Updated: May 23
Podcast Drop Date: 11/2/22
FMF: Welcome to 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. So we're back with episode three, Amber Warren here at Functional Medicine Foundations. And I'm interviewing again our medical director, Dr. Mark Holthouse. We've already talked about female health. We touched on hormonal imbalances within our female patient population, and we're now here talking about the guys. So I can't speak as much to this, but I know Dr. Holthouse, this is one of your really big passion areas of expertise that you love talking about. So we have this this program called Optimal Men, and I think it's such a great name in you know, you obviously see more men in your your patient population than I do, but they come to you, most of them probably a little bit encouraged by their female counterparts to come and see you. Right. They maybe are getting into their thirties, forties, fifties, they've got dad bod thing going on, their cholesterol starting to climb. Libido is not where it was. What's your approach? Where do you start?
Dr. Mark Holthouse, MD: So the first thing I do is kind of give him an atta boy on the back, like, I'm glad you're here. We try to quickly get over the my arm. I'm here because my arm has been twisted behind my back. My wife gave me an ultimatum and I try to win them over because that's where they're going to get the best benefit. Usually that takes about 5 minutes because I'm a guy, because I'm middle aged and because I've experienced some of the frustrations a lot of them are having. And, you know, you can kind of relate and and I kind of know what they're after. Some of them are are really proactive. You know, they've done their homework. They they're aware of every podcast, wherever, every YouTube. They've been to summits and webinars. And they've got a little bit of knowledge, sometimes enough to be dangerous. Sometimes they're really sophisticated and it's fun, they're motivated. So I get everybody that whole spectrum kind of like I'm here because the wife told me or else, and then I've got the biohackers that are there to stump the doctor. And I love those guys because.
Amber Warren, host: There's more and more, more and more of them coming.
Dr. Mark Holthouse, MD: Out, more of them. And I'm always learning from my patients. Have you heard about Methylene blue? Yeah, The first time I heard that was from a testosterone patient that was was seeking support on that. And I said, you know, I've heard about it when I was in in undergrad, and we used to use it probably to stain slides and things, Right. What are you talking about in a medical context? So, yeah, you get the whole spectrum. But the way I start with these guys is literally to try to build rapport with them so that it really guys are we're very clannish. If they feel that I am and I am, I'm very genuine in the way I approach medicine in it for them, in it for their quality, in it, for optimizing their life, I get their ear and then they're loyal. You know, it's long gone that I was initially here because my wife had gave me an ultimatum. It's like, No way, man. I'd come see this guy once a week if I could get off work. And that's my first goal is to build rapport. You know, anyone acquainted with this therapeutic readiness to change stages know that if you don't have rapport, you're kind of dead in the water.
Dr. Mark Holthouse, MD: People aren't buying what you're selling. And what I'm selling is a team approach to getting them back to being an optimal male. So we start with rapport. The second thing we do is I really try to work with them and this is really part of that same issue where they're at. Some guys are coming in, you know, they're already on testosterone, they're already doing HCG injections, they're already doing Clomid, they're already doing peptides and they're doing this Ester, this variety of testosterone, you know, this day a week, and they're following it up with an aromatase inhibitor 5 hours later and they're just like an engineer. They've got this thing Excel, spreadsheet it out. And I'm just I'm saying, Wow. And then we've got the guys that are coming in saying, My wife says I'm a jerk. And they're kind of looking at their shoelaces and begrudgingly admitting I'm irritable. I don't know what's wrong with me. I feel depressed. I've never felt so unmotivated in my life. I used to be athletic. I can't even get out of my chair.
Amber Warren, host: I don't have the endurance I had.
Dr. Mark Holthouse, MD: Yeah, my stamina is gone and everyone in between. So I meet them where they are after gaining rapport. And then we start with these same things we talked about in our last episode with women with the Radiant Women Program, with therapeutic lifestyle, testosterone. In my experience, more than any other hormone is influenced by lifestyle. We say that there are kryptonite or weaknesses that can take potshots at testosterone levels. One of them is stress. The other one is, and that's because of cortisol. Cortisol is definitely the kryptonite to t. The other one is sleep deprivation, poor sleep, because we, after all, secrete most of our testosterone in a pulsed dose fashion while we sleep. And it happens in a part of our sleep architecture that really it's a jealous mistress. It has to be healthy good quality sleep, not Jack Daniels, and do sleep where I'm unconscious and not really getting good quality sleep. And we talk about lifestyle and the fact of exercise as well. So the right kind of exercise, the whole toxin discussion, super important with the interference of testosterone. You know, we see so many people that have phthalates, which are a class of chemicals and self care products, things that make guys smell really good during their shower without incriminating any labels can be filled with these things.
Dr. Mark Holthouse, MD: Parabens and phthalates that we know are known endocrine disruptors, heavy metals, a lot of guys that are doing indoor shooting here in Idaho. Yeah, there's a lot of lead that they're inhaling. And we know that lead and mercury in particular affect testosterone levels. So we talk about their community involvement. Do they feel isolated? Do they feel loved by their significant other? Are they eating fast foods and just grab and go foods and living on energy drinks? A lot of these guys will come in and they're you know, they're cross fitting to beat the band and they're doing carnivore diet and they're really stressed out. You know, they're going through hard times. They're not sleeping well. They're a business owner. And they might look really good. The outer package might look really cut and really ripped until we start. Unappealing, the layers of the onion, looking at labs and such. So we always start with therapeutic lifestyle, with the guys, with this program.
Amber Warren, host: Wow. So you laid out a lot and there's a lot of different directions we can go there. I think one that stands out most to me as a provider and honestly, probably it's the nail on the head for most of our providers is the concept of stress, right? Busyness society. I mean, how does how does stress directly relate to low t hormonal imbalances? Inflammation in our inner men?
Dr. Mark Holthouse, MD: Yeah, just like in the in the females, we've got this kind of hierarchy where when we're stressed we tend to make cortisol and we will do that in preference over testosterone in this discussion and estrogen. And so when guys have unrelenting stress, I'm not talking about jumping out of the way of the speeding bus, adrenaline surges, which we all need. There's healthy and there's unhealthy stress. It's that unresolved. I really don't like my supervisor. I don't like my job. My wife and I are arguing, yeah, we're having issues over finances that are just there day in, day out. Yeah, That's the kind of hyper cortisol state that brings testosterone down. So we know that cortisol is is a big deal from emotional stress. It's also a big deal, though, with chronic pain and a lot of a lot of the guys I see in all ages have pain that they deal with. You know, some of these guys are retired football players or, you know, they were jocks and they've got back in knee issues that they're living with still.
Amber Warren, host: Or they just have a ten hour a day desk job and they have really poor, poor form at work or they lift poor and they don't have great form as they are trying to exercise to improve their health.
Dr. Mark Holthouse, MD: Right. Shift workers. Yeah, they're they're doing jobs on a on a medevac chopper or they're firefighters or their law enforcement. A lot of them are in health care now. I'm glad I didn't know what I know now about the lifestyle of a resident. Yeah. You know, it's like, how did I father children? You know, I think I slept 6 hours total every three days for many months at a time, early on in residency. So, yes, sleep deprivation is part of that whole hyper core Islamic State, just like we talked about in the women. So cortisol is probably one of the strongest leverage points in moving the needle towards raising T by by muting that modulating it. It's hard to get guys to go do things like yoga. Yeah, it's hard to get guys work. Yeah, yeah, right. They want to get home and they want to get their remote in their hand and kick back with a brewski and just like watch football. And so that's the last thing on their mind. Yeah. So we try to work with where they're at. What can you give me when you start your day as a tradition? You know, if you're not going to do mindfulness based meditation activities, maybe you'll do a guided imagery. Maybe you can use the power of a narration that's an audible thing you listen to that uses the power of your imagination to go to your happy place. And it's funny, surprising how many guys get into this. And then once they start doing it, they're they're almost more committed than a lot of my female patients is getting them to start. Yeah, which can.
Amber Warren, host: Be a buy in.
Dr. Mark Holthouse, MD: Yeah, the buy in. So I often have to show them their labs first. And again, we'll do salivary testing. Looking at cortisol curves. Yeah. Especially some of these shift workers. And they're like, Wow, that's normal. And here's me. Yeah, it's like I'm making my own curve and I'm like, Yeah, you're like, Never normal. So how can your t ever have a chance? So, yeah, addressing their stress, whether it's chronic pain, whether it's problems with the stress of having obesity, you know, carrying a lot of central tummy fat that's driving inflammation, which is very stressful.
Amber Warren, host: I'm always redefining stress for my patients. Hey, your marriage might be great. You might have a job that you love, that you can work part time and still be a mom, but you're sleeping 6 hours a night, right? Or or you're taking a lot of really low quality supplements with a ton of fillers or you're on a lot of medications that are very toxic for your system or your nutrition's really poor. You're actually not getting enough quality nutrition or you're eating too many foods that your body can't recognize. So stress is not just psychological, right? Like you kind of touch on that.
Dr. Mark Holthouse, MD: It's all areas of life. Everyone just thinks it's the it's the I got in a fight a minute ago and it's so much more we know and the sleep discussion that guys after just five nights of getting 5 hours or less drop their T 15% and that's in young man it's huge.
Amber Warren, host: Yeah.
Dr. Mark Holthouse, MD: So sleep sleep is a big deal.
Amber Warren, host: So most most men, they're black or white, right, Doc? Just tell me what to do. Right? Okay. Okay. You've convinced me. I see the labs. I see the salivary cortisol. How many hours of sleep do I need? What do you tell them?
Dr. Mark Holthouse, MD: Most of the data is pretty clear that seven is kind of the magic number. 7 hours is a minimum. Yeah, I'm looking at sleep architecture too. Some of these new wearable devices can help us. Yeah, the aura ring and some of the other things on the phones and whatnot that are recording sleep stages are important. We know that growth hormone and things like that are secreted during these very deep stage three, four delta wave sleep cycles and that things like testosterone are actually secreted during REM, which is a more superficial form of sleep that is come to find out incredibly helpful for logging in memories and learning from the day before into your long term memory. So sleeping quality and sleeping quantity are two questions that I ask all of the guys that come in for this program.
Amber Warren, host: How, how, how often or how much does do things like obstructive sleep apnea play a role in in upsetting testosterone, if you will?
Dr. Mark Holthouse, MD: Yeah, we like to say that obstructive sleep apnea is the number one underdiagnosed cardiovascular disease. I see this all day long and it's it's anymore in my 30 year olds as much as it's seen in my 60 year olds and all body types. Yep. I like you said earlier in our other episodes, I've seen this in £100 young females who are this big around, and I've seen it in my big football player guys with the big neck the size of my thigh, which is how we classically always thought of Pickwick and Syndrome or sleep apnea. It's extremely common. It's one of the first things we look at. We know that there's an association between sleep apnea, obstructive sleep apnea, and low t. We don't know exactly the relationship because it's interesting. And guys that have low T with apnea, if you treat them with CPAP. Their testosterone don't always recover. So there's something else going on there. We do see that it's related often to the obesity and to the hypoxia, the low oxygen levels that occur with apnea. But the obstruction itself, it's unclear. The relationship, it does seem to be mediated through a central mechanism. In other words, the little little messenger molecules in our brain as guys that tell the boys the gonads to make tea, that gets suppressed when we have apnea. So we always look for it. There's home studies you can do so you don't have to worry about.
Amber Warren, host: Those are those have become so nice people. Our patients don't want to go stay in the night in a hospital. 3000 sleep study. Yeah. These at home ones are really affordable. Really? I just did one on my son. Really easy to do. The convenience is great.
Dr. Mark Holthouse, MD: Great For convenience. You don't need a lot of time to get enough data. You know, these guys will come in and say, I slept 45 minutes in the hospital out of that whole night. That was a waste of my time. And I said, You know, you'd be surprised how little data they need to get what I need. But the home sleep evaluations have just made it so much easier. But apnea is one of the cornerstones in working a natural how to correct naturally.
Amber Warren, host: I love that. Something else I want to go back because I think I think this is I think I'm trying to go through your list that you laid out as kind of as far as order of priorities as I can. And toxins is just up there. It just is. We're bathed in this toxic soup. It's such a big deal. I see it impacting my patients health, see see it in their lab work. What do you recommend? How are you working this up? What are your how are you seeing this impact testosterone levels in your guys?
Dr. Mark Holthouse, MD: Yes, Thanks, Amber. Part of the questionnaire of our program solicits their risk. You know, do they work for a Terminix company? Are they are they the termite guy or are they the pest guy? Have they been working in a plastic manufacturing facility for years? Are they a firefighter? Some of my firefighters are end up with the highest levels of toxins that I see farming. Being an old farm kid, you know, I really my heart goes out to these guys. Yeah, we are exposed to a lot of things that we did not know were problematic back when we were kids as farm kids. And I see an Idaho here. A lot of people that are actively family farming still. So we'll ask them what their risk assessment is on these questionnaires. But we know that things like these personal care products, plastics, just simply drinking out of bottles that have been sitting out behind Costco in the July heat in Idaho on a pallet for a month that were leaching these plastic esters into the water, it gets cooled down and we drink it. We don't think it's in there, but it's still in there. And these things are acting like estrogens in our bodies. And so it's affecting our our hormone balance.
Amber Warren, host: Can you break that down if it's acting like an estrogen? And I know as I love I love your workup when I see your workup on these guys, you're checking estrogen levels, you're checking THG. Let's nerd out a little bit. Why explain that relationship toxins, estrogen mimicking chemicals, why should guys care about testosterone levels with regards to that?
Dr. Mark Holthouse, MD: Yeah, a lot of the guys come in with the man breasts. You know, they're really upset that their their bra size is potentially bigger than their wives. They're they're feeling really disempowered and emasculated, to be honest. And I'll say, look, these are these estrogens that are potentially doing this to you, some guys that are overdosing tea that are aromatase causing their testosterone to estrogen can have the same issue. And that's where having someone that knows how to balance that aromatase transition is crucial. But these toxins, not only are they affecting their actual testosterone and estrogen levels, they're affecting their body fat, they're affecting their inflammation levels in their bodies through having excessive toxins and estrogen toxin, estrogen mimicking toxins. Fertility is affected. You know, in the last 40 years, we've seen about a 40% drop in sperm counts. And the World Health Organization is throwing their hands up saying we have really no clue. We suspect that it might be chemicals, these endocrine disrupting chemicals that are lowering not just testosterone, not just promoting erectile dysfunction, but also decreasing fertility and causing some fertility, which is just difficult fertility, not just in and in men, but in women as well. We're seeing it on both sides of the equation. So toxins are a huge part of testosterone optimization, evaluating them, looking at drug levels and and metabolite levels in urine with the special kits we use. And then using detox protocols to rid them specifically and buying these things and get them out of their body. It's all part of seeing if they really need a prescription the rest of their lives. I think that that's what we do better than other clinics in town is that we're looking at the long game. Anybody can write a prescription that's got a license for this stuff for testosterone or Clomid or HCG or what have you. I think it takes somebody that understands how testosterone works in the body within a world that's toxic and in in people that have imperfect quality of life and lifestyle practices to really do them justice.
Amber Warren, host: So we know there's all these things that you've identified that stimulate, stimulate aromatase. But a lot of these things, you can't reverse it overnight. Right, Right. So this this aromatase enzyme, which is so fascinating to me still. What are what are things that you implement in your practice that can help inhibit aromatase so that while we're working on root cause, we improve their libido, we get we naturally improve testosterone. What are you like?
Dr. Mark Holthouse, MD: Great question. And this is really the crux of my conversation with. It brings in kind of that cardiometabolic pre-diabetic situation to the hormone discussion, which these are my two areas that I'm passionate about.
Amber Warren, host: And you're so good.
Dr. Mark Holthouse, MD: At. Well, I'm always trying to figure out a way to tie it in because. Because they are so interrelated.
Amber Warren, host: Oh, yeah.
Dr. Mark Holthouse, MD: But yes, really, you've got to take a step back and say what makes aromatase the enzyme that turns testosterone into estrogen work more, which is what we want to fight against. Right in, guys. It's it's central obesity. It's inflammation, which is caused by all these things. We're talking about standard American inflammatory diet.
Amber Warren, host: Insulin does it. Still, 60% of our nation is pre-diabetic with high fasting insulin levels, which you're your typical primary care doc isn't even checking a fasting insulin, which is usually the first thing to go up. As most don't know they have it.
Dr. Mark Holthouse, MD: Exactly. Exactly. As of 2018, the CDC statistics are that 47% of us adults over 18 either are pre-diabetic or have diabetes, almost half of us. So and that's projected to be a majority very soon. So, yeah, I always tie those two things in, but it's that high insulin level of pre-diabetes that upregulates aromatase, high leptin, which is another topic, but associated with tummy fat, which is where leptin, the hormone of feeling full comes from.
Amber Warren, host: And we can check leptin in the blood.
Dr. Mark Holthouse, MD: And we can.
Amber Warren, host: Do blood testing to check leptin levels and it's not insane expensive.
Dr. Mark Holthouse, MD: Now fasting insulins and fasting leptons, you know, as a family practitioner, I never used to do that, right? As an integrated practitioner, we do that as part of the routine workup because so many of them are elevated. Mm hmm. Having insulin resistance, having leptin resistance, which is stimulating that aromatase is tied directly to inflammation that stimulates aromatase, being low in vitamin C, being low, and zinc, upregulates, things like aromatase.
Amber Warren, host: Again, all things we can test.
Dr. Mark Holthouse, MD: These are lifestyle, right?
Amber Warren, host: Lifestyle things. Yeah.
Dr. Mark Holthouse, MD: Chronic stress, lots of cortisol. These are the things. And BPA plastics are known to upregulate aromatase things that decrease it kind of the antithesis of that that that can keep our t t are going to be just the opposite of that having a loss of that tummy fat anti-inflammatory antioxidative diets, decreasing pre-diabetes and insulin levels with intermittent fasting with peptides. Yeah, with time restricted protocols, reducing cortisol in all the ways that we've been talking about with good good sleep, better diet, managing chronic pain which we often forget to do.
Amber Warren, host: Yeah.
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Dr. Mark Holthouse, MD: Yeah. Managing this glycemic. The problem is when you've got this pre-diabetic patient who's having 10:00 sugar that's just dropping into the basement for a few years before they declare themselves as full on diabetic. Those people have got high cortisol, high insulin. Everything that drives aromatase is going to make their tea that they have become estrogen more predominantly. So we really look at all of those elements on an enzyme basis. The other side of that question is the other way that testosterone gets stolen. We call these the thieving enzymes of testosterone aromatase. There's another one, five alpha reductase, which is, again, a little geeky. But hold on with me. We're going to bring this back and make it real. The five Alpha reductase, not unlike the aromatase, steals your reserve, your pool of testosterone, and it takes it down to another metabolite. In this case, it's not the estrogen, but it's the dihydrotestosterone. It's a very active form of testosterone that happens to be incredibly potent. And you only need small, small amounts of this stuff to to do what you need. Too much of it. And you get problems like hair loss and great big prostates and maybe things like acne. So we're always trying to modulate, not shut down completely aromatase and five alpha reductase. And it's ironic that the very same things that upregulate aromatase that we mentioned earlier, most of those same things upregulate this five alpha reductase enzyme.
Amber Warren, host: So and we can check DHT in the blood as well.
Dr. Mark Holthouse, MD: A DHT is just a simple blood test. And if it's if it's going down a pathway where you've got too much what we call androgen ization. Yeah. These guys grow ginormous prostates and they have male pattern pattern, hair loss. And so whenever we see guys with overdosing of testosterone or testosterone being given and no one's paying any regard to the downstream drift, we call it on how these enzymes work. Often they've got crazy high levels of DHT. Yeah. And crazy amounts of estrogen. So and those things in too much into high levels are deleterious to guy's health. So dealing with the high blood sugar, dealing with the blood pressures, the inflammation, the stress directly inhibits those two enzyme pathways to keep your t. T.
Amber Warren, host: How about supplements? Botanicals that where we can also calm down those enzymes and help hold onto the test from testosterone? I know there's a lot. What are some of your favorites?
Dr. Mark Holthouse, MD: Yeah, there's several enzyme systems that will help with really hormone metabolism and things like hops, extract and rosemary and ind all three carbon oil and some diagonal methane. Some of these molecules that our bodies make that you get from eating things like broccoli seeds, broccoli seed extract can be incredibly helpful for determining which way testosterone is getting metabolized. I always talk about those as kind of a secondary effect. It's those lifestyle effects that have the biggest impact. That being said, there are some things that we can use in the natural world that can can naturally raise t that can help. There's a lot of buzz out there about tribulus Terrestris really not a lot of data that supports it raising testosterone serum levels. There's good data that it can help with sperm and semen quality. Not so much testosterone itself. The things that have the best data as far as naturally raising t in the botanical world are probably ashwagandha and something called Makena. There's something called Long Jak. These are all botanicals that have great data on improving not just sperm quality but raising serum total testosterone levels as well. But I use those as kind of a last recommendation because my my experience has been that they're kind of minuscule players.
Amber Warren, host: To these lifestyles.
Dr. Mark Holthouse, MD: To these lifestyle.
Amber Warren, host: Changes. I tell a lot of my patients, I can spend a lot of your money. We can we can we can recommend all the supplements in the world, but they won't work if we're not sleeping, if we're not in community, if we're not putting good, quality, nutritious, organic foods into our bodies. Right. So, yeah, it is absolutely foundational. There's one biomarker we didn't touch on that I know is part of your workup in your guys.
Dr. Mark Holthouse, MD: Mm hmm.
Amber Warren, host: I find that pretty significant when I'm working out my guys for hormonal stuff. Can you speak to that a little?
Dr. Mark Holthouse, MD: Yes. Sex hormone binding globulin fbg is a liver produced hormone that is a or a protein that chaperones the the hormones, in particular, testosterone and estrogen. Progesterone kind of has its own thing, chaperone molecule. And the idea being that we know these sex steroid hormones are like oil and oil and water, which the blood is like water don't mix. So they have to have a detergent. What we used to call in biochemistry on my cell, something that will help them kind of mix and be okay together, or they've got to have a transport mechanism. So that transport mechanism for estrogen and testosterone is HPG. And come to find out, there's really good data now showing that there's a direct correlation when fpg and total t testo are low, that there's a much higher risk of getting metabolic syndrome and pre-diabetes. So Fbg now has come into its own kind of its heyday. It used to be marginalized as just this carrier thing for hormones and and that matters. We're going to talk about that, which really answers your question more directly in a minute. But it has its own independent risk factor apart. For prediabetes and metabolic syndrome, how in its own right, when it's when it's insufficient, the fpg discussion gets a little convoluted because it's a little different conversation, whether you're talking about women or whether you're talking about men when we're talking about men. We'll keep this simplified. We want less of it so that the testosterone that's circulating around in our blood is more bioavailable. It's not bound up.
Amber Warren, host: So that's represented by the free testosterone totals, a great number to look at. But the free is actually what's bioavailable unbound by this HPG.
Dr. Mark Holthouse, MD: Right. That's right. That's right. And so many of my guys who've had work done come in having their primary care physician only having looked at it total.
Amber Warren, host: Yeah.
Dr. Mark Holthouse, MD: And the total testosterone, if this sex hormone binding globulin is elevated, can really misrepresent the true circulating bioavailability of T So free T is a huge deal. But in guys, we're trying to optimize testosterone. So we want less HPG around in women, not so much because when there's less of it around, there's more estrogen that's free and estrogen dominance in that whole discussion. So it's not quite the same issue with them. Things that will help that that will help with your fpg not being too high are going to be things like nettle root, like omega three fish oils. There's some data that of some other things as well. But my more pragmatic guidance with diet and how that fits into this whole discussion is really probably the most relevant topic with lifestyle and CPG, and that is low fat and low protein. We know that low fat diets, low protein diets, veganism, vegetarianism is associated with higher HPG levels. And there's studies now showing that the higher that FPG is, the lower the free available T is. So a lot of those guys all try to introduce other forms of protein, especially my older guys. You know, they tend to sometimes forget about protein or they're eating not enough fats, you know, I'll get them on avocados, seeds, nuts, good oils. It doesn't have to be animal fats.
Amber Warren, host: Well, and I find, you know, intermittent fasting, especially for our guys, because we don't have the same pre-menopausal issues with the younger patients. It's such a great tool as you've described for so many of the reasons that to naturally increase testosterone. But I find a lot of my patients that start this intermittent fasting and love it, all of a sudden they they're limiting the amount of fat and protein they're getting in, which, as we're learning from, you can have a lot of effects on on testosterone. So it's not always that with an intermittent fasting regimen, you teach this really well. It's not always we're eating less, our macros are going down. It's just we're shortening that eating zendo.
Dr. Mark Holthouse, MD: Yeah, exactly. The work that Valter Longo has done at USC on mirroring on rat and mouse models now has been reproduced in humans. And it's really clear that it's, it's, it's the iso caloric same caloric. Yeah, that's, that's the issue. We're taking that same number of calories and just squishing it into that smaller window of time the data and there's stuff from Harvard to Dr. Stephen Feeney out of UC Davis. Jason Fung, Toronto nephrologist, have written extensively on this how it's it's that window of time not the amount of calories that matters. And in fact, we know from the biggest losers television studies. We went and looked in the Obesity Journal published in 2016 that even six years out from that event, people's metabolisms were permanently altered and they were much slower. So caloric restriction where you limit the number of calories per day doesn't have the same effects as taking that same number of calories. And instead of eating it over a 12 hour window, eating it over an eight hour window, we were talking in the last episode with women and stress and cortisol, premenopausal with intermittent fasting. And one of the things we emphasize is, look, we know a 12 hour fast helps anything you can do to lengthen the amount of time where you're not putting anything in that obligates us to raise insulin allows us more time during a 24 hour period to burn peripheral fat.
Amber Warren, host: I love that.
Dr. Mark Holthouse, MD: Yeah. Same is true with the guys.
Amber Warren, host: Yeah. Yeah. Just really cool data that I think is coming out even more recently on how we can use that as a great resource. We touched on this in the women really exciting stuff we're doing with with peptide therapies. How are you using peptides and what benefits are you seeing in your male population?
Dr. Mark Holthouse, MD: Yeah, great question. This is kind of the latest thing to what I'm offering. I've been doing hormones for years. Peptides are kind of the new kid on the block. Yeah, we're trying to learn as much as we can and discover compounding pharmacies that are making these great products for us and great combinations of products that are synergistic, that support. The effects of growth hormone. Without giving growth hormone, I would never feel comfortable giving guys growth hormone. Not just because of the legality issues, but because of the known cancer risks and other things that go along with that kind of therapy. We know that the peptides that help release and have a growth hormone like effect are very different than giving growth hormone itself. But yes, I talked about little earlier that counter regulatory response when we intermittent fast is to raise glucagon, raise cortisol, raise growth hormone, and growth hormone is this beautiful hormone that starts to unfortunately decline in our thirties and really takes a dive 40 and fifties that promotes leanness and inhibits having an accumulation like biogenesis of fat in our bodies. So as that wanes, it really does promote this this inflammatory, premature aging cellular senescence that we talk about. So peptides are a wonderful way to dose in the evenings and sometimes even again in the morning to support the effects of growth hormone like that, not just with body composition, but also with regenerative health, with for tissues for recovering from a workout.
Dr. Mark Holthouse, MD: So you start optimizing testosterone along with optimizing the effects of growth hormone in a safe way. It's far more effective synergistically. Not everybody needs both, right? A lot of them don't need them at all. And again, a lot of these guys that take seriously the therapeutic lifestyle stuff, they do just as well. But gone are the days of looking at trying to optimize the molecular effects of these hormones to those of just short stature. And now that we have ways that we can do this safely, it's really exciting. You can optimize their body comp, their recovery, their detox, their aging, their immune. We haven't even touched on that. The immune system support that we can find with these same cell signaling molecules that our cells use. And they kind of just stop producing. Can, can. It's wonderful to have that knowledge. Again, it's in its infancy and it's bringing personalized medicine where we can say, Here are your labs, here are your unique concerns with your body, your risks. Let's stay away from this group. Let's tweak this one. It's a pretty exciting time.
Amber Warren, host: I love to see new modalities come out for for, like you said, really safe evidence based regenerative medicine. Right. We're kind of expanding into this field within functional medicine. We're now we're as kind of functionally trained practitioners. This whole concept of regenerative medicine and how it can really add to the foundations that we've already been doing to our patients. It is really cool stuff.
Dr. Mark Holthouse, MD: It's it's kind of a natural progression.
Amber Warren, host: It is.
Dr. Mark Holthouse, MD: We needed to make sure we spend so much time studying mitochondria thatthis and the mitochondria, which really dictates a lot of how the cells age. Yep. And these other organs, organelles within the cells, it's, it's molecular medicine at this point and peptides are at the forefront of that. And to be able to understand that there are stages that the cells go through where they're trying to recover from a stress that we need to be respectful of where they are in that phase, that stage, this so called cell danger response. You can't just over methylated people with B vitamins as they come in the door. One size fits.
Amber Warren, host: All, give everyone a ton of curcumin to get their inflammation down. Right. It doesn't always.
Dr. Mark Holthouse, MD: Work. Sometimes inflammation is exactly what the body needs. Yeah, it's it's knowing how to determine where it's starting to become deleterious, I think, is where all the wisdom is. Mm hmm.
Amber Warren, host: I like to end each one of my discussions, and this has been a phenomenal discussion. I've learned a lot. If there's as a as a as a physician, if there's one piece of advice you offer to your patients that makes the most dramatic impact on their health, what is it?
Dr. Mark Holthouse, MD: Yeah. Know, I'm famous for being quoted and saying that it's the human touch and I've always got to go there to be true to myself. Yeah. After doing this for 30 something years, the biggest piece to seeing results is that rapport is. Is that caring. Is that? Oh, my gosh, I have somebody sitting in front of me who's actually listening to what I'm saying.
Amber Warren, host: And trust. Trust goes a.
Dr. Mark Holthouse, MD: Long way, right? That that still is always my my number one. I think it's it's the combination of high tech and high touch. If they see you care and they see your competent and your skilled in an area of biology that's practical, that's applicable, that's looking out for their optimization within the context of safety, they realize they're somewhere special. And that's that's what does it.
Amber Warren, host: Well, that's pretty much you in a nutshell. I know I speak for a lot of your patients when I say that. Well, thank you for being here. What an exciting conversation, exciting direction we're going with with functional medicine foundations.
Dr. Mark Holthouse, MD: My pleasure. Thank you.
Amber Warren, host: Thank you. Thank you for listening to the Functional Medicine Foundations podcast. For more information on topics covered today, programs offered at WMF and the highest quality of supplements and more, go to Fun Med Foundations.