Podcast Drop Date: 2/5/2025
In this episode of the Functional Medicine Foundations Podcast, host Amber Warren, PA-C, sits down with Dr. Mark Holthouse, Chief Medical Officer of FMI and the FMI Center for Optimal Health, to explore cholesterol from a functional medicine perspective. They discuss key testing and markers to watch for, dietary recommendations for healthy cholesterol, the truth behind seed oils, and effective exercise options. Together, they highlight a holistic approach to managing high cholesterol, offering listeners valuable insights for better heart health.
Transcript:
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 everybody. I have Doctor Holthouse here. Doctor Mark Holthouse, M.D., 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 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 in hormone health across the nation over the past ten years as an Assistant Professor of Medicine on the teaching faculty at Loma Linda University School of Medicine. He is an expert on cardiometabolic disease prevention, reversing type two diabetes, heart disease, high cholesterol, obesity, and metabolic syndrome. In addition to his clinical and teaching experience, he has over 30 years of owning his own private practice as Acting Medical Director, implementing strategic models in clinical practice and the business of functional medicine. Doctor Holthouse and his lovely wife Tammy enjoy photography, snowshoeing, skiing, sailing, hiking, kayaking, and of course, good food. I've tasted a lot of that good food that your wife makes. You can't take credit for that good food that you get to eat. Because I see how you eat when you're away from her. Like weeks like this when you hang out with us and God love you, but you need more Tammy whole house food in your life.
Dr. Mark Holthouse: I get derailed quickly without her.
Amber Warren, PA-C: I am just so excited for this conversation. Um, it actually it caused me last week when I was doing some of my own research to pause and actually pull up our podcast website and look back and say, I can't believe we haven't discussed this topic before. Um, we're talking about high cholesterol in the general, uh, arena of, of cardiometabolic disease. Um, and I just am like, oh my gosh. We have like the genius of cardiometabolic medicine that we get to practice with and see, see patients with all the time. And we haven't talked about the importance of high cholesterol and how we treat it versus a conventional approach and blending of the two approaches. So this is just going to be gold. Um, LDL conventional lipid panels. Let's just dive right in. What is LDL cholesterol. Why do we care about it. What do we do about it?
Dr. Mark Holthouse: Yeah, there's a whole cholesterol story that's really interesting history where this started in the 1950s. Um, and a lot of it had to do with a fellow by the name of Ancel Keys, who was a physiologist. And back in the 50s, he was a very influential. In fact, he was involved with Dwight D Eisenhower's personal doctor, a guy by the name of Doctor White. Uh, these guys went on to later be founding members of the American Heart Association in the late 50s, early 60s. And, um, what what the the hypothesis was at the time was that basically eating. Uh, saturated fats and animal products, um, was the cause of heart disease. And this was based on some very, by today's standards, the studies that that, uh. Doctor Keyes did were, um, we'll just say less. They would not withstand the rigors of today's analysis by any stretch. Very weak. Um, a lot of the dietary guidelines that we have today, even the 2020 guidelines up to 2025, have been influenced by this early hypothesis that by eating saturated fats, we're driving LDL and even ApoB levels up and that, um, there is a cause and effect relationship.
Dr. Mark Holthouse: This is where a lot of the controversy is, is in the dietary, um, choices that people make, the diet, the food wars, vegetarian versus carnivore and everything in between. I've really, um, in looking at the history of it, it's, uh, it's paralyzing when you get into the full breadth and width of the data. You can literally cherry pick studies and come to opposite conclusions.
Amber Warren, PA-C: Yeah.
Dr. Mark Holthouse: When it comes to saturated fats being the cause of cardiovascular events versus the other way around, I've come to the point where I've stopped really caring about that question and looking at the labs. Um, there's a few labs that are important that matter, and there are a whole lot of labs that are probably less important historically. Um, initially When these first thoughts were came out with these early scientists, it had huge impacts on public health policy and some of the recommendations that were put out by the American Heart Association in the 1960s, which still today, we're dealing with these things 40 years later.
Amber Warren, PA-C: Like the food pyramid.
Dr. Mark Holthouse: Right, right. Exactly. The traditional pyramid. And, um, you know, there's been a lot of work on looking at full fat dairy, uh, pasteurized and unpasteurized are some of the things that we need to really tease out a lot of these studies that looked at meat and, and high levels of saturated fat. We're looking at processed meats early on. And so a lot of these initial, uh, recommendations were based on eating animal products in a, in a way that's different from we now know that it's optimal. Right. Um, the problem is we don't have a definitive answer as to following the bouncing ball between eating saturated fats, which we know raises ApoB and LDL, and actually having a causative effect with actual events, as in an ironclad statement I wish we could.
Amber Warren, PA-C: Right, yeah.
Dr. Mark Holthouse: We know that once your ApoB and your LDL numbers in particular are elevated, that there's no question independent of insulin resistance, cardiometabolic health, hypertension, smoking, there's an independent risk for cardiac disease and risk.
Amber Warren, PA-C: I have to interrupt you, ApoB. I'm sure there's a lot of our listeners that have never heard that term. What is it?
Dr. Mark Holthouse: So some of the more important tests would come to find out at analyzing LDL particles, which it appears is has the tightest association with predicting heart risk, even more so than LDL cholesterol.
Amber Warren, PA-C: So that's a very important statement. We actually have a test that is more predictive of looking for cardiometabolic disease, the progression of plaque formation. Then your LDL panel that everybody knows what that is, your conventional lipid panel, you get it at every screening appointment you've ever had in your life. But there's actually a better test.
Dr. Mark Holthouse: There is. We know that when you get a traditional lipid panel, it includes a total cholesterol, which is all of the cholesterol in your whole body, good and bad. We're going to talk about that in the fallacy of that thinking. We have LDL cholesterol, which is just a different lipoprotein protein particle, a carrying agent and a vehicle.
Amber Warren, PA-C: Right.
Dr. Mark Holthouse: Which to transport cholesterol and fats around the blood, because the blood is like water, it's aqueous. And these fats are oil. Oil and water don't mix. So we have to have a means of moving things from what we eat and what our body is doing, and metabolizing in the liver and getting it into the bloodstream, getting it through to the liver, having things metabolized out. And they get excreted in a way where it's going to mix in the blood. So the idea of LDL cholesterol, LDL is just a one of these vehicles. It's a protein envelope. And you have multiple types of of lipoprotein particles, vehicles, all of which transport cholesterol around. And what we're realizing is that it's not so much the cholesterol itself that's the evil villain in this heart risk story, but it's the protein, the lipoprotein particle that it's transporting, cholesterol trafficking around the body, if you will, that confers either good or less than noble intent. So we used to call HDL high density lipoprotein, the good cholesterol. And we used to call LDL the bad cholesterol. And now lipid ologists know better. We know that there is no good and bad cholesterol. There's just cholesterol. And it's the vehicle that it's being transported around in the body, the lipoprotein that makes it have either good or bad effects. And when you get into it, it's a little bit more complex than that.
Dr. Mark Holthouse: When you have too much of the HDL in certain scenarios, it can it can be destructive and dysfunctional. We call it, um, but in general, LDL cholesterol has ruled the day since the very beginning as the marker of predicting heart risk. And that's what a lot of our our pooled cohort equations, which are population based guidelines, are based on. We had the American Heart Association come out with this in 2013. And there's been several modifications of this over time. And even they are acknowledging that LDL, an LDL centric world, is becoming less and less apparent as the only marker. And in fact, we know from studies that the LDL particles, the number of particles that are floating around in the body, is more important than the total LDL cholesterol itself, as far as being tightly regulated to pointing to cardiovascular risk. ApoB is is really a poor man's test of what we call an LDL particle number. It's a much less expensive version. You can get these pay cash for. There's some labs that are doing it for $10. If the insurance doesn't cover this, this is still something you should pay out of pocket to get. It's that important. ApoB, and this is not an integrated practice. This is well known whether the insurance companies let the doctors order. It is another thing.
Amber Warren, PA-C: Right.
Dr. Mark Holthouse: But the science is clear that ApoB as a representation of LDL particle number is the number one lipid marker to predict risk. The total cholesterol we talked about earlier correlates with this ApoB. About 80% of the time.
Amber Warren, PA-C: Okay, okay.
Dr. Mark Holthouse: LDL that we're traditionally used to ordering correlates with ApoB be about 90% of the time. There's a newer kid on the block that came out called Non-HDL cholesterol, which is basically just taking the total cholesterol and subtracting out the good stuff, HDL.
Amber Warren, PA-C: It's no fancy calculation. It's pretty straightforward.
Dr. Mark Holthouse: A third grade math kid could figure this out. And this was better than LDL. LDL was better than total cholesterol at approximating what we've really needed to get to this whole time, which was particle number, i.e. the ApoB. So ApoB is one of those labs that has really risen to what's most of a priority for me. Along with triglycerides, now triglycerides are on a basic lipid panel, as well as that total cholesterol, LDL and the HDL, and triglycerides are really measuring how much you've been taking in in carbohydrates, simple carbohydrates, the liver takes those and converts them into fat. And that is released into the bloodstream in the form of something called a VLDL, which is either all lipoproteins. These are all vehicle names Chevy, Ford, you know, Tesla, what have you. They all have varying mixtures of cholesterol and triglyceride, and that's what gives them the density. So we've got low density. We've got very low density. Those are going to be higher up on the production line. And we've got HDL which is you know there's there's high density and low density, and it has to do with the relative amount of triglyceride to cholesterol, all coming from the liver, from this little triglyceride that dumps it out into the blood, eventually becoming VLDL or something called a remnant particle.
Dr. Mark Holthouse: And then LDL and on down to HDL. All of these different varieties, if you will, of transport vehicles having different functions in in the body. So we look at triglyceride because it's a measure of metabolic health. Is the liver getting inundated with too much sugar. People with insulin resistance and type two diabetes have too much triglyceride. Therefore their VLDLs go up and you'll see a lot of these lipid disorders, these lipoproteins follow suit. We know that there's a specific pattern when this when this happens. This is called metabolic dysfunction. Insulin resistance is part of that metabolic syndrome. Prediabetes, fatty liver these are all the epidemic diseases that we're seeing. 33% of the US population now with fatty liver replacement from eating too many carbs. When your liver has no where else to go, it deposits these carbs in the form of fat in the liver and literally changes the fat to the liver to fat from it's working cells. So detox. It's a production of proteins and all it's its duties get compromised. Um, what leads to that is what we call insulin resistance, where your skeletal muscle, for the most part, it's about 85% of your insulin sensitivity comes from how well your skeletal muscle can take up sugar.
Dr. Mark Holthouse: And if you can't do that, it goes back to the liver. And the And the liver has three options. It can basically convert it to fat and burn it called beta oxidation. It can get rid of it and send it out into the bloodstream in the form of VLDL and triglycerides, or it can store it and create a fatty liver. It's the only three options that it has. And this is why I think we're seeing so many people, 33% that have this fatty replacement. Um, there's many people that have problems with they just can't handle their glucose correctly. They can't switch between burning fat and burning glucose. They have lost what's called metabolic flexibility. And it's all part of this cardio metabolic disease driven by eating carbs, ultimately ending up in the liver as fat getting released into the blood. So we have patterns. And when you see a prediabetic with metabolic dysfunction. Often you'll see fatty liver. So their liver enzymes are off showing there's damage going on. We see this all day long.
Amber Warren, PA-C: Yeah.
Dr. Mark Holthouse: As as you and I see.
Amber Warren, PA-C: But we even sometimes don't see the liver enzymes climb. Sometimes that's not always.
Dr. Mark Holthouse: Sometimes.
Amber Warren, PA-C: It's a reflection of liver health. Yeah.
Dr. Mark Holthouse: Um, together with that, we'll see. High triglycerides. And now we know why. Um, what's interesting is that you see a suppression, a lowering of the HDL and the LDL may be okay. Yeah. It may go up. It may not. It may stay the same. So LDL ironically, the thing that we've been so focused on for looking at cardiovascular risk is probably my least important marker. Uh, maybe second only to total cholesterol being less important. So when I, when I look at a lipid panel now, I want to know about ApoB or the particle number. The LDL particle number is you can look at particles for HDL, LDL, VLDL. It's just a more expensive test.
Amber Warren, PA-C: So you're not getting that that more extensive panel on most of your clients?
Dr. Mark Holthouse: Not as much because of the cost difference.
Amber Warren, PA-C: Yeah, okay.
Dr. Mark Holthouse: So I'll look usually especially if they have a high risk of family history, risk of cardiac disease or smoker or diabetic folks that are at higher risk for having heart disease. I'll look right off the bat at triglycerides. ApoB I will sometimes look at the HDL as well. And LP(a), which we haven't gotten to yet. Um, but it's really changed the way I look at a standard lipid panel. Picking those analytes is less expensive than doing a full what's called an NMR, a full, um, panel, uh, for the particle numbers, you know, that can be much more expensive.
Amber Warren, PA-C: Yeah
Dr. Mark Holthouse: It's a little bit more information. Um, LP(a) is that other important lab test that you want to do because it's 80-90% genetic, has nothing to do with lifestyle.
Amber Warren, PA-C: He's a little devil.
Dr. Mark Holthouse: A little devil.
Amber Warren, PA-C: He's a little devil.
Dr. Mark Holthouse: Now, LP(a) is a particle. It's a lipoprotein particle just like LDL, just like HDL, VLDL. In fact, it's a subtype of LDL. It's just a nasty little critter. ApoB, going back just a little bit is a lattice, a structure, a template protein that has to be there for all of these plaque forming particles. What are those? Well, it's the triglycerides VLDL remnant particles, LDL. It's pretty much everything except the HDL. We call them atherogenic lipoprotein particles. And all of those contain this ApoB protein as a lattice. And to that we add cholesterol, triglycerides. And now it's a full particle.
Amber Warren, PA-C: But dysfunctional HDL can't serve as an atherogenic particle.
Dr. Mark Holthouse: No HDL. Come to find out, has a different lattice protein called ApoA100.
Amber Warren, PA-C: That's right, A100.
Dr. Mark Holthouse: Yep, that's right.
Amber Warren, PA-C: You can also check in the blood, and you can get an ApoB to ApoA1 ratio, which is helpful, but clinically probably not that significant.
Dr. Mark Holthouse: I don't do as many as I used to. Right? I don't know that it changes my management to be honest. When I have an HDL, I kind of know what's going on. Um, but this ApoB is a protein that is core to all the bad particles that lead to heart disease. It appears, and there's so much data on that now an independent risk factor and marker. Um, so we look at ApoB very, very seriously. It is Um, it is the fact that LP(a) is a subtype LDL particle, so it's got ApoB in it. It's got another player in there. Uh, that makes the little a part of the nomenclature, in addition to the cholesterol and triglycerides and everything else that you see in a standard LDL. Now, the reason this thing is so sneaky is that it's it's basically a, a separate gene that's being transcribed in our livers, that's making a coil. They called it a kringle because it looked like a Danish pastry to the guys that first saw this thing. So it's like taking a LDL particle with an ApoB that has this extra protein in it that's dragging a tail around its particle throughout the The bloodstream and it promotes clotting. And it's a much bigger risk factor for heart disease in especially in people that don't have prior risk factors for heart disease. They might not have anything else going on. I have it I have LP(a). My dad had LP(a). He didn't have any risk factors for stroke or cardiovascular disease. Um, and as elite athlete, um LDL cholesterol was unbelievably great. I mean, like 70. And he had a stroke.
Amber Warren, PA-C: Yeah.
Dr. Mark Holthouse: And the neurologist that he saw said everything else looked great. All the imaging. There's no plaque. What is going on? So we got him in and we did a deep dive on looking at vascular inflammation markers. We looked at LP(a) and a lot of these other things we've been talking about. And what we found out was that dad had a high LP(a).
Amber Warren, PA-C: And statistically speaking, does it matter how high it is. The higher, the more severe it does.
Dr. Mark Holthouse: Yeah, there's degrees of bad. Come to find out. And what it appears in the data to show you need at least a 50 or higher normal is usually less than 29. And and patients that are over 50, that's considered enough to promote cardiovascular risk. The ones that we worry about the most are obviously are the higher ones that are out there.
Amber Warren, PA-C: And how high is severe?
Dr. Mark Holthouse: Oh, you get into the, you know, above 180, 150.
Amber Warren, PA-C: Closer to 200. Okay.
Dr. Mark Holthouse: Yeah. Right now we've got I think 3 million, uh, in the United States that are above 180.
Amber Warren, PA-C: Okay.
Dr. Mark Holthouse: It's estimated that we've got around 60, 66 million that are, um, probably above 50.
Amber Warren, PA-C: So the data is still 1 in 4 or 1 in 5 people have this.
Dr. Mark Holthouse: Yeah. It's very it's still prevalent.
Amber Warren, PA-C: Yeah. So ask if you haven't had this test run really there's two LP play APB. And if your provider won't order it for you, find a new provider. Those two tests are paramount.
Dr. Mark Holthouse: It is not integrative. Complementary alternative. This is mainstream science. And, um, our even our guidelines from traditional docs are starting to pivot and focus more on these additional risk factors. Coronary artery calcium scores, imaging studies, sed rates, CRP markers.
Amber Warren, PA-C: So true.
Dr. Mark Holthouse: You know, not just LDL.
Amber Warren, PA-C: Yeah. It's so true.
Dr. Mark Holthouse: Yeah.
Amber Warren, PA-C: Yeah.
Dr. Mark Holthouse: So LP(a) is genetic. You really can't change it much at all with diet exercise. There's statins that raise the thing.
Amber Warren, PA-C: Right.
Dr. Mark Holthouse: We find out. And there are injectable medications that work very differently at lowering cholesterol by impacting the LDL receptor in the liver. And when we inhibit that enzyme, that tears down these these receptors in the liver that grab LDL out of the blood and, and metabolize it in a way where they're not impacting. And we can pull LDL out without any interference, and we drop LDL. Um, these newer injectable drugs can actually these are monoclonal antibodies, uh, lower LP(a).
Amber Warren, PA-C: Can I ask you a question? What do you think's. And I think I know the answer to this what you will say. What's more important? Lowering LP(a) or lowering ApoB.
Dr. Mark Holthouse: Uh, yes and yes.
Amber Warren, PA-C: If you can only lower one.
Dr. Mark Holthouse: If I could only lower one, I would go after LP(a).
Amber Warren, PA-C: I figured you'd say that. Yeah.
Dr. Mark Holthouse: That is how dangerous that that genetic mutation is.
Amber Warren, PA-C: Yeah.
Dr. Mark Holthouse: And, um, so I have this. I'm at 149 as I sit here today. It's lower than that, but I can't use a statin because the data is clear that if anything, it anything, it.
Amber Warren, PA-C: Probably raises it.
Dr. Mark Holthouse: The approach right now with cardiology is to put people on a baby aspirin a day and high dose statins to mitigate overall cardiovascular risk. The problem is it's not addressing the the LP(a).
Amber Warren, PA-C: Well because a lot of them probably aren't checking it. So they don't have that data.
Dr. Mark Holthouse: A lot of them don't. In fact, the majority of people that are being managed, even post MI have never had an LP(a) post heart attack or stroke.
Amber Warren, PA-C: Does LP a rise as you age?
Dr. Mark Holthouse: That's a great question. LP(a) rises as you age, not necessarily. In fact, they think it's at adult levels by age five.
Amber Warren, PA-C: Wow, okay.
Dr. Mark Holthouse: And most people feel like you only need to check it one time in a life lifetime. I take a little different approach on that because I'm still trying to figure out ways to lower it. Um, historically we've used niacin, which in some people can work as a supplement. The problem is the amount that it impacts it is usually less than what we now know is enough to make a difference. Yeah, we're hearing that we're needing to lower this stuff, you know, 50-80%. And the PCSK9 inhibitors that I mentioned earlier. On a good day, 25-35% at the most.
Amber Warren, PA-C: Yeah.
Dr. Mark Holthouse: Where it's going to do that. And these are very expensive medications. You're taking them every other week as a shot. There are phase two and phase three clinical drug trials going on right now. One of these trials is the HORIZON Trial due to finish in 2025 this year. The other one that's promising is the 2027 release is the OCEAN Trial. And these are looking at really interesting molecules that are basically interfering with the RNA, the ability to Um, basically make this LP(a) protein that makes it so, so evil. It literally stops it in its tracks from being transcribed or produced from the DNA. So and there's four of them. Four of them out there right now that are under development. Some of these are, you know, every other week. Some of these are they're most of them are all of them are injectable.
Amber Warren, PA-C: Yeah.
Dr. Mark Holthouse: Some are once a year potentially or once every six months. Um, but they have shown now in some of those that are further along, up to an 80% reduction and more.
Amber Warren, PA-C: I mean, that's lifesaving!
Dr. Mark Holthouse: This would be a life saving pharmaceutical. You know, an integrated medicine, FMI we kind of pride ourselves on being anti-pharma anti-drug, but with folks that have got mutations, just luck of the draw.
Amber Warren, PA-C: If we know lifestyle doesn't doesn't affect it at all. We we have no have no choice.
Dr. Mark Holthouse: These are your friends who are doing CrossFit or doing, you know, everything, right with their diet. They're managing stress. Who have no risk factors for cardiovascular disease, who die.
Amber Warren, PA-C: Yeah.
Dr. Mark Holthouse: If there's a way to mitigate that with a medication, a nonstatin medication, my goodness, I'm going to take it when it's available. And I don't want to be on anything any more than the next person. But I've also seen, you know, my dad, two-time world champion, Olympic distance triathlete with a body fat of, you know, probably 10%, 12%, eating perfectly, doing everything right. No smoking, doesn't drink, have a stroke right in front of me. Signing autographs on a podium post his event.
Amber Warren, PA-C: Yeah.
Dr. Mark Holthouse: And I left an impression.
Amber Warren, PA-C: For sure.
Dr. Mark Holthouse: To see I've got the same levels that he had.
Amber Warren, PA-C: Yeah.
Dr. Mark Holthouse: You know, the only difference is I'm a few years younger and so yeah, I'll be signing up for that.
Amber Warren, PA-C: So you alluded to just because I know so many of our listeners are going to be mostly intrigued by this, this part of the conversation you alluded to the the just the confusion over nutrition and how it relates to cardiovascular disease. So what are you recommending for your clients?
Dr. Mark Holthouse: The whole dietary issue and how it affects actual heart attack risk really is an individualized one.
Amber Warren, PA-C: Yeah.
Dr. Mark Holthouse: I have people that don't have metabolic syndrome that don't have pre-diabetes.
Amber Warren, PA-C: Their fasting insulin, their hemoglobin A1C, their triglycerides all look beautiful. Optimal.
Dr. Mark Holthouse: Optimal. They're on a low carbohydrate diet usually.
Amber Warren, PA-C: Yeah.
Dr. Mark Holthouse: And yet you check their ApoB and their LDL particle number, and they're sky high.
Amber Warren, PA-C: Yeah.
Dr. Mark Holthouse: Uh, these are folks that often meet this new criteria of what we what we call lean mass hyper responders, where they have an LDL of over 200, a triglyceride of less than 70, and an HDL over 80. Very unlike the Prediabetic bucket, the subpopulation that I talked about earlier where they have a pattern. These fly in the face of the pattern. We don't know yet if those folks that are cardio metabolically healthy and yet have high ApoB, which we know independent of risk factors, other confounding factors is associated with cardiovascular disease.
Amber Warren, PA-C: But we don't know. Is is the data extrapolated to LP(a), do we know that?
Dr. Mark Holthouse: LP(a) is totally different.
Amber Warren, PA-C: So we're not talking about whether or not they have. We don't know if these people have LP(a) or not.
Dr. Mark Holthouse: Correct. And as far as anything you can do with diet and lifestyle, we don't see any real leverage with LP(a) anyway.
Amber Warren, PA-C: That's true, that's true. I was just curious what it was doing for their overall atherosclerosis risk factor and those lean mass hyper responders.
Dr. Mark Holthouse: Well, anytime you have a mutation with LP(a) elevated, you are adding it's a multiplicative effect.
Amber Warren, PA-C: Yeah.
Dr. Mark Holthouse: Above and beyond ApoB. And so really what we're trying to do is remove these multipliers of risk whether it's smoking, high blood pressure, crappy diet.
Amber Warren, PA-C: Yeah.
Dr. Mark Holthouse: You know eventually having something to treat LP(a). The big uestion is what to do with these folks that are fit athletes that are eating ketogenic. That have these high ApoBs but don't have metabolic dysfunction.
Amber Warren, PA-C: Right.
Dr. Mark Holthouse: We have nothing to show that they're at the same risk as the other group, the more typical in the population. But we have nothing to show that they're safe. So my argument is why not eat in such a way where you can bring that down, that LDL and that ApoB by giving yourself just a little bit of carb? Eat that sweet potato. You know, have a piece of complex carbs. I'm not talking about eating a Snickers.
Amber Warren, PA-C: Yeah.
Dr. Mark Holthouse: And we know that when they eat just a little bit more carb that that ApoB and LDL-C, they fall and it doesn't take much. So if they can get the benefits of a lower carb diet, avoiding the inflammation, avoiding a lot of why they're doing that, some of it's for body composition. Some of it's for bipolar depression, swelling, edema. There's so many epilepsy. There's a lot of reasons people do low low carb. The low carb community does it. But my argument is why not have both? Why have it either or? Why can't we just do a little bit of carb, get their risk down by bringing ApoB, you know, down out of the 130s, 140s. And closer to 100. We know that south of 100 is less risk. Ideal is probably 80 or less. 90 or less is a cutoff that a lot of us use for normal ApoB without impacting the benefits they're getting of their low carb diet, until we know more.
Dr. Mark Holthouse: And these studies are ongoing, those studies, as we speak, those studies are ongoing in that subpopulation. So when we look at epidemiological studies in the United States, like the Framingham data.
Amber Warren, PA-C: Right.
Dr. Mark Holthouse: It doesn't answer these kinds of questions. And honestly, the people that first started engaging with ketogenic diets were folks that were doing it to lose weight, that were metabolically unhealthy. Now that you've got these athletes and healthy people that don't have pre-diabetes, obesity, fatty liver showing up with these same markers, we're not sure.
Amber Warren, PA-C: We don't know what to do with.
Dr. Mark Holthouse: It's a hole in our knowledge right now.
Amber Warren, PA-C: So different subset of people. Just the people that are, you know, either menopausal or climbing in age. Their cholesterol is starting to climb. Their practitioner is not doing much about it. I'd love to hear, lifestyle wise, what you're doing, nutrition, exercise recommendations for those people.
Dr. Mark Holthouse: Yeah. So I'm a plant guy, but I'm also not promoting vegan or vegetarianism either. Um, I am always looking at it from my longevity practice where we're trying to balance detox, recycling old worn out cell parts, misfolded proteins, mitochondria that needed to check themselves out of the hotel years ago that are hanging around. We call that autophagy mitophagy mitogenesis, making new mitochondria. And, um, it's all brought about by a pathway called AMP kinase. Anti-aging, sirtuins, NAD that you guys talked about in earlier podcast are working over there. On the other side of the teeter totter is mTOR. MTOR, mammalian target of rapamycin, which is stimulated by leucine and other mostly proteins, branched chain amino acids, but also things like insulin that is very pro growth, bone growth, muscle mass, shredded. It's what everyone's seeking right now. Right? They want to look ripped. I'm trying to balance that pro growth mTOR with anti-aging, anti-inflammatory. And it's important because if you just focus on the one side and and you're doing nothing but saturated fats, uh, what we find is that there is an elevation and we don't think it's necessarily a good thing of IGF-1, which is basically something made by the liver that we use to measure growth hormone adequacy and where people are at. And I've got a lot of my, you know, my folks that are very pro ketogenic diet. They, you know, they're in the gym. They're doing a lot of great stuff that are eating carnivore, for example.
Amber Warren, PA-C: Right.
Dr. Mark Holthouse: And they don't want to eat anything with fiber or that's green or a plant or produce, you know. So they're going to miss out on fiber, which is the most anti-inflammatory substance on the face of the earth as far as food goes. Um, and I feel like then there's the vegans over here that are just carbitarians, you know, and they're saying, I'm healthy if I don't eat meat. And the other side is saying, if I just eat meat, I'm healthy. And I don't think either one of them are correct.
Amber Warren, PA-C: Both aren't nutritionally sound, I would agree. Yeah.
Dr. Mark Holthouse: So there's a lot of data on saturated fats, you know, which are obviously much higher in, uh, meat, dairy, eggs and um, looking at the breakdown of saturated fats, palmitic acid being the most prevalent 25% of the saturated fat in animal products. For the most part, we know it raises LDL and it raises ApoB. It raises IGF-1. Too much IGF-1 is a growth hormone, which is great when you're growing and your bone is still growing and you're a kid. But what happens when we're adults, when we push the mTOR, push the cell growth hormones too hard? We worry about the data that's out there showing cancer. Too much cell growth equals cancer. IGF-1 not only stimulates cell growth and regeneration like testosterone and other anabolic hormones. So there's a sweet spot. It's a U-shaped curve. In fact, there's more problems when it's too low and there's problems when it's too high. So a U-shaped curve and somewhere in the middle sweet spot what's been published somewhere between 120 and 160 is probably where we want to be shooting for. Where we're not promoting cancer and premature aging, and yet we're not going to have bone and muscle loss and be cachectic and and look like, you know, somebody that's not been eating, you know, somebody that's malnourished. There's probably a sweet spot. And we know that saturated fats raise IGF-1. And the question is when you do saturated fats and they're raising IGF-1, raising ApoB, raising LDL in people that, again, are not metabolically sick.
Amber Warren, PA-C: Right.
Dr. Mark Holthouse: Does that still translate to an increased risk of cardiovascular disease? And that's where the diet wars are centered over that issue.
Amber Warren, PA-C: That's what I was going to say. It's not as easy as does does eating eggs make you have high cholesterol? It's so much more complicated than that.
Dr. Mark Holthouse: So we have to treat everybody as an individual.
Amber Warren, PA-C: Absolutely.
Amber Warren, PA-C: Are you looking for high quality supplements? Shop is carefully curated by the wellness experts at Functional Medicine of Idaho. You'll find high quality supplements to support your health and optimize your body's natural functions. Rooted in responsible sourcing and utmost commitment to purity ensures that you're getting products that are not only effective, but also safe and reliable. Plus, you'll find our own line, Functional Medicine Foundations, which is carefully formulated using the best ingredients available so you can trust that you're giving the body the support it needs. Visit funmedshop.com today and take the next step in your health journey. That's funmedshop.com.
Amber Warren, PA-C: And look at those biomarkers, right.
Dr. Mark Holthouse: Ask if you've got, you know, family history of early heart attack 40s and 50s in your genetics. Do you smoke? Do you have high blood pressure? Are you sedentary? These are the big issues as well. What is your blood sugar. What's your hemoglobin A-1c.
Amber Warren, PA-C: Yep.
Dr. Mark Holthouse: Um, do you have metabolic dysfunction or do you not? Because depending on which subtype you find yourself, there's areas that are very, very, very clear.
Amber Warren, PA-C: Right.
Dr. Mark Holthouse: And we know exactly what to do. It's a very small group of the population that is growing, luckily, that are less metabolically ill, where there's still some questions to be answered. So what do I do? I tell patients to do clean, lean, organic sources of protein. And I am not afraid of non-GMO soy. I am not afraid of beans, peas, lentils, legumes, seeds, and nuts. The data is clear. I'm not even afraid of the omega sixes.
Amber Warren, PA-C: You went there!I was gonna ask.
Dr. Mark Holthouse: I went there.
Amber Warren, PA-C: I was gonna ask! Seed oils!
Dr. Mark Holthouse: Yeah. So I and I do have them do eat from the colors of the rainbow. You know, I want them to get the fiber, the polyphenolic chemicals that are that are anticancer, that are feeding the good bacteria, the akkermansia strains in our gut to make butyrate, which is a precursor to ketones. Hey, my low carb people resonate with that. That's a ketone body, butyrate. Um, you know the other short chain fatty acid that's created when we eat plants by our bacteria and our gut is acetate, acetone, another ketone. So we try to make it so polarized, but kind of like our, our politics. There are there is some common ground you guys to be had. And I think that as we get some of these, um, these other answers coming in with data, good data. Clinical trials, not just epidemiologic observational trials, because we know that observational trials and epidemiology, looking at populations and comparing what we do here with someone on a on a placebo or what have you, doesn't always tell us about causative. Cause and effect. It tells us about associations only. So we need that data to know more. So I have them eating plants. And I think what we can all agree and good sources of protein both protein that is complete and there's plant proteins are complete. You talk about high digestibility and the quality of the protein. Soy is right there just beneath whey isolate. You know soy got a bad rap because it's genetically modified. I don't shy away from having my patients eat edamame and tef and miso. Because the data does not show problems. In fact, it's very positive for things like cancer risk and cardiovascular disease. Uh, nuts. Same thing. Seeds.
Amber Warren, PA-C: Right.
Dr. Mark Holthouse: So, and a lot of these things are PUFAs, polyunsaturated fatty acids. Um, so I don't know if you want to go there or not. We can on seed oils. You can you can direct that if you want to go there.
Amber Warren, PA-C: Yeah. No, I mean I do I, I mean I think you and I can agree that that as, as, um, significant as we've made it an issue in mainstream media and on social media and just in our integrative world, it's really lacking clinical data. It really is. And we've just blown it up when there's probably a lot of other issues that really should be addressed way before, um, the overall like, I yeah, I don't know. I mean, I think glyphosate and high fructose corn sirup should be given way more attention than seed oils. But I feel like you, you see seed oil on a bag before you see high fructose corn sirup. And that's the first thing you pay attention to. And maybe that's just that's just my opinion in the world I live in, but.
Dr. Mark Holthouse: I have biases too.
Amber Warren, PA-C: Yeah.
Dr. Mark Holthouse: I want canola in the data to look horrible.
Amber Warren, PA-C: I know. Yeah
Dr. Mark Holthouse: I really want corn oil to look bad because of the way these things are processed and extruded. Uh, and a lot of that. The devil's in the details on the transformation.
Amber Warren, PA-C: That's true.
Dr. Mark Holthouse: The processing of of making them harmful. What's what we wanted to bring up. It's flies in the face of most of what's on the internet right now. Is that the data that that polyunsaturated fatty acids, specifically omega six seed oils, cause inflammation and heart disease just isn't bearing out.
Amber Warren, PA-C: Does it match, yeah.
Dr. Mark Holthouse: In fact, the opposite is what is shown. Yes, omega threes are even more anti-inflammatory.
Amber Warren, PA-C: Yeah, I think that's the point. It doesn't take away from your organic, high quality extra virgin olive oil um or in some in some people good quality organic grass fed butter. Um, in some people I'll say that again. But like, I think we we need to focus on the really good and not make such. Yeah. It's just so interesting what we like to do with am I going to inaccurate data.
Dr. Mark Holthouse: Am I going to eat margarine tomorrow?
Amber Warren, PA-C: Right,absolutely not. Yeah.
Dr. Mark Holthouse: No. But am I going to be afraid of, um, you know, eating, eating flax seed and, a lot of these nuts and things that are you look at the composition of, you know, canola oil, for example, and how much saturated fat versus monounsaturated fat versus polyunsaturated. None of these fats are pure. They're a mixture of all the different types saturated, monounsaturated and polyunsaturated. Um, we can all agree that trans fats are horrible, and the data is extremely clear on heart disease and everything else bad. Um, I think the jury is still out on omega six. You know what I've seen so far and when I listen to people like Kevin Maki, who, uh, Doctor Gabrielle Lyon just interviewed a few weeks ago.
Amber Warren, PA-C: It was phenomenal.
Dr. Mark Holthouse: He's got a PhD in the epidemiological, you know, setting up of studies to analyze this topic.
Amber Warren, PA-C: Yeah.
Dr. Mark Holthouse: The guy's you know...
Amber Warren, PA-C: Brilliant.
Dr. Mark Holthouse: Brilliant in this area. Um, he's looking at at the evidence from a way that I, as a clinician am humbled by.
Amber Warren, PA-C: Right.
Dr. Mark Holthouse: Uh, it it was it's cause for pause.
Amber Warren, PA-C: Right.
Dr. Mark Holthouse: And so I've stopped bashing seed oils and really talked about process, the process of how they're getting made as, as more of the issue and trying to find things that are are less processed. Ultra processed food period is what's killing us.
Amber Warren, PA-C: And I think that's what really takes away from that message. The whole seed oil it that that whole conundrum really takes away from that message of just avoiding the ultra processed, highly sprayed, food dye type food. And I always look at things to like, your body wants everything to be in balance and omega sixes shouldn't be demonized. They just need to be in good balance with omega threes. And thankfully, we have good ways to test that. We can look at omega three to omega six ratios in the blood. It's not that expensive of a test. Kind of like the ApoB you were you were talking about, right? So yeah, the devil's always in the details. But I do think we need to be really careful listening to one social media influencer and that dramatically changing how we purchase and consume food and demonizing certain decent, good quality foods or being able to enjoy eating out. And, you know, like there's I mean, I didn't know this, but there's apps where you can actually find restaurants that don't use seed oils, which I do think, again, could could be good. But it's like, man, we're really taking this far, aren't we?
Dr. Mark Holthouse: Well, you know, peanut butter is gone.
Amber Warren, PA-C: Yeah.
Dr. Mark Holthouse: The good stuff. Right? I agree, the stuff that's.
Amber Warren, PA-C: With with decent amounts of protein and food that that God intended us to eat, that comes from the ground. That's always what I'm about to like. Where I go back to, like, ancestrally, what were we intended to consume? And it was food without labels. And a lot of those foods are food without labels that we were intended to eat. So I think it's. Yeah. No, I'm glad you went. I was going to go there and I'm so glad you did.
Dr. Mark Holthouse: Heat extracted, you know, expel the expeller, the excipients, the things that they're use, things that they're using to extract these oils are the issue.
Amber Warren, PA-C: Yes.
Dr. Mark Holthouse: The actual nutrition-ism is focused on on that process more than it should be. And we have a lot of really charismatic folks, um, on the internet that I think have really just become talking heads, repeating the same talking points without actually looking at the full scope of the data on the..
Amber Warren, PA-C: I agree.
Dr. Mark Holthouse: Polyunsaturated fats.
Amber Warren, PA-C: Yeah.
Dr. Mark Holthouse: Um, but yeah, that's a that's that rocked my world. Uh, probably two months back is all.
Amber Warren, PA-C: Yeah.
Dr. Mark Holthouse: This is recent.
Amber Warren, PA-C: Yeah. It is newer data. You're right. Yeah, yeah. Go listen to that episode. If you're intrigued by that. Uh, doctor Gabrielle Lyon interviews him, and it's a phenomenal episode. I was Maki.
Dr. Mark Holthouse: Maki.
Amber Warren, PA-C: Maki. That's right. Yeah, it's a great listen.
Dr. Mark Holthouse: Another podcast on this besides ours, is one that, uh, Simon Hill did. Uh, he's a guy from the UK interviewing, um, Doctor William Crowley, who's a lipidologist. Brilliant. And, uh, he talks with an engineer, who's also kind of a citizen scientist, who looked at this lean mass hyper responder in himself, and he's actually working on designing some studies himself in that subpopulation, which I'm going to be fascinated to hear, um, you know, how how things turn out. But I'm going to be equally fascinated to hear about some of these newer studies on LP(a).
Amber Warren, PA-C: Yeah, we have a lot to follow up on.
Dr. Mark Holthouse: To be able to really make an impact on that.
Amber Warren, PA-C: Absolutely. Um, it's a big deal.
Dr. Mark Holthouse: Really can't modify much. Yeah. Is amazing. I used to use a lot of niacin to try and help and what I after reading the efficacy of niacin and what we really need to reduce risk. It's just it's just a little bit too, too, too low of a well.
Amber Warren, PA-C: And people don't tolerate it.
Dr. Mark Holthouse: And we have the issues of side effects with it.
Amber Warren, PA-C: You can get to a certain level of efficacy, but most of the time those clients aren't tolerating those higher doses. Liver enzymes. The flushing out. Yeah. It's it's yeah it can be a problem.
Dr. Mark Holthouse: Yeah. So um, that that topic is kind of a standalone multiplier of risk. That's, that's really just think of it as a genetic bad luck that you drew the short straw.
Amber Warren, PA-C: And a lot of us did I did too say my dad, my brother, me. Yeah. It's all of us.
Dr. Mark Holthouse: So you and I are both athletic people. Um, we're doing everything we can, and yet we're the ones that will have that early event if we don't address that. That's what the data shows, because we're dragging around that little kringle.
Amber Warren, PA-C: Right.
Dr. Mark Holthouse: And it's it's promoting clotting. You know. Um, there's some speculation that that from an evolutionary perspective in, in North America, where a lot of us came from that have this mutation that it was it conferred some kind of a, an improvement in survival at some point in our history.
Amber Warren, PA-C: Oh, interesting.
Dr. Mark Holthouse: Being that it, um, helps with coagulation, who knows, maybe you and I would have lived longer and not.
Amber Warren, PA-C: Bled out when we got attacked.
Dr. Mark Holthouse: Run through with a a norseman's sword.
Dr. Mark Holthouse: Well, then yeah,
Dr. Mark Holthouse: It's a liability now.
Amber Warren, PA-C: Yeah, I don't I don't see how that benefits my life. I'm raising little boys that are wild, but I still don't think I have a risk of bleeding out. Some days I might.
Amber Warren, PA-C: Final question. And if I know we're running short on time. But, um, if someone says, doc, I know my cholesterol is climbing and I'm going to try and do all these other things, but I really only have 30 minutes three times a week to exercise. What should I do? Should I lift heavy? Should I do hit interval training? Should I walk? What should I do to make the most of that 90 minutes a week that I have to do it?
Dr. Mark Holthouse: Yeah. Um, some of that's dependent on age. Um, if it's a premenopausal female, um, I'm going to focus on, um, more of a balance between high intensity interval cardio and lifting heavy.
Amber Warren, PA-C: Good.
Dr. Mark Holthouse: You know, I might do two days, three days a week, max, and let them do cardio. Uh, whereas if it's a post-menopausal female where I really have an estrogen deficit, and I know that's associated with losing lean muscle mass, estrogen is what modulates that in addition to controlling glucose, which can drive metabolic syndrome.
Amber Warren, PA-C: So that's another podcast episode completely. Don't go there! We don't want to be here for another hour.
Dr. Mark Holthouse: No. So I'm thinking that, um, in that age group, I'm focusing more on lifting heavy with some high intensity cardio, which is much shorter duration but more intense cardio once or twice a week.
Dr. Mark Holthouse: In guys, a little bit more ubiquitous through the lifestyle, but focusing on, again, high intensity interval, Tabata drills for cardio once or twice a week, and heavy lifting, you know, anywhere from 3 to 5 days a week.
Dr. Mark Holthouse: I'm I'm not uh, I'm not one that goes without 1 or 2 days of recovery, um, for either gender because of the fact that I'm seeing so many injuries in folks that don't do that, who are doing high intensity intervals daily before their heavy lift. And they're doing that five, six, seven days a week. Um, our bodies need to recover no matter how much testosterone, no matter how much peptide and IGF-1 we pump into these folks. Um, which again, has some concerns. Um, we just need to let our bodies recover.
Amber Warren, PA-C: Yeah.
Dr. Mark Holthouse: Uh, naturally. And a good recovery allows you to train beyond mediocrity. We used to say with periodization in sport that if you did the same level of intensity all the time, you were mediocre as a performer, as a performer on race day. And it was the it was the folks that learned how to recover correctly that that were on the podium.
Amber Warren, PA-C: That excelled. Yeah, yeah, I love it. What a great way to end that. Thank you. Your your wisdom is just so vast and so thorough. And it's just like, I just I can't wait to send this to friends and colleagues and even our conventional cardiology friends and just say, this is this is gold, and what do you think? And pick it apart and let us know.
Dr. Mark Holthouse: I'm sure, it'll be a little bit of a lightning rod too. That's okay. Because if I thought this was a slam dunk discussion and and one side was right, right. And one side was wrong, that's one thing. But there are some things we know pretty clearly.
Amber Warren, PA-C: Yeah.
Dr. Mark Holthouse: And to ignore it is is is to me scary and irresponsible.
Amber Warren, PA-C: Right.
Dr. Mark Holthouse: There are subgroups of folks though, where we just don't. I wish we had all the answers.
Amber Warren, PA-C: More data.
Dr. Mark Holthouse: But until we do, I want to mitigate and minimize risk as much as I can.
Amber Warren, PA-C: Well, and even if just our message can be clear, ask for the test. Find a provider who will run it. Get the get the data because that data can be truly life saving. And last time I checked I say this a lot. I feel like on this podcast, COVID's still not killing as many people as cancer, is still not killing as many people as cardiovascular disease is. And oftentimes it is a silent killer. And I just my heart is just is just to really maybe if we can change that statistic in our country. So yeah.
Dr. Mark Holthouse: Number one cause of death worldwide. Um and in both men and women. So it's a big topic. Statistically it's what's going to take most of us. So if you can figure out a major player outside of the obvious ones treating the blood pressure, the quitting smoking, not being sedentary. Dealing with inflammation in the body, which we didn't talk as much about. But we all talk about that constantly here. In addition to cholesterol and blood and metabolic dysfunction. Knowing that inflammation, high sugar, saturated fat, all three can drive these ApoB markers, uh, is important. And chronic infection drives inflammation. Periodontal disease.
Amber Warren, PA-C: Gosh, I feel like I need to stop you. You're going to just keep going on and on. You're going to keep talking root cause. And I'm just going to pull them on in. Thank you for joining everybody. I'm going to go ahead and stop Doctor Holthouse right now.
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 funmedFoundations.Com.