Revisiting the 2024 Trending Topics in Functional Medicine

Kalea Wattles, ND, IFMCP:
As a systems-based approach, the functional medicine model looks all facets of health; evaluating why disease occurs and uncovering what each patients needs to thrive. Over the past year, we’ve discussed how this personalized approach to dysfunction and disease makes a difference in clinical outcomes. On this special episode of Pathways to Well-Being, we’re revisiting some of the trending topics and highlights of 2024. From brain health and thyroid health to Long COVID, menopause, the gut microbiome and beyond, we’ll explore how the core concepts of functional medicine, such as precision nutrition, lifestyle modifications, and honoring the patient's story, can impact these diverse areas of care because they make health goals achievable and sustainable long-term. 

First up, we had Dr. Jaquel Patterson on to discuss how inflammation can impact brain function, and what we can do to help.

From Episode #70: Neuroinflammation, Brain Function, & Mental Health

An interview with Jaquel Patterson, ND, MBA, IFMCP

Kalea Wattles
Well, I think brain health is something that is relevant to all of us. It’s something that we all want to think about over the lifespan, and I think it’s really, functional medicine is really well-suited to address brain health because typically we think about neurology as its own separate or distinct discipline. But now we have all this research showing us that the health and the function of the brain has significant impact on disease in other areas of the body. And I think this feels so well-aligned with the systems biology approach that we use in functional medicine. So I wanted to start our episode today talking a little bit about symptoms because I think a lot of us, it’s intuitive, maybe memory loss or some kind of cognitive decline, okay, we can understand how that’s related to the brain, but there might be some other symptoms or clusters of symptoms that are indicative of brain dysfunction. Will you walk us through some of those things that you’re looking for? Maybe some red flags you’re looking for?

Jaquel Patterson, ND, MBA, IFMCP
Yeah, so one of the pieces is that we tend to, especially as we get older, we’re in a very busy, fast-paced lifestyle. We tend to sometimes write these things off as due to stress, or due to overwhelm, or a busy mom, for example. And so the symptoms can include things like not just general cognitive decline that people are aware of, brain fog, memory. So a lot of people will have it start beginning with, like, short-term memory issues, inability to focus attention. Also, there’s a huge interrelation too as well with brain health and also the gut microbiome. So a lot of individuals might be having digestive issues as well, which can also impact their brain health. So I think inattentiveness and focus is something that we tend to just write off again as stress or overwhelm. But things that, those small little baby things that we kind of disregard might actually be the beginnings of things like neuroinflammation. Sleep issues, insomnia, chronic stress will cause brain inflammation. So it really affects all different systems of our body, just like many things in our approach in functional medicine. And what I love about this topic is neuroinflammation and the causes of it and how that can affect brain health because oftentimes we’re just looking at things like our neurotransmitters, but how does inflammation actually also impact our brain health negatively where there’s this interrelationship between that as well as our neurotransmitter function?

Kalea Wattles
So if someone has structural changes to the brain that are kind of manifesting as symptoms and you do all this workup and we have all of these interventions and all the lifestyle factors, is it reversible? Will the structure change again or it’s enduring and then we just have to manage the downstream effects?

Jaquel Patterson
It depends. If it’s structural, when you look at like our neurons and neuroplasticity, there’s definitely ability to heal and to improve it. It just often takes, when there’s been more issues with the neurons, it just takes longer to heal. They don’t heal as fast as when you’re looking at like muscle fibers and other parts of your body. They just take a longer period of time when there’s actually structural changes like things like dementia, if you look at things like Parkinson’s, or our goal is really to keep them as stable as possible. You might not necessarily have that reversing or changing in the structure of the brain. But being able to improve the quality of life and also to kind of keep things at a standstill.

You will see definitely many more changes on things like mental health conditions. Even studies have shown that an individual, which is something you should as like a pearl look out for as a clinician, if you have a patient that has a psychiatric condition, particularly like anxiety, depression, and schizophrenia, and they continue to have basically where their medication has become less effective, like where they need to keep changing, which we see all the time, keep changing their medications or they need to go on higher amounts, there has definitely been connection with higher levels of inflammation will cause it where there’s a greater need for higher dosing of medication, same as you’ll see for thyroid condition. Like if a person’s thyroid medication needs to keep increasing, there’s connections with things like cortisol and cortisol interrupting thyroid hormone. And you’ll notice the person needs to keep taking more and more and more thyroid medication. So those to me are always like red flags if I’m finding like, okay, the person was managed, and now they need to keep changing medications or they need to keep going up higher. You know, what is the reason why, what’s going on physiologically in their body that can help and kind of bring them backwards? And to your point and your question of can we fix, especially if it’s something like that, that some other physiological change is actually interrupting it, which is preventing like good progress, those things are much easier to be able to like fix and resolve.

Kalea Wattles
As Dr. Patterson reminds us, decreasing systemic inflammation not only supports brain plasticity and function, but has systems-wide benefits. Nutrition is a powerful tool for addressing inflammation and an important modulator of the gut microbiome. In our next clip, Dr. Michael Ruscio discusses how gut interventions to address dysbiosis can improve the absorption of nutrients and medications that help regulate and rebalance thyroid hormone.

From Episode #72: Improving Thyroid Function by Targeting the Gut Microbiome

An interview with Michael Ruscio, DC

Kalea Wattles
I want to focus on the microbiome because of course in functional medicine, we love to talk about the microbiome, and you’ve done some compelling work that highlights this connection between the gut microbiome and thyroid health. And you’ve dubbed this term nutrient-GI-thyroid axis. Can you unpack that for us a little bit? Tell us what that connection looks like.

Michael Ruscio, DC
Yeah. I mean, some of the broad strokes there are in those who do have Hashimoto’s, estimates vary, but it’s between 20 to 40% of those individuals will have a deficiency of either an intrinsic factor, HCl, or both. So they’re at risk to be iron anemic or B vitamin, B12, not the only one, but they may be a number of B vitamin insufficient due to low ionization of the minerals and the vitamins. So that’s one in terms of someone might be fatigued because of low ferritin or low B12. Maybe a lot of the people that we work with aren’t because I’m assuming they’re on multivitamins and B vitamins because they’re just so proactive, but it’s certainly something to be attentive to, especially depending on your population. Our population is just so well-read and so proactive that they’re usually on a number of vitamins already, but that is one important factor. Another, in regards to thyroid conversion and autoimmunity like we discussed earlier, vitamin D, selenium, and myo-inositol. And those aren’t necessarily broadly deficient, but they have been documented to help lower antibodies and improve conversion of T4 to T3. The other is iodine. There was one study, and I think this has been replicated by others, that found long-term adherence to a paleo diet actually did pose a risk of iodine insufficiency. So it’s not something that I think is on the population level. But if someone’s been on a restrictive diet for a long period of time, thinking about the Paleo diet cutting out some of the main foods that are fortified with iodine, which would be iodized salt, dairy, and grains, then inadvertently, these people might be eating their way into iodine insufficiency. So it’s just something to maybe have them use an iodized salt. And there’s even, I believe, an iodized sea salt out there where the iodine has been added back. And then gastrointestinal absorption. The other thing that happens in some of these cases is they’re not absorbing nutrients well. So wrapped in with the IBS, SIBO, whatever it is, especially if it’s chronic diarrheal type, they’re just not able to extract adequate nutrition from their food. And that’s where some of the, let’s say, fatigue, depression, thinning hair, and dry skin is coming from. It’s not thyroid, but it’s nutrient deficiency. 

Kalea Wattles
Yeah, the gut health seems to be pretty high yield. And my last question about it is, let’s say someone is, they’re already on thyroid hormone replacement. They come to see you. You start doing some of this gut restoration. Are you able to lower their dose or take them off their medication at some point once the gut health has been restored?

Michael Ruscio
Absolutely. Yeah. And for some people, actually, they will express signs of being over-medicated because their absorption improves. So definitely. And it’s an important thing to just keep an eye on. If someone does have frank gastrointestinal symptoms and they’re on hormones, they may start having palpitations, insomnia, feeling hot, which could indicate that, again, they’re overly absorbed. I guess they’re correctly absorbing the thyroid hormone. And coming back to that meta-analysis, because this is a common patient question, well, I’ve been on hormone for five years, ten years. Does that mean my gland is kind of wrecked and I can never get off of it? This study looked at these factors, and length of time someone was on hormone did not predict their ability to come off. So it was really reassuring, but what did was at time of diagnosis, TPO levels and TSH levels. So that’s something else you can do if you can get that data from before they started on hormone, what diagnosed them, then that can be used as a prognostic indicator of if they’ll be able to come off the thyroid hormone or not, or at least reduce their dose.” 

From Episode #68: Drug-Induced Nutrient Depletion and How Functional Medicine Pharmacists Can Help 

An interview with Dr. Lara Zakaria and Dr. Melody Hartzler

Kalea Wattles
For patients with long-standing chronic illnesses who begin to resolve symptoms through diet and lifestyle modifications, the next step is often medication therapy management and prescription tapering. Pharmacists are essential partners of a functional medicine care team; Drs. Melody Hartzler and Lara Zakaria continue the discussion on nutrient depletion and how pharmacists can work with primary care providers to identify areas of support for patient health.

People find functional medicine because they’re so excited about it being lifestyle-focused and nutrition-focused. And oftentimes they are specifically trying to avoid having to use a medication. But they might come in, they have hypertension, they have something that actually would really benefit from pharmaceutical treatment. How do we talk to them about the potential nutrient depletions in a patient that’s already not super excited about…

Dr. Lara Zakaria and Dr. Melody Hartzler
Right, yeah.

Kalea Wattles
Pharmaceuticals. And making it, you know, approachable and having them feel confident that we have the skills to kind of balance these issues.

Melody Hartzler
Yeah, you know, I always talk about things as tools in our toolkit. You know, we have a tool of this drug therapy, we have a tool of the nutraceutical, and we also have risk, right? So we have a risk of if your blood pressure remains high and you increase your risk for kidney disease or, you know, other, you know, cardiovascular complications. And I also, you know, normally probably bring in the conversation of, you know, the earlier we get your blood pressure controlled, the earlier we get your blood sugar controlled, we also have better outcomes because we don’t have this metabolic memory piece. And so sometimes we frame it as we’re going to use this tool, this drug therapy tool for this period of time while we work on the lifestyle modifications. Because yes, weight loss can bring down your blood pressure, but do I want to wait six months to a year for you to bring down your weight enough to affect your blood pressure? So when I think when we frame use of drugs in that way, especially for chronic disease, we’re not talking about rare disease or acute things that need treated like infections with medications. But I think helping them understand that drugs aren’t always, like, the evil thing. Like, there’s a reason that we have this modern information, and sometimes the use of drugs, it can be really helpful to them. Bringing in, like, when we’re talking about side effects of drugs, I also bring up there’s side effects to nutraceuticals too. So it’s not always just, you know, a side effect or a nutrient depletion related to a drug. There can be things that happen if we take too much zinc, we get our copper imbalance. And so that also is sort of, and not that it’s necessarily a depletion, but there are ways we can throw the body out of balance. We can methylate too much and cause issues there with people throwing all kinds of methylated B vitamins. So I just try to explain that they’re not, like, these opposing things all the time, and that, you know, they’re probably pretty more similar. We got drugs derived from a lot of plant-based things.

So we’re really just using a different tool and, you know, and when we’re talking about statins, I think, you know, that conversations with the CoQ10, you know, we know that we need to supplement with CoQ10. So that’s one thing we’re going to be asking, like, someone, okay, if we are recommending you take a statin, we’re going to recommend that you take 100 milligrams, or at least maybe 200 milligrams of CoQ10 a day. But it also depends on the risk. Are they a primary prevention patient? Have they had a heart attack before? Did their dad die at 50 of heart disease? Like, so there’s so much other nuance to I think the whole conversation with a patient and helping them understand, like, why drug therapy may be your best option right now. And also, I think helping them understand that drug therapy isn’t always a forever thing. Most people think they get started on a drug, I’m going to take this for the rest of my life when it’s related to a chronic disease. And so they’re always, you know, fearful of that decision because they feel like whatever decision they’re making in the office today means that this is the decision they’re making forever. And I think helping them understand that that’s not necessarily the case either. So understanding that, you know, while we work on these lifestyle things, like, our goal is to de-prescribe these drugs if we can. But again, like, safety and efficacy conversations and you know, what’s the risk/benefit. I mean, there’s always a risk to everything we do. There’s a risk walking across the street, there’s a risk if I decide to travel or I don’t decide to travel, or if I take a car or I take a plane. Like, so anything they choose to do, you know, whether it’s a nutraceutical or a drug, is always going to come with some conversation. So trying to make them not, like, opposing things, but sort of like both options in our toolkit, I think, has been my approach to things.

Lara Zakaria
I love using that analogy of a toolkit, because it truly is just another option, right? And we have data that helps guide some of those decisions. And then there’s personal, like, needs and family history and genetics that are really going to shift for one person or another. I like to give some specific examples. Like, antibiotics is my go-to example of just the vast change that we’ve seen in public health with the advent of antibiotics. Now could they be overprescribed? Absolutely. Can they create unintended consequences in terms of disrupting the microbiome and the gut health? And yeah, that’s all absolutely part the conversation, but sometimes we have to use that tool in order to save somebody’s life, right? And that is going to then mean, okay, well, that’s step one. Step two is now how do we reverse some of the adverse reactions that we saw as a result of needing that particular intervention? The other example that I give is in hormone replacement therapy, specifically thyroid. I find too often my patients assume that having to take thyroid medication means that they lost the battle somehow. That needing to take it or not being able to discontinue it means that they’re not doing a good job in terms of managing their thyroid condition. And that’s one of the first, you know, goals that a lot of people share with me when they’re working with me on their thyroid health. And part of it is, well, you know, you need thyroid hormone. It’s kind of the master metabolite. She is very important in terms of every single function that we have in the body. So if you are not able to make enough thyroid, that is a life-threatening condition, in my opinion. It starts off with superficial things, like losing your hair, changing your skin texture, changing your nail beds, and it just very quickly evolves into being more and more serious if we don’t actually address that deficiency. And there’s no shame in actually needing to take a replacement.

The other myth that I hear around this is around levothyroxine somehow being inferior to bioidentical hormones or T3/T4 compounds. And I don’t think that’s true for everybody. I think some people do really well on levothyroxine, and we’ve done an amazing job in public health of being able to get a cheap medication out to the masses to help to supplement their thyroid function. But what we can do if you are not indicated for a bioidentical or a T3/T4 combination is actually improve the conversion of T4 to T3. And I think that’s a missing conversation that you actually need certain nutrients, particularly zinc, vitamin A, vitamin E, antioxidants to help to improve the conversion from the inactive T4 to the active T3. And then from there making sure that T3 interacts well with the cell receptor so that it goes on to open that door and do the job that it’s supposed to do metabolically. And I think this really starts to open the conversation about empowering the patient with things that they can actively do. They can seek out foods that have these particular nutrients in them. If needed, we can supplement them with supplements, right? We can talk about the lifestyle prescription and how stress impacts that conversion and impacts that interaction with the cell receptor. We could talk about an anti-inflammatory diet and the role of antioxidants, right? We could start talking about how other hormones start to impact thyroid function, like insulin resistance and estrogen levels and things like that. And of course, we could talk about the foundational gut health component so that all of these things are functioning synergistically. And I think to me that conversation starts to shift from, “I have to take this HRT,” to, “How do I make this HRT work best for me?”

From Episode #69: Whole-Person Care for Perimenopause Symptoms

An interview with Carrie Levine, CNM, IFMCP

Kalea Wattles
Hormone replacement therapies are often considered controversial but recommendations in recent medical literature indicate that hormone replacement is an effective therapy for menopausal women who meet certain criteria. However, patient preference and availability of other therapeutic modalities are important considerations. A functional medicine approach to menopause and perimenopause care addresses the underlying issues that are known to contribute to hormone imbalances in order to alleviate symptoms and reduce long-term health risks. This might include nutraceutical and lifestyle treatments, hormone replacement therapies, or a combination thereof. In our next clip, Dr. Carrie Levine discusses the importance of hormone testing during perimenopause to help weigh the individual risks and benefits of HRT for each patient. 

We’ve talked about a lot of things to support women during this transition…you know, looking at hormones, looking at inflammation, looking at the gut, looking at the liver. Do you find that sometimes when you’re working on supporting all of these body systems that your patients don’t actually end up needing hormone replacement therapy or maybe they need less hormones or maybe you extend the time before they need hormone?

Carrie Levine, CNM, IFMCP
I love this question because as you know, hormone therapy is so hot right now. It is experiencing quite a resurgence with the redacting of the Women’s Health Initiative findings and the finding that hormone therapy increases the risk of breast cancer, which has been redacted, just to be very clear for listeners so that they get it right. And so women are calling and they’re like, “I want it. I want it.”

And I’m grateful for the way that I was trained around hormone therapy because the way I practice still feels aligned with what’s happening in the world, which is one woman at a time, a risk-benefit analysis for each individual woman, that the benefits may outweigh the risks no matter what they are, whether it’s a personal cancer history or a personal history of blood clotting, that we can do a lot to ensure people’s safety and wellness, which is one of the reasons I love comprehensive hormone testing, that absolutely positively includes the 2, the 4, and the 16-hydroxyestrone. That’s actually the thing I care most about. That’s the thing that compels me to ask women to invest in that kind of testing because I want to know, how is she detoxing estrogen? And is she doing it in a way that is increasing her risk for disease or protecting her? Because there’s stuff we can do, right? There’s stuff we can do to influence how our body detoxes estrogen.

So I’m all about meeting women where they are. And it was super helpful for me to go to AIC and hear Stacy Sims’ presentation on menopause and exercise and be reminded that exercise does everything that estrogen does plus. It might not be as awesome at treating vaginal dryness, but that’s easier, right? And that’s actually really targeted. Like if that’s all a woman’s coming for, then you can just give her estrogen for her vagina. You don’t have to give it to her systemically. But if you’re concerned about your brain, you’re concerned about your bones, you’re concerned about your heart, you’re concerned about your body composition, you’re concerned about your cognition, these are the reasons women want hormone therapy, right? Except that they think that it’s going to be a magic bullet to weight loss, many do. But if those are the benefits, if those are the concerns, and those are the potential benefits of estrogen, exercise hits all of them. So it was really good in the fury of hormone therapy to be reminded how therapeutic our lifestyle can be and to share that teaching with women so that they can choose from a place of knowing. That has been really helpful and compelling. 

Kalea Wattles
I think you’re really underscoring the importance of this functional medicine approach that is very patient-centered, that is going to blend the medical management aspect with the patient’s experience and their intuition. And you mentioned earlier that there’s this resurgence and an interest in hormones because we’re learning more, we’re more aware, we’re more in tune with our body. And so I’m wondering if you’re finding that there are more perimenopausal women who are, you know, still menstruating, who are reaching out to you and saying, “I’m interested in trying hormone therapy because I’ve learned that this might help me in my menopausal transition, and I just want to be proactive and start now.” Is that coming up for you?

Carrie Levine
Oh, 100%, yeah. Or they’re putting together the dots of family history and wanting to be preventive or proactive about that.

Kalea Wattles
And so in that scenario, are you saying let’s start with, you know, the cortisol and the inflammation and some of our standard evaluation first and see how much traction we get, or is it okay to kind of say, oh, right, let’s try some hormones?

Carrie Levine
It depends on the woman, right? I mean, always for me, you know, I have plenty of women who walk through the door and say, “I’m depressed, I want an antidepressant.” And I have women who walk through the door and say, “I’m depressed, I don’t want an antidepressant.” You know, I have women who walk through the door and say, “I want hormones.” And I have women who walk through the door and say, “I don’t want hormones, but I gotta deal with some of this stuff.” So for me, it’s really about meeting women where they are and what their preferences are. I will definitely say to a woman, if she says, “You know, I’m afraid of hormones, or I don’t want to consider hormones,” or whatever, I will get into the research a little bit with her because I want to dispel fear. If there’s unfounded fear about that as a tool in the toolbox, I want to dispel it so that she knows like, here’s this giant continuum of things that are available to me to help me feel my best. And I don’t want to vilify something that doesn’t need to be vilified when used appropriately, right?

And so I will sometimes say that, and I will on occasion say to a woman, “I think you’re a great candidate for hormone therapy. Is it something that you want to give a try?” You know, I don’t know. Sometimes people don’t respond the way I think they’re going to respond. It surprises me still to this day, but every now and again, I will prescribe progesterone in particular, thinking it’s going to be super duper helpful, and it has the absolute opposite effect, and that’s okay. You know, that’s what I tell women, like, most of the time, people do really well. Every now and again, I have someone who has a response that I did not expect, and I do not write that off, you know? I’m like, okay, it didn’t work for you. Let’s see, what else do we have in our bag of tricks that can support you?

From Episode #67: Mental-Emotional-Spiritual Connections to Physiology

An interview with Kara Parker, MD

Kalea Wattles
One of the foundational tools in Functional Medicine, the Matrix, maps out clinical imbalances in various body systems to help clinicians make these kind of data-driven, personalized recommendations for patients. Not only mapping out physiological dysfunctions to consider, but also contextualizing the patient’s mental, emotional, and spiritual needs as well. Supporting patients on their healing journey is more than addressing physical symptoms, it extends to strengthening all dimensions of their health and well-being. And this support for patients can take many forms, depending on where they are at in their unique journey. Dr. Kara Parker discusses her work with low-resourced communities, the connections between physiological and mental-emotional-spiritual health, and how mind-body practices can help these patients take control of their health.

Kara Parker, MD, IFMCP
As I advance through this practice and look at what’s the biggest bang for our buck with patients, we really keep coming back to adding as much mindfulness and mind-body practices for patients. And that really hits on the center of the mental, emotional, and spiritual aspect. When you think about what do we do in medical care, especially in a standard clinical system, that really impacts people’s capacity. It’s not unique to our clinic and our system that we have low access to psychologists, especially psychologists in the language and of the culture that people may need their mental health care. We don’t easily have access to, you know, health coaches and things like that. And so we do what we can to help empower people, give them agency, and work on their own self-regulation of understanding what their thoughts are, understanding what their emotions are, what they’re utilized for, and finding some ways to self-regulate that, to work with then, therefore, their physiological processes and symptoms, ultimately even down to labs and certainly behaviors.

Kalea Wattles
It’s clear how important our mental, emotional, spiritual health is. We’ve made a case for that. I think we can all agree that’s so important. But when someone is facing challenges to their basic needs of not knowing when their next meal is, where that will come from, or, you know, do they have housing insecurity? It was a little bit hard for me to understand how I make the case for dedicating the time to a meditative practice or prayer or mindfulness when there’s this sense of urgency. But maybe that’s my own urgency and not so much the patient’s. So I would love to hear, how do you hold those two occurrences?

Kara Parker
Yeah, well, I’ll tell you what happened today. I asked the patient, you know, a person with severe asthma and allergies who a colleague sent to me, and we go through the story and, you know, mold, mold, mold, mold, that he was unaware of. He’s now 48 and he’s like, oh my gosh, throughout my whole life and my current situation? Huh. You know? So I said, well, how’s your thinking? And he’s like, ugh. Muddled, unclear. I can’t think, my mood is so low. And now that you’re telling me about what mycotoxins can do, my mood cleared up quite a bit when I myself got out major allergens. But there’s still a long way to go. And I can see that, you know, what I need to do is get out of this apartment. I can’t afford to do that right now. This is going to be a bit. I’m going to be in this situation for a bit, and I know that it’s toxic for me, so let’s talk about how we can reduce that. But what he said when I said, well, what about your emotional health and your spiritual health? And he’s like, you know what? I don’t even know who I am. I don’t even know who I am. And I don’t know who I am because I think I’ve been under such a barrage of stress my entire life and so unstable in my basic needs and then in my health issues. He’s like, let’s come back to that question. You’re going to know I’m better when I can answer that question. I thought that was really great, right? But he’s telling me this is a marker of my health that I want you to ask about again, when I can say who I am and what’s meaningful to me, I’m there to be able to even answer the question. 

The mental, emotional, spiritual piece of that, if you can help people with their suffering, with what things mean to them, with how they think about it, sometimes that’s all you have with a low resource population. And that can be the most important medicine that you’re giving when, you know, other resources are lacking. So it becomes, in that way, a focus of the therapy itself. And as I look over people and think about stories, I think about just how important that is to be a person in someone’s life that they trust and that you can map their health journey with and watch ways in which they’ve suffered be released over time.

From Episode #61: Long COVID and the Functional Medicine Approach to Care

An interview with Elroy Vojdani, MD, IFMCP

Kalea Wattles
Taking time to listen to a patient’s story provides additional insight into how their past health history influences the current symptoms and concerns. In the case of Long COVID syndromes, tracking viral infections can identify underlying immune dysfunction over the course of a patient’s life and provides important clinical clues about the mechanisms that increase their susceptibility to infections. COVID researcher Dr. Elroy Vojdani explains how the functional medicine model helps clinicians evaluate and address immunologic burden from multiple clinical angles, providing an in-depth example of how mitochondrial dysfunction in insulin resistance exacerbates a pro-inflammatory state in the body which may explain why cardiometabolic conditions increase the risk of severe COVID-19 infection.

We all have those patients that have this history of all kinds of viral parts of their story. When we make the timeline, they’ve had all of these viruses. How can we prepare that type of patient knowing that COVID is a part of the ecosystem out there? Is there anything that we need to consider, any special considerations for that specific kind of persona almost?

Elroy Vojdani, MD, IFMCP
Yeah, I think the most important question to ask in that scenario is, “Why was that individual so susceptible to a very common virus tipping things into such an uncontrolled place,” right? So what do we know about that? And this is where I think functional medicine is perfectly suited to answer these questions because we’re in the mindset of asking a “why” question from a whole body perspective. And quite frankly, very few other people are going to ask that question. So, if you kind of dive in and look at why, let’s say not in the long COVID state, but just let’s say the general population, why are certain individuals so triggered by EBV and others aren’t? There’s a whole slew of explanations for that. There was an article that was published just a couple weeks ago [January 2024] that showed specific immune haplotypes are incapable of dealing with an acute EBV infection. And it looks like those are the ones that are going to be susceptible to something like MS being triggered. But just open up the functional medicine toolbox, and you’ll have all the other explanations for it. Somebody who had preexisting immunological burden is going to be primed for EBV creating a problem where otherwise they wouldn’t. So did they have intestinal permeability? Are they dealing with chronic emotional stress? Do they have some type of environmental toxin exposure? All the things that we learn about in our functional medicine training pertain perfectly to this question.

Kalea Wattles

Yes, I can see clearly how functional medicine is particularly well suited to answer these questions. And thinking about all of the antecedents and triggers and mediators that might contribute to viral susceptibility or severity, let’s start to layer on this piece of metabolic health, and will you help us understand how comorbidities, things like diabetes, obesity, how that can also potentially contribute to the development of long COVID?

Elroy Vojdani
Absolutely. So this is going to involve us opening our biochemical understanding once again. So I think one of the earliest signals in the early days of the pandemic was that individuals with certain comorbidities were much more prone to severe COVID or life–threatening COVID. And since then, those same comorbidities have been known to be the same risk factors for the development of long COVID, and what are they? Primarily metabolic dysfunction, obesity, I think, being at the top of the list. So you kind of like break down obesity and you look at the mechanisms of viral defense and what are the connections between those two. In other words, how does an obese individual end up in a situation where their viral defense is inefficient for what it’s being faced with and therefore will suffer the consequences of that?

So in metabolic dysfunction, let’s say insulin resistance, type 2 diabetes, we have a situation in which cells are incapable of receiving adequate chemical energy into a cell. So their glucose transport from the plasma into a cell to be converted into ATP is dramatically hindered by the insulin resistance. The end result is that the mitochondria for those individuals are much more inclined to be running on aerobic glycolysis or anaerobic…Sorry, anaerobic glycolysis instead of oxidative phosphorylation. So again, going back to kind of basic biochemistry, when someone is running on anaerobic glycolysis at the mitochondrial level, the amount of ATP that they produce per molecule that comes in is dramatically less. They’re producing two to four ATP versus when somebody is working through oxidative phosphorylation, they’re getting somewhere between 30 to 36 ATP. So huge differences in the amount of cellular energy being produced for the amount of food energy coming in, essentially.

Now, mitochondria are extremely fascinating in that the amount of energy produced will actually dramatically change the balance of reactive oxygen species being produced at the mitochondrial level. In other words, for a mitochondria to go through anaerobic glycolysis, to have to produce those two ATP, there are massive amounts of reactive oxygen species that are beginning to be produced at the mitochondrial level compared to someone who’s going through oxidative phosphorylation, who have a much smaller amount of those reactive oxygen species necessary. So person A in metabolic dysfunction, insulin resistance, type 2 diabetes is in a massive deficit of antioxidants because of the massive production of reactive oxygen species from that energy dysfunction. Person B who is metabolically healthy has plenty of antioxidants because they’re not producing so many reactive oxygen species to create the same amount of ATP. Mitochondria are incredibly sensitive to oxidative balance, so person A will end up further damaging their mitochondria by having to produce this ATP in this inefficient manner because the reactive oxygen species that they’re producing through the energy chain will end up going back into the mitochondria and damaging the very fragile DNA. The next thing that you know, you have mitochondria that are basically stuck in a permanent dysfunctional state. And the fascinating part of it is that they also are inhibited from mitophagy. So when you kind of look at what that means from an immunological perspective, the damaged mitochondria in the insulin–resistant metabolic dysfunction individual leads to what we call permanent inflammasome activation, which is a pro–inflammatory prothrombotic state with a handcuffed immune system because of a lack of antioxidants. And if you look at what happens to somebody with severe COVID, it is exactly that, it’s viral persistence with an uncontrolled prothrombotic and proinflammatory state.

So the metabolic conditioning equaling the mitochondrial conditioning equaling the immunological function is the linear progression of how someone with metabolic dysfunction means immunological dysfunction. And of course, we term this now immuno–metabolism, because through our understanding of COVID, the link
between metabolic health and immunological health has now been seen as one–to–one with the mitochondria at the center of that discussion. 

Kalea Wattles
Throughout the conversations this year, it’s clear how a functional medicine approach provides effective, whole person care for a range of health conditions. As clinicians, helping patients on the path towards health is more than just fixing what is physiologically wrong with them; it’s also about understanding what is important to each of those individuals in front of us. Functional medicine helps us do both, creating new inroads to make clinical connections about dysfunctions and disturbances at the cellular level, all the way up to the mental-emotional level. 

In the new year, we’re looking ahead to more advancements in the field of functional medicine and having more of these great conversations so we can all continue to advance our practice together. Thanks for tuning in today. I’m your host, Dr Kalea Wattles, wishing you a wonderful holiday season in good health.

To stream the full episodes of the clips presented today, please visit ifm.org/podcast

Stream Pathways to Well-Being on Apple Music, Spotify, and your favorite platforms today. 

The future is functional!

SHOW NOTES

Use the links below to listen to the full episode of the clips presented in today’s show.

Neuroinflammation, Brain Function, & Mental Health - An interview with Jaquel Patterson, ND, MBA, IFMCP

Improving Thyroid Function by Targeting the Gut Microbiome - An interview with Michael Ruscio, DC

Drug-Induced Nutrient Depletion and How Functional Medicine Pharmacists Can Help - An interview with Dr. Lara Zakaria and Dr. Melody Hartzler

Whole-Person Care for Perimenopause Symptoms - An interview with Carrie Levine, CNM, IFMCP

Mental-Emotional-Spiritual Connections to Physiology - An interview with Kara Parker, MD

Long COVID and the Functional Medicine Approach to Care - An interview with Elroy Vojdani, MD, IFMCP