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Episode 31: The Correct Metabolic Weight Loss & Strategies for Preventing Cardiometabolic Diseases with Dr. Mark Holthouse, MD

Updated: Mar 19

Podcast Drop Date: 3/6/2024

In this episode of Functional Medicine Foundations, Dr. Mark Holthouse takes us on a journey to optimal health, focusing on Metabolic Weight Loss, GLP1 Agonists, and Cardiometabolic Risk Factors. Uncover the secrets of metabolic mastery, explore the transformative power of GLP1 Agonists, and gain insights beyond conventional weight loss approaches. Dr. Holthouse, a leading figure in Functional Medicine, empowers listeners with practical strategies to take charge of their metabolism and understand critical factors influencing cardiometabolic health. Join us for an illuminating discussion that bridges the gap between science and holistic wellness. It's time to embark on the road to inside-out wellness!



Amber Warren, PA-C: Okay, well, we'll go ahead and get started. All right. Welcome back everybody. We're here for another one. I can't even keep track anymore. I don't know what number we're on, but I'm so glad to have, um, Doctor Mark Holthouse back. We'll do a quick, quick bio introduction. Doctor Mark Holthouse is the Chief Medical Officer of FMI center for Optimal Health and Functional Medicine of Idaho, specializing in hormone optimization, age reversal, metabolic health, and longevity. With over 32 years of family practice experience, he graduated from Loma Linda University School of Medicine and completed his family practice training at UC Davis Medical Center through the Air Force Scholarship Program. As an expert in functional and integrative medicine, Doctor Holthouse has been part of the teaching faculty for the Institute for Functional Medicine, educating practitioners worldwide for the past decade. Additionally, he serves as an Assistant Professor of Medicine at Loma Linda University of School of Medicine, focusing on preventing cardiometabolic diseases and reversing conditions such as type two diabetes, heart disease, high cholesterol, obesity, and metabolic syndrome. Doctor Holthouse is available to see patients in Idaho, Oregon, Nevada, and California. Outside of his medical career, he and his wife, Tammy, enjoy various outdoor activities such as photography, snowshoeing, skiing, sailing, hiking, kayaking, and savoring good food, and soon to be surfing on the coast of Oregon where he currently resides, which we're still not actually accepting here in Idaho that he is no longer in Idaho. And I know right when he finally got his California license plate off and switched it to Idaho, I gave him such a hard time. I'm like, you have to get that off. Like, it's embarrassing to be walking into the office with you and you have California plates. And now I.

Dr. Mark Holthouse, MD: Still have my Idaho plates on.

Amber Warren, PA-C: You should probably just keep them on. We know you're gonna move back.

Dr. Mark Holthouse, MD: I will. Yeah, I can justify it. I'm here often enough. I'm just gonna keep that DMV registration going.

Amber Warren, PA-C: Yeah, yeah, I think you should. I think you should. Oh, well. Welcome back. It's been such a pleasure having you here all week, seeing patients in person. He's doing telemedicine, um, seven weeks of the month, and then his eighth week. He's. He's back here, um, hanging out with us.

Dr. Mark Holthouse, MD: So it's a fun week.

Amber Warren, PA-C: Yeah. It is.

Dr. Mark Holthouse, MD: Yeah. I'm hoping that this is enough to keep me my my social need to engage with colleagues and people. We're fun. Yeah. You guys are a lot of fun. We have.

Amber Warren, PA-C: A lot of fun here in.

Dr. Mark Holthouse, MD: Eagle. Just killed me with my schedule this week. But it's good. It's what I asked for.

Amber Warren, PA-C: You're busy. Thank goodness. We had a snowmageddon and an ice storm that at least lightened your load a little. Yeah, for patients coming from afar, but, yeah.

Dr. Mark Holthouse, MD: No, it's amazing. We'd get a little bit of snow. Uh, back in the day in Northern California, you know, people would take a snow day at the drop of a hat in here. I mean, we've got, you know, a waiting room full of people. And there's, you know, look at the roads out there. It's amazing. Yeah. Different breed.

Amber Warren, PA-C: We're tough Idahoans. Yeah. I should mention I don't want to leave our our wonderful audience out. This is our third podcast where we've now done had a live audience. So we'll be getting, um, live questions coming in from our audience. And it's so fun to have have some of the community members here to hang out with us tonight. So we want to spend some time this evening talking about, um, metabolic weight loss. This is kind of a part two to some other conversations we've had. And, um, behind the scenes, you and I have been talking the last couple of months about developing. We rerun a metabolic weight loss program that has been wildly successful and is on. I know both of our hearts and some other other individuals hearts here in Eagle to develop kind of a phase two to that program. So we have lots of different ideas on how we're going to implement that. So stay tuned because that is in the works. But um, there's so much that we've learned. I know so much you've learned at even some recent conferences you've gone to about this concept of metabolic weight loss, how to do it right, and the tools and the resources that we have. Yeah. So, um, should we start with GLP one agonists as a starting point? Because that's a hot topic right now it.

Dr. Mark Holthouse, MD: Is GLP one aka semaglutide Ozempic Manjaro Rybelsus Ragovoy goes by a lot of different trade names and generics. Uh, all about that, right? With the shot for weight loss. And if your neighbor's not doing it, they will be soon kind of a thing. Right? So you know what's been interesting watching this over the last year unfold. And we kind of predicted this was going to happen, uh, whenever there's a new wonder drug for weight loss that comes out or fad or what have you, um, whether it's FDA approved or not, this one happens to be, uh, there's this magic bullet theory, right? If if I just do this, I can still get away with that. And and kind of short sheeting, the whole process of looking at a holistic approach. We a year ago thought, well, we're seeing all these prescriptions coming in for the GLP one peptides. And we'll talk a little bit about what those are without any other education. A lot of docs, endocrinologists and and primary care folks writing a prescription for these folks coming in in droves saying, hey, my neighbor is on this for weight loss. Uh, can I get a prescription? And, um, they lo and behold, you know, the weight comes off 20, 30 pounds over the six months. Four months, and they're back six months later with. That much more weight on and more and frustrated. And so we're seeing that kind of self-fulfilling prophecy where there's a lack of education on how to promote sustained weight loss with these very effective tools. That's not being the opportunity is being missed, largely because the docs that are writing these scripts don't have the training.

Dr. Mark Holthouse, MD: They don't have the training on nutrition. They don't understand how important it is to give branch chain and essential amino acids and exercise prescriptions that are the right type of exercise to maintain lean muscle. Yeah. So consequently, we have a lot of folks saying that things like Tirzepatide and semaglutide cause muscle wasting and muscle loss. Um, my trainers in the gyms are very concerned about these drugs because they see the negative effects and what's really going on here, when you look behind the curtain is that these folks are just malnourished. Yeah. It's not that the drugs promote muscle wasting or lost of fat free mass. What's happening is they promote a decreased appetite, which is how one of the ways they work, they turn off the food noise, the serotonergic drive to seek carbs by affecting the serotonin pathways in the brain and basically, um, make it to where you do not eat as much, uh, it slows gastric emptying. And this is why nausea is one of the side effects. But, uh, nobody really ever stopped to think about, hey, let's really be intentional about making sure they're getting enough of the right type of protein. Yeah, let's get them on strength training exercises to maintain and actually build lean muscle. We know people lose weight, and we know people lose fat and they lose muscle. They're losing more of a proportion of muscle than they really need to when they don't get this extra information. And I think that's what makes our approach so much, uh, more successful.

Amber Warren, PA-C: Yeah, absolutely. I want to take a step back. And you being so good with obesity medicine and cardio metabolic medicine, why do we care much more than the esthetic piece of being overweight? Why do we care that we have so many millions of Americans walking around with excess adipose tissue, even just a little bit of excess belly fat? Why is that so hard on our system and so, so, so difficult. Yeah. For our bodies.

Dr. Mark Holthouse, MD: Now, it's a great question. I think it's because it's so pivotal to, uh, pivotal to all of these other diseases on the top ten causes of death in the United States and worldwide. I mean, we talk about the Four Horsemen and Peter Attia's terminology. You got to give him credit for that. Uh, basically cardiovascular disease in the form of heart attacks and stroke and cancers, uh, dementias and type two diabetes, those four things. And central obesity is that white destructive, inflammatory fat, visceral fat very different from our, our, our subcutaneous brown fat, which is our healthy fat. Um, and this is the driver of all four of those four horsemen, uh, there are so many cancers that are upregulated with diabetics, you know, more risk of bone loss and the inflammation associated with high sugar dementias and Alzheimer's associated with high blood glucose, high insulin levels, and certainly the driver of stroke and heart disease. Uh, so when we have excess central or visceral fat, it's driving fatty liver, it's driving the Four Horsemen. And the only way to get off of that train is, is to try to unravel and reverse that feed forward cycle of inflammation. So it's a it's a driver of most of the chronic diseases that are killing us. Right. That's why we should care.

Amber Warren, PA-C: Yeah. And that's why maybe we should think twice before we throw GLP one out the window. Right. And really see the different mechanisms of action, how they can truly save lives.

Dr. Mark Holthouse, MD: It's a great tool. Yeah. Um, you know, we talk a little bit about how they work. Um, it's an exercise mimetic, which means they work like exercise in that, um, not in replacement of exercise, but they raise something called AMP kinase, Ampk, which is your way to bring sugar into the cell, the muscle cell, without having to rely on insulin. So it's an insulin dependent pathway of of managing blood sugar. Yeah. 85% of our pre-diabetic state or insulin resistance, if you will, is driven by muscle skeletal muscle resistance and an inability to bring glucose in and control blood levels. And too high of a glucose level we know is toxic to our nerves. You know, our eyes, our retinas, um, our kidneys, our heart. And so if you can use something that's going to advocate along. With the right exercise, the right diet. Managing stress. Managing cortisol. Managing adequate amino acid. Protein balance so that you're not losing the weight. This is where it gets it gets pretty sexy. One of the things that people really miss is how widespread the effects are, beyond just controlling blood sugar and weight with GLP one. Yeah. And, um, tell me when to stop. But I got to share those because that's that's my passion. Um, it lowers waist circumference. Uh, it lowers systolic and diastolic blood pressure. Increases nitric oxide inside the blood vessels.

Amber Warren, PA-C: What does nitric oxide do?

Dr. Mark Holthouse, MD: So nitric oxide is is no is our friend. It's what allows our blood vessels to be supple and and have compliance. So they're not stiff. Uh, it also helps the guys. This is how Viagra works, you know, to get blood flow to the region. Um, it's incredibly helpful at preventing oxidative and autoimmune inflammatory reaction that occurs in the wall of your blood vessels, which is the first step towards an atherosclerotic plaque, which is really what's leading to most stroke and heart disease. Right. Um, so in addition to this cardioprotective benefit, uh, you've got, you know, the ability to affect triglycerides, LDL cholesterol in a positive way. Uh, it lowers something called apob, which is a, a specific type of a marker, a protein that's found on atherogenic particles like LDL and triglycerides.

Amber Warren, PA-C: You're worried about heart disease. Make sure your doctor has checked your.

Dr. Mark Holthouse, MD: Apob.

Amber Warren, PA-C: You haven't had that. Checked in a profile. Get a new doctor.

Dr. Mark Holthouse, MD: Yeah, I mean, really, when it comes to statin therapy, I know a lot of people are down on statins. Uh, there's a couple of populations of folks that that really are much higher risk than the general population for heart disease. Um, one of those is the inherited LP little a, the dreaded LDL subtype that's completely genetic and unfortunately unaffected by lifestyle. Uh, we don't really have a drug yet that's that's used to lower that. Niacin can help.

Amber Warren, PA-C: Do we have data on GLP one and LP? Layla?

Dr. Mark Holthouse, MD: Uh, not that.

Amber Warren, PA-C: I'm aware of, I think so, no, that would be interesting to look at anecdotally, though, to see if in our patient population here, if we see that, yeah, we lower. It's hard because we're doing so many things with these patients. So it'd be hard to isolate just putting them on a GLP one because we don't do that. Right. But I would sure be interested to see data on that.

Dr. Mark Holthouse, MD: It's interesting. The data is really strong on lowering triglycerides and lowering Appleby, and Appleby is probably the the single most important predictor of cardiovascular risk. Uh, so ask your doctors whether you see us or not, to always look at an LP. Little A yep. Especially if there's a genetic history of heart attacks in in seemingly healthy family members. They don't have typical risk factors as well as this ApoE apob capital B um, it's very, very important subgroups within folks. Um, in addition to that, I mean, we're seeing it help reverse fatty liver, prevent fatty liver, which is an epidemic we're going to talk about later tonight. Um, incredibly helpful on, um, for, for for satiety decreasing the cravings, as we mentioned earlier, as well as, um, helping folks with, uh, really, uh, keeping, uh, you know, this, this distraction of food, food, food, that food noise.

Amber Warren, PA-C: My patients call it food noise. Yeah, I thought that was a good way of describing it. Yeah.

Dr. Mark Holthouse, MD: And it's that serotonergic, uh, neuropeptides that that drive food. You know, we talk about orexigenic, which is pro eating and anorexigenic, which is is not wanting to eat. Yeah. It affects those in ways that just takes really kind of our appetites away. But unless you've done things that are intentional to prevent this, this muscle wasting, um, when you aren't eating as much, um, it will occur. Most people that lose weight will always lose a little bit of muscle mass. It's impossible really not to, uh, but the ratio of muscle mass loss to fat loss is, is improved when you go about it with doing these intentional efforts. Yeah. Yeah. So it's pretty exciting. Um, but cardioprotective, um, I mean, even after an MRI, there's data showing that this whole reperfusion injury phenomenon that can occur, it's it's involved with, uh, other areas of the cell with misfolded proteins, um, that leads to cellular aging and we call cellular senescence. Uh, it's one of the what is it? 13 now causes the hallmarks of aging. I think we're up to, um, protein misfolding is one of those things. Um, so it has receptors, these these natural peptide proteins.

Dr. Mark Holthouse, MD: Teen hormones, which our body makes from the intestinal cells. The little L cells in our small bowel has receptors all over the body the pancreas, the liver, the lung, the brain, the peripheral nervous system, central nervous system, the heart, kidneys. So it has actions on and is protective in many, many different organs. So I always it's always frustrating when I hear people feel like that's a class of, of pharmaceuticals or in this case, peptides, uh, that, that are not useful. It's a misuse of the terms. Um, you know, if you rely on just the, the drug. Um, yeah, it's it's not great. But the thing that's easy to forget is that we make this stuff naturally, and there are lots of things we can do herbally botanically from a lifestyle which will help increase our own natural production of our own GLP one's, our own tirzepatide, our own semaglutide, if you will. And that's something that we do in our weight loss package, which helps people not gain the weight back when the drug is discontinued. Right?

Amber Warren, PA-C: Absolutely. Yeah. Well, plus, I tell patients that our job when we see these weight loss patients is to cast a wide net, no stone left unturned, all their different reasons. You aren't losing weight for a lot of our, you know, pre peri post menopausal women. It's getting their hormones balanced men too right. Men are not exempt from that. So yeah. Um stress sleep. Um so we're looking at all the other reasons, not just the things that these GLP ones are doing. So we're that's what I try to explain. We're casting a wide net. And if we do that right then yeah the weight will stay off. And um, so it's great. We have our first question coming in from our audience. Once people get to their desired weight, should they stay on tours appetite, and if so, at what dose?

Dr. Mark Holthouse, MD: That's a great question. Um, so most folks are finding that they lose adequate weight at middle doses. Yeah. There's not a need to rush to a max dose or every month titrate up. I think that's a common myth. And people have that expectation that they need to do that and press forward. And I say, look, if you're if you're continuing to lose weight, you're all going to plateau. And depending on how much weight you have to lose, that occurs at different times. Right. But when you plateau, I tell them to persist with it and continue these other lifestyle things that we're talking about. We assess their toxic burden, look at their urine for chemistry, chemical toxins. We look at heavy metals. We talk to them about their sleep. We measure their cortisol and their saliva and see if, you know, we call them the saboteurs. Yeah. Are you sleeping? Seven hours minimum per night? If not, there's a really good chance that you're not going to lose weight because you're in a hypercortisolemia state.

Amber Warren, PA-C: We're waking up every two hours. Yes.

Dr. Mark Holthouse, MD: Yeah. And it just puts it right there. Uh, dysbiosis, uh, abnormal gut flora. We know that there are certain probiotics and bacteria in our gut which promote being svelte, lean leanness, uh, that manage blood sugar, that manage our cholesterol. Uh, who would have ever thought that? I mean, in school that we'd be talking about the gut microbiome as a way to manage your weight or your LDL, or your fasting blood sugar? Uh, so it's really been exciting to see what, what's come from this new information. Yeah. But you got to look at all of it. And you've got these these the Four Horsemen, you've got the four saboteurs. Uh, you have this pharmaceutical, you have what you make. There's ways to potentiate it. Um, one of the biggest things that's overlooked is diet. Yeah. Uh, everyone knows about avoiding white foods. You know, the chips, the burritos, the bagels, the pasta, the breads. Uh, which is great, but what about what we should be eating? You know, all these. The plants are where the polyphenolic compounds are. Polyphenols are these chemical wonderful chemicals that are in our brightly colored plants and veggies that are shown not only to upregulate longevity pathways, the sirtuins and Ampk kinase pathways to balance out all the pro-growth mTOR pathways. But they're antioxidative, they're pro detox, they're detoxifying, um, they're feeding our microbiome and the product, the offspring, if you will, of our bacteria and our gut munching on these these plants, these polyphenolic compounds and fibers are something called. And it's a beautiful something short chain fatty acids butyrate propionate acetate and butyrate is this amazing short chain fatty acid that causes our own body, our intestinal cells to make GLP one.

Amber Warren, PA-C: Yeah it's amazing. So and you can supplement. That butyrate you can supplement.

Dr. Mark Holthouse, MD: Butyrate, you can make sure you're getting a lot of plants so that your bacteria are making it for you. So, um, there's this beautiful cycle of getting the right types of, of a variety of foods in place. You know, you can do meat, protein and help with high biologic grade quality proteins and aminos and branched chains. You can get a lot of plants in there to make sure you're getting this, this polyphenols and fibers in there, uh, to balance out not just being a muscle head and mTOR Pro growth 12% body fat cross fitting person who looks great. But we used to say that, you know, they're the best looking body in the morgue. Um, they're inflamed, they're acidotic, they're getting more cancers. It's all this mTOR heavy, and they're forgetting that there's this dance between longevity and looking good and having leanness. Right. Um, we don't have to be vegan or vegetarian. In fact, I don't necessarily recommend that. Yeah, but we should also be avoiding extremes like the carnivore diet where.

Amber Warren, PA-C: You're going to go there.

Dr. Mark Holthouse, MD: You've got issues, um, if you're going to do something like that or ketosis, for goodness sakes, pulse in and out of it, right. You know, and there's that's a whole nother podcast. But, um, I try to avoid the whole diet wars because I just don't think there's a one size fits all for anybody. We just want to look at what works for the person sitting in front of us. Absolutely. The labs don't lie, you know? And when we look at inflammatory markers, when we look at plaque burden, I see just a big a problem in my vegans as I do my carnivores. So it's there's obviously a lot more to consider genetically and with all these other topics like cortisol and toxins.

Amber Warren, PA-C: Um, that's a good segue into protein, the importance of protein, especially as we're talking muscle wasting potentially with these these metabolic patients, is they lose dramatic amounts of weight. Um, I know we were talking a little bit offline in clinic this week about, um, intermittent fasting, the importance of protein, especially when it comes to longevity and aging proteins, really important as a macronutrient. And if we're really shortening these eating windows, it does make it a lot more difficult to get protein in in any given day. So have you changed your recommendations for your patients? I have what do you saying? What's your are you saying body weight of kilogram for gram of.

Dr. Mark Holthouse, MD: Yeah. For the most part assuming people have a healthy kidney function. Yeah. And assuming that they're, um, you know, we're looking at other parameters. Of course, I'm as a general rule, looking at, um, taking a gram of protein per pound of body weight. So for 150 pound female, uh, that's 150g a day, which is.

Amber Warren, PA-C: Really hard to get if you're doing a eight hour eating window. Almost impossible.

Dr. Mark Holthouse, MD: It's it's almost impossible to intermittent fast and and get in fact, I would say it probably is impossible to do a 16 eight protocol where you're fasting 16 hours eating in an eight hour window. So I don't really recommend that anymore unless somebody's got serious metabolic dysfunction. Uh, I think that the benefits of doing that in folks that don't have a lot of weight to lose or don't have prediabetes for, for example, um, are outweighed by the risks of losing lean muscle mass by not getting enough protein.

Amber Warren, PA-C: And why is lean muscle mass so important to so lean?

Dr. Mark Holthouse, MD: Leanness is a big deal, right? Because I'm supposed to be a longevity guy. And, you know, muscle is the currency of of of anti-aging, right? Uh, we are only as old as our arteries is what I learned in residency. And now I would add to that, that we're our age is directly dependent on how much muscle mass we've got left. It's what keeps us from tripping and falling and breaking hips. It's directly correlated with longevity, right? We do grip strengths in here as a vital sign now because it's correlated not just with dementia and frailty and strength. Uh, but how long are you going to live? Right. And not just in how many years, but your quality of years, your actual health span, years of healthy living can be determined by things as is simple as a grip test. Yeah. And we want to be in in our Middle ages. We want to be on the top of our game so that when we're 80 and 90, we can still do things and we're functional. Uh, these centenarians in the blue zones, um, they get all the same diseases and die the same stuff we do. They just do it 30 years later. Uh, and so I think part of that's genetics. Sure. But a lot of it seems to be related to some of these intentional things that they're doing. Right. And there's a lot of people on podcasts making a lot of money selling supplements and, and, um, ads on, on YouTube. Because it is such a hot topic. There are so many people looking for answers. And lifestyle is at the core, and we have a few of these hacks that we can add in there to really help move the needle. I think it's exciting. It's exciting time to be in metabolic medicine for sure.

Amber Warren, PA-C: I couldn't agree more. I've come to really love it. Um. Um, exercise? What are the specific exercise recommendations? Because I think we it's hard to be specific with nutrition because, yeah, we have to evaluate labs and look at the person in front of us. But I think it's a little bit easier for us to make more concrete exercise recommendations with these metabolic patients. It is. What are you recommending?

Dr. Mark Holthouse, MD: Yeah. Exercise data is is better than nutritional data. I mean, nutritional studies are so fraught with, uh, interference it's so hard to tease out. And a lot of these dietary studies are self-reported dietary diaries that people who knows if they're accurate or not. Yeah. Or who.

Amber Warren, PA-C: Funded them. What? Big Food corporation funded the nutrition studies. Right. Exactly. Yeah, exactly.

Dr. Mark Holthouse, MD: I don't know that we'll ever have good nutritional data to make super informed decisions on, like we do exercise, like we do some other areas exercise. There's some great data. And I mean, um, there's there's exercise and there's movement and there's the right movement. Uh, we start with walking. Let's start at the ground level. I mean, you've got to move to maintain muscle. You can't do it with the things on our shelves exclusively. Protein powders, branched chain amino acids. Creatine only gets you so far. You have to stimulate that neuromuscular unit. And the way you do it seems to matter. So what we have people do, depending on their their experience with with walking and exercise and movement, their orthopedic limitations, we get them walking. Phase one, um, there's something called zone two, where your heart rate is in a place where you're burning a maximum amount of fat before you start burning carbs. And this is different for all of us depending on your fitness level, how metabolically flexible you are. Um, I might be at 130 before I'm so breathless that I start burning carbs. And so that's my fat max, my max heart rate where I'm still burning the maximum amount of fat possible. And that's what we call a walk. That's kind of breathless. The talk test, you know, if you're out on a walk and you can talk, but it's not easy. You're it's hard to finish your sentence. You're in zone two and you're burning fat like nobody's business, even more so than in an orange theory type workout. When you're in zone three, four, five and you're really going after more carb burning at that point. Um, next I would talk about, uh, and that's just general. That's kind of where we start. Next, I would talk about strength training, and I like group strength training, only that you're with a trainer. It's more affordable. Um, the Bodypump class at the Axiom Gym. I have no affiliation with them. Maybe you guys should look me up because I've sent a lot of people your way. I know I was.

Amber Warren, PA-C: Going to say you talk about their body foam class. Yeah, the the body. Check this.

Dr. Mark Holthouse, MD: Out. The body pump class is a is 30, 40 people in this huge studio room. It's away from the the meat market side of the gyms where everyone's afraid to go and, you know, be ogled. Ogled at, uh, and that's not fun when you're over 40. So we go over there to the mature side of the gym where, um, there's a bunch of us in there, and it's mostly women. There's a token few guys in there. My wife got me into this, and I remember that. This is ridiculous. It's a bunch of housewives. And I was like, so it was terrible. And I was hooked after a month. Yeah. And it's fun. It's great because you have really well trained folks up there teaching you the right form. They're watching you. And if you're doing stuff when you're hinging doing your deadlift wrong, they're going to let you know and they're good about it without public embarrassment. But you can go as hard or as light as you want. Um, it's multiple times during the day and it's inexpensive. But the point being, you are exercising all of your major muscle groups four days to five days a week. So this is what we need to be doing, especially over age 4045 when we're our growth hormone is is dropping 15% every decade after about age 35. And it really accelerates after age 50 to avoid sarcopenia, losing lean muscle mass.

Dr. Mark Holthouse, MD: And remember what we said about muscle being the currency to avoid premature aging. Right. And then a couple other things which we often forget. I'm from the era where everyone was doing Jazzercise and aerobics. Nobody lifted weights except for the real serious guys over at Gold's Gym. Yeah. Bodybuilders. Yeah. And now it's really come full circle where, you know, the same guys and gals that are bragging about, you know, I haven't eaten anything green for six months. Uh, and I haven't done any aerobics. It's a waste of time for a year. If the pendulum is swung the other way, where everyone's just doing strength training, and really, we need to be doing both things. If you look at the data on longevity, uh, the the tracking of VO2 max with longevity is a linear relationship, and that's an aerobic function. Fitness. How do you train that? We. Call it Norwegian four by fours. And I'm not Scandinavian, I don't think. But it resonated with me. And so you're going at 80% of your maximum predicted heart rate, and you're doing this for about four minutes, and then you recover for 3 to 4 minutes. And you do that cycle four times 4x4. You do that twice a week is all. It's because they're intense. But that's training this VO2 max. This aerobic capacity hit is different. High intensity interval training. You're going 30 60s all out, not 80% your max heart rate but 100% max heart rate.

Dr. Mark Holthouse, MD: What's your max heart rate? 220 minus your age. So that's the heart rate you're at for a hit workout. 30 60s. And then you're recovering for a couple of minutes. And you do that maybe six, seven, eight times. They're called Tabata drills. There's a lot of different names. You might do that once or twice a week. You might do the four by fours for aerobic capacity two times a week max. So the walking and the strength training really occupy most of your time. We aren't talking we haven't talked about flexibility and and balance in those other kinds of things. But we do give those their due diligence as well. But those three types of activities, walking is kind of foundational. And then hit aerobic capacity and strength training are really what I focus on so that they don't lose lean muscle. Yeah. And it has to be fun. Yes. And we have to work around their limitations. You know, if all they can do is stuff in floaties in the pool, they've got orthopedic limitations. So be it. Um, movement is movement. Um, we do what we can. It's really hard to sustain weight loss and muscle mass with diet restriction alone. It's the best way to lose weight through your diet changes, but it's very difficult to maintain it as a monotherapy.

Amber Warren, PA-C: Yeah, well, you haven't even touched on we don't have time. But touching on the the benefits in the brain of exercise, those kinds of exercise. Right Bdnf.

Dr. Mark Holthouse, MD: Yes.

Amber Warren, PA-C: Meditation mental health. Right. That we all that everyone needs needs some support with. Yeah. We have another really good question that came in. Intermittent fasting was touted highly for mitochondrial cleansing. If we aren't fasting, are we losing that benefit? And if we are, how do we make up for it?

Dr. Mark Holthouse, MD: So intermittent fasting is one of the ways that you upregulate sirtuins and the longevity gene pathways AMP kinase. It's one of the ways that your body, um, uncouples mitochondria so that they're not just making converting your, your, your food into ATP energy, but they're actually taking time to reproduce themselves. We call it mitochondrial biogenesis making more mitochondria. It's where they clean themselves. Might mitophagy autophagy is the process where our cells throw out the worn out protein and cell parts. The old batteries, if you will, in the flashlight. And this only occurs when our mitochondria are in a state where AMP kinase this longevity pathway is being allowed to function. It's not occurring when we're pounding protein and stimulating this this mTOR pathway that's pro growth. Um, one of the things that we look at is catabolic catabolic versus anabolic catabolic is when your body is in a state of kind of recovery and repair and detoxification longevity anabolic is where we're stimulating growth and repair. And unfortunately in some times cancers. And so you've got to have this yin and yang balance in your in your metabolic sensing pathways. Yeah. Yeah.

Amber Warren, PA-C: So I'm curious a thought about this idea of we need to get enough protein and micronutrients in while we're doing an intermittent fast. Would you ever think and but but also balancing that with this idea of metabolic flexibility for longevity and healthy metabolism and healthy BMI and getting rid of insulin resistance, what about like 1 or 2 days a week of fasting and those other five days you're really optimizing, getting your 150, 160g of protein in. Exactly. Do you think there's benefit there? Do you have people cycle through that?

Dr. Mark Holthouse, MD: I do, you know, there's the alternate day fasting. Yeah, there's the five two where five days a week you're eating more of a, you know, modified med or something, kind of a plan. Two days a week, you might be getting around 5 to 750, 500 and 750 uh, calories a day, is all. Yeah. Um, that works quite well. Uh, because of the majority of the time you're getting adequate nutrients. Uh, the I'll give a plug to the fast like a girl book. This is revolutionized. Time restricted. Eating Doctor Pelzer's book in women especially that are premenopausal timing. When is the right time to fast with the hormone cycles through your your monthly cycle? Right. Come to find out really matters. Yes it does. Um, so intermittent fasting, time restricted eating is just one form of, uh, a type of caloric restriction. We know caloric restriction works. Most of the studies, unfortunately, in, in, uh, rats and rodents, uh, have shown that there is increased longevity when you have the protein restriction, methionine restriction in particular. The problem is that the way that humans metabolize and respond to these types of diets are very, very different from rodents. For example, a rodent lives two years, we live a whole lot longer, so a 16 hour fast for a human is going to be way different on a life scale, on a day to day basis from a rodent. So what they do with the the rodent chow in these studies at the NIH and at Wisconsin, which are kind of landmark trials demonstrating these these things, they they showed disparaging different, conflicting results.

Dr. Mark Holthouse, MD: And we think part of it had to do with the different rat chow that the two experimental groups were using. But we think that, um, there is limited extraction of extrapolating the data from rodents to the human physiology when it comes to how much protein we need. So I am not necessarily in agreement agreement with the 0.8, uh, you know, uh, grams per kilo RDA recommendation anymore. I think we need at least double that. Uh, because of that lack of you shouldn't be extrapolating. I don't think looking at the data. Yeah. Intermittent fasting has a wonderful, powerful place. And it's an incredibly strong tool for weight loss detox and for mitochondrial health. Absolutely. It upregulates um, AMP kinase, the sirtuins, all of those pathways, mitochondrial function oxidative stress is largely reduced. Uh, you just have to balance it with the person in front of you. Where is their cortisol? Uh, are they still menstruating? Um, if they're on a GLP one and they're already have no appetite, and you just took them down to two meals a day, you've just made it impossible to maintain lean muscle mass. So I think that it's fine if you if you're using it as a tool and you understand how to individualize it within the contextualization of all those nuances.

Amber Warren, PA-C: Yeah, I really like the idea of cycling through it or using other resources to help get those benefits, but maybe not smash you nutritionally or hammer the cortisol levels.

Dr. Mark Holthouse, MD: And I think that's, you know, that's why Prolon has been effective. Yes. Valter Longo's. Yes. Wonder, uh, deal out of USC because it's it's every, you know, three weeks out of four, you're eating a more regular meal and then you have some experience with this more recently. I did it last week. Yeah, yeah. And then five days out of the month, you're doing this, what we call a box lunch that's provided for you. And basically doing that for a three month continuous cycle is considered one cycle. Right. And, um, you know, that's that's shown promise as well. What I've really gotten away from doing is telling people that don't have significant metabolic dysfunction that they should be intermittent fasting with a 16 eight schedule, right? Yeah. So I would not tell you to intermittent fast because I know you're not pre-diabetic. Yeah. Even if you had 15 pounds that you wanted to lose, I wouldn't have your premenopausal. Right. You know, I wouldn't have you do that now if you had PCOS, you had acne, insulin resistance, and you came with dysfunctioning menstrual cycles. I would probably consider a modified version. So it really depends. As I've gotten I've got gotten away from just a one size fits all. It's great for everybody. Yeah. To more of a yeah yeah approach.

Amber Warren, PA-C: Yeah. No it's all personalized medicine. That's the beauty of functional medicine and kind of what we do. It's wonderful. Well wow. So many good takeaways from that conversation and tidbits. Thank you so much Doctor Holthouse. Fun stuff. Wonderful conversation. Yeah it was great. Thank you so much. Thank you.

Dr. Mark Holthouse, MD: Thank you everybody.

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

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