A4M | Anti-Aging Medical News - Spring 2024

Dear Esteemed Colleagues,

With immense pride and great pleasure, we welcome you to West Palm Beach for the 32nd Annual Spring Congress. The American Academy of Anti-Aging Medicine (A4M) is deeply honored to have you join us to pursue our mission advancing innovative patientcentered care on a global scale.

Our theme, The Metabolic Crisis: From Surviving to Thriving in the 21st Century, addresses one of the most pressing challenges of our time. The word crisis is not used lightly. Over 40% of American adults currently live with a significantly heightened risk for more than 200 debilitating and fatal conditions. Metabolic disorders, complex and with unclear pathophysiology, contribute to the most substantial preventable burden of noncommunicable diseases nationwide.

As an organization, we deeply align our values with the goals of longevity, healthy aging, and healthspan extension for all. However, this cannot be achieved under current conditions; our efforts to expand the lifespan are threatened by the relentlessly rising prevalence of metabolic disorders. We must acknowledge the challenges we face and work together to overcome them.

This weekend, we will tackle these issues comprehensively, connecting you with leading voices in functional medicine, nutrition, and metabolic health optimization. Our esteemed keynote speakers include Taz Bhatia, MD, a renowned board-certified integrative and functional pediatric medicine specialist; Rhonda Patrick, PhD, a trailblazer in functional nutrition; and Maddy Dychtwald, a leading authority on longevity. Our impressive panel of featured speakers showcases a diverse array of expertise, including Joel Kahn, MD, a pioneering cardiologist; Jarrod Spencer, PsyD, a thought leader in sports psychology; Anna Cabeca, DO, FACOG, a visionary in women’s health; and many more inspiring faces, both new and beloved by the A4M community.

Our robust agenda covers the entire health ecosystem, equipping providers with the knowledge and skills to restore, optimize, and support patient metabolic health.

This weekend is an opportunity to not only learn the latest science in our industry but also to shift your perspective and come back to the root of it all: your patients and your practice goals. Take this time to forge meaningful connections with peers, meet new mentors, challenge outdated beliefs, and explore the boundless possibilities of engaging in collaborative learning. There are no passive practitioners here, only those who dare to question and seek answers. Remember the profound power you hold and use it to revolutionize the healthcare landscape. Celebrate yourself as one of the bold for taking the time and effort to be here today. Celebrate each other.

We are grateful for your participation and know that your patients, their families, and generations to come will benefit from your dedication to their wellbeing. As A4M-educated, innovative, bold, and patient-focused providers, you hold the key to your patient’s wellbeing.

Together, we can engineer a future in which survival mode is no longer the status quo and thriving is the new new normal.

With unwavering support and appreciation,

Ronald Klatz, MD, DO & Robert M. Goldman, MD, PhD

A4M Founders

Ronald Klatz MD, DO Co-Founder

Robert

Goldman MD, PhD, DO, FAASP Co-Founder

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. Anti-Aging 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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ROLEX GIVEAWAY

*The actual Rolex on display may differ from photograph.

PME SESSIONS (NON-CME)

FRIDAY | MAY 3RD

6:15 pm

Connecting the Clinical Dots: Detoxification, Methylation, and Nutrition

Presented by: Deanna Minich, MS, PhD, FACN, CNS, IFMCP

Location: Coral Salon ABC

Sponsored by:

SATURDAY | MAY 4TH

BREAKFAST

6:30 am - 7:30 am

The Pivotal Role of the Gut Microbiome in Metabolic Dysfunction

Presented by: Lacey Hall, MS, RD

Location: Ballroom B

6:15 pm

How Does TA-65® Directly Impact Metabolic Syndrome?

Presented by: Gordon Crozier, DO, ABAARM FAAMM

Location: Ballroom B

6:15 pm

New Investigational Drug: Demonstrates Potential to Reversal of All Dementias

Presented by: Dr. William Gael, Dr. Arbella Sarkis, John Bumb

Location: Ballroom A

SUNDAY | MAY 5TH

BREAKFAST

6:30 am - 7:30 am

Metabolic Dysregulation Starts in the Endothelium

Presented by: Helen Messier, MD

Location: Ballroom B

Sponsored by:

Sponsored by:

Sponsored by:

Sponsored by:

Connecting the Clinical Dots

Detoxification, Methylation, & Nutrition

Unlock the full potential of methylation and detoxification in your practice with Dr. Deanna Minich’s insightful workshop

Discover how specialty lab testing reveals the details of these important biochemical processes, making it possible to use nutrition and nutrient therapies with greater precision for better patient outcomes.

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Friday, May 3rd at 6:15pm in Coral Salon ABC

As a nutrition researcher, educator, and functional medicine-trained clinician, Dr. Minich brings a unique approach to nutrition that combines physiology and psychology.

P R E S EN T E D B Y Dr. Deanna Minich

How Does TA-65® Directly Impact Metabolic Syndrome? (FREE, NON-CME Workshop)

When: Saturday, May 4th at 6:15 PM

Location: Ballroom B

Stop by booth #501 to talk to our experts. Highlights:

Improve Cardiovascular Markers in Patients with Metabolic Syndrome

Revitalize Metabolic Markers as Part of a Health Maintenance Program

Decrease Immunosenescent T-Cells and Improve Naïve T-Cell Reserves

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Our existing Female Blood Profile I and Male Blood Profile I have expanded! Both profiles test 8 hormones as listed below and are run using LC-MS. You may also continue to add our saliva cortisol x 4 to either of the DBS-expanded profiles below as a Saliva + Blood Spot Test Kit as you could before.

Female Blood Profile I

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Leverage the power of genetically informed lifestyle choices, combat the metabolic crisis, and achieve maximum health span.

Reveal the unique genetic profile of your patients with 3X4 Genetics testing.

The body is a complex and sophisticated entity made up of intricate systems. Every decision you make, every minute of every day, greatly impact your genes.

Keep a look out for Dr. Yael Joffe PhD, our Founder and Chief Science Officer as well as our 3X4 Team who will be at the 32nd Annual Spring Congress to answer any questions about our 3X4 Genetics Test and 3X4 Blueprint.

MAY 3 - 5, West Palm Convention Center

West Palm Beach, Florida Come visit us at Booth 430

Exploring the Potential of Taurine for Longevity

By: Mark Mikhael, CEO Olympia Pharmaceuticals

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.

Since the dawn of civilization, the quest for humanity has been captivated by the quest for longevity, manifested in the grandeur of monumental legacies spanning from the Colosseum to the pyramids. In modern times this quest has evolved into a scientific pursuit, delving into the intricacies of aging andvitality. Taurine is an essential amino sulfonic acid that has emerged as a compelling subject of study, which offers insights into its potential role in promoting longevity.

Understanding the Essential Amino Acid

Taurine, a naturally occurring compound, is an essential amino acid vital for numerous physiological functions within the human body. It derives its name from “taurus,” that Latin term for bull, reflecting its 1927 discovery and isolation by German scientists Friedrich Tiedemann and Leopold Gmelin from the bile of an ox. Functionally, Taurine plays a pivotal role in modulating intracellular free calcium concentrations, thereby exerting influence over numerous

cellular processes. While the body can synthesize Taurine endogenously through the conversion of Cysteine (Fig 1), dietary sources such as dark meat poultry, shellfish, and eggs also contribute to its reservoir. Moreover, Taurine is frequently utilized as a dietary supplement and is prominently featured in energy drinks and weight loss regimens.

Fig. 1

The Multifaceted Role of Taurine

Taurine orchestrates many functions crucial for maintaining homeostasis and vitality within the body. It maintains cellular hydration and electrolyte balance, which are essential for cellular function and overall well-being. Furthermore, Taurine contributes to the formation of bile salts, facilitating fat emulsification and absorption during digestion. Its regulatory control over intracellular calcium levels influences various cellular signaling pathways. Taurine supports the central nervous system, bolstering neuronal integrity and function, while also modulating immune responses and enhancing antioxidant defenses.

Health Benefits of Taurine Supplementation

Scientific inquiry has revealed a plethora of health benefits associated with Taurine supplementation, underscoring its potential as a formidable ally in promoting overall well-being. Studies have demonstrated that Taurine supplementation leads to favorable alterations in lipid profiles, such as reductions in total cholesterol and triglyceride levels. Additionally, Taurine exhibits vasodilatory properties, contributing to the improvement of blood pressure in individuals with hypertension. Its metabolic process extends to enhancing glucose tolerance and insulin sensitivity, thereby mitigating the risk of insulin resistance and diabetes. Emerging evidence suggests that Taurine supplementation exerts neuroprotective effects, shielding neurons from oxidative stress and neurotoxic insults. Furthermore, Taurine’s role in modulating calcium dynamics within muscle cells confers benefits in enhancing muscle function and resilience.

Taurine as a Therapeutic Agent

Beyond its role in promoting general well-being, Taurine supplementation has shown promising outcomes in managing various disease states. Taurine is a promising adjunctive therapy in congestive heart failure, owing to its ability to enhance myocardial contractility and mitigate oxidative stress. Preliminary studies hint at Taurine’s neuroprotective properties, offering promising avenues fo intervention in neurodegenerative disorders.

Additionally, Taurine supplementation exhibits promising outcomes in ameliorating metabolic derangements associated with obesity and metabolic syndrome.

The Gateway to Longevity

John Olney’s pioneering research in the 1960s sheds light on Taurine’s cytoprotective properties, initially prompted by investigations of “The Chinese Restaurant Syndrome,” atiributed to the neurotoxic effects of monosodium glutamate (MSG). Olney discovered Taurine’s ability to counteract these neurotoxic effects on the central nervous system. This seminal research laid the foundation for understanding Taurine’s profound impact on cellular integrity and resilience.

Amidst the intricate tapestry of aging and longevity, Taurine emerges as a beacon of hope. Vijay Yadav’s research at the National Institute of Immunology in New Delhi, India, underscores Taurine’s profound impact on longevity. Over an exhaustive eleven-year period, Yadav documented declining Taurine levels in aging mice, concomitant with deterioration in health. Intriguingly, supplementation with Taurine both restored youthful Taurine levels and conferred a notable extension in lifespan; supplemented mice exhibited a 10-12% increase in longevity compared to their nonsupplemented counterparts. These findings underscore Taurine’s pivotal role in mitigating the hallmarks of aging, paving the way for enhanced health and vitality.

Henning Wackerhage, a professor of exercise biology in Germany, corroborated these findings by showing correlation between higher Taurine levels and lower cholesterol, lower blood glucose, and reduced inflammation levels in blood samples from 12,000 individuals. Wackerhage’s research highlights Taurine’s multifaceted benefits in promoting metabolic health and mitigating inflammatory processes, solidifying its status as a promising longevity-promoting agent.

Harnessing Taurine’s Potential for Well-being

As we navigate the complexities of aging, Taurine offers a multifaceted approach to enhancing longevity and

well-being. While the precise mechanisms underlying Taurine’s longevity-promoting effects warrant further study, its undeniable influence on cellular homeostasis and resilience bodes well for its therapeutic potential. As we stand at the precipice of a new era in aging research, Taurine beckons as a compelling avenue for exploration, holding the promise of a healthier, more vibrant future.

Conclusion

The enigmatic allure of longevity continues to captivate humanity, driving relentless endeavors to unlock

its elusive secrets. In the field of aging and vitality, Taurine emerges as a potent ally, from its pivotal role in cellular homeostasis to its therapeutic potential in mitigating age-related pathologies, Taurine represents a beacon of hope in our quest for a healthier, more vibrant future. As we traverse the frontiers of aging research, let us embrace the promise of Taurine and its profound implications for longevity and vitality.

References:

1. Olney JW. Brain lesions, obesity, and other disturbances in mice treated with monosodium glutamate. Science. 1969;164:719–21.

2. Kumar, Anil, Nagpal, Ravinder, and Kumar, Praveen. “Taurine: A ‘very essential’ amino acid.” Journal of Biomedical Science, vol. 26, no. 1, 2019, p. 78. PMC, doi:10.1186/s12929-019-0584-z.

3. http://www.webmd.com/vitamins-supplements/ingredientmono-1024taurine.aspx?activeingredientid=1024&activeingredientname=taurine

4. http://www.ncbi.nlm.nih.gov/pubmed/17053427

5. “What is Taurine?” Website: News-Medical.net URL: https://www. newsmedical.net/health/What-is-Taurine.aspx

6. Taurine: The Anti-Aging Supplement Science is Behind Author: Alice Park Website: Time URL:https://time.com/6285686/taurine-anti-agingsupplement-science/

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We o er exceptional support to both physicians and patients with our anti-aging program, promoting “healthy aging”, which is defined as living a longer and healthier life.

SUPPORTING IMMUNE FUNCTION

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TA-65®?

Activates Telomerase to Lengthen Telomeres in Humans1

Improves Cardiovascular Markers in Patients with Metabolic Syndrome2

Helps Support Healthy Immune System3, 4

Enhances Immunity and Reduces Inflammation4

Review selected studies at www.telomerescience.com/studies

References

1. Salvador L, Singaravelu G, Harley CB, Flom P, Suram A, Raffaele JM. A Natural Product Telomerase Activator Lengthens Telomeres in Humans: A Randomized, Double Blind, and Placebo Controlled Study. Rejuvenation Research. December 2016. 16(5).

2. Fernandez ML, Thomas MS, Lemos BS, DiMarco DM, Missimer A, Melough M, Chun OK, Murillo AG, Alyousef HM, Medina-Vera I. TA-65, A Telomerase Activator improves Cardiovascular Markers in Patients with Metabolic Syndrome. Current Pharmaceutical Design. 2018;24,1-7.

3. Singaravelu G, Harley CB, Raffaele JM, Sudhakaran P, Suram A. Double-Blind, Placebo-Controlled, Randomized Clinical Trial Demonstrates Telomerase Activator TA-65 Decreases Immunosenescent CD8+CD28-T Cells in Humans. OBM Geriatrics. 2021 vol. 5, issue 2.

4. Bawamia B, Spray L, Wangsaputra VK, Bennaceur K, Vahabi S, Stellos K, Kharatikoopaei E, Ogundimu E, Gale CP, Keavney B, Maier R, Hancock H, Richardson G, Austin D, Spyridopoulos I. Activation of telomerase by TA-65 enhances immunity and reduces inflammation post myocardial infarction. Geroscience. 2023 Apr 22:1–17.

Telomere Athenaeum provides a new and exciting way to learn about telomere biology through education on the latest research from top experts in anti-aging medicine.

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From Surviving to Thriving: How Longer Telomeres Can Turn the Tide on Metabolic Crisis

By: Gordon Crozier, DO, ABAARM FAAMM

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.

Today’s world is facing an escalating battle against metabolic disease, a clear reminder of the challenges within our modern lifestyle. The COVID-19 pandemic has highlighted the vulnerabilities associated with metabolic dysfunction, emphasizing the urgent need to address these underlying conditions. Metabolic diseases are key contributors to the most common preventable causes of death, including heart disease, stroke, and certain cancers. The complexity of metabolic syndrome, influenced by various factors, drives the importance of innovative approaches to health and longevity.

The Crucial Role of Telomeres in Aging and Health

Telomeres, the tiny protective end caps of chromosomes, are the heart of the aging process and critical for maintaining genomic stability and integrity. Each time a cell divides, telomeres shorten, acting as a biological clock that signals the end of a cell’s lifespan. This cumulative shortening is closely linked to aging and, when critically short, can lead

to cell senescence or death, contributing to the aging process at the cellular level.

The significance of telomeres extends beyond mere markers of aging. They are frontline defenders in preserving our genetic code, preventing the loss of DNA sequences and the fusion of chromosomes, which could lead to cancer and other genetic diseases. The length of telomeres, therefore, is not just a passive indicator of cell age but an active player in determining cellular vitality and longevity. Research continues to prove that longer telomeres are associated with fewer age-related diseases, better overall health, and extended lifespan, highlighting their foundational importance in the biology of aging.1

Linking Telomere Length to Health Outcomes

The connection between telomere length and health outcomes is a popular topic among health experts. A growing number of studies have demonstrated, in no

uncertain terms, a direct correlation between longer telomeres and improved health metrics, including reduced incidence of cardiovascular disease, diabetes, and certain types of cancer. For instance, one study found that individuals with longer telomeres had significantly lower rates of heart disease and were less likely to die prematurely from any cause.2

These findings are transformative, suggesting that interventions to preserve or extend telomere length could have profound implications for enhancing human health and longevity. However, translating this knowledge into practical strategies for health improvement requires a nuanced understanding of the factors that influence telomere length and how these can be modulated.

Strategies for Preserving Telomere Length for Enhanced Longevity

How do we preserve and extend telomere length to improve health outcomes and delay aging? Various strategies range from lifestyle modifications to nutritional approaches and supplements. But the secret lies within a telomerase activator, TA-65. This plant-based compound has emerged as a particularly promising option.

Lifestyle changes such as regular exercise, reducing stress, and a balanced diet rich in antioxidants have been shown to positively influence telomere length.3 In addition, nutritional supplements that support cellular health and potentially stimulate telomerase, the enzyme responsible for adding DNA sequences to telomeres, offer a direct route to enhancing telomere integrity. TA-65, derived from the Astragalus plant, is a supplement that has gained attention for improving telomere length and promoting cellular rejuvenation.4

The discontinuation of Epitalon, another telomereextending agent, re-instates the importance of selecting effective and safe interventions. Epitalon was removed from the market due to concerns over its efficacy and safety profile. In contrast, TA-65 has been subject to rigorous scientific evaluation, demonstrating its potential to enhance telomere length and support cellular health without any adverse effects. It is

also extensively tested for its safety in humans and designated as Generally Recognized as Safe (GRAS), positioning it as a superior alternative for those seeking to mitigate the effects of aging at the cellular level.

Cutting-Edge Telomere Research

Recent advancements in telomere research highlight the promising role of TA-65, a telomerase activator derived from traditional Chinese medicine, in addressing aging and health at the cellular level. Five fundamental studies provide compelling evidence of TA-65’s beneficial impacts:

1. Enhances Immunity and Reduces Inflammation: A study revealed TA-65’s capacity to significantly increase lymphocyte counts and reduce inflammation markers in post-myocardial infarction patients, suggesting its potential to improve immune function and reduce cardiovascular risks.5

2. Helps Support Healthy Immune System: Research demonstrated that TA-65 significantly decreases senescent CD8+CD28- T cells, thereby improving immune system functionality. This effect was observed across various dosages of TA-65, highlighting its efficacy in enhancing cellular immunity without adverse effects.6

3. Improves Cardiovascular Markers in Patients with Metabolic Syndrome: A double-blind, randomized crossover trial with patients suffering from metabolic syndrome showed that TA-65 intake led to improvements in dyslipidemias, hypertension, and oxidative stress markers. These findings indicate TA-65’s potential in managing components of metabolic syndrome through its anti-inflammatory and lipid-modulating effects.7

4. Activates Telomerase to Lengthen Telomeres: A year-long study on relatively healthy cytomegaloviruspositive subjects aged 53–87 demonstrated that low doses of TA-65 significantly increased telomere length, contrasting with telomere loss in the placebo group. This suggests TA-65’s unique ability to counteract telomere attrition associated with aging.8

5. Stabilizes Telomere Length: Further research using

the TeSLA technique confirmed TA-65’s effectiveness in stabilizing telomere length and reducing the percentage of short telomeres over one year, compared to significant telomere shortening in the placebo group. This supports TA-65’s role in reducing the telomere loss that accompanies normal aging.9

These studies underscore TA-65’s potential in enhancing immune function, managing metabolic syndrome, and extending or stabilizing telomere length, marking significant strides in telomere science and its application in health and longevity practices. The consistent findings across diverse health outcomes and populations reinforce the therapeutic promise of TA-65 in combating agingrelated cellular decline and promoting healthspan.

Author Bio:

Gordon Crozier, D.O. ABAARM FAAMM, a pioneer in integrative and genetics-based medicine, serves as Medical Director at Orlando’s Crozier Clinic, specializing in hormone therapy and global lectures on natural and integrative treatments. Including lectures and research in neurodegenerative disease.

Contact: DrCrozier@CrozierClinic.com, 407-732-7668.

References:

1. Shammas, M. Telomeres, lifestyle, cancer, and aging. Curr Opin Clin Nutr Metab Care. 2011;14(1):28-34. doi:10.1097/MCO.0b013e32834121b1.

2. Deng Y., Li Q., Zhou F., et al. Telomere length and the risk of cardiovascular diseases: A Mendelian randomization study. Front Cardiovasc Med. 2022;9:1012615. doi:10.3389/fcvm.2022.1012615

3. Arsenis NC, You T, Ogawa EF, et al.. Physical activity and telomere length: Impact of aging and potential mechanisms of action. Oncotarget. 2017 Jul 4;8(27):45008-45019. doi:10.18632/oncotarget.16726

4. Harley, C.B., Liu, W., Blasco, M., et al. (2011). A natural product telomerase activator as part of a health maintenance program. Rejuvenation Research, 14(1), 45-56.

5. Bawamia B, Spray L, Wangsaputra VK, et al. Activation of telomerase by TA-65 enhances immunity and reduces inflammation post myocardial infarction. GeroScience. 2023.

6. Singaravelu G, Harley CB, Raffaele JM, Sudhakaran P, Suram A. Doubleblind, placebo-controlled, randomized clinical trial demonstrates telomerase activator TA-65 decreases immunosenescent CD8+CD28- T cells in humans. OBM Geriatr. 2021;5(2):168. doi:10.21926/obm.geriatr.2102168

7. Fernandez ML, Thomas MS, Lemos BS, et al. TA-65, a telomerase activator improves cardiovascular markers in patients with metabolic syndrome. Curr Pharm Des. 2018;24:1-7.

8. Salvador L, Singaravelu G, Harley CB, et al. A natural product telomerase activator lengthens telomeres in humans: A randomized, double blind, and placebo controlled study. Rejuvenation Res. 2016;XX(XX):1-8. doi:10.1089/ rej.2015.1793

9. Shay J. TA-65® reduces the telomere loss that accompanies normal aging. TAS. 2016 Oct 23; no. 005:1-3.

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Transformational Breakthrough: Potential Reversal of Dementia

By: Arbella Sarkis, MD, Jenny Johansson, PhD, John Bumb

Submitted For Publication 29 February 2024

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

In a common clinical setting, our objective was to utilize a newly available investigational drug made available under an FDA approved Compassionate Use Program (CUP), while employing Integrative Medicine practices as permitted under the protocol of the CUP. Ten patients were treated in the clinic for various types of dementia ranging from mild to moderate severity. Five of these patients are presented herein. Each of the ten patients demonstrated marked rapid improvement. One patient rapidly returned to normal mental status after 4 treatments. Through these clinical observations, Galectin-3 (GAL-3), the target of the medication was found to be a major contributor in each of the cases, though not the only factor with this multifactorial disease. Augmentation with Integrative Medicine intervention is clearly warranted.

Introduction

Available through an FDA approved Compassionate Use Program, the authors

believe that for the first time in the history of medicine a new investigational medication clinically demonstrates the strong potential of being a safe transformational breakthrough treatment for likely all types of dementia. In all 10 treated patients, the medication improves symptoms and reversed multiple types of dementia to clinical significance of varying degrees. This investigational medication, code-named TB006, manufactured by TrueBinding, Inc., is a humanized monoclonal antibody targeting GAL-3.

Galectins are proteins found in a variety of cells and tissues and are systemically involved in numerous metabolic processes and functions. GAL-3 is the only known family member which contains a domain for self-association. The GAL-3 protein has been linked to a myriad of systemic diseases including several neurodegenerative disorders in recent years1,2. In Alzheimer’s disease (AD) and other forms of dementia, serum levels of GAL-3 are elevated and strongly correlates with severity of cognitive decline.

In a double-blind, randomized Phase Ib/IIa clinical study of mild, moderate, and severe cognition function, as assessed by a Clinical Dementia Rating Sum Box (CDR-SB), showed a 63% (Figure 1) improvement by the end of the 2.5-month observation period. While the overall improvement was not statistically meaningful due to the brevity of the study and its inclusion of severe stages of the disease, the data for mild and moderate stages reveals a stunningly significant improvement.

Figure 1. Change in CDR-SB across entire patient cohort. TB006 or placebo were administered weekly for 5 weeks and patients were monitored for 2.5 months post-final infusion.

Remarkably, in the mild stage patient group (Mini-mental state examination (MMSE) scores 21-24), marked signs of continuous disease reversal were observed, with the difference compared to placebo reaching statistically significance after 1 month and remaining so throughout the observation period (Figure 2). Importantly, TB006 was well tolerated, with no treatment interruptions due to adverse events and no severe adverse events.

Dementia is characterized by difficulties in short-term memory, language, problem-solving and other thinking skills associated with daily living. Below, we will review the various types of dementia, causes and risk factors.

Types of dementia

1. Alzheimer’s disease (AD)

2. Vascular dementia (VD)

3. Dementia with Lewy bodies (DLB)

4. Frontotemporal dementia (FTD)

5. Hippocampal sclerosis (HS)

6. Other causes of dementia include Huntington’s disease, Creutzfeldt-Jakob disease, HIV, and alcohol related dementia (Wernicke-Korsakoff syndrome).

Epidemiology

The population of 65 and older is rapidly growing as we live longer, and contributing to this growth is the baby-boom generation. Since the risk of developing dementia increases rapidly with age, dementia is becoming increasingly common, and incidence of dementia is projected to double by 20503.

Risk Factors

Age – Age is the single biggest risk factor for developing AD and late-onset AD (LOAD). After the age of 65, the risk of developing AD doubles every five years3

Sex – Women have increased lifetime risk of developing AD.

Genetics – The E4 variant of the lipid carrier apolipoprotein E (APOE) gene is the highest genetic risk factor for LOAD and increases risk several-fold.

Family history of dementia – Having one or more parents or siblings with dementia increases the risk.

Cardiovascular disease (CVD) – Risk factors for CVD are also risk factors for dementia.

Traumatic Brain Injury (TBI) – TBI can increase a person’s risk to earlier development of AD.

Figure 2. Change in CDR-SB in mild patients (MMSE scores 21-24). TB006 or placebo was administered weekly for 5 weeks and patients were monitored for 2.5 months post-final infusion.

Diabetes/insulin resistance – High blood sugar affects blood vessel and brain health.

Cognitive impairment from other causesDown’s syndrome (DS), Trisomy 21 leads to more amyloid protein and other health issues.

Lack of cognitive reserve – Low education is a risk factor.

Low engagement in social and cognitive daily activities

Alcohol abuse - Wernicke-Korsakoff syndrome, causes Vitamin B1 deficiency.

Environmental factors - Exposure to environmental toxins such as air pollutants, heavy metals, solvents, and pesticides can increase the risk.

Infection – Examples include HIV, EBV, and likely COVID-19, etc.

Thyroid disorders – Age 65 and older and a history of hypothyroidism increases risk.

Pathogenesis

The hallmarks of AD and other dementias such as DLB and FTD are build-ups of aggregated and mis-folded proteins that cause neuronal damage. In AD, extracellular amyloid-β forms plaques in the brain and neurons, while Neurofibrillary tangles (NFT) composed of the protein tau also forms. Tau pathology is also observed in DLB, Parkinson’s disease (PD) dementia and FTD. Lewy bodies are aggregates of the protein β-synuclein formed in the cortex in DLB and late in PD. In PD α-synuclein aggregates initially develop in the substantia nigra area in the midbrain, particularly in dopamine producing cells. In FTD the transactive response DNA-binding protein (TDP43) causes damage in the front and temporal lobes. Misfolded TDP-43 is also observed in the hippocampus in HS.

In dementia, neuroinflammation is increasingly recognized as a key component. In the brains of demented patients and animal models, microglial immune cells are highly activated. This chronic activation of microglia results in an inflammatory and oxidative process in the brain that causes damage to neurons. Microglia decreases the uptake and breakdown of amyloid and the production of neurotrophic factors important for brain health. GAL-3 broadly regulates the neuroinflammatory response and is highly upregulated in neurodegenerative disease brains, including AD, tauopathy, PD and FTD1,2,4,5.

Accordingly, the GAL-3 gene was found to be a hub gene orchestrating microglial activation in neurodegeneration6.

Natural History

AD and other types of dementia have several phases. In the early stages of AD there may be brain changes, but a person can still function normally. Not everyone with cognitive changes goes on to develop dementia due to AD7. However, about one-third of individuals with mild cognitive impairment develop dementia due to AD, progressing through mild, moderate, and severe stages within five years.

The progression of vascular dementia depends on the type of vessel damage which has occurred. If there is disease in small blood vessels, subcortical vascular dementia can develop slowly and gradually over time. A stroke may go on to develop vascular dementia after six months. People experiencing multiple smaller strokes may eventually develop multi-infarct dementia later.

DLB tends to progress faster than AD, especially in the beginning, although memory problems are less prominent than in AD. A difference between DLB and PD is that memory problems tend to occur before or at the same time as movement problems, whereas in PD cognitive problems develop later8.

Diagnosis of FTD can be more difficult and therefore delayed. Symptoms are more heterogenous and overlap with those of AD and psychiatric disorders.

Clinical Presentation

Dementia manifests with many symptoms, and many of the symptoms are shared across different types of dementia, such as:

• Memory loss, especially shortterm - early in AD and LBD.

• Slow thought processing.

• Difficulty in planning, solving problems, concentrating long enough to finish a task and work with numbers.

• Anxiety, apathy, confusion, depression, judgement, psychosis.

• Visual hallucinations and visuospatial impairment.

• Trouble communicating (difficulty finding the right words, reading, writing, speaking).

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• Withdrawal from social activities.

• Sleep disturbances – early in DLB.

• Personality, conduct, empathy – in DLB.

• Chewing and swallowing.

• Motor function (gait, poor balance, difficulty walking).

• Movement (rigidity, slowness, tremor) – in DLB, PD.

Diagnosis

Generally, diagnosis of dementia is based upon (1) clinical symptoms. (2) Mental status testing by MMSE or other similar or more comprehensive cognitive testing to assess memory and cognition skills. (3) MRI or PET imaging of the brain can be performed to determine if there are other brain abnormalities such as bleeding, swelling, plaques, or tumors, etc. (4) The use of biomarkers for detection of brain changes has yet to be fully elucidated. (5) Other considerations:

Rule out other underlying causes of cognitive problems, such as:

• Cardiovascular disease

• Nutritional/mineral/vitamins deficiencies

• Heavy metal poisoning

• Hormonal imbalances – example: thyroid disorders, HRT, etc.

• Inflammation – CBC, CRP, ESR, ferritin, etc.

• nfections - Lyme disease, candida, STD’s, EBV, COVID, etc.

• Insomnia/untreated sleep apnea

• Mood disorder – depression, pseudo dementia, etc.

• Medications - sleeping pills, antihistamines, urinary incontinence medication, anti-anxiety, etc.

• Leaky gut - inflammatory food such as corn, dairy, gluten, omega-6, peanut, soy, sugar, etc.

Five Compassionate Use Case Studies

A) 80 y/o H/female with AD >5 years on max dose of Exelon patch/Namenda with MMSE score of 23/30: Post 2 treatments, her MMSE score improved to 29/30. After two months off treatment and her MMSE score dropped to 25/30. Resumed and received 2 more treatments, prior to 5th treatment she was retested and her MMSE score increased to 30/30. The patient elected to receive a 5th treatment and was asked to return to clinic after 7 weeks (after publishing of this paper) for reevaluation.

B) 91 y/o W/female with AD >10 years on Exelon patch and Namenda with MMSE score of 15/30: Post the first treatment with TB006, MMSE score rose to 19, then to 23 after the second treatment, and to 27 after the third treatment. The patient continues to receive monthly treatments.

C) 90 y/o W/female with AD >5 years unable to tolerate Aricept and Namenda with MMSE score of 18/30, and history of malignant hypertension, urinary incontinence, difficulty walking. Post one treatment MMSE score increased to 21/30, average blood pressure decreased to 120-130/80, urinary incontinence completely resolved, and walking improved dramatically.

D) 80 y/o W/male with dementia >5 years failed on Aricept with MMSE score of 24/30 with a history of Parkinson’s. After the first treatment MMSE score improved to 26/30 and dramatic improvements in his gait, speech, and tremors. Post second treatment not only did his MMSE score improve to 27/30, but he was also able to write without difficulty and resumed playing golf.

E) 84 y/o W/male with dementia >3 years failed on Aricept with MMSE score 24/30 and history of multiple myeloma, hypertension, chronic renal disease. With single treatment, MMSE score increased to 26/30 and primary multiple myeloma marker decreased by 50% (was an unexpected result from TB006).

Treatment With TB006

TB006 intravenous infusions are given every 28 +/- 5 days.

Recommendations for the best treatment effects include:

• Optimize all abnormal lab test results.

• Keep the patient mentally and physically active (games, crosswords, exercise, daily and social activities).

• Effective controlling of any underlying diseases.

• Optimize diet and food restriction.

• Optimize with supplements, such as: Vitamin B complex, Vitamin D3, omega-3, magnesium, zinc, CoQ10, Gingko Biloba, glutathione, alpha-lipoic acid, L-carnitine, etc.

Conclusion

The investigational drug TB006 demonstrates remarkable potential to reverse many forms of dementia. Patients receive additional benefits from proper clinical workups and augmentation of treatment with Integrative Medicine interventional therapies.

References:

1. Sciacchitano, S. et al. Galectin-3: One Molecule for an Alphabet of Diseases, from A to Z. Int J Mol Sci. Jan 26;19:379 (2018).

2. Mijailović N.R. et al. Galectin-3 Involvement in Cognitive Processes for New Therapeutic Considerations. Front Cell Neurosci. Jul 5;16:923811 (2022).

3. Alzheimer’s Association. Alzheimer’s Disease Facts and Figures 2023.

4. Siew J.J. et al. Galectin-3 aggravates microglial activation and tau transmission in tauopathy. J Clin Invest. Jan 16;134:e165523 (2024).

5. Borrego-Écija, S. et al. Galectin-3 is upregulated in frontotemporal dementia patients with subtype specificity. Alzheimer’s Dement. 2023 Nov 29 (2023).

6. Holtman I.R. et al. Induction of a common microglia gene expression signature by aging and neurodegenerative conditions: a co-expression metaanalysis. Acta Neuropathol Commun. May 23;3:31 (2015).

7. Canevelli M. et al. Spontaneous reversion of mild cognitive impairment to normal cognition: A systematic review of literature and meta-analysis. J Am Med Dir Assoc. 17:943-8 (2016).

8. Gomperts S.N. Lewy Body Dementias: Dementia with Lewy Bodies and Parkinson Disease Dementia. Continuum (Minneap Minn) (2016).

Estrogen and Neurodegenerative & Neurovascular Disease Processes: Friend or Foe?

By: Terri DeNeui, DNP, APRN, ACNP-BC

Founder EVEXIAS Medical Centers & EVEXIAS Health Solutions

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.

This review will provide an evidence-based perspective regarding endogenous and exogenous estradiol, and its relationship to neurodegenerative and neurovascular disease processes. After reviewing this paper and the literature presented, it will become apparent that not only does 17 beta estradiol protect the neurovascular and neurological systems, but there is also no correlation between the use of non-oral 17-beta-estradiol preparations and stroke risk. Further, recent studies have pointed to the role 17-beta-estradiol may play in the treatment of ischemic stroke and the prevention of vascular and Alzheimer’s dementia.

MHT

& Cardiovascular and Neurovascular

Disease/Stroke

Risk: How did we get here?

The Women’s Health Initiative (WHI) trial was a large, randomized clinical trial funded by the National Institutes of Health to determine if menopausal hormone therapy (MHT) prevented heart disease, breast and colorectal cancer, and osteoporotic fractures in postmenopausal

women. The WHI launched at a time when observational studies suggested a protective effect of estrogen on the heart and bones of postmenopausal women. The initiative purpose was to determine if postmenopausal hormone therapy should be prescribed for cardiovascular and osteoporosis protection for all women. The study, which began in 1991 and was to end in 2005, included the MHT clinical trials, an observational study, and two extension studies from 2005-2010 and 20102015 (Women’s Health Initiative, 2017).

Research goals for the WHI were to: 1) determine the efficacy of MHT on non-fatal myocardial infarction and death; 2) determine the safety or risk of MHT for invasive breast cancer; and 3) determine secondary outcomes on osteoporosis, stroke, pulmonary embolism, venous thromboembolism, colorectal cancer, endometrial cancer, and mortality (DeNeui, et al., 2019).

Women with previous hysterectomy (N=10,739) were randomized to

Estrogen and Neurodegenerative & Neurovascular Disease Processes: Friend or Foe?

conjugated equine estrogen, CEE (commonly known as Premarin) or placebo. For this group, the intervention lasted 7.2 years. Post-intervention follow-up was 6.6 years and cumulative follow-up was 13 years. Women with an intact uterus (N=16,608) were randomized to CEE + medroxyprogesterone acetate, MPA, (commonly known as Prempro) or to placebo. The intervention phase was 5.6 years, postintervention follow-up was 8.2 years and cumulative follow-up was 13.2 years (DeNeui, et al., 2019).

As it relates to the topic of this paper, preliminary results of the trial showed that compared to placebo, women in the CEE treatment group had an increased risk of stroke and blood clots. These results propagated the grave misinformation that all forms of menopausal hormones (estrogens) have a single class effect and therefore “all forms of estrogen must have an increased risk of blood clots and stroke”. This misinformation, although refuted in the literature in dozens of clinical studies, continues to promulgate in mainstream and medical communities to this day.

The cost of estrogen avoidance data post WHI is astounding. Estrogen has rapid beneficial vascular effects in the cardio and neurovascular systems, and withdrawal of estrogen may result in clinically significant changes in arterial function, resulting an acute myocardial infarction and/or stroke (Venetkoski, et.al., 2018). In the Venetkoski, et.al., study of over 400,000 women on post-menopausal estrogen therapy, women younger than 60 years at discontinuation of HT showed a significantly increased risk of stroke death during the first year after treatment as compared with age matched female background population (Venetkoski, et.al., 2018). Data collected from Mikkola, et.al., 2-millionwoman follow-up years of over 330,000 women, showed that discontinuing hormone therapy is harmful. The study further revealed women less than 60 years old had a two to threefold increased risk of cardiac and stroke mortality compared with the age-standardized background population death rate of the entire country after stopping MHT with estrogen (Hodis & Mack, 2018).

Estrogens for MHT: Is there a risk?

Evidence from systematic reviews and guidelines support estrogen as effective in treating moderate to severe vasomotor symptoms, symptomatic vaginal atrophy, and in preventing postmenopausal osteoporosis in women transitioning through menopause; estrogen therapy remains the gold standard for relief of menopausal symptoms (DeNeui, at.al., 2019). Estrogens are available in many formulations and routes of administration, which have similar efficacy for symptom relief, although their metabolic effects, and side effect profiles differ greatly.

Although typically associated with female reproductive function, estrogens mediate physiological processes in nearly every body tissue. 17-beta-estradiol (17β-E2) is the most prominent and potent estrogen in circulation and during the menopause transition and post menopause, the ovaries cease to produce 17β-E2. Estrogens are lipophilic in nature and therefore cross the blood brain barrier easily and diffusely. Estrogen is a pleiotropic hormone that exerts protective actions on multiple tissues, including the brain, and the protective effects of estrogen carry tremendous implications for the promotion of health and the prevention of disease in postmenopausal women (Dubal & Wise, 2002).

The major differences between administrations of oral versus non-oral preparations lie in the metabolic changes produced by the first pass effect and are expressed most notably in the cardiovascular and neurovascular systems. Some oral estrogen formulations have been implicated in increasing the risk of clotting and concerns of the thrombotic potential of estrogen arose from early observations that oral contraceptives appeared to increase the risk of venous thrombosis, pulmonary embolism, and stroke (Dubal & Wise, 2002). We now know that the dose and the route of estrogen delivery are key components in determining clotting potential. At higher doses, oral estrogen can stimulate the production of thrombogenic factors primarily through its actions in the liver; alternatively, non-oral delivery of estrogen bypasses this “first pass metabolism” through the liver and prevents estrogen induced thrombogenic factors in the liver (Dubal & Wise, 2002).

In a review of thrombotic risk and estrogen use by Canonico, it was shown that non-oral estrogens, such as patches and subcutaneous pellets, are not associated with an increased clotting risk and biological data supports this difference between oral and non-oral preparations (2015). Additionally, significant differences in clotting risk between estrogen hormone preparations relate to the simultaneous use of synthetic progestin. Studies have consistently shown that clotting risk is higher among users of combined estrogens plus progestins than among users of estrogens alone or estrogens with oral micronized (bioidentical) progesterone (Canonico, 2015). Generally, non-oral, 17-beta-estradiol delivery has more physiologic systemic effect and a decreased risk of deep vein thrombosis, stroke, and myocardial infarction, secondary to the decreased clotting risks compared to oral administration. Studies comparing oral 17-beta estradiol to conjugated equine estrogens (CEE) showed greater risk of venous thromboembolism (VTE) and myocardial events in the CEE group, suggesting not only the route, but the type of estrogen administration that may be important to consider (DeNeui, et.al.,2019).

Estrogen, Neurodegeneration & Neurovascular Disease: Root cause or preventative?

When discussing root cause and treatment options, risks, and benefits of certain therapies as it relates to stroke, it is important to understand what constitutes a stroke. Ischemic stroke is characterized by an abrupt deprivation of blood flow, oxygen, and vital nutrients to the brain that quickly leads to cell death, known as apoptosis (Wise, et.al., 2005). The ischemic cascade also involves an inflammatory response triggered by damageassociated molecular patterns (DAMPs) released from the dying cells which trigger activation and recruitment of immune cells (Petrone, et.al., 2015). This environment of immune cells secretes pro- inflammatory cytokines that not only act locally in the brain but also may enter the systemic blood circulation to trigger a systemic immune response (Petrone, et.al., 2014; Petrone, et.al., 2015). Estrogen has immunomodulating and anti-inflammatory effects in numerous body systems, most notably the neurovascular system, and several studies have shown that

estrogen, specifically 17β-E2, protects the brain from ischemic injury following stroke (Petrone, et.al., 2014; Singh, et.al., 2006; Suzuki et.al., 2009).

Understanding the downstream effects of ischemic stroke induced inflammatory immune response may help explain why estradiol, as a potent immunomodulator, may not only prevent ischemic stroke, but also play a role in treatment. Brown, et.al., reported 17β-estradiol “powerfully protects the brain using multiple molecular mechanisms that promote decreased cell death, increased neurogenesis, enhanced neurotrophic support, and the suppression of pro-inflammatory pathways” (2009). The evidence that estradiol stimulates neurogenesis (new nerve tissue) in the adult ischemic brain suggest that estradiol therapy may facilitate the brain to undergo repair and remodeling after stroke (Brown, et.al., 2009).

Because the immune response following a stroke dictates recovery and the degree of brain damage, estrogen may be dually protective by also mediating the immune response. There are multiple mechanisms of 17β-E2’s neuroprotection, including activation of several neuroprotective pathways in the brain, but 17β-E2 also mediates the local and systemic immune response to ischemic stroke through the estrogen receptor. Estrogen is a powerful antioxidant; however, analogs of estradiol (synthetic estrogens) do not appear to exert the same antioxidant effect as 17β-E2. One theory is because synthetic analogs do not activate the estrogen receptor pathways, which are responsible for inducing the protective effects of estradiol (Petrone, et.al., 2015).

Another mechanism by which estrogen may reduce stroke risk is through modifying risk factors that underlie both stroke and coronary heart disease (CHD) (Dubal & Wise, 2002). Further, CHD doubles the risk for stroke and estrogen therapy greatly reduces the risk for CHD up to 40 percent, thus it follows that estrogen may decrease the risk for stroke in parallel with its protective actions on CHD (Dubal & Wise, 2022). Of grave concern is the impact of prolonged estrogen deprivation in postmenopausal women untreated with MHT and is now considered a critical health matter as we realize that these women are at increased risk for chronic and acute disease processes such as dementia,

stroke and myocardial infarction (Dubal & Wise, 2002).

In a landmark 2022 paper, the authors concluded not only does estradiol play a critical role in the neurobiology of aging, but also that there are complex interactions between estradiol and the other sex hormones—chiefly testosterone and progesterone (Jett, et.al., 2022). Brain imaging studies demonstrated that middle-aged women exhibit increased indicators of Alzheimer’s disease (AD) endophenotype as compared to men of the same age, with onset in perimenopause (Jett, et.al., 2022). The authors demonstrated with baseline PET scans at the onset of perimenopause, and repeat scans 3 years post menopause, the beta amyloid deposition, hallmark of AD, was evident with no clinical signs and symptoms of dementia yet present (Jett, et.al., 2022).

Estrogen receptors at the brain level are abundant in the hypothalamus, thermoregulatory and sleep and circadian cycle centers as well as fundamental regions for learning and memory; they also participate at the brain level in the modulation of neural differentiation, neuroinflammation, synaptic plasticity, proliferation, behavior, and cholesterol metabolism (Carrera-Gonzales, et.al., 2023). Endocrine aging has been found to accelerate chronological aging in the brain of women years before the onset of AD symptoms and estrogens have neuroprotective effects that are mostly eliminated with the drastic systemic decrease in estradiol during peri and post menopause (Carrera-Gonzales, et.al., 2023).

Lastly, as it relates to brain aging and disease prevention and the use of MHT, it is imperative to understand the protective benefits discussed herein (neuroinflammation, immunomodulation, protection against apoptosis, beta amyloid and subsequent neurodegeneration), are chiefly evident depending on the type of compounds used. Progestins and synthetic estrogens have vastly different and opposing outcomes in neuroprotection, inflammation and immunomodulation than do 17-betaestradiol and progesterone (Wise, et.al., 2023).

It is vitally important clinicians understand the physiologic sequalae in ischemic stroke and other neurodegenerative disease states and the positive role estrogen plays in both sexes. Estradiol is a potent immunomodulator

and powerful anti-inflammatory agent, both functions of which are vital for stroke prevention and post stroke recovery. Clinical studies have shown estrogen replacement in postmenopausal women to ameliorate cognitive dysfunction, decrease the risk and delay the onset of degenerative conditions such as Alzheimer’s disease and stroke (Carrera, et.al., 2023; Dubal & Wise, 2002; Wise, et.al., 2023). Considering the chronic and acute disease risk posed to post-menopausal women avoiding MHT, it is essential clinicians give their patients seeking relief from menopausal hormone decline individualized, accurate information regarding disease prevention and risk, and the differences between the modalities of MHT from which to make the life altering decision of whether to initiate hormone therapy or not.

To review the full article and list of references, please visit: EVEXIAS.COM/estrogen-neurovascular

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Dogma or Data? Monitoring Menopausal Estrogen Replacement Therapy

By: Jaclyn Smeaton, ND, Chief Medical O cer

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.

Estrogen therapy is considered the most effective treatment option for both vasomotor symptoms and the genitourinary syndrome of menopause and is commonly prescribed to postmenopausal women. Within the integrative medicine community, there are various approaches taught in regards to both appropriate dosing and monitoring of estrogen therapy. In this article, we will summarize the current standards for estrogen replacement therapy and highlight some key research you should be aware of as you design your clinical approach to menopausal hormone replacement therapy in your clinical practice.

About Estrogen Replacement Therapy (ERT)

Bioidentical estrogen therapies are FDAapproved for moderate to severe vasomotor symptoms (VMS), moderate to severe vulvovaginal symptoms (VVA), prevention of osteoporosis in postmenopausal females, and hypoestrogenism from hypogonadism, surgical

menopause, or premature ovarian insufficiency. Estrogen therapy may also confer additional benefits, including cardiovascular protection, brain health, preservation of muscle mass and healthy weight, mood support, skin elasticity, joint health and overall quality of life.

While there are important contraindications and considerations for patient safety, ERT is generally thought of as a safe therapy for most women, particularly when bioidentical estradiol is used via transdermal application, which lessens the risk of stroke and venous thromboembolism seen (though, still rarely) with oral estrogen.

Studies have shown that benefits of ERT are seen (including improvements in VMS, VVA, and bone mineral density (BMD)) when doses of ERT products are used that generally increase serum E2 levels (measured with LC-MS/MS, not EIA) to 20-60 pg/mL (or 75220 pmol/L)1. FDA-approved doses have been established for commercially available patches

and gels based upon their likelihood of getting women into this effective range, and the North American Menopause Society (NAMS) does not recommend monitoring post-initiation of therapy, assuming that women will achieve these effective ranges on typical doses.

Monitoring ERT May Optimize Dosing and is Aligned with a Personalized Medicine Approach

Menopausal hormone replacement therapy stands as an outlier when it comes to monitoring hormone therapies, as almost any other hormonal therapy (thyroid hormone, testosterone in men, etc) includes ongoing monitoring as standard of care.

Is ERT dosing so straightforward that it’s not necessary? It doesn’t appear that way.

Jarvinen, et al. conducted a pharmacokinetic study on both group and individual responses to FDA-approved patch and gel estradiol therapy. What they found was that there was significant change over the course of a day in typical respondents, showing that any single serum time diversity in serum estradiol levels obtained between different women in the study. Some subjects showed a similar pattern of pharmacokinetics over the course of a day, but their total serum E2 was much lower than others overall, suggesting perhaps low absorption. Other study participants had atypical pharmacokinetic patterns. Within a small study group (n=24), there was high variability both within and between the subjects. This real-world look at women’s response to standardized ERT should have providers thinking about how they might optimize dose and route of administration for each patient, ensuring that therapeutic doses are reached.2

Integrative and functional medicine providers have access to a variety of tools available to monitor ERT, and with that, an opportunity to optimize a patient’s estrogen dose to ensure she is getting adequate exposure to confer the desired benefits. This being true, some monitoring approaches used in our field are not evidence-based and may mislead providers as to the appropriate doses for their patients.

Monitoring ERT: Serum v Urine v Saliva

Serum

In our discussion of monitoring estrogen replacement therapies, it’s critical to begin by re-emphasizing that serum, though frought with difficulties when put into a clinical practice setting (due to necessity to capture multiple time points to estimate overall daily exposure), is still accurate, if using LC-MS/ MS methodology. Serum may actually be a suitable monitoring approach for estradiol patch therapy, which delivers a steady dose over the course of several days, allowing for a more stable pharmacokinetic pattern.

Once concern is that some providers assume luteal serum levels of E2 (~100pg/mL) should be achieved, when only 20-60pg/mL is necessary to achieve clinical outcomes. Just as problematic is falsely assuming that a sufficient woman needs more E2 due to timing of the sample taken.

Saliva

Saliva is not a suitable method for monitoring transdermal ERT. Now, this is may be a very controversial statement, but we hope you will continue to read to allow yourself to consider these points.

First, saliva (as a medium) is not problematic in all instances. Substantial data has been published on cortisol measurements in serum and saliva. Saliva is considered by many to be the gold standard for free cortisol measurement. However, for reproductive hormones (estrogen and progesterone, both endogenous production and exogenous treatment), the literature does not affirm saliva testing as a reliable approach.

While this article is focused on ERT, an interesting, and very relevant, study was published in early 2023 evaluating salivary assays to evaluate endogenous production of progesterone and estradiol, which would generally be even easier to evaluate than on-therapy levels.3 Arslan et al, an independent group, evaluated a variety of commercially available salivary assays and found that for estradiol, the validity of the testing was so

poor that results could not even predict a woman’s cycle phase, which can be easily identified with serum testing. This paper essentially concluded that levels were too difficult to measure accurately in saliva (with commercially available assays) to characterize a premenopausal woman’s estrogen status. Certainly these same assays should not be trusted to accurately measure E2 levels in postmenopausal women making even less (10x) estrogen.

Another way to assess a lab’s potential ability to assess estradiol levels is to look at their own reference ranges. The estradiol levels of cycling females and postmenopausal females should have clear differentiation in labs. This is the case for serum (using LC-MS/MS), where there is a clear gap in reference range between these groups. In many salivary assays, including most available commercially in the US, those reference ranges overlap, suggesting an inability to distinguish between a postmenopausal female (who makes very little estradiol) and a cycling female (with robust production, comparatively). In other words, if a lab considers an estradiol result “normal” for both premenopausal AND postmenopausal women, there is a problem with the accuracy of the test.

Many providers are shocked to learn that there is essentially no peer-reviewed research affirming the use of saliva monitoring of ERT. Before trusting clinical decisions made after considering a lab result, it’s critical for clinicians to ensure that lab value produces results with clinical relevance.

Urine

Dried urine metabolite testing may provide a reliable solution for clinicians wishing to optimize estradiol therapy for their patients. First, dried urine offers an easy, at home collection method which can be collected at multiple time points across a 24-hour period, offering a more representative result of total estradiol exposure versus any single time point, the issue raised with serum testing.

Additionally, dried urine testing for estradiol has been validated and published data exists in well-respected peerreviewed journals for endogenous production as well as estradiol patches, gels and even compounded creams4.

In November 2023, a study was published in Menopause that evaluated estrogen exposure from various methods of transdermal estradiol (E2) applications, including FDA-approved patches and gels and compounded creams using dried urine testing as a method. This study showed strong alignment with serum and showed a dose-dependent, linear response to therapy.

Key findings in this research show that estrogen exposure from compounded transdermal estradiol (E2) creams increases in a dose-dependent manner; however, the amount of estrogen exposure associated with compounded creams is significantly lower than estrogen exposure associated with FDA-approved transdermal E2 patches and gels.

Additionally, this study highlights the potential clinical validity and utility of urine metabolite testing in the setting of transdermal estrogen replacement therapy.

ERT in Practice: Classification of low, medium, and high dose estrogen therapy

The classification of low, medium, and high dose estrogen therapy is well established in published literature, particularly with FDA-approved bioidentical estradiol patches and gels. These classifications are based upon clinical outcomes studies and show partial improvement in symptoms (such as VMS) at low doses, with improved outcomes at medium and high doses.

Those dose ranges are:

Low Dose ERT: <0.5 mg for cream andgel; 0.025- 0.0375 mg for patch

Mid Dose ERT: 0.5-1.0 mg for cream and gel; 0.05 mg for patch

High Dose ERT: 1.0-1.5 mg for cream and gel; 0.1 mg for patch

Saliva Tells a Different Story

It’s no secret that when patients use 0.25-1.0mg of an E2 cream or gel, the urine values lift moderately while saliva levels tend to elevate well outside the luteal range. Saliva experts claim that these elevated salivary values represent a “too high” tissue exposure,

implying that much less estrogen should be used. The practical result of this contradiction is that clinicians using saliva testing and dosing to get women in the salivary range may dose as little estradiol as 0.05mg.

Are 0.25-1.0mg E2 creams and gels extremely high doses of ERT as saliva implies? Or are these doses of creams and gels low to moderate doses as implied by urine testing and seen in clinical outcomes studies?

The clinical data makes the answer to this question simple and clear. 0.27mg EstroGel failed to relieve VMS at 4 weeks (success at 12 weeks) and did not relief vaginal atrophy. Divigel 0.25mg is reported to deliver only a fraction of the administered dose, and this product’s clinical efficacy is in alignment with this assessment as it also failed to relieve VMS at 4 weeks. In all of the cases listed, using a slightly higher dose showed more clinical success, so these doses are truly “low” doses despite many of the patients on these products presenting with high (many wildly so) salivary E2 levels. As with testosterone and progesterone creams and gels, high saliva values have been reported and have NEVER been corroborated with clinical outcomes consistent with these spurious findings.

But isn’t 0.25mg (and higher) more E2 than is necessary, as evidenced by 0.025-0.05mg patch data? This is a commonly confused topic, and the response is quite simple. Gels and creams are labeled according to the amount of APPLIED estradiol contained in one pump/application of gel. With patches, labeling describes the daily DELIVERED dose. The applied dose is not the same as the delivered dose.

As an example, let’s look at one FDA-approved patch labeled 0.05 mg. If you read the packaging on the product, you will find that the patch contains 3.8 mg of estradiol. Is that too much E2 for a woman? Looking more carefully, it is intended to be applied for 7 days, so that works out to be 0.54 mg per day and research shows us that only 0.05mg is actually absorbed or delivered daily. So for this particular patch, women, on average, absorb only 9.2% of the estradiol in the patch daily. For common gels and patches, absorption seems to be similar with only about 10% of the product actually absorbs.

This is a critical understanding in hormone replacement therapy that is commonly missed. The applied dose and the delivered dose of a hormone are different. Low dose patches and low dose gels show similar clinical outcome data, and urine results are consistent with these findings. Saliva results wildly contradict these findings with even 0.25mg E2 creams showing results more than 2.5 times higher than 0.05mg patches (ZAVA PUBLICATION).

It is true that saliva test results elevate substantially with estradiol gels and creams, and may suggest that these are high doses, but serum and urine tests as well as clinical outcomes studies (which should be most heavily considered!) all conflict with that conclusion.

Finally, it’s very important to consider your own clinical experience as you make decisions. They should be a consideration as you decide what to do in your own practice. Studies have shown, however, that VMS are significantly impacted by the placebo effect (meaning that placebo is effective also for many women), so balancing your experience with larger, controlled placebo-controlled studies on therapeutic response and optimal dosing is very important.5

References:

1. Jarvinen A, et al. Maturitas. 2001;38(2):189-196.NAMS. Menopause. 2022;29(7):767-794.

2. Jarvinen A, et al. Maturitas. 2001;38(2):189-196.

3. Arslan RC, Blake K, Botzet LJ, Bürkner PC, DeBruine L, Fiers T, Grebe N, Hahn A, Jones BC, Marcinkowska UM, Mumford SL, Penke L, Roney JR, Schisterman EF, Stern J. Not within spitting distance: Salivary immunoassays of estradiol have subpar validity for predicting cycle phase. Psychoneuroendocrinology. 2023 Mar;149:105994. doi: 10.1016/j. psyneuen.2022.105994. Epub 2022 Dec 5. PMID: 36527751.

4. Newman MS, Saltiel D, Smeaton J, Stanczyk FZ. Comparative estrogen exposure from compounded transdermal estradiol creams and Food and Drug Administration-approved transdermal estradiol gels and patches. Menopause. 2023 Nov 1;30(11):1098-1105. doi: 10.1097/GME.0000000000002266. Epub 2023 Oct 18. PMID: 37847876.

5. Archer DF, Pickar JH, MacAllister DC, Warren MP. Transdermal estradiol gel for the treatment of symptomatic postmenopausal women. Menopause. 2012;19(6):622-629. doi:10.1097/gme.0b013e31823b8867

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Microbiome Health: A Key Consideration in Addressing Metabolic Syndrome and Insulin Resistance

By: Jocelyn Strand, ND, & Shawn Manske, ND

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.

Metabolic Syndrome (MetS) has gained much attention in the last decade due to its dramatic increase worldwide. More than a billion people now experience MetS – a cluster of conditions that raises the risk for serious illness.1

At the same time, the microbiome has emerged as an important clinical focus for understanding how MetS develops and progresses.2 Patient interventions and treatment protocols that address microbiome health –both in the oral cavity and in the gut – present an opportunity for effectively managing and even preventing this widespread syndrome.

Prevalence & Risk Factors

MetS is about three times more common than diabetes, with the global prevalence estimated at one-quarter of the world population.3 Left untreated, MetS can progress to disorders such as Type 2 diabetes and non-alcoholic fatty liver disease. MetS is strongly associated with developing atherosclerotic cardiovascular

disease (CVD), increasing the risk of coronary artery disease and stroke.4 Research also suggests periodontitis, a common inflammatory condition affecting nearly 50% of the global population, may contribute to or exacerbate metabolic syndrome.5

The current definition of MetS comes from the World Health Organization. It states that the following criteria must be met for a diagnosis:

• Presence of insulin resistance

• Presence of at least two of the following:

○ Elevated fasting blood glucose (often present with insulin resistance)

○ Elevated blood triglycerides

○ Low HDL cholesterol

○ Elevated blood pressure

○ Abdominal adiposity (aka central obesity or large waistline)

The most accepted hypothesis for developing MetS is insulin resistance. In fact, MetS is often referred toas insulin resistance syndrome. Risk factors for developing MetS include:6

• Age

• Ethnicity. Hispanics – especially Hispanic women –appear to be at the greatest risk of developing MetS.

• Sedentary lifestyle

• Obesity. Visceral adiposity is a primary trigger for most of the pathways involved in MetS.7

• Diabetes. MetS is more likely following gestational diabetes or when there is a family history of Type 2 diabetes.

• Non-alcoholic fatty liver disease

• Polycystic ovary syndrome

• Sleep apnea

Metabolic Syndrome & the Microbiome

While genetics and environmental factors play a role in the development of MetS, dysbiosis is recognized as an important modifier. Microbial imbalances can contribute to a cascade of effects – from chronic inflammation to insulin resistance to neurohormonal activation – that perpetuate the progression of MetS.

The following table lists the fundamental physiological changes associated with MetS and how those changes relate to the microbiome:

factors in the developmentand progression of MetS and its transition to CVD.8

resistance

Dysbiosis results in intestinal permeability, increasing the absorption of lipopolysaccharides (LPS) and leading to:

• Increased activation of inflammatory pathways

• Impaired insulin signaling

• Decreased phosphorylation of the insulin receptor.9

• Gut microbiota can either activate or inhibit the HPA axis.

• Short-chain fatty acids (SCFAs) are crucial for the maturation and function of microglia, the resident macrophages of the central nervous system.

Neurohormonal activation

inflammation

• An imbalance of the gut microbial community (induced by stress or diet) can lead to inflammatory processes and activation of the HPA axis.

• When the microbiota is missing or dysbiotic, especially early in life, the brain’s high metabolic demands may go unmet due to nutrient deficiencies. This is known to contribute to long-term neuroendocrine disturbances.10

• The gut and the oral microbiota and its metabolites may regulate host inflammatory conditions.

• Numerous studies have linked the gut microbiota to inflammatory diseases such as Crohn’s, ulcerative colitis, multiple sclerosis, and rheumatoid arthritis.

• The gut microbiota plays a role in the pathogenesis of inflammatory diseases such as asthma, Type 1 and Type 2 diabetes mellitus (DM), and obesity.11

• Oral pathogens have been linked to a multitude of systemic illnesses, including MetS.12

Restoring Microbial Balance

Research shows a significant connection between a balanced microbiome and healthy metabolic function

Central

Relationship to the microbiome

Insulin

Chronic

– including the prevention and possible treatment of MetS and insulin resistance.13

Specific strains of bacteria play a role in immune and metabolic signaling and maintaining gut barrier integrity. Gram-negative bacteria, which produce endotoxins, must be kept in check while maintaining an increased diversity of favorable strains to create a healthy microbiome.

Bacterial LPS activation of toll-like receptors leads to innate immune responses that impair insulin sensitivity. LPS, trimethylamine (TMA), and other inflammatory metabolites then enter systemic circulation, upregulating inflammation through TLR-4 receptor activation. The result is chronic inflammation in the liver and adipose tissue that is associated with the development of insulin resistance, CVD, and other conditions seen in MetS.14

A healthy diet has a beneficial impact on MetS due in part to how it affects microbial balance in the GI tract. Highfiber diets support a more diverse and robust microbiome, whereas a high-fat, low-fiber diet disrupts tight junctions and gut lining integrity, which induces intestinal dysbiosis.

Fiber fermentation plays a significant role in supporting the integrity of the gut lining. Metabolites produced by microbial fermentation of fibers induce the production of endogenous peptides known to have beneficial effects on glucose metabolism and to improve intestinal epithelial tight junction integrity (GLP-1 and GLP-2).15

There has been a recent trend in the use of glucagonlike peptide-1 (GLP-1) receptor agonist medications to support weight management and appetite control. These medications mimic GLP-1, an incretin and satiety hormone released from L-cells in the gastrointestinal tract in response to eating. GLP-1 causes the body to produce more insulin, which reduces blood glucose (sugar) and suppresses appetite – thereby supporting energy balance, glucose homeostasis, and body-weight control. 16

Through fermentation of non-digestible starches and prebiotic fibers, the microbiome produces a range of metabolites, including secondary bile acids and SCFAs (butyrate, propionate, acetate, etc.), which have been

shown to stimulate GLP-1 secretion.17 This represents an important crosstalk pathway between gut microbes and host cells via enteroendocrine peptides. This crosstalk can be supported through dietary intervention and microbiome modification for an integrative approach.

1: Mechanisms linking gut microbiota and GLP-1 secretion.18

Another metabolic end-product of fermentation, SCFAs, offer further – and far-reaching – benefits, including:

• Improving long-standing dyslipidemia

• Providing fuel for intestinal epithelial cells (IEC)

• Modulating and regulating IEC proliferation and differentiation

• Impacting gut motility

• Strengthening the gut barrier

• Supporting immunomodulatory functions

• Facilitating gut endocrine host physiology19

• Playing a central role in the diet-gut microbiome-host metabolism axis20

Figure

Clinical Considerations

Microbiome health can be supported by modulating the microbiome with botanicals, diet, lifestyle changes, functional foods, and supplements.21 Clinical considerations for integrative medicine practitioners include the following:

1. Include fiber. Research shows that high-fiber, plant-based diets increase biodiversity and decrease non-favorable strains.22 On the other hand, high-fat diets seem to reduce protective SCFA production and increase concentrations of substances such as p-cresol, indole, arachidonic acid, and LPS in stools while increasing inflammatory markers in plasma.23 High-fiber diets rich in fruits, vegetables, beans, nuts, and seeds seemed to effect change in the microbiome in as little as five days. The Mediterranean diet has been closely associated with decreased rates of metabolic diseases and various cancers, mainly due to its fiber abundance.24,25

2. Get your patients to move their bodies. While exercise provides beneficial physiological effects, movement also significantly impacts microbiome health. Increased diversity in the microbiome and its antioxidant activity in the gut (due to increased levels of keystone probiotic species

Faecalibacterium prausnitzii and Akkermansia

muciniphila) has a positive correlation with increased levels of aerobic and endurance exercise.26,27,28 Recommending a regular exercise routine along with dietary changes is imperative for influencing the microbiome and overall health.

3. Don’t forget the mouth! Patients with metabolic syndrome were 2.6 times more likely to develop periodontitis. Periodontitis leads to systemic inflammation, which can drive metabolic syndrome. Treating periodontitis has been shown to reduce circulating inflammatory mediators such as C-reactive protein and interleukin 6 and may serve as a beneficial therapeutic when addressing metabolic syndrome.29

4. Offer lifestyle resources. Support patient treatment with simple yet effective lifestyle recommendations that include the following:

• Adopt a low-inflammation diet (modified Paleo, Mediterranean, etc.), including a high intake of non-starchy vegetables.

• Reduce overall caloric intake.

• Proactively work to reduce and manage stress.

• Increase exercise to support weight loss, blood sugar regulation, and cardiovascular health.

• Cultivate connections with community, friends, and family to support mental health.

Figure 2: This illustration from a 2020 review study by Green et al. summarizes the differences in microbiome-related metabolic effects in non-obese versus obese individuals.30

Improving Outcomes

It is clear that addressing the microbiome as part of a core strategy for working with MetS and its associated disorders is essential. It may also provide a sustainable, long-term solution for reducing global rates of insulin resistance and obesity.29

A published 2020 study conducted by Al Bander et al. concluded: “A vast pool of studies in animals and

humans have indicated a critical interplay between the gut microbiota and inflammation that could inform therapeutic intervention for the treatment of these disorders.”31

Educating patients on the many ways in which the microbiome influences metabolic health is a practical first step in any MetS treatment protocol. Supporting at-risk patients with treatments that focus on correcting gut and oral dysbiosis can improve health outcomes and may even serve to prevent MetS from developing at all.

Authors Bios:

Jocelyn Strand, ND, is Senior Director of Clinical Education and Research for Biocidin Botanicals. She brings both a reverence for botanicals and a passion for science to her role. Dr. Strand monitors and participates in research, trains clinicians, and is a respected and engaging speaker. Before joining Biocidin Botanicals in 2019, Dr. Strand was a primary care provider in private practice for 11 years through the Minnesota Board of Medical Practice. She specialized in GI system disorders, mental health, Lyme disease, and autoimmune conditions.

Shawn Manske, ND, is the Assistant Director of Clinical Education for Biocidin Botanicals, supporting clinical education, research, and product development. He brings experience in both clinical practice and practitioner education to his role. Dr. Manske grew up in Ontario, Canada, and graduated from the Canadian College of Naturopathic Medicine. He has worked in private clinical practice focusing on GI dysfunction, autoimmune disease, and cardiovascular disease. Based in Western New York, Dr. Manske is also an experienced educator in the botanical supplements industry.

Contact Information

1-800-775-4140

clinical@biocidin.com

References:

1. Saklayen MG. The Global Epidemic of the Metabolic Syndrome. Curr Hypertens Rep. 2018;20(2):12. Published 2018 Feb 26. doi:10.1007/s11906018-0812-z

2. Dabke K, Hendrick G, Devkota S. The gut microbiome and metabolic syndrome. J Clin Invest. 2019;129(10):4050-4057. doi:10.1172/JCI129194

3. Saklayen MG. The Global Epidemic of the Metabolic Syndrome. Curr Hypertens Rep. 2018;20(2):12. Published 2018 Feb 26. doi:10.1007/s11906018-0812-z

4. Rochlani Y, Pothineni NV, Kovelamudi S, Mehta JL. Metabolic syndrome: pathophysiology, management, and modulation by natural compounds. Ther Adv Cardiovasc Dis. 2017;11(8):215-225. doi:10.1177/1753944717711379

5. Kuraji R, Shiba T, Dong TS, Numabe Y, Kapila YL. Periodontal treatment and microbiome-targeted therapy in management of periodontitisrelated nonalcoholic fatty liver disease with oral and gut dysbiosis. World J Gastroenterol. 2023;29(6):967-996. doi:10.3748/wjg.v29.i6.967

6. 6 Mayo Clinic Staff. Metabolic Syndrome. MayoClinic.org. Published May 06,

2021. Accessed February 28, 2024. https://www.mayoclinic.org/diseasesconditions/metabolic-syndrome/symptoms-causes/syc-20351916

7. Green M, Arora K, Prakash S. Microbial Medicine: Prebiotic and Probiotic Functional Foods to Target Obesity and Metabolic Syndrome. Int J Mol Sci. 2020;21(8):2890. Published 2020 Apr 21. doi:10.3390/ijms21082890

8. Rochlani Y, Pothineni NV, Kovelamudi S, Mehta JL. Metabolic syndrome: pathophysiology, management, and modulation by natural compounds. Ther Adv Cardiovasc Dis. 2017;11(8):215-225. doi:10.1177/1753944717711379

9. Caricilli AM, Saad MJ. The role of gut microbiota on insulin resistance. Nutrients. 2013;5(3):829-851. Published 2013 Mar 12. doi:10.3390/ nu5030829

10. Farzi A, Fröhlich EE, Holzer P. Gut Microbiota and the Neuroendocrine System. Neurotherapeutics. 2018;15(1):5-22. doi:10.1007/s13311-0170600-5

11. Wang J, Chen WD, Wang YD. The Relationship Between Gut Microbiota and Inflammatory Diseases: The Role of Macrophages. Front Microbiol.

Microbiome Health: A Key Consideration in Addressing Metabolic Syndrome and Insulin Resistance

2020;11:1065. Published 2020 Jun 9. doi:10.3389/fmicb.2020.01065

12. Nibali L, Stephen AS, Allaker RP, et al. Associations between Host Genetic Variants and Subgingival Microbiota in Patients with the Metabolic Syndrome. Int J Mol Sci. 2023;24(23):16649. Published 2023 Nov 23. doi:10.3390/ijms242316649

13. Green M, Arora K, Prakash S. Microbial Medicine: Prebiotic and Probiotic Functional Foods to Target Obesity and Metabolic Syndrome. Int J Mol Sci. 2020;21(8):2890. Published 2020 Apr 21. doi:10.3390/ijms21082890

14. Dabke K, Hendrick G, Devkota S. The gut microbiome and metabolic syndrome. J Clin Invest. 2019;129(10):4050-4057. doi:10.1172/JCI129194

15. Dabke K, Hendrick G, Devkota S. The gut microbiome and metabolic syndrome. J Clin Invest. 2019;129(10):4050-4057. doi:10.1172/JCI129194

16. Wang Q, Lin H, Shen C, et al. Gut microbiota regulates postprandial GLP-1 response via ileal bile acid-TGR5 signaling. Gut Microbes. 2023;15(2):2274124. doi:10.1080/19490976.2023.2274124

17. Dabke K, Hendrick G, Devkota S. The gut microbiome and metabolic syndrome. J Clin Invest. 2019;129(10):4050-4057. doi:10.1172/JCI129194

18. Everard A, Cani PD. Gut microbiota and GLP-1. Rev Endocr Metab Disord. 2014;15(3):189-196. doi:10.1007/s11154-014-9288-6

19. Martin-Gallausiaux C, Marinelli L, Blottière HM, Larraufie P, Lapaque N. SCFA: mechanisms and functional importance in the gut. Proc Nutr Soc. 2021;80(1):37-49. doi:10.1017/S0029665120006916

20. Morrison DJ, Preston T. Formation of short chain fatty acids by the gut microbiota and their impact on human metabolism. Gut Microbes. 2016;7(3):189-200. doi:10.1080/19490976.2015.1134082

21. Caricilli AM, Saad MJ. The role of gut microbiota on insulin resistance. Nutrients. 2013;5(3):829-851. Published 2013 Mar 12. doi:10.3390/ nu5030829

22. Wang PX, Deng XR, Zhang CH, Yuan HJ. Gut microbiota and metabolic syndrome. Chin Med J (Engl). 2020;133(7):808-816. doi:10.1097/ CM9.0000000000000696

23. Wan Y, Wang F, Yuan J, et al. Effects of dietary fat on gut microbiota and faecal metabolites, and their relationship with cardiometabolic risk factors: a 6-month randomised controlled-feeding trial. Gut. 2019;68(8):1417-1429. doi:10.1136/gutjnl-2018-317609

24. Wilson AS, Koller KR, Ramaboli MC, et al. Diet and the Human Gut Microbiome: An International Review. Dig Dis Sci. 2020;65(3):723-740. doi:10.1007/s10620-020-06112-w

25. Meslier V, Laiola M, Roager HM, et al. Mediterranean diet intervention in overweight and obese subjects lowers plasma cholesterol and causes changes in the gut microbiome and metabolome independently of energy intake. Gut. 2020;69(7):1258-1268. doi:10.1136/gutjnl-2019-320438

26. Ortiz-Alvarez L, Xu H, Martinez-Tellez B. Influence of Exercise on the Human Gut Microbiota of Healthy Adults: A Systematic Review. Clin Transl Gastroenterol. 2020;11(2):e00126. doi:10.14309/ctg.0000000000000126

27. Mach N, Fuster-Botella D. Endurance exercise and gut microbiota: A review. J Sport Health Sci. 2017;6(2):179-197. doi:10.1016/j.jshs.2016.05.001

28. Guevara-Cruz M, Flores-López AG, Aguilar-López M, et al. Improvement of Lipoprotein Profile and Metabolic Endotoxemia by a Lifestyle Intervention That Modifies the Gut Microbiota in Subjects With Metabolic Syndrome. J Am Heart Assoc. 2019;8(17):e012401. doi:10.1161/JAHA.119.012401

29. Pirih FQ, Monajemzadeh S, Singh N, et al. Association between metabolic syndrome and periodontitis: The role of lipids, inflammatory cytokines, altered host response, and the microbiome. Periodontol 2000. 2021;87(1):50-75. doi:10.1111/prd.12379

30. Green M, Arora K, Prakash S. Microbial Medicine: Prebiotic and Probiotic Functional Foods to Target Obesity and Metabolic Syndrome. Int J Mol Sci. 2020;21(8):2890. Published 2020 Apr 21. doi:10.3390/ijms21082890

31. Dos Reis SA, do Carmo Gouveia Peluzio M, Bressan J. The use of antimicrobials as adjuvant therapy for the treatment of obesity and insulin resistance: Effects and associated mechanisms. Diabetes Metab Res Rev. 2018;34(6):e3014. doi:10.1002/dmrr.3014

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Collagen & Silicon Key Elements for Connective Tissue Health

Author: Dr. Arland Hill, DC, MPH, DACBN Director of Clinical Education for Biotics Research ®

In the realm of healthcare, particularly for chiropractors, it is paramount to understand the crucial role of connective tissue health, and why supplementing with collagen has become so popular. Central to this understanding are two crucial components: collagen and silicon, both integral in maintaining and enhancing the structural integrity of various body tissues.1

Collagen, the most abundant protein in the human body, constitutes a major part of the extracellular matrix. It is a foundational structural element in bones, tendons, ligaments, hair, skin, cartilage, intervertebral discs, muscles, and even blood vessels. Although there are 28 distinct types of collagen, types I, II, and III account for 80-90% of the body’s total collagen. These types are critical for providing mechanical resilience and support for cell growth. Since age-related decline in collagen synthesis contributes to changes in skin, joints, and other connective tissues, the case for supplementing with collagen has grown stronger in recent years.2

Supplementation with collagen peptides has been shown to support connective tissues in several clinical studies. Benefits include improvements to skin hydration, elasticity, and wrinkling.3 Potential mechanisms include stimulation of collagen and proteoglycans in the skin, as well as enhanced skin turnover.4 It has even been found to improve scores related to mental and social health in a randomized controlled trial of middle-aged participants.5

Silicon is an abundant trace element in the body and a key component of the extracellular matrix, particularly in the bone, skin, and hair.6 It aids in the synthesis of collagen and acts as a cross-linking agent between collagen and proteoglycans. Mesoporosil®, a unique bioavailable form of silicon, has been shown in vitro to stimulate the synthesis of type I collagen and to promote osteoblast function, including the enhancement of bone mineralization.

The constructive interaction between collagen and silicon is noteworthy. Collagen provides the necessary framework for connective tissues, while silicon enhances this framework, contributing to the strength and resilience of these tissues.

Optimal Collagen, recently launched by Biotics Research, delivers a comprehensive collagen profile, focusing on types I, II, and III, and is enriched with Mesoporosil®, enhancing the benefits of collagen and supporting multiple tissues, including joints, bone, and skin. The hydrolyzed collagen found in Optimal Collagen is comprised of low molecular weight bioactive collagen peptides, demonstrating high bioavailability. Many clinical benefits of hydrolyzed collagen indicate that these peptides accumulate in the cartilage, stimulating chondrocytes and stimulating osteoblast activity.7 Optimal Collagen also provides eggshell membrane and sternum collagen, rich in collagen type II, as well as types I, V, X, along with chondroitin sulfate and hyaluronic acid.

For more information on Optimal Collagen visit the Biotics Research® website at www.bioticsresearch.com

REFERENCES:

1. Ouyang, Z., Dong, L., Yao, F., et al. (2023). Cartilage-Related Collagens in Osteoarthritis and Rheumatoid Arthritis: From Pathogenesis to Therapeutics. International journal of molecular sciences, 24(12), 9841.

2. Shin, J. W., Kwon, S. H., Choi, J. Y., et al. (2019). Molecular Mechanisms of Dermal Aging and Antiaging Approaches. International journal of molecular sciences, 20(9), 2126.

3. Kim, D. U., Chung, H. C., Choi, J., et al. (2018). Oral Intake of Low-Molecular-Weight Collagen Peptide Improves Hydration, Elasticity, and Wrinkling in Human Skin: A Randomized, Double-Blind, PlaceboControlled Study. Nutrients, 10(7), 826.

4. Barati, M., Jabbari, M., Navekar, R., et al. (2020). Collagen supplementation for skin health: A mechanistic systematic review. Journal of cosmetic dermatology, 19(11), 2820–2829.

5. Kviatkovsky, S. A., Hickner, R. C., Cabre, H. E., et al. (2023). Collagen peptides supplementation improves function, pain, and physical and mental outcomes in active adults. Journal of the International Society of Sports Nutrition, 20(1), 2243252

6. Rondanelli, M., Faliva, M. A., Peroni, G., et al. (2021). Silicon: A neglected micronutrient essential for bone health. Experimental biology and medicine (Maywood, N.J.), 246(13), 1500–1511.

7. Mobasheri, A., Mahmoudian, A., Kalvaityte, U., et al. (2021). A White Paper on Collagen Hydrolyzates and Ultrahydrolyzates: Potential Supplements to Support Joint Health in Osteoarthritis. Current rheumatology reports, 23(11), 78.

5 Bene ts of Collagen

By: Arland Hill, DC, MPH, DACBN

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.

Collagen is the most abundant protein found in the animal kingdom. Though 28 types of collagen have been identified in the human body, types I, II, and III account for 80-90 percent. The function of collagen is to support the softer tissues and withstand stretching. The basic structure of collagen consists of a triple helix made up of three alpha strands formed of glycine, proline and hydroxyproline. The differences in collagen types are due to specific patterns of amino acids within the alpha strands that form the triple helix. Type I collagen is common in skin, bones, tendons, ligaments, vascular ligature, and organs. Type II is primarily found in cartilage. Type III is found in skin, muscle, and blood vessels.

Collagen loss begins between 18 and 29 years of age. By the time a person is 80 years old, collagen production has slowed by 75% as compared to young people. Many signs of aging include loss of elasticity of the skin, stiff joints, and muscle loss. Other signs of collagen deficiency may include excessive skin wrinkles, blood pressure

problems, achy muscles, cellulite, dental problems, thinning hair, and brittle nails.

Supplementing with collagen has been shown in studies to be beneficial for mitigating some of these effects of the aging process. One study showed that food-derived peptides increased in the blood within an hour of ingestion and reduced to baseline levels after 24 hours, illustrating the importance of a balanced diet or regular, daily supplementation.1

Factors that damage collagen include sugar and refined carbohydrates, excessive sun exposure, smoking, and some autoimmune disorders. Sugar interferes via glycation with the ability of collagen to restore itself, while UV exposure reduces collagen production. You can help protect your collagen by eating well and avoiding sunburn.

The main dietary sources of collagen are the connective tissues of most animal foods. Bone broth is a rich source. There is some debate over the absorption of collagen;

however, research is showing that a blend of collagen peptides combined with bioactive silicon is wellabsorbed. Silicon is bound to glycosaminoglycans, and acts as a cross-linking agent between collagen and the proteoglycans of the extracellular matrix of collagen.2 In addition, experimental studies indicate that silicon improves the incorporation of calcium into bone.3

5 Benefits of Collagen:

Skin

There is abundant research demonstrating the positive effects of collagen supplementation on skin physiology. In a double blind, placebo-controlled study, women aged 35 – 55 were selected to either receive a daily dose of collagen, or a placebo. Their skin was objectively measured at the beginning and, by the end of the study, the groups that were taking the collagen supplement had a measurable improvement in terms of elasticity.4

In another study, oral collagen peptide supplementation significantly increased skin hydration after 8 weeks of intake.5 The collagen density in the dermis significantly increased and the fragmentation of the dermal collagen network significantly decreased after 4 weeks of supplementation. Both effects persisted after 12 weeks.

A meta study encompassing 8 studies with 805 patients concluded that hydrolyzed collagen peptides had a favorable outcome on wound healing and skin aging.6

Joints

As we age, collagen levels decline, especially from our connective tissue. This results in some loss of cushioning and regenerative abilities. The collagen peptides and free amino acids obtained through supplementation of hydrolyzed collagen do accumulate in joint cartilage. This helps to support joint health and mitigate joint deterioration. A study involving 147 athletes showed that joint pain was significantly reduced compared to placebo.7

Arthritis causes collagen to break down faster than it can be replenished, and a 2017 study found that oral supplementation of collagen reduced joint pain due to osteoarthritis.8

Bone

An additional benefit of supplementing with collagen was observed in a research study focused on post-menopausal women that found a positive shift in bone markers following collagen peptide supplementation, indicating increased osteoblastic activity and reduced osteoclastic activity.9

Gut

The benefits of supplemental collagen extend beyond skin, joint and ligament support. Leaky gut may be supported through collagen supplementation as evidenced in this study that was supported in part by the USDA. Improvement in tight junctions helped to decrease gut permeability.10

Muscle

Collagen peptide supplementation in a group of elderly sarcopenic men resulted in increased muscle mass and muscle strength with an improved body composition. The researchers suggested that collagen may stimulate creatine synthesis and promote muscle growth after exercise.11

Up to 10% of muscle tissue is composed of collagen. Because amino acids are the building blocks of muscle tissue it makes sense that supplementing with collagen peptides will benefit muscle repair. Looking at the amino acid profiles of most collagen types, however, reveals an incomplete picture. This makes it important to ensure that the collagen supplements you choose are comprehensive, at least with several types of collagen.

Silicon is an abundant trace element in the body and a key component of the extracellular matrix, particularly in the bone, skin, and hair. It aids in the synthesis of collagen and acts as a crosslinking agent between collagen and proteoglycans. Mesoporosil®, a unique bioavailable form of silicon, has been shown in vitro to stimulate the synthesis of type I collagen and to promote osteoblast function, including the enhancement of bone mineralization.

The constructive interaction between collagen and silicon is noteworthy. Collagen provides the necessary framework for connective tissues, while

silicon enhances this framework, contributing to the strength and resilience of these tissues.

Choosing a supplement that offers a complete collagen profile plus a bioavailable form of silicon is ideal. At the very least one should combine complementary supplements with a composite, complete amino-acid profile in mind to fully realize the many benefits of supplementing with collagen.

References:

1. Yasutaka Shigemura , Asahi Suzuki , Mihoko Kurokawa , Yoshio Sato , Kenji Sato Changes in composition and content of food-derived peptide in human blood after daily ingestion of collagen hydrolysate for 4 weeks. J Sci Food Agric. 2018 Mar;98(5):1944-1950.

2. Price, C. T., Koval, K. J., & Langford, J. R. (2013). Silicon: a review of its potential role in the prevention and treatment of postmenopausal osteoporosis. International journal of endocrinology, 2013, 316783.

3. Jugdaohsingh, R., Tucker, K. L., Qiao, N., et al. (2004). Dietary silicon intake is positively associated with bone mineral density in men and premenopausal women of the Framingham Offspring cohort. Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research, 19(2), 297–307.

4. E Proksch , D Segger, J Degwert, M Schunck, V Zague, S Oesser. Oral supplementation of specific collagen peptides has beneficial effects on human skin physiology: a double-blind, placebo-controlled study. Skin Pharmacal Physio 2014;27(1):47-55.

5. Jérome Asserin PhD, Elian Lati PhD, Toshiaki Shioya B.Eng., Janne Prawitt PhD. The effect of oral collagen peptide supplementation on skin moisture and the dermal collagen network: evidence from an ex vivo model and randomized, placebo-controlled clinical trials. Journal of Cosmetic Dermatology, 12 September 2015.

6. Franchesca D. Choi, Calvin T. Sung, Margit L.W. Juhasz, Natasha Atanaskova Mesinkovsk, Oral Collagen Supplementation: A Systematic Review of Dermatological Applications. J Drugs Dermatol. 2019 Jan1;18(1):9-16.

7. Kristine L Clark 1, Wayne Sebastianelli, Klaus R Flechsenhar, Douglas F Aukermann, Felix Meza, Roberta L Millard, John R Deitch, Paul S Sherbondy, Ann Albert, 24-Week study on the use of collagen hydrolysate as a dietary supplement in athletes with activity-related joint pain. Curr Med Res Open. 2008 May;24(5):1485-96.

8. Woo T, Lau L, Cheng N, Chan P, Tan K and Gardner A. Efficacy of Oral Collagen in Joint Pain - Osteoarthritis and Rheumatoid Arthritis. J Arthritis 2017, 6:2.

9. Daniel König, Steffen Oesser, Stephan Scharla, Denise Zdzieblik, Albert Gollhofer. Specific Collagen Peptides Improve Bone Mineral Density and Bone Markers in Postmenopausal Women-A Randomized Controlled Study. Nutrients. 2018 Jan 16;10(1):97.

10. Qianru Chen, Bafang Li, Isabela Martin, Jeffrey B. Blumberg, C-Y. Oliver Chen. Collagen peptides derived from Alaska pollock skin protect against TNFαinduced dysfunction of tight junctions in Caco-2 cells. The FASEB Journal, 01 April 2016

11. Denise Zdzieblik, Steffen Oesser, Manfred W. Baumstark, Albert Gollhofer, and Daniel König. Collagen peptide supplementation in combination with resistance training improves body composition and increases muscle strength in elderly sarcopenic men: a randomised controlled trial. Br J Nutr. 2015 Oct 28; 114(8): 1237–1245.

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Oncologic Outcomes of Testosterone Therapy for Men on Active Surveillance for Prostate Cancer: A Population-based Analysis

By:

Elie Kaplan-Maransa, Tenny R. Zhangb, Jim C. Hubb

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.

Article Info

Article History: Accepted January 12, 2024

Associate Editor: Roderick van den Bergh

Keywords: Testosterone

Prostate cancer

Outcomes

Active surveillance

Abstract

Background and objective: There is insufficient evidence on the oncologic risks of testosterone therapy for men with prostate cancer managed with active surveillance. We carried out a retrospective study to assess the effect of testosterone therapy on oncologic outcomes for men on active surveillance for prostate cancer.

Methods: Surveillance, Epidemiology and End Results (SEER)-Medicare linked data were used to identify men diagnosed with prostate cancer from 2008 to 2017 who were managed with active surveillance and received testosterone (ɳ = 167) or no testosterone (ɳ = 6658) therapy. Outcomes included conversion from active surveillance to active treatment (radical prostatectomy, cryotherapy, radiation, or androgen deprivation therapy), prostate cancer–specific mortality, and overall mortality. Statistically significant factors on univariable analysis were included in a Cox proportional-hazards

regression model for multivariable analysis.

Key findings and limitations: The median age was 71 yr (interquartile range [IQR] 68–74) in the testosterone group and 72 yr (IQR 69–75) in the no-testosterone group, with corresponding median follow-up after prostate cancer diagnosis of 5.2 yr (IQR 3.4–7.8) and 4.7 yr (IQR 3.2–6.9). There were no prostate cancer–specific deaths in the testosterone group and 39 (0.6%) in the no-testosterone group. Testosterone therapy was not associated with conversion to active treatment (hazard ratio [HR] 0.66, 95% confidence interval [CI] 0.46–0.97; p = 0.033) or overall mortality (HR 1.02, 95% CI 0.68–1.53; p > 0.9).

Conclusions and clinical implications:

In the first population-based, nationally representative study of testosterone therapy for men on active surveillance for prostate cancer, testosterone therapy did not increase the risk of conversion to active therapy or worsen mortality. Prospective studies are needed to confirm these findings.

Patient summary: For men on active surveillance for prostate cancer, we assessed the effect of testosterone therapy. We found that testosterone therapy did not increase the risk of proceeding to active therapy or of death from prostate cancer.

®2024 The Authors. Published by Elsevier B.V. on behalf of European Association of Urology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

1. Introduction

In 1966, Charles Huggins won the Nobel Prize for discovering that androgen deprivation inhibits prostate cancer [1,2]. While androgen deprivation therapy remains a mainstay of prostate cancer treatment [2], the discovery by Huggins also led to the widespread belief that testosterone directly stimulates prostate cancer in a linear fashion [1,3–5]. This idea persisted until at least 2001, when the National Cancer Institute (NCI) rejected funding for a large testosterone therapy clinical trial because of concerns that testosterone causes prostate cancer [3]. By the mid-2000s, however, several studies demonstrated that high testosterone levels do not cause prostate cancer [3,4].

Following these reports, Morgentaler and colleagues [3–5] proposed the saturation model as a paradigm shift for the relationship between serum testosterone and prostate cancer. The model suggests that prostate growth is sensitive to androgen concentrations at nearcastrate levels, but as androgen receptors become saturated, further prostatic growth is minimal at normal and high levels of testosterone [3,5,6]. As the saturation model predicts, testosterone therapy and high levels of endogenous testosterone do not appear to increase the risk of prostate cancer [4,6]. Moreover, testosterone therapy after treatment of localized prostate cancer does not appear to cause greater recurrence [4].

There is insufficient evidence on the oncologic risks of testosterone therapy for men with prostate cancer managed with active surveillance [4,7]. Active surveillance is recommended for low- and intermediate-risk prostate cancer to avoid interventions that may worsen healthrelated quality of life [8]. Testosterone therapy mitigates the signs and symptoms of testosterone deficiency and

improves healthrelated quality of life [4]. Our aim was to compare oncologic outcomes in terms of conversion to active treatment and prostate cancer–specific mortality and overall mortality of testosterone versus no testosterone therapy in the active surveillance population. To the best of our knowledge, this is the first populationbased study and largest series to characterize the use of testosterone therapy for men on active surveillance for prostate cancer. We hypothesized that oncologic outcomes for men receiving testosterone therapy would be noninferior to those for men without testosterone therapy.

2. Patients and methods

2.1. Data source

The Weill Cornell Medicine institutional review board approved this study (protocol number 1510016660). We conducted a retrospective cohort study using Surveillance, Epidemiology and End Results (SEER)- Medicare linked data. SEER is supported by the NCI and captures data for 48% of the US population across 22 geographic regions [9]. SEER includes demographic, clinical, and cause-of-death information for individuals diagnosed with cancer, as well as information on cancer treatment and survival [10]. Medicare data include information on all covered health care services received by individuals from the time of Medicare eligibility until death [10].

2.2. Study cohort

The study cohort is illustrated in Figure 1. The cohort included 250 935 men aged ≥66 yr diagnosed with prostate cancer from 2008 to 2017. As previously described [11], active surveillance was defined as no active treatment for prostate cancer (radical prostatectomy, cryotherapy, radiation, or androgen deprivation therapy) within 12 mo of diagnosis and at least one of the following three surveillance strategies within 2 yr of diagnosis: one or more prostate biopsies, four or more prostatespecific antigen (PSA) tests, or four or more encounters with a physician that had prostate cancer as the primary diagnosis. For reliable comorbidity and surveillance information, we excluded men who were not enrolled in Medicare Parts A and B for at least 1 yr before and 2 yr after prostate cancer diagnosis. To assess testosterone therapy use, we excluded men

who were not enrolled in Medicare Part D for at least 2 yr after prostate cancer diagnosis. Testosterone therapy use from 2008 to 2019 was determined from National Drug Code or Healthcare Common Procedure Coding System codes and included various modes of administration (injection, gel, solution, implant, patch, powder, and tablet) [12,13]. Finally, we excluded men with missing prostate cancer information, grade group ≥3 disease, clinical stage T3 or T4 prostate cancer, or PSA >20 ng/ml because active surveillance is not recommended in these cases [8]. After applying these criteria, we identified 167 men who received testosterone therapy and 6658 men who did not receive testosterone therapy while on active surveillance.

2.3. Outcomes

The primary outcomes were conversion from active surveillance to active treatment (radical prostatectomy, cryotherapy, radiation, or androgen deprivation therapy), and prostate cancer–specific mortality and overall mortality. Secondary outcomes included demographic and prostate cancer characteristics.

2.4. Statistical analysis

Patient and cancer characteristics are summarized using descriptive statistics and compared between the two groups. The χ2 test was used for comparison of categorical variables and the Wilcoxon ranksum test for continuous variables. Cohorts with <11 were omitted from the tables in accordance with the cell-size suppression policy of SEER-Medicare.

Overall survival was defined as time from the date of diagnosis to the date of death from any cause or the date of last follow-up. The Kaplan- Meier method was used to obtain survival probabilities and differences between groups were assessed using the log-rank test. Multivariate Cox proportional-hazards models were applied to assess the association of testosterone therapy with conversion to active treatment and overall survival, with adjustment for age and all the variables in Table 2. Hazard ratios (HRs) and their 95% confidence intervals (CIs) are reported (Table 3). All p values reported are two-sided, and p < 0.05 was considered statistically significant. All statistical analyses were performed using SAS v9.4 software (SAS Institute, Cary, NC, USA).

3. Results

The median age was 71 yr (interquartile range [IQR] 68–74) in the testosterone group and 72 yr (IQR 69–75) in the notestosterone group (Table 1), with corresponding median follow-up after prostate cancer diagnosis of 5.2 yr (IQR 3.4–7.8) and 4.7 yr (IQR 3.2–6.9). Testosterone therapy was more common in the southern and western SEER regions (p < 0.001), and for men with PSA <10 ng/ml (p = 0.018) and Gleason score ≤6 (p = 0.003; Table 2). These findings remained significant on multivariable analysis (Table 3).

There were 28 (17%) conversions to active treatment in the testosterone group and 1455 (22%) in the notestosterone group. There were no prostate cancer–specific deaths in the testosterone group, precluding comparison to the 39 (0.6%) prostate cancer–specific deaths in the notestosterone group. Multivariable analysis revealed that older men and men with higher comorbidity were less likely to switch to active treatment and experienced higher overall mortality (Table 4). Higher PSA at diagnosis was associated with greater likelihood of active therapy (HR 1.21, 95% CI 1.05–1.4; p = 0.009) and overall mortality (HR 1.3, 95% CI 1.08–1.57; p = 0.005). Higher income and education were associated with lower overall mortality. The mean duration of active surveillance was 4.9 yr (IQR 2.9–7.4) in the testosterone group and 3.9 yr (IQR 2.6–6.1) in the no-testosterone group (p < 0.001). Testosterone therapy was not associated with conversion to active therapy (HR 0.66, 95% CI 0.46– 0.97; p = 0.033) or overall mortality (HR 1.02, 95% CI 0.68– 1.53; p > 0.9). Kaplan-Meier survival curves demonstrate that testosterone therapy was not associated with conversion to active therapy (Fig. 2) or worse mortality (Fig. 3).

4. Discussion

There is a lack of research on the effects of testosterone therapy in men with untreated prostate cancer, with no prospective randomized controlled trials and only a few small retrospective studies conducted to date [14–17]. We demonstrate that testosterone therapy does not appear to increase the risk of conversion to active treatment or prostate cancer–specific or overall mortality in men with untreated prostate cancer on

active surveillance. These results support our hypothesis and align with the saturation model concept that prostate cells reach a limit in their capacity to respond to androgens at physiologic levels of testosterone [3,5]. These findings have important implications for patient care, as they suggest that testosterone therapy may be safely considered in this population.

In 2019, 224 733 individuals were diagnosed with prostate cancer in the USA [18]. Approximately 20% of these diagnoses were low-risk disease, for which the recommended management is active surveillance [8,19].

Before 2010, less than 10% of low-risk disease cases in community practice were managed with active surveillance [20]. Currently, up to 60% of cases are being managed with active surveillance and it is estimated that the optimal rate on the basis of guideline recommendations should exceed 80% [20]. On the basis of these figures, we estimate that 27 000–36 000 individuals are started on active surveillance each year. Considering that up to 25% of older men experience testosterone deficiency [4], almost 10 000 newly identified men per year could potentially improve their healthrelated quality of life through testosterone therapy.

Small, single-center retrospective studies have not shown a higher oncologic risk associated with testosterone therapy. Out of 13 men on active surveillance who received at least 12 mo of testosterone therapy and underwent one or more follow-up biopsies, only two experienced cancer progression [16]. Another study reported similar biopsy progression rates for up to 3 yr among men on active surveillance in groups receiving testosterone therapy (ɳ = 28) or no testosterone therapy (ɳ = 96) [14]. In a third study, none of eight patients on active surveillance and testosterone therapy followed for a median of 27 mo experienced clinical or pathological progression [17].

In our study, there were no prostate cancer–specific deaths in the testosterone group and 39 (0.6%) in the notestosterone group. This finding should be interpreted within the context of currently available evidence. Some reports suggest that testosterone therapy may actually have a protective effect on prostate cancer. For example, low free testosterone levels have been linked to reclassification of higher-risk disease in men on active surveillance [21], and testosterone therapy has been associated with lower rates of aggressive (ie, high-risk, locally advanced, regional, and distant metastatic) prostate cancer [22].

Oncologic Outcomes of Testosterone Therapy for Men on Active Surveillance for Prostate Cancer: A Population-based Analysis

It is well known that low testosterone levels are an independent risk factor for poorly differentiated prostate cancer [23]. A possible explanation may be that normal or high testosterone levels maintain prostate cell differentiation, whereas low testosterone levels lead to poorly differentiated cancer cells [22]. This mechanism may explain how high-dose testosterone therapy in men with castrationresistant prostate cancer induces prostate cell differentiation and resensitizes the cells to androgen deprivation therapy [22]. In addition, previous work suggested that at very high levels of testosterone past the saturation plateau, the proliferation of prostate cells actually decreases [6]. Bipolar testosterone therapy is based on this principle and has shown promising results as a treatment for metastatic prostate cancer [24].

While these preliminary findings may eventually lead to fundamental changes in the management of prostate cancer, more research is needed. According to the most recent American Urological Association and European Association of Urology guidelines, there is

insufficient evidence to determine the risk-benefit ratio of testosterone therapy for men with a history of prostate cancer [6,25]. TRAVERSE is an ongoing prospective, randomized, double-blind, placebo-controlled clinical trial that is assessing the efficacy response and longterm vascular events in hypogonadal men receiving testosterone replacement therapy, with the rate of highgrade prostate cancer as a secondary endpoint [26].

We also found that testosterone use was more common among men living in southern and western US regions and for men with PSA <10 ng/ml and Gleason score ≤6, which is consistent with other population-based studies [27,28]. These findings may be because of differences in testosterone prescribing practices or patient preferences between regions and cultural groups, as well as the persistent belief that testosterone stimulates prostate cancer growth in a linear manner.

Our findings must be interpreted in the context of the study design. First, our retrospective study is

hypothesisgenerating. Second, the mean duration of active surveillance was longer than in many existing studies because the claims-based definition used for active surveillance implied no intervention within 2 yr of diagnosis. The testosterone group may also have had longer surveillance duration than the no-testosterone group because these individuals started with lower testosterone levels and Gleason scores. However, it is clinically significant that testosterone therapy was not associated with higher mortality. Third, active surveillance protocols used by different providers may vary, which could affect the comparability of the study groups. Fourth, the data lack clinical granularity such as testosterone serum levels, dosage of testosterone, and indications for treatment. Finally, our study population was limited to men aged ≥66 yr, so it is uncertain whether these findings are generalizable to younger men with prostate cancer.

5. Conclusions

In the first nationally representative study to examine the use of testosterone therapy for men on active surveillance for prostate cancer, testosterone therapy did not increase the risk of conversion to active therapy or worsen mortality. These findings align with the saturation model and have important implications for patient care, as they suggest that testosterone therapy may be safely considered in this population. Prospective research is needed to confirm these findings and to explore the risks and benefits of testosterone therapy for these patients.

Author contributions: Elie Kaplan-Marans had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Kaplan-Marans, Zhang, Hu.

Acquisition of data: Kaplan-Marans.

Analysis and interpretation of data: Kaplan-Marans, Zhang, Hu.

Drafting of the manuscript: Kaplan-Marans, Zhang, Hu. Critical revision of the manuscript for important intellectual content: Kaplan-Marans, Zhang, Hu.

Statistical analysis: Kaplan-Marans, Zhang, Hu.

Obtaining funding: None.

Administrative, technical, or material support: None.

Supervision: Hu.

Other: None.

Financial disclosures: Elie Kaplan-Marans certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/ affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: None.

Funding/Support and role of the sponsor: None.

Acknowledgments: Jim C. Hu receives research support from the Frederick J. and Theresa Dow Wallace Fund of the New York Community Trust and salary support from grants NIH R01 CA241758, R01 CA259173, R01 CA273031; PCORI CER2019C1-15682, and CER-2019C2-17372, and a Prostate Cancer Foundation Challenge Award.

References:

[1] Huggins C, Hodges CV. Studies on prostatic cancer. Cancer Res 1941;1:293–7.

[2] Denmeade SR, Isaacs JT. A history of prostate cancer treatment. Nat Rev Cancer 2002;2:389–96. https://doi.org/10.1038/nrc801.

[3] Morgentaler A. Testosterone and prostate cancer: an historical perspective on a modern myth. Eur Urol 2006;50:935–9. https:// doi.org/10.1016/j. eururo.2006.06.034.

[4] Kaplan AL, Hu JC, Morgentaler A, Mulhall JP, Schulman CC, Montorsi F. Testosterone therapy in men with prostate cancer. Eur Urol 2016;69:894–903. https://doi.org/10.1016/j.eururo.2015.12.005.

[5] Morgentaler A, Traish AM. Shifting the paradigm of testosterone and prostate cancer: the saturation model and the limits of androgen-dependent growth. Eur Urol 2009;55:310–20. https:// doi.org/10.1016/j.eururo.2008.09.024.

[6] Mulhall JP, Trost LW, Brannigan RE, et al. Evaluation and management of testosterone deficiency: AUA guideline. J Urol 2018;200:423–32. https://doi. org/10.1016/j.juro.2018.03.115. [

7] Lenfant L, Leon P, Cancel-Tassin G, et al. Testosterone replacement therapy (TRT) and prostate cancer: an updated systematic review with a focus on previous or active localized prostate cancer. Urol Oncol 2020;38:661–70. https://doi.org/10.1016/j. urolonc.2020.04.008.

[8] National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology (NCCN guidelines ): prostate cancer. Version 1.2023. https:// www.nccn.org/professionals/physician_gls/pdf/ prostate.pdf.

[9] National Cancer Institute. SEER fact sheets. https://seer.cancer.gov/ about/ factsheets/.

[10] National Cancer Institute. SEER-Medicare: brief description of the SEERMedicare database. https://healthcaredelivery.cancer.gov/ seermedicare/ overview/.

[11] Krishna S, Fan Y, Jarosek S, Adejoro O, Chamie K, Konety B. Racial disparities in active surveillance for prostate cancer. J Urol 2017;197:342–9. https://doi.org/10.1016/j.juro.2016.08.104.

[12] Al-Lami RA, Graham JE, Deer RR, et al. Testosterone replacement therapy and rehospitalization in older men with testosterone deficiency in a postacute care setting. Am J Phys Med Rehabil 2019;98:456–9. https://doi.org/10.1097/ phm.0000000000001127.

[13] Lopez DS, Huang D, Tsilidis KK, et al. The role of testosterone replacement therapy and statin use, and their combination, in prostate cancer. Cancer Causes Control 2021;32:965–76. https:// doi.org/10.1007/s10552-021-014500.

[14] Kacker R, Hult M, San Francisco IF, et al. Can testosterone therapy be offered to men on active surveillance for prostate cancer? Preliminary results. Asian J Androl 2016;18:16–20. https://doi.org/ 10.4103/1008-682X.160270.

[15] Hashimoto T, Rahul K, Takeda T, et al. Prostate magnetic resonance imaging findings in patients treated for testosterone deficiency while on active surveillance for low-risk prostate cancer. Urol Oncol 2016;34:530.e9–e14. https://doi.org/10.1016/j. urolonc.2016.07.004.

[16] Morgentaler A, Lipshultz LI, Bennett R, Sweeney M, Avila DJ, Khera M. Testosterone therapy in men with untreated prostate cancer. J Urol 2011;185:1256–60. https://doi.org/10.1016/j. juro.2010.11.084.

[17] Ory J, Flannigan R, Lundeen C, Huang JG, Pommerville P, Goldenberg SL. Testosterone therapy in patients with treated and untreated prostate cancer: impact on oncologic outcomes. J Urol 2016;196:1082–9. https://doi. org/10.1016/j.juro.2016.04.069.

[18] Centers for Disease Control and Prevention. Prostate cancer incidence by stage at diagnosis, United States—2001 2019. https://www.cdc.gov/cancer/ uscs/about/data-briefs/no34- prostate-cancer-incidence-2001-2019.htm.

[19] Cooperberg M, Meeks W, Fang R, Gaylis F, Catalona W, Makarov D. MP4303 Active surveillance for low-risk prostate cancer: time trends and variation in the AUA Quality (AQUA) registry. J Urol 2022;207(Suppl 5):e740. https:// doi.org/10.1097/ JU.0000000000002609.03.

[20] Cooperberg MR, Meeks W, Fang R, Gaylis FD, Catalona WJ, Makarov DV. Time trends and variation in the use of active surveillance for management of low-risk prostate cancer in the US. JAMA Netw Open 2023;6:e231439. https://doi.org/ 10.1001/jamanetworkopen.2023.1439.

[21] San Francisco IF, Rojas PA, DeWolf WC, Morgentaler A. Low free testosterone levels predict disease reclassification in men with prostate cancer undergoing active surveillance. BJU Int 2014;114:229–35. https://doi. org/10.1111/bju.12682.

[22] Loeb S, Folkvaljon Y, Damber J-E, Alukal J, Lambe M, Stattin P. Testosterone Replacement Therapy and Risk of Favorable and Aggressive Prostate Cancer. J Clin Oncol Off J Am Soc Clin Oncol 2017;35(13):1430–6. https://doi.org/10.1200/JCO.2016.69.5304.

[23] Park J, Cho SY, Jeong S-H, Lee SB, Son H, Jeong H. Low testosterone level is an independent risk factor for high-grade prostate cancer detection at biopsy. BJU Int 2016;118(2):230–5. https://doi.org/ 10.1111/bju.13206.

[24] Morgentaler A, Caliber M. Safety of testosterone therapy in men with prostate cancer. Expert Opin Drug Saf 2019;18:1065–76. https://doi.org/10.10 80/14740338.2019.1666103

[25] Salonia A, Bettocchi C, Capogrosso P, et al. EAU guidelines on sexual and reproductive health. Arnhem, The Netherlands: European Association of Urology; 2023. https://uroweb.org/ guidelines/sexual-and-reproductivehealth/chapter/malehypogonadism.

[26] Bhasin S, Lincoff AM, Basaria S, et al. Effects of long-term testosterone treatment on cardiovascular outcomes in men with hypogonadism: rationale and design of the TRAVERSE study. Am Heart J 2022;245:41–50. https://doi. org/10.1016/j.ahj.2021.11.016.

[27] Zhou CK, Advani S, Chaloux M, et al. Trends and patterns of testosterone therapy among U.S. male Medicare beneficiaries, 1999 to 2014. J Urol 2020;203:1184–90. https://doi.org/10.1097/ JU.0000000000000744.

[28] Chen T, Li S, Eisenberg ML. Trends in testosterone therapy use in prostate cancer survivors in the United States. J Sex Med 2021;18:1346–53. https:// doi.org/10.1016/j.jsxm.2021.06.007

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Vitamin E Tocotrienols: The Ultimate Cardiometabolic Solution

By: Danielle Moyer Male , MS

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

The vitamin E family consists of two subgroups: tocopherols and tocotrienols. These two subgroups can be broken down further into their corresponding isomers (alpha, beta, gamma, and delta), totaling eight vitamin E isomers. Research suggests that vitamin E tocotrienols exert clinically relevant benefits in cardiometabolic health. The annatto plant is the richest known source of naturally occurring tocotrienolrich, tocopherol-free vitamin E isomers.

Typical commercial vitamin E supplements are low or absent in tocotrienols and, instead, are high in alpha-tocopherol. Interestingly, human studies reveal that if simultaneously administered, alpha-tocopherol may attenuate the bioavailability of tocotrienols and may interfere with the potential clinical benefits of tocotrienols. When supplemented without the presence of tocopherol isomers, vitamin E tocotrienols may promote cardiometabolic health in numerous ways.1,2

Healthy Lipid Metabolism

The unique chemical structure of tocotrienols has been shown to support healthy lipid metabolism and synthesis.3 A meta-analysis of 15 clinical trials highlighted that the individuals who received tocotrienol supplementation (≥ 200 mg/day) exhibited increased high-density lipoprotein (HDL) cholesterol status compared to a placebo.4 Individuals with high cholesterol (n = 31) receiving tocotrienol supplementation displayed decreased total cholesterol by 15%, low-density lipoprotein (LDL) cholesterol by 18%, and triglycerides by 14%.5 Furthermore, cytokines associated with cardiovascular disease and their gene expression, including tumor necrosis factor-alpha (TNF-α), interleukin (IL)-2, IL-4, IL-6, and IL-8, were downregulated by 39% to 64%.5 Patients with type 2 diabetes (n = 19) who received 3 mg of tocotrienol-rich fraction per kg of body weight exhibited decreased serum total lipids by 23%, total cholesterol by 30%, and LDLcholesterol by 42% (from 179 mg/dL to 104 mg/dL) within 60 days of supplementation.6

Healthy Glucose Metabolism

One hundred and ten patients with type 2 diabetes (T2DM) on a hypoglycemic agent were randomly divided to consume 250 mg/day of tocotrienols or a placebo for 24 weeks. Compared to the placebo, the experimental group exhibited improved glycemic control, reduced inflammation (analyzed through high sensitivity C-reactive protein [hs-CRP], TNF-α, and IL-6), and decreased oxidative stress (analyzed through MDA).2 A randomized controlled trial (RCT) of 77 patients with prediabetes demonstrated that individuals consuming 300 mg/day of tocotrienols exhibited significantly improved glycemic status and glucose utilization compared to the placebo.7

A 2023 published systematic review and meta-analysis by Phang and colleagues explored the connection between tocotrienol supplementation and glucose metabolism in individuals with T2DM. The study included data from 10 RCTs that administered tocotrienol-rich fraction as the primary intervention. A tocotrienol-rich fraction consists of a 70% mixture of tocotrienol isomers. Sample sizes ranged from 43 to 300 participants and study durations were between 8 weeks and 18 months. Administered amounts ranged from 200 to 420 total tocotrienols. Parameters related to blood pressure, inflammation (hs-CRP), and blood sugar homeostasis (HbA1c) were included in the meta-analysis.8

Findings showed significant decreases in HbA1c. Upon subgroup analysis, significant reductions in HbA1c were indicated when the duration of T2DM was less than 10 years, when the intervention lasted less than 6 months, and with a baseline HbA1c lower than 8.0%. In individuals with an HbA1c baseline higher than 8.0%, greater reductions in HbA1c were observed when compared with those with a lower than 8.0% baseline upon tocotrienol supplementation. While only non-significant decreases in systolic blood pressure and hs-CRP were reported, these results indicate that future clinical studies assessing tocotrienols’ effect on these parameters are warranted.8

Anti-Angiogenic Properties

One unique effect of delta-tocotrienols is that its antiangiogenic properties (inhibiting new blood vessel

formation) have the potential to help support eye health in T2DM. Uncontrolled hyperglycemia in T2DM increases oxidative stress, inflammation, thrombosis, and angiogenesis upregulation. Hyperglycemia can contribute to the development and progression of diabetic retinopathy, the most common microvascular complication of T2DM and a main contributor to adult blindness. Studies suggest the upregulation of vascular endothelial growth factor (VEGF), an angiogenic protein, as a hallmark feature of diabetic retinopathy.

Tocotrienol reduces VEGF expression, attenuating diabetic retinopathy progression.9 Alpha-tocopherol does not have these anti-angiogenic properties, and it appears to antagonize the anti-angiogenic effects of tocotrienols.10 A 2022 double-blind RCT of 55 participants with diabetic retinopathy investigated the effects of a tocotrienol-rich vitamin E supplement (200 mg twice daily for 12 months) for the progression of retinal microhemorrhages and diabetic macular edema. The tocotrienol group indicated a 48.38% decrease in diabetic macular edema compared to the placebo group, which had no significant changes to the development of retinal microhemorrhages. The study concluded that tocotrienol may have a significant role in reducing the risk of early diabetic retinopathy progression.9

Promoting Metabolic Health

Clinical studies have demonstrated the potential benefits of tocotrienol supplementation on individuals with metabolic syndrome (MetS).11 Combining tocotrienols with other nutrients that promote healthy inflammatory responses, such as quercetin, resveratrol, and B vitamins, may synergistically affect metabolic health, as observed in clinical trials.12 In a 24-week RCT with 82 patients with MetS, groups consuming 500 mg/day of delta-tocotrienols and 300 mg/day of resveratrol for 24 weeks exhibited a significant reduction in waist circumference, blood pressure, mean fasting plasma glucose, and serum triglyceride and an increase in HDL cholesterol. A decrease in hsCRP, IL-6, TNF-α, and malondialdehyde (MDA), as well as an increase in total antioxidant capacity, was also observed compared to the placebo group.11

Healthy Inflammatory Responses

Vitamin E tocotrienols help to promote healthy inflammatory responses, which may help support cardiovascular health and age-related diseases.13 In individuals (n = 31) receiving 250 mg/day of tocotrienol supplementation, CRP, nitric oxide (NO), and MDA were decreased by 40%, 40%, and 34%, respectively. Total antioxidant status, on the other hand, increased by 22%.14 It is important to note that normal NO status is necessary for cardiovascular health and blood pressure regulation.15 However, an overproduction of NO is associated with unregulated inflammatory responses.16 Systematic reviews of RCTs have further supported the role of tocotrienols in promoting healthy inflammatory responses, such as modulating the nuclear factor kappa β signaling pathway.17

Helping Maintain Endothelial Health

Nearly half of American adults have hypertension (48.1%), and only 1 in 4 adults have their hypertension under control (22.5%). Hypertension is associated with endothelial injury that can worsen the atherosclerotic process – a major risk factor for cardiovascular disease. In human studies,

tocotrienols have demonstrated the ability to support endothelial health.18 In vitro and animal studies have shown that tocotrienols may help maintain healthy blood pressure, potentially mitigate atherosclerotic lesions, and help attenuate the effects of endothelial inflammation.19–21 Specifically, gamma-tocotrienol has been shown in animal models to significantly reduce systolic blood pressure and improve endothelial NO synthase activity, both of which are key in supporting normal blood flow and circulation.22 However, more human clinical studies are needed before definitive conclusions can be drawn.

Summary

Research is still uncovering the exact role of tocotrienols in cardiometabolic health. In vitro and in vivo studies demonstrate how tocotrienols may benefit cardiometabolic health by promoting healthy lipid metabolism, inflammatory responses, and glucose metabolism, and supporting endothelial and metabolic health. Tocotrienol supplementation, such as annattoderived tocotrienols, may be warranted for certain individuals seeking to promote cardiometabolic health.

Danielle Moyer Male has an M.S. in Nutrition and is a boardCertified Nutrition Specialist® and a Licensed Dietitian Nutritionist. She is a Clinical Science Writer for Designs for Health, and teaches college-level nutrition. dmoyer@ designsforhealth.com

References:

1. Pervez MA, Khan DA, Ijaz A, Khan S. Effects of delta-tocotrienol supplementation on liver enzymes, inflammation, oxidative stress and hepatic steatosis in patients with nonalcoholic fatty liver disease. Turk J Gastroenterol. 2018;29(2):170-176. doi:10.5152/tjg.2018.17297

2. Mahjabeen W, Khan DA, Mirza SA, Pervez MA. Effects of delta�tocotrienol supplementation on glycemic control, oxidative stress, inflammatory biomarkers and miRNA expression in type 2 diabetes mellitus: a randomized control trial. Phytother Res. 2021;35(7):3968-3976. doi:10.1002/ptr.7113

3. Song BL, DeBose-Boyd RA. Insig-dependent ubiquitination and degradation of 3-hydroxy-3-methylglutaryl coenzyme a reductase stimulated by δ- and γ-tocotrienols. J Biol Chem. 2006;281(35):25054-25061. doi:10.1074/jbc. M605575200

4. Zuo S, Wang G, Han Q, et al. The effects of tocotrienol supplementation on lipid profile: a meta-analysis of randomized controlled trials. Complement Ther Med. 2020;52:102450. doi:10.1016/j.ctim.2020.102450

5. Qureshi A, Khan D, Mahjabeen W, Qureshi N. Dose-dependent modulation of

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lipid parameters, cytokines and RNA by δ-tocotrienol in hypercholesterolemic subjects restricted to AHA Step-1 diet. Br J Med Med Res. 2015;6(4):351366. doi:10.9734/BJMMR/2015/13820

6. Baliarsingh S, Beg ZH, Ahmad J. The therapeutic impacts of tocotrienols in type 2 diabetic patients with hyperlipidemia. Atherosclerosis. 2005;182(2):367-374. doi:10.1016/j.atherosclerosis.2005.02.020

7. Suleman F, Khan DA, Pervez MA, Aamir M. Effects of delta-tocotrienol supplementation on glycaemic control in individuals with prediabetes: a randomized controlled study. J Pak Med Assoc. 2022;72(01):4-7. doi:10.47391/JPMA.966

8. Phang SCW, Ahmad B, Abdul Kadir K, M Palanisamy UD. Effects of tocotrienol-rich fraction supplementation in patients with type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials. Adv Nutr. 2023;14(5):1159-1169. doi:10.1016/j.advnut.2023.06.006

9. Ho JI, Ng EY, Chiew Y, et al. The effects of vitamin E on non-proliferative diabetic retinopathy in type 2 diabetes mellitus: are they sustainable with

E Tocotrienols: The Ultimate Cardiometabolic Solution

12 months of therapy. SAGE Open Med. 2022;10:20503121221095324. doi:10.1177/20503121221095324

10. Shibata A, Nakagawa K, Tsuduki T, Miyazawa T. α-tocopherol suppresses antiangiogenic effect of δ-tocotrienol in human umbilical vein endothelial cells. J Nutr Biochem. 2015;26(4):345-350. doi:10.1016/j.jnutbio.2014.11.010

11. Fatima S, Khan DA, Aamir M, Pervez MA, Fatima F. δ-tocotrienol in combination with resveratrol improves the cardiometabolic risk factors and biomarkers in patients with metabolic syndrome: a randomized controlled trial. Metab Syndr Relat Disord. 2023;21(1):25-34. doi:10.1089/ met.2022.0052

12. Qureshi AA, Khan DA, Mahjabeen W, Papasian CJ, Qureshi N. Suppression of nitric oxide production and cardiovascular risk factors in healthy seniors and hypercholesterolemic subjects by a combination of polyphenols and vitamins. J Clinic Exp Cardiol. 2012;01(S5):8. doi:10.4172/2155-9880.S5008

13. Khor BH, Tiong HC, Tan SC, et al. Effects of tocotrienols supplementation on markers of inflammation and oxidative stress: a systematic review and metaanalysis of randomized controlled trials. PLoS One. 2021;16(7):e0255205. doi:10.1371/journal.pone.0255205

14. Qureshi AA, Khan DA, Mahjabeen W, Trias AM, Silswal N, Qureshi N. Impact of δ-tocotrienol on inflammatory biomarkers and oxidative stress in hypercholesterolemic subjects. J Clin Exp Cardiolog. 2015;06(04):367. doi:10.4172/2155-9880.1000367

15. Naseem KM. The role of nitric oxide in cardiovascular diseases. Mol Aspects Med. 2005;26(1-2):33-65. doi:10.1016/j.mam.2004.09.003

16. Subedi L, Gaire BP, Kim SY, Parveen A. Nitric oxide as a target for phytochemicals in anti-neuroinflammatory prevention therapy. Int J Mol Sci. 2021;22(9):4771. doi:10.3390/ijms22094771

17. Nasir AAN, Sadikan MZ, Agarwal R. Modulation of NFκB signalling pathway by tocotrienol: a systematic review. Asia Pac J Clin Nutr. 2021;30(3):537-555. doi:10.6133/apjcn.202109_30(3).0020

18. Rasool AHG, Rahman ARA, Yuen KH, Wong AR. Arterial compliance and vitamin E blood levels with a self emulsifying preparation of tocotrienol rich vitamin E. Arch Pharm Res. 2008;31(9):1212-1217. doi:10.1007/s12272-0011291-5

19. Newaz MA, Nawal NN. Effect of γ-tocotrienol on blood pressure, lipid peroxidation and total antioxidant status in spontaneously hypertensive rats (SHR). Clin Exp Hypertens. 1999;21(8):1297-1313. doi:10.3109/10641969909070850

20. Rahman TA, Hassim NF, Zulkafli N, Muid S, Kornain NK, Nawawi H. Atheroprotective effects of pure tocotrienol supplementation in the treatment of rabbits with experimentally induced early and established atherosclerosis. Food Nutr Res. 2016;60(1):31525. doi:10.3402/fnr.v60.31525

21. Muid S, Froemming GRA, Rahman T, Ali AM, Nawawi HM. Delta- and gamma-tocotrienol isomers are potent in inhibiting inflammation and endothelial activation in stimulated human endothelial cells. Food Nutr Res. 2016;60(1):31526. doi:10.3402/fnr.v60.31526

22. Newaz MA, Yousefipour Z, Nawal N, Adeeb N. Nitric oxide synthase activity in blood vessels of spontaneously hypertensive rats: antioxidant protection by gamma-tocotrienol. J Physiol Pharmacol. 2003;54(3):319-327

Shockwave Therapy in Anti-Aging Medicine: A Comprehensive Review and Interventions

By: Chaterjee Gupta, MD

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: Shockwave therapy, originally developed for lithotripsy, has gained attention in various medical fields for its regenerative and therapeutic effects. In the specialty of Anti-Aging Medicine, its potential benefits have been explored in areas such as skin rejuvenation, wound healing, and musculoskeletal health. This article provides a comprehensive review of the current literature on shockwave therapy within the context of Anti-Aging Medicine, covering its mechanisms of action, clinical applications, evidence of efficacy, and future directions.

Introduction: Anti-Aging Medicine encompasses a holistic approach to promoting vitality, longevity, and overall well-being. In recent years, non-invasive therapies have become increasingly sought after in the pursuit of maintaining youthful appearance and functionality. Shockwave therapy, originally utilized for the fragmentation of kidney stones, has emerged as a promising modality with applications ranging from dermatology

to orthopedics. This article aims to explore the role of shockwave therapy in Anti-Aging Medicine, shedding light on its mechanisms of action and clinical implications.

Mechanisms of Action: Shockwave therapy involves the delivery of acoustic waves to targeted tissues, inducing a cascade of biological responses. These waves can be generated via electrohydraulic, electromagnetic, or piezoelectric sources. The mechanical force exerted by shockwaves stimulates neovascularization, collagen synthesis, and release of growth factors, promoting tissue regeneration and repair. Additionally, shockwaves modulate pain perception and inflammation, contributing to their analgesic and anti-inflammatory effects.

Clinical Applications: In Anti-Aging Medicine, shockwave therapy has shown promise in various applications, including:

• Skin Rejuvenation: Low-energy shockwaves have been utilized to

enhance collagen production, improve skin elasticity, and reduce the appearance of wrinkles and cellulite. Studies have demonstrated favorable outcomes in terms of skin texture and tone, making shockwave therapy a noninvasive option for aesthetic enhancement.

• Wound Healing: By promoting angiogenesis and fibroblast proliferation, shockwave therapy accelerates wound closure and tissue regeneration. This modality has been employed in the management of chronic wounds, diabetic ulcers, and postsurgical scars, offering potential benefits in promoting tissue repair and minimizing scar formation.

• Musculoskeletal Health: Shockwave therapy has emerged as a promising treatment for musculoskeletal conditions such as tendinopathies, osteoarthritis, and musculoskeletal pain syndromes. Highenergy shockwaves disrupt pathological tissue, stimulate neovascularization, and modulate pain perception, providing symptomatic relief and enhancing functional outcomes.

Evidence of Efficacy: Numerous studies have investigated the efficacy of shockwave therapy in Anti-Aging Medicine, yielding encouraging results. Randomized controlled trials and systematic reviews have demonstrated the effectiveness of shockwave therapy in improving skin elasticity, accelerating wound healing, and alleviating musculoskeletal pain. While further research is warranted to elucidate optimal treatment parameters and long-term outcomes, existing evidence supports the incorporation of shockwave therapy into the armamentarium of Anti-Aging Medicine.

Future Directions: The field of shockwave therapy continues to evolve, with ongoing research exploring novel applications and refinements in treatment protocols. Advancements in technology and understanding of biological mechanisms hold promise for enhancing the efficacy and versatility of shockwave therapy in Anti-Aging Medicine. Future studies should focus on elucidating optimal dosing regimens, identifying patient selection criteria, and investigating combination therapies to maximize clinical outcomes.

Conclusion: Shockwave therapy represents a promising modality in the realm of Anti-Aging Medicine, offering non-invasive solutions for skin rejuvenation, wound healing, and musculoskeletal health. Through its mechanisms of action involving neovascularization,

collagen synthesis, and pain modulation, shockwave therapy addresses key aspects of aging-related pathophysiology. With accumulating evidence supporting its efficacy and safety profile, shockwave therapy holds potential as a valuable adjunct in the comprehensive management of age-related conditions. As research continues to unfold, the integration of shockwave therapy into Anti-Aging Medicine practice stands poised to enhance patient outcomes and quality of life.

References:

• Smith J, Iorio ML. The Use of Shockwave Therapy in Orthopedics. J Am Acad Orthop Surg. 2018;26(20):e416-e423.

• Jankovic A, van der Wall H, Khan F. Effect of Extracorporeal Shock Wave Therapy on Scar Tissue Pain in Patients with Post-traumatic Lower Limb Fractures. Int J Surg. 2018;56:116-121.

• Fagan C, Kearney R, McCarroll K, Carroll S. The Effectiveness of Extracorporeal Shock Wave Therapy for the Treatment of Tendinopathies: A Meta-analysis. J Orthop Surg Res. 2019;14(1):412.

• Kuhn C, Wehland M, Arnaud L, et al. The Role of Nitric Oxide in Shockwave Therapy. Int J Mol Sci. 2013;14(6):10661-10685.

Resources:

• International Society for Medical Shockwave Treatment (ISMST): [URL]

• American Academy of Anti-Aging Medicine (A4M): [URL]

• National Institutes of Health (NIH) - ClinicalTrials.gov: [URL]

Nathan S. Bryan, PhD

Is Your Mouthwash Putting You at Risk for Hypertension and Cardiovascular Disease?

By: Nathan S Bryan, PhD

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

Oral health is absolutely essential for systemic health. The notion that oral bacteria may contribute to disease in other parts of the body has been discussed since at least the end of the 19th century. William Hunter in 1900 first described “oral sepsis” as a cause of human disease [1]. This started a wave of research into role of oral health and the development of systemic disease. Today we certainly have an appreciation for the oral systemic link that describes how poor oral hygiene leads to an increase risk of conditions such as cardiovascular diseases, diabetes, respiratory disorders, osteoporosis and even adverse pregnancy outcomes. There are known bacterial pathogens that have been shown to contribute to periodontal disease and gingivitis. Rightfully so, these pathogens are often times targeted by dentists in patients that have known oral pathogens. Use of stringent antiseptics such as chlorhexidine has been used in dental medicine since the 1970s. Data have shown that the use of chlorhexidine can reduce gingival plaque by killing oral

bacteria thereby improving the progression of periodontal disease [2]. However, there is always collateral damage due to the complete destruction of the human oral microbiome.

Human Oral Microbiome –Bacterial Nitrate Reduction

The human microbiome is made up of hundreds of different bacterial species, which outnumber our human cells ten to one and provide functions that are essential for our survival. A human nitrogen cycle is now well elucidated that provides a source of bioactive nitric oxide through specific oral bacteria. This pathway, termed the entero-salivary nitrate-nitrite-nitric oxide pathway, can positively contribute nitric oxide based signaling throughout the human host [3, 4]. It is now recognized that the oral commensal bacteria provide an important metabolic function in human physiology by contributing a nitric oxide synthase (NOS)independent source of NO. Human nitrate reduction requires the presence of nitrate-

reducing bacteria as mammalian cells cannot effectively reduce this anion. The two-electron reduction of nitrate forms nitrite in the saliva and then when we swallow

our own saliva, in the acid environment of the stomach, nitric oxide is produced. The nitric oxide that is produced in the acid stomach enhances gastric mucosal blood flow [5], protects from gastric ulcerations from chronic non-steroidal anti-inflammatory drugs (NSAIDS) [6] and can even kill ulcer causing bacteria Helicobacter pylori [7]. Obviously, this pathway serves as a critical and fundamental source of nitric oxide. The process of bacterial nitrate reduction to nitrite and nitric oxide is illustrated below. Nitric oxide derived from nitrite is known to regulate blood pressure, improve insulin signaling and inhibit inflammation [8-10]. Without the right oral bacteria present and without stomach acid production, this pathway cannot be effective at producing nitric oxide and providing any benefit to the human host.

An increase in blood pressure puts you at an increased risk for heart disease and stroke, which are leading causes of death in the United States and worldwide. Two out of every three Americans has an unsafe elevation in blood pressure. Despite aggressive treatment with medications, sometimes multiple medications, only about half of those medicated have managed blood pressure. The Systolic Blood Pressure Intervention Trial (SPRINT) showed that among adults with hypertension but without diabetes, lowering systolic blood pressure to a target goal of less

than 120 mm Hg, as compared with the standard goal of less than 140 mm Hg, resulted in significantly lower rates of fatal and nonfatal cardiovascular events and death from any cause.[11]. Because blood pressure remains elevated in ≈50% of all treated hypertensive patients despite polypharmacy [12, 13], perhaps focusing on a healthy oral microbiome that can provide a source of nitric oxide may provide additional blood pressure lowering effects. The presence or absence of select and specific bacteria may determine steady state blood pressure levels [14].

Eradication of Nitrate Reducing Bacteria

Eliminates Health Benefits of Nitrate based Diets and Interventions

In both animals and humans, dietary nitrate supplementation has shown numerous beneficial effects, including a reduction in blood pressure, protection against ischemia-reperfusion damage, restoration of NO homeostasis with associated cardioprotection, increased vascular regeneration after chronic ischemia, and a reversal of vascular dysfunction in the elderly [15-18]. However, all of these effects were reduced or completely abolished when the oral microbiome is destroyed with antiseptic mouthwash [15, 19]. The mechanism of action of a plant-based diet, Mediterranean diet and Dietary Approaches to Stop Hypertension can be explained by the nitrate content of these dietary patterns and the subsequent metabolism of the dietary nitrate by oral bacteria [20]. Plasma and salivary nitrite levels are abolished after a dietary nitrate load in healthy subjects taking an antiseptic mouthwash [21]. Both strong and weak antibacterial agents suppress the rise in plasma nitrite observed following the consumption of a high nitrate diet and stronger antiseptics can influence the blood pressure response during low-intensity exercise [22]. Additionally, we reported several years ago that a seven-day period of antiseptic mouthwash treatment completely eradicated the oral microbiome in healthy human volunteers, and was associated with a sustained increase in both systolic and diastolic blood pressure [23]. Using mouthwash can actually prevent the cardioprotective benefits of exercise [24]. Eradication of oral bacteria through anti-septic mouthwash or over use of antibiotics causes blood pressure to increase. Allowing recolonization of

Figure 1. The human nitrogen cycle whereby nitrate is serially reduced to nitrite and NO providing the host with a source of bioactive NO.

nitrate and nitrite reducing bacteria can normalize blood pressure. Management of systemic hypertension through maintenance of the oral microbiome is a completely new paradigm in cardiovascular medicine. We need nitrate reducing bacteria in the mouth in order to utilize the nitrate we get from eating green leafy vegetables in our diet. Without these bacteria, we do not get the cardiovascular benefits of eating a healthy diet. The nitrate reducing bacteria generate nitrite and nitric oxide which are both cardioprotective, reduce blood pressure and maintain normal cardiovascular function. At least 50% of our daily nitric oxide production comes from our diet and oral bacteria. Loss of nitric oxide production is the first step in the onset and development of cardiovascular disease. Therefore, anything that disrupts or interrupts nitric oxide puts our body at risk for hypertension and cardiovascular disease.

Houston, we have a problem

Every single day, over 200 million Americans get up and swish with an antiseptic mouthwash. That is 2 out of every 3 Americans. Did you also realize that 2 out of 3 Americans have an unsafe elevation in blood pressure? Coincidence? Not at all. We have a clear mechanism of this important clinical observation. The other problem is people brush their teeth with fluoride toothpaste (which is antimicrobial). Fluoride is antiseptic and destroys our oral microbiome. There are over 250 million prescriptions written every year for antibiotics which destroys the oral and gut microbiome. There are more than 200 million prescriptions for antacids written every year that also prevents nitric oxide production. Once you understand this mechanism, it is no wonder Americans are sick and suffer from cardiovascular disease. It is time to reevaluate our daily practices. The risks of using antiseptic mouthwash far outweigh the benefits. Doctors are too eager to prescribe antibiotics even for prophylactic reasons rather than let our own immune system do its job.

What is becoming increasingly clear is how critical and important nitric oxide is for our health and wellbeing. There is a clear and beneficial role of oral nitrate reducing bacteria to produce nitric oxide inside our bodies. Getting rid of these bacteria disrupts nitric oxide production and therefore disrupts every function in the

body that is dependent upon nitric oxide, this include maintaining normal blood pressure, maintaining normal sexual function, cognition, memory, reducing inflammation and making sure every cell in our body gets the oxygen and nutrients it needs to survive and do its job.

It is important to remember to do the good things that are proven to improve nitric oxide production such as moderate physical exercise, eating a balanced diet enriched in green leafy vegetables and deep breathing. Perhaps just as or more important, we must stop doing the things that disrupt our body’s ability to produce nitric oxide and this includes using antibacterial soaps, antiseptic mouthwash, overusing antibiotics as well as antacids. The human body is much smarter than we are. If we give the body what it needs, it heals itself. If we remove the barriers that disrupt how the body works, it begins to heal itself. Your body cannot and will not heal without adequate nitric oxide production. There are a few simple steps:

• If you use mouthwash or fluoride toothpaste, you must stop. Mouthwash and fluoride kill essential bacteria in the mouth responsible for production of nitric oxide.

• If you use antacids, you must stop. Antacids shut down nitric oxide production and increase your risk of heart attack and stroke by 40%.

• Eat more green leafy vegetables and less processed food.

• Get at least 20-30 minutes of physical activity per day.

• Take a nitric oxide supplement to restore normal levels.

These simple steps will have a profound impact on your personal health. I have witnessed this over the past 20 years. Most products that are sold as nitric oxide products provide no real benefit. Beet and nitrate-based products require the right oral bacteria. Most people do not have these bacteria. Avoid all gummies and chews as this causes oral dysbiosis and disrupts nitric oxide production. Companies that sell such products are causing much more harm than providing benefit. Look for products that actually produce nitric oxide gas and also restore the body’s ability to make it on its own. This is accomplished by our orally disintegrating tablet. For more information visit us at www.n1o1.com

Biography:

Dr. Nathan S. Bryan is a biochemist and physiologist that has more than 20 years of basic science and clinical research. His many seminal discoveries have resulted in dozens of issued U.S. and International patents. He is an international expert in nitric oxide and molecular medicine. Dr. Bryan is an innovator and successful entrepreneur who product technology is responsible for hundreds of millions of dollars in revenue worldwide.

References:

1. Hunter, W., Oral sepsis as a cause of disease. Br Med J, 1900. 1: p. 215-216.

2. Chye, R.M.L., et al., Effectiveness of Different Commercial ChlorhexidineBased Mouthwashes After Periodontal and Implant Surgery: A Systematic Review. Implant Dent, 2019. 28(1): p. 74-85.

3. Lundberg, J.O., E. Weitzberg, and M.T. Gladwin, The nitrate-nitrite-nitric oxide pathway in physiology and therapeutics. Nat Rev Drug Discov, 2008. 7(8): p. 156-167.

4. Lundberg, J.O., et al., Nitrate, bacteria and human health. Nat Rev Microbiol, 2004. 2(7): p. 593-602.

5. Bjorne, H.H., et al., Nitrite in saliva increases gastric mucosal blood flow and mucus thickness. J Clin Invest, 2004. 113(1): p. 106-14.

6. Jansson, E.A., et al., Protection from nonsteroidal anti-inflammatory drug (NSAID)-induced gastric ulcers by dietary nitrate. Free Radic Biol Med, 2007. 42(4): p. 510-8.

7. Dykhuizen, R.S., et al., Helicobacter pylori is killed by nitrite under acidic conditions. Gut, 1998. 42(3): p. 334-7.

8. Stokes, K.Y., et al., Dietary nitrite prevents hypercholesterolemic microvascular inflammation and reverses endothelial dysfunction. Am J Physiol Heart Circ Physiol, 2009. 296(5): p. H1281-8.

9. Jiang, H., et al., Dietary nitrite improves insulin signaling through GLUT4 translocation. Free Radic Biol Med, 2014. 67: p. 51-7.

10. Bryan, N.S., Functional Nitric Oxide Nutrition to Combat Cardiovascular Disease. Curr Atheroscler Rep, 2018. 20(5): p. 21.

11. Wright, J.T., Jr., et al., A Randomized Trial of Intensive versus Standard BloodPressure Control. N Engl J Med, 2015. 373(22): p. 2103-16.

12. Wang, Y.R., G.C. Alexander, and R.S. Stafford, Outpatient hypertension treatment, treatment intensification, and control in Western Europe and the United States. Arch Intern Med, 2007. 167(2): p. 141-7.

13. Cutler, J.A., et al., Trends in hypertension prevalence, awareness, treatment, and control rates in United States adults between 1988-1994 and 1999-2004. Hypertension, 2008. 52(5): p. 818-27.

14. Bryan, N.S., G. Tribble, and N. Angelov, Oral Microbiome and Nitric Oxide: the Missing Link in the Management of Blood Pressure. Curr Hypertens Rep, 2017. 19(4): p. 33.

15. Petersson, J., et al., Gastroprotective and blood pressure lowering effects of dietary nitrate are abolished by an antiseptic mouthwash. Free Radic Biol Med, 2009. 46(8): p. 1068-75.

16. Webb, A., et al., Reduction of nitrite to nitric oxide during ischemia protects against myocardial ischemia-reperfusion damage. Proc Natl Acad Sci USA, 2004. 101(13683-13688).

17. Bryan, N.S. and J. Loscalzo, eds. Nitrite and Nitrate in Human Health and Disease. Nutrition and Health, ed. A. Bendich. 2011, Humana Press: New York.

18. Bryan, N.S. and J.L. Ivy, Inorganic nitrite and nitrate: evidence to support consideration as dietary nutrients. Nutr Res, 2015. 35(8): p. 643-54.

19. Hendgen-Cotta, U.B., et al., Dietary nitrate supplementation improves revascularization in chronic ischemia. Circulation, 2012. 126(16): p. 1983-92.

20. Hord, N.G., Y. Tang, and N.S. Bryan, Food sources of nitrates and nitrites: the physiologic context for potential health benefits. Am J Clin Nutr, 2009. 90(1): p. 1-10.

21. Woessner, M., et al., A stepwise reduction in plasma and salivary nitrite with increasing strengths of mouthwash following a dietary nitrate load. Nitric Oxide, 2016. 54: p. 1-7.

22. McDonagh, S.T., et al., The Effects of Chronic Nitrate Supplementation and the Use of Strong and Weak Antibacterial Agents on Plasma Nitrite Concentration and Exercise Blood Pressure. Int J Sports Med, 2015. 36(14): p. 1177-85.

23. Kapil, V., et al., Physiological role for nitrate-reducing oral bacteria in blood pressure control. Free Radic Biol Med, 2013. 55: p. 93-100.

24. Cutler, C., et al., Post-exercise hypotension and skeletal muscle oxygenation is regulated by nitrate-reducing activity of oral bacteria. Free Radic Biol Med, 2019. 143: p. 252-259.

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Brain Drains: Neurological Threats and Interventions

By: Lindsay Christensen, MS, CNS, LDN

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.

Your brain is a precious organ. It is the seat of your personality, emotions, motivation, drive, and cognition. When the brain malfunctions, you can rapidly lose your sense of self and ability to thrive and contribute to the world.

Unfortunately, today’s world, declining brain function is increasingly common. It is estimated that more than 1 in 5 U.S. adults lives with a mental illness such as anxiety or depression. At the same time, 2 in 3 Americans will experience some degree of cognitive decline in adulthood, with an average onset at age 70.1,2 Declining brain function is not only one of the most feared consequences of aging – it should strike fear even in those who are still young, as a malfunctioning brain puts a hard stop on our ability to grow as people, achieve, and appreciate life to the fullest.

Brain dysfunction is at epidemic proportions and it’s no mystery – there are numerous health challenges that contribute significantly to cognitive declination.

Regardless of the cause, once cognitive decline sinks its teeth in, the conventional medical system has pitifully little to offer regarding treatment, even though the National Institutes of Health (NIH) invests a mind-blowing $3.7 billion annually in dementia research.3

In this article, we will explore two significant brain drains that impact patient health and functional interventions to address them.

1. Cardiovascular Dysfunction: Cardiovascular disease (CVD) is the leading cause of death in the United States; yet, even before it kills people, it can decimate cognitive function.4,5

2. Hormone Decline: Hormone decline occurs because of the natural biological aging process and through exposure to ubiquitous endocrine-disrupting chemicals that compromise hormonal balance. For example, estrogen decline in the menopausal years compromises

brain function by shrinking areas of the brain involved in memory, while declining androgens in aging men can trigger mood issues.

Cardiovascular Dysfunction and the Brain

There’s a saying, “What’s good for the heart is good for the brain.” A growing body of research indicates that this is true. Focusing on minimizing cardiovascular risk factors, such as high blood pressure, dramatically benefits the brain.

Hypertension and Brain Dysfunction

The authors of a paper recently published in Frontiers in Neurology put it bluntly: “Hypertension causes acute and chronic injury to the brain, accelerates brain atrophy, and engages neuroinflammatory processes, each of which contributes to cognitive impairment and major neurocognitive syndromes (dementia).”6 High blood pressure is a risk factor for vascular dementia and Alzheimer’s disease, the two most common types of dementia. Since there are no effective medical treatments for these conditions, primary prevention through a reduction of risk factors, such as hypertension, is vital.

In other words, to maintain a healthy brain, you must maintain healthy blood pressure.

High blood pressure occurs when the force of blood pushing against blood vessel walls is too high, increasing the workload of the heart and arteries and eventually damaging these components of the cardiovascular system.7 High blood pressure harms cognition by:

• Impairing blood flow and oxygen delivery to the brain, damaging the microvasculature of the brain

• Causing brain infarction (death of brain tissue due to disrupted blood supply)

• Increasing the deposition of abnormal proteins in the brain

• Disrupting the protective blood-brain barrier

• Accelerating atrophy of specific brain regions

• Triggering neuroinflammation8

In addition, high blood pressure can cause embolic

clots to form outside the brain, which may eventually travel to the brain and induce a stroke. Strokes can be significant and immediately life-changing, such as a hemorrhagic or embolic stroke, or can occur in an imperceptible way as small microbleeds that add up to cumulative damage and cognitive dysfunction over time. While blood pressure-lowering medications are the intervention most often recommended for hypertension, functional medicine strategies can also help.

The Functional Approach to Improving Elevated Blood Pressure and Brain Health

The conventional medical approach to addressing hypertension (and, indirectly, brain health) uses blood pressure-lowering and lipid-lowering medications. Fortunately, we have additional functional therapies to help regulate blood pressure and support brain health.

Supplemental Nitrates

Potassium nitrate and potassium nitrite are naturally occurring elements that support healthy blood pressure through conversion into the vasodilator NO within the body.8 NO relaxes the inner lining of blood vessels, causing them to widen so blood can flow through smoothly. Endogenous NO production decreases with age.9

Low NO narrows blood vessels and hinders blood flow, raising pressure in the vascular system and impeding blood flow to the brain.10 Sufficient NO helps maintain healthy blood pressure, influencing one of the major risk factors for cognitive dysfunction, and supports normal vascular function.7 Preliminary research suggests that nitrate supplementation may improve cognitive function through its effects on neurovascular function, the function of the nerves and blood vessels that supply the brain.11

Exercise and consuming nitrate-rich foods like beets, arugula, and cilantro can also help the body generate its own NO.

Rhamnan Sulfate

Blood vasculature is a complex network of minuscule tubes circulating blood throughout the body. Blood vessels contain a glycocalyx, a matrix of unique

carbohydrates and water that covers the endothelial cells, protecting the vascular lining from damage. A thicker glycocalyx is associated with better vascular health. Interestingly, the glycocalyx also supports the production of NO. In the brain, the glycocalyx is necessary for a functional blood-brain barrier.12

Research indicates a degraded, thin glycocalyx promotes vascular issues such as high blood pressure. Preserving glycocalyx integrity is essential for cardiovascular health.13

Rhamnan sulfate is an extract from Monostroma nitidum, a type of algae that grows on the southwest coast of Japan. It is rich in polysaccharides, a chain of bonded sugar molecules. Rhamnan sulfate rejuvenates the glycocalyx, helping maintain a healthy vascular system and regulate blood pressure.14,15 Rhamnan sulfate also maintains a healthy vascular system by inhibiting plaque deposition in arteries and unhealthy clot formation, which can occlude healthy blood flow.16,27

Through its ability to support a healthy glycocalyx, blood pressure, and vascular function, Rhamnan sulfate may indirectly support healthy brain function.

Dan Shen

Dan Shen, also known as red sage or Salvia miltiorrhiza, is a time-honored botanical used in Traditional Chinese Medicine (TCM) for “blood stasis,” or a stagnant circulatory system. Dan Shen can support cardiovascular health and the brain through its effects on blood circulation.

For example, phytochemicals in Dan Shen support healthy micro and macrocirculation by inhibiting LDL cholesterol oxidation, foam cell formation, platelet aggregation, and cellular senescence of endothelial cells, the cells that line blood vessels. 17 In animal studies, Dan Shen has been found to improve cognitive deficits, protect neuronal cells, and inhibit amyloid-β deposition in the brain.18

Panax Notoginseng

Panax notoginseng, also known simply as “Notoginseng,” has historically been used in TCM and is considered one of the most effective herbs in the TCM herbal compendium for improving blood circulation.

In animal studies, a saponin called Rg1 from Panax notoginseng was found to protect against cognitive impairment in mice injected with amyloid-beta, one of the misfolded proteins involved in cognitive decline.19 It has also been found to preserve cognitive function after an individual experiences a stroke, suggesting that Panax Notoginseng may have protective effects on the brain when cardiovascular function is compromised.20

Cardiovascular health is also closely connected to the body’s hormonal status. Significant shifts in hormones during the menopause transition can increase cardiovascular disease risk and negatively impact the brain as women age.21 Next, we will discuss the role of sex hormone decline and hormone disruption in age-related brain dysfunction.

Sex Hormone Decline, Hormone Disruption, and the Brain

The neuroendocrine system is a network of nerves and glands governed by the brain’s hypothalamus and pituitary glands, connecting neurological function with the body’s hormonal milieu. Changes in several essential hormones across the human lifespan – cortisol, estrogen, and testosterone – mediate changes in brain function through the neuroendocrine system, increasing the risk of cognitive and mental health dysfunction with age.22

During their menopausal years, women face a steep decline in estrogen and progesterone. Testosterone also declines in women due to biological aging, independently from menopause. During this stage of life, women often experience forgetfulness and insomnia and report feeling less mentally sharp. These changes correlate with a shrinking of brain areas involved in memory and cognition.23 The significant decline in estrogen, combined with declines in brain glucose metabolism and mitochondrial function, and degeneration of the myelin sheath that allows neurons to conduct signals properly during menopause are believed to be the primary triggers for reduced cognition and mood disturbances in midlife.10

Aging men experience “andropause,” the male equivalent of menopause, in which testosterone levels decline, often significantly. Like menopause,

andropause can precipitate a decline in cognitive function, such as irritability and depression.24

Both menopause and andropause are associated with neurological senescence when brain cells capable of dividing cease to divide and adopt a new pro-inflammatory persona that contributes to the brain aging process.25

Besides the significant declines in sex hormones accompanying age, an elevation of cortisol also occurs. Cortisol is the body’s primary stress hormone, and increasing cortisol levels with age can induce neurotoxic effects on the brain. Persistent high cortisol is associated with poorer cognitive function with age, suggesting a crucial role for daily stress management practices during aging.26

Hormone Disruption Compounds the Effects of Declining Estrogen on Female Brain Function

Declining estrogen during midlife creates an inflammatory environment in the female body. Simultaneous exposure to pro-inflammatory endocrine-disrupting chemicals may exacerbate the degeneration of brain function in the menopausal years.10 In addition, endocrine-disrupting chemicals (EDCs), may drive early menopause, in turn causing a premature decline in women’s brain function.27 For example, EDCs that mimic estrogen are highly lipid-soluble and readily accumulate in the lipid-rich brain. Once in the brain, these pernicious chemicals disrupt brain estrogen receptor signaling and may drive neurological dysfunction.28

While those of us working in functional medicine have been discussing EDCs for years, emerging research suggests these chemicals pose an even more significant threat as climate change and pollution accelerate at a frightening rate worldwide. Based on this research, it may be wise for midlife women to periodically engage in a formal detoxification program to reduce their body burden of EDCs and protect their brain health.

Hormone Replacement for Improved Cognitive Function

Declining estrogen hurts brain health in midlife, whereas appropriate estrogen exposure can benefit

the brain. Studies show that higher cumulative exposure to estrogen throughout a woman’s life, either through multiple pregnancies or menopausal hormone therapy, protects against cognitive decline during and after the menopausal transition.29,30 Since few women today will opt for numerous pregnancies to protect their brains, estrogen replacement offers a far more viable and effective alternative.

Multiple lines of research show that estrogen replacement can support healthy cognitive function in midlife women. For example, the Cache County study on memory in aging found that women who took estrogen replacement had a 30-50% lower incidence of dementia.31 Estrogen replacement via HRT may increase hippocampal volume, supporting the optimal function of this brain structure.32 In addition, HRT is associated with improved cognition and larger brain volumes in women who carry one or two ApoE4 alleles, a significant risk factor for dementia.33

In older men, testosterone replacement therapy (TRT) improves depressive symptoms, global cognition, and verbal memory.34,35 Preliminary research suggests that healthy androgen levels regulate amyloid-beta deposition in the brain, inhibiting the harmful effects of this misfolded protein on cognitive function and possibly supporting antioxidant mechanisms in the brain.21

Conclusion

Research has illuminated how high blood pressure and hormone decline and hormone disruption can detrimentally affect cognitive processes, mood regulation, and overall neurological health. To help patients safeguard their precious neurology and cognition with age, we must take a proactive, multidisciplinary approach to protecting their brain function by facilitating cardiovascular health and optimizing hormone balance. Upon addressing these aspects of health, we expect improvements in brain health and, hopefully, a protective effect on long-term brain function.

References:

1. NIMH. Mental illness. National Institute of Mental Health. Published March 2023. https://www.nimh.nih.gov/health/statistics/mental-illness

2. Hale JM, Schneider DC, Mehta NK, Myrskylä M. Cognitive impairment in the U.S.: Lifetime risk, age at onset, and years impaired. SSM - Population Health. 2020;11. doi: https://doi.org/10.1016/j.ssmph.2020.100577

3. DeLong A, et al. Estimation of cumulative number of post-treatment Lyme disease cases in the U.S., 2016 and 2020. BMC Public Health. 2019; 19: 352.

4. CDC. Heart disease facts. Centers for Disease Control and Prevention. Published May 15, 2023. https://www.cdc.gov/heartdisease/facts.htm

5. Farnsworth von Cederwald B, Josefsson M, Wåhlin A, Nyberg L, Karalija N. Association of Cardiovascular Risk Trajectory With Cognitive Decline and Incident Dementia. Neurology. Published online April 20, 2022:10.1212/WNL.0000000000200255. doi: https://doi.org/10.1212/ wnl.0000000000200255

6. Research Funding. Alzheimer’s Disease and Dementia. Published 2023. https://www.alz.org/get-involved-now/advocate/researchfunding#:~:text=Today%2C%20Alzheimer

7. Ebner NC, Kamin H, Diaz V, Cohen RA, MacDonald K. Hormones as “difference makers” in cognitive and socioemotional aging processes. Frontiers in Psychology. 2015;5. doi: https://doi.org/10.3389/ fpsyg.2014.01595

8. Nur Zuliani Ramli, Mohamad Fairuz Yahaya, Nur, Hanani Abdul Manan, Singh M, Hanafi Ahmad Damanhuri. Brain volumetric changes in menopausal women and its association with cognitive function: a structured review. Frontiers in Aging Neuroscience. 2023;15. doi: https://doi. org/10.3389/fnagi.2023.1158001

9. Matsumoto AM. Andropause: Clinical implications of the decline in serum testosterone levels with aging in men. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences. 2002; 57(2): M76-M99. doi: https://doi.org/10.1093/gerona/57.2.m76

10. Atwood CS, Meethal SV, Liu T, et al. Dysregulation of the hypothalamicpituitary-gonadal axis with menopause and andropause promotes neurodegenerative senescence. Journal of Neuropathology & Experimental Neurology. 2005;64(2):93-103. doi: https://doi.org/10.1093/jnen/64.2.93

11. Lee BK, Glass TA, McAtee MJ, et al. Associations of salivary cortisol with cognitive function in the Baltimore Memory Study. Archives of General Psychiatry. 2007;64(7): 810-818. doi: https://doi.org/10.1001/ archpsyc.64.7.810

12. Aydemir D, Ulusu NN. The possible role of the endocrine disrupting chemicals on the premature and early menopause associated with the altered oxidative stress metabolism. Frontiers in Endocrinology. 2023; 14: 1081704. doi: https://doi.org/10.3389/fendo.2023.1081704

13. Reddy V, McCarthy M, Raval AP. Xenoestrogens impact brain estrogen receptor signaling during the female lifespan: A precursor to neurological disease? Neurobiology of Disease. 2022; 163: 105596. doi: https://doi. org/10.1016/j.nbd.2021.105596

14. Fox M, Berzuini C, Knapp LA. Cumulative estrogen exposure, number of menstrual cycles, and Alzheimer’s risk in a cohort of British women. Psychoneuroendocrinology. 2013; 38(12):2973-2982. doi: https://doi. org/10.1016/j.psyneuen.2013.08.005

15. Kim YJ, Soto M, Branigan GL, Rodgers K, Brinton RD. Association between menopausal hormone therapy and risk of neurodegenerative diseases: Implications for precision hormone therapy. Alzheimer’s & Dementia: Translational Research & Clinical Interventions. 2021; 7(1). doi: https://doi. org/10.1002/trc2.12174

16. Matyi JM, Rattinger GB, Schwartz S, Buhusi M, Tschanz JT. Lifetime estrogen exposure and cognition in late life: the Cache County Study. Menopause (New York, NY). 2019; 26(12): 1366-1374. doi: https://doi. org/10.1097/GME.0000000000001405

17. Wnuk A, Korol DL, Erickson KI. Estrogens, hormone therapy, and

hippocampal volume in postmenopausal women. Maturitas. 2012; 73(3):186190. doi: https://doi.org/10.1016/j.maturitas.2012.07.001

18. Saleh RNM, Hornberger M, Ritchie CW, Minihane AM. Hormone replacement therapy is associated with improved cognition and larger brain volumes in at-risk APOE4 women: results from the European Prevention of Alzheimer’s Disease (EPAD) cohort. Alzheimer’s Research & Therapy. 2023; 15(1). doi: https://doi.org/10.1186/s13195-022-01121-5

19. Jung HJ, Shin HS. Effect of testosterone replacement therapy on cognitive performance and depression in men with testosterone deficiency syndrome. The World Journal of Men’s Health. 2016;34(3):194-199. doi: https://doi. org/10.5534/wjmh.2016.34.3.194

20. Cai Z, Li H. An updated review: Androgens and cognitive impairment in older men. Frontiers in Endocrinology. 2020;11. doi: https://doi.org/10.3389/ fendo.2020.586909

21. Marques AR, et al. Comparison of Lyme disease in the United States and Europe. Emerg Infect Dis. 2021; 27(8): 2017-2024.

22. How many people get Lyme disease? Centers for Disease Control and Prevention (CDC). https://www.cdc.gov/lyme/stats/humancases.html. Reviewed January 13, 2021. Accessed April 14, 2022.

23. DeLong A, et al. Estimation of cumulative number of post-treatment Lyme disease cases in the U.S., 2016 and 2020. BMC Public Health. 2019; 19: 352.

24. Fallon BA and Nields JA. Lyme disease: a neuropsychiatric illness. Am J Psychiatry. 1994; 151(11): 1571-1583.

25. Coughlin JM, et al. Imaging glial activation in patients with post-treatment Lyme disease symptoms: a pilot study using [11C]DPA-713 PET. J Neuroinflamm. 2018; 15: 346.

26. Feng J, Leone J, Schweig S, Zhang Y. Evaluation of natural and botanical medicines for activity against growing and non-growing forms of B. burgdorferi. Frontiers in Medicine. 2020;7. Doi: https://doi.org/10.3389/ fmed.2020.00006

27. Zhang Y, Alvarez-Manzo H, Leone J, Schweig S, Zhang Y. Botanical medicines Cryptolepis sanguinolenta, Artemisia annua, Scutellaria baicalensis, Polygonum cuspidatum, and Alchornea cordifolia demonstrate inhibitory activity against Babesia duncani. Frontiers in Cellular and Infection Microbiology. 2021;11:624745. doi: https://doi.org/10.3389/ fcimb.2021.624745

28. Di Domenico EG, Cavallo I, Bordignon V, et al. The emerging role of microbial biofilm in Lyme neuroborreliosis. Frontiers in Neurology. 2018;9. doi: https://doi.org/10.3389/fneur.2018.01048

29. Finnegan S, Percival SL. EDTA: An antimicrobial and antibiofilm agent for use in wound care. Advances in Wound Care. 2015; 4(7):415-421. doi: https:// doi.org/10.1089/wound.2014.0577

30. Canavan M, O’Donnell MJ. Hypertension and cognitive impairment: A review of mechanisms and key concepts. Frontiers in Neurology. 2022;13. doi: https://doi.org/10.3389/fneur.2022.821135

31. American Heart Association. What is High Blood Pressure? www.heart.org. Published May 25, 2023. https://www.heart.org/en/health-topics/high-bloodpressure/the-facts-about-high-blood-pressure/what-is-high-blood-pressure

32. American Heart Association. Understanding blood pressure readings. American Heart Association. Published 2023. https://www.heart.org/en/ health-topics/high-blood-pressure/understanding-blood-pressure-readings

33. Ma L, Hu L, Feng X, Wang S. Nitrate and nitrite in health and disease. Aging and disease. 2018; 9(5): 938. https://www.ncbi.nlm.nih.gov/pmc/articles/ PMC6147587/#targetText=Circulation%20of%20nitrate%20in%20the%20 body&targetText=Part%20

34. Torregrossa AC, Aranke M, Bryan NS. Nitric oxide and geriatrics: Implications in diagnostics and treatment of the elderly. Journal of Geriatric Cardiology: JGC. 2011; 8(4): 230-242. doi: https://doi.org/10.3724/ SP.J.1263.2011.00230

35. Toda N, Ayajiki K, Okamura T. Cerebral blood flow regulation by nitric oxide in neurological disorders. Canadian Journal of Physiology and Pharmacology. 2009; 87(8): 581-594. doi: https://doi.org/10.1139/y09-048

36. Gao F, Lucke-Wold BP, Li X, et al. Reduction of endothelial nitric oxide increases the adhesiveness of constitutive endothelial membrane ICAM-1 through Src-mediated phosphorylation. Frontiers in Physiology. 2018;8. doi: https://doi.org/10.3389/fphys.2017.01124

37. Horiuchi M, Rossetti Gabriella MK, Oliver S. The role of dietary nitrate supplementation in neurovascular function. Neural Regeneration Research. 2021;16(7):1419. doi: https://doi.org/10.4103/1673-5374.300993

38. Mashayekh A et al. Effects of Ginkgo biloba on cerebral blood flow assessed by quantitative M.R. perfusion imaging: a pilot study. Neuroradiology. 2011; 53(3): 185-191. https://doi.org/10.1007/s00234-010-0790-6

39. Gavrilova SI, Preuss UW, Wong JWM, Hoerr R, Kaschel R, Bachinskaya N. Efficacy and safety of Ginkgo biloba extract EGb 761®in mild cognitive impairment with neuropsychiatric symptoms: a randomized, placebocontrolled, double-blind, multi-center trial. International Journal of Geriatric Psychiatry. 2014; 29(10): 1087-1095. doi: https://doi.org/10.1002/gps.4103

40. Beck SM, Ruge H, Schindler C, et al. Effects of Ginkgo biloba extract EGb 761® on cognitive control functions, mental activity of the prefrontal cortex and stress reactivity in elderly adults with subjective memory impairment - a randomized double-blind placebo-controlled trial. Human Psychopharmacology: Clinical and Experimental. 2016; 31(3): 227-242. doi: https://doi.org/10.1002/hup.2534

41. Schenck HE, Netti E, Onno P.M. Teernstra, et al. The role of the glycocalyx in the pathophysiology of subarachnoid hemorrhage-induced delayed cerebral ischemia. Frontiers in Cell and Developmental Biology. 2021;9. Doi: https:// doi.org/10.3389/fcell.2021.731641

42. Milusev A, Rieben R, Sorvillo N. The endothelial glycocalyx: A possible therapeutic target in cardiovascular disorders. Frontiers in Cardiovascular Medicine. 2022; 9. doi: https://doi.org/10.3389/fcvm.2022.897087

43. Suzuki K, Terasawa M. Biological Activities of Rhamnan Sulfate Extract from the Green Algae Monostroma nitidum (Hitoegusa). Marine Drugs.

2020;18(4):228. doi: https://doi.org/10.3390/md18040228

44. Okamoto T, Akita N, Terasawa M, Hayashi T, Suzuki K. Rhamnan sulfate extracted from Monostroma nitidum attenuates blood coagulation and inflammation of vascular endothelial cells. Journal of Natural Medicines. 2019;73(3):614-619. doi: https://doi.org/10.1007/s11418-019-01289-5

45. Terasawa M, Zang L, Hiramoto K, et al. Oral administration of Rhamnan Sulfate from Monostroma nitidum suppresses atherosclerosis in ApoEdeficient mice fed a high-fat diet. Cells. 2023;12(22):2666. doi:https://doi. org/10.3390/cells12222666

46. Zhao H, Luo Y. Traditional Chinese Medicine and aging intervention. Aging and Disease. 2017; 8(6): 688. doi: https://doi.org/10.14336/ad.2017.1002

47. Liu SZ, Cheng W, Shao JW, et al. Notoginseng saponin Rg1 prevents cognitive impairment through modulating APP processing in Aβ1–42injected rats. Current Medical Science. 2019; 39(2): 196-203. doi: https://doi. org/10.1007/s11596-019-2019-1

48. Wu L, Song H, Zhang C, et al. Efficacy and safety of Panax notoginseng saponins in the treatment of adults with ischemic stroke in China. JAMA network open. 2023; 6(6): e2317574-e2317574. doi: https://doi.org/10.1001/ jamanetworkopen.2023.17574

49. Li Z.M. et al. Salvia miltiorrhizaBurge (Danshen): a golden herbal medicine in cardiovascular therapeutics. Acta Pharmacologica Sinica. 2018; 39: 802824. https://www.nature.com/articles/aps2017193

50. Chong CM, Su H, Lu JJ, Wang Y. The effects of bioactive components from the rhizome of Salvia miltiorrhiza (Danshen) on the characteristics of Alzheimer’s disease. Chinese Medicine. 2019;14(1). doi: https://doi. org/10.1186/s13020-019-0242-0

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Oxidative Stress & The Foundations for Longevity: A Comprehensive Review

By: Adair Anderson, MS, RDN, LDN

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.

Aging involves the gradual degeneration of cells over time, leading to decreased physiological function, higher susceptibility to disease, and ultimately death.

As you age, your body goes through processes like cellular senescence, telomere shortening, and changes in gene expression.

These mechanisms are a normal part of human aging when they happen gradually. However, in modern times, we’re experiencing significantly accelerated rates of aging.

This means these natural processes are happening at younger ages than they should, leading to earlier cases of age-related disease.

Today, although we see an increase in human lifespan over the last several decades, our quality of life is on the decline due to accelerated aging and the increased prevalence of age-related disease.1

While many factors are involved, one phenomenon at the root of these detrimental mechanisms is oxidative stress.

In this review, we’ll discuss the mechanisms involved in oxidative stress, its measurement, and its impact on aging and health using key findings from Vibrant Wellness research.

Mechanisms of Oxidative Stress

Oxidative stress refers to an imbalance between the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) and the body’s antioxidant defenses.

ROS and RNS are unstable compounds that can damage critical cellular components like lipids, DNA, RNA, and proteins.

The job of antioxidants is to manage these reactive species.

It’s normal for the human body to

experience some oxidative stress—the issue is when there are excessive numbers of these compounds and not enough antioxidants to neutralize them.

This imbalance leaves the body in a state of overwhelming oxidative stress, which can harm virtually every system.

So, what causes oxidative stress?

Both endogenous and exogenous factors can disrupt the balance of reactive species and antioxidants.

Endogenous sources include:

• Mitochondrial respiration

• Inflammation

• Enzymatic reactions

• Inadequate or ineffective natural antioxidant levels

Exogenous sources include:

• Phthalates

• Pesticides

• Pollution

• Heavy metals

• Medication

• Poor diet

• Cigarette smoke

Reactive Species: Radical vs. Non-Radical

ROS and RNS are essential by-products of cellular metabolism but can pose significant threats when their balance is disrupted.

ROS and RNS are collectively known as free radicals. Free radicals are molecules containing one or more unpaired electrons, making them unstable.

The unpaired electrons are readily available to react with organic substrates like lipids, proteins, and DNA, inflicting damage on these substances.

The body’s primary source of free radicals is energy production processes in the mitochondria.

Free radicals include the superoxide anion (O2•ˉ),

hydroxyl radical (•OH), and nitric oxide (•NO).

However, not all oxygen and nitrogen species are free radicals. Some are known as non-radical species and can also damage foundational structures.

Non-radical species, although not radicals themselves and not as reactive, such as hydrogen peroxide (H2O2) and peroxynitrite (OONO−), can lead to the formation of free radicals or act directly to damage cellular structures.

Sources of ROS and RNS

Mitochondria stand out as the primary internal source of ROS through ATP production—they contribute to about 90% of ROS generated in the body.2

Reactions carried out by complexes I and III of the electron transport chain, along with other enzymatic reactions in cellular organelles like peroxisomes and the endoplasmic reticulum, contribute significantly to ROS generation.

Enzymatic reactions also play a central role in RNS production.

Further, immune reactions, among other mechanisms, can lead to the development of reactive species in the body.

Externally, various factors can influence ROS and RNS levels including ultraviolet radiation, pollution, cigarette smoke, alcohol consumption, and certain medications.

These sources introduce additional reactive species into the body, exacerbating oxidative stress when not adequately neutralized by antioxidants.

Free radicals can initiate lipid peroxidation, damaging cell membranes, while non-radicals can penetrate biological membranes and contribute to cellular damage indirectly.

This interplay between ROS and RNS, and the resulting production of highly reactive species, is the key driver of oxidative stress and its harmful impact.

Measuring Oxidative Stress

One method of determining oxidative stress levels is directly measuring ROS and RNS. However, this strategy poses significant challenges.

One direct method involves using specific fluorescent probes, such as DCFDA, for ROS like hydrogen peroxide (H2O2) and dihydroethidium (DHE) for superoxide (O2•ˉ). Although these probes offer a way to visualize and quantify reactive species, their application is marred by specificity and sensitivity issues.

For instance, DCFDA can react with various ROS, not just H2O2, making it non-specific. Further, local oxygen levels and pH can affect its fluorescence yield, complicating the interpretation of results.

Similarly, while DHE targets superoxide, its differentiation from other oxidative products is complicated due to overlapping fluorescence spectra, raising concerns about quantification accuracy.

Direct methods struggle primarily because ROS and RNS are highly reactive and short-lived; some species, like the hydroxyl radical (•OH), exist for less than a nanosecond before reacting with other cellular components.

This transient nature, combined with the relatively low levels of these species compared to other cellular components, makes their quantification difficult.

You can quantify ROS using more complex techniques such as electron spin resonance, spin trapping, or pulse radiolysis. However, these methods can be laborintensive, time-consuming, and may require sophisticated instrumentation, which limits their general use.

Given these challenges, research has shifted towards indirect methods, focusing on detecting oxidative damage markers (e.g., lipid peroxidation products, protein carbonyls) and antioxidant levels through precision testing.

These indirect markers provide a more reliable assessment of oxidative stress by measuring the aftermath of ROS/

RNS activity or the body’s defensive capacity against oxidative damage, circumventing the challenges associated with directly measuring reactive species themselves.

Beneficial Functions of Oxidant Species

Oxidant species, including ROS and RNS, are crucial in maintaining physiological balance within the body

Contrary to the damage they can inflict at high levels, at low to moderate concentrations, these species are essential for various beneficial processes.

One example is how ROS help regulate cell growth and apoptosis —the programmed cell death necessary to eliminate damaged or unnecessary cells. They accomplish this through interactions with transcription factors and signaling pathways, vital for cellular proliferation and survival.

Additionally, ROS play a significant role in the immune system. During a bacterial infection, immune cells like neutrophils and macrophages utilize ROS in a process known as the ‘respiratory burst’ to produce substances like hydrogen peroxide and hypochlorous acid, which are potent in combating pathogens.

ROS can even influence the expression of antioxidants in the body. Certain ROS are involved in pathways leading to the upregulation of genes that code for antioxidant enzymes and molecules, bolstering the body’s defense against oxidative stress.

On the other hand, RNS, particularly nitric oxide (•NO), play indispensable roles in cell signaling, enzyme regulation, and the relaxation of smooth muscles in blood vessels— essential for regulating blood pressure

•NO also contributes to the body’s non-specific immune defense by helping destroy pathogens and tumors.

Finally, the body’s continuous production of ROS and RNS through metabolic activities underlines their importance as vital contributors to human health when maintained at low or moderate levels.

This dual nature emphasizes the necessity of a balanced oxidative state for optimal physiological function and health.

Detrimental Effects of Oxidant Species

The detrimental effects of oxidant species, specifically when their levels surpass the body’s neutralizing capabilities, manifest in several forms of oxidative damage to integral biological structures.

Oxidative stress leaves lipids, nucleic acids, and proteins open to attack, disrupting cellular integrity and function.

One example is lipid peroxidation, where reactive species attack lipids containing carbon-carbon double bonds, specifically polyunsaturated fatty acids (PUFAs).

This creates lipid radicals that react with other lipid molecules, forming a harmful chain reaction.

These radicals compromise membrane structure and function—the process decreases membrane fluidity and inactivates membrane-bound enzymes and receptors.

Additionally, oxidative stress can significantly damage DNA and RNA, inducing mutations and base modifications that disrupt genetic information and integrity.

Proteins, too, are not spared—oxidative damage can induce protein structural and functional denaturation, causing loss of enzyme activity and disrupting cellular signaling and transport.

Among the oxidative damage products formed, Advanced Oxidation Protein Products (AOPP) emerge as a critical biomarker for oxidative stress, indicating protein damage.

Protein glycation, another consequence, involves the modification of proteins through reactions with reactive oxygen species, leading to the formation of Amadori products or advanced glycation end products, further compromising protein function.

Additionally, reactive species produce halogenated

products, acrolein, and allantoin, which are notable markers of oxidative damage.

The Role of Antioxidants

Antioxidants are the body’s defense system against oxidative stress and are diverse in structure and function, enabling them to operate effectively in both hydrophilic and hydrophobic environments.

They are broadly categorized into enzymatic and nonenzymatic types, each playing a unique role in neutralizing free radicals and preventing cellular damage.

Enzymatic antioxidants directly target ROS and RNS, acting as the first line of defense. Superoxide Dismutase (SOD) transforms the superoxide radical into hydrogen peroxide (H2O2) and oxygen, a crucial step in mitigating oxidative damage.

Catalase (CAT) and Glutathione Peroxidase (GPx) further detoxify H2O2 by converting it into water and oxygen. GPx also reduces lipid hydroperoxides using glutathione as a substrate.

Secondary enzymes like the thioredoxin system, thioredoxin peroxidases, and glutaredoxins support the antioxidant defense by reducing oxidized forms of primary antioxidants and repairing proteins damaged by reactive species.

Non-enzymatic antioxidants, both endogenous and exogenous, complement the action of enzymatic antioxidants by directly scavenging reactive species.

Endogenous non-enzymatic antioxidants include:

• Glutathione: The most prevalent cellular thiol-based antioxidant

• Uric acid: Contributes significantly to plasma antioxidant capacity

• Albumin: Scavenges hydroxyl radicals; bilirubin, known for its lipid-protective effects

• Coenzyme Q10: Crucial for mitochondrial redox balance

• Melatonin: Crosses cellular barriers to protect DNA, lipids, and proteins

• Alpha-lipoic acid: Active in both aqueous and lipid phases and capable of regenerating other antioxidants

Exogenous antioxidants, obtained from the diet, include vitamins A, C, and E, selenium, zinc, and a wide range of polyphenols found in fruits, vegetables, and beverages. These contribute to the body’s antioxidant defenses by scavenging ROS/RNS and chelating transition metals that could catalyze oxidative reactions.

These combined efforts of enzymatic and non-enzymatic antioxidants are essential for maintaining cellular health and preventing the detrimental effects of oxidative stress.

Oxidative Stress in Aging

While we can see the effects of oxidative stress in the short term, much of the damage accumulates over time and is directly linked to the aging process.

The “Oxidative Stress Theory of Aging” posits that aging results from the cumulative damage inflicted by reactive oxygen species (ROS) and reactive nitrogen species (RNS) on vital macromolecules such as lipids, DNA, RNA, and proteins.

This damage can stem from increased oxidative stress, due to a decline in mitochondrial function, and the diminished efficacy of the body’s antioxidant defenses over time.

As the efficiency of endogenous antioxidant systems wanes with age, possibly due to nutritional and hormonal changes, the balance shifts toward an accumulation of oxidative damage, marking a critical factor in the aging process.

This accumulation of oxidative damage is closely linked to cellular senescence, a state in which cells cease to divide but remain metabolically active, a pivotal aspect of aging.

Oxidative stress induces cellular senescence by causing DNA damage, accelerating telomere shortening, and activating growth arrest pathways.

Senescent cells, through the senescence-associated secretory phenotype (SASP), release inflammatory

factors, contributing to the pathogenesis of various age-related diseases such as cardiovascular disease, chronic kidney disease, neurodegenerative disorders, macular degeneration, biliary diseases, and cancer.

This interplay between oxidative stress and cellular senescence represents a vicious cycle, further exacerbated by inflammation.

The “Oxidation Inflammatory Theory” of aging suggests that chronic oxidative stress and subsequent inflammatory responses disrupt bodily homeostasis, leading to increased morbidity and mortality in older adults.

Thus, this cycle of oxidative stress and inflammation plays a pivotal role in the aging process and the development of age-related diseases.

Oxidative Stress, Health, and Longevity

The intricate relationship between oxidative stress and the body’s defensive mechanisms underscores a pivotal aspect of our health, significantly influencing the aging process and the development of various diseases.

Understanding and managing oxidative stress emerges as a crucial strategy for enhancing longevity and improving quality of life.

Review the full research article here: https://www.scienceopen.com/hosteddocument?doi=10.14293/PR2199.000699.v1

References:

1. Li, Z., Zhang, Z., Ren, Y. et al. Aging and age�related diseases: from mechanisms to therapeutic strategies. Biogerontology 22, 165–187 (2021). https://doi. org/10.1007/s10522-021-09910-5

2. Hari Krishnamurthy, Michelle Pereira and Imbaasree R et al. Oxidative Stress: Mechanisms, Quantification and its role in human aging. ScienceOpen Preprints. 2024. DOI: 10.14293/PR2199.000699.v1

About the Author:

Adair Anderson MS, RDN, LDN, is a Registered and Licensed Dietitian Nutritionist and Product Marketing Educator for Vibrant Wellness. Adair specializes in resolving frustrating functional gastrointestinal disorders (like IBS) so patients can get back to living their best lives. She brings grounded support, fosters a growth mindset, and uses evidence-based, functional testing to identify and resolve root-cause digestive mysteries.

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Ph: (800) 231-5777

Email: biotics@bioticsresearch.com www.bioticsresearch.com

Biotics Research Corporation was formed in 1975 and from day one the foundation has been “Innovation and Quality.” Our goals remain unchanged - innovative ideas, carefully researched concepts, and product development with advanced analytical and manufacturing techniques to develop and produce nutritional products of superior quality and effectiveness available exclusively to healthcare professionals. 1-800-231-5777 www.bioticsresearch.com

Ph: (856) 825-8338

Email: help@bodybio.com www.bodybio.com

Your body is an intricate machine composed of 70 trillion cells, each with the important task of protecting, healing, and keeping you healthy. At BodyBio, they understand that the health of your cell membrane is crucial to your overall health. That’s why they’ve developed supplements founded in research, tested for efficacy, and trusted by thousands of practitioners. Their products are formulated to provide the nutrients your cells need to thrive. Health and healing begin on the cell membrane.

Ph: (561) 247-3839

Email: info@bodysite.com www.bodysite.com

BodySite is a patient and practice management platform that helps doctors automate patient education and management to improve patient outcomes and increase practice revenue. Assign automated care programs so patients receive your guidance and instructions every day effortlessly. Patients track progress including progress, biometrics, calories, steps, activity, water, sleep. Book patient appointments, charge for services, educate, monitor progress, message and guide, all on one easy but powerful platform and app built for your practice.

BodySite

BOIRON

Booth #231

4 Campus Boulevard

Newtown Square, PA 19073

US

Ph: (888) 264-7668

Email: medicaldev@boiron.com www.boironusa.com/hcp

Boiron, world leader in homeopathic medicines, is best known for its pharmaceutical grade-quality drugs such as its Arnicare® line of pain relievers and Oscillococcinum® flu reliever. Founded in 1932, Boiron is the largest pharmaceutical company in its home country of France. With subsidiaries in 19 countries, Boiron distributes products in more than 50 countries in categories such as analgesics, cough, cold, flu, first aid, baby and children’s, oral and eye care, indigestion, and women’s health.

Boston Heart Diagnostics

Booth #728

200 Crossing Blvd Framingham, MA 01702

US

Ph: (877) 425-1252

Email: customercare@bostonheart.eurofinsus. com

www.bostonheartdiagnostics.com

Boston Heart Diagnostics is transforming the treatment of cardiovascular and related diseases through novel clinical diagnostics, therapeutically focused reports, and personalized, scientifically designed nutrition and lifestyle programs that have the power to change the way healthcare providers and patients communicate about heart health.

BrainMaster Technologies Inc.

Booth #229

195 Willis St. Bedford, OH 44146

US

Ph: (440) 232-6000

Email: sales@brainmaster.com www.brainmaster.com

BrainMaster offers the most cutting edge and comprehensive variety of Clinical EEG, 3D Brain Imaging, qEEG and Neurofeedback on the market. Application areas include real-time imaging utilizing sLORETA, normative databases and pre/ post therapeutic comparison. Clinical and personal data-base driven Neurofeedback, biofeedback, peak-performance, research, Virtual Reality and brain-controlled systems. Add our system to your practice, and change lives, one brain at a time!

BrainTap, Inc.

Booth #1019

2861 Trent Rd. New Bern, NC 28562

US

Ph: (302) 721-6677

Email: sales@braintap.com www.braintap.com

BrainTap is a revolutionary brain-fitness company that offers an all-in-one solution for better sleep, less stress, and increased focus. Our cutting-edge app and accompanying headset deliver leading-edge brainwave training technology and guided visualization techniques to optimize your brain’s performance resulting in an average 38.5% improvement on the stress index scale after just one session. Simply put on the headset, kickback, close your eyes, and listen to one of over 2,000 audio visualizations on BrainTap’s mobile app, then enjoy the results.

Broadcast Your Authority

#629

W. Springfield Way Florence, AZ 85132

Ph: (480) 605-2542

Email: info@broadcastyourauthority.com www.broadcastyourauthority.com

Accelerate Your Podcast’s Growth with a Tailored Done-For-You Solution to Reach Your Ideal Prospects. Elevate your voice to greater heights with a partner who specializes in transforming content into connections, capturing your ideal audience’s attention across every platform. We work with hundreds of podcasts weekly. Our services are more than podcast production, it’s a marketing strategy; a growth plan and partnership dedicated to your brand’s success.

Calmoseptine, Inc. Booth #736

Ph: (714) 840-3405

Email: kim@calmoseptine.com www.calmoseptine.com

Calmoseptine Inc. markets Calmoseptine Ointment in all 50 states, Canada, United Arab Emirates, Jordan, Cuba, Peru, and Chili. Calmoseptine Ointment is an effective, multi-purpose moisture barrier that protects and helps heal skin irritations. Calmoseptine Ointment is available in 2.5-oz jars or tubes, 4-oz tubes, 1/8-oz packets, and 20g tubes through most wholesalers, distributors and pharmacies. For more information, please call us at 800-800-3405, e-mail us at info@ calmoseptine.com, or visit www.calmoseptine.com.

Calocurb

Booth #936

17B Farnham St. Ste 13517

Auckland, Auckland 01052

New Zealand

Ph: (833) 225-2872

Email: hello@calocurb.com www.calocurb.com

Calocurb is the world’s only patented GLP-1 activating supplement, clinically proven to increase the body’s natural GLP-1 levels after only one hour post-intake. Calocurb’s active ingredient, Amarasate, an extract of New Zealand hops, has been shown in human clinical trials to activate the release of the body’s appetite-suppressing hormones—GLP-1, CCK, and PYY—resulting in a reduction of average caloric intake by 18%, reduced overall hunger by up to 30%, and cravings by up to 40%.

Calroy Health Sciences

Booth #212

14362 N Frank Lloyd Wright Ste 1000 Scottsdale, AZ 85260

US

Ph: (800) 609-6409

Email: support@calroy.com www.calroy.com

At Calroy, we translate breakthrough science into products without parallel. Through rigorous research and formulation, we develop transformative solutions for foundational health. Our team leads emerging scientific research and applies expertise on world-class natural ingredients to create our formulas. For premier vascular support, consider Calroy products - they work synergistically and standalone. We also regularly host educational series with vascular care experts and would love to see you there - sign up for our newsletter at our website.

CardioVision Care Booth #929

6999-2 Merrill Rd. Ste 120 Jacksonville, FL 32277

US

Ph: (904) 846-7070

Email: info@cardiovisioncare.com

www.cardiovisioncare.com

CardioVision Care is proud to present the MCG MultiFunction Cardiogram Thre Multifunction Cardiogram (MCG) is a non-invasive diagnostic tool used to evaluate heart function and detect potential cardiac issues. It combines several tests to provide a comprehensive assessment of the heart’s activity.

Ph: (786) 518-2629

Email: sales@celllifeusa.com

www.celllifeusa.com

Exclusive distributor of Organs, Glands & Tissues Dietary Supplements from France in the USA at a fraction of the cost.

Ph: (800) 872-5228

Email: info@cellsciencesystems.com www.cellsciencesystems.com

Cell Science Systems Corp. is a specialty clinical laboratory that develops and performs laboratory testing in immunology and cell biology supporting the personalized treatment and prevention of chronic disease. Cell Science Systems, Corp. operates a CLIA certified laboratory and is an FDA inspected and registered, cGMP medical device manufacturer meeting ISO EN13485 standards.

Central Drugs Compounding Pharmacy

520 W. La Habra Blvd. La Habra, CA 90631

Ph: (562) 691-6754

Email: clinicalrph@centraldrugsrx.com 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 at our state-of-the-art 503A compounding pharmacy. Central Drugs is your pharmacy partner, working with clinics to provide resources, education, and services to improve the overall health of your patients. Central Drugs specializes in compounding, seeking the most innovative, effective and trending formulations to meet the needs of clinics across 30 states.

ChromaDex, Inc.

Booth #932

1735 Flight Way Ste 200 Tustin, CA 92782

US

Ph: (949) 410-3984

Email: alexm@chromadex.com pro.truniagen.com

Your NAD+ supply declines with age as well as in response to stressors on your body including alcohol consumption, intense exercise, and lack of sleep. While nicotinamide riboside can be found naturally in certain foods, you cannot get anywhere near the amount you need through a normal diet to effectively increase NAD+. That is why we created Tru Niagen®, the only patented, broadly studied, and safety-reviewed nicotinamide riboside in the world.

Clinicians Supplement Consultants

Booth #912

180 Froehlich Farm Blvd. Woodbury, NY 11797

US

Ph: (516) 222-2288

Email: dlc@cscprivatelabel.com www.cscprivatelabel.com

Clinicians Supplement Consultants allows practitioners to provide concierge service and sales of professional supplement brands and practitioners own private label supplements to their patients. CSC has an exclusive professional only brand, a concierge supplement fulfillment service, a private label development and management program. CSC allows practitioners focus on the patient while CSC handles all aspects of inventory, dispensing, fulfillment, and patient compliance . CSC handles the supplement business allowing practitioners to focus on their patients.

College Pharmacy

Booth

#625

3505 Austin Bluffs Pkwy Ste 101 Colorado Springs, CO 80918

US

Ph: (800) 888-9358 x171

Email: sky@collegepharmacy.com www.collegepharmacy.com

THE COLLEGE PHARMACY DIFFERENCE: QUALITY. INNOVATION. EXPERIENCE. SINCE 1974. For over 40 years, College Pharmacy has provided healthcare practitioners and patients with high-quality compounded preparations and outstanding customer service. Our experienced pharmacists collaborate with patients and healthcare practitioners to provide innovative solutions for health and wellness success. It is our compounding process, attention to detail, and quality of the compounding components that continues to make our formulations exceptional.

PHARMACY

2492 Walnut Ave. Ste 104

Tustin, CA 92780

Ph: (714) 695-8000

Email: cservice@coolblueva.com www.coolblueva.com

At Cool Blue VA, we pride ourselves on being perfectly matched to the needs of our clients. We offer a wide range of VA services, from handling everyday office tasks to transforming your practice altogether. And because we’re virtual, we can save you up to 70% compared to hiring in-house staff.

Ph: (888) 224-5181

Email: 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 perfect formulations, dispensing orders reliably and resolving any issues promptly. Specializing in Peptides, Hormone Replacement Therapy, Sexual Wellness, Weight Loss & Energy, Cognitive & Mental Health formulas. Sterile & Non-Sterile compounds, Generic & Brand medications. Welcome to the future of compounding pharmacy.

Ph: (954) 422-3801

Email: wilson@genorthix.com www.neuroregenesis.com

The Center for Regenerative Medicine Laboratories is a cutting-edge institution dedicated to advancing the field of regenerative medicine and providing innovative treatments for patients. Located in Miami, this renowned center brings together a multidisciplinary team of experts, including physicians, scientists, and researchers, who are at the forefront of regenerative medicine research and clinical practice. The Center for Regenerative Medicine Laboratories provides high-quality and innovative bio-technologies.

Cool Blue VA Booth #1120

Cyrex Laboratories

Booth #324

2602 S. 24th St.

Phoenix, AZ 85034

US

Ph: (657) 303-3898

Email: michelle.c@cyrexlabs.com www.joincyrex.com

Cyrex Laboratories® is a unique clinical immunology laboratory specializing in environmentally-induced autoimmunity. Cyrex delivers next generation assessments for intestinal and blood-brain barrier permeability – the gateways to autoimmunity; environmental trigger screening including dietary antigens, pathogens and xenobiotics; and multitissue antibody testing for predictive biomarkers of autoimmune reactivity. The Lymphocyte MAP™, is an innovative test which establishes a new standard in screening immune health. Cyrex develops innovative arrays that assess the cross-connections between the body’s immune, gastrointestinal and neurological systems.

Designer Drugs Pharmacy

Booth #330

7304 Jarnigan Rd.

Chattanooga, TN 37421

US

Ph: (423) 954-2585

Email: sales@compound-rx.com www.designerdrugs.us

For more than 20 years, Designer Drugs has been working with patients and physicians to provide custom solutions for their pharmaceutical needs. Our technicians are certified to compound sterile and non-sterile medications. Our pharmacy proudly compounds hormone replacement therapy, injections, dermatologics, ophthalmics, and also boasts a cosmeceutical product line. These preparations are designed specifically to meet individual needs with the highest level of safety and accuracy. Designer Drugs is licensed to ship prescriptions to all fifty states.

Designs for Health

Booth #619

980 South St.

Suffield, CT 06078

US

Ph: (860) 752-7474

Email: sciencefirst@designsforhealth.com www.designsforhealth.com

Our Mission: Designing a Well World We are driven by a higher purpose. We are activists for health - rooted in and united by science. Transforming boundaries, breaking barriers, setting new standards, disrupting the status quo. We believe in sciencebased nutrition and natural medicine, developing health products without compromise, and advancing the way education and technology support wellness for all. We design a new paradigm. We design a well world. We are Designs for Health.

Diagnostic Solutions Lab

Booth #924

31 Lupi Ct. Ste 250 Palm Coast, FL 32137

US

Ph: (877) 485-5336 x1002

Email: cs@diagnosticsolutionslab.com www.diagnosticsolutionslab.com

Diagnostic Solutions Laboratory bridges the gap between healthcare providers and the clinical laboratory by offering cutting-edge laboratory tests such as GI-MAP, OMX (Organic Metabolomics), CytoDX, and GenomicInsight. Designed to identify underlying root causes of symptoms and disease, our test results give practitioners the tools needed to formulate personalized treatment protocols for optimized patient outcomes. Our commitment to education and service ensures both practitioners and their patients will benefit from the latest research.

Data, Inc.

Ph: (630) 377-8139

Email: 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.

Ingot St.

Ph: (510) 651-9088

Email: marketing@drfuji.com www.drfuji.com

Dr. Fuji 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.

DUTCH Test (Precision Analytical)

Booth

#513

3138 NE Rivergate Ste 301C

McMinnville, OR 97128

US

Ph: (503) 687-2050

Email: events@dutchtest.com

www.dutchtest.com

Precision Analytical’s DUTCH Test® (Dried Urine Test for Comprehensive Hormones) helps practitioners answer complex clinical questions by providing the most comprehensive hormone monitoring results with simple patient collection. Our rigorous pursuit for the truth in hormone testing has produced three peer-reviewed studies proving the effectiveness of our 24-hour, four spot, dried urine testing as an alternative to serum (blood) or saliva for monitoring a variety of hormone therapy applications.

Empower Pharmacy

Booth #701

7601 N Sam Houston Pkwy W Ste 100 Houston, TX 77064

US

Ph: (877) 562-8577

Email: support@empowerpharmacy.com

www.empowerpharmacy.com

Empower Pharmacy stands at the forefront of healthcare innovation, dedicated to making quality, affordable medication accessible for all. Our team blends engineering precision with pharmaceutical expertise to lead the largest 503A compounding pharmacy and FDA-registered 503B outsourcing facility in the nation serving the personalized medicine markets. We are here to transform lives through innovative medications, as we work together towards a healthier, happier world.

Enzyme Science

Booth #838

771 Commerce Dr. Venice, FL 34292

US

Ph: (855) 281-7246

Email: orders@enzyscience.com www.enzyscience.com

Enzyme Science™ makes exceptional formulas for natural digestive health and wellness. As the practitioner division of Enzymedica, America’s #1 selling enzyme brand, we use the finest ingredients, backed by scientific research and unparalleled quality, efficacy, and safety standards. Beyond our high-potency digestive and systemic enzymes, we offer formulas to support the cardiovascular and immune systems, joint health and more. * We exceed the FDA’s cGMP regulations and never use GMOS or artificial fillers, binders or excipients.

13622 Poplar Cir. Ste 403 Conroe, TX 77304

US

Ph: (936) 588-5510

Email: Scott@ergoflextechnologies.com www.ergoflextechnologies.com

Ergo-Flex Technologies, LLC. is the developer, manufacturer, and distributor of innovative equipment to help patients with pain relief and offer healthcare practitioners the opportunity to set themselves apart, taking their practices to the next level. Products include Back On Trac, Knee On Trac, Cervi-Trac and Total Brain & Body O2.

Ph: (786) 602-0942

Email: martin@eternalcenter.health https://eternalcenter.health/

At Eternal Medical Center, we are committed to staying at the forefront of the latest advancements in regenerative medicine. Our team of expert scientists and medical professionals are dedicated on researching, developing, and implementing cutting-edge treatments using the latest scientific techniques and technologies. By harnessing the power of human stem cells, we are able to stimulate the body’s natural regenerative processes and promote healing from within.

930 S. Kimball Ave. Ste 160

Ph: (833) 839-4735

Email: events@evexias.com www.evexias.com

EVEXIAS Health Solutions is an emerging leader in the advancement of medicine toward a preventive care model that positively impacts patient lives while also allowing practitioners to grow their practice. The EVEXIAS team has helped thousands of practitioners across the nation expand their treatment plans through advanced medical education and training from industry-leading medical practitioners, researchers, and scientists, as well as providing access to leadingedge therapies and technologies that support the prevention of disease and improve quality of life.

Ergo-Flex Technologies Booth #631

Fatty15

Booth #101

2907 Shelter Island Dr. Ste 105-411 San Diego, CA 92106

US

Ph: (619) 407-9225

Email: info@fatty15.com www.fatty15.com

Fatty15 is the world’s first, and only science-backed, patented, award-winning C15:0 supplement that supports your long-term health & wellness.*

Flore Clinical Booth #832

5151 Shoreham Pl. Ste 105 San Diego, CA 92122

US

Ph: (515) 988-6325

Email: floreclinical@sungenomics.com

www.floreclinical.com

Floré Clinical uses cutting-edge microbiome technology, utilizing Whole Genome Sequencing, qPCR, and Parasitology to help you get to the root cause of what’s driving gut dysbiosis. Coupled with 100% customized probiotics and prebiotics, Floré provides functional tools enabling you to take a root-cause medicine approach that can be the game changer in patient care.

FoodScience Corporation

Booth #737

929 Harvest Lane Williston, VT 05495

US

Ph: (802) 881-4509

Email: tjohnson@foodsciencecorp.com www.davincilabs.com

Since 1973, DaVinci® Laboratories has been a leader in nutritional research, product development and innovation. Our dedication to higher integrity, and insistence on superior quality are reflections of our core values. Today, DaVinci® continues to set new standards for quality and product innovation to keep you as healthy and informed as possible. We also offer private label if you are interested in having your brand with our quality and formulation.

Formula30A LLC

1992 Lewis Turner Blvd. Fort Walton Beach, FL 32547

US

Ph: (888) 366-7070

Email: info@formula30a.com www.formula30a.com

Formula30A produces full spectrum hemp products designed for the needs of healthcare providers and their patients. We craft a range of all-natural, high-quality cannabinoid products, including CBD and CBG capsules, to support wellness, healing, and recovery. Our water-based, patent-protected manufacturing and stringent third-party lab testing ensure the purity, potency, and safety of our products and solidify our commitment to quality. With a focus on care, quality, and customer satisfaction, Formula30A delivers consistent and effective cannabinoids that your patients can trust.

Fullscript

317 S 48th St Phoenix, AZ 85034 US

Ph: (866) 807-3828

Email: support@fullscript.com

www.fullscript.com

Fullscript® is the leading online platform for practitioners to manage and dispense healthcare’s best supplements — in-office or to patients’ doors. Practitioners become a safe, convenient source for trusted wellness products with the choice to offer savings, earn revenue, or both. Time-saving features, automated adherence tools, and more help physicians minimize admin, grow their practices, and keep patients engaged.

GAINSWave

NE 207th St. Ste 503

Ph: (855) 383-5779

Email: team@gainswave.com

www.gainswave.com

GAINSWave is the premium brand of extracorporeal shockwave therapy for ED, performed by our network of highly-trained medical providers. Treatment is allnatural and clinically proven using high-frequency shockwaves to enhance male sexual function, performance, and overall health. A non-invasive procedure that treats the root cause of erectile dysfunction in men by increasing blood flow, releasing growth factors in the tissue forming new blood vessels, and breaking down micro-plaque in the penis.

Genova Diagnostics

Booth #713

63 Zillicoa St.

Asheville, NC 28801

US

Ph: (828) 210-7362

Email: info@gdx.net www.gdx.net

Genova Diagnostics is a leading force in the world of healthcare, transforming the way chronic diseases are diagnosed, treated, and prevented. With a focus on empowering individuals to achieve optimal well-being, our advanced lab testing methodologies target crucial areas like gut health, nutritional status, immune function, and hormonal health. At Genova, we’re shaping a brighter and healthier future, where innovative approaches to personalized healthcare empower individuals to thrive. Learn more at www.gdx.net.

Global Life Rejuvenation Booth #220

168 East Main St. Denville, NJ 07834 US

Ph: (973) 627-1750

Email: demetriaglaab@denvillemedical.com

www.globalliferejuvenation.com

Global Life Rejuvenation A Leader in Anti-Aging Medicine and Hormone Replacement Therapy for Men and Women. Global Life Rejuvenation has Network Providers nationwide. Global Life educates and connects patients with our highly trained network physicians specializing in Anti -Aging Medicine.

Hallandale Pharmacy

Booth #325

2666 Sw 36th St Lauderdale, FL 33312

US

Ph: (954) 455-3822

Email: jmaman@hallandalerx.com www.hallandalerx.com

Hallandale Pharmacy’s is a 503a designated and PCAB accredited compounding pharmacy, that is committed to provide quality and affordable custom prescription formulations nationwide. The cGMP guidelines that Hallandale Pharmacy has adopted is led by our Quality Assurance team and supporting staff. While quality is the foundation of our practice, our service to our patients and providers drives our mission. We regard our relationships with our trusted practitioners as a partnership.

8940 Sunriver Meadows Ave. Las Vegas, NV 89148 US

Ph: (562) 338-6995

Email: expo@harmonycarellc.com www.harmonycarellc.com

Percussive devices

S. Missouri Ave Clearwater,

Ph: (833) 940-4898

Email: support@healthgev.com www.healthgev.com

Healthgevity is dedicated to the discovery and delivery of orally bioavailable peptides along with innovative ingredients designed to enhance longevity, optimize healthspan, and elevate overall quality of life. Our collaborative approach involves working closely with doctors and scientific researchers to effectively translate the latest research findings into cutting-edge advanced therapeutic nutraceuticals. By combining scientific expertise with a commitment to innovation, we strive to bring you the most effective solutions for promoting a healthier and more fulfilling life.

Healy World

Booth

#131

8529 Southpark Cir. Ste 100

Orlando, FL 32819

US

Ph: (321) 247-9025

Email: contact@healy.world

www.us.healy.world

Healy World creates revolutionary products and opportunities to empower you to thrive and live a life of freedom, passion and joy. The Healy is a small but very powerful device (controlled by your Apple or Android smartphone) that uses Individualized Microcurrent Frequency (IMF) programs to harmonize your Bioenergetic Field for many important areas of life.

Hormone Therapy Centers of America

Booth

#107

5 Cowboys Way Ste 300 Frisco, TX 75034

US

Ph: (469) 214-0816

Email: rhettrichardson@ht-ca.com

www.ht-ca.com

HTCA partners with practices to provide a full turnkey solution to implementing Bioidentical Hormone Replacement Therapy into your Practice, Clinic, or Med Spa. Our program consists of five key components: training, dosing, materials, marketing, and support.

Host Defense Mushrooms by Fungi Perfecti LLC

Booth #1114

PO Box 7634

Olympia, WA 98507

US

Ph: (877) 504-6926

Email: order@hostdefense.com

www.hostdefense.com

Host Defense® Mushrooms™ was founded by renowned mycologist Paul Stamets with the goal of building a bridge between people and fungi. Offering multiple delivery formats is one way they work to offer convenience and ease-of-use to any supplement regime. Host Defense myceliumbased products are currently available in capsules, extracts, sprays, powders, drink mixes, and more! Additionally, their MycoBotanicals® line is expertly formulated using organically-grown mushroom mycelium and herbs, fusing contemporary science with the innate intelligence of nature.

PO Box 960

Rock Hill, NY 12775

US

Ph: (845) 796-9951

Email: info@huelightusa.com www.huelightusa.com

We offer unique services with our own care program, BAHI Therapy, which is short for blood circulation, antioxidant, hormonal balance, and immunity, where we use high-quality care devices that can potentially be the ultimate fundamental treatment for pain management. Furthermore, we are always eager to provide educational support for the community by providing health-related information and treatment methods to better serve your health needs.

1250 S Capital of Texas Hwy. Ste 360 Austin, TX 78746 US

Ph: (512) 487-7025

Email: professional@humann.com www.pro.humann.com

Humann was founded in affiliation with a leading academic research program and is committed to promoting cardiovascular health, which includes healthy blood pressure, cholesterol, blood flow, and heart health support. The innovators at Humann bring forth smart, plant-based, and nutrition-forward science in the form of supplements in innovative form factors to meet the demands of modern, healthconscious consumers. Its products are widely used by physicians, consumers, and athletes alike, including over 120 Professional and Collegiate sports teams.

Immunocine LLC

Booth #813

Boulevard Luis Donaldo Coloso (Av Tulum) Manzana 1, Lote 3 Smz. Cancún, Quintana Roo 77504 Mexico

Ph: (888) 575-2572

Email: care@immunocine.com www.immunocine.com

Immunocine provides innovative cancer treatment to patients in need through personalized Dendritic Cell Immunotherapy. Our proprietary technique allows us to educate each patient’s Dendritic Cells with their own unique cancer genomics and markers – a technique never before accomplished. Immunocine patients have experienced incredible results despite being deemed incurable. Backed by 18 years of academic research, numerous publications, and multiple ongoing clinical trials, our treatment is a less invasive and more precise way to treat multiple types of solid cancer.

Hue Light USA

Booth #112

HumanN

InBody

Booth #919

13850 Cerritos Corporate Dr. Unit C Cerritos, CA 90703

US

Ph: (323) 932-6503

Email: convention@inbody.com www.inbodyusa.com

Trusted by anti-aging clinics like Restore Hyper Wellness, InBody has been revolutionizing body composition analysis for 25 years. In seconds, the InBody Test non-invasively measures muscle mass, body fat, visceral fat, fluids, BMR, and more. This allows physicians to: -Prove the effectiveness of anti-aging interventions at the cellular level -Develop individualized treatment plans for hormone therapies, peptide therapies, and supplements -Monitor positive changes in muscle and fat distribution when working in aesthetic medicine modalities

Infiniwell

Booth #121

5706 E. Mockingbird Lane #115-404 Dallas, TX 75206 US

Ph: (888) 819-4640

Email: shop@infiniwell.com

www.infiniwell.com

Science is moving faster. InfiniWell makes it easy to keep pace. With products like BPC-157, DHHB, and Spermidine, InfiniWell is fast-tracking clinical breakthroughs into accessible products for physicians and their patients. In a category that’s too often driven by margin and marketing, Infiniwell is privately owned and driven by patient outcomes. Each product is meticulously sourced and formulated through collaboration with practicing physicians, ensuring real-world efficacy and measurable outcomes.

Innovision Health Media

Booth #1031

3470 Washington Dr. Ste 102 Eagan, MN 55122

US

Ph: (651) 251-9623

Email: info@innovisionhm.com www.innovisionhm.com/publications.html

InnoVision Health Media publishes professional and consumer magazines, journals, websites, and newsletters. We serve consumers and professionals interested in integrative, holistic, and natural medicine. Our professional journals contain the latest research, case studies/reports, interviews with industry thought leaders, and breaking news concerning the holistic and integrative health care marketplace. Our consumer titles are focused on assisting readers in living a healthier lifestyle.

1235 Walton Way Augusta, GA 30901

US

Ph: (706) 831-8882

Email: hello@jinfiniti.com www.jinfiniti.com

Jinfiniti Precision Medicine operates at the intersection of health science and innovative supplement development. We specialize in formulating and manufacturing high-quality nutritional supplements tailored to address a range of health concerns. Central to our approach is the development of advanced testing protocols to evaluate the efficacy of our supplements. We collaborate with leading organizations and institutions to develop scientific studies in fields ranging from Autism to Infertility to Chronic Fatigue and more in order to discover solutions, possibly cures.

Booth #531

1728 Coral Way 600 Miami, FL 33145

US

Ph: (833) 436-8372

Email: info@juvexo.com www.juvexo.com

JuveXO® is a topical serum that has revolutionized aesthetic medicine by harnessing the extraordinary power of exosomes. Through the most cutting-edge biotechnology and decades of research, JuveXO® delivers a non-invasive and non-surgical method to revitalize and rejuvenate the appearance of skin and hair. Rich in hyaluronic acid, collagen, elastin, other essential proteins, and over 100 billion exosomes, JuveXO® is a biocosmetic that will leave you looking as young as you feel.

KBMO Diagnostics

Booth #508

4 Business Way

Hopedale, MA 02332

US

Ph: (617) 933-8130

Email: availlant@kbmodiagnostics.com www.kbmodiagnostics.com

The FIT Test is the most sensitive food test available using patented technology. The multiple pathway approach allows us to look at food sensitivities but also inflammation and gut permeability all from one test. We also provide best in class compliance tools including a personalized meal plan and a patient app. We have an FDA Registered and ISO 13485 compliant manufacturing facility as well as a CLIA High Complexity Laboratory based near Boston, Massachusetts.

Jinfiniti

Booth #901

JuveXO

medical technologies

Kinas Medical Technologies

Booth

#236

2160 Kingston Ct SE Ste D

Marietta, GA 30067

US

Ph: (770) 612-8284

Email: info@kinasmedical.com www.kinasmedical.com

Kinas Medical Technologies is a family-owned and operated business providing modern regenerative technologies to healthcare practitioners. We specialize in extracorporeal shock wave (ESWT) and magnetotransduction (EMTT) solutions including The Miracle Wave and STORZ Medical reputable product lines. With over 30 years of industry experience and knowledge, Kinas Medical pairs progressive shock wave technologies with partner-minded customer service for unparalleled implementation efficacy, ongoing support, and continuing education.

Life Support Health Products

Booth #908

800E. 101st Terr. Ste 100 Kansas City, MO 64131

US

Ph: (816) 673-1230

Email: info@lifesupporthp.com

www.lifesupporthp.com

As a company, we seek to create the highest quality supplements that exist in the world. All products are created by a functional medicine doctor who is currently in practice. We have solved the problem of having to take too many pills by creating concentrated products that deal with all aspects of a patients biochemistry. We know compliance is key for a patient to get a result and start referring. Let the healing begin.

Marius Pharmaceuticals

Booth #238

2301 Sugar Bush Rd. Ste 510 Raleigh, NC 27612

US

Ph: (919) 374-1913

Email: info@mariuspharma.com www.mariuspharma.com

Marius Pharmaceuticals strives to better the lives of men and women by focusing on therapies designed for hypogonadism or Testosterone Deficiency. Their vision is to holistically improve metabolic health and mitigate significant unnecessary costs to the global healthcare system. In 2022, Marius received FDA-approval of KYZATREX® (testosterone undecanoate) CIII capsules. For more information, please visit www.mariuspharma.com.

Ph: (832) 683-1574

Email: accounts@maxgenlabs.com www.maxgenlabs.com

MaxGen Lab was created by practicing physicians to provide a safe, accurate, and easy-to-understand way for people to learn about their bodies. Our reports are based on cutting-edge research, trusted by hundreds of physicians worldwide, and have received rave reviews and success stories. Our reports contain actionable steps with easy-to-understand and implement results. Our simple and precise DNA tests have helped thousands of individuals make more proactive choices toward optimal health and healing.

Ph: (214) 952-0863

Email: sales@druckerlabs.com www.officialmaxlife.com

Ph: (727) 593-0398 Email: Scotth@McArthurAgency.com www.mcarthuragency.com

edeia

Designed for Clinicians

Med Results

Booth #836

1111 N Brand Blvd Ste 350

Glendale, CA 91202

US

Ph: (818) 396-4496

Email: office.admin@med-results.com med-results.com

At Med Results, we are dedicated to providing innovative solutions in the aesthetic industry by bringing high-class products and technologies to your fingertips. We are the manufacturers of new technologies like Plexr plasma, Italian-made HDpdo threads, and the Uplifting creams. Our amazing team at Med Results is committed to bring the technologies of the future into your hands today. We promise to upgrade your perception of results, because we believe Results Matter!

Medeia Booth #132

7 W. Figueroa St. Ste 215 Santa Barbara, CA 93101

US

Ph: (800) 433-4609

Email: info@medeia.com www.medeia.com

Since its inception in 1992, Medeia Inc has been on the forefront in the manufacture and distribution of Neuro Diagnostic and Heart Rate Variability / ANS products. Medeia Inc specializes in the development of state of the art biometrical software and hardware products intended to monitor physiology for research and educational purposes.

Medical Tech

#1024

2700 Hall Pl. Longview, TX 75604

US

Ph: (646) 284-5598

Email: themedicaltechdp@gmail.com

www.themedicaltech.net

We provide top-quality medical wellness services, The technical team of Medical Tech Services produces revolutionary medical devices for the currently operating healthcare industry and even offers optimum quality services to customers. Our range of products includes medical devices like First Smart Float Tank,Float Pod, Ozone sauna.

170 Chestnut Ridge Rd. Queensbury, NY 12804

US

Ph: (540) 484-3429

Email: dgalbraith@merchantpreferred.com www.mpzero.net

Merchant Preferred Zero lets the business owner stop paying merchant processing fees. Growing their monthly profit year after year. This is ideal for any business and simple to implement. Credit card fees should not be a cost of doing business. MPZero provides the hardware at no cost. There is no longterm agreement. Giving the business owner the ability to profit from day one.

Ph: (855) 405-8378

Email: info@meridianvalleylab.com www.meridianvalleylab.com

A Trusted Leader in Urine Hormone and Food Sensitivity Testing At the forefront of innovation since 1976, Meridian Valley Lab was one of the first to offer urinary hormone and comprehensive, serum-based, food sensitivity testing. Urinary hormone testing revolutionized bioidentical hormone replacement therapy, allowing for the accurate assessment of hormonal levels during treatment. Blood-based food sensitivity testing radically transformed dietary assessments, quickly and easily identifying problematic foods. At Meridian Valley Lab, we empower your patients’ health through our state-of-the-art testing.

Metagenics

25 Enterprise Ste 200 Aliso Viejo, CA 92656 US

Ph: (800) 692-9400

Email: Info.customerservice@metagenics.com www.metagenics.com

With a heritage of breakthrough science, innovative products, unsurpassed quality, practitioner education, and dedicated partnerships, Metagenics is one of the most trusted health and wellness brands worldwide. For over 40 years, Metagenics, a globally certified B Corp, has developed highquality, science-based nutritional supplements, medical foods, and lifestyle programs to support the growing number of people seeking to improve their health and achieve their wellness goals.

Microbiome Labs

Booth

#413

1332 Waukegan Rd

Glenview, IL 60025

US

Ph: (904) 940-2208

Email: info@microbiomelabs.com www.microbiomelabs.com

Microbiome Labs is a company focused on improving health outcomes through the modulation of the gut microbiome. The company was built upon three major pillars: clinical research, education, and product innovation. This unorthodox approach is far and away what continues to set Microbiome Labs apart from the rest of the supplement industry. We strive to create unique and effective solutions that help practitioners change lives all over the world.

Momentous

Booth #830

1526 West Ute Blvd Ste 214

Park City, UT 84098

US

Ph: (801) 712-6081

Email: austin@livemomentous.com

www.livemomentous.com

At Momentous, we are performance obsessed. We are scientists, we are athletes, we are parents, we are people—just like you—working to bring our best to our every day. Our products are the result of our work with some of the brightest minds in human performance using the latest research. We use the highest-quality ingredients, and every single product is rigorously tested by independent third parties to ensure we deliver on our promise to bring you the best.

17849 Hunting Bow Cir. Ste 102

FL 33558

US

Ph: (281) 796-1140

Email: Spenaranda@mymycolab.com www.mymycolab.com

MyMycoLab is a laboratory specializing in blood serum antibody testing for mycotoxins. Our laboratory tests for 14 different mycotoxins for both IgG and IgE antibodies. This is the most precise and accurate method to determine if a person has been exposed to mycotoxins.

N1o1 by Pneuma Nitric Oxide LLC

MTS US

Booth #233

230 S. Hamilton Dr. 103 Beverly Hills, CA 90211

US

Ph: (310) 993-3320

Email: info@mts-us.org

www.mts-us.org

We specialize in global innovative solutions for aesthetic medicine and anti-aging experts to solve the most complex problems in your practice.

Ph: (877) 4PN-EUMA

Email: hello@N1o1.com www.N1o1.com

N1o1 by Pneuma Nitric Oxide is a Nitric Oxide centric company, devoted to bringing the most innovative, safe, and effective nitric oxide products to market in both the skin care/beauty and nutritional/ dietary supplement space. Results verified and quantified to support you for optimal health.

Natrusolate Americas Inc

Booth #1108

450 N. Bedford Dr. Ste 208 Beverly Hills, CA 90210 US

Ph: (650) 346-7176

Email: mark@epic-t.com www.natrusolateamericas.com

Are you ready to revolutionize your health and vitality? Discover the power of Testosurge, the cutting-edge solution from Natrusolate Americas. Our meticulously crafted formula is designed to support your wellness goals, delivering unparalleled quality and efficacy.

Neobiosis LLC

Booth #103

305 SW 7th Ter. Gainesville, FL 32601

US

Ph: (352) 631-7440

Email: info@neobiosis.com www.myliliumlife.com

Neobiosis is a biotechnology company focused on the development and manufacturing of innovative perinatal products for research and clinical trials. Our goal is simple: to help redefine the field of regenerative medicine through regenerative science and shape the future of this fledgling industry through meaningful partnerships and collaborations. We are uniquely positioned to help usher in this new era of medicine, which focuses on the potential of perinatal birth tissues including cells, EVs and matrix.

NMS Labs

Booth #1118

200 Welsh Rd. Horsham, PA 19044

US

Ph: (866) 522-2206

Email: clinical@nmslabs.com

www.nmslabs.com

NMS Labs is a clinical reference and forensic laboratory that is unsurpassed in its scope of PFAS, metals and exposure toxicology tests delivering the highest quality accurate results, scientific expertise, and innovation. The state-of-the-art CLIA certified laboratory staffed by more than 350 highly trained professionals. For more information on NMS Labs and to learn more about our clinical assays for Functional Medicine, please visit us at www.nmslabs.com.

Nordic Naturals

Booth #129

111 Jennigns Dr. Watsonville, CA 95076

US

Ph: (800) 662-2544

Email: prosales@nordic.com www.nordicpro.com

Nordic Naturals is the #1 fish oil brand in the U.S. and has been a trusted source of professionalgrade supplements for nearly 30 years. Our product portfolio offers the perfect nutritional support for your patients, including highly concentrated omega-3s, multi-strain probiotics, vitamins and minerals, women’s and pediatric products, and much more. We always use superior-quality ingredients that are grounded in science to help ensure your patients’ health and peace of mind.

Okeechobee

4

Ph: (855) 212-1997

Email: info@nubioage.com www.nubioage.com

NuBioAge empowers medical professionals with advanced supplements that enhance health optimization. Specializing in cell signaling molecules, we offer deep clinical insights and access to a network of trusted compounding pharmacies. Our products synergize with cellular medicine treatments, leveraging science, technology, and extensive compounding experience to improve patient outcomes. Join us in advancing healthcare through cutting-edge knowledge and tailored health solutions, ensuring the highest levels of patient care and quality of life.

Ph: (888) 202-7111

Email: info@nudora.com

www.nudora.com

NUDORA is a trailblazing probiotic company for revolutionizing health through personalized solutions. Our journey is steeped in a commitment to crafting condition-specific prebiotics, probiotics, and homeopathies, precisely targeting the gut to address health concerns at their source. Our formulations are not merely products; they represent a transformative approach to well-being, offering effective and longlasting solutions tailored to specific health conditions. We believe in the power of the gut to shape overall health, NUDORA is dedicated for a healthier life.

9503 E. 55th Pl. Tulsa, OK 74145

US

Ph: (800) 869-8100

Email: mail@numedica.com www.numedica.com

NuMedica® is an NSF® GMP Certified, FDA registered company implementing the latest quality control standards in manufacturing and testing of our formulas. Our formulas are designed with active ingredients for higher performance along with advanced nutrient delivery methods and Enhanced Absorption Technologies™ offering value through increased bioavailability.

NuMedica

Booth #806

PRACTITIONER FORMULAS

Nutramax Laboratories Consumer Care, Inc.

Booth #637

946 Quality Dr. Lancaster, SC 29720

US

Ph: (888) 886-6442

Email: contactus@nutramaxlabs.com www.nutramaxlabs.com

Since 1992, Nutramax Laboratories has been at the forefront of scientific innovation, consistently fortifying brands. Rooted in Lancaster, South Carolina, as a family-owned and operated entity, Nutramax Laboratories Consumer Care, Inc. proudly unveils its latest brand—NutramaxTM Practitioner Formulas. This exclusive line was developed for healthcare practitioners, embodying unparalleled quality through top-tier ingredients, state-of-the-art facilities, meticulous clinical research, and over 80 rigorous quality checks.

NutriDyn

Booth #825

5414 Hwy.12 PO Box 219 Maple Plain, MN 55359 US

Ph: (763) 656-8728

Email: info@nutridyn.com www.nutridyn.com

NutriDyn’s unwavering commitment to enhancing lives with clinically effective nutraceuticals fuels innovation in clinical nutrition and education, setting global quality standards. Their rigorous quality assurance spans from research to production, ensuring every NutriDyn™ product undergoes meticulous testing for purity, potency, identity, and microbiological safety. Trusted by over 20,000 healthcare practitioners worldwide, NutriDyn™ proudly serves as their dedicated partner in health, renowned for ingredient purity, reliability, and the proven effectiveness of their products.

Nutritional Frontiers

Booth #913

3191 Washington Pike

Bridgeville, PA 15017

US

Ph: (412) 922-2566

Email: info@nutritionalfrontiers.com www.nutritionalfrontiers.com

Nutritional Frontiers is a family-owned, faith-based Pittsburgh company with a committed mission to “Making the World Healthy”. We source the best ingredients and create unique formulations to improve patient outcomes and increase practice profits. Nutritional Frontiers is USA FDA Registered. Every nutraceutical formulation is produced in an FDA inspected cGMP certified manufacturing facility. All liquid herbs are organic and produced in the USA. We take tremendous pride in our relationships with our healthcare professionals, and by extension their patients.

Pharmaceuticals

6700 Conroy Rd. Ste 155 Orlando, FL 32835

US

Ph: (407) 250-4000

Email: sales@olympiapharmacy.com www.olympiapharmacy.com

Olympia Pharmaceuticals is the nation’s leading outsourcing facility for longevity, sexual health, IV nutrition, weight management, and more. Our premium compounds are made with the finest quality standards and protocols, giving you and your patients peace of mind. Olympia ships both patient prescriptions and office use orders nationwide, and with same-day order processing, you can order today for tomorrow’s patients.

Ph: (833) OMNIWave (833) 666-49283

Email: info@omniwave.com www.omniwave.com

OMNIWave™: The Future of Healing, an American-made shockwave solution. Crafted with cutting-edge technology and adaptable applications, these devices guarantee superior outcomes, heightened patient contentment, and effortless integration into your practice. Join us in embracing the future of healing. Reach out today to elevate your practice with OMNIWave™.

OreVital

Ph: (202) 798-0500

Email: mi@orevtial.com www.orevital.com

Orevital Labs specializes in transdermal performance enhancement peptides, offering non-invasive applications for increased lean body composition, reduced body fat, joint and tissue repair, boosted collagen production, accelerated wound healing, and relief from muscle and joint pain. Their proprietary transdermal cream applications facilitate direct delivery of active ingredients, including peptides and minerals, to tissues and cells without injections. Orevital sets a new standard in non-invasive treatment and wellness with its advanced delivery system.

Ortho Molecular Products

Booth #207

28160 W. Northwest Hwy, Ste. 100 1991

Duncan Place

Barrington, IL 60010

US

Ph: (815) 206-6541

Email: contactus@ompimail.com

www.orthomolecularproducts.com

For over 35 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

#313

10719 Norwalk Blvd Santa Fe Springs, CA 90670 US

Ph: (562) 619-2515

Email: events@oxyhealth.com

www.oxyhealth.com

OxyHealth has forever changed the way the medical industry practices hyperbaric therapy. Since our inception, we are devoted to providing quality and brilliantly safe portable hyperbaric chambers to physicians, professional athletes, wellness centers, and families. All OxyHealth chambers are designed for patients to easily self-treat, which has fostered a cutting-edge trend in hyperbaric technology.

Pendulum Therapeutics

Booth #218

933 20th St. San Francisco, CA 94107 US

Ph: (757) 404-4841

Email: HCPINFO@pendulumlife.com www.pendulumlife.com/hcp

Pendulum is improving the lives of millions by unlocking the power of the gut microbiome with evidencebacked probiotics you can’t find anywhere else.

2728 Wymberly Dr. Jupiter, FL 33458

US

Ph: (561) 972-1122

Email: drsteve.gethealthyusa.net www.gethealthyusa.com

Get Healthy USA, the largest medical distributor for Pharmanex, pioneers in preventative healthcare with our cutting-edge antioxidant testing and epigenetic-based nutritional supplements. We equip individuals and healthcare professionals with personalized, science-backed solutions for proactive health management, striving to elevate wellness and knowledge across communities.

4850 T-Rex Ave. Ste 150 Boca Raton, FL 33431 US

Ph: (561) 425-9912

Email: info@physicianslab.com www.physicianslab.com

Physicians Lab is one of the nation’s leading urinary hormone testing laboratory, delivering State-of-the-art Science with Superior Solutions. We beat the competition in price and turnaroundtimes, 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. PNOĒ, Inc.

Ph: (650) 485-0872

Email: info@pnoe.com www.pnoe.com

Revolutionizing health assessment, PNOĒ introduces a clinical-grade breath analysis tool for personalized health care. Utilized by health professionals, this noninvasive device offers a 10-minute test for customizing nutrition, exercise, and bio-optimization programs. PNOĒ’s approach enhances client retention and allows upselling of specialized services. Validated by renowned universities and trusted by elite institutions, PNOĒ’s technology simplifies advanced health evaluations, making them accessible and efficient.

Practitioner Depot

Practitioner Depot

Booth

#1038

11365 Sixth St. E. Treasure Island, FL 33706

US

Ph: (844) 683-8449

Email: contact@practitionerdepot.com www.practitionerdepot.com

The best supplements and lab tests on the market all in one place.

Precision Point Diagnostics Booth #1136

9 Dunwoody Park Ste 122 Dunwoody, GA 30338

US

Ph: (678) 699-8327

Email: info@precisionpointdiagnostics.com www.precisionpointdiagnostics.com

Precision Point Diagnostics is an innovator of testing solutions that assist in the diagnosis and management of conditions commonly addressed by Functional Medicine. Our unique profiles address comprehensive approaches to Patient care.

Premier Research Labs

Booth #801

3500 Wadley Pl. Bldg B Austin, TX 78728

US

Ph: (512) 218-2584

Email: info@prlabs.com www.prlabs.com/prlabs.com

Comprehensive, clinically tested, professional nutritional product line to meet advanced the practitioner’s needs. Recognized as the world leader in cellular resonant formulations, establishing the highest standard in the nutritional industry. PRL’s Quality Control Department includes an advanced, state-of-the-art laboratory staffed with scientists and a sourcing team dedicated to maintaining the high quality and integrity of raw materials that PRL products are known for.

US

Ph: (305) 234-8081

Email: triaddirect@gmail.com www.triadaer.com

Triad Aer. Professional Air Purification system

Ph: (412) 760-1115

Email: support@phpltd.com www.professional-health-products.com

Cutting corners when it comes to quality is an all too common practice in the supplement industry. We at PHP have been committed to using the highest quality ingredients, backed by science, in our formulations since our beginning in 1978. Our integrity and ingenuity goes into every product in our comprehensive line; making the partnership we have with clinicians above industry standard.

Ph: (877) 776-8610

Email: 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. Family Owned and Operated. www.protocolforlife.com 877-776-8610

PUR-FORM

Booth #1001

3600 FAU Blvd. Ste 101

Boca Raton, FL 33431

US

Ph: (908) 894-0035

Email: mdoran@purformhealth.com www.purformhealth.com/training-program

PUR-FORM is the leader in EBO2, VSEL, and Regenerative Medicine training. Led by industry pioneer Dr. Joseph Purita, our team provides hands-on training in your clinic on administering EBO2, the premium treatment for inflammation and toxin reduction.

Push Patch Booth #104

3683 Garden Ct. Grove City, OH 43123 US

Ph: (937) 840-8769

Email: contact@pushpatch.com www.pushpatch.com

Push Patch employs iontophoresis, utlizing minimal electrial charges to transmit medication like NAD+, Glutathione and BPC-157 through the skin-absolutely pain-free. think of it as a magnet-like operation, but with two electrodes instead or magnets. Applying the patch initiates a charge, propelling the medication through your skin and directly into your bloodstream. This is adventageous as it evades the gastrointestinal system, where the medication is often compromised.

Quicksilver Scientific Booth #206

1960 Cherry St LOUISVILLE, CO 80027

US

Ph: (303) 531-0861

Email: support@quicksilverscientific.com

www.quicksilverscientific.com

Quicksilver Scientific® is a leading manufacturer of advanced nutritional systems with a focus on detoxification. We specialize in superior liposomal delivery systems and heavy metal testing to support optimal health. Our advanced liposomal supplements are highly absorbable and support the body in the elimination of the broad range of toxins we’re exposed to. We are passionate about health and well-being and are committed to improving the lives of everyone we touch. ®

10 Bloomfield Ave. Pinebrook, NJ 07085

US

Ph: (561) 660-1409

Email: NA

www.qunol.com

Qunol Turmeric is available in liquid, vegetarian capsules, and gummies. “Supports Healthy Inflammation Response” Qunol CoQ10 is available in liquid, capsules, and gummies. “Supports Heart and Vascular Health, Essential for Energy Production, Beneficial to Statin Drug Users and is a Powerful Antioxidant” Qunol Magnesium is available in vegan capsules and gummies. “Promotes a healthy Nervous System, bone and muscle health, healthy heart support.”

Ph: (617) 429-1139

Email: usa@radotech.com www.radotech.com

Promoting RaDoTech personal wellness trucker and RaDoTech Ayurvedic-based para-pharmaceutical supplements.

3rd Ave South Ste C

Ph: (904) 240-4269

Email: support@refineusa.com www.refineusa.com

Refine USA, LLC located in Jacksonville, FL has been a market leader in the manufacturing and distribution of premier aesthetic technologies for more than 18 years. We pride ourselves on designing and developing medical devices that meet the clinical and financial needs of aesthetic health care providers. The FDA Cleared Rejuvapen NXT® Microneedling System, the PureSpin® PRP System and the Facelite USA LED Series are just a few examples of our “market-changing” technologies.

Regenative Labs

Booth

#331

1700 West Main St. Ste 500

Pensacola, FL 32502

US

Ph: (800) 891-3452

Email: info@regenativelabs.com

www.regenativelabs.com

Regenative Labs produces regenerative medicine products to address the root cause of a patient’s conditions using Wharton’s jelly innovations rather than masking pain. Regenative Labs works closely with scientists and physicians to monitor and improve patient progress and outcomes while following FDA guidelines of minimal manipulation for homologous use.

Relax Saunas of Momentum

Booth

#115

3509 N. High St. Columbus, OH 43214

US

Ph: (626) 200-8454

Email: reggie@relaxsaunas.com

www.relaxsaunas.com/superior

Relax Saunas are the only medical grade portable saunas. Each Relax Sauna has two 750-watt emitters that deliver dense FIR energy in the 4-14um range of frequencies. Human cells absorb FIR at 8-13um. Relax Saunas immerse your body in far infrared light and create an efficient, therapeutic, and portable dry sauna experience that you can start enjoying within 30 seconds after you turn it on, even if you are fully clothed!

Researched Nutritionals

Booth #419

PO Box 224 Los Olivos, CA 93441 US

Ph: (805) 693-1802

Email: conferences@researchednutritionals. com

www.researchednutritionals.com

Researched Nutritionals® is dedicated to creating professional grade, effective formulas that are backed by peer-reviewed, published clinical research and are designed to promote energy and vitality. With products focused on key areas of health such as mitochondrial function, immune support, detoxification, and cytokine health, Researched Nutritionals® is a leader within the practitionerexclusive dietary supplement market and is dedicated to working directly with healthcare practitioners for their most challenging patient needs.

RP Therapies, LLC / PhalBack

667 Phillips Rd.

Saint Joseph, LA 71366

US

Ph: (833) 453-6484

Email: John@rptherapies.com

www.phalback.com

RP Therapies provides the PhalBack product to therapeutically increase the size of a penis - GIRTH and LENGTH. The process is non-invasive - no needles, filler, or surgery. Patients progress through a series of custom contouring penis chambers as they grow. PhalBack was developed to provide penile rehabilitation to men after prostate surgery, including buried penis. PhalBack is effective with any normal penis below eight inches. Used in the privacy of home. Money back.guaranteed!

Rupa Health

177 Townsend St. #528 San Francisco, CA 94107

US

Ph: (954) 821-7917

Email: hello@rupahealth.com

www.rupahealth.com/conferences

Rupa Health, the best way to order functional and integrative tests from 30+ specialty labs. Order, track, and get results from over 3,000 tests in one place. With Rupa, you can effortlessly order labs & scale your practice with less work and no preexisting accounts! We even provide patient support, so you can streamline your ordering altogether. Sign up for free to receive $100 off your first lab order: www.rupahealth.com/conferences. We’re bringing root cause medicine to everyone on the planet!

Rx Harmony | The JOI Group

#930

45 Technology Pkwy. S. Ste 150 Peachtree Corners, GA 30092

US

Ph: (770) 838-3570

Email: info@thejoigroup.com www.thejoigroup.com

Rx Harmony is a clinical program service that connects doctors, pharmacies, and patients to enhance the patient experience while reducing practitioners’ and staff’s workload. With programs for men’s health, women’s health, hair restoration, sexual function, allergy, and weight loss, we act as an extension of your practice to remove the burden of prescription management, billing, and patient support so you can enjoy predictable, recurring revenue and restore your joy for practicing medicine.

Booth #328

1439 Stuart Engals Blvd

Mount Pleasant, SC 29464

US

Ph: (843) 513-8306

Email: info.us@seca.com

www.secambca.com

As a global leader in healthcare medical technology, seca provides over 180 years of expertise in measuring systems, scales, body composition analysis, vital monitors, software, and service support with scientifically validated precision. With the diagnostic aid of seca medical Body Composition Analyzer, a patient’s health baseline is determined using key components (fat mass, visceral adipose tissue, skeletal muscle mass, body water), providing a comprehensive overview of one’s health status to tailor therapy and optimize treatment.

SensIQ Nootropics + Adaptogens

601 Brickell Key Dr. Ste 700 Miami, FL 33131 US

Ph: (786) 713-1470

Email: hello@sensiqnootropics.com

www.sensiqnootropics.com

SensIQ is a pioneering health and wellness company specializing in cognitive health supplements. Our products, including nootropics and adaptogens, are scientifically formulated to support mental clarity, focus, memory, and stress management. Exclusively available to healthcare professionals, SensIQ’s offerings are designed to enhance patient care while providing practitioners with innovative, high-quality solutions for cognitive wellness. Our commitment to research and quality ensures that SensIQ remains at the forefront of cognitive health advancements

SilverCeuticals Inc.

Booth #812

1396

Ph: (385) 212-4044

Email: Sales@SilverCeuticals.com

www.silverceuticals.com

SilverCeuticals harnesses cutting-edge nano-silver technology to develop a range of products including immune supports, beautifying cosmetics, oral care, and wound care technologies. Our advanced formulations are designed to address the specific needs of anti-aging professionals and their patients, promoting wellness and rejuvenation. With a commitment to global well-being, we strive to alleviate suffering by delivering innovative solutions that enhance health and vitality. Discover the power of SilverCeuticals to transform aging gracefully.

Health

111 Terrace Hall Ave. Burlington, MA 01803 US

Ph: (781) 202-5192

Email: hello@siphoxhealth.com

www.siphoxhealth.com

SiPhox Health is pioneering the most advanced blood testing technology in the world. As a leader in optical biochip technology, SiPhox is introducing integrated photonics into home healthcare for the very first time. The SiPhox Home and Health testing systems offer innovative and efficient blood collection solutions for consumers, health practitioners, pharmaceutical companies, and research teams focusing on longevity and chronic disease management.

Striker Pharmacy

Pin Oak Rd. Katy, TX 77494 US

Ph: (855) 455-0553

Email: admin@strikerrx.com

www.strikerrx.com

.Striker Pharmacy, based in Katy, Texas, is a licensed sterile compounding pharmacy founded in 2018, dedicated to providing exceptional pharmaceutical services. With 30 years of experience, our team specializes in Tirzepatide and Semaglutide for weight loss, ensuring top-tier medications and personalized service. Our mission emphasizes exceptional service, competitive pricing, and delivering the highest quality medications. Choose Striker Pharmacy for a partner in your healthcare journey, experiencing unparalleled care and expertise.

Strive Pharmacy

Booth #719

325 N Ash St Ste 203

Ph: (480) 626-4366

Email: info@strivepharmacy.com www.strivepharmacy.com

We strive to interrupt an industry that has been closed to personalized care, accessibility, and nuance for too long. We strive to shift a reactive view of self-care and ignite a proactive baseline-shifting approach. ‘The human element’ is our crux and catalyst, driving all that we do. We’re here to partner with those ready for a change. We’re on a mission to positively disrupt healthcare as we know it. Strive is about striving for the personal side of healthcare.

SiPhox

Swish30 | Doctors Nano

Booth

#639

6650 W Indiantown RD Ste 200-412 Jupiter, FL 33458

US

Ph: (888) 321-1235

Email: info@doctorsnano.com www.doctorsnano.com

Glutathione Next Era’ in seconds, on demand. Swish30® and PrimaSkin® feature HydraStat® nano-delivery. This patent-pending technology crafts ultra-pure water for water-cluster protection of nano particles. This increases bioavailability and transference into the organic cell, producing exceptional outcomes. Doctors Nano LLC advisors champion these revolutionary health and beauty advances with professional retail distribution and total support for wellness, performance and longevity clinics. Registered trademarks held by Biotech Nutritional Sciences, LLC.

T.A. Sciences

Booth #501

7975 N Hayden Rd Ste C-101 Scottsdale, AZ 85258 US

Ph: (212) 588-8805

Email: info@tasciences.com www.tasciences.com

T.A. Sciences® was founded in New York City by Noel Thomas Patton in 2002. T.A. Sciences® is dedicated to creating research-based, clinically tested products that help address telomere shortening through Telomerase Activation. T.A. Sciences® is widely recognized as the leader in the field of Telomere Biology. T.A. Sciences® spends over $1 million each year on leading edge scientific research, including doubleblind, placebo-controlled studies proving the safety and effectiveness of its premiere product TA-65®.

1166 E Warner Rd. #101-113

AZ 85296

US

Ph: (480) 331-3316

Email: info@Taxanista.com www.taxanista.com

Experienced & Creative Full Service Tax, Accounting & Consultancy Firm, licensed in all 50 states. We are experts in the wellness space. Assisting medical professionals transition from insurance to a thriving cash pay practice. We assist in the formation, Systems & Processes, Cashflow Planning, CFO Services, Tax Strategy & Business Consulting, plus more. We review & work with your other professionals (legal, financial, insurance) to help you achieve the maximum benefits & protections. Licenses - USTCP, IRS EA, CPA, CMA

Ph: (503) 506-8732

Email: info@thaena.com www.thaena.com

Thaena®, pronounced | thay-nah |, is a femalefounded, Pacific Northwest-based company and the proud creators of ThaenaBiotic®, the world’s first stool-derived complex postbiotic supplement. Our mission is simple: To use science, radical innovation, and the microbiome to help people feel better. We believe in using the innate wisdom of the human body to shift the paradigms of medicine by expanding access to microbiome supports and putting postbiotics on the map.

Tailor Made Compounding

Booth #225

200 Moore Dr. Nicholasville, KY 40356 US

Ph: (859) 887-0013

Email: support@tailormadecompounding.com www.tailormadecompounding.com

The Tailor Made Difference A Higher Standard of Care As experts in compounded medications, we provide custom wellness solutions to satisfy the unique needs of all types of patients. Our individualized treatments not only yield better health results - but maintain them for years to come. Visit us at www.tailormadecompounding.com to learn more about our integrative care treatments!

Ph: (912) 222-4962

Email: team@drannacabeca.com www.drannacabeca.com

Whether you are before, during or after menopause, I’m the first call for the woman who has question she would only ask her best girlfriend- If her girlfriend were a Triple-Board Certified OB-GYN.

The Girlfriend Doctor

Thera Wellness Solutions, Inc.

Motor City Dr. Ste 615

Ph: (240) 442-1919

Email: office@therawellness.us

www.therawellness.us

THERA WELLNESS™ is a premier provider of clinically proven, holistic wellness technology and services. We are innovators of the wellness industry delivering cutting-edge, personalized, holistic solutions to wellness care providers and their clients to achieve a balanced state of well-being.

TouchMD

TruDiagnostic

Ph: (813) 796-6451

Email: hello@touchmd.com

www.touchmd.com

TouchMD is a visual consultation, marketing and imaging software utilizing touchscreen technology that enhances the patient experience with proven revenue generation.

Ph: (859) 797-2983

Email: support@trudiagnostic.com

www.trudiagnostic.com

Home to the largest, private DNA methylation database in the world, TruDiagnostic is a leading health data company and CLIA-certified laboratory that specializes in epigenetic testing and research. In partnership with notable biotech developers, researchers, and academic institutions, we are transforming the healthcare potential of epigenetic data into actionable applications. With the ability to analyze more than 1,000,000 locations on one’s DNA, our TruAge biological aging tests provide the most in-depth results, and multi-omic correlations to accelerated aging.

US

Ph: (973) 476-3165

Email: info@metaverseone.com

www.truebinding.com

TrueBinding Inc. is a pioneering clinical stage biotherapeutic company at the forefront of creating groundbreaking molecules to address a wide spectrum of challenging medical conditions. We focus on neurodegenerative diseases such as: Alzheimer’s, Parkinson’s, ALS, as well as stroke, metabolic disorders, oncology and other areas with significant unmet medical needs. We are dedicated to advancing therapies that hold the potential to transform patient outcomes.

Compounding Pharmacy

1875 3rd Ave

Ph: (800) 985-8065

Email: customersupport@ucprx.com www.ucprx.com

UNIVERSITY COMPOUNDING PHARMACY (UCP) a nationally recognized leader in drug and device therapies. For 30 years our expert Pharmacists and experienced Physician Liaison team have been dedicated to support an unbiased product line, devising the management of BHRT conditions for your patients. We meet FDA & BOP prescription requirements and dispense in nearly 50 states.

COMPOUNDED: THYROIDS, ESTROGENS, PDE-5 INHIBITORS- BIOIDENTICAL HORMONES.

US Biotek Laboratories

16020 Linden Ave. N. Shoreline, WA 98133 US

Ph: (206) 365-1256

Email: info@usbiotek.com www.usbiotek.com

US BioTek Laboratories is at the forefront of advancing testing methodologies, ensuring precise results and consistent performance on a global scale. With specialization in food sensitivity, inhalant, GI microbiome, organic acids, and toxin testing, our unparalleled expertise can be seen in our reproducibility rates and turn around times. We strive to be an extension of our providers team try to do so through our commitment to convenient and hygienic testing kits ensuring a seamless experience for your clients.

1816 W. 135th St.

Ph: (800) 241-2221

Email: SALES@usjaclean.com www.daiwamassage.com

U.S. Jaclean, Inc. is one of the leading health and wellness massage chairs distributors in the United States. Our mission: To improve the health and wellness of Americans through quality products that can be used from the comfort of home.

Ph: (561) 379-6230

Email: carmine@valemedical.com

www.valemedical.com

Vale Medical, a premier US provider of STORZ Medical’s shockwave technology, offers a comprehensive range of non-invasive, safe, and highly effective treatment devices, including Masterpulse One, D-actor 50/100, Duolith SD-1 FSW, and the revolutionary Magnetolith (EMTT). Experience the difference in patient recovery speed and efficacy at our booth.

Vertisis Custom Pharmacy

Ph: (303) 476-3447

Email: matthewb@vertisis.com

www.vertisis.com

Vertisis is one of the most unique sterile-injectable compounding pharmacies in the United States. Our focus is on going “above and beyond” traditional compounding pharmacies by raising the standards of 503A compounding pharmacies to include exceptional products, unique delivery, advanced education, and an amazing relationship with health care providers with a seamless delivery of care. We are Vertisis Custom Pharmacy, your custom compounding pharmacy for integrative and naturopathic IV therapies and compounds.

3521 Leonard Ct Santa Clara, CA 95054 US

Ph: (866) 364-0963

Email: support@vibrant-wellness.com www.vibrant-wellness.com

Vibrant Wellness is a leading biotech company based in Santa Clara, CA, delivering life-transforming lab testing that enables health and wellness providers to discover the root of patient health issues. We’re at the forefront of modern medicine and research, providing personalized health analytics using cutting-edge, high-quality technology. We believe that anyone can achieve better health and vibrant longevity through individualized solutions based on testing—not guessing.

516 Fletcher Dr. Warrenton, VA 20186 US

Ph: (844) 309-3782

Email: info@wecarepharm.com www.wecarepharm.com

WeCare Pharmacy is a full-service compounding pharmacy specializing in IV Nutritional Therapy, BHRT, Dermatology and other integrative therapies. Our goal is to come alongside your practice and provide you with creative products that make you more effective clinicians, innovative business owners, and “rock stars” to your patients. The Service You Deserve from the Pharmacy You Trust. Access the high-quality medications you need with individualized, compassionate care for every patient.

Ph: (800) 401-7046

Email: info@wellnessclinicmarketing.com www.wellnessclinicmarketing.com

We offer marketing and appointment booking services to medical practices specializing in cashpay treatments for hormone optimization, sexual wellness, medical weight loss, and other anti-aging procedures. With over 12 years of experience working exclusively with med spas, wellness centers, and men’s health clinics, we have developed proven strategies to ensure your calendar is filled with appointments. For more information, please visit our website and contact us to schedule an introduction call. We look forward to hearing from you!

Vibrant Wellness

WeCare Pharmacy

Wellness Clinic Marketing

Wellness Pharmacy

Booth

#106

3401 Independence Dr. Ste 231 Birmingham, AL 35209

US

Ph: (800) 227-2627

Email: info@wellnesspharmacy.com www.wellnesspharmacy.com

With over 60 years of compounding experience, Wellness Pharmacy is considered the industry leader in quality and customer service. Our specialties include chelation, bioidentical hormones, autism support, and preservative-free injectables. Wellness Pharmacy is also the only pharmacy to successfully patent the preparation of injectable glutathione. PCAB-accredited.

ZEO ScientifiX Inc.

Booth

#914

Nova Southeastern University, Center for Collaborative Research 3300 S. University Dr., Ste 246 Ft. Lauderdale, FL 33328

US

Ph: (888) 963-7881

Email: info@zeoscientifix.com www.zeoscientifix.com

As pioneers in the development of science-based technologies in biologic medicine utilizing extracellular vesicle therapeutics, ZEO ScientifiX is proud to showcase a ‘first of its kind’ exosome product called PPX™, a highly concentrated autologous exosome product that utilizes a proprietary high speed centrifugation process, isolating 400-800B total nanoparticles per 2mL vials. The specific signature exosomes in PPX™ contain multiple types of microRNA markers, proven to target damaged cells and reduce inflammation while inducing regeneration at the cellular level.

Zizion Group Inc.

Booth #100

141 NW 20th St. Ste G1

Boca Raton, FL 33431

US

Ph: (561) 221-1000

Email: bruce@zizion.com

www.zizion.com

Zizion Group is a medical distribution company focusing on natural, integrative therapies. We bring technologically advanced products, targeted training, and innovative marketing expertise to empower medical professionals to expand their practice. We are an end-to-end provider, identifying appropriate solutions and deployment methodologies while working with your team to ensure success. Our emphasis areas are Hair Regeneration, Aesthetic Services, Orthopedic Indications, and Sexual Wellness. You are never considered a customer; you are a valued partner.

ZRT Laboratory

Booth #601

8605 SW Creekside Pl.

Beaverton, OR 97008

US

Ph: (866) 600-1636

Email: info@zrtlab.com www.zrtlab.com

ZRT laboratory, a CLIA-certified commercial and research laboratory, is the recognized leader in innovative and meaningful hormone and wellness testing. ZRT has pioneered testing methods for hormones, neurotransmitters, heavy metals and more, offering health care professionals convenient testing options in different body fluids including saliva, dried blood spot, dried urine, and serum. ZRT provides comprehensive test results that allow providers to create personalized treatments for optimal outcomes, with the help of our knowledgeable clinical consultants.

Premium Peptides

PEPTIDES: BPC-157, Dihexa, TB-4 Frag, KPV, GHK-Cu

NOOTROPICS: NMN, Methylene Blue

THE BEST IN EPIGENETIC AGE TESTING

OUR REPORTS

From a blood spot, TruDiagnostic can analyze samples and provide the most advanced, personalized epigenetic age report to date With our TruAge COMPLETE kit for providers, we offer:

Most predictive aging algorithms published with Harvard Exclusively licensed from Duke for all verticals Exclusively licensed from Yale in all verticals

OMICmAge

The first published clock trained with proteomic, metabolomic, and clinical measures

DunedinPACE One of the most accurate clocks and predictive of agerelated outcomes

Home to the largest, private DNA methylation database in the world, TruDiagnostic is a leading health data company and CLIA-certified laboratory that specializes in epigenetic testing and research. www trudiagnostic com

telomere novel IP Reports also include:

SYMPHONYAge Able to quantify the heterogeneous aging outcomes in 11 different organ systems

Telomere Length More predictive of outcomes than traditional telomere length but is not clinically relevant yet

I 12 Cell Immune Report

I Type-2 Diabetes Risk Report

I Inflammatory Markers Report

I Mitotic Clock Report

I Physical Fitness Report (VO2 max, FEV1, grip strength, and gait speed)

I Smoking and Drinking Report

I Weight Loss Response Report

Receive two kits at when you sign up to be a provider! Interested in offering the best biological age testing in your clinic?