Depression: A Functional Root Cause Approach

Your Depression Might Not Be What Your Doctor Thinks It Is.

What If Your Antidepressants Aren't Working Because Nobody's Looking at the Real Problem?

You've tried the medications, and you've done the talk therapy, but nothing seems to be working. Or perhaps—you're stuck on drugs with side effects you hate, wondering if you'll ever feel normal again.

Most doctors follow a predictable script: you describe depression → they immediately get out the Rx pad and write for Prozac, or one of its many cousins. But what if your depression isn't a chemical  or neurotransmiter mbalance at all? What if it's really due to a correctable cause that's been overlooked the entire time?

In this episode of Wellness Connection MD, Dr. McMinn and Coach Lindsay Mathews reveal a completely different approach to depression—one that asks "Why do you have depression?” instead of "What drug should I put you on?” They walk through what may be the most complete list of root causes of depression that has ever been presented- the causes that most doctors never think about or look for. As usual on the Wellness Connection MD podcast- everything is supported by the evidence. Dr. McMinn and Coach Lindsay have done the homework for you. 

Key Root Causes Explored

Nutritional & Biochemical Factors: Vitamin D deficiency, B vitamin deficiencies (especially B12), omega-3 fatty acids, magnesium, zinc, iron, selenium, and amino acids all directly impact mood regulation.

Hormonal Imbalances: Thyroid dysfunction, cortisol dysregulation, low pregnenolone, DHEA, estrogen (particularly during menopause and perimenopause), progesterone fluctuations, and low testosterone in both men and women can all trigger or worsen depression.

Inflammation & Food Sensitivities: Neuroinflammation disrupts mood-regulating neurotransmitters. Gluten sensitivity and other food triggers can significantly worsen depression.

Blood Sugar Dysregulation: Insulin resistance doubles the risk of major depression and can be corrected.

Infections: Chronic infections including Lyme disease, Epstein-Barr virus, chronic sinusitis, recurrent UTIs, viral myocarditis, and parasitic infections are frequently overlooked depression triggers.

Gut-Brain Connection: Dysbiosis (altered microbiome) affects serotonin and dopamine production. Chronic yeast overgrowth can produce mood-altering metabolites.

Lifestyle Factors: Exercise, sleep quality, stress reduction, social connection, purpose, sunlight exp

Chapters

• 0:00 Welcome & Mission
• 2:35 Why Root Causes Matter
• 6:40 The Rising Tide of Depression
• 11:40 Case Study: Vitamin D Turnaround
• 17:10 Nutrient Gaps Beyond Vitamin D
• 22:30 Inflammation, Food Sensitivities & Gluten
• 27:45 Blood Sugar, Diet Patterns & Mood
• 31:45 Hormones: Thyroid, Cortisol, Estrogen, Progesterone, Testosterone
• 40:20 Infections Linked to Depression
• 46:00 Gut-Brain Axis & Microbiome
• 50:45 Lifestyle Levers: Exercise, Sleep, Sunlight, Community
• 55:10 Toxins, Mitochondria & Medications
• 1:00:20 Screen Time, SAD & Early-Life Imprinting
• 1:05:20 Other Underrecognized Drivers
• 1:08:30 How to Start: A Practical Roadmap
• 1:12:00 Closing Insights & Resources

Transcript

SPEAKER_00: 0:00

Greetings and welcome to the Wellness Connection MD Podcast. I'm your host, Dr. McMinn. October was Depression Awareness Month, so in this episode, we are going to take a deep dive into a root cause approach to depression. Depression is a complex condition that can profoundly affect the lives of millions of people, and I'm sorry to say that it's getting worse. Medications and talk therapy have been the cornerstones of therapy for many years for such concerns. And to be clear, these therapies are valuable tools in our toolbox. However, in many instances, depression is actually a manifestation of an underlying root cause condition. A functional medicine approach can uncover the root cause, which is often treatable, sometimes resulting in great improvement or even a complete cure. In this episode, we present the most evidence-based, complete list of the causes of depression that you will find anywhere. So listen to the end, it may be life-changing. Find this at McMinMD.com and subscribe to Wellness Connection MD Podcast for the latest information about functional integrative lifestyle and wellness medicine. Enjoy the show.

SPEAKER_01: 0:57

Welcome to the Wellness Connection MD Podcast with Dr. McMinn and Coach Lindsay, where we bring you the latest up-to-date evidence-based information on a wide variety of health and wellness topics, along with practical take-home solutions. Dr. McMinn is an integrated functional MD. Lindsay Matthews is a registered nurse and IIN Certified Health Coach. Together, our goal is to help you optimize your health and wellness in mind, body, and spirit. To see a list of all of our podcasts, stay up to date on the latest topics. Be sure to subscribe to our podcast by your favorite podcast player, which you'll be notified when future episodes come out. Discussions continue this podcast for educational purposes only. And diagnose your three disease do not apply any of this information without approval from your personal doctor. And now, on to the show with Dr. McMahon and Coach Lindsay.

SPEAKER_00: 1:54

Hello and welcome to the Wellness Connection MD Podcast. Thank you so much for joining us today. I'm Dr. Jim McMinn, and I'm here with our very own Coach Lindsay Matthews. Together we bring you the evidence-based podcast with honest, commercial-free, unbiased, up-to-date information about functional, integrative lifestyle and wellness medicine. Our goal is to empower you with practical solutions, to overcome your health care challenges, to optimize your wellness, and to help you become a captain of your ship when it comes to your health. So let's get going. Good morning, coach.

SPEAKER_02: 2:25

Morning, Dr. Mack. It's great to be back on the show. Excited to approach another important topic.

SPEAKER_00: 2:31

Well, coach, it occurred to me that October was National Depression Awareness Month. So it's high time we shine a light on this dark and important corner of healthcare. Sometimes in modern medicine, it seems we focus almost entirely on our physical concerns and we sweep mental health under the rug.

SPEAKER_02: 2:47

But if you or a loved one have ever been affected with depression, then you know it can be a very serious disease, which can have a profound impact on a person's life and can even be fatal for some people. Depression is one of the most misunderstood conditions in healthcare. You can't see it on an x-ray or find it in lab work. So sometimes it's hard to wrap our heads around it. And a lot of times depression is not just depression, it's a manifestation of some underlying problems. So we're going to unpack it today by taking a deep dive into a functional root cause, integrative and lifestyle approach to depression.

SPEAKER_00: 3:26

You know, coach, I think some of the other things like chronic fatigue syndrome, fibromyalgia, and dysautonomia, anything that once again you can't see on an X-ray and doesn't show up on the labs, then we we just can't really understand it. And sometimes we think the patient is anxious or stressed out or malingering or whatever. And so um we're we're happy to kind of shine some light on this today. Over the years, doing the podcast, we've talked about what I call the symptom pill or diagnosis pill approach to medicine. The doctor hears certain symptoms or makes a particular diagnosis, and the next thing that he or she does is to get out the prescription pad. Well, unfortunately, it's the way doctors are trained to think. But the functional medicine movement is trying to move the needle towards a more root-cause approach to healthcare.

SPEAKER_02: 4:10

Just as many doctors are quick to, at like, as you said, Dr. McMahon, get out that script pad. But patients also have come to expect that approach as well when they go to the doctors. And the pharmaceutical companies are there in the background, and they're, you know, they're the ones in the main benefit of this. So I'm sure that you've seen the Ask the Doctor commercials on TV where half the commercial is taken up with a list of possible side effects and dot dot dot death at the very end, right?

SPEAKER_00: 4:38

Aaron Powell Coach, I remember back in the ER days, uh people would come in with a sniffle, and I actually kept some literature from the CDC which showed that you don't need antibiotics for that sniffle. And so I wouldn't write them. And next thing you know, you're getting a complaint letter that I I waited for two hours in the waiting room and I came to the ER and the doctor didn't even give me antibiotics. So, you know, people have been programmed that they have to have antibiotics when most of the time they don't. And so anyway, it it's it's a struggle. But try sitting in the waiting room of your doctor sometime and see the parade of drug reps that come in who who often serve lunch to the entire staff. I'm just saying, coach, follow the money.

SPEAKER_02: 5:17

The traditional approach to depression is just another example of this drug-focused type practice. When a patient sees their doctor with symptoms of depression, the doctor makes the diagnosis and then writes for Prozac, for example. But we feel that we owe it to the patient to look under the hood a bit to do a thorough workup to see if there's some other treatable cause of depression so that we don't have to get the patient on what turns out to be maybe a lifetime of meds. And those meds, by the way, also could have untoward side effects, not to mention the cost of the to the patient and the healthcare system at large. So it's worth noting that once you get on those drugs, it can be hard to also get off of them due to something called antidepressant withdrawal syndrome.

SPEAKER_00: 6:05

And coach, uh from an integrated medicine point of view, we also feel that we need to expand our therapeutic toolbox to include other proven evidence-based therapies besides drugs and talk therapy.

SPEAKER_02: 6:15

And before we go further, though, I know Dr. McMahon, we both share that we want to be perfectly clear that we're not anti-drug. We understand that there's definitely a time and place for such meds. These have helped many people, and we're fully supportive of that. But the Wellness Connection MD podcast is also a no-judgment zone. And we feel that it's important that a patient deserves a thorough eval to look for the root cause of the problem and consider other treatment modalities, expand that toolbox besides just drugs and talk therapy.

SPEAKER_00: 6:47

Coach, you know, I think a lot of people really don't appreciate the impact of depression on our society. So let's uh set the stage just a bit by describing the scope of the problem. Here in the United States, about 37% of women have been diagnosed with depression, and about 25% of American women actually take antidepressants. Oh my gosh, coach, what's going on in this world that we live in that that results in over a third of our women uh being depressed? And I would also contend that many others have depression but have not been diagnosed for various reasons, including lack of access to care.

SPEAKER_02: 7:19

Yes, agreed. And depression, by the way, is another, I would say, sexist disease, Dr. Mack. It appears to be more common in women than in men. And it's hard to say why. Maybe women are just in more in touch with our feelings or men have this denial mode. But, you know, I think there might be a couple, lots of possible reasons for this conglomerating to yield this higher incidence of depression in women. And maybe some examples might be that estrogen affects serotonin production differently, and how this can also, estrogen can also affect the activity in the amygdala. The HPA axis in the brain is different for women as far as how cortisol is regulated. There's a lot of different mechanisms that could be it. So I just think that's also interesting to think about. I found that there was a study by the American Journal of Psychiatry and Lancet Psychiatries between 2022 and 2024 that showed the perceived role, even for women, this overload that we have, social comparison that also can really be predictive for depression symptoms in women. So I think there could be like physiological things, but also just our role in society in general plays a plays a part of this picture.

SPEAKER_00: 8:29

Yeah, coach, I do think that women are just inherently more complicated hormonally than men are uh for good and bad. So but the data is particularly worrisome for young females, Lindsay. And as of 2025, the CDC and the World Health Organization indicate that 57% of girls in America report symptoms of depression. Wow, coach, that's let me repeat that. And even scarier is the data from recent survey that showed that 30% of high school age girls said they seriously considered attempting suicide in the past year. Oh my gosh, coach, it just breaks my heart when I read the stats like that. And I'm sure as a mom of two young precious kids, one of whom is a girl, I'm sure this trend must be pretty concerning for you.

SPEAKER_02: 9:12

This topic is extremely personal to me. And just recognizing the sheer numbers, like you said, having a daughter myself, but then also honestly, having experienced depression myself. I'm one of those numbers.

SPEAKER_00: 9:25

You know, Coach, uh, let me be clear that men and boys can also suffer depression. Us men just tend to withdraw into our igloos. We're often reluctant to seek help. It's just not a manly thing to do. And let's face it, there are social stigmas for a man to admit he has depression. I remember, Coachie remembered this. There was a guy um years ago, I forg I forget his name. He was actually a vice presidential candidate. They found out he got depression and they had to withdraw him from the ticket. Now he had a broken arm, no, they wouldn't have drawn him, but he had depression, so they had to withdraw him from the presidential ticket. So uh yeah, there's a stigma with us guys. Um and you know, we're supposed to be strong like bull. Studies have shown that in men, depression is vastly underdiagnosed and underreported. My beloved father-in-law Gordon, who was a true, don't fence me in Western cowboy who really used to ride the range and rope stray doggies, he had this illustrative uh saying that went like this: cowboy up or suffer in silence. So that's exactly what us men folk tend to do.

SPEAKER_02: 10:22

Unfortunately, the trend is moving in the wrong direction. Overall rates of depression in America are getting worse and now at an all-time high. In fact, depression rates have nearly doubled in less than 10 years, with the steepest increase, to your point, Dr. Mack, in young adults and women particularly, and those also with lower incomes. The reason for this increase is definitely multifactoral. Certainly, there's some lingering effects of the whole COVID epidemic. But also the science is clear that high levels of political rancor and division in our country significantly contributes to these rising rates of depression, anxiety, and other forms of psychological distress. And of course, the ever-present and ever-growing kind of baby tiger of social media and the stress and negativity related there, think about it. It's when when was the last time you heard a happier uplifting news story there on your feed? It's been probably quite a while. So all of those things, Dr. Mack, they're all part of this.

SPEAKER_00: 11:24

Mm-hmm. From time to time, many of us have the blues. Stuff happens in life, but as a physician who is taking care of patients who were hospitalized with incapacitating depression, and as an old ER doc who's been on the receiving end of many suicide attempts, uh, some successful and some not. I've seen the face of depression firsthand, and it's not a pretty psychoach. So this issue is kind of personal to me, and so I'm glad that we're finally bringing about some awareness to this topic and also bringing to the audience a functional approach to depression, because as we've said many times, awareness is the first step to change.

SPEAKER_02: 11:57

So, Dr. Mack, as always, let's look at the scientific evidence. Break it down for our listeners out there as far as the root causes. And as we proceed, I'd like to also just say this for us to keep in mind it's a profound saying, or also it comes from the what's known as the serenity prayer. Grant me the serenity to accept the things I cannot change, and courage to change the things I can, wisdom to know the difference.

SPEAKER_00: 12:24

Well, thanks for sharing that, coach. And it is very applicable to our topic today. For instance, uh, this science tells us that there is a strong link between genetics and depression. So we can't change our genes that we were born with. So we have to learn to accept that.

SPEAKER_02: 12:38

Here's the good news the vast majority of things that cause depression are manageable to a great degree. So that's what we're really going to focus on today.

SPEAKER_00: 12:47

You know, coach, I think we're going to present to the audience probably the most comprehensive list of the causes of depression today, ever in the history of the world. And I counted them up. I think it's about a hundred of them, coach. And guess what? Most of them are manageable. Isn't that interesting? You know, control the things we can control. So most of these things you can control. And let's start with a very interesting true uh case history. Years ago, I saw this uh 35-year-old woman who presented to me in the office with major depression. And in the functional medicine space, we always try to take a thorough history, including a timeline of events. And so I asked her, when did the depression start? And sadly, she told me she couldn't ever remember not being depressed. From her very first memories of life, she had always been sad. She had never known joy. And at numerous points in her life, she had often struggled with uh suicidal thoughts.

SPEAKER_02: 13:38

That's heartbreaking, Dr. Mack. Wow.

SPEAKER_00: 13:41

Yeah. Coach, it really was. It made me sad to hear it. Uh and she had been to many psychiatrists and had tried just about every medication in the book, but nothing really worked. She had also been to psychologists and counselors, had years of talk therapy and analysis, but again, sadly, no relief.

SPEAKER_02: 13:57

And I'm sure that only compounded things. Um, so she'd basically tried everything the traditional system had to offer, and she was feeling desperate on top of feeling depressed enough that she wanted to try something out of the box. And that's the way it often happens in a functional medicine practice. When the people fall through the cracks of traditional medicine and nothing's working, and that's when they really show up on the doorstep, miserable, desperate, really just hoping for a miracle cure. And the good news is that more often than not, the that miracle cure can be found for them by getting back to the basics and treating the root cause. As you always say, Dr. Mack, why? Why are we here? Why the depression? Why?

SPEAKER_00: 14:42

Now, Coach, you you worked with me for years in the clinic, and didn't you witness that? I mean, these people would come in and and I say the vast majority of them, we got them a lot better. Would you agree? Agreed. Yeah, yeah. Okay, good. Agreed. I was often the last stop for these patients, and they would tell me so right off the bat. But no pressure, right, coach? Uh so anyway, I patiently listened to her story, and as we talked about it, I vividly remember telling her there's no point in me reinventing the wheel and doing everything the other doctors already done, which had failed miserably. I'm not going to just get you on another antidepressant if none of them have ever worked before. And I suggested we take a functional root cause approach and see if we could outsmart her depression. So she put her trust in me and agreed to give it a try.

SPEAKER_02: 15:24

I love that. Outsmart the depression. So now we're on the edges of our seats. So what did you find?

SPEAKER_00: 15:31

Well, coach, I put on my detective cap while still wearing my white coat, and I ran a comprehensive panel of tests. And when I got the results back, here's what really stood out to me the most. Her vitamin D level was extremely low. I mean rock bottom, coach. And it was the lowest I'd really ever seen. And now the list of uh low vitamin D causes goes on and on, and we don't have time to go into that today. That's a topic for another whole podcast. However, it is important to point out that that is the next step to figure out why her vitamin D is low.

SPEAKER_02: 15:59

And so that was it. V low vitamin D was truly the culprit for her.

SPEAKER_00: 16:04

Well, coach, uh the proof's always in the pudding, isn't it? So here's what we did. We got her on proper vitamin D supplementation, and within a few months, her depression was completely resolved. I mean, coach, 100% gone. When I saw her back in the office at her next visit, I could hardly recognize her. She was like an entirely new person. I was blown away. And needless to say, she was thrilled with the outcome. And for the first time in her life, she knew the real meaning of the word joy. And guess what, coach? I treated her for years and the depression never came back.

SPEAKER_02: 16:36

That's profound.

SPEAKER_00: 16:38

It really isn't it.

SPEAKER_02: 16:40

Every time I hear stories like that, I get so inspired and encouraged. And I remember, like to your point, we uh had I had the privilege of working with you for many years. And it's a gift to think back on those stories and those faces and to think about the families that are impacted just by the health of the patients. So a functional medicine root cause approach enabled us to help so many people that regular medicine had limited or no answers for. And this isn't just a one-off antidote about vitamin D. There's real science behind vitamin D and depression, that connection there. A major systematic review in the British Journal of Psychiatry found that people with depression had significantly lower vitamin D levels compared to the controls. And here's the striking part about this people with lower levels of vitamin D were 60% more likely to have depression than those with higher levels. 60%.

SPEAKER_00: 17:38

Yeah, coach, there's really definitely a connection here. And you know, many people with depression never get their vitamin D checked, right? Right. I'd been sure to say few to none, unless you happen to have a functional medicine doctor. Most providers just uh do the same old knee-jerk reaction of getting out the prescription pad and writing a prescription for an antidepressant. If you've got depression, there's your Prozac, often for life, along with all the side effects and the cost of the drug. It's really sad to me, coach, that we're missing the root cause of depression with so many of these patients. And let me be clear, as I've said many times, my purpose here is not to bash doctors. These are kind, caring, compassionate, hardworking folks who go to work every day to help people. Yes. And the symptom pill approach to medicine is what these doctors have been taught. My goal is to enlighten patients and hopefully providers to the fact that there is a different and sometimes more effective way of caring for these patients.

SPEAKER_02: 18:33

One might be tempted, if you're listening, to think that this was just a rare finding about the vitamin D. But according to Cleveland Clinic's report in 2025, approximately 35% of US adults are vitamin D deficient. And multiple sources cite a figure closer to about 42% for vitamin D deficiency among Americans. Certain subgroups are at even higher risk for deficiency. For example, the rate of vitamin D deficiency is about 70% in kids from the ages 6 to 11, 69.2% in Hispanic individuals, and up to 82.1% in African Americans.

SPEAKER_00: 19:12

So Lindsay, you got kids. No, I'm just saying 70% in kids.

SPEAKER_02: 19:21

Yeah.

SPEAKER_00: 19:21

Oh well. Might might want to think about it. Yeah. But uh wow, coach, uh that's a lot of deficiency, isn't it? And uh so there could be a lot of depression hiding in there among those groups with the low vitamin D, as well as other healthcare concerns caused by low vitamin D. Uh, vitamin D is not just depression, osteoporosis, whatever, I mean you you name it. And uh quite frankly, coach, I checked vitamin D levels on just about every patient who came to see me. It's just such a big deal. I think that this vitamin D uh situation is really underappreciated, not only for depression, but also for the other healthcare concerns. I want you all out in the audience there to think about it. When was the last time your doctor ever checked your vitamin D? I'm just saying.

SPEAKER_02: 19:58

Aaron Ross Powell I also think it's important at this point to say perhaps your doctor does check your vitamin D, but what are the levels they're trying to achieve? You know. Would you care to comment on that, Dr.

SPEAKER_00: 20:08

McMahon, what the appropriate levels are? Aaron Powell Well th this segues into a whole nother conversation about uh normal levels versus optimal levels. Right. You know, you you have to understand where they get those normal ranges. It's basically what we call a 95% confidence interval. In other words, if you took the general population and and checked the vitamin D, 95% will fall between here and here. But that's 95% of people, most of whom are deficient. Right.

SPEAKER_02: 20:30

Right.

SPEAKER_00: 20:31

So you have to uh look at you know what's the optimal range, and the optimal range is different. And it should be I always like to keep it around, say, 50 to 100. And I think if you uh check out uh, for instance, I looked at uh the recommendations from Harvard Medical School, and they were also in about that range. They I think they said around maybe 40 to 80, but uh I'd like to keep it about fifty to one hundred. And my patient with the severe depression, her level is five.

unknown: 20:54

Yeah.

SPEAKER_00: 20:54

Wow. Yeah, wow. And that's gonna cause her a lot of problems, not just depression down the road, but a lot, a lot, a lot of problems.

SPEAKER_02: 21:01

Yes. So to top off this discussion of vitamin D and depression, meta-analysis of randomized controlled trials showed that vitamin D supplementation leads to a statistically significant reduction in depressive symptoms for all comers with depression compared to placebo or controls with greater benefits for those with baseline deficiency. And this came from the Journal of Frontiers in Psychiatry, Hot Off the Press, 2025.

SPEAKER_00: 21:28

And coach, that's really important. Let me emphasize that because it's it's one thing to say vitamin D can uh contributes to depression, but it's a whole nother thing to say does treating with vitamin D improve depression? And the answer is yes, right, as uh shown in that hot off the press study. Back to the concept of controlling the things we can control, optimizing vitamin D levels is highly controllable and easy peasy. We just have to think about it, coach, and then test for it and then treat it. It's a piece of cake. And so why aren't we doing it, coach? That's that's the big deal. Why aren't we doing it?

SPEAKER_02: 22:01

I guess the analogy would be it's like you're driving along and your check engine light bing comes on. You could cover that light up with some duct tape and ignore the problem and probably end up with a blown engine down the road, or you can do the appropriate diagnostic test, figure out what's wrong with the engine, fix it at that root level cause before it gets bad, and ultimately save yourself a lot of trouble later on. And the beautiful thing is when you address and find the root cause, you're not just masking symptoms, you're actually solving the problem.

SPEAKER_00: 22:32

But coach, vitamin D-related depression is just one example of a treatable cause of depression. You know, uh, we're this whole podcast today is not just about vitamin D. We're gonna list a whole ton of them for you. So uh put your seatbelt on. Um and uh so we're going to take a deep dive into a comprehensive, evidence-based list of potential root causes for depression that most people, including many healthcare providers, never consider. We think that we are going to present to you the most comprehensive list ever in the history of uh of the world. And so I have painstakingly put this together over many years of practicing functional medicine. I do apologize, this podcast is a bit longer than I would like, uh, but we always err on the side of being thorough. So bear with us. If you need to break this up into chunks, then feel free to. But our hope is that by bringing awareness to these treatable causes, we can save some folks from a lifetime of depression.

SPEAKER_02: 23:22

Now, certainly, people can have what we would call situational depression. You get fired from your job, you're on your way home, your car breaks down, you get home, your house is burned down, and your wife has left you, your dog's died. Then you have the right to be depressed. That is very real depression. And unfortunately, it's all too common in the world these days. Sometimes life just doesn't go your way. And a lot of people are struggling out there. This is situationally related depression, and it's very real, and it needs to be treated as such.

SPEAKER_00: 23:52

Genetics can also play a role in depression. And as we said uh earlier, we can't change our genes, but we can sometimes affect what we call epigenetic expression, mainly through the power of lifestyle medicine and some other things as well. But the the main thing is lifestyle medicine. An example of this is when two twin sisters have the exact same genetic risk of getting breast cancer, yet one gets it and one doesn't. And this is often results of certain lifestyle factors that affect those uh genes. Uh for instance, maybe one of the sisters smoked or had a terrible diet and the other didn't.

SPEAKER_02: 24:22

So maybe to make an analogy, your your genetics can certainly load the gun for depression, but epigenetics is what's going to pull the triggers.

SPEAKER_00: 24:30

Oh, great, great analogy. Yeah, thanks.

SPEAKER_02: 24:32

So, Dr. Mack, let's move on to examining some other nutritional and biochemical factors that affect depression, starting with the B vitamin family. These are like the spark plugs of your brain's engine. B12 deficiency, for instance, can cause symptoms that look identical to depression. And B12 deficiency is way more common than people think. Certain populations are more at risk. Vegetarians, vegans, people over 50, people on certain medications like metformin or proton pump inhibitors like prilosec or the purple pill naxium. Many digestive issues like celiac disease can also cause B vitamins to be low.

SPEAKER_00: 25:15

But here's what's crazy, coach. It could take years for vitamin B deficiencies to show up on standard blood tests. Standard vitamin B12 tests measure what's in your blood, but that doesn't necessarily reflect accurately what's going on inside your cells where the B is needed. So someone could have a quote normal end quote B12 basic blood test, but still be functionally deficient. That's why we often looked at tests like methylmalonic acid and homocysteine levels, since these tend to be much more sensitive markers for B vitamins at the tissue level.

SPEAKER_02: 25:45

Same thing happens with folate and other B vitamins. And here's where it gets interesting. Some people have genetic variations like MTHFR mutations that affect how they process these nutrients. It has been estimated that about 60% of people with depression have an MTHFR mutation, much higher than the general population.

SPEAKER_00: 26:09

Now, MTHFR stands for methylene tetrahydrofolate reductase. That's a mouthful, isn't it, Coach?

SPEAKER_02: 26:15

Right.

SPEAKER_00: 26:16

But basically, it's an enzyme that helps your body process fully in vitamin B12 via a process called methylation. If you have certain genetic variations in this enzyme, you might not be able to use these vitamins efficiently, even if you're getting plenty in your diet. This can affect neurotransmitter production like serotonin, dopamine, and norepinephrine, all the brain chemicals that regulate mood. So the end result of this is potentially depression.

SPEAKER_02: 26:53

Also, multiple high-quality studies published in major medical journals have shown that patients with depression and certain MTHFR mutations experience significant improvement in depressive symptoms with appropriate treatment.

SPEAKER_00: 27:08

Now, coach, there are many ways we can treat a MTHFR mutation, but importantly, again, it starts with lifestyle medicine. I can't get into a complete treatment protocol here due to the length of the podcast, but certainly a good starting point beyond healthy lifestyle would be a supplementation with L-methylfolate. And by the way, if you want to learn more about uh lifestyle medicine, which I call the most powerful medicine on earth, then please check out our entire podcast that we did devoted to this subject back in 2023. And I guess another thing, Coach, is if you have an MTHFR mutation, it would be really helpful to see a good functional medicine doctor. I think your average doctor's not going to know much about this.

SPEAKER_02: 27:43

So again, proof is in the pudding. What do the studies show? Clinical trials and systematic reviews show that supplementation with B12, folic acid, B6, or complex of B vitamins can improve mood and lower depressive symptom scores, especially in patients with measured deficiencies. And this is described in the Open Neurology Journal. So once again, we have another treatable root cause of depression if we just look for it.

SPEAKER_00: 28:12

And the next nutrient that we'll mention is the omega-3 fatty acids, aka, also known as fish oils. Omega-3s, particularly EPA and DHA, are crucial for brain health. They help reduce inflammation, support neurotransmitter function, and maintain healthy brain cell membranes. Many studies have shown that omega-3 fatty acid levels contribute to depression, and likewise, multiple studies have shown that omega-3 supplementation can significantly reduce depressive symptoms.

SPEAKER_02: 28:39

Most people are not getting near enough, not even close. So unless you're eating fatty fish several times a week or supplementing, then you probably are deficient. And I will say, Dr. Mack, this is our main jam at our house as far as supplementation goes. Everyone in our house takes and has been taking an omega-3 supplement. Our kids since birth. Well, actually, let me correct that prenatally, since basically conception, since I supplemented my entire pregnancy. I think this is a super important nutrient.

SPEAKER_00: 29:08

And that's why they're so brilliant, right?

SPEAKER_02: 29:10

Yes, of course. Exceptionally so.

SPEAKER_00: 29:14

Yeah, the research from the British Medical Journal revealed that about 68% of adults and over 95% of children in the United States have low levels of omega-3 fatty acids. Wow, coach, 95% of children. That's just kind of scary, isn't it? Meaning they do not consume enough to meet the current nutritional guidelines, making them susceptible to many healthcare problems, including depression.

SPEAKER_02: 29:36

And another important factor is the ratio of omega-6 to omega-3 fatty acids. Meta-analysis have shown that too much of those omega-6s from processed foods can promote inflammation, and that can directly contribute to depression.

SPEAKER_00: 30:00

Analyses of randomized controlled trials report statistically significant improvements in depressive symptoms with omega-3 supplementation. So, once again, coach, here we have another correctable cause of depression.

SPEAKER_02: 30:11

Amazing. And other key nutrients that cause depression, also let's list some. Magnesium. Deficiency with magnesium can impair neurotransmitter function and our stress response contributing to depressive symptoms. Zinc as well. Zinc influences neurotransmitter metabolism and neuroplasticity. Low levels of zinc are strongly associated with depression.

SPEAKER_00: 30:38

Iron is required for oxygenation and neurotransmitter production. Low levels may trigger fatigue and depression, and selenium is involved in antioxidative and anti-inflammatory responses that protect neural tissues. Studies have shown that low levels of selenium are linked with depression.

SPEAKER_02: 30:53

Calcium is important for neuronal signaling, and low levels may contribute to mood changes. And amino acids from protein are needed for neurotransmitter synthesis, including serotonin, dopamine, and norepinephrine. Deficiency of certain amino acids can cause depression by limiting the production of these crucial neurotransmitters.

SPEAKER_00: 31:14

Persistent deficiency in vitamin C has also been associated with chronic depression and fatigue, and studies have shown that low levels of vitamin A, manganese, inositol, chromium, iodine, and potassium can also contribute to depression. So the bottom line is that we have many nutrients that are important for mood regulation. And when deficient, a lack of these nutrients can directly contribute to depression. The good news is that all of these are testable and treatable if we just take the time to look for the underlying root cause.

SPEAKER_02: 31:43

So let's segue our conversation into talking about inflammation, since in some cases it can be related to nutrition. And this seems to be another big piece of the depression puzzle. We're learning that depression isn't just a chemical or neurotransmitter imbalance. It's often linked to neuroinflammation, which diverts resources away from making our mood-regulating neurotransmitters. We did an entire podcast on inflammation back in 2023. So you might want to check that out if you want to learn more about this important topic.

SPEAKER_00: 32:16

Okay, coach. With the inflammation, though, presents another opportunity to talk about the power of functional medicine. Let's say the patient presents to the doctor with depression. First question should again not be what drug can I put her on, but it should be why does the patient have depression? Right. And then there are numerous lab tests that the doctor can do to look for inflammation and other causes. And if the doctor concludes that inflammation is a factor, then the next question is, why does the patient have inflammation? So, of course, you just keep peeling back the layers of onion with that question, why? I have put together an extensive list of all of the causes of inflammation, which you can find and download at McMinMD.com under the documents section. The cause of inflammation should be investigated and the patient should be put on an aggressive program to reduce inflammation, which may then result in improved mood.

SPEAKER_02: 33:02

One major cause of inflammation that we'll briefly mention is food sensitivities. And gluten is a great example here. Double-blind trials have shown that people with celiac disease, a gluten-induced autoimmune disease, and also people with non-celiac gluten sensitivity experience statistically significant increase in depression scores when exposed to gluten compared to gluten-free diets.

SPEAKER_00: 33:29

And also, again, does uh change the diet help? Well, here's what the studies show. Removing gluten from the diet of a depressed patient with celiac disease usually leads to substantial improvement in mood. Also, meta-analyses and systemic reviews show that gluten-free diet significantly improves depression in people with non-celiac gluten sensitivity. So here's another great example of a correctable cause of depression just by changing the diet.

SPEAKER_02: 33:53

Yes. And I love that second part of that statistic that it's not just if you are diagnosed with celiac disease, but you could have that, you could not have that as well and see improvement. When it comes to other food sensitivities besides gluten, these also can affect inflammation and neuroinflammation and thus depression. Food sensitivity testing can be very helpful here, although it's not perfect. Such testing can have false positives and false negatives. So sometimes we do elimination diets to actually figure out trigger foods for patients. See the McMinnMD.com for an explanation about how to do an elimination diet properly. But the key point here is that what you eat can directly affect your mood. And of course, this is another easy correctable issue that can improve your depression without pills and without counseling.

SPEAKER_00: 34:46

So, coach, let's move on to blood sugar. Blood sugar roller coasters can look a lot like mood disorders. When your sugar crashes, it can trigger anxiety, irritability, fatigue, and yes, depression. And insulin resistance, which is way more common than people realize, can cause brain inflammation and depression.

SPEAKER_02: 35:02

Numerous studies have shown this, including a Stanford-led study published in the American Journal of Psychiatry, which found that insulin resistance doubled the risk of developing major depressive disorder, even in people who had never experienced depression before. So here we have another correctable cause of depression. These people don't need Prozac, they just need to stabilize their blood sugar.

SPEAKER_00: 35:27

So to wrap up the nutrition portion of this discussion, the bottom line is that solid science shows us that improving your diet and avoiding nutrient deficiencies can make a big difference in your mood. Your doctor can check for all of these nutrient deficiencies, like I did with my patient with a low vitamin D, and the deficiencies can be corrected, which in some cases can be very helpful for these patients.

SPEAKER_02: 35:47

And while we highly recommend testing to find out what nutrients you might be deficient in, in the absence of testing, the Mediterranean diet is most strongly associated with improved mood and reduced risk of depression. Multiple randomized controlled trials show that following Mediterranean diet, which is rich in fruits, vegetables, whole grains, beans, nuts, fish, and olive oil with minimal processed foods, leads to significant reduction in depressive symptoms compared to typical diets. So check out McMinMD.com for more info on the Mediterranean diet.

SPEAKER_00: 36:23

And let me just interject here that I think the diet has to be personalized for each patient. If you look at the uh the data, uh uh there is more data to support the Mediterranean diet for this purpose than any other diet. However, that's not true for every patient. And uh Lindsay's husband, for instance, Tyler, who has dysautonomia, the best diet for him was not the Mediterranean diet. The best for him was the carnivore diet, which uh improved him greatly in many areas, including mood. Am I right there, Clay?

SPEAKER_02: 36:49

Yes. Yes, sir.

SPEAKER_00: 36:50

Right. So it really has to be individualized for every patient. So let's move on to talk about the effects of hormones on depression. I know from many years of experience that this is a huge factor, especially for women. I've witnessed it firsthand. We'll begin with the thyroid. Studies have shown that both hypo and hyperthyroid conditions are linked with higher depressive scores. And studies confirmed that correcting these conditions significantly improves mood and depressive symptoms. So here we have another correctable cause. So let's think about it and check for it when appropriate.

SPEAKER_02: 37:20

So we recommend a thorough thyroid workup and then thyroid optimization. Again, we did an entire podcast on hypothyroidism back in 2019. So we won't go into great detail here at this point. However, if you're interested in taking a deeper dive into that, then we highly recommend you go back and listen to that.

SPEAKER_00: 37:40

Cortisol is another hormone associated with depression. Cortisol is our stress hormone, and it's kind of like Goldilocks in that too little can be bad for you, and too much can also be bad for you when it comes to depression. It needs to be just right. An article from the journal Endocronology discusses how low cortisol may indicate HPA axis exhaustion, and it's observed with patients with persistent stress or trauma history, leading to a depleted stress response system. Along with this low cortisol, you can often see certain subtypes of depression, such as chronic atypical depression, PTSD-related depression, and later life depression. Again, this is easily correctable if you just take the time to look for it. And by the way, we did an entire podcast on this subject called adrenal fatigue, which is available for your listening pleasure.

SPEAKER_02: 38:25

And next on our hit list is a hormone called pregnenolone, which is considered to be the mother of all hormones. It is the first hormone made from cholesterol. Pregnenolone then goes on to make all of the other sex hormones. A randomized controlled trial from the journal Neuroendocrinology in 2021 found that patients with depression had lower pregnenolone levels, and pregnenolone supplementation was associated with significant improvement in depressive symptoms, especially in patients with bipolar depression, particularly.

SPEAKER_00: 39:00

Well, coach, next up is DHEA. And again, we find that multiple high-quality studies show that patients with major depression often have lower DHEA levels compared to healthy controls. And DHEA supplementation can reduce depressive symptoms in some patients.

SPEAKER_02: 39:15

Moving on to estrogen, clinical studies consistently show that naturally occurring periods of low estrogen, such as the premenstrual phase of the cycle, late perimenopause, and then aftermenopause, are linked to greater vulnerability to depression. Estrogen modulates serotonin and other neurotransmitters, exerts anti-inflammatory effects, and supports neural circuits involved in mood regulation. So it's very important.

SPEAKER_00: 39:41

And research demonstrates that estrogen withdrawal or low levels can disrupt the stress response, can result in emotional reactivity, and can affect cognitive processes and can contribute to the onset of worsening depression. Furthermore, estrogen replacement therapy has been found to improve mood in many low estrogen women with depressive symptoms.

SPEAKER_02: 40:01

Of all the hormones, estrogen therapy stands out as the hormone consistently shown to help depression in women. Randomized controlled trials and reviews indicate that transdermal bioidentical estrogen is significantly more effective than placebo in treating depressive disorders. And if done correctly, it's safe and effective for the vast majority of women. But you need to make sure that you do have a provider who knows what he or she is doing. And just to be crystal clear, we do not recommend oral estrogen or non-bioidential estrogen due to the potentially dangerous side effects.

SPEAKER_00: 40:39

Pegesterone is another potential culprit when it comes to depression, particularly in women during times of hormonal fluctuation like the luteal phase of the cycle, perimenopause, menopause, and postpartum periods. Clinical studies find that low progesterone is associated with increased risk of anxiety, irritability, fatigue, insomnia, and severe depression in vulnerable individuals. Low progesterone is also associated with premenstrual syndrome, premenstrual dysphoric disorder, and postpartum depression. And again, this is easily diagnosed and treated.

SPEAKER_02: 41:10

Unlike estrogen, oral progesterone is recommended for these women. The oral form seems to have a greater effect on the central nervous system than the transdermal form does. What we often recommended was a transdermal cream in the morning so it doesn't cause drowsiness, and then the oral capsule at night, and this can help with sleep, but also help with mood. And again, you want to make absolutely sure that the progesterone that you're taking is bioidentical. It really matters in this case. The artificial or synthetic progesterone drugs, which we call progestins, can actually make things worse since we find that large epidemiological studies have actually linked common synthetic progestins with an increased depression. So we'd have the opposite effect.

SPEAKER_00: 42:02

When I transitioned into the integrative functional mode of my medical practice, I had many learning curves ahead of me, which included things like better understanding of nutrition, detoxification, lifestyle medicine, and hormone replacement therapy, among many others. All those things that you never learn in medical school and residency, which are so important. But ultimately, after seeing thousands of patients for hormone replacement therapy, I found the HRT to be one of the most powerful tools in my therapeutic toolbox. For so many women, they it was really life-altering for them. They came in feeling absolutely miserable and they came back feeling great. And when they came back feeling great, like everything was better. It was just almost too good to be true, coach. I at first I couldn't believe it, but when I saw it over and over and over again, you realize how powerful optimal hormones can be for many of these women dealing with issues including depression.

SPEAKER_02: 42:51

Unfortunately, the sad truth is that primary care doctors get almost no significant training in hormone replacement therapy for women. And then you look at your OBGYN doctors, who are often considered the hormone doctors, and less than 20% of them get significant training in hormone replacement therapy. And when they do, it's often with the non-bioidentical hormones due to the influence of drug companies, which, as we said at the very beginning, can actually make things matters worse.

SPEAKER_00: 43:19

Multiple studies have shown that a properly designed hormone replacement therapy regimen is considered highly beneficial for most women when evaluating the full spectrum of menopause-related health concerns. And yet most women are not getting this message and are not being offered proper HRT therapy. So, bottom line to me, coach, it seems kind of simple. We as a medical community are really letting these women down. We do not seem to value women's health. And I guarantee you, if some of these same symptoms were happening in men, we would be all over it. We would probably pass laws and make sure that all the men were treated properly. But instead, we tend to let these women suffer needlessly.

SPEAKER_02: 43:57

I love when you get passionate about that, Dr. Mack. You're one of the few, few men, doctor, met male doctors out there, I think you would who would take up women's cases the way that you have. Grateful for that.

SPEAKER_00: 44:09

Well, coach, you know, I have a wife I care deeply about, uh, you Dr. Cheryl, and uh two amazing daughters. And I have been backed into a corner, Coach, and have been forced to become a closet feminist. Now, please don't tell my guy friends. I think that women's lives matter, and we all need to be advocates for every man, woman, and child to get the care that they deserve and need. For instance, it's crazy that some insurance companies will cover Viagra, but they won't cover birth control pills. Are you kidding me, coach? That just screams sexism.

SPEAKER_02: 44:39

And we'll move on here and take a look at testosterone. It's not just a guy thing, right, Doc? Women have testosterone too, and it can help them in many ways. A large meta-analysis in 2021 showed a significant association between serum testosterone levels and depression in women. Along with low mood, many of these women also had low energy, poor motivation, brain fog, and low libido. Furthermore, some studies have found that testosterone augmentation improved mood and decreased depressive symptoms in women, particularly among those with treatment-resistant major depressive disorder.

SPEAKER_00: 45:18

I clearly saw it in my practice, coach. I recall a particular woman who had major depression for years, was being treated with drugs and talk therapy, but nothing was helping. It was clearly impacting her life and her marriage. I checked her labs and her tea level was quite low, tea being testosterone. So I optimized her tea, and the depression magically went away, coach. I mean, completely. Her energy was much improved. She felt great, and she was blown away and extremely grateful. And it brought great joy to me to witness that amazing transition in her due to hormone optimization, especially with testosterone. Again, another simple treatable cause.

SPEAKER_02: 45:54

And let's not forget the men here. Multiple large cross-sectional and prospective studies confirm that men with lower testosterone levels are more likely to report depressive symptoms. Testosterone influences brain neurotransmitters like dopamine and serotonin, and low levels may reduce neuroplasticity and increase the vulnerability to depression. And again, yes, testosterone replacement therapy for men with low T has been shown in multiple clinical trials and systematic reviews to significantly improve depressive symptoms. The proof is in the pudding. So here we have yet another treatable cause for depression.

SPEAKER_00: 46:33

The last hormone that we'll look at in the context of depression is melatonin. A 2024 analysis of randomized control trials published in the Journal Archives of Women's Mental Health found that melatonin intake significantly reduced depression in postmenopausal women.

SPEAKER_02: 46:48

The bottom line on hormones is that many of them have a direct and powerful effect on brain health and mood in particular. At our clinic, we always embrace the concept of the symphony of hormones. The hormones don't act independently, they all work together, just like an orchestral symphony. And when they are balanced and optimized, they can make beautiful music together, including an improvement in mood. We did an entire podcast on hormones back in 2019. So you might want to go back and check that out to learn more about hormones. We also did podcasts on testosterone in men and testosterone in women in 2023, and you might want to listen to those as well.

SPEAKER_00: 47:28

You know, coach, let me uh try to give credit where credit is due. The first time I came across that uh phrase, the symphony of hormones, was Dr. Pamela Smith at an A4M conference years ago. And I don't know if she's the one who originally came up with it, but she's the one I learned it from. So I again I have to give her credit. She was a professor at the, I think, the University of South Florida, and and uh so really sharp lady. I really like her work. But uh now let's move on from hormones and talk about infections. How can infections cause depression? Well, uh chronic low-grade infections contribute ongoing inflammation, including neuroinflammation, that affects brain function. Lyme disease is a classic example. People with this can have depression and many other symptoms for many years without anyone connecting the dots to a tick-borne infection that the patient may have picked up years earlier.

SPEAKER_02: 48:14

Another quite common infection is a viral infection by the Epstein-bar virus. Most adults have been exposed to it, but in some people it can reactivate and cause ongoing symptoms, including depression. We also see increased depression with other viruses like cytomegalavirus, HIV, hepatitis C, and even chronic reactivation of chickenpox virus. Unfortunately, the treatment of these viruses can be difficult and controversial. Most docs really don't have an answer. My favorite podcast on Epstein Barr virus is by Dr. Aviva Romm, MD, on her podcast on health. It's the podcast number 47 called Epstein Barr virus, a stealth infection. I find Dr. Rom to be quite experienced, informative, and credible. So if you're interested in a protocol for EBV, then you might want to check that one out.

SPEAKER_00: 49:07

And now we're hearing so much about depression associated with long COVID. Estimates suggest that up to 30% of people with long COVID experience depression. There are clinics who claim to have protocols for prolonged COVID, but unfortunately, there's no standard agreed upon protocol at this point, which I can share with you. It's an evolving and controversial issue.

SPEAKER_02: 49:25

And the next thing on our list of infections is chronic sinusitis. Multiple large studies and reviews demonstrate that people with chronic sinusitis are significantly more likely to develop depression compared to those without the condition, with more than a 50% increased risk. And there is substantial evidence that a successful treatment of chronic sinusitis can improve depressive symptoms in affected patients. So check out episode 49 of Wellness Connection MD podcast for an in-depth look on natural microbiome-based treatment protocol for sinusitis. And also you might be interested in Dr. McMinn's book, McMinn's Sinusitis Microbiome Protocol, available on Amazon. Yeah, you can't. I have my own copy.

SPEAKER_00: 50:11

I've had some pretty good uh feedback from some of the patients who've uh tried the protocol from the book, and uh, so that's really rewarding for me to hear that. Uh a lot of these are patients who have failed uh traditional therapies with antibiotics and surgery. But anyway, uh likewise with urinary tract infections, uh chronic or recurrent urinary tract infections are significantly associated with increased risk of depression. Multiple clinical studies have found that people, especially women who experience frequent UTIs, report much higher rates of depression, anxiety, and reduce quality of life compared to those without recurrent infections.

SPEAKER_02: 50:42

In one study, 61.9% of patients with recurrent UTIs exhibited some degree of depression at baseline. And again, we find that successful treatment or prevention of these recurrent urinary tract infections can significantly improve depressive symptoms and overall mental health.

SPEAKER_00: 51:02

Another treatable cause. And another infection that is frequently associated with depression is viral myocarditis. Recent studies have shown that nearly half of myocarditis survivors experience clinical depression, sometimes persisting for years after their initial diagnosis and recovery. And furthermore, there seems to be a heart-brain connection. You've heard us talk about the gut brain connection, the the gut-skin connection, but here's a heart-brain connection, since about 40% of people have significant depression after a heart attack, much higher than the general population. This type of depression should be identified, addressed, and is considered treatable to a greater extent.

SPEAKER_02: 51:40

And the next infection that we'll mention is parasitic infections, which are more common than many people realize, even in developed countries like the United States. Meta-analysis found that the prevalence of mental illness, including depression, was fourfold higher among individuals with parasitic infection. Several studies specifically highlight Toxoplasma gondi, a common protozoa, often found in cat feces and undercooked meat, was strongly associated with depression, suicidality, and other severe adverse cognitive and psychiatric outcomes. Late-stage syphilis also frequently caused depression, and syphilis is making a comeback globally, including in the U.S.

SPEAKER_00: 52:23

Moving on now to the gut brain connection, there are numerous documented mechanisms by which the gut-brain connection can influence depression, starting with dysbiosis, which is an altered gut microbiome, which creates neuroinflammation via many different mechanisms. And there is also a direct effect on vagus nerve signaling, contributing to low mood.

SPEAKER_02: 52:43

Gut microbes also influence the production of key neurotransmitters like serotonin, dopamine, and GABA, as well as metabolites like butyrate, which have direct effects on brain function and behavior. Interestingly, fecal microbiota transplants from depressed individuals into germ-free animals induced depressive-like behaviors, demonstrating a causal link.

SPEAKER_00: 53:09

Isn't that interesting, Coach? So you basically you're putting fecal material from depressed humans into, for instance, a mouse, and then you get a depressed mouse. Fascinating. I I think they've actually done it the other way as well. They they take uh fecal material from normal individuals and put them into depressed people and they they feel better. It improves them. Yeah, yeah. So again, we have good news, Coach. Clinical studies show that intervisions aimed at restoring a healthy gut microbiome, such as probiotics, dietary changes, and fecal microbial transplantation can improve depressive symptoms.

SPEAKER_02: 53:44

You know, I remember many days just looking at Tyler's eyes, dealing with his dysautonomia stuff, which was also ended up being very gut related. But I remember looking at his eyes and just seeing the hopelessness there and the deep depression and just telling him, I'm gonna have the faith for you that you're gonna get better. But those were heavy days, and certainly his gut health and infection in his gut was a huge part of his picture. And we really saw with treating his small intestinal bacterial overgrowth, his cyboinfection there, huge improvement in his mood and his brain symptoms. And I would definitely say brain fog was a huge component for him that we saw improve, but also just his, you know, will to live and keep going.

SPEAKER_00: 54:30

You know, I think that would be just another interesting point, Coach. I I think that people who are diagnosed with or suffer with a chronic illness, especially when there's a sense of hopelessness, that in to oneself causes depression. I'm really kind of fascinated and love to do a podcast sometimes on the emotional and psychological effects of chronic illness. Yes. But I think that's uh it's another one on our list today here. But one variation of dysbiosis that we'll single out today is chronic yeast overgrowth. Now, this is a subject that's once again controversial, but we did a whole podcast on it, and I think we've made a pretty strong case for it. You may want to go back and uh check that out. Anyway, candida, which is yeast, can produce toxic metabolites that affect brain function. And while there's not a whole lot of research on this subject, since it's not really on the belief system of the mainstream medical doctors and researchers, some observations in small studies report that people with significant candidate overgrowth can experience mood disorders, including depression, as well as fatigue, anxiety, brain fog, and irritability. So again, our experience with this is that yeast treatment protocol can significantly improve these symptoms. We have seen it time and time again with our own eyes.

SPEAKER_02: 55:40

Now let's take a look at some lifestyle factors that may contribute to depression. And the main lifestyle factors are as follows eating a healthy diet, which we've discussed, maintaining an ideal body weight, no smoking, exercise, stress reduction, restorative sleep, adequate hydration, limited alcohol, socialization, and having a strong sense of community, loving relationships, spending time with friends and family, taking time for fun and pleasure and remaining sexually active if that works in your life, maintaining good hygiene, like your dental hygiene, connecting with nature, getting direct sunlight, and having a sense of purpose and life and living mindfully.

SPEAKER_00: 56:24

And coach, you know, I'd love to have the time to go into each of these individually, but I I promise you I did my homework and feel free to go back and fact-check me if you want to. But here's the bottom line: every single lifestyle factor on this list is associated with a measurable risk of depression. That's according to current research. And as I've said before, lifestyle medicine is the most powerful medicine on earth when it comes to many issues that we have, but including depression.

SPEAKER_02: 56:50

And I'd like to just take a moment to shine a spotlight on one of those, and that is exercise. Exercise is like a natural antidepressant, it increases endorphins, BDNF, or brain-derived neurotrophic factor, and helps reduce inflammation. But here's the key it doesn't have to be intense. Even regular, consistent walking can make a significant difference. Even better, walk in nature and in the sunlight.

SPEAKER_00: 57:20

You know, coach, I remember one time I read this really interesting article about just hearing birds chirp improves depression and lessens anxiety. So if you get out there and walk down a nice trail, you know, you get the sunlight, you hear the birds chirp. There's somehow that connection with nature is so powerful. And yeah, the coach, the this the science is overwhelming supporting exercise for improved mood, including a review encompassing 97 meta-analysis, which found exercise to be one and a half times more effective than medication or counseling for managing mild to moderate depression.

SPEAKER_02: 57:54

I love that. You know, I've been doing a lot of walking up where we live now, but I have noticed that of all the walkers, I would say 75% of them have their ear pods in or they're looking down at their phones even while they're walking. So I just want to encourage you, listeners, leave the phone in the car.

SPEAKER_00: 58:12

Yeah, yeah, yeah. You know, and okay, here's another thing. Lindsay lives on a lake. And and I I don't know that there are any studies, I'd have to look it up. Are there any studies showing that that looking out at the water reduces the pressure? I bet there is. To me, it just has such a calming effect to look at the water. I just love it. So I'm I'm very jealous that you live on the lake, Lindsay.

SPEAKER_02: 58:33

It's a it's a good life.

SPEAKER_00: 58:34

Good for your mental health.

SPEAKER_02: 58:35

Lake life is good life.

SPEAKER_00: 58:37

Yes.

SPEAKER_02: 58:37

So next on our list is toxins. There are three main types of toxins that we like to look at: heavy metals like lead and mercury, organic toxins like PFAS, the forever chemicals, and mycotoxins from mold. And these toxins are much more common than most folks realize. Again, evidence is clear that increased exposure to any of these may be associated with depression. But the first step to deal with this is avoidance. And then there are also specific detox protocols for these substances. We did an entire podcast on toxins back in 2021 that you might find interesting. But the bottom line is that removing toxins can result in an improvement in depressed mood.

SPEAKER_00: 59:26

And our next cause of depression is mitochondrial dysfunction. Mitochondria are the little energy factories in all of your cells, and your brain cells are particularly high energy cells, so they need mitochondria to be running on all cylinders. Mitochondria play a significant role in the pathophysiology of depression by impairing brain energy metabolism, neurotransmitter regulation, cellular resilience, and neuroplasticity.

SPEAKER_02: 59:50

Studies clearly show that patients with mitochondrial diseases or mitochondrial DNA mutations have a much higher prevalence of depression. Symptoms compared to the general population.

SPEAKER_00: 1:00:02

Again, the good news is poor mitochondrial function can often be improved through a combination of lifestyle interventions, dietary adjustments, targeted supplements, and individualized medical therapies. And as mitochondrial function improves, so does depression.

SPEAKER_02: 1:00:15

Now, here is another treatable cause of depression that may be surprising for some folks. Low cholesterol is associated with an increased risk of depression, with numerous studies supporting this connection across different populations and age groups. Several studies, including research in both men and women, report that individuals in the lowest cholesterol percentile have significantly more depressive symptoms than those with higher cholesterol levels. This is particularly noticeable with low LDL and is likely due to effects on brain neurotransmitter systems and cell membrane function. Interestingly, one of the listed potential side effects of statins is depression. Go figure.

SPEAKER_00: 1:01:01

Yeah, that's right. You know, coach, we often think with uh cholesterols, especially with LDL, the lower the better, but that's not quite the case. I think uh it gets too low, it can have an effect on brain health, including depression. Many other prescriptions and over-the-counter medications list depression as a potential side effect. Some of the more common ones are beta blockers, clonidine, ACE inhibitors, tamoxifen, oral contraceptives, benzodiazepines like Valium, antieleptics, antiparkins meds, opioids, NSAID drugs, steroids, proton pump inhibitors, H2 blockers, antibiotics, especially the fluoroquinolones, antivirals, antihistamines, digitalis, cyclobenzaprine, a muscle relaxer, and some of the GLP1 drugs like ozimbic and wigovi. So the cause of your depression may be right there in your medicine cabinet. Again, another correctable cause, but never stop meds without the approval of your doctor.

SPEAKER_02: 1:01:52

Another treatable cause of depression is seasonal affective disorder. Therapy for this may include light therapy, psychotherapy, medications, vitamin D supplementation, exercise, healthy diet, managing stress, and increased daily natural light exposure. Such treatment usually helps and the mood does improve.

SPEAKER_00: 1:02:12

And coaches a new kid on the block when it comes to the causes of depression. That is the issue of screen time. Studies show that increased screen time is strongly associated with higher risk of depression across all age groups, but especially in children, adolescents, and young adults.

SPEAKER_02: 1:02:27

There is a subset of screen time that is particularly worrisome, and that is excessive social media use, especially passive scrolling. The average American teen spends five hours per day on social media.

SPEAKER_00: 1:02:42

Say that again, coach.

SPEAKER_02: 1:02:43

Five hours per the average American teen on their phones.

SPEAKER_00: 1:02:48

Where do they find five hours to do that? Is it take is it taken away from their sleep or from their homework or whatever? That's incredible, coach. Five hours a day.

SPEAKER_02: 1:02:56

It's startling. And this can actually, not unsurprisingly, increase depression and anxiety. And that's where we kind of have this word doom scrolling.

SPEAKER_00: 1:03:07

No wonder they call it doom scrolling, huh?

SPEAKER_02: 1:03:08

Mm-hmm.

SPEAKER_00: 1:03:09

So, okay, folks, we're about to wrap this up, but bear with us just a bit longer. Before we close out, I would just uh briefly like to mention an interesting concept called metabolic imprinting in infancy, also known as micrometabolic imprinting. It has to do with epigenetic modifications induced by early influences during infancy that can result in stable, long-lasting alterations in gene expression via epigenetics relevant to brain function, emotional regulation, including depression. For instance, people who were bottle fed as infants appear to have a higher risk of experiencing depression as adults compared to those who were breastfed, according to multiple studies. Again, in many instances, this is preventable. We should be strongly encouraging breastfeeding when possible. And we get it that not all women can breastfeed, and that's fine, no judgment here, but I'm just saying that when possible, breastfeeding is a good thing.

SPEAKER_02: 1:03:58

A huge advocate of that. And I currently work with moms and babies, and breastfeeding is hard. Yeah, right. It is so hard. And I'm very passionate about people having education about it during pregnancy and pre-pregnancy, so that in those early postpartum times, they know and they have the strength to keep going. Like, why am I doing this? Why am I trying to breastfeed? Um, I turned out okay, but they don't recognize what are some of the long-term effects of bottle feeding or or not getting that good breastfeeding in.

SPEAKER_00: 1:04:32

Well, coach, they say that I turned out okay, but but the problem is we never connect the dots. Like let's say they move on in life and and and they're 40 years old and they get depression. They don't realize that bottle feeding made them more susceptible to that.

SPEAKER_02: 1:04:45

Yes.

SPEAKER_00: 1:04:45

Right? It's all about connecting the dots.

SPEAKER_02: 1:04:48

I agree. I think connecting the dots is so important and just really educating people on facts. So we've got longitudinal studies that show that exposure to antibiotics during infancy and early childhood, especially the first two to three years of life, is associated with a 10 to 50% increased risk for mood disorders later in life. And that's definitely not something you hear in the moment when you're when you're giving this to your child. And certainly there are times when antibiotics are needed and we're 100% supportive of that. And the modern medicine is is very good for many situations. However, all of the experts agree that antibiotics are vastly overused. As patients, we become expectant of a script for antibiotics for every sniffle. While we don't fully take into account the long-term connecting those dots, the long-term consequences, for example, like changes in our microbiome, and then long-term consequences like mood alteration and depression.

SPEAKER_00: 1:05:50

Yeah, there are some other direct causes of depression that we'll mention here, but due to time constraints, we won't go into in great detail because we're trying to wrap this up for you. But I've done my homework on this, and the science is very solid. Every one of these factors is related to increased risk of depression. And the factors are trauma in early childhood events, brain injury, even many years prior to the onset of depression, systemic autoimmune conditions, cultural factors and stigmas, especially for minority groups, substance abuse, including alcohol and drugs, chronic pain, obesity, neurodivergent conditions such as ADHD, and autism spectrum disorder, sensory loss, including hearing and vision loss, PCOS, which is polycystic ovary syndrome, prenatal mood disorders, anemia, neurologic diseases such as Parkinson's and MS, the epidemic of loneliness, air pollution, histamine intolerance, and mast cell activation syndrome. Well, that's a mouthful, coach. Yes.

SPEAKER_02: 1:06:46

And we've covered a lot of ground here. And the health coach in me is recognizing that this might feel overwhelming to someone who's listening or struggling with depression. So where do we start, Dr. Mack?

SPEAKER_00: 1:06:58

Well, coach, it starts by taking a why approach. You know, why does the patient have depression? Or why do you have depression? And then I I I'm a big believer in taking a thorough history. So you look at the timeline, you focus on the antecedents. Uh, was there anything going on or right around the time depression started or just before? And the potential triggers. Um, and if needed, start digging with a good medical workup like I did with that patient with vitamin D. And start with the potential causes that are most likely based on the history and physical. Coach, this should all be in the wheelhouse of a good functional medicine doctor. In order to find a good functional medicine doctor, you may you may want to check out IFM.org for someone in your area. And let me be clear, coach, any doctor can become a functional medicine doctor. It's not a private invitation-only fraternity. It's all about changing your mindset as a provider from a knee-jerk symptom pill approach to a why approach. Why does the patient have the problem? And then putting in the work to overcome your learning curves, like topics such as hormone replacement therapy, nutrition, toxins, lifestyle medicine, just to name a few that you were never taught in medical school.

SPEAKER_02: 1:08:04

The next thing you'll want to do is pay close attention to lifestyle factors again. The most powerful medicine on earth. It takes some time and dedication, but start today to move your major lifestyle factors in the right direction.

SPEAKER_00: 1:08:18

On the nutrition part, Coach, consider working with someone like our friend Rachel Olson, who has been on the show a couple times. It may be difficult for you to find your own personalized diet to help you overcome your healthcare challenges, including depression. So Rachel can definitely help you make that transition. You can find her contact information and her bio at bigmenmd.com, or you can find another similar nutritionist and health coaches at ifm.org.

SPEAKER_02: 1:08:43

So listen up, listeners. This is super important. Never stop psychiatric medications, including antidepressants, without working closely with your prescribing doctor. And at the end of the day, you may just need to take those medicines, and that's perfectly okay. No judgment and no guilt. Do whatever you need to do to get better. And if you ever find yourself in a crisis, here's a great resource. Call or text 988 or contact 988lifeline.org. You're not alone.

SPEAKER_00: 1:09:15

And remember, this is a journey. It's never a quick fix when it comes to things like depression. And if you can successfully treat your depression at the root cause level, then it can be life-altering for you. So keep plugging away. Leave no stone unturned. Keep in mind that it may not be one big thing, but it might be a lot of little things here that you have to fix. So fix those small things, and you may be able to achieve an optimal outcome.

SPEAKER_02: 1:09:38

The body and the brain have an amazing capacity to heal when we give it what it needs and remove what it's what's harming it. And that's really what functional medicine is all about: working with your body's natural healing capacity rather than working against it or covering up symptoms with drugs. This podcast is basically about realistic hope and empowerment. For many people, you don't have to accept that depression is just something you have to live with for the rest of your life. By addressing the above causes, you can often outsmart it.

SPEAKER_00: 1:10:10

So, due to the length of this podcast, which focuses on a functional approach to depression, we're unable to really delve into the integrative therapeutic options for depression, but we'll make a point of circling back around to that and doing a separate podcast on this subject. So don't forget to subscribe to the show and so you won't miss our episode on integrative therapies for depression.

SPEAKER_02: 1:10:29

Well, that about does it for this edition of Wellness Connection MD. Thank you so much for listening, and we hope that we were able to share something with you today that informed and inspired you.

SPEAKER_00: 1:10:40

And if you like the show, please help us by taking a moment to rate us on iTunes. These reviews really do make a difference for us. Also, if you like the podcast, then take a moment today to let a friend know about it and help us spread the word about evidence-based, holistic, functional lifestyle and integrative medicine. We're trying to build a tribe of people who are passionate about holistic optimal health, and we hope that you'll join the tribe.

SPEAKER_02: 1:11:03

If you'd like to reach out to us to comment on the show or to make recommendations for future topics, then you may do so at drmcmin at yahoo.com.

SPEAKER_00: 1:11:13

And if you'd like to have a complete transcript of the show, then go on over to McMinn M D.buzzsprout.com. That's B-U-Z-Z-S-P-R-O-U-T.com. And now, coach, can you leave us with another of your wonderful Coach Lindsay Pearls of Wisdom?

SPEAKER_02: 1:11:29

Thanks, Dr. McMahon. You know, we've discussed today how we've examined nutritional, genetic, environmental, inflammatory reasons for depression. And I hope that this has really painted the picture that depression is not just simply a mental health disorder, but it's a brain disorder. There's very physical reasons that can be behind it. And I say this not to minimize the lingo of mental health, which is critical, but to challenge our entire concept of how we're thinking about this. Our brains are precious. I tell my kids that all the time. I'm always like, you only have one brain. And this pertains to them wearing helmets when they're bike riding. It pertains to when we're eating food at the table and or we're out socially and they're wanting something else. They say, Well, we're taking care of our brains. We need to treasure our brains and take care of them when they are malnourished, inflamed, or toxic, toxin overloaded, as well as trauma overloaded. So just want to encourage us to learn to love our brains and then they'll love our bodies back too.

SPEAKER_00: 1:12:26

You know, your Pearl of Wisdom reminds me of a wonderful old uh James Taylor song. Now, you're too young to remember a guy named James Taylor.

SPEAKER_02: 1:12:32

I love JT. My dad made sure I grew up knowing James Taylor.

SPEAKER_00: 1:12:36

That was my generation. Uh but uh he did a wonderful song called The Secret of Life is Enjoying the Passage of Time. Um love that song. And I think there's some truth to it. However, it's hard to enjoy the passage of time when you're depressed, right? And so this is a serious disease. And we're we're trying to empower you, and hopefully it's with providers. We're trying to empower providers to take it seriously and do whatever is needed, whether it be drugs or treating one of these treatable root causes to help people live a life where they can enjoy the passage of time.

SPEAKER_02: 1:13:07

Yes.

SPEAKER_00: 1:13:07

Okay. Well, coach, that should do it. Until next time, stay curious, stay informed, keep it real, and remember small actions can lead to big change. Take that first step towards better health.

SPEAKER_02: 1:13:18

This is Coach Lindsey signing out.

SPEAKER_00: 1:13:21

And this is Dr. McMinn. Take care and be well.