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Episode 35: From Prevention to Intervention: Tackling Non-Alcoholic Fatty Liver Disease with Dr. Mark Holthouse, MD

Updated: May 9

Podcast Drop Date: 5/1/2024

Join host Amber Warren, PA-C, as she uncovers the hidden complexities of Non-Alcoholic Fatty Liver Disease (NAFLD) with Dr. Mark Holthouse. In this episode, Dr. Holthouse shares essential insights into NAFLD's prevalence, progression, and prevention strategies. From lifestyle adjustments to lesser-known triggers, this discussion offers actionable steps for protecting liver health and combating NAFLD effectively. Tune in to gain a deeper understanding of this silent epidemic and empower yourself with knowledge for a healthier future.



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. Okay. Well, we're back here with our fourth podcast with a live audience. Thank you so much for being here, everybody. I'm back here with Doctor Mark. Holthouse. Doctor Mark Holthouse is the Chief Medical Officer of FMI center for Optimal Health and Functional Medicine of Idaho, specializing in hormone optimization, age reversal, metabolic health, and longevity. With over 32 years of family practice experience, he graduated from Loma Linda University School of Medicine and has completed his family practice training at UC Davis Medical Center through the Air Force Scholarship Program. As an expert in functional and integrative medicine, Doctor Holthouse has been part of the teaching faculty of the Institute for Functional Medicine, educating practitioners nationwide, nationwide for the past decade worldwide. I should say we know that's worldwide now. Additionally, he serves as an assistant professor of medicine at Loma Linda University School of Medicine, focusing on preventing cardiometabolic diseases and reversing conditions such as type two diabetes, heart disease, high cholesterol, obesity and metabolic syndrome. Doctor Holthouse excuse me, heart. Holthouse.

Amber Warren, PA-C: House. That should be your new nickname, doctor.

Mark Holthouse, MD: Whole house a lot of things.

Amber Warren, PA-C: That's not one to see patients in Idaho, Oregon, Nevada and California. Outside of his medical career, him and his wife, Tammy, enjoy various outdoor activities such as photography, snowshoeing, skiing, sailing, hiking, kayaking, and savoring good food. Thank you so much for coming back.

Mark Holthouse, MD: Food is house fun.

Amber Warren, PA-C: Yeah, you guys are kind of foodies. Well, your wife is a phenomenal cook.

Mark Holthouse, MD: Tammy is amazing.

Amber Warren, PA-C: Yeah, I've had her meals before.

Mark Holthouse, MD: Yeah, I think I have to exercise just to continue to eat, be able to eat good food.

Amber Warren, PA-C: What she makes.

Mark Holthouse, MD: That's the real reason.

Amber Warren, PA-C: No, she makes good quality food.

Mark Holthouse, MD: She does, she does, she does.

Amber Warren, PA-C: She's good. Clean ingredients.

Mark Holthouse, MD: Tasty, healthy, healthy food.

Amber Warren, PA-C: That's what we should aim for.

Mark Holthouse, MD: Not cardboard.

Amber Warren, PA-C: No. On the somewhat of a topic of food. Today we want to talk about this new kind of epidemic of fatty liver disease that I don't think is spoken about enough. Right. We talk a lot about I think we talk a lot about cardiometabolic disease and obesity and even cancer. Now is a big hot topic, but not a lot of people are talking about fatty liver.

Mark Holthouse, MD: Yes, fatty liver is a big deal. It's now 30% of the US population is walking around with replacing functioning liver cells with fat because of our poor nutrition and excess calories, mostly in the form of refined carbs and sweetened drinks tops that list. Um, we, uh, know that it's a problem because it's associated with, well, like ten, 20% of the time, this fatty liver progresses to hepatitis and inflammatory version of itself. And of that group, another 15 to 20% of them go on to become cirrhotic, liver failure, permanent fibrosis, scarring like we used to see with alcoholics. But alcoholic liver disease is is not near as common now as nutritionally induced fatty liver, which is what we're talking about. When it gets bad enough, it becomes inflamed, and when it gets really bad, it gets scarred down and your liver gets to be like this little shriveled, dysfunctional organ. And the liver is pretty resilient. It's a little bit like a starfish where you take off or cut off an arm. It'll grow a new one or a lizard's tail. Your liver has that. Stop laughing. Carly, I can see you. Um, it has that regenerative ability, and, um, it will take a lot of insults, but everything has its. It's its time where it's going beyond the point of no return. So there are ways and what we want to talk about, I think a little bit tonight is what causes it. Some of the risk factors, uh, associated risks, why we should care and what we can do about it. Um, but it's largely driven by a bad diet. There's some genetic and ethnicity predispositions, for sure. Uh, we know that African Americans are at lower risk. We know that Hispanics are at little higher risk, as are, um, folks from the Middle East and Southeast Asia. Uh, so there is an ethnicity behind how prevalent it is. Um, but it's associated with all of these diseases we've been talking about on some of these other episodes prediabetes, type two diabetes, metabolic syndrome, uh, hypertension, Sibo, small intestinal bacterial overgrowth, and dysbiosis. Imbalances of the intestinal microbiome are more prevalent in patients that end up having fatty liver disease.

Amber Warren, PA-C: What's that mechanism?

Mark Holthouse, MD: We think the mechanism is that when you've got a disrupted microflora in your gut, you have what's called increased permeability of the lining of the intestinal tract, or the lay term is leaky gut. And all of this goes through the portal vein. Into the liver, and it promotes an inflammatory condition via the kupffer cells, which are kind of your little macrophages, if you will, in the liver, not unlike the microglial cells in the brain that act as these inflammatory cells. And this gut inflammation, we call it metabolic endotoxemia. You have things that normally don't come into the blood vessels that drain our food and nutrients from our small intestinal tract, leaking through what's on the other side for them. Lo and behold, 80% of our immune system hangs out around the gut and it gets all twitterpated about this, what's going on? And we lose what's called oral tolerance. Things that normally don't bother us cause antibodies, cause systemic inflammation. But it it goes via the portal vein, which is where all of our intestinal blood vessels are, are draining to through the liver before it gets circulated to the rest of the system. So it's it's a direct shot to the liver. And when you've got an insult to the lining of the intestinal tract, whether it be a leaky gut or this Sibo, small intestinal overgrowth of excess bacteria, you can have inflammation and fatty liver develop. So it's not just eating too many carbs, too much sugar, which goes into the liver and becomes fat when you get so much extra glucose in your muscles that your your liver doesn't know what to do with it, it starts converting it to fat.

Mark Holthouse, MD: This is how they make what's phlegra the stuff, the geese, the gourmet gross fatty liver that people actually eat. They literally stick a funnel down a goose's throat and they feed it dextrose, sugar. No. And this is how they make the liver and the goose fatty. And this is how they produce this stuff. So when you do that, you know, imagine taking a human and pouring a sugary drink or a lot of tortillas or chips frequently in the diet. Eventually our bodies are nutritionally starving and calorically over nourished, and there's nowhere for this excess nutrient glucose to go. So the skeletal muscles used it all. It starts spilling over into the subcutaneous safe fat reservoir for energy. But then after that, it has really nowhere else to go except the liver and and the other organs. And we call that visceral fat, fatty pancreas, fatty liver. Our organs are filling up with fat because of the food we're eating, guys. And the lack of exercise, exercise where you really get your skeletal muscle muscles burning, a lot of that energy can take us a long ways towards preventing that. But at the end of the day, if we're getting too much gut inflammation, if we've got dysbiosis, if we're just taking in too many refined carbs, we get this fatty liver.

Amber Warren, PA-C: Do toxins impact the liver in that same way you do? The blood sugar disposal does the same mechanism, right?

Mark Holthouse, MD: Yes same same often same mechanism. So a lot of our folks were looking at things like chemicals in their urine to see if this is problematic. The problem is that it takes our liver, which has this vital function of detox, and it's out of commission. Yeah.

Amber Warren, PA-C: So we're very concerning in today's day and age to have an out-of-commission liver.

Mark Holthouse, MD: Out of commission liver's not good. That's how we're metabolizing all of our toxins right from inside, from our process of metabolism and all the stuff we take in from the outside is now stuck in us. When we've got a liver that's 50, 60% fat, that's, you know, 40% functioning. Now, it's it's like a V8 engine that's on four cylinders.

Amber Warren, PA-C: I came across an article last week where they were talking about, I don't remember some scientists saying that the, this whole, um, arena of talking about detoxification and detox protocols and why we need to detox is totally bogus because we all have functioning livers. And I was thinking about, like, what you just said, like, no, we actually don't all have functioning livers, so we do need to detox. We actually need to worry about clearing out the liver on a consistent basis.

Mark Holthouse, MD: The national data is now government studies showing that a third of us don't actually. Yeah. And that's not even taking into account alcohol abuse. Right. You know which is going to add to this. Yeah. Um, so if a third of us are walking around with dysfunctional livers, 47% of the United States population is either type two diabetic or pre-diabetic. Um, you start adding these things up. Uh, it's amazing that the body does it as well as it does with all this abuse. Yeah, but this is what we see in our offices, right? All day long are elevated liver enzymes. Yeah. I've been doing this long enough to remember, just not too long ago, ten, 15 years ago, I did not see that unless there was hepatitis. Right. Viral hepatitis or were, you know, closet drinking.

Amber Warren, PA-C: Well. And it's concerning because it's not just elevated liver enzymes outside the normal range. Right. We're looking to have actually optimal liver enzymes. And then there's this other biomarker we look at in the blood called a GT. And that can actually climb before our two liver enzymes we look at on a metabolic panel. So you sometimes have to dig a little deeper and ask more questions. Yeah. Um, on that metabolic panel and ask for more, more blood tests or really look at how healthy your liver is or how healthy it isn't. So that's actually a question that just came in from our live audience. How do we diagnose fatty liver.

Mark Holthouse, MD: So fatty liver is usually seen, um, by lab tests. And then we confirm it with an ultrasound. Uh, we'll look at liver tests very commonly. The GT is a little bit more sensitive. We stopped doing that 20 years ago on the chem panels because it was always coming back positive. And I was told not to order it because we didn't know what to do with it. That's what we do.

Amber Warren, PA-C: We know that's a good reason not to order a tests by the way. Right.

Mark Holthouse, MD: Um, so the GT's are something we actually value highly because they're a more sensitive indicator for liver cell damage, whether it's alcohol use, whether it's a statin use, whether it's too much fat. Come to find out, by the time the Alt and the AST liver enzymes are elevated predominantly that alt in this this case, um, things are well underway as far as fatty liver replacement. And so you confirm these abnormal labs by having them do an ultrasound of your liver and it's, it's it's there. Now, the ultrasounds don't always show it when it's there. It's it's not always apparent. It's a spectrum. Um, but the liver tends to enlarge before it scars down and gets cirrhotic. So we've got this, this inflammatory phase that it follows the fatty replacement which we call Nash, nonalcoholic steatohepatitis, Nash. And that's hepatitis because you've got markers showing it's inflamed. That's the liver test we're talking about. After that, there's a good number of those folks that sometimes can go on. Now the first two stages, there's three stages of this thing. Um, the first two stages are reversible nonalcoholic liver disease. And now we call it metabolic dysfunction. Liver disease. There's a new name floating around, and Nash can be reversed pretty quickly pretty quickly.

Amber Warren, PA-C: This is not a long. Yeah.

Mark Holthouse, MD: You know what is it. 5 to 7% body weight loss will reverse. Uh, NLD the first phase, it takes about 8 to 10 pounds of body weight loss to reverse Nash the hepatitis. Once you get to the fibrosis where it's starting to scar down and shrink and literally you think of a scar, how it shrinks as it heals. Um, that's past the point of no return. So minimal weight loss. And it just so happens when we talk about what what do we do about it? It ends up being incredibly helpful yeah, absolutely to reverse this.

Amber Warren, PA-C: Yeah amazing. So, um, where do we start with our patients? If there's concerns, where do you start? What are your recommendations for treatment.

Mark Holthouse, MD: Yeah.

Mark Holthouse, MD: So who's who's at risk. You know, uh, in our patients it's our diabetics. You know, it's our prediabetics. It's our obese patients. Um, it's our hypertensive patients. 50 to 90% of people with high blood pressure have fatty liver. I didn't know that 80 to 90% of our obese patients, that's a BMI over 30 have fatty liver. So high blood pressure patients, people with pre or full on type two diabetes, uh, people with rapid weight loss, people on tirzepatide, GLP ones, uh, are at risk for fatty liver. This is why when you have rapid weight loss, sometimes you'll see problems with the liver like this. Or gallstones occur. People ending up having to get their gallstone out with fatty liver. Um, being behind that. With rapid weight loss, people with high levels of uric acid are at risk for fatty liver. Why? Uric acid is a metabolic downstream marker of fructose metabolism. So if you're getting a lot of fructose fruit sugar in your diet, the only place that metabolizes fructose is your liver. Unlike glucose that gets metabolized all over the place, including skeletal muscle, the liver has got an exclusive, unfortunately, and that's why it gets hit really hard with too much fructose. This is why we don't have people doing agave sirup and things like this, or cane, a lot of cane sugars and things like that. Because of the high fructose. Um, it's not just the high fructose stuff, it's just fructose in general that's metabolized very differently. Um, you guys remember probably that table sugar, sucrose is made up of a. Molecule of glucose and fructose. Glucose is metabolized much more easily than the than the latter, so uric acid people with high uric acids are at risk for fatty liver. What are the doses? What are the ranges? Ideally we want to see and this is a hard one. Amber. We want to see females with a uric acid south of four. That's low.

Mark Holthouse, MD: That is low.

Mark Holthouse, MD: That's a minority of my patients I'll tell you. It tells you about well, 93% of the US population has what we call metabolic dysfunction and inability to use fats and ketones and free fats over just glucose. And so this is and there's lots of reasons for this besides just obesity and eating too many carbs. It has to do with things like toxicity, mitochondrial dysfunction, whatnot. But um, my goodness. Um, and for guys it's five or less for uric acid. I can count on one hand in the last few months, how many guys. And I checked this on all my patients, I've seen less than five. Agreed. You know, it's not just a marker for gout. It's a marker of insulin resistance. But more importantly, it's a marker for excess fructose. So it's a key when you see that to intervene with diet and solicit a dietary history and work with your nutritionist to find out. And that's what our, our DD Hayley here is so good at looking at. She's using these CGM machines, um, along with the chronometer macro counter to get an idea. These two things interface, um, not just on getting adequate amino acids, but looking at, um, some of these things with carbohydrate, uh, other patients at high risk, um, are really your patients that have abnormal lipids, high triglycerides, dyslipidemia, cholesterol issues? Um, for sure. Sure. To really help move the needle, I think it's exciting. It's exciting time to be in metabolic medicine

Amber Warren, PA-C: For sure I couldn't agree more. I've come to really love it.

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Amber Warren, PA-C: Um, exercise. What are the specific exercise recommendations? Because I think we it's hard to be specific with nutrition because yeah, we have to evaluate labs and look at the person in front of us. But I think it's a little bit easier for us to make more concrete exercise recommendations with these metabolic patients. It is what are you recommending?

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

Amber Warren, PA-C: Who funded them?

Amber Warren, PA-C: What? Big Food Corporation funded the nutrition studies. Right. Exactly.

Mark Holthouse, MD: Yeah, exactly.

Mark Holthouse, MD: I don't know that we'll ever have good nutritional data.

Amber Warren, PA-C: So seed oils are a really big deal. And fatty liver. Right.

Mark Holthouse, MD: That's what I hear. Yeah.

Mark Holthouse, MD: I don't know a lot about that. Maybe you can enlighten me.

Amber Warren, PA-C: Yeah. From what I understand. I mean, that's that's a lot of the metabolic dysfunction but directly related to fatty liver, right. These safflower, sunflower, um, peanut oil, um, canola or canola. I don't even think we can call it a real oil. Um, but, yeah, the body doesn't know how to recognize these oils. Grapeseed. Yeah. So, um, getting my patients, um, to not be fearful of good quality, grass fed organic butter, um, maybe cooking with that instead of these fake refined inflammatory oils, um, using organic, high quality, being careful with the olive oil that you purchase. Um, even coconut oil has a time and a place in moderation. Um, gosh, someone sent me something recently. Actually, a local dietitian I know on the dangers of avocado oil and I'm like, oh no. So I need to look into that because I use a lot of avocado avocado oil in my home. That's um, but yeah, just just being a more processed oil, um, but yes, more anti-inflammatory oils, which makes it really difficult to eat out. Um.

Mark Holthouse, MD: Mufa monounsaturated fatty acids have been like our only safe fat. Not only safe fat, obviously, polyunsaturated fatty acids are great, too, and we're all short of marine based EPA, DHEA, omega three seconds, right. Um, but my goodness, I mean, if you listen to a lot of the folks I really respect Peter Attia, you know, on fats and olive oil, extra virgin olive oil and, um, and safflower oil are some of the have the highest content of pure mufa. Yep. Uh, that are out there that are. That are safe. And yes, some of these other seed oils you try to minimize as much as possible. You think about it, the more highly processed these things are, um, the more harmful they can be and how they were processed. What kind of heat treatment was it? You know, cold expeller pressed. And it's so important how they they were prepared. We know that these um, and we won't even talk about c-15 we'll save that for another.

Amber Warren, PA-C: I was going to bring that up.

Mark Holthouse, MD: Are you going to bring that up? It's probably too soon.

Mark Holthouse, MD: Uh c-15. Is the new odd chain saturated fat acid that's taken the whole fatty discussion by storm. There is some data. It's very, very limited, uh, showing superiority in anti-inflammation and some of the areas that we've always, you know, done the genuflect for with omega three fatty acids, EPA and DHEA. I'm not to the point yet where I'm replacing those things, but I'm certainly I'm certainly considering it as an add on the C15.

Amber Warren, PA-C: I was actually going to ask if you are aware of the C15 on data on fatty liver.

Mark Holthouse, MD: I'm not assume it's there.

Mark Holthouse, MD: Other than what I heard at a single lecture in Las Vegas, uh, recently. I'm not. And the claim there was that it has some benefit.

Mark Holthouse, MD: Okay. Um, I assumed. Yeah. Yeah.

Mark Holthouse, MD: So a little early.

Mark Holthouse, MD: Okay. I'm an early adopter, but I'm not that early. I want to see more data. We've really got just the one company that's out there promoting their product, and it's not inexpensive. And what's which is what is interesting is that, uh, C15 is less expensive in, you know, raw resource than omega three. So I'm. Yeah, I've got more. I need to vet on that before I'm.

Amber Warren, PA-C: Time will tell.

Mark Holthouse, MD: Yeah. So for now, you know, focus on getting a more omega three. We're all, for the most part high in omega sixes. In this culture which can be pro-inflammatory. They're still very, very important. But if you look at the the ratios, whether it's in a red blood cell index or in the, in the blood, uh, whole blood, we're usually quite low on EPA and DHA, which are really almost exclusively gotten from fish and algae sources.

Amber Warren, PA-C: I love that that there's another test that I don't think is ran enough or acknowledged enough in omega check. Um, so valuable for us to see total omega three seconds in the human body. Um, um, and, and again, we're, you know, I think normal rains are saying is above maybe 5% or higher risk patients, 88%, 80.

Mark Holthouse, MD: Even more optimal, you know, and it takes a while for that to change. You're you're looking at incorporating fats into the red blood cell phospholipid membrane, which can take 2 to 3 months, as opposed to just a serum level of omega three, which can change within a couple of weeks. Yeah.

Mark Holthouse, MD: Right. Right.

Mark Holthouse, MD: So that's a that's a great in the in the context of plasmalogens and phosphatidylcholine and some of these other hot topics on lecithin and uh, lipid medicine, uh, that are out there.

Mark Holthouse, MD: So yeah.

Amber Warren, PA-C: So we have inflammatory oils. We've got some of the white, white sugars. We should be avoiding white foods in general. Excess carbohydrates. What other foods are you saying we're worried about? Fatty liver. Yeah.

Mark Holthouse, MD: Gatorade. There you go. I said it.

Mark Holthouse, MD: Uh, juices in general, you know, without the fiber. I'm not a fan of juicing. Yeah, because you're you're you're eliminating the fiber, which we talked about in last episode. All the wonderful things it does for short chain fatty acid and and GLP and oh, and those things. But it slows the rate of absorption of that glucose spike and consequent insulin spike. And what we're trying to do with these cgms on our arms, and I'm seeing more and more people in the supermarket walking around with them.

Mark Holthouse, MD: I love it. It's awesome.

Mark Holthouse, MD: We're teaching people what foods to avoid, not just because it spikes their sugar and sends their alarm off, but because those are correlated with spikes in insulin. And we know that every time that happens, that's taken time off their life. It's associated with a decrease in longevity. Yeah. So um.

Amber Warren, PA-C: Well, and it's behavior modification as well. Um, because it's also interesting to see what your blood sugar will do after a toxic conversation or after a poor night's sleep, or after not enough exercise or too heavy or too intensive exercise. So I think it also is just creates more body awareness and um, yeah, allows you you.

Mark Holthouse, MD: Talk about fats.

Amber Warren, PA-C: Yeah. Yeah.

Mark Holthouse, MD: Let's talk about that more because this is Nash. This is fatty liver. Does eating fat cause fatty liver? Yes and no.

Mark Holthouse, MD: Yeah.

Mark Holthouse, MD: Not in the way you might think. Um, eating refined grains, refined carbs.

Mark Holthouse, MD: Juices.

Mark Holthouse, MD: You know fructose. That's how you get a fatty liver.

Mark Holthouse, MD: Like like that.

Mark Holthouse, MD: Um, if you eat a lot of saturated fats, there's data that shows if you're obese and or you eat a lot of saturated fats, certainly trans fats. Right. You open up this gut, this leaky gut thing, you increase your gut permeability, you get this metabolic endotoxemia, which just means that you've got inflammation in your system because you've let things in across your gut wall. That shouldn't be. And the immune system sees that and goes kind of nuts and it overreacts and you get, voila, a systemic inflammatory scenario. So indirectly, if you're one that when you eat saturated fats, a lot of dairy, a lot of red meats. You're getting leaky gut from that. You could create inflammation in your liver. Secondary to that, it's creating a dysbiosis. We know that studies are pretty clear. If you eat a ton of fat in your diet, it changes your microbiome. And that dysbiosis, that imbalance can lead to fatty liver. That's been proven. Um, fatty liver is dangerous. It's not only associated with hypertension. Diabetics in studies that have fatty liver versus diabetics, type two diabetics that do not have much higher rates of heart attacks. Fatty liver by itself predicts heart disease, cardiovascular disease. So it's that's why we care for horsemen. Top causes of of what's killing us in this country. Chronic diseases. So it's really just another symptom. So avoiding carbs possibly avoiding excess saturated fats. Who are those people? Test.

Mark Holthouse, MD: Don't guess.

Amber Warren, PA-C: I was gonna say, you know.

Mark Holthouse, MD: Look at their genetics. Look at their ApoE. If they've got a four mutation, there's a good chance that that saturated fats may be not only increasing their, their, um, atherogenic, LDL and Apob. So if you see a high apob on someone who's doing carnivore, you got to you got to worry that that's not all good, right? Um, I'm not as concerned about Ldl-c as I am Apob or LDL particle number. If you see those going up, you can't just ignore that and say LDL doesn't matter, right? That's not at all what the studies show. And I see that all over the internet. I know it's just not true. Um, the, um.

Mark Holthouse, MD: Do you see a correlation.

Amber Warren, PA-C: With fatty liver and low HDL or good happy cholesterol?

Mark Holthouse, MD: You know. Yes, absolutely. The pattern in the cholesterol that you'll see most every time. Uh, with fatty liver is high triglycerides and low HDL. It's that pre-diabetic.

Mark Holthouse, MD: Pattern.

Mark Holthouse, MD: And the LDL doesn't seem to matter as much. Um, and this is what we see in our diabetics, right? Many of them have normal LDL, but their trigs are high and their HDL is low, right? Um, so that is the pattern you often will see with with fatty liver.

Amber Warren, PA-C: I'm just thinking if we start cleaning up the liver because there's, there are patients, genetically speaking, that just have low HDL and that HDL can be very cardiac protective. So I'm just in my mind thinking if we offload the liver, even if it's a pre fatty liver condition, can we start to see those hdls climb and therefore protective.

Mark Holthouse, MD: That's the holy grail raising HDL. We haven't been able to figure out a way to do that outside of estrogen. Estrogen is one of the only things associated with maintaining HDL. Um, ironically, one of the medications associated with creating fatty liver is estrogen. So when we take estrogen orally.

Mark Holthouse, MD: Yeah.

Mark Holthouse, MD: Which some people promote.

Mark Holthouse, MD: Yeah.

Mark Holthouse, MD: Taking estrogen orally, not only does it raise C-reactive protein our systemic inflammation, it fouls up our triglycerides. But it's now known to be associated with creating fatty liver. There are several drugs that can do that. That's just one of them. Uh, methotrexate is one which is used in rheumatoid arthritis. Um, and there's several other medications that, that are actually now known to create fatty liver.

Mark Holthouse, MD: Fatty liver.

Mark Holthouse, MD: Some of the things that can reverse it, pharmaceutically that are being looked at pretty seriously are pioglitazone actos, um, and metformin.

Mark Holthouse, MD: And.

Mark Holthouse, MD: Rosiglitazone as well. So some of these tzds, these insulin sensitizing drugs that are used in diabetes medicine, um, that raise something called ppargamma, which is instrumental in fatty acid metabolism. It stands to reason can help prevent fatty accumulation in the liver. Anything that boosts burning fats, we call it beta oxidation in the mitochondria, the utilization of fat for energy decreases the fat in that tissue and in particular in the liver. Uh, this is why intermittent fasting has been so helpful. Is that anything you can do to keep the insulin low? That's really the only time that you burn fat. So when you're constantly in a post fed state and insulin is always bumping, you can't mobilize your stored fat from your liver or anywhere else. Bring it in and burn it.

Amber Warren, PA-C: Well, there's also the relationship of, you know, tracking metabolic endotoxemia, leaky gut, intermittent fasting, giving the digestive system a break, gut healing. So there's that link to that. The intermittent fasting can help heal the gut.

Mark Holthouse, MD: Absolutely.

Amber Warren, PA-C: And allow you to eat maybe more, a little more saturated fat and handle it and not become so inflamed. I think there's probably a couple of different links there where that's therapeutic used in the right person. Mhm.

Mark Holthouse, MD: Um, I just it's.

Mark Holthouse, MD: The whole reason we intermittent fast. We, we red light therapy. Right. We do cold water plunges you and the cow trough. Um the um what else are we doing. We're eating polyphenols plants with brightly colored exercising. Uh, we're doing hit high intensity interval training. All these things uncouple the mitochondria, upregulate longevity sirtuins AMP kinase. If I keep saying these weird words that you don't know what they mean over and over, you're going to at least remember to write them down, and you're going to go look them up on Google tonight, and then you're going to oh, okay.

Mark Holthouse, MD: That's what that meant. Yeah.

Mark Holthouse, MD: Or send it in as a question I'll clarify it.

Mark Holthouse, MD: But so I know I'm throwing these things.

Amber Warren, PA-C: Well you have to stop talking because we've got two great questions that I'm so excited about. Um, I love this one. I've been reading about new evidence about the benefits of full fat dairy. What are your thoughts?

Mark Holthouse, MD: Mhm.

Mark Holthouse, MD: Wow.

Mark Holthouse, MD: You are making me a lightning rod tonight. Um, so full fat dairy has gone I understand points on both sides of the argument. Yeah. I'm not a fan personally. Full transparency. I have to tell you honestly what I do. Yeah, I'm not a fan of it because I'm a hormone specialist, and I know that the hormones from mammals that are pro growth reside in the.

Mark Holthouse, MD: Fat, right.

Mark Holthouse, MD: Along with all the toxins. Right. So why would I ingest pro growth pro cancer hormones even in organic sources of this stuff? And particularly the part that's loaded with all the toxins into my own body.

Mark Holthouse, MD: Yeah.

Mark Holthouse, MD: Full stop. Mic drop. I can't get beyond that. Okay, I understand some of the benefits of full fat dairy from a nutritional perspective. From from, you know, whether it's the choline and brain health and membrane health and, and and the wonderful quality proteins and fats. Get it not lost on me, but knowing what I do about endocrine disruption, knowing what I do about cancer, breast and prostate in particular with that topic, I can't get.

Mark Holthouse, MD: Over it.

Amber Warren, PA-C: Even Rodari do you think maybe.

Mark Holthouse, MD: There's a oh, I think I think you're better.

Mark Holthouse, MD: Off there as far as, um.

Amber Warren, PA-C: The microbiome.

Mark Holthouse, MD: The microbiome, the lack of, you know, the treatments that are destroying some of the naturally occurring enzymes that are going to help people tolerate it. But even then, you know, I still think you're not getting away from the two issues I brought.

Amber Warren, PA-C: So, um, are you supplementing calcium or just eating a lot of leafy greens and citrus fruits with calcium? Are you concerned about that or for your wife?

Mark Holthouse, MD: So come to find out, milk drinking is associated with more bone loss.

Amber Warren, PA-C: I know, it's amazing.

Mark Holthouse, MD: And yet all my colleagues in primary care are saying load up on the dairy to prevent osteoporosis, which is one of the worst things you can do. Those are those are foods that are high in phosphorus, mag and calcium, but they're not bioavailable and they're pro-inflammatory, which drives bone loss even further down. So green leafy salmon, there's so many nondairy, you know, dried figs. There's so many things that you can do outside of dairy to get calcium. Calcium, in my mind, with bone loss since we're going there, how do we get there from Nash? Um, I know.

Mark Holthouse, MD: I know, sorry.

Mark Holthouse, MD: Is is, um, you know, is one of the least important things to supplement. I think vitamin D3 at 5000 units a day, coupled with at least 180 micrograms of MK seven vitamin K2 is is where we want to be. Um, we know that that's going to help, not just put the calcium that we absorb from our food, uh, from taking that vitamin D into our bone. It prevents making bone in our arteries. So along with pomegranate extracts, uh, I'm really keen on vitamin K2 to prevent plaquing in the artery. It's part of my cardiometabolic deal. So my osteoporotic and my my recommendations. There are calcium hydroxyapatite. I like the bone builder product with boron, and I don't do too much. I like to get most of the calcium from whole food. Yep. And yes, plants predominantly. Um, magnesium. I was.

Amber Warren, PA-C: Going to say cooking.

Mark Holthouse, MD: Magnesium.

Mark Holthouse, MD: Whether it's magnesium malate, magnesium glycinate, glycinate take your pick. Um, those are all really bioavailable along with D3, K2, and weight bearing.

Mark Holthouse, MD: Exercise and movement. Yeah.

Mark Holthouse, MD: And to bring it back, treat the insulin resistance. Right. Because we know that diabetics are at higher risk for osteoporosis. Insulin can drive inflammation also can drive bone loss. And these are not things you're ever going to hear from your ob gyn, right. Um, I didn't know this stuff. I had to go back to school to learn how those things affect bone, right? It's not just about smoking alcohol. When you started having periods, your mom's history, you know, it's so much further down the line. Um, but I think as far as, you know, with a fatty liver, some of the things we can do to treat it, um, I'm always looking at natural stuff, right? Because we're supposed to be integrative, right? And we want to avoid synthetic and the harms of pharmaceutical medicine. Uh, some of the stuff that's got data, because I like to be evidence based. People deserve that. They come, they pay us money. We need to have a better, um, have a better option. Uh, wow. Uh, you know, there there are just some things that are new again, retreading old things for me. Bergamot. Um, tops. Tops. My list. Uh, bergamot is a full of polyphenolics. It's antioxidant. Anti-inflammatory. It's an insulin sensitizer, along with berberine. Um, you know, another botanical insulin sensitizer helps with lowering cholesterol as well. Um, uh, we've got globe artichoke. New one for me.

Mark Holthouse, MD: Cool. You know.

Mark Holthouse, MD: We used to use Jerusalem artichoke as a prebiotic, right? Inulin, phos and, uh, but globe artichoke. Amazing. Insulin sensitization. Um, can can help with, um, preventing lipogenesis the production of excess fat in the liver. So, bergamot, uh, globe artichoke. Um, some of my new favorites are. Aged black garlic. Love it. There's great studies on this stuff now that it's antineoplastic. Uh, it's it's cardioprotective. It's it's neuroprotective. Um, it helps prevent building up excess fat lipogenesis. So it promotes lipolysis, the metabolism, beta oxidation. Right. Everyone say it after me and the mitochondria. Beta oxidation of the fat. That's how you burn your fat. Um, aged black garlic does this. Uh, it improves and helps to prevent fatty liver. Um, some of the things on weight loss, which is the number one treatment for this problem, by the way. Um, other than a lot of the basic lifestyles we talk about with just eating a good whole organic, whole foods diet are some of these botanicals are pretty amazing. Hibiscus tops. The list there. Um, this is something that's going to naturally help to raise, um, some of these GLP ones that I'm talking about in your own intestinal tract. Hibiscus. Whoever knew? Um, um. Lemon verbena.

Amber Warren, PA-C: Oh, cool.

Mark Holthouse, MD: And there's great studies. Controlled randomized trials, right. Combining hibiscus and lemon verbena on its effect on lowering blood pressure. Not insignificantly but mostly systolic weight loss promoting. It's it's it's a great regimen coming off of your shot your your your appetite to get people on these things. We have a couple of products back here that.

Mark Holthouse, MD: Are full of phenolics.

Mark Holthouse, MD: Acids that we've been talking a lot about from plants tonight. But hibiscus, lemon verbena, uh, really topped the list. And then the third real action packed one is, um, uh, Green Coffee bean, um, which usually this most studies about 400mg a day. It's been studied, uh, to help with blood sugar, help with preventing these fatty liver, uh, issues as well as promoting weight loss. Uh, none of these things are magic bullets. Um, when you take them together with the lifestyle, I think it sets people up for long term weight loss success. And that's what they're coming in for when they have failed. Right? And they've gained it back. And they say you're supposed to know stuff. What do I do? Yeah. And you know, sometimes we have to put them back on the pharmaceutical. But then we have them focus on the aminos getting adequate protein right. Focus on the right type of strength training. Maintain that lean muscle the currency of youth. Right. We get them on some of these botanicals. We change their diet. We avoid those. Go here um, movement, super important insulin sensitizing. So it really helps to treat fatty liver. Yes. Um exercise in general. And then there's some pharmaceuticals that are being developed that I mentioned that are not yet FDA approved for that, but will probably be used off label metformin being one of them. Uh, pioglitazone, rosiglitazone, some of the others that are that are being talked about. Uh metformin's got some pretty amazing things. Yes, it has some side effects and there's certain folks that shouldn't use it. Right. But it's a it's an amazing anti-aging, um, hack out there. And now we're finding it does some amazing things for, uh, promoting weight loss and and helping with fatty liver, in addition to its original FDA attended use, was a diabetic drug for type two diabetics. Um, it helps with weight loss.

Mark Holthouse, MD: And that's affordable. It's cheap, which is nice. Yeah.

Mark Holthouse, MD: It's inexpensive. It's French lilac, you know, from the 1960s and was re re looked at in the 90s and, and um, this biguanide was made into a medication and yes, it's got some side effects, but it's got some amazing things. So don't count out don't count out pharmaceuticals. We don't want to jump to them first step. But it can in the right person use the right way with the right combination of things. It can be very helpful, even if it's used transiently with minimal safety concerns. Yeah. Number one risk of that stuff is diarrhea. And so it can be a game over if you have problems with that. But just um, looking at kind of what people can do. Yeah. You know, diet, exercise, some of those plants I mentioned, um, managing your stress, uh, and staying away from that doggone refined carbohydrates. That's the number one thing you can do. Yeah. And that's why, you know, it's such a high number. I didn't know that. I learned that last week. I was doing a podcast with a gal on the East Coast, and we were sharing before the show a paper she just read, Marcel Pick, and she she blew my mind and said, did you know it's up to a third of the US population now that's wild. Um, so it's it's surpassed alcoholism. It's surpassed hepatitis C. Um, you know, just a few years ago, hep C was the number one cause of chronic liver disease. Now it's this thing this because.

Mark Holthouse, MD: Of lifestyle, lifestyle.

Mark Holthouse, MD: Induced we're eating too many.

Amber Warren, PA-C: Doing it to ourselves.

Mark Holthouse, MD: Doing it to ourselves. Yeah.

Mark Holthouse, MD: And it's totally fixable. Yep.

Amber Warren, PA-C: Great awareness. That's a good that's a really good stopping point. Thank you so much, Doctor Holthouse, for your wisdom and knowledge and your time with us.

Mark Holthouse, MD: Thank you all.

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

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