Optimize Your Mitochondria: Secrets Of Hormesis Unveiled

Ari Whitten, MS

It is a big question. I will do my best to answer it very succinctly first. then we can delve into more aspects and nuances to that question as we go, more limbs of the branches of the trees. I had a personal experience with chronic fatigue when I was in my mid-twenties, and that is what led to my interest in this topic because I have been interested in health science since I was a little kid. We were just talking about it before starting this interview, but we were both athletes growing up, and my interest as an athlete, an aspiring bodybuilder, I was a soccer player, I was a martial artist, and I was an aspiring bodybuilder. So fitness, body composition, sports performance—that was my wheelhouse. That is what I did for my undergraduate degree. I went on to be a personal trainer, corrective exercise specialist, performance enhancement specialist, expert in nutrition, and all these kinds of things. 

Then, in my mid-twenties, something odd happened, which was that I got mononucleosis, and I was left with chronic fatigue for close to a year after that. That was the catalyst for me, shifting my focus away from the realm of fitness, athletic performance, and body composition towards energy. I already had well over a decade of knowledge of health science. I was reading college-level exercise, physiology, and nutrition textbooks by the time I was 14. I had already gained a large amount of knowledge of that landscape. Initially, what I did was gravitate towards the people who were talking about energy. I said, Well, I do not know about energy. Who are the people who do know about this subject? I sought out conventional medical doctors initially for my chronic fatigue from which I was suffering. They have nothing to offer and I am not trying to be mean. It was just a fact. 

If you look up the official information within conventional medical circles and evidence-based circles on chronic fatigue or chronic fatigue syndrome, they say the etiology is unknown. They do not know what causes it. The best evidence-based treatments that they have for it are anti-depressant pills, stimulant pills, cognitive behavioral therapy, and a recommendation to do some walking each day. These are the official recommendations based on a paper that is a collection of the research that exists that is presented as guidelines, quote-unquote, evidence-based guidelines for physicians, and how to treat fatigue. It is called Fatigue and Overview. If you want to look up that paper, it was published in the American Journal of Family Physicians, and those are the four treatments that they recommend. They recommend standard testing, but they go on to say that in 95% of cases, there is nothing found in that testing that explains the person’s fatigue. 

I sought out them, and then they had nothing to offer. I sought out the natural health types and functional medicine types. Everybody was talking about adrenal fatigue and the idea there was chronic stress of various kinds, taxes the adrenal glands, which produce a hormone called cortisol, which is involved in the stress response and regulating blood sugar levels, and things of that nature. This theory is that chronic stress, taxes, and exhaustion wear out the adrenal glands so that they cannot produce enough cortisol. That leads to all these common symptoms of fatigue and several other problems. I have a whole long story about this because I spent about a year of my life dedicated to this topic. 

But the very short version of it is that I initially went into the research. I initially found out that conventional medicine brushed off the whole idea of adrenal fatigue as nonsense and pseudoscience. That irked me because a lot of my mentors, people I looked up to, were talking about adrenal fatigue. I believed in them. I believed I had adrenal fatigue. What I had the idea to do was dig into the scientific literature, prove it, and write a book, essentially proving to the conventional medical community that adrenal fatigue was real and supported by scientific evidence. 

What I found, I spent a year of my life finding every single study that was relevant to this topic in existence. What I ultimately found is that the science does not support the existence of adrenal fatigue. We could talk specifics on that if you want, but the gist of it is that adrenal fatigue is not the explanation for chronic low energy levels. What all of this study ultimately led to was that the core of it centered around mitochondria. Mitochondria are cellular energy generators. These are what we all learned in high school or college biology and physiology courses, are the powerhouse of the cell. That is if you want to get the answer on the multiple-choice exam. You have to remember the powerhouse of the cell. That is the organelle responsible for producing ATP (adenosine triphosphate), which is cellular energy. 

Virtually all of the trillions of cells in our body run predominantly, almost entirely, on energy produced by mitochondria. Now, the way that we are taught about mitochondria in biology and physiology, even graduate-level and post-graduate-level physiology courses in biochemistry courses, is essentially that mitochondria are these mindless energy generators that just take in carbs and fats and pump out energy. Well, would not it be great if the problem of chronic fatigue was solvable just by telling people to eat more carbs and fats and provide more fuel to their mitochondria? But, of course, that does not work. In fact, for most people, it will just make you more fatigued if you try to do that. 

There is something more complex going on in the story. There is a lot more complexity going on in the story, but the bulk of it can be centered around the work of Dr. Robert Naviaux and the Cell Danger Response. What his work explains is that this is a scientist; he is an MD, PhD, who runs a lab for mitochondrial medicine at the University of California, San Diego. This was a seminal paper that he wrote that synthesized a huge amount of research from researchers all over the world on mitochondria. What they found is that mitochondria are not just mindless energy generators. They are environmental sensors in our bodies. They are not only producing the energy that supplies virtually all of the trillions of cells in our body. But they are deciding how much energy to produce. The way that they decide that maybe just briefly, I will explain that there is a difference between a component that is involved in a process, energy production, and something that is regulating how much energy is produced or when it is produced, the degree to which it is produced. 

As an example, if you think of a car, there are lots of components in that car that are necessary for that car to function. The wheels, tires, spark plugs, pistons, crankshaft, and engine block. If you remove any one of those parts, the car will not work. They are all important. But those things I just mentioned are not what regulate whether or not that car is driving down the road. That is the human being in the car deciding whether to start the engine or not, whether to press the accelerator pedal or the brake pedal, and how hard. What is doing that in our body is mitochondria, and they are doing it largely as a function of testing the safety of their environment. They are probing the environment and asking the question, Is it safe for us to produce energy? 

In Dr. Robert Naviaux’s words, mitochondria essentially have to follow fundamental rules. One is as an energy generator, and the other one is in coordinating cellular defense. They are testing the environment to detect the presence of threats, stresses, and dangers. To the extent that they are picking up on threats and danger signals that exceed their capacity to handle them, they are shifting from energy production mode into wartime defense mode. These two roles are mutually exclusive. To the extent they are doing one, they are turning down the dial on the other. To the extent that your cells have to defend against threats, they turn down the dial on energy production. That is the first big layer—the first of two big layers to understand when it comes to what is controlling our energy levels.

David Jockers, DNM, DC, MS

That is good to know. So mitochondria, as you were saying, we always learn that they produce all the energy, but there is also in a sense that, they have a sensory function. They are sensing the environment and responding to it. They are either going to be in a defense mode, in which case they can turn up inflammation and oxidation, and we can feel fatigued and lousy. If we get the flu, for example, we can go from one day feeling great, working out, and having tons of energy, and all of a sudden wake up in the middle of the night and feel lousy and have no energy the next day. That is the response of the mitochondria, just shunting down energy and going into defense. That is what you are saying there.

Ari Whitten, MS

That is right. There is one other important component to this story, though. If we think of mitochondria as a cellular engine, like the engine of a car, the other big component of this story, that is massively neglected even today, as en vogue mitochondria have become in natural health and functional medicine circles. When I first started talking about this issue 10 years ago, nobody was talking about mitochondria. Now everybody’s talking about mitochondria. Mitochondrial dysfunction is the catchphrase in functional medicine. But it is often framed as saying that we have these mitochondria in our cells. They are these static entities that are just there. Mitochondrial dysfunction means they are damaged or otherwise deficient in cofactors for energy production. The response to the mitochondrial dysfunction protocol, if you will, to correct this problem of mitochondrial dysfunction is to take B vitamins, magnesium, CoQ10, alpha-lipoic acid, PQQ, and things like that, and acetyl L-Carnitine, and so on.

Of course, mitochondria can have a deficiency in nutrients that are necessary for them to function, and that can be helpful in certain circumstances. But for the most part, this is how mitochondria are conceptualized by most people, and it is missing a huge part of the story. Here is the part of the story they are missing. If we think of mitochondria, these are 1,000, 2,500, or sometimes 10,000 mitochondria per cell. If we think of it as our cellular engine, we also have to understand that the cellular engine is not a static entity; it is highly dynamic and highly malleable. We need to ask the question: do we have a Ferrari V8 engine in our cells or do we have a lawnmower engine in our cells?

The reason this is important is that, if you just give a lawnmower engine in your cells more B vitamins or magnesium or CoQ10 or L-Carnitine, etc., you still have a lawnmower engine in your cells, and it will not function like a Ferrari V8 engine. Now what does this have to do with anything? Is this real? Am I just making up concepts? Well, let me put some numbers to this. We know that every decade of life, once we reach adulthood, most people’s mitochondrial capacity declines by about 10% per decade, which might not seem that much. Let me put it another way. The average 70-year-old has lost 75% of their mitochondrial capacity, which is a decline of 50% of the amount, the number of mitochondria per cell, and each mitochondria has generally shrunk to about half the size and is only capable of producing half the amount of energy as youthful mitochondria would produce. Okay, so if you do the math on that, it’s a loss of 75% of your mitochondrial function. That is what I am talking about when I say going from a Ferrari V8 engine when you are 20 to a lawnmower engine in your cells when you are 70.

Now here is the thing: some people might be listening to that thinking, Well, that sucks! That aging does that to our cells, our mitochondria, and our engines; our supply of cellular engines decreases massively. The good news is, we know that this is not a natural, normal product of the aging process itself. This is a product of modern lifestyles. The reason we know that it is very simple; If we look at a 70-year-old who is a lifelong athlete and exerciser, they do not lose 75% of their mitochondrial capacity. They have the same mitochondrial capacity as young adults do. What this is is a deficiency of core mimetic stress, a deficiency of challenge to the mitochondrial system. 

As an analogy, people understand this concept much better at the macro level than we do at the micro level. When things are big and visible, we can see them. We tend to understand them much better than, when things are happening on a small scale over longer periods, at a micro level in the body, we have all been indoctrinated into a medical paradigm that has convinced us that when things happen inside of this body, this mysterious black box of a body of ours, are all due to these, micro-level chemicals, biochemicals, pathways, enzymes, and telomeres, this gene, that gene, SNPs and senescent cells, NAD plus, neurotransmitters and hormones, all this complex mix of all these micro levels. 

Here is the big-picture concept. If I go and lift heavy objects frequently, my muscles will adapt to that signal. By growing bigger and longer, I will physically grow larger muscles as a result of that. On the other hand, if I break a bone and I immobilize my arm or my leg in a cast for two months, when I go to the doctor and they see that past two months from now, I look down at my leg and notice that it is half the size of the other one and half that it was before. That is because muscle tissue atrophied from disuse from lack of challenge. That same principle is at play in lots and lots of different systems of our body. The systems of our body are designed to require our regular challenges, and if they do not, they shrivel, shrink away, and atrophy. In some cases, they die off.

This goes all the way down to the cellular level, at the subcellular level, to our mitochondria. If we do not challenge our mitochondria regularly, they atrophy just like muscle atrophies from disuse. If you think about this, imagine what I just said about muscles. That is just two months of nerves. Lack of using your muscles. Now imagine what happens with two years, five years, ten years, or 50 years of not challenging your mitochondria—massive amounts of atrophy. That, of course, hugely influences our energy levels.

David Jockers, DNM, DC, MS

That is a good explanation. We need to be stressing those mitochondria because, ultimately, they get stronger and more resilient to that stress when we do it. But we have to do it appropriately. If we overwhelm our system, then we are not going to be able to respond and adapt effectively. So as people are aging, what you are saying is one of the main reasons why people are noticing a lot of these types of symptoms, where they have cognitive decline, low energy fatigue, and just do not have that same get-up-and-go. That has to do with the fact that their mitochondria are shrinking. Their energy capacity is reducing. Ultimately, they have not been stressed enough or adapted enough to stress. Therefore, they are noticing all of these different types of symptoms. What are some of the best ways to stress them appropriately and adapt effectively so we can optimize mitochondrial health?

Ari Whitten, MS

Yes. One of the big misconceptions about hormetic stress is that it is often talked about as if a little bit of poison is good for you. This is largely not correct in many cases. A better way of describing it is biologically appropriate and compatible stressors—specific types of stress that are not novel for the human species but are ancestral stressors—are extraordinarily beneficial for our bodies. Not only are they not stressful to our bodies in the sense that we all have this negative connotation with the word stress, but they are helpful for the body. Not only are they beneficial, but they are also required nutrients. In the same way that we require nutrients in our diet, we also require nutrients for our body to function normally.

If I can extend this analogy a little bit further, imagine that we have to understand that our body is an intelligent, adaptive system. It is not most systems, most machines, in the sense that if we took a simple clock, a computer, a bicycle, a car, a chair, or anything else, the more stress we were subjected to, the faster that thing would break down. If I take my bicycle or my car and drive it down a bumpy dirt road, the more I do that, the more it gets mud, water, and sun and has to absorb bumps. The faster it is going to break down, the more stress it is exposed to, and the more it breaks. It is a very linear equation. More stress means more breakdown.

Most people think of the human body in this way, but it does not work this this. The proper way of thinking about it is to imagine that you have a sports car. That is a magical sports car. It has a supernatural power where, when you take the sports car out, you drive it hard and fast on windy mountain roads, push it to its limits, and crank that engine as fast as it can go. Then you go park your car in the garage overnight. You come back to your car the next day, and it grows a bigger, stronger engine and becomes more fuel-efficient. The tires develop more friction to grip the road better. The car became more aerodynamic, and it alerted. The frame became stronger, and the suspension learned to absorb the bumps better. Everything about that car became better and stronger as a result of being challenged and stressed. That is how the human body works. Stress when they are biologically compatible stress makes us stronger. 

But the downside of this magical ability that this sports car has is that if you leave it in the garage for two months and you do not challenge it, you come back to it a couple of months later and the wheels are falling off and the frame is rusting and that Ferrari V8 engine shrank to a lawnmower engine, and so on. That is how the human body works. It is an intelligent, adaptive machine, not a simple machine. Because of that, because of that magical ability that is programmed into us, it comes with that trade-off. It can be resilient to not only survive stresses but to be made stronger and healthier by them. But the downside is that if you do not regularly challenge the system, it grows weaker. That is the context of how the human body needs to be understood. From there, we need to understand that there are many different ways that the human body can be challenged and grow stronger. You asked me a minute ago to remind me of your question, David. 

David Jockers, DNM, DC, MS

What are the best strategies? What do we need to do to strengthen the mitochondria?

Ari Whitten, MS

The first thing that we need to understand, and what you were talking about a minute ago with the dose, is that the dose is going to be individual to the person. If you have a lawnmower engine in your cells, you are going to have way less capacity to tolerate stress than somebody who has a Ferrari V8 engine in their cells. First of all, to get the dose right, it needs to be individualized to a person’s level and a person’s capacity. The way we do that is very simple. Test your capacities in different ways, whether it is fasting, whether it is a sauna, whether it is different types of exercise, whether it is breath-holding practices, test your capacities slowly and cautiously, and define where your limits are. You find that you brush up against discomfort. Stop there the first few times. You do not need to have some objective amount. I am supposed to be doing this amount of exercise, this type of exercise, for this many minutes per session. I am going to go from 0 minutes of exercise now to 45 minutes of this type of exercise starting tomorrow.

No, start with 5 minutes; start with 10 minutes. Start with however many minutes you can do before you feel a lot of discomfort. Let that be day one, and you build on that next time, do slightly more, do slightly more next time, and so on. That is the issue of dose. The other issue is biological compatibility. We need to understand that not all stress is created equal. That cigarette smoking, the chemical stress from environmental toxicants, sleep deprivation, chronic psychological stress, or any other type of novel stress in the modern human environment is not the same as our ancestor’s general stresses. Our ancestral stresses were that we had certain things built into our lives where we had to. We were exposed to periods without access to food, for example. We had to deal with famine and a food shortage. We had to deal with lots of movement and exercise intensity, whether it was to hunt, build, fight, or run away from stuff. We had to deal with heat and cold. We had to occasionally deal with hypoxia at the tissue level, whether from activity, breath holding, or other conditions, like being in a cave or things like that.

Some groups of humans had underwater hunting strategies and that was more prominent. We had to deal with exposure to phytochemicals in the foods we were consuming and several other stressors. Those are the stressors that are specifically built into our biology, that we are designed for over thousands and thousands of generations of human beings. We evolved the capacity to handle not only those structures, but also the biological capacity to adapt to them and grow stronger, be made stronger and healthier, and be more energetic and disease-resistant. This is why, for 75 years, we have had modern medicine pursue, study disease, and study the presence of disease. then, based on this, trying to go to a chemistry lab and invent chemicals that are targeted to those mechanisms of disease, with the idea that we are going to have targeted chemicals that interrupt this mechanism of atherosclerosis or this mechanism of, say, that serotonin levels certain levels in the brain of depressed people, or we are going to alter the formation of amyloid plaques and cause disease.

For 75 years, modern medicine has been doing that. We have invested trillions of dollars into that, and we have invested millions of potential candidates. 19,000 of these have been FDA-approved and are in use. Out of those millions of drug candidates and trillions of dollars spent on hundreds of thousands of scientists pursuing this model of human health, we do not have a single one that is anywhere close to as powerful in promoting health or preventing disease as simply moving your body vigorously for half an hour or getting into a sauna for half an hour. That, if I can conceptualize it in a nutshell, that is the power of these kinds of strategies that I am talking about. That is how essential they are to human biology and human longevity.

David Jockers, DNM, DC, MS

Yes. Again, such a great approach to this, and looking at what our ancestors did and how they approached their lives regularly, What stresses are they under? Now, let us go into nutrition principles. How do we eat for healthy mitochondrial function?

Ari Whitten, MS

Well, there are several components. This could be a long discussion. I know we discussed this previously on your podcast. Let us look at nutrition through the hormetic lens, through the lens of these kinds of challenges to the system that I am describing. This is the Fasting and Longevity Summit. Of course, fasting and food shortages are a major challenge for mitochondria. It puts stress on that energy production system because what happens if you have an engine that is deprived of fuel sources because you do not have as much fuel coming into that system from, in this case, food? 

There are different ways that this challenge could happen. It could be a shortage of a particular macronutrient, carbs, or fat, or it could be a shortage of total fuel; carbs and fats in particular, which are much more than protein, are used by mitochondria to produce energy. It could be a food shortage where you have low amounts of food, or it could be a full-blown famine for a prolonged period where you have had almost no food for days and days and days. These represent challenges to the bioenergetic system and the cellular energy machinery, and fortunately, because we evolved with those challenges, our system developed redundancy, where it has multiple different types of different ways and layers of ways to get fuel and to be able to pump out energy. 

One of those ways is if it is using the fuel that is coming in. If you have carbs coming in, you can burn carbs. If you have fat coming in, we can burn fat if you do not have carbs or fat coming in. Let us tap into our glycogen reserves, our stores of carbohydrates in our liver and our muscles.  

That only lasted a day or two. Now, we ran out of that. What do we do now? Let us tap into our body’s fat stores and our adipose tissue, and let us pull fatty acids from there and burn them as fuel. Let us also say that if we have a shortage, we need to start using hormones to break down the muscle tissue in our body into amino acids, which we can convert into glucose, which we can burn as fuel. We start pulling from our own bodies’ tissues, and it is much better to pull from your fat reserves than from your muscle tissue. But that is the system. 

At the energetic level, we can produce energy in the mitochondria itself through beta-oxidation. We can produce energy in the mitochondria from fat; we can produce it from carbs; we can produce it from ketones; and we can burn energy outside the mitochondria too. We have layers and layers and layers of this system, but fundamentally, when we challenge the system in these ways, whether it is a low-carb ketogenic diet, a low-calorie diet, or multiple days of fasting, we are presenting a challenge to that bio-energetic machinery. A couple of things happened in response to it. A few things happen. 

One, we ramp up autophagy and mitophagy, and this helps clean out the junk in our cells because, in the strained state and in the state of being challenged and under that increased demand, any dysfunction that is present there starts to become more noticeable. The body becomes more sensitive to it. It starts to throw off more free radicals, causing more inflammation. The more challenge and strain that systems are under, the more problems you get from dysfunctional machinery. One of the things that it does in response to being challenged is clean out the damaged and dysfunctional machinery through autophagy and mitophagy, which is autophagy at the mitochondrial level, cleaning up the damaged and dysfunctional mitochondria to have a healthier supply of mitochondria.

In addition to that, we also, from this challenge, get the stimulation of what is called the Nrf2 pathway, which is a pathway that is stimulated when there is an increase of oxidants in the system. This also happens with exercise as well. We get a big burst of oxidants. Those oxidants have typically been thought of as bad guys, but it turns out they are vital signaling molecules that perform very important and beneficial roles, one of which is to do a couple of things. They signal for mitochondria to produce their supply of internal antioxidants. Things like glutathione, superoxide dismutase, and catalase, that internal antioxidant supply, a system called the ARE, the antioxidant response element, is much more important than any external antioxidants we get in our diet or via supplements. It is building up and having a robust internal antioxidant system that stimulates the robustness of that system.

It also stimulates simultaneously, mitochondrial biogenesis. The creation of more, bigger, stronger mitochondria and more new mitochondria from scratch. I previously talked about 70-year-olds losing 75% of their mitochondrial capacity. Well, that is opposed. We can combat that and reverse that through the process of mitochondrial biogenesis of growing bigger, stronger mitochondria and more of them, and fasting, food shortage, or nutrient cycling is one way to create that strain, that challenge on the system that communicates a signal to your mitochondria, Hey, to better survive this environment, because that is what the body cares about; it cares about surviving the environment.

To better survive in this environment, we need stronger energy production machinery at the cellular level. Just if you lift heavy weights, your body goes up. To survive in this environment, we need stronger muscles. When you create those inputs on the bio-energetic system inside your cells, your cellular engine, the body does the same thing. To survive this environment, we have to grow a bigger, stronger cellular engine to keep up with these energetic demands on the system so we can better survive these periods of food shortage or famine.

David Jockers, DNM, DC, MS

Again, great explanation there. Ultimately, I always say the quality of our lives comes down to the amount the overall functionality of the amount of stress-resilient mitochondria that we have in our system and our ability to turn on and off that parking brake. That cell danger response is so important. Now, we turn that on in certain circumstances, but we need to be able to turn it off once the danger has been controlled. I think that is so key, as well. So yes, so good stuff when it comes to fasting you were talking about there. Now, how about food and nutrients? You mentioned our ancestors being exposed to different phytonutrients and that being a hormetic stressor on the cells and the mitochondria. Let us talk about some of the key nutrition principles in foods that people should be looking to get in their diet.

Ari Whitten, MS

Yes. There is a popular dietary ideology that has come into vogue in recent years, and that is the carnivore diet. Many of these gurus of this diet have promoted the idea that plants have phytochemicals. What phytochemicals are? These are plant poisons, essentially those that evolved to ward off insects or animals consuming them because they have a slightly toxic effect. The evolution of these compounds was, Do not eat me because I will make you sick if you eat a lot of me. That makes sense. Yes. They have the idea that plants produce these toxic defense chemicals, and therefore, you do not want to eat toxic poisonous compounds, do you? They were designed and evolved to dissuade animals from eating them. There is a certain logic to that now that makes sense. The only problem with it is that this has been known for decades, and there is a whole field of research called Xenohormesis, Xeno with an X. X YN O, hormesis. If you want to look it up on PubMed or Google Scholar, you will find hundreds, if not thousands, of studies on this topic.

It turns out that because we co-evolved with those plants that also produce those phytochemicals, we evolved our capacities in response to that. We evolved the capacity to not only detoxify and not be damaged by those compounds but to benefit from them and be made stronger by them. Let me present an analogy for you. If the idea of; “Do not eat stuff that is toxic for you, that is stressful for your body”, makes sense to you, Well consider this. What if I said that moving your body vigorously and with intensity and putting a lot of strain on your muscles creates a big surge of stress hormones? Adrenaline, noradrenaline, and cortisol create a huge spike of oxidants, and everybody knows oxidants or free radicals are bad guys. They are toxic to our cells. There is a lot of literature on oxidative stress and oxidative damage, driving all kinds of health problems. What if I logically extended that to say, Well, exercise is harmful to you because it creates such stress on the body with these stress hormones and with these stressful, damaging oxidants? 

Well, the only problem with that is we know that exercise is tremendously beneficial to our body. 

What is going on there is that our bodies, as I explained earlier, evolved the ability to not only handle those sources of stress but to be made stronger by them, to use them as signaling molecules, to build and engineer into the different systems of our body at multiple different levels, from the mitochondrial level to the muscular level to tendons to bones, to the cardiovascular systems, to the lungs, to the brain, even to the nervous system. Many different layers of the system grow stronger and increase their stress buffering capacity and their working capacity in response to that brief, stressful encounter with vigorous, intense, demanding movement. 

The same principle is at play when it comes to consuming phytochemicals; in the vast majority of cases, these phytochemicals are easily neutralized by our bodies. They do not cause harm unless you consume ridiculous abnormal amounts of concentrated, specific chemicals. They are easily neutralized by your body.  Not only are they neutralized, they are signals; much like exercise is to make the system stronger. I mentioned the Nrf2 pathway earlier about fasting. Well, phytochemicals also stimulate the Nrf2 pathway so does exercise, by the way. These phytochemicals, whether it is sulforaphane, curcumin, or a long list of hundreds of other compounds, specific phytochemicals found in different plant foods, mushrooms, and things like that.

These phytochemicals stimulate the Nrf2 pathway, which creates a low level of oxidative stress on the system that is not damaging and stimulates the growth or the increase in the antioxidant supply of that ARE, that antioxidant response element, and works to also simultaneously stimulate mitochondrial biogenesis, the growth and strengthening of mitochondria, and the creation of new mitochondria from scratch. 

Anyway, all of this is to say: do not be fooled by the idea that phytochemicals and plant defense chemicals are harmful to you and you have to avoid them. Of course, there are also truly harmful poisonous compounds in plants. You can find those in the animal world too. There are things in the animal world that are truly toxic for you, that you should not eat, and that will kill you. But the vast majority of these phytochemicals in plant foods are enormously beneficial for us. It is not just the theory or the field of Xenohormesis that we know that from. Of course, there is a body of tens of thousands, if not hundreds of thousands, of studies on specific phytochemicals and their health effects on different systems of the body.

David Jockers, DNM, DC, MS

That is good. I would say that the best diet is a varied diet where you are consuming a lot of different types, different colors, and different types of things when you are eating. At the same time, a lot of people are eating the same ten foods all the time, and it’s easy to get into that trap. Then you are putting less of that hermetic stress on the system. The body starts to adapt to those specific things that you are getting, and you are not getting the full benefit, as opposed to when you are getting a very varied diet, all things from nature. But I think that is going to work best. 

With some of your metaphors, I always get the slinky effect, too. It is slinky to propel it to the next step and build this internal resilience, it needs stress. It needs to be primed. a lot of these things that we are getting from plants, whether or exercise age, wherever it is, it is stressing our system, it is priming, pushing down in that slinky. When you release now, the slinky jumps up to the next step. It increases its potential and increases its overall endogenous antioxidant defense systems. when it comes to a human’s overall adaptive potential because it has that stress and priming effect.

Ari Whitten, MS

That is right. If you do not keep pushing and pulling on that slinky in that way, the slinky starts to rust and become dysfunctional.

David Jockers, DNM, DC, MS

Good. Let us talk about the circadian rhythm and how important that is. I think that particularly for a lot of younger people, I know for myself, just dealing with a lot of health issues, when I look back in my early 20s, I had my circadian rhythm was way off track, and I think that was at the root of and for me, I had irritable bowel, there were a lot of things to which I responded poorly to higher-fodmap foods, eating foods that naturally would be healthy. I had to eliminate those for some time to get my gut health back so I could have a varied diet. But when I look at it, it was not those foods that made me sick—processed foods or toxins, things like that in food. But if I were to point my finger at one thing that I could have done better in my late teens and early 20s, that would be at the root of the irritable bowel. It was circadian rhythm dysfunction. Let us talk about why that is so critical.

Ari Whitten, MS

Maybe, if I could zoom out and present a bit of context and tie this into the concepts that we were talking about previously. Humans need to think hard to be healthy. One is that we need, as I explained before, the essential nutrient to challenge the systems of our body. For those systems to either grow stronger or just maintain their level of youthful structure and function. One of the main deficiencies that modern humans have is that we have a massive deficiency in those types of physiological stressors that used to be part of the ancestral human lifestyle that used to be just that we did not have to think about them or do them consciously. They were embedded in our lives. Modern humans are massively deficient in that. 

The systems of our body, are atrophying and degenerating in large part due to that deficiency. But the other thing is that we also need powerful regeneration and repair time, and we need this oscillator of stress and challenge on the systems and then deep restorative repair time where those systems can adequately and truly repair and not only just repair to go back to baseline, but the idea with the challenge is that you grow stronger and better and healthier, literally improving the physical structure and function of the systems of your body down to the mitochondrial level that is growing bigger and stronger to be able to produce more energy. To do that, well, you have to have good what I call regeneration rituals in place and the several components to that. 

One of the things I want to mention is that most modern humans are deficient in both. Instead of having this oscillation of challenge demand on the systems, intense demand on the systems is enough to stimulate adaptation and growth and strong regeneration rituals. We are flatlining it. We are not making that oscillation. We are constantly in this middle ground where we are doing neither of those two things very well. Now, when it comes to the regeneration rituals, we need a few things. We need good nutrition to provide the raw nutrients needed to repair the physical structure of our body. We need relaxation to be relatively free of chronic psychological and emotional stress. We need a calm environment. This is where healthy relationships and things like meditation and yoga come into play, as well as time with family and people that you love. 

We also need to have strong circadian rhythms and sleep habits. That circadian rhythm piece of it is what links the sleep and wake cycles. We have a biological clock built into our brain, into a part of the brain called the suprachiasmatic nucleus. It is a literal biological clock, a 24-hour clock, hopefully, the 24-hour clock it is supposed to be. It is synched up primarily. It is linked up to the day and night cycles, primarily through light signals and specific wavelengths of light, largely a light blue spectrum of light. When you look at a blue sky and see blue light entering your eyes, that blue light feeds back through your eyes and into receptors and nerves that go into this biological clock in your brain and say, it is daytime, the time to be awake, alert, active, and energetic. Then when we do not have that blue light entering into it, that is also interpreted as a signal. Okay, it is nighttime. It is time to wind down, relax, and go into sleep mode so we can regenerate and recharge the systems after this day of stress and demand on the systems. 

That system links up with almost every part of our physiology, down to the subcellular level. We also have peripherals. This is a newer scientific discovery, and in more recent years, we have peripheral biological clocks, and almost every tissue from our skin to our internal organs, our intestines, our liver, our heart, and our mitochondria also have essentially clock functions built into them. They are designed to link up to this circadian clock. What we ultimately want is to synchronize, as much as possible, the central clock in the brain with the peripheral clocks in the other tissues of our body. The central clock is primarily sensitive to light; the peripheral clocks are sensitive largely to food inputs; but also, the clocks are sensitive to movement, temperature, and other forces such as stress, stress hormones, and things like that. There are several forces at work. But the central part, the dominant force, is light. 

The way that these link up with all of our physiology is through lots and lots of different chemicals, through neurotransmitters that are tied to the circadian rhythm, through different specific what are called clock genes, and through hormones that are tied to the circadian rhythm. Some of the hormones that operate on diurnal curves or are tied into the circadian rhythm are things like melatonin and cortisol, testosterone, and thyroid hormones. There are others as well. These hormones, neurochemicals, and clock genes, touch if you think of the tentacles of an octopus, for example, they touch every system of our body. What is going on with this light signal from the environment feeding back into the brain is sending signals that affect, in one way or another, either very directly or indirectly, pretty much everything in our body. Because this regulates the sleep-wake cycles, whether you should be awake, active, and energetic, or whether you should be in rest and regeneration mode and sleep mode, this is a critical mechanism for human health. 

One of the things that we need to get when it comes to this is that we need to prioritize light exposure, getting bright light, ideally outdoor sunlight in our eyes, ideally within the first half an hour after waking up, and at least a couple of minutes of bright light if it is a sunny day; if not, you might need more than five, 10, or 15 minutes of outdoor light to get that circadian rhythm going. We need to reset that every day. We also need to, as much as possible, get bright outdoor light throughout the day and create a big difference between the intensity of the light that we are getting during the day and the intensity and wavelength spectrum of light that we are getting at night. We want, and then in the hours preceding bedtime, we want the intensity of the light to be ramped down. We want the spectrum of the light to be shift red. We want to get away from the intense blues and be shifting more toward the amber and red wavelengths of light. Those are also part of the biological signals for increasing melatonin and suppressing and promoting sleep and regeneration at the cellular level.

David Jockers, DNM, DC, MS

That is key. There is a proverb that says If you want to have great energy during the day, watch the sunrise. If you want to sleep great at night, watch the sunset, and you can add in there, get some time in the middle of the day where you get that full UV spectrum, at least some of that into your, not looking straight at it, but into your cells. Into all the cells of your body. Then, at night, block as much of the light as possible; you want minimal light exposure. Like what you mentioned, thinking about our ancestors. They did not have electricity, they did not have any light. If they were exposed to anything, it was fire candles. It was that red spectrum. What do you do?

Ari Whitten, MS

It turns out that the promotion of melatonin. Everything you said was spot on. I will add a few things to what you said since you brought those things up. One is that we need to understand melatonin. Most people think of it as a sleep hormone or just a supplement. A lot of people do not even realize it is a hormone. It is a critically important hormone. Not only does it promote sleep, but it is directly tied to the mitochondria. It is a critically important mitochondrial antioxidant that essentially not only protects your mitochondria but also recharges them. It interacts with that internal antioxidant defense system and is designed to recharge that system each night while you sleep so that it is ready for the next day’s exposure to stress. 

Imagine, as a point of reference, there is research showing that just simple exposure to indoor home lighting, standard, ceiling lighting of LEDs, and fluorescent lights suppresses melatonin levels by about 70%. Melatonin, again, a critically important mitochondrial antioxidant, is also neuroprotective and cancer-protective. What happens if you are chronically, massively suppressing a critically important neuroprotective, cancer-protective, mitochondrial protective hormone that is designed to recharge this part of your cellular engine each night while you sleep and you are doing that night after night after night, for years or decades? 

David Jockers, DNM, DC, MS

You cannot recharge effectively.

Ari Whitten, MS

Yes, do you think it might lead to having chronically low energy levels, having poorer brain function, and having an increased risk of cancer? Absolutely.

David Jockers, DNM, DC, MS

Yes and that is one of the major contributors that we are seeing in our society. Last question, Ari, what are you doing daily? How do you set up your circadian rhythm? What is your ritual like?

Ari Whitten, MS

Well, the first thing I do when I wake up is take my dogs here outside, get them on the land of my property, or take them for a walk just to get some light in my eyes. You get to allow them to do their own business. I kill two birds with one stone. I take care of myself, and I take care of them at the same time. Usually, after that major gaze, one.

David Jockers, DNM, DC, MS

Of mine, you are getting outside and you are getting movement in, which is key. That is also a way to teach your body wakefulness, which is the cortisol release needed to have wakefulness in the morning.

Ari Whitten, MS

Exactly. After that, when the movement starts beyond just walking, I will either surf or I will go play tennis most days. If I do not do that, what I will do is do a gentle mobility routine workout, take care of my soft tissues, do some breathing practices, do some opening up of the joints and muscles of my body, and take care of my joints at the same time, making sure that the tissue quality of my muscles and my joints is healthy. But, as a lot of people said earlier, we have all been indoctrinated into this paradigm to believe that our health is largely a product of what shows up on our blood tests, microbiome tests, organic acid tests, and things like that. But we need to understand that at the macro level, we are a collection of organ systems; we are a collection of muscles and bones, a cardiovascular system, a brain, a nervous system, and tendons, joints, and ligaments.

We need to understand that the health of those macro-level organs is not purely a product of what shows up on your blood tests. It is largely a product of things that do not show up on your blood test. What I mean by that is how much movement you get, your circadian rhythm habits, how much sauna exposure, or how fit you are. Those things do not show up well on your blood tests, whether you got light in your eyes that day. But, specifically, what I wanted to say is that taking care of this physical meat soup of ours with our physical muscles, bones, and joints is a critically important piece of longevity. We have to take care of the health of those systems daily because we need to realize that people do not die just from diseases that are being driven by things at the micro level, such as senescent cells and inflammation, this hormone and that hormone, this chemical, and this gene mutation and that new gene mutation. 

They are driven by simple things like falling down. Losing your balance and falling down, physically tripping over something, and not having the capacity to stop your fall. Now, you broke a bone. Now you are in the hospital. A third of people are dead within a year; another third never fully recover from, for example, broken hips and end up in care homes; and only one-third recover full functionality. We need to understand that simple accidents that are the result of dysfunctional deficiencies are in the structure and function of our physical body, which is not a product of what shows up on your blood test. This is a hugely important component of this. In my personal life, I spent a lot of time caring for the physical structure and function of my body. I play tennis, I surf, and I do a lot of weight training and I do a lot of mobility work to keep my body moving. I am a supple athlete, a very youthful, high-performance person. That is something that I think is very important. 

I also challenge my brain cognitively because we have to understand that our brain, much like our muscles, also maintains robust structure and function largely as a result of cognitive demand. We have something called cognitive reserve capacity, which is the same as energetic reserve capacity at the mitochondrial level or muscular reserve capacity at the muscular level. How much workload can that system handle? We know that people who go on to get higher education—people who have cognitively demanding jobs—have more cognitive reserve capacity built into their brains. This is hugely protective against neurodegenerative conditions like Alzheimer’s and dementia, for example. A large part of my work day is also spent doing cognitively demanding stuff, caring for my physical body and my brain, and the rest of my time is spent with my family and my kids.

David Jockers, DNM, DC, MS

Then, at night, are you turning off all the lights? What are you doing? You set yourself up for a great sleep.

Ari Whitten, MS

In my main living area, in the bedroom, we have all incandescent and halogen lighting. It is all amber and red-shifted lighting. That is the lighting we use after the sun goes down. That does a couple of things. It is not LED in fluorescent lighting. This is important for two reasons: the lack of blue light, which is important for not secreting melatonin, and the presence of red and near-infrared light, which promote melatonin secretion so that that amber and red-shifted environment, not just the color, but the presence of red, and the near-infrared, and especially near-infrared, which you will not have with LEDs or fluorescent, even if they are of the right kelvin color temperature. 

David Jockers, DNM, DC, MS

You cannot see infrared. It is not on the visible spectrum.

Ari Whitten, MS

That is correct. That is also promoting melatonin onset and melatonin release, and yes, I hop into bed with my. After dinner, we hang out in the living room, we play, we dance, and sometimes we play board games or Jenga or something, or we play with a ball where we are a tennis family. Sometimes I play tennis with my kids in the living room. I am just hitting the ball back and forth, or hitting a balloon back and forth. Then we go to bed, read stories, and fall asleep. We have a, as you mentioned earlier, pristinely dark room at night, which is equally as important as a very large amount of bright light during the day.

David Jockers, DNM, DC, MS

It is great. Great interview, Ari. We could talk all day about this stuff. That routine sounds a lot like what my family and I do as well. I appreciate your expertise here and all the great work that you are doing out there. Guys, you can check out his books, where he goes into all of this in a lot more detail and gives you step-by-step action steps. His most recent one is Eat for Energy: How to Beat Fatigue and Supercharge Your Mitochondria for All-Day Energy. Fantastic book. I read that book. It was a wonderful book. He also has The Ultimate Guide to Red Light Therapy. Wonderful books. Ari, you are doing great work. I appreciate your time. It is always great to connect with you, my friend. We will see you soon.

Ari Whitten, MS

Thanks so much, my friend. I will talk to you soon. 

David Jockers, DNM, DC, MS

Bye-bye.