Advanced Serial TPE: The Science, The Evidence, and The Opportunity for Your Patients

Okay, I'll go ahead and get started. So I'm going to introduce our speaker today is Dr. Paul Savage. He's the founder and chief medical officer of MD Lifespan. Dr. Savage is a former emergency medicine physician by training with fellowships in stem cell therapy and metabolic medicine. He has spent the past 2 decades advancing personalized data-driven care, including the development of patent-pending protocols centered around what we're talking about today, advanced serial therapeutic plasma exchange. His work integrates therapeutic plasma exchange with diagnostics and targeted therapies to address inflammation and toxin burden in complex patients. Dr. Savage is also the author of the newly released book Avoiding Toxins, a trusted resource for reducing toxic exposure and living a more toxin-free life. So welcome, Dr. Savage. I'm gonna turn it over to you and hello.

Yeah, thanks, Lisa.

Welcome, everybody. I'm actually very glad to have everybody here, and I'm looking forward to this conversation as well as answering questions that you may be having. There's been a lot of talk in the literature about plasma exchange and the new uses that plasma exchange can be utilized for, and I just want to clear up all the misconceptions and give you some hard data and some hard facts on how MDLifespan has been utilizing plasma exchange. Thank you, Paul.

this procedure and the changes that we're seeing in the patients themselves.

So I'm going to start sharing my screen here for presentation, which will be available to everyone.

And I'll just ask Lisa to confirm for me that she's able to see the screen.

Yep, we can see it. Perfect.

Great. So we're going to be talking about what we call advanced serial TPE, which is therapeutic plasma exchange, or also known as plasmapheresis, and the science, the evidence, and the opportunity to incorporate this type of procedure into your practice.

Today I'm going to talk about some things that I think are fairly obvious to most people, and I'm going to try to clear up some of the questions about toxins, which in my opinion is one of the most serious health risks facing our patients today. We're gonna talk about the mechanism of therapeutic plasma exchange, and why different types of serial treatments matter clinically, and how MDLifespan has made serial TPE more advanced and different from just standard TPE. We're gonna talk about key biomarkers and clinical cases. I'm gonna talk about how we select patients, safety concerns, and appropriate use cases. And we're gonna talk about the MDLifespan referral model, How we can work together. Why this matters now is because we've never seen patients with so many chronic inflammatory diseases. We've never seen patients presenting with so much toxins as we have in the past 10 years. This is a new and evolving area of medicine which impacts every single other part of medicine. Many patients continue to have persistent symptoms even though we've done our best to try to get them detoxed and try to get them on the right track of health. And so we're gonna talk about how plasma exchange offers a mechanical dilutional process which provides a rapid intervention on removing pathologic substances, including toxins. We're gonna talk about advanced serial plasma exchange and how it expands beyond the traditional indications With measurable biomarker changes, and we're going to talk about you, healthcare providers, on how you— we can be partners in a very cooperative and effective manner. The problem is relatively clear.

You can't open up a paper every week without seeing One or two articles about toxins in the brain, toxins in the arteries, toxins in the environment, the water, the food. But we do know a lot of this has really gotten the attention of the media in the last 5 or 6 years, especially the articles that talk about microplastics in various tissues, including the fact that the average American eats about 5 grams of plastic per week.

That's about the equivalent of one credit card per week.

Per week. And that about a spoonful of plastic exists in each brain, and that the arteries of the body—

and in this case, the carotid arteries—

the plaques that we've removed and how much plastic we found in those plaques, which actually increase the incidence of heart disease and heart attacks 4 times, 5 times higher in people within just a matter of just a few years. We're all aware of the forever chemicals, the PFAS, which are in the water, which we've known about, and they're just increasing in quantity and numbers. You can look at through any of the articles in any major journals, and just within the last year, we see landmark studies raising the concerns of microplastics and cardiovascular health, new studies showing chemicals such as PFAS in the drinking waters are linked to increased rates of cancer, and studies about environmental pollutants such as pesticides and herbicides and heavy metals as it's in our air, our soil, our water, and how that causes many different associated disease risks, whether we're talking about respiratory, reproductive, cardiovascular, or cancer. Toxins are everywhere and we're the cause. We've known that since the '70s when we started using herbicides and pesticides on our fields and in the crops. The mycotoxins, which have been in our environment forever, are more proliferative now. It is believed because we store the mycotoxins in the silos and then harvest, you know, harvest these grains after a period of time. Fossil fuel consumption is increasing. It's over 65 million tons per year in the United States. We're unearthing heavy metals for the rare earths. Where there's the industrial boom of chemicals, which is going unhindered, and our unfettered use of plastic. It is estimated that over 200 different diseases can be linked to the toxins. So whether the toxins are causing them or exacerbating them, it doesn't really matter because in both cases it's problematic, including in the areas of cancer, cardiovascular disease, and neurologic issues.

Okay.

degenerative diseases. As mentioned, there's a plastic— a teaspoon of plastic in all of our brains. We inhale about 70,000 microplastics per day, and brain samples, vascular samples, they're everywhere in the body. They're also even in the first meconium of the child. And we don't really have an effective way to remove a lot of these forever chemicals, and the forever chemicals now include The PFAS and also the vast majority of the plastics. So let's understand some of the mechanisms behind what therapeutic plasma exchange is. TPE is also known as plasmapheresis. It's also on occasion called apheresis. It's a process by which the blood is removed from the body, put into a machine which centrifuges it and separates it— the liquid part, which is of course the plasma, from the cellular part, which is the red blood cells, the white blood cells, and the platelets. At this point, the plasma is discarded and the cellular component is recombined with human albumin and reinfused back into the patient. The purpose of plasma exchange is to basically remove everything that's in the plasma, including harmful substances, historically things like antibodies and immune complexes. And most commonly, historically, plasma exchange was used in a series of 5 or 6 plasma exchange Within a 1 to 2 week period of time. The rationale about plasma exchange is very simple. It's to take things out of the body. So many diseases which are caused by toxic substances like the autoantibodies, immune complexes, toxins, and abnormal proteins can be removed by using plasmapheresis. It's kind of like an oil change for humans. The solution, as I mentioned, is to remove these substances so it halts their damage that they're causing to the system itself. How it works is, as I mentioned, a patient is brought in, we measure their weight, we get their hematocrit, and then we calculate out their estimated plasma volume. From this, we sit them in a chair, and then we establish 2 large-bore IVs, usually one in each arm, And then what happens is once you have it connected to the machine that's primed, and there's a number of different companies, the machines essentially work the same. The body is brought out of the— the blood is brought out of the body, it's circulated through the machines, it's centrifuged into 2 components, the plasma part and the cellular part. The plasma part is disregarded and the cellular part is reinfused. And this is the separation. And this is the replacement. In most cases, albumin is the most commonly used replacement fluid. The reason for this is albumin is human-derived, but it's a very clean product. It's been tested for various things over 50 years, including the possible risk of virus transmission like hepatitis and HIV, as well as COVID. They've never found any association with any patient on any viral contamination or transmission by using plasmapheresis. Same thing with cancer. They've never seen any cancer being transmitted through albumin as well. So it's considered to be a very safe substance. The biologic data risk assessment gives it an estimated risk of about 1 in a million of causing any associated transfusion diseases. So it's essentially a very safe product to be giving to people. As opposed, on some occasions you may use fresh frozen plasma, but these are cases where people need clotting factors and things put back in. For example, somebody with TTP, and this is mostly done in the hospital and usually in the intensive care. For all practical purposes, there's no reason that any patient on an outpatient basis should ever be given fresh frozen plasma. The reason's very simple. The side effect profile of giving back albumin is a very safe adverse reaction rate, nationally less than 6%, and we'll go through some of those known adverse reactions. But with plasma, that adverse reaction rate is up to 26%, including severe anaphylaxis and death. Transfusion-related acute injury to the lung, or TRAIL. So all these different longevity centers that are exchanging old blood for new blood or old plasma for new plasma is not safe to be done on an outpatient basis. So let's talk about how what we're doing at MD Lifespan is different than what people are doing In the, in the industry, and mostly about the different competitors that are out there that are doing TPE. So we call this Advanced Serial Plasma Exchange because what we traditionally— you can go into many different wellness centers and get a TPE done, which isn't really very effective because one plasma exchange is like changing a quarter of your oil. It doesn't really change the mechanisms at all. You really need to do TPE in a series of Phoresis, a series of procedures, because it's the dilution effect over and over again that actually is what makes the plasma cleaner and cleaner. So on the left, you can see the process of what is the traditional therapeutic plasma exchange. But on the right is what we do at MD Lifespan, in that we are doing 3 to 5 standard normal TPEs, but we also go a step further by Adding in nutrients that have been removed, both IV and orally. We teach the patient on how to minimize their exposure to toxins, which has a significant effect both during the procedure and post-procedure, as we'll discuss. Then we may add also in some regenerative therapies to help repair tissues that have been damaged by the different entities that you're removing from the blood. And finally, The maintenance program, which has been so successful that none of our patients have had to come back for more TPE in the past 3 years. The phases of advanced serial TPE include the detoxification phase, which is essentially the plasmapheresis along with the nutrients that we give back that the TPE has removed. Then we move into a regenerative phase. Once the toxins are out, The inflammation is down, the oxidative— oxidation down. You can start introducing some regenerative therapies like exosomes and stem cells. You can give them both IV and orally. All right, I mean IV and nasally. We might use low-dose naltrexone to capture a little bit more of certain heavy metals. We may use— I'm sorry, chelation to trap some of the heavy metals. We may use low-dose naltrexone to moderate the immune system, and we may even use— something like beta cyclodextrin to help remove some of the plaques from the arteries if we're looking to gear this type of procedure towards improvement in vascular health. Also, then the maintenance phase that we send patients home is really about avoidance therapy. That's 90% of the game there. Once they've learned how to minimize their exposure in their homes and at work, the reintroduction of these toxins back into the system is very slow, and actually we see patients' toxin levels continue to fall. Again, the difference between serial, just regular serial TPE and advanced serial TPE are pretty significant. The purpose of TPE is focused on plasma exchange to reduce certain pathologic substances. Its primary use is for different medical conditions, TTP, any of the autoantibody diseases, many of the demyelinating chronic neuropathies, But they don't really go much past that, and there is no maintenance phase that's included with this type of therapy. Whereas advanced serial TPE, the purpose is to use plasma, plasma pheresis with regenerative wellness techniques and maintenance protocol, designing it for improvement in health and wellness, and including in that factor IV and oral nutrients, regenerative therapies, and lifestyle guidance. When did we used to use plasma exchange? When has— where has it been used historically? Well, again, a lot in neurology with all these antibody-associated diseases including Guillain-Barré, myasthenia gravis, chronic inflammatory demyelinating polyneuropathies, and including Alzheimer's. But also in hematology and nephrology, things like TTP, Goodpasture syndrome and antibody-mediated rejections. But now we're looking at using TPE more looking through the lens of toxins causing chronic inflammation. So now we're looking at it for chronic toxicities removal, and in that manner to increase the biomarkers of aging. So it may potentially improve the longevity, but it certainly improves the healthspan. We can use this on mold toxic patients. We can use this on patients with chronic infections. Typically, patients with chronic infections have a lot of toxins, and the toxins are causing difficulties with the immune system. If you don't— if you can get the immune system cleaned up and on your side, you have a much more effective tool on treating these chronic infections. Also, for patients with chronic fatigue and fibromyalgia or hypersensitivities, These patients do well once you get enough of the toxins out of the system itself, and so that the immune system can settle down and stop attacking all these different pathogens. Cognitive decline and early Alzheimer's, from the AMBAR study on the part with the early Alzheimer's, but also these patients with brain fog, with cognitive decline, cognitive issues, they do remarkably well. After you've been able to eliminate the toxins and reduce the neuroinflammation. Also with heart disease, there's a big component of heart disease that has to do with oxidative stress and inflammation. Removing the toxins removes a cause and maybe the primary cause of both of those processes. And also for talking to patients when we're really looking at the next future generation on all these women carrying all these toxins and transmitting them to their baby in There may be a significant part here available at some time to think about getting these women who want to get pregnant toxic minimum before they get pregnant so they don't transmit those toxins to the baby. Can you imagine what would happen if we lowered the neurotoxins and the plastics that are being delivered to the in utero fetus? Perhaps it may have an impact on autism or ADHD or childhood obesity. or many of these other things that are related to chronic inflammation.

Why it matters clinically is that TPE is a much faster method of removing toxins than anything we've seen before. Whether you're looking at chelation or whether you're looking at infrared saunas or binders, plasma exchange rapidly reduces virtually every toxin that we've tested. And so it's a unique use by MDL— MD Lifespan— is by utilizing the plasma exchange to remove every type of toxin that we've tested, whether it's mycotoxins, heavy metal, plastics, PFAS, pesticides, herbicides, phenols, phthalates, and others.

At MD Lifespan, we have a very high amount of quality control on our processes because this is all we do and we do it very well. Although the national average of adverse reactions and side effects is about 3%, ours is about 6%. Our average is less than 3%. Some of those things that we see and we include in this is hypoglycemia, because when you do plasmapheresis, you remove the plasma, which contains the glucose, so people can get low blood sugar. Since you're moving fluids around and removing toxins, which relatively quickly decrease inflammation and may give you some vasodilation, people can experience some low blood pressure. There is possibility that because of the anticoagulant that we use, citrate, to help the blood travel through the machine tubing easier, that it lowers calcium levels, which some patients can get tingling and cramps. We've had people have vagovagal syncope as well as vasodilation syncope. And allergic reactions, although Quite uncommon. We have seen a patient with a citrate reaction, but we just—

but it wasn't dramatic in the fact that his blood pressure did go down, he did break out in a rash, he did not lose consciousness, he did not have trouble breathing. We gave him some antihistamines, we gave him some fluids, he did fine.

But this is what some of the side effects that we explain to patients could happen during your procedure, although it's—

Very rare.

Quite uncommon. One of the things that certainly makes MDLifespan better than any of the competitors is the medical evaluation and nurse interventions that we do with all of our patients. You can't just come in and order a TPE or come in that day and see the doctor and get the TPE because patient selection is always about safety. So although there's very little exclusion criteria for plasma exchange, At MDLifespan, we've expanded that because it's done on an outpatient basis. So, in the— for example, patients who've had recent heart attacks or strokes or recurrent congestive heart failure or unstable angina, we don't recommend that these patients get plasma exchange for at least 6 months. Not that plasma exchange complicates these diseases, it may in fact help them, but because most of these processes have a follow-up event. So if you have a heart attack, you're at a higher risk of having a heart attack in the next 6 months, and we don't want to start plasma exchange during that period of time that the patient may experience a recurrence of their heart attack or strokes and then think, oh, that's the plasma exchange that did that. We know that's not the case, but this is just to protect the company as well as the patient during the process itself. There are certain medical conditions that should not be done in an outpatient basis with patients who are tightly controlled with certain medications. For example, people with liable epilepsy. You know, if you start messing with their anti-seizure medicine, they could have a seizure. Therefore, we don't do these patients because plasma exchange removes everything, including the medications. People with significant asthma, especially on the chronic use of steroids, we're very concerned about using that because if we don't We don't want to send anybody into an asthma attack by removing the steroids and their other medications from their plasma. People with ventricular arrhythmias, especially people on things like amiodarone, again, plasma exchange removes everything, including amiodarone. And patients that are on blood thinners because of recurrent DVTs and pulmonary embolisms, not necessarily preventative for people like on AFib or preventative stroke treatments, Using some of the anticoagulants. But we're talking about people who have known and documented DVTs and recurrent PEs that they're on anticoagulants. It's just probably not wise to do these patients in an outpatient setting. We simply can't treat uncooperative patients. So any of the patients that have autism or Alzheimer's or aren't able to follow commands, sit calmly in a chair, Work with the nurse as they go through this procedure. We just simply don't do these type of patients in the outpatient setting. Of course, pregnancy and under 18 of age has to do more— and individual consent and assessment is done on each and single patient that we move forward. Patient safety protocols that we institute at MDLifespan are significant. All of our nurses are ICU, ER, or trauma team trained. They all come with at least 5 years' experience in ultrasound-guided IV insertion and maintenance. They're all trained by the University of South Florida in personalized medicine. They're all trained by Fresenius Kabi in apheresis. They're all ACLS and BLS certified and have ongoing education. throughout the whole time that they work with us, because patient safety matters. Each patient has a medical evaluation by a qualified clinician. Each patient undergoes a pre-TPE procedure interaction with the TPE nurse. As I mentioned, we use ultrasound-guided catheters. Patients are instructed on how to take their medications and supplements. Patients are instructed on how to eat before they come in that day for their procedure. to help prevent hypoglycemia. We give calcium supplements back IV with the albumin to help mitigate hypocalcemia. And all of our nurses are very highly educated in emergency preparedness, which is one of the reasons every patient we've ever treated has gone home after the procedure, and our adverse reaction rate is markedly low. The patient experience is something that we take very seriously and we're very proud of at MDLifespan. We have very high reviews from our patients. It's been a joy to work with these patients, especially when they come in a little fearful of the plasma change, but the nurse puts them at ease. Because these processes usually take about 4 hours every time we do them. We do them traditionally once a month, where previously in other traditional settings, it was done 5 to 6 times over a 2-week period of time. The sensation that the patient has, Generally painless and enjoyable, but sometimes because of the liquid change, and these are at room temperature, the patient may experience a little bit of coolness. What does our data show? Because we're now 3 years out with a lot of data on a lot of different patients. So let me share that with you. So we have patients that come in who get the advanced serial protocols, and we'll go through some of those in just a little bit. But we also have patients that come in who just want plasma exchange themselves, and that's fine. We can accommodate both this type of patient. But when you start comparing the TPE-only patients to the patients that have gone through the TP protocol, I think you're going to see something pretty amazing. Within 6 weeks after their last procedure, we recheck all the test numbers that we did on the front side, including their B cells, their T cells, and their natural killer cell. Even with TPE alone in series, you see an improvement of the lymphocyte system. You see a marked, almost 3 to 5 times more improvement when we do the TP protocol. Not only that, but we're seeing patients 6 months, year, 2 years out that continue to have improvement in their lymphocyte counts. It just keeps going up. Same thing with inflammation, although plasma exchange itself brings down inflammation, The protocol when we institute IV and oral nutrients and avoidance therapy has a markedly higher rate of reduction in inflammation. Oxidative stress markers, again, between 2 to 3 times more reduction. Longevity markers such as clothoprotein, which is up about 30%, NAD by 100%, and beta-galactase up by 77%. We can talk about all 200 and some odd toxins that we test, but let's be clear, I'm just showing you some of the samples from each one of the categories. But every one, every one of the heavy metals comes down, and not a small amount, significantly. And many of them close to 100%. Environmentals like the organic volatile organic chemicals come down significantly. Herbicides, pesticides, much effective in this area, much more so than TP alone. You can talk about the phenols or the phthalates or the volatile organic chemicals and even the mycotoxins because we test over 40 of them. We see a significant reduction in every single toxin that we've been able to study to date. So how does this apply to our clinical patients in real case Well, one of the things with the publication of the Berkeley study with Dobri Kiprov on 60— or on 6 patients that had 5 serial TPEs done with immunoglobulins, we have a very similar experience, but our results are significantly improved because of our advanced serial protocol. So, in this patient, a 70-year-old who came in with a number of different controlled medical issues, she has quite a family history. She was on quite a few medications, but she wanted to do the plasma exchange because she had seen some studies about reversing some of the biomarkers of aging. She went through some clinical evaluation. She went through testing including biomarkers of aging from TrueAge, LabCorp immune and inflammatory markers, Vibrant America toxin testing. The protocol that we did was 5 serial plasma exchange with the IV and oral nutrients IV immunoglobulin, nasal exosomes, and the outcome for this patient was a decrease in the toxic burden, an increase of the cognitive function, increase of immune markers, and an increase in her telomeres. How so? Well, this is her omic age, her epigenomic age, which although she's 70, she came in at 69, and by the time we were through and tested her again, her omic age had reduced to 65 years of age. Her pace of aging as measured through TruAge diagnostics was good to begin with at 0.86, but by the time she left, her pace of aging had reduced to 0.8 per year. So she basically aged only 8 months or 10 months out of a 12-month period of time.

Her telomeres got longer, so her telomere age decreased.

She was very good at 57.6, but improved to 56.7. Usually we see about a 2.5-year change in their telomere biologic age, but because she was already so significantly younger than her stated age, you know, this patient with a 1-point difference was acceptable. We do a lot of patients that have chronic toxicities. These may present as chronic fatigue, or fibromyalgia, or mast cells, or hypersensitivities, but most of the time these patients know they have a relatively significant amount of mold burden as well.

Sure.

So in this case, we have a 48-year-old man who had severe mold exposure over time. He presented with brain fog and fatigue, and elevated mycotoxins. He was on hormone therapy and thyroid support, and what we did was we tested his mycotoxins and his inflammatory markers. We put him through what we call our mold protocol, which is advanced serial TPE, IV and oral nutrients that matches our backbone of our procedure, but we're also adding in other supplements that really are more geared toward mold, such as binders and phosphatidylcholine. We gave immunoglobulins and avoidance therapy, and what we saw in him was a significant decrease in his mycotoxic burden, increase in his cognitive function, as well as in the immune markers. This is a sample of his toxin test before and after. You can see he had a marked reduction in the number in the upper and the moderate range over a 6-month period of time.

The goal here is not to get people's toxin levels down to zero.

is to reduce the number that are in the high episodes and reduce the quantitative amount of each of them so that the body can start detoxing again and it becomes a toxic burden load that the patient's physiology can manage. In this area, you can see a significant improvement. I'm sorry, I have the slides a little bit backwards there, I believe. No, that's right. You can see a significant improvement as most of his Average moved to the above average range. His immune system, his T cells, the 3, 4, and 8s, went up by about 30%. The B cells, the 19s, went up 121%, and the natural killer cells went up by 47%. And that was 6 weeks after his final plasma change. As well, his oxidative markers like his TMAO went down. And his inflammatory markers went down as well.

We did a lot of different markers on this person.

I'm just showing the ones that were elevated prior to our instituting therapy. We use this protocol, the backbone of our protocol, with the TPE, IV and oral nutrients, and avoidance therapy, and then we gear it more towards immunity, so we're giving more immunoglobulins and other nutrients that are Significantly active in immune system repair and support. So this is a 42-year-old with an autoimmune profile. She had chronic inflammation, fatigue, cognitive issues, immune dysregulation. She has a family history of this. She had been treated by her doctor on hormone therapy, thyroid therapy, anti-inflammatory support, and she came in for the plasma exchange to see if we could reduce the level of her toxic burden. After doing the appropriate testing of her immune panel or inflammatory markers or toxin panel, we set up her with our immune protocol, which is 5 TPE sessions with IV and oral nutrients, immunoglobulins, and adjunctive therapies, in this case, low-dose naltrexone. The key outcome that we noted in most of these patients, or the vast majority of these patients, is a much improved immune system function and strength in the lymphocytes, a much lower inflammatory profile and much improved on their symptoms as well. So you can see here again with their B cells and the T cells, a significant improvement, a drop in their TMAO, their CRP, and a significant drop in their complement C4a as the activity against the infective agents dropped significantly as well. One of my favorite protocols is the brain protocol. So this is for patients with brain fog or people with early Alzheimer's. We're not really doing moderate or severe Alzheimer's just because of the difficulty it is. The patient can be frequently uncooperative. That's the part about the Alzheimer's that I get most concerned about because they have to be able to follow orders. Also, although we've done some patients with moderate Alzheimer's, we certainly see a better response in the people earlier in their disease, which probably isn't surprising. Early intervention is the key in most of the diseases that we treat as clinicians. This was a 72-year-old female with mild Alzheimer's, as diagnosed by a positive PET scan. She had memory decline, cognitive impairment. Her Montreal score was 21. She had a neurodegenerative history, or she had— her mother and her sister both had Alzheimer's. So we did do some laboratory testing, including Alzheimer's biomarkers, inflammatory markers, and the toxicology. We followed this up, and the brain protocol is our backbone protocol again with TPE, IV, oral nutrients, and avoidance therapy, but we add in nasal exosomes after every TPE, as well as some brain nutrients that are not included in our other protocols.

This is the patient's toxic panel. You can see a significant reduction in not only the number but the concentration of the toxins in this patient. We actually saw her P-tau factor revert from abnormal at 0.25 up to 1— or down to 0.17, as well as her beta-amyloids from 0.092 increased to 0.103. But probably what was the most pleasing was seeing how her memory score improved, as you can see here. This 72-year-old female had been a previous Master bridge player, and she hadn't played for 2 years prior to being seen by MD Lifespan. Afterwards, I'd just seen her in her year follow-up, and she's back playing competitive bridge once again. How do we work together? Well, first understand that MD Lifespan has developed this backbone protocol and then modified it to address more Patient-centric problems like patients that come in with just a lot of toxins, patients that come in with cognitive issues, patients that come in with vascular health issues, people that come in with autoimmune issues or chronic infections, people that come in with toxicities, especially things like mold, people that come in with previous history of cancer wanting to know if they could get the toxins out in the hopes of decreasing the recurrence of a cancer. Also, a protocol put together for moms before they get pregnant, as well as the longevity program to help reverse the biomarkers of aging. The business commitment of NB Lifespan is the patients always first. We have 20 medical and scientific advisors. We've always believed in putting quality over the price. We actually made MDLifespan a public benefit corporation, which means that this company will always work to the betterment of the patient's care, and that includes the financial costs associated with this. We've been able to reduce our prices over 20% in the last 3 years. We're more than just competitively priced because what the patients get from us is certainly at a higher degree on the competitive advantages than what they get from standard doctors' offices or any of these clinics offering TPE as a service. The pricing of plasma exchange, if you look through the United States, for one plasma exchange is between $5,000 and $10,000 each time. Depends on which part of the country you are on, depends on different types of availability of different parts. But at MDLifespan, we've been able to keep that price at $6,000 And we have no indication that we're going to need to increase that price. Not only are they getting a high-quality experience, but they're getting it with trained clinicians and trained nurses. But as I mentioned, typically we recommend a series of 3 or 5 because one protocol is good to help people through if they want to experience it and get over the fear of it, because I understand that patients can be, and usually are, a little intimidated by the machine. I certainly know I was when I had my first TPE done. So we've been able to manage the price even— so the pricing then increases per protocol based on additive regenerative therapies.

So, you know, how many we do and how many of these other things we add in.

And the average protocol can range anywhere from $16,000 up to $60,000. But again, many of these clients are— many of these locations are charging $10,000 per TPE, so that would be $50,000 for 5 TPEs, where in our situation with 5 TPEs and the labs and the doctor visits and the IV and oral nutrients and the avoidance therapy, it's essentially at the same price as our competitors are giving just for TPE alone. There are different ways that you can refer patients to MDLifespan: by fax, by patients scheduling themselves on our website, and we can absolutely provide you with other resources including automated evaluation forms that can bring the patient right directly and quickly into a visit with one of our clinicians. We have a lot of different patient- and physician-facing educational material that's available in both digital and print. The key takeaways is I'd like you all to remember that TPE is a valid mechanism-driven intervention for removing things in the blood, including toxins. Serial treatments enhance that clinical impact. Advanced serial TPE integrates this whole process with IV and oral nutrients and avoidance therapy for improved inflammation reduction and regenerative support. Our clinical observational data and case studies demonstrate measurable biomarker improvements, and we'd like to work with all these different physicians that are attending here because there's a referral program that I'm going to get into a little bit right here. Before we go forward, I do want to let you know that we acknowledge that physicians are an important part, and as such, we always give them a provider discount. I want to make it clear that the return on investment of each of these protocols for MD Lifespan is very low. We really have worked hard. What we're doing is making a profit on the quantity that we're doing, not on the individual volume. So we've actually got— we've actually been able to open 12 centers.

We've gotten to profitability.

And so when I offer a 5% discount, that's a substantial part of our investment, our return on investment, because we're only about 25% to 30% of the entire amount that we collect. So just so healthcare providers understand, typically in most of these places it's over 100% markup. In MDLifespan, we're less than 50%. In most cases, we're around 40%. If you choose to partner with us, there's a number of different ways to do that. One of the things about MDLifespan is we are not long-term functional medicine providers. We don't do anything other than this with the patients. So they're our patients for a 6-month period of time while we go through this process. And afterwards, 62% of the patients that come to see us are looking for functional medicine doctors. So we're interested in building a referral network of physicians around our locations So that when patients are done, many of these patients, if not all of them, need hormone therapy. They need GI support. They also need to keep going with their detoxification. They need to be retested on their toxins and their immune system down the road to make sure that they're continuing to improve down the road. There's another level up from that with the physicians and providers that are more active with our company and not only just referring a number of patients but also giving us feedback and providing surveys and possibly even some lectures as affiliate partners. For that, the company has set aside some shares which are pooled between these partners. Then we have other doctors who want to have even a more active role in MDLifespan and being part of— they have a skill set, they have business knowledge, they have an opportunity all these different things that they can provide to MDLifespan that makes us want them to be one of our advisors, in which in case of pooled shares, this would be vested shares in the company. And finally, there's opportunities for healthcare providers to talk to us about putting one of our services inside your clinic. We find this model works the best. Again, one of the things we do with any of our centers around the country is all these locations are typically in doctors' offices. These partners of ours in that office understand there's a no solicitation clause associated with working with us, so your patients are safe to be referred there. They're going to come back. They understand that model just as well as we understand why it's important for you to understand that model as well. But location owners can also obtain rent, and the rent can be negotiated. at different levels. And so we welcome any opportunity that you may think you may be interested in to work with Envy Lifespan. We want to be the provider of the most effective patient-oriented services in the field. I'd like to thank you all, and at this point I'm going to open up the floor to Lisa Byer for some questions I think you may have.

I've got a couple for you, Dr. Savage. We have one person who asked, can patients use plasma donations after TPE? How many plasma donations would equal to one TPE session?

So that's a great question. Typically, when a patient does, you know, there's been a couple studies out there that looked at instead of using plasmapheresis, use plasma donation for getting down the toxin levels. And typically, the results that they've seen, patients had to give plasma twice a month for a year and a half. And that's a lot of time every time you do a plasma donation. So you have a patient going in for about a 3-hour period of time every 2 weeks for about 18 months. They noticed that that's on the PFAS, the PFAS, that they saw some reduction. It wasn't as much as you're seeing with plasmapheresis, but it was able to get the reduction down. I suspect it got all toxins down because it's— in that way, it's similar to plasmapheresis. It's just the time requirement is a little bit different. The equation is a little bit misguided, but if every time that you're doing a plasma donation, a plasma pheresis on a patient, you're doing a full donation, so that's 2/3 of the plasma volume, you're looking at, in most patients, about 2.5 liters that you do for 5 different times. So you're looking at somewhere around 10 to 15 liters of plasma. So divide that by 500, you get 30, which is kind of what matches up to doing 2 plasma donations for 18 months.

Thank you, Dr. Savage. We have another question. What is the threshold for kidney failure patients with regard to their labs? For example, a patient with X fun or X CR?

I'm not sure what XDR is, but what I can tell you is, you know, we're very cautious. There is no contraindication of doing plasma exchange for patients with renal dysfunction, especially in the hospital. But because, again, we're in the outpatient basis, we certainly don't do anybody with a GFR under 30.

And most of the time, we like patients to have above a 60.

Thank you. Next question is, can you expand on the oral and IV supplements patients are getting post-TPE?

Sure. So, if you want to think of the oral or the IV supplement as a souped-up Myers cocktail, you know, we're doing—

we have many different vitamins, vitamin C, B vitamins, minerals, magnesium, calcium.

We also have some amino acids and glutathione that we give in Separate different pushes or IV extensions. We also have the oral supplement, which is a supplement that was put together by myself, some functional medicine doctors, a couple nutritionists. It has over 65 different supplements in it in the way of anti-inflammatory, antioxidant, energizers, detoxification, and methylation support for the mitochondria.

So it's a very robust formulation that we put together. We've also done a lot of work to actually make it taste good. It's kind of an interesting story that the 3rd patient that we did was a retired chef from Nestlé, and she was able to make this taste much better because once you start putting glutathione and start putting B vitamins together in a powdered mix, it can be pretty hard to swallow, but it's actually very good. The reason we put it in a powder mix is either put it in a powder mix or give people 70 capsules every day, and that just wasn't feasible.

It's a very robust nutritional supplement that we give to people to get there.

Like, as I say, if the TP is an oil change, then the nutrients are the gas for the tank, the air for the tires, and the spark for the plug.

Thank you. We have another question. Do you see many patients who are already detoxed and I don't. Before TPE?

I don't.

I mean, I don't— that's—

if they don't have a lot of toxins and they're immune competent, they're probably—

I mean, if they're coming to see me for longevity, we can have that discussion as well.

We don't know yet to what degree each of these different toxins that we're testing might play with the others.

But again, I kind of step back and take a big picture view. Typically, the patients we see come to us because they want to improve their biomarkers of aging.

I say that's something we do.

We do it with quite frequency. We do it very well with very good results. Does that translate into longevity? I don't know.

I think it makes sense that it would, but I tell patients, the only thing I can tell you for certain based upon the studies out there is that your toxin levels will go down, your immune system will get stronger, your inflammation will go down, oxidation will eventually go down. That you'll see improvement in different Alzheimer's markers.

That's— those—

these are the studies that have been done, but they're observational studies. There's not been any controlled double-blind study to this point. We have a lot of experience with a lot of patients over the last couple of years.

I would say that our observational data is very solid and, in my opinion, irrefutable. But again, it isn't— it hasn't been done in the controlled setting.

At this point.

But to have someone come in who doesn't have a lot of toxins and doesn't have immune dysfunction, I would really ask them why they were interested in doing these procedures because I do turn patients away because I'm like, I had a patient yesterday that came in and just like that presentation, I'm like, there are much better things you could be spending the money on than doing plasma exchange.

I don't deny patients the process if they wish to do it because it's relatively safe with low risk.

But I just always question the patient, the amount that they're spending for that protocol or for these procedures as to what kind of benefit that I think and that I know can be the result of that procedure.

So the answer would typically be I don't see a lot of people with low toxins and competent immune systems presenting to us.

Okay. Couple more questions. Are you looking to put centers in larger practices in larger towns or open to smaller but robust Well, what we're looking for—

and typically I would say the town matters— we're looking for— because it's just about marketing and draw. So we're currently in Chicago, Miami, Atlanta, Dallas, Houston, Denver. So we're, we're in the bigger cities because that's just where the better marketing is. I'm not really at this time looking to put something in a more rural setting. And again, on the practice, what we're looking for is engagement. When you have one machine doing 5 protocols or 5 TPEs per protocol, and the machine does essentially one patient per day, you only need about 50 patients to fill up that machine for the full year. We're doing very good at bringing patients in, and that's why we're looking for doctors in the area that we can refer patients out to, including if we're in one of the location owners place. But what we're looking for is the location owners who have enough clientele that would be able to afford this kind of procedure to help us fill up the seats. We're 3 years out, and the clients that we've had for 3 years, although they provided about 50% of the patients in the first year, by the time the second year comes around, it's usually about 70% us. By the time the third year comes around, it gets up to be about 90% by us. So But we're looking for a partnership both in the area of helping it be beneficial to your patients as well as helping the financial part of our company, but also at getting this word out to the industry and the area around it about the importance of this and the availability of this, because this is still a relatively little-known process, especially what we've been doing at MDLifespan. But our account manager, Marian, would be very happy to talk to anybody who's on the line here who would like to talk about location or would like to talk about being a referring physician, because again, we're just not looking for physicians to refer to us, we're looking for physicians for us to refer back to, because we have a lot of patients in our centers. We generally have about 20 new patients per month per center, and 62% of those patients don't have a functional medicine doctor, And we're kind of stressed out actually trying to find doctors that have a knowledge base, that have the aptitude, that have the skill set that this patient may need. So we invite you to contact us and talk to Marion.

And we can share her information in the chat. A few more questions. Can you explain how you ensure— I believe this is asking— the plasma is free from toxins, infections, and spike proteins?

So I think that they're referring to the albumin that we reinfuse back. All I can tell you is we only use Griswold albumin. Again, we have made a commitment that we're only using the quality products. Albumin from Griswold is an American-based company. It mostly comes from the American Red Cross.

That type of albumin has been studied for over 50 years.

They've never seen any viral transmission of hepatitis, HIV, COVID, Or any of these different infectious agents or cancer. They do a significant screening process literally every day on all the different batches. They do a process that they do MRI analysis of their sample for certification of authenticity, and the spike is only around the albumin mark. So I can't give it 100%, it's absolutely safe. Of course it's not. It still comes from humans. But there's really been no documented transmission of any of those things that you mentioned in the time period since the advent of albumin use about 50 years ago. Okay.

Next question is, what toxicity testing would you recommend we do in our clinics to help educate our patients that they need this procedure?

So I'm not affiliated with any of these lab testing, and they all do a very good job depending on what's We chose Vibrant America Total Tox Burden with the add-on of the PFAS because that gave us 109 different toxins of various different categories. We also did separately, independently, we did split samples of the toxins—

toxin testing.

We also did sequence of toxin testing, and the variance between all those was less than 7.2% by our calculations, which when you come to a test is incredible. That's incredibly good when you're looking at 109 different profiles. So we favor Vibrant America Total Tox Burden with the PFAS. Also, if your patient comes to us with that test, we won't have to repeat it, and the patient can receive a discount.

We reduce the cost of every protocol by $850, which is what we assume to be somewhere around the cost that you paid and charged the patient so that they're not doubly incurring it.

Okay.

We have absolutely every favor of doing what we can in the patient's best interest.

Okay, we've got 2 more questions. Do you have any patients who have combined TPE with chelation TX or DAPA-1 protocol?

Not sure what you're saying with the second part, but Chelation. The problem with combining chelation with TPE is chelation, you're putting in a chelator, and TPE, you're taking out everything, including the chelator. So we haven't done that, but we do do oral chelation at low dose in many of our different protocols just to increase the effectiveness of the TPE procedure. Our goal at MD Lifespan is to add in other modalities around the TPE that makes the TPE so much more effective. That we can do fewer TPEs, which we've been able to do, which reduces the prices overall to the patient. By our calculations, people who do our protocol TPE 3 get the same result they would do if they did individual TPE times 5. Similarly, you can do a TPE protocol with us of 5, which is equivalent to about 8 TPEs serial But just by the TPE itself.

So that's another way that we have a competitive advantage by the things that we've added around the TPE to make it much more effective.

Thank you. And last question is, what is the investment to bring this into a clinic?

There is no investment except for opening up your marketing ability to introduce and announce our Working with you. There is no financial commitment from the location at all. We provide the machinery, we provide the medication, we provide the nurses, we provide the ultrasound, we provide everything. We're just renting a room in your office for which we pay you on what's called a block lease agreement. It's a very good agreement in many different ways because not only does the location get paid for the use of the room, but if patients are unassigned to a doctor at this point and you have the facility and the aptitude and skills to take care of these patients, the number of new patients that you will get from us per month can be significant. Again, MDLifespan, we're only doing TPE. We're not doing long-term follow-up or care, so you don't need to worry about sending patients to us to do your TPE because We don't have doctors to do long-term care, and the clinics that we are in, people can refer in because we've never had a patient poached by one of the clinics because we make it absolutely clear that that cannot happen.

To date, for 3 years, it's worked out incredibly well.

It's a very good relationship that we have with our referring physicians, and we're just looking to get more information out because, again, We need referring physicians in many of these different locations as well. I'd like to thank you all very much for attending today.