We have a great question today. It revolves around the gut, one of our favorite topics, and in particular the connection between the gut and the heart, which is something we haven’t talked about a lot. We know there are connections between the gut and just about everything, but this is one area we haven’t explored in a lot of detail.
In this episode, we cover:
2:21 What Chris ate today
5:13 TMAO and heart disease
11:15 Four gut-heart connections
Links We Discuss
- Choline and TMAO: Eggs Still Don’t Cause Heart Disease
- Red Meat and TMAO: Cause for Concern, or Another Red Herring?
- SIBO is associated with cardiovascular autonomic neuropathy.
- H. pylori has been detected within plaque in coronary and carotid artery walls using polymerase chain reaction (PCR)—a way of testing for the DNA of microorganisms.
- Intestinal permeability may contribute to coronary heart disease via increasing production of inflammatory cytokines and weakening the stability of plaque.
- Intestinal permeability has been associated with an increase in visceral fat.
- Patients with coronary disease, characterized by increased intestinal permeability, have been shown to have increased intima media thickness of carotid arteries.
- Studies link changes in gut microbiome with intestinal permeability, inflammation, insulin & leptin resistance, and metabolic problems: all major risk factors for coronary heart disease.
Steve Wright: Good morning, good afternoon, and good evening. You are listening to the Revolution Health Radio Show. I’m your host, Steve Wright, co-author at SCDlifestyle.com. This episode of the RHR Show is brought to you by 14Four.me. This website and this program is a 14-day healthy lifestyle reset program that Chris Kresser has put together to help you if you’re still struggling with, for instance, weight loss, maybe even weight gain, sleep issues, autoimmune conditions, digestive health. Basically if you’re having any health-related conditions and you’re still not where you want to be, optimizing your diet, your sleep, your movement, and your stress are really the foundational principles to getting these problems resolved, and what has Chris has done is put together a 14-day step-by-step program that’s going to walk you through fitting all these new changes into your life. As we all know, implementing healthy habits can be a real struggle, so it’s really good and really wise to work with somebody who has done this with hundreds and thousands of other people and using science-based principles and habit-based principles that can really make it easy for you to implement these things into your life and take your health up to the next level, so check out 14Four.me.
Now, with me is integrative medical practitioner, healthy skeptic, and New York Times bestselling author, Chris Kresser. Chris, how are you?
Chris Kresser: I’m great. How are you doing, Steve?
Steve Wright: I’m very wonderful. It’s a great day.
Chris Kresser: Fantastic. So, we have a great question today. It — guess what? — revolves around the gut, one of our favorite topics, and in particular the connection between the gut and the heart, which is something we haven’t talked about a lot. I mean, we know there are connections between the gut and just about everything, but this is one area we haven’t explored in a lot of detail, so I’m looking forward to it.
What Chris Ate Today
Steve Wright: Yeah. Now, before we get to the question, Chris, people would love to know, what have you been eating all day?
Chris Kresser: Yeah, I thought you might ask that. This morning I skipped breakfast and just had coffee and cream. There was a lot going on, and I had a few things I needed to get done, and so, yeah, that’s what I did, as you know I’m prone to do sometimes, and then I worked out, did some exercise around 10, and then at 11 I had kind of a brunch, I guess you’d call it. I had some plantains, a raw spinach salad with carrots and beets and a balsamic vinaigrette dressing, and then I had some lamb merguez sausage from my favorite local charcuterie, The Fifth Quarter.
Steve Wright: Nice. And no bottomless mimosas at brunch today?
Chris Kresser: Not today. I did have a glass of kefir afterwards, but that’s not quite the same.
Steve Wright: Perfect. Sounds delicious, man.
Chris Kresser: All right, so let’s give this question a listen. It’s from Simas. I hope I’m pronouncing that right.
Simas: Hi, Chris. You have briefly mentioned about the gut-heart connection in one of your podcasts, and I find it really, really interesting because I’ve had all kinds of heart problems through the years, which include high blood pressure and heart rhythm problems like various kinds of extrasystoles and just a general feeling that something’s not really right in that area, and so I wanted to hear how gut health can affect that. I mean things like H. pylori, SIBO, lipopolysaccharides, and nutrient deficiencies, do they play a role in heart rhythm problems and how it all works? I would love to hear about that. Thank you.
Chris Kresser: OK, yeah, so as I said, we’ve talked about the gut-brain connection, we’ve talked about the gut-skin connection, the gut-immune connection, so of course, why not the gut-heart connection? It shouldn’t surprise us that there is a strong connection between gut health and heart health. There are, in fact, a wide range of connections, and in this podcast I’m going to talk about the ones that I think are significant. I’m also going to spend a little time talking about one that I don’t think is significant that’s gotten a lot of attention in the media, so maybe we should probably start there.
TMAO and Heart Disease
All right, so I’m not sure if those of you who are listening to this know, but a year or maybe it was two years ago now — it’s all a blur! — there was a lot of discussion about TMAO and heart disease. I wrote a couple articles about it at the time, but it was really kind of the latest attempt to blame red meat and foods like eggs for heart disease. It’s pretty complex. As I said, I wrote two articles about it. They have a lot of detail. We’ll put those links in the show notes so you can do a deep dive if you want. I’m just going to cover the basics here, and that’s that there’s a chemical called trimethylamine N-oxide, which is TMAO for short, and the theory is it increases the risk of heart disease, and eating red meat and choline-rich foods like eggs supposedly increase TMAO. Therefore, red meat and egg increase heart disease. That was the argument that was being made, and there were articles published in The New York Times, and there was this whole big brouhaha about it. But there were a lot of problems with that research, and, again, you can check the articles for details, but I’m going to just highlight the biggest ones here.
First, most previous studies have shown that the only food that significantly increases TMAO reliably is seafood and fish, but of course, seafood and fish are inversely associated with heart disease in just about every study you can look at, and you don’t hear these researchers going out and telling people not to eat fish because of TMAO. And shockingly, the researchers that were really kind of advocating this TMAO-red meat connection just entirely ignored that in their papers. This was Stanley Hazen’s group out of the Cleveland Clinic, a group that’s kind of notoriously anti animal product and pro-vegetarian, kind of vegan agenda. So nobody’s explained that. If TMAO is increased by eating seafood and fish by orders of magnitude more than by eating red meat, than how is it that eating fish isn’t killing people?
Number two, even if there is an association between TMAO and red meat consumption, there’s no evidence that meat consumption is actually what’s causing the higher levels of TMAO. If you’ve been listening to the show, the most recent episode on how to do proper scientific research, you know that correlation is not causation. So if you see high levels of TMAO in people who eat more red meat, it doesn’t necessarily mean that the red meat is what’s causing the high levels of TMAO. We’ve talked before about the healthy user bias, which means that people who engage in one unhealthy behavior or healthy behavior are more likely to engage in other similar behaviors, and since red meat has been demonized for so long, typically people who eat more red meat in studies do things like smoke more cigarettes, they exercise less, they don’t eat as many fruits and vegetables, they engage in all kinds of behaviors that are less healthy, so how do we know that it’s not these other things that are leading to the higher TMAO levels? How do we know that people who tend to eat more red meat have a messed-up gut microbiome because of all these other behaviors that I mentioned and that’s what’s causing the higher TMAO levels, which is certainly possible?
And third, if eggs do increase TMAO, and TMAO causes heart disease, we should see a clear association between people who eat more eggs and heart disease, and in fact, we don’t. I’m sure many of you heard that for the first time ever the US Dietary Guidelines have removed dietary cholesterol from the list of foods that need to be avoided because there’s just no evidence to support that link between dietary cholesterol and heart disease. Other industrialized countries removed that a long time ago. The US finally joined the club and did it this year.
Along those same lines, in some of the more recent larger studies, we don’t see even any association between fresh red meat consumption and heart disease, and that’s in spite of all these confounding factors that I just mentioned related to the healthy user bias. If you go into PubMed and you look at studies on the connection between the gut microbiome and heart disease, a lot of the papers you’ll find initially will be related to this idea that TMAO causes heart disease and meat and animal products increase TMAO, but this is not, in my opinion, something that’s really significant and that we should be paying attention to, so I just wanted to start by kind of getting that out of the way.
Steve Wright: Yeah, you’ve done a lot of research on that, and I think there have been a lot of write-ups in this community about the lack of scientific evidence there.
Chris Kresser: Yeah. So now let’s talk about what I think is worth paying attention to, and there’s some really interesting stuff. I’m sure we’re going to be seeing a lot more of it in the months and years to come.
Four Gut-Heart Connections
There are four lines of evidence that I looked at in terms of connections between the gut and the heart. The first one is our old friend, SIBO, small intestine bacterial overgrowth. There aren’t a lot of studies on the connection between SIBO and heart health, but I did see one study showing that SIBO is associated with cardiovascular autonomic neuropathy. We also know that SIBO is linked very convincingly with nutrient deficiencies, and of course, there’s tons of research showing various nutrient deficiencies connected to heart disease. And then SIBO has been shown to cause both inflammation in the gut and then, by extension, systemic inflammation, which, of course, conceivably could contribute to heart disease because we know it’s an inflammatory condition, and anything that causes continual low-grade inflammation is definitely going to contribute to inflammatory diseases like heart disease.
The second connection is with H. pylori. This is the bacterium that’s associated with ulcers, as many know, and there are a few different lines of evidence connecting H. pylori infection with higher rates of heart disease. There’s observational or epidemiological evidence showing higher rates of heart disease and heart attack in people who have H. pylori, but then there are studies that have found a significant relationship between H. pylori and endothelial dysfunction, although it’s worth pointing out that some other studies didn’t find a relationship, so there’s a little bit of uncertainty there. But most interestingly, because we can’t rely on observational or epidemiological data, as we’ve been talking about kind of ad nauseam at this point, to establish causality, there are some studies that have found that eradication of H. pylori decreases risk factors associated with atherosclerosis; such as oxidative stress; myeloperoxidase activity; C-reactive protein, which is a marker of systemic inflammation; fat mass; and blood pressure, which is actually the single greatest risk factor for heart disease. So that’s convincing evidence that there may be a causal relationship because if you observe that people with H. pylori are more likely to have heart disease, that’s just an association, but then if you find that eradicating H. pylori decreases all these risk factors that are associated with heart disease, that’s one factor that makes it more likely there’s a causal relationship. And finally — this is another factor leaning towards showing causality — is H. pylori has been detected within the plaque in coronary and carotid artery walls using DNA-PCR analysis, so they’re actually finding this bacteria in plaque. Again, that could be more a consequence of another problem and not the causal event, but it’s interesting, nonetheless.
OK, so we’ve covered SIBO and H. pylori. I’m sure many of you are wondering if there’s any connection between leaky gut or intestinal permeability and heart health, and there definitely is. There was a study published in The American Journal of Cardiology that found that intestinal permeability may contribute to heart disease by increasing the production of inflammatory cytokines and weakening the stability of plaque. And as I think we’ve talked about before, the stability — or lack thereof — of plaque is a major factor in terms of heart disease because the initiating event of a heart attack is the rupture of plaque, which then occludes the artery and prevents blood from getting to the heart, and that causes the cells of the heart to die, and that’s what a heart attack is. Instability of plaque can be the main precipitating event of a heart attack, so that connection between intestinal permeability and plaque instability is, I think, particularly significant.
Then there were a couple studies showing that leaky gut is associated with an increase in visceral fat or abdominal fat. This is fat that accumulates around the viscera or the abdominal organs, and we know from numerous studies at this point that that type of fat is a strong risk factor for heart disease.
And then we can kind of extend our search and look at patients with celiac disease. Even if there aren’t a lot of studies directly looking at intestinal permeability and heart disease, we know that patients with celiac, especially untreated celiac, suffer from intestinal permeability. So we can look at the connection between patients with celiac disease and heart disease, and sure enough, there are studies showing that patients with celiac disease tend to have an increased intima-media thickness of their carotid artery, and that is, again, a well-known marker of endothelial dysfunction and vascular disease and a risk factor for heart disease and for stroke. So several different lines of evidence suggesting a connection between intestinal permeability, AKA leaky gut, and heart health.
And then last, but not least, of course, we have to talk about the gut microbiome and not TMAO, just because there’s not necessarily a strong connection between red meat and TMAO — and even TMAO and heart disease, although I’m not ruling that out, per se — I’m just criticizing the idea that our diet is the major contributor to TMAO production. But there are lots of studies linking changes in the gut microbiome with things like intestinal permeability, which we just established is related to heart disease; inflammation, which is extremely well established in terms of its connection to heart disease; insulin and leptin resistance and all kinds of different metabolic problems. I’m sure a lot of listeners have heard now, over the last few years, a lot about the connection between the gut microbiome and diabetes and metabolic syndrome and metabolic health, and of course, diabetes and metabolic syndrome are very strong risk factors for heart disease. We can link changes in the gut microbiome to heart disease pretty directly via those mechanisms. The research here is still kind of young in terms of just directly looking at changes in the gut and cardiovascular disease, but there’s enough already, both direct and indirect, to convince me that there is a strong connection, and given what we know about the gut, that’s not at all surprising.
Steve Wright: Yeah. Not to mention, Chris — I’m guessing you have this point of view, but you’ll obviously clarify — the gut sort of feeds the rest of the body. So if we want a healthy heart or a healthy brain or any healthy organ, being able to assimilate nutrients out of our food and keeping our inflammation as low as possible, the gut seems like the central player just at a high level sort of as a feeder to the rest of the organs that will never be able to be quantified, I don’t think, in research.
Chris Kresser: Yeah, absolutely. I mean, it probably could be quantified to some extent in the sense of just measuring nutrient absorption and things like that, but when I was talking about SIBO, I mentioned that SIBO is linked with nutrient deficiencies, and then nutrient deficiencies are strongly linked with heart disease, so, yeah, I completely agree. I think that at the most simple level if we’re not absorbing nutrition from food, then our whole body isn’t going to function right, including our heart! And heart disease is the number-one killer in the modern world still. And that may change. Cancer is catching up, but still right now in the industrialized world heart attack is the leading cause of death. So we want to do everything we can to protect our heart health, and a lot of people don’t necessarily think about the gut when it comes to living a heart-healthy lifestyle.
This is a little anecdote from my clinic and work with patients. I have quite a large number of people that come to me who have started a paleo diet and their cholesterol has gone through the roof, and in some cases I have patients — usually men, but sometimes women — who their only complaint is very high cholesterol. These are, maybe, competitive athletes, people who are at the top of their game. They don’t have any other symptoms that bother them. They’re just concerned about their really high cholesterol. And when they come to see me, one of the first things I do is I run a full suite of gut tests, and fortunately my patients are often up for this because they’re people who have listened to my podcast or read my book and they’re kind of expecting that. I think a lot of patients, if they were to go to see a health practitioner about high cholesterol, might be surprised and reluctant to go pay hundreds of dollars for gut testing when their only complaint is high cholesterol, but so far I haven’t had anyone resist. But they have often been surprised to find out that they have SIBO or fungal overgrowth or something like that. For whatever reason, it’s not causing a lot of symptoms for them in the gut, which is something we’ve talked about before. And let’s say they have an LDL particle number of, like, 2400 or 2500, which is quite high. Then we treat their SIBO or fungal overgrowth, confirm eradication by follow-up testing, and then we retest their LDL particle number and it drops down to 1300, which is a huge, huge drop. It’s gone from the extremely high category to the borderline high category and to a level that probably doesn’t even require treatment for most people if they don’t have any other significant risk factors. We’ve seen this a lot in our practice, and it’s direct evidence between the gut and gut health and major risk factors that at least conventionally have been strongly associated with heart disease.
Steve Wright: Well, it seems like for anybody who’s concerned about long-term heart disease issues investigating gut health would be a top priority. What about any sort of short-term heart arrhythmia-style stuff that was mentioned in the question?
Chris Kresser: Yeah, I didn’t find anything direct on that, but something that can cause cardiac neuropathy, I assume, could certainly affect the rhythm of the heart. I would assume that anything that we talked about that could cause heart disease could also affect the rhythm of the heart and how the heart pumps blood. I mean, those, to me, seem pretty closely connected.
Steve Wright: OK.
Chris Kresser: Although I didn’t find any specific studies linking SIBO and arrhythmia, for example. That’s what I meant by saying I think the research is still kind of in the early phase. We’re not seeing that level of specificity yet, but I imagine we will at some point in the not-too-distant future.
Steve Wright: Yeah, I would think so. I mean, the amount of money that’s pouring into gut health research right now is pretty staggering.
Chris Kresser: Mm-hmm.
Steve Wright: So I think there are going to be a lot of things that we might be chatting about in two years that are finally proven.
Chris Kresser: Yeah. I agree. So that’s it, the gut-heart connection. I imagine eventually we’ll get through every organ or organ system in the body and its relationship with the gut.
Steve Wright: I can’t wait for you to do the gut-calf connection.
Chris Kresser: The gut-calf connection. Well, we could do sort of, like, the gut-muscle-joint connection. I mean, there’s certainly a strong connection between the gut and things like rheumatoid arthritis and muscle fatigue and exercise intolerance and things like that, so maybe you can call in and record a question, Steve.
Steve Wright: All right, I might just go over to ChrisKresser.com/PodcastQuestion and give you a ring!
Chris Kresser: Use a fake name, disguise your voice, you know?
Steve Wright: I will use my sexy voice. All right. Well, if you’d like your question, please, as I just mentioned, go to ChrisKresser.com/PodcastQuestion and submit it there. And in between shows, make sure you’re following Chris on social media, Facebook.com/ChrisKresserLAc and Twitter.com/ChrisKresser. On social media is where you’re going to get his latest updates on new posts, but also he’s sharing things like the scientific research that he’s looking at for the shows and things that don’t necessarily make the blog for many months, so it’s a great place to keep up with what Chris is looking at on a daily basis.
Chris Kresser: All right, everybody, thanks again for listening. Talk to you next time.
Steve Wright: Yeah. Thanks, everyone.