How To Keep Your Mitochondria Healthy For Better Energy

Intro:

Welcome to Dr. Ruscio, DC radio, providing practical and science-based solutions to feeling your best. To stay up to date on the latest topics, as well as all of our prior episodes, make sure to subscribe in your podcast player. For weekly updates, visit DrRuscio.com. That’s DRRUSCIO.com. The following discussion is for educational purposes only and is not intended to diagnose or treat any disease. Please do not apply any of this information without first speaking with your doctor. Now let’s head to the show.

Dr Ruscio:

Hi everyone. Today I spoke with Ari Whitten. This is his, I believe, third time on the podcast and we always have just terrific conversations. Today’s topic was a real unpacking of mitochondrial health. Ari introduced a concept that is far different than most of what you’ll hear, I believe anyway, in functional health chatter regarding mitochondria. He discusses that mitochondrial dysfunction is often a reaction, a protective reaction known as a cellular defense response, and he did an excellent job helping us to better appreciate that. We should be careful about trying to quantify mitochondrial dysfunction or get too swept up in assessing and or supporting mitochondrial function because, again, a lot of this dysfunction—the symptoms that we’ll see mainly of fatigue— are a byproduct of the fact that the body is shutting down energy production as a protective response. And so we want to intervene upstream so as to allow the body to shut off this defense response and therefore allow the mitochondria to produce the appropriate level of energy that they should.

Dr Ruscio:

We also discuss some of the limitations with adrenal testing. And Ari made a fantastic point that I was not aware of fully, that many adrenal supports actually also help to support and bolster not only mitochondrial function, but neurotransmitters function as anti-inflammatories. And so if someone says, “I felt better from adrenal support”, we should be very careful not to conclude erroneously that it was because there was some sort of adrenal dysfunction.

Dr Ruscio:

We went into what he feels to be the best mitochondrial test. Although, spoiler alert, you probably don’t want to perform this test. And we also had a nice conversation about a couple supplements that seem to be effective for mitochondrial function and when we should consider them. Because it’s not to say just because mitochondrial supplements are often overused in the field that we should never use them, but knowing the appropriate time and context to use them is important.

Dr Ruscio:

One thing, if you’ll humor me here, I’m trying to get better about doing is reading the guest bio before the actual conversation begins. So Ari is the founder of the Energy Blueprint System, a comprehensive lifestyle and supplement program, which has helped more than 2 million people around the world to have better health, performance, and energy. He’s also the best-selling author of the Ultimate Guide to Red Light Therapy, which we discussed on the podcast a few years back. And that was a great interview and fantastic book. He hosts the Energy Blueprint podcast and he has also been studying and involved in health for more than 25 years. He holds an MS in human nutrition and functional health and a BS in kinesiology with additional certifications in corrective exercise and performance enhancement from the National Academy of Sports medicine and has completed some coursework towards a clinical psychology PhD.

Dr Ruscio:

One of the things I really appreciate about Ari is he’s open minded and progressive, willing to seek out therapies that can help people, but he also has an excellent filter through which he passes various theories through scrutiny of a scientific lens. And you’ll hear how well versed he is in the scientific literature throughout the body of our conversation. So with that guys, we will now go to the conversation with Ari. And I’m sure you will benefit from this just really rich unpacking of this topic of mitochondrial health.

Dr Ruscio:

Hey, everyone, welcome back to Dr. Ruscio, DC radio. This is Dr. Michael Ruscio, DC back again with, I think third time appearance, Ari Whitten, who has written a few books. But he has a new book out today, Eat For Energy. And he’s discussed with us in the past many techniques for optimizing mitochondrial function and this should be a nice continuation of that. And so, alright. It’s great to have you back. I always appreciate your balanced evidence-based perspective on things. So it’s a pleasure to have you back because I always enjoy our chats.

Ari Whitten:

Yeah, me too. The feeling’s so mutual, I have an enormous amount of respect for your knowledge and how rigorous you are as far as digging into the primary literature and coming to your own conclusions. So, I really always enjoy our time together. And I think between your podcast and my podcast, this is maybe conversation number five or something like that.

Dr Ruscio:

Yeah. We’re racking ’em up. So tell us about the new book.

Ari Whitten:

So the new book is Eat For Energy: How to Beat Fatigue, Supercharge Your Mitochondria, and Unlock All Day Energy. And I’ve been studying nutrition and health science more broadly since I was a little kid. This is a lifelong obsession for me since I was 12 years old. I’m 38 now. And this is really the distillation of my over 25 years of study of that topic, specifically. Everything I know about nutrition as it relates to energy and optimization and mitochondrial optimization.

Dr Ruscio:

Now there’s a few things here that I’d love to unpack in a little more detail regarding some of the nuance applications for how do we need to optimize mitochondria. But before we get there, so as to make sure we don’t go to the 201 level discussion, maybe just frame for people from a high level a reminder what the mitochondria are, why they’re important, and then some of the basics in terms of mitochondrial health.

Ari Whitten:

Yeah, absolutely. So this is super important to understand. I’ll do a broad picture here before I talk mitochondria specifically. So my personal journey was that I dealt personally, when I was in my mid twenties, with severe chronic fatigue after a bout of heavy mononucleosis. And it left me debilitated for many, many months with severe chronic fatigue. And I saw a lot of conventional practitioners who had almost nothing to offer. And I saw a lot of alternative practitioners and functional health doctors and natural health experts, holistic health experts who universally were focused on the adrenals and the HPA axis and cortisol as an explanatory factor. And I ended up spending about a year of my life digging into the literature on, specifically, on adrenal function and HPA axis function as it relates to chronic fatigue, ultimately coming to the conclusion that the research really didn’t support the idea that the adrenals were the cause of fatigue. And really didn’t support the idea of adrenal fatigue, even the concept of that, as a medical condition.

Ari Whitten:

So there’s all kinds of theories out there as far as what controls human energy levels. A lot of people talking about cortisol and the adrenals, a lot of people talking about thyroid hormone or talking about testosterone and sex hormones and neurotransmitters and all these other AMPK and mTOR and NRF2 and this pathway and that pathway… The truth is there’s a million different mechanisms that are in one way or another related to energy production in the body.

Ari Whitten:

But what I’ve learned through digging into the literature obsessively for over a decade now is that the most upstream thing, the thing that is really controlling and regulating our energy levels, is actually our mitochondria more than anything else. And the mitochondria were taught to us in high school and college biology classes as these sort of mindless energy generators that just “they’re the powerhouse of the cell”. And their job is basically to take in carbs and fats and pump out energy in the form of ATP (adenosine triphosphate). And they are that, they are energy generators and they are incredibly important in that role.

Ari Whitten:

However, in the last 10 years, it’s also been discovered that mitochondria have a second role that is just as important as their role as energy generators. And that is they are involved in cellular defense. So it turns out mitochondria are also environmental sensors. They’re exquisitely sensitive environmental sensors. They’re basically like the canaries in the coal mine of our body. And they are constantly taking samples of the environment, basically of what’s going on in the body, basically asking the question, are we under attack? Is it safe to produce energy? And these two roles of energy production and cellular defense are two sides of the same coin, they are mutually exclusive.

Ari Whitten:

So to the degree that they are picking up on threats or dangers present in the body, they are turning down the dial on energy production and shifting resources towards cellular defense. So mitochondria are not just these mindless energy generators. They are actually the main thing that is deciding whether or not to produce energy. They’re deciding whether the body’s going to be in energy mode or defense mode and where on that spectrum the body’s going to operate.

Ari Whitten:

Now, if all of that sounds sort of abstract, here’s a couple of ways of thinking about it that will sort of make it sink in. Think of the last time you got a cold or a flu or COVID, what was one of the key symptoms of that? It was fatigue. Your body decreases energy levels in response to being under attack. And this general principle is widespread in nature. Many, many different animal species when they are….and probably this is really universal, but some sort of more extreme examples of it are, why doe a bear or many other mammals go into hibernation when the environment gets extreme, when the climate gets extreme?

Ari Whitten:

Because the body better survives a harsh environment by turning down the engines. So that’s one way of thinking about it. Another analogy that I’ll say here is sort of to understand why the body does this. Let’s say you and I were together in this moment and we were in the Ukraine somewhere. And all of a sudden the Russians started attacking. They dropped poison gas in the streets. It would be a terrible mistake for us to just go about business as normal and continue our sort of usual, typical daily routines; keep the windows of the house open, let the fresh air in, go for a walk outside in the park. Like what you do when you’re under attack is you seal things off, you close yourself in, and you stop your normal routines. And that’s exactly what our body does at the cellular level orchestrated by mitochondria. So fundamentally our energy levels, what’s regulating whether we have high energy levels or low energy levels, is a function of our mitochondria either operating in energy mode or defense mode. Our energy levels are basically a reflection of the degree to which our mitochondria perceive themselves to be under threat or not under threat.

Dr Ruscio:

Ari, slow clap for you. That was fantastic. It so beautifully maps on to everything that I’ve tried to bring to people’s awareness regarding gut health and how you can have inflammation in the gut. And this can lead to brain fog, fatigue, depression. It’s such an eloquent way of tying another layer of causality to so much of the observation that I see. It’s not necessarily your adrenals or the fine tuning of the thyroid function, but boy, if someone’s got a gut problem, SIBO, or something similar (not to say it’s only about gut infections but this is just the area that I see so much of) then this explains why you’re tired for so many of the occurrences. I didn’t realize that you would actually downregulate mitochondrial energy production. That is incredibly insightful to know, and I hope this is resonating with our listeners as much as it is for myself in that we want to stop looking at adrenals and thyroid as this ubiquitous cause of problems with energy. Sure, thyroid, if you’re frankly hypothyroid but outside of that, we’ve gotta start looking upstream. And just the way you phrased that was was beautiful. That’s absolutely fantastic.

Ari Whitten:

Thank you so much. And maybe I can just play off of what you just said and add a bit to it. There’s a paper called Fatigue and Overview, it was published in the Journal of American Family Physician several years ago, and it’s basically a compilation of the scientific literature. It’s meant to be basically “here’s everything we know about people with chronic fatigue and how to treat them, how to diagnose it, how to figure out what’s growing wrong with them, and how to treat them.” And so it’s essentially evidence-based guidelines for physicians, how to treat their patients with chronic fatigue.

Ari Whitten:

There was a few mind blowing things from this paper. One is they have four basic treatments to offer people with chronic fatigue, antidepressants, a recommendation to do 30 minutes of walking per day, cognitive behavioral therapy, and using stimulants as needed. That’s basically all they got. And we could talk a lot about that and the fact that, for example, nutrition isn’t even mentioned at all in the paper. And it’s supposed to be sort of the best of modern medicine, what they have to treat chronic fatigue. But they also say, this is more directly related to what you’re saying about thyroid and adrenals, they also talk about testing in people with chronic fatigue and they say, this is actually in the paper, they say that “only in 5% of cases does anything show up on the lab tests that is an explanatory factor in their fatigue.” Meaning 95% of the time, 95 out of every 100 people that come in with chronic fatigue have nothing detectable on their lab test that shows up that can explain their chronic fatigue.

Ari Whitten:

Now, I mean, that is pretty mind blowing in and of itself because so many people are walking around thinking “I’ve got these symptoms, I’m going to go to my doctor. And it’s 2022 with the best of modern medicine and all this sophisticated technology and all this fancy research, of course, they’re going to be able to do a blood test on me and figure out what’s causing my fatigue.” And 95% of the time they tell they can tell you nothing about what’s causing your fatigue. And in the 5% of cases, it’s usually something like anemia or diabetes, or maybe hypothyroidism or something like that. But these are not common causes of chronic fatigue. They are more the exception than the rule.

Ari Whitten:

Also, I mentioned before that I did about a year-long full-time obsession deep dive into the literature on fatigue syndromes, as it relates to adrenal function, HPA axis function, and cortisol. The very brief summary of a year of my life is this: that research overwhelmingly shows no discernible connection, no correlation whatsoever between cortisol levels, adrenal function, and the symptom of fatigue. None. So all of this is to say that in general, people who are sort of trying to explain chronic fatigue through the lens of thyroid function or through the lens of adrenal function are largely barking up the wrong tree. Yes, those can be factors sometimes, but they are not the majority of what’s causing the chronic fatigue epidemic.

Dr Ruscio:

And oftentimes the answer from the alternative medical community is, “well, your conventional doctor is using thyroid ranges that aren’t narrow enough and when we apply these ranges then we see, well, you’re actually low thyroid or sluggish thyroid.” But what’s so unbelievably irritating about this is in the model of subclinical hypothyroidism, where TSH is frankly high according to the conventional ranges (so your TSH shouldn’t be above 4.5 in subclinical hypothyroid) you might have a 5, 6, or 7; it’s been very well studied and documented that these patients don’t benefit from thyroid hormone replacement.

Ari Whitten:

Exactly.

Dr Ruscio:

But we also know that the placebo effect in randomized control trials can be close to 50% in some cases. So when Mary Sue (and there’s not a Mary Sue who I don’t like and I always pick on guys, but that’s just the example we always use in terms of the name you just throw on that avatar), when she goes and reads about the thyroid problem causing her thinning hair, her fatigue, her depression, and her constipation and then she goes and sees a provider and he says, “yes, it’s your thyroid take this pill, it’ll make you feel better.” And what do you know, when she says, “gosh, you know what? I think I feel better.” That will last for a number of months, but then eventually the placebo effect wears off. And people are left right back where they were before.

Dr Ruscio:

And the same thing with the adrenals. And I think the adrenals is even more misleading because some of the herbal treatments and vitamin treatments do improve energy, but they’re not doing so in the majority of cases because they’re correcting these abbarent adrenal findings because it’s a coin toss, so you said, if the person’s symptoms and the adrenal tests will match. But if you give someone ginseng or Rhodiola there’s evidence showing that these things help. And then that further entrenches, “well, it must be my adrenals and I need to do a lab test every time I’m not feeling well.” And this runs away and turns into a very ugly and unproductive scenario for patients, clinicians, I think are doing the best they can. They’re just operating underneath a lot of assumptions that are truly a priori, they lack any good evidence and they’re predominantly based upon theory. So this makes complete sense, again, very well said.

Ari Whitten:

Yeah. I actually love what you just said and I’m so happy you brought it up because I love talking about this particular topic because I find that not a lot of people understand it very well. And it actually rarely comes up in interviews so I’m relishing this opportunity. So if someone comes to me and let’s say I diagnose them with adrenal fatigue and then so they’re sitting there thinking, “okay, I’ve got adrenal fatigue. This explains all my symptoms. Wonderful.” And then I prescribe to them […] Rhodiola…ginseng…ashwaganda. I want you to meditate and start doing some deep breathing, relaxation practices. I want you to start eating more broccoli. I want you to get rid of the processed food. I want you to start an exercise regimen three or four days a week. I want you to start focusing on your circadian rhythm and sleep habits and get those dialed in. I want you to start sleeping an hour more per night. All of those recommendations are very, very likely to make dramatic improvements in that person’s health.

Ari Whitten:

And the tricky part is, given the context in which those recommendations were made. I diagnosed them with adrenal fatigue. They are convinced that the cause of their symptoms is adrenal fatigue. Then they go implement those changes, they notice those improvements, they are likely to conclude, “oh wow, all these things really fixed my adrenal function and now I’m feeling better.” Except all of those things that I just mentioned act on dozens of other pathways and mechanisms and systems of the body beyond just the adrenals.

Ari Whitten:

And in fact, for example, Rhodiola and all those different adaptogenic herbs that I just mentioned are well established to act directly on the mitochondria to stimulate mitochondrial biogenesis, mitochondrial growth, to upregulate the NRF2 pathway and the ARE (the antioxidant response element) to build up a more robust internal antioxidant system at the mitochondrial level. Of course, circadian rhythm and sleep have a massive effect on mitochondria, on many different hormones, and on neurotransmitters and many, many different aspects of our physiology. Exercise, same thing. Eating well, same thing. Meditating and relaxation, same thing. All of these things, it’s not like these are targeted adrenal interventions. They act on dozens of systems of the body and the mitochondria. So the point is we have to be cautious with how we interpret certain events and if our a priori assumptions are inaccurate, then our conclusions will also be inaccurate.

Dr Ruscio:

And this negatively leads to conclusion formation amongst patients, but also the healthcare provider, right? Because the healthcare provider comes back and thinks the same thing. And there’s another side to this, which is for those who have adrenal tests that are in the tank. And we published a case study in our clinicians newsletter about this about a year ago of a gentleman who was feeling pretty well overall, he was just trying to buffer some of the jet lag and circadian disruption from flying and having to do work from the US to Asia and his adrenal test came back “in the tank”. So he had to give up coffee, which he enjoyed. He had to cut back exercise, which he enjoyed. And he had to start taking boatloads of supplements, which he didn’t necessarily want to and didn’t feel any differently.

Dr Ruscio:

And so for some people, this stuff helps especially, as you so nicely said, that when we get people to make healthy changes that have a myriad of benefits, they’re going to feel better. But in some cases people are told, “well I know you really enjoy the CrossFit that you’re doing (let’s say a reasonable amount, not like seven days a week, let’s say you’re doing it two or three days per week and you’re recovering adequately and you enjoy the community) Sorry, Tom, can’t do that anymore. And the caffeine, really can’t do that. But you can have your lemon grass tea in the morning, which you’re probably going to hate.” So these things do add up and especially if we additionally weave into this, “well, we’ve gotta do a baseline test and then retest you in about six weeks.” And then you get pulled into a lot of spending and a lot of contortion of your lifestyle that in some cases you don’t need to do and may not serve you. In other cases may help you but were not really needed to be personalized based upon the tests.

Ari Whitten:

Exactly. I’ll also mention, just to add to that a bit, that there are some people who might be listening to this thinking, “well, I got my cortisol tested and I really do have low cortisol levels.” Okay. Well, as I mentioned before, the research does not support any correlation whatsoever between various fatigue syndromes. And this has been measured in many different fatigue syndromes from chronic fatigue syndrome to several other stress related exhaustion disorder, clinical burnout, burnout syndrome. 25 years of research all over the world that has tested the relationship of HPA axis function and cortisol levels to these various fatigue syndromes, and overwhelmingly that body of evidence shows no correlation between the symptom of fatigue and cortisol levels. But here’s what does show a huge correlation with cortisol levels, and that is something you mentioned in the case that you were just talking about, which is circadian rhythm disruption.

Ari Whitten:

It has been shown in several studies that, just taking healthy people, not even people with fatigue, but healthy people who have no symptoms who are either morning people or night-owl chronotypes and you measure their cortisol levels in the morning. And the night owls have literally half of the cortisol of a morning person. I mean, massive reduction in the level. We’re not talking like 5 or 10% lower that’s like, oh, you could say it’s statistically significantly lower. I’m talking half. I’m talking in, if you tested those people who, again, don’t even have the symptom of fatigue, they’re healthy people, but they’re simply night owls. If you tested their cortisol, if they saw a practitioner who believes in adrenal fatigue, they would walk out of that diagnosed with adrenal fatigue. And so that’s purely because of their chronotype, not because of having fatigue or chronic stress wearing out their adrenals or anything like that. So anyway, that’s one of the key factors that actually is linked with disrupted circadian rhythm of adrenal function and low cortisol levels in general.

Dr Ruscio:

And one other point here that I don’t know that this has been studied formally, but it certainly makes sense that if the standard protocol—at least from when I used to do the testing here which, gosh, was about seven years ago since I’ve ran an adrenal profile probably—but you were supposed to not use caffeine before the test. If someone’s habituated caffeine use and you take them off that, it’s almost like saying, “Hey, Joe, we have you on testosterone replacement therapy, but we’re going to check your levels, go off your testosterone before the test.” I mean, what do you think you’re going to find? So that’s another concern that I had that leads to a lot of false positives.

Ari Whitten:

100%.

Dr Ruscio:

And one other thing this has been, gosh, maybe two years since I’ve dove into this, but I do remember that the one test that seemed to have some correlation was the cortisol awakening response. And just wondering if you have any thoughts? Not that I think we should be advocating for the testing, because I don’t think the testing is really telling you the cause. And to your point, the awakening response, perhaps depending on chronotype may be a little bit falsely skewed. But is it fair to say that of the testing, this is the one that seems to have the most accuracy in quantifying something that shouldn’t be quantified to begin with? But is this one maybe fair to say is the most accurate?

Ari Whitten:

Yes, definitely. It is. But you said that it’s correlated, I would ask you correlated with what?

Dr Ruscio:

Right. Yeah. And so this, I think is a key question to ask and it may have been, I’m not sure what they correlated against, but I guess what you found when looking at it was a subjective wellness measure that it was attempted to be correlated to show poor agreement between the test and, let’s say, subjective wellbeing or energy indices, I’m assuming.

Ari Whitten:

So this is where looking at the full body of evidence becomes really important. Because depending on what I want to convince people of, I can go cherry pick a study or two that supports almost any narrative. So let me give you a specific breakdown. And I actually have all of this published, including the screenshots of all of these dozens of studies that examined cortisol levels. The vast majority of these studies basically just take a group of people with chronic fatigue syndrome or burnout syndrome or clinical burnout or stress related exhaustion, any of these fatigue syndromes, and they take an age matched, gender matched group of healthy people (control group) and then they basically just measure their cortisol levels. And if the adrenal fatigue hypothesis is true, this is extraordinarily easy to verify from this study. This is science 101.

Ari Whitten:

If it’s true that the major factor driving most people’s stress-related fatigue is poor adrenal function and abnormal cortisol levels, these studies will show that very easily. And there have been 59 studies done all over the world over about 25 years that have done these kinds of studies and of these 59 studies, 15 of them gave evidence for slightly lower morning cortisol levels in a morning awakening cortisol response, which is what you were just referring to. So, slightly lower, not abnormally low, but you could say statistically significantly lower than the healthy control group. 11 of the 59 studies found the exact opposite finding, slightly higher morning cortisol levels in the group that’s fatigued relative to healthy people. And 33 of the 59 studies found no discernible difference whatsoever in cortisol levels.

Dr Ruscio:

Why we shouldn’t cherry pick. This is a fantastic overview.

Ari Whitten:

Exactly. So If I was inclined to cherry pick, I could go find the minority of studies that showed that it was linked with slightly lower cortisol levels and I could say, “aha, adrenal fatigue is real, you see, look at this study.”

Dr Ruscio:

And write a compelling article, right? Citing study after study after study supporting your position. But that would still be leaving out the majority of the data. It’s so challenging, I think, to be a health consumer. And sometimes I feel so, so bad for healthcare consumers who are trying to educate themselves because you can be very convincing, but you can be making a convincing argument out of really poor data.

Ari Whitten:

Exactly. And that’s 100% true. In fact, you have 15 studies to pull from to make that argument right. And as long as you ignore the other 44 that didn’t support that conclusion, then you can make a really compelling argument.

Dr Ruscio:

That’s fantastic. You remind me when you made the earlier comment, which was also fascinating by the way that the adrenal supports oftentimes support mitochondrial function. One of the things that we don’t do much of in the clinic is direct antiviral support. Sometimes you’ll see improvements with antivirals, but the more I looked at them, a lot of these antivirals are also either immune modulating, meaning they’re antihistamine as one example, or they may be antimicrobial. And I think the small signal that we were getting from natural antivirals that is having some sort of benefit were likely due to being antihistamine for those people who had a problem with histamine intolerance or modulate the microbiata. So I’ve seen something similar in my own right, where we could have falsely concluded that we were seeing benefit from antiviral function, but it was probably some of the other benefits conferred from natural medicines. And that’s one of the challenging things, it’s both beneficial but perhaps more amenable to misreading the fact that many natural agents act on multiple pathways.

Ari Whitten:

Yes. 100%. I think that’s, that’s so important.

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Ari Whitten:

To give you an idea there’s research, let’s say on Rhodiola rose as an example, looking at multiple actions, there’s research on it looking at how it modulates the HPA axis. Okay. There’s also research looking at how it modulates mitochondrial functions. Well-established lots of research. There’s also research looking at how it modulates neurological function and neurotransmitter levels in the brain. That’s another mechanism of how it affects energy and mood. There’s also research on how it modulates levels of inflammation, which is another mechanism of how it works. There’s research looking at it in terms of anti-anxiety and anti-depression depression effects, which is part of how it’s going to mediate you feeling better, right? There’s so many mechanisms of action of just that one compound. And this is just to take one example. If we look at exercise, we can show a similar effect, right?

Ari Whitten:

Exercise doesn’t just work your muscles and make your muscle stronger or even just your cardiovascular system, it helps prevent diseases throughout almost all the systems of your body. Like why would exercise help prevent neurological disease? But it does. Why would it help alleviate depression? But it does, right? It’s not working the brain necessarily in any sort of direct way. That’s not what it’s targeting. It’s like you’re lifting weights and targeting your muscles or you’re going for a run. Why would we expect brain diseases to be lowered by that? And this really, I think gets at a broader concept that I really harp on a lot and I don’t think gets enough attention and appreciation, and that is that every system in the body is connected and nothing occurs in isolation. We almost never just have one problem in the body. Like you specialize in the gut; there’s a gut-brain axis, what’s going on in the gut affects what’s going on in the brain. There’s a gut-lung axis. There’s a gut-immune axis. There’s a gut-skin axis. There’s a gut-mitochondria axis. What’s going on in the gut massively impacts mitochondrial function.

Dr Ruscio:

Gut-butt too right? We’ll go with that too. There’s a gut-constipation connection. So we can go there too.

Ari Whitten:

Yeah. And if we look at something like circadian rhythm and sleep, this affects so many different neurotransmitters, so many different hormones, it affects your mitochondria, it affects what’s going on in your brain, it affects autophagy and mitophagy, I mean, it’s affecting everything. So to go back to what we were talking about earlier, where people are looking for sort of the one thing, “oh, it’s your thyroid, your thyroid’s out of whack. We’ll just supplement. We’ll just use some thyroid hormones,” or “it’s your adrenals. We’ll just use these adrenal supplements,” or “it’s this one thing, it’s that one thing.” It’s almost never one thing in the body.

Ari Whitten:

Everything is interconnected and I really argue that if we want to optimize things, we want to figure out what the key levers are that we need to pull to reverse downward spirals of worse and worse physiology in all these different systems of our body and turn them into positive upward spirals, create more positive inputs into the system at the level of nutrition, at the level of the gut, at the level of removing toxicants, at the level of psychological stress, at the level of body composition and blood sugar levels, and circadian rhythm and sleep and light deficiencies and toxicities. We start to pull on these levers and we can create positive, upward spirals of physiological input that improve the health and the function of every system of our body.

Dr Ruscio:

Exactly. I mean, treating these things as far upstream as we can. And I think we’re all on the same page in that regard, but unfortunately there does seem to be this drift in the field toward reductionistic [application of] natural medicines in a model that seems to be more conventional medicine in it’s framework. And that’s where we have to be, I think a little bit careful. And so then that would pose a question of, with what you’re trying to bring to the forefront regarding mitochondrial health, it’d be the same thing and knowing you and pulling from our past conversations, I know this to be the case where you’re not zooming in on, “well, here’s the specific test or here’s some speculative electron transport test, and we’re looking for these ratios. And if you don’t have those ratios, here’s a highly uber specific reductionist supplement plan that’s going to target and treat those lab values.” But rather, as you said, look at these things like circadian disruption and like factors and try to intervene as far upstream as we can.

Ari Whitten:

Yeah. There’s obviously a value of tests and there are certain tests that have really good, amazing clinical utility and can be extraordinarily helpful in identifying a problem. But it’s also the case that functional health is riddled with tests that are not well validated and that are largely speculative. And that test may not even have much usefulness at all. And SIBO testing is a great example of this, the hydrogen breath testing, which I know you’ve talked about as compared to like glucose breath testing or using multiple of the different breath tests. Food intolerance testing is notorious for being inaccurate. I mean, you can send the same exact sample but with different names on it and get totally different results back. And there are many other examples like this of tests that are commonly used that are just not well validated.

Ari Whitten:

Conversely, within the conventional medical realm, I already mentioned that they do testing that is clinically well validated. But the problem with it is that it only identifies something in five out of every 100 cases for people with chronic fatigue. So we have enormous limitations. I would say our testing for fatigue and mitochondrial function is even way more limited in terms of accuracy and clinical validity. Then let’s say like gut testing, like a lot of the testing you do, which many of those tests do have strong validity.

Dr Ruscio:

And let’s linger here just for one second, because I wanted to ask you about, and this comes up once every few months when we discuss mitochondrial function, any testing that you like. When we had John Kaiser on the podcast, he had mentioned the seahorse test. We looked into it. I believe it was an electron transport chain, one through four assessment that could be done via a buccal swab. We looked into it, but the more we looked into it…I mean maybe, but you really have to be making a lot of inferences to use that test in clinical practice. Now we could have, right. And we could have put together a whole spurious argument about your mitochondria need to convert these electrons and this is the backbone of ATP. And we could have probably convinced people that they needed this test, but obviously we don’t do that. We try to do the exact opposite of that. But just to impress the point that if you fish for enough cherry picked mechanisms and spin those into an attractive description, you can motivate people to buy or to act. But it’s vitally important that we pass this stuff through a filter of, will this allow us to do anything that we could not have done otherwise?

Ari Whitten:

Yes, 100%. And let me add a few nuances to what you just said specific to this topic of mitochondria. Okay. So there are several tests that are available. There’s one, the one you mentioned, there’s the Mito swab test. There’s a test from some chronic fatigue researchers out of the UK, (Sarah Mayhill and a few other scientists who created an ATP profile test that tests mitochondrial function and they’ve actually validated that that’s linked with chronic fatigue). There are a number of other studies that have found certain markers associated with mitochondrial function, carnitine, Coq10, things like that are lower in people with chronic fatigue. Some of those things are not easy to test for.

Ari Whitten:

There’s other limitations though, that are important. We have to be cautious with some of the assumptions that we’re making. So a test that tests for mitochondrial dysfunction is not necessarily the same as what I’m talking about. So let’s say that you get a flu tomorrow and you’re fatigued. Okay. You have fatigue as a symptom of that flu that is happening to you in this moment. That is not because from today where you’re feeling good and healthy and tomorrow where you’ve got the symptom of fatigue, because you have a flu. It’s not because you have widespread mitochondrial dysfunction all the time throughout your body. It’s actually the result of mitochondrial shutdown of what’s called the cell danger response. Okay. This is what I was explaining before. It’s this dual role of mitochondria where they, in response to being under attack—whether that’s a pathogen or psychological stress or poor nutrition or poor gut health and leaky gut and endotoxin leaking into the bloodstream or other byproducts of dysfunctional gut health or sleep deprivation or any number of other stressors—they are turning down the dial on energy production. That doesn’t mean that they are dysfunctional. It means they are switching out of energy mode into defense mode.

Dr Ruscio:

And the test don’t delineate this, right? You’re just seeing the end result, almost like analogous to the person who stops drinking caffeine and then they have a poor adrenal test. Again, we’re not recommending these tests because the validity is questionable, but just looking at that one example of you may have a false positive in that case. And you may see a falsely low mitochondrial function test because what you’re seeing is a quantification of the end result not necessarily at the cause.

Ari Whitten:

Exactly. That’s exactly right. And there’s one other nuance here, which is, there’s actually another type of mitochondrial testing that could be done. This is not done in any widespread way, but it’s been done in some research and I would actually argue that this would be a useful and very insightful way to test mitochondria. And that is to (this is going to sound really primitive), but it is to physically count the number of mitochondria in your cells. Okay. So let me delve into this a bit because basically the way I conceptualize energy there’s two fundamental causes: one is what’s going on in the environment and lifestyle level (terms of psychological stress, environmental toxicants, gut health, body composition, circadian rhythm, sleep, nutrition, all these types of things), the other thing is what is actually the status of your mitochondria in your cells?

Ari Whitten:

And what I mean by that is it is possible to have cells filled with big, strong mitochondria and lots of them, or it’s possible to have cells with weak, fragile, small mitochondria, and very few of them. So you literally have much less mitochondria. Let me give you some specific numbers and data on this. It’s been shown that when you measure the mitochondria, the mitochondrial capacity of a typical 70 year old, they on average have only about 25% of the mitochondrial capacity of a young adult. And it’s been shown in studies.

Ari Whitten:

And the way that they do these studies, this is the type of test that I’m referring to, they take a big hollow needle and they jab it into your thigh and they pull out a chunk of your quadricep muscle and they look at it under a microscope and literally count the number of mitochondria in your cells. And they can do that with a 20 year-old and a 40 year-old and a 50 year-old and a 70 year-old. And they’ve done these studies. And what they’ve shown is that mitochondrial capacity (basically the number of mitochondria you have in each cell) declines on average by about 10% with each decade of life. So again, the typical 70 year old has only about 25% of the mitochondrial capacity of a young adult. In other words, they’ve lost 75% of their mitochondrial capacity.

Ari Whitten:

Now actually just to make the point, loop it back in with testing, I would actually argue that if that type of testing was easy to do, if it didn’t involve sticking a big hollow needle in your thigh and taking a chunk of muscle tissue out, which is pretty painful and most people don’t want to do that, that test would actually be extraordinarily insightful because how many mitochondria you have in your cells, your total mitochondrial capacity is enormously important to determining your cellular energy producing capacity. And since mitochondria have this role in responding to and dealing with threats of various kinds, the total number of mitochondria that you have is also massively important in determining what I call your resilience threshold—the level of stress load that your cells can tolerate before they are overwhelmed and start shutting down into defense mode and you experience the symptom of fatigue.

Ari Whitten:

So in other words, a person with big, strong mitochondria and cells filled with lots of them is going to have a much higher resilience threshold, a much higher capacity to tolerate stressors and maintain health and homeostasis and high energy levels. Whereas a person with very few mitochondria in their cells, those mitochondria are going to be much more easily overwhelmed and sent into defense mode and energy mode turned off.

Ari Whitten:

And the last thing I’ll say on this, just so it’s not all pessimistic bad news, is people might be listening to what I just said and think, wow, I’m 60, I’m 65. This really is awful news that we lose so much of our mitochondrial capacity as we age. Well, the good news is it’s actually not just a normal product of the aging process itself. And the reason we know that is because if we look at 70 year olds who are lifelong athletes and exercisers, they have the same mitochondrial capacity as a young adult. So what that means is the loss of mitochondria is actually a product of lack of hormetic stress, lack of challenging your mitochondria through hormetic stressors, like various types of exercise, breath-holding practices, heat exposure, cold exposure, phytochemicals, [etc]. And the other good news I’ll mention here is not only can this loss be prevented, but it can be reversed to a large extent by adopting hormetic stress into your life. You can actually stimulate what’s called mitochondrial biogenesis, the creation of new mitochondria and you can build back, maybe not all the way to when you were a 20 year old, but you can move a lot in that direction.

Dr Ruscio:

I didn’t know that breath holding was a stimulus, but I guess it’s probably a similar hormetic stressor of causing hypoxia-like exercises and that’s going to create this healthy adaptation. But that’s fantastic. And I just love the entire framework of… And sure, Coq10 and the like supplementation, for that. But I think the thing we want to we’d want to make sure, and correct me if there’s any nuance here that maybe I’m glossing over, but we want to get these foundational pieces in place first and look at the supplement truly as a adjunctive support, cherry on top. But if someone’s not sleeping well, has a poor circadian rhythm, is not exercising, and isn’t maybe doing sauna or contrast therapy, what have you, these are really important foundational aspects to have in place first and should be weighted with equal or more emphasis than some sort of, even an evidence-based, mitochondrial supplement. As good as I think those can be and of which I use. Having this perspective I think is important and where I think it becomes the most pernicious is for those who aren’t feeling well. There does seem to be—and I’ve been there, so I’m not pointing a finger, I’ve fully felt myself get pulled into this—the worse you’re feeling, it seems the more the exotic thing/supplement/magic bullet seems to have appeal. And these other things are ignored.

Ari Whitten:

Yeah. I have to say I’m actually shocked at the level at which foundational nutrition and lifestyle habits are ignored in favor of exotic solutions. And I will also say that, in general, a lot of functional health practitioners are guilty of facilitating that trend. And you’re not, but many, many of them are because there is this attitude that I’ve seen so many people take of almost assuming that everybody is already dialed in, in terms of their nutrition and lifestyle habits. And then of course, they’re brushing that off. Of course, they’ve got all that stuff dialed in. Everybody knows that. And now we need to do the testing to figure out what supplements they need to be on for their thyroid or for their gut health or for this neurotransmitters or adrenals or whatever.

Ari Whitten:

There is an immediate jumping to exotic solutions and testing a person’s unique bio individuality and tailoring these custom solutions. And I would really argue while of course there is a time and a place for that, where it is absolutely enormously helpful for the percentage of people who are genuinely have tried everything and really have dialed in their nutrition and lifestyle habits to a very high level and still have some symptoms that we need to do detective work and troubleshoot and figure that out. But a couple ways, a couple things that I think are important to think about in this context, number one, the rates of things like obesity and diabetes and cancer and heart disease and neurological disease are skyrocketing in recent decades. It’s not because of people’s unique bioindividuality that all of a sudden is causing rates of these diseases to go up by 300, 500, 1000% percent in the span of a few decades.

Ari Whitten:

It’s not their unique genetics. It’s not their unique biochemistry that all of a sudden decided to cause these epidemics of all these different diseases and chronic fatigue. It’s also the case that over 80% of the chronic disease burden—all those diseases, like the ones I just mentioned, and many others—are diseases of nutrition and lifestyle. They’re not diseases of individual genetics and biochemistry, they’re diseases of nutrition and lifestyle. And what is going on at the environmental level and at the lifestyle level, and at the societal level.

Ari Whitten:

So to put this another way […] let’s say you owned dozens of zoos across the world and all the tigers in your zoos started getting cardiovascular disease and they started becoming obese and diabetic and depressed and chronically fatigued. The solution to the rise of that epidemic and all those tigers in the zoo is not to do individualized testing and figure out what each one of them, their unique biochemistry is, and then tailor custom solutions for each one of their unique biochemistry based on all the testing. And so on. What you should realize is that the epidemics of those problems in those tigers don’t exist in natural tigers that are still living in the wild and you need to go, why is that the case? And if that’s the case, if tigers living in the wild don’t have all these diseases, maybe what we should do is not a whole bunch of individualized testing and customize supplement and drug protocols to treat their individual biochemistry. But we should modify their fundamental lifestyle and environment to mimic that of the healthy tigers that don’t have any of those diseases.

Dr Ruscio:

That’s a fantastic analogy. As you’re saying that I’m seeing this split screen in my mind, on the one hand, your analogy coming to life. And then on the other side of the screen, I’m envisioning this screenshot that one of the doctors in our clinic sent to me in our, our group WhatsApp. And it was a screenshot of, I’m not going to name the body, but it’s one of the biggest educational bodies in functional health. And it was their treatment guidelines for mitochondrial dysfunction. And it’s essentially 16 supplements. Period, nothing else. And this is where a lot of this comes from is supplement company influence combined with this reductionistic educational appeal where for some reason, some providers still think the doctor up there on stage—who says the most pleonastic argument with all these details, some of what you can understand some of what you can’t, but you can’t quite understand it so it means they’re really smart and you better pay attention and just do what they say—still resides as a preferential method of education. And that’s how we end up where we are. So yeah, I totally get where you’re coming from and I appreciate you making the points.

Ari Whitten:

Yeah. 100%. And what I talk about a lot in my new book is really it is nutrition and lifestyle, right? And what I’m trying to do is help people understand the connection of these nutrition and lifestyle habits and environmental things with our energy, with the mitochondria, to understand the mechanisms of how they connect. For example, circadian rhythm, how that ties into mitochondrial function. Just to name a couple examples, circadian rhythm and sleep tie into autophagy and mytophagy. This process of breaking down dysfunctional mitochondria, rebuilding healthy new ones every night while you sleep, that depends on healthy sleep and an optimal circadian rhythm. We also know that melatonin is not just a sleep hormone. Many people think it’s just a sleep supplement. It’s not just a sleep hormone. It is actually the most important mitochondrial antioxidant there is.

Ari Whitten:

We have just standard indoor room lighting is suppressing our melatonin levels by upwards of 70% every night. So you’re suppressing levels of this critically important mitochondrial protective compound that gets into our mitochondria and actually recharges the internal ARE (antioxidant response element). It recharges our internal antioxidant defense system with glutathione and catalyses and superoxide dismutase so that mitochondrial protection system and detoxification system can work properly the following day. So if your sleep and your circadian rhythm are not optimal, your mitochondria are suffering through multiple different mechanisms. Body composition, how much fat and muscle you have ties directly into your mitochondrial function through things like, for example, insulin resistance and oxidative stress and levels of inflammatory cytokines. Those inflammatory cytokines that are literally being produced by the fat cells on your body when you have excess body fat are directly toxic to mitochondria and mitochondria sense the presence of those inflammatory cytokines and respond to them as a danger signal.

Ari Whitten:

So purely by having excess body fat on your body, your mitochondria are always responding like there’s danger present in the body. We also know that what we eat and how and our body composition ties into our blood sugar regulation. Over 80% of people are experiencing daily spikes into the prediabetic or diabetic ranges of blood sugar after eating meals. Another 1/3 of adults experience hypoglycemia, reactive hypoglycemia, 2-5 hours after eating a meal. Both of those are mitochondrial stressors. And this is ubiquitous. Like I said, over 80% of people.

Ari Whitten:

We also know of course, gut health is a massive factor and how widespread gut health problems are in the world today. And there’s a very direct link, a gut-mitochondria axis. And what’s going on in our gut has a huge impact on our mitochondria. What’s going on in our brain has a huge impact on our mitochondria. So once we start to understand these different mechanisms of how nutrition and circadian rhythm and the factors that affect our body composition and our blood sugar regulation, how these are tying into our mitochondria, we can start to really understand that connection with nutrition and lifestyle. Instead of just having our understanding of mitochondria be disconnected from nutrition and lifestyle, where we just think, “oh, if you have mitochondrial dysfunction take some Acetyl-L-carnitine, take some Coq10, take some PQQ.”

Dr Ruscio:

By the way, very well said,

Sponsor:

Hi, everyone. If case you are in need of help, or would like to learn more, I wanted to quickly point out what resources are available to you. “Healthy Gut, Healthy You”, my book and your complete self-help guide to healing your gut. If you’re not a do-it-yourselfer there is always the clinic and myself or any one of our doctors would be more than happy to help you. And as a quick aside there, we just had accepted for peer review a six-part case series where in we demonstrated the gut-thyroid connection and how crucially important it is to make sure you are not overlooking someone’s gut health as it pertains to thyroid health and thyroid symptoms more broadly. Through the clinic we also offer health coaching. And independent of the clinic, if you’re reading the book or need some general advice, we offer health coaching also. There’s our store where you can find our Elemental Diet line, our probiotic line, and other health and gut-supportive supplements. And finally, there is our clinician’s newsletter, the FFHR, AKA the Future of Functional Health Review database with research reviews, case studies, and other helpful resources for healthcare providers. Everything for any of these resources can be found at the overview page DrRuscio.com/resources. That’s DrRuscio.com/resources.

Dr Ruscio:

This next question just popped up in my mind, which is I’m assuming that for those who are recovering from presumed mitochondrial defense syndrome, if you will, this is where you’re going to want to do maybe two things in parallel and please correct me or adjust the nuances to whatever you see fit, but you’re going to want to address the causal factors, of course, and that might be partially lifestyle and diet. There might be some sort of infection or overgrowth also in this same umbrella of addressing the cause. And then in tandem, I’m assuming this is where nutritional support for the mitochondria are a nice lever to help facilitate the causal changes that you’re deploying at the same time.

Ari Whitten:

100%. Yes. And I don’t have any opposition to using mitochondrial targeted supplements at all. And I think they’re wonderful. There’s a whole chapter in my book, which is it’s an awesome chapter, and it’s packed with information you really won’t find anywhere else though. That chapter is really worth the price of the book itself. It’s talking about so much amazing science about all these different compounds that are proven to enhance mitochondrial function and improve energy levels. So I have no opposition to that at all. It’s an important tool of in the arsenal. It’s also an incredibly important tool for a specific context of person who is severely chronically fatigued, who is burnt out, who feels like they have tried a whole bunch of stuff, they’ve spent thousands of dollars, they’ve seen a whole bunch of practitioners, and they still are suffering from those symptoms and they maybe don’t have the energy and the drive to go do more intensive lifestyle alterations.

Ari Whitten:

In those cases, there are supplements that have been shown to massively improve energy levels in people with stress-related fatigue and exhaustion. In a matter of, some studies have shown as much as 50% reductions, in seven days or 30-40% reductions in 4-8 weeks. So even though I philosophically position supplements as supplementary to the foundations of good nutrition and lifestyle habits, in that particular context, it can actually be appropriate to start with some of these supplements, to give somebody some energy to get going, to start see some results pretty quickly with very low effort things. And then from there now they have the energy to start to implement some of those foundational nutrition and lifestyle habits.

Dr Ruscio:

You make a great point, which is this cohort that has maybe said loosely this post exertional fatigue, you’ll see some great improvements as you improve their gut health, but that doesn’t work for everyone. And I think any provider who says “we do this and it works for everyone, they’re either biased or they’re lying.” And I can say in the clinic we have very good results with the swath of therapies that we use, which would include gut health, hormone, health, diet, lifestyle, and the sleep apnea piece is becoming increasingly important for a smaller subset of people, but for others I do see there being merit for this. And I’ve experimented with a few people. I don’t feel like I have my hands around this fully yet, in terms of the formula. And you sent me a sample of, I believe it was mitogenesis is the name of the formula that you made, and I’m wondering…

Ari Whitten:

Energenesis.

Dr Ruscio:

Energenisis, thank you. Would this be the formula that you would say for someone in this position, now I’m asking selfishly as a clinician, would that be where you would start someone or is there a different supplement? Or is the question not that easy to answer?

Ari Whitten:

Yeah, no, that’s the supplement for sure. And I’ll just mention some of the research on just one of the compounds in this—and there are many compounds in there that have proven energy boosting effects in studies between 4-12 weeks, huge benefits—but this is just one that has amazing research on it that most people are unaware of. It’s called NT factor. It’s a phospho lipid supplement. There’s an amazing paper by a researcher called, named Garth Nicholson who wrote a paper called lipid replacement therapy. And this specific patented extract of phospho lipids (and phospho lipids for people that don’t know also make up our cellular and mitochondrial membranes, things like Phosphatidyl Choline and Phosphatidylethanolamine and several others) and this patented form of phospho lipids has actually been tested in numerous studies in people with various kinds of chronic fatigue.

Ari Whitten:

They’ve tested people with chronic fatigue syndrome. They’ve tested people with aging associated chronic fatigue, with obesity related chronic fatigue, with Gulf war illness, with several other conditions and numerous studies on each one of those. And those studies have consistently shown 30, 40% improvements in energy levels in as little as three weeks. And some of these studies go out to 8 weeks or 16 weeks, but massive improvements in energy levels just by doing this one thing. And the reason why, the mechanism, is actually those phospho lipids get digested intact and actually make it to our cells where they end up helping to replace and repair damaged mitochondrial membrane so mitochondria can work better and produce more energy.

Dr Ruscio:

That’s fantastic. Okay. Now this is a good reminder for me to consider experimenting with this in that cohort of individual. And this also leads to one other question I wanted to ask, which is for some people, and this includes myself, I do not do well on keto and trying to do fasting of more than a day, a kind of pseudo-strict water fast, my sleep that night will be hellacious. I mean, I won’t even be able to sleep until I eat something. And this is even after taking something like Unisom. Do you see this as evidence of a mitochondrial problem? The context would be important as for someone like me who is in generally excellent health, but also has a fairly heavy training regimen and cognitive load associated with his work. Would you consider it normal for that sort of person not to be able to tolerate something like Keto or extended fasting? Or do you see that as an indicator of some other item being out of whack?

Ari Whitten:

Well, if it wasn’t you saying that to me, someone who I know is in great health and like great fitness, I would suspect metabolic inflexibility. But no, to be honest, I don’t have a good explanation as to what’s causing that for you. I would suspect there’s probably just maybe some genetic aspect as to why you, your physiology, is not very tolerant of longer periods of fasting. I would say, like you, I also don’t do great on keto. My body definitely likes to have carbs in the diet, but I am actually tolerant of fasting. I have no problem with fasting and I can…

Dr Ruscio:

Multiple day fasting? Cause I can fast a day and I’ll feel great, but if I don’t eat anything and then I try to go to sleep, I just, I won’t sleep well.

Ari Whitten:

I’ve never done anything beyond three days of total fasting.

Dr Ruscio:

Okay. That’s more than I’ve done.

Ari Whitten:

I know my brother, who like us is, is also very fit and healthy. He’s done some five day fast and he actually says he sleeps great. He sleeps better, which I haven’t experienced that either. But yeah, I don’t know. I wouldn’t know how to explain your issue there. I would just say don’t try to force it since you’re already in good health, right? Like there’s no sense in forcing yourself to go experience hellacious sleep. That’s only going to make your health worse.

Dr Ruscio:

Well, that’s the other thing I’m wondering, have you seen anyone who maybe needs to push through one bad night and then there’s this metabolic switch that flips?

Ari Whitten:

I haven’t. The research I’ve seen on fasting thus far is not that compelling. And a lot of it is cherry picked. Like there are some, a lot of it’s based on animal models where they extrapolate from these animal models, but the effects of long term fasting actually vary considerably, depending on the genetics of the animals you’re studying, depending on the genetic strain of the specific mice or rats that are being studied. They actually have widely varying responses to long term fasting and some don’t experience any longevity benefits at all. Some experience big longevity benefits. So some of the research that’s been done linking fasting with longevity is actually cherry picked in that regard. It’s specific genetic strains of mice that respond with the longevity benefit.

Ari Whitten:

Overall, I would say that my impressions are this: I am open to the possibility that longer term fasting probably does has have some unique benefits in terms of maybe activating stem cells or rejuvenating immune function or gut health or something like that. However, I am, I would say the majority of the evidence I’ve seen has not made a compelling argument for why it’s really important to do long term fasting, as opposed to optimizing our daily feeding and fasting windows and having an adequate fasting window every night. 14 or so plus plus hours each night I think takes care of a lot of those benefits of Autophagy and Mitophagy, and many of the other benefits of fasting.

Ari Whitten:

Again, I think there’s probably some unique benefits of extended fasting, but it’s also the case that there are some harms from that. Not just the subjective discomfort of hunger pings and fatigue from not eating, or in your case and probably many others, disrupted sleep. And maybe from blood sugar and people who are not in great health, they may have blood sugar regulation problems with extended fasting. And loss of muscle mass, which is something that most people don’t have a lot of muscle mass to spare or to lose. And so I, as of right now, I would say I don’t regularly engage in longer term fasting because I have not seen really compelling evidence that the benefits of that outweigh the downsides.

Dr Ruscio:

Sure. And you also make a good point, which is maybe we could cherry pick study of someone who has metabolic resistance and fasting works really well for them. But if you’re looking at a fairly healthy cohort who has a lot of these things dialed in, does fasting offer any additional gain over just getting to a good place with your macros, your calories, and having some intermittent fasted window on most days?

Ari Whitten:

Exactly. And in general, the research that compares—I mean, this is not a perfect illustration of the point you were just making—but there are studies that compare daily calorie restriction to intermittent fasting approaches and in general, they show no significant differences between the two groups. They show them equally effective in reducing weight and improving metabolic health.

Dr Ruscio:

Right. Yeah. And this is why I think the meta-analyses are so helpful because, like you said earlier and like we’ve discussed so many times on the podcast, you can cherry pick one study, but that may not be something that’s been replicated a number of times. So important to get the meta view whenever we can.

Dr Ruscio:

Well, all right. This has been fantastic. Tell us again where they can track down the book and or any website you want to point them to or anything else you want to announce.

Ari Whitten:

Yeah. Thank you so much. The best place to go is just wherever you want to buy books online, go to Amazon and grab the book. Again, it’s called Eat for Energy: How to Beat Fatigue, Supercharge Your Mitochondria and Unlock All Day Energy. And, Dr. Ruscio, DC thank you so much for having me. It’s really always a pleasure to chat with you. I really enjoy our conversations and this one, especially.

Dr Ruscio:

Yeah, same here my friend. Really appreciate it. Take care. We’ll talk to you soon.

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