A4M MMI | Anti-Aging Medical News - Spring 2023

Dear Colleagues,

We are delighted to welcome you to the 31st Annual Spring Congress presented by the American Academy of Anti-Aging Medicine (A4M). As the foremost leaders in anti-aging medicine and advanced education, we at A4M continuously strive to make excellence the standard of modern healthcare, based on a whole-person, patient-centered model that addresses current and future barriers to health. Our primary goal is to equip you, our committed community of passionate medical professionals, with the latest research and skills to overcome any clinical challenge with confidence and superior training.

This year’s Spring Congress, themed “The Fire Inside: Inflammation: The Common Pathway to Disease,” confronts one of the most significant hurdles to optimal health and longevity. Chronic inflammation is one of the greatest threats to modernday public health and a key driver of many of the deadliest diseases, including cancer, obesity, and diabetes. As such, it demands our urgent attention and intervention.

As well-informed health professionals, we see evidence of the staggering toll that chronic inflammation can take on patient lives, from spurring disease progression to exacerbating pain, fatigue, and other debilitating symptoms that lower quality of life. We have a responsibility to our patients to stay at the forefront of the industry and provide them with the most effective treatments available. It is our duty to urgently address inflammation as the root cause of the dysfunctions we commonly encounter in practice today.

We come together here to explore the latest research developments, therapeutic advancements, and evidence-based approaches for preventing, treating, and managing inflammatory states. As forward-thinking practitioners, we strive to optimize the human healthspan, not just to alleviate symptoms of chronic disease; as such, A4M aims to deliver an all-encompassing learning experience that leaves you with a comprehensive understanding of what to do next.

This weekend, we proudly bring together a diverse panel of the world’s top clinicians, researchers, and industry innovators who will guide you through current clinical strategies to take on the insidious causal agent of chronic disease. Alongside the brightest minds in medicine, we welcome some of the most disruptive companies specializing in functional medicine and health optimization.

We kick off on Thursday with two pre-conference workshops investigating therapies for biological age optimization and nutritional and hormonal interventions for inflammation. Come

Friday, a star-studded panel of educators will take the Main Stage to lead impactful and targeted sessions accompanied by captivating keynote presentations from renowned authorities Tom Rifai, MD, FACP, and John La Puma, MD.

Featuring faculty members representing all corners of the medical industry, the Congress agenda offers a unique opportunity to learn about chronic inflammatory conditions, functional wellness, and longevity science from various perspectives. Throughout the two-day conference, over forty prominent educators will cover a range of relevant topics, from interconnected biological systems and underlying pathways contributing to inflammatory conditions to hormone balance, autoimmunity, and gut health.

Our signature conference provides unparalleled educational and networking opportunities through dynamic sessions, interactive workshops, and social receptions, empowering you with the tools and support to address inflammation and its dangerous implications. We urge you to connect with leading experts and colleagues gathered here, sharing ideas and insights that can drive innovation and inspire new clinical approaches. By working together, we can extinguish the flames of chronic inflammation and lead the paradigm shift toward excellence in healthcare.

On behalf of the entire A4M team, we sincerely thank you for joining us at this event. A special welcome goes out to first-time attendees as we introduce you to the world of A4M. As you immerse yourself in the 31st Annual Spring Congress throughout the weekend, we hope your experience is enlightening and fulfilling. And that it encourages you to confidently tackle the challenges and seize the opportunities of modern medicine as we continue to redefine it.

Please enjoy your stay in Orlando; we wish you a safe journey back home.

In Good Health,

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Dementia Reversal And Wound Healing May Be Two Sides Of The Same Coin

By: Allen Meglin, MD & Jason Sonners, DC, PhD(c)

31 67 61 75

The Microbiome- Mitochondrial Nexus – The Influence Of Microbial Health On Mitochondrial Function

By: Pamela W. Smith, MD, MPH, MS

37 81

Exploring Protective Effects Of Telomerase Activator TA-65 On Mice With SAR Induced By Cigarette Smoke

By: Ron Rothenberg, MD

43 97 103

Aging Gracefully: The Power of Glutathione and Nicotinamide Adenine Dinucleotide in Anti-Aging Medicine

By: Jonathan Ramnauth, PharmD, RPh & Charmaine Saratan, PharmD, RPh

53

The Endothelial Glycocalyx: A Critical Link to Endothelial Function

By: Thomas G. Guilliams, PhD

Vaginal Dryness and Vaginal Atrophy

By: Pamela W. Smith, MD, MPH, MS

BPC 157: GI Therapy and Beyond

By: Erika Schwartz, MD & Daniel L. Cajigas

Probiotics, Resistant Starch, and Vitamin E Tocotrienols for Healthy Aging

By: Caitlin H. Higgins, MS, CNS & Danielle Moyer, MS, CNS, LDN

Shockwaves Are Changing The Future Of Ed Treatment And Are Quickly Becoming The Gold Standard Of Care

By: Rangan Patel

Extinguish the Fire of Inflammation with Nitric Oxide

By: Nathan S. Bryan, PhD

Hiding in Plain Sight: A Classic Detoxification Nutrient for Longevity

By: Lindsay Christensen, MS, CNS, LDN, A-CFHC, CKNS

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Dementia Reversal And Wound Healing May Be Two Sides Of The Same Coin

Dementia Background

The neuropathological process of dementia typically begins between 15 to 35 years before clinically overt symptoms, providing a window of opportunity for early detection and prevention. It may be considered to have the prodromal states of subjective cognitive impairment and mild cognitive impairment. Although minimal cognitive decline is considered to be a normal part of aging, substantial memory loss is not. Once considered incurable, some forms of dementia have been shown to be reversible (1). Conventional wisdom suggests that previous attempts to treat dementia have failed due to delay in diagnosis as well as failure to identify and remediate the single underlying metabolic perturbation. While potentially true, it is more likely that prior monotherapy treatment

failures are due to the multifactorial nature of the disease. Monotherapy has not worked because dementia represents a final common pathway for a multiplicity of metabolic failures. As a result, screening, diagnosis and treatment may require a multidisciplinary approach involving integrative, translational, functional and HBOT providers in addition to neurologists, psychiatrists, nutritionists, and life coaches.

From a hyperbaric oxygen therapy (HBOT) providers perspective, dementia resembles both aging and a complex non-healing wound. Both processes involve a multiplicity of simultaneously impaired homeostatic mechanisms. In dementia homeostatic regulation failures converge upon the governance of neuroplasticity. As a result of multiple metabolic insults, the requisite

normal balance between synapse formation and synapse destruction has shifted away from synapse building (synaptoblasis) towards synapse loss (synaptoclasis).

In dementia the altered neuroplasticity may be the result of exposure to multiple dementogens which include genetic, epigenetic, environmental (toxicities and deficiencies), metabolic (hypoxia) and behavioral contributors. Like aging or wound healing, successful regeneration and repair requires five basic processes: injury discontinuation (or prevention), cellular debridement (autophagy), replacement of the damaged tissue with healthy tissue (hormones, growth factors and stem cells), information and cell signaling (transcription factors, growth factors, cytokines, chemokines, hormones, inflammatory and anti-inflammatory signaling) and time.

In dementia treatment, the overarching goal is to rebalance both the synapse forming and synapse removing processes in order to restore neuroplasticity. When successful, evidence of neuroplasticity rebalancing can be seen anatomically on MRI scans, physiologically with perfusion MRI, PET brain and PET amyloid scanning and functionally on cognitive testing.

Alzheimer’s Disease:

Globally, dementia cases will likely triple over the next 30 years. As the largest subset of dementia diagnoses, Alzheimer’s disease (AD), accounts for nearly 60-80% of all dementia cases. It effects almost 6 million patients and is considered by many to have no known cure. It is estimated that AD will cost the US $1.1 trillion U.S. dollars by 2050 due to healthcare, long term care and hospice care. It is a devastating disease, not only for the patient, but for the family and care givers as well.

common etiology, brain inflammation (due to chronic inflammation or infection), represents approximately 60% of all cases. The other four root causes can be defined as toxicity (due to exposure to heavy metals, man-made or naturally occurring toxins), deficient essential metabolic factors (including hormones and nutrients), and vascular and traumatic injuries. As will be discussed later, both inflammatory and vascular subtypes of Alzheimer’s are well suited for treatment with Hyperbaric Oxygen Therapy (HBOT) (2) . Genetic factors also play a role. The APOE4 Gene and its’ epistatic interactions with other genes are known to increase the risk of AD, and patients with these genetic markers may want to consider surveillance. (3). Central to the metabolic changes of inflammatory Alzheimer’s is CNS insulin resistance, which some have labeled type 3 diabetes.(4). The AD diagnosis is based on neuropsychiatric testing and confirmed using several csf and blood markers, brain PET, amyloid sensitive PET, and MRI with volumetric analysis.

Alzheimer’s can be broadly categorized as the result of five types of insults: The most

All forms of AD may be viewed as the end result of multiple metabolic processes gone awry. By definition, these processes are dynamic and if treatment is stopped, symptoms are likely to reappear. Due to the complexity and sheer number of inciting events, treatment protocols are complex and lengthy. It took years to create the requisite disease-causing metabolic shifts. It is unlikely that they can be reversed quickly. Unfortunately, patient compliance is inversely related to complexity of treatment and number of interventions required. The ideal treatment modality would address multiple metabolic abnormalities at once. The appeal of an effective monotherapy is the unrealized promise of a simple treatment resulting in rapid improvement.

Treatment Approach

To date, successful treatment protocols have required a high level of commitment and compliance by both patients and providers. Pioneered by Bredesen, the Recode or Reversal of Cognitive Decline protocol targets many biologic pathways simultaneously.

(1). It does so largely by reversing lifestyle contributors that lead to Alzheimer’s.(5). Treatment protocols are individualized, based upon the pre-treatment evaluation of contributing factors (dubbed cognoscopy). Essential treatment pathways reverse the neuropathology induced by inflammation, poor diet, lack of aerobic exercise, and lack of adequate sleep. The biochemical changes are induced by fasting, insulin resensitization, meditation, stress reduction, removal of toxins, neuro-psychological training and nutritional supplementation. It is believed that a “critical mass” of metabolic correction must be achieved to reverse the cognitive decline. The Recode protocol and the science behind is not universally accepted. Some say the recode protocol is unproven and the studies that support it are flawed. Further, it has been posited that the authors of the Recode protocol may have inherent conflicts of interest. (6) . Since Alzheimer’s is such a devastating disease and there are no proven treatments, skepticism is healthy.

By definition, the Recode protocol is an intricate set of lifestyle changes which must be strictly followed. Broad based application is more likely to be successful if treatments are easy to initiate, follow and maintain. Ideally there would be early successes so that the treatment would be self-reinforcing.

Not included in Recode, Hyperbaric Oxygen Therapy (HBOT ) may an overlooked treatment option. It affects a large number of metabolic processes simultaneously. HBOT may be

Bredesen’s “silver buckshot”, as opposed to the monotherapy “silver bullet” (1). A vital first step in any treatment, Hbot is known to offer protection from additional insults. (7) In a paper from 2020, HBOT was shown to ameliorate cognitive impairment in patients with Alzheimer's disease and amnestic mild cognitive impairment (8).

HBOT is defined as treatment with pressure at virtually anything greater than one atmosphere while breathing either air (21% oxygen) or enriched oxygen (up to 100%). HBOT has been safely In use since biblical times when the afflicted would travel to the Dead Sea. At 1,414 feet below sea level, with a barometric pressure 800 mm hg or 1.052 atmospheres the Dead Sea offers a mild form of Hbot. Today, hyperbaric practitioners are able to modify the amount of pressure, the percentage of oxygen and the frequency/duration of sessions in order to match to the patients’ need for increased oxygenation. Interestingly, part of Hbot success resides in what is known as the hyperoxia/ hypoxia paradox. Although Hbot causes hyperoxia during treatment, rest intervals are sensed as relative hypoxia by hypoxia sensing pathways. That is, Hbot offers advantages of improved mitochondrial oxygenation during treatment and activation of survival pathways between treatments.

Hbot is known to reduce inflammation, lower glucose levels, increase insulin sensitivity and increase oxygenation to ischemic tissues (9). It increases autophagy, improves immune function, and enhances neurogenesis and angiogenesis. (10). Hbot increases Stem cell activation and release from bone marrow(11). Hbot enhances immune function. It increases production of naturally occurring anti-oxidants such as superoxide dismutase and glutathione reductase. It improves mitochondrial oxygen supply and therefore ATP production, even downstream from vascular inefficiencies and occlusions. Hbot is known to increase humanin, a mitochondrial peptide that demonstrates

neuroprotective properties. During treatment, Hbot causes a shift away from sympathetic and towards parasympathetic tone. This is considered a relaxing and meditative experience by most patients. Hbot increases angiogenesis and focal cerebral perfusion to selected areas of the brain often involved with dementia. It seems that perfusion to areas experiencing relative hypoxemia can be selectively enhanced (11) . Interestingly, in a recent placebo-controlled trial, older adults (>60 years) with normal cognitive function, demonstrated improved cognitive function with repeated treatments with HBOT. (12) This is believed to be a result of improved oxygenation of under functioning tissues.

There are, however, only 14 FDA approved indications for treatment with hbot. Almost all of these represent some form of wound healing. Treatment of dementia is therefore an off-label use and not insurance reimbursable at the time of this writing. With the guidance and support of the International Hyperbaric Association (IHA) access to Hbot is becoming far more common and inexpensive. Mild hyperbaric treatment is available at numerous centers worldwide and can include the convenience of treatment in the home.

Overlapping Pathways

The utility of Hbot is likely due to its ability to address multiple metabolic aberrations that affect the neuroplasticity balance. There is significant overlap of the therapeutic targets for the Recode protocol and Hyperbaric oxygen. Essential in both is angiogenesis with improved perfusion to the brain. Improved perfusion may lead to enhanced removal of amyloid.(12, 13). Hbot is unlikely to be successful as a stand-alone monotherapy as it does not address metabolic abnormalities relating to vitamins B1, B12, A, D, C, E, K and of Zn, Mn, CU and Se, choline, estrogen, pregnenolone, thyroid hormones

and omega 3 fats. Hbot is not known to decrease heavy metal or other toxic burdens directly, but It may enhance detoxification pathways in the liver and be secondarily helpful in increasing toxin resilience.

The strength of Hbot is that is affects multiple cellular signaling and metabolic pathways simultaneously. (14). Rather than being viewed as another monotherapy, it may best be thought of as a multichannel regulator of several metabolic processes. HBOT reduces oxidative stress, inflammation and neural apoptosis. It increases neurotrophic factors and neurogenesis. It increases cerebral blood flow and improves blood flow regulation (explaining the improvements seen in the treatment of vascular dementia). Hbot has been shown to increase brain volume after stroke and trauma. Similar to Recode, Hbot increases neuroplasticity (15).These effects persist for several months after last the Hbot treatment. As previously mentioned, the hyperoxia/ hypoxemia paradox results in intermittent hypoxemic signaling. The relative hypoxemia during rest or air breaks causes increased production of HIF1 and HIF2 alpha (hypoxia inducible factor). The HIF increase results in endothelial progenitor cell release and activation, thereby increasing angiogenesis in distressed regions of the brain. HIF is also a master regulator of cellular metabolism. As a transcription factor, it regulates the on/off switch in aerobic metabolism. During treatment, Hbot paradoxically blunts cellular level effects of HIF, allowing increased brain glucose utilization. As seen on PET, the net result is increased blood flow and glucose utilization in areas of the brain affected by AD..

Insulin is a key growth factor for neurons. Loss of neuronal insulin sensitivity results in a decrease in synaptoblastic activity. Hbot is known to increase insulin sensitivity by increasing adiponectin, resisten and plasminogen activator (PAI-1) expression(9) Insulin is such a strong

contributing factor to brain health that virtually all inflammatory Alzheimer’s patients can be viewed as having CNS insulin resistance. Even in prediabetics, cerebral atrophy has been found in the amygdala and hippocampus.

Hbot is known to have strong anti-inflammatory effects. In work done with Covid-19 patients, Hbot has been used successfully to reduce brain fog. The rapid response is due modulation of the Covid induced inflammatory cytokine storm. Blood markers of inflammation such as interleukin 6, TNF, NK (kappa delta), and C-reactive protein, are known to decrease during treatment with Hbot.(16) Hbot also plays a role in decreasing inflammatory bowel disease and leaky gut which are suspected major causes of brain inflammation (17). Hbot also treats oral dysbiosis and inflammation.

Healing of all types involves the cellular debridement of senescent cells. Hbot improves autophagy in neuronal tissue via AKT/TSC2/ mTor pathways.(17) The resulting senescent cell removal allows for both new cell in-growth and decrease of their inflammatory secretome.

In addition to decreasing inflammation and increasing autophagy, hyperbaric oxygen increases neurogenesis. BDNF (brain derived neurotrophic factor) has been shown to increase significantly after just three hbot treatments. Hyperbaric oxygen also increases SIRT-1, il-10, VEGF, Glial Line neurotrophic factor, and androgen receptor activity.(18) Hyperoxia increases Nrf2 which is felt to be neuroprotective by stimulating the repair and degradation of damaged proteins. NF-kappa beta (an inflammation and immune regulator) is activated during hyperoxia and is involved in neuroplasticity. These signaling molecules enhance neurogenesis, neuroprotection and axonal sprouting.

Perhaps the greatest testimony for Hbot as an essential adjunct treatment lies in its’ ability to

improve cognitive function in otherwise healthy aged adults. That is, treatment with Hbot has been shown to improve cognitive function even in the absences of cognitive impairment. It is effective in improving cognitive function in an otherwise normal aged population. (12) (19). Combination therapy using diet, exercise, sleep, stress reduction, cognitive training, nutritional supplementation and HBOT may the best way to improve cognitive function and overall health. Using Recode, 50% of patients improved, 23% halted progression of disease and 27% showed continued decline. (1). Could Hbot be the missing ingredient in these treatment failures?

Conclusion:

Research has shown that by simultaneously addressing and correcting many errant metabolic processes, Alzheimer’s may be reversed. Early treatment of the prodrome (SCI, MCI) may prevent it completely. The complexity of treatment is dictated by the complex nature of the disease. Alzheimer’s disease may represent the final common outcome of a critical combination of metabolic failures. Perhaps the best hope for widespread adoption of treatment protocols is early, self-reinforcing clinical improvement. HBOT may be a useful adjunct treatment as it may allow earlier successes while addressing multiple biochemical processes simultaneously. Hbot improves cerebral blood flow, brain metabolism and brain microstructure, leading to improvement in cognitive function, memory, sleep, and gait. (18). The convergence of multichannel remediation protocols may be the key to dementia arrest and reversal. HBOT is easy and relaxing for the patient and the provider. It may offer a great option for long term or lifelong treatment commitment and compliance. It is unlikely to be a monotherapy as it does not address all or even most of the root causes. It does, however, offer promise as part of a multimodality, multispecialty approach to reversing and preventing cognitive decline.

Dementia Reversal And Wound Healing May Be Two Sides Of The Same Coin

Resources:

(1). ReCODE: A Personalized, Targeted, Multi-Factorial Therapeutic Program for Reversal of Cognitive Decline. Rammohan V Rao, Sharanya Kumar, Julie Gregory, Christine Coward, Sho Okada, William Lipa, Lance Kelly,1 and Dale E Bredesen.Biomedicines. 2021 Oct; 9(10): 1348. Published online 2021 Sep 29. doi: 10.3390/ biomedicines9101348

(2). Impact of Hyperbaric Oxygen Therapy on Cognitive Functions: a Systematic Review. Anna B. Marcinkowska, Natalia D. Mankowska, Jacek Kot,3and Pawel J. Winklewski. Neuropsychol Rev. 2022; 32(1): 99–126. PMCID: PMC8888529 Published online 2021 Apr 13. doi: 10.1007/s11065-021-09500-9

(3). Genome-wide epistasis analysis for Alzheimer’s disease and implications for genetic risk prediction. Hui Wang, David A. Bennett, Philip L. De Jager, Qing-Ye Zhang and Hong-Yu Zhang, Wang et al. Alzheimer's Research & Therapy (2021) 13:55 https://doi.org/10.1186/ s13195-021-00794-8

(4). Hyperbaric oxygen therapy increases insulin sensitivity in overweight men with and without type 2 diabetes. David Wilkinson 1, Mirjam Nolting 2, Mohd Kaisan Mahadi 3, Ian Chapman 3, Leonie Heilbronn 3 Diving Hyperb Med. 2015 Mar;45(1):30-6. PMID: 25964036

(5). Clinical Lifestyle Medicine Strategies for Preventing and Reversing Memory Loss in Alzheimer’s. Paulina Shetty, MS, RDN, LD and Wes Youngberg, DrPH, MPH, CNS, FACLM Am J Lifestyle Med. 2018 Sep-Oct; 12(5): 391–395. Published online 2018 May 11. doi: 10.1177/1559827618766468

(6). Can we trust The End of Alzheimer’s?, Joanna Hellmuth, MD. Lancet Neurol. 2020 May; 19(5): 389–390. doi: 10.1016/S1474-4422(20)30113-

7. PMCID: PMC7377549 NIHMSID: NIHMS1608084 PMID: 32333896

(7). A review on the neuroprotective effects of hyperbaric oxygen therapy.Fahimeh Ahmadi and Ali Reza Khalatbary, PhD* . Med Gas Res. 2021 Apr-Jun; 11(2): 72–82. PMCID: PMC8130666 Published online 2021 Mar 26. doi: 10.4103/2045-9912.311498 PMID: 33818447

(8) Hyperbaric oxygen ameliorates cognitive impairment in patients with Alzheimer's disease and amnestic mild cognitive impairment. Jianwen Chen, Feng Zhang, Li Zhao, Cheng Cheng, Rujia Zhong, Chunbo Dong, Weidong Le.First published: 14 June 2020 https://doi. org/10.1002/trc2.1203

(9). Hyperbaric oxygen therapy affects insulin sensitivity/resistance by increasing adiponectin, resistin, and plasminogen activator inhibitor-I in rats. Cemil KAHRAMAN and Hüseyin YAMAN. Turk J Med Sci. 2021; 51(3): 1571–1577.Published online 2021 Jun 28. doi: 10.3906/sag2011-76

(10). Hyperbaric oxygen therapy improves cognitive function in D-galactoseinduced aging via restoring autophagy, apoptosis, microglia activation and synaptic plasticity in hippocampus Molecular and cell biology/neurodegeneration and neuroprotection . Thazin Shwe, Cherry Bo-Htay, Tom Leech, Wasana Pratchayasakul, Nipon Chattipakorn, Siriporn C Chattipakorn First published: 07 December 2020 https://doi.org/10.1002/alz.039217

(11). Hyperbaric Oxygen Increases Stem Cell Proliferation, Angiogenesis and Wound-Healing Ability of WJ-MSCs in Diabetic Mice. Isaac Peña-Villalobos 1 2, Ignacio Casanova-Maldonado 2, Pablo Lois 2, Catalina Prieto 2, Carolina Pizarro 2, José Lattus 3, Germán Osorio 4, Verónica Palma 2 ront Physiol, 2018 Jul 30;9:995. doi: 10.3389/ fphys.2018.00995. eCollection 2018. PMID: 30104981,PMCID: PMC6078002, DOI: 10.3389/fphys.2018.00995

(12). Cognitive enhancement of healthy older adults using hyperbaric oxygen: a randomized controlled trial . Hadanny Amir, 1,2,3 DanielKotovsky Malka,1 Suzin Gil,1 Boussi-Gross Rahav,1 Catalogna Merav,1 Dagan Kobi,1 Hachmo Yafit,5 Abu. Hamed Ramzia,1 Sasson Efrat,1 Fishlev Gregory,1 Lang Erez,1 Polak Nir,1 Doenyas. Keren,1 Friedman Mony,1 Tal Sigal,4 Zemel Yonatan,1 Bechor Yair,1 and Efrati Shai 1,2,5,6 .Aging (Albany NY). 2020 Jul 15; 12(13): 13740–13761. PMCID: PMC7377835 Published online 2020 Jun 26. doi: 10.18632/ aging.103571

(13). Hyperbaric oxygen therapy alleviates vascular dysfunction and amyloid burden in an Alzheimer’s disease mouse model and in elderly patients. Ronit Shapira, 1 Amos Gdalyahu, 1 Irit Gottfried, 1 Efrat Sasson, 4 Amir Hadanny, 4 Shai Efrati, 2 , 3 , 4 Pablo Blinder, 1 , 2 and Uri Ashery1 , 2 Aging (Albany NY). 2021 Sep 15; 13(17): 20935–20961. Published online 2021 Sep 9. doi: 10.18632/aging.203485

(14). Hyperbaric oxygen therapy as a new treatment approach for Alzheimer’s disease. Ronit Shapira, Shai Efrati, and Uri Ashery*.Neural Regen Res. 2018 May; 13(5): 817–818. doi: 10.4103/1673-5374.232475.

(15). Hyperbaric Oxygen Treatment—From Mechanisms to Cognitive Improvement. Irit Gottfried,1 Nofar Schottlender,1,2 and Uri Ashery1,2,* Biomolecules. 2021 Oct; 11(10): 1520. Published online 2021 Oct 15. doi: 10.3390/biom11101520

(16). The Effects of Hyperbaric Oxygenation on Oxidative Stress, Inflammation and Angiogenesis. Silke D. De Wolde,1,2,* Rick H. Hulskes,1,3 Robert P. Weenink,1,2 Markus W. Hollmann,1 and Robert A. Van Hulst1,2 Biomolecules. 2021 Aug; 11(8): 1210. Published online 2021 Aug 14. doi:

(17). A Review of Hyperbaric Oxygen Therapy for Inflammatory Bowel Disease Naif Alenazi, 1 Hesham Alsaeed, 1 Adel Alsulami, 1 and Turki Alanzi 2. Int J Gen Med. 2021; 14: 7099–7105. Published online 2021 Oct 24. doi: 10.2147/IJGM.S336678

(18). Hyperbaric oxygen relieves neuropathic pain through AKT/TSC2/ mTOR pathway activity to induce autophagy Yong-Da Liu, Zhi-Bin Wang, Guang Han, Li Jin,2 and Ping Zhao, J Pain Res. 2019; 12: 443–451. PMCID: PMC6361320 Published online 2019 Jan 23. doi: 10.2147/ JPR.S189353

(19). Hyperbaric oxygen therapy for healthy aging: From mechanisms to therapeutics. Qiaoyu Fu,a Ran Duan,a Yu Sun,b,c,d, and Qingfeng Lia, Redox Biol. 2022 Jul; 53: 102352. Published online 2022 May 27. doi: 10.1016/j.redox.2022.102352

Allen Meglin, MD

Allen Meglin MD initially trained as an Interventional Radiologist at The Johns Hopkins Hospital and Walter Reed. He transitioned to Regenerative Medicine in 2018 and now owns Regenerative Medicine Clinics (Advanced Regenerative Therapy) in Savannah, Ga and Asheville, NC. He trained with A4M, IHA, ABRM, IBUM, George Washington University, International ATMO. He is board certified by the ABR and ABRM. He thanks his mentors, Jason Sonners DC and Shannon Kenitz.

Dr. Meglin earned his Medical Degree at University of Pittsburgh, graduating AOA. He completed a surgical internship, followed by diagnostic radiology at Walter Reed Army Medical Center. He received additional training in needle placement and minimally invasive procedures at The Johns Hopkins Hospital. Dr. Meglin has authored several medical publications, was a featured lecturer, and has several medical device patents.His love of minimally invasive procedures and desire to practice cutting edge medicine led him to regenerative medicine. Dr. Meglin has received training from the American Academy of Regenerative Medicine, with coursework accredited by The Mayo Clinic, the Regenerative Medicine Training Institute, and the American Medspa Association. Dr. Meglin’s application to the American Board of Regenerative Medicine has been accepted, and he is now one of a handful of physicians that are board eligible in regenerative medicine. He is a frequently invited speaker on the topics of Regenerative Medicine basic science, Hyperbaric oxygen therapy and comprehensive treatment of disease using regenerative techniques.

Dr Meglin is a member of the American Academy of Regenerative Medicine. (AARM), InternationalHyperbaric Association (IHA), undersea and hyperbaric medicine society (UHMS) International board of hyperbaric medicine (IBUM) He has participated in trials studying biologic age and how to reverse aging. Dr. Meglin has studied the biologic effects of COVID and treatment with biologics.

Dr. Meglin has patent pending on a regenerative medicine delivery device and process, and is participating in several 510(k) FDA applications. He has trademarked “stack the hack”(tm).

Jason Sonners, DC, PhD(c)

Dr. Jason Sonners: A Doctor of Chiropractic, Dr Sonners has also earned his Diplomate of the Chiropractic Board of Clinical Nutrition (DCBCN) and Diplomate of the International Board of Applied Kinesiology (DIBAK).  Dr. Sonners is currently enrolled at the University of Miami School of Medicine, where he is completing his PhD in molecular biology with a concentration in regenerative medicine.

In 2020, Dr. Sonners published an Amazon best-selling book, Oxygen Under Pressure, describing the science and benefits of using hyperbarics for a variety of indications, longevity and performance enhancements. He serves on the board and faculty of the International Hyperbarics Association (IHA), the International Board of Undersea Medicine (IBUM), the Medical Academy of Pediatric Special Needs (MedMaps) and the Age Management Medicine Group (AMMG).  Dr. Sonners is a frequent lecturer at functional medicine conferences throughout the country and teaches hyperbaric certification courses for doctors and technicians.

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The MicrobiomeMitochondrial Nexus

– The In uence Of Microbial Health On Mitochondrial Function

As humans, we are home to and caretakers of a vast and diverse collection of microorganisms. While the bulk of this microbiota lives in the gastrointestinal tract, their total number is roughly equivalent to our own human cells. However, their total microbial genetic diversity is far greater than ours and can impact human physiology in a multitude of ways. Research suggests that a higher diversity of microorganisms in our GI tract is associated with optimal health and less disease.

Most of our human cells are host to tiny organelles known as mitochondria, which are the sites for producing energy in the form of adenosine triphosphate (ATP). These mitochondria also participate in critical central metabolic pathways,

including intracellular signaling networks that regulate diverse cellular functions.

Research continues to highlight the importance of the microbiome and its systemic influences – which extend to mitochondrial function. Diversity and abundance of microbes support robust intestinal and immune function, as well as healthy levels of inflammation throughout the body - all of which depend upon and influence mitochondrial function.

In contrast, microbial dysbiosis can result in the production of metabolites and signaling molecules that increase inflammation and disrupt mitochondrial function. Poor outcomes with infectious illnesses are often correlated with dysbiosis. Could the mitochondria play a role?

Recent evidence shows there is a bidirectional interaction between mitochondria and microbiota. The gut microbiota is involved in mitochondrial biogenesis. At the same time, its secondary metabolites, such as short-chain fatty acids (SCFAs) and secondary bile acids, also contribute to host energy production, reactive oxygen species (ROS) modulation, and inflammatory balance. Conversely, mitochondria, particularly mitochondrial ROS production, regulate the gut microbiota via modulating intestinal barrier function and mucosal immune responses.

• Infection (chronic and acute)

• Toxicity (environmental, foodborne and/or endogenous)

• Tissue Injury

• Excessive exercise

• Carbohydrate and caloric excess

• Stress

• Some medications

Our understanding of the spectrum of ROS levels throughout the lifespan and in various disease states is only beginning to unravel the complexity of interactions. Low levels of ROS are necessary for healthy cellular

https://www.frontiersin.org/articles/10.3389/fphys.2017.00319/full

What are some causes of elevated ROS?

• Dysbiosis (overproduction of inflammatory mediators)

function and even signal mitochondria to initiate a cascade of events that ultimately protects the cell from further damage by those same ROS (mitohormesis). Moderate

ROS levels may benefit younger animals in natural settings but may harm aging animals in a non-stressful laboratory or sanitized environment. Excess ROS is damaging, even if needed for acute circumstances such as injury and infection. Human intestinal diseases and aging result in an increase in ROS levels, and higher levels have been shown to decrease

towards OXPHOS, which generates high oxygen consumption and maintains the hypoxic environment in the intestinal lumen, in turn helping to maintain the intestinal microbial community dominated by obligate anaerobes.2

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9623293/

the diversity of microbes in the gut. With regards to microbial metabolites that influence host function, in addition to affecting mitochondria, recent studies have highlighted the importance of three key microbiome metabolites: (i) SCFAs, (ii) the urolithins, and (iii) lactate.

SCFAs are important signaling molecules for intestinal epithelial cells. SCFAs regulate PGC1α, a master regulator of mitochondrial biogenesis. These responses to SCFAs result at the organelle level in increased glucose uptake, fatty acid oxidation (FAO), oxidative phosphorylation (OXPHOS), and mitochondrial biogenesis. Studies have shown that the metabolism of colonic epithelial cells is biased

Both urolithin A and butyrate have been shown to enhance microbial diversity and promote the abundance of bacteria that generate these compounds. Meanwhile, lactic acid produced by lactobacilli and bifidobacteria (and possibly mitochondria) supports the production of butyrate from SCFA-producing microbes (e.g., clostridia), accompanied by the production of ATP.5

Regarding intestinal homeostasis, these responses to SCFAs in colon epithelial cells facilitate the development of a tolerant mucosal immune system, promote epithelial barrier integrity, promote “physiologic hypoxia,” and suppress colitis. SCFAs also mediate the steady-state NLRP3 inflammasome by dampening overt inflammatory responses through modulation of IL-18.6

Dysbiosis plays a potentially critical role in the activity of mitochondria. When the gut microbiota becomes disordered, it can affect the mitochondrial metabolic pathway in intestinal epithelial cells and destroy intestinal homeostasis.2 Dysbiosis is linked with reduced microbial diversity, a thinner protective mucus, decreased antimicrobial defense, diminished fatty acid production, and reduced ATP. Mitochondrial dysfunction will impair the ability of the intestinal stem cells (ISCs) to produce ATP, leading to altered ISC selfrenewal and differentiation, which drives a loss in barrier integrity and subsequent bacterial invasion of the underlying intestinal tissue.6

Furthermore, pathogenic bacteria produce toxins that directly damage the mitochondria of the intestinal epithelial cells, initiating membrane hyperpolarization, apoptosis, and subsequent impairment of epithelial barrier function.6 Impaired mitochondrial function is a defining mechanism contributing to gut epithelial barrier disruption in chronic degenerative diseases of the gastrointestinal tract, including inflammatory bowel diseases and colorectal cancer.7

At the same time, mitochondrial dysfunction can increase the oxygenation of colonic epithelial cells, which can cause changes in the oxygen environment of the intestinal cavity, changing the communities of the gut microbiota and ultimately leading to the growth of opportunistic and pathogenic organisms.2

Additionally, dysfunctional mitochondria are emerging as key activators of the NLRP3 inflammasome, which can lead to ongoing inflammation both locally in the GI tract and systemically.6 Perturbed enterocyte mitochondrial function is believed to initiate inflammation and relapses in inflammatory bowel disease.

Risk Factors Affecting the Microbiome-Mitochondria

Pharmaceutical medications, in addition to environmental chemicals, negatively impact the microbiota and mitochondria, leading to possible dysbiosis and mitochondrial dysfunction.

• Antibiotics (particularly quinolones, aminoglycosides, beta-lactams)

• Proton-pump inhibitors

• NSAIDs

• Pesticides

• Heavy metals

Restoring the Microbiome to Benefit Mitochondria

Addressing the microbiome offers a novel therapeutic approach to support improved mitochondrial dynamics. Botanicals offer a welltolerated and effective approach to balancing the microbiome. The immune activity and antimicrobial constituents of plants can be called upon - and have been shown to retain beneficials while selectively addressing opportunistic and/ or pathogenic microbes. A bonus is that each plant contains multiple mechanisms of action that support host health, such as antioxidant capacity, immune modulation, biofilm disruption, and more. Targeted supplementation to support microbial balance with botanicals may ultimately benefit mitochondrial function.

Clinical Pearl #1 - Include Prebiotics

Encourage consumption of fiber, prebiotics, and resistant starches to increase the production of SCFAs – the main products of fermentation by gut microbiota. This can help optimize microbial diversity and support mitochondrial function.

Clinical Pearl #2 - Don’t Forget the Mouth

Mitochondrial dysfunction has been positively correlated to aggravated periodontitis in diabetes and might represent a therapeutic target for diabetic periodontitis. Include a basic oral exam and questionnaire as part of your physical exam, and address oral dysbiosis.

Therapeutic and Lifestyle Recommendations

• Utilize the power of botanicalsAntimicrobial herbs modify the gut microbiome to bring about a healthy balance and support digestive function

º Bilberry, Grape Seed, Shiitake, Goldenseal, Noni, Garlic, White Willow, Milk Thistle, Raspberry, Echinacea purpurea, Echinacea angustifolia, Black Walnut, Lavender Oil, Oregano Oil, Galbanum Oil, Tea Tree Oil, Fumitory, Gentian

• Nutritional supplementation known to optimize mitochondrial function and improve energy production and cellular dynamics.

º N-acetyl cysteine, Acetyl-L-Carnitine, R-Alpha Lipoic Acid, Ribose, Coenzyme Q10, Nicotinamide Riboside, B-complex, Resveratrol

• Adopt a low-inflammation diet (Modified Paleo, Mediterranean, etc.), including a high intake of non-starchy vegetables. Be sure to include prebiotic-rich foods.

• Daily movement and exercise support healthy gastrointestinal function, support healthy microbial diversity, and improve mitochondrial biogenesis and function.

• Stress reduction techniques and activities such as deep breathing, meditation, journaling, walking, time spent in nature, massage, and others can help to lower

inflammation, improve mitochondrial function, and modify the gut microbiome.

Exploring Protective E ects Of Telomerase Activator TA-65 On Mice With SAR Induced By Cigarette Smoke

Cigarette smoking is the single greatest risk factor in industrialized countries for the development of chronic obstructive pulmonary disease (COPD), and COPD is the most frequent chronic respiratory disease and a major threat to public health, especially among older adults.1 Not only the prevalence but the morbidity increases with age – with most (86%) COPD deaths occurring among individuals aged 65 and over.2

In the U.S., almost 4.5 million adults aged 60 and above continue to smoke. More importantly, they account for 70 percent of all smoking-related deaths. The use of tobacco is the leading cause of preventable disease, disability, and death.3 So with the highest risk of COPD coupled with the highest rates of death related to cigarette smoking,

older adults face inordinate increases in risk and morbidity related to COPD.

Characterized by a progressive decline in lung function, COPD is an obstructive lung disease primarily associated with small airway remodeling (SAR) and emphysema. While emphysema is defined by the loss of alveolar walls and subsequent enlargement of alveolar spaces, SAR occurs in small airways without cartilage and results in an increased thickness of airway walls. SAR tends to occur early in the course of COPD and actually exceeds emphysema in its contribution to airflow limitation.1

Interrupting the development of SAR could potentially be a game changer in reducing COPD morbidity. SAR is characterized by a

On Mice With SAR Induced By Cigarette Smoke

variable combination of peribronchiolar fibrosis with increased fibrous tissue and mesenchymal and inflammatory cell accumulation in the walls of membranous and respiratory bronchioles. While the pathogenesis of SAR remains unclear, recent data suggests that altering telomerase activity could represent a possible underlying mechanism of SAR.1

A recent study conducted by Tiendrébéogo, A.J.F., Soumagne, T., Pellegrin, F. et al. at Université Paris Est-Créteil examined the potential protective role of TA-65, a pharmacological telomerase activator, in a cigarette smoke (CS) model of SAR in mice – while also investigating extra-telomeric effects of telomerase, involving oxidative stress modulation.

Telomerase Activation and Its Importance in Addressing SAR in COPD

Studies that explore the pathogenesis of SAR in COPD are uncommon - especially compared to those related to the pathogenesis of emphysema. According to the few studies available, it seems cytokines, chemokines and/ or receptors such as Interleukin-1β, growth factors, Tumor Necrosis Factor Receptor I and II, as well as proteases/antiproteases and oxidants/antioxidants imbalance play a role in cigarette smoke (CS)-induced SAR.4-9

Recent studies indicate premature aging could be a possible mechanism underlying SAR pathogenesis.10-12 Pharmacological activators of telomerase activity - as they may counteract the progressive shortening of telomeres that characterizes premature aging - are considered an interesting approach for treatment of premature aging-related diseases like COPD.11,13

In recent years, telomere length has been recognized as one of the best biomarkers of an organism’s biological age as well as

aging-related pathological conditions.14 Other than genetics, no other factor has a bigger impact on telomere length than aging. Its attractiveness as a biomarker of aging includes, among others, its predictive power for susceptibility to disease and mortality.15

Their ability to enhance extra-telomeric functions may explain the benefits of telomerase activators on SAR. The noncanonical functions of telomerase, that are non-obligatory extra-telomeric, could influence essential cellular processes – including mitochondrial function, gene expression, stress resistance, cell survival, and signaling pathways.16

Developing the Study

Tiendrébéogo, A.J.F. and colleagues developed the study to identify a potential protective role of TA-65, a pharmacological telomerase activator, in a cigarette smoke (CS) model of SAR in mice. They also attempted to confirm whether if extra-telomeric effects of telomerase (involving oxidative stress modulation) could explain why TA-65 exerted a protective role.1

Mice were exposed daily to air or cigarette smoke during four weeks with or without a concomitant administration of TA-65 for seven days before exposure to the cigarette smoke.1

Morphological analyses were conducted. Mucus production, myofibroblast differentiation, collagen deposition and transforming growth factor-β1 (TGF-β1) expression in the small airway walls were examined. The effects of TA-65 treatment on TGF-β expression, fibroblastto-myofibroblast differentiation, reactive oxygen species (ROS) production and catalase expression and activity were evaluated in primary cultures of pulmonary fibroblasts and/ or mouse embryonic fibroblasts in vitro.1

Results

It was clear that exposure to the cigarette smoke during the four-week study did indeed induce SAR in mice. This was characterized by small airway walls thickening and peribronchiolar fibrosis (increased deposition of collagen, expression of α-SMA in small airway walls), without mucus overproduction. The study’s findings demonstrate that telomerase plays a critical role in SAR, probably through extra-telomeric anti-oxidant effects, and therefore providing new insights in the understanding and treatment of COPD.1

It was also determined that treatment of mice with TA-65 protected them from SAR induced by cigarette smoke. This effect was associated with the prevention of CS-induced TGF-β expression in vivo, the blockade of TGF-β-induced myofibroblast differentiation, and the reduction of TGF-β-induced ROS production that correlates with an increase of catalase expression and activity.1

Source: https://www.nature.com/articles/s41598-022-25993-7

Exploring Protective Effects Of Telomerase Activator TA-65

On Mice With SAR Induced By Cigarette Smoke

References:

1. Tiendrébéogo, A.J.F., Soumagne, T., Pellegrin, F. et al. The telomerase activator TA-65 protects from cigarette smokeinduced small airway remodeling in mice through extra-telomeric effects. Sci Rep 13, 25 (2023). https://doi.org/10.1038/s41598-02225993-7

2. COPD Trends Brief: Mortality. American Lung Association. Accessed February 16, 2023. https://www.lung.org/research/ trends-in-lung-disease/copd-trends-brief/copd-mortality

3. Tobacco prevention and control: Older Adults, Behavioral Health and Smoking: Why Quitting Smoking is Still a Conversation Worth Having. National Behavioral Health Network for Tobacco & Cancer Control. Updated July 19, 2019. Accessed February 16, 2023. https://www.bhthechange.org/resources/older-adultsbehavioral-health-and-smoking-why-quitting-smoking-is-still-aconversation-worth-having/

4. Churg, A., Tai, H., Coulthard, T., Wang, R. & Wright, J. L. Cigarette smoke drives small airway remodeling by induction of growth factors in the airway wall. Am. J. Respir. Crit. Care Med. 174(12), 1327–1334 (2006).

5. Churg, A., Dai, J., Tai, H., Xie, C. & Wright, J. L. Tumor necrosis factoralpha is central to acute cigarette smoke-induced inflammation and connective tissue breakdown. Am. J. Respir. Crit. Care Med. 166(6), 849–854 (2002).

6. Churg, A. et al. Effect of an MMP-9/MMP-12 inhibitor on smoke-induced emphysema and airway remodelling in guinea pigs. Thorax 62(8), 706–713 (2007).

7. Churg, A., Zhou, S., Wang, X., Wang, R. & Wright, J. L. The role of interleukin-1beta in murine cigarette smoke-induced emphysema and small airway remodeling. Am. J. Respir. Cell Mol. Biol. 40(4), 482–490 (2009).

Author Bio:

Ron

760-635-1996

ronrothenbergmd@gmail.com

8. Wang, R. D., Wright, J. L. & Churg, A. Transforming growth factorbeta1 drives airway remodeling in cigarette smoke-exposed tracheal explants. Am. J. Respir. Cell Mol. Biol. 33(4), 387–393 (2005).

9. Churg, A. et al. Late intervention with a myeloperoxidase inhibitor stops progression of experimental chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 185(1), 34–43 (2012).

10. Armanios, M. Telomerase and idiopathic pulmonary fibrosis. Mutat. Res. Mol. Mech. Mutagen 730(1), 52–58 (2012).

11. Chilosi, M., Carloni, A., Rossi, A. & Poletti, V. Premature lung aging and cellular senescence in the pathogenesis of idiopathic pulmonary fibrosis and COPD/emphysema. Transl. Res. 162(3), 156–173 (2013).

12. Gansner, J. M. & Rosas, I. O. Telomeres in lung disease. Transl. Res. 162(6), 343–352 (2013).

13. Le Saux, C. J. et al. A novel telomerase activator suppresses lung damage in a murine model of idiopathic pulmonary fibrosis. PLoS ONE 8(3), e58423 (2013).

14. Vaiserman A, Krasnienkov D. Telomere Length as a Marker of Biological Age: State-of-the-Art, Open Issues, and Future Perspectives. Frontiers in Genetics. 2021;11. doi:10.3389/ fgene.2020.63018

15. Hastings WJ, Shalev I, Belsky DW. Translating Measures of Biological Aging to Test Effectiveness of Geroprotective Interventions: What Can We Learn from Research on Telomeres?. Front Genet. 2017;8:164. Published 2017 Nov 22. doi:10.3389/ fgene.2017.00164

16. Ségal-Bendirdjian, E. & Geli, V. Non-canonical roles of telomerase: Unraveling the Imbroglio. Front. Cell Dev. Biol. 7, 332 (2019).

Among the first 10 physicians recognized by the American Board of Anti-Aging and Regenerative Medicine, Dr. Ron Rothenberg has always forged new paradigms in medicine. After Columbia University College of Physicians and Surgeons he practiced medicine and studied indigenous healing in the Amazon Basin. He did his Emergency Medicine residency at LA County-USC Medical Center then founded the Postgraduate Institute for Primary & Emergency Physicians at UC San Diego’s medical school and was a former professor of clinical preventive medicine. He lectures worldwide and has educated 25,000+ physicians with his continuing ed seminars. He is currently medical director of California HealthSpan Institute located on the campus of Scripps Memorial Hospital, Encinitas.

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Aging Gracefully: The Power of Glutathione and Nicotinamide Adenine Dinucleotide in Anti-Aging Medicine

Introduction

Nicotinamide adenine dinucleotide (NAD+) and glutathione (GSH) are two important molecules that play a crucial role in anti-aging medicine. NAD+ is a coenzyme involved in energy metabolism, DNA repair, and regulation of gene expression. It helps to maintain the activity of sirtuins, proteins that play a role in regulating aging and longevity. GSH is a tripeptide that acts as a potent antioxidant and detoxifying agent (1). Both NAD+ and GSH levels decline with age, which is thought to contribute to the aging process. NAD+ and GSH supplementation have been shown to improve cellular metabolism, reduce oxidative stress, and promote longevity in animal models.

Nicotinamide adenine dinucleotide (NAD+)

Nicotinamide adenine dinucleotide (NAD+) is a vital coenzyme that occupies a central position in energy metabolism and many cellular processes, such as metabolic pathways, DNA repair, chromatin remodeling, immune cell function, and cellular senescence. NAD+ is found in all eukaryotic cells, where it plays a crucial role in redox reactions and serves as a cofactor for non-redox NAD+-dependent enzymes including sirtuins, CD38, and poly(ADP-ribose) polymerases. NAD+ is synthesized from a variety of precursors, including niacin, nicotinamide (NAM), nicotinic acid (NA), tryptophan (Trp), nicotinamide riboside (NR), and nicotinamide mononucleotide (NMN). Niacin, also known as vitamin B3, can be obtained from dietary

sources

such as eggs, fish, meat, dairy, vegetables, and whole grains (2-5).

Clinical Uses

The efficacy of NAD+ supplementation has been investigated through numerous clinical trials, which have yielded promising results in mitigating symptoms associated with an extensive array of medical conditions. These include, acute kidney injury, Alzheimer's disease, chronic fatigue syndrome, dementia, heart disease, hypertension, obesity, Parkinson's disease, skin aging, and various forms of diabetes. For instance, the results of the European Nicotinamide Diabetes Intervention Trial demonstrated the efficacy of daily nicotinamide supplementation in retarding the progression to type 1 diabetes. On the other hand, a clinical trial evaluating the effect of oral and infused NADH in Parkinson's disease patients revealed a positive outcome in 80% of the patients. NAD+ also plays a crucial role in DNA repair as a cofactor for PARP enzymes and has been proposed to provide protection against photoaging-induced precancerous skin lesions and other adverse effects (6-9).

Anti-aging rationale

In addition to its potential therapeutic applications, NAD+ has been extensively studied for its impact on aging and has been referred to as a "Fountain of Youth elixir." Research has established the decline of NAD+ levels with age and demonstrated that restoring NAD+ levels could have anti-aging effects (26-29). The gradual decline with aging of NAD+ and its precursors has been extensively documented. As individuals age, an increased accumulation of DNA damage leads to an increased utilization of NAD+, resulting in a downregulation of NAD+ overall as the body attempts to combat comorbidities that are inherent with aging. This redirection of NAD+ causes a gradual degradation of cellular energy pathways, which ultimately reaches

the minimum level to maintain homeostasis. Supplementation with NAD+ or its precursors can aid the body in repairing the damages of aging and combating comorbidities when combined with diet, and exercise(10-14).

Glutathione

Glutathione is a crucial antioxidant synthesized within the human body. It is a tripeptide of cysteine, glycine, and glutamic acid that is found in every cell. Glutathione performs multiple essential functions in the body, including its role as a powerful antioxidant and as a thiol buffer. These tripeptides are then reabsorbed by cells and reassembled into glutathione (15,16).

Glutathione is synthesized de novo in the cytosol, then actively transported into the mitochondria. It is made available to cells through three mechanisms: de novo enzymatic synthesis, regeneration of oxidized GSSG by glutathione reductase, and recycling of cysteine from conjugated glutathione. Glutathione also acts as a catalyst for glutathione S-transferases and glutathione peroxidases, playing a key role in the elimination of toxic molecules and reactive peroxides.Glutathione is involved in several other essential cellular reactions, including regulation of gene expression and protein synthesis, reduction of DNA and RNA nucleotides, and exchange reactions. The ratio of reduced glutathione to glutathione disulfide is critical for cell survival and tightly regulated (25,29).

Clinical Uses

Deficiencies of this vital antioxidant have been observed in individuals with various health conditions such as asthma, viral infections, psoriasis, Parkinson's disease, and multiple sclerosis. Oxidative damage has been linked to various pathologies, including cancer, neurodegenerative disorders, cystic fibrosis, HIV, and aging. (17,31).

Glutathione can be administered via various routes including oral, transdermal, rectal, or injection. It is broken down into its three amino acid components by peptidases in the bloodstream. A clinical study involving healthy volunteers who took oral glutathione at a dose of 500 mg twice daily for 4 weeks, showed no significant adverse effects. However, there were reported side effects such as increased flatulence, loose stools, flushing, and weight gain (28).

A small-scale clinical study (N=21) found that administering IV glutathione at a dose of 1,400 mg three times per week for four weeks was generally well-tolerated. However, a separate case report linked the use of IV glutathione at a daily dose of 1,200 mg (for a total of 36,000 mg in one month) to a severe, but reversible, liver injury (18).

In patients with mild asthma, nebulized glutathione led to bronchial hyperreactivity, coughing, and difficulty breathing. This may have been due to the formation of sulfites or lack of buffering (18).

Given the crucial role of glutathione in health, many scientists have sought ways to enhance its intracellular and intramitochondrial levels. Fortunately, there are several effective methods to do so. Some methods aim to reduce the body's need for glutathione, which can be achieved by decreasing exposure to harmful substances, such as reducing alcohol intake. Another approach is to supplement with other antioxidants to combat oxidative stress (19).

Other approaches aim to directly increase glutathione levels through various administration routes, including oral, topical, intravenous, intranasal, and nebulized forms. These delivery methods have been shown to increase systemic glutathione levels, particularly when delivered intravenously, inhaled, or intranasally. Although IV glutathione has a short half-life, it has

demonstrated short-term effectiveness in various medical conditions (24, 31).

Both direct administration and stimulation of glutathione production have demonstrated efficacy in a diverse array of pathological conditions, including but not limited to Parkinson's disease, peripheral obstructive arterial disease, cystic fibrosis, emphysema, COPD, autism in preterm infants, contrastinduced nephropathy, chronic otitis media, lead exposure, nail biting, nonalcoholic fatty liver disease, and exercise-induced fatigue.

Anti-aging rationale

Recently glutathione has gained attention for its potential anti-aging effects as a key antioxidant that helps protect cells from free radical damage. It exists in two forms, reduced (GSH) and oxidized (GSSG), and the GSH/GSSG ratio determines the redox status of cells. Healthy cells have a ratio greater than 100. The ratio drops to between 1 and 10 in cells exposed to oxidant stress. Studies suggest that glutathione levels decline with age, and this reduction may contribute to various age-related conditions including cognitive decline, immune dysfunction, and skin aging. Some research has indicated that glutathione supplementation can enhance the body's antioxidant defenses and potentially slow the aging process, although further studies are necessary to confirm its effectiveness (33).

Drug Interactions

The potential for drug interactions and side effects of glutathione and NAD+ supplementation have been investigated in several clinical studies. Oral supplementation of glutathione can interact with certain drugs such as warfarin, causing an increased risk of bleeding. This results in a pharmacodynamic effect where the correlation between glutathione depletion causes an increase in N-acetyl-p-benzoquinoneimine (NAPQI), which can interfere with the vitamin K cycle (36). Also, it is important to

note that high doses of Acetaminophen have been shown to cause glutathione depletion, primarily in the liver (34). Moreover, it can also interact with certain chemotherapy drugs and reduce their efficacy (35).

Oral supplementation of NAD+ precursors such as nicotinamide riboside (NR) has been well tolerated in clinical trials, but the longterm safety and potential side effects of NR and NAD+ supplementation remain unknown (35).

It is also important to note that individuals with certain medical conditions should consult with a healthcare professional before taking glutathione or NAD+ supplements. For example, individuals with liver or kidney problems should avoid taking glutathione supplements as it may worsen their condition due to not being able to excrete the drug (34).

Little information exists regarding the safety and efficacy of NAD+ and glutathione during pregnancy and lactation.

NAD+ and Glutathione Clinical Practices

The human body relies on various essential metabolic processes, which are supported by cofactors such as NAD+ (Nicotinamide adenine dinucleotide) and glutathione. NAD+ plays a vital role in energy metabolism, serving as a coenzyme in the transfer of electrons in the mitochondrial electron transport chain. Glutathione, on the other hand, is a tripeptide that acts as a cellular antioxidant and detoxifying agent, shielding cells from oxidative stress and toxicity.

Due to the critical functions of NAD+ and Glutathione, there is growing interest in the use of supplements to augment their levels in specific patient populations. This includes:

Older adults: With aging, NAD+ levels naturally decline, resulting in decreased energy metabolism and increased risk of age-

related diseases. Supplementation with NAD+ precursors has been demonstrated to increase NAD+ levels and enhance energy metabolism in both aging animals and humans (14).

Patients with chronic fatigue syndrome: Chronic fatigue syndrome is a complex condition that is characterized by persistent fatigue and weakness, among other symptoms. NAD+ supplementation has been demonstrated to improve energy metabolism and reduce fatigue in some patients with chronic fatigue syndrome (32).

Cancer patients: Cancer treatments, including chemotherapy and radiation therapy, can induce oxidative stress and damage cells, leading to cellular dysfunction and associated side effects such as fatigue and immunosuppression. Glutathione supplementation has been demonstrated to reduce oxidative stress, protect cells from damage, and improve cellular function in some cancer patients (23).

Patients with liver disease: The liver is critical in the detoxification process, including drugs and environmental toxins. Glutathione is a key component of the liver's detoxifying system, and its levels can be reduced in liver disease, leading to increased toxicity and cellular damage. Glutathione supplementation has been demonstrated to improve liver function and reduce toxicity in some patients with liver disease (27).

It is important to note that the use of NAD+ and glutathione supplements should be guided by a healthcare professional and should be based on an individual's specific needs and health status.

Conclusion:

Nicotinamide adenine dinucleotide (NAD+) and glutathione (GSH) are important molecules that play critical roles in cellular metabolism, redox homeostasis, and cellular defense mechanisms. Growing evidence from peer-

reviewed studies and clinical trials suggests that NAD+ and GSH supplementation can have beneficial effects on a wide range of diseases and comorbidities, including aging, cardiovascular disease, neurodegenerative diseases, cancer, liver disease, and oxidative stress-related disorders. More research is needed to fully understand

Resources:

1. Cantó C, Menzies KJ, Auwerx J. NAD(+) Metabolism and the Control of Energy Homeostasis: A Balancing Act between Mitochondria and the Nucleus. Cell Metab. 2015;22(1):31-53. doi:10.1016/j. cmet.2015.05.023

2. Wallace DC. Mitochondria and cancer. Nat Rev Cancer. 2012;12(10):685-698. doi:10.1038/nrc3365

3. Fang EF, Lautrup S, Hou Y, et al. NAD+ in Aging: Molecular Mechanisms and Translational Implications. Trends Mol Med. 2017;23(10):899-916. doi:10.1016/j.molmed.2017.08.001

4. Bieganowski P, Brenner C. Discoveries of nicotinamide riboside as a nutrient and conserved NRK genes establish a PreissHandler independent route to NAD+ in fungi and humans. Cell. 2004;117(4):495-502. doi:10.1016/s0092-8674(04)00416-7

5. Yang H, Yang T, Baur JA, et al. Nutrient-sensitive mitochondrial NAD+ levels dictate cell survival. Cell. 2007;130(6):1095-1107. doi:10.1016/j.cell.2007.07.035

6. Birkmayer, J.G.; Vrecko, C.; Volc, D.; Birkmayer, W. Nicotinamide adenine dinucleotide (NADH)—A new therapeutic approach to Parkinson’s disease. Comparison of oral and parenteral application. Acta Neurol. Scand. 1993, 146, 32–35

7. Radenkovic D, Reason, Verdin E. Clinical Evidence for Targeting NAD Therapeutically. Pharmaceuticals. 2020; 13(9):247. https://doi. org/10.3390/ph13090247

8. The effects of nicotinamide adenine dinucleotide in cardiovascular diseases: Molecular mechanisms, roles and therapeutic potential, Genes & Diseases, Volume 9, Issue 4, 2022, Pages 959-972, ISSN 2352-3042, https://doi.org/10.1016/j.gendis.2021.04.001. (https:// www.sciencedirect.com/science/article/pii/S2352304221000556)

9. Gale, E.A. European Nicotinamide Diabetes Intervention Trial (ENDIT): A randomised controlled trial of intervention before the onset of type 1 diabetes. Lancet 2004, 363, 925–931

10. Gomes, A. P., Price, N. L., Ling, A. J., Moslehi, J. J., Montgomery, M. K., Rajman, L., ... & Sinclair, D. A. (2013). Declining NAD+ induces a pseudohypoxic state disrupting nuclear-mitochondrial communication during aging. Cell, 155(7), 1624-1638.

11. Braidy, N., Guillemin, G. J., Mansour, H., Chan-Ling, T., Poljak, A., & Grant, R. (2011). Age related changes in NAD+ metabolism oxidative stress and Sirt1 activity in wistar rats. PloS one, 6(4), e19194.

12. Massudi, H., Grant, R., Braidy, N., Guest, J., Farnsworth, B., & Guillemin, G. J. (2012). Age-associated changes in oxidative stress and NAD+ metabolism in human tissue.

13. Shade C. The Science Behind NMN-A Stable, Reliable NAD+Activator and Anti-Aging Molecule. Integr Med (Encinitas). 2020;19(1):12-14.

the mechanisms of action and the optimal dosing and administration regimens for NAD+ and GSH in the treatment of these conditions. Nevertheless, the current evidence supports the potential of NAD+ and GSH as promising candidates for the development of novel antiaging and disease-modifying treatments.

14. Johnson S, Imai SI. NAD + biosynthesis, aging, and disease. F1000Res. 2018;7:132. Published 2018 Feb 1. doi:10.12688/ f1000research.12120.1

15. Smeyne M, Smeyne RJ. Glutathione metabolism and Parkinson's disease. Free Radic Biol Med. 2013;62:13-25.[PubMed 23665395]

16. Wu G, Fang YZ, Yang S, Lupton JR, Turner ND. Glutathione metabolism and its implications for health. J Nutr. 2004 Mar;134(3):489-92. doi: 10.1093/jn/134.3.489. PMID: 14988435.

17. Hauser RA, Lyons KE, McClain T, Carter S, Perlmutter D. Randomized, double-blind, pilot evaluation of intravenous glutathione in Parkinson's disease. Mov Disord. 2009;24(7):979983.[PubMed 19230029]

18. Reynaert NL. Glutathione biochemistry in asthma. Biochim Biophys Acta. 2011;1810(11):1045-1051.[PubMed 21281701]

19. Rae CD, Williams SR. Glutathione in the human brain: review of its roles and measurement by magnetic resonance spectroscopy. Anal Biochem. 2017;529:127-143.[PubMed 28034792]

20. Naito Y, Matsuo K, Kokubo Y, Narita Y, Tomimoto H. Higher-dose glutathione therapy for Parkinson's disease in Japan: is it really safe? Mov Disord. 2010;25(7):962.[PubMed 20131395]

21. Ballatori N, Krance SM, Notenboom S, Shi S, Tieu K, Hammond CL. Glutathione dysregulation and the etiology and progression of human diseases. Biol Chem. 2009;390(3):191-214.[PubMed 19166318]

22. Perricone C, De Carolis C, Perricone R. Glutathione: a key player in autoimmunity. Autoimmun Rev. 2009;8(8):697-701.[PubMed 19393193]

23. Balendiran GK, Dabur R, Fraser D. The role of glutathione in cancer. Cell Biochem Funct. 2004;22(6):343-352.[PubMed 15386533]

24. Anderson, M.E., Glutathione Injections: an overview of biosynthesis and modulation. Chem Biol Interact, 1998. 111-112: p. 1-14.

25. P., M. and C. G.P., Glutathione reductase: regulation and role in oxidative stress, in Oxidative stress and the molecular biology of antioxidant defenses. 1997, Cold Spring Harbor Laboratory Press

26. Lu, Shelly C. “REGULATION OF Glutathione SYNTHESIS.” Molecular aspects of medicine 30.1-2 (2009): 42–59. PMC. Web. 2 Oct. 2017.

27. Biswas SK, Rahman I. Environmental toxicity, redox signaling and lung inflammation: the role of glutathione. Mol Aspects Med. 2009;30(1–2):60–76. [PMC free article] [PubMed] [Google Scholar] [Ref list]

28. Allen J, Bradley RD. Effects of oral glutathione supplementation on systemic oxidative stress biomarkers in human volunteers. J

Aging Gracefully: The Power of Glutathione and Nicotinamide Adenine Dinucleotide in Anti-Aging Medicine

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29. Wu G, Fang YZ, Yang S, Lupton JR, Turner ND. Glutathione metabolism and its implications for health. J Nutr. 2004;134(3):489492. doi:10.1093/jn/134.3.489

30. Wozniacka, A.; Szajerski, P.; Adamus, J.; Gebicki, J.; SysaJedrzejowska, A. In Search for New Antipsoriatic Agents: NAD+ Topical Composition. SPP 2007, 20, 37–4

31. Pizzorno J. Glutathione!. Integr Med (Encinitas). 2014;13(1):8-12.

32. Zhu, X. H., Lu, M., Lee, B. Y., Ugurbil, K., & Chen, W. (2015). In vivo NAD assay reveals the intracellular NAD contents and redox state in healthy human brain and their age dependences. Proceedings of the National Academy of Sciences, 112(9), 2876-2881.

Author Bios:

Jonathan Ramnauth, PharmD, RPh

Jonathan.R@olympiapharmacy.com

33. Weschawalit S, Thongthip S, Phutrakool P, Asawanonda P. Glutathione and its antiaging and antimelanogenic effects. Clin Cosmet Investig Dermatol. 2017;10:147-153. Published 2017 Apr 27. doi:10.2147/CCID.S128339

34. Baker, E., Allison, R., Baker, H., Naumann, C., & Ismail, A. (2002). Interactions between oral glutathione and anticoagulants. Journal of Clinical Pharmacy and Therapeutics, 27(5), 375-378.

35. Broughton, K. S., Green, C. J., Phillips, S. A., & Cairns, M. J. (2019). The use of NAD+ precursors in anti-aging and age-related disease: a review of the current literature. European Journal of Clinical Nutrition, 73(10), 1211-1217.

36. Leong D, Wu PE. Warfarin and acetaminophen interaction in a 47-year-old woman. CMAJ. 2020;192(19):E506-E508. doi:10.1503/ cmaj.191532 2018;24(18):1947–1956.

Dr. Ramnauth is a highly qualified pharmacist, holding the ASHP Certified Sterile Compounding Pharmacy designation. He earned his Doctor of Pharmacy degree from the University of Florida in 2018 and has since developed a strong interest in both sterile and nonsterile compounding. Presently, he is employed at Olympia Pharmaceuticals, where he serves as a clinical representative for intravenous sterile compounding

Charmaine Saratan, PharmD, RPh

Charmaine@olympiapharmacy.com

Dr. Saratan obtained a Bachelor's degree in Pharmacy from the esteemed University of the Philippines, following which she graduated Magna cum Laude with a Doctor of Pharmacy degree from Centro Escolar University. She holds licenses in several states and has developed a keen interest in the intricacies of sterile and non-sterile compounding. Presently, Dr. Saratan holds the position of Pharmacist Supervisor for nonsterile compounding at Olympia Pharmaceuticals, where she is also serving as the consultant for hormone replacement therapy.

One-Size-Fits-All Prescribing No Longer Fits

It’s important to assess hormone levels with reliable and convenient testing methods to ensure physiologic levels.

What’s the best way to manage dosages and symptoms in patients considering BHRT?

Prescribing without testing, going by symptoms alone or using the wrong lab tests can lead to overdosing.

While regular serum labs may be used to monitor some supplementation methods, saliva and blood spot testing more closely reflect tissue levels of estradiol and progesterone in women, and testosterone in men, for patients who are using topical hormone creams. Follow-up testing and regular monitoring allows the dose to be adjusted as needed.

The Endothelial Glycocalyx: A Critical Link

to Endothelial Function

It is now widely recognized that the vascular endothelial surface is coated with a complex carbohydrate matrix known as the glycocalyx (GCX), which is critical for both the protection and function of the endothelial cell.1 First recognized after the advent of electron microscopy in the late 1960s, the endothelial GCX is mainly formed by long chains of glycosaminoglycans (GAGs) attached to proteoglycans and glycoproteins to create a protective hair-like coating on the cell surface. Proteoglycans such as syndecans and glypicans are the core proteins upon which sulfated glycosaminoglycan are attached (primarily heparan sulfate and chondroitin sulfate), whereas long chains of the nonsulfated hyaluronic acid are linked via their association with the CD44 protein. Heparan sulfate proteoglycans are the most abundant

of the GAGs expressed on the surface of the endothelial cells, accounting for 50-90% of the total endothelial proteoglycans. The synthesis, composition and turnover of the endothelial GCX is a highly regulated process; but is also greatly influenced by many of the factors that affect endothelial function.

Initially, the GCX was thought to function simply as a physical barrier for the cell. However, we now know that the endothelial GCX plays many important roles in optimizing endothelial cell functions including things like vascular permeability, mechano-transduction and monocyte transmigration from the lumen to the intima.2 As a barrier, the GCX does impede the attachment of monocytes, but it also functions as an ionized filter for important bioactive compounds, creating a unique

Overview of the modulation of glycocalyx under activated conditions. Under healthy conditions, intact endothelial glycocalyx maintains endothelium homeostasis, regulates permeability, and plays an anti-inflammatory and antithrombotic role. When activated in pathological conditions (during inflammation, diabetes, and other pathological conditions), there is increased shedding of the glycocalyx. An increased expression of adhesion molecules under inflammatory conditions is also observed. [Figure modified from Hu Z, Cano I, D'Amore PA. Update on the Role of the Endothelial Glycocalyx in Angiogenesis and Vascular Inflammation. Front Cell Dev Biol. 2021;9:734276.

microenvironment at the cell surface. The highly sulfated heparan sulfate and chondroitin sulfate molecules create a strong net negative charge within the GCX, which allows the cell to form controlled gradients of important cytokines, chemokines, cations, and cells along the membrane based on their ionic charge. The GCX can also modulate vascular permeability and hydraulic conductivity by limiting the flux of water and macromolecules at the cell surface.

As we discussed in the main text of this monograph, shear stress along the surface of the endothelial cell is able to trigger

mechanoreceptors, a process that helps activate the production of nitric oxide and maintain endothelial cell function. This process of mechano-transduction is now known to be highly dependent upon an intact endothelial GCX, as well as the syndecan glycoproteins.3,4 The syndecan family of proteoglycans also interact with cytoskeletal proteins and actin fibers to alter the shape of the cell, suggesting that the GCX plays an important role in communicating shear stress signals to several important features influencing endothelial cell integrity and function.

However, nearly all of the benefits of the endothelial GCX described above are diminished when it is damaged through a variety of insults, leaving the cell vulnerable to monocyte adhesion and permeable to oxLDL particles.5 In general, targeted degradation of the components of the GCX is driven by enzymes such as heparanase, hyaluronidase, and matrix metalloproteinases (MMPs).6,7 Not only do these enzymes remove large portions of the glycosaminoglycans and the proteins to which they are attached, the debris caused by these enzymes (which can be recognized as damage-associated molecular patterns [DAMP] molecules) can trigger inflammation when binding to nearby immune cells.8 GCX-damaging enzymes are upregulated by inflammatory cytokines, reactive oxygen species, hyperglycemia, advanced glycation end products (AGEs) and other factors that are already known to cause endothelial damage and dysfunction.9,10,11,12,13

Consequently, recent studies have investigated the endothelial glycocalyx as a therapeutic target for cardiovascular disorders.14 These studies have investigated several non-invasive biomarkers of GCX status or function, as well as explored therapies that preserve or restore GCX structure and function.15 The biomarkers most commonly cited are measures of GCX debris in serum or urine (e.g., syndecan or GAGs) or the estimation of GCX thickness using optical devices on small capillaries under the tongue. Each of these methods of predicting GCX health and cardiovascular vulnerability has limitations, especially with regard to predicting GCX health at vulnerable areas along the arteries. 16,17,18 Nonetheless, these measures may be helpful surrogate markers for testing potential therapies intended to support the endothelial GCX.

A number of different bioactive compounds have been investigated for their ability to regenerate GCX structure. These mostly include agents that have already been shown to reduce biomarkers of endothelial injury (i.e.,

inflammatory cytokines, ROS, oxidized lipids, hyperglycemia, or hypercoagulation) or provide precursors for GCX components.xv While some of these compounds are repurposed drugs (e.g., statins, metformin, TNF-a inhibitors), several studies have investigated the oral intake of GAGs such as chondroitin sulfate, hyaluronic acid, or precursor sugar molecules derived from seaweed or shellfish components (e.g., glucosamine, fucoidan, rhamnan sulfate, etc.).19,20,21 Cell-culture and animal data show great promise for this therapeutic strategy, though controlled human clinical trials have yet to definitively reveal the best strategy to employ these compounds (i.e., dose, duration, endpoint measure and patient phenotype). The discovery of the endothelial glycocalyx has added a new understanding of the complexity of endothelial function, but it also helps explain the changing vulnerabilities of endothelial cells along the vasculature. It seems reasonable to assert that where the GCX is healthy and properly regulated, the endothelial cells function properly, produce adequate NO and are less vulnerable to injury and plaque initiation. Additionally, while many of the insults which had already been identified as being harmful to endothelial cells have now also been shown to trigger the degradation of the GCX (suggesting similar therapeutic strategies). Therefore, understanding the complexity of the structure and function of the GCX has opened the door to new therapeutic options–especially those that provide precursor molecules for the GCX structure itself.

The Endothelial Glycocalyx: A Critical Link to Endothelial Function

Resources:

1. Villalba N, Baby S, Yuan SY. The Endothelial Glycocalyx as a DoubleEdged Sword in Microvascular Homeostasis and Pathogenesis. Front Cell Dev Biol. 2021;9:711003.

2. Moore KH, Murphy HA, George EM. The glycocalyx: a central regulator of vascular function. Am J Physiol Regul Integr Comp Physiol. 2021;320(4):R508-R518.

3. Jiang XZ, Luo KH, Ventikos Y. Principal mode of Syndecan-4 mechanotransduction for the endothelial glycocalyx is a scissor-like dimer motion. Acta Physiol (Oxf). 2020;228(3):e13376.

4. Zeng Y. Endothelial glycocalyx as a critical signalling platform integrating the extracellular haemodynamic forces and chemical signalling. J Cell Mol Med. 2017;21(8):1457-1462.

5. Patterson EK, Cepinskas G, Fraser DD. Endothelial Glycocalyx Degradation in Critical Illness and Injury. Front Med (Lausanne). 2022;9:898592.

6. Masola V, Zaza G, Arduini A, Onisto M, Gambaro G. Endothelial Glycocalyx as a Regulator of Fibrotic Processes. Int J Mol Sci. 2021;22(6):2996.

7. Masola V, Greco N, Gambaro G, Franchi M, Onisto M. Heparanase as active player in endothelial glycocalyx remodeling. Matrix Biol Plus. 2021;13:100097.

8. Stahl K, Hillebrand UC, Kiyan Y, et al. Effects of therapeutic plasma exchange on the endothelial glycocalyx in septic shock. Intensive Care Med Exp. 2021;9(1):57.

9. Uchimido R, Schmidt EP, Shapiro NI. The glycocalyx: a novel diagnostic and therapeutic target in sepsis. Crit Care. 2019;23(1):16. Published 2019 Jan 17.

10. Sieve I, Münster-Kühnel AK, Hilfiker-Kleiner D. Regulation and function of endothelial glycocalyx layer in vascular diseases. Vascul Pharmacol. 2018;100:26-33.

11. Pesonen E, Passov A, Andersson S, et al. Glycocalyx Degradation and Inflammation in Cardiac Surgery. J Cardiothorac Vasc Anesth. 2019;33(2):341-345.

12. Targosz-Korecka M, Malek-Zietek KE, Kloska D, et al. Metformin attenuates adhesion between cancer and endothelial cells in chronic hyperglycemia by recovery of the endothelial glycocalyx barrier. Biochim Biophys Acta Gen Subj. 2020;1864(4):129533.

13. Qu J, Cheng Y, Wu W, Yuan L, Liu X. Glycocalyx Impairment in Vascular Disease: Focus on Inflammation. Front Cell Dev Biol. 2021;9:730621.

14. Milusev A, Rieben R, Sorvillo N. The Endothelial Glycocalyx: A Possible Therapeutic Target in Cardiovascular Disorders. Front Cardiovasc Med. 2022;9:897087.

15. Banerjee s, Mwangi JG, Stanley TK, et al. Regeneration and Assessment of the Endothelial Glycocalyx to Address Cardiovascular Disease. Industrial & Engineering Chemistry Research 2021 60 (48), 17328-17347.

16. Valerio L, Peters RJ, Zwinderman AH, Pinto-Sietsma SJ. Sublingual endothelial glycocalyx and atherosclerosis. A cross-sectional study. PLoS One. 2019;14(3):e0213097.

17. Bol ME, Huckriede JB, van de Pas KGH, et al. Multimodal measurement of glycocalyx degradation during coronary artery bypass grafting. Front Med (Lausanne). 2022;9:1045728.

18. Hahn RG, Patel V, Dull RO. Human glycocalyx shedding: Systematic review and critical appraisal. Acta Anaesthesiol Scand. 2021;65(5):590-606.

19. Regier M, Drost CC, Rauen M, et al. A Dietary Supplement Containing Fucoidan Preserves Endothelial Glycocalyx through ERK/MAPK Signaling and Protects against Damage Induced by CKD Serum. Int J Mol Sci. 2022;23(24):15520.

20. Yuan L, Cheng S, Sol WMPJ, et al. Heparan sulfate mimetic fucoidan restores the endothelial glycocalyx and protects against dysfunction induced by serum of COVID-19 patients in the intensive care unit. ERJ Open Res. 2022;8(2):00652-2021.

21. Patil NP, Le V, Sligar AD, et al. Algal Polysaccharides as Therapeutic Agents for Atherosclerosis. Front Cardiovasc Med. 2018;5:153.

n

Take Action Against Minor Aches & Pains

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• Willow bark (14% salicin)

• Ginger root (5% gingerol)

• Boswellia serrata (10 mg AKBA†)

With AprèsFlex®, a patented Boswellia extract, that:

• Promotes joint comfort, function and mobility*

• Helps maintain the normal balance of key immune mediators*

• Has been clinically studied using validated tests of joint function*

Vaginal Dryness and Vaginal Atrophy

2023

Vaginal dryness is the reduction in lubrication of the luminal surface of the vagina. It occurs in 14 to 31 percent of women and can occur at any age. More specifically, 50% of postmenopausal woman have vaginal dryness and 63% of women with breast cancer experience this symptom.

There are two types of vaginal dryness: simple and complex. Simple vaginal dryness occurs in healthy patients and resolution of symptoms occurs with treatment. Complex vaginal dryness occurs in people that have pelvic floor dysfunction and resolution may not occur. This form is seen in individuals with diseases such as diabetes and hypertension.

Vaginal atrophy is also called atrophic vaginitis. It is an inflammatory condition of the vagina

and outer urinary tract and is associated with thinning and shrinkage of the tissue and/pr decreased lubrication. Vulvovaginal atrophy is a common condition associated with decreased estrogen levels of the vaginal tissue. Symptoms of vaginal atrophy include the following: vaginal dryness, irritation, itching, soreness, burning, dyspareunia (painful sexual intercourse), vaginal discharge, urinary frequency, and urgency. It can occur at any time in a woman’s life, although more commonly in menopause where the incidence is about 50%.

The following are risk factors for vaginal dryness and vaginal atrophy.

• Low estrogen levels can occur after delivery and during breast feeding. Low estrogen is also common in women that are

menopausal, have premature ovarian failure, have had their ovaries removed, and in women that have had radiation to the pelvis.

• Furthermore, other medical conditions are associated with vaginal dryness. Some include:

º Dermatoses

º Diabetes

º Lichen sclerosis

º Metabolic syndrome

º Neuropathies (particularly autonomic neuropathy)

º Pituitary disorders

º Psoriasis

º Sjogren’s syndrome

º Type I diabetes

º Type II diabetes

• Prescription medications can also cause vaginal dryness.

º Anti-estrogen therapy for chemotherapy

º Anti-estrogen therapy for endometriosis or fibroids

º Antihistamines and decongestants

º Chemotherapy

º Diuretics

º Progestin predominant oral contraceptives

º SSRI’s

º Tricyclic antidepressants

• Environmental factors moreover are an etiology of vaginal dryness.

º Dehydration due to the abuse of alcohol

º Lack of sufficient arousal before intercourse

º Smoking

º Use of douches, very hot baths, or strong detergents and dehydrating soaps

º Use of highly absorptive tampons

º Use of male condoms with not enough external lubricant

Fortunately, there are many therapies for vaginal dryness and atrophy. For ease of explanation

they will be broken down into conventional treatments and Anti-Aging Medicine therapies.

Conventional treatments includes estradiol vaginal cream, topical vaginal lubricants of which some are water-based, some are polymer-based, some are liquid silk lubricants which are both water-based (moisturizing) and moisture sealing (dimethicone) and are made from propylene glycol and parabens which can cause skin irritation, pink silicone lubricants, and liquid organic silk lubricants which are water-based with silicone. In addition, conventionally, the vaginal renewal program is commonly used which helps to recondition the health and flexibility of the skin of the vulva and vagina by increasing blood flow through dilation and reduces friction tearing of the skin. It also increases blood flow to the vulva and vaginal canal. The vaginal renewal program is suggested for women just starting hormone replacement therapy, women who have had pelvic radiation therapy, and women who have vaginal atrophy which have skin tearing and pain with intercourse.

Anti-Aging therapies for vaginal dryness and atrophy have been proven to be very beneficial and range from lifestyle changes, to nutrients and botanicals, to medications. There is no single therapy that has been shown to be helpful for all individuals. That is the beauty of Anti-Aging Medicine, it is a customized approach for every person. Let’s examine these treatments.

Lifestyle changes are the place to start in treating any disease process. Instruct the patient to stop smoking, if they are a smoker, since smoking increases the risk of vaginal dryness. In addition, a consistent exercise program is beneficial. It is a good method to help decrease the rate of vascular aging. It also increases the function of small vessel

blood flow and increases the perfusion of the vagina. Furthermore, it affects nitric oxide positively, improves endothelial health including heart health and improves lubrication if the patient exercises just before intercourse. Moreover, of course diet is important. Instruct the patient to eat a Mediterranean diet since it is ideal for vaginal dryness due to its anti-inflammatory effect.

Nutrients have also been shown to be beneficial for vaginal dryness and atrophy. L-arginine is an amino acid that acts as the protein substrate for nitric oxide production. The dose is 500 to 1,000 mg a day if the patient has normal renal function. Vitamin D also is a great therapy for vaginal dryness since it helps the formation of the calmodulin cofactor needed for nitric oxide production and elevates the bioavailability of nitric oxide after production. Patients can become vitamin D toxic. Therefore, always measure levels on a regular basis.

Botanicals are also a wonderful therapy for vaginal dryness and atrophy. Alfalfa is a phytoestrogen that contains genistein, biochanin A, and daidzein. It may have a beneficial effect on estrogen. Consequently, do not suggest this botanical to patients that have had a history of breast cancer. Calendula is a cream that is applied to the affected area twice a day. It soothes vaginal tissue and heals abrasions and helps to prevent viral and bacterial infections. It is suggested bye ESCOP and the German Commission E. Furthermore, comfrey is another botanical that moistens, heals, and soothes irritated and inflamed tissues. Some of its components have anti-inflammatory activity and promote tissue healing, such as allantoin and rosmarinic acid. When used as a vaginal salve, comfrey oil has been shown to increase epithelial cell growth and tissue integrity. The German Commission E approves topical use of comfrey only on unbroken tissue and it is to be used only

for 4 to 6 weeks. Moreover, ginkgo promotes vasodilation and inhibits platelet activation. It is a blood thinner and should not be used in patients that are on a prescription blood thinner. Possible side effects include headaches, dizziness, heart palpitations, upset stomach, constipation, and allergic skin reactions. Ginseng (Panax ginseng) facilitates endothelial nitric oxide release and is an antioxidant. Taken orally or used on the skin, it may be effective for vaginal dryness. It is a phytoestrogen and is therefore not suggested for individuals with a history of hormonally related cancer. Possible side effects of ginseng are agitation and insomnia. Therefore, instruct the patient to take it in the morning. Hops also has estrogenic effects since it contains 8-prenylnaringenin. It, in addition, has strong estrogen receptor-binding bioactivity. Therefore, it may help with vaginal dryness along with hot flashes and night sweats. It may also decrease insomnia since it has a sedating effect. It should not be used in patients with a history of hormonally related cancer. In some patients it may exacerbate depression. It may also interfere with barbiturates. Lastly, red clover contains phytoestrogens and may help with vaginal dryness. It is also not to be used in patients with a history of hormonally related cancers.

Local medications have also been shown to be of major benefit for vaginal dryness and atrophy. Compounded Estriol (E3) vaginally applied helps maintain muscle tone of the vagina and urethra. It reduces vaginal irritation and prevents drying and thinning of the vaginal tissues. It may be used with the vaginal renewal program. In addition, compounded DHEA cream vaginally applied is very effective. It can be used in combination with estriol vaginally. Furthermore, hyaluronic acid is a polysaccharide that keeps body tissues hydrated and lubricated and is an excellent choice for patients that have vaginal dryness that cannot use estriol vaginal cream. Lastly, Phosphodiesterase-5 inhibitors

prolong vasodilation, which has a good effect on genital perfusion. The oral form is not recommended for vaginal dryness. It should not be used in patients taking prescription nitrates or alpha1 blockers. Possible side effects include nausea, headache, nasal congestion, kidney impairment, liver impairment, low blood pressure, change in vision, and hearing toxicity.

Systemic hormone replacement therapy is typically reserved for patients experiencing systemic menopausal symptoms (night sweats, hot flashes, and flushes) in addition to vaginal atrophy. In patients who do suffer from these symptoms, bio-identical hormone replacement

therapy has been shown to have significant results. Vaginal lubrication is very dependent on the availability of nitric oxide. The enzymatic activity of nitric oxide synthase is increased by estrogen and other sex hormones. Females using systemic BHRT have experienced growth and revascularization of the vaginal epithelium, normalized vaginal pH, and increased lubrication.

The great news is that there are many therapies to offer to the patient that has vaginal dryness or atrophy, both from a conventional, as well as an Anti-Aging customized approach.

References:

1. Smith, P., What You Must Know About Women’s Hormones. 2nd Ed., Garden City Park, NY: Square One Publishers, 2022.

2. Bleibel, B., et al., Vaginal Atrophy. StatPearls (Internet). Treasure Island, FL: StatPearls Publishing, 2022.

3. Labrie, F., et al., “Efficacy of intravaginal dehydroepiandrosterone (DHEA) on moderate to severe dyspareunia and vaginal dryness, symptoms of vulvovaginal atrophy, and of the genitourinary syndrome of menopause,” Menopause 2016; 23(3):243-56.

4. Archer, D., “Dehydroepiandrosterone intra vaginal administration for the management of postmenopausal vulvovaginal atrophy,” Jour Steroid Biochem Mol Biol 2015; 145:139-43.

5. Naumova, I., et al., “Current treatment options for postmenopausal vaginal atrophy,” Int Jour Womens Health 2018; 10:387-95.

Author Bio:

6. Lindahl, S., “Reviewing the options for local estrogen treatment of vaginal atrophy,” Int Jour Womens Health 2014; 6:307-12.

7. Lethaby, A., et al., “Local oestrogen for vaginal atrophy in postmenopausal women,” Cochrane Database Syst Rev 2016; 2016(8):CD001500

8. Mahjabeen W, Khan DA, Mirza SA, Pervez MA. Effects of deltatocotrienol 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):39683976. doi:10.1002/ptr.7113.

9. 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(1):4-7. doi:10.47391/JPMA.966.

Pamela Wartian Smith, M.D., MPH, MS spent her first twenty years of practice as an emergency room physician then 28 years as an Anti-Aging Medicine specialist. She is a diplomat of the Board of the American Academy of Anti-Aging Physicians and is an internationally known speaker and author on the subject of Anti-Aging and Precision Medicine. She is the author of eleven best-selling books.

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BPC 157: GI Therapy and Beyond

Gastrointestinal Conditions Affect 40% of the Population

Gastrointestinal conditions are increasingly common in modern society, with up to 40 percent of people experiencing a functional gastrointestinal (GI) disorder at some point in time.1 Functional gastrointestinal disorders include irritable bowel syndrome, functional dyspepsia, and functional constipation, among many others.1 Of the 40 percent of the population that may experience any of these conditions, approximately two thirds of them will have chronic, fluctuating symptoms that often have no organic explanation.1 This can result in significant frustrations for the patient as well as increase the difficulty of finding a successful therapeutic option.

Symptoms in GI patients can come in many different forms, frequencies, and intensities. Common symptoms include abdominal pain, constipation, diarrhea, bloating, fullness, nausea, and vomiting.1 Gastrointestinal issues can negatively affect a patient, both physically and emotionally, resulting in a significant impact on their quality of life.1 The lack of definitive, organic cause can bring about negative attitudes and hopelessness regarding a possible treatment.1

The pathophysiology of GI conditions is complex and likely includes bidirectional dysregulation of the brain-gut axis, microbial dysbiosis, altered immune function of the gut mucosa, intestinal inflammation, visceral hypersensitivity, and abnormal gastrointestinal motility.1

which can cause distress in patients provides avenues for the research and development of e ective therapies. Recommended approaches for the management of GI conditions include lifestyle modi cation, dietary changes, use of probiotics, and pharmacotherapies that target various aspects of GI physiology.2 However, pharmacotherapy treatment options often come with adverse e ects.2 As such, nding safer, e ective alternatives remains an area of great interest.

BPC 157 (body protection compound 157) has emerged as a promising option for individuals with GI conditions. It is a pentadecapeptidemeaning a peptide composed of 15 amino acids (Gly-Glu-Pro-Pro-Pro-Gly-Lys-Pro-AlaAsp-Asp-Ala-Gly-Leu-Val).3 It is native to human gastric juice and therefore remains stable in stomach acid, which provides advantages over other therapeutics and may increase the likelihood of e cacy as it can be easily ingested via the mouth and survive initial stages of digestion.3 It is innately stable in the human stomach, resisting degradation in gastric juice for more than 24 hours.4

BPC 157 is safe for human consumption as determined by the FDA and is designated as generally recognized as safe (GRAS).

In order to appreciate the potential impact of BPC 157 on GI conditions, it is important to understand the mechanisms that likely contribute to poor gastrointestinal health and gastrointestinal disorders. Mechanisms involved in gastrointestinal disorders include mucosal immune activation, increased intestinal permeability, enterendocrine cell products, excess bile acids, and gut dysbiosis.5 These are in addition to psychosocial factors and stress hormones that a ect gut health via the gut-brain axis.5

Speci cally, intestinal immune activation is characterized by the in ltration of in ammatory cells which produce mediators that sensitize primary a erent neurons, leading to visceral hypersensitivity and therefore increased pain

sensitivity.5 Mast cells, innate immune cells, are important in this process.5 Entero-endocrine products include serotonin, which is a key mediator of gastrointestinal secretion and motility, and can active a erent nerves, also contributing to pain.5 While the research is not de nitively, preliminary studies suggest that enterochroma n cells increase in patients with GI conditions, leading to signi cantly greater production of serotonin which was correlated to increased mast cell counts and increased severity of pain.6 Additionally, increased intestinal permeability seen in GI patients enables bacteria or other pathogens to cross the intestinal barrier, triggering an in ammatory response.5 The in ammatory mediators released during this response can increase visceral hypersensitivity and therefore pain.5 Targeting tight junctions and intestinal permeability remains a promising avenue for treatment in patients with GI conditions.

Other mechanisms relevant to GI conditions include alterations to the gut microbiome, the billions of bacteria and other cells that reside in the GI tract including the colon.5 Although exact mechanisms through which dysbiosis, or imbalance of the gut microbiome, are not precisely known, it is thought that changes can alter intestinal motility, GI secretions, intestinal barrier function, or interactions with the gut-brain axis.7 While GI disorders are diverse and often have complex causes, some conditions can be grouped based on symptoms or causes to help categorize diagnoses and treatment and inform research endeavors.

BPC 157 and Gastrointestinal Health

Preliminary research investigating the e ects of BPC 157 in gastrointestinal health has produced promising results. BPC 157 is known for its anti-ulcer e ects and has been shown to successfully treat lesions of the esophagus, stomach, duodenum, and intestines, recover lower esophageal sphincter and pyloric sphincter function, heal intestinal anastomosis

and stulas, and improves adaptation of the intestinal wall after massive resection.3,8-14 It also has been demonstrated to be safe in trials focusing on in ammatory bowel disease.3

Mechanistically, it is thought to mediate Robert’s cytoprotection, thereby maintaining GI mucosa integrity.3,8-14 Its origins in gastric juice may explain why it is able to counteract GI lesions induced by various procedures as well as maintain GI mucosa integrity.8 It also displays angio-modulatory e ects, possibly to a greater extent than traditional antiulcer agents.8 The process of wound healing is not a static event but rather a dynamic balance of positive and negative events that ultimately dictates timing and extent of healing. In this regard, BPC 157 has a clear advantage over other therapeutic options. It was able to heal stulas, promote mature collagen in granulation tissue, and healed gastric lesions even when there was a major vessel occlusion by rapidly activating collateral pathways occlusion.8 The rapid recovery of blood ow may contribute to the rapid recovery seen with treatment of BPC 157.8 BPC 157 also counteracted free radical-induced lesions, which may be due to the antioxidant capabilities of its carboxylic groups.8 This speci c mechanism is especially noteworthy as BPC 157 is found in most tissues, including those which are not reachable by other antioxidants.8 It may also be able to act as a membrane stabilizer which may have implications for individuals that su er from ulcerative colitis.8

Improving bioavailability of BPC157

The largest challenge in effectively utilizing biological peptides, including BPC 157, is limited delivery due to poor bioavailability.15 One solution to this challenge may be the chaperone carrier salcaprozate sodium, or SNAC (sodium N-(8-[2-hydroxybenzoyl]amino)caprylate. SNAC is an amino acid derivative of salicylic acid that is able to deliver peptides to the gastric lining.15,16 Compared to other vehicles, it does not require a protective enteric coating.16 SNAC was assigned

GRAS status by the FDA and early research indicates that it may be more successful at delivering certain compounds to the GI tract.15,16 In the case of semaglutide, an analog of the human peptide hormone GLP-1, SNAC is able to increase absorption possibly by increasing gastric pH which may protect semaglutide from enzymatic degradation, allowing it to reach its target site intact.15 SNAC may also alter the membrane of gastric epithelium cells to allow the passage of semaglutide.17 Clinical research is limited but one trial demonstrated that SNAC was able to enhance the bioavailability of oral cyanocobalamin.18 While research is in the beginning stages, mechanisms and effectiveness of SNAC-mediated delivery of peptides deserve increased attention.

BPC 157 and Musculoskeletal Healing

The bene cial e ects of BPC 157 extend beyond the gastrointestinal system, with results indicating a signi cant ability of BPC 157 to heal wounds of the musculoskeletal system, including both traumatic and systemic injuries.19 It promotes wound healing in deep skin burns, injured muscles, tendons, ligaments, and bones, and nerve healing.3 While most therapeutic options for musculoskeletal soft tissue injuries and disorders have focused on growth factor pathways, BPC 157 may o er an alternative and safer approach.19 In an animal model BPC 157 promoted healing and sustained its healing e ects for 72 days while also supporting functional restoration.20 This in addition to its prolonged half-life, which allows it to exert a stimulating e ect on connective tissue growth, ultimately increasing its therapeutic abilities.8

Beyond muscle, the musculoskeletal system also consists of tendons and ligaments which often exhibit poor wound healing due to a limited blood supply. However, in preclinical models, treatment with BPC 157 resulted in improved recovery measures, assessed via biochemical, microscopic, and macroscopic measures.19,21 Speci cally, microscopic analysis

demonstrated an increase in broblasts, superior formation of the reticulin and collagen bers, as well as greater mononuclear count and fewer granulocytes.19,21 In a separate study, BPC 157 was able to promote tendon-to-bone healing and the authors suggested that it may counteract corticosteroid aggravation.22 Mechanistically, BPC 157 stimulates the outgrowth and proliferation of tendon broblasts and can bene t skeletal muscle microscopically, macroscopically, enzymatically, and functionally.19,23

An original study investigating BPC 157 nearly thirty years ago revealed that BPC 157 upregulated the triad of collagen-in ammatory cells and angiogenesis required for general wound healing.24 This triad appeared at earlier intervals, and was more rapid and advanced with BPC 157 treatment.24 Despite the di erent characteristics and pathologies of skin versus gastrointestinal wounds, BPC 157 appears to exert a general wound healing e ect.8 It is likely that BPC 157 works through various mechanism on skin burns including interacting with in ammatory cells, modulating reticulin, collagen, necrosis, blood vessel formation and water content of skin, among others.8

Emerging Data for BPC 157

BPC 157 demonstrates general wound healing actions in the GI tract as well as musculoskeletal system. Its inherent ability to protect cells and maintain endothelium tissue has also made it a successful intervention in other conditions including periodontitis, alcohol-induced lesions of the liver, both acute and chronic, and adjuvant arthritis in animal models.3 It can also counteract toxicity from non-steroidal anti-in ammatory drugs (NSAIDs), modulate the nitric oxide system and blood vessels, and may play a role in the gut-brain axis in tandem with modulation of central nervous system disturbances and stress disorders.8 Within the central nervous system, BPC 157 has been found to have other bene cial e ects,

including counteracting encephalopathies, alleviating vascular occlusion disturbances and dopamine disturbances, as well as reducing in ammation, and aiding in nerve recovery and vessel function.25 It also can modulate serotonin and dopamine metabolism which resulted in a bene cial e ect on behavioral disturbances in addition to several neuroprotective e ects, with no toxic e ects seen in a preclinical model.25

As it relates to cancer, BPC 157 has been shown to not only inhibit but also counteract uncontrolled cellular proliferation, inhibiting the growth of several tumor lines and counteracting tumor cachexia.26 The ability of BPC 157 to support angiogenesis and bypass occluded vessels may explain why it is able to bene t recovery from ischemiareperfusion injury and heart disturbances.8,27 BPC 157 may also reduce prolonged bleeding and thrombocytopenia after amputation, organ perforation, and anticoagulant use.8

BPC-157: Strong Potential as a GI Therapy

While much of the research on the mechanisms underlying the bene cial e ects of BPC 157 were conducted in animal models, the e ectiveness has been demonstrated on larger animals, supporting a high possibility that ndings will translate to humans.8 Treatment options in animal models have included intraperitoneal, topical, and oral administration, with the most translatable ndings coming from oral administration in drinking water.19 A particular strength of utilizing BPC 157 for gastrointestinal, musculoskeletal, and general wound healing includes its increased e ectiveness compared to other therapeutic options, even when it is administered alone.8

Peptides have diverse and vital functions in the body. BPC 157 is a particularly unique peptide due to its wound healing e ects. Additionally, its mechanisms are not limited to one speci c time of wound; they are general

and have demonstrated very positive e ects on wounds of the skin, musculoskeletal system, and gastrointestinal tract. While much of the research on BPC 157 remains in the preclinical stage, there are exciting ndings that indicate strong potential for this therapeutic

References:

1. Black CJ, Drossman DA, Talley NJ, Ruddy J, Ford AC. Functional gastrointestinal disorders: advances in understanding and management. Lancet. 2020;396(10263):1664-1674.

2. Camilleri M. Management Options for Irritable Bowel Syndrome. Mayo Clin Proc. 2018;93(12):1858-1872.

3. Sikiric P, et al. Brain-gut Axis and Pentadecapeptide BPC 157: Theoretical and Practical Implications. Current Neuropharmacol. 2016;14(8):857-865.

4. Sikiric P, Seiwerth S, Rucman R, Kolenc D, Vuletic LB, Drmic D, et al. Stable Gastric Pentadecapeptide BPC 157, Robert’s Stomach Cytoprotection/Adaptive Cytoprotection/Organoprotection, and Selye’s Stress Coping Response: Progress, Achievements, and the Future. Gut Liver. 2020;14(2):153-.

5. Crisan IM, Dumitrascu DL. Irritable Bowel Syndrome: Peripheral Mechanisms and Therapeutic Implications. Clujul Med. 2014;87(2):73-79.

6. Cremon C, Carini G, Wang B, Vasina V, Cogliandro RF, De Giorgio R, et al. Intestinal serotonin release, sensory neuron activation, and abdominal pain in irritable bowel syndrome. Am J Gastroenterol. 2011;106(7):1290-1298.

7. Simrén M, Barbara G, Flint HJ, Spiegel BM, Spiller RC, Vanner S, et al. Intestinal microbiota in functional bowel disorders: a Rome foundation report. Gut. 2013;62(1):159-176.

8. Seiwerth S, Milavic M, Vukojevic J, Gojkovic S, Krezic I, Vuletic LB, et al. Stable Gastric Pentadecapeptide BPC 157 and Wound Healing. Front Pharmacol. 2021;12:627533.

9. Sikiric P, Seiwerth S, Rucman R, Turkovic B, Rokotov DS, Brcic L, et al. Toxicity by NSAIDs. Counteraction by stable gastric pentadecapeptide BPC 157. Curr Pharm Des. 2013;19(1):76-83.

10. Sikiric P, Seiwerth S, Rucman R, Turkovic B, Rokotov DS, Brcic L, et al. Focus on ulcerative colitis: stable gastric pentadecapeptide BPC 157. Curr Med Chem. 2012;19(1):126-132.

11. Sikiric P, Seiwerth S, Rucman R, Turkovic B, Rokotov DS, Brcic L, et al. Stable gastric pentadecapeptide BPC 157: novel therapy in gastrointestinal tract. Curr Pharm Des. 2011; 17(16):1612-1632.

12. Sikiric P, Seiwerth S, Brcic L, Sever M, Klicek R, Radic B, et al. Revised Robert’s cytoprotection and adaptive cytoprotection and stable gastric pentadecapeptide BPC 157. Possible significance and implications for novel mediator. Curr Pharm Des. 2010;16(10):12241234.

13. Sikiric P, Seiwerth, S, Brcic L, Blagaic AB, Zoricic I, Sever, M, et al. Stable gastric pentadecapeptide BPC 157 in trials for inflammatory

peptide. The ability of one peptide to support wound healing in the gastrointestinal tract, and without serious adverse e ects, warrants further research and clinical studies.

bowel disease (PL-10, PLD-116, PL 14736, Pliva, Croatia). Full and distended stomach, and vascular response. Inflammopharmacology. 2006;14(5-6):214-221.

14. Sikirić P, Petek M, Rucman R, Seiwerth S, Grabarević Z, Rotkvić I, et al. A new gastric juice peptide, BPC. An overview of the stomachstressorganoprotection hypothesis and beneficial effects of BPC. J Physiol Paris. 1993;87(5):313-327.

15. Aroda VR, Blonde L, Pratley, RE. A new area for oral peptides: SNAC and the development of oral semaglutide for the treatment of type 2 diabetes. Rev Endocr Metab Disord. 2022;23(5):979-994.

16. Twarog C, Fattah S, Heade J, Maher S, Fattal E, Brayden DJ. Intestinal permeation enhancers for oral delivery of macromolecules: a comparison between salcaprozate sodium (SNAC) and sodium caprate (C10). Pharmaceutics. 2019;11(2):78.

17. Brayden DJ, Hill TA, Fairlie DP, Maher S, Mrsny RJ. Systemic delivery of peptides by the oral route: formulation and medicinal chemistry approaches. Adv Drug Deliv Rev. 2020;157:2–36.

18. Castelli MC, Wong, DF, Friedman K, Riley MGI. Pharmacokinetics of Oral Cyanocobalamin Formulated with Sodium N-[8-(2hydroxybenzoyl)amino]caprylate (SNAC): An Open-Label, Randomized, Single-Dose, Parallel-Group Study in Healthy Male Subjects. Clin Ther. 2011;33(7):934-945.

19. Gwyer D, Wragg NM, Wilson SL. Gastric pentapeptide body protection compound BPC 157 and its role in accelerating musculoskeletal soft tissue healing. Cell Tissue Res. 2019;377(2):153-159.

20. Staresinic M, Petrovic I, Novinscak T, Jukic I, Pevec D, Suknaic S, et al. Effective therapy of transected quadriceps muscle in rat: gastric pentadecapeptide BPC 157. J Orthop Res. 2006;24:1109–1117.

21. Staresinic M, Japjec M, Vranes H, Prtoric A, Zizek H, Krezic I, et al. Stable Gastric Pentadecapeptide BPC 157 and Striated, Smooth, and Heart Muscle. Biomedicines. 2022;10(12):3221.

22. Krivic A, Anic T, Seiwerth S, Huljev D, Sikiric P. Achilles detachment in rat and stable gastric pentadecapeptide BPC 157: promoted tendon-to-bone healing and opposed corticosteroid aggravation. J Orthop Res. 2006;24:982–989.

23. Chang CH, Tsai WC, Lin MS, Hsu YH, Pang JHS. The promoting effect of pentadecapeptide BPC 157 on tendon healing involves tendon outgrowth, cell survival, and cell migration. J Appl Physiol (1985). 2011;110(3):774-7780.

24. Seiwerth S, Sikiric P, Grabarevic Z, Zoricic I, Henzevacki M, Ljubanovic D, et al. BPC 157’s effect on healing. J Physiol Paris. 1997;91(3-5):173-178.

25. Vukojevic J, Milavic M, Perovic D, Ilic S, Cilic AZ, Duran N, et al. Pentadecapeptide BPC 157 and the central nervous system. Neural Regen Res. 2022;17(3):482-487.

26. Kang EA, Han YM, An JM, Park YJ, Sikiric P, Kim DH, et al. BPC157 as potential agent rescuing from cancer cachexia. Curr Pharm Des. 2018;24(18):1947–1956.

Authors Bios:

Erika Schwartz, MD 477 Madison Avenue Suite 420, New York, NY 10022

212-873-3420

info@eshealth.com

Daniel L. Cajigas

180 Froehlich Farm Blvd, Woodbury, NY 11797

855-272-7220

dlc@cscprivatelabel.com

27. Sikiric P, Udovicic M, Barisic I, Balenovic D, Posilovic GZ, Strinic D, et al. Stable Gastric Pentadecapeptide BPC 157 as Useful Cytoprotective Peptide Therapy in the Heart Disturbances, Myocardial Infarction, Heart Failure, Pulmonary Hypertension, Arrhythmias, and Thrombosis Presentation. Biomedicine. 2022;10(11):2696.

Erika Schwartz, MD is a leading expert in preventative medicine, bioidentical hormone therapy, peptides, and longevity medicine. She is the founder and CEO of Evolved Science the premier longevity medical practice with multiple locations headquartered in Manhattan where she sees patients from all around the globe. Dr. Erika is the author of 8 bestselling books and a TEDx speaker.

Daniel l. Cajigas is the founder of Clinicians Supplement Consultants and has dedicated himself to serving the needs of healthcare professionals and their patients for over 26 years. Daniel has hosted live call-in health shows in New York on WOR 710, WABC 770, AM 970 in addition to syndicated shows nationally and Sirius XM. Daniel has worked closely with practitioners and manufacturers to develop cutting edge formulas that help practitioners and their patients achieve a longer and healthier life.

Probiotics, Resistant Starch, and Vitamin E Tocotrienols for Healthy Aging

Probiotics and Resistant Starch for Healthy Aging

The topic of aging (and methods to combat it) has become exceedingly popular both in mainstream and nutritional science. Even the United Nations has proclaimed 2021 to 2030 to be “the decade of healthy aging.”1 Aging is a natural process that typically accompanies biochemical and physiological changes that disrupt normal cellular function. Two primary factors shown to contribute to cellular dysfunction during aging include chronic lowgrade inflammation (a phenomenon coined “inflammaging”) and intestinal dysbiosis, or an imbalance in gut microbial composition.2

Although mutual causality has not been fully determined, continuous, low-grade inflammation and gut dysbiosis are strongly intertwined, as evidenced by studies that demonstrate a well-balanced gut promotes a healthy inflammatory response and reduces pro-inflammatory activity, particularly in the aging microbiome.3 One may trigger the other and vice versa. As cellular structure and function decline during aging, these can contribute to a variety of concerns such as cardiovascular disease, intestinal permeability, increased susceptibility to infection, disorders of the gastrointestinal tract, nutrient malabsorption, impaired immune function, suboptimal cognitive function, sarcopenia, and gut dysbiosis, which contribute to inflammation in the body.

Tocotrienols for Healthy Aging

In a 2022 review published in the journal Nutrients, Warman and colleagues examined the potential role that probiotics and two types of prebiotics (resistant starch and resistant proteins) play in supporting health in aging populations, specifically how they impact the inflammatory response.4 It is well-known that prebiotics and probiotics promote gut health, but until recently, little research has shown their effects on inflammatory activity in older adults.

The researchers highlight several strains and species of Lactobacillus spp. and Bifidobacterium that possess anti-inflammatory activity and demonstrate gut and immune benefits in aging populations.4 In elderly humans and aged animals, supplementation with shortchain fatty acid (SCFA)-producing bacterial strains attenuated age-related loss of mucin and imparted other health and immune benefits.5 Akkermansia muciniphila and Faecalibacterium praunitzii are butyrateproducing bacteria that were shown to activate colonic mucus production and reduce colonic expression of proinflammatory genes and pathways in accelerated aging animal models.5 Maintaining a thick layer of mucus acts as a barrier against potential pathogenic bacteria that promotes pro-inflammatory mediator production and activity.

Resistant starches are unable to absorb liquid or do not fit into the enzymatic binding site of amylase, so they resist the action of amylase in the small intestine. The undigested starch progresses to the large intestine and is fermented by resident microorganisms, producing metabolites such as SCFAs that provide numerous health benefits.

Two of the most sought-after health benefits of resistant starches are optimizing commensal microbes and supporting glycemic control.6 These benefits provide secondary health effects

for patients, such as weight management, improved metabolic markers, modulation of inflammation, and oxidative stress, which can support healthy aging.6-8 Bacterial fermentation of resistant starches produces gases, SCFAs (acetate, propionate, butyrate, and valerate), and lesser amounts of organic acids, branched SCFAs, and alcohols. Many of these byproducts lower the pH of the large intestine, which positively influences the classes of bacteria that survive and grow, in addition to the gene expression of both bacteria and colonic cells. Butyrate is the preferred energy source for human colonocytes and plays a vital role in maintaining microbial balance and a healthy inflammatory response by modulating the immune system.9 Prebiotic intervention in the form of resistant starches ensures a more effective optimization of gastrointestinal health and the microbiome than probiotics alone.

On the other hand, resistant proteins are less well-known, but they possess comparable properties to resistant starches and are derived from proteins that are resistant to human proteases. Gut bacteria also ferment resistant proteins. Resistant proteins are found naturally in soybeans, buckwheat, rice, potato, sericin, and eggshell membrane and have low digestibility. Resistant proteins have been shown to restore populations of SCFAproducing bacteria,10 contribute to overall microbial diversity, and reduce dysbiosis,11 all of which support healthy aging.

Practitioners are becoming familiar with the use of prebiotics to enhance the effects of probiotics and optimize the microbiome. In addition to supplemental prebiotics, dietary resistant starches and resistant proteins, which are another form of prebiotic, fermentable fiber, confer similar benefits as other prebiotics, but these may augment the benefit because they can be incorporated into daily meals. Although

more research is needed to fully understand the significance of probiotics, resistant starches, and resistant proteins in supporting a normal inflammatory response during aging, the current evidence suggests that collectively they have the potential to promote healthy aging.4

Vitamin E Tocotrienols for Healthy Aging

Vitamin E consists of eight isomers: four tocotrienols and four tocopherols. Each isomer has a different molecular weight and a slightly different chemical structure; this imparts distinct properties that influence their biochemical function. Commercial vitamin E supplements are typically rich in tocopherols and may be low or absent in tocotrienols. However, research suggests that tocotrienols may have uniquely beneficial effects on metabolic health and healthy aging.12

Unlike tocopherols, tocotrienols may be incorporated into the tissues with saturated fatty layers (e.g., brain and liver) more efficiently due to their unsaturated side chain and unique antioxidant properties.13 Furthermore, human studies have revealed that alphatocopherols may attenuate the bioavailability of tocotrienols and interfere with its potential clinical benefits if simultaneously administered.14 Annatto seeds are the richest source of naturally occurring tocotrienols and are free of tocopherols. Tocotrienol supplementation, such as annatto-derived tocotrienols, may be clinically relevant to the general population, and it may support healthy aging, a healthy inflammatory response, and metabolic health.14

In human studies, tocotrienols have shown a potential role in the modulation of several signaling and transcriptional pathways that regulate inflammation, including nuclear factor-kappa B, which may support metabolic health and healthy aging.14,15 A systematic

review and meta-analysis concluded that individuals receiving supplementation with tocotrienols (between 180 mg/day and 600 mg/day) had significantly reduced CRP.13 In a pilot study for a randomized controlled trial with 71 participants, decreased inflammatory markers after tocotrienol supplementation were observed in subjects with suboptimal liver function.14 The same results were observed in individuals with suboptimal cholesterol metabolism in an open-label randomized study with a total of 33 participants.16

Prospective and case-controlled studies reveal that individuals with increased plasma tocotrienol levels were associated with favorable outcomes for cognitive function, such as improved cellular health.12 The researchers concluded that tocotrienols may be clinically relevant to those with neurological health concerns. A randomized clinical trial assigned 64 individuals to receive either a placebo or 160 mg of tocotrienol-rich supplements per day for 6 months. The participants in the intervention group displayed significantly decreased DNA damage compared to the placebo group. Reduced DNA damage appeared to be greater in a subgroup of adults aged 50 years or older, which may support healthy aging.12

After receiving annatto seed-derived tocotrienol supplements for 12 weeks with 90% delta- and 10% gamma-tocotrienols at 430 mg per day or 860 mg per day, postmenopausal women with osteopenia (n = 89) in both groups displayed decreased bone resorption and improved bone turnover rates, potentially through reduced oxidative stress.17 In vitro, benefits on bone health were only observed in the case of tocotrienols.12

A randomized controlled trial with 110 participants observed the effects of supplementation with delta-tocotrienols (250

Tocotrienols for Healthy Aging

mg per day) or a placebo for 24 weeks in patients with type 2 diabetes mellitus. Compared to the placebo, the intervention group displayed many significantly improved indicators, such as glycemic control, microRNA expression, and various inflammatory and oxidative markers, including high-sensitivity C-reactive protein (CRP).18 Another randomized controlled trial was conducted with 77 pre-diabetic individuals. This study demonstrated significantly improved blood glucose markers for these individuals after supplementation of 300 mg of deltatocotrienols per day compared to a placebo.19

Vitamin E tocotrienols not only help support cellular and DNA health and antioxidant status

References:

1. World Health Organization. What is WHO’s role in the UN Decade of Healthy Ageing? Accessed February 15, 2023. https://www.who. int/initiatives/decade-of-healthy-ageing#:~:text=The%20United%20 Nations%20Decade%20of,improve%20the%20lives%20of%20older.

2. Di Giosia P, Stamerra CA, Giorgini P, Jamialahamdi T, Butler AE, Sahebkar A. The role of nutrition in inflammaging. Ageing Res Rev. 2022;77:101596. doi:10.1016/j.arr.2022.101596.

3. DeJong EN, Surette MG, Bowdish DME. The gut microbiota and unhealthy aging: disentangling cause from consequence. Cell Host Microbe. 2020;28(2):180-189. doi:10.1016/j.chom.2020.07.013.

4. Warman DJ, Jia H, Kato H. The potential roles of probiotics, resistant starch, and resistant proteins in ameliorating inflammation during aging (inflammaging). Nutrients. 2022;14(4):747. doi:10.3390/nu14040747.

5. van der Lugt B, van Beek AA, Aalvink S, et al. Akkermansia muciniphila ameliorates the age-related decline in colonic mucus thickness and attenuates immune activation in accelerated aging Ercc1-/ Δ7 mice. Immun Ageing. 2019;16:6. doi:10.1186/s12979-019-0145-z.

6. Keenan MJ, Zhou J, Hegsted M, et al. Role of resistant starch in improving gut health, adiposity, and insulin resistance. Adv Nutr. 2015;6(2):198-205. doi:10.3945/an.114.007419.

7. Yang X, Darko KO, Huang Y, et al. Resistant starch regulates gut microbiota: structure, biochemistry and cell signalling. Cell Physiol Biochem. 2017;42(1):306-318. doi:10.1159/000477386.

8. Esgalhado M , Kemp JA , Azevedo R , et al. Could resistant starch supplementation improve inflammatory and oxidative stress biomarkers and uremic toxins levels in hemodialysis patients? A pilot randomized controlled trial. Food Funct. 2018;9(12):6508-6516. doi:10.1039/ c8fo01876f.

9. Liu X, Wu Y, Li F, Zhang D. Dietary fiber intake reduces risk of inflammatory bowel disease: result from a meta-analysis. Nutr Res. 2015;35(9):753-758. doi:10.1016/j.nutres.2015.05.021.

but also support bone health, healthy blood glucose metabolism, neurological function, and a healthy response to inflammation in the body. Probiotics and prebiotics, including resistant starch, are well-known for their role in maintaining proper GI function and supporting a healthy gut microbiome, but evidence now suggests they also can play a fundamental role in inflammation and healthy aging. Collectively, incorporating all three of these beneficial compounds into one’s daily regimen through dietary intake or supplementation may significantly impact the natural aging process by supporting health at the cellular level.

10. Ramli NS, Jia H, Sekine A, et al. Eggshell membrane powder lowers plasma triglyceride and liver total cholesterol by modulating gut microbiota and accelerating lipid metabolism in high-fat diet-fed mice. Food Sci Nutr. 2020;8(5):2512-2523. doi:10.1002/fsn3.1545.

11. Jia H, Hanate M, Aw W, et al. Eggshell membrane powder ameliorates intestinal inflammation by facilitating the restitution of epithelial injury and alleviating microbial dysbiosis. Sci Rep. 2017;7:43993. doi:10.1038/ srep43993.

12. Georgousopoulou EN, Panagiotakos DB, Mellor DD, Naumovski N. Tocotrienols, health and ageing: a systematic review. Maturitas. 2017;95:55-60. doi:10.1016/j.maturitas.2016.11.003.

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

14. 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.

15. Nasir NAA, 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.

16. Qureshi AA, Khan DA, Silswal N, Saleem S, Qureshi N. Evaluation of pharmacokinetics, and bioavailability of higher doses of tocotrienols in healthy fed humans. J Clin Exp Cardiolog. 2016;7(4):434. doi:10.4172/2155-9880.1000434.

17. Shen CL, Yang S, Tomison MD, Romero AW, Felton CK, Mo H. Tocotrienol supplementation suppressed bone resorption and oxidative stress in postmenopausal osteopenic women: a 12-week randomized doubleblinded placebo-controlled trial. Osteoporos Int. 2018;29(4):881-891. doi:10.1007/s00198-017-4356-x.

18. Mahjabeen W, Khan DA, Mirza SA, Pervez MA. Effects of deltatocotrienol 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):39683976. doi:10.1002/ptr.7113.

Authors Bios:

19. 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(1):4-7. doi:10.47391/JPMA.966.

Caitlin Higgins and Danielle Moyer hold their M.S. in Nutrition and are board-Certified Nutrition Specialists®. Danielle and Caitlin are Clinical Scientific Writers for Designs for Health; Danielle also teaches college-level nutrition.

Caitlin Higgins  chiggins@designsforhealth.com

Danielle Moyer: dmoyer@designsforhealth.com

Shockwaves Are Changing The Future Of Ed Treatment And Are Quickly Becoming The Gold Standard Of Care

From curing ED to managing benign prostatic hyperplasia and fixing Peyronie's disease, Low-intensity extracorporeal shock wave therapy (Li-ESWT) is touted as the 'goto' treatment for men who are seeking to optimize sexual wellness and performance. But one claim is certainly valid, shock wave therapy is a safe treatment for men with erectile dysfunction and many studies are showing a series of non-invasive 15-minute treatments can improve, and even cure ED in many patients.

But there still remains crucial unanswered questions, including which patients are suitable candidates, which type of shockwave device is most effective and what can shockwave therapy combine with to optimize patient outcomes.

Who are suitable patients?

Results with shock wave therapy from several multinational clinical trials demonstrate it is a well-tolerated treatment for many men. These same studies prove safety and efficacy, especially with the most common form of ED, vasculogenic erectile dysfunction, which is a blood vessel disorder that affects blood flow to the tissues in the penis.

In theory, anyone experiencing chronic ED can be a candidate. Though current research states it may work best for vasculogenic ED, a 2021 narrative review found that while some studies show that Li-ESWT is more effective in cases of mild ED when used with a combination of other treatments, others revealed the opposite, where shockwave therapy used by itself worked best in moderate to severe ED.

The European Association of Urology guidelines for erectile dysfunction recommends use of lowintensity shock wave treatment in mild organic erectile dysfunction patients or poor responders to sildenafil (Viagra®), tadalafil (Cialis®) and other commonly prescribed phosphodiesterase type-5 (PDE-5) inhibitors.

Dr. Ranjith Ramasamy, assistant professor of urology and director of male reproductive medicine and surgery at the University of Miami, is part of the team that conducted a phase II trial looking at shock wave therapy for ED management. The trial compared two different dose regimens. In group 1, a total of 3,600 shocks were given over a period of 5 days. In group 2, the regimen was a total of six treatments given 3 days a week (Monday, Wednesday, and Friday) for 2 weeks in a row.

The trial revealed Li-ESWT worked well to restore erectile function in men with mild to moderate vasculogenic ED. However, it did not have an effect in men with severe erectile dysfunction resulting from diabetes or in those who had undergone non-nerve sparing prostatectomy, cystectomy, or radiation. Nor did it have a prominent effect in men with Peyronie’s disease except management of the pain associated with the disease and a slight reduction in curvature.

“In the trial that we have completed, over 60% of men appear to respond to shock wave therapy by achieving the minimal clinically important difference in International Index of Erectile Function scores at the end of 6 months without taking any kind of PDE-5 inhibitors." Dr. Ramasamy said. “Some of the trials have demonstrated a benefit up to 12 months."

Remarkably, shock wave therapy is unlike other ED treatment options in that it offers a potential cure for ED. “I think that in patients with mild to moderate erectile dysfunction, it can reverse the pathophysiology of the disease and not merely

treat the condition but potentially restore erectile function,” Dr. Ramasamy said.

What type of shockwave machines are the best...radial or focus?

In the USA, FDA approval for Li-ESWT to treat ED likely is years away, however, there are many FDA cleared machines available in the US that are being used ‘off-label’ to treat ED, improve erectile function and optimize male sexual wellness. There are two types of shockwave technology, radial and focus.

While radial shockwave machines are currently the most common type of machine used in treating ED, focus machines are becoming increasingly popular. So, what exactly is the difference between radial and focused shockwave technology?

Radial wave therapy (rWT) is suitable for both small and large treatment areas. Radial machines emit a 'fan shaped' wave (think of the Wi-Fi signal strength bars on your smart phone) with slow impulses and low energy density. Radial devices deliver up to 6 centimeters of treatment depth.

In contrast, focused shock wave (fSWT) provides a smaller focal point (think of a laser beam) and emit fast impulses and high energy density. Focus devices deliver a treatment depth of up to 12 centimeters. Radial waves lose power the deeper they enter the body. Focus waves can penetrate deeper into the body. When treating the penis (on the left and right side), waves that penetrate at least 3 centimeters are all that’s required.

It's important to note, that in Dr. Ramasamy's trial (and many other studies) his team used a focus device. Bruce Sloane MD, a urologist in private practice in Philadelphia, whose practice specializes in men’s health, offers the radial technology and said it has shown good results in treating ED.

“I’ve had some men in their 30s who are diabetic and men in their 80s. Some outcomes are more dramatic than others. But every man I've treated has had improvements in the quality of their erections,” said Dr. Sloane, who has treated over 200 patients. "I'm happy using the radial technology and most importantly my patients are getting good results. The key for good patient outcomes is to prioritize adequate patient selection."

In 2020, the Cleveland Clinic published a retrospective comparison of focus shockwave therapy and radial wave therapy for men with erectile dysfunction. It examined a total of 48 men, 24 treated with focus and 24 with radial technology. Men with a history suggesting nonvascular ED were excluded. All men received 6 consecutive weekly treatments. The rWT group received 10,000 shocks per treatment at 90mJ and 15 Hz. The fSWT group received 3,000 shocks per treatment at 0.09mJ/mm2. The study concluded "In our patient population, both rWT and fSWT were effective with no observable difference in efficacy between the two modalities".

What can shockwave therapy combine with to optimize results?

Good medicine typically combines several modalities and therapies that synergistically complement each other to deliver more robust outcomes. Treating ED is no exception. LiESWT when combined with sildenafil (Viagra®), tadalafil (Cialis®) and other commonly prescribed phosphodiesterase type-5 (PDE-5) inhibitors has been shown to amplify erectile function. Over the counter products such as Nitric Oxide supplements that support endothelial function, and vacuum erection devices such as penis pumps used often, can also benefit and support in-office shockwave treatments. There has been recent interest in the use of stem cells to treat ED. In animal studies, the injection of stem cells following prostate

radiation has shown restoration of erectile function via the regeneration of cavernosal nerves. Small phase 1 studies in humans have shown promising results in terms of tolerability, safety, and efficacy of use of intracavernosal stem cell transplant for the treatment of ED. Interestingly, a recent study has suggested that the combination of Li-ESWT and stem cell therapy may promote the growth of new blood vessels and decrease the destruction of cells within the penile corpora, more than either therapy alone. In addition to stem cells, platelet rich plasma (PRP) is also being used in conjunction with Li-ESWT to improve outcomes. Platelets produce growth factors which are important in wound healing and the growth of new blood vessels. Intracavernosal injection of PRP in animal models has shown improvement in erectile function in cases of neurogenic ED. This has been translated into human studies, and a recent study of patients with ED treated with PRP resulted in improvement in erectile function, with no serious adverse events.

Thomas A. Masterson M.D., a Miller School fellow in reproductive urology, is involved in a double-blind trial, randomized study in which 61 participants will receive PRP from their own blood. “When platelets are activated, they release many kinds of growth differentiation factors and a few types have been found to facilitate nerve repair and regeneration.”

Dr. Masterson continues “Moreover, corporeal dysfunction in ED due to smooth muscle atrophy or other intra-cavernosal pathology can lead to corpora-venous occlusive erectile dysfunction despite a normal arterial inflow. Rejuvenating the Corporeal tissues with PRP, which is well known for its growth and healing factors, is a possible modality as a potential treatment for erectile dysfunction.”

Restorative therapies specifically for ED, that combine low-intensity shock wave therapy, autologous platelet rich plasma and stem cells,

are promising but lack rigorous experimental data conclusively validating these therapies, according to a Sexual Medicine Society of North America (SMSNA) position statement. “Thus, given the current lack of regulatory agency approval for any restorative (regenerative) therapies for the treatment of ED and until such time as approval is granted, SMSNA believes that the use of shock waves combined with stem cells or platelet rich plasma is experimental and should be conducted under research protocols in compliance with Institutional Review Board approval.”

A novel combination treatment has recently received a lot of attention within the field. Many providers are turning to amniotic fluid as an acellular alternative to cellular treatments. Amniotic fluid can be comparable in costs to PRP, but with the potency of cellular treatments. This off-the-shelf product has been used extensively as an adjunct to shockwave by providers either through direct injection into the penis or by systemic administration.

Dr. Ian White of Neobiosis, a clinical stage manufacturer of amniotic fluid (AF) products, has been collecting data and observations from providers. “It’s remarkable but we’re hearing over and over again anecdotal accounts where AF alone has been given to patients and morning erections, long a thing of the past for many patients, have spontaneously returned. The pro-neurogenic and pro-angiogenic growth factors in AF are an essential cocktail, which when combined with shockwave therapy, appear to turn back the clock on reproductive health” said White.

The movement to make shock wave therapy a credible and widespread ED option is well on its way. As of writing, there are over 1,000 private practices In the US who are currently offering shockwave therapy for not just ED management, but also as a preventative and proactive modality designed to maintain and optimize a man’s sexual wellness.

PRODUCT ANNOUNCEMENTS

allergE+

Booth #311

Access Medical Laboratories

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allergE+ by Access Medical Laboratories is a state-of-the-art environmental & food allergy profile measuring total IgE antibodies for a vast array of environment and food sources. allergE+ evaluates 295 allergens using nano-bead technology. Results assist practitioners to curate diet and lifestyle guidance for their patients to reduce and eliminate symptoms related to adverse allergen reactions. Results are available within 24 hours!

G.I. InnerCalm™

Booth #701

Biocidin Botanicals

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G.I. InnerCalm™, an innovative gut powder from Biocidin Botanicals, is the next step in functional gastrointestinal support. The cliniciancrafted formula contains GutGard®, a clinically researched, flavonoid-rich, natural bioactive for daily digestive health.* Additional key ingredients include glycine to support collagen structure and vagus nerve function and chamomile and lemon balm for a healthy inflammatory and stress response.* An easy-to-mix powder in a delicious lemon-ginger flavor, G.I. InnerCalm™ offers localized support for widespread benefits.

BioDoph-3 GI™

Booth #211

Biotics Research Corporation

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BioDoph-3 GI™ is a synergistic probiotics formula containing three clinically validated probiotic strains shown to be effective in randomized and controlled trials. Mediated by targeted mechanisms such as production of short chain fatty acids, acetylcholine and polyphosphate granules, BioDoph-3 GI™ promotes intestinal barrier integrity, balances gut microflora, helps break down lactose and supports a healthy mood.

Vascanox HP

Booth #423

Calroy Health Sciences

Ph: 800-609-6409 . | www .calroy .com

Breakthrough Nitric Oxide Support* - Vascanox HP® is a breakthrough product providing nitric oxide support for up to 24 hours with a single dose.*† Vascanox HP supports the natural production, storage, and release of nitric oxide.*

*These statements have not been evaluated by the Food and Drug Administration.

This product is not intended to diagnose, treat, cure or prevent any disease. †As measured by saliva NO test strips in an open label IRBapproved study.

BPC 157

Booth #629

Clinicians Supplement Consultants

Ph: 855-272-7220 | www .cscprivatelabel .com

BPC 157 500mg with SNAC. BPC 157 (body protection compound 157) has emerged as a promising option for individuals with GI conditions. The largest challenge in effectively utilizing biological peptides, including BPC 157, is limited delivery due to poor bioavailability. One solution to this challenge may be the chaperone carrier salcaprozate sodium, or SNAC (sodium N-(8-[2hydroxybenzoyl]amino)caprylate. SNAC is an amino acid derivative of salicylic acid that is able to deliver peptides to the gastric lining. Compared to other vehicles, it does not require a protective enteric coating. SNAC was assigned GRAS status by the FDA and early research indicates that it may be more successful at delivering certain compounds to the GI tract.

Metabolomics Spotlight™

Booth #417

Designs for Health

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The Metabolomics Spotlight test provides an in-depth analysis of the function and efficiency of multiple aspects of an individual’s unique biochemistry to assist you in evaluating your client’s metabolic pathways and revealing their unique metabolic status.

AutoShip for Nutraceuticals

Booth #205

EVEXIAS Health Solutions

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Improve patient compliance, ease staff workload, and drive revenue with Autoship. EVEXIAS Health Solutions makes it simple to order, ship, and track supplements. Make it easy for your patients to stay on plan and maximize outcomes with recurring nutraceutical orders that ship automatically.

Patients deserve quality supplements

Booth #617

Fullscript www .fullscript .com

Fullscript’s quality standards ensure patients only access supplements from trusted brands and not large retailers or third-party resellers that can’t always pinpoint their sources. With one place to dispense and manage healthcare’s best supplements, you can become your patients’ best (and safest) source for wellness products. Learn more about how Fullscript evaluates quality, so you don’t have to: fullscript.com/lp/ supplement-quality-control

Microbiomix

Booth #705

Genova Diagnostics

Ph: 800-522-4762 . | www .gdx .net/products/microbiomix

Microbiomix offers metagenomic shotgun/ whole genome sequencing to assess your patient’s complete gut microbiome as well as its potential function. Metagenomics is considered the gold standard method to study the gut microbiota.1. Genova is proud to offer this to you and your patients in collaboration with Microba, who have world-leading technology in metagenomic analysis and interpretation. Microbiomix is available as a stand-alone profile or as an add-on to GI Effects Comprehensive Profile. Microbiomix complements the information provided on the GI Effects. This additional information may reveal treatable abnormalities that are not seen on GI Effects.

Fasting Shake

Booth #403

L-Nutra

Ph: 310-775-3655 . | www .ProLonProfessional .com

New from L-Nutra, the leader in fasting mimicking technology, comes ProLon Fasting Shake. This shake is the latest secret bio-hack for fat burn, performance, and a longevity lifestyle, allowing your patients to reap the benefits of intermittent fasting without hunger! Your patients can use ProLon’s Fasting Shake to replace breakfast, extend their intermittent fasting window and fat burn, or as a snack between meals.

Zenbiome™ DUAL

Booth #511

Microbiome Labs

Ph: 904-940-2208 . | www .microbiomelabs .com/home/

Announcing Zenbiome™ DUAL, a dual-action probiotic/psychobiotic combination supporting the gut-brain axis for digestive comfort and mood self-regulation. It is clinically demonstrated to support relieving occasional gastrointestinal discomfort and psychological stress. Zenbiome™ DUAL provides around-the-clock digestive maintenance for optimal gut health and overall well-being. *Supports the gutbrain axis for healthy mood balance * Helps address and overcome occasional stress * Supports energy, vitality, and mental acuity * Maintains normal, regular digestive processes * Addresses occasional episodes of functional GI distress

Semaglutide

Booth #711

Olympia Pharmaceuticals

Ph: 407-673-2222 . | www .olympiapharmacy .com/

SEMAGLUTIDE is now available from Olympia Pharmaceuticals! Stop by our booth to learn more about the popular weight loss product.

Glycocalyx Pro

Booth #202

Ortho Molecular Products

Ph: 800-332-2351 | www .orthomolecularproducts .com

Glycocalyx Pro helps to preserve, protect, and regenerate the endothelial glycocalyx by providing the foundational building blocks that make up the arterial wall’s defensive barrier. Using a combination of high-dose glucosamine sulfate, hyaluronic acid, and an organic complex of fucoidan and marine polyphenols, Glycocalyx Pro delivers full-spectrum support to strengthen and protect the glycocalyx. Glycocalyx Pro supports optimal circulation and blood flow, promotes the synthesis of nitric oxide and helps to maintain healthy vascular permeability.

Oxyhealth Mobile Clinic

Booth #305

Oxyhealth

Ph: 562-906-8888 . | www .oxyhealth .com

Oxyhealth is proud to present our newest offering A MOBILE CLINIC. Our Mercedes Mobile Clinic can be customized in many ways by bringing in all modalities. Hyperbaric therapy can be combined with IV therapy, light therapy and many more. Best of all you can bring it anywhere!

N1O1 Nitric Oxide Releasing Lozenges

Booth #401

Pneuma Nitric Oxide LLC

Ph: 877-476-3862 | www .N1o1 .com

Description: Developed by Dr. Nathan S. Bryan, the world’s leading expert on Nitric Oxide production, this nitric oxide generating supplement is specially formulated to rapidly help boost production in the body. It works to support the body’s natural Nitric Oxide production and provides a source of N.O. as it is dissolving in the mouth. Our innovative formula uses an advanced delivery system that provides an exogenous source of nitric oxide that may support the following: -Improve Nitric Oxide production. -Enhance oxygen and nutrient delivery to cells. -Support cardiovascular health. -Aid normal heart function. -Support healthy blood circulation and blood pressure. -Create healthy blood flow to the brain and other organs. -Deliver antioxidant support.-Support cognitive function and memory.

Longevity Phyto Caps

Booth #523

Quicksilver Scientific

Ph: 303-531-0861 . | www .quicksilverscientific .com

Biological aging is a natural progression where cellular processes and tissues begin to deteriorate over time resulting in age-related health declines.* Longevity Phyto Caps is an anti-aging formula specifically designed to support healthy aging by facilitating better cellular function, clearance of damaged cells, and stimulation of longevity pathways. Each two-capsule serving provides a proprietary blend of curcuminoid complex, quercetin, resveratrol, and trans pterostilbene in our highly bioavailable SEDS delivery technology for fast and efficient absorption of ingredients.*

Rupa Labshops

Booth #411

Rupa Health

Ph: 669-294-2703 . | www .rupahealth .com/labshop

We’re so excited to announce the launch of Rupa LabShops! With LabShops, you can create a custom e-commerce store to make testing available to your community or educational program participants. This is a new way for you to grow your business and improve access to testing for your clients! Here are some of the features you have access to with LabShops: • Access to over 3000 lab tests your clients can purchase through a signing physician • Add your own custom fee to each test or bundle and get paid out via Stripe once results come in for each client • Branded and custom to you – you can include your own logo, description, and video on the LabShop so your clients know the testing is recommended by you! • This is just the beginning of what LabShops has to offer – we can’t wait to see how you’ll use it to scale your impact and improve access to testing for your clients! support@rupahealth.com

New Compounded Thyroids

Booth #517 University Compounding Pharmacy

Ph: 800-985-8065 . | www .ucprx .com/physicians-how-toprescribe New Thyroid Formulas with no fillers

Stimulate the Power of the Vagus Nerve

The Vagus Nerve

The vagus nerve is the longest cranial nerve in the body and extends from the brainstem to the abdomen. It plays an essential role in communication between the brain and the other organs, and modulates various systems and functions along the way.

What is nVNS?

Non-invasive vagus nerve stimulation (nVNS) is an established therapy that sends gentle, patented electrical stimulation through the skin to stimulate the vagus nerve without surgery. nVNS offers a multi-modal mechanism of action, and the overlap and interplay of these mechanisms help to restore, reset, and replenish the parasympathetic balance.

Why gammaCore?

gammaCore (nVNS) is a hand-held, useradministered therapy that is proven to stimulate the vagus nerve1,2. Designed as an easy-to-use device with no downtime, it can be used alone or in combination with other chiropractic-based treatments you are already using in your practice. FDA-cleared with 6 indications for migraine and cluster headache, gammaCore can be used for acute and preventive use with short, 4-minute treatment times.

Neurotransmitter regulation and nociceptive modulation

Extinguish the Fire of In ammation with Nitric Oxide

All of the major chronic diseases, despite their underlying etiology, have the same hallmarks of ischemia, oxidative stress, immune dysfunction which all lead to uncontrolled chronic inflammation. Inflammation has been regarded as the “silent killer” for many decades now. Inflammation refers to your body’s process of fighting against things that harm it, like infections, injuries, and toxins, in an attempt to heal itself. Signs of inflammation refers to the heat (calor), pain (dolor), redness (rubor), and swelling (tumor) that characterize the clinical symptoms of inflammation as they were defined in the first century AD by the Roman scholar Celsus. The first stage of inflammation is when immune cells and platelets start to stick to the lining of the blood vessels. This causes a disruption in blood flow, activation of immune cells and production of oxygen

radicals that causes oxidative stress. When left unresolved, this causes damage to organs and to the blood vessels. In order to effective treat and mitigate inflammation without affecting our body to respond normally to injury and infection, we must first understand the mechanism of inflammation and then apply principles of applied physiology to restore normal biological functions. It appears that a single molecule, nitric oxide may be the master regulator of inflammation.

Nitric oxide is an endogenous signaling molecule that is produced throughout the body in many cell types to regulate many important physiology processes. In 1998, the Nobel Prize in Physiology or Medicine was awarded to three U.S. Scientists responsible for its discovery. The science is clear on what NO is

and how it affects every major chronic disease and mitigates the hallmarks of chronic disease, including ischemia, oxidative stress, immune dysfunction and inflammation. It can no longer be ignored by medical health care practitioners. NO is a gas with an extremely short half-life once it is produced [1]. However, there is clear evidence that NO can act as a hormone affecting distal tissue from original site of production [2]. Once produce NO dilates blood vessels and improves blood flow and oxygen delivery to every organ, tissue and cell in the body.

Nitric oxide has been shown to inhibit the earliest stages of microvascular inflammation [3]. Nitric oxide also controls the oxidative stress and immune dysfunction that occurs during inflammation [3]. If you can turn on nitric oxide production during earliest stages of inflammation you can control the inflammatory response as intended. Without nitric oxide production, the inflammation does not turn off and chronic inflammation occurs and chronic inflammation contributes to every major chronic disease.

Since nitric oxide appears to be critical for controlling inflammation, the key question becomes, how do we restore the production of NO. In order to answer this fundamental question, we must first understand how the body makes NO and then what goes wrong in people that become deficient. The functional loss of NO production through the enzyme nitric oxide synthase (NOS) in the endothelium is termed endothelial dysfunction. This enzymatic loss of NO precedes the structural changes (arterial stiffness, plague deposition, etc) in the blood vessel by many years sometimes decades and correlates with cardiovascular risks [4-7]. This type of vascular dysfunction occurs throughout the entire cardiovascular system and affects every organ in the body. Without sufficient NO production, this leads to the loss of regulation

of blood flow and circulation in every organ. As a result, blood pressure, inflammation, oxidative stress and immune dysfunction increase. Young and healthy persons can produce NO through the oxidation of L-arginine by the NOS enzyme. However, as we age, we lose our ability to synthesize NO from L-arginine (endothelial dysfunction) [8]. Therefore, products that contain L-arginine or L-citrulline can provide no benefit to the production of NO. Endotheliumindependent vasodilation does not change significantly with aging, demonstrating that the responsiveness to NO does not change only the ability to generate it. These observations enable us to conclude that reduced availability of endothelium-derived NO occurs as we age, and it is this abnormality that sets the stage for chronic inflammation that occurs in every major disease. This is illustrated in Figure 1.

Figure 1: The functional loss of endothelial nitric oxide production precedes the structural changes that occur in cardiovascular disease by many years. There is an age-related decline in nitric oxide production that leads to the onset and progression of CVD.

A compensatory pathway exists for nitric oxide production involving oral bacteria. This pathway is commonly referred to as the enterosalivary nitrate-nitrite-nitric oxide pathway and contributes bioactive nitrite and nitric oxide to the host that is independent of the NOS

derived NO [9, 10]. Human nitrate reduction is dependent upon bacteria since humans do not express a nitrate reductase gene and thus cannot metabolize nitrate. Inorganic nitrate (NO3-) and nitrite (NO2-) are naturally found in green leafy vegetables [11, 12] and are produced

Figure 2: Metabolism of nitrate to nitrite and nitric oxide. Nitrate requires oral bacteria for the 2-electron reduction to nitrite. Nitrite has biological activity itself but can also be reduced to nitric oxide by a number of mammalian systems and natural product chemistry.

endogenously in humans from the oxidation of NO [1]. Nitrate and nitrite are now considered essential nutrients [13, 14] necessary to form NO and other bioactive nitrogen oxides [1518]. The reduction of nitrate and nitrite to NO is complementary and compensatory to any disruptions in the NOS oxidation of L-arginine. After consuming a meal rich in nitrate, plasma nitrate increases after about half an hour and remain elevated for several hours (the plasma half-life of nitrate is 5–6 hours). Approximately 25% of the nitrate found in blood is actively taken up by the salivary glands and concentration can increase up to 20-fold in saliva [19, 20]. Now for the next 8-10 hours, each time we salivate, commensal facultative anaerobic bacteria found primarily in the crypts of the dorsal tongue reduce salivary nitrate to nitrite [10, 21]. If the

persons have the right oral microbiome, this leads to an increase in plasma nitrite approximately 90 minutes after consumption of a nitrate rich meal [20]. If the person does not have the correct nitrate reducing bacteria, then there is no nitric oxide benefit. Now for the next 8-10 hours every time saliva is swallowed and enters the acidic stomach (1–1.5 L per day), nitrite becomes protonated and forms nitrous acid (HNO2; pKa 3.3), which then becomes NO [17, 18]. A simplified human nitrogen cycle is illustrated in Figure 2. However, in people that use mouthwash or antacids, nitrate from diet or from supplementation will not lead to any increase in NO production [22, 23]. The increase in nitrite in plasma and saliva after nitrate supplementation are abolished in healthy subjects taking an antiseptic mouthwash. Over 200 million Americans use mouthwash daily. Not coincidently, over 200 million Americans have an unsafe elevation in blood pressure and do not and will not respond to dietary nitrate.

How do you find a product that can overcome all the limitations of patients who are nitric oxide deficient? Now comes the confusion. There are many companies out there promoting nitric oxide products. There are 4 categories of nitric oxide products.

1. Products that contain L-arginine and/ or L-citrulline. These products are useless. Our body makes sufficient levels of L-arginine to fully saturate the binding site of the NOS enzyme. L-citrulline is a bi-product of NO so it is not involved in NO production.

2. Beet root-based products. Most of these products do not contain sufficient nitrate or nitrite to lead to any NO formation. Most of these are “dead beat” products.

3. Nitrate based products. These products will not and do not work in the majority of

the population. Nitrate is inert in humans. Humans are unable to metabolize this molecule. The human body requires the presence of nitrate reducing bacteria to metabolize nitrate into nitrite and nitric oxide. If you don’t have the right nitrate reducing bacteria, you get no nitric oxide benefit from nitrate. In America alone, over 200 million people use antiseptic mouthwash on a daily basis. These mouthwashes have been shown to kill the good nitrate reducing bacteria and actually cause an increase in blood pressure. Many more Americans have active oral infections that disrupt the normal oral microbiome and disrupt nitrate reduction to NO. As a result, a nitrate-based product may only work in less than a third of the population. Nitrate is an important nutrient, but only if you are able to metabolize it to NO. Most people cannot and that is why they are nitric oxide deficient. Nitrate does not equal nitric oxide.

4. Nitriceuticals or products that produce authentic NO gas. This is a new product category based on my research and innovations over the past 20 years. Now that we understand how the hormone effects of nitric oxide work, we can develop product technology that actually generates nitric oxide gas in the human body. We can do this in the form of a lozenge that releases nitric oxide gas as it is dissolving in the mouth that is completely independent and does not rely on the oral microbiome or stomach acid. We can do this through powder forms that when dissolved in water and taken as a shot generate nitric oxide gas. There is really no other way to deliver nitric oxide outside a clinical setting.

As you can see from above, if you simply fix your nitric oxide production, the nitric oxide does everything else. It prevents the inflammation, oxidative stress and immune dysfunction that causes chronic disease. Nothing is more important for your health than ensuring your body makes enough nitric oxide and to restore endogenous NO production. We know how to make nitric oxide. More than 185,000 scientific publications reveal just how important this molecule is. Without it, you get sick and disease. With it, you have good health, free of disease. It’s that simple.

Resources:

1. Kelm, M., Nitric oxide metabolism and breakdown. Biochimica et Biophysica Acta, 1999. 1411: p. 273-289.

2. Elrod, J.W., et al., Nitric oxide promotes distant organ protection: Evidence for an endocrine role of nitric oxide. Proc Natl Acad Sci U S A, 2008. 105(32): p. 11430-11435.

3. 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.

4. Vita, J.A., et al., Coronary vasomotor response to acetylcholine relates to risk factors for coronary artery disease. Circulation, 1990. 81(2): p. 491-7.

5. Egashira, K., et al., Effects of age on endothelium-dependent vasodilation of resistance coronary artery by acetylcholine in humans. Circulation, 1993. 88(1): p. 77-81.

6. Taddei, S., et al., Age-related reduction of NO availability and oxidative stress in humans. Hypertension, 2001. 38(2): p. 274-9.

7. Celermajer, D.S., et al., Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet, 1992. 340(8828): p. 1111-5.

8. Torregrossa, A.C., M. Aranke, and N.S. Bryan, Nitric oxide and geriatrics: Implications in diagnostics and treatment of the elderly. Journal of Geriatric Cardiology, 2011. 8: p. 230-242.

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

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

11. Nunez De Gonzalez, M.T., et al., Survey of residual nitrite and nitrate in conventional and organic/natural/uncured/indirectly cured meats available at retail in the United States. J Agric Food Chem, 2012. 60(15): p. 3981-90.

12. Nunez de Gonzalez, M.T., et al., A survey of nitrate and nitrite concentrations in conventional and organic-labeled raw vegetables at retail. J Food Sci, 2015. 80(5): p. C942-9.

13. 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.

14. 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.

15. Bryan, N.S., et al., Nitrite is a signaling molecule and regulator of gene expression in mammalian tissues. Nat Chem Biol, 2005. 1(5): p. 290-7.

16. Zweier, J.L., et al., Enzyme-independent formation of nitric oxide in biological tissues. Nat Med, 1995. 1(8): p. 804-809.

17. Lundberg, J.O., et al., Intragastric nitric oxide production in humans: measurements in expelled air. Gut, 1994. 35(11): p. 1543-6.

18. Benjamin, N., et al., Stomach NO synthesis. Nature, 1994. 368(6471): p. 502.

19. Spiegelhalder, B., G. Eisenbrand, and R. Preussmann, Influence of dietary nitrate on nitrite content of human saliva: possible relevance to in vivo formation of N-nitroso compounds. Food Cosmet Toxicol, 1976. 14(6): p. 545-8.

20. Lundberg, J.O. and M. Govoni, Inorganic nitrate is a possible source for systemic generation of nitric oxide. Free Radic Biol Med, 2004. 37(3): p. 395-400.

21. Duncan, C., et al., Chemical generation of nitric oxide in the mouth from the enterosalivary circulation of dietary nitrate. Nat Med, 1995. 1(6): p. 546-51.

22. 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.

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

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NAD+, NMN, and spermidine – These are just a few of the nutraceuticals enthusiastically endorsed by the medical community for supporting healthy aging and longevity. However, what if another powerful longevitysupporting nutrient was hiding in plain sight?

Glutathione (GSH) is an antioxidant nutrient commonly found in detoxification supplements. However, its beneficial effects on aging have only recently begun to be investigated and appreciated by the medical community. Multiple lines of research point towards the essentiality of glutathione for healthy aging and longevity. There are four crucial drivers of biological aging: Free radical activity, detoxification, immune function, and genome stability – and all can be impacted by a patient’s glutathione levels. For instance, low serum glutathione levels are associated with a higher

incidence of age-related chronic diseases in older adults, suggesting that low glutathione may be a biomarker for biological aging.1 Low glutathione levels may also drive mitochondrial dysfunction, a hallmark of aging.2 In addition, glutathione is essential for detoxification, ridding the body of toxins that accelerate aging, and supports a resilient immune system, protecting us from microbial stressors that may drive the biological aging process.

Glutathione Provides Free Radical Control for Healthy Aging

The free radical theory of aging, proposed in 1954 by the doctor and scientist Denham Harman, argued that aging is caused by free radicals inflicting oxidative damage on molecules, cells, and tissues throughout the body.3 Free radicals are highly reactive

molecules with unpaired electrons that steal electrons from other molecules within the body, such as DNA and proteins, damaging those molecules in the process. When free radical activity outweighs the body’s antioxidant resources, which are necessary for quenching free radicals, oxidative damage results. Free radicals are produced internally as byproducts of cellular energy production and in response to external environmental exposures, such as excessive UV light and air pollution.

Recently scientists have proposed updating the free radical theory of aging to specifically highlight the harmful impact of free radicals on mitochondria, the cellular organelles responsible for generating energy and regulating cellular aging. Excessive mitochondrial free radical activity without sufficient antioxidant activity to counteract it, damages these delicate organelles, promoting mitochondrial dysfunction. Mitochondrial dysfunction is one of the nine hallmarks of aging, driving biological aging by damaging mitochondrial DNA, impairing ATP production, and compromising the synthesis of other critical coenzymes, such as NAD+.4,5

Few antioxidants are more important than glutathione for maintaining healthy mitochondrial function. While mitochondria naturally produce some free radicals as byproducts of ATP synthesis, mitochondrial glutathione defends against excessive mitochondrial free radical activity. It also plays a role in ATP production pathways.6,7 Mitochondrial glutathione levels decrease by up to 50 percent with age, rendering these organelles more susceptible to oxidative damage and dysfunction.8,9 Therefore, a glutathione deficiency may drive biological aging by compromising mitochondria.

Preliminary research suggests that bolstering glutathione levels may restore healthy mitochondrial function and promote

longevity. For example, supplementation with GlyNAC, a combination of glycine and N-acetylcysteine, in older adults raises red blood cell glutathione levels, reverses mitochondrial impairments, tempers oxidative stress, and alleviates other symptoms of aging, including increased body fat and slow gait speed.10 In mice, glutathione supplementation improves cardiovascular function by restoring a healthy antioxidant balance within mitochondria.11 Finally, in a cell culture study, liposomal glutathione has been found to protect neurons against oxidative stress.12 These thought-provoking findings suggest that glutathione replenishment may control free radical activity, supporting a mitochondrial environment favorable for healthy aging.

Glutathione Supports Detoxification of Gerontogens

The human "exposome" is defined as the milieu of toxins we are exposed to throughout our lifetime. A growing body of research points towards the exposome as a causative factor promoting biological aging. In fact, the term “gerontogen” was created in 1987 to specifically describe environmental toxins that are associated with biological aging. Examples of gerontogens include air pollution, such as nitrogen dioxide and PM2.5, and heavy metals.13,14

Studies indicate that environmental toxins significantly contribute to many age-related health conditions. For example, lead and aluminum exposure are both associated with accelerated aging in organisms. Lead alters DNA methylation and the integrity of histones, the tiny proteins around which DNA is wound, promoting brain aging through epigenetic mechanisms.15 Prolonged exposure to low levels of aluminum can also promote brain aging and neurodegeneration and may play a role in the development of neurodegenerative diseases like Alzheimer's disease.16

Glutathione is well known for its role in detoxification, and its importance for gerontogen detoxification is no exception. It is required for Phase I and Phase II of detoxification, in which chemicals are activated and then conjugated in preparation for elimination. It is necessary for detoxifying age-accelerating heavy metals and particulate matter.17,18 Glutathione deficiency slows down detoxification and may lead to an increase in biological susceptibility to toxins, which may subsequently accelerate the aging process and reduce longevity. Conversely, raising glutathione levels may improve the body's detoxification capacity, capabilities, and resilience, supporting a healthier aging process.

Glutathione Regulates Immune Function

Several significant changes occur in the immune system during the aging process. For example, the bone marrow and thymus gland reduce the production of B and T cells, crucial cells involved in the body’s immune responses to pathogens. In addition, lymphocytes, a type of white blood cell, decline in function, becoming less efficient at targeting harmful microbes.19 Together, these shifts in the immune system make the body more susceptible to infections and subclinical, nonproductive inflammation. These significant shifts in immune function with age help explain why older adults are more vulnerable to various infections, including COVID-19, influenza, and nosocomial infections.20,21,22

A decline in glutathione status may underlie the adverse immune system changes during aging and replenishing glutathione may attenuate these changes and support a healthier immune response. In aging mice, glutathione supplementation has been found to improve glutathione levels in the spleen, a crucial and underappreciated immune organ, and enhanced T-cell-mediated immune responses.23 T-cell immune responses are vital for protecting the body against viruses and other pathogens. In healthy adults, oral liposomal glutathione supplementation for

one month was found to increase natural killer cell cytotoxicity and lymphocyte proliferation, both indicators of enhanced immune function.24 An immune system without sufficient glutathione is significantly limited in its ability to protect the body against microbial stressors; glutathione deficiency is likely a significant but underappreciated driver of immune dysfunction with age.

Glutathione Supports Genome Stability

Genome instability, defined as the increased tendency for DNA mutations and other genetic changes to occur during cell division, is a hallmark of aging.25 Genome instability reduces the fidelity with which genetic material is copied during cell division, resulting in cells with potentially problematic mutations.

Supplemental GlyNAC, a glutathione precursor discussed earlier for its impacts on mitochondrial function, improves genomic stability in mice. In fact, it increased their lifespan by 24 percent compared to mice not supplemented with GlyNAC.26 Therefore, glutathione may play a role in preventing and correcting genomic damage and improving genomic stability.

Glutathione: An Underappreciated Longevity Nutrient

Understanding glutathione’s impact on biological aging can be a huge benefit to your practice. Checking glutathione status in your patients and including glutathione supplementation in your longevity protocols is a great place to start.

You can test your patients’ glutathione status directly with a red blood cell glutathione test. Indirect testing for glutathione status with an organic acids test (OAT) can also be helpful. An OAT measures levels of organic compounds in the blood and urine that are produced in the body as byproducts of biochemical pathways. On the OAT test, pyroglutamate

is a functional marker of glutathione status; when elevated, it signifies an increased demand by the body for glutathione.

If red blood cell glutathione is low and pyroglutamate is high, glutathione supplementation is warranted to increase glutathione levels. However, the bioavailability of encapsulated glutathione supplements is limited in the gastrointestinal tract due to the presence of stomach acid and intestinal enzymes that may denature glutathione. Liposomal glutathione, on the other hand, provides a way to significantly

Resources:

1. Perez LM, Hooshmand B, Mangialasche F, Mecocci P, Smith AD, Refsum H, Inzitari M, Fratiglioni L, Rizzuto D, & Calderon-Larranaga A. Glutathione serum levels and rate of multimorbidity development in older adults. J Gerontol. 2020; 75(6): 1089-1094.

2. Thomas NO, Shay KP, & Hagen TM. Age-related loss of mitochondrial glutathione exacerbates menadione-induced inhibition of Complex I. Redox Biol. 2019; 22: 101155.

3. Harman D. Free radical theory of aging: history. EXS. 1992; 62: 1-10.

4. Ziada AS, Smith MSR, & Cote HCF. Updating the free radical theory of aging. Front Cell Dev Biol. 2020; 8: 575645.

5. Van der Rijt S, Molenaars M, McIntyre RL, Janssens GE, & Houtkooper RH. Integrating the hallmarks of aging throughout the tree of life: A focus on mitochondrial dysfunction. Front Cell Dev Biol. 2020; 8: 594416.

6. Mari M, de Gregorio E, de Dios C, Roca-Agujetas V, Cucarull B, Tutusaus A, Morales A, & Colell A. Mitochondrial glutathione: Recent insights and role in disease. Antioxidants. 2020; 9(10): 909.

7. Nguyen D, Samson SL, Reddy VT, Gonzalez EV, & Sekhar RV. Impaired mitochondrial fatty acid oxidation and insulin resistance in aging: novel protective role of glutathione. Aging Cell. 2013; 12(3): 415-425.

8. Sastre J, Pallardo FV, & Vina J. The role of mitochondrial oxidative stress in aging. Free Radic Biol Med. 2003; 35(1): 1-8.

9. Suh JH, Heath SH, & Hagen TM. Two subpopulations of mitochondria in the aging rat heart display heterogeneous levels of oxidative stress. Free Radic Biol Med. 2003; 35(9): 1064-1072.

10. Kumar P, Liu C, Hsu JW, et al. Glycine and N‐acetylcysteine (GlyNAC) supplementation in older adults improves glutathione deficiency, oxidative stress, mitochondrial dysfunction, inflammation, insulin resistance, endothelial dysfunction, genotoxicity, muscle strength, and cognition: Results of a pilot clinical trial. Clin Transl Med. 2021; 11(3): e372.

11. Strutynska N, Goshovska Y, Mys L, Strutynskyi R, Luchkova A, Fedichkina R, Okhai I, Korkach Y, & Sagach V. Glutathione restores the mitochondrial redox status and improves the function of the cardiovascular system in old rats. Front Physiol. 2023; 13:1093388.

12. Zeevalk GD, Bernard LP, & Guilford FT. Liposomal-glutathione provides maintenance of intracellular glutathione and neuroprotection in mesencephalic neuronal cells. Neurochem Res. 2010; 35(10): 1575-1587.

13. Ward-Caviness CK et al. Long-term exposure to air pollution is associated with biological aging. Oncotarget. 2016; 7(46): 74510-74525.

enhance glutathione bioavailability, elevating glutathione stores and reducing oxidative stress.24

Glutathione status is a profoundly modifiable variable involved in healthy aging and longevity. By supporting robust glutathione levels in your patients, you can reduce multiple drivers of biological aging - free radical activity, detoxification, immune function, and genome stability – stemming the tide of aging and supporting youthful health and vitality.

14. Bondy SC et al. Prolonged exposure to low levels of aluminum leads to changes associated with brain aging and neurodegeneration. Toxicology 2014; 315: 1-7.

15. Eid A & Zawia N. Consequences of lead exposure, and it's emerging role as an epigenetic modifier in the aging brain. Neurotoxicology. 2016; 56: 254-261.

16. Bondy SC. Prolonged exposure to low levels of aluminum leads to changes associated with brain aging and neurodegeneration. Toxicology 2014; 315: 1-7.

17. Sears ME. Chelation: Harnessing and enhancing heavy metal detoxification—A review. Sci World J. 2013; 2013: 219840.

18. Romieu I, Castro-Giner F, Kunzli N, & Sunyer J. Air pollution, oxidative stress and dietary supplementation: a review. Eur Respir J. 2008; 31: 179197.

19. Montecino-Rodriguez E, Berent-Maoz B, & Dorshkind K. Causes, consequences, and reversal of immune system aging. J Clin Invest. 2013; 123(3): 958-965.

20. Mueller AL, McNamara MS, & Sinclair DA. Why does COVID-19 disproportionately affect older people? Aging (Albany NY). 2020; 12(10): 9959-9981.

21. Keilich SR, Bartley JM, & Haynes L. Diminished immune responses with aging predispose older adults to common and uncommon influenza complications. Cell Immunol. 2019; 345: 103992.

22. Katz MJ & Roghmann MC. Healthcare-associated infections in the elderly: What’s new. Curr Opin Infect Dis. 2016; 29(4): 388-393.

23. Furukawa T, Meydani SN, & Blumberg JS. Reversal of age-associated decline in immune responsiveness by dietary glutathione supplementation in mice. Mech Ageing Dis. 1987; 38(2): 107-117.

24. Sinha R, Sinha I, Calcagnotto A, Trushin N, Haley JS, Schell TD, & Richie JP. Oral supplementation with liposomal glutathione elevates body stores of glutathione and markers of immune function. Eur J Clin Nutr. 2018; 72(1): 105-111.

25. Vijg J & Suh Y. Genome instability and aging. Annu Rev Physiol. 2013; 75: 645-668.

26. Kumar P, Osahon OW, & Sekhar RV. GlyNAC (Glycine and N-acetylcysteine) supplementation in mice increases the length of life by correcting glutathione deficiency, oxidative stress, mitochondrial dysfunction, abnormalities in mitophagy and nutrient sensing, and genomic damage. Nutrients. 2022; 14(5): 1114.

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EXHIBITOR LISTINGS

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A4M

Booth #500

1801 N Military Trail, Ste 110 Boca Raton, FL, 33431

Ph: (561) 997-0112

Email: info@a4m.com

www.a4m.com

Rooted in a forward-focused mission to redefine modern medicine, The American Academy of Anti-Aging Medicine (A4M) is the global leader for continuing medical education in longevity medicine, metabolic resilience, and whole-person care. A4M provides an advanced network of educational and networking opportunities including traditional CME events, intensive curriculum-based courses, certification programs, in-depth workshops, and more. A4M has acquired membership of over 26,000 members, which includes physicians, nurses, and researchers, that represent over 120 nations.

Access Medical Labs

Booth #311

5151 Corporate Way, Jupiter, FL, 33458

Ph: (866) 720-8386

Email: info@accessmedlab.com

www.accessmedlab.com

Access is the nation’s premier specialty diagnostic lab. We offer a broad menu of testing from blood, saliva, urine & swab samples. We perform all of your tests in our 25,000 sq. ft. ultra-automated facility in Jupiter, Florida & provide results within 24hrs. Since 2003, we continuously strive to innovate, inspire and improve solutions for physicians by providing an exceptional personalized experience with the most accurate testing.

Acigi / Dr. Fuji

Booth #1016

4399 Ingot Street, Fremont, CA, 94538

Ph: (510) 651-9088

Email: marketing@drfuji.com

www.drfuji.com

Dr. Fuji, the King of Medical Massage Chair Health & Wellness massage equipment, is the fruit of further evolution of intelligent pneumatic and mechanical milttechnology designed to partner with medical and health professionals in their clinical stress managements.

Aesthetic Management Partners

Booth #1019

9109 Macon Road, Ste 120 Cordova, TN, 38016

Ph: (877) 267-2670

Email: info@amplifimd.com

www.aestheticmanagementpartners.com

At AMP we believe that patients come first. Delivering on the experience and result for the patient is the key to building a thriving practice. We do that by getting the patient a phenomenal result, which in turn will get the physician an excellent financial result. If it’s good for the patient, good for the physician, and good for AMP, and it’s right course of action. This is what guides us in everything we do.

Affordable Anti-Aging

Booth #1116

515 E. Las Olas Blvd., Ste 120 Fort Lauderdale, FL, 33301

Ph: (888) 610-3068

Email: affordableantiaging@protonmail.com

www.affordableantiagingcenter.com

Our company brings an accessible and innovative science-based program to physicians’ offices to increase patients’ health span. We offer a 360º approach to anti-aging by using advanced diagnostic technology and systems that help to slow and even reverse the aging process in an affordable and effective way.

Alami

Booth #129

1720 Diplomacy Row, Orlando, FL, 32809

Ph: (407) 927-6000

Email: info@organoleaf.com

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Organoleaf Hemp based Wholesale, Private Label, Distribution, Packaging, and Manufacturing, Company. We’re a trusted manufacturer of premium hempderived CBD topicals and more. Our products contribute to the overall balance of a healthier lifestyle. We source our hemp and CBD from organic farms in USA, and our products are manufactured in an FDA registered facility that practices GMP.

Algaecal

Booth #223

300 - 1128 Homer Street, Vancouver, B.C, V6B 6M5

Ph: (888) 573-4591

Email: clinicalsupport@algaecal.com

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AlgaeCal is the ONLY calcium formula supported by 3 clinical studies to INCREASE bone density. Our exclusive red algae provides over a dozen bone-essential minerals. Our companion product Strontium Boost helps speed bone-building while also improving bone quality. Stop by our booth for a free gift (while supplies last) that reveals the latest bone-health research and provides a roadmap to offer your patients better bone-health outcomes. Or contact us at hcp.algaecal.com or 1 (888) 573-4591.

Alletess Medical Laboratory

Booth #1115

14 Howard Street, Rockland, MA, 02370

Ph: (800) 225-5404 Ext. 312

Email: chloe@foodallergy.com

www.foodallergy.com

Founded in 1980, Alletess Medical Laboratory has been providing allergy and immunology testing services to clinicians worldwide. Our highly knowledgeable staff, cutting-edge medical technology, and customized wellness programs allow us to provide high-quality laboratory testing and services to our clients. We understand that test results impact patient lives, every day we strive to provide test results with actionable information to clinicians to improve patient’s health and quality of life. The test result is the beginning of the journey.

American Biotech Labs

705 E 50 South, American Fork, UT, 84003

Ph: (801) 756-1000

Email: larissa.valdez@ablmedical.com

www.silverbiotics.com

American Biotech Labs is a Utah-based developer and manufacturer of silver based products. We believe that strengthening one’s physical well-being will further the ability to live a more balanced life, including mentally, spiritually, and empower an active lifestyle with confidence. By combining the healing properties of nature and the power of science, American Biotech Labs develops products in an affordable way so that everyone has the ability to live life to it’s fullest.

One Amgen Center Drive, Thousand Oaks, CA, 91320

Ph: (805) 447-1000

Email: medinfo@amgen.com

www.amgen.com

Amgen is committed to unlocking the potential of biology for patients suffering from serious illnesses by discovering, developing, manufacturing and delivering innovative human therapeutics. This approach begins by using tools like advanced human genetics to unravel the complexities of disease and understand the fundamentals of human biology. For more information, visit www.amgen. com and follow us on www.twitter.com/amgen

190 Corporate Blvd., Georgetown, KY, 40324

Ph: (888) 388-1119

Email: hello@anandaprofessional.com

www.anandaprofessional.com

Ananda Professional is the leading practitioner only hemp derived cannabinoid brand. With a mission to champion the knowledge, safety and efficacy of cannabinoid products, we’ve invested over $40 million in research to advance the clinical evidence of hemp extract. We transcend the ‘CBD’ category, harnessing the full potential of the many cannabinoids and terpenes found in hemp for rapid patient outcomes.

Anazaohealth

Booth #632

5710 Hoover Blvd, Tampa, FL, 33634

Ph: (800) 995-4363

Email: jvillalona@anazaohealth.com

www.anazaohealth.com

AnazaoHealth is a national specialty compounding pharmacy. With a 30,000-square-foot 503B FDARegistered Outsourcing Facility in Las Vegas and a 46,000-square-foot traditional 503A compounding pharmacy in Tampa. Both facilities have the appropriate licensure to conduct business in all 50 states, District of Columbia, and selected U.S. territories. AnazaoHealth compounds preparations for Aesthetics, Age Management, Weight Management, IV & Injection Therapy Solutions, Sexual Wellness Solutions, Hormone Replacement, Personalized Hair Care Solutions, Mental Clarity & Acuity &and more.

Apex Energetics

Booth #811

16592 Hale Ave., Irvine, CA, 92606

Ph: (800) 736-4381

Email: Inezcossio@apexenergetics.com

www.apexenergetics.com

Our motto—Patient Health First™—reflects our mission. It is also our guiding principle that dictates all decisions, from raw material acquisition to manufacturing to our strong practitioner relationships. Over the past 30+ years, we have built a reputation of integrity by infusing everything we do with this principle, and we remain at the forefront of Functional Medicine discoveries and advances with formulations spearheaded by Datis Kharrazian PhD, DHSc, DC, MS, MMSc, FACN.

Argentyn 23 By Natural-Immunogenics

Booth #529

7504 Pennsylvania Ave, Sarasota, FL, 34243

Ph: (941) 702-6100 Ext 303

Email: seth@n-icorp.com

www.argentyn23.com

Since its launch in 2001, thousands of clinics worldwide have chosen Argentyn 23 Bio-Active Silver Hydrosol™ and First Aid Gel. Argentyn 23 is produced through a proprietary manufacturing technique that results in the smallest particles achievable with greater than 98% positively charged bio-active silver ions and silver nanoclusters. Visit us at our booth to learn more about you can harness the power of silver and copper, our newest hydrosol, in your practice.

Aspen Laser-Theralight

Booth #103

175 North 1800 West, Ste 108 Lindon, UT, 84604

Ph: (303) 916-7673

Email: kathy@aspenlasers.com

www.aspenlaser.com-theralight.com

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Avacen Medical

Booth #1123

2365 Camino Vida Roble, Unit C Carlsbad, CA, 92011

Ph: (619) 417-8319

Email: djforsgren@avacen.com

www.avacen.com

AVACEN Medical® is a leading provider of drug-free, noninvasive, over-the-counter pain relief and wellness devices, as well as diagnostics for cardiovascular stress and disease. Our devices provide pain relief using heat therapy and negative pressure on the palm of your hand and are classified as FDA Cleared Class II medical devices indicated for: minor muscle pain, join pain and stiffness, joint pain associated with arthritis, muscle spasms, minor strains and sprains, muscle relaxation, and temporary increase of local circulation.

Aviv Clinics

Booth #836

2955 Brownwood Blvd., Ste 100 The Villages, FL, 32163

Ph: (352) 488-2848

Email: info@aviv-clinics.com

www.aviv-clinics.com

Aviv Clinics offers the world’s most advanced hyperbaric oxygen therapy treatment protocol, the Aviv Medical Program, at their clinics in the United States and Dubai to combat the cognitive and physical effects of aging.

Ayumetrix Llc

Booth #234

17387 63Rd Ave, Lake Oswego, OR, 97035

Ph: (503) 344-1344

Email: info@ayumetrix.com

www.ayumetrix.com

AYUMETRIX is a “smart lab of the future” and has been founded to empower individuals to take charge of their health and wellness using innovative sample collection and laboratory testing technologies. It is a global hormone testing laboratory that partners with clinicians all around the world and offers a practice building package that is inclusive of integrative and functional laboratory testing services, personal health data acquisition/ analysisall under the guidance from industry experts.

Berkeley Life

Booth #622

355 East Ohio St., Ste 200 Chicago, IL, 60661

Ph: (773) 750-7745

Email: john.halbert@lifes2good.com

www.berkeleylife.com

Berkeley Life’s Nitric Oxide support products are used by top practitioners around the country. Nitric Oxide is produced naturally by your body. It’s responsible for promoting artery vasodilation which relaxes the muscles in your blood vessels allowing for healthy blood flow and circulation. Berkeley Life’s Nitric Oxide support products include a Dietary Nitrate Supplement, patented Test Strips. Used together, this system provides tools for assessing and supporting Nitric Oxide levels from head to toe.

Biocidin Botanicals™

Booth #701

18 Hanger Way, Ste A Watsonville, CA, 95076

Ph: (800) 775-4140

Email: questions@biocidin.com

www.biocidin.com

Biocidin Botanicals™ is a leader in botanical supplements and a pioneer in the arena of microbiome health. Its flagship broad-spectrum botanical blend Biocidin® was formulated in 1989 in response to challenging health conditions related to microbial imbalances. More than 30 years later, the company offers a curated line of targeted support products to boost patient health. Healthcare practitioners have utilized these clinically effective, evidence-based products for over three decades to help millions of patients achieve vibrant health and wellness.

Bioclinic Naturals

Booth #730

#104-3686 Bonneville Place, Burnaby, B.C, V3N 4T6

Ph: (888) 826-9625

Email: customerservice@bioclinicnaturals.com

www.bioclinicnaturals.com

Bioclinic Naturals® is a Canadian nutraceutical manufacturer of a professional product line comprised of fertility kits and supplements, Essential Fatty Acids, mitochondrial support, detox support, PCOS support, and natural stress and sleep aids.

Our goal is to provide the best quality, tested, raw materials. Whenever possible we grow our own plant-based ingredients and any raw material we do not produce ourselves is subjected to the highest level of scrutiny to ensure the quality and purity.

Bioprotein Technology

Booth #436

5706 Benjamin Center Dr., Ste 114 Tampa, FL, 33634

Ph: (800) 280-2456

Email: info@bioproteintech.com

www.bioproteintech.com

BioProtein Technology is the home of BioPro+, the first of its kind Bioidentical alternative to synthetic Rx HGH - Growth Hormone treatments. Since 2009 BioProtein Technology has been developing & providing physicians with cutting edge alternatives to common invasive antiaging and regenerative treatments that work FASTER, are EASIER to use, and are 100% SAFE.Whether it’s hormones, weight loss, libido, vitality or even sleep & stress, BioProtein Technology has you covered.

Bioreference Laboratories

Booth #633

41 Slater Dr., Elmwood Pk., NJ, 07407

Ph: (516) 659-0761

Email: afein@bioreference.com

www.bioreference.com

For more than four decades, BioReference has built a legacy based on scientific excellence, innovation and world-class service in laboratory testing solutions. Amidst a tidal wave of change in healthcare in recent years, BioReference has evolved, adding significant services and solutions aimed at addressing the needs of today’s customers. BioReference offers scientific expertise and laboratory innovation in oncology, urology, and women’s health, with a focus on streamlining services to create a unique healthcare experience.

Biosculpt

Booth #1001

72 SE 6 Ave., Apt E Delray Beach, FL, 33483

Ph: (833) 692-4626

Email: info@bioantiage.com

www.biosculpt.info

BioSculpt shrinks fat and builds muscle by using Magnetic Muscle Stimulation (MMS) technology to force extremely powerful muscle contractions that are not possible with even the most rigorous workouts.

Biotics Research

Booth #211

5245 Business Park Drive, Rosenberg, TX, 77469

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. Biotics Research’s Lab is now ISO Certified! 1-800-231-5777 www.bioticsresearch.com

Body Logic Md

Booth #1101

4850 T Rex Ave, Boca Raton, FL, 33431

Ph: (561) 452-8544

Email: dastern@bodylogicmd.com

www.bodylogicmd.com

Founded in 2003, BodyLogicMD continues to grow! We are one of the nation’s largest networks of highly-trained practitioners specializing in integrative medicine, bioidentical hormone replacement therapy, and supplements. BodyLogicMD is a turn-key solution for practitioners who are looking to maximize their practice revenue and personal time, while gaining clinical support from a network of practitioners with diverse board certifications and specializations.

Bodysite

Booth #1012

230 N. Congress Avenue,Bay A12 Lake Park, FL, 33403

Ph: (561) 247-3839

Email: info@bodysite.com

www.bodysite.com

BodySite is a remote patient care and monitoring platform that helps doctors automate patient education and manage patients between encounters to improve patient outcomes and increase practice revenue. Easily enroll patients into care programs so patients receive your guidance and instructions everyday. Patients can track progress including body metrics, calories, steps, activity, water, sleep and more. Provide better care and support in a fraction of the time, right from the palm of your hand.

Boiron

Booth #433

4 Campus Blvd., Newtown Sq., PA, 19073

Ph: (610) 325-8358

Email: carol.angelo@boiron.com

www.boironusahcp.com

Boiron, world leader in homeopathic medicines, is best known for its popular Arnicare® line of pain relievers and Oscillococcinum® flu medicine. Founded in 1932 by Jean and Henri Boiron, the company provides a full line of low-risk options to benefit consumers and health care professionals in more than 50 countries.

Boston Heart Diagnostics

Booth #114

200 Crossing Blvd, Framingham, MA, 01702

Ph: (877) 425-1252

Email: customercare@bostonheartdx.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 #932

195 Willis St., Bedford, OH, 44146

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!

Brooksville Pharmaceuticals

Booth #116

16410 Flight Path Dr., Brooksville, FL, 34604

Ph: (352) 667-8135

Email: admin@brooksvillerx.com

www.brooksvillerx.com

Brooksville Pharmaceuticals is an independent pharmacy located in Brooksville, Florida. We are dedicated to providing friendly, outstanding, personalized service to all of our customers. Brooksville Pharmaceuticals is privately owned and operated by pharmacists. Our team has extensive experience in our current product offering and in the retail side of our business. As a result of this, we have established a great name for ourselves and take great pride in providing extra special service and individualized attention to our customers.

Bti Biotechnology Institute

Booth #635

Jacinto Quincoces 39, Vitoria-Gasteiz, Pais Vasco, ES5801007

Ph: 945160652

Email: pheredia@bti-health.com

www.bti-biotechnologyinstitute.com/en

BTI Biotechnology Institute was founded in 1999 by Dr. Eduardo Anitua, current President and Scientific Director of the company and today it is one of the leading companies in implantology and oral rehabilitation, as well as an international scientific benchmark in the application of regenerative therapies in different areas of medicine, from the field of oral surgery to specialties such as traumatology, dermatology, ophthalmology, sports medicine, cardiovascular, plastic and aesthetic surgery, among others.

Calmoseptine, Inc.

Booth #636

16602 Burke Lane, Huntington Beach, CA, 92647

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.

Calroy Health Sciences

Booth #423

14362 N Frank Lloyd Wright, Ste 1000 Scottsdale, AZ, 85260

Ph: (800) 609-6409

Email: support@calroy.com

www.calroy.com

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

Cell Life Usa

Booth #432

7427

33173

Ph: (305) 492-5341

Email: sales@celllifeusa.com

www.celllifeusa.com

Our Organ Cell Therapy dietary supplement products are distributed to Doctors throughout the USA. Cell therapy is the administration of specific peptides, or processed cells from specific organs, to support human health problems and prevent deterioration due to aging of the targeted organs and organ systems. The purpose of cell therapy is to repair or enhance the function of aged tissues or organs.

Cell Science Systems

Booth #832

852 S. Military Trail, Deerfield Beach, FL, 33442

Ph: (800) 872-5228

Email: rweldon@cellsciencesystems.com

www.cellscienesystems.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 a FDA inspected and registered cGMP medical device manufacturer meeting ISO EN13485 standards.

Cellustrious Hair Restoration

Booth #233

11630 Woodleaf Dr., Bradenton, FL, 34211

Ph: (727) 231-6689

Email: info@cellustrious.com

www.cellustrious.com

We offer a non-invasive, plant peptide-based treatment for hair loss developed by a biochemist and trichologist, backed by clinical trials with a 90% success rate.We offer training that allows doctors and med spa professionals.

Center For Pain & Stress Research Ltd.

Booth #918

3679 Lake Shore Boulevard West, Toronto, ON, M8W 1P7

Ph: (800) 859-8869

Email: drbruce@mpstherapy.com

www.dolphinmps.com

Center for Pain and Stress Research Ltd. (CPSR) is an educational and research-based company focused on studying the effect and magnitude scars & traumas have on health, cognitive functioning and human longevity. CPSR research direction is currently exploring the influence of Vagal Nerve stimulation on COVID vaccine-related POTS and dysautonomia

Central Drugs Compounding Pharmacy

Booth #317

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 #332

10900 Wilshire Blvd., Ste 600 Los Angeles, CA, 90024

Ph: (310) 560-2918

Email: tommyu@chromadex.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.

Clarke Bioscience

Booth #1037

17448 Highway 3, Ste 140 Webster, TX, 77598

Ph: (281) 217-0092

Email: chris@clarkebioscience.com

www.clarkebioscience.com

Clarke Bioscience focuses on manufacturing specialized nutraceutical compounds to support overall health and wellbeing, including brain, bone, and immune health.With neuroscientist Dr. Lewis Clarke as the founder, Clarke Bioscience uses the same protocols Dr. Clarke has been using in hospital and clinical settings for decades.We emphasize a biochemical-based approach to health maintenance, completely backed by a strong foundation of cutting-edge scientific research and evidence.

Clinicians Supplement Consultants

Booth #629

180 Froehlich Farm Blvd., Woodbury, NY, 11797

Ph: (855) 272-7220

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.

Cognivue

Booth #919

7911 Rae Blvd., Victor, NY, 14564

Ph: (585) 203-1969

Email: events@cognivue.com

www.cognivue.com

Cognivue® is leading the way with Cognivue Thrive® and Clarity®, the first FDA-cleared, computerized cognitive testing devices. Our passion it to elevate the gold standard of cognitive health assessment and empower action with early detection. Cognivue® can help differentiate your practice through a holistic, patient-centered approach.

College Pharmacy

Booth #729

3505 Austin Bluffs Pkwy, Ste101 Colorado Springs, CO, 80918

Ph: (800) 888-9358 Ext. 171

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.

Cre8 Pharmacy Group

Booth #328

3700 Nw 126Th Avenue, Coral Springs, FL, 33065

Ph: (888) 224-5181

Email: david@cre8rx.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.

Cryoconcepts

Booth #1004

1100 Conroy Place, Easton, PA, 18040

Ph: (855) 355-2796

Email: support@cryoconcepts.com

www.cryoconcepts.com

CryoConcepts offers world class cryotherapy products that are designed to be used by skincare professionals to treat a variety of skin indications and skin issues - from removing hyperpigmentation and skin tags to tightening and firming fine lines and wrinkles.

Cyrex Laboratories

Booth #428

2602 S. 24Th Street, Ste 307

Phoenix, AZ, 85034

Ph: (602) 759-1245

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 antigenic intestinal and blood-brain barrier permeability – gateways to autoimmunity; environmental trigger screening including dietary antigens, pathogens and xenobiotics; and multitissue antibody testing for predictive biomarkers of autoimmune reactivity. Through continuous collaboration with leading experts in medical research and clinical practice, Cyrex develops innovative assays that assess the cross-connections between the body’s immune, gastrointestinal and neurological systems.

Cytox Ltd

Booth #833

40 Hampshire Road, Mahwah, NJ, 07430

Ph: (551) 427-5143

Email: alzheimers@vanguardpharma.com

www.alzheimers-risk-test.com

Cytox provides non-invasive, risk assessment and patient stratification tools for Alzheimer’s disease and dementia. It’s primary technology is genoSCORE(TM) a genetic test to predict future risk of cognitive decline due to Alzheimer’s disease (AD). The test, which uses a simple blood or saliva sample, analyzes patient genotypes against an array of over 100,000 single nucleotide polymorphisms (SNPs) associated with AD. The test is available in the US as the Sampled Alzheimer’s Risk Test.

Daiwa By U.S Jaclean, Inc.

Booth #905

1816 W. 135Th St., Gardena, CA, 90249

Ph: (310) 538-2298

Email: sales@usjaclean.com

www.daiwamassage.com

U.S. Jaclean has been a pioneer in bringing healing techniques into your home through original, expertlydesigned productssince 1982.Headquartered in California with facilities nationwide, we run our own warehouses right here in the United States. Our mission: To improve health and wellness through quality products that can be used from the comfort of home. Our family of brands has grown and diversified, always staying on the cutting edge of health and wellness technologies.

Davinci Laboratories

Booth #1018

929 Harvest Lane, Williston, VT, 05495

Ph: (802) 878-5508

Email: bkanya@foodsciencecorp.com

www.davincilabs.com

Our focus is on improving lives by producing quality doctor formulated supplements derived from real nutrients—create supplements that make a difference and take standards to a higher level. Within every DaVinci product, you can trust that you will always receive the very best.

Designer Drugs Pharmacy

Booth #823

7304 Jarnigan Rd., Chattanooga, TN, 37421

Ph: (423) 954-2585

Email: form-submission@squarespace.info

www.designerdrugs.us

For more than 20 years, Designer Drugs has been working with patients and physicians to be the preferred sterile and non-sterile compounding, anti-aging, and specialty pharmacy destination for providers and patients through delivering bestin-class service and designing specialty solutions for our patients and offering creative clinical consultations and precision protocols to our providers. Our pharmacy proudly compounds ophthalmics, injections, dermatologic preparations, hormone replacement options, and more. Designer Drugs is licensed to ship prescriptions to ALL 50 STATES.

Designs For Health, Inc.

Booth #417

980 South Street, Suffield, CT, 06078

Ph: (860) 623-6314

Email: kdouglass@designsforhealth.com

www.designsforhealth.com

Our Mission: Designing a Well WorldWe 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 science-based 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.

141 Peyerk Ct., Unit D

Romeo, MI, 48065

Ph: (586) 532-1150

Email: torlando@dexaplus.com

www.dexaplus.com

DEXA+ is a provider DEXA Scanners and an educator of the benefits of DEXA and the 3 Critical Health Markers (Bone Health, Body Composition and Visceral Fat, the number predictor of heart disease and Type 2 Diabetes.) Our Scanners and Programs provide State of the Art equipment and leading technology for clinics. If you would like to include DEXA in your clinic DEXA+ is the leader in the industry. Contact us to learn more.

Diagnostic Solutions Lab

Booth #728

31 Lupi Court, Ste 250 Palm Coast, FL, 32137

Ph: (877) 485-5336 Ext 8010

Email: Heather.Whitt@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.

Doctor Multimedia

Booth #1024

8070 La Jolla Shores Dr., #528 La Jolla, CA, 92037

Ph: (800) 679-3309

Email: info@doctormultimedia.com

www.doctormultimedia.com

We’re a team of energetic, young professionals. We’re successful for one simple reason: no one can outwork us. We’re open 24 hours a day, 7 days a week, 365 days a year. We do it out of passion, and because that’s when our clients need help. We have graphic designers, WordPress developers, social media masters, content creators, SEO wizards, IT problem solvers, and marketing gurus, ready to help your medical practice thrive.

Doctor’S Data, Inc.

Booth #611

3755 Illinois Ave., St. Charles, IL, 60174

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.

Dutch Test

Booth #505

3138 NE Rivergate, #301C

McMinnville, OR, 97128

Ph: (503) 678-2050

Email: events@dutchtest.com

Precision Analytical created the DUTCH Test (dried urine test for comprehensive hormones) to help providers solve complex patient cases. DUTCH is a group of validated tests that provide a complete evaluation of sex and adrenal hormones, including metabolites._ The simple and convenient at-home collection for patients, and clinical support on every DUTCH report, puts you in the driver’s seat—allowing you to solve your patients’ most complex hormone issues.

Electrocore, Inc.

Booth #900

200 Forge Way, Ste 205 Rockaway, NJ, 07866

Ph: (888) 903-2673

Email: CustomerService@electroCore.com

www.gammacore.com

gammaCoreTM is the first non-invasive vagus nerve stimulator (nVNS) indicated for preventive and acute treatment of migraine and cluster headaches in adolescents (age 12 and older) and adults. As well as the acute treatment of episodic cluster headache, hemicrania continua, and paroxysmal hemicrania in adults. The device utilizes mild transcutaneous electrical stimulations to activate the vagus nerve. gammaCore can be used as a stand-alone treatment or with pharmaceuticals without concerns of adverse drug interactions.

Empower Pharmacy

Booth #835

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

Ph: (877) 562-8577

www.empowerpharmacy.com

Houston-based Empower Pharmacy is the nation’s most advanced compounding pharmacy PCAB®-accredited 503A. Their 503B outsourcing facility strictly adheres to the FDA’s current good manufacturing practices (CGMPs). Empower’s vision is to expand access to quality, affordable medications and mission is to be premier compounding pharmacy and outsourcing facility delivering innovative pharmaceutical solutions to patients and providers.

Enara Health

Booth #137

3050 S. Deleware St., Ste 130 Santa Mateo, CA, 94403

Ph: (650) 319-8654

Email: partnerships@enarahealth.com

www.enarahealth.com

Enara helps clinics launch, manage, and staff insurancecovered cardiometabolic and obesity programs. Our platform includes: revenue cycle management, nutrition and exercise programs, obesity medication protocols, a mobile app for patients , and virtual provider staffing. The platform delivers an average weight loss of 17-19% at 24 months. We operate on a risk share model and you only pay us after insurance has paid you. Stop by our booth and join our network today.

Ergo-Flex Technologies

Booth #435

136 Poplar Circle, Ste 403 Conroe, TX, 77304

Ph: (936) 588-5510

Email: sales@ergoflextechnologies.com

www.ergoflextechnologies.com

Ergo-Flex Technologies, LLC. is the developer, manufacturer, and distributor of the Total Brain & Body O2 a software-driven (IHHT) Intermittent Hypoxia/Hyperoxia Training system. Total Brain & Body O2 Therapy is designed to facilitate healing by super-saturating nearly all body tissues (especially brain, kidney, liver), plasma and lymph with very high levels of oxygen that permeates the tissues through an exercise component.

Evexias Health Solutions

Booth #205

920 S. Kimball Ave., Southlake, TX, 76092

Ph: (833) 839-4735

Email: vic.kuzmovich@evexias.com

www.evexias.com

EVEXIAS Health Solutions is the single solution that opens a world of possibility in your practice. When join the EVEXIAS network, you gain access to tools and education that fuel your integrative medicine practice, giving you an edge on the competition and optimizing care for your patients. From strategic partnerships with leading compounding pharmacies to medical education on the latest therapies and business strategies designed for cash-based integrative medical practices.

Fagron Genomics

Booth #1117

807 Las Cimas Parkway, 145 Austin, TX, 78746

Ph: (844) 258-5564

Email: Info@gxsciences.com

www.gxsciences.com

Fagron Genomics / GX Sciences is an advanced genetic testing company / laboratory based in Austin, TX that empowers providers and their patients with the most comprehensive Nutrigenomic (NGx) and Pharmacogenomic (PGx) testing interpretation platform available. Our customized reporting platform is specifically designed for clinicians by medical professionals and allows the provider to validate a patient’s specific nutritional needs, laboratory recommendations, lifestyle recommendations, and health precautions based on the patient’s individual DNA findings.

Floré By Sun Genomics

Booth #817

5151 Shoreham Place, Ste 105 San Diego, CA, 92122

Ph: (661) 888-4799

Email: Customerservice@sungenomics.com

www.flore.com

Truly custom-formulated probiotics based on a Complete Gut Microflora Test. We analyze the trillions of microbes in your gut microflora and craft a unique formula for your unique gut health needs. Our formulas are designed so you only have to take onepill-a-day and we cold ship it directly to your door.

1992 Lewis Turner Blvd., Fort Walton Beach, FL, 32547

Ph: (888) 366-7070

Email: info@formula30a.com

www.formula30a.com

Formula30A produces premium all-natural fullspectrum hemp extracts, including CBD and CBG oils, for healthcare providers and their patients. We prioritize purity, quality, and effectiveness, with patent-protected, water-based manufacturing processes and multistage third-party lab testing to ensure products meet the standards healthcare professionals expect. Formula30A’s goal is to become the most trusted cannabinoid source for the medical community by aligning with industry experts and offering products containing pure ingredients, accessible only through licensed healthcare providers.

Fotona

Booth #134

4343 W Royal Lane, Ste 116 Irving, TX, 75063

Ph: (972) 598-9000

Email: info@fotona.org

www.fotona.com

Globally recognized for exceptional product performance and versatility, Fotona’s award-winning aesthetic lasers include the revenue-boosting SP Dynamis, TimeWalker and StarWalker. With over 50 years of laser expertise and industry leadership, Fotona has sold over 30,000 lasers worldwide with distribution in over 60 countries. Fotona’s reputation for excellence is earned from its dedication to R&D, unparalleled quality, reliability, ease-of-use and durability.

Fullscript

Booth #617

9185 E Pima Center Pwky , Ste 200 Scottsdale, AZ, 85258

Ph: (866)-807-3828

Email: marketing@fullscript.com

www.fullscript.com

Fullscript® is a digital health platform that helps practitioners build better patient relationships through quality supplementation and intuitive tools for treatment adherence — all at no cost.Practitioners write online supplement plans or dispense supplements in-office, giving patients easy access to high-quality products and education for optimal health.

Gainswave®

Booth #623

2980 NE 207Th St., Ste 503

Aventura, FL, 33180

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 #705

63 Zillicoa St., Asheville, NC, 28801

Ph: (828) 210-7362

Email: kworley@gdx.net

www.gdx.net

Genova Diagnostics is a leading clinical laboratory applying systems-based testing approaches to the diagnosis, treatment and prevention of complex chronic disease. Genova specializes in clinical laboratory services with actionable information. Testing service areas include gut health, nutritional status, immune function, hormonal health and specialty testing. To learn more, visit www.gdx.net.

German-French Society For Thymus Therapy

Booth #930

Place Du Marche, Grimaud, 83310

Ph: +66 816639399

Email: info@thymus-therapie.org

www.thymus-therapie.org

German-French Society for Thymus TherapyThymus Therapy and many other natural Therapies used in medicine for stimulating the immune system, but mostly applied in beauty for skin rejuvenation, mesotherapy, anti-wrinkles and cell vitality. Ask us and we will educate you.

Global Life Rejuvenation

Booth #206

168 East Main Street, Denville, NJ, 07834

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.

Grail

Booth #1028

1525 Obrien Drive, Menlo Park, CA, 94025

Ph: (650) 542-0372

Email: customerservice@grail.com

www.galleri.com

GRAIL, LLC. has the mission to detect cancer early. The Galleri test complements guideline-recommended screenings, and can detect a cancer signal across more than 50 types of cancer through a routine blood draw. When cancer is detected, the Galleri test can predict the cancer signal origin with high accuracy. For more information visit Galleri.com.

Hallandale Pharmacy

Booth #111

2666 SW 36Th St, Ft. Lauderdale, FL, 33312

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.

Harmony Care Llc

Booth #1118

9940 Sunriver Medaows, Las Vegas, NV, 89148

Ph: (562) 338-6995

Email: expo@harmonycarellc.com

www.harmonycarellc.com

Percussive Devices

Hawaiian Moon

Booth #1119

321 S. Missouri Ave., Clearwater, FL, 33756

Ph: (888) 256-3276

Email: customerservice@hmaloe.com

www.aloecream.biz

Say Goodbye to Dry Skin with Hawaiian Moon Organic Aloe Cream! It is free of dyes, fragrance, parabens, sulfates, mineral oil_, and any other harsh chemicals, including petroleum. Our cream penetrates the skin up to 7 layers deep, and absorbs into the skin instantly.

Healthgevity

Booth #429

21A Allen Ave, Allenhurst, NJ, 07711

Ph: (833) 940-4898

Email: support@healthgev.com

www.healthgev.com

Healthgevity is focused on supporting healthy aging, increasing healthspan and prevention. We partner with leading healthcare professionals and organizations around the globe to translate breakthrough science into advanced nutritional supplements that you can count on with your patients.

Heart Care Corp.

Booth #924

25 E Main, Chattanooga, TN, 37408

Ph: (423) 580-0246

Email: lbroyles@heartcarecorp.com

www.heartcarecorp.com

We are the authorized distributor of the Multifunction Cardiogram.

Hormone Therapy Centers Of America

Booth #922

5 Cowboys Way, Ste 300 Frisco, TX, 75034

Ph: (469) 213-2792

Email: tyrichardson@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

Booth #106

P.O. Box 7634, Olympia, WA, 98507

Ph: (800) 780-9126

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. We specialize in mushroom mycelium-based supplements to support natural immunity and whole body wellness.* We are based near the Olympic Rainforest in Washington state.*These statements have not been evaluated by the Food and Drug Administration. These products are not intended to diagnose, treat, cure, or prevent any disease.

Hue Light Usa

Booth #117 & 118

P.O. Box 960, Rock Hill, NY, 12775

Ph: (845) 796-9951

Email: info@huelightusa.com

www.huelightusa.com

Hue Light is always here to help you on your healing journey. We know that nothing can compare to good vibes and healthy energy, so let us provide them for you—your health means everything to us.

Human Power Of N Company

Booth #122

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

Ph: (512) 487-7025

Email: events@humann.com

www.humann.com

HumanN was founded in affiliation with a leading academic research program and is committed to promoting healthy circulation and blood flow. Its products are widely used by physicians, consumers, and athletes alike, including over 120 Professional and Collegiate sports teams. HumanN is a pioneer in the field of beet-based and polyphenol enervation of Nitric Oxide, a vital molecule in healthy circulation. HumanN’s product lines include #1 selling beetbased brands and leading product franchises such as SuperBeets, BeetElite, and Neo40.

Hushmail For Healthcare

Booth #731

580 Hornby St., Ste 360 Vancouver, B.C, V6C3B6

Ph: (778) 945-3240

Email: sales@hushmail.com

www.try.hushmail.com/a4m2023

Hushmail is an all-in-one, HIPAA-compliant solution for small healthcare practices to communicate with their patients securely. Send and receive confidential information with any patient using our secure email service. Get patients to fill and sign your forms online – no more lost, illegible, or incomplete forms.

Immunocine Cancer Center

Booth #628

3422 Business Center Dr. , Ste 1123 Pearland, TX, 77584

Ph: (888) 575-2572

Email: care@immunocine.com

www.immunocine.com

Immunocine was founded with the sole purpose of bringing a revolutionary immunotherapy to cancer patients unable to participate in ongoing FDA Clinical Trials.The Immunocine team is comprised of a talented medical team, leading cancer researchers, and a dedicated concierge team. Based out of Cancun, Mexico, Immunocine treats the cancer patients of today seeking the cancer treatment of tomorrow.

Inbody

Booth #1017

13850 Cerritos Corporate Dr.,Unit C Cerritos, CA, 90703

Ph: (323) 932-6503

Email: convention@inbody.com

www.inbodyusa.com

Since 1996, InBody has helped our medical clients to provide the highest standard of care. We equip healthcare professionals with in-depth insights and custom solutions that empower you to design personalized treatment plans for your patients. Utilizing non-invasive technology proven in over 5,500 clinical studies, InBody’s BIA devices deliver highly accurate assessments of fluid balance, muscle mass, and fat distribution. This data has versatile applications for the anti-aging, functional, sports, bariatric, diabetes, and regenerative medical fields. Learn more by visiting inbody.com.

Ixcela

Booth #214

135 South Rd, Bedford, MA, 01730

Ph: (781) 538-6614

Email: info@ixcela.com

www.ixcela.com

Ixcela is the only company using a fingerstick blood test to measure metabolites related to the functionality of the gut microbiome. Using values obtained from Ixcela’s CLIA-certified lab testing, physicians can attain key details about their patients’ health—such as the presence of gut dysbiosis or damage to the gut lining, whether the individual is missing nutrients in their diet, and whether stress and inflammation are drivers of symptoms—as well as targeted interventions to address them.

Jinfinit Precision Medicine

Booth #906

1235 Walton Way, Augusta, GA, 30901

Ph: (706) 831-8882

Email: hello@jinfiniti.com

www.jinfiniti.com

Jinfiniti Precision Medicine, under the leadership of Professor Jin-Xiong She, is a leading CLIA laboratory for biomarker testing and nutraceutical formulation, with a specific focus on longevity and human performance optimization. The company uses datadriven solutions to optimize health and extend healthspan for clinicians and individuals. Jinfiniti’s athome NAD test kit is the only commercially available test of its kind. Additionally, Jinfiniti offers a variety of nutraceuticals, specialized longevity biomarker panels, and senolytic tests crucial for anti-aging programs.

Kbmo Diagnostics

Booth #301

4 Business Way, Hopedale, MA, 02332

Ph: (617) 933-8130

Email: jwhite@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.

King Kongin LLC

Booth #933

4928 Pointe Midtown Way, Palm Beach Gardens, FL, 33418

Ph: (410) 805-3447

Email: info@kingkongin.com

www.kingkongin.com

KING KONGIN is here to inspire you and give you the energy you crave and the power you need. Our Zero Sugar Energy Drinks are designed to support healthy immunity while providing a boost of energy and hydration. King Kongin contains 200mg of Natural Caffeine from Tea and Essential Vitamin we need to boost energy all day. Come find your Beast Mode. Mango Pineapple will provide an excellent source of energy that is perfect for Intermittent Fasting.

L-Nutra

Booth #403

5905 Legacy Drive, 5th Floor Plano, TX, 75024

Ph: (310) 775-3655

Email: aperez@l-nutra.com

www.l-nutra.com

At L-Nutra, we’re spearheading a global movement to turn sick care into health care. We believe food – one of the few things you consume continually – is a key to health, longevity and preventing and curing disease. We’re using groundbreaking science and natural, plantbased solutions to prove it. In short, we’re here to change the world and usher in an entirely new kind of proactive health care. This is the nutritech revolution.

Lumisque

Booth #107

304 Indian Trace, Ste 276 Weston, FL, 33326

Ph: (469) 907-4908

Email: support@co2lift.com

www.lumisque.com

CO2Lift Carboxy gel, the fastest way to better skin, is a medical grade brand of cosmeceuticals that utilizes the powerful benefits of Carbon Dioxide to regenerate. The line features: CO2Lift Pro, an advanced super-hydrating gel treatment that helps solve aging skin problems. It can be used as a stand alone for skin health or for pre-treat/post -treat to reduce complications, speed healing and enhance results. CO2LiftV, a vulva/vaginal carboxy treatment which can be done in the privacy of the home.

Medico Bio Corporation

Booth #430

500 N State College Blvd, Ste 1100 Orange, CA, 92868

Ph: (949) 508-5605

Email: rose.c@medicobiomed.com

www.medicobiomed.com

Our Medico Bio Corp produces FDA Cleared PDO Threads which are in great quality with latest technology. Our mission is to provide the leading industry of PDO threads with an unbeatable quality and to coordinate with all physicians and nurses with low price compared to other companies. Our threads are called Accel PDO Threads which come in various sizes that fulfill the needs of different preferences that each practitioners own themselves.

Metagenics Llc

Booth #829

25 Enterprise, Ste 200 Aliso Viejo, CA, 92656

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 30 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 #511

1332 Waukegan Rd, Glenview, IL, 60025

Ph: (904) 940-2208

Email: info@microbiomelabs.com

www.microbiomelabs.com

At Microbiome Labs, we pioneer health by connecting the dots of the human biological system, so we can discover new solutions that revolutionize healthcare. As your practice partner, we strive to help and support through education, inspiration, and by bridging the therapeutic gaps of what global consumers—who face ever-growing modern life health challenges—need for healing. Backed by Novozymes OneHealth, a biotech world leader, we control every step of the innovation and formulation process, from strain discovery to final product.

MNML Aesthetics

Booth #733

2360 Campbell Creek Blvd, Ste 530 Richardson, TX, 75082

Ph: (214) 945-3044

Email: info@mnmlaesthetics.com

www.go.mnmlaesthetics.com

MNML Aesthetics is a global leader in the sale of top aesthetic laser technology and other energy-based devices. Our company’s vision derives from the modernization and development of aesthetic therapies with exclusive attention towards supplying efficacious technologies and optimizing return on investment for our clients.

Mosaic Diagnostics

Booth #535

8400 W 110Th Street, Ste 500 Overland Park, KS, 66210

Ph: (913) 341-8949

Email: sales@mosaicdx.com

www.mosaicdx.com

Mosaic Diagnostics delivers the industry’s most respected diagnostics, research, and educational support providing practitioners with actionable data from a partner they can trust. With over 25 years of experience, first as Great Plains Laboratory and now as Mosaic Diagnostics, we have been at the forefront of functional medicine testing, bringing clarity to complex health conditions and providing practitioner with the tools to create personalized treatment protocols.

Myadvice

Booth #634

1850 West Ashton Blvd., Ste 500 Lehi, UT, 84043

Ph: (435) 575-7470

Email: sales@myadvice.com

www.myadvice.com

Your business needs to be online to stand a chance against your competitors. MyAdvice provides a proven, comprehensive suite of products designed to simplify and maximize your marketing efforts and increase revenue. Transform your practice with any of our Digital Marketing Power Suite products. No matter your practice’s needs, we have a wide selection of products that are made to improve your online presence.

Mymycolab

Booth #229

5230 Land O’ Lakes Blvd., Ste 2002 Land O’ Lakes, FL, 34639

Ph: (813) 575-7934

Email: testing@mymycolab.com

www.mymycolab.com

MyMycoLab is a laboratory specializing in blood serum antibody testing for mycotoxins. Our laboratory tests for 12 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.

Neo7Bioscience

Booth #216

539 W. Commerce St., Ste 2886 Dallas, TX, 75208

Ph: (619) 850-1610

Email: customer.care@neo7bioscience.com

www.neo7bioscience.com

Neo7Bioscience specializes in the development of individualized peptide designs for patients with active diseases as well as for patients seeking to prevent disease and enhance longevity. Every custom design is based on genetic and expressed risk factors unique to each patient and guides the manufacturing of individualized peptide therapies.

Neobiosis

Booth #917

305 SW 7th Terrace, Gainesville, FL, 32601

Ph: (864) 353-5781

Email: kathy@neobiosis.com

www.neobiosis.com

Neobiosis is shaping the future of regenerative therapies through clinical research, product development, and manufacturing.

NES Health

Booth #1112

3702 W Spruce St, #1100 Tampa, FL, 33607

Ph: (407) 949-8674

Email: tracy.teclaw@neshealth.com

www.neshealth.com/p/drtracynd

NES Health leads the world in Bioenergetics with over 30 years of scientific research and provides a complete system to restore health and energy at its source. By looking at the physics underlying the biochemical nature of the body, we can now analyze and correct the body’s bio-field and information which has been shown to be the master control system for the body’s health. NES identifies and corrects these distortions, so the body can more naturally return to optimum function.

6130 W Flamingo Rd, Ste 865

Las Vegas, NV, 89103

Ph: (888) 321-1235

Email: info@doctorsnano.com

www.doctorsnano.com

Neumi® manufactures glutathione and related peptide formulas via HydroStat® Nano-Technology. This proprietary process uses ultra-pure water to maximize absorption, bioactivity and efficaciousness ~ achieving cell penetration within seconds and unprecedented health results. Steven K. Scott, 17-year glutathione expert, acclaimed author and famed TV infomercial master, founded Neumi®. Doctors Nano LLC represents a collective of Neumi® professional members distributing these affordable, convenient and powerful formulas for recovery, performance and anti-aging to health professionals and their clients.

Next Wellness

Booth #1100

8762 Lake Tibet Court , Orlando, FL, 32836

Ph: (800) 639-8609

Email: Jay@nextwellness.com

www.nextwellness.com

BRINGING YOU WHAT’S NEXT IN WELLNESS EQUIPMENT! NEXT Wellness is here to provide you with state of the art equipment, top notch training, and support. We are excited to bring you the 100% electric PowerCab, 100% electric e*Cabin, the Kaasen for localized cryotherapy, body sculpting and pain management, ContourPod with infrared lights and vibration bed, ZeroBody Dry Float for state of the art floating experiences, BodyStyler AIR for lymphatic drainage and body sculpting! We look forward to collaborating with you!

Nudora. Com Inc.

Booth #231

1013 Centre Rd., Ste 403-B

Wilmington, DE, 19805

Ph: (702) 712-1461

Email: info@nudora.com

www.nudora.com

Nudora is an innovative probiotic company with an outside of the box mindset. Nudora probiotic’s proprietary formulation was developed and created using scientific studies to help reduce one’s body’s inflammation-pain, improve sleep and aid in weight loss management. Nudora Probiotic are in vegetarian delayed release capsules. Nudora prides itself on supporting our partners. Included with all orders will be exclusive product knowledge training on how to sell & inform your patients about the benefits of Nudora provided by a pharmacist.

Numedica

Booth #722

9503 E. 55th Place,

Tulsa, OK, 74145

Ph: (800) 869-8100

Email: projectmanager@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.

Nutramax Laboratories Consumer Care, Inc.

Booth #228

946 Quality Drive, Lancaster, SC, 29720

Ph: (888) 886-6442

Email: contactus@nutramaxlabs.com

www.nutramaxlabs.com

Avmacol®, Avmacol® Extra Strength, and Avmacol® Physician’s Formula are formulated with beta glucans for additional immune health support, and manufactured in the US by Nutramax Laboratories Consumer Care, Inc. All are formulated with glucoraphanin and active myrosinase enzyme for production of sulforaphane to help increase phase 2 enzyme activities essential for elimination of certain toxins from the body. Avmacol® has been the brand chosen for numerous clinical trials in the United States and other countries.

Nutridyn

Booth #528

5414 Hwy. 12, P.O. Box 219 Maple Plain, MN, 55359

Ph: (800) 444-9998

Email: info@nutridyn.com

www.nutridyn.com

NutriDyn is proud to be a 3rd generation familyowned business that continues to focus on providing healthcare professionals with premium-quality nutritional supplements and educational services to optimize the health of their patients.We pride ourselves on continually providing cutting-edge research and products to our partners in health by hosting conferences, workshops, and seminars. The purity of ingredients, reliability of claims, and product effectiveness is why many practitioners worldwide trust NutriDyn as their partner in health.

Nutritional Frontiers

Booth #923

3191 Washington Pike, Bridgeville, PA, 15017

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.

O3UV

Booth #1106

11968 Sweetwater Dr., Grand Ledge, MO, 98837

Ph: (517) 282-9772

Email: https://o3uv.com/pages/contact

www.o3uv.com

O3UV provides cutting-edge Ozone and UV light equipment to integrative clinics. It’s our mission to see the widespread relief of physical suffering all over the globe. In order to see this goal realized, we believe medicine must be practiced in a different way. By integrating alternative modalities such as Ozone/UV light into medicine, we hope to achieve a future where wellness and physical restoration is realized through the union of traditional and progressive treatments.

Olympia Pharmaceuticals

Booth #711

6700 Conroy Road, Ste 155 Orlando, FL, 32835

Ph: (407) 673-2222

Email: sales@olympiapharmacy.com

www.olympiapharmacy.com

At Olympia Pharmaceuticals, we understand the importance as well as the necessity of offering both 503A and 503B compounding pharmacy capabilities. Each of these designations of compounders plays a crucial role in filling today’s compounding landscape. With our two separate, state-of-the-art facilities, Olympia supports both patient-specific and office-use needs across the U.S., enabling our customers to comply with all national and state regulatory requirements while having the convenience of a single-source pharmacy partner.

Ortho Molecular Products

Booth #202

28160 W. Northwest Hwy, Ste 100 Barrington, IL, 60010

Ph: (800) 332-2351

Email: l.grendel@ompimail.com

www.orthomolecularproducts.com

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

Outcomemd

Booth #323

9000 Sunset Blvd, Floor 3 West Hollywood, CA, 90069

Ph: (878) OUT-COME

Email: sales@outcomemd.com

www.outcomemd.com

OutcomeMD, Inc., based in Los Angeles, CA, is a digital outcome tracking platform that helps healthcare professionals elevate care and allows patients to celebrate their medical outcomes. Patients are empowered with coordinated care, timely symptom management and medical goal transparency. Providers receive data that informs treatment decisions and drives new business. OutcomeMD is delivering the future of healthcare today!

OxyHealth

Booth #305

10719 Norwalk Blvd, Santa Fe Springs, CA, 90670

Ph: (562) 906-8888

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.

Booth #800

111 Canfield Ave, Ste A7 Randolph, NJ, 07869

Ph: (973) 714-9136

Email: melissa@pellecome.com

www.pellecome.com

Pellecome is a medical company that introduced the Re3 Advanced Pellet Delivery System for Men and Women, a medical device kit that enables clinicians of any specialty to insert pellets easily and safely, every time. The kit includes an insertion tool with needle guide, precision scalpel and convenient needle filler. The Pellecome insertion device places pellets in a perfect line every time, providing consistent hormone absorption and minimizing patient discomfort and risk of pellet extrusion.

Pharmanex / Get Healthy Usa

Booth #929

2728 Wymberly Dr., Jupiter, FL, 33458

Ph: (561) 972-1122

Email: drsteve@gethealthyusa.net

www.gethealthyusa.net

Get Healthy USA offers an end-to-end solution of objective assessment, nutrigenomics, and product solutions coupled with the ability to monitor a patient’s progress while adding significant cash revenue to the practice.The program utilizes a small, in-office, non-invasive device that measures antioxidants and oxidative stress with lab equivalent test results provided in real-time. This technology is revolutionary and changing the way physicians make nutrition and nutrigenomic recommendations to improve tissue regeneration, inflammation and the overall health of the patient.

Physician Lab Inc.

Booth #1103

4850 T-Rex Ave., Ste 150 Boca Raton, FL, 33431

Ph: (877) 316-8686

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.

Pneuma Nitric Oxide LLC

Booth #401

2407 S. Congress Ave., Ste E-134 Austin, TX, 78704

Ph: (877) 476-3862

Email: hello@N1o1.com

www.n1o1.com

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.

www.N1o1.com for Pneuma Nitric Oxide LLC

Pnoe,

Inc.

Booth #1000

67 Maplewood St., Malden, MA, 02148

Ph: (650) 670-4450

Email: info@pnoe.com

www.pnoe.com

PNOĒ’s mission is to enable health professionals to provide training and nutrition as medicine by leveraging the power of breath analysis. We founded our solution on breath analysis because it’s the most holistic assessment of human physiology and provides vital insights for personalized nutrition and training programs. Through the PNOĒ ecosystem, any doctor, gym, or health-related business can provide the most advanced nutrition and health optimization program possible without any training, hiring, or upfront cost.

Precision Point Diagnostics

Booth #1136

9 Dunwoody Park, Ste # 122 Dunwoody, GA, 30338

Ph: (678) 735-6374

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.

Prestige Products Direct

Booth #1109

12440 SW 117 Ct., Miami, FL, 33186

Ph: (305) 234-8081

Email: triaddirect@gmail.com

www.triadaer.com

Triad Aer. Professional Air Purification system

Prevencio, Inc.

Booth #333

11335 NE 122 Way, Ste # 105 Kirkland, WA, 98034

Ph: (832) 590-9803

Email: arao@prevenciomed.com

www.prevenciomed.com

Prevencio offers highly accurate, novel AI-driven HART blood tests for cardiovascular disease developed in partnership with Massachusetts General Hospital (MGH). HART tests use Machine Learning + Multiple Proteins + Proprietary Algorithms to surpass accuracy of currently available cardiovascular tests.Two tests available for patients: • HART CVE™ –blood test for 1-year risk of heart attack, stroke or cardiac death; • HART CADhs™ – blood test for obstructive coronary artery disease diagnosis.

Prism Light Pod

Booth #723

13303 E. Adams Aircraft Circle, Englewood, CO, 80112

Ph: (720) 664-4929

Email: info@prismlightpod.com

www.prismlightpod.com

Prism Light Pod is the leading innovator of wholebody red light therapy systems for the wellness industry and winner of the 2020, 2021 & 2022 LuxLife Award for Best and Most Powerful Red Light Bed. Developed by a team of passionate health professionals and industrial engineers, Prism Light Pod, headquartered in Denver, CO, develops the most powerful, energy efficient and 100% automated/ optimized full-body, photobiomodulation systems in the industry that speeds recovery up to 10 times faster.

Professional Health Products

Booth #901

P.O. Box 97227, Pittsburgh, PA, 15229

Ph: (800) 245-1313

Email: hlord@phpltd.com

www.phpltd.com

Cutting corners when it comes to quality is an alltoo-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 1978. Our integrity and ingenuity go into every product in our comprehensive line; making the partnership we have with clinicians above industry standard. From homeopathy to pristine NZ glandulars, we offer a wide range of products that can be used by clinicians for various conditions.

Progenabiome

1835 Knoll Dr., Ventura, CA, 93003

Ph: (805) 339-0549

Email: marketing@progenabiome.com

www.progenabiome.com

A genetic sequencing research laboratory dedicated to continuing the work of the late Dr. Sydney Finegold, a man who recognized the power of anaerobic bacteria and spent his life correlating microbes to diseases.Our mission: Crack the genetic code of a trillion bacteria, fungi and viruses that live in our gut. Our hopes: Find cures to diseases that we feel are caused by alteration of the gut flora

Progressive Medical

5161 Magnolia Bay Circle, Palm Beach Gardens, FL, 33418

Ph: (561) 379-6230

Email: carmine@progressivemedicalusa.com

www.progressivemedicalusa.com

We provide “STORZ Medical Devices,” world’s most advanced Shockwave technology.

ProMed Beauty

10349 Los Alamitos Blvd., Los Alamitos, CA, 90720

Ph: (562) 326-5720

Email: info@promedbeauty.com

www.promedbeauty.com

ProMed Beauty parent company, ProMed Solutions, Inc., was established in 2011 with the intent to provide the best cutting-edge solutions for a wide variety of aesthetic practices including but not limited to dermatologist, plastic surgeons, PA’s, nurses and estheticians. ProMed Beauty is 100% committed to providing you with quality products and incredible service that you expect and deserve from an aesthetic equipment distributor

Protocol For Life Balance

Booth #1005

244 Knollwood Drive, Bloomingdale, IL, 60108

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

Pulse Pemf

Booth #236

34 Center Rd., Centerville, GA, 30068

Ph: (770) 367-2597

Email: pmcalvanah@pulsepemf.com

www.pulsepemf.com

For over 15 years, Pulse PEMF has manufactured the world’s leading Pulsed Electro-Magnetic Field (PEMF) therapy machines.PEMF is a holistic supplement that infuses the body with natural energy at the cellular level. The body may use that energy to:-heal and regenerate itself-enhance its natural recovery process-assist with muscle fatigue and discomfort after exercise-increase energy or support relaxationbalance the body’s interconnected systems

Pur-Form

Booth #805

3600 Fau Boulevard, Ste 101 Boca Raton, FL, 33431

Ph: (561) 368-1880

Email: info@purformhealth.com

www.purformhealth.com/specialists.html

PUR-FORM provides physician and clinician trainings on highly sought-after regenerative medicine treatments and protocols. Trainees are taught by industry pioneer, Joseph R. Purita, MD, and his expert staff of specialists either in his modern clinic or yours. Treatment supplies and support are provided in perpetuity. Learn hands-on how to do EBO2, the most advanced ozone therapy on the market, as well as autologous cell therapy and other biologic modalities.

Qualigen

Booth #1105

2042 Corte Del Nogal, Ste B Carlsbad, CA, 92011

Ph: (877) 709-2169 Option 3

Email: fastpack@qualigeninc.com

www.qualigendiagnostics.com

Qualigen is working to change how diagnostics is used in hospitals and clinics with FastPack technology. We strive to create solutions that help save patients’ lives and provide better care.FastPack®, A Quick, Simple, and Accurate Immunoassay for the doctor’s office and lab. Better patient care. Save on time and costs

Quartermaster Tax Management, Llc

Booth #110

805 Trade St. NW, Ste 101-A Concord, NC, 28027

Ph: (704) 490-4111

Email: info@quartermastertax.com

www.quartermastertax.com

Quartermaster Tax Management is a proactive tax management firm that elevates our clients’ financial well-being through collaborative services designed to reduce taxes, increase revenue, profits and net worth, through proactive tax planning and Research & Development credits.

Quest Diagnostics / Cleveland Heartlab

Booth #912

6701 Carnegie Ave., Cleveland, OH, 44103

Ph: (216) 767-3638

Email: Bryan.C.Kilbane@questdiagnostics.com

www.clevelandheartlab.com

Cleveland HeartLab, the Quest Diagnostics

Cardiometabolic Center of Excellence, is dedicated to helping you uncover hidden risk for heart attack, stroke, diabetes, chronic kidney disease, and liver disease via our comprehensive suite of innovative biomarkers & value-added solutions. Innovation, test menu breadth & depth, and our large reach offer customers a one-stop partner for laboratory testing needs. Visit www.clevelandheartlab.com or www.questdiagnostics.com for more information.

Quicksilver Scientific

Booth #523

1960 Cherry St, Louisville, CO, 80027

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.

Quten Research Institute

Booth #1110

10 Bloomfield Ave, Building B Pine Brook, NJ, 07058

Ph: (561) 660-1409

Email: Kim.hassett@mkmkting.com www.qunol.com

Specializing in CoQ10 and Turmeric Supplements. When it comes to supplements, it’s not what you take that matters, it’s what you absorb that matters. Here at Qunol, that’s our 100% focus. We work tirelessly to provide the best quality supplements on the market.

Rapid Release Therapy

Booth #537

3303 Harbor Blvd., Ste D-10 Costa Mesa, CA, 92626

Ph: (949) 415-4778

Email: calvin@rapidreleasetech.com

www.rapidreleasetech.com

The Future of Pain Relief.High speed vibration therapy uses acoustic waves to precisely target fascia and connective tissue to provide physical and neurological effects for quick relief of aches, pains and restrictions. Short wavelength provides comfortable treatment for extremities, joints, knots, trigger points and restrictions. See why it is the favorite tool for over 30,000 health care professionalsStop by for a quick session to release your stress and tension, leaving you refreshed, relaxed and pain free.

Receptra Naturals

Booth #928

P.O. Box 2979, Littleton, CO, 80161

Ph: (303) 521-5485

Email: mdahl@receptranaturals.com

www.receptrawholesale.com

Established in 2015, Receptra has redefined the standards for premium hemp-based products through their exceptional cultivation of hempcertified plants grown in Colorado, as well as their cutting-edge cold ethanol extraction techniques. Our commitment ensures that Receptra’s Full Spectrum Hemp Extract stands unrivaled in efficacy and superiority, offering a powerful anti-inflammatory solution for those in pursuit of a healthier lifestyle.

Recharge Biomedical

Booth #1137

3980 Wilshire Boulevard, Unit 735 Los Angeles, CA, 90010

Ph: (714) 369-8633

Email: drpark@rechargebiomedical.com

www.rechargebiomedical.com

We provide concierge medical care for anti-aging and regenerative medicine in NY, CA, TX, FL, and HI. Dr. Park created an online, self-directed course for providers wanting to master Clinical Use of MSC Exosomes. Recharge Biomedical also distributes exosomes for providers.

Refine Usa

Booth #1011

340 3rd Ave South, Ste C Jacksonville Beach, FL, 32250

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 #334

1700 W Main St, Ste 500 Pensacola, FL, 32502

Ph: (800) 891-3452

Email: info@regenativelabs.com

www.regenativelabs.com

Regenative Labs’ mission is to facilitate predictable patient outcomes by providing the highest quality human tissue allografts available. With the goal of addressing the root cause rather than masking pain, Regenative Labs’ birth tissue allografts provide a nonaddictive, non-invasive option for patients. Our stateof-the-art production facility is in Pensacola, Florida. We spare no expense when it comes to the technology, we insist is necessary to produce the quality regenerative products we expect for our partners.

Researched Nutritionals

Booth #1023

P.O. Box 224, Los Olivos, CA, 93441

Ph: (805) 693-1802

Email: customerservice@ researchednutritionals.com

www.researchednutritionals.com

Researched Nutritionals® is passionate about research because we know facts make all the difference. This is why we publish peer-reviewed clinical research on our industry-leading formulations. 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 practitioner-exclusive dietary supplement market and is dedicated to working directly with healthcare practitioners for their most challenging patient needs.

Revive Rx

Booth #1036

3831 Golf Dr., Houston, TX, 77018

Ph: (888) 689-2271

Email: info@reviverx.com

www.reviverx.com

Revive RX is a premier licensed compounding and mail order pharmacy. We focus on treating the source and not just the symptoms. Unlike commercialized medicine, we use industry-leading technology to optimize your treatment. We collaborate with the most innovative pharmacists, healthcare providers, and pharmaceutical manufacturers to provide the highest quality of care to our patient. We offer unique therapy options: Hormone Optimization, Fertility, Peptide Therapy, Sexual Performance, Anti-Aging, Weight loss, Nutrition, and custom compounded formulas.

Rupa Health

Booth #411

177 Townsend St., San Francisco, CA, 94107

Ph: (669) 294-2703

Email: hello@rupahealth.com

www.rupahealth.com/conferences

Rupa Health is your one-stop-shop as a platform to order 30+ specialty and basic blood work labs. From beginning to end, Rupa takes care of the entire lab work experience, including patient support. With a single login, we make it streamlined, quick, and easy to place and track orders — as well as offer educational resources. Rupa helps alleviate hours for practitioners and their admin, while increasing patient compliancy and giving people back the time that is so valuable!

Rx Harmony | The Joi Group

Booth #735

45 Technology Pkwy S., Ste 225 Peachtree Corners, GA, 30092

Ph: (770) 838-3570

Email: info@thejoigroup.com

www.thejoigroup.com

Rx Harmony is a management services organization that connects doctors, pharmacies, and patients to enhance the patient experience while reducing practitioners and staff workload. With clinical programs for mens health, womens health, peptides, sexual function, 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.

13601 Benson Avenue, Chino, CA, 91710

Ph: (800) 542-7322

Email: info.us@seca.com

www.seca.com/554

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.

Shield Nutraceuticals

Booth #637

801 Forest Ave, Johnson City, TN, 37601

Ph: (423) 202-6145

Email: info@shieldnutra.com

www.shieldnutra.com

Good Health Starts in the Gut! At Shield Nutraceuticals, we create products that help people who have digestive problems or who may need help with digestion as they age. Our flagship product, DigestShield®, contains 20 digestive enzymes, 11 Probiotics, and 5 prebiotics, in just the right amounts, all in one capsule. DigestShield® helps your patients, saves time, and makes money. Contact Steve Nice at steve@shieldnutra.com to purchase wholesale. https://shieldnutra.com/wholesale-application/

Shields Pharmacy

Booth #133

2196 Main St., Ste A Dunedin, FL, 34698

Ph: (724) 977-5653

Email: jill.shieldspharmacy@gmail.com

www.shieldspharmacy.com

We are a STERILE | NON-STERILE Compounding pharmacy. Every day, we make a choice to define ourselves by high quality - because we know the best results begin with the best products and practices. We have stringent quality requirements which exceed regulatory compliance requirements; and we use state-of-the-art equipment. We are also Nationally Accredited. _ Anti-Aging _ Bioidentical HRT _ IV | Micronutrients _ Palliative Care _ Pain Management _ Peptides _ Sexual Dysfunction _ and more!

SignatureMD

Booth #834

6001 Broken Sound Pkwy, Ste 340 Boca Raton, FL, 33487

Ph: (561) 309-5242

Email: Sales@signaturemd.com

www.signaturemd.com

At SignatureMD, we pride ourselves on developing customized concierge medical programs that meet the individual needs of both physicians and patients. Our concierge program does not require affiliated physicians to terminate patients, but rather provides patients options that best fit their personal goals and objectives. We’d welcome the opportunity to explain in detail how you can become one of the 95 percent of physicians who report greater satisfaction after converting to a physician concierge service.

SilverCeuticals Inc.

Booth #916

1396 W. 200 South, Ste 2C Lindon, UT, 84042

Ph: (385) 212-4044

Email: Sales@SilverCeuticals.com

www.silverceuticals.com

SilverCeuticals utilizes the most modern and effective nano-silver technology which we implement into immune products, beautifying and healing cosmetics, oral care products, and more. All these products assist us in fulfilling our purpose to help alleviate suffering worldwide.

SmartGraft And LOCKrx

Booth #331

46 Regency Plaza, Glen Mills, PA, 19382

Ph: (610) 680-7676

Email: ccox@smartgraft.com

www.smartgraft.com www.smartsolutionsrx. com

Vision Medical, the manufacturer of the SmartGraft FUE device for hair replacement surgery, offers total hair restoration solutions. LOCKrx products feature topical Growth Factors and nanoparticle solutions, proven nutraceutical supplements, and LLLaser Hair Devices to support in-clinic treatments and at-home therapy. Protocols, education, customer engagement tools, marketing and exceptional support are our hallmarks.

Smartlife Chocolate, Llc

Booth #1029

907 River Rd, Granville, OH, 43023

Ph: (740) 641-9795

Email: barry@smartlifechocolate.com

www.smartlifechocolate.com

SmartLife Chocolate offers two premium dark chocolate squares with one containing Probiotics and the other containing a high level of Antioxidants. SmartLife Chocolate is a functional food that provides benefits beyond basic nutrition. One piece of each chocolate per day provides all the Probiotics and Antioxidants that you need for an entire day. This new team of Chocolates with Probiotics and Antioxidants deliver healthful benefits to your well-being and allows you the permission to indulge in a great tasting treat.

Strive Pharmacy

Booth #230

3906 Cragmont Dr, Tampa, FL, 33619

Ph: (813) 644-7700

Email: info@strivepharmacy.com

www.strivepharmacy.com

Strive Compounding Pharmacy is a sterile and nonsterile compounding pharmacy. With our state of the art facility we house a sterile cleanroom suite and multiple non-sterile compounding labs. We have gone above and beyond to ensure our quality remains un touched. We specialize in Hormone Replacement, Weight loss, Veterinary, Thyroid, Pain Management, Dermatology, Erectile Dysfunction, and much more.”

T.A. Sciences

Booth #605

7975 N Hayden Rd, Ste C-101 Scottsdale, AZ, 85258

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®.

Tailor Made Compounding

Booth #1102

200 Moore Drive, Nicholasville, KY, 40356

Ph: (859) 887-0013

Email: ataylor@tailormadehealth.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!

Thera Wellness Solutions, Inc.

Booth #1121

10411 Motor City Drive, Ste 615

Bethesda, MD, 20817

Ph: (240) 442-1919

Email: office@therawellness.us

www.therawellness.us

THERA WELLNESS™ 5-In-1 Biofield Technology helps you support your client’s well-being with noninvasive healing energy therapy that delivers results in just a few sessions. Following the principles of holism, THERA WELLNESS™ creates its therapy using the body’s own frequency information to address a great number of issues. Discover the applications for physical discomforts, sensitivities, stress management, emotional well-being…. Over 800 applications to help your clients with targeted and personalized therapy. 40 Years of experience in energy healing. Made In Germany.

Thor Photomedicine

Booth #534

8375 Jumpers Hole Road, Ste 110 Millersville, MD, 21108

Ph: (877) 355-3151

Email: mark.granic@thorlaser.com

www.thorlaser.com

THOR Photomedicine is the internationally recognized authority in Photobiomodulation (PBM) equipment and have presented to the US Congress, United Nations, and NICE (UK) on the use of PBM for pain management. While analgesics cover up pain, our devices actually treat the source of the pain. THOR products are indispensable tools at world class institutions including Harvard, NYU, The Veterans Administration, and others — revolutionizing pain management and injury recovery programs.

Trudiagnostic

Booth #910

881 Corporate Drive, Lexington, KY, 40503

Ph: (859) 797-2983

Email: hannah@trudiagnostic.com

www.trudiagnostic.com

TruDiagnostic is a company focusing on methylation array-based diagnostics for life extension and preventive healthcare serving functional medicine providers. TruDiagnostic has a commitment to research with over 30 approved clinical trials investigating the epigenetic methylation changes of longevity and health interventions. Since TruDiagnostic’s inception, they have created one of the largest private epigenetic health databases in the world with over 15,000 patients tested to date.

Uberlube

Booth #329

7316 Ridgeway, Skokie, IL, 60076

Ph: (888) 391-8082

Email: med@uberlube.com

www.uberlube.com

Uberlube Luxury Lubricant is designed to enhance intimacy. Always slippery, never sticky. There is no reason to experience painful sex. Uberlube may be just what you are looking for. Not harmful to healthy bacteria or pH levels. Physician recommended, used in OB-GYN practices. Cruelty free without animal products and vegan friendly. No alcohol, no gluten, no glycerin, no parabens, no scents and flavors. Latex safe but not recommended for use with silicone. Made in USA.

Universal Arts Compounding Pharmacy

Booth #936

14350 NW 56th Ct., Ste 114 Miami, FL, 33054

Ph: (305) 556-2673

Email: compoundrx@uaprx.com

www.uaprx.com

Since 1992, Universal Arts Compounding Pharmacy has been compounding sterile and non-sterile medications utilizing the latest pharmacy knowledge and stateof-the-art technology. As the first PCAB Accredited Compounding Pharmacy in Florida, we maintain a strong reputation for high-quality compounded drugs, expertise in formulating unique preparations, and creating safe compounding conditions for our personnel. Located in Miami, FL, we operate a groundbreaking 12,500-square-foot facility, proudly serving Arizona, Colorado, Florida, Georgia, Idaho, Illinois, Massachusetts, New York, South Dakota, Tennessee, Utah, Wyoming, and Wisconsin.

University Compounding Pharmacy

Booth #517

1875 3rd Ave., San Diego, CA, 92101

Ph: (800) 985-8065 Ext 5700

Email: dave@ucprx.com

www.ucprx.com

UNIVERSITY COMPOUNDING PHARMACY (UCP) a nationally recognized leader in drug and device therapies. For 27 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.

Venus Concept

Booth #1010

235 Yorkland Blvd., Ste 900 Toronto, ON, M2J 4Y8

Ph: (888) 907-0115

Email: info@venusconcept.com

www.venusconcept.com

Venus Concept Inc. is a global leader in the medical aesthetic industry, pairing best-in-class technology with our industry-unique comprehensive business solutions. We offer a broad product portfolio of minimally-invasive and non-invasive aesthetic and hair restoration device platforms that address today’s most in-demand aesthetic needs.

VeroScience

Booth #937

1334 Main Road, Tiverton, RI, 02878

Ph: (401) 816-0525

Email: contact@veroscience.com

www.veroscience.com

VeroScience is a biotechnology company focused on the development of therapies and products to improve human health. The company has a strong pipeline of metabolic disease products and therapies for immunological disorders. VeroScience is a hybrid of academic environment mindset and industrial focus within a small and efficient organization. The company conducts preclinical and clinical research nation-wide, utilizing strong academic and pharmaceutical industry collaborations to advance its development programs.

Vertisis Custom Pharmacy

Booth #431

9343 E. Bahia Drive, Ste 200 Scottsdale, AZ, 85260

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.

Vibrant Wellness

Booth #904

1360 Bayport Ave, Ste B San Carlos, CA, 94070

Ph: (866) 364-0963

Email: support@vibrant-america.com

www.vibrant-wellness.com

Vibrant Wellness is a leading biotech company based in San Carlos, 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.

Weave

Booth #434

1331 W Powell Way, Lehi, UT, 84043

Ph: (801) 458-2808

Email: shauna.simmons@getweave.com

www.getweave.com

Weave is the all-in-one customer communication and engagement platform for small business. From the first phone call to the final invoice and every touchpoint in between, Weave connects the entire customer journey. Weave’s software solutions transform how local businesses attract, communicate with, and engage customers to grow their business.

WeCare Pharmacy

Booth #1022

516 Fletcher Drive, Warrenton, VA, 22551

Ph: +18443093782

Email: info@wecarepharm.com

www.wecarepharm.com

WeCare Pharmacy is a full-service compounding pharmacy specializing in integrative therapies. Our team of dedicated professionals is committed to the success of your practice and helping you develop innovative treatments. Our goal is to come alongside your practice and provide you with creative products that make you effective clinicians, innovative business owners, and “rock stars” to your patients. WeCare specialize in the following: Men’s Health, Women’s Health, Dermatology, Hormone Replacement, Weight Management, IV Therapy

Wellness Pharmacy

Booth #104

3401 Independence Dr., Ste 231

Birmingham, AL, 35209

Ph: (800) 227-2627

Email: info@wellnesspharmacy.com

www.wellnesspharmacy.com

With over 55 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.

Wells Pharmacy Network

Booth #1113

3420 Fairlane Farms Rd., Ste 300 Wellington, FL, 33414

Ph: (561) 793-1568 Ext 2631

Email: info@wellsrx.com

www.wellsrx.com

Wells Pharmacy Network is a privately held, nationwide, compounding pharmacy specializing in solutions for wellness and anti-aging medicine including: Bio-Identical Hormone Replacement Therapy, Peptide & Regenerative Therapies, Weight Management, Sexual Wellness, Aesthetic Dermatology and Thyroid & Adrenal Health. This includes operating a 20,000SF 503A pharmacy and a 21,000SF FDA Registered 503B Outsourcing Facility that produces bulk medication. Our mission is to elevate compounding industry standards through a unique combination of superior science and service.

WholeScripts

Booth #123

6800 Kingspointe Parkway, Orlando, FL, 32819

Ph: (800) 647-6100

Email: jaime.robarts@wholescripts.com

www.wholescripts.com

WholeScripts is an integrative medicine platform powered by XYMOGEN, a family-owned health sciences company headquartered in Orlando, Fla. that has been delivering high quality nutraceuticals to the healthcare community for over 30 years.

WholeScripts’ mission is to be an integrative medicine tool that provides educational events, marketing support, and excellent customer service. It is the dispensary of choice to purchase and recommend XYMOGEN formulas and other professional-grade herbal and nutritional supplements. For more information visit wholescripts.com or XYMOGEN.com

Zizion Group Inc.

Booth #100

141 NW 20th Street, Ste G1

Boca Raton, FL, 33431

Ph: (561) 221-1000

Email: bruce@zizion.com

www.zizion.com

Zizion Group is a medical distribution company with a focus on natural integrative therapies. We bring technologically advanced products, targeted training, and innovative marketing expertise, to empower physicians to expand their practice. We are an endto-end provider, identifying appropriate solutions and deployment methodologies while working with your team to ensure success. You are never considered a customer; you are a valued physician partner.

ZRT Laboratory

Booth #217

8605 SW Creekside Pl, Beaverton, OR, 97008

Ph: (503) 466-2445

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.

The Perfect Combination for Vascular Health

Supports the structure and normal functions of the endothelial glycocalyx*

†As measured by saliva NO test strips in an open label IRB-approved study. To learn more please visit Calroy.com

Up to 24-Hour Nitric Oxide Support*†

*These statements have not been evaluated by the Food and Drug Administration. These products are not intended to diagnose, treat, cure or prevent any disease.