How mitochondria function & produce energy
Today we have a return guest, Dr. Molly Maloof, on the show for a discussion with our lead product formulator, Dr. Greg Kelly. Molly is a brilliant doctor whose goal is to maximize human potential by dramatically extending human healthspan through medical technology, scientific wellness, and educational media. Their conversation is all about healthspan and optimizing mitochondrial function. They also dive into the science behind the formulation of our product, Eternus, which was designed to support cell energy for better aging. We discuss:
- The 9 hallmarks of aging
- Mitochondria as Chi
- What gives us “glowing” skin
- Measuring mitochondrial health
- Lifestyle tips to optimize mitochondrial function
- The research behind Eternus
Full Episode Transcript:
Dr. Maloof:Okay, think about somebody who's really healthy, they glow. The reason why people glow when they're healthy is because they have robust energy production in their body. They have adequate, even beyond adequate, they have enough energy and more to handle anything that happens in their life. In scientific terms and western terms, this is actually called skin autofluorescence. Skin autofluorescence is essentially your body's ability fluoresce. Your body creates light. Essentially, when we create these electrochemical gradients and we consume food, and we make charge, we're literally charging our batteries of our body.
Dr. Maloof:To me, when I look at somebody, I can tell if somebody's healthy by literally just the way they look. Are they making and storing enough charge? Is that showing in their skin? If you look at someone who's unhealthy, their skin is sallow. They don't produce that amount of light. They often, ... I mean most people in western culture, the biggest complaint you see in medicine is I'm tired. I don't have enough energy. In eastern medicine, this has always been their fundamental purpose of Chinese medicine is how do you balance an individual's energy? How do you balance the yin and the yang? We haven't really until very recently integrated this concept. It wasn't until really Wallace and this discovery of the ... and unbelievable importance of mitochondria in metabolic health that I think we've been starting to piece together this connection.
Dr. Maloof:From what I've gathered, Wallace is actually doing research in China specifically dedicated to figuring out how to bridge these two things, these two worlds. I think it's just fascinating though that we've been so obsessed with anatomy and physiology. We've glossed over this massively important facet of health, which is energy production.
Jacquelyn Loera:Hey there. Welcome back Neurohacker community. I'm Jacquelyn. I'm the producer of the Collective Insights podcast. Welcome to episode number 53. Today, we've invited Dr. Molly Maloof on to the show for a discussion with our lead product formulator, Dr. Greg Kelly. Molly is a brilliant doctor whose goal is to extend human healthspan through medical technology, scientific wellness, and educational media. Their conversation today is all about healthspan, optimizing mitochondrial function and they also dive into the science behind the formulation of our newest product, Eternus, which was designed to support cell energy for better aging.
Jacquelyn Loera:I want to thank all of you guys for listening. Due to your support, we're climbing at the ranking on iTunes and we're not number 26 in top shows for the entire category of science and medicine on iTunes. We're so grateful for you being on this journey with us. Remember, we release an episode every two weeks, so be sure to stay tuned for our next episode with Amy [inaudible] on the connection between the mind and exercise. As a thank you, we're giving our podcast listeners 15% off their first order of any of our products including our featured product in this episode, Eternus. Visit neurohacker.com and use the code podcast 53. Again, that's podcast 53 to claim that discount. Now, without further ado, let's jump into the show. Here's Molly and Greg.
Dr. Kelly:Welcome to Collective insights. I'm Dr. Greg Kelly, the lead formulator here at Neurohacker Collective and joining us today is Dr. Molly Maloof. Molly's a really brilliant doctor and an innovator. She's co-founder of NutriSense and on a mission to radically extend healthspan and maximize human potential using scientific wellness, health technology, educational media and health optimization medicine. She's worked in Silicon Valley with a number of high tech companies innovating the biotech space as an advisor and consultant in areas of nutrigenomics, continuous glucose monitoring, other forms of quantified self bio data and personalized medicine. She's been on our podcast before with Daniel Schmachtenberger discussing personalized medicine, health technology and blood sugar. Today, we've invited her back to have a discussion about healthy aging and our newest product here at Neurohacker Collective Eternus. Molly, thank you so much for joining us.
Dr. Maloof:Thank you for having me.
Dr. Kelly:This is going to be great. For our audience, Eternus is going to be ultimately what we want to speak about but really what Molly and I pre-talked about was that we really are passionate about mitochondria performance and wanted to start off our conversation. Given the big picture about why our mitochondria such an important part of health aging. I'm going to turn it over to you and let you lead in with that.
Dr. Maloof:Sure. Well, when we study aging and when we look at these nine hallmarks of again, in the past most people who are interested in longevity really thought that all nine hallmarks were equally contributing to aging. As it turns out, it's looking more and more like mitochondrial dysfunction perceived almost all of them. It looks like it's upstream to these hallmarks of again. The way that I described the importance of mitochondria is thinking about a house that ... think about a house. Imagine if you cut its power, what would happen to that house over time. The house would fall apart. Things just wouldn't work. All of the appliances would stop working. The air conditioning wouldn't work.
Dr. Maloof:Before you know, it would be broken down. Your body's similar like that. If your body loses its power supply and you basically die. If you take cyanide, it immediately turns off mitochondrial function and you're dead. That's why mitochondria are so important. When we think about mitochondria and aging, we have to think about what happens when we age. A lot of people don't realize but as we get older, we lose mitochondrial structure and function. One of the biggest problems and plagues to society today are the fact that we're overtaxing our mitochondria.
Dr. Maloof:We're overeating and we're eating all day long. We're never giving our metabolism a rest. We're essentially running our cars 24/7, seven days a week. Maybe getting like a small time off, a small fast overnight but really realistically, most people just are overtaxing their metabolism and their mitochondria break down, wear down. Before you know it, you've developed chronic lifestyle-related diseases. The work that I really turn to when I think about mitochondrial health and aging is this work by this physician, Picard out of Columbia. He's really tried to explain that essentially overeating, inactivity, and too much stress are essentially the three main drivers of disease that damage mitochondrial function.
Dr. Maloof:As we lose mitochondrial function, we lose capacity because mitochondria are not only power plants but they're capacitors. They make and they store charge. Essentially, the battery of ourselves. If we don't regularly regenerate these batteries by doing things like ketosis or fasting or hight intensity interval training, essentially what we're doing is recycling these batteries. If we don't do that, we end up having poor quality batteries and insufficient numbers of them.
Dr. Kelly:I think you just covered a lot and I want to make sure we back track and-
Dr. Kelly:... I guess go in to just a few areas more quickly. When you mentioned the hallmarks of aging, there's nine of these as Molly said. Mitochondria dysfunction is one and as she mentioned, it [inaudible] upstream. Meaning, it might be the most important of the nine to address. Really by hallmarks of aging, these are the characteristic things that go wrong as cells get older and cause our disease to breakdown. One of the other things that Molly mentioned, this researcher Columbia, Picard, who ... brilliant, brilliant person. His work at least a large part of it, I would say interfaces our mitochondria, what we might think of as mind, body medicine-
Dr. Kelly:... and stress response. Do you want to give our audience a little bit more insight into some of his, I guess what their findings have been?
Dr. Maloof:Yes. I grew up studying ... in basic biology, when you're a kid, you learned, "Oh, there's mitochondria in a cell and they're the power plants." Everybody knows that, but what I didn't realize and that I felt so ... I couldn't believe that I didn't even realize this when I started studying. I started studying mitochondria again over the last year is that they're signal transducing organelles. They're not just providing us energy, but they're actually reacting to the environment around us and sensing our environment and actually integrating those signals, and sending messages to the nucleus and telling it what to do.
Dr. Maloof:One of the things that it integrates is the stress response. Believe it or not, mitochondria are the site of cortisol production in the adrenals. They're also the site of the enzymes that create catecholamines. They are hugely important for the stress response. They're literally stress integration organelles. If you think about this, we being sickly absorb mitochondria in the endosymbiotic hypothesis many, many thousands of millions of years ago. That we basically, we're able to expand our ability to sense and find energy in our environment. In that process, we develop the symbiotic relationship and then, it became more organelle. The fascinating thing about mitochondria is that they aided in our evolution.
Dr. Maloof:They're constantly aiding in our ability to adapt to stress, to essentially survival and even to sex hormone production. To me they're so much than just power plants. They are vital to our ability to survive and reproduce, which is fundamental why we're here essentially. It's really what our biology wants us to do, whether we like it or not.
Dr. Kelly:I know that piece that our mitochondria actually make glucocorticoids and other steroid molecules, I must've missed that day in biochemistry and physiology because I have no recollection of ever hearing that until reading Picard's work. It's super fascinating because as a wholistic practitioners, stress ends up being a big area of focus and that our mitochondria are really at the crossroads of building our resiliency and then communicating throughout our system in terms of how we respond to it. Doug Wallace who is one of really, I think it's who Picard studied under, but he had this seminal paper, I think around 2005 where he introduced this idea that our mitochondria might be the nearest equivalent to this TCM or traditional Chinese medicine idea of chi. Like I almost think of it in Star Wars [inaudible] are what gave them more force ability that our mitochondria-
Dr. Kelly:... in a sense, that's what they delivered to us when they're functioning at full power. I just wanted to see if you had anything you wanted to share about that.
Dr. Maloof:Yeah. If you think about somebody who's really healthy, they glow. The reason why people glow when they're healthy is because they have robust energy production in their body. They have adequate, even beyond adequate. They have enough energy and more to handle anything that happens in their life. In scientific terms, in western terms, this is actually skin autofluorescence. Skin autofluorescence is essentially your body's ability fluoresce. Your body creates light. Essentially, when we create these electrochemical gradients and we consume food, and we make charge, we're literally charging our batteries of our body.
Dr. Maloof:To me, when I look at somebody, I can tell if somebody's healthy by literally just the way they look. Are they making and storing enough charge? Is that showing in their skin? If you look at someone who's unhealthy, their skin is sallow. They don't produce that amount of light. They often, ... I mean most people in western culture, the biggest complaint you see in medicine is I'm tired. I don't have enough energy. In eastern medicine, this has always been their fundamental purpose of Chinese medicine is how do you balance an individual's energy. How do you balance the yin and the yang? We haven't really until very recently integrated this concept. It wasn't until really Wallace and this discovery of the ... and unbelievable importance of mitochondria in metabolic health that I think we've been starting to piece together this connection.
Dr. Maloof:From what I've gathered, Wallace is actually doing research in China specifically dedicated to figuring out how to bridge these two things, these two worlds. I think it's just fascinating though that we've been so obsessed with anatomy and physiology. We've glossed over this massively important facet of health, which is energy production.
Dr. Kelly:For sure. I know one of the things here at Neurohacker Collective that we're always super excited about is things that have to do with complex system science. The analogy I'll give to our listeners is if you think of an ant or a bee on their own, they're not particularly great at solving real world problems. If you put a colony of ants together, good luck getting that out of your yard. In complexity of science, you often hear that as a super organism. It's the organism, all of the ants, the colony that's intelligent and is adapting to real world challenges. Our mitochondria, we're often when we see a picture of a cell in a textbook, you'll maybe be see one a couple mitochondria in a cell but the truth is there's hundreds to thousands inside those cell.
Dr. Kelly:Within any given cell, it's this complex network that's always reshaping itself to adapt to the real world. Then, there's some thought they're somehow communicating between the ones in other cells remotely. Mitochondria in our gut might be doing things to communicate with the mitochondria in our brain. They're this just amazingly cool thing and it's great that they're getting attention. I'll throw it back to you for a moment.
Dr. Maloof:Sure. I have a friend named Ben Gibson, who's actually an investor. He ended up doing a really, really big deep dive into mitochondrial research because he was looking to invest in this space. I ended up basically forcing him to teach me everything he knew. I literally showed up in this door one day and I said, "Ben, we're supposed to hang out right." He's like, "Yeah, I totally forgot." Ended up being a three-hour session where he just taught me everything he knew about mitochondria. One of the most unbelievable things that I discovered was that we've been so obsessed with this idea of the microbiome but really what I think is fascinating is this idea of the holobiome, which is that we have our DNA. We have mitochondrial DNA. We have microbiome DNA. Then, there's also the microbiome DNA. We are just this massive complex system of organisms.
Dr. Maloof:It's so fascinating that everybody ... people get excited about the microbiome and they're like, "Oh, yeah. This is the next frontier." Really, their next frontier is complex system science. It's actually figuring out how do we make sense of something that's actually fairly immeasurable. We don't have good measurement tools for mitochondria, but we know that it's fundamental to health. Turns out VO2 max might be one of the best test for your mitochondrial health. Every time I ask people who are experts in mitochondria, the same thing that they keep on saying to me is, "Molly, don't worry so much about measuring it. Ask a person how they feel."
Dr. Maloof:I was like, "Well, look. How a person feels is actually very dependent on a bunch of different things." If you actually think about it as a reasonable question like do you have enough energy to maintain your daily function. To do all the things that you want to do, to do all these things and more. If you do have energy to do all those things, then you probably have robust mitochondrial health. If you don't have that level of vital force, then there might be something wrong. The way that I think about this is also are you doing things on your daily basis and your daily life that are essentially optimizing for mitochondrial biogenesis and mitophagy.
Dr. Maloof:These are big terms that are actually fairly simple if you break them down. I'm going to get into it really quickly, just to summarize them for people. Mitochondrial biogenesis is are you making mitochondria? Are you building more batteries? Mitochondrial mitophagy is like autophagy but it's mitochondria. Are you actually throwing out the bad mitochondria that no longer store charge? How do you do this? How do you do mitochondrial biogenesis? It's essentially like it's a ... it's like a cycle essentially. What blew my mind is that, okay, we've seen people getting excited about exercise, getting excited about fasting and integrating these into their lives because we know, turns out that all the animal research suggest that these are pretty much like the most statistically significant things that you can do to enhance your longevity. At least in animal studies, we know this.
Dr. Maloof:Then, I got into this really from my Stanford course I was teaching on healthspan. I started figuring out like, "Okay, let's get specific." Does everyone know you're supposed to do a little bit of fasting but [inaudible] knows you're supposed to exercise. What does that even mean in terms of practical terms? Essentially, what I think is the future of this approach to essentially this complex system is trying to integrate different behaviors as metabolic conditioning. Just like you would cross train your fitness and try different things to optimize it with fitness parameters, like doing a little bit of high intensity interval training. Doing a little bit of yoga to enhance flexibility. Doing some weight lifting then hand strength. Then, going out a few ... making sure you do adequate walking to make sure that you just have that baseline non-exercise activity thermogenesis. With metabolism, you can do the same thing with different types of fasting.
Dr. Maloof:The way that we need to integrate this is by looking at person's stress levels. If you take a person who is highly stressed in low capacity, and you add these metabolic conditioning agents to their body like fasting and fitness, you can actually overload them. A perfect example of this is somebody who has chronic fatigue. If you give a person with chronic fatigue syndrome too much exercise, they literally tanked. The reason why they don't have enough capacity, they don't have enough capacitors. They don't have batteries to maintain that stress load. The way that I see the future of health is like how are we going to personalize the dose of these metabolic conditioning agents, whether it's supplements, whether it's fasting and whether it's fitness. Different dietary styles to give a person the ability to optimize these cycles mitochondrial biogenesis mitophagy.
Dr. Kelly:That's good. I want to unpack a couple of different things for our audience.
Dr. Kelly:A few terms, what I think of as basically mitochondrial quality control. That would be the big category things that sounds like a lot but a couple of things that Molly mentioned stayed under that. Mitochondrial biogenesis would be the creation of new mitochondria would be in a simple sense. What I think of that as is equivalent to lifting weights. If you lift weights, you muscle will get bigger and stronger. Mitochondrial biogenesis is a bit like that for a mitochondria. They're essentially becoming a bigger stronger network. [inaudible 00:18:53].
Dr. Maloof:It's happening [inaudible 00:18:55].
Dr. Kelly:Yeah. Absolutely. Exercise is absolutely one of the best things [inaudible 00:18:59]. Then mitophagy or anything with autophagy is basically a cleaning function. It's getting rid of the damaged things. Usually, proteins. Intermittent fasting is one of the big things to stimulate autophagy so we have these two things like building a new stronger network but also cleaning up the broken to the old one, so that it can be reassembled as you put together these new bigger robust ones. Some of that, the Circadian function, if I followed the literature correctly. That's part of the reason why naturalistic thing, so we had Dr. Kruse on not too long ago. I think his one recommendation how to improve your mitochondria function was get out and see the sunrise. Now, maybe that's not doable for everyone but in addition to exercise and some type of fasting types of behaviors, exposure to nature is hugely important for a mitochondria.
Dr. Maloof:Totally. Yeah. I mean I think we forget the importance of light in our life. Turns out because we spend so much time indoors. I personally experienced a massive improvement of my health from moving from a dim apartment to a bright apartment. It was astonishing and how much more energy I just go from moving to an apartment that enabled me to wake up with light every day. I'm talking I went from apartment with a light well to an apartment with only big giant windows. It was amazing because I just felt my Circadian rhythm's snap into shape. The weirdest that happened is that my menstrual cycle began to be in sync with the moon. It literally changed. My cycle changed to literally come in sync with nature.
Dr. Maloof:I think it sounds hippie but actually we're really designed to be more aligned with the natural cycles of life and our environment. We're so detached from our natural world that I think ... I actually have to prescribe this patient. I have a client with chronic fatigue and I said to him, "How much time do you spend around trees?" He's like, "Pretty much none." I was like, "Well, every weekend I'm going to need to go into nature for two hours minimum." I actually prescribed this to patients because it's so important that people make contact with the earth and ground their bodies. This connection, it's our body battery. It seems like we're actually meant to ground our energy in the earth. We're actually meant to get energy, not only from food but light.
Dr. Maloof:I think this is a pretty new and exciting science. It looks like there is some research that's fairly, I don't know if you read this but it's fairly obscure. There is this one paper that's floating around PubMed that essentially describes that if you consume a high chlorophyll diet, you might be able to actually capture more light independent of food intake through mitochondria through your skin, which is mind boggling.
Dr. Kelly:I'm sure there's spirulina and chlorella people out there in the world would love that.
Dr. Maloof:Yeah, exactly.
Dr. Kelly:I think ... I'm a naturopathic doctor. I don't know that I mentioned that in our lead in. That evolved out of in part European nature cure and so back hundred plus years ago, the naturopaths back then used air, water, light, food, movement. That was their core toolkit. The mitochondria in a way starting to give us an explanation for why some of those what aren't super sexy tools necessarily to make such profound differences.
Dr. Kelly:One thing I did also want to touch on, you've mentioned fatigue. There's a couple things I want to make sure our audience understands about mitochondria and essentially healthy aging. I know in general the thought among some people is that each decade we tend to lose more and more mitochondrial function. That maybe as much as 80% of what we think of as diseases of aging might be related to subpar mitochondrial performance. Because of that a lot of the what I think of is the signs and symptoms of getting old or less healthy tend to also correspond to that.
Dr. Kelly:Things like fatigue, super important but sleep issues. That could be a problem. This is something I didn't realize until fairly recently doing some work on the sleep formulation. There's a big ATP surge in our brain just as we kick into sleep. ATP is the core molecule that the mitochondria make and one thing that Molly's mentioned a few times. That Eternus was generated or created really to facilitate is this idea that our mitochondria make this chemical compound. It's super important to allow cells to do work. If we don't have enough of this, we just can't get to all the important job cells need to do. When that happens, that shows up in our life with these low level things that medicine has a hard time dealing with. Fatigue, sleep issues, trouble even being motivated to do things.
Dr. Kelly:What I would think of is mood problems. Our mitochondria like ... another thing mitochondrial dysfunction, swallowing would be one of the things you would see on the questionnaires for that. These things that we don't have solutions for but in essence, it means somewhere in our body, there's not enough energy to get a job done.
Dr. Kelly:Mitochondria, the focus is if we do more for them, they can do more for us. That translates into often improving across the board these symptoms that we didn't have solutions for.
Dr. Maloof:Yeah. I mean what I find really fascinating is all I need to do is just not exercise for a few days and I see my energy levels drop. What people don't realize is that there's essentially this concept of the adaptive capacity model, which is that your body need signals sent to it to promote mitochondrial biogenesis. One of those signals is movement and exercise, whether it'd be endurance exercise or lifting or high intensity internal training. Point is is that those are signals sent to your body to say I need to increase the capacity to do this work. That means that your body is going upregulate mitochondrial function every time you do an exercise. This is the point of it is that you actually are sending the signals to produce capacitors, capacity and batteries.
Dr. Maloof:When you don't exercise, your body sends ... it gets signal sent that, "Oh, well, I don't have any need for these." I'm going to produce less mitochondria because I don't have a demand. Why would I spend energy making things that I need if I don't have any need for them. That to me blew my mind and actually got me exercising more regularly. One of the problems is that a lot of people suffer from such profound fatigue that ... actually, I talked with Daniel Schmachtenberger about this a long time ago. This is actually part of the reason why supplements are important in medicine is that some people really do suffer [inaudible] profound fatigue that even just walking to the mailbox is too much for them.
Dr. Maloof:We have to get them to a point where they can actually have even enough capacity to get started on exercise. One of the things that I like to use supplements for is actually just getting this process started. I think honestly, frankly the Eternus product is pretty profoundly intellectual approach to mitochondrial quality control. I mean if you actually look at all of the ingredients and the explanation of why you guys have chosen these ingredients, it makes a lot of sense. When you think about those people who are really struggling with energy and they just don't have enough to get on that treadmill I think starting with the supplement can sometimes be a good boost and just getting them to sit outside.
Dr. Kelly:Yeah. I would agree. I'm a big fan of starting low and pushing the bar up from below instead of overestimating what we think we can do. It's one of the things I always feel bad for people that go to an athletic trainer and they put them through a grueling workout right out of the gate.
Dr. Kelly:It wouldn't be how I would approach it.
Dr. Kelly:Maybe that's just because I know from when I saw patients and I'm sure the same, is then you overdo it with a patient. Then, you've taken many steps back. It's much better to work slowly and incrementally build health and fitness. Then, one of the things you mentioned with supplements, there's ... we've mentioned a few times, exercise and then, calorie restriction types of behaviors. With certain supplements, they would be considered exercise, mimetics or calorie restriction mimetics.
Dr. Kelly:By that, what I mean is if you take this substance, it gives you some aspect of the same physiological response. Your cells and mitochondria are responding somewhat the same way they would be if you'd done the calorie restriction or the exercise. When we developed Eternus, that was one of the key things we looked for. What were some of these things that could duplicate or I guess mildly stretch your physiologies in ways that would be similar to exercise and calorie restriction. Then, allow your system to essentially toughen up but in a less aggressive way than going out and doing a spinning class.
Dr. Maloof:Sure. I mean a great example of this is just weirdly enough, apple cide vinegar actually activates AMPK. It's not a supplement. I mean it's a substance you can consume but curcumin as well and fiber. All of these things actually activate AMPK, but what else does this? Exercise. I think as far as I can tell, I can berberine actually down regulates IGF1 pathway. It's similar. It's part of the reason why it helps with glucose metabolism. Maybe you could tell me a little bit more about some of the exercise or calorie restriction mimetics that are in Eternus because I think that'd be really interesting to learn more about.
Dr. Kelly:Sure. Before I touch about it, I just wanted to talk about AMPK or AMP-K.
Dr. Maloof:Sure, yeah.
Dr. Kelly:AMPK, AMP-K is a what I think of as master regulator. It's main job is it senses ATP levels. If we're exercising, we're going to deplete ATP because we're using it to move our muscles. That responds by boosting ATP production, so essentially taking the air we're breathing, the food we may have eaten and stored as glycogen or fats in our tissues and converting it into energy. The other big things that AMPK does is it boost these others things like mitochondrial biogenesis, so that in the future, when we exercise next whether that's tomorrow or next week, we'll be able to have more capacity, which is something that you mentioned.
Dr. Kelly:AMPK is the master sensor for really ATP upregulation. What you see for a lot of these super important cell signaling pathways is they're causing adaptations. One of the complexity science understanding is our system, our complex adaptive systems are great at learning and figuring out essentially a prediction for the future. When we lift weights, our muscles get bigger and stronger. Not so much because we lifted weights now but in case, we lift them again. AMPK, there's lots of things that stimulate that. Things like creatine, which body builders and athletes have been using for quite a while. Creatine's really a first line defense if we're acutely depleting ATP because of like say doing a 100-yard sprint, our body uses creatine to replenish that quickly.
Dr. Kelly:Creatine then also boost AMPK, so that the next time we sprint, we'll have more too. There's other things like lipoic, which is I think of as a mitochondrial nutrient. That would also be an AMPK booster and then, lots of phytochemicals too. Resveratrol tends to hit a lot of-
Dr. Maloof:A lot of pathways, or [inaudible] pathway.
Dr. Kelly:... a lot of pathways. Yeah. That's a great one for AMPK upregulation. Resveratrol for our audience that may not know is it was originally found in grapes. What you find with a lot of these plant chemicals is they tend to be the stress response mechanism of plants. If a grape is stressed by the climate's dry, there's lots of sun. There's pest nearby, it'll make more resveratrol. When we consume that resveratrol, it access a mild stress on us. Essentially, some people think that it allows us to forecast, "Oh, the future might be a little tougher than we expected, we better toughen out to be prepared."
Dr. Maloof:They love that. It's funny because I've actually read papers on xenohormesis. You really phrased it beautiful there with that because I actually really think back into this whole adaptive complex science concept. It's like really we're meant to interact with our environment. We're meant to actually ... foods that are grown in wild environment because those send us the signals of what the environment looks like. That makes perfect sense. That's brilliant.
Dr. Kelly:What you find is you start to dig into the research on mitochondria is that it's [inaudible] especially with polyphenols. They come up over and over.
Dr. Kelly:When we developed Eternus, one of the things that this would be a truism, just like the average American diet's fairly poor in fruits and vegetables but also a variety of fruits and vegetables. Polyphenols, our ancestors would've got a lot more because they were eating things that were wild, that were raised in tougher environments where plants foods aren't necessarily.
Dr. Kelly:There would be a generally, I think you could say there's a huge deficiency in the US diet of both the amount and variety of polyphenols. When you look at Eternus, that's one thing that if you knew what all the polyphenols, like the resveratrol, we use a strawberry seed extract that has an ingredient called tiliroside in it.
Dr. Kelly:Rosemary has some polyphenols. We have a brand of product called ElevATP that's actually be studied to boost ATP but part of that product is trace minerals and the other part is alpha polyphenol. Polyphenols just super, super important and good for us for boosting mitochondrial performance.
Dr. Maloof:I think the trace minerals piece is actually fascinating as well. I've been getting more and more into why are minerals so important? Why are we so mineral depleted? A lot of it is because our water is no longer mineralize. We don't get water from springs. We get water from cities. It's astonishing when you ... I think one of the reason why people have gotten obsessed with these mineral waters like Topo Chico and Gerolsteiner is that there's mineralize. I don't know if you've gotten it all into the quintan world of the sea mineral extracts and what not. It does look like a lot of modern life makes us more mineral depleted. Whether it'd be because of stress, whether it'd be because of the poor water supplies we're consuming, whether it'd be because people don't miss eating a standard American diet that doesn't have a lot of minerals in it.
Dr. Maloof:I think we need to think about nutrition in terms of what's missing and why? I think it's really cool that you guys considered that. I've never even heard of that supplement before. That ingredient is so new to me and I think that's what I love about frankly ... actually, I'm not paid by the company Neurohacker. I'm not a spokesperson yet but I definitely love that you guys really go deep into the research when you're designing these formulas. It's really rare to see. I think to have so many ingredients in one stack is fascinating. The fact that you guys have such deep reasoning behind each ingredient is really cool.
Dr. Maloof:Just out of personal experience, today I woke up. It's an interesting day. I woke up with all this motivation initially to ... I woke up. Last night I went to bed and I told myself, "All right, I'm going to wake up in the morning. I'm going to do high intensity interval training, sauna and a cold shower." I ended up having colds and I got really busy. I had way too much to do and [inaudible] not have time to do it all. I also just weirdly enough woke up today with not feeling as much energy that I usually have.
Dr. Maloof:I said, "Okay, I'm going to be on this podcast. I'm going to be taking the supplement. I'm going to be talking about a supplement today, I might as well try it." I read about the supplement and it looked liked some people respond immediately. Some people respond over time. Some people don't respond at all. I was actually pretty surprised at how quickly, like within a couple hours of taking it, I noticed my motivation return. I noticed my energy levels went up. It was quick. I'm definitely susceptible to placebo response because I have the genetics for that. However, it was a pretty quick response. I wasn't expecting that because you don't always feel that way with the supplement.
Dr. Maloof:I'm curious to know a little bit more about your thoughts on what people should expect when they take this. I know you got some numbers on who responds to it and may not respond to it. Curious to know your thoughts on that.
Dr. Kelly:Sure. Quickly before we get to that. Are you more keto or any special diets right now?
Dr. Maloof:I can just say I actually ate a fairly high carb meal last night. I'm pretty low carb almost all the time. I had a friend come over and she's a vegan. I decided to make a higher carb meal for her because vegan diets are generally higher carb. I might've actually been part of the reason why I woke up today I feel like a little bit off because I usually eat pretty low carb and it was fairly higher carb meal last night.
Dr. Kelly:Okay. I know we've seen ... At Neurohacker, we think of response grouping. When we formulate and then, test a product, we're looking for ... I would view this the same with something like exercise. It's going to be always a subset of people that are super responders. Back when I was in the navy, my lifting buddy at the time for six months when we were deployed, we pretty much did the same workout. He put on 20 pounds of muscle. I maybe put on two-
Dr. Kelly:... so frustrate. He was a super responder. You could say I was a responder. I didn't get a bad response. I just didn't get anything near him. There's always that super responder group. There's a responder group. There's a group that it doesn't work for. Most things, you'll find some subset of people that were non-responders. Then, even with exercise, someone could get hurt. You could get some negative responders. When we formulate and test a product, we're looking always at those and our goal is to have about a third to 40% super responders, above 40% responders. Then, we typically feel like it's super hard to get anything that's going to have more than that four out of five people that get a good response. Because of that we offer a money-back guarantee because we know there's going to be always some small sliver that a product just doesn't work for them.
Dr. Maloof:That's the truth. I actually tried Qualia and it did not work for me. I definitely noticed the caffeine effect but it really wasn't the right supplement for me. That's okay. I think that's the fascinating thing about personalized nutrition is that we're just beginning to truly be able to prescribe people the right stacks and it's ... the very beginning, it can be a little trial and error. I think I generally do like to test before I treat. The thing about mitochondria is it can't actually test. You can't measure these things that are constantly changing, which most people don't realize is that mitochondria, this network, it's not like that its static organelle.
Dr. Maloof:They're literally constantly coming together and then, they're breaking apart. The way that they come together is when we fast actually. They come together when they're under stressed. Fasting is a stress. When they come together, they communicate and they all start vibrating and resonating. Then, the ones that are not carrying the right charge get thrown out. They get tabbed with this thing called parkin. Then, they get internalized by lysosome when they get thrown out. That's mitophagy. Then, when they only eat, they come apart. It's called fission. It's fusion and fission. We don't actually have a good measurement for this right now.
Dr. Maloof:Essentially, the best measurement you've got for this I think this supplement is how do you feel? Maybe you're going to be an early responder or maybe after a month that's when you're going to start feeling a difference. I think the fact that you guys have a money-back guarantee and there's really no reason not to try it if you have energy issues. I think we're just starting to see this whole mitochondrial supplementation world emerge. I want to Paleo f(x) effects and I was astonished at the fact that people are picking up on this movement. This is not just us. This is actually getting to be a global awareness.
Dr. Maloof:A few years ago, it was like everything was about the microbiome and everything was about inflammation. Now, I think things are moving towards everything's about mitochondria and a lot of these things that we're worried about are actually downstream. There's actually a bunch of research that claims that even inflammation is downstream to mitochondrial dysfunction. There's a lot we still have to figure out. I'm excited about the opportunity of even biophysicist to attack this problem because if somebody can figure out how to measure mitochondria, they should win the Nobel Prize. Arguably, was it Wallace who discovered mitochondrial DNA?
Dr. Maloof:I think he was. Yeah.
Dr. Kelly:I don't know.
Dr. Maloof:He should've won ...
Dr. Kelly:I don't know if he discovered it or discovered it was inherited from-
Dr. Maloof:Yeah, the maternal.
Dr. Kelly:... yeah.
Dr. Maloof:He should've won a Nobel Prize. This is easily one of the most important discoveries in science. The guy who actually discovered autophagy in Japan, he won no Nobel Prize. This is becoming globally and very fascinating interest. I think what people ... we should link to this video that Wallace has on YouTube that my friend Ben told me about. Essentially, if you really look at all these chronic lifestyle related disease, you see them cluster in people. They don't just get one. They get a few.
Dr. Maloof:To me, it's like the house breaking down. If your power supply's cut, then your air conditioning breaks and your lights don't work. To me, if we can just generate more and better mitochondria over time and throw out the garbage of ourselves, and do these behavior and have these lifestyle that contribute to this function. Then, we should see ourselves live longer and healthier lives.
Dr. Kelly:I absolutely agree. I think at least what I'm seeing is something similar to you. It's getting a lot more intention. I think NAD as an example, so think in general things in the healthspan space, so senolytics would be a big thing. For our audience, these are things we have ... what are often referred to as zombie cells. There are cells that were damaged enough that they got essentially frozen. They weren't eliminated but they're not healthy cells. They can send out inflammatory molecules. Senolytics would be things that destroy those cells. Super important for healthy aging, but then things that the mitochondrial piece, so NAD.
Dr. Kelly:NAD, we haven't really touched but NAD is used to make ATP. If we don't have NAD+ specifically, we can't make that NAD+ is also used to activate sirtuins, one of the anti-aging pathways. Sirtuins activate AMPK, which we spoke about. Then, AMPK feeds back [inaudible] to make more NAD+. It goes in this big virtuous circle. NAD does what I think of as three jobs. They would be making cells able to make more ATP. Upregulating these longevity pathways. Then, they also do a lot with cellu defenses, so detoxification, antioxidant defenses. They sit at a cross roads but then, one of the things I did not realize until digging into NAD is that, there's three different ways that our cells make NAD. They can make it from tryptophan, which is amino acid. They can make it from the flushing niacin and from non-flushing niacins. Each of those pathways, we need ATP to make NAD.
Dr. Maloof:There you go.
Dr. Kelly:These things are all interconnected. At Neurohacker Collective, when we were creating Eternus, we want to boost NAD but doing that without also paying attention to ATP just seemed like we were missing half of the equation. One of the things that we would tell people is that if you are doing NAD boosting stuff, absolutely great but pay attention to doing things that support your mitochondria more directly as well. At a minimum, eat more polyphenol-rich foods.
Dr. Maloof:Yeah. I mean I think one of the things I found interesting in the Eternus research was that you guys really made a strong stance that you just weren't going to include nicotinamide ribo [inaudible] the nucleotide in your supplementation. A lot of the new research seems to suggest that these are broken down before they actually get into our cells. I think that's a pretty ... I think it's a very current stance on this. Yet, I still find that people including myself have in the past supplemented with this for the ideal goal of regenerating or providing a source of NAD. I think it's pretty forward-thinking and maybe you can touch a little bit upon how you guys approach NAD in terms of your ... the goals that you have to produce this. You're including these substances your belief is that they get broken down. You boost NAD through what mechanisms? I'm a little ... it's a little fuzzy for me.
Dr. Kelly:Yeah. There's three pathways that we make NAD. They're called the de novo, that means from scratch. We can take the amino acid tryptophan and through a series of about 11 steps, we can make NAD. Usually, the ratio is, and this is just a ballpark, about a 60 to 1. 60 parts tryptophan, one part NAD comes out at the end because tryptophan also can be made into lots of other things. Another way is called the Preiss-Handler pathway. That's niacin, the flushing vitamin B3 that's made from that. Then, the third is called the salvage pathway. The salvage pathway is super cool. One of the things that I've seen documented a few different times is this idea that we essentially make and use about our body weight of ATP a day.
Dr. Maloof:Cool. That's crazy.
Dr. Kelly:Like a huge amount, right. This is just getting constantly turned. NAD isn't quite that much but we're using and remaking lot of NAD every day. We can make the core molecule from those two pathways and also from another, the salvage pathway. The salvage pathway, there's three niacins that can make it. That's where the NR comes in, the NMN, or the niacinamide. They all are salvage pathway intermediates. Just entering ...
Dr. Maloof:Got you.
Dr. Kelly:It's a big loop. They all entered the same places in the loop. The cool thing about the salvage pathway is the salvage pathway is what gets activate as soon as you use any B+ to activate sirtuins. Sirtuins for our audience, that's another prolongevity signaling pathway and to activate them, they literally consume any NAD+ molecule and spit out niacinamide at the other side.
Dr. Maloof:That's cool.
Dr. Kelly:That niacinamide is then salvaged and turned back into NAD+ in two steps with the middle step being NMN.
Dr. Maloof:Got you.
Dr. Kelly:Where AMPK comes in, the rate limiting enzyme and for our audience, that means the slow spot in the loop is an enzyme called [inaudible 00:47:21]. Upregulating that is the key thing. What I would say whether using NR, NMN, the older niacins, all those things are super important for building it once, but we don't just build that once. We're using it. It's getting salvaged over and over. From a complexity science perspective, we think the real, I guess, where the real diamonds are is salvaging it. Upregulating that whole pathway so your body can regenerate it as much as it needs over and over. What do you often see with the NR supplement, it will be recommended ... take this once, twice, three times a day. You're just pushing, pushing the substrate but none of the levers.
Dr. Maloof:That's [inaudible]
Dr. Kelly:As an example, when you can do things that there's another pathway that consumes it besides sirtuins called CD38, that's an inflammation in this pathway. It's also one that senescent cells super aggressively upregulate. There's some research that suggest the reason that NAD levels are lower as we age is because of CD38. It's basically consuming more than its fair share.
Dr. Maloof:I see.
Dr. Kelly:If we can use a leverage and dial that back, so it's more like a nice house guest than someone eating all your food, there's more NAD+ available. Believe it or not, in studies, what you often would see is giving these precursors, they'll do the job boosting NAD+ level. If you can slow the activity of some of these aggressive consumers, they boosted even more.
Dr. Maloof:Got you. Remind me what slows the consumers down?
Dr. Kelly:That CD38, the biggest thing is the polyphenol apigenin in terms of what's being investigated today.
Dr. Maloof:Cool. This is super interesting because I'm looking at the formulation, and I'm seeing tryptophan. I'm seeing niacinamide, niacin. Then, I'm seeing the apigenin. I actually think this is really fascinating. I think for anybody who's been confused by NAD, this podcast should really shed some beautiful light on this complex topic. People, I mean there are so many people that are coming to me asking me, "What should I take for NAD+?" I'm just like, "Well, you could do this and you could this, and you could do this." I like that you have included all of these in your supplement because it's ... if you actually look at all these ingredients, there's a ton. I was taking a lot of these things individually. The fact that you can take a stack without having to go buy separate bottles is always nice. It's really ... it could be a hassle to formulate your perfect stack and you guys can give ... done this pretty well.
Dr. Kelly:Well, so far we're very pleased to even release it in the first place because we do a lot of testing before we would ever put a product into the wild. I know one of the ingredients ... I think this would be more obscure. We mentioned ElevATP, something that's been studied to boost ATP and it's been athletes specifically they've looked at. There's a plant in there called black ginger or black turmeric are the common names.
Dr. Maloof:Yeah, yeah. I've never heard of this.
Dr. Kelly:Yeah. Earlier, we talked about like if your mitochondria aren't working, it can show up in a lot of different ways. Grip strength, there's a couple different what I think of as great functional markers of aging. You mentioned VO2 max earlier. A grip strength is another one and then, gait speed.
Dr. Kelly:How quickly someone just happens to walk. The black ginger is something that's actually been studied for grip strength and has today, it's just one study but in humans and it made a difference. Grip strength would be another one of those things where we can't directly measure your mitochondria. Grip strength is a great biomarker to people for people to test as they age.
Dr. Kelly:Then, how quickly we just walk, our normal gait speed. I know way before we did a big test of Eternus, I took two months of the formula. One of the things and this could be placebo response for sure. I noticed I felt like I was walking quicker. It seems like over time put more pep in my step. There's these cool things that no matter what products you're taking, that you can start measuring for yourself. We want to get these baselines so that ... you used the word healthspan and we use that as well, so that we can see how healthy we're aging. One of the, I guess distinctions we use, we all have our birth age like how old we are based on our birthday or that's called our chronological age.
Dr. Kelly:We also have a couple other ages. One's our biological age is how we aged our cells are. Another would be our perceived age. How old do we feel or felt aged, I think is what it's called? Do you feel older than your years, younger than your years? Most of us would say we feel younger. Then, there's perceived age, which is how old other people looking at us think we are. We have multiple ages and for me, the big win in life is making sure that those other ones are less than my chronological one.
Dr. Maloof:Yeah. I actually ... I really agree with that. I think perceived age is fascinating. I love getting into lifts because they always ... you get into conversation with people. I didn't really know there's called perceived age, but generally [inaudible] the lift test. What if the lift ... how old is the lift driver think you are? This is some stranger who doesn't know you. If a lift driver thinks that you're younger than your age, there's a pretty good chance that your perceived age is lower because they don't know who you are. They've only glanced at you right.
Dr. Maloof:VO2 max is a great one. My VO2 max went up from just high intensity interval training. That was one thing that I added since [inaudible] and slowly ramped it up one day a week. I would do 20 minutes a time. One minute of sprint, one minute of rest. That caught me into the outstanding range of VO2 max, which was pretty awesome. I was on the cusp of it before. I was right below and I was annoyed. I thought I would just try to boost it that way. Walking seems great. Any time you look at an elderly person, who's walking really slowly through a grocery store, you can tell that walking speed does indicate age.
Dr. Maloof:Then, I actually brought a dynamometer, if that's what they're called, a grip strength measurement tool to my class at Stanford and had all the students measure their grip strength. Because I want to show them first hand where they lie. I was sad to see my grip strength went down as my weight lifting went down from January to April because I stopped weight lifting in January because I was in Japan for February. Turns out that your grip strength can change fairly quickly over a few months. I definitely recommend that people want to optimize these biomarkers to slowly integrate different things into their lifestyle.
Dr. Maloof:One of the simple things that you can do is just gradually increase your steps. I really like the Garmin Vivosmart 4 because it gradually adapts to your step count and if you don't meet your step goal, it reduces your step goal the next day so you can achieve it. Then, once you achieve it, it increases it. It gets you to slowly up your steps over time. If you're not moving, the next ... the thing that people usually get wrong with exercise is they start with a hard workout with a trainer. Then, they feel like garbage like you said.
Dr. Maloof:You got to get people to slowly adapt to these changes in their lifestyle. Then, once you got your steps up then starting to add some formal exercise into your life. I really like yoga frankly because it incorporates a lot more parasympathetic activity than most exercise does. It really gets you to calm your nervous system down, which most people frankly need. Yoga is just so good for flexibility. Frankly, what people don't realize is that if you fall when you get older, you can limit your life dramatically. A person who is again and has a fall, and breaks a hip has a gigantic risk of death within the next four years.
Dr. Maloof:I don't remember the exact numbers but it's really high. Avoiding the possibility of dying prematurely from something like a fall as you age is really important. Then, sarcopenia of aging is super common. You have to lift weights. Otherwise, you're just going to lose your muscle mass. It's just part of life. There's also this called anabolic resistance that occurs as we get older, where we actually respond less to the same amount of stimulus as we exercise. It's actually pretty key to start exercising when you're younger. For anybody whose in there ... hitting 30, turns out that 30, everything's downhill. You got to start an exercise regimen by 30.
Dr. Maloof:If you don't, it's going to be downhill from there because your hormones are trying to shirt when you hit 30. All of this stuff is within your control. It's actually within your ability to do and that's what people forget is that you actually have a say in how you age. I believe that largely the best medicine for aging is exercise turns out.
Dr. Kelly:Yeah. I would definitely agree with that. I usually just think of a portfolio of exercises. You mentioned high interval training. Some type of sprint type things. I tend to personally do a lot of ... I skip rope as fast as I can for about 100 skips.
Dr. Maloof:There you go.
Dr. Kelly:I'm a big fan of rest recovery. The big piece I missed when I was younger, when my friend gained all that muscle mass and I gained very little. I was horrible at taking rest and recovery.
Dr. Maloof:Yes, yes. We forget those.
Dr. Kelly:I was in the navy and completely sleep deprived so that just didn't work. He didn't stay on midnight watch just like I did. He have that edge going for him.
Dr. Kelly:One of the things ... this was a few years back, so weight training is another. To get benefits as we age, we don't have to do crazy amounts-
Dr. Kelly:... but one of the things I think that I like to point out to people is I saw the study probably three years ago. It had I think men, mid to late 50s and what they varied was the amount of time between sets. They had one group do the next set within about a minute of finishing the last one. Another group wait three to five minutes. What they noticed over, it might've been an eight weeks study but overtime was that both groups got stronger but the group that waited more got bigger and stronger.
Dr. Kelly:They also measured immediately after and I believe it was either 48 or 72 hours after both hormone, testosterone. Now, testosterone becomes a big thing. That's a metabolic thing and it's made by our ... I'll let you say it.
Dr. Maloof:Mitochondria, right?
Dr. Kelly:You got it. What they found is there was a huge difference in the testosterone response to the same weight training with a much better response if you waited longer between the sets. My rule of thumb is three minutes minimum. I took the ... because I would like one of those-
Dr. Maloof:I love that.
Dr. Kelly:... 30 seconds guy [inaudible] and ever since then, I looked. There was other studies that have looked at the same dynamic. I literally keep an app with me. I set three minutes and wait for countdown.
Dr. Maloof:I love that.
Dr. Kelly:It's made a big difference I think in my strength and performance gains. I'm hitting my late-
Dr. Maloof:That's so great to know.
Dr. Kelly:... late 50s, so I would say [inaudible] put on mass and starting that routine. One of the things I would say is it's complexity science, it's what you do but timing almost always plays a super important role. Sometimes, we can be really well intentioned but the timing piece will be just a little bit off and it will prevent us from getting our best results. With that, is there two or three things that you would give as advice to our audience? Two things, maybe three things that they could be doing to really up their game when it comes to mitochondria performance.
Dr. Maloof:Yeah. The first thing that people totally underestimate is the role of relationships and health. Your relationships are either helping you build mitochondria or they're destroying your mitochondria. Whenever you deal with a really high emotional response, you're draining your batteries. You only have so much energy to actually commit to your day, do the work and your relationships and your life. Really nourishing health relationships can dramatically improve your chances of living a long, long healthy life. Relationships take work. They're essentially like anything else in life, like a company or plants you're growing. They require care and attention. You can expect relationship to flourish unless you actually commit time and effort into it. That's something that I would actually really recommend is focus on relationship quality and focus on building healthy relationships if you want to live a long time.
Dr. Maloof:The second thing is blood sugar management. You are constantly spiking your blood sugar. You are literally burning hot and you are making smoke in yourselves essentially. That smoke is damaging the lining of your blood vessels. When your blood vessel lining gets damaged, then your LDL has to come in and patch it up. If you want to limit your chances of getting heart disease and cancer, you got to lower your blood sugar levels. Most people have silent insulin resistance and imperative glucose tolerance. Not to plug my own company but we are using continuous glucose monitoring to actually unveil what's really happening in your body when you eat different food.
Dr. Maloof:Limiting overeating and limiting over amount ... too much sugar is actually one of the best things you can do to actually just reduce the burden of damage on your mitochondria as you age. I would really recommend those two things. Yeah, I think the third thing is just constantly exercise your mind with learning. There's just so much evidence that continuously learning and continuously engaging with the world around you and the people that you have in your environment and the environment itself is one of the best things you can do to age well for your brain to age well. With that, I'll say bye and thank you so much. If you want to find me online, go to @drmolly.co on Instagram and just email me at [email protected].
Dr. Kelly:Awesome. Thank you so much for joining us today. Real pleasure.
Dr. Kelly:Bye Molly.
Jacquelyn Loera:Thanks for staying through to the end with this conversation with Dr. Molly Maloof. We hope you enjoyed it and learned something new to apply to your own life. Remember our podcast is made possible by Neurohacker Collective and you can 15% off your first order at neurohacker.com using the coupon code podcast 53. If you have any questions about this content, then please leave them on our site at neurohacker.com/podcast. We'll work to get those answered by Molly on a future episode. If you like this episode, then please leave us a five star review on iTunes and share it with all of your friends who are interested in living longer, healthier lives. Make sure to subscribe to Collective Insights wherever you listen to podcast so you don't miss an episode. See you next time.
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