The Melanie Avalon Biohacking Podcast Episode #164 - Ari Whitten

TRANSCRIPT

Melanie Avalon: Hi, friends, welcome back to the show. I am so incredibly excited about the conversation that I am about to have. I have been wanting to have this conversation for probably about two and a half years now. Ever since I launched this show, The Melanie Avalon Biohacking Podcast, at the very beginning, I would get requests for guests. And there's a name that has been coming up from the very beginning, I promise you. And that is Ari Whitten. And he wrote a book called The Ultimate Guide To Red Light Therapy. And that's why a ton of my audience was begging for an interview with him. And so, I was really hoping that it could manifest. And then it came to me recently or probably, a little bit a while ago now, but Ari has a new book called Eat for Energy: How to Beat Fatigue, Supercharge Your Mitochondria, and Unlock All-Day Energy. It's funny because I get a lot of requests on this show. And when the email came in from Ari's, either agent, or publicist, or whoever it was, I was just like, "Yes, please book him right now." And then I read the book and it was absolutely incredible. It's about one of my favorite topics, of course, energy production and the mitochondria. And it's extremely comprehensive. 

It goes into what causes fatigue on the cellular level, and then the dietary and lifestyle choices for that, and then an overwhelmingly comprehensive guide to supplements related to energy production. It's really a valuable resource. It's one of those books that listeners and friends, you just have to get, because there's so much information in there and it would be a really good reference book, I think, in addition to an amazing read the first time around. So, definitely get that. We were talking before this about just how many questions and things we could talk about. But I am just so excited. So, Ari, thank you so much for being here.

Ari Whitten: Thanks so much for having me, Melanie. It's an absolute pleasure.

Melanie Avalon: I do think most of my listeners are pretty familiar with your work. But for those who are not, you do have a Bachelor of Science from San Diego State University in Kinesiology. You have two advanced certifications from the National Academy of Sports Medicine as a Corrective Exercise Specialist and a Performance Enhancement Specialist. And I'm curious, because I know sometimes the bios aren't that updated. Was it still recently that you completed your PhD in Clinical Psychology?

Ari Whitten: Yeah. Well, yeah. There's a long story. I've done a whole lot of years of graduate school without any fancy letters after my last name to show for it. I was in medical school for a couple of years. I left medical school, because I hated the allopathic paradigm. I just couldn't take it anymore. It was making me sick to be in a hospital setting, watching people with diabetes and heart disease, just prescribed one drug after another after another on 12, 15, 18 different prescription drugs being taught nothing about nutrition and lifestyle, about the actual causes of their condition. I've been studying nutrition and lifestyle since I was a little kid, since I was 12 years old. And at a certain point, I just couldn't stomach being in that environment anymore, made the decision to leave. And then I thought I'd do a PhD program in Clinical Psychology. I did all three years of my coursework for that and then decided ultimately, I didn't really want to be a psychologist either. There's a number of aspects of that. One of which is the paradigm there was also disturbing to me, because you're dealing with mental health issues. And there is absolutely no discussion, again, of nutrition and lifestyle factors. And there's a large body of evidence that we have on how nutrition and lifestyle ties into mental health and brain health, that simply isn't discussed at all when you're doing training in psychology or psychiatry for that matter. 

And then, I started to realize, "Okay, if I continue to go down this path, if I go complete my PhD at--" I did all the three years of coursework, basically what I needed to do is a dissertation and internship hours. And if I do that, and if I go pursue licensure, if I jump through all these hoops, then at the end of getting my licensure to practice it, not only does is it not really a boon for me, but it actually creates a limitation for me, because now, if I try to integrate the nutrition lifestyle piece into what I'm doing, it's considered practicing outside of the scope of what I'm licensed to do and therefore, they can revoke my licensure if I do that. It's this very counterintuitive paradoxical thing, where I'm actually more free to do what I want to do by not having that licensure than by having it. And then I'm actually in the next few weeks about to wrap up a Master's Degree in Human Nutrition and Functional Medicine. 

Melanie Avalon: Oh, wow. Congratulations in advance.

Ari Whitten: [laughs] Thank you. I appreciate it.

Melanie Avalon: Well, knock on wood, [giggles] but I'm sure you'll get that. Where are you studying that?

Ari Whitten: The University of Western states. It's the only school that offers that degree program with a Master's in Functional Medicine and Human Nutrition.

Melanie Avalon: Very cool. When you do get that credential, are you still going to keep doing what you're doing now, or will that change what you're actually doing job wise?

Ari Whitten: No, I'll carry on doing what I'm doing now. To be honest, it's largely just two things. It's because there's a segment of the population that won't listen to anything you have to say unless they see some kind of impressive formal credential written on your book or something like that. I wanted that just to appease those people, so that it'll at least open their mind to considering what I have to say for those kinds of people who think that way. And then the second thing is, if I'm going to go do something like that to get a credential like that, I might as well learn something along the way. And the program is very good, it has really excellent professors in a variety of different specialties, gut health in particular. The professor for that course is absolutely world class. I figure, if I'm going to do a program to get a credential, I want to learn some stuff along the way, and I've learned some good stuff in some areas that were not within my wheelhouse previously.

Melanie Avalon: Well, that is super amazing. And actually, this is a random tangent to start on, but just talking about the psychology aspect of it, so, yesterday, I was watching a documentary. Have you seen Unrest, the 2017 documentary about people with--? Okay, here we go. How do you say it? Myalgic encephalomyelitis, the fancy word for chronic fatigue? 

Ari Whitten: Encephalomyelitis.

Melanie Avalon: It's a documentary by a woman who has that. We're going to talk about this defining what chronic fatigue is. But she has the end of it, like, she can't even move, and she made a whole documentary from her bed essentially about it. She was talking about how hysteria back in the-- Was at the 1800s in France and how possibly that actually related to chronic fatigue, which was something I hadn't heard before?

Ari Whitten: In what sense was she saying that?

Melanie Avalon: It was a broader picture, but it was about-- [crosstalk] 

Ari Whitten: In terms of the medical history aspect of it, like, how certain people and women in particular are treated by the medical profession? 

Melanie Avalon: Yes. Basically, women getting these medical conditions or psychological conditions and being treated like it was all in their head. But it even linked more specifically to it. And she was saying that maybe all these things have been happening throughout history, like, outbreaks in hysteria and all this was actually related to this broader picture of inciting incidents related to chronic fatigue syndrome. It was very interesting.

Ari Whitten: Yeah, that's an interesting relationship there. Yeah, there's definitely a pretty ugly history around some of this in terms of how the medical profession has treated women. In some instances, hysteria, of course, basically going, "Hey, women are these very strange, illogical creatures sometimes and they act in these crazy ways that we men can't understand. Maybe it's coming from their uterus. Let's cut out their uterus and see if that solves the problem." There's that and then with chronic fatigue syndrome, for a long time, and this is partly due to limitations in testing technologies for a long time. But basically, you could run a blood test on people with chronic fatigue syndrome. The vast majority of the time, their markers will come back perfectly normal. 

Based on that a lot of these doctors concluded, "Hey, there's nothing actually, physiologically wrong with you. This is all in your head." And so, they were prescribed antidepressants and basically, treated hypochondriacs and treated like it was all psychosomatic. And that, of course, is very wrong. We now know chronic fatigue syndrome is in fact, a very real condition and we have sophisticated enough testing that we've established many, many different biochemical abnormalities in people with chronic fatigue syndrome. 

Melanie Avalon: Questions about that, actually. Just to get some definitions here. Clearly, it has a long history. We just discussed of not seeming a credible disease or condition. And you just mentioned the metabolites, which you mentioned in the book there being like 600 or so metabolites related to chronic fatigue. So, stepping back, what is it exactly?

Ari Whitten: Well, this is also interesting, because despite the fact that, as I just said, we have a number of metabolites that have been linked to chronic fatigue syndrome, there is actually still no definitive test, single test that you can do that says, "If you test positive on this particular marker, these two markers, then that means you have chronic fatigue syndrome." It's still a diagnosis that's largely based on symptoms. And basically, the symptoms are severe debilitating levels of fatigue combined with something called post-exertional malaise, which means that for a day, or two, or three, following even brief bouts of physical activity, even maybe moderately strenuous physical activity, someone might be pretty wiped out. They might be in an extreme amount of soreness, and pain, and severe fatigue, and brain fog, and things like that. That symptom is to a large extent diagnostic for chronic fatigue syndrome. 

Now, having said all that, I really don't focus specifically on chronic fatigue syndrome, specifically for a couple reasons. One is, there's a legal aspect to it. I don't want to talk about medical conditions, because it can get me legally into hot water, if it's implied that I'm saying, "Hey, here's these recommendations I'm making which can treat this specific medical condition." Now, so, for that reason, I take things out of the realm of chronic fatigue syndrome and talk purely about fatigue or chronic fatigue, which are not medical diagnoses, but a description of low levels of energy. 

The second reason even more important than that is that chronic fatigue syndrome really just represents the extreme end of that spectrum of how debilitated someone can become as a result of low energy levels. But this is not an on off switch. It's not like, "Oh, you either have amazing high energy levels bouncing off the walls with energy like a little kid or you're debilitated with chronic fatigue syndrome." There's a hundred degrees of gray areas in between those two ends of the extremes. And most people, most adults are somewhere in the middle, if not maybe slightly in the direction of or moderately in the direction of chronic fatigue without necessarily meeting the diagnostic criteria of chronic fatigue syndrome and having this severe post-exertional malaise, but they have poor energy levels relative to what they had when they were in their youth.

Melanie Avalon: I'm glad you're talking about that, because that was one of my big questions. So, on that spectrum of fatigue levels from the beginning to the end where we might see it manifest as chronic fatigue syndrome, if we actually get down to the mitochondria, is it the same thing happening or is it different? What's happening with the mitochondria and not being able to create energy?

Ari Whitten: Yeah, it's a good question. The principles are the same. However, there's probably a thousand different variations on this. For your listeners who haven't read the book, let me give a brief explanation of what we're really talking about here. It's long been taught that the mitochondria are our cellular energy generators. In biology, of course, they're taught about as the powerhouse of the cell. But they're really framed whether we're talking high school biology, or college, university level biology, or medical school biology courses, they're really talked about as, "Oh, they're just one of many organelles in the cell and over here's the endoplasmic reticulum, and here's some lysosomes, and here's the Golgi apparatus, and here's the mitochondria. Remember, the mitochondria is the powerhouse of the cell." They're taught about as, first of all, just one of many. And in fact, they're much more important than that. They're critically important for our physiology and they deserve a central role in the way we teach physiology, which isn't the way that physiology is taught. And that's number one. 

And then second, they're talking about is these mindless energy generators that take in carbs and fats and just pump out energy in the form of ATP, adenosine triphosphate. And of course, they are energy generators, but what has not been taught in physiology and has not really been known-- We know we've known about mitochondria for over a hundred years. But what has only really been uncovered in the last decade or so is that mitochondria actually have a second role that is just as important as their role as energy generators. And that is as cell defenders. It turns out our mitochondria are like the canaries in the coal mine of our body. They're these exquisitely sensitive environmental sensors that are constantly trying to assess, if the body is under attack. They're asking the question, "Is it safe for us to produce energy?" They're taking samples of the environment constantly and going, "Is it safe to produce energy? Are we under attack?" And if not, we'll produce lots of energy. If we are under attack, if we start to get signals that we are under attack," and they can sense by the way, virtually, every type of stressor or threat that you can think of. If they start to pick up on those signals that the body is under threat or under attack, then they shift resources out of energy production towards cellular defense. And this process is fundamentally, the most important thing to understand about human energy levels and human energy regulation. 

When I first started going down this path of really focusing my life around the science of human energy production a decade ago, I didn't know where to start, because nobody had put together a coherent synthesis scientific framework of this topic before. I started exploring different avenues, what's the relationship of sleep and circadian rhythm to energy? Obviously, we know that if you don't sleep well, you're tired the next day. What's going on there? What are the mechanisms? If you don't eat well, that ties into low energy levels? Of course. If you don't exercise, that ties into it. If you're very overweight, maybe that makes you fatigued. What are the mechanisms? I spent years just diving into each one of these topics, diving into the research, figuring out what are the physiological mechanisms. And at the end of all of those years, basically, I was left with a long list of 150 plus different physiological mechanisms that in one way or another tie into the energy story, everything from oh, AMPK, and mTOR, and glucagon, and insulin, and blood sugar regulation, and what about testosterone, and the sex hormones, and thyroid hormone, and growth hormone, and cortisol, and melatonin, and neurotransmitters, GABA, and dopamine, and serotonin, and all these different physiological pathways. 

The analogy is this. If you look at a car and you start peeling back the layers of the car, opening it up, it would be wrong to say, "Oh, here's the sparkplug in the engine." This is the critical piece that makes this car go. It would be wrong to open up the exhaust and look at the catalytic converter and be like, "Oh, this is the part that makes the car go." And then to look at the piston and the engine, you'd be like, "No, this is the part or the engine block. No, this is the part that makes the car go." Yet, all of those pieces are important and in one way or another are indirectly involved in that car going down the street. But none of them are the thing that is actually regulating, the most upstream thing that is regulating whether or not that engine is running, how much gas is being pumped into it, and whether or not it's driving down the road slow or fast. The thing that's doing that is the person sitting inside the car and the mitochondria are that. 

It wasn't until I discovered Robert Naviaux work, who runs a lab for Mitochondrial Medicine at the University of California, San Diego. And his paper, The Cell Danger Response, where he put together a really novel scientific framework that was a breakthrough in our understanding of mitochondria around this second aspect of mitochondrial function. Again, they have these two roles, energy generators and cell defenders. And they are two sides of the same coin. To the extent that they're doing one, they're turning down the dial on the other. Another way of saying that is, to the extent, your mitochondria are picking up on threat or danger signals in the body, they're turning down the dial on energy production. And that is fundamentally the most upstream thing, the most important regulatory mechanism of what really controls human energy levels.

Melanie Avalon: Some follow-up questions. One, how many mitochondria are in each cell?

Ari Whitten: It varies wildly. On average, it's 500 to 2,000. But there's some cells in certain parts of the brain, in the heart, in the eye, in places like that that can have tens of thousands per cell. 

Melanie Avalon: Oh, wow. And do these mitochondria, if they have this dual role and they're reacting to threats and stressors, how synchronous is that reaction in mitochondria all throughout the body and how encompassing does that thread have to be to cause feelings of fatigue? And so, for example, what I mean is, if these mitochondria are in all the cells of our body, is there's one threat to mitochondria in one part of our body and that's all we need? Does it communicate to other mitochondria throughout the body? And in one cell, if it gets "attacked or if it senses an issue," do all the mitochondria react the same way? Do they talk to each other?

Ari Whitten: That's an excellent question and I've never been asked that as well as you just asked it, but very smart question. Imagine, let's say, a respiratory infection as just one example, where you have stuff going on, you have this virus that's infecting your sinus and nasal mucosa in the back of your throat, maybe in your lungs, and it's causing damage and inflammation in those tissues, okay? But that respiratory virus isn't affecting your muscles, your skeletal muscles, your back muscles, and biceps, and triceps, and legs. Yet, it can cause fatigue systemically to have a respiratory infection. One of one of the key symptoms of having a cold, or flu, or COVID is, of course, fatigue. And this is also true with many other kinds of things. Even a physical injury can cause something called sickness behavior. And this term, sickness behavior is actually a medical term. There's lots of studies written on it, where they've examined it in humans, and animal models, and things like that. And it involves fatigue, and lethargy, and lack of motivation, and depression, and feeling crappy when you're sick. [laughs] You don't have a lot of energy, you don't feel you're in a good mood, you don't feel driven to get up and do lots of work. You just want to lay in bed. It's that feeling. It's actually called sickness behavior. 

Even something like a physical injury, if you broke an arm, had a bad sprain, or cut open your ankle, or something like that, that can cause enough inflammation in the body to create this sickness behavior. To be fair, sickness behaviors also mediated a bit neurologically, not just at the mitochondrial level. But these are just a couple of many types of examples that are localized in one area. But to answer your question more directly, first of all, we have things that float around in the blood and those things go systemic. They can be many different kinds of things. Maybe I should first ask, "Well, what kinds of things can the mitochondria actually sense? How are they sensing that there's a threat, or stress, or damage taking place in the body?" It all boils down to a few things. They can sense three or four fundamental things. One is inflammatory cytokines. Elevated levels of inflammatory cytokines from any cause will cause some degree of shutdown at the mitochondrial level. It is elevations in inflammation in the body is considered a systemic danger signal. And those inflammatory cytokines do go systemic, even if the injury is localized like it's a respiratory infection or a physical injury one in your leg or something like that. You get systemic elevations in the blood of inflammatory cytokines. 

Now, in addition to that, it can also send oxidative stress. Elevations in oxidative stress can cause this. And cellular damage itself will cause certain signaling molecules to be released that goes systemic, specifically something called purinergic signaling. And these purinergic molecules are ATP and ADP, so, the energy molecules themselves are actually produced by mitochondria. They're supposed to be localized within the cell. You're not supposed to have a whole bunch of ATP or ADP floating around in your bloodstream. Yet, it's also true of DNA, by the way. Mitochondria have their own DNA called mitochondrial DNA and that's also supposed to be localized in the cell. Well, it's been shown that when you have cellular damage that occurs, you get a leakage of ATP, ADP, and mitochondrial DNA leaking outside of the cell and getting into the bloodstream. This has even been shown in a field called Mitochondrial Psychobiology, where they subject people to psychological stress and they show elevations in mitochondrial DNA and bloodstream within a matter of minutes as a result of psychological stress. So, those signaling molecules, it turns out other cells have receptors for these purinergic molecules. 

When they sense the presence of these purinergic molecules, where they're not supposed to be in the blood floating around the body, they interpret that as a dangerous signal. That's how they know throughout the rest of the body, "Okay, there's damage being done in the body. There's a threat present. There's something here that's causing tissue damage and destruction. We're under attack." And so, there is a systemic communication of that signaling and a systemic response to it.

Melanie Avalon: So, to clarify, there can be a stressor and then the mitochondria on purpose leak their DNA to tell the other mitochondria or is it just a happenstance?

Ari Whitten: I don't know, it's quite the right wording to say that they on purpose leak their DNA and these purinergic molecules. But it is a byproduct of cellular damage, and the body has been wired, presumably by millions of years of evolution or God, if you prefer that that to respond to those signaling molecules that circulate in response to cellular damage. 

Melanie Avalon: Okay, gotcha. 

Ari Whitten: As an example, just to clarify the distinction and language, if you slice open your leg from a cut, let's say, an animal attacks you and it's cuts you open, it's the mitochondria don't go, "Oh, let's release these purinergic molecules." They are physically damaged and ruptured and releasing them as a function of the damage, not their decision to release them.

Melanie Avalon: Okay, gotcha. And I'm really curious on the spectrum of how this could be happening. Because you just mentioned, for example, that psychological stress can cause this. Then on the flip side, we could have actual injuries causing this. Presumably, you could have two extremes. You could have a person who actually isn't experiencing any threats like real threats, but it's all psychological. But they're having this. Well, on one end, you could have that, and you could have them reacting very extremely with mitochondria with the stress response. On the other hand, you could have somebody who's experiencing so many stressors and I'm guessing their mitochondria would, I'm just trying and make two extremes, not be instigating that response. Is that possible? People who seemingly get hit with all of the stressors and they're just fine, is that because their mitochondria are not reacting in a defense mode?

Ari Whitten: Yeah, that is a wonderful question, and I really like your questions. The answer to it is not a short one, unfortunately. But it does get into my favorite topic and I'm happy to go down this path.

Melanie Avalon: I love favorite topics.

Ari Whitten: [laughs] You asked me earlier how many mitochondria we have per cell? And I'll circle back to that question for a moment. I gave you a simple answer to that question. Here's a more complex answer. We have that many mitochondria per cell, roughly, on average, 500 to 2,000, excuse me, per cell. However, it is also important to understand that those mitochondria are dynamic and respond to their environment. And just as think of somebody who's super skinny and anorexic versus a professional bodybuilder. Do they have a difference in the amount of muscle fibers on their skeletal muscles? Yes, they have a huge difference in response to the stimuli that they've exposed their bodies to and ask their body to adapt to. The same is true with mitochondria. 

Mitochondria are not just environmental sensors, because they're also these energy generators, they are tasked very directly in responding to stress and threats. Take exercise, for example. This is an easy one to think about. If you're asking your body to respond to exercise, the mitochondria have to ramp up their energy utilization, mainly of carbs and fats, and energy production in order to meet the demand that is being placed on them to do the physical work to generate that energy, so you can perform that activity. Again, they're being tasked very directly in responding to stressors, okay? So, keep that in mind. 

Now, what happens if you exceed their capacity? Well, this is something I call the resilience threshold. It's basically how much stress can your mitochondria handle? What is their capacity for handling stress and for generating energy to meet the demands that's being placed on that? That's your resilience threshold and it directly ties into the physical size and amount of mitochondria you have in your cells. Now, getting back to this question of, how many mitochondria we have in our cells? I said 500 to 2,000. However, that differs dramatically between individuals. It is possible to have more like 500 and it's possible to have more like 2,000. And to be more specific, it's been shown that on average, people lose about 10% of their mitochondrial capacity within each decade of life. That might not sound like that much, but to state it more directly, it's been shown that in the typical seven-year-old, they only have about 25% of the mitochondrial capacity they had when they were young. In other words, they have lost 75% of their mitochondrial energy production capacity as they've aged. 

To be more specific, what's happening there? It's been shown that they lose about 50% of the mitochondria themselves. The actual number of mitochondria that are present declines by about 50% and the energy production capacity of those individual mitochondria that are left is cut in half by about 50%. So, you do the math on that, you've reduced your energy generation capacity at the cellular level by 75%. This is going from a Ferrari engine to a two-stroke moped engine in your cells. And how does that tie into your question? Well, it very directly means that the person with the very small engine in their cells has a way, way lower capacity to handle demands, stress, energetic demands, metabolic demands that are being placed on that system, then the person with a Ferrari engine in their cells. 

Now, the other aspect of this, people might be thinking, "Wow, that really is crappy news that we lose so much of our mitochondrial capacity as we age." Well, the good news is this. You actually don't have to. It's been shown that in seven-year-olds, who are lifelong athletes and exercisers, they have the same mitochondrial capacity as a young adult. They don't lose 75% of their mitochondrial capacity. What that tells us is that this loss of mitochondria is not a natural byproduct of the aging process itself, but is a result of modern lifestyles, specifically, lack of hormetic stress that drives this loss of mitochondria. In very much the same way that if you've ever broken a bone, an arm or a leg, you get a cast on, and then cast stone off your leg eight weeks later, and you look down at your legs, and you see that one leg is half the size of the other one. Why is that? It's because the body is ruthless about getting rid of energetically costly tissue that isn't needed for survival. So, as soon as you get that cast on within literally days, within weeks, the body is immediately going, "Well, I guess, we don't need that energetically costly tissue anymore to survive the demands that are being placed on us. Let's get rid of it. It's only a hindrance to our survival. Let's drop it." 

And the body does the same exact thing with mitochondria. If you're not stimulating them and challenging them, they atrophy. They shrink, they shrivel, they become weak. And if you can picture what I just described happening with your muscles in just a matter of eight weeks, imagine what happens to your mitochondria over 50 years of not challenging them adequately.

Melanie Avalon: Wow. Okay. I have some questions about that. But before that, one other question about the mitochondria. Is there a genetic or an inherited component to how well they're set up to function? And since we inherit them from our mother, are our vitality levels probably more reflective of our mother than our father?

Ari Whitten: That's a really good question and I actually don't know the answer to it. I don't know, if anybody does. There might be somebody who's a mitochondrial researcher, who's really looked at the mitochondrial DNA piece. What you said is true. We get that mitochondrial DNA from our mothers, specifically, not our fathers. I would venture to guess that there is almost certainly something to what you're saying. How could there not be? But I don't know of any specific research that's really examined that where I could tell you anything, any specifics about what we know about that topic. But it's a great question.

Melanie Avalon: The studies like the inherited stress factors and they say that stress travels through generations, a certain amount of generations, do you know if that's related to the mitochondria or is that something else in the epigenome?

Ari Whitten: I know that there's a neurological component to it in terms of how the brain gets wired. Certainly, it's related to the epigenome, but mitochondria also tie very directly into epigenetics as well. I don't know that I've ever encountered something specifically on mitochondria as it relates to that. But yeah. Another great question that I would say, I don't know, if anybody knows the answer too and I certainly don't.

Melanie Avalon: I'll keep it on my list to be looking for it. Speaking about these hormetic stressors and these things which challenge our mitochondria, you mentioned exercise. You talk all throughout the book about these different supplements and compounds. I'm assuming red light therapy. Is there one that is stronger like the crème de la crème of stimulating mitochondria biogenesis? Is it exercise or is it all the things?

Ari Whitten: Yeah. Exercise certainly is a big one. However, in people with severe chronic fatigue, exercise tends to be a bad place to start, because it's so energetically demanding compared to other types of hormetic stress. To give a breakdown of some of these types of hormetic stress that stimulate mitochondria, that challenge them and stimulate them to adapt very much like lifting a heavy weight, that's challenging for your muscles. Stim creates this challenge, this stress that stimulates your body to respond to it by saying, "Hey, we need to adapt to the demands that are being placed on us by growing stronger in this area to handle this." The mitochondria do the same thing. And there are different types of hormetic stress that do that at the mitochondrial level, and they all have their own unique fingerprint of specific adaptations that they stimulate. 

Some are more energetically demanding than others, but some of them are exercise, first of all, and there's different subtypes of exercise. Resistance training, steady state endurance training or cardio, high intensity interval training, and sprint interval training. There's hypoxic practices, breath hold practices, or altitude, things like that. There is heat and cold thermal stress. So, things like ice baths and saunas. There's light hormetic stress from ultraviolet light from red and near infrared light. There's also fasting and there's certain kinds of chemicals that provide hormetic stress things like methylene blue, for example. And there's also phytochemicals that are in a category called xenohormetic stressors or xenohormetons and they stimulate a lot of the same pathways involved here. 

Now, if you think about how energetically demanding it is to consume a phytochemical versus doing a 30-minute workout, the phytochemicals a lot gentler. Now, I'm not saying they have equivalent effects. But I am saying that starting with gentler hormetic stressors that don't create such a huge energetic demand is a better place to go for people who are chronically ill or chronically fatigued. I find sauna and breath holding practices to be the most powerful place to start for people with chronic fatigue. 

Now, another aspect to consider here is that, they do have somewhat unique effects. They may not all stimulate and they almost certainly, I should say more strongly. They do not all stimulate the same degree of mitochondrial growth and biogenesis as one another. There's, for sure, differences in that. There's even differences among different types of exercise. I would say, this is the only research that's possible to speak of to answer that question, where they've actually tested different types of hormetic stressors in terms of the degree of mitochondrial biogenesis stimulation. Mitochondrial biogenesis, for people listening is the creation of new mitochondria from scratch. Actually, growing more mitochondria, rebuilding from let's say, 500 mitochondria per cell to a thousand. It's possible to do through mitochondrial biogenesis by using hormetic stress. 

Now, in this paper which was done, I believe it was a thesis paper done by a PhD student somewhere in Europe. I think in a Scandinavian country. I think the guy's name was Nicolas Psilander. I think it was P-S-I-lander. They looked at a number of studies, they performed a number of studies, where they tested different types of exercise in different groups of people. There was a mix of, I think, five studies or six studies. But they looked at steady state endurance training versus weight training versus high intensity interval training and sprint interval training. And they also looked at some of these different types of exercise in either untrained or trained individuals, so, either taking people who are not exercisers or taking people who are regular exercisers of various types. That also will influence the result. And they also did some modification of the state that one was in. Are you in a fed state or fasted state doing these exercises? 

There were a number of findings. One of which was, for example, they found that doing sprint interval training in a fasted state was more effective than a fed state in stimulating mitochondrial biogenesis. They found that in people who are untrained doing really any type of exercise will stimulate plenty of mitochondrial biogenesis. But the more trained you become, the more you need to-- This is a bit of my own extrapolation. But the more you need to do something different compared to something novel stimulus on your body, novel challenge compared to what your body's used to. And I would say the other key finding from this research was that, in trained people, in people who were already trained, I believe they tested endurance athletes and maybe also weight training, people who were doing resistance exercise, they found that sprint interval training was highly effective in inducing mitochondrial biogenesis more so than doing steady state interval, or steady state cardio, or resistance exercise was in those already trained people. So, that's a very brief overview off the top of my head from a paper that I haven't looked at in a couple years.

Melanie Avalon: No, it's super helpful. I'm just thinking about how so many of the daily habits I do are unified by this mitochondria concept. I do a cryotherapy session, typically every day, infrared sauna, red light. I do fasting every day. The exercise piece is the piece I don't have a concentrated exercise routine, but I feel I should probably be integrating interval training into it. Another question about this. What role does perception play? For example, even with exercise or I guess, stepping back actually a little bit before that. Do the mitochondria just react and do all of this on a cellular level or is there also a neurological perception piece to every single hormetic stress? If you're exercising and you think you're doing it better or you embrace it, does that have a better effect than if you don't? And with psychological stressors, if you see them as building resilience versus not, what role does the conscious mind play in all of this?

Ari Whitten: Yeah, I have to say, you ask some of the best questions that I've ever had from an interviewer. So, bravo on that. This is another really excellent question. And yes, there is an effect there. I don't know that any study has quantified it exactly at the mitochondrial level. I'm going to step back for a second. I mentioned the study before about how psychological stress was shown to induce leakage of mitochondrial DNA into the bloodstream. And this is from a field of research called mitochondrial psychobiology, looking at the link between the mind and mitochondria. 

This particular study, it's a funny design. They basically asked people to get on stage and do public speaking. And people have a tremendous fear of public speaking. Most people fear it more than they fear death. And in addition to having them get on stage and do public speaking, they had hecklers in the crowd, basically, shouting profanities or personal insults, and attacks, and booze. It was all simulated, but they subjected people to this state of psychological stress, and they showed leakage of mitochondrial DNA within a matter of minutes. But you can also imagine that if somebody wasn't particularly stressed by that, let's say, they thought it was fun or let's say, they were used to public speaking, though or they're a standup comedian and it's no big deal for them, they've done it thousands of times, it doesn't even change their heart rate to get up on stage in front of people. You can imagine that their physiological response is going to be considerably different. And if they don't have this intense surge of all these stress hormones and this intense stress reaction, they probably wouldn't have a leakage of mitochondrial DNA in the bloodstream. 

Extrapolating from that kind of thinking, we can certainly deduce that one's perceptions greatly changed this. Now, on a day-to-day level, it's also the case that just in our daily lives, certain things which might be stressful to one person might not stress another person or the same event from day-to-day might stress you or not stress you. And so, perception matters, of course, in a big way, whether you're getting into a stress response or not has very real physiological effects. And we even know that from this field of mitochondrial psychobiology. The mind ties into the mitochondria within a matter of seconds. So, yes, is the answer, certainly. 

Now, the other layer to this is that the attitude that you're bringing into hormetic stress is, it's a golden opportunity to do something very profound at the physiological level and at the level of what's going on in your mind. Because what you're doing is, you're self-imposing stress in this particular case. You are choosing voluntarily to subject yourself to a physiological stressor as compared with just you're going about your daily life and somebody cuts you off, or your boss is giving you crap, or just the happenstance of life. In this case, we are deliberately, intentionally, voluntarily subjecting ourselves to this type of physiological stressor in a controlled and systematic way. 

Let's use the tub as an example of this. What happens if you go in that ice bath and you are going in and you're going, "I hate this. Oh, my gosh, it's so cold. It's so uncomfortable. Oh, my God, oh, why am I doing this?" Versus if you're breathing, if you center your mind, if you calm yourself down, you get in the tub [sighs] put yourself into a peaceful place. Are those two things different physiologically? Yeah, absolutely. What you're doing when you're doing that is actually creating-- You're deliberately exposing yourself to physiological stress, while also controlling your mind state. What you can essentially do as a result of this is, you can self-inoculate yourself against stress and you can train yourself to be calm and resilient in the state of physiological stress, so that you're disconnecting the hormonal stress response from certain reactions that you have to it. 

In other words, we all are responding reflexively to discomfort, to pain, to stress in this way, this type of metabolic stress, whether it's exercising and feeling this intense burning your muscles and being fatigued, or whether it's the intense heat and discomfort of the sauna, or whether it's the pain and discomfort of an ice tub, you get a strong response of stress hormones, adrenaline, norepinephrine, cortisol, things like that. And then in response to that, that creates certain psychological effects, where we have reactions to get ourselves out of that situation, our heart rate speeds up, we're annoyed, we're angry, we're unhappy, we're uncomfortable, we want to move away from this painful stimulus. And what you're doing is you're calming all of that energy down and training yourself to be able to physiologically experience the hormonal state of stress, that stress physiology and disconnect it from that reflexive mind response. You're again self-inoculating yourself against stress, you're training yourself to be resilient under stress.

Melanie Avalon: I'm glad you talked about just how fast that DNA leakage can occur. I'm super curious, all of these effects on the mitochondria. What is the lifespan of mitochondria and how fast does it turn over? And when we're doing these things, how fast can we make new mitochondria? And you talked about in the book, when we go to sleep, we have mitophagy and we make new mitochondria. Do we replace all of our mitochondria? You know how they say that every seven years, you're an entire new body. How long would it take for you to have entire new mitochondria?

Ari Whitten: [laughs] I had another question. I don't know if anybody knows the answer to. I think that mitochondria, very much like cells. Well, actually, let me step back. This is a better place to start in answering your question. The idea that our body replaces itself every seven years and we have all new cells every seven years is actually a myth. It's not true. 

Melanie Avalon: I thought you're going to say that, [laughs] myth buster.

Ari Whitten: [laughs] The truth is, we have cells that replace themselves every few days and we have other cells that I believe are thought to live a lifetime in the brain that I think stick around for decades. The answer to this particular question-- I'm going a bit off the top of my head about things that I've heard and read over the years. So, none of this is top of mind as far as looking at actual research on this. But my general understanding of physiology is that some cells replace themselves every few days. For example, gut cells in the inner lining of the gut. Other cells like neurons in the brain can last decades, can live decades, if not our whole life. And then there's many other types of cells that are somewhere in between that. 

Yeah, it's a myth that our bodies replace itself every seven years. Mitochondria probably have something similar going on. There's probably mitochondria that are much more dynamic than others depending on the specific cells and tissues that they're in. They've got a lot more going on in terms of--. And it's not so much replacing themselves. It's more like what's called fission and fusion. And Mitophagy and mitochondrial biogenesis, all of these are dynamic processes that are constantly reshaping our mitochondria and our cells. 

We have processes that are involved in stimulating mitochondrial growth, we have processes that are involved in stimulating mitochondria to divide and then create more mitochondria, we have processes that separate mitochondria to combine and form bigger mitochondria, fusion, and we have processes that are clean up processes like mitophagy that are quality control processes to identify chunks of mitochondria or entire mitochondria that are dysfunctional, that are unhealthy, and then to either break off that chunk, where let's say, the membrane of that particular mitochondria on the left side of it has become damaged and depolarized. And so, break off that chunk, and do this fission, and then basically send the dysfunctional part over to a lysosome for degradation and break down. So, we're cleaning up that mitochondria only leaving the healthy part there and getting rid of the unhealthy dysfunctional part. 

It's not quite as simple of a question as saying like, "How often are mitochondria replacing themselves or creating new ones?" There's a constant daily dynamism as far as all of these growth, and fusion, and fission in mitophagy processes. So, I think that question is probably impossible to answer, but it's better to think of it in terms of, it's always shifting and dynamic.

Melanie Avalon: Fueling all of these processes, so, creating these new mitochondria, and doing all those cleanup processes, and all of that, your book is called Eat for Energy. So, what is the role in nutrition for fueling all of this?

Ari Whitten: Oh, that's a big topic. I just wrote 300 plus pages on that.

Melanie Avalon: I know. [giggles] I know. Listeners, get the book. It's all in there. 

Ari Whitten: The way I break it down in the book-- I'll give an overview here and we can dive into specific aspects of this. In terms of how nutrition ties into the story of mitochondrial function, there's multiple different mechanisms of how nutrition relates to mitochondrial health, mitochondrial growth, mitochondrial function, or mitochondrial harm, and mitochondrial shutdown. In the book, I break it down in terms of, Chapter 1 is explaining all these things I talked about here about how mitochondria work and how they energy production and cellular defense are two sides of the same coin to the extent they're doing one, they're not doing the other. 

From there, Chapter 2 is on circadian rhythm. Our circadian rhythms, we've got a central clock in the brain, that's primarily responsive to light inputs. And we've got peripheral clocks. This is a newer scientific discovery. We've got peripheral clocks throughout the tissues of our body that are primarily responsive to food inputs. And the circadian rhythm, then impacts upon mitochondrial function in many different ways, which we can talk about if you want to dive into that one. And then the next chapter is all about body composition. So, how having too little muscle, especially excess body fat ties into mitochondrial function. The next one is all about blood glucose control. So, how hypoglycemia and hyperglycemia, high blood sugar causes mitochondrial dysfunction and shut down. The next chapter is all about gut health, the next one is all about brain health, and there are multiple mechanisms going on at those levels as well how those tie into mitochondrial function. And then the final two chapters of the book are on energy super foods and supplements that enhance mitochondrial function.

Melanie Avalon: I think in the interest of time, what I might do is, there's just so much content and there's so much information. And listeners, just have got to get the book. Would you be okay, if I just ask you some just random questions I have from all of this? This is just things I'm just dying to ask you. Well, this is a big question, which probably doesn't have a simple answer and I know that you have opinions about this. There's so much debate about low carb diets, ketogenic diets, low fat, high carb diets. So, if you're in a ketogenic state or not, what are your thoughts on that and its role with the mitochondria and glucose burning versus not?

Ari Whitten: Yeah, I guess, my way of answering that question is-- Well, let me say this. I think that there's been a lot made of this topic that isn't grounded in good scientific evidence. There's been really this whole kind of ideology, and philosophy, and almost dietary religion, and cult that's been made out of some of these ideas and theories about the differences and how our cells or mitochondria process carbs versus fats and ketones. My biggest gripe with it is that most of the claims, the original claims that the low carb and keto camps were founded upon have turned out to be not true. There's a lot of aspects to this. I'll give you a couple examples. One is the idea that all of our hunter-gatherer ancestors, human ancestors ate low carb diets or ketogenic diets, and that fats or ketones are our body's preferred fuel source. These things are just plain wrong. We can look at lots of analysis of ancestral human diets. There's been studies by, for example, Stefan Lindberg, who wrote a textbook around the world decades ago to go see many of these hunter-gatherer tribes that still exist in the world today. None of them eat ketogenic diets. Many of them eat diets that are 50%, 60%, 70%, even 90% carbohydrate. So, that aspect of it is false. 

The other aspect that these things are our preferred fuel source is also false. When the body has carbohydrates, it preferentially burns carbohydrates and virtually all tissues of the body. And so, it's just simply a distortion to claim that the body is preferring fats or ketones. It clearly isn't, if it has carbohydrates available, it uses them preferentially over fats and ketones. Even the Inuit are not on a ketogenic diet. They live in a place where almost no plant foods grow. Number one, they go to great lengths to obtain the few plant foods like berries that are available to them. When they eat fresh meat, they actually get enough carbohydrates in the form of glycogen, in the form of the fresh meat that's stored in that muscle tissue to keep them out of ketogenesis. 

And then, let's do two other layers to this. One is the idea that it was promoted for many years that, if you were running on fats for fuel that you'd have just amazing energy levels, and you have amazing endurance and your sports performance would be vastly superior and those things have been tested. We've tested people on low carb and ketogenic diets versus higher carb diets in various kinds of athletic performance. The claims have not held up at all. in fact, best case scenario, in steady state endurance racing, let's say, running a marathon, people who are running on fat can perform as well as people who are running on carbohydrates. But the higher the performance, the higher the intensity, the activity, the more that having carbohydrates in your diet provides an athletic performance advantage. 

And then certain specific studies like Phinney and Volek are researchers that were instrumental in popularizing low carb ketogenic diets. And there's some distortion in what they did. I don't remember the exact name of the study, but it was a specific study, I think that they did in cyclists, where they put people on this low carb ketogenic diet and they showed on average, it improved performance in the low carb ketogenic group relative to the higher carb group. But when you actually dug into the specifics of the data, what you found was that-- I forget the number of participants. They had maybe 16, or 20, or something like that participants. Almost all of the participants with the exception of one or two in the low carb ketogenic group had declines in their performance. 

And then one or two specific individuals had these massive improvements in their performance that were unlike the other 90% of individuals. And when you average out the numbers, the magnitude of the effect for that one person who had this enormous improvement was enough to pull the average of the entire group slightly ahead of the carbohydrate group. And so, you could make a claim based on that statistics that, "Oh, the low carb group performed better." But in fact, 19 of the 20 people in the low carb group performed worse. You can do these kinds of misleading statistical calculations to make whatever claim you want to make. There's a lot of stuff like that that's gone on.

And then the last thing I'll say is, probably the biggest thing is, the bulk of it was founded around the carbohydrate hypothesis of obesity, which is basically the idea that insulin is a fat storing hormone and insulin is the thing that's regulating body fatness and carbs cause you to produce more insulin. Therefore, carbs cause you to gain fat. And if you just lower your carbs, then you lower your insulin, and therefore, you lose fat. This is logical enough and I actually adhered and promoted that diet for many years until it was tested, until I discovered research back in 2013, thanks to the work of obesity researcher, Stephan Guyenet, who was writing about that topic back then. And he educated me [laughs] on the actual research that tested that and which showed that I was wrong. And that body of evidence has continued to accumulate over the last decade continuing to show the same thing. 

And basically, what it shows is that, well, insulin is one of many things that are required for fat gain. It is not the thing that regulates body fatness. In very much the same way as the analogy I gave before the sparkplug, or the piston, or the catalytic converter is not the thing that regulates whether the car goes down the street, but it is one part of the overall car that allows it to function. And basically, what this body of research shows, and it's most directly tested in what's called metabolic ward studies, where they give people the same amount of calories in each group, but different macronutrient ratio. So, you give people, let's say, 70% carbohydrate diet, that's 5% fat versus a 70% fat diet. That's 5% carbohydrate, but they both have the exact same number of calories. You can show that there are dramatic differences in the amount of insulin being produced. But if you measure them several weeks later, you showed no discernible difference in body fat whatsoever. They have the exact same levels of body fat.

You can do the experiments in reverse too in overfeeding studies. Feed people a high carb versus a low carb high fat diet. Overfeeding them, asking them to gain fat, does that the group eating carbs gain more fat? No, they gain the same amount. These studies have been done ad nauseam. They've even been done by Gary Taubes' institute, which collected many, many millions of dollars to fund research with the intention to prove his carbohydrate hypothesis of obesity. What they actually found in studies by Kevin Hall funded by NuSI was that it disproved the hypothesis. So, anyway, I could go on. There's also other aspects of that fat gain and fat loss discussion. 

But the short version of it is that pretty much all of the central claims about the superiority of low carb and ketogenic diets in terms of fat loss, and athletic performance, and it being our ancestral fuel, and all these kinds of things are just simply wrong and there's lots of evidence showing that they're wrong. None of that means that low carb or ketogenic diets are bad. I'm not saying they're bad or that you should avoid them. In fact, I think that it's a smart idea to at least cyclically go into low carb diets, just like I think it's if you're on a low carb ketogenic diet. I think it's cyclically a good idea to go off of it. But it's one way of doing things that has certain advantages for certain demographics, maybe obese diabetics in particular, but many of the central claims are not our distortions that are refuted by the scientific evidence.

Melanie Avalon: Yeah, it's definitely an ongoing age old it seems to be at this point. I think my perspective on it now, because I as well was very steeped in the low carb keto world for a bit and now, I have a slightly different perspective and I actually eat a really high carb diet. But it seems I agree that when it's in a controlled, like, calorie controlled metabolic ward type study that they seem to be the same with their effects. I just wonder, if the real-world applications, if some people just respond better to one versus the other. And even in that study, you talked about-- The data was misleading, because they average together the numbers. So, even in that study, the two people who did really great on the low carb, so, are they just more suited in their life to follow that type of lifestyle?

Ari Whitten: Yeah. Well, in that particular study, the most likely explanation was that it was an anomaly. Maybe the first time the guy tested, he was sick, or something like that, or had a horrible day, or had terrible sleep deprivation the night before. And so, had horrible performance and then the next time he tested, he performed much better. He was in a better place or whatever. There's also something called, I forget that term. But it's basically like test, retest improvements. Once you already have some familiarity with the test, the second time you do it, you perform a lot better. And there also can be individual variation in that kind pf thing. 

But to your point, yeah, it's almost certainly the case that certain individuals do respond better to one way of doing things over another, whether it's exercise or whether it's diet. So, yeah, I would say, there's certainly truth in what you're saying, and it is very likely that certain individuals would find a particular way of doing things. I've had some clients over the years who have done a vegan diet with enormous success, despite the fact that I've advised them not to do a purely vegan diet. But they're doing awesome on it. I've had other people that have gone low carb keto and are doing amazing. And they find that when they eat a vegan diet or a high carb diet, they don't do nearly as well. They feel tired, or they have trouble with their blood sugar regulation, or they have trouble managing their appetite, they're much more prone to overeating. So, for sure, those individual variations exist. 

Melanie Avalon: I don't want to miss attribute something to Kevin Hall. There was one review that was really expansive and looking at all of these low carb versus low fat studies and the conclusion was that they're basically identical. But then, if you look at the actual breakdown at the data, it seemed it was really heterogeneous. There was an average situation.

Ari Whitten: I'm glad you brought this up, because I meant to mention it earlier. But there have been said several meta-analyses of different dietary approaches, low carb versus low fat diets, as well as even named diets like Atkins versus Ornish versus the Zone versus South Beach, and things like that. And those generally conclude that the differences between those weight loss outcomes are very minor, despite very big differences in macronutrient ratios between the diets, emphasizing my point that the hype around carbs and fats of the diets has largely been way over exaggerated in terms of its importance. 

But the one that I think you're referring to is a 2018 study called DIETFITS, I believe. And it was a really groundbreaking study, because it's by far the best study on the low carb, high fat stuff that's ever been done for a number of reasons. It involved a huge number of participants for an unprecedent length of time in a randomized controlled study. So, normally, those kinds of studies, because they're so expensive to do, they last maybe 3 weeks, 6 weeks, 8 weeks, 12 weeks, 16 weeks. This one was a yearlong, and it was also remarkable, and the number of participants, I think over 6,000 participants that they had in the study, and it was also remarkable in the sense that they actually gave good dietary advice, [chuckles] which unlike a lot of the studies, which just prescribe crappy diets, or just prescribe macronutrient ratios without much focus on dietary quality, or they don't match for protein, which is another huge confounding variable, which is the main reason why certain studies show low carb diets are superior, it's because they're higher in protein and they didn't control for that variable. 

But this study gave good dietary advice in the sense that they advised people to eat whole unprocessed foods for the most part, whether they were in the low carb or low-fat group. And I think they maybe also came close to matching for protein intake as well. And so, at the end of 12 months, basically, they showed that there was no significant difference between weight loss outcomes on low carb versus low fat diets, which is very consistent with the overall body of evidence. However, to your point, I think there was significant heterogeneity in terms of the individuals, and some did indeed lose more weight on either the low carb or low-fat diets.

Melanie Avalon: It might be a bit of individuality, but there's definitely a lot of myth busting that needs to happen. So, I'm glad we're having this conversation. Okay, just some random rapid-fire questions. Listeners, like I mentioned and Eat for Energy, in every chapter, there's all of these compounds, and nutrients, and supplements that can affect all of these different factors. And I'm curious, because you do talk about a lot of individual nutrients. Do you have thoughts on nutrients from Whole Foods form versus supplements versus IVs or injections, for example? I go to a place called Restore, where they have a lot of intramuscular injections that I like to get. Do you know if those are more beneficial for getting things? They'll have like CoQ10 and carnitine, and things like that.

Ari Whitten: To be honest, I wouldn't mess with it. 

Melanie Avalon: Really? 

Ari Whitten: Yeah. And if you try to look at the research, you'll find that there's almost no research on it. And for me, as a general principle, and I know there's maybe going to be some naturopaths and other doctors who do that kind of work that might object to what I'm going to say and they're really fans of that. So, that's fine. But as of right now, the body of evidence on it is really, extremely unimpressive. There's really no compelling research on it. And as a general principle, if you're going to break the surface of my skin barrier, there better be a compelling reason for doing that. 

Melanie Avalon: This is IVs and injections? 

Ari Whitten: Yes, I would say in general. Now, maybe an exception is B12. And the distinction here is bioavailability. If something has poor bioavailability orally, there is good reason to inject it. And however, if you don't have that problem with oral bioavailability, I would argue, you should not play around with directly injecting it. Because now, you're introducing it into the body in an unnatural way. The way it's designed to enter is orally. Whether we're talking carnitine, for example, or lipoic acid, or something like that. So, yeah, I don't think, until there's compelling data showing that injected or IV glutathione and CoQ10, and other B vitamins, and things like that with the exception of B12 have some benefit above and beyond what can be got from oral. I wouldn't mess with anything that does injection or IV. That's my personal approach. Again, I know that there's going to be docs who do that work, who disagree with me.

Melanie Avalon: No, that's fascinating. And on the flip side, you do seem to have a pretty favorable view on multivitamins, if they're the correct one, right? Am I putting words in your mouth? 

Ari Whitten: No, no, I'd say that's accurate. Yeah, multivitamins are a very mixed bag, because there's a lot of cheap, crappy ones that are using synthetic forms of vitamins, non-optimal forms, for example, like d,1-alpha-Tocopheryl for vitamin E as instead of mixed tocopherols. And we have research showing actually harm from that. So, there's good reason, I would say, to avoid multivitamin supplement that is cheap multivitamin supplement that's doing that kind of thing. Synthetic non-optimal, non-methylated forms of B vitamins, ascorbic acid as opposed to natural sources of vitamin C makes a difference as well. Yeah, there's a number of things to be cautious about when it comes to multivitamins. But if you are getting a good one from a reputable company and I make one, but there's other companies like Dirty Genes.

Melanie Avalon: Oh. Ben Lynch.

Ari Whitten: Yes. His brand seeking health is excellent. He knows how to formulate great stuff. Thorne makes a good voltage multivitamin and mineral supplement. There's a few other companies as well, but indefinitely avoid cheap ones. And if you get a good quality one, yes, I do think that there is compelling evidence to suggest that it's associated with lower risk of various diseases, longer lifespan, and in the case of chronic fatigue, that it's been shown to create significant improvements in sleep quality and energy levels in the span of a few weeks.

Melanie Avalon: Wow. I'm so fascinated by it, because I actually, recently launched my own supplement line as well and I've just always been so torn about the multivitamin concept. So, it was interesting to read your thoughts on it. One more supplement question.

Ari Whitten: I'll say that I for, actually, many years was opposed to them and didn't take them myself. 

Melanie Avalon: What made you change your mind?

Ari Whitten: Learning about why there's some negative data on it. Because there is negative data on multivitamins and there's also negative data on number of individual vitamins like vitamin C, and vitamin E, and things like that not being associated with longer life. And in some cases, even creating elevated risk, let's say, prostate cancer or something like that. And it's almost always for the reason that I just talked about that they're using non optimal forms of these compounds. When I learned that, and I started to look at some of the evidence on positive effects of these compounds, and then how to mitigate the downsides by simply doing things like mixed tocopherols instead of d,1-alpha, natural sources of vitamin C, as opposed to ascorbic acid and things of that nature that the optimal balance between these nutrients as well. For example, zinc, and copper, and some formulations, they don't have copper, or they don't have adequate amounts of copper, or some formulas, they have iron and I wouldn't recommend using iron in the formula. So, once you avoid issues like that, then I think it's a perfectly great idea to use them, particularly, given how rampant nutrient deficiencies are.

Melanie Avalon: Well, that is definitely a paradigm shift for me. So, thank you. I've got to look into it even more. Something that blew my mind. It's a supplement that I tried years ago, and I haven't heard about a lot recently. But is it true that PQQ is the most potent mitochondria biogenesis stimulator?

Ari Whitten: Most likely. Yeah, as far as what's been studied. It's hard to say definitively, because a lot of these things haven't been compared directly in head-to-head trials under the exact same circumstances. But yeah, it's widely regarded to be an extremely potent stimulator of mitochondrial biogenesis.

Melanie Avalon: I might have to make that in my line. Well, thank you so much, Ari. This has been absolutely amazing. I just can't thank you enough for your work and all that you're doing, and can't recommend enough that listeners get your books. The last question I ask every single guest on this show and it's just because I realized more and more each day how important mindset is, especially after everything that we talked about. So, what is something that you're grateful for?

Ari Whitten: I would say, there's so many things that I'm grateful for. Right now, I'm actually in this beautiful house, this Airbnb, that's ocean front. I'm staring out at the ocean on a beautiful sunny day and looking out at a surf spot. I love surfing, I love being in the ocean. So, I'm hugely grateful for that. I'm grateful for the Sun and all of the amazing benefits that it has on our physiology, something I've written a lot about and plan to write more about. And I'm enormously grateful for my children. I have a five-year-old son and my daughter just turned three yesterday. We just had a beautiful party for her. And yeah, they're really the joy of my life. So, I would say, above all, that's what I'm grateful for. 

Melanie Avalon: I have to ask, happy late birthday to your daughter. Was it a themed party?

Ari Whitten: [laughs] No, not really, but she does love unicorns.

Melanie Avalon: I love unicorns too. That's fabulous. Okay. [giggles] Well, thank you so much, Ari. This has been absolutely amazing. I can't wait for listeners to hear this. I love following your work. I look forward to your future work. Are you working on your next book?

Ari Whitten: I am. Yeah. I'm going to hear from Hay House, actually, in the next few days, what their team's vote is for the topic of my next book. But it's looking like it's going to be on hormetic stress and mitochondria. 

Melanie Avalon: Oh, my goodness. Well, hopefully, you can come back for that, because that would be absolutely amazing.

Ari Whitten: Yeah, I would love to. And I have to compliment you. I think of all the, I don't know, how many hundreds. Maybe I'm in the thousands of interviews at this point. But I would say, you asked some of the best questions of any interviewer I've ever had. So, well done on that.

Melanie Avalon: Thank you so much. That makes my week. I'm going to be [laughs] so happy. Well, thank you. This has been absolutely amazing. I wish you the very best of the rest of your day and I will talk to you later.

Melanie Avalon: You too, Melanie. It was a pleasure. I look forward to the next one.

Melanie Avalon: Thanks, Ari. Bye.

Ari Whitten: Bye.

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