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Dr. Raffaele received his B.A. in philosophy from Princeton University and his M.D. from Drexel University Medical School in 1989. He trained at The New York Hospital/Cornell University Medical Center and was formerly a clinical assistant professor of medicine at Dartmouth Medical School. Dr. Raffaele is board certified in internal... Read More
Christopher Shade, PhD, founder and CEO of Quicksilver Scientific, continues to be the driving force of development and innovation. Dr. Shade’s vast depth and breadth of knowledge, passion for healing, and intuitive understanding of chemistry and biology are reflected in Quicksilver Scientific’s well-designed detoxification protocols, unique supplement delivery systems, and... Read More
- How does detoxification impact telomeres?
- Telomere attrition causes mitochondrial dysfunction leading to senescence
- What would the perfect detox program for protection and repair look like?
Joseph M. Raffaele, M.D.
Welcome to another episode of the “Telomere Summit” of the Dr. Summits. I’m your host, Dr. Joseph Raphael. I am very happy to be here today with Dr. Christopher Shade, who is going to be talking about his work over the past few decades in detoxification, mercury systems, and then he’ll get into his longevity wheel and its effect in detoxification. And we’ll talk a little bit about telomere biology as well. Welcome, Dr. Shade.
Christopher Shade PhD
Thank you, pleasure to be here.
Joseph M. Raffaele, M.D.
So Dr. Christopher Shade is the founder and CEO of Quicksilver Scientific, continues to be a driving force of development and innovation. Dr. Shade’s vast depth and breadth of knowledge, passion for healing, and intuitive understanding of chemistry and biology are reflected in Quicksilver Scientific’s well-designed detoxification protocols, unique supplement delivery systems, and patented mercury speciation test. Dr. Shade is a recognized expert on mercury and liposomal delivery systems.
He has lectured and trained doctors in the U.S. and internationally on the subject of mercury, heavy metals, and the human detoxification system. Dr. Shade’s current focus is on the development of cutting edge lipid-based delivery systems for nutraceuticals such as liposomes and microemulsion systems to address the growing need of high quality affordable detoxification solutions. Well, let me just start, as I do with many of my guests, because I’m sure you have a fascinating journey to get to where you got in this field. What started you out in this kind of training, did you do, and tell us a little bit about your journey to where you are now.
Christopher Shade PhD
Yeah, you know, it’s kind of a funny and long journey. I always had a lot of interest in health and it really began in college, I didn’t think about it a whole lot. And then I had this sort of break from, you know, what I was studying, which was environmental science. And, you know, I realized they were just sort of helping the polluters and I took this kind of radical break and I went into organic farming. And a joke that I went out of business as an organic farmer the year that whole foods came around.
So I was a little bit early and then I stayed some organic farming research. I worked for Rodale Institute, they had this motto, healthy soil, healthy plants, healthy people, or healthy soil, healthy food, healthy people. And, you know, I was looking at it that way and then I went to graduate school and I got a PhD, and I was looking at what’s called biogeochemistry. And it was mercury biogeochemistry. So elements cycling through the environment, how they transform, you know, a lot of these are toxic elements, and here we’re looking at mercury becoming a toxin, building up in the food chain in that scene.
Got my PhD and I finished some testing for different forms of mercury, where we could separate the mercury from dental amalgams from the mercury from fish, and look at what’s compartmentalizing in the body and how it’s starting to come out. And I brought it over into integrative and functional medicine, and I realized they really had no idea what they were talking about. I mean, people are doing detox and they’re using chelators, but their understanding was very unsophisticated compared to what it was in environmental science. Now, I think this is because no money was put into a clinical mercury science, really because of all the controversy around thimarisol and vaccines. And so the government shuttled all this money into environmental science, and we knew everything about mercury going through phytoplankton to zooplankton to fish, where it compartmentalize where it goes in the cell. And so I wanted to apply some of that and get us away from this sort of heavy-handed approach to mercury in, chelators, mercury out, to, you know, how does this cell suppose to deal with this?
And so I focused a lot on the glutathione system and how that gets turned up, the transporters, the transferases that go with it, things that link toxins like mercury onto glutathione, how they get shuttled out of the body. And that led me to these big gene switches, Nrf2 and AMPK that worked with that. And, you know, frankly at the beginning, you know, I started coming to A4M and doing anti-aging shows back in like 2010. And, you know, I was a little jealous, you know, they’re doing like stem cells and, you know, telomerase activation, and all I’m doing is taking out the trash. But the farther I got into it, you know, the farther I looked into it, the more you see that, you know, it’s a very deep, deep biochemical picture when you’re cleaning things up.
It’s not just cleaning up environmental trash, but a lot of this is metabolic trash. You know, we’re making proteins all the time, we’re misfolding them, they’re building up, they’re becoming inflammagens, they’re crowding the cell. And we see there’s this rhythm of anabolism and catabolism. And, you know, we need to sort of link those two together so that during catabolism that’s activating AMPK and Nrf2 wants to go with it, and we clear all that stuff out of there and we tune up our antioxidant system at the same time. And guess what, things like telomerase are activated when glutathione is high and it’s highly reduced, when all these inflammagens are getting out of the cell.
So over time, I sort of built up this idea of the longevity wheel. What are the things that we have to hit? This Nrf2, AMPK, NAD, sotulins, telomere attrition, telomerase activation, senescence, dealing with that, and the neuroendocrine system, and we see they all go together and sort of all those paths lead back into this cellular cleanup and this maintenance of a clean redox poison in the cell. And, you know, it really goes back to these old, you know, 100, 200-year old ideas of a clean terrain, both outside the cell and inside the cell. And so as we go on to talking about the “Telomere Summit,” you know, it’s natural for me to talk about detox ’cause, you know, over time I built up my whole company around developing these nanoparticle deliveries to support that, but then also support these higher order metabolic things like the sotulins and the NAD levels. So that’s a Quicksilver came to be back, you know, around 2009-10. And we’d built up now over the years to, you know, making our lifestyle on this.
Joseph M. Raffaele, M.D.
Really interesting. So let me just step back a little bit and talk about specifically mercury and how it was interested to hear, because I know if you talk to the toxicologists that, you know, the state laboratories are like, “Well, we don’t care if the mercury levels, as long as it’s under 50, we’re good.” And then you get the call. And then you talk about the integrative physicians who are using the culation stimulation to see whether or not, you know, you have mercury overload. But what you’re saying is you have a way of looking at it without having to do stimulation and then separating out methyl mercury, which is organic mercury that you measure in the blood from inorganic. Sometimes people get that confused where, you know, let’s just get rid of mercury. Well, you know, maybe you have a lot of one kind, but not a lot of the other. Tell me about how you separate those out and then we can get into how that starts to affect the body.
Christopher Shade PhD
Yeah, so we use something called mercury speciation testing. This is why I did my PhD on was to have one method where all the mercury forms go in, but then we chromatographically separate them out and measure them individually. We do this in blood, hair, and urine. So toxicology would only measure total mercury. And if you’re exposed to inorganic mercury, they’d look to the urine. And if you’re exposed to organic mercury, they’d look to the blood. But you know what we found, you know, once you separate these two, urinary inorganic mercury should be proportionate to blood inorganic mercury.
And when it’s not, that shows that there’s some damage to the transport mechanisms that are in the proximal tubules of the kidney. So it’s got, you know, some glomerular damage in there, and that’s one of the easiest places to scar up, especially when you have metals and endotoxin together. So you’ve got a bunch of amalgams and he got leaky gut, maybe periodontal disease. You can really knock out the kidneys and you can build up a large amount in the blood, but a low amount in the urine. And in fact, when people do the chelation test, if you have this kind of transport damage, you’ll take the chelator and you won’t get much out in the urine, you’ll get a false negative.
So that was a really nice thing to have those two independent, and then the organic or methylmercury in the blood is related to what comes out the hair and they should be linearly chelated. When they’re not this one’s not as direct, but it reflects more of a disorder in cycling related to glutathione and and liver processes. So we’ve got a load of what’s in the body in the blood separated into the two forms: the organic from fish, the inorganic from dental amalgam, and the excretion paths in hair and the urine.
Now, this story had always built up that the chelator is gonna to show you your body burden, which you couldn’t get any other way. Like the chelator would go into every cell and take a representative amount and dump it all out so you knew what was going on. Well, that was a story that was built up because they don’t go even into the cell, they don’t go across the blood brain barrier. They’re taking proteins that are in the blood and lymph, solubilizing the mercury that’s protein-bound into a water soluble kidney filterable form. So they’re taking what was already there, but making a lot easier to see. So 30 years ago, when they started doing this, you just could measure very high. In urine and blood, it was just like, you know, it didn’t relate to amalgams. So they kinda made up these stories around there. So once we had really good analytical technology that could measure down into the parts per trillion level and separate the different forms, the whole picture’s right there for you.
And so that was the move forward that we took in the analytical. And then in the treatment, it was, all right, how do we get it out? Well, it’s up in the tissues, it’s in the cell. How do you get it out naturally? You’ll link it to glutathione. So we’ve got to get glutathione in there. We need to have the transferase that pulls the mercury off the cellular proteins and links it on to the glutathione and then phase III. So people talk about detox and phases. There’s phase I, phase II, phase III.
Phase I are more oxidative reactions to take non-reactive things like flame retardants, some of the pesticides and herbicides, make them a bit of a radical and then link them in phase II, all right. And that’s, you know, when Jeff Bland talked. It was phase I and phase II hepatic detoxification, but then phase III is like a relay race out. And so they’re transmembrane transporters that actively move this toxin conjugate out of the cell into the blood, from the blood pull it into the liver, from there dump it into the bile flow. So all of a sudden it’s like, oh wait, we gotta do all this stuff in this cell, we gotta dump it into the blood, then we need the liver to harvest it and coordinate it with bile flow because actually the toxin transporters out of the liver are also bile transporters. So anything that blocks bile flow blocks toxin flow. So that was our movement forward to get all of that harmonized and then make sure you have the proper binders in the GI, specific ones for metals or mold toxins to catch all that and get it all out to fecal excretion.
Joseph M. Raffaele, M.D.
What are those binders?
Christopher Shade PhD
So for metals, we use something called IMD. That’s a proprietary thoil-functionalized silica. So, you know, the blood-borne chelators, DMPS, DMSA, those we’ll have dithiols onto a central carbon molecule that’s negatively charged and they’ll make these complexes in P amount. So we take these very high surface area silica particles and covalently bind on carbon chains that terminate in thiol groups. So you’ve got just millions of thiols coming off every little particle and those go through the GI. And as those metals come out with glutathione or metallothionein into the bile, they then grab them and hold on to them so that you don’t reabsorb them.
And the most famous of the reabsorbing metals is methylmercury, it’s got about 95% re-uptake, cadmium’s got a lot of re-uptake, a little bit for arsenic. So that just ensures that you take everything all the way out. And when you’re talking about mold toxins and more environmental toxins using a combination of charcoals and zeolites and chitosan, chitosan is an allergic but shellfish-derived, that’s repeating amine groups. It’s analogous to Welchol or Cholestyramine, a little bit weaker than Cholestyramine but similar to Welchol.
Joseph M. Raffaele, M.D.
So you don’t use any of these actual EDTA-type or DMSA chelators?
Christopher Shade PhD
The one that we use is EDTA. We do a lyposomal EDTA. I mean, you’ve got four main metal. You got mercury, cadmium, arsenic, and lead. Mercury, cadmium, and arsenic are very thiol reactive, they get linked onto glutathione to get out of the body. You can take them all out with a glutathione system upregulation. Glutathione system upregulation block the toxic effects of lead, but it won’t export it. And so there some EDTA is very effective. DMSA is effective there too, you know, and a lot of people, you know, like Mark Hyman’s group, they’ll use our system as a base. And then they’ll over top of it a little DMPS, or little DMSA, or EDTA in various forms. But within our system, EDTA and the liposome is the only one of the chelators that are part of the system.
Joseph M. Raffaele, M.D.
And how do you follow the effectiveness of it? Do you do laboratory testing?
Christopher Shade PhD
Yeah, we’re doing the blood testing. Yeah, the speciation testing before and after and, you know, making sure everybody’s come down. Do you know, Neil Nathan and Eric, I forgot the guy who worked with him now, I forgot his last name. They ran a big clinic out at Santa Rosa. They’d been doing DMPS chelation for 20, 30 years. And they did a whole thing comparing ours to what they’re used to seeing. And they said, it’s as good or better. The beauty of it is you’re getting the body to do what it’s supposed to do. And so turning that up to this trigger, Nrf2 is turning up the intracellular formation of the antioxidants and all these molecules. And in fact, if you’re doing chelation with DMSA or DMPS, you’re not getting into the intracellular stores.
The only way they can get out of the cells is through Nrf2 upregulation, ’cause with Nrf2 come synthesis of glutathione. We bring in liposomal glutathione to just help that, but Nrf2 is bringing in synthesis of glutathione and activation of all these enzymes to dump things into the blood. In fact, if you really strongly upregulate Nrf2, you’ll see the blood levels come up for a little bit as the transport mechanisms clearing the blood or trying to keep up with it. And then when you stop, it’ll go down below where it was before. So at some point you need to turn up the, you know, squeeze the sponge of the cells, get them into the blood.
Joseph M. Raffaele, M.D.
Just for our listeners, talk a little bit about the Nrf2 system, and the kinds of things you use, I guess, sulforaphane and other things like that for upregulating it and how important it is.
Christopher Shade PhD
Yeah, so Nrf2 is a stress response trigger in the cell and it’s located in the cytoplasm and there’s a pair of proteins, Nrf2 and held in place called something Keap1.
Joseph M. Raffaele, M.D.
What one, Keap1?
Christopher Shade PhD
Keap1, K-E-A-P-1, like it keeps it in place. And so it’s got these sensitive dithiols on it. Dithiols are very sensitive to oxidative damage or electrophilic damage. Electrophiles are like reactive oxygen species and that they pull away electrons, electrophiles. But that would be any of the metals, various environmental toxins, mold toxins. And so if you have a buildup of chemical or oxidative stress in the cell, you oxidize these dithiols and it releases Nrf2, and it goes into the nucleus and it activates transcription of a family of genes that has a promoter region called the antioxidant response element. And this family of genes includes intracellular antioxidants, like glutathione, like superoxide dismutase, thioredoxin and all of the things that go with them, like the transferases, the transporters, different things for cleaning up old proteins, molecular chaperones, and all these clean up the cell and lead to cell survival under these stress conditions.
Now, over age, just like telomeres go down, the activity of Nrf2 goes down. So Nrf2 is inducible, meaning under stress, it induces, but it also has a rhythm with which it naturally goes in and cleans up the cell. In fact, all these proteins, they used to be called housecleaning proteins before they subsume them all within this whole chemo protection system. And so over time, this rhythm with which it gets induced goes down. But we can bring things into the system, which induce it to turn up transiently.
And these are things like our lipoic acid, sulforaphane. In fact, we’ll hit on quercetin a bunch of times in this talk ’cause it does so many different things for us. So the general classes you’ve got the sulfur molecules, like the sulforaphane, isothiocyanates, like you get from wasabi and then lipoic acids, the one I use the most, and then the polyphenols. So the polyphenols would be like EGCG, Haritaki extract, quercetin, resveratrol, and tri to a lesser extent. All of these have this effect. And interestingly, you know, we think of these as antioxidants, like, oh, lipoic acids, antioxidant, green tea extract, antioxidant, they’re actually little free radical generators, but they don’t have collateral damage and they’re light but effective at changing that confirmation of Keap1 so that Nrf2 translocates and upregulates all these good genes.
Joseph M. Raffaele, M.D.
Right, well, that’s a great explanation. And so you try to upregulate these systems. Maybe we should talk a little bit about your longevity wheel sort of protocol.
Christopher Shade PhD
Yeah, so, you know, it kind of looks like a Star of David. You know, there’s the six points around it and at the top is Nrf, AMPK. And we’re gonna start there for even a couple of months and like, we have a program now we call the Bio age Reversal Program and we took 44 people through this program and we did true age diagnostics epigenetic age clocks on before and after. And we’ve done some serum markers as well. And in the first month we’re focusing on Nrf2 with glutathione, and we use the little cat’s claw to try to address some of the latent viral activity and trying to turn up the cleaning up of the system.
And, you know, we do the Nrf2 upregulators with the bile flow modulators as a dose, and it’s something called liver sauce. And so you’ve got traditional beta compounds in there. Yeah, I know, it’s like A1 sauce for your liver. And so it’s got traditional beta compounds like gentiana and myrrh and dandelion root to turn a bile flow along with these polyphenols and sulfur-based upregulators Nrf2 and AMPK. And in the nanoparticle format, they gets in and gets absorbed and peaks in the blood between 20 and 30 minutes. So it activates all this flow, couples at the bile, and then a half hour later, we come in with a binder mix, you know, the thiol silica, the charcoal, the clay, the chitosan, and carry that all away.
So we do that for a month, then we switch over to doing the same, what we call push catch, like activate and then bind. But now it’s a little bit more AMPK focused and we’ll do that for another month and add in NAD precursors. We use nicotinamide mononucleotide, liposome, and some membrane builders. So in this longevity wheel, the mitochondria is sort of the center of the focus and the mediators of everything are the membranes, membranes on cell membrane, the mitochondrial membranes, and the plasma in particularly, the golgi, they’re the communicators that talk about everything. And they get all damaged by the reactive oxygen species, the toxins. And so we’re moving out toxins, and then we’re trying to activate AMPK. This is a big one these days.
You know, I talked about it at a forum and David Perlmutter followed up right behind me talking about it as well. And AMPK is pushing us into lean metabolism. It’s what happens when we water fast, when we carbo strict, when we do keto diets, when we exercise, it’s saying, “Oh, we’re using up the available energy, let’s mobilize fats and make ketones out of them. And thus, we’re gonna mobilize fat-soluble toxins. Let’s mobilize glycogen, glucose, let’s turn up glucose transporters and go into a lean metabolism.” And so we do that for another month and then focus another month on membranes and NAD. And so this is to get, you know, the poise of the system back really tight. You know, and it’s so effective when you do these things. In fact, just that first month protocol, we had a guy named Chang Won use this system for looking at fatty liver, and he got 82% resolution of fatty liver in one to two months just doing this kind of a system.
Joseph M. Raffaele, M.D.
Yeah, I did interview Dr. Won.
Christopher Shade PhD
Yeah, at the time he did 100 patients and he’s got 800 that he’s ran through this since then. And so we’re gonna get that together and publish it. So you see, you know, there’s ability to move into clean metabolism. And, you know, one of the things, you know, when the toxins go in, they’ll hit the telomeres and there’s different toxins that do that, you know, the most, and probably Cadmium’s the worst, arsenic and lead right behind that, tobacco’s really renowned for that. I think as we look more and more these, even if we look at like mold toxins, we’ll find there’s a lot of telomere attrition from that, leading to mitochondrial dysfunction, leading to cellular senescence, leading to the propagation or the spreading fields of inflammation that are recruiting everything else into that.
So we want, when we’re choosing these compounds, be able to address that already accumulated damage, and you know, that load of senescent cells that we have, and our choice of the compounds, you know, we use a lot of quercetin because it’s a good Nrf2 upregulator, great AMPK activator, stimulates mitochondrial biogenesis, and it’s a acetylenic as well. And so we did find at the end of this three month period that the beta galactosidase, which is well a marker of cells that are releasing it, meaning you’re breaking down senescent cells that the beta galactosidase had gone quite a bit up. And then we wanna follow up after we stopped at a couple of months and see it come back down. So it’s really exciting to–
Joseph M. Raffaele, M.D.
Did you measure that with Infinity?
Christopher Shade PhD
Yeah, with Infinity, you know, and a lot of these things, you know, we’re still working out what’s ready for prime time and what’s not, you know. NAD, where are we gonna measure it? You know, what does it mean to measure it in plasma? You know, ’cause it doesn’t mean the cells are higher or low but it means something. What does it mean to measure it and red blood cells? And do we have that assay wound up? Where should we measure AMPK? Certainly not in plasma, but maybe in the PBNCs
Joseph M. Raffaele, M.D.
For sure, yeah. We’re definitely in the early days on that. You mentioned true age, did you get pre and post?
Christopher Shade PhD
Yeah, we did. We got pre and posts, we got a nice, very highly significant reversal on the new DunedinPoAm algorithm, the original Horvath algorithm. And they’ve got another one I think out of Yale, they’re gonna run on that now. And that’s in the early days. Okay, we moved that back, what are the genes affected? Well, I don’t really understand, you know. And so digging into these and which ones really mean something. But one of the really nice things, you know, we’re in the age of, you know, immune challenge. And so we saw a nice reverse on natural killer cells, T-cells and beta cells, and, you know, at least in their epigenetic profiles. And, you know, we don’t realize how–
Joseph M. Raffaele, M.D.
So you did the intrinsic indication, which is the Horvath true age. And then you also did the next one. And you saw some changes in the T-cell subsets based on their DNA methylation panel?
Christopher Shade PhD
Yeah, yeah, yeah. Those are really nice. You know, it was B’s, T’s, and natural killer cells. And so with that, you know, well, Nrf2 and AMPK both relate heavily to immune function. Glutathione levels, and specifically the amount of reduced versus oxidized are very strong modulators of immune response. When glutathione goes down, you shift into like teach TH2 and TH17 type of inflammatory activity and away from your TH1 activity. In fact, interferon goes way down and then you bring the glutathione back up and the interferon comes back. And then with AMPK activation, you have activation of STING genes, those are interferon genes. And the process of autophagy comes with AMPK activation.
We know that more for mitophagy and endoreticulopathy taking, you know, old mitochondria, breaking them down so that you can make new ones, but that autophagosome that’s produced in autophagy, and then it’s linked together with a lysosomes to break it down, when you do that with microbes, virus, bacteria, parasites, that’s called xenophagy, and it’s allowing you to break it down into subsets so that you can form the right antibodies to it.
And yeah, so these are huge elements of our immune response and then like glutathione its relationship to telomeres. The higher the glutathione, the higher the telomerase activity. But it’s not just total glutathione, you’ve got to be shifted the more reduced versus oxidized, the more telomerase activity. So that all comes from glutathione synthesis, glutathione reductase, which are subsets of what’s upregulated during Nrf2 upregulation. So we see a lot of these things tying back together, and yes, we got significant changes there. The phenotypic changes are amazing. You know, I mean, looking at changes in fatty liver composition, looking at changes in energy, brain clarity that come with these things, and as you said, you know, with the ginfinity analysis, we’re just getting into, what should we really be looking at with all these things, and what compartment should we be looking at them?
Joseph M. Raffaele, M.D.
Yeah, so there are couple of studies, the Trim trial and Kara Fitzgerald study recently published results on epigenetic age reversal. Do you have a number? I’m just curious about.
Christopher Shade PhD
No. You know, I just got these results back from them from this three-month trial. And so I’m gonna meet with Ryan next week and we’re gonna go deeper into them, you know. And then I gotta break up in all 44 people and say, “Oh, this guy went three years back and this guy went three months back?
Joseph M. Raffaele, M.D.
Right, right. Okay, so it’s early. I didn’t know how long ago or you done it.
Christopher Shade PhD
No, we just got this stuff back and, you know. And so we have to translate these into amounts of time. And then we wanna go through this second part, ’cause the first part you’re kinda stirring up the pot too. I’m gonna move all these fat-soluble toxins out. You know, I’m gonna to try to get them out before they do any damage, but you can have a little bit of back and forth going on there. And then you get into the second level of this. And there you’re just, you know, feeding NAD, feeding sirtuins, feeding neuro-endocrine, bringing in pure astragaloside, different high-end adaptogens, ginsenosides and looking to drive the whole thing forward. So, you know, give them another six months on the nurturing side and look at them again now that we have that baseline data, their three-month intervention to clean up and restore the terrain. And then, you know, six months to build it back up and see where we go from there.
Joseph M. Raffaele, M.D.
So just in your overall protocols, what types of doses are we talking about for alpha-lipoic acid and for NMN and those sorts of things? I mean, I guess it’s there lyposomal systems. It may be that they’re lower than you might expect.
Christopher Shade PhD
Yeah, you know, you look at like when we’re doing quercetin and the AMPK activator, you know, 40 milligrams of that.
Joseph M. Raffaele, M.D.
Yeah.
Christopher Shade PhD
Yeah, and then you do the pharmacokinetics study and it’s a 25 fold increase in bioavailability. So, you know, now you’re 40 is a gram and it’s happening twice a day. And the other thing is how much you focus it into a window. You’re going up and you’re peaking between 20, there’s another peak at 40 minutes, and at 90 minutes, you’re out of the system. And it’s these very high levels that are really inducing. You know, these are all inducible things; Nrf2, AMPk, sirtuins. And so having everything focused in at once and having a bunch of overlapping ones. So in the AMPK product, you’re bring in quercetin, resveratrol, berberine, silymarin, and dim, all hitting same targets and different targets.
And so that’s where you’re really able to generate a lot of work. In fact, a lot of people, you see them go from sub nutritional ketosis into nutritional ketosis in, you know, 30 to 60 minutes because you’re able to hit AMPK from so many levels. So you do that twice a day with the binder systems. When we’re bringing in NMN, we’re bringing in 100 milligrams twice a day, We had to do Caco2 studies on that ’cause they’re harder to get a good blood measurement off of, and that looked like about a four-fold increase in bioavailability. So, you know, the insolubles tend to get larger increases versus the water solubles.
You can also get more into the particles. So, you know, as we go, you know, we’re refining, you know, we’ve got LCMS triple quad in here. So we’re try to get all the bioavailability equivalencies. And one of the interesting things when you get them in a nanoparticles, you don’t have them metabolized. So like curcumin. Unmetabolized non-glucuronidated curcumin in large amounts, and then you see the glucuronidation come up and a lot of these are much more biologically active before they go through that phase II metabolism.
Joseph M. Raffaele, M.D.
So this is a proprietary out liposomal sort of formulation?
Christopher Shade PhD
Yeah yeah, we’re making either liposomes or lipid nano emulsions and sometimes microemulsions. Everything’s sub 100 nanometers, we make everything in house. We’ve got one patent issued and nine patents pending on different forms of this. You know, we do even things like, you know, making emulsions for Molson Coors, cannabis systems, cannabis beverages in Canada. So we’re putting this technology into a number of things, always try to keep particle sizes a certain size. We have a lot of controls on that system and just trying to advance bioavailability so that we can get these like really powerful results.
You know, we know what the potential of these small molecules is. You know, everybody in the research world knows that natural small molecules have great potential, but bioavailability is what holds them back. And so we get rapid and high blood levels in and then we get the changes from those. You know, that’s how I was able to, you know, move things like adiposity in the liver and, you know, one to two months, just to getting so much in right away.
Joseph M. Raffaele, M.D.
At the same time, you’re measuring sort of more conventional things like hemoglobin A1C, you see kind of major changes with that?
Christopher Shade PhD
Yeah, you know, ironically, we hadn’t been tracking that all that much, and we just started doing oral glucose tolerance tests. And we see, you know, people coming from, you know, peaking up around 180 to staying on 135, 140, you know, with those AMPK activators. So that was really nice to see. And, you know, as we move forward in the beginning, you don’t have a lot of money, you know, to do these larger trials. And now we’re trying to bring in, you know, other groups and get larger trials going and, you know, just fill in all this data sets. Yeah, originally our strategy was everybody knows what the molecule does. We’re just gonna go in and shall we get more in. And then as we grew the company, we have more money to throw at it, now we’re doing these outcome tests.
Joseph M. Raffaele, M.D.
Well, that’s important. And I think the supplement industry in general is starting to realize that because there’s starting to be overlap between pharma and the supplement industry, because natural molecules are sort of where it’s at. And if you don’t show that same, not just pharmacokinetic data, but efficacy data, you’re not–
Christopher Shade PhD
Pharmacodynamics and the yeah, the end points on the study, you know that we’re getting there.
Joseph M. Raffaele, M.D.
So, yeah, I’d be very excited to hear about what the epigenetic age reversal was. Do you do any telomere testing?
Christopher Shade PhD
We haven’t yet. We do wanna start doing that and, you know, look at, you know, blendings and different things, you know, adaptogens and the astragalus products at the same time, along with all these. And so, you know, there’s various intellectual property around that we gotta be careful of.
Joseph M. Raffaele, M.D.
Yeah, sure, yeah, yeah.
Christopher Shade PhD
So, you know, get CA to let us do it.
Joseph M. Raffaele, M.D.
Well, yeah. I mean, I guess you could put the molecule in one of your overall systems. That would be interesting.
Christopher Shade PhD
Yeah, I think that would be a great way to go with it, you know, and I’d love to team up with them and get some of the data around that.
Joseph M. Raffaele, M.D.
Yeah, ’cause it might well be synergistic and you’d see, I’m sure it would be synergistic and that would be helpful. Well, I mean, it sounds like you’re on a real pathway towards a very comprehensive approach to age reversal. Let me ask you, are there any other things that you wanna talk about, to tell us about that you’re involved in before we wrap it up?
Christopher Shade PhD
No, I mean that about hits, except we just got into hormones and that’s been a lot of fun. We did a female system over the counter with nano DHEA and pregnenolone and some modulators like tizanidine and some adaptogens. And we found, you know, in the nanoparticle because it comes in unsulfuted, it can go into testosterone like that. And so it’s been really great watching even middle-aged, you know, premenopausal women and then menopausal women, you know, refilling their baskets with that. And for men, we did a nanoparticle testosterone that’s going out through college pharmacy. And we’re really interested in being able to–
Joseph M. Raffaele, M.D.
As a transdermal.
Christopher Shade PhD
No, as a sublingual. We did transdermal progesterone works, which works great, but the sublingual will take you say, you run in like three, 400. Take 12 to 15 milligrams, you’ll go up through 2000 to 2,500 and then come back down to baseline over about three, four hours. And the idea is to go up, activate the androgen receptors and get down so that you stop suppressing LH and FSH so that your testicles still make the natural amount they’re going to and do all the things that they’re gonna do, not have the testicular atrophy. This is incredibly. Go ahead.
Joseph M. Raffaele, M.D.
It’s quite similar to Natesto, I guess, essentially the nasal delivery system that pharma has.
Christopher Shade PhD
Yeah, exactly. So come in and then go away. So, yeah, and especially in the younger men who’ve had maybe TBIs that are lowering their testosterone to give them the androgen activity without having the contraceptive effect of doing like constant cypionate injections.
Joseph M. Raffaele, M.D.
‘Cause I mean, you know, they have micronized progesterone and you’ve used a transdermal form, I’d be interested to see, I don’t know, you would be able to speak to this more than I would. You’re talking about nanoparticles, that’s I presume smaller than a micronized progesterone. Could you potentially get, you know, a more effective progesterone in a lower dose?
Christopher Shade PhD
Yeah, we’re using eight milligrams right now and it seems to be enough. And when you look at the peak–
Joseph M. Raffaele, M.D.
Really?
Christopher Shade PhD
Yeah, you look at PK like–
Joseph M. Raffaele, M.D.
Eight milligrams of progesterone in a transdermal?
Christopher Shade PhD
In a transdermal, you know, some people will double that and stuff, but it like really chills you out and makes you sleep. And when you watch, like there’s a peak in about 100 minutes, that goes up to about, well, in that PK, we did 20 milligrams and a went up to about 20, I forget, is it nanograms per deciliter.
Joseph M. Raffaele, M.D.
Kilograms per mL.
Christopher Shade PhD
Yeah, came down and then went back up and came down and then went back up. And then after about 12, 18 hours, it’s back to running, you know, about one, but it goes transiently. So we have people put it on at night. It goes through some really high peaks and really works well. It’s truly dissolved, and it’s in these nanoparticles that are about 30, 40 nanometers. You do that topically and they really run in. So we’ll do that with test two, but we did the topical ’cause we’re a supplement company and we can’t do a sublingual. We have a sublingual and there’s people already been using that for changing endometrial You know, there’s a guy treating endometrial cancer with it and the sublingual has to be gone through a pharmacy, but the topical really blew our minds.
Joseph M. Raffaele, M.D.
Oh, I know the other reason you using such a low dose is ’cause you can use up to 20 milligrams topically, right? I think that that’s the magic number.
Christopher Shade PhD
Yes, up to 2% and that tends to be up to about 20 milligrams, but 20 milligrams, some people are doing 20 milligrams every day. We’re too tired.
Joseph M. Raffaele, M.D.
So when you’re measuring those peak levels, you’re using LC mass spec to do those?
Christopher Shade PhD
Yeah.
Joseph M. Raffaele, M.D.
Is it actual–
Christopher Shade PhD
Yeah, we just send them in into Access Labs.
Joseph M. Raffaele, M.D.
Oh, okay, you send them into Access Labs.
Christopher Shade PhD
And we couldn’t even do saliva ’cause blow out the–
Joseph M. Raffaele, M.D.
Yeah, that’s a whole another discussion. In terms of blood, I’m just curious ’cause I do a lot of hormone optimization, of course, whether or not you can get actual progesterone levels that high or, you know, what your metabolite profile is ’cause the progesterone is metabolized into many things and a lot of them are acetylates, you have the hydroxyprogesterone. And then the sleepy component is the allopregnanolone that you get. And, you know, so if you can do it with such a small amount of progesterone, that’s really interesting. And usually you don’t get the sleepy effect when you use it topically. You’d more often get it when you use it orally. So I’m curious about that as well. We should talk a little more about that.
Christopher Shade PhD
Yeah, it’s stony and sleepy, and there’s just no doubt. And everybody’s like, man, that stuff’s great. So we’re gonna do metabolites with Frank Norte from Ryan. He does 24 hour urine collection and does all the metabolites, he doesn’t dry it down. So we want to find out more what was going on, but it was really relevant blood levels, you know, for a couple hours after the dose. So, you know, we’d stopped at six and it was up at 20 and, you know, between there and, you know, 12, 18 hours, it comes back down. So you could do more than once a day if you wanna keep it up there, but it really does the trick.
Joseph M. Raffaele, M.D.
Well, very, very interesting. Well, I’m glad we talked about that. It sounds like you’re doing a lot of really exciting work advancing the field and it’s been a real pleasure talking to you about all this stuff and educating our listeners about it. Is there any stuff you wanna tell our listeners about to social media or your website or anything?
Christopher Shade PhD
Yeah, quicksilverscientific.com, go there, doctors get a doctor account, you’ll have access to all of our educational resources. I’ve done so many webinars. I do about one and a half hour webinars. I think we have 40, 50 online for the doctors to access. The consumers can get accounts and get access to some of our educational material. We do some direct-to-consumer. On social media, there’s Dr. Christopher Shade on Instagram, you can tell I’m not a social media guy. There’s Dr Christopher Shade PhD, Dr. Christopher Shade PhD. I do a podcast series and that’s a website and then Quicksilver Scientific on Facebook and Instagram to follow what we’re up to.
Joseph M. Raffaele, M.D.
Well, great. Well, thank you very much for taking the time to speak to us and look forward to seeing you at one of the conferences soon.
Christopher Shade PhD
Absolutely, thank you.
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