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Episode 26: The Future of Healthcare is Precision Medicine with Dr. Mark Holthouse, MD

Updated: Jan 15

Podcast Drop Date: 12/20/23

Join us as our very own Chief Medical Officer, Dr. Mark Holthouse, discusses the years of research that he has completed to create customized proactive, preventative medicine in our latest podcast episode. Our host, Amber Warren and Dr. Mark Holthouse will dig into the real meaning behind optimizing your health utilizing cutting-edge technology to prevent and reverse chronic diseases. Dr. Mark Holthouse’s new Precision Age Reversal program has been developed to help combat cancer, individualized to your genetics, and guaranteed to increase your quality of life!


Amber Warren, PA-C: Welcome to the Functional Medicine Foundations podcast, where we explore root cause medicine, engage in conversation with functional and integrative medicine experts, and build community with like minded health seekers. I'm your host, Amber Warren. Let's dig deeper. Welcome back. We're here for part two of our precision age reversal. All things Doctor Holthouse area of expertise and new love. I'm here again with doctor Mark Holthouse. Uh, doctor Mark Holthouse is the chief medical officer for FMI center for Optimal Health and Functional Medicine of Idaho. He graduated from Loma Linda University School of Medicine and went on to obtain his family practice training at UC Davis Medical Center. While in the Air Force Scholarship program at David Grant Medical Center, Travis AFB, doctor H has over 32 years of family practice experience and bring brings years of practice in the areas of functional and integrative medicine. As part of the Institute for Functional Medicine Teaching Faculty, he has educated thousands of practitioners and hormone health across the nation in the past ten years as an as an Assistant professor of medicine on the teaching faculty at Loma Linda University School of Medicine, he is an expert on cardiometabolic diseases, disease prevention, reversing type two diabetes, heart disease, high cholesterol, obesity, and metabolic syndrome. In addition to his clinical and teaching experience, he has 30 years of owning his own practice as Acting Medical Director, implementing strategic models in clinical practice and the business of functional medicine. Doctor Holehouse and his wife, Tammy, enjoy photography, snowshoeing, skiing, sailing, hiking, kayaking, and good food. Welcome back Doctor Holthouse.

Mark Holthouse, MD: Thank you and maybe kitesurfing in the future.

Amber Warren, PA-C: I was actually going to make fun of you. Like body surfing, bodyboarding. Oh, yeah.

Mark Holthouse, MD: No. Glad to be here.

Amber Warren, PA-C: Thanks, Amber. Thank you. We're here in Eagle, Idaho, at our new, um, center for Optimal Health. And this evening we wanted to spend, um, probably more time than not discussing Precision age reversal, a program that we just launched ten days ago. Seven days ago here in Eagle. Um, and I know it's really like your. I mean, I can't even speak to how excited, excited you are. I want you to be able to speak to that. Just your vision for this has been, has been, um, a long time coming. This has been a lot of hard work and dreaming and scratching notes and whiteboard sessions, and I love it. It's taken a lot, but we're here and we're launching this really exciting program. So tell us what it is and how it came to be.

Mark Holthouse, MD: Yeah. So this is really acknowledging age as a disease of its own, as the number one risk factor for what's killing most of us in this country. Uh, whether it's heart disease, whether it's diabetes, whether it's bone loss, dementia, arthritis. Um, we know that cells age. And we now understand a lot of. Well, they call them the nine hallmarks of aging at a cell level. And some people have added ten even. There's there's books now that have an 11th, but it's it's really, um, acknowledging that there with technology and advances, with testing and genetics and being able to analyze some of the things at a cell level, protein level, metabolomic level, what's happening? What's your cell actually doing? We can now measure a person's age. You can look at vascular age in your vessels and tell how old you are. So your your birth certificate is going to mean less and less with this new era, what your chronologic age. And so that's going to throw a real monkey wrench into age of retirement and insurance and a lot of things in our culture, um, as healthspan our biologic age, uh, takes the place of just looking at lifespan. Uh, I'm excited about this, though, because these chronic diseases are what I'm dedicating my life to. I don't work in the ER, urgent cares, ICUs anymore. That was the first part of my career, and I was just utterly depressed at the revolving door of the same 5 or 6 diseases, and often the same 100 people in my small community that we saw where nothing was being done differently, and yet we were expecting a different outcome definition of insanity, right? So fast forward 17 years of integrative care.

Mark Holthouse, MD: This I see for the first time is a way to it's a it's an advanced operating system, if you will, on how to organize chronic diseases like this and have a measurable for the first time. Right. Smart goals measurable and all those things. That's the M of smart. My nursing friends tell me because they love Smart goals. Um objective way when you enter the program. This program we're talking about tonight in particular is a year long program. And then repeat several of those same markers of age, whether they're genetic biologic age markers, whether they're lab tests, whether they're imaging tests. And then do it again at the. The end of the year. And after doing these interventions, being able to prove to people, hey, we moved the needle before and after, you are a younger. Uh, and here's how we can prove it. Don't just take my advice and my word for it anymore. So I guess that's why it's a conglomeration of how to get at all these diseases. Really. Root of the root as far as cause upstream, it's like the ultimate upstream medicine. It is. And it's something that you can now measure. So people that are skeptics, my engineers, my CEOs that want to see the data, love those guys and women. They come in now and they can see it. And they're your best evangelists when they see these results. So this is what this program is about.

Amber Warren, PA-C: Part one take a step back. Precision medicine. We talk a lot about how functional integrative medicine have been on the, you know, have been talked about for a long time now, several years, which is exciting. Why is precision medicine kind of the new, new buzzword? Yeah.

Mark Holthouse, MD: So precision is just that. It's a precise objective measurement as opposed to more of a subjective. I think I feel better since you started doing whatever better. My brain fog is better, my gut bloating is better, my bowel movements are what have you. My kids behavior is less ping pong and off the walls, which those are great observations to have. Those things though now coupled with hard actual analytes that you can measure, you can now measure these. The burden of zombie cells, these senescent cells that check out because they're, they're um, they've got problems with their DNA. Why do we.

Amber Warren, PA-C: Care about zombie.

Mark Holthouse, MD: Cells? So zombie cells are big. Zombie cells are basically, um, cells that have stopped dividing and they stopped dividing permanently. Uh, it was it was really a protective mechanism originally to stop people in their 30s and 40s from getting cancers. Uh, what would happen is the the cell would sense that there's a break in the DNA. We have a problem with the shortening of the DNA, and it exposes the DNA. The histones are no longer there. These little proteins that protect our our double helix and the telomerase activity drops off. And and the body senses this. And something called sirtuin, which splices damaged DNA and repairs it gloms on to these areas of damage where there's shortening and it stops the cell from replicating. This is was a protective mechanism for cancers. You know, when you have this happen and you can have, uh, a chromosome then attaching to some other random piece of DNA, um, this is how cancers occur. And so it was thought to be an advantage to halt these kinds of cells and prevent early tumors in our third and fourth decade of life. The problem is now that as we're living longer and we're living well beyond our reproductive ages of 30 and 40s, we've we develop and accumulate these masses of senescent non-dividing cells, which are secreting inflammatory cytokines and molecules that tell the healthy cells, the stem cells to go and become zombies as well.

Mark Holthouse, MD: And so this ages our organs, our macular. Uh macules. The eye, the retina, the eye is where a lot of this stuff is being studied. The optic nerve, you know, again, initially in, in yeast cells, then in round and nematodes and worms, Drosophila fruit flies and then in things like mice, rodents. And it's these ancient pathways that seem to be conserved across multiple species that are consistently being found in different cell types, tissue types and organs as a root cause for not working very well. So zombie cells started off as maybe a good idea from from a cell biology evolutionary perspective initially. But as we started to live longer, it has become more of a liability. And now we've got the ability to measure that. And there's a bunch of stuff you can do with different types of agents which have different names.

Amber Warren, PA-C: Yeah. It's interesting. I think this whole anti-aging longevity, um, arena that we're living in and everyone's talking about, we talk a lot about the preventable diseases like osteoporosis, cardiovascular disease, heart attack, stroke, um, you know, Alzheimer's, dementia. We don't talk a lot about these things being anti-cancer. Right, right. It's not as big of a focus for some reason. I don't know why. Yeah. So do you think you would be bold enough to say this precision. Age reversal program is anti-cancer.

Mark Holthouse, MD: I mean, absolutely, we're always careful to say we're not going to cure cancer. We can't reverse cancer, or I'll be I'll be canceled and defrocked of my license within a week. And honestly, we don't have that kind of data to show randomized, double blinded, placebo controlled trials. Yet. We've got plenty of evidence that is shown. For example, I'll pick metformin as a pharmaceutical. Metformin is a drug that developed in the 60s. Um, originally it's it's it's developed basically from the idea of the French lilac flower that's high in something called guanidine in these biguanides, um, have been altered to basically help upregulate some of these ancient longevity pathways. Now, they were patented as diabetic drugs because they also do some wonderful things as far as improving insulin sensitivity and lowering glucose. It's the first drug, usually that a type two diabetic gets put on. There's a lot of folks using this stuff. However, now because of its anti-aging and what it does for mitochondria and this AMP kinase pathway and sirtuins. Um, but metformin is just one example of, of how you can follow these pathways. There are so many other things in the natural world that do the same thing. And they they act in similar ways. Yeah. So the medications are not 100%, uh, they are not always clean. Whenever you block an enzyme or a receptor, there's always something to pay. And, um, you know, I think the wonderful thing is that when you look at, um, the way that these different pathways work and that you can hit them from a multi mechanistic angle, along with intermittent fasting along with, um, high intensity interval training and strength training and good sleep and the right food. Um, they have these synergistic effects.

Amber Warren, PA-C: Um, I forgot to mention in the beginning of the podcast, we're here doing our second ever, um, live podcast where we have members of the audience that are texting questions. So I'll just kind of dig in a couple of these. Um, this was interesting. Where do you start with care? If you're generally in good health and you don't really have symptoms? I guess as it relates to what we're talking about, you know, age reversal, anti-aging.

Mark Holthouse, MD: Yeah. You know, I think that is is a wonderful question because it speaks to the paradigm shift. Right. Um, if you're waiting to have something physically wrong with you, uh, traditional medicine, traditional Chinese medicine, are you? Vedic medicine believes homeopathic medicine. Uh, by the time you have physical symptoms, you're well into a problem and you're way down the line. Um, proactive care, which is preferentially where we get people in their 20s and 30s or even younger, they are coming in saying, I feel great. I'm not fatigued. I don't have any dysfunctions or diagnoses or medications. I just don't want to I don't want to follow the default.

Amber Warren, PA-C: Or. My dad became a type two diabetic at age 47. How do I not follow in his footsteps? Right? I've got family history of colon cancer.

Mark Holthouse, MD: You know who gets it? My financial advisors.

Amber Warren, PA-C: So true. Right? It's so true.

Mark Holthouse, MD: It's a 401 K for your health. So if you don't plan, why do we all do that and make those deferrals from our W-2 income. Well we understand if we don't have a plan there will be nothing there at the end. But yet we don't do that with our bodies. We do it with our cars. We have scheduled maintenance. That's preventive. We don't wait till we're on the side of the road, broken down preferentially before we start thinking about our our cars. And yet we we completely disregard that with our own bodies and our own health. Um, we'll spend 20, 30, 40,000, $60,000 on a vehicle 4 or 5, six times in our lifetime. Um, and yet we won't spend a quarter of that for a year to learn intense information that can be life changing, life altering once on ourselves. And it's a value issue.

Amber Warren, PA-C: Taking a deep dive and really looking at the biomarkers that you're looking at in the testing you're doing in this program, it's what are some of the tests that you're running in this program? I think it'd be good. Yeah.

Mark Holthouse, MD: Yeah. So getting into the specifics, you know what I like about this program? We we looked at most of the longevity books I've read in the last year by most of the big authors, and we went and shouted a couple of folks, Sammy, our marketer, my marketer and I, we we went out to Sarasota and shattered a couple of programs like this. And literally what we've done is taken and cherry picked the best parts of multiple programs left behind some things, and added some newer technology and made our own. And what that looks like is evaluating a genetics. In a practical way, not having a report this big that no one can get through. But meeting with the nutritionist and deciding, hey, your genetics says this is the kind of food your body wants. This is the kind of exercise your body.

Amber Warren, PA-C: Wants is so.

Mark Holthouse, MD: Amazing. Yeah the three by four genetics. So you know we've got we've got advanced cancer screening for cancers that we don't currently have screening tests for. We have intestinal stool testing that looks at digestion, malabsorption, the health of your gut inflammation. Do you have parasites. Do you have yeast? Uh, we look at arterial aging with ultrasounds. We look at soft plaque at some of the levels of engagement for people that are higher risk who have cardiovascular disease. Soft plaque, for those of you who don't know, is is the holy grail for a vulnerable artery. Uh, the calcification scores we get with coronary CTS now that are readily available, still not paid for by insurance, only looks at the stable, calcified plaque. And these programs, one in particular, has included in it, uh, this new technology, AI technology that's looking at total plaque burden, three dimensional scan, noninvasive test of your heart, both soft and calcified plaque.

Amber Warren, PA-C: And we care about that because it's not cancer. It's actually not Covid. It's still cardiometabolic disease that's killing men and women by far.

Mark Holthouse, MD: Oh yeah. Number one, number one. Number two, distance to number two is cancers. Um, so the the programs looking at all kinds of things with there's a special cell senescence aging panel, uh, which I'm particularly excited about because no one else is doing this in the area that I'm aware of. And this is measuring things like beta galactosidase, which is a marker that stains blue on cell tissue. Uh, when there's a lot of cells that are zombies, they make this enzyme when they're in their zombie state, when they're checking out, it's the last phase of the cell before it's it does die. Um, we're looking at markers of, uh, sirtuin function. We're looking at measures of actual intra and extracellular NAD levels. I don't know of anyone doing that. I didn't.

Amber Warren, PA-C: Even know you could do.

Mark Holthouse, MD: That. Right. This technology, that lab panel was added a month ago to the to this program. Uh, this program will continually evolve as this story is, is rapidly evolving to keep it relevant, but to be able to know what your NAD levels are and as opposed to just blindly going to the IV drive by shooting, uh, parlors here in town and getting nad and spending hundreds of dollars when that might not be where you need. That's where the word precision comes from. It's no longer just, oh, this is what you do if you want to be healthy. This is what your body actually is deficient in. And you don't need to spend money on that. You need to focus on that. A good point. So genetics cellular specialty aging testing. We're looking at cortisol saliva testing. We're looking at food allergy food testing with sensitivities. Um we've got RDDs that are working with me on the diet programs. We've got affiliations with exercise programs that are very specific as well as personalized nutrition plans. Um, we've even got health coaching in there to help people lower their cortisol, which we know can. It's it's like I said, it's Kryptonite to so much of the good work we're trying to do. So from the gut to the genes to advanced cardiovascular testing to looking at markers of inflammation and imaging, this thing really has it all. It does.

Amber Warren, PA-C: Yeah, I love it. We're starting to get some specific clinical questions coming in. Um, so I'll read off a few. Who is this program geared towards? We have a family member who is late in their late 40s and very morbidly obese, who is wanting to turn his health around. He just got declined by insurance for wegovy and doesn't know what his next step is. Is this program for someone like him?

Mark Holthouse, MD: Absolutely. Uh, my perfect client. There really isn't any perfect one client. I had a guy this week who's a CEO and has zero health problems, and he's 51, 57 years of age, and he just says, I want to I want to live as long as I can, as as healthy as I can, and I want to I want to be engaged with my grandkids, not watching from the sideline. What do I do? How do I get there? That's a person that's ideal for this program, as well as somebody who comes in like this who's got maybe some type two diabetes, some arthritis, fatty liver disease, who's already diabetic. Um, absolutely can help those folks within these programs, we've got built in, uh, options to talk about peptides and weight loss programs. We've got hormone optimization. Which is huge for a person like this. Um, but working with all of those pieces of data and then having a specific nutrition protocol to follow, an exercise protocol to follow, and having something.

Amber Warren, PA-C: You Google and say is going to help you lose weight.

Mark Holthouse, MD: Right? Right. This modified for you this program came from people who said, I'm tired of watching podcasts and going to summits and webinars. I'm I'm awash with information overload, and I need somebody that's legitimately a professional medical person that's trained in this stuff, not a traditional MD, and maybe not somebody who doesn't have a degree. Right. Um, to help hold my hand through this maze, this labyrinth of information. We live in a time of information overload. Some of it's completely irrelevant and distracting, and and it's driven by marketing and bringing you to buying a product. But some of it's actually aimed at getting you legitimate information that can be life changing. And this one year program, whether you do the entry level, the middle or the high level, is is meant to be inclusive of those core pieces of information that can literally change the trajectory of your life and your children's and their children's lives. Uh, what we don't always talk about is the impact we can have, especially as we get middle aged and older on our kids and our grandkids, and the choices that they make when they see you thriving and doing things that other people your age can't do anymore. That's the best testimony of any program. So true.

Amber Warren, PA-C: I've got another good one here. I'm a postmenopausal woman who has recently been diagnosed with prediabetes and fatty liver. I have a family history of type two diabetes and cancer in my family. How would this program specifically benefit me?

Mark Holthouse, MD: Great question. One of the things on metformin that I got distracted and totally spaced, but metformin has now been shown in human trials to, um, reduce multiple cancers, breast cancer, pancreatic cancer, lung, colon cancer, to name a few. Um, and so we see a lot of these same pathways of longevity being anti-cancer pathways, um, for multiple reasons. And I won't get into the weeds there, but know our diabetics are at higher risk for cancers. Our diabetics are at higher risk for osteoporosis. They're at double the risk of cardiac disease and stroke. Um, and that's not any surprise. It's driven by inflammation. So why do zombie cells matter? You asked me earlier. And why should we care about how many are around? They drive inflammation, and inflammation drives aging in each of these diseases. Most all of those diseases you just rattled off that she asked about are literally driven by inflammation gone amuck. Inflammation is driven by infection. It's driven by too much tummy fat. It's driven by periodontal disease. It's driven by, uh, some of the medications we're taking. It's driven by some of the, um, toxins, toxins in our life.

Mark Holthouse, MD: Infections, mold, Lyme and and unless you go look for these things and all you do as a CBC and a chemistry panel and a PSA every year, you're never going to see them. I liken it to flying and landing successfully at Jumbo Jet. With an altimeter as your only source of feedback, you're going to crash that plane every time. We are in an era now where we with the most complex piece of machinery on the earth, I would say certainly more so than a jet, the human body, what we get and the meaningful changes that we make are directly proportional to the data that we put in. And so if we're just using the same tests that we've been using for 50, 60 years, we're going to get that kind of information back, which is not very relevant. So and so was just given a perfect bill of health, had a physical a week ago and they just dropped dead. How does that happen? If you don't look for things, you're not going to find them?

Amber Warren, PA-C: Well, and a lot of times back to the inflammatory component, we often refer to these autoimmune diseases that we're seeing continually on the rise as autoinflammatory as well. We've come back to the source is probably just dysregulated inflammation. So it really does all stem.

Mark Holthouse, MD: To Hashimoto's.

Amber Warren, PA-C: Hashimoto's, Hashimoto's often silent. Yeah. It often is pretty a pretty silent autoimmune condition.

Mark Holthouse, MD: I tell people all day long when they come in with Hashi, they're really worried. Well, what did I do to get that? How did I get this? How come no one else has it? I tell them, look, when I first started my career, 30 years ago, I diagnosed a new autoimmune thyroid. Hashimoto condition once every six. Months. And now it's like once a week and our genes haven't changed. But the toxins that affect our genes, what we call the epigenetics of our our our expression of our genes, our DNA book of Life we've inherited from parents has has altered, been altered severely. And and autoimmune thyroid is kind of that canary in the coal mine. It's the sentinel on the hill that's that's getting taken out by the sniper. It's it's running point. Uh, it's very vulnerable for us. And so you'll see this especially in women, but even in adolescent boys, you know, we're seeing autoimmune thyroid. Doctor Brus or one of our pediatricians here and I were talking about how much more of that he's seeing at younger and younger ages. And we think it's probably because of toxins, you know, the foods and and what's in our air, our food and our water when we measure those things which this package, the PA one package age reversal in all three levels has an environmental chemical urine test because I can't do anything without knowing. Do you have endocrine disrupting chemicals or problems with obesogens chemicals that keep weight on you? So the gal that's questioning diabetes and obesity, that's an endocrine disrupting disorder, diabetes, insulin hormone problem. And it's an obesogen an obesity issue. And so chemicals are one of the saboteurs that no one really talks about with these problems. Too many chemicals, heavy metals, stress, high cortisol not sleeping well and infections. When we traditionally think about weight loss, we always think about exercising more and eating less. But that's just one little piece, uh, of of the thing. So when we don't get the results we want, we got to look at those other saboteurs.

Amber Warren, PA-C: Yeah. And they're everywhere. Yeah. I was at a, uh, a little off topic, but I was at a environmental health summit and there were six pediatricians all being interviewed, and it was a Q&A, and someone said, why do you think we're seeing the illness in children, the autism, the ADHD, why? If you could say the number one thing that's driving this, a few mentioned vaccines, but four of the six said glyphosate.

Mark Holthouse, MD: Yeah. Because we know glyphosate opens up those tight junctions. Um, I mean, kids are so resilient and they want to be healthy. They haven't had enough time to get the baggage of cell senescence to drive a lot of disease. Right? So often we just remove the dyes, we remove some of the herbicides that are opening up their their gut. We remove the gluten and dairy. And these autistic kids start talking these kids with, um, you know, they're bouncing off the walls. Yeah. Too much sugar. Sure. Whatever. But it's often the data is more about the dye than it is the sugars with hyperactivity. So I always laugh when they say, oh, yeah, grandparents who went over and fed a bunch of grandkids, a bunch of sugar and then left kind of laughing under their breath. Well, it's probably actually the the red 40 in the velvet cake, not the high fructose corn, right. The high fructose corn sirup and the leaky gut. So if you can heal their gut, you know, and eliminate some of these foods that are triggers, uh, that are not organic. And so and, you know, there's problems with organic, that's a whole nother podcast, um, you know, and things like that. But healing the gut, they're going to bounce back very quickly. And that's what it's so fun impedes they get like instant reward. Really instant.

Amber Warren, PA-C: Get better pretty.

Mark Holthouse, MD: Quickly. Yeah.

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Amber Warren, PA-C: So on topic of that, how can programs like this potentially help kids or even adults with things like significant ADHD or even autism?

Mark Holthouse, MD: Yeah. You know, I don't know that the anti-aging programs in particular were set up for kids. I mean, I'm thinking of that in the inception. It's probably 18 and older. Um, the concepts, however, are absolutely go across age lines. Um, the concepts with the genetics. We know their genetics when they're conceived. Uh, they're going to be there. So some of those constructs will be there. The food issues, the counseling regarding inflammation and the drivers of inflammation are certainly relevant for kids. Toxins, toxins, experimental toxin.

Amber Warren, PA-C: Absolutely.

Mark Holthouse, MD: Dietary guidelines I would suggest they they would be a better fit in some of the other packages where we're doing those things. Um, personally, yeah.

Amber Warren, PA-C: This is a good one from a little bit earlier, you spoke about diet strength training and walking for longevity. I guess that was a little bit part one. We honed in on the walking and the strength training. What are some of the other top activities, impacts and supplements that can contribute to increased, um, lifespan Healthspan longevity?

Mark Holthouse, MD: Yeah, so that's a huge, huge, huge question. Um, I, you know, as far as exercise and then we'll get into the bye bye mechanism, maybe some of the supplements. So it's not just exercise, it's the right kind of exercise. It's not just doing this with a dumbbell. It's multiple joints. You want to be lifting and and doing things that, uh, overhead presses. You want to be doing things with kettlebells with a trainer so they can watch your form so that you don't destroy your shoulders by going back too far, doing chest exercises that did that. Okay. So that's personal. You know, go back to 90 and stop. Not this where you're bouncing it off your sternum. Uh, when you do the kettlebells, you know, don't swing it wildly, keep it in close and you got to have form so you don't destroy your lumbar spine. I have so many folks that have good intentions, and they injure themselves and they're on the sick list. Then healing for six months. So go to a gym. You know, I don't want to say a particular gym, but the one I go to here in um, in the village is, is very inexpensive, less than $30 a month, unlimited access for group strength training. I got a bunch of friends. We all give each other a hard time when we miss and we laugh at each other.

Mark Holthouse, MD: You know, when we're sweating really hard and we've added more weight and they can tell we're suffering because we know each other really well, this camaraderie and that kind of thing. Group community is really necessary, I think, to having a longevity and changing a habit. But strength training like that is huge, where you actually get a trainer to help you, even if you just go around with a clipboard for a couple months or a month and, and you learn how to do it, learn how to do the form correctly. It's not about resistance. It's about getting your form down so you don't injure yourself and then work on the the the the resistance, the weight later. Um, walking. We talked about cardiovascular. When you're doing cardiovascular it should be high intensity interval training. Gone are the days of, you know, the Ken Cooper aerobic recommendations of 220 minus your age, 75% of that number for an hour, slogging away on, um, some instrument of torture in the upper level of the gym, uh, on a treadmill or something like that. You see these folks, you know, they're on their they're slogging away their bodies about three feet behind the handrails. They're watching the TV. And, you know, some of them may get some benefit, but it's creating a lot of oxidative stress. Much better to do Tabata drills to do 7 to 15 minutes of, you know, on all out recover two minutes on, and you're doing this for 4 or 5, six, eight cycles, maybe twice a week.

Mark Holthouse, MD: These take a lot out of you. Your perceived level of exertion is eight, nine, ten. You do not feel comfortable at all during the on part and you can't wait to stop. But this is the the outcomes, the yields you get from high intensity interval training and how that in it induces these ancient survival genes, these longevity pathways is is amazing. So you're getting an amazing workout in a much shorter period of time generating a lot less oxidative damage. Um, so with cardiovascular, I say if you can do a high intensity form of interval training at least twice a week, um, five days a week, strength training, making sure that you're recovering the different muscle groups in between. You don't want to go after the chest the same day twice in a row. You do back you alternate. So back, legs, triceps, biceps, chest, um, glutes. You know you don't want to do the same thing. Day in and day out. Your body likes change. It likes to be a changed up. Do different kinds of exercises, go out and mountain bike a little bit. Don't just spend all your time in the gym.

Amber Warren, PA-C: Um, there's benefits with nature bathing. Oh man.

Mark Holthouse, MD: Outside it's it does stuff here too, you know, I go to the gym because it's a way for me to consistently do what I want to do. I go out on my mountain bike because it's fun, and I'm. Oh, by the way. Oh, I just got a kick butt exercise workout. But I didn't really realize it because I was just trying to keep up with my son, and my tongue's on the ground and we're having fun. We just climbed Mount Saint Helens, um, right around there in Oregon or Washington. Switched back through the woods. It was it was arduous. And they're like, dad, you kept up, man. I said, my goal is to see your spandex, man and not lose it through the trees. Keep you in vision the whole way. It's getting harder and harder every year that goes by. I want to buy an e-bike really bad, but I've resisted the temptation. But you want to keep it fun too. You know, it's not all about just being a gym rat. Some people aren't into the gym. It's cool. Um, I need to do it to be motivated. Um, if I had a really nice personal home gym, um, you know, great. But. Yeah. So that's the type of exercise. Okay, then about things, other things you can do besides movement. So there's really a couple different categories.

Mark Holthouse, MD: There are things out there called stacks which are sirtuin activating compounds. That's things like Fisetin which is a polyphenolic compound found in things like persimmons and strawberries. You can buy it in a supplement back there too. Uh, quercetin green tea extract, um, something called butane, which is from found in flowering butane found in not butane the gas, but butane found in flowering plants. Resveratrol, which is probably one of the stronger of the polyphenolics, not probably panned out to be the panacea we thought it was going to be because it's not really soluble in the human gut, and as a drug, it was looked at and didn't really make the cut. The most recent stack that's out there is NAD, and that's been a big fad in everybody. If you've watched any podcasts on mitochondrial health and energy and neurologic and neurodegenerative diseases, you're going to run into NAD, uh, which is basically just a vitamin B3 derivative that our mitochondria and our cells use to help with sirtuin. There's that word again, it's kind of a keystone. Everything is focused on supporting sirtuins and sirtuins in turn come back and upregulate things like AMP kinase, which are ancient, uh, part of our ancient way of autophagy and detox and, and cellular making more mitochondria. Um, so stacks nad is a stack, a sirtuin activator chemical.

Mark Holthouse, MD: And, um, after stacks, you've got senolytics senile aging and lytic lytic means getting rid of Anxiolytics are drugs that get rid of anxiety, for example. So senolytics there are prescriptions out there, one of the most potent is a prescription. Not that I'm using this, but there's incredible data on a drug used to treat leukemia that is amazing at getting rid of zombie cells. Zombie cells are the focus of senolytic agents. They do away with them. Uh, physician. From these strawberries and persimmons I talked about, uh, quercetin, uh, are a couple of botanical senolytics. Uh, there are peptides, something called thymosin alpha one, which is a senolytic kills zombie cells. Uh, TB 500 thymosin beta four. It's a little different action on senolytic cells. It doesn't get rid of them, but kind of changes them morphologically for the good. So we've got prescription medications, we've got botanicals. Uh, a lot of them are polyphenolics. Where why is why is that a thing? You know, these are all from plants. The Pinot noir grape is is a varietal that's incredibly high in, in a senolytic called resveratrol because it's really sensitive to soil conditions and dryness. So if you plant these things where soils not the best and this really hot climate, they produce a ton of resveratrol because it's a stress response in the plant.

Mark Holthouse, MD: We eat those things and it's found in multiple different kinds of foods. That's just one example. Usually brightly colored plants. These polyphenolics. Are anti-aging because they are stacks. Some of them are also senolytics. They have a dual mechanism. So that's a long winded answer. So good. Um, to and there's also prescription drugs too. I mentioned, uh, where I am on this is lifestyle first. If somebody's really got some issues and we're measuring that, they've got a high burden of senescent cells, you know, there might be a place for some of the prescription stuff if it's safe. You know, they're working on Rapalogs as we speak, pharmaceutical companies. Um, Rapa Nui is the Easter Island where this stuff was discovered in a bacteria on the base of one of the 900 statues around Easter Island. It's an island 2500 miles west of of Chile. Nobody knows how they got there, but in the 60s, they found this streptomycin. Hygroscopicus was the bacterium that's an antifungal. All that it's immune suppressor. And they found this stuff. Rapamycin not only suppresses the immune system, but wow, it's an incredibly strong way to inhibit mTOR, which is a cancer generating pro-growth side of things that we're trying to always strike a balance with. So by inhibiting this anabolic pro-growth side of things, the teeter totter goes back towards more autophagy and catabolism and longevity and sirtuin and AMP kinase.

Mark Holthouse, MD: Um, this has been probably this is probably to date, the most effective molecule that we've got for anti-aging is rapamycin. The problem is in its existing form, it can be toxic to the kidney and it's an immune suppressing. So it's FDA approved for people that get kidneys and grafts so that we don't reject them. Um, in in smaller doses, on a cyclic basis, people are using it for anti-aging. We don't have a lot of data on that. And there's certainly some safety concerns. Um, so certainly off the beaten path, but this is the kind of thing that they're now developing are what we call rapalogs with that same mechanism of action that are cleaner. They don't affect the kidney and they're not immunosuppressing. So the pharmaceuticals are all over this stuff because they see this as a real I see dollar signs with anti-aging. We got the boomers and the Graying of America. Um, and so it's an opportunity for them. And honestly, um, if they can develop some things like that to move the needle and prevent not just longer years of life, but prevent all these diseases that are causing us to live shorter lives. Wow, wouldn't that be amazing? Yeah. So we'll.

Amber Warren, PA-C: See. Can we touch on what I still think is really an underestimated health value and for longevity specifically sleep? Yeah. We touch on.

Mark Holthouse, MD: Sleep. Yeah, absolutely. So some of these things like NAD are connected um to our biologic clock, our circadian rhythm. And in fact there's a pathway where we regenerate the salvage pathway of NAD that has components that are directly related to our circadian rhythm. This is why we think there's problems with more cancers, more obesity, with folks that work at night, swing shifts that have irregular sleeping hours where their circadian rhythms are screwed up. High cortisol is a consequence of living out of a natural rhythm, where our biological clocks are set a certain way, and we're trying to kind of go against the grain when we don't sleep. Well, not only do we not secrete very efficiently growth hormone and the regeneration of using testosterone and hormones, but our glymphatic that lymphatic system in our brain, we call it the glymphatic system, isn't able to get rid of the metabolites and the toxins that have accumulated in our brains. Cortisol, though when you don't sleep well, you're by definition often having abnormally high cortisol at night. A lot of our patients that can't fall asleep at night or have early awakening and they're just awake, it's because of spikes in cortisol. And there's a number of reasons why that can happen.

Mark Holthouse, MD: Low glucose being one of those. And problems with insulin resistance, um, metabolic inflexibility. Uh, these folks have atrophy of the hippocampus, which is the part of the brain that's dealing with memory and dimension Alzheimer's. So prolonged exposure to poor sleep leads to not only inflammation from this glymphatic detox process not being around, but high levels of cortisol, which is pro-inflammatory and leads to not only leaky gut, but systemic inflammation and an upregulation of what we call our sympathetic fight or flight. Nervous system. It's hard wired. When you get enough bathing of your brain in cortisol over time, it causes depression. That's the way that the SSRI medications antidepressants work in. Typical depression is by, we think, affecting high cortisol levels. When you don't have high cortisol and you're depressed, those medications don't work very well. And we call that atypical depression. So cortisol is a nasty thing for dementia, for memory, for immune system, for cancer risks, for gut health, for immune health, for cardiometabolic disease, for blood sugar, for obesity. The list goes on and on and on. So why is stress bad? There you go. We need cortisol to live. But like oxygen, too much will kill you. Yeah.

Amber Warren, PA-C: No, that was good. I know I'm constantly trying to educate my patients on cortisol and melatonin and how they're always in flux. And you want to optimize melatonin, obviously, at a certain part of the day and optimize cortisol to feel awake and alert. But they. Yeah, they can't both be high and both be low. We have to live our life and follow our ancestors regarding circadian rhythms to keep those things in flux.

Mark Holthouse, MD: Yeah, this whole light at night phenomena is kind of a recent thing really, in our in our biology. And so if you go over to Amber's house after five, you might see her in some funky looking blue blocker glasses.

Amber Warren, PA-C: Keep calling me out. Yeah, I know the kids will go flip on one of the bright lights and I'm like, turn it off. It's past sunset. What are you doing? Oh my.

Mark Holthouse, MD: Goodness. So many people are looking at their devices with blue light, lowering melatonin right up until they try to go to sleep. And good luck. Yeah. You know so well.

Amber Warren, PA-C: And COVID's taught us that melatonin is actually pretty potent antioxidant. And it can be really good when we're trying to fight a virus.

Mark Holthouse, MD: So you know, I don't know if this is true or not, but I heard from some really smart people with a lot of alphabet soup after their name, that melatonin is the second most powerful antioxidant in the mitochondria to glutathione. I had no idea it's being used in higher doses, you know, for things like breast cancer and things like that. Not in standard treatments, but certainly not to cure or make any claims. But there are people that are that there are there is data out there on that. So it's so much more than just a sleeping deal out of your pineal gland. So there was a.

Amber Warren, PA-C: Good question that came in on your recommendations for hit training. Back to the exercise topic hit training and adrenal adrenal dysfunction. Mm.

Mark Holthouse, MD: Great. That's good. Well and to tag on to that is intermittent fasting. So my my premenopausal single moms I don't want you doing 16 hour fasts intermittently third week of your cycle that you're going to get a counter-regulatory surge of cortisol, which is not necessarily what you should be doing. Um, so everybody's individualized. My older guys, my my guys in general that are overweight, I don't have any problem doing a 16 hour fast eight hour feeding window of 16 eight protocol. Um, women, depending on your stage of life where you are, how stressed out, uh, where your cortisol is at, that all has to be taken into effect. The same thing is true with hit. Now you get a bump with exercise, with cortisol. But ultimately, when you're a regular exercise is your cortisol levels are ultimately lower on average. So it's kind of like blood pressure. It kind of goes up certain aspects of it while you're exercising, and then it goes down. And the ultimate effect there is, is that you have lower blood pressure. Um, the best two ways to lower blood pressure are to lose weight, number one and exercise is number two. And that's even in our standard medical guidelines. Expert expert data on that evidence is is un un refutable. So yes, everything in moderation and personalize these programs. You know, if somebody's got a lot of stress and adrenal dysfunction and we measure their their salivary cortisol, which is why it's in this package and they've got adrenal dysfunction. Hyperfunction DHEA is suffering the other hormone from the adrenal. That's kind of the counterweight to cortisol. You have to you have to modify nutrition and exercise recommendations. That's why we call it precision medicine. It's not one size fits all. And that's what a lot of the standard medical practice is trying to fit everybody under one, you know, a square peg in a round hole. And some people aren't going to fit and they don't do well. So yeah, no, that was a great question from them. It was.

Amber Warren, PA-C: Really good. Um, any topics regarding the precision age reversal that we're offering here now that we didn't touch on or cover that you want to make sure I mentioned?

Mark Holthouse, MD: Oh, man, you know, without.

Amber Warren, PA-C: Spending another hour.

Mark Holthouse, MD: Yeah, exactly. No, I think I think we did a pretty good job. It's you know, we have a silver, a gold and a platinum level of engagement. They they cost different amounts. We have tried to look at the cost of each of these vendors. We've negotiated the best rates. Most all of them are better than what? You can just go online and get a biologic age test for as provider rates. And we're buying a lot of these things in bulk so that we can get more of a wholesale rate. So the cost of the program with a margin to pay the people that are running it, it's not meant to gouge people. It's expensive. And again, I don't apologize for it because of what you're getting over that year. And a lot of the testing that's done initially, we repeat it at the end, which is my report card, to prove to you that what you paid for, you get what you paid for. Um, the different programs are really just how much information you want in one year. It's meant to be a. Every year. The follow on to that is, is something that's going to be sustainable financially, where you've still got some connection to us and we can do surveillance based on what came back abnormal.

Mark Holthouse, MD: So you don't lose everything we just learned about and you gained. Um, and and so that that is the that's the concept. And the concept is to look at it personalized. Some people might need hormone optimization, some people might need some of these peptides, which is a whole nother discussion. Um, other people might not need any of that. And it's more about diet nutrition based on their genes. They didn't know they were full of soft plaque. You know, they did a stress treadmill and the cardiologist said, you're fine, which we know is very insensitive compared to some of these new eye imaging. So I don't want to guess anymore. I want to test and know what's anatomically there in their artery, how much plaque, what type and where is it, how much blockage, what is the degree of stenosis and when should I recheck it to see if you've got it? Are we moving the right way? Is it declining? Um, so again, precision medicine, looking at you from multiple aspects, indulging yourself to spend a little bit of money over a year once to know what you can do to change the trajectory of the rest of your life.

Amber Warren, PA-C: So mic drop and on that, I think we can say that that's a good conclusion. Oh thank you. Thank you for your time, doctor.

Mark Holthouse, MD: Honored honored to be here.

Amber Warren, PA-C: Study well into 2024. Now after talking with you for these last few hours. Thank you so much. Thank you for tuning in.

Mark Holthouse, MD: Thanks to everyone.

Amber Warren, PA-C: Thank you for listening to the Functional Medicine Foundations podcast. For more information on topics covered today. Specialties available at the FMI center for Optimal Health and the highest Quality of supplements and more. Go to Fun Med


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