How Did We Miss This Study?! (ft' Mike Mutzel)

The headlines should have been running breaking news.

1 in 4 adults over the age of 40 is on a statin.

Increasing GLP-1s, they were able to do it in this paper.

Knowing the drug-nutrient interactions is just good medicine.

Be a metabolic tug of war.

Creating the illusion that everything is very objective.

You get a lot of hate from being not in the majority, but the majority isn't actually any sort of validation of what the truth is. If you are on statin therapy, you could just buy this thing off Amazon and boost your GLP-1 levels significantly. All right, I am super excited for this discussion. This is part 2 of my interview with Mike Mutzel from the High Intensity Health Channel. We teased before that we were going to be talking about the most underread and underrated paper in basic science from 2024. Mike, what's the punchline?

The punchline here is when you take statins over a long period of time, they reduce the protective gut hormone called GLP-1 by about half. So that's really important because, as we know, the GLP-1 craze has really been popularized by Ozempic, semaglutide, and is linked with improvements in body composition and beyond. So it turns out that this could be a major contraindication to taking a statin because this gut hormone is particularly important for metabolic health and body composition. And if it's going to be cut almost in half by taking a lipid-lowering medication, that's problematic for other aspects of whole body health, but also implications when it comes to long-term risk of cardiovascular disease. So yeah, this is really intriguing to me. I'm surprised this did not get more airtime.

Yeah, I was I was really— I mean, I was excited and angry. I mean, science like this does excite me, but I just want to like take a step back and identify the irony here, which is that the world's most profitable drug class of all time, statins— I think it's like a $20 billion per year industry— reduces levels of what is now, you know, being mimicked by the trendiest drug class and probably on, on track to be the most profitable, which are GLP-1 receptor agonists. To be clear, neither of us are one, giving medical advice— this is YouTube, don't get your medical advice off YouTube— or saying either of these medications are bad. But the fact that they're in basically a metabolic tug of war of sorts— I mean, caveated by the fact that you give supra-physiologic doses of GLP-1 when you give the agonist— but the fact that statins lower GLP-1, which are now like the focus of cardiovascular and obesity medicine, They're being talked about left and right for not only obesity and diabetes, but like neurological disease, mental health, PCOS. They get talked about all the time. The fact that there is data, human data, in a major journal, Cell Metabolism, showing that like in this case it was atorvastatin 20mg cuts GLP-1 levels by half, and that doesn't get talked about at all. This came out when I was in my third year at Harvard Medical School, medical school, like about halfway through. So not only is it not in like the public, Zeitgeist, which it should be. The headline should have been running, breaking news: statins cut GLP-1 levels by half in human trials, a 16-week human trial. But that it doesn't get talked about in academic medicine, I just find appalling. And I don't say that to point fingers at any physician, but how have we gotten to a place in academia and medicine where that doesn't get discussed about and also doesn't get passed on to patients in the doctor's office as a relevant bit of information before they start a medication. I'm at a little bit of a loss for words.

Uh, I'm with you. And this is not the first time that we've seen sort of these conflicting mechanisms. If we look back at thiazide diuretics and beta blockers, right, you know, of course those will reduce blood pressure, but they also do what? They cause insulin resistance. So this is, you know, this is not an uncommon thing, but, um, I think this really helps us better understand a new mechanism by which it's well recognized that statins will cause, you know, changes in a negative way in blood glucose tolerance and blood glucose levels and, and can exacerbate prediabetes and diabetes in patients. So yeah, the risk-benefit ratio really needs to, you know, be, be looked at here. Um, why wasn't this talked about? I'm not really sure. It seems like if this was a multivitamin, right, or a, a natural product that reduced GLP-1 levels, this would be all over the news and so forth. But You know, I think statins are so widely prescribed. Something like 1 in 4 adults over the age of 40 is on a statin, right? So it's wild.

It's, it's, it really is. And to your point, like I said, and I did a newsletter and some solo coverage on it, like if you had headline statins lower GLP-1 levels by half, if you— that's not a headline. Evidently it didn't make the headlines. But if you had replaced statin with steak, it would have been everywhere. So I do think there's selective reporting. And to your point, It actually makes a lot of sense when you stop and think about it, because what we know is statins can increase insulin resistance. They did in this paper. So they show that in humans, in a controlled 16-week trial, 20 mg of sorvastatin— torvastatin made insulin higher, insulin resistance worse, blood glucose HbA1c worse. And when you stop to think about, well, what might be happening to GLP-1 levels, you would predict that that hormone probably would go down. It might actually be a contributing mechanism by which statins cause worse blood glucose control, worse insulin resistance, and can increase the risk of type 2 diabetes, which are all known things. And actually, after I read this paper, like same day, I went and polled doctors. I live in a very medical area. I asked 12 of them what they thought. All of them said they didn't know, like they weren't aware of data. That's one thing. But, um, 5 of them were willing to guess, and 4 of those 5 guessed correctly that, um, statins would reduce GLP-1. So it's actually a logical thing. It's interesting then that this isn't just part of the common knowledge base, I guess. What do you think about that? What do you think about the fact that people, physicians, can deduce that statins actually would decrease GLP-1s?

You know, it's a great question, Nick. To be honest, I mean, I've— not to undermine doctors or criticize, I think the whole topic of these incretin hormones, GLP-1, GIP-1, CCK, PYY, all that, this is so new to a lot of doctors unless you're a gastroenterologist. I mean, now with Ozempic, we know about GLP-1. A lot of people— this is like a kitchen table topic now. But up to, you know, leading up to the— up hitherto, we didn't really know. Not unless you studied the gut, you didn't know much about it. So, um, Yeah, I don't think many doctors would, would pay attention to it. But thankfully, GLP-1 has really put the incretin hormone category right on sort of the, the clinical toolbox. A lot of people recognize that these hormones are really powerful. Um, yeah, and I think what's cool about that is we have a lot of natural ways to improve GLP-1 and GIP and PYY with food and exercise and diet. So yeah, it's interesting.

Well, I mean, to that point, increasing GLP-1s— they were able to do it in this paper. Right. So do you want to give the mechanism or should I?

Why don't you dive into it?

Sure. So basically what they found was that there were decreased levels of secondary bile acids. So when you take a medication, an oral medication, say like a statin, goes down to your intestines, it can change your microbiome. The whole last discussion we had was about changes in the microbiome. And, um, the microbiome produces different metabolites. Sometimes they take primary bile acids and they modify them into secondary bile acids. And these aren't just for fat digestion, they are hormones that circulate throughout the body and do a whole host of things in your heart and your brain, your fat tissue, all over. And one is, um, called UDCA. And what they found basically was that the statins reduce the generation of UDCA. They change the microbiome in such a way as to decrease UDCA levels. And then UDCA was something that increased GLP-1. So what they were able to do was basically just give back, um, yeah, UDCA, or potentially microbes that make UDCA, and recover the insulin sensitivity, recover the GLP-1 levels. Actually quite remarkable. And they first did this in mice, and then they did a human trial. I'll actually pop up the graph for people to look at. It's this one on the paper. I think it's— what is it— Figure 7. But it's literally a human study. Now admittedly, it's a small human pilot trial where they gave— I'm looking at it now— people on statins who had increased blood sugar 500 milligrams per day of UDCA for 8 weeks. What happened? HbA1c significantly down. So blood sugar down, insulin down. Insulin resistance improved, GLP-1 levels increased significantly. So just supplementing back this bile acid was able to improve, you know, markers substantially in these patients. And this is actually a medication that's already given in the clinic for liver disease. So again, the reason this frustrates me so much is not because I think statins are rat poison or anything like that. It's because the data are here to say, hey, There's a little bit of attention here. Oh, and here's an easy solution based on human data, and yet patients aren't told about it. Like, why? What's going on there? If you want best care, here's a sense of best care. And the extra irony is UDCA has another form that's conjugated to taurine called TU-DCa. Not recommending this per se. Go on Amazon, type in TU-DCa. There's so many TU-DCa supplements. So is it possible, based on these data and cell metabolism, which you can go read, that if you or a loved one are on statin therapy, you could just buy this thing off Amazon and boost your GLP-1 levels significantly. If I were a, you know, clinician talking to my patient, I will be talking to them about this, right, along with coenzyme Q10, right? You want to tell us why?

Yeah, well, because the enzyme that statins inhibit is called HMG-CoA, and as a downstream metabolite of that, that is the isoprenoid and jaranol, jaranol. There's all these different metabolites below this pathway. And, one of the critically important enzymes involved in mitochondrial function, coenzyme Q10, involved in the electron transport chain, when you inhibit HMG-CoA, you basically suppress the cholesterol production or, sorry, cholesterol synthesis, but also you inhibit the formation of coenzyme Q10. So, Yeah, I think it's important knowing the drug-nutrient interactions is just good medicine. It makes a lot of sense. So, um, recommending bile acids in conjunction with Coenzyme Q10 for people that take statins, that makes a lot of sense. I don't know why that this is not talked about. Great point, Nick.

You reminded me of another paper. I was just Googling it to make sure I got the title right. It was in, um, uh, JCI Insights. High dose atorvastatin, same medication, same statin, very commonly prescribed. They used in this paper progressively decreases skeletal muscle mitochondrial respiratory capacity in humans. If I recall correctly, what they did did in this study is they looked at very, like, patients who were asymptomatic and found that even very, very low doses of statins could significantly decrease mitochondrial function. I think it was specifically around, um, complex IV, um, so one of the, the last components of the electron transport chain. And, and the reason this is interesting— a couple reasons. One, these were, um, I believe asymptomatic patients, um, and even in them there was a defect in mitochondrial function, which again dovetails with the insulin resistance the abnormal glucose metabolism we see. And it just should be part of the risk-benefit analysis, especially for primary prevention. Like, if you've had a heart attack and you need secondary prevention, your, you know, cost-benefit analysis is different. But the idea that like any given medication, and particularly statins, are God's gift to medicine and don't have significant side effects that patients need to be told about, or even asymptomatic metabolic harms is, I think, problematic. And even now, looking at this JCI Insights paper, which is not a bad journal, I'm looking at the metrics. Um, there's something called Altmetric. If people don't know what that is, it's a media tracking score based on how much the media talks about it. This paper got a 38. That is abysmally low, which basically is just like, people don't talk about this. And I guess the point of my conversation here, again, not medical advice, not to say anything negative about physicians, because I I don't believe that. I think this is just not in their scope of awareness for most of them, at least the dozen I pulled, um, or necessarily even that these medications are bad or people are bad for using them. It's just that the data are here to not only understand some of the major downsides, like cutting your GLP-1 levels in half, inducing insulin resistance, increasing risk for diabetes, but also potential solutions. Like, literally You could take a bile acid off Amazon and it could potentially help this. And how would you actually monitor if it does? You know, put on a CGM, get your HbA1c, get your insulin, get your HOMA-IR, and do an n=1 experiment on yourself. It's pretty safe and it actually might have substantial benefits. So I think even if there's not a multi-million dollar double-blind RCT on this to make it standard of care, it's just logical that patients should want these options and that we should have a medical infrastructure that can help support n=1 experimentation so people can get the best care they possibly can. And I don't feel like that's happening. Thoughts?

It takes a long time to change the practice of medicine. You know, I think it— there's various quotes and people talk about, you know, medicine changes when the elderly people that are practicing retire. You know, the younger people have these new ideas, they gotta adopt them.

Progresses one grave at a time is what I've heard, right?

So yeah, it just takes a long time. And, and this is why people are just taking health into their own hands and doing their own labs and, you know, working with concierge doctors and things like that.

So yeah. All right, I'm gonna, I'm gonna now zoom out and we'll give some high-level questions to bring us home on this two-part interview. Um, I guess dovetailing on what we just said, um, I said recently that the compass guiding medical decisions points towards profits, not to patients. Do you agree? What would you add?

Yeah, I would agree with that. Um, from what I know about healthcare in general, like I said, I used to be in sales and I would work with family medicine doctors and internal medicine doctors, not in a hospital-like setting, but an outpatient setting. But yeah, it definitely does seem that, um, profits and not so much outcomes are driving the practice of care, but it seems that the reinsurers like Swiss Re and these other companies are now looking at the cost and looking at more natural ways to, particularly when it comes to managing very expensive conditions like autoimmune disease. So it is exciting that we are starting to see sort of a top-down level change in approach in considering these things. But the system is just slow, so big and slow. I think it's gonna take a long time. All these companies, these hospitals and HMOs and so forth, they're losing money hand over fist, right? And so the way that they can recoup costs is by,— you know, just seeing more volume. And higher volume doesn't improve patient care. And so that's, I think, part of the problem.

Yeah.

It's very expensive and volume-based. And, you know, people really need these lifestyle prescriptions, which they're not getting in 7- to 9-minute office visits.

Yeah, it's hard. It's— again, it's not a matter of anybody at fault. It's an incentive structure problem. So, I mean, the most optimistic view I have is just, again, access to information that you don't need to wait for the system to change, to change yourself. And with that, I want to ask, like, I guess a little bit more of an academic-themed question, but we've talked about some interesting studies over the past two-part interview, including how people can misinterpret them. So my question is, do you have any structured practices to combat confirmation bias when you're reading the literature?

Yeah, Nick, this is a great question. I just— I'm trying to be more mindful and aware of that when I start to read a paper. And I get excited about something, I'm just more mindful of why am I getting excited about this? Is this confirming a pre-existing mechanism or condition that I feel would benefit, you know, my audience in a certain way? So try to just read this and, you know, whether it's— and this really comes to mind when I read articles about polyunsaturated fatty acids and the associated so-called positive effects of having more PUFAs in the diet as it's related to a reduction in risk of cardiovascular disease. I find myself understanding, you know, sort of where, you know, canola oil and cottonseed oil, how they were derived and that they're really relatively unnatural. They have antitoxins, glycoprotein, and uric acid respectively. So, um, I find myself getting a little bit irked by that and I just try to be mindful of, you know, hey, you know, maybe there's a lot of things that we don't know. What you, what you don't know, you don't know. So I think we're all biased. You know, there's a great book about, it's called Decisive., by the Heath brothers, and they talk about cognitive biases. We're all biased. And I think just being more mindful of this, and that just helps me, you know, accept new information. I think, you know, we, we can't expect that we know everything about the human body, you know, even, you know, um, when it comes to health. There's so many new mechanisms in the interrelationships between the microbiome and epigenetics, and all these things are really complex. So just being— having more of an open mind, but definitely being mindful when I start to get sort I'm super excited about something, knowing that another paper down in 3 weeks might conflict what I was just reading.

Yeah, that's a good point. It's interesting having enthusiasm and excitement as a trigger to self-assess and reflect. I like that. All right, how about if you could have one biomonitoring or biohacking tool that does not yet exist yet, what would it be?

I think a Breathable that could look at various exhaled gases and metabolites that would give an overall insight into the diversity and the health of your microbiome on a meal-to-meal basis for that individual would be really interesting, you know. So in the first part of this interview, folks probably recognize that, you know, we talked about various gut bacterial-derived secondary fatty acids and fatty acid-like compounds. And so having a Breathable or even some sort of AI camera where you take a picture of your stool to look at the fatty acids in the stool and so forth, that would be really interesting because it would help us just better understand how the foods that we eat are impacting the diversity and the structure of our microbiome. That to me would be super exciting. And, and, you know, we do have the lactulose mannitol SIBO tests and these other things, but, um, That would be cool to look at something in the breath. Look at the volatile organic acids or volatile compounds.

We brought up dogs before, but I'll bring them up again. There are data showing that dogs who have an amazing sense of smell can smell certain VOCs, volatile organic compounds, at a 1 in 1 trillion concentration. They can detect like different forms of cancer or viral infections, including pandemic-causing viral infections. There's actually studies showing that they have like 95% sensitivity and specificity with PCR, but they can do it not in over a day, but in less than 10 seconds. I bring this up because the machinery, be that in a dog's brain and nose or like in a, you know, handheld, is actually there. You're right to detect all these different volatile organic compounds, not just like, you know, breath acetone and figure out how deep your, you know, ketosis is. But to give you a really deep profile, that would be a pretty cool tool. I like that. Uh, all right, amazing. Second to last question: is science a democracy? Why or why not?

I think ostensibly yes, but realistically probably not. I think there's probably— it's more of like an autocracy where there's your prestigious journals and editors and the editorial reviewers and so forth that are creating the illusion that everything is very objective and being able to question things and so forth. But I mean, if we just go back to something like the Minnesota Coronary Experiment or Sydney Heart Study, these are older studies. Some of the results didn't get published for years, you know, after the fact because they conflicted with the narrative at the time about polyunsaturated fats and its links with— and this, you know, Sydney Heart Study looked at outcomes. So I don't think it's as much of a democracy as we are led to believe. And I do think there is a lot of influence from industry, from whether it's device companies, pharmaceutical companies, et cetera, and the conflicts of interest of people that are reviewing, whether they're editors or peer reviewers and so forth. So yeah, it's ostensibly, sure, it's like, it's science, right? This is open access and all that. But we saw throughout the pandemic that wasn't the case. And I think we see that often, like the study that we were just talking about with regards to statins lowering GLP-1. Why didn't that— get airtime because 1 in 4 individuals over the age of 40 is on this drug, and that would be a little bit of a, you know, problem for, um, bottom line of, of, um, pharmaceutical companies. Yeah, I don't know, what do you think?

I really didn't expect that answer because I guess, I guess what I was leading to, I guess where my mind went is like, of course science not— it's— science shouldn't be a democracy. It's about the process of the pursuit of truth, and the human vote doesn't matter. It doesn't matter if 100 people in the room think X is the truth if Y is the truth. And so I think one of the really difficult things about being a scientist who doesn't go with the grain, which is being intellectually honest, is that you get a lot of hate from being not in the majority. But the majority isn't actually any sort of validation of what the truth is. But because we're human, We need— and there's so much science— we need some sort of process to serve as a proxy for what is truth. And what does that become? The consensus, which is, you know, just a term for what is the majority opinion, the democratic opinion of the experts, even when it's wrong. Even when, you know, you get told medical school all the time, like, half of what you're learning now is wrong, we just don't know which half. So I, I, I find your answer very interesting, I guess. In some ways it parallels what I'm thinking, but in other ways it's diametrically opposed because I'm thinking science is almost anti-democracy. And sometimes it takes a lot of courage to go against the majority and also be willing— to be a good scientist, you need to be willing to appear the fool in the end and stand by your guns. So that was my two cents. Any further thoughts?

Yeah, I mean, if you look at, you know, the— I can't remember the name of the two physicians that discovered that H. pylori causes ulcers. In order to prove to, you know, the gastroenterology community, they had to give themselves H. pylori to cause— I think they were Australian scientists. You might know the names of these individuals.

I think it was Barry Marshall and then Robin Warren.

Yes. And then the story of Ilya Metchnikoff.

I don't know.

He was the Austrian physician who recommended handwashing for obstetricians, and he was a heretic. He eventually, you know, I think went to an insane asylum because the community said, what are you doing? Handwashing has nothing to do with helping mothers, you know, if you're going to, you know, birth the baby, assist with the birthing process. And, you know, his research showed that it reduced both maternal and fetal mortality rates and so forth. But he was considered a heretic. So, so yeah, there is sort of this tribalism that has existed pre-internet within health and medicine and if you do question the status quo, you're considered oftentimes a heretic until enough inertia gets behind your idea or movement that it becomes sort of status quo. So it's interesting to me.

Awesome. Well, yep, I guess this brings me to the end. And my last questions are, anything I didn't ask that I should have? And then of course, where can everybody find and follow you?

Yeah, Nick, we covered a lot. This was awesome. Um, both interviews were great. And my website, highintensityhealth.com, and on YouTube, High Intensity Health as well. That's where I post most of my content.

Awesome. Well, thanks for joining us, Mike.

This was great.

Wow, you guys are incredible. You can change science and medicine, and here's proof. I recently wrote a letter and made a video on what I called the most underrated study of 2024. It was a human-controlled trial showing that statin drugs significantly reduced GLP-1 levels. I was stunned that so few doctors and cardiologists seemed to be aware of this research, and I felt these were really relevant data that should be disclosed to patients to facilitate just responsible informed consent. Turned out that content took off. It was picked up by major media outlets and inspired other creators. And as of the morning that I record this, the paper, which had largely gone unnoticed under the rug for over a year and a half, is now on Cell Metabolism's most read list. That's all thanks to you. Your passion can generate a groundswell, a bottom-up influence to direct the spotlight of academic medicine. You are powerful. Thank you.