors

*US Bureau of Labor Statistics. Based on appointment hour.

For more information, please visit JOIN.BodyLogicMD.com or contact Deborah Astern, Franchise Sales Manager, at dastern@BodyLogicMD.com or 561-972-9529 © 2019 BodyLogicMD Franchise Corp. All rights reserved. This information is not intended as an offer to sell, or the solicitation of an offer to buy, a franchise. It is for information purposes only. Currently, the following states regulate the offer and sale of franchises: California, Hawaii, Illinois, Indiana, Maryland, Michigan, Minnesota, New York, North Dakota, Oregon, Rhode Island, South Dakota, Virginia, Washington, and Wisconsin. If you are a resident of or want to locate a franchise in one of these states, we will not offer you a franchise unless and until we have complied with applicable pre-sale registration and disclosure requirements in your state. This advertisement is not an offering. An offering can only be made by a prospectus filed first with the Department of Law of the State of New York. Such filing does not constitute approval by the Department of Law. The franchisor, BodyLogicMD Franchise Corp., is located at 4850 T-Rex Avenue, Suite 125, Boca Raton, Florida 33431, and is registered as File Number F-6930 in the state of Minnesota. BLMD-A4M-FP-AD-2019-02-07

CAREstream America • Booth #126 774 South Northlake Boulevard, Suite 1016, Altamonte Springs, FL 32701 US 855-892-3872 ● 407-960-2758 jzuhr@carestreamamerica.com ● www.carestreamamerica.com CAREstream America is the premier distributor of cutting-edge aesthetic and regenerative solutions. Our innovative Pro-Nox is a 50/50 Nitrous Oxide and Oxygen analgesic that is patient controlled and avoids the use of opioids. The safe and effective tool to relieve procedure pain and anxiety. Our comprehensive regenerative therapies include APIC-A2M with FAC Testing, Exosomes, PRFM, 100% Pure Amniotic Fluid, Non-Centrifuge Bone Marrow Aspirate and Body Jet Evo/Eco for Autologous Adipose Transfer. Visit our website to view our complete portfolio offering imaging, patient care products, cell counting and more.

Carie Boyd’s • Booth #335 122 Grapevine Highway, Hurst, TX 76054 US 817-282-9376 ● 817-282-1709 info@carieboyd.com ● www.carieboyd.com Carie Boyd’s Prescription Shop Is an FDA Registered Outsourcing Facility under section 503B of the Federal Food, Drug, and Cosmetic Act (FD&C Act). Has a sterility validation process for all sterile products, compliant with FDA standards. Has developed a proprietary bio-identical hormone pellet compounding process for consistent, repeatable quality. Performs sterility, potency, and endotoxin testing. Completes environmental monitoring for every bio-identical hormone pellet batch, compliant with FDA standards. Has a dedicated quality assurance unit.

Cellular Medicine Association • Booth #131 52 South Section Street, Suite A, Fairhope, AL 36532 US 888-920-5311 Support@VampireMarketing.Zendesk.com ● www.cellularmedicineassociation.org This group of scientists, physicians, and nurse-practitioners works to discover and become expert at the best uses of cell biology to improve health and beauty. The methods include stem cells, peptides, glycosaminoglycans, retinoic acid, platelet rich fibrin matrix, hormones, nutritional strategies, and cosmetic peels. http://vampirefacelift.com/members/workshops//vampirefacelift.com/members/workshops/

Central Drugs • Booth #323 520 West La Habra Boulevard, La Habra, CA 90631 US 877-447-7077 ● 562-694-3869 www.centraldrugsrx.com Central Drugs is an industry leader in the art and science of custom compounding and individualized health-care solutions with a team of expert pharmacists. Serving practitioners from our new Outsourcing facility and our state-of-the-art 503A compounding laboratories. Central Drugs is your pharmacy partner working with you and your team to provide resources, education and services to improve the overall health of your patients.

CFH, Ltd. • Booth #923 1067 South Hover Street, #140, Longmont, CO 80501 US 303-415-2516 info@cfh.ltd ● www.cfh.ltd CFH, Ltd. is a vertically integrated hemp production and CBD oil bioscience company producing consistent, high quality, therapeutically effective CBD products. CFH partners with clinicians, nutraceutical companies and wellness product providers around the globe to formulate and manufacture Full Spectrum Hemp Flower Oil derived products targeting specific health issues. From our 1100 acre farm and research & development facility located in Colorado, CFH is proud to be The Science Inside Your Brand.

Chromadex/Tru Niagen • Booth #635 10005 Murilands Boulevard, Suite G, Irvine, CA 92618 US 949-419-0288 Practitioner@truniagen.com ● www.practitioner.truniagen.com TRU NIAGEN® is a unique cell-charging form of vitamin B3 clinically-proven to safely and effectively increase levels of the critical co-factor, nicotinamide adenine dinucleotide (NAD+). NAD+ regulates the response of important genetic pathways to stressors, including aging. Increased NAD+ levels encourage healthy mitochondrial function, stimulate cellular energy production, and support healthy sirtuin activity. Learn more at Practitioner.TruNiagen.com

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ANTI - AGING MEDICAL NEWS

• SPRING 2019

Cognitive Clarity, Inc. • Booth #135 7500 212th Street Southwest, Suite 214, Edmonds, WA 98026 US 425-678-8485 dralansnow@cognitiveclarityinc.com ● www.perceptabrain.com Cognitive Clarity Inc. (CCI) is a Edmonds, Washington-based nutraceutical product Company that has developed breakthrough nootropics for the aging brain, cognition and memory, backed by numerous issued patents. The Company was founded by Dr. Alan Snow, CEO and Dr. Rudy Tanzi, Chief Scientific Advisor, two of the world’s leading researchers in the brain aging and memory fields. Percepta® is the world’s first nootropic to target the real reason we lose memory as we age -brain “plaques and tangles”. Percepta Sport is NSF Sport Certified and provides natural plant-based memory support for athletes. Percepta Professional is specifically designed for physicians and healthcare companies.

College Pharmacy • Booth #730 3505 Austin Bluffs Parkway, Suite101, Colorado Springs, CO 80918 US 800-888-9358 ● 800-556-5863 customerservice@collegepharmacy.com ● www.collegepharmacy.com Knowledge Changes Everything: Quality. Innovation. Experience. Since 1974. It is College Pharmacy’s compounding process, attention to detail, and quality of the compounding components that continues to make our formulations exceptional. Our expertise includes: Specialty Injectables, IV Protocols, Environmental Medicine, Chelation, BHRT, Thyroid, Age Management, Aesthetic Medicine, and more. Visit our booth #730 or contact us directly to learn more about our comprehensive compounding services and practitioner resources.

Complete Medical Services • Booth #108 141 Peyerk Court., Unit D, Romeo, MI 48065 US 586-532-1142 torlando@completemedicalservices.com ● www.completemedicalservices.com Complete Medical Services is committed to supporting the forward thinking physician who is interested in learning and implementing Integrative/Functional or Regenerative Medicine. We work with healthcare professionals to create programs that focus on the reversal of chronic diseases for their patients. Our objective is to help the physician focus on patient-centered medicine, increase clinic revenue and increase the time the physician has available. Our focus is to positively affect doctors and patients alike. For more information on how to implement these programs in your practice please visit us at Booth 108.

Compression Components & Service LLC • Booth #937 364 Valley Road, Unit 100, Warrington, PA 18976 US 267-387-2000 ● 267-387-2001 pmallee@CCSTabletPress.com ● www.ccstabletpress.com Compression Components & Service, LLC provides Stokes tablet press equipment, control systems, spare parts and support to tablet press end users. Our tablet presses are used in multiple industries including: pharmaceutical, nutritional, confectionery, battery, air-bag, chlorine, munitions, powder metals, as well as other industrial applications. We are showing our Stokes Model 511, used by many pharmacies and compounding shops to produce hormone pellets and pharmaceutical companies to produce tablets.

CosmoFrance • Booth #834 1444 Biscayne Boulevard, Suite 218, Miami, FL 33132 US 305-538-0110 contact@cosmofrance.net ● www.cosmofrance.net CosmoFrance Inc., specializes in the import and distribution of medical devices designed exclusively for non-surgical aesthetic procedures. DermaSculpt: The blunt-tip, flexible microcannula. #1 in the USA for atraumatic filler injections. ezPRF: Platelet-Rich Fibrin for a 100% natural autologous solution. The Ultimate Blood Concentrate. The next level of PRP. Novathreads: The original Absorbable PDO Thread. #1 in the USA. CosmoPen: The CosmoPen and MesoMedica solutions are the best choice for micro-needling. www.cosmofrance.net

COS M O FR ANCE

CRE8 Pharmacy Group • Booth #217 3700 Northwest 126th Avenue, Coral Springs, FL 33065 US 754-529-8353 ● 754-529-8294 communications@cre8pharmacy.com ● www.cre8pharmacy.com CRE8 Pharmacy offers compounding services for personalized medicine and patient-specific prescriptions. We are a team, working at creating formulations, dispensing orders reliably and resolving issues promptly. Specializing in Peptides, functional medicine and hormone replacement. Sterile & Non-Sterile compounds / Generic & Brand medications / Nutritional Supplementation with our own CRE8 Vitality Nutrition supplement line. Everything a patient needs is shipped in one simple order. Welcome to the future of compounding pharmacy.

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• SPRING 2019

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Crystal Clear Digital Marketing • Booth #717 5750 Major Boulevard, Suite 500, Orlando, FL 32819 US 888-611-8279 sales@crystalcleardm.com ● www.crystalcleardm.com Crystal Clear is the industry leader in providing world-class software, marketing and consulting solutions for the modern medical/aesthetic practice. Named “Top Aesthetic Service Provider 2016-2018” by Aesthetic Everything®, “Best Practice Marketing Company 2016-2017” by THE Aesthetic Guide, and ranked #210 on the Inc. 500 List of America’s Fastest-Growing Companies, Crystal Clear strives to help practices around the globe find, serve and keep more patients profitably through one fully-integrated system.

Cyrex Laboratories • Booth #224 2602 South 24th Street, Phoenix, AZ 85034 US 877-772-9739 ● 602-845-1374 michelle.c@cyrexlabs.com ● www.joincyrex.com Cyrex® is a clinical laboratory specializing in functional immunology. Cyrex offers multi-tissue antibody testing, and assessments of predictive antibodies to a variety of antigens, for the early detection and monitoring of today’s complex autoimmune conditions.

DaVinci Laboratories of Vermont • Booth #222 929 Harvest Lane, Williston, VT 05495 US 802-878-5508 bkanya@foodsciencecorp.com ● 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 #411 980 South Street, Suffield, CT 06078 US 860-623-6314 info@designsforhealth.com ● 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.

DiagnosTechs, Inc. • Booth #118 19110 66th Avenue South, Building G, Kent, WA 98032 US 800-878-3787 ● 425-251-0367 cnewland@diagnostechs.com ● www.diagnostechs.com C L I N I C A L & R E S E A R C H L A B O R AT O R Y

DiagnosTechs is a leading international salivary and noninvasive clinical and research laboratory. The company was the first laboratory to introduce saliva cortisol testing into routine clinical practice, creating a powerful tool for evaluating stress and adrenal function. The company has added saliva, urine and stoolbased panels to include hormone measurement, bone health, food sensitivity and gastrointestinal health.

Diagnostic Solutions Laboratory • Booth #936 31 Lupi Court, Suite 250, Palm Coast, FL 32137 US 828-506-5021 ● 470-239-5017 jeff.Ingersoll@diagnosticsolutionslab.com ● www.diagnosticsolutionslab.com Diagnostic Solutions Laboratory is a leader in innovative DNA-based testing. Our flagship test, the Gastrointestinal Microbial Assay Plus (GI-MAP), is the only stool test to offer quantitative polymerase chain reaction (qPCR) on multiple GI targets. We are again on the forefront of laboratory science with the introduction of GenomicInsight™, the first genomic health profile to incorporate comprehensive SNP analysis with today’s most advanced artificial intelligence platform, Opus 23 Explorer®.

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Doctor Multimedia • Booth #1028 8070 La Jolla Shores Drive, #528, La Jolla, CA 92037 US 800-679-3309 exhibits@doctormultimedia.com ● www.doctormultimedia.com Doctor Multimedia is a full scale agency that is your one-stop solution to marketing your medical practice. We have graphic designers, WordPress developers, social media masters, content creators, SEO wizards, IT problem solvers, marketing gurus, and all around ninjas ready to solve any and all problems your practice may face online. We help your practice grow, and succeed, in every facet of digital marketing.

Doctor’s Data, Inc. • Booth #734 3755 Illinois Avenue, St. Charles, IL 60174 US 630-377-8139 ● 630-587-7860 info@doctorsdata.com ● 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.

FUNCTIONAL TESTING EXPERTS

DoseLogix | Topi-CLICK • Booth #1033 300 Parkbrooke Place, Suite 140, Woodstock, GA 30189 US 877-870-8448 info@doselogix.com ● www.doselogix.com DoseLogix manufactures accurate and easy-to-use metered dosing dispensers for compounded medications. Every dispenser features built-in applicators and CLICK dosing. Dosing solutions are available for a wide variety of patient needs including HRT, pain management and dermatology. Visit booth 1033 for FREE products and a demo of Topi-CLICK Micro® and the Perl™ Vaginal Dosing Kit. Receive a copy of the ARL PEER Reviewed Accuracy Study proving Topi-CLICK® is the most accurate dispenser among those tested.

DoseLogix

Douglas Laboratories • Booth #104 112 Technology Drive, Pittsburgh, PA 15275 US 800-245-4440 dlcusservice@atrium-innovations.com ● www.douglaslabs.com From that humble beginning, Douglas Laboratories has grown into a globally recognized leader in the development and manufacturing of innovative, science-based nutritional supplements, designed to help healthcare practitioners who are focused on the healthy aging and active lifestyles of their clients.

Dr Fuji / ACIGI • Booth #916 4399 Ingot Street, Fremont, CA 94538 US 510-651-9088 ● 510-651-6188 marketing@drfuji.com ● www.fujichair.com Dr. Fuji Cyber-Relax Health & Wellness 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. Sangeeta Pati - MD Prescriptives • Booth #804 3025 Silver Star Road, Orlando, FL 32808 US 877-963-7737 information@mdprescriptives.com ● www.mdprescriptives.com Regenerative Protocols that work and are simplified to the least number of steps and capsules for the most effectiveness. Proven over 15 years, our 5-point model system has perfected regenerative healing protocols that achieve greater than 85% results in our most difficult cases. Doctors say, “These protocols have grown my practice results and revenue with ease.” Visit our booth for the answers you’ve been looking for...

ANTI - AGING MEDICAL NEWS

• SPRING 2019

MD PRESCRIPTIVES

Regenerative Protocols That Work

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Dunwoody Labs • Booth #912 9 Dunwoody Park, Suite 122, Atlanta, GA 30338 US 678-736-6374 ● 770-674-1701 info@dunwoodylabs.com ● 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.

Dutchtest by Precision Analytical Inc. • Booth #511 TM

3138 Northeast Rivergate, Suite 301C, McMinnville, OR 97128 US 503-687-2050 info@dutchtest.com ● www.dutchtest.com Precision Analytical Inc. is improving global wellness by providing important insight into hormones and their function. Their state-of-the-art innovation in hormone testing uses the acronym DUTCH (Dried Urine Test for Comprehensive Hormones). Precision is now the world leader in hormone testing as their DUTCH™ test provides the most comprehensive look at hormones through simple collection and helps practitioners answer the most complex clinical questions. Lastly, DUTCH testing is built to optimize HRT monitoring.

Edge Pharmaceuticals • Booth #925 7264 Northwest 63rd Terrace, Parkland, FL 33067 US 877-580-3343 ● 877-581-3343 sales@edgepharmaceuticals.com ● www.edgepharamceuticals.com Allergies represent a common source of chronic inflammation. Diagnosing and treating those allergies is the mission of Edge Pharmaceuticals, LLC. We have everything you need, from skin testing systems, fingerstick IgE testing, allergens and supplies for subcutaneous immunotherapy (SCIT), sublingual immunotherapy (SLIT) and now oral mucosal immunotherapy (OMIT), or allergy toothpaste. Let’s explore how we can partner to re-balance the allergic patient’s immune system.

Elixinol • Booth #816 555 Burbank Street, Unit J, Broomfield, CO 80020 US 844-804-3504 amanda.boyd@elixinol.com ● www.elixinol.com Colorado-based Elixinol is widely regarded as one of the most influential CBD brands in the world. With a proven track record of growing and extracting premium-quality hemp, Elixinol is one of the few CBD hemp extract brands with complete seed-to-sale control over its products. Elixinol also conducts rigorous third-party laboratory testing and quality control. Elixinol distributes hemp-derived CBD products in 40 countries globally including North and South America, throughout Europe, Asia, and the Pacific Region under its own label as well as bulk CBD and wholesale CBD.

Enzyme Science • Booth #134 771 Commerce Drive, Venice, FL 34292 US 855-281-7246 ● 941-575-6310 orders@enzyscience.com ● www.enzyscience.com Enzyme Science™ represents exceptional solutions for digestive health and wellness. In addition, we offer unique enzyme blends formulated with nutraceuticals to support various health functions including cardiovascular, immune, and joint support. All materials used are from the most premium, high quality sources available. Enzyme Science™ spares no expense to make natural solutions that never contain binders, artificial fillers, or flow agents. This guarantees the purest supplements available that inspire confidence in their safety and effectiveness.

Offical Brand Speciﬁcations

Erchonia Corporation • Booth #1007 650 Atlantis Road, Melbourne, FL 32904 US 888-242-0571 Info@erchonia.com ● www.erchonia.com Erchonia Corporation was founded in 1996 as a small family business, and even though we have grown into an international enterprise, we still operate under the founding principles that guided us to our present success. Our commitment to the legitimate advancement of low-level laser therapy (3LT®) through scientific and clinical research has transformed Erchonia into a world leader in the field of LLLT technology.

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Essential Formulas • Booth #1013 1861 Valley View Lane, Suite 180, Farmers Branch, TX 75234 US 972-255-3918 ● 972-255-3918 info@essentialformulas.com ● 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 ontain 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.

FirstSense Medical • Booth #137 6239 East Brown Road, Suite 101, Mesa, AZ 85205 US 602-602-0749 ● 480-306-4466 info@firstsensemed.com ● www.firstsensemedical.com First Sense Medical is a medical device company dedicated to saving lives by providing low cost, automated, early breast cancer detection equipment. We are changing the paradigm for early screening by utilizing advanced thermal imaging technology and sophisticated algorithms to detect heat patterns which are associated with breast cancer. Our test is pain free, radiation free, compression free and takes less than 5 minutes to perform. Visit us at www.firstsensemed.com

Functional Genomic Analysis • Booth #1000 15 Pleasure Road, Ephrata, PA 17522 US 717-466-5700 yvonnel@dnasupplementation.com ● www.functionalgenomicanalysis.com Starting with a custom DNA test kit from Your Genomic ResourceTM paired with our proprietary interpretation cloud-based software, Functional Genomic AnalysisTM, and education courses through the NutriGenetic Research Institute, practitioners are better equipped to investigate and analyze influential genes and enzymatic function within pathways. This critical insight enables you to translate the science of genomics into personalized nutrition when addressing impaired function (expressed SNPs), while enhancing results with optimal nutritional support in the proper order.

GAINSWave • Booth #110

GAINSWave®

2920 Northeast 207th Avenue, Suite 901, Aventura, FL 33180 US 855-383-5779 team@gainswave.com ● www.joingainswave.com GAINSWave is the brand consumers ask for by name - the most renowned and respected trademark in shockwave therapy for ED and male sexual health. Our turn-key program enables healthcare professionals to enter the growing field of male sexual wellness, better serve patients and grow cash-based practice revenues.

Genomind • Booth #223 2200 Renaissance Boulevard, Suite 100, King of Prussia, PA 19648 US 877-895-8658 customerservice@genomind.com ● www.genomind.com Genomind is a unique personalized medicine platform that brings innovation to healthcare around the world. Genomind, comprised of pioneering scientists and thought leaders in brain health and genetics, delivers actionable insights to clinicians, healthcare partners and individuals in order to improve the quality of human life. Learn more at www.genomind.com.

Genova Diagnostics • Booth #305 63 Zillicoa Street, Asheville, NC 28801 US 800-522-4762 info@gdx.net ● 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.

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Global Life Rejuvenation • Booth #229 161 East Main Street, Denville, NJ 07834 US 973-627-1750 ● 973-627-4158 bharris@globalliferejuvenation.com ● www.globalliferejuvenation.com Leader in Anti-Aging Medicine, medical weight loss, practice development and patient education. 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.

Great Plains Laboratory • Booth #1010 11813 West 77th Street, Lenexa, KS 66214 US 913-341-8949 sales@gpl4u.com ● 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 Alzheimer’s disease, chronic fatigue, fibromyalgia, migraines, multiple sclerosis, Parkinson’s disease, rheumatoid arthritis, and more.

GX Sciences, In. • Booth #934 4150 Freidrich Lane, Suite H, Austin, TX 78744 US 844-258-5564 info@gxsciences.com ● www.gxsciences.com GX Sciences™, a biotechnology company / laboratory is proud to introduce a provider only Nutrigenomic testing and interpretation platform for the medical marketplace. Our experts have designed a solution for practitioners to offer patients affordable Nutrigenomic Testing through a simple cheek swab and the choice of 14 nutrigenomic panels and PGx testing. Our proprietary software, SNP Genius™, provides interpretation of the abnormal genetic results and reports targeted nutrition, lifestyle recommendations and potential lab work.

Hallandale Pharmacy • Booth #423 2666 Southwest 36th Street, Fort Lauderdale, FL 33312 US 954-455-3822 newaccounts@hallandalerx.com ● www.hallandalerx.com With our inception in 2004, Hallandale Pharmacy’s growth has been propelled by the increase in demands of custom medications. While quality is the foundation of our practice, our service to our patients and providers, drives our mission. We look forward to earning your trust. Discover for yourself why some of the leading Doctors in the U.S. trust and use Hallandale Compounding Pharmacy for our reliability, service and prices.

Hawaiian Moon • Booth #911 321 South Missouri Avenue, Clearwater, FL 33756 US 727-466-1856 ● 866-618-6480 customerservice@hmaloe.com ● 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.

I.M. Drip Bar • Booth #230 250 Centerville Road, Building E, Warwick, RI 02886 US 401-921-5934 shannon@im-120.com ● www.im-dripbar.com Intellectual Medicine supporting IV Vitamin Infusions, Chelation, Cancer Support & Lyme Disease Treatments.

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www.TheVeritasFarms.com

1.833.691.4367 facebook.com/veritasfarmsofficial @veritasfarmsofficial

Immuno Laboratories • Booth #922 6801 Powerline Road, Fort Lauderdale, FL 33309 US 954-691-2500 boonez@immunolabs.com ● www.immunolabs.com If there was just one food triggering your patient’s symptoms, would you want to know which food? For 40 years we’ve been precisely identifying inflammatory foods through our proprietary algorithms using the most advanced testing methodologies. We’re the only laboratory with a 100% money-back guarantee, proving our dedication to reliable, reproducible, and relevant results. We partner with physicians to achieve the best clinical outcomes. Visit us for tradeshow specials on getting your own Bloodprint® test!

InBody • Booth #234 13850 Cerritos Corporate Drive, Unit C, Cerritos, CA 90703 US 323-932-6503 ● 323-952-5009 convention@inbody.com ● www.inbody.com Since 1996, InBody has made one of 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.

Innovation Compounding, Inc. • Booth #810 6095 Pine Mountain Road Northwest, Suite 108, Kennesaw, GA 30152 US 800-547-1399- ● 866-635-2329 info@innovationcompounding.com ● www.innovationcompounding.com Innovation Compounding is a wellness-based, PCAB-accredited, compounding-only pharmacy that takes an integrative approach to meeting our patients’ and providers’ needs. We support over 7,000 prescribers and annually provide 70,000 prescriptions across the nation. We’re here to listen to you, research your needs, and provide you not only with medications, but also the knowledge to help your patients reach their desired health goals.

Integrative Peptides, LLC • Booth #106 103 West Main Street, Hudson, MI 49247 US 888-699-4150 info@integrativepeptides.com ● www.integrativepeptides.com Integrative Peptides was born out of the idea that there had to be a better way for patients and their healthcare providers to gain access to safe, pure, potent and authentic peptide supplements. Physicians interested in peptides are currently limited to high priced options and unvetted overseas research-onlysuppliers and those selling “BPC like” supplements that contain no BPC. Our goal is to bring more oral, bio-available peptides supplements to market this year.

Intelligent Bioenergetics • Booth #436 317 North El Camino Real, Suite 407, Encinitas, CA 92024 US 858-539-6111 ● 866-319-1361 lisa@intellbio.com ● www.intellbio.com Intelligent Bioenergetics, Inc. was established to present and distribute the most advanced bioenergetic microcurrent devices, specifically our exclusive technologies the Electro-Equiscope® and Nueroscope-Facilitator.

Japan Bio Products Co., Ltd. • Booth #337 1-30-22, Tomigaya, Shibuya-ku, JP40 1510063 JP 819039102472 ● 81334816065 a_choi@placenta-jbp.co.jp ● jbpglobal.placenta.co.jp Japan Bio Products Co., Ltd Directs the Great Blessing of Placenta forward to the Most Advanced Medical Technologies. Japan Bio Products co., Ltd located in Tokyo, Japan, is the best company specialized in developing, distributing and marketing placenta-based products of both pharmaceutical, medical devices and cosmetic categories. Japan Bio Products is a family owned company established in 1954. Since the inception, the company focuses its activities in development, manufacturing and marketing of placenta derived products.

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Quicksilver Scientific® • 1376 Miners Dr. Ste 103 • Lafayette CO. 80026 (303) 531-0861 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. Clinical study references are for informational purposes only.

quicksilverscientific.com/CBD

Kashi Clinical Laboratories • Booth #336 10101 Southwest Barbur Boulevard, Suite 200, Portland, OR 97219 US 877-879-1815 ● 503-206-6939 aknapp@kashilab.com ● www.kashilab.com Kashi Clinical Laboratories provides a customer focused application of our wide range of DNA testing services. Kashi Labs offers SNP genetic testing panels for Integrative Medicine practitioners, and Autoimmune, Mold, and Lyme related HLA testing. We also offer pre- and post-transplant/transfusionrelated services for the oncology and HLA communities in our CAP, CLIA and ASHI certified lab. Toxicology testing, drug sensitivity, disease association, and private bone marrow testing are also offered.

KBMO Diagnostics • Booth #731 4 Business Way, Hopedale, MA 01747 US 617-933-8130 ● 617-933-7660 Info@kbmodiagnostics.com ● www.kbmodiagnostics.com KBMO Diagnostics is a fully integrated medical diagnostics company offering multi-pathway food sensitivity testing. Using the Food Inflammation Test (FIT) panel, KBMO measures up to 132 foods, colorings and additives. We provide a color-based report, meal plan and mobile app access for each patient. We also offer the Zonulin Test for gut permeability. Our recent IBS Clinical Study shifted KBMO from Biological Plausibility to Clinical Efficacy, a Gold Standard in laboratory testing.

L-Nutra • Booth #403 8000 Beverly Boulevard, Los Angeles, CA 90048 US 310-775-3655 aperez@l-nutra.com ● www.l-nutra.com Recent breakthrough science has uncovered the power of fasting as a way to optimize the body’s aging process and disrupt chronic diseases such as obesity, diabetes, cancer, autoimmune disorders, Alzheimer’s and cardiovascular disease. Our mission is to educate the world about the health benefits of fasting and introduce it back into the human diet in a safe and effective way via the Fasting Mimicking Diet (FMD).

Laboratory for Advanced Medicine • Booth #1022 711 Burnet Street, Coppell, TX 75019 US 844-489-4363 info@ivygenelabs.com ● www.ivegenelabs.com The Laboratory for Advanced Medicine, Inc. (LAM) is a bio-pharmaceutical company dedicated to developing revolutionary non-invasive, non-toxic technologies for disease diagnosis and intervention, with an emphasis on cancer. From research and development through commercial offerings, LAM is focused on building and growing world-class technologies geared towards detecting and treating disease at its earliest stage. LAM operates scientifically, ethically, and efficiently to bring these cutting-edge technologies from concept into mainstream medicine.

Legally Mine • Booth #201 1337 East 750 North, Orem, UT 84097 US 801-477-1750 ● 801-888-6454 info@legallymineusa.com ● www.legallymineusa.com Legally Mine is an asset protection and tax strategy group. The mission of Legally Mine is to empower members of the healthcare and business communities with the knowledge and tools to protect their assets from lawsuits, build professional license safeguards into their legal structures and legitimately reduce their tax liability.

Life Path Solutions | Alocyte & Matrix • Booth #835 12087 Sheraton Lane, Cincinnati, OH 45246 US 513-851-8790 ● 513-851-0434 lifepath.solutions103@gmail.com ● www.partnersinwellnessinc.com Life Path Solutions is a registered distributor for all Alocyte Stem Cells and Matrix Exosomes products.

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LightStim • Booth #729 16552 Von Karman Avenue, Irvine, CA 92606 US 949-502-4088 ● 949-502-4090 info@lightstim.com ● www.lightstim.com LightStim, the industry Leader in LED Light Therapy offers a unique approach to a clinically proven integrative treatment that will help you deliver the best possible results to your valued patients. LightStim MultiWave® Patented Technology improves overall skin function, diminishes fine lines and wrinkles, effectively reduces post procedure inflammation and bruising, and dramatically accelerates healing. Used and recommended by physicians and skin care professionals for nearly 20 years, LightStim products are designed and manufactured at our Corporate Headquarters in Irvine, CA.

Live Oak Health LLC • Booth #120 1396 Ameryllis Lane, West Palm Beach, FL 33415 US 561-602-0484 lohheatlh@gmail.com ● www.qcmedicine.com Quantum Cellular Medicine “QCM” is the field of medicine that focuses on Cell function and cell communication. QCM Centers are being set up throughout the USA and the world The core technologies in QCM Centers will be featured in our booth *Exosome Stem Cell therapy *QRS PEMF Therapy, *Ulimate Light Photobiomodulation Therapy *Enzyme Fermented Ginseng *Ionic Minerals. Visit this booth to experience where QCM therapy is moving into the future .

Liveyon LLC • Booth #417

22667 Old Canal Road, Yorba Linda, CA 92887 US 844-548-3966 support@liveyon.com ● www.liveyon.com With a renowned team of world class scientists and clinicians backed by a full time in-house regulatory team, Liveyon is pushing the existing boundaries of regenerative medicine in product research, development, manufacturing and distribution. Liveyon is entering the realm of clinical trials with its industry leading Pure Series - a clinical trial grade stem cell concentrate made at its very own Liveyon Labs CGMP facility. Liveyon is your partner in incorporating regenerative medicine into your practice.

Masterthreads USA • Booth #1015 953 Franklin Avenue, Suite #200, Garden City, NY 11530 US 844-284-7323 info@masterthreadsusa.com ● www.masterthreadsusa.com MasterThreads is the #1 aesthetic supplier of PDO threads in North America. We stand behind our FDA cleared PDO Threads and offer the highest quality threads available in the world! We stand behind every single thread we sell and offer post care assistance as well as marketing and business support to all our clients. Our training and off site support is top-notch and our sales and marketing team is always ready to help! Call us today for more information!

MED 7 • Booth #1034 12248 South Lone Peak Parkway, Suite 108, Draper, UT 84020 US 801-577-4223 med7cbd@gmail.com ● www.med7cbd.com Med 7 a clinical strength full spectrum hemp oil for healthcare professionals.

Medical Wave LLC • Booth #334 30 Potomac Court, Freehold, NJ 07728 US 800-595-0577 info@medicalwave.com ● www.medicalwaveus.com Medical Wave is the leader in EPAT technology. We specialize in providing preventative and anti-aging medical professionals the world’s most effective and advanced EPAT technology reporting a 91 % success rate according to clinical studies. Practices across the country utilize our technology to optimize their patient’s quality of life. We are committed to helping physicians in the fields of integrative, preventative functional and regenerative medicine improve their patient outcomes while creating new revenue streams.

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Metagenics • Booth #517 25 Enterprise, Suite 200, Aliso Viejo, CA 92656 US 800-692-9400 Info.customerservice@metagenics.com ● 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.

Microbiome Labs • Booth #623 101 East Town Place, Suite 210, St. Augustine, FL 32092 US 904-940-2208 ● 904-940-2209 info@microbiomelabs.com ● www.microbiomelabs.com 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.

MitoQ • Booth #422 1278 Rahway Avenue, Westfield, NJ 07090 US 908-625-4793 garabatzis@mitoq.com ● www.mitoq.com It’s Proven Science MitoQ® is the leader in cellular rejuvenation and is committed to helping humankind experience the benefits of this breakthrough science. MitoQ® has supplied sample product to a number of top universities around the world, to help explore the application of MitoQ® across a range of healthrelated research studies and uncover its true potential. The results demonstrate that MitoQ® rejuvenates human cells creating a never-seen-before breakthrough in human health.

Mushroom Science • Booth #904 1025 Conger Street, Suite 6, Eugene, OR 97402 US 541-344-1396 shannon@mushroomscience.com ● 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.

My Practice Connect • Booth #129 2744 Summerdale Drive, Clearwater, FL 33761 US 866-801-8411 ● 727-230-1437 info@mypracticeconnect.com ● www.mypracticeconnect.com Need medical protocols and pharmacy options? Founded by integrative physician, Brent Agin, MD MyPracticeConnect™ allows you to electronically prescribe, track, and manage your wellness meds from multiple compounding pharmacies - including Empower Pharmacy, Wells Network, APS, and more - in one centralized portal. Toggle between pharmacies and price comparison shop with the click of a button. With over 20 Nutrient IV protocols, patient resources, physician training and more -- we have what you need to streamline and build your practice!

Nature-Throid • Booth #237 1850 E. Riverview Drive, Phoenix, AZ 85034 US 877-797-7997 ● 480-513-8952 customerservice@rlclabs.com ● www.getrealthyroid.com Nature-Throid® and WP Thyroid® are natural hypothyroid medications containing both T4 and T3 hormones. Two natural thyroid solutions because no two people are alike. RLC Labs also manufactures a-Drenal® and i-Throid®, (iodine 12.5mg & 6.25mg) which can be used alone or with either NatureThroid® or WP Thyroid® for a well-rounded thyroid protocol.

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NewULife • Booth #107 225 North Mill Strret, Suite 114, Aspen, CO 81611 US 970-340-9222 susangershon7@gmail.com ● www.newulife.com SOMADERM GEL is formulated using a nearly identical version of the naturally occurring human growth hormone, called SOMADERM. As a homeopathic form of Somatropin, SOMADERM GEL has been shown to be safe and effective for both men and woman over 18. Since SOMADERM Gel is applied topically, within 5-10 minutes the gel quickly absorbes into the bloodstream. Taking human growth hormone orally is shown to be effective as it is easily destroyed by the enzymes in our saliva and our gut, rendering these products ineffective. This makes SOMADERM GEL superior to any other growth hormone supplement on the market.

Nitric Oxide Innovations • Booth #109 512-773-9097 drnathanbryan@gmail.com ● www.pneumanitricoxide.com Nitric Oxide Innovations is a portfolio of nitric oxide technology companies specializing in the commercialization of patented nitric oxide products and technology. The company was Founded by Dr. Nathan S. Bryan in 2018 based on more than a dozen of his issued US and International patents related to nitric oxide delivery systems. Nitric oxide is one of the most important molecules produced in the human body. Science based nitric oxide solutions will transform health and the healthcare industry. Trust the science of nitric oxide, trust the innovators. Nitric Oxide Innovations is bringing nitric oxide to life.

Novus Optimum • Booth #218 840 South Rancho Drive, #4-372, Las Vegas, NV 89016 US 702-405-7999 ● 702-982-0480 novusoptimum.sales@gmail.com ● 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 #900 9503 East 55th Place, Tulsa, OK 74145 US 800-869-8100 ● 877-270-2005 mail@numedica.com ● www.numedica.com NuMedica®—Leading Clinical Nutrition Through Science & Research: Innovation at NuMedica® starts with our commitment to quality, safety and performance. As one of the leading brands of clinical nutrition in the professional market, we partner with healthcare professionals in helping their patients achieve better health. NuMedica® is an NSF® GMP Certified, FDA registered company implementing the latest Good Manufacturing Practices and quality control standards. Learn more at www.numedica.com.

NuSkin • Booth #100 2251 North Ramparat Boulevard, #353, Las Vegas, NV 89128 US 561-685-9200 johwhittak@aol.com ● www.nuskinusa.com AgeLOC Youth delivers an all-encompassing anti-aging protection. It promotes a wide range of functions from your heart to your brain, your bones to your metabolism. A variety of aging aggressors cause us to age, but our aging defense mechanisms help keep us young. Now you can hold onto your youth so you can keep doing what you love throughout your life.

Nutritional Fontiers • Booth #913 3191 Washington Pike, Bridgeville, PA 15017 US 412-922-2566 jamiedorley@nutritionalfrontiers.com ● www.nutritionalfrontiers.com Nutritional Frontiers’ mission is to create, develop, and provide safe, effective, and therapeutic natural solutions plus educational programs for healthcare professional and patients worldwide. We have invested great efforts to research the top nutraceutical manufacturers in the world and only utilize the best ingredients and facilities. Our goal is to make the world healthy by providing natural solutions and educational programs.

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Olympia Pharmaceuticals | Olympia Pharmacy • Booth #801 6700 Conroy Road, Suite 155, Orlando, FL 32835 US 407-673-2222 ● 407-673-1234 info@olympiapharmacy.com ● www.olympiapharmacy.com Olympia Compounding Pharmacy, located in Orlando, Florida, is a state of the art, FDA 503B pharmaceutical outsourcing facility and pharmacy partner committed to setting new standards in compounding while providing access to high quality age management medications. We offer a growing line of anti-aging therapy products including IV Nutrition, Erectile Dysfunction, Age Management, Men’s Health, Women’s Health, Weight Loss, Vein Care, Sexual Health and Dermatology. As a 503B, Olympia can provide both office use and patient specific medications across the United States.

Omax Health • Booth #929 2601 Ocean Park Avenue, #214, Santa Monica, CA 90405 US 609-288-8514 sales@omaxhealth.com ● www.omaxpro.com Omax Health is a leading nutraceuticals company focused on developing premium, science-based supplements including Omax3® Professional Strength Omega-3. Founded in 2008, Omax Health’s latest innovations include a full line of CBD products, eye health, gut health, pain management, and brain health. Omax is committed to delivering exceptionally pure, concentrated, and third-party tested products that are trusted by thousands of consumers, athletes, and healthcare practitioners.

Ortho Molecular Products • Booth #311 1991 Duncan Place, Woodstock, IL 60098 US 800-332-2351 contactus@ompimail.com ● www.orthomolecularproducts.com For over 30 years, Ortho Molecular Products has partnered exclusively with health care providers to deliver nutritional solutions of the highest efficacy. The most trusted voices in health care put their trust in our products to help patients get better, faster. Our commitment to science, careful raw ingredient selection, and strict quality standards goes into every supplement we formulate. To learn more, visit www. orthomolecularproducts.com or call 1-800-332-2351.

OxyHealth LLC • Booth #317 10719 Norwalk Boulevard, Santa Fe Springs, CA 90670 US 562-906-8888 information@oxyhealth.com ● www.oxyhealth.com OxyHealth is the world’s leading provider of hyperbaric chambers. Presently, OxyHealth is the pioneer of the industry with over 15,000 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.

Pellecome LLC • Booth #310 111 Canfield Avenue, Suite A-7, Randolph, PNJ 07869 US 888-773-9969 info@pellecome.com ● www.pellecome.com Pellecome LLC is an independently owned company that is setting a new standard in pellet Bio-identical Hormone Replacement Therapy (BHRT). In 2018, Pellecome launched the Re3 Advanced Pellet Delivery System for Men and Women, which enables clinicians of any skill level to insert hormone pellets easily and safely using patent pending technology. In 2019, Pellecome will launch the Re3 Advanced Pellet Formulations and is also partnering with companies in other therapeutic areas for pellet delivery.

Pharmacy Solutions • Booth #736 1921 West Pioneer Parkway, Arlington, TX 76248 US 817-366-0799 kim@rxcompound.com ● www.rxcompound.com Pro-Pell is a turnkey BHRT pellet program that provides you with marketing, training, ongoing support, and more! Training includes 6 hours CME and business development.

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Physicians Lab, Inc. • Booth #500 4850 T-Rex Ave. Suite 150, Boca Raton, FL 33431 US 5613191410 ● 877-631-0769 valbano@physicianslab.com ● www.physicianslab.com Physicians Lab is the nation’s leading urinary hormone testing laboratory, delivering State-of-the-art Science with Superior Solutions. We beat the competition in price and turnaround-times, while providing accurate, reliable LC/MS/MS results. With our tools, education and training, we give you everything needed to offer patients convenient, affordable, and error-free testing.

PhysioAge • Booth #208 30 Central Park South, Suite 8A, New York, NY 10019 US 212-888-7074 jerry@physioage.com ● www.physioage.com PhysioAge is an integrated clinical system that combines everything you need to deliver next-generation physical exams. Our software can tell you how well your patients are aging using sophisticated Biomarkers of Aging that are highly correlated with age: arterial stiffness, lung function, skin elasticity, cognitive function, immune function and telomere lengths. Tracking physiological age over time can help you measure the effects of your treatment programs. Contact us for a software demo!

Plattr • Booth #704 1889 East Maule Avenue, Las Vegas, NV 89119 US 949-378-4983 served@plattr.com ● www.plattr.com At Plattr, we’ve established ourselves as pioneers in the marketing industry after founding the #1 enterprise digital marketing association, Digitalmarketer.com. With other 17 years of marketing experience, leave it to the Digital Marketing Pros to get your practice discovered. We can find the RIGHT patients, build patient loyalty, and keep a constant stream of patents always looking for your expertise when it comes to their health needs. Let us help you grow your practice while you continue to improve the lives of many.

PlusCBD Oil by CV Sciences • Booth #1018 10070 Barnes Canyon Road, Suite 100, San Diego, CA 92121 US 855-758-7223 wholesale@cvsciences.com ● www.pluscbdoil.com At CV Sciences, we are pioneering the future of hemp. Providing high-quality CBD since 2012, our #1 selling CBD supplement brand (according to SPINS®), PlusCBD Oil™, is available in over 1,300 practitioner offices. We are proud members of trade organizations working on the safe use and responsible commerce of products derived from agricultural hemp. As advocates for positive hemp public policy and regulation, the time of establishing hemp as a true agricultural commodity is here!

Power2Practice • Booth #101 2907 Butterfield Road, Suite 100, Oak Brook, IL 60523 US 800-590-7459 info@power2practice.com ● www.power2practice.com Power2Practice (P2P) is a driving force in integrative health, helping foster healthier practices and healthier lives. Built on a specialized EMR and practice management platform, P2P helps practices improve their business, simplify care, and increase patient satisfaction.

Predictive Biotech • Booth #528 2735 East Parleys Way, Suite 205, Salt Lake City, UT 84109 US 888-407-9761 mherbert@predictivebiotech.com ● 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.

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Premier Research Labs • Booth #103 3500 Wadley Place, Austin, TX 78728 US 800-325-7734 info@prlabs.com ● www.prlabs.com Premier Research Labs was founded to deliver uncompromising quality and effectiveness by providing 100% non-toxic and effective products. In fact, PRL has achieved an industry first in creating premier nutritional products based on quantum cellular resonance technology. Our products are free of undesirable chemical tag-alongs and are designed to deliver the very best quality to you and your patient.

Prestige Products Direct / TriadAer • Booth #919 12440 Southwest 117 Court, Miami, FL 33186 US 305-234-8081 triaddirect@gmail.com ● www.triadaer.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.

Professional Health Products • Booth #917 PO Box 9722, Suite 1, Pittsburgh, PA 15209 US 800-245-1313 hlord@phpltd.com ● www.phpltd.com Since 1978, our philosophy at PHP® has been to offer the finest quality nutritional products, exclusive to health care professionals, at a reasonable price. It is our belief nutrition should be administered & monitored by a licensed practioner familiar with an individual’s health. MethylGenetic Nutrition is the most comprehensive line of genomic products on the market, offering targeted nutrition for individual gene function & interaction. BOTH lines offer 450+ tailored nutritional & homeopathic solutions for the patient.

Protocol for Life Balance • Booth #1030 244 Knollwood Drive, Bloomingdale, IL 60108 US 877-776-8610 ● 855-833-9012 sales@protocolforlife.com ● 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.

Quest Diagnostics - Cleveland HeartLab CardioMetabolic Center of Excellence • Booth #235 500 Plaza Drive, Secaucus, NJ 07094 US 216-426-6081 x1310 komalley@clevelandheartlab.com ● www.clevelandheartlab.com The Quest Diagnostics-Cleveland HeartLab Cardiometabolic Center of Excellence is committed to advancing the prevention of the most costly and debilitating cardiovascular events. Our broadly available comprehensive menu of novel biomarkers spanning the cardiometabolic continuum provides deeper insights into hidden risk that go well beyond traditional testing. By combining this enhanced diagnostic capability with solutions to help engage patients in their care, we empower people to take action to reduce cardiometabolic risk, while improving long-term health outcomes.

Quicksilver Scientific • Booth #711 1376 Miners Drive, #103, Lafayette, CO 80026 US 303-531-0861 support@quicksilverscientific.com ● www.quicksilverscientific.com Quicksilver Scientific was founded in 2005 in Lafayette, Colorado. Quicksilver Scientific is a CLIA-certified laboratory specializing in superior liposomal delivery systems and blood metal testing for human health. We use state-of the-art technology, including patented mercury speciation, for the most accurate, reliable testing available on the market. Our liposomal supplements incorporate Quicksilver Delivery Systems™, which brings the power of intravenous therapy to oral delivery and dramatically increases absorption and effectiveness. Our product lines and protocols help restore the body’s natural detoxification system, supporting health and optimum functioning.

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Rapid Release Technology • Booth #228 3303 Harbor Boulevard, D-10, Costa Mesa, CA 92626 US 949-415-4778 jeff@rapidreleasetech.com ● www.rapidreleasetech.com Headquartered in Costa Mesa, California, Rapid Release Technology, LLC is the innovator of targeted, high-speed vibration therapy, PRO2, designed to relieve aches, pains and stiff muscles. Rapid Release, founded by chiropractor Stanley Stanbridge, D.C., is dedicated to improving people’s lives and well being through the development and production of innovative, proprietary products designed to achieve measurable results.

Regenative Labs LLC • Booth #811 1700 West Main Street, Pensacola, FL 32502 US 800-891-3452 tyler@regenativelabs.com ● www.regenativelabs.com Regenative Labs manufactures human tissue products for homologous use . Their injectable Celltext™ product has proven more effective than invasive conventional treatments. Celltext™ utilizes growth factors found in umbilical cord tissue to add structural support to injured joints and surrounding tissue. The tissue, ethically obtained from full-term C-Sections with patient consent, is safety tested according to FDA and AATB criteria.

RegenMedix LLC • Booth #114 3730 7th Terrace, Suite 302A, Vero Beach, FL 32960 US 772-492-6973 ● 772-257-6956 jgriffeth@regenmedix.com ● www.regenmedix.com RegenMedix partners with physicians to enable them to offer the highest quality Regenerative Medicine treatments to their patients. RegenMedix developed the TruGenta™ family of regenerative therapies to ensure physicians are providing True Regenerative Medicine to their patients based on scientific facts. With over 15 years in the field of Regenerative Medicine, the RegenMedix team has the knowledge and experience to ensure physicians get the appropriate training, equipment, products and marketing support to make their regenerative medicine program a success.

Remedio Laboratories, Inc. • Booth #437 610 York Road, Unit 400, Jenkintown, PA 19046 US 310-560-0017 info@remediolabs.com ● www.remediolabs.com Remedio Laboratories is bringing pharmaceutical and medical device development expertise to address unmet patient and clinician needs for high quality organic cannabidiol. Our products are independently batch tested for purity, pesticides, heavy metals, microbials and residual solvents. Remedio Laboratories was created specifically for healthcare professionals, by healthcare professionals. Visit us at booth 437 to find out more about our products and if they would be a good fit for your patients and medical practice.

Restorative Formulations • Booth #434 93 Barre Street, Suite 1, Montpelier, VT 05602 US 800-420-5801 ● 800-621-1878 info@restorative.com ● www.restorative.com Restorative Formulations has been serving the community since 2000 and are privately-owned by physicians, who have more than 50 years of combined experience. We offer physicians a range of therapeutic formulations designed to maximize hormone, cardiac, and immune function in the clinical setting. 95% of the herbs we use are certified organic, setting us apart from every other professional brand of dietary supplements.

Riordan Technologies • Booth #301 11496 Luna Road, 900, Farmers Branch, TX 75234 US 972-590-8732 aidan@aidanproducts.com ● www.neilriordan.com Riordan Technologies strives to improve the human condition through innovation in scientific research, regenerative medicine, and stem cell therapy. Riordan Technologies comprises companies founded by Neil Riordan, PA, PhD: Dallas-based Aidan Products, Signature Biologics, and Riordan Medical Institute, and Panama-based Stem Cell Institute and Medistem.

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Sanesco International, Inc. • Booth #836 1010 Merrimon Avenue, Asheville, NC 28804 US 866-670-5705 info@sanescohealth.com ● www.sanescohealth.com We know the HPA-T Axis. 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, and we offer licensed healthcare practitioners innovative, evidence-based solutions, including: non-invasive functional laboratory testing, personalized patient-centered reporting, and targeted 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.

Seca • Booth #918 13601 Benson Avenue, Chino, CA 91710 US 800-542-7322 info.us@seca.com ● www.mbca.seca.com Because every patient is unique, therapy must be individualized. Gain valuable insights on how hormone replacement therapy is affecting skeletal muscle mass in andropause and menopause patients. Detect muscle mass deficiencies, excessive visceral fat and monitor fluid distribution with the seca mBCA—the only body composition analyzer designed for medical use and validated to the gold standard. Transform how you optimize hormones with quantifiable results.

Slyngshot Health • Booth #1023 2036 North Kenmore Avenue, Chicago, IL 60614 US 502-553-8131 contact@slyngshothealth.com ● www.slyngshothealth.com Slyngshot Health (SSH) is a medically focused company specializing in Personalized Medicine with access to novel technology capabilities. SSH offers Healthcare Providers free access to an all new medical education portal, expert clinician consultations/webinars in various therapeutic areas, and the best in class pharmacy network to deliver custom tailored solutions to patients. SSH is excited to introduce a medical approach to CBD in its flagship product – SmartCBD - approved and used by Physicians & Pharmacists nationwide!

Sovereign Laboratories • Booth #322 2020 Contractors Road, Suite 5, Sedona, AZ 86336 US 480-553-7768 support@prosovlabs.com ● www.sovlabs.us Sovereign Laboratories is dedicated to developing natural products that provide the most efficacious solutions for optimal health, vitality, and aesthetics. Sovereign Laboratories’ signature product PRO 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. PRO 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 #316 10401 Town Park Drive, Houston, TX 77072 US 800-227-5227 ● 713-758-0160 support@spectracell.com ● www.spectracell.com SpectraCell Laboratories, Inc. is a leading clinical laboratory specializing in personalized disease prevention and management solutions. Our pioneering nutritional and cardiometabolic testing, driven by state-of-the-art technology, assesses a spectrum of risk factors and biomarkers for optimum wellness. Through our dedication to research and development, SpectraCell also provides innovative solutions for hormone health and genetics. The SpectraCell Solution is integral to your goal of optimizing patient outcomes by facilitating the prevention and early detection/ diagnosis of deficiency and disease, while helping guide effective treatment options.

Standard Process • Booth #817 1200 West Royal Lee Drive, Palmyra, WI 53156 US 800-558-8740 info@standardprocess.com ● 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.

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Stellar Biomolecular Research • Booth #125 Klosterstraße 205, Edenkoben, DE08 67480 DE 60-12-813-0633 info@sbi-europe.com ● www.sbi-europe.com Stellar Biomolecular Research (SBR) is a German scientific research company specializing in a diverse range of biomolecular products that are distributed to and used by an extensive network of medical practitioners and consumers in over 77 countries. SBR also offer consulting expertise that includes 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.

Suneva Medical • Booth #1017 5870 Pacific Center Boulevard, San Diego, CA 92121 US 888-278-3345 info@sunevamedical.com ● www.sunevamedical.com Privately‐held regenerative aesthetics company, Suneva Medical, develops, manufactures and commercializes innovative products, including flagship brand, Bellafill®. Building out their regenerative aesthetics product portfolio in 2019, Suneva Medical added an innovative PRP technology and Puregraft, the most predictable fat graft in the market. For more information, visit www.sunevamedical.com.

T.A. Sciences • Booth #505 420 Lexington Avenue, New York, NY 10170 US 212-588-8805 ● 212-588-0058 michael@tasciences.com ● www.tasciences.com T.A. Sciences® is dedicated exclusively to creating research-based, clinically tested wellness products that help address telomere shortening through the science of Telomerase Activation. Telomeres are the caps at the end of each strand of DNA that protect our chromosomes, like the plastic tips at the end of shoelaces. Telomeres get shorter as we get older, which may leave chromoses unprotected. T.A. Sciences® products focus on lengthening telomeres. © T.A. Sciences | TA-65 Supplement | Telomerase Activation Source: https://www.tasciences.com/ © Protected by WebToMed

Tailor Made Compounding • Booth #605 200 Moore Drive, Nicholasville, KY 40356 US 859-887-0013 ● 859-406-1242 admin@tailormadecompounding.com ● www.tailormadecompounding.com We have established ourselves as one of the top compounding pharmacies in the nation through our compounding expertise, knowledge, and experience. Together, with our sister pharmacies around the world we have been able to establish a reputation for working closely with our physicians and being the problem solvers for hard to source and hard to compound pharmaceuticals.

Theragun • Booth #901 2803 Colorado Avenue, Santa Monica, CA 90404 US 310-773-5830 info@theragun.com ● www.theragun.com Theragun is a health and wellness company founded by chiropractor Dr. Jason Wersland, D.C., in 2008 and officially launched in 2016. As the world leader in percussive therapy, our scientifically-calibrated Theragun Percussive Therapy is a faster, more effective, 100% natural approach to relief, recovery, and wellness.

Thermi, an Almirall Company • Booth #1021 3131 West Royal Lane, Suite 100, Irving, TX 75063 US 866-981-5017 info@thermi.com ● www.thermi.com Thermi, an Almirall company, is a global leader in advanced temperature-controlled radiofrequency technology. Thermi systems offer versatile modalities (ThermiTight®, ThermiSmooth® Face, ThermiSmooth® Body, ThermiRase® and ThermiVa®) and safely delivers rapid results through controlled heating using RF to impact positive tissue change and naturally stimulate collagen. Clinicians use Thermi technology to help address common signs of aging and/or rapid weight loss, which may include wrinkles, post-baby body, cellulite, loose skin and intimate tissue laxity, and empower people to take control over their skin, body and intimate life.

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THOR Photomedicine • Booth #1001 5021 Michael’s Meadow Drive, Hampstead, MD 21074 US 877-355-3151 mark.granic@thorlaser.com ● www.thorlaser.com THOR Photomedicine specializes in photobiomodulation (PBM) technology and as an industry leader have presented to the US Congress, United Nations, and NICE (UK) on the use of PBM for pain management. While drugs cover up pain, our devices actually heal people and treat the source of the pain. THOR products have become indispensable tools at world class institutions including Harvard, NYU, The Veterans Administration, NHS (UK) and others, revolutionizing pain management and injury recovery programs.

TruGen3 • Booth #800 733 Washington Road, Suite 211, Pittsburgh, PA 15228 US 412-668-3831 ● 412-668-2165 support@trugen3.com ● www.trugen3.com TruGen3® is built on the bedrock of three trusted generations of the Lioon family’s nutraceutical knowledge and experience. And yet, we’re a new kind of company, delivering a carefully selected, limited group of exceptionally high quality, condition-specific nutritional supplements. Every product is backed by the highest ethical standards and clinically-researched ingredients, and available only through certified health care professionals.

U.S Jaclean, Inc. • Booth #328 & 725 1816 West 135th Street, Gardena, CA 90249 US 310-538-2298 ● 310-538-4521 order@usjaclean.com ● www.daiwamassage.com Based in California, our corporation, U.S. Jaclean, Inc., offers a wide range of Health and Wellness Products. We are one of the pioneers in the massage chair industry in the United States. U.S. Jaclean, Inc., has been in business for 38 years, earning the trust and loyalty of our customers. With seven locations across the country, we dedicate ourselves to assisting our customers wherever they live. We welcome you to contact the office closest to you: (1) Gardena, CA, (2) Dallas/ Houston, Texas, (3) Oahu, Hawaii, (4) Las Vegas, Nevada, (5) Chicago, Illinois, (6) Orlando, Florida, or (7) Kent, Washington.

Üforia Sciences LLC • Booth #331 149 Fieldview Drive, Versailles, KY 40383 US 859-230-9409 joel.guerin7@gmail.com ● www.wellspan.uforiascience.com Üforia Sciences LLC offers DNA-guided, fully customized nutritional supplement to patients based on a Healthy Aging panel that determines SNPs on key genes that significantly influence long-term health and wellness.

University Compounding Pharmacy • Booth #617 1875 Third Avenue, San Diego, CA 92101 US 619-683-2005 ● 619-683-2008 info@ucprx.com ● www.ucprx.com University Compounding Pharmacy specializes in the formulation of drugs that are not commercially 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.

Veritas Farms • Booth #828 1512 East Broward Boulevard, Suite 300, Fort Lauderdale, FL 33301 US 561-288-6603 hello@theveritasfarms.com ● www.theveritasfarms.com Veritas Farms is a Full Spectrum farm manufacturer and brand. Veritas Farms is a vertically integrated farm and manufacturer of Full Spectrum Hemp Oil wellness and lifestyle products.

ANTI - AGING MEDICAL NEWS

• SPRING 2019

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Vital Nutrients • Booth #1019 45 Kenneth Dooley Drive, Middletown, CT 06457 US 888-328--9992 support@vitalnutrients.net ● www.vitalnutrients.net Vital Nutrients was founded on a desire to make consistent, high quality, clean products that are clinically reliable. Vital Nutrients is an American-owned supplement manufacturer that is widely known as The Leader in Quality Assurance. The Vital Nutrients product line includes hundreds of science-based and pharmaceutical-grade supplements, including vitamins, minerals, botanicals, fish oils, protein powders and specialty formulas.

Weave • Booth #935 2000 West Ashton Boulevard, Suite 100, Lehi, UT 84043 US sdrs@getweave.com ● www.getweave.com Weave is a communication tool that brings business owners together with their clients. Yes, Weave gives you advanced texting, automated reminders, email marketing tools, reviews and more-- but we also give you an unparalleled, relationship-building solution for your office.

Welife Naturals • Booth #843 403 S Florence Ave, Sandpoint, ID 83864 US 208-920-1512 info@welifenaturals.com ● www.welifenaturals.com Reinforcing healthy bio-regulation by harmonic resonance with biological vibrational patterns is our first goal. Restoring systemic communication between mental, emotional, the biofield and physical levels is our main expertise. Equisalud Laboratories (Spain) has been manufacturing dietary supplements and natural cosmetics for more than 25 years. Our working method is based on the respect of nature and the environment, in the detailed study of the active ingredients and in the exhaustive quality controls. Welife Naturals represents Equisalud Laboratories at the US.

Wells Pharmacy Network • Booth #205 1210 Southwest 33rd Avenue, Ocala, FL 34474 US 800-622-4510 ● 877-401-5653 Info@wellsrx.com ● www.wellsrx.com Wells Pharmacy Network is a compounding pharmacy operating as a 503A pharmacy in Florida and a FDA Registered 503B Outsourcing pellet & numbing cream facility in Tennessee. Wells specializes in wellness, anti-aging, sexual health, peptide & regenerative therapy, and weight management. Our comprehensive formulary encompasses an array of strengths and sizes of medications including Testosterone, hCG, and Vitamin Injectables. Preparations come in many dosage forms such as creams, capsules, injectable, troches and sterile implantable pellets.

Women’s International Pharmacy • Booth #1012 2 Marsh Court, Madison, WI 53718 US 800-279-5708 ● 800-279-8011 info@womensinternational.com ● 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 #202 6900 Kingspointe Parkway, Orlando, FL 32819 US 800-647-6100 ● 407-445-0204 info@xymogen.com ● www.xymogen.com ABOUT XYMOGEN has been providing high-quality dietary supplements to licensed health care practitioners for more than a quarter century. The nutraceutical company has introduced numerous innovations to the functional medicine community. Its Medical Board of Advisors consists of clinical practitioners who are industry experts in a broad range of specialties. XYMOGEN’s 253,000 square-foot manufacturing and fulfillment facilities are GMP and GMP for Sport Athletic Banned Substances Program registered by NSF International and TGA Certified.

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ANTI - AGING MEDICAL NEWS

• SPRING 2019

Y Lift • Booth #501 2 East 61st Street, Suite 413, New York, NY 10065 US 212-861-7787 info@ylift.com ● www.ylift.com Founded and developed by Dr. Yan Trokel, a board certified surgeon specializing in facial aesthetics, the Y LIFT® is a patented and revolutionary non-surgical facial contouring procedure based on three tenets: Structural Volumizing®, Closed Facelift®, and the Leading Edge®. Y LIFT® restores youthful facial contours by replenishing lost volume in specific anatomic layers and zones utilizing a specialized anatomically correct marking device and methodology resulting in instant and dramatic rejuvenation of the face and upper neck.

Yolanda Cintron DMD PA • Booth #435 2021 East Commercial Boulevard, Suite 208, Fort Lauderdale, FL 33308 US 954-938-4599 ● 954-938-4519 info@drcintron.com ● www.gonaturaldentistry.com All phases of Dentistry for optimum health, holistic, biocompatible dentistry. -Sedation dentistry. -Removing toxic metals and replacing them with bio-compatible materials. -Laser dentistry for painless surgeries & extractions. -Zirconia/ Ceramic Implants. Natural bone augmentation. -Plasma Rich Growth Factor. -Oral DNA testing.

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ZRT Laboratory • Booth #611 8605 Southwest Creekside Place, Beaverton, OR 97008 US 866-600-1636 ● 503-466-1636 krwiencek@zrtlab.com ● www.zrtlab.com ZRT is a CLIA certified diagnostic laboratory and the leader in hormone and wellness testing. We provide accurate and meaningful test results that assist health care providers in making informed treatment decisions.

ZyCal Bioceutials Healthcare Co., Inc. • Booth #123 5 Executive Drive, Suite A, Toms River, NJ 08755 US 888-779-9225 ● 888-373-0594 marketing@zycalbio.com ● www.rts.ostinol.com Regenerative Tissue Science, LLC. (RTS) is a healthcare professional only company, focused on 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. Ostinol™ brand products are powered by Cyplexinol® - Nature’s BMP-Complex, the only natural stem-cell activating ingredient.

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

Together We Can Support Systemic Balance Through Nutrition

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Browse our full line of whole food-based supplements, including our newest addition, Hemp Oil Complex™.

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Find out more about our whole food philosophy at the 27th Annual A4M Anti-Aging Spring Congress. Visit us at Booth 817!

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Since 1929, Standard Process and our healthcare partners have been supporting patient health with whole food-based nutrition.

Our unique formulation of key ingredients includes hemp oil, omega-3 oil, TrueBroc® and broccoli to provide a 3-in-1 benefit for the whole body – supporting the endocannabinoid systems, healthy inflammatory response and endogenous antioxidant pathways.

Standard Process is a Midwest-based company dedicated to making high quality, nutrient-dense therapeutic supplements. We believe that our regenerative farming process is a key to advancing human health and changing people’s lives. *These statements have not been evaluated by the Food and Drug Administration. These products are not intended to diagnose, treat, cure, or prevent any disease. STANDARDPROCESS.COM

JOIN.BodyLogicMD.com Make More. Work Less. Gain Support. Visit Booth #705 to learn how BodyLogicMD network practitioners make nearly 9x More per hour than average conventional medicine practitioners.*

Join Us for Food & Drinks Non-CME Event: Enjoy a cocktail (or two!) and join Dr. Jennifer Landa alongside other successful BodyLogicMD network practitioners and discover how you can MAKE MORE with BodyLogicMD.

When: Thursday, May 16, 2019 6:15 PM EST

Hosted by: Jennifer Landa, MD—Chief Medical Officer of BodyLogicMD,

Where: Gaylord Palms Resort

Medical Director of BodyLogicMD of Orlando

Sun Ballroom C

BodyLogicMD is a turn-key solution exclusively for top-level practitioners who are looking to practice integrative medicine and BHRT, and maximize their revenue and personal time, while gaining clinical support from a network of practitioners with over 15 diverse board certifications and specializations.

More Means More with BodyLogicMD... Revenue. Support. Time.

Jennifer Landa, MD

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Cash-Based Medicine

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Administrative Support

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Active and Passive Revenue

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Sales and Marketing Support

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Practitioner Brain Trust

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More Time for Personal Endeavors

Please Visit Us at Booth #705 or Contact Deborah Astern for More Information. Email: dastern@BodyLogicMD.com | Phone: 561-972-9529 *US Bureau of Labor Statistics. Based on appointment hour. © 2019 BodyLogicMD Franchise Corp. All rights reserved. This information is not intended as an offer to sell, or the solicitation of an offer to buy, a franchise. It is for information purposes only. Currently, the following states regulate the offer and sale of franchises: California, Hawaii, Illinois, Indiana, Maryland, Michigan, Minnesota, New York, North Dakota, Oregon, Rhode Island, South Dakota, Virginia, Washington, and Wisconsin. If you are a resident of or want to locate a franchise in one of these states, we will not offer you a franchise unless and until we have complied with applicable pre-sale registration and disclosure requirements in your state. This advertisement is not an offering. An offering can only be made by a prospectus filed first with the Department of Law of the State of New York. Such filing does not constitute approval by the Department of Law. The franchisor, BodyLogicMD Franchise Corp., is located at 4850 T-Rex Avenue, Suite 125, Boca Raton, Florida 33431, and is registered as File Number F-6930 in the state of Minnesota. BLMD-A4M-FP-AD-2019-02-25

SEPTEMBER

OCTOBER

DECEMBER

Marriott Marquis San Diego Marina San Diego, CA

Eau Palm Beach Resort Manalapan, FL

Venetian/Palazzo Resort Las Vegas, NV

Clinical Endocrinology Fall Symposium September 26-28

IV Therapy Symposium October 11-12

World Congress December 13-15

ABAARM & ABAAHP Exams September 25-28

Module IV: Gastroenterology October 10-12

ABAARM & ABAAHP Written Exams December 12

Module III: Neurology September 26-28

Pellet Therapy October 11-12

ABAARM Oral Exams December 13-15

Module XVI- A: Advanced Cardiovascular Health September 26-28

Module I - Endocrinology December 13-15 Module V: Clinical Intensives December 13-15

GI Workshop September 27-28

Module XVI-B: Advanced Cardiovascular Health December 13-15

Peptides Certification: Modules III & IV September 25-28 Nutriceutical & Herbals Science And Clinical Application Workshop September 26

ONLINE CERTIFICATIONS Enhance Your Practice On Your Own Time! www.a4m.com

561.997.0112

| www.a4m.com