Mitochondrial Health: The Ultimate Guide to Feeling Your Best

Coming up on this episode of the Doctor's Pharmacy.

Key to understanding longevity, the key to understanding health, the key to understanding basically every disease is understanding how the mitochondria work, how they get harmed, what you can do to optimize them, and how you can actually even improve the number and function.

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Key to understanding longevity, the key to understanding health, the key to understanding basically every disease is understanding how the mitochondria work, how they get harmed, what you can do to optimize them, and how you can actually even improve the number and function. So let's kind of deep dive into mitochondria. What are they? Well, they look like little tiny bacteria that are in your cells, and they actually come from bacteria. And their DNA is actually only from your mother. It's kind of cool. And they have kind of taken up residence in our cells in this ancient evolutionary biology, and they figured out how to convert food and calories into energy by combining with oxygen. And basically, it's like a car's engine. You bring in the air intake and the gasoline, and you combust them, and you get energy that moves your car. Same thing with your mitochondria. You take oxygen and food, and you burn it, and you get something called ATP, which is the body's gasoline, let's say. And that is. Stands for adenosine triphosphate. Phosphate is that bright sparkler kind of color you see on the Fourth of July. That actually is. releasing heat, energy and power to drive every cell in your body, every function in your body, every chemical reaction in your body. And so you, you need to really understand how to optimize your mitochondrial Health. Now, sometimes what happens is you, when you produce energy, is you get a byproduct. So you, you get food and calories in and oxygen in and out comes ATP, but also, also you produce water, which you pee out. you produce carbon dioxide, which you breathe out, and you also produce a little bit of what we call reactive oxygen species. These are basically molecules that are a little bit damaged in the process of making energy. We call them like the exhausts that comes from your car, let's say. And they are called reactive oxygen species or free radicals. And, but they're not terrible. They actually do have this process of regulating ourselves, of stimulating antioxidant systems. But it's really important to not get them to be too much and have them just in the right balance. Now, what happens as we age is our mitochondrial quality and number go down. They don't function as well. We don't have as much of them. We end up having less ATP and more reactive oxygen species and free radicals, and that causes more damage, more decline, more inflammation. It's like a snowball effect throughout the body. So besides aging, what causes our mitochondria to kind of become dysfunctional. What causes them to decline in their number and ability? One is a lot of lifestyle habits, right? Overeating, too much food, too many calories, too much sugar. That's the main reason we have damaged mitochondria. And then the list gets even more concerning with the environmental toxins. They're very sensitive to environmental toxins, pesticides, herbicides, heavy metals, Valaids, plastics, everything we're exposed to is damaging in some way or mitochondria. Smoking is a terrible thing for mitochondria, stress, chronic stress of any kind, lack of sleep, all these things drive mitochondrial dysfunction. But the good news is that there's a lot you can do to optimize your mitochondria, to make more mitochondria, to make them work better. And it's critical to understand how to take care of your mitochondria. It's one of the seven key physiological systems in functional medicine. so when we look at the body, there are root processes that affect everything. So when you look at mitochondria, you know, oh, you know, I don't, you know, unless you have some genetic inherited mitochondrial dysfunction or disorder, most of us have an acquired mitochondrial dysfunction. And, and the good news is that this, this is fixable, but the bad news is that it contributes to almost all the known diseases like diabetes, heart disease, Alzheimer's. It's, it's dysfunctional cancer. in so many diseases, depression, autism, you name it, mitochondria play a huge role. And so we have to understand that there are some real non-negotiables when it comes to mitochondrial health. And there are four key things that I recommend, and there's obviously more, but these are the four key ones. First is your diet. Get rid of all the sugar, starch, processed food or dramatically limit it. Get rid of things that create a lot of oxidation, like fried foods. Make sure you're increasing your intake of polyphenols and phytochemicals in plants that are anti-inflammatory that boost mitochondria. You have to eat real food, don't eat processed food, and. And have foods that are as close to their original form as you can. You know, I just came back from a bike trip in Greece, and I ate fruits and vegetables there that tasted phenomenally different. They were so rich in flavor, and that's because of the way they grow them, because the soils, because of the lack of chemicals in their agriculture. And I. It was like. an explosion of flavor. Now, what's contained in that flavor are the phytochemicals, are the medicines. And those are the things that help regulate mitochondria. It's why you see these blue zones where they're eating all these foods. Like I was in Greece, they had all these wild greens every, every time at the restaurant. So they literally collected wild greens and served it up. And those wild greens are full of phytochemicals. And it's one of the things that I think contributes to longevity in some of the blue zones. So really important now. exercise is also critical. It is the way we stimulate our body, we stress our body, and that stress makes us create more energy. We want to stress our body in exercising. And what's happening? It's increasing the demand for energy. So when you run or when you jog or when you do interval training or when you sprint, you're actually stressing your mitochondria. And that little bit of stress causes them to become more resilient. It causes them to make more mitochondria to become more efficient. So exercise is so critical to optimizing our mitochondrial function. You need to do both cardio, right? Like zone two training, which is sort of low, long-term exercise, half an hour, an hour of jogging and so forth, or something similar. Also interval training, which is VO2 max training, to train your mitochondria by stressing to be more like sprinting those, those severe exertions where you kind of run as fast as you can for 30, 60 seconds. That increases something called VO2 max, which is actually your ability of your mitochondria to burn energy. It increases it. So even when you're sitting still doing nothing, you're burning more energy if you do that type of exercise three or four times a week. And then there's strength training, which is so important because that recruits more, more mitochondria, builds more muscle, activates mitochondrial biogenesis, makes your mitochondria more efficient. So really important to optimize your mitochondria. The third thing is make sure you get the right kind of light and not any kind of light. But what's happened is our mitochondria are very sensitive to light and they are stimulated by the right kind of light and they're harmed by the wrong kind of light. So we're now flooded with artificial light from TV, electricity, buildings, computers, tablets, phones, alarm clocks, everything. And we don't have enough natural sunlight, which helps our mitochondria. so all the blue light from our devices really screws up our circadian rhythms, especially when we use them at night, and that affects our mitochondrial function. So making sure our circadian rhythms are regulated by waking up and getting morning sun, by not using your devices at night, really important. The other thing you need to know about is that you need to sleep for your mitochondria. It really helps to reset your mitochondrial function. It requires deep, restful sleep. That's why you feel tired. You don't sleep enough because your mitochondria are not doing well. the next thing that's really important. And I think this is unfortunate that we need this now, but I think we do because of our, our horrible diet and our, our lack of nutrients in this sort of food because of the way we grow them and, and all the stresses we're exposed to and all the toxic environment, all the depletion of our soils, all the, the foods that are, you know, packaged and processed and shipped across the country. I mean, the average Apple you eat is, you know, probably a year old. I'm in a storehouse. We don't need your heirloom vegetables anymore. We monocrop, we have genetic modifications, you know, basically, even if you have a perfect you're not getting enough nutrients. So we really need the right supplements. And mitochondrial supplements are really important. I make these a foundation for me. I had chronic fatigue syndrome, so I know my mitochondria are a little, little bit needed a little extra love. But there's some really important mitochondrial superstars that we'll talk about in a minute. But you can take them. I take all of them personally to charge on my mitochondria and to keep them functioning well. So what are the top ways to fuel your mitochondria? Let's sort of kind of recap a little bit. What are the activities you can to do to build on these four non-negotiables that we just discussed? Well, there's a lot of things you can do to support your mitochondria, but there's about five practices I think are a good start. First, we discussed a little bit, focus on eating real food, healthy diet, lots of phytochemicals, lots of good fats, your mitochondria love fats like avocados, olive oil, MCT oil, have the right amount of protein, plenty of micronutrients, vitamins and minerals, all these are important. You know, Bruce Ames talked about how to get a metabolic tuneup. by using micronutrients that drive so many of these chemical reactions. Because making energy in your mitochondria requires all the B vitamins. It requires cooking 10. It requires lipoic acid, and acyl cysteine, so many different compounds, ribose, carnitine, the list goes on. And so you need, you know, to actually, in the assembly line, to turn food and oxygen into energy, you need all these helpers to go along the way. So this is what nutrients are, and you need to get them from your diet and from supplements. The next is, you know, can try things that actually stress your mitochondria a little bit. Time restricted eating, fasting. These are great ways to improve your mitochondrial number and function and clean out the old ones. So maybe don't eat for at least 12 hours between dinner and breakfast, ideally up to 16, or even do a longer fast once a week. And that can really help your mitochondria. The next is make sure your light exposure is right. You know, get rid of the screens and device it at night, at least two or three before bed, get light exposure in the morning, sunlight in the morning, 20 minutes, really important. It also helps your vitamin D, which is good for you as well. Also, exercise, get your exercise routine sorted because you need to make sure you do both cardio and, and also interval training, the high intensity interval training and strength training and, and, you know, start slow, but, you know, I, I'm, you know, 63. I'm gonna be 64 this year, and I keep increasing my activity and cre, increasing the challenges I put myself through. And I'm finding, you know, at any age, it's possible to get fit and healthy. So, you know, start slow, but, you know, if you need work with someone as a trainer to learn what to do, if you have limitations, and I have things that I got my knee thing and my back thing and my shoulder thing and this and that, but you find a way to work around it. Um, and, and do something. It's really important. And lastly is eating the right supplements. And there's a number out there and we can talk about all of them. I've written a lot about mitochondria. You can kind of see in the show notes. We'll link to some articles I've written. But there's something I want to talk about particularly. One is CoQ10 and I think at least 100 milligrams a day is really important. And I take ubiquinol, which is a special form of CoQ10. Lipoic acid is a superstar. It's one of the most powerful antioxidants critical for mitochondrial function, at least, you know, 300 up to 600 milligrams a day. If you're diabetic, I'd recommend 1200 milligrams a day. Resveratrol, also really important for mitochondrial function. It's a phytochemical. You can take, you know, 50 to 200 milligrams a day. Also green tea extract, we call it EGCG or epigallocatechin gallate. And you can take, you know, 200 to 500 milligrams of that. Really important. Carnitine also is important in metabolizing fats. And you can take acetyl-L-carnitine or L-carnitine. about 500 to 2,000 milligrams a day can be powerful depending on what's going on with you. But usually 500 once or twice a day is fine. So those are the basic supplements I recommend. There's many more. There's ribose, heneicosylcysteine, all the B vitamins and more that help the mitochondria function better. And it's important to see what you need, what your particular body requires, do some testing and figure it out.

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We have this pandemic of fatigue. And, and personally, I, I've had chronic fatigue syndrome. So sadly, unfortunately, I've had to become an expert in fatigue, both from the inside out and the outside in. And it's really been a journey to understand what causes people to be tired because it's one of the most common symptoms that people go to the doctor for. Now, sometimes it's silly and simple. Like one guy years ago gave a lecture and I said, I'm tired all the time. I said, how many hours you sleep? He said, I sleep five and a half, six hours. I'm like, sleep eight. I said, that'll be 500, please. But it's more complicated than that for most people. So we just sort of internalized and accepted the idea that, oh, we should be tired, but it's not normal. so what's causing this energy crisis? It's not an energy crisis of oil, it's energy crisis of ATP, which is everybody's own energy system. So what is the driver of all this?

Well, I think there's multiple drivers, and I certainly get into that in the Energy Paradox. But if I was going to break it down into two really actionable items, number one, we talk about chronic inflammation and that most of us somehow think that chronic inflammation in one way or another is driving most of our chronic disease processes in one way or another. And people go, well, where does chronic inflammation come from? I think, and many others now think that chronic inflammation is actually coming from leaky gut. and if you had asked me, I think 15 years ago what I thought about leaky gut, I probably would have called it pseudoscience and said, oh, come on, really, there's very little evidence. But I think thanks to Alessio Fasano and others, we now know that leaky gut probably confirms what Hippocrates said 2500 years ago, that all disease begins in the gut. In fact, Dr. Fasano from Harvard now has a new paper out saying all disease begins in a leaky gut. I think he's absolutely right. And certainly in our practice, I see that really as one of the major driving forces. chronic inflammation. Now, why does that reduce energy? Because 70 to 80% of our immune system, as you know, lives in our gut, lives along the lining of the gut. And the immune system is a big time energy hog, an energy burner. And we devote a huge amount of our resources to powering our immune and an example I use in the book, which I use with my patients constantly, yeah, before COVID there was obviously the flu and the flu is a virus like COVID, and the flu in and of itself is just a protein that our immune system looks at and says, oh my gosh, this is a bad actor, and we've got to mobilize our forces and we've got to be ready to get this guy. So what we do, the flu does not cause you to be aching and have ache and pain and just want to lay in bed. The flu does not give you brain fog. The flu does not make you channel surf and not think. Your immune system actually needs all that energy. So what we do is we ration energy. We make ourselves hurt, our immune system makes ourselves hurt so we don't move. If our muscles hurt, we don't move. And we make our brain go into standby mode because our brain is the biggest energy hog of all. And if you're using 20% of your energy to think, you're taking away from your immune system. And so imagine that the same thing happens in our gut when we have leaky gut. a huge amount of the energy that we would normally have goes to our immune system and our gut. That's number one.

So, what you've been saying is quite incredible, which is that a lot of the fatigue that we think may have other causes might start in the gut because when your gut is damaged or injured, it literally, quote, leaks the bad toxic crap literally in your immune system. and your immune system goes, ah, what's this? And I better do something about it. It's very busy and sucks a lot of energy, but it also creates inflammation. And inflammation and fatigue just are, you know, neck and neck. That's what they, that's what the, the body actually does when you're having inflammation. It creates a lot of fatigue. You kind of repair, I guess it's sort of a natural thing. You want to stop and not do anything and let your body heal like animals. Go lay down until they get better. So you talk about You talk about the warning signs. How do people know if they're just like a normal tired or if they have something more severe kind of fatigue? What are the warning signs?

Well, I think certainly we're seeing even in a younger and younger and younger patient population brain fog. I think if you had asked me about brain fog 20 years ago when I first started this area, this was a common complaint in 70 year olds, 80 year olds, but now we see it in 20 year olds and 30 year olds, millennials come in with complaining of brain fog and malaise, and it's.

Like.

I'm really getting old, but I thought I was just 30. I just don't have my get up and go that I used to have. This is a warning sign. We're not supposed to have that. We're not supposed to have to be powered by double espressos three times a day and 12 Red Bulls to get through the day. And I think part of the problem is we've thought that our modern lifestyle, particularly social media, we see everybody happy, happy, happy doing everything wonderfully. And we somehow go, oh my gosh, that's what I should be like too. And we have to power through our day or I'm a mom with two young kids and I've got to be there to get them to their 27 events every day. And that's normal to be fatigued, to be not knowing what to do, but it's not normal. And surveys actually show that at least 50% of the population is fatigued or tired at any particular time. and we've accepted that as normal, and it's absolutely not normal.

You know, for sure. You know, in the book, you talk about the, the seven deadly energy disruptors. And as a functional medicine doctor, I, I noticed a few missing, but we can talk about those. But, I mean, things that I see regularly in my practice. But these are really a great starting list.

So tell us about these seven deadly energy disruptors.

Yeah.

You know, I had seven disruptors in in the Plant Paradox book. And I tweak that list in terms of energy because I think there's some real mistake makers that deserve our attention. First of all, antibiotics. We still not only overuse antibiotics to treat things that have no business being treated with antibiotics, such as viral illnesses. We still, unfortunately, practitioners anytime someone comes in with a sore throat or a cough, the gut sense is to give them broad-spectrum antibiotics. What none of us realized until recently is that broad-spectrum antibiotics kill off not only a bug that we thought we were going to kill, but also our entire gut microbiome. It may actually take two years to reestablish an entire healthy microbiome after a single round of antibiotics. we had no idea of this dense tropical rainforest that we had in our gut that drove so much of our energy. And we'll talk about that in a little bit. Plus, the antibiotics, as you and I know, are in our food supply, particularly in animals from factory farms. It is still legal for veterinarians to dose entire flocks of chickens or entire herds of animals with the claim that they're treating one sick animal. And still, as long as the veterinarian says that they need it, they still legally can do it. And as you and I know, some of these organic or natural chickens have been tested for antibiotics from certain farms, and they may have a 60% antibiotic pickup rate in normal, natural chickens that aren't supposed to get any antibiotics.

Really?

I didn't know that.

That's frightening.

Yeah, it is actually really frightening.

Yeah.

Is that because they use them anyway? If one animal sick, they give it to everybody.

Yeah. Yeah.

That was the, that was the, there's always loopholes, as you and I unfortunately have learned in laws. And the loophole was, if the veterinarian thinks there's a sick chicken and there's a flock of 100,000 chickens in a warehouse, then he is allowed to treat the entire flock to treat that one sick chicken. And the vet, there's great vets and great doctors and there's bad vets and bad doctors. If the vet is on the payroll of the big corporation, you see where I'm going.

Absolutely. So what are the other seven, the six disruptors?

So I think glyphosate has rapidly rose to kind of my number two mischief maker of all time. It is, it is a, it's an antibiotic against the earth, in my opinion. It was actually patented by Monsanto as an antibiotic initially. And what we didn't know, what you and I didn't know is that Yes, it works with this crazy, it works against the shikimate pathway, how plants make protein synthesis. And Monsanto said, don't worry, humans don't use this shikimate pathway, so you're safe, it can't hurt you. What they didn't bother to tell us was that bacteria and fungi use the shikimate pathway, so that when you swallow glyphosate, it actually kills off your microbiome rather effectively. Plus, recent evidence is that it in itself, without any other effect, is a gut wall disrupter. It breaks tight junctions. In one paper, I show that glyphosate actually interferes with mitochondrial function. That's actually not too hard to believe because mitochondria, as your listeners know, are actually engulfed ancient bacteria, and they actually carry a bacteria signature, and they work as a functioning bacteria within all of our cells. So it's actually was not surprising as I was researching this to find out that in fact, glyphosate affects mitochondrial function. so it's, and it's everywhere.

I mean, it's on 70 of our agricultural crops. It's the most abundant agrochemical in use today. It's on over 90 of our corn, soy and, and, and cotton. It's kind of scary. It's out there. It's, and it's really being looked at from the legal point of view. There's over 14, 000 lawsuits pending. against the herbicide. And I think, and as for its human, human effect, but I think what you're speaking to is something really more important, which is its effects on the microbiome of the soil and also the microbiome of humans. And they're interconnected. And I think we, we literally are, are destroying the microbiome of the soil, which fills the organic matter and leads to increased greenhouse gas emissions from loss of soil carbon. And then you've got the microbiome effects on humans, which has all the consequences that you just talked about.

Yeah, you know, you're right. We talk about you are what you eat, but you are what the things you're eating ate. Well, the same thing is true with plants. And plants, as you and I know, have this incredible rich soil microbiome that would normally assist in feeding the plant and allowing the plant to absorb nutrients. And now, as a bifosate and other biocides, our soil is dead. And so we could have a plant that looks like bok choy or spinach, but it does not have the nutrients that it used to have. In fact, our soil is so depleted of the common nutrients that we need, like magnesium, for instance, that we don't have a chance.

No, it's huge. I mean, and the data on glyphosate is people don't understand, oh, it's just Roundup, it's used on Roundup Ready soybeans. It's not, it's used on 70% of crops and it's 220 million pounds a year. That's used in the United States. I think since 1974, it's 1.6 billion kilograms have been used on crops in the United States alone and it's on 70 different food crops including corn, soy, canola. If you have a slice of bread, a bowl of Cheerios, a sushi roll, a plate of pasta, slice of pizza, chicken nugget, it's probably got a round up on it. And it just, you know, it's scary.

When you look at the work from.

The Environmental Working Group, your Cheerios has more glyphosate per serving than vitamin D or B12, which actually have to be added to the cereal to enrich it. It's a big problem. And I think you're right, this understanding of what's role in the microbiome is really quite important. So you've got antibiotics, glyphosate, and there's more chemicals that are problem, right?

Yeah, I mean, we're surrounded with environmental toxins. You know, one of the favorite old ones was BPA in plastics, and most of BPA has now been banned, but BPS looks to be even more mischievous than BPA. And these these are endocrine disruptors, they're hormone disruptors. And one of the things people should realize is that estrogen, for instance, is one of the best fat storage hormones that's ever been invented, as any young woman in her teenage years knows that estrogen is designed to make you store fat. And we now have chemicals that mimic estrogen. And we're awash in these things. For instance, phthalates, another very important plasticizer, is present in our food wraps, any plastic food wrap. So you may get your organic pasture chicken breast, and if it comes in a shrink wrap plastic, you'll actually pick up phthalates off of that plastic. and one of the really scary things is that there's really scary correlation between boys penis sizes and the amount of chicken their mother ate during pregnancy. And it's a inverse relationship.

Yeah, that's interesting. So, so you mentioned environmental chemicals and the couples that you haven't mentioned, these are the, these are the sort of we call persistent organic pollutants that are really petrochemical driven from oil derivative things, plastics and so forth. But there's another class which is heavy metals. And for me, that was the massive driver of fatigue. And for many patients, so mercury lead are the two biggest. And how do you think about those?

That's a great question. I look at mercury and lead and cadmium in a great number of my patients. I can tell you that the vast majority of people with high mercury levels in my practice are dentists and sushi eaters. Dentists for obvious reasons, sushi eaters hopefully for obvious reasons. But once- Mercury in the sushi. Yeah, mercury. One of the interesting things that at least I see is that heavy metals in general are contained in our fat cells. And it's like a tuna, maybe in have toxic levels of mercury, but that tuna is doing perfectly fine because the heavy metals are actually in the fat. It's when people have weight loss that we release those heavy metals from fat. And this was actually demonstrated by Ray Walford in Biosphere 2. You and I probably old enough to remember Biosphere 2, the experiment in the Arizona desert where they locked everybody in a geodesic dome for a year to stimulate a mission on Mars. And everybody had to grow their own food and produce their own food. And long story short, it was a horrible failure. People lost about 30% of their weight in six months. And one of the findings was that heavy metals and organopesticides went up precipitously, very rapidly, and stayed elevated for over a year. year before they went down. And it was because those heavy metals were there in these participants' fat cells. And we, as you know, have a horrible system for detoxifying heavy metals. Our liver does a horrible job of it, and they're excreted by our liver into our bile, thinking that we'll get rid of it through our stool, except we're really good at absorbing heavy metals out of our gut. So we actually set up a vicious cycle. so we excrete it and then pick it up. And as I talk about in the book, anyone who's actually on a weight loss program really should be supplementing with chlorella and activated charcoal during that time period because they will complex with heavy metals and knock on wood, we've been very effective with those two treatments in bringing down people's heavy metals without the need for chelation.

Yeah, I mean, pleiotropy is a bigger term, but it's basically there's ways to up regulate your body's detox system and reduce the inputs. And I think it's so key. When you look at NAD, you know, the mechanism of action, it does so many different things, from DNA repair to the activation of sirtuins, to increasing energy production in the cell, to lengthening our telomeres, which shorten to making new brain cells and making new brain connections, reducing inflammation, boosting mitochondrial function, improving insulin resistance and exercise performance. It's really quite remarkable. I remember David Ziegler talking about a study where they had a mouse treadmill that only goes to, I don't know, one or two kilometers and they never saw anybody like mouse go longer than that. And then when they gave them NMN, the thing just broke the treadmill because it went three kilometers or something.

The secret now or the trick now, once we've recognized this, is how do we get NAD levels back up? How do we preserve them? How do we preserve people who are reasonably healthy and give them optimal performance? And how do we help people who have low NAD who are in trouble and get them back to a reasonable level? So to do that requires, like any medicine, it means giving something to somebody that they're missing. So there's several ways that initially people started giving NAD. It made sense. You have low NAD, give the person NAD. The problem with that is that NAD is a chemical or a molecule that's made inside cells. It's so valuable and so important to the cell itself that the cell is very clever and it embeds within NAD, it changes the molecule in such a way that it can't leak out. It's precious. NAD has been designed to stay inside the cell. And if you give a person NAD, it won't fall out of the cell once it's there, but the big problem is it won't get into the cell. So, if you have a lot of NAD, that's great. It's all floating around doing all this stuff, but in order for it to work, it needs to be inside the cell. Now, getting NAD into a cell is no mean feat because you've got a problem there. It's designed not to cross cell membranes. So what do you do? So you see all these health products out there, you know, take NAD. Take this pill, it's got a lot of NAD, but the problem is, yes, you can get it into the body, but you can't get it where it needs to go, which is inside the cell.

Interesting.

But created the interest in other ways to boost NAD. So what people did is they said, well, where does NAD come from naturally? How does the body make NAD? Well, it turns out that there are two steps along the way. First, there's something called NMN, and then there's something called NR, and then there's something called NAD. And so they thought, well, if we give the molecule before you get NAD, it can cross the cell membrane more successfully. It can cross the gut when you swallow it. There are all of these good things that could happen maybe if you took a precursor, an earlier step. so you'll see all these products now that have something called NR, right? So nicotinamide riboside, yeah. Their studies and cell studies and human studies looking at NR, and it seems to do good things. First of all, it gets in a little bit better than NAD, but more importantly and significantly, you can see the NAD levels go up in the cell when you take NR. So that was a good thing. and then people went out to the ultimate step, which was to give NMN. And they asked, is this a good way to deliver NAD? Will this do it? First of all, when you swallow a pill with NMN, it crosses into the body a lot better than NAD and NR. And that's because the body has created a special shuttle in the cell that recognizes NMN when it's outside and provides a lovely tunnel, if you will, for it to right through the membrane and end up on the inside of the cell. So the body has neared a way for NMN to get in there. And of course, once it's in the cell, that's great, because then it can be sliced up and form NAD and all is good. And that's been shown. So we now believe that the most efficient way to deliver NAD is actually not NAD itself, but it's in the form of NMN. And that's why our focus has been to use NMN to make these necessary changes to boost NAD.

Interesting.

Now, just to kind of loop back.

For a minute before we want to get into the delivery forms and what it does and so forth, do you know why NAD levels decrease as we age? Is this inevitable? Is there a way to prevent it? can we naturally increase them? Is there any understanding about how that may work?

No, there really isn't a lot understood on that.

Okay, good. I thought I missed it, but I thought maybe you knew because you're the expert.

I'm like.

Let'S just go, let's talk about where it's actually made. The first part is when you take sugar, and again, glucose is a good example, and that is broken down by glycolysis. and there you get something that's spun out. The next part is a cycle called the Krebs cycle, and in that you take what comes out of glycolysis and you whiz it around with all these different enzymes and you make more NAD. And then the last step is where it enters the mitochondria, which is the powerhouse of the cell, the ATP unit, if you will, of the cell. Mitochondria, the NAD is grabbed ahold of, and it is used to fuel the production of ATP, which is the ultimate thing which comes out of the mitochondria. So those are the three different things. If I had to guesstimate where the deficit lies, it's almost surely in the last one. So we don't think that as you age, you lose glycolysis and you lose the Krebs cycle. We think the mitochondria are really the point where with aging we start to see this degradation. It's not just, first of all, it's in the number of mitochondria. Let's take a professional basketball player and they run up and down the court for 60 minutes. They're not even sweating. Okay, how on earth would that be? If you take the muscle out of someone like, you know, Michael Jordan, you will be astonished what you see under a microscope. It's not normal. at all.

The number of mitochondria means you can jump over the rim.

And, I'd imagine the amount of mitochondria in that muscle itself. So, when he takes a quiet breath, he's producing so much more energy than I could ever even imagine. That's why he can run up and down the court for 60 minutes because he's just loaded with these mitochondria bulging out everywhere in the muscle cell. Then take the same guy and he's now 75 and he's still working out, still doing his thing. If you look at the number of mitochondria in his cell at that age, it's fewer. Now, why is that? Well, in the last five years, we've learned a lot about what controls the number of mitochondria in your cell. There's actually a pathway that tells us, tells the body how to make or when to make or how many to make of these mitochondria. So we now know that one of the stimuli, for example, is low oxygen tension. So if you were to exercise, you're using up your oxygen very quickly and the muscle is in a state where it doesn't have enough. It's hungry. And that is a powerful stimulus to make new mitochondria. That's why a guy who's 75 who works out every day he will actually create new mitochondria, whereas someone who's a couch potato, he has no stimulus and so you won't see those mitochondria being formed. So the aging process diminishes our mitochondria and that's probably, I can't say for sure, but this is probably the prime reason that NAD levels fall with age. It's fewer mitochondria.

Yeah, that makes sense.

Yeah.

That's interesting because you know, you look at some therapies that are used for longevity, for example, they're like hypoxia therapies. And so, when you look at Vilcabamba in Ecuador, they live a long time because they live at 17,000 feet. Maybe it's because of that. Or maybe, you know, when you use this technology called the cell gym, which essentially takes you up to Mount Everest and then back down, it makes you hypoxic. It activates your mitochondrial production. Or, when you use these hypoxia masks that athletes do, or when they go to the altitude to go train for running a marathon, they'll run it you know, 7,000 feet when they're going to run a thousand during the race because it actually helps them build more mitochondria. So, it's really all about little tricks and building muscle through strength training, through the right amount of protein, through actually using some of these compounds like NMN and actually help to maintain and actually activate mitochondrial biogenesis, making new ones and mitochondrial bioreenergetics, which is the efficiency through which we make energy in ourselves, right? Is that fair to say?

I think there's so many serious athletes who exercise at elevated altitude for that reason and it provides them, well, I mean, you'd get the same thing, I suppose, if you're doing a lot of activity even at sea level, but being at an elevated altitude forces you into this domain where you're already stressing your system with hypoxia and athletes who train at an elevated altitude and then come down. are in far better shape, right? So they have a lot more loading of mitochondrial, we call it mitochondrial biogenesis. And that's just, we now know how the hypoxia is actually influencing the creation of new mitochondria. We know the molecular pathway. We know the molecules involved. And those, they haven't yet, but those will become drug targets.

So useful hypoxia factor, things like that.

Hypoxia induction factor, HIF, is it responds to low oxygen environment. But what would happen if you had a drug that could turn that on? I wonder if that's how blood restriction exercise works.

Is it some blood flow restriction where you put, let's say, a blood pressure cuff equivalent on your arms or legs, and then you weight train at much lower levels, but you get far more exhaustion sooner and it actually increases muscle synthesis better than regular string training, which is really interesting.

Sure. Yeah, it's the same mechanism. And I think that we can do that through being active by exercising. And ultimately, I think there will be nutrients that stimulate mitochondrial biogenesis. There should be research going on both in the pharmaceutical space, but also in the natural health food space.

Yeah, for sure.

Things that we can eat on our own or drugs that we can take perhaps. but we can change our lifestyle through the, through what we eat if we can identify diets that potentiate hif and other factors in that turn on mitochondria. And I think that's a wonderful area of research.

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