Mitochondrial Dysfunction, Not Adrenal Fatigue

Deb Matthew, M.D.

Hey, thanks so much for having me. It’s great to be here.

Laura Frontiero, FNP-BC

Oh, I’m so excited for you to be here because we’re gonna be talking about a really big topic, the topic of adrenal fatigue. And actually we’re gonna unpack why current thinking around this concept has shifted, and that perhaps the real problem is mitochondrial dysfunction, not adrenal fatigue. So we’re gonna dig into that. And you’re super qualified to talk about this, you are the happy hormones doctor. You’re known as that, you’re our bestselling author, an international speaker, an educator, a wife and a mom of four boys. I can’t even imagine what it was like having a busy medical practice and being a mom to a big family as well, you’re just amazing. But you actually have a personal story where you suffered for years with fatigue and irritability and you had hormone imbalances, that was the underlying problem. And you really had this quest to resolve your personal health problems, and that led you to change everything about your practice of medicine. And since then you’ve been featured on podcast, radio, TV, you’re all over the place. NBC, ABC, CBS, Fox, you’re really an authority in this space. So I’m grateful that you’re coming to share your wisdom today, thank you.

Deb Matthew, M.D.

I’m glad to be here ’cause I’ve lived this so I unfortunately and sadly have firsthand experience with adrenal fatigue, mitochondrial dysfunction, et cetera.

Laura Frontiero, FNP-BC

Yeah, so let’s unpack that right away. Is it that your adrenals are broken or is it that your mitochondria can’t generate energy? So let’s talk about that current thinking on the concept of adrenal fatigue, and how that’s shifting in the space.

Deb Matthew, M.D.

Yeah, personally, I kinda like the name, the idea adrenal fatigue ’cause people can understand that they’re fatigued and there’s some kind of a problem with their stress system. But the reality is it’s not your adrenal glands that are broken. Really, what we’ve come to understand is, initially, the problem is that the signaling between your brain and your adrenal glands is off-kilter. So your brain recognizes when there’s stress and it tells your adrenal glands if it’s supposed to be making cortisol. And so cortisol levels can change because the system, the messaging system is out of kilter. But what we’ve really come to understand, even deeper than that, is that our mitochondria are actually intimately involved in this whole stress response. And of course your mitochondria are like Energizer batteries that are generating energy for you. And so if they are not doing a good job at generating energy, of course you’re gonna feel fatigued. And so while I like the concept, it’s easy for people to understand the idea, “I’m fatigued. Something’s wrong with my stress system, my adrenals,” in reality, it’s not even coming close to explaining what’s really happening in your body.

Laura Frontiero, FNP-BC

Well, I love how you said your mitochondria are intimately connected here, it is. I mean, we are the product of what’s happening at the cellular level in our body. And I think you’ve run probably thousands of adrenal tests on people and I’ve run thousands of adrenal tests. And what we see oftentimes is that people are really wiped out and their cortisol level isn’t even low, right? That kind of final end-stage adrenal fatigue where we’ve got flat line cortisol levels. People are actually ramping high cortisol levels and they’re just wiped out. So what else about this? What’s going on with the mitochondria that’s really creating this problem?

Deb Matthew, M.D.

When our bodies are under stress, it changes our mitochondria, it damages our mitochondria, and it makes them not function properly. And there’s actually a difference between if it’s an acute stress or a chronic stress. So under an acute stress, the house is on fire and you’re running outside for your life. The rushing cortisol level that we get, actually can change our mitochondria function, it can change the shape and size. We call that the morphology of our mitochondria. It can also change how our mitochondria generates antioxidant enzymes that help to protect the mitochondria. And so in the very short term, those changes are meant to help us generate more energy, so that we can run for our life. So in the very short term, that’s helpful, that’s how we were designed. But if that acute stressor is more, if it’s longer than really within a few hours, our mitochondria can start to become damaged and start to become dysfunctional. So lots of acute stress is not really good for our system.

Laura Frontiero, FNP-BC

Within a few hours.

Deb Matthew, M.D.

Within a few hours, we can start to see changes in the mitochondria. And while that short term, rapid change in things is meant to help generate more energy and help us, most of us have chronic stress, right? We’ve got stress day in and day out. And over time, the chronic stress is what really causes the problems. And instead of the increase in energy to help save our lives, our energy production drops. Those antioxidant enzymes drop, which means that we don’t have as much antioxidants to protect our cells anymore. And so that’s when we really start to feel exhausted, overwhelmed, hard to cope, hard to deal with things, because our body’s energy production mechanisms are just not working properly.

Laura Frontiero, FNP-BC

Yeah, and somehow, we lump this into the basket of it’s adrenal fatigue.

Deb Matthew, M.D.

Right, and like I said, I think it’s because that so sounds so simple, but in reality, it’s kind of sent us looking in the wrong direction. And so I think so much about what we do in functional medicine is we wanna treat the root cause. And so we have to understand what’s the real root cause of why you’re not feeling your best. And we have to address that because otherwise we’re not really gonna get the full results that we need to get.

Laura Frontiero, FNP-BC

Yeah, so mitochondria, it’s so interesting because mitochondria are a target of stress. So they’re damaged, they’re the target of stress. But they simultaneously impact and control the stress response.

Deb Matthew, M.D.

And they do.

Laura Frontiero, FNP-BC

Can you shed some light on that ’cause that’s really fascinating?

Deb Matthew, M.D.

Yes, now this is an area where there’s not nearly enough medical research. So this is like ongoing new information and it’s just unfolding. And it’s really changing how we think about things to learn about this stuff. But it turns out that the mitochondria regulate almost all aspects of our stress response. And when we’re under stress, there’s all kinds of things that change in our body, cortisol production changes and blood flow patterns change. And lots of different things are going on. Our heart rate speeds up, et cetera, but mitochondria are intimately responsible for this. And when we have chronic stress, we can see chronic changes. And a lot of the time we’ve been choking that up to the effects of cortisol. And we know that chronic cortisol release is harmful to our body. 

And one of the things that can happen is that shrinks our brain, especially our hippocampus, which is one of the regulating centers in our brain. But it turns out that when we see that, when we see shrinkage in the hippocampus as a result of chronic stress, it’s actually indicative of mitochondrial dysfunction. And so there’s this really important connection there. So we also know that there are some people who are born genetically with dysfunctional mitochondria, they’ve got different diseases where their mitochondria don’t work properly. And in those people, we see very elevated cortisol levels. In fact, their cortisol levels can be double what a typical cortisol level would be, which indicates that if your mitochondria are not functioning properly, then your cortisol is not properly being regulated. And so that can cause even more problems.

Laura Frontiero, FNP-BC

That’s so interesting because we always think about cortisol being linked with blood glucose levels and being linked with just the stress itself. But what you’re saying is there’s a link with mitochondria as well. There’s more to it than we suspect.

Deb Matthew, M.D.

There’s more to it than we suspect. And I think that as the research continues that we’re gonna learn all kinds of new things that we really didn’t understand. And I think that’s gonna be so helpful because that gives us now that we understand, we can do more things to try to help protect your mitochondria, boost your mitochondria, support your mitochondria, that can really help in a lot of different ways.

Laura Frontiero, FNP-BC

Okay, so can you go back and can you just touch, now, that we’ve laid that foundation, there’s a difference between acute, the house is burning down stress and chronic, every day you come home you’re in a situation of your relationship isn’t where you want it to be. And this is just underlying stress, stress, stress, stress every day, right? So both of those types of stress affect your mitochondria function differently. So you started to touch on that, go a little deeper there because everyone listening has kind of a different scenario. Some people are in amazing or supportive relationships and they have amazing jobs. But they have these things that hit them. Like all of a sudden it’s a stress with their teenagers or it’s a stress with something that’s short lived. So what’s the difference?

Deb Matthew, M.D.

Okay, when we have acute stress, something that happens short term, our body compensates. And that’s the beauty of the human body in its wisdom. It changes how it’s doing things in order to help us cope with whatever we gotta cope with going on. And so some things are good about that. And some things aren’t so healthy but overall, our body is attempting to get us through this stress. It’s attempting to help us to survive. And so generally speaking, what’s happening at your mitochondria is they are changing their function, but they are also changing what we call morphology, the size, the shape. If we look at them under the microscope, they look different when they’re under acute stress and what’s happening is they are changing in a way that is trying to help us generate more energy. It is upregulating or increasing the amount of these enzymes that help us to make antioxidants in order to try to help us have more energy so that we can run for our lives and survive. 

But sometimes it goes a little overboard. When the stress acutely is more than what we can really keep up with and maintain, then upregulating all of these things can sometimes cause harm, it can go overboard. So for example, part of what happens here is more cortisol is released. And we know that excessive amounts of cortisol, cortisol is like long-acting adrenaline. And if you’ve got too much cortisol pumping through your system, then it’s like too much adrenaline. You can feel anxious and jittery and you don’t sleep well, and your blood sugar goes up and your blood pressure goes up. So acute stress is harmful, but all of those things, including the blood sugar going up and the blood pressure going up, those are all things that are trying to help us survive. When it goes on and on, and we’ve got the chronic stressors in our life, so the relationship issues, the job issues, we have a family member who’s sick, all the thing, pandemic, all the things that are going on. 

Then over time, things kind of shift down and things change. So now our mitochondria become more dysfunctional, they’re not able to generate the energy that we need, they’re not able to create those antioxidant enzymes anymore. We get more and more cell damage, more and more things break down, we can’t make enough cortisol anymore. So even if your body needs more cortisol, it just isn’t getting the signals to make it. And it’s not that your adrenal gland is incapable of producing it, it’s the signals aren’t being sent to make it. And that’s when you feel really overwhelmed, exhausted, it’s hard to get outta bed in the morning. And little things can feel stressful, like things that don’t have to be stressful. Things like just getting your groceries home from the grocery store and getting them all unpacked and getting dinner on the table feels exhausting and overwhelming because your body’s energy production systems are just not able to keep up with your body’s demands, so-

Laura Frontiero, FNP-BC

Yeah, so I have a question as we’re talking about this because I know you and I have both run adrenal protocols on people where we’re giving adaptogenic herbs, we’re giving blood glucose, regulating supplements like lipoic acid, we’re giving maybe desiccated adrenal hormone to support people. And some people get a really good benefit from this. And then some people just don’t notice much of a difference. So what do you say? So why do those things seem to help? And is it good to continue giving those type of protocols? And what about the people who don’t respond? I’m assuming it’s a deeper mitochondrial issue. So can you talk about that? Is it worth it to give those protocols still? And what else needs to be done or what’s missing?

Deb Matthew, M.D.

Okay, so I think, yes it is worth it because if somebody comes in the door and they’re exhausted and overwhelmed and they’ve got stress in their lives and usually what happens when we’re exhausted and overwhelmed is we’re not eating as well as we should. And we’re maybe not exercising, we’re not maybe doing all the best things that we can to take care of ourselves ’cause we’re just exhausted and overwhelmed. And if we start off with all the things that can help with adrenal health. So healthy diet and meditation and some of the adaptogenic herbs, the things that support our HPA axis, our hypothalamic, pituitary, adrenal access which is that messaging system between your brain and your adrenal glands. I think that’s a good place to start. And a lot of people are gonna feel better. 

But there are gonna be the people where it just we don’t get the results that we’re looking for. And that’s where we really need to go deeper and understand what are the underlying factors that are preventing this system from resetting itself. And it can be heavy metals, it can be some kind of inflammatory condition like hidden food sensitivity or an autoimmune condition, some kind of low grade chronic infection, any of these things that can be damaging to our mitochondria or nutrient deficiencies, right? There are certain nutrients that your body really needs for your mitochondrial function. So that’s when we need to start digging deeper to understand what are the underlying factors at play and we need to go after those things.

Laura Frontiero, FNP-BC

Yeah, so what I’m hearing is if somebody’s done a basic adrenal reset protocol, where you’ve got some lifestyle pieces and you’ve got some supplements and you’re not getting the results, you’re just not improving, then there’s probably something bigger going on. It’s probably something that’s damaging at the mitochondria level and in order to support that we really need to get down to root cause of what’s causing the problem there. So there’s nothing bad in adrenal protocols but there may be more that you need to do. Is that what I’m hearing?

Deb Matthew, M.D.

Absolutely.

Laura Frontiero, FNP-BC

Okay, good. So everybody, who’s got your adrenal protocols, they’re helpful, but you may need to dig a little deeper. So let’s talk about the things that make your mitochondria vulnerable and what’s harming them? ‘Cause there’s a whole bucket of things that harm mitochondria. So in your experience in your practice, what’s going on here?

Deb Matthew, M.D.

Yeah, well, some of the things that make your… If we sort of specifically talk about stress here for just a minute. So when somebody is under stress, that damages their mitochondria. And when we say stress, we mean, like you said, busy, marital problems, worried about things. Like the emotional stressors that you know about, but there are lots of other stresses that impact too. So dietary factors, if you’re not getting the right nutrients, the hidden infections, other kinds of things, those are all actually stressors on your body. But specifically things that make your mitochondria more vulnerable are behavior things. So if you’re not exercising, if you’re not sleeping, if you’re stressed out all the time, if you’re not doing all the things that are really important to help you look after yourself, those actually set your mitochondria up so that when more stress happens, that’s sort of the tipping point and things get worse. 

Another thing is nutrition. If you’re feeding your body all of the nutrients that your mitochondria need in order to function well, then when more stress happens, less likely that they’re gonna tip over and go into the problem zone. And then another really interesting thing is that genetically, some people are more just genetically predisposed to having vulnerable mitochondria. And this is an area that again, we know a little bit, but we don’t really know enough to be able to go off and measure your genes and tell you exactly if you’re that person. One of the things that we see is that when people have had a lot of stress and trauma as a child, we call that adverse childhood events, that those adverse childhood events actually seem to change the DNA in our mitochondria. So our mitochondria are really interesting ’cause they have their own DNA. And adverse childhood events can actually change the DNA in your mitochondria, so that going forward through your life, you are more at risk for having mitochondrial dysfunction. 

And we should say mitochondrial dysfunction from stress, from anything causes more inflammation. And of course inflammation is the root cause for most of the chronic diseases that none of us really wanna get. And we know that having a traumatic childhood, having a lot of stress in childhood increases the chances that you’re gonna have problems when you’re older, it increases the chances of heart disease and diabetes and all kinds of conditions. But there’s a mitochondria link because the stress in childhood affects your mitochondria. And that’s part of the piece that sets you up for the inflammation, which doesn’t mean that you’re destined for this. It doesn’t mean that if you had a difficult childhood that all hope is lost, it just means that if that’s you, first of all, we wanna help you deal with the trauma. But also if we use nutrition, lifestyle changes and things, those are things that we can help to make your mitochondria less vulnerable to the impacts of stress. And that can make things a lot better.

Laura Frontiero, FNP-BC

Yeah, so so many factors hurting our mitochondria. Now mitochondria are responsible as you’ve laid out so beautifully for regulating all aspects of our stress response. So can you unpack what happens in your brain and your HPA access when the dysfunction is occurring?

Deb Matthew, M.D.

Yeah, so the mitochondria are important for our messaging systems. They help to regulate our endocrine system, which is our hormones. They help to regulate our nervous system, and they help to regulate our immune system. And like I said, we’re still working on exactly all the fine tuned details, but we didn’t have any idea of this. When I went to medical school, the mitochondria just generated ATP, which is energy. That’s really all that we knew that they did. So this is really kind of mind blowing that they really do so much more, but they are intimately involved in regulating all of those different aspects. And your endocrine system means all the hormones that go through your body. And your hormones are the chemical messengers that tell your cells what to do. 

So they are actively, like cortisol, for example, is a hormone, it’s one of your chemical messengers that tell your cells that they need to adapt to stress by changing your blood sugar, et cetera. And so the mitochondria are actually regulating how your body is releasing cortisol as well as your mitochondria are being impacted by cortisol. So it’s a two way street. And it’s really interesting that when your mitochondria are not doing a good job, all of those systems, your nervous system, your hormone system, your immune system, aren’t gonna be functioning as they should, which just leaves you not feeling your best. And interestingly, when we look at people who have depression, PTSD, chronic mood disorders, when we look at their mitochondria, we see that their mitochondrial function is not great. And so I think there’s a little bit of a chicken and the egg here, how much of it is that mood symptoms depress mitochondrial function, and how much of it is mitochondrial problems cause mood problems. And there’s a lot more for us to learn here.

Laura Frontiero, FNP-BC

There is. So real quick, how do you like to identify mitochondrial problems in your patients? What are you doing to identify? Testing, or what are you doing?

Deb Matthew, M.D.

Yeah, so sometimes we go by symptoms, ’cause it’s always important. We always want to look at a person and not just focus on a number on a lab test. But we do organic acid testing in order to look at function and biochemical processes in the body that can help us to understand if there are problems with mitochondrial function, so that’s my go to.

Laura Frontiero, FNP-BC

Super simple urine test, I love that test too. It gives us a real quick idea of, are your mitochondria hypo metabolic? Are they just like land flat doing nothing? Or are they just a little bit under functioning? And from there you can build protocols for people. It’s so good.

Deb Matthew, M.D.

Exactly, yeah.

Laura Frontiero, FNP-BC

Okay, so what are some practical tips that you can share with our audience on how to cope? I mean, so stress, you spend a lot of time talking about stress, how can we cope with this? I mean, it’s one thing to tell people you just need to de-stress, you need to reduce stress. And I know that people listening right now are like, “If one more person tells me to de-stress, I’m gonna kill somebody.” So what do you do?

Deb Matthew, M.D.

Yeah, I like to give some practical stress reducing tips and then go move past that. But some of the things that I think are really practical is gratitude, because when we are in the state of gratitude, we can’t also simultaneously be in a state of bitterness, anger, anxiety, et cetera. And so I have a gratitude journal every day. I write around three things that I’m grateful for. I feel like that really helps me a lot, puts things into perspective, so that’s one. The other, there’s breathing exercises, there’s meditation, there’s all those things that we can do, walking, those are important. But another really important thing I think is to recognize that what goes on in your brain impacts your physical body, including your mitochondria. 

So if you are constantly thinking negative thoughts, worrying about things, ruminating over that same conversation over and over again, like I can’t believe she said that to me, you are actually taking that stressful situation and making it worse. Whereas if you are able to catch yourself thinking those negative thoughts and make yourself stop and turn to something positive, that literally changes the chemistry in your body. And sometimes you have to say, stop out loud. You put your hand up, stop, and that will break the thought patterns. But what you think about really, really matters. And changing what you’re thinking is powerful medicine. The trick is you just have to catch yourself doing it and find a good trick to turn on. But having some healthy means of coping with stress is important for all of us, ’cause we’re always gonna have stress in our lives. 

Nobody’s gonna be completely stress free, but it’s really not so much how much stress you have. And it’s much more about how you allow the stress to affect you. So healthy ways of coping with stress is one thing that’s really important. Another thing that I would say specifically here is exercise, because we know that exercise actually helps to boost mitochondria. And so exercising can help boost the mitochondria. So if you’ve got stress pushing down your mitochondrial function, then exercise can kind of counterbalance that. So that’s another really important tip. You wanna feed your body a healthy diet. Your mitochondria, just like the rest of you needs vitamins, nutrients, healthy fats, needs the right fuel. So you wanna fuel your mitochondria with healthy food and avoid the damaging nutrients like sugar, the refined seed oils. We wanna use the healthy fats, olive oil, avocado oil, that kind of thing. 

So a healthy diet is another really important tip. And then there are certain nutritional supplements that can be really healthy. So adaptogenic herbs is one interesting one, because interestingly, the way that these adaptogenic herbs, which is just a category of herbs that help us to cope with the stress response. And these herbs have been used for thousands of years all over the world in all sorts of different cultures because people have learned that they help us cope with stress. But interestingly, the reason that they help us cope with stress is because at the cellular level, some of them are actually acting like cortisol. So they help in that way. And some of them are acting by protecting ourselves from cellular damage on the inside. And these are the same damaging pathways that are harming our mitochondria. So adaptogenic herbs actually are helpful. Other things that can be really helpful are CoQ10 and carnitine, because these are really important nutrients for mitochondria. Some of the B vitamins are really important. But typically what I like to do is do the testing to really understand what’s going on for you personally, which nutrients seem like they’re gonna be the best fit and really kind of targeting recommendations.

Laura Frontiero, FNP-BC

Yeah, such good stuff. All right, we still have a few minutes. So I would love if you’re open to dig into a little bit about gut health and mitochondria. Because I think this is super foundational, it’s super important. If we don’t address gut health, then you’re probably not gonna have long term results or success. I’m sure you’d be agreeing to that. So dig into that a little bit. What are you experiencing in your practice when it comes to rebalancing people’s health and fixing their bodies? How much attention are you paying to gut health?

Deb Matthew, M.D.

Yeah, so for me personally, my special area of interest is hormones. So most people come to me because they feel like they have a hormone problem. And a lot of times they think it’s adrenal fatigue. And so we have to dig to get to the root. But we always want to address hormones and gut health and toxins in the environment and lifestyle habits because all of those things go together. And it is so, so, so common that when someone comes in, especially women, comes in with any kind of a hormone problem, whether it is this adrenal issue, whether it is menopause, thyroid issue, whatever it is, it is so common for us to find underlying gut issues. 

Either they’ve got IBS, or constipation or heartburn, or they’ve just always had a sensitive stomach. So, so common for there to be an underlying gut issue. And this is true because our gut is so integral to our overall health. And if you don’t have a healthy gut, you’re not gonna have a healthy immune system, you’re not gonna have a healthy brain, you’re not gonna have healthy hormones. They’re all linked together. And your gut lining is so delicate. It’s only one cell layer thick. And that lining of your intestinal tract is what decides what things are gonna get absorbed into your bloodstream, like healthy nutrients, and what things are gonna go straight on through, like bacterial particles. But when we are under stress, when our mitochondria are dysfunctioning, when we have too much inflammation, there there’s many, many reasons for our digestive tract lining to become inflamed. And then it’s not absorbing nutrients properly.

The wrong things are getting in your body. That’s triggering inflammation and immune system response. And it promotes autoimmune conditions, mitochondrial dysfunction, any kind of mental health symptoms, any kind of brain symptoms, fatigue, poor memory, bad sleep, anxiety, depression, bad focus, ADD, all sorts of things. So I feel like as a general statement, when we’re starting with somebody who has a whole bunch of symptoms, they’re not feeling good, really focusing, or at least including a discussion about gut health is a really, really important part of it. If you can’t absorb the nutrients your mitochondria need, then you’re not gonna be able to fuel your mitochondria.

Laura Frontiero, FNP-BC

Yeah, I mean, we’re doing these organic acid tests and we’re seeing deficiency, so what’s causing the deficiency. Toxicity causes deficiency, not being able to digest your food causes deficiency, not being able to absorb your food, your nutrition causes deficiency. So thank you for shedding light on that, because I think that’s so critical. You are amazing. There’s so much incredible information in this talk for everyone listening. I know people are gonna rewind and go back and take notes and listen some more because it’s just mind exploding that, wait, what do you mean? It’s not just all about my adrenals. What do you mean there’s something else going on there? So thank you for explaining that so, so perfectly, I really appreciate it.

Deb Matthew, M.D.

Thank you. I think this is really important and I think it’s important to say that as practitioners, we are learning too, and we have to. I think this is really important for any practitioners that are listening. Listening is we have to be willing to take new information and roll with it, and learn from it and not be so stuck in our ways that just because this is what we used to think that we’re not able to change our thinking and adapt.

Laura Frontiero, FNP-BC

Absolutely, I’ve always said practicing medicine is the art of really trying to figure out what we think we know and shifting it. And it’s constantly ever changing, science is constantly evolving and our understanding of the human body. So Deb, where can people get ahold of you? Where can we find you? I’m sure you’re all over the place.

Deb Matthew, M.D.

Yeah, well, my website is signaturewellness.org. And I also have a website called, isityourhormones.com. And you can find more information there as well.

Laura Frontiero, FNP-BC

Perfect, and do you work with people virtually? Do people come to see you in clinic practice? How do people-

Deb Matthew, M.D.

I have an in person practice in North Carolina and I am licensed in North Carolina. So if you really wanna come and see me, you’d have to come to North Carolina.

Laura Frontiero, FNP-BC

And then you have virtual options for people as well. People can get a hold of you online?

Deb Matthew, M.D.

Yes, but we can only really take on patients if they come to North Carolina ’cause we can’t see people across the country.

Laura Frontiero, FNP-BC

Well, you’re worth it.

Deb Matthew, M.D.

We do have people come from all over.

Laura Frontiero, FNP-BC

Yeah, I love it, I love it. Thank you so much, Deb, this has been wonderful. I appreciate you so much.

Deb Matthew, M.D.

Thank you.

Laura Frontiero, FNP-BC

All right, you take good care now.