Ben Greenfield [00:00:00]: My name is Ben Greenfield, and on this episode of the Boundless Life podcast.

Dr. Hemal Patel [00:00:04]: Instead of having to do a blood draw, you basically take one of these cards that you get in the kit. It's got two windows in it. You poke your finger, you bleed into that first window, that bilayer system then wicks the serum away. The card effectively dries, and it archives the sample. We've shown stability of that sample out to two months at room temperature. And so now you can literally capture a sample from anywhere in the world, get it into our facility, we reanimate the serum in our proprietary buffer that we've created that's optimized for these mitochondrial tests, and then we're off to the races. We can essentially run the NASA type assay on your sample and look to see what types of cells are being impacted by mitochondria. MeScreen in our initial launch has really optimized the muscle cell.

Dr. Hemal Patel [00:00:50]: We think the muscle cell is a unique and sort of global capture of an individual's metabolic state. And so that becomes a huge reporter of how efficient and, and well your mitochondria are behaving.

Ben Greenfield [00:01:03]: Welcome to the Boundless Life with me, your host, Ben Greenfield. I'm a personal trainer, exercise physiologist, and nutritionist. And I'm passionate about helping you discover unparalleled levels of health, fitness, longevity, and beyond.

Ben Greenfield [00:01:24]: Well, welcome to the show. I have been asked many, many times by many folks how you can actually test the health of your mitochondria. Because when you go to the doctor for an average blood test or even get a lot of these fancy at home blood tests, they can give you clues, but they don't actually show you things like your direct mitochondrial health or efficiency. And I've always been curious about that. I had no clue that it actually could be tested until a kit arrived at my home and I actually did a mitochondrial test. And I was so intrigued by the results. And the folks who over saw this test for me from a company called MeScreen, they did a call with me, bringing me through my results, and I got done with a call and I said, you guys, we have to do a podcast about this.

Ben Greenfield [00:02:18]: So they graciously agreed. And my guest on this show is Dr. Hemal Patel. He's a tenured professor and vice chair for research at the Department of Anesthesiology at University of California, San Diego. And he does a lot of studies on mitochondria, along with heart failure, diabetic cardiomyopathy, aging, pulmonary hypertension, cancer, neurodegeneration, but his specific focus is on the energetics of cell biology, which of course, the mitochondria are intimately links to. So he is able to look at the results from a mitochondrial test like the one that I did and gather a lot of data about the body. So I'm hoping that during this show, you guys learn a lot about the mitochondria and how you can learn more about your own mitochondria with this pretty simple at home test. So, Dr.

Ben Greenfield [00:03:13]: Dr. Patel, welcome to the show.

Dr. Hemal Patel [00:03:14]: Yeah, great to see you, Ben.

Ben Greenfield [00:03:16]: Yeah. And it seems like there's this buzzword about mitochondria almost not to get negative. It almost annoys when people just say, oh, they're the tiny powerhouses of the cell. And everyone kind of nods like they understand what that means. And there's a lot more going on with the mitochondria than that. So how do you describe the mitochondria in people?

Dr. Hemal Patel [00:03:38]: Yeah, I think the powerhouse of the cell is something that is easy for people to conceptualize in their mind and that at a basic function is what mitochondria are. But they're way much more. There are these living organisms that live inside us. So about 1.5 billion years ago, some eukaryotic cell, like our cells are engulfed a microbe. And that microbe began a symbiotic relationship that lasts till now. Basically, it provides a unique advantage to that cell to adapt in its harsh envoronment. And the adaptive advantage it gave it, it allowed it to harness biochemistry in a way that it made energy at a much higher level than a cell could before. And as we think about what energy means is energy is the key to growth, the key to resiliency, the key to lasting and outliving the harsh environment that you're existing in.

Dr. Hemal Patel [00:04:33]: And so it's that symbiotic relationship that's lasted all of these years that's led to this complexity. So it is, in a nutshell, a living organism living inside us. They're old bacteria that got incorporated in. They have their own DNA. They get transmitted in a unique kind of way. All of your mitochondria come from your mother. This is why people have this unique relationship, that there's this biochemical aspect to it. Then the genetics of the mitochondria, there's a circular DNA that sits in it.

Dr. Hemal Patel [00:05:04]: It's called plasmid DNA. This encodes for a small subset of genes that the mitochondria need that are core functionality. What it's done in that symbiotic relationship over that 1.5 billion years is it's now sharing additional information with the cell that it exists in. And so a lot, and probably 95% of the proteins, 99% of the proteins that come from inside the mitochondria actually come from the nuclear genome. So now it's co opted the nuclear genome to create unique elements that allow it to adapt and do other things. The main function is to make energy. But it turns out that these mitochondria also are a huge conduit to cell survival, resiliency. And they become a key dynamic feature in every non communal chronic disease that you can think of.

Dr. Hemal Patel [00:05:54]: So any disease that can't be transmitted to an individual, so diabetes, heart failure, neurodegeneration, ultimately comes down to a demise of your mitochondrial functionality in one way or another, whether it's their structure or their function.

Ben Greenfield [00:06:08]: So when it comes to something like the production of ATP, people say, well, they help produce the body's ATP energy currency. That's how they're the powerhouses of the cell. That's based on what you just described, kind of a myopic understanding of the mitochondria.

Dr. Hemal Patel [00:06:25]: It is, I mean they do have to create energy as an example. So my pet organ that I've studied for the last 25 years is the heart. The heart is a bag of mitochondria, right? 30% of the volume of the heart is mitochondria. And it makes sense. The heart has to constantly work from the minute you're conceived to the minute you die. And that energy is used to create that beat that keeps you alive and pumps blood to the rest of your body. There's no battery in your body, so once the energy gets generated, it basically has to be consumed. And it can't be stored in any long term fashion or long term form.

Dr. Hemal Patel [00:07:03]: ATP has to be consumed. And so if you think about just the math and the gravity of it, the heart makes anywhere from 2-6 kg of ATP a day. Yet you don't gain that mass in any way because as soon as it's made, you're consuming it. When you actually dissect the heart into the unique cells, the cardiac myocyte, which is the large cell that makes up most of the heart tissue, and you look at it under an electron microscope, you actually see three different populations of mitochondria that sit in there. There are these things that sit right under the membrane of that cell and these are called the sub sarcolemmal mitochondria. And they actually make no energy. They're not an ATP factory.

Dr. Hemal Patel [00:07:44]: They're there to signal, they respond to the outer environment. They basically sit close to that outer environment on that plasma membrane. They take in the signals that come to the cell and they create a response element for that cell to decide what to do in terms of how to respond to stressors, the external environment, pressures and other things that happen. There's a second set of mitochondria called the interfibrillary mitochondria that sit within and inside the cell. This is the powerhouse of the heart. This is where all of that ATP is made. And then there's a third population that we've been looking at and hasn't really been defined. And we call it the sub sort of perinuclear mitochondria.

Dr. Hemal Patel [00:08:23]: There's a set of mitochondria that sit around the nuclei of cells and heart cells in particular. And we think that these are the ones that are the dynamic control points. So there's a big buzzword in mitochondrial biology is mitigation and autophagy, right? The self eating and digesting of things to replenish the system. And so we think that these perinuclear mitochondria may be the key to the mitophagic pathway within the heart and other cells. And so it turns out that, you know, there's lots of mitochondria in the cell, but they don't all create the same functionality. And they have unique dynamic functions depending on where they're located and what they ultimately do. And this happens in virtually every other cell type as well.

Ben Greenfield [00:09:04]: So if these three subsets of mitochondria have different functions, does that mean if you were to like analyze them anatomically, they'd also appear different? Or are all mitochondria built the same but just do different things?

Dr. Hemal Patel [00:09:16]: I mean, the core components are the same, right? If you look at them under electron microscope, you can, you wouldn't be able to distinguish them. If you sub fractionated and looked at those sets, they'd look like the same bag of bacteria, like sort of organelles. They have the cristae structure in them, they have the dense sort of elements, they have proteins. If you start looking at unique proteins, you may find unique variants in different types of proteins in these subpopulations. But then the functionality becomes very different, right? Because of where they're located, they do something completely different than if they're located in a specific other part of the cell.

Ben Greenfield [00:09:51]: Interesting. You know, next time somebody gains unexpected weight, I'm just going to tell them that 6kg is just ATP.

Dr. Hemal Patel [00:09:58]: Your heart's doing nothing, right?

Ben Greenfield [00:09:59]: Yeah. So I know a lot of people's heads are probably spinning because there was a lot of physiological terminology that you threw around. And I think people are probably most interested in how they can analyze how healthy their mitochondria actually are. And I actually hear in many cases not just the term mitochondrial health thrown around, but also mitochondrial efficiency. When you hear that term mitochondrial efficiency, how do you describe that?

Dr. Hemal Patel [00:10:32]: I mean, it's this notion of how healthy an individual is. Right. When you think of, I guess the easiest thing to think of would be a disease where mitochondria compromised. A simple thing that I think the world is facing right now epidemically is overweight. Right. If you look at every country in the world, there is an issue of obesity that then ultimately leads to diabetes, which then leads to multi organ failure and other things. Interestingly, the majority of deaths that are tied to diabetes ultimately are a result of cardiovascular dysfunction. So your heart dysfunctions in a unique kind of way.

Dr. Hemal Patel [00:11:09]: And this gets back to this notion of mitochondria, an organ that has such a huge component of mitochondria that's then having to fight this resolve, where in diabetes basically you can't get enough sugar into the cell because you've changed the way the receptors and other things are working on there. And it's unable to process the fuel states that the heart needs, that other organs need to function in a normal kind of way. And you see this decline in efficiency, the mitochondria become less able to utilize the fuel sources, less able to respond to stressors, less able to maintain a homeostatic state. The goal then in this efficiency state is to rebalance the mitochondria in any kind of way. A lot of these diseases, as we study in my lab, at a basic level in science, we try to manipulate the mitochondria as a way to increase the conduit for health. We've done this through manipulation of the plasma membrane. We've done this through direct manipulation of the mitochondria. And so then the question becomes, what is a healthy individual that's not dealing with disease? Consider mitochondrial efficiency.

Dr. Hemal Patel [00:12:15]: We see this in unique ways as well, right? Take the other extreme, right? If you're not chronically ill and you don't have this morbid disease, you're at this high peak of health and you're trying to elevate to this next level of resiliency and endurance. One of the things we see in highly active individuals that have really good mitochondria and we'll get to your test in a little bit. You looked amazing on our MeScreen test. One of the things we notice on this test is biohackers tend to do the worst on our MeScreen test because they're overhacking their mitochondria. Whatever you're doing, you're doing amazingly. And we'll get to your results in a little bit.

Ben Greenfield [00:12:50]: I know a lot of people are going to be surprised to hear you say that. I'm not over hacking.

Dr. Hemal Patel [00:12:55]: Well, you may be hacking in the right way, which is a good thing to see. We see that this. This extreme individual, there's room for improvement as well. Right. And there's ways to improve their mitochondrial efficiency in a unique state where they can ward off these chronic diseases and get to this state where they are ultra efficient. And that heightened state. One of the things that we're starting to look at with various athletic teams and others is how do you resolve injury? Right. One of the things that happens at these peak performances, you're more prone to be injured and other things when you're working at that high acute level.

Dr. Hemal Patel [00:13:33]: And mitochondria become this resilient aspect of recovery as well. So we're starting to look at all elements of that, not only in the chronic form, but in the optimized form as well.

Ben Greenfield [00:13:42]: Okay. So this test that I did for the mitochondria, it's called a me screen.

Dr. Hemal Patel [00:13:47]: Yeah.

Ben Greenfield [00:13:48]: Does the me stand for something like mitochondrial something? Yeah.

Dr. Hemal Patel [00:13:51]: So we, you know, we were batting around ideas of what to call this thing, and some amazing marketing person in our company came up with this idea of this moniker of a healthier you. Begins with me, and me is really mitochondrial efficiency screen. And that's what this test ultimately does, is it screens your efficiency level of your mitochondria and how well they're working.

Ben Greenfield [00:14:12]: Okay, got it. And by the way, if you're listening, I'll link to the test in the show notes at bengreenfieldlife.com/MeScreen podcast, just like it sounds. MeScreen. So the test, you know, I have to admit, embarrassingly, Dr. Patel, I think I did it about three months ago. And I do so many of these kind of tests. I don't recall the exact details, but I seem to remember it was a blood spot. Is that correct?

Dr. Hemal Patel [00:14:37]: It's little more than a blood spot. It's a prick of your finger and then really a wet pool of blood that then separates into the blood red component in the serum. And then we analyze the serum, which is cell free, mitochondrial free, but it has your biochemical environment that you're creating in your body from your genetics, from your microbiome. Everything that's creating this environment we're capturing on that card.

Ben Greenfield [00:15:01]: So what you're capturing on the card is like a proxy for mitochondrial health and efficiency because there's not actual mitochondria in the sample provided itself.

Dr. Hemal Patel [00:15:12]: Yeah. So we've been through this path of how to sort of look at this. So for many, many years we've been involved in multiple clinical trials on campus where the gold standard has always been a muscle biopsy. Right. So you come into the health system here, you're part of a clinical trial. We've done lots of studies with a good friend of yours, Sachin Panda. So Sachin and I have become strong collaborators. And so Sachin and Pam Taub are very interested in time restricted eating.

Dr. Hemal Patel [00:15:39]: And so we've been using this as a paradigm to look at pre diabetics and do they improve their mitochondrial health in unique kinds of ways. And I got pulled in to look at mitochondrial functionality. And so being on campus, being on site where we can do slow recruitment of individuals, we can actually do the gold standard, right? The patient comes in, their leg gets numbed, you take a needle that has a boring feature to it, you plunge it into that muscle, you pull that needle out and about 200 milligrams of muscle tissue comes out. My lab then gets that tissue and then it takes about six hours to do a really deep profile of fuel states, how that mitochondria functioning. We can do structural analyses and other things from that as well. It's low throughput, but you're looking at someone's genetics and their mitochondria, right. And so you have gold standard access to all of their functionality. There's no way to commercialize something like that.

Ben Greenfield [00:16:33]: You could, but I don't think a lot of people are going to use a biopsy. Many guillotine on their thighs at home. It's, I doubt it. It's, it's anything but boring. But I think you meant boring by a different definition.

Dr. Hemal Patel [00:16:46]: True. And the other aspect is it has to be fresh tissue, right? You can't freeze it in any way really to get the core action of mitochondrial functionality. And so we were pulled into an interesting study about five, six years ago with the NASA twin study. So the center from Arizona, who is the ground twin and his twin monozygotic identical twin brother who went up into space for a year, NASA's challenge to us. And so they selected 10 groups across the US. UCSD was one of these sites. My good collaborator on campus, Brenda Rana, was the site PI here on campus. And then she brought us in to do some mitochondrial aspects to this.

Dr. Hemal Patel [00:17:26]: The challenge that NASA had was we know that when an individual goes into space for any amount of time, one of the biggest things that declines is mitochondrial functionality. But we don't know which organ dysfunctions in which order. And we don't know how to test this in a unique kind of way as a resiliency measure in unique individuals that we want to test for ground. And so NASA's big interest is we're going to put people on the moon and Mars in short order and how do we pick these people? Right? And I was sort of shocked to hear that. When they get one application for an astronaut out, there's usually about 10,000 people that apply. There's about a thousand of them that qualify to get to the next stage. But they have advanced degrees, they're you know, Olympic level athletes. And out of that you got to pick one or two people that then make it to the final stage and you have to pick that right individual.

Dr. Hemal Patel [00:18:15]: The concern they have is they have such an investment in this pool of picking these individuals and who will go to Mars and the moon is they don't know how to test their stress resiliency and mitochondria become a core conduit. And so their challenge to us is we can't give you tissue. The only thing we can give you is blood plasma. And we'll give you blood plasma at unique time points before flight, every three months during flight. So Elon Musk would send a rocket up every three months and SpaceX would send the samples back. And then we archived all of these and then we had samples after they returned to Earth as well. And then so we had the ground twin throughout all this time, and we had the space twin throughout all this time. We basically built a human on a plate assay for them.

Dr. Hemal Patel [00:18:59]: So the concept was because we can't get tissue, the plasma becomes this biochemical capture of that person's exposure, right? So everything that they're experiencing from the inside out, so their mind, their thoughts, their isolation, their radiation exposure, outside exposures to the environment, all of that gets captured in their plasma, right? Your genetics is creating biochemical entities that are spewing out into your plasma. Your microbiome is creating things that are responding to these stressors. And so that plasma becomes this unique time capture of that individual. The thought I had was that plasma Then also bathes all of your cells. Your cells are seeing that information in a unique way. So what we built for NASA was basically a human on a plate. So we can buy cells from a company called ATCC that represent every organ of the body. So we can buy cells that look like your neurons, that look like your eye cells, that look like your skin cells, your heart cells, kidney.

Dr. Hemal Patel [00:19:59]: So we built essentially a human on a plate. And the way we exposed it to the individual is we transferred that plasma onto that cell at those unique time points that we captured. And so now those cells are responding based on that environment that's changing that that individual's created. We were able to predict at a unique specific time point in flight when there would be muscle dysfunction. That was published in the big science paper that came out on this with the twin study. And then sort of subsequent studies have shown unique differences in immune dysfunction and an endothelial dysfunction that track with these specific time points of care capture. Right. All based on this blood based assay.

Dr. Hemal Patel [00:20:40]: Now you have scalability. You can go to Quest or LabCorp to do these kinds of blood draws. They can come to our lab and we can do these kinds of testing. You're not tied to this muscle biopsy, but there's still that other barrier. Right. Most humans don't want to leave their home. They're hermits, they like to hang out, they like to do things on their own, especially in the biohacker community. Right.

Dr. Hemal Patel [00:21:00]: They don't want other involvement. They want to do everything on their own.

Ben Greenfield [00:21:03]: Yeah. I mean, as much as much fun as driving to a lab and getting the tourniquet on your arm and, you know, standing in line for a half hour and, you know, submitting multiple tubes of blood and hoping they get the right vein the first time. It is kind of nice to be able to stay at home.

Dr. Hemal Patel [00:21:17]: Yeah. So MeScreen miniaturizes all of this. So now instead of having to do a blood draw, you basically take one of these cards that you get in the kit. It's got two windows in it. You poke your finger, you bleed into that sort of, you know, that first window, that bilayer system, then wicks the serum away. The card effectively dries and it archives the sample. We've shown stability of that sample out to two months at room temperature. And so now you can literally capture a sample from anywhere in the world, get it into our facility, we reanimate the serum in our proprietary buffer that we've created that's optimized for these mitochondrial tests.

Dr. Hemal Patel [00:21:53]: And then we're off to the races. We can essentially run the NASA type assay on your sample and look to see what types of of cells are being impacted by mitochondria. MeScreen in our initial launch has really optimized the muscle cell. We think the muscle cell is a unique and sort of global capture of an individual's metabolic state. And so that becomes a huge reporter of how efficient and well your mitochondria are behaving.

Ben Greenfield [00:22:20]: Wow, it's fascinating. And my hack, because I have big, meaty, thick fingers and thick skin, is I. I go in the sauna to do these tests. I flip on the sauna like a half hour before I'm gonna go, and then I just bleed like a, pardon the expression, stuck pig when I go in there in the sauna. So until then I just had to fight even these small blood spot tests. But heating the extremities seems to help a ton.

Dr. Hemal Patel [00:22:45]: It is doable. Right. So I do a lot of research with Joe Dispenza. So we run all of his research at his events. And we were just at his 10 day event in Cancun. And Cancun's a tough place to get blood draws from the arm. And so we decided to pilot these blood cards. We had 750 people enroll in this study.

Dr. Hemal Patel [00:23:06]: And so we had a whole team downstairs poking people's fingers and doing this. Out of 720 pokes that we did, I think there was maybe one or two cards out of all of that. We did them three times that we may not be able to get a sample from, but we'll be able to figure something out. And there was some interesting. People who have climbers tend to have really calloused hands. Right. And you got to find the right place to go on their finger. And then the nervous individuals as well, who are constantly shaking as we're trying to get this.

Dr. Hemal Patel [00:23:37]: But it is, I mean, it's an easy thing to do at home. I poke my fingers all the time. I'm a constant source of blood in the lab for people, testing out unique things and trying different things on the assays as well. So it's fairly easy to do.

Ben Greenfield [00:23:54]: Yeah. It's interesting you mentioned Joe Dispenza. I'm assuming you must have been doing some kind of a study, I'm guessing on what, like meditation and its effect on mitochondria.

Dr. Hemal Patel [00:24:04]: Yeah. So we, we've been working with Joe five years. We had our fifth year anniversaries coming up in February. We started working with him before the pandemic and so it's an independent thing that we've come in. And so UC San Diego has been funded by a nonprofit. $10 million over the next five years to come up with what happens in mindfulness approaches and meditation approaches and how they change the human body. And so we're looking at multi omic profiles of how the body completely changes in response to a meditative experience. And Joe does it better than anyone else.

Dr. Hemal Patel [00:24:39]: Right. I don't know if you've ever been to a week long event.

Ben Greenfield [00:24:42]: No, I have some of his tracks downloaded where he's talking like this as you meditate, but I've never actually been to one of his seminars.

Dr. Hemal Patel [00:24:53]: It's transformative. And the Cancun was the first 10 day event. And so we were looking at unique elements of how an individual changes from an individual to a collective to a consciousness state. And mitochondria become a key piece of that.

Ben Greenfield [00:25:08]: Wow. Maybe I'll be the next book. Mito Meditation. So you mentioned that you've got your hands on my results. I think for illustrative purposes it would be fascinating to to see what it is that you find on a typical test. So everybody who's watching the video, and if you want the video, just go to BenGreenfieldLife.com/MeScreen podcast or you're checking this out on YouTube. You can see the results right here. So take it away, Dr.

Ben Greenfield [00:25:33]: Patel.

Dr. Hemal Patel [00:25:34]: Yeah. So I'll walk you through what you did here. Right, so we sent you a kit that had this card and all the other things that you needed to collect your sample. Poked your finger, you bled onto this thing. Jokingly, I've been saying we're six drops better than Theranos to our investors and stuff. These guys are like, stop saying that, man. But you know, there is so much information in blood that you can capture. And these cards, a lot of companies are using these and there's lots of things that come out of this.

Dr. Hemal Patel [00:26:00]: Right? And so that, that six, four to six drops of blood, basically that serum migrates. That card dried, you sent it back to the lab. When it came to our facility, we reanimated that serum in our buffer and then we put it onto our system in a unique way. We have these muscle cells that are sitting on. It's an Agilent system that measures metabolic flux. Essentially. We've tweaked the assays in unique ways that we can get different elements of your mitochondrial biology and functionality out of this. We adapt your environment that we've captured on this serum sample onto this muscle cell that's sitting on this machine and that muscle cell is being constantly probed.

Dr. Hemal Patel [00:26:41]: And that system is measuring oxygen in real time and it's measuring extracellular acidification, so it's measuring ph. And by looking at those two things, we get the two basic measures of energetics in a cell. Mitochondria are the more efficient, faster way of making ATP and then glycolysis is the less efficient. But the thing that's always working in the background is making energy as well. The oxygen flux gives us what your mitochondria are doing and the ph gives us what the glycolytic pathways are doing in yourself. And so when we add your environment onto the cell, the first thing we look at is baseline respiration. So respiration is how much oxygen is being consumed. And so I mentioned to you earlier that when we look at biohackers, we tend to see weird changes.

Dr. Hemal Patel [00:27:27]: And so the first thing we notice in biohackers is most of them either have a suppressed baseline respiration, so that they've overtaxed their mitochondria and they're sort of something toxic in their environment that's shutting them down, or they're over activating their mitochondria. Right. They're on too many supplements that are over hyper driving everything.

Ben Greenfield [00:27:47]: Yeah, and I'm going to actually, I'm going to actually interrupt you right there, you know, because you say biohacker, I'm assuming when you use that term, you mean, you know, like a hardcore health enthusiast who's taken lots of supplements, exercising a lot, maybe doing a ton of red light oxygen electrical therapy, like they're using a lot of modalities, many of which paradoxically are championed as being good for metabolic health.

Dr. Hemal Patel [00:28:12]: Yeah, and we can get to that when we think about sort of how to optimize your mitochondrial health. There's a thousand ways to change your mitochondria, but unfortunately not all thousand ways work the same way in every individual. And so if you're just consuming all of these different pathways to optimize your mitochondrial health, it may be that one or two may be optimal for you, but then the other things are actually detrimental and they're hindering your mitochondria and the potential that you have. Right. And we see this on our test, we see that most biohackers, that individuals that are on these 10, 15 supplements that are doing sauna, red light, time restricted, eating, cold plunge, all of these things, they tend to have a higher baseline respiration. Right. They're over activating their mitochondria when they shouldn't be activated. Okay, so yours is right where we'd want to see it.

Dr. Hemal Patel [00:29:01]: So when we add your environment to that muscle cell, it does nothing. Right. It doesn't suppress its respiration, it doesn't heighten its respiration.

Ben Greenfield [00:29:10]: And again, for clarifying purposes, people hear respiration, they think, how many breaths I take. This is different than that. Right.

Dr. Hemal Patel [00:29:16]: So it's, it's related to that. Right. So when you take a breath, you're taking oxygen into your body. Right. And that's called respiration. When the mitochondria respiring, they're using oxygen to make energy. And so that's the biochemical reaction that's happening in your mitochondria.

Ben Greenfield [00:29:31]: Yeah. So it's basically measuring your mitochondrial breathing.

Dr. Hemal Patel [00:29:36]: Yeah, oxygen, essentially. Yeah. So the probe is measuring oxygen. So basically you're even keel. So then what we start doing to the mitochondria is we add chemicals to the system and we stress them. We actually exercise them in a dish. And so we add what's called an agent that blocks the ATPase.

Ben Greenfield [00:29:57]: I thought you just added tiny treadmills to the dish.

Dr. Hemal Patel [00:29:59]: We do. We can do tiny treadmills as well, but I don't know how well the mitochondria would do on those. So basically you've got this, this cell that's cooking away, and then you block the one stop part in the mitochondria that stops the ATP from being produced if there's still oxygen movement through the system. So if the system is still trying to consume and respire, it suggests that there's an inefficiency in the system. Right. You're telling the system stop if it continues to try to move that oxygen through it suggests that there's a leak somewhere happening. And so we've essentially created an efficiency number through this. So we're looking at the inefficiency, but we look at the inverse, which is then the efficiency state.

Ben Greenfield [00:30:40]: Okay. And by the way, a quick question about the inefficiency, the respiration. Would the reason that you wouldn't want excessive mitochondrial respiration instead of sweet spot be because of the free radicals and reactive oxygen species damage potentially done by excess? I suppose. Anaerobic glycolysis.

Dr. Hemal Patel [00:31:03]: Yes. Yeah. So if your mitochondria constantly working, what'll happen is you'll get faster enzyme degradation in different parts of the mitochondria. So proteins will dysfunction at a faster rate. As they start to degrade, you'll get higher potential to create these reactive oxygen species. And then it becomes a vicious cycle. So these reactive oxygen species will damage proteins at a faster rate and you'll get this constant sort of demise of your mitochondria. And so this is why you want your mitochondria to work when you need them to work.

Dr. Hemal Patel [00:31:34]: So when you're exercising, when you're stressed, essentially fight or flight, right? When you're trying to flee a line, you want your mitochondria to become active, create that energy, allow you to live, and then when you're resting, you want the system to rest, you don't want it to start, keep cooking and making energy when you don't need that energy. And so that efficiency is testing some element of that. And then the final component is your mitochondrial potential. So in this, what we do is we uncouple the mitochondria and make them work as hard as they can to see what the capacity of your system is. So when your biochemistry is adapted to the cell and we uncouple that cell and make it work, we see how much of that reserve spare capacity that you have. And yours is in an optimal range, right? So when we stress that system, it's able to respond to that stress and it creates an energy profile in response to that.

Ben Greenfield [00:32:25]: When you say uncoupling, I often hear the term mitochondrial uncoupling referring to the idea of mitochondria creating heat instead of ATP. You'll hear people say cold baths or mitochondrial uncoupling agents like say Birds of Paradise, pepper extract or something like that, as ways to increase heat production by the mitochondria. Common practices amongst people who want to say lose weight or sweat more or something like that. Is this the same uncoupling that you're referring to?

Dr. Hemal Patel [00:32:54]: It's the same, but we're doing chemically. So there's certain cells in your body that uncoupled or have high levels of uncoupling proteins. And you hit right on the nail on the head, right? This is brown adipose tissue, which humans lose a lot of as they move from a baby to an adult. Typically it's on our back. So if you're taking a cold shower, you want to sort of hit this backspace right here. The reason why brown adipose tissue is called brown is if you look at it under a microscope, it looks very different from white adipose tissue. And the reason it looks brown is because it's chock full of mitochondria. And so if you look at the heart and brown adipose tissue next to each other, they look very similar.

Dr. Hemal Patel [00:33:31]: And remember I said 30% of the heart is mitochondria. And so it's got this huge pool of mitochondria that are sitting in there. And so what this tissue does is essentially creates heat. So it sucks up all the metabolic energy and creates this fuel state where you're burning all that sugar and that energy and you're making heat in response to that. Which is why people who have large amounts of brown fat storage, you do these in rodent animal model systems as well. This is a way to limit obesity and other things that happen, right? And so it's a way to create some efficiency in your system.

Ben Greenfield [00:34:04]: And one last question about the mitochondrial potential. Could you have too much of that? Like would you see unbalanced mitochondrial potential and say somebody who was excessively using ice baths or taking too much of a mitochondrial uncoupling agent as a supplement or something like that?

Dr. Hemal Patel [00:34:19]: So this, the mitochondrial potential is a double edged sword, right? And so we'll get to your other results in this. So MeScreen really has to be looked at as a large test altogether. So then any number in isolation doesn't mean much when you look at all of the numbers in totality. So an example of this is your mitochondrial potential could be high if you're making ATP with it, but it could also be high if you're making free radicals, right? And so both of those things will consume oxygen and move oxygen through that system. So you really have to look at the other element of that as well. But we'll get to the, we'll get to your free radicals. And so ME screen is really this global test that not only looks at one aspect of your mitochondria, but it's looking at multiple aspects of it at the same time. Right.

Dr. Hemal Patel [00:35:03]: And gives you a complete picture. And like you mentioned, right? So there are certain individuals that we see, their mitochondrial potential is way higher than this. So elite athletes tend to have a hugely high mitochondrial potential. They're pushing probably 85, 90 on a normalized scale. And so you've got some room to improve here if you wanted to get to that stage. But it's doable, right? So the next part of the test that we do is we actually look to see in a homeostatic state on this cell, when we adopt your environment, is that cell using mitochondria to make energy or is it using glycolysis and is it balanced in a unique kind of way? Mitochondria is the more optimized way of making energy, glycolysis is less efficient. You want to be able to use both, but you want to be able to use mitochondria in a more optimal kind of way. So when we look at your system and we add your environment to this, we see that you're more aerobic, using mitochondria to make energy than glycolytic, but you're still able to use glycolysis to make energy.

Dr. Hemal Patel [00:36:04]: So this suggests that you have that flexibility. But under a homeostatic sort of normalized condition, your system tends to prefer mitochondria, which is what we'd want to see. So this is spot on to what we would expect.

Ben Greenfield [00:36:18]: Now, in someone who has a low glycolytic score, would that be, I imagine, a common pattern among people who have some amount of carbohydrate restriction?

Dr. Hemal Patel [00:36:27]: Possibly. Right. We see people who are, you know, Sachin's a good example of this. He likes to do a lot of intermittent fasting and he goes on these long fasts as well.

Ben Greenfield [00:36:38]: Yeah, well, he kind of has to. He painted himself into a corner by writing a whole book about it.

Dr. Hemal Patel [00:36:42]: No, I know, yeah, yeah, we're doing lots of studies with him on this. But the idea that when you go into this long fast, you actually start making ketones and using those as fuel states, and that's where you'd start seeing dramatic changes in this, this energy balance. Right. You'd shift more into this aerobic pool, less into the glycolytic pool.

Ben Greenfield [00:37:02]: Yeah, that makes sense. I not only supplement pretty heavily with ketones, but I also eat, for an active person, what many would consider to be a low carb diet, around 200 to 300 grams per day, or about maybe 30% of my total dietary intake.

Dr. Hemal Patel [00:37:15]: Yeah, and. And one of the ways we would recommend people who have an imbalance in their energy profile is diet modulation. Right. Whether they do intermittent fasting or they add in specific elements into their diet to then balance those two pools in a unique way. But, yeah, yours look pretty optimal from that perspective.

Ben Greenfield [00:37:33]: Fascinating. Cool.

Dr. Hemal Patel [00:37:34]: The next thing we look at. So now this is done on a separate assay that we've developed. It's a fluorescence based assay. So basically the cell lights up when there's free radicals floating around in the system. And so we're looking at reactive oxygen species. And so there's lots of different reactive species that the mitochondria can make. The major ones are superoxide and hydroxyl radical. The mitochondria is also a major storage site for nitric oxide synthase.

Dr. Hemal Patel [00:38:00]: And so nitric oxide and nitric oxide synthase can make peroxy nitrite, which is a very toxic radical as well. And these sort of nitroxy radicals in this system as well. So ours is looking at a global mix of reactive oxygen species that the system is generating through this fluorescence based assay. So what we do is we have a baseline condition. So the cell sitting there, we adopt your cell, your biochemical environment onto that cell and we look to see how much fluorescence there is as a marker of ROS. And so you're in this optimal range where you're really not making a lot of these free radicals. Then what we do is we stress the system, right. We make it exercise and function at its high capacity.

Dr. Hemal Patel [00:38:40]: So we uncouple the system, making it go as hard as it can to look to see under that stress condition is that ROS pool going up or down. So your biochemical environment actually maintains a very sort of even keel ROS level.

Ben Greenfield [00:38:55]: Right.

Dr. Hemal Patel [00:38:56]: Its baseline is 46, it's not doing much. When we stress the system, the system's able to tolerate that, that stress and, and we're not creating additional free radicals.

Ben Greenfield [00:39:05]: Right. And we should emphasize again that lower is not necessarily better. On a test like this, you're looking for balance because if someone had very low levels of ROS, that would be a potential indicator of poor cell signaling capability, right?

Dr. Hemal Patel [00:39:19]: Possibly, yeah. And so that's sort of the, the double edged sort of reactive oxygen species as well is you need them to do certain things, right? You need nitric oxide to vasodilate and signal and do all the other things. You need superoxide to do unique things in a cell. You need hydroxyl radical to do certain things as well. So low levels of free radicals are quite important at the micro level in the cell to create these signaling paradigms. But then high levels are not very stressful. So in this, we're looking more at this high sort of stress level generation of free radicals rather than the micro environment sort of low level stress of free radicals that we want to see.

Ben Greenfield [00:39:57]: Got it.

Dr. Hemal Patel [00:39:58]: But no. Yeah, you look perfect on the ROS as well. The final thing we do gets at this other unique element of what mitochondria are, right. And so they're dynamic elements, are constantly moving in a cell. They're constantly attaching, forming, detaching. If you describe it as a sort of a social system, they're a social organism, right. They like to be well connected to each other. If you actually look under an electron microscope at any cell type, you see that most or highly structured and organized cells like the cardiac myocyte or the neuron have these mitochondria that are held together by these tight connections between each other.

Dr. Hemal Patel [00:40:34]: In the heart, they actually look like a pearl like structure across the myocyte. And there's a reason for this. It allows the mitochondria to communicate. So they can send stressors in different remote parts of the organ, remote parts of the cell, and they can tell the other mitochondria what's happening because they're connected through the system. If you look at non communal chronic diseases, right, these things that tend to lead to multi organ dysfunction in individuals, in every one of these you see this separation of mitochondria, they become isolated, so they become separate from each other. When they're separate from each other, they're more prone to being toxic, they're more prone to making free radicals, they're less adaptive to the environment and the stressors that they face. And so the way to get to that, that we've sort of developed through MeScreen is we've created a cell line that tags all the mitochondria with a green protein.

Dr. Hemal Patel [00:41:28]: So when you look at it under our live cell microscope, all of the mitochondria light up and they become green and you can see the entire dense network of mitochondria in the cell. So now what we do with this network dynamic score is we adapt your biochemical environment onto this cell with these glowing mitochondria and we can look to see what they're doing in a dynamic sense. We can look to see if they're shifting or not, or if they're separating from each other and that network is becoming disconnected. A lower score on this means that the network stays tight and isn't dissipating. And a higher score means that that network is starting to disintegrate and separate and the mitochondria become isolated. Under baseline conditions, your network seems to be optimal. And then when we stress the system, it continues to stay optimal. It's not separating apart.

Dr. Hemal Patel [00:42:17]: We see that in certain individuals that have certain ailments that they're dealing with long Covid other things. We see unique patterns that start to emerge in this. We're not making any diagnostic claims and we're not going down that pathway. But it's a way to look at where to see what your mitochondria are dysfunctioning and potentially to see where we can start intervening in a unique kind of way from an interventional perspective.

Ben Greenfield [00:42:42]: Interesting. You know, one of the things I've been thinking about for the past few minutes is obviously you're doing a lot of these tests on people and I assume you know a little bit about the people that you're testing when it comes to the 80, 20 and what seems to be making the biggest impact on favorable test results. Have you gathered any data or had any insights at all into anything from lifestyle strategies like say fasting or thermal stress supplement strategies? There's so many out there that people say are mitochondrial supports like Timeline Nutrition has their Urolithin A or Spermidine mitoperia, et cetera, or even certain exercise modalities. Is there anything that really stands out as having a really favorable or unfavorable impact on mitochondria?

Dr. Hemal Patel [00:43:32]: Yeah. So since the test has come out, we've actually had unique interest from all of these companies. They've wanted to test their supplements. Right. One of the things I call this thing early on is the bullshit detector. Right. This gives you a way to see if those supplements you're spending hundreds of thousands of dollars on is actually doing anything right. We actually did an internal test.

Dr. Hemal Patel [00:43:55]: I can't tell you what the supplement was, but we bought the top shelf mitochondrial supplement that's out there, that has all the marketing around. Take this and you'll improve your mitochondrial health. I had my postdocs eat it for a month and then we tested them pre post. Nothing, nothing happened in a couple of these individuals.

Ben Greenfield [00:44:12]: Are you telling me that there might be over exaggerated extrapolation from rodent studies to humans?

Dr. Hemal Patel [00:44:17]: Oh, you think? Maybe, possibly. So this gives companies a way to actually do human studies to validate this. Right? You can actually. And we're doing studies with a lot of companies right now where we'll do a pre collection in a group of individuals, they'll give them their product to try for a certain amount of time and then we'll do post collection at unique time points and we'll see if their product actually creates an effect and we'll detect the bullshit if it's actually there or not. And some of the things we've run through there, that's proprietary kinds of things where I can't really talk about which ones we've run through, but we see some unique aspects. And that's the other aspect of this. For that individual that's involved in these studies, this is a way for them to finally track their mitochondrial health. There's no wearable device you can put on.

Dr. Hemal Patel [00:45:03]: There's no real test that you can do where you can actually know what your mitochondria are doing day in, day out. This is a test that allows you from a way to perspective wise to look at where you sit, mitochondrial efficiency wise, do whatever you're doing, whether it's a lifestyle change, a diet change, an exercise regimen, supplements that you're going on and see if those are optimized for your body and are working in a unique way and continually probe that aspect of are you improving your health in a kind of way. And we've created this model where you can do subscriber service to the program where you can get the test done multiple times a year and actually track this for yourself as a, as an individual that's interested in these health paradigms and those sorts of things. We are doing some far out studies that I can talk about. So we've done. And this is where you get into the what's good versus bad, right. Hot area in everything. Meditation and mind body right now are psychedelics.

Dr. Hemal Patel [00:46:04]: And so we've been able to get about 100 individuals that have done a week long ayahuasca journey. And so we look at a pre sample before the journey starts, we look at a sample midpoint after their first ceremony and then we look at a sample at the end of the week. I've never seen mitochondria change in 48 hours. And we see it with ayahuasca in a large percentage of these individuals that are on these journeys.

Ben Greenfield [00:46:29]: You mean in a favorable manner?

Dr. Hemal Patel [00:46:30]: Yeah, I mean it, it favorable is a loose term. Right. We see this accentuation of mitochondrial functionality. The, the sort of flaw with that study, and we're trying to resolve this right now is we don't have the, the time post collections after. I suspect you're going to see a very acute shift in your mitochondrial biology. And there's literature to support this, right? There's lots of evidence in the literature that supports that ayahuasca, psilocybin, these things have a mitochondrial target conduit.

Ben Greenfield [00:46:59]: Well, we do derive our mitochondria, as you noted, from our maternal lines. And ayahuasca is known as the mother plant. So who knows.

Dr. Hemal Patel [00:47:08]: But I think the key to this is what sustains this long term. And I don't think these things will create a 2, 3 month shift in your mitochondrial functionality. You may see improvements for a week, but I don't think you're going to see it two, three months out. I think there's other approaches where you can, you know, the mind body approaches that lots of people are doing. I Think those are routine ways of maintaining mitochondrial health and then maintaining it long term. But again, it comes down to your routine and regimen and can you stay consistent with it. One of the things that I think about biohackers is I think there's a fad to this where there's a new thing that comes online every other week and they're shifting and transitioning. Right.

Dr. Hemal Patel [00:47:51]: I think one of the things to think about is what's your base and keep that foundation firm and then you can experiment with a few other things. But that foundation really maintains your mitochondrial health long term.

Ben Greenfield [00:48:02]: Yeah. Anecdotally, and I have no clue if this impacts what appear to be decent scores for me, is the base foundation of my practice is kind of around the concept of biohacking for mitochondrial optimization. And what I mean by that is I focus pretty heavily on earthing, grounding and PEMF from an electrical standpoint. I do exercise with oxygen therapy and hyperbaric oxygen therapy. I do red light, good clean, pure water and minerals. And those five things are kind of my stack. And then I typically, prior to the PEMF, red light and oxygen will use mitochondrial support compounds, probably the two most notable being C60 and methylene blue. And that's something I've been doing for about a year and a half now.

Dr. Hemal Patel [00:48:53]: Yeah, I mean, it seems like that's working well on this test. Be interesting to put a whole group of people in that regimen and see if it works on those individuals the same way. Right. Again, it's, everyone's biology is a little different.

Ben Greenfield [00:49:07]: Most of my clients are doing it, but that's not a huge population. But yeah, it would be interesting. I mean, I definitely would like to do a little bit more testing and tweaking. So this is fascinating. And is this available now to anybody, anywhere in the world? This US only or how's that work?

Dr. Hemal Patel [00:49:22]: No, it's available anywhere in the world. So we're applying to other markets. We have a strong collaborator in the UK. We're in Dubai. Africa, we're starting to move into Africa, Australia, China, all these other places, all over.

Ben Greenfield [00:49:36]: Okay, awesome. Well, I'll link to [email protected]/mescreenpodcast I know you guys have some offers for my audience that'll be sure to put in there. I'd be very curious if you're listening right now and you have questions or comments or feedback, or you get tested and find out some interesting things. Leave them in the comments section. Let's build a discussion around this because I'm just fascinated by this emerging frontier of being able to test what, as you established, Dr. Patel, early in the podcast is a pretty darn important part of our biology.

Dr. Hemal Patel [00:50:07]: Yeah, yeah. I mean, it's in every one of your cells except your red blood cells, right? Trillions of mitochondria in your body.

Ben Greenfield [00:50:12]: Yeah. All right, folks, well don't spend too long in the ice bath and go do some ayahuasca. Those are your two big takeaways from today's show. Dr. Patel, thank you so much for coming on and joining. This was fascinating.

Dr. Hemal Patel [00:50:24]: That was great, Ben.

Ben Greenfield [00:50:25]: All right, folks, go to BenGreenfieldLife.com/MeScreenpodcast again for the show notes. Until next time, I'm Ben Greenfield and I apologize for the head cold today. Woke up a little congested, but I I didn't want to cancel this one, so hope you enjoyed it and have a wonderful week.

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