Episode Transcript
[00:00:00] Speaker A: Welcome to the Heart Rate Variability Podcast.
[00:00:02] Speaker B: Each week we talk about heart rate.
[00:00:04] Speaker A: Variability and how it can be used to improve your overall health and wellness.
Please consider the information in this podcast for your informational use and not medical advice. Please see your medical provider to apply any of the strategies outlined in this episode. Heart Rate Variability Podcast is a production of Optimal LLC and Optimal HRV. Check us out at optimalhrv.com Please enjoy the show.
[00:00:32] Speaker B: Welcome friends to the Heart Rate Variability Podcast. I am Matt Bennett. I am really excited for our guest today. Anna had written what I felt was an incredibly important article on allostatic loads, so I reached out. I know we just met a few minutes ago, so I am so excited, Anna, to have you on the episode to talk about some of the great research you did. You also sent me some of your past research as well, which I've been geeking out about since you sent that to me. So I know we have a lot to talk about.
I'm excited to have you on the show. So welcome as always, I love for our guests just to give a little bit of introduction to yourself and how you came across heart rate variability.
[00:01:21] Speaker C: Okay. Hello to everybody. Thanks so much for the invitation.
Well, my name is Ana and Lucia Miranda.
I am from Colombia, South America. I am a medical doctor.
I got my MD degree from University of Antioquia here in Colombia.
And then I also took like had like a master degree in genetics. And then I moved to the United States where I did my PhD and postdoctoral training. I did my PhD at Johns Hopkins and my postdoctoral training at NIMH.
Then I came back to Colombia and I have been working on the topic of the gut microbiota brain axis and its relationship with stress response.
During the last 10 years, I have been very interested on understanding the stress response in humans.
Because of that reason, I came across the HRV field.
Awesome.
[00:02:28] Speaker B: Awesome. And you know, I'm curious, you know, how that where, where your research started because one of the things I love about, you know, your article as well is, you know, sometimes when we think about the autonomic nervous system, you know, there's not a whole lot of brain research in there. It's hard enough just to measure one complex system of the body. And so I'm, I'm curious about, you know, how when you look at the brain, when you look at the autonomic nervous system, just when you talk about stress and the stress response, I'm curious how both of those aspects of our nervous system frame your understanding of the stress response. And we can Start talking about allostolic load as well.
[00:03:15] Speaker C: Okay. Well, the stress response involves many steps.
The first step is the exposure to stressors, right? And here it's very important to differentiate that. We have two big kinds of stressors.
One group is called, like the biogenic stressors, which are usually substances or physical changes that will activate the stress response without any thinking or emotional, like involving.
But then there is another set of stressors, which are called psychosocial stressors. For that it is very important. The perception that you have of this event.
After you get this perception, then also mixed with memories and emotions, then there is an activation of different systems.
The first one is the activation of the autonomic nervous system.
As a result of that, then you get all these autonomic responses like increasing heart rate and also increase breathing speed and many other things, like increase also the muscle tension because this is the fight or flight response.
Then after that, you get also an activation of the HPA axis, which involves the secretion of cortisol.
Like two systems, the sympathetic nervous system and then the production of cortisol are kind of the main hormones that are involved in the stress response.
[00:05:00] Speaker B: I love that. And one of the words that they use, which wasn't fully new to me, but I like the sympathetic. Sure, I say this right.
[00:05:16] Speaker C: Sympathetic.
[00:05:19] Speaker B: It looks so easy to say on paper, but I love, you know, how you, you think about, you know, those two, because kind of that dance between the sympathetic, I think, in the vagal nerve as you talk about, you know, utilizing heart rate variability to kind of measure allostolic load and other stressors.
[00:05:44] Speaker C: Okay, so the symphonic bagger quotient is a way to call the DLF HF ratio, which is one of the metrics that are used to measure hrv.
So this ratio is a little bit controversial. It initially was thought to indicate just a very simple relationship between the vagus and the sympathetic activation.
But then this was challenged with research. And right now it is not considered like, simply like a relationship between the parasympathetic and the sympathetic nervous system. It also has other influences, like hormonal influences, and it also is related to the baroreceptor activation.
The heart also has chemosensing receptors. So some hormones and other things like changes in circadian rhythms are influencing this ratio. In addition, if you are sitting or if you are standing or the time of the length of the recording and many other contextual factors are going to influence this ratio.
However, if you look at the literature, you can see an increased ratio is related with psychiatric disorders like Anxiety, depression, panic disorder.
But if you look at, for example, very old people and if you look at some longitudinal studies that were done in older people, you see that the risk of death or cardiovascular disorders was related with a low ratio. So you can see kind of a controversy there.
If you look at metabolic disorder, an increased ratio is going to also be related to risk. So in summary, it's like in some population you are going to find that low ratio is related to risk.
And then in other group of people, like in the psychiatric disorders people, you're going to find there is a higher ratio related to a risk of developing these disorders.
[00:08:04] Speaker B: I love that and I appreciated your article because one of the things that I'm really struggling with now, somebody who reviews, I'd like to say every article published on hrv, though I'm assuming I'm missing a few here and there is you'll see the LF HF ratio without any disclaimers. And I really appreciate your article because you just put the controversy on the table. And I would, if I were just a researcher from the outside and said, you know, hey, and I'm thinking about using the LF HF ratio, you know, would you, from, from a research perspective, would you encourage me to not use it? Use it, Use it in certain circumstances, depending on what I'm researching.
I'm just curious because about. I'd say over half the articles I review use the LF or HF ratio, but they don't give the great disclaimer that you did in your article. So this is a question more for Matt than maybe anybody else. But I would love, I'd love to hear, you know, sort of maybe advice that, that you would give others, having thought substantially about this.
[00:09:28] Speaker C: Well, you know, there are some papers that like, please let me say, like, do that use LFHF ratio because you don't know how it is originated. We don't know exactly what is the physiological origin of it. But then when I think about it, it's like, well, when I did my analysis, I found that it was this ratio what was associated with, to the allostatic load index. So I cannot say now, like, okay, so even though it is associated, I'm not going to use it because someone else said that is not clear what is the origin of it. So I mean, I think it's important to use it to be clear about interpretation and it's important to evaluate it in different contexts, like different population, different ages, sex. And then with all this research together, we might get later a more clear view of what is going on with it. Like, I think it is informative because like, I don't think is, I think it's. Even if it's controversial, what in general is saying is that it point out to you that there are many factors involved in that ratio and those many factors are the ones which are related to your, to your phenotype, something that you are studying. So the fact that you don't know exactly what it is means that it's a complex metric that is putting together many different physiological factors. So to me it is informative.
[00:11:09] Speaker B: Yeah.
And so as you looked at allostolic load and I would love to get your definition of that. It's a term I know we've talked a lot about on our show.
You know, one of the interesting, I think was equally interesting to me as we talk about my obsession with the LF HF ratio. But what you found, how you measured it and also what you didn't find because I think that was, you know, I would assume that as my allostolic load would increase, you would see certain HRV metrics decrease. And it wasn't necessarily, you know, what you found in the way that I think simplicity. I would assume you would. So why don't we start out with, you know, what is, you know, as you kind of gave us that definition of allostatic load but you broke it down really different ways to assess it in the paper itself. So I'd love to sort of do a deep dive into some of that research and how you structured the measurement of allostolic load.
[00:12:20] Speaker C: Okay, so allostatic load is a measure of the burden that chronic stress has on different tissues. Right. And the allostatic load index was a measure that was proposed like long time ago. I think it was.
Well, I don't remember exactly the time, but I remember it was Simon who proposed the first allostatic load index and she measured many different biomarkers. And from that point to now, different researchers have tried different combinations of biomarkers, different methods to calculate the static load index.
But in 2023, McCrory, he reported a meta analysis which put together many studies. Most of them were longitudinal studies. So this is very important information.
And he came about like he created an illustrative index composed of five different biomarkers.
So because of the, like the, the very well done research that he did, we took that as a starting point.
And from that five biomarkers, allestatic load index, we built two different alleles. We built one that was short.
So it has all the markers that McCrory had, except one of them, which was resting heart rate.
And then we built an Additional Ali called Ali7, which has all the markers that McCrory proposed.
We eliminated heart rate and we added the DHEAs, which is an endocrine marker, and added also blood pressure, diastolic and systolic blood pressure. So the other markers in total, like the ali7 is composed of the blood pressure, the dheas.
It also has a morological marker, which is the C Reactive protein. It has glycated hemoglobin, it has dhdl, which is a metabolic indicator as well as the glycated hemoglobin. And so. And it also has an anthropometric measurement, which is the relationship between hate and the waist circumference.
So basically in summaries, what we did was we took that macrotis alley and then we built like two different alleys and tested if they were related to different variability metrics. And the only one that was associated controlling for confounders was the LF HR ratio.
[00:15:10] Speaker B: And did that surprise you as much as it surprised me?
Because I would assume we would see high frequency RMSSD, SD.
My assumption would be as allostolic load increases, you would see a decrease in those metrics as well. So I'm curious, what was your surprise as great as mine with some of the results you were getting?
[00:15:44] Speaker C: Well, I'm not really that surprised because a year ago I published my first paper on this topic and it was also the LFF ratio, which was related to brain connectivity and gut microbial composition.
I think it is because of the population that we're using. We're only using men and they are young.
And I think this metric is collecting more information than the other metrics that, for example, rmssd, which only focus on mostly vagal information.
The SDNN is a very well recognized marker of cardiovascular disease risk.
But these were young men, healthy.
So I think I'm not that surprised.
I was not very surprised with that.
[00:16:45] Speaker B: And do you think with.
If different populations, do you think the population. I guess if we looked at, I mean, just a randomized sample from society with different ages and health conditions and fitness levels and nutrition and sleep quality. Do you, do you think that we. And again, I always give my guests the ability to speculate with.
Will never hold you to this speculation because obviously we need research to back it up eventually. But do you think it was due somewhat to the population, the specific population you looked at, that we didn't get some of these other metrics trending you know how I guess I would expect them to with allostolic load.
[00:17:40] Speaker C: Yes, I do think that it has to be with the characteristics of the population. Like if we take a sample, like a larger sample, very mixed up.
Well, I don't know. I think maybe the SDNN will show up more likely.
But yes, I think this, as I told you at the beginning, when you look at the research with the LF HF ratio, you see different results depending on the age, depending on the disorder.
So if there is a lot of variability in a sample, I don't think the LFHF pressure might show up.
[00:18:22] Speaker B: Okay, gotcha. I just kind of wonder also, any other surprises?
I'd love to talk about some of the conclusions that, that you made along the way as well. And obviously for the audience, we'll put the link to the article here in the show notes to ensure everybody has access to it. But I would love, love to just like conclusions, surprises along the way that you know, you might have had.
[00:18:57] Speaker C: Yeah, well, I mean something that is interesting to highlight is that in the index we added the dhea, the endocrine marker. This, this hormone is very interesting because it is synthesized from cholesterol as well as cortisol. Is so. And they have like an opposite relationship when you have, when you have a high cortisol you have these other dheas low.
So usually they are even used together like the cortisol DHIS ratio. Instead of one of them together, one of them separate.
So I think to me it was very kind of surprising when I read MacRoy's work and when we did the analysis because I used to think that cortisol was the hormone that was going to tell us that someone has been chronically stressed. Find out that McCrory reported in his paper that cortisol was not one of the biomarkers that were included in the allostatic load index.
And he even suggested in his paper that this other hormone, the dheas, should be the one that should be added to future indexes because when they added just this hormone, all the analysis in their different indexes improved.
When I came to my data and analyzed my data, I didn't find a clear relationship with cortisol and HRV, but the DHAs did show an important association.
I think that was the biggest surprise that I had during this research because is kind of a dogma to talk about cortisol and chronic stress. And then you look at this huge meta analysis from macro cortisol. It's not, I think, I think it's not because of course it is a hormone that is involved in the stress response. However, cortisol has many different ways to be measured. From hair, from urine, from blood, and it changes during the day. So it's very hard to get like homogeneous sampling. And I think that that makes very difficult to find an association across many different studies.
[00:21:24] Speaker B: So, so I would love, you know, I.
[00:21:26] Speaker A: Your.
[00:21:26] Speaker B: Your paper got me thinking. I haven't drawn any like epiphany level conclusions about it yet, but should we be thinking differently about allostolic load? Because I would. From a being a nerd about the autonomic nervous system, I would think the more stressed you are, the more the load burns up, you know, builds up, the more the vagal would withdraw, the more the sympathetic would start to influence.
And you know, we did see quite some of the things that I would assume.
You know, I think pretty educated as I am on a heart rate variability, I did see some of that.
Is there a way that let's say the layperson on the street comes up, you know, hey, Anna, I know you're an expert on allostolic load.
You know, tell me what it means for me as an individual. Did this change how you would talk about that or did it reaffirm what you already sort of knew? I'm just curious because I had to kind of rethink some things as I was went through the article because it did not follow the way I was planning for to as far as some of the metrics.
[00:22:44] Speaker C: Okay, well, you know, I have been very interested on preventive medicine. So I think we should do a lot of education and try really hard with people to motivate them to do as much as they can to avoid getting sick.
I think that's real medicine.
So that's the reason I'm studying healthy volunteers.
So what I think is important to notice here is like what this is saying is that if you measure these biomarkers and build this index, what you're going to be able to measure is what is the risk you have to develop future diseases. Right. Future disorders, physical or mental. Because we know that allosteric load is, is related to like chronic disorders.
And as well as hrv, HRV is also an indicator of risk.
[00:23:46] Speaker A: Yeah.
[00:23:47] Speaker C: So the reason we, we did an association between. We tested the association between the allosteric load that we built and the HRB metrics is because HRV metrics is recognized as a risk indicator. So if we test these two, what we will say is like, if you have high static load, you have an Abnormal HIV metrics. And this is telling you that you have a. You're in risk of developing mental or physical disorders or even you have an increased risk of die for any cause.
So what this is saying is like with this kind of index, you can measure risk to get sick or die in the future for some disorder. Right.
[00:24:37] Speaker B: I'd love to hear too your thoughts on chronic stress versus acute stress. And all of a sudden, because you could have a.
And correct me if my use of any terminology here is, you know, I'll simplify it. But if, if I'm way off is you could have a really bad day and have a high allostolic load. Like obviously don't have to experience trauma to get there, but if you just have a horrible day all the way around, your allostolic load is going to build up during that day. However, you could have, you could be in a dysfunctional relationship. You could be struggling with poverty, you could be struggling with a chronic illness. You could have more of a chronic, chronic day after day after day after day, you know, burnout that I see in some people, that's that really, you know, puts a burden on the autonomic nervous system. And I, I would love to get your thinking around allostolic load, acute versus chronic and sort of how, you know, the, the research informs your, your thinking around that as well.
[00:25:46] Speaker C: Okay, well, I think here is important to kind of describe some different terminology. Like allostasis is something that explains the ability that our body has to face different situations. Right. So let's say it's like if you had some of these bands that you use for your hair and then you just pull it like this.
And then because you have a loss disease, if you just stop pulling it outside and then it will return to the normal shape. Right. Without any problem.
[00:26:23] Speaker B: Yeah.
[00:26:23] Speaker C: That will be the way you will respond to an acute stressor.
It's like you go back to the normal situation and this is an allostatic response. But if you keep pulling and pulling and pulling and you pull and stay there for a long time, then what will happen with many times that this is happening during your life is that you're going to build a load that will be the allostatic load.
This means that the allostatic load implies that it's a chronic process.
You cannot say that you have a static load because of acute stress or one situation. It has to be a cumulative effect.
Yeah. So then, and after the allostatic load, you have the overload.
You can have something that is called allostatic Overload. And then at that point you just, you're sick, you have your disorder as a consequence of the chronic stress and after that it's death.
So I think that's like the sequence of the events.
[00:27:35] Speaker B: I love that I'm curious about sort of maybe you're jumped on and I know by the time I read your article it's been several months since you've worked on it. So I'm curious, are you or do you plan to do more work in this area?
Your article just shines such a, a light on this for me.
You know, I'm surprised every once in a while when I read an article but, but this one was really one of those ones that I was like, I had to think about and chew it around in my brain and see if anything positive came out of it. And this is why I've been looking forward to this. But I'm curious, you know, do. Where do you think the research around this can and should go? And just any thinking that you might have about how do we further really the biological understanding of allostolic load? You know, so, so I continue to be dumbfounded by some of the findings and learn from, you know, how to shift how I talk about it due to research like yours. Like are you going somewhere else with this in the future or where would you like to see others go as well?
[00:28:57] Speaker C: Yeah, so.
Well, I would like to validate this ALI as a diagnostic tool for like, for risk to develop disorders, psychiatric or physical disorders.
So I think this is the first step to, towards that validation.
I was so.
But one of the strategies is that we're going to start using these ALI and collecting more information about patients that attend to a neurological center.
And the other way is we want to do a follow up to the people who participated in the research. So all these men who participated in this research, all these measurements were taken several years ago and we would like to know how they are doing now.
That's another way to advancing in the validation because I think it is very important to give a tool to be able to avoid the development of these chronic disorders and to teach people how to stay healthy. And I think if they know how they are doing, they might be more motivated to reduce their allostatic load or if it's low, like to avoid that, it gets high.
[00:30:25] Speaker B: So yeah, I love that. So sort of, you know, I would love to also ask the question of, and I'm sure you thought about this with, with the research as well, the best way to measure, you know, or to get HRV data. When we're looking at allostolic load, I know, you know, you can wear rings and watches and straps, you know, that can measure anywhere from three to five minutes to 24, seven monitoring. And I would love whether you learned anything from this, the research you've done, whether you have any thoughts about future research.
Whereas heart rate variability doesn't necessarily have to be measured in a laboratory setting, even though it's probably way more accurate when we can control some of those variables.
I'm curious if there's anything about how we collect, you know, HRV data that could inform your or your or you would suggest inform others future research around allostolic load.
[00:31:28] Speaker C: Well, you know I used for my research I used these 24 hours recording because we had a specialized cardiovascular disorder center here and we worked with them. They at that point we had, they just had like a new software, the custom software which is from Germany and it gives like a very nice and detailed report, everything that happens, even that those 24 hours recording. So I mean if I think the selection of which recording method are you going to use depends on your research question. You know, like if you want to collect naturalistic information like you know what you are doing during 24 hours, then it gives you like more information and what it even tells you.
This software gives you information during the day, during the night or during the whole day. So you have like many different ways, ways to analyze it when you do it in the lab and it's just five minutes I think. I know there is research that shows that there are almost perfect correlation between short recordings and some long term recordings.
But I think it's like yeah, it will depend on what is your question for us we thought like it was better to use the 24 hours and I think I'm not very familiar with the different devices but I've seen very little devices that can be used during the day because you know the ones that we use like were really high, like very big kind of recorders and some people feel very uncomfortable with them. But I recently saw, I think it was in the Harvard Institute, there was very little machine and yes, so it will depend on different, different aspects of your question and also the possibility to get the recorders and the, the way people feel wearing these big quarters or smaller quarters.
[00:33:37] Speaker B: Yeah, yeah. So I'm curious, you know, if you were to look into the future around this topic. What again pure speculation, you know, so nobody's going to hold you accountable for this.
What do you think? Especially you know, again bringing in, you know, you connecting the brain so well into this research as well, you know, we talked about maybe it being predictive of risk factors, those sort of things, you know, as our technology, as AI improves, where do you think, you know, and I'll throw this question out more generally than just allostolic load. Where do you think the opportunities lie knowing that stress has so much impact on our overall health? To really learn more moving forward, what would be if you could wave a magic wand and get unlimited funding and time?
Where do you think that unlimited magical grant that would hit your desk?
What would you like to spend a couple years just trying to figure out to understand us as humans and our stress response better?
[00:34:56] Speaker C: Well, this is an interesting question.
I am a neuroscientist. I have always thought, or maybe I used to think, that the brain was the most important place in the body that will control everything. But during all these years doing research about the stress response, I now know that we have at least three very big and important brains. We have the central nervous system, we have our heart, and we have the gut.
I think it would be for me very interesting to study how visceral information, particularly the gut information and the heart information, is influencing on like the brain function.
[00:35:47] Speaker A: Yeah.
[00:35:47] Speaker C: And why I think this is important. Like, let's say, for example, if we focus on the interaction between the, the heart and the brain.
You know, like, to me it's amazing that we, that when we use biofeedback, because I use biofeedback, HRT biofeedback, I. I can modulate my brain response. And, and this is very interesting because, you know, I used to do, I used to do neurofeedback to patients with very sophisticated equipment. And I also do neuromodulation with audiovisual training and cranial electrical stimulation and have to put on these like earphones and your lights and everything. But it's complicated to do all that. You know, like when someone tells me, can you help me with sleep? I say, like, I wish I could give you my neuromodulator and you can do it yourself, that you cannot take it with you. So what I'm doing now is you need to breathe. And this optimization of the HRB2 breathing, I think is very, very useful.
I think it's very important to keep understanding how the heart modulates the brain function and develop different protocols to influence different areas of the brain.
Regarding the gu, what I would like to know is how the gut communicate with the heart. Because I have, like, with my previous research, kind of there were Some hypothesis that the heart and the gut were communicating. And here there's like a big gap in research, like how I said the gut communicates with the heart and then the heart goes. Takes this information to the brain. Like the gut can communicate directly to the brain, but it might also modulate the heart and that there is a big gap on that connection.
So that's something I would like to investigate too.
[00:37:53] Speaker B: Yeah, I would love that. You know, that's. You know, your work with the microbiome is just as fascinating as the Alastair Cload article. And I think, you know, we've talked at least, you know, I think a lot more about. I mean, I think we try to separate everything. So it's like, oh, your second brain is in your gut. Well, I always like to say it's all one integrated system. One way or the other, we can break it up because it's easier to understand.
And I really think we've thought a lot about. At least nerds like me have thought a lot about, like, diet and nutrition and inflammation and leaky gut syndrome and, you know, sort of how the brain and gut interact and all the chemicals the gut releases. It's astounding stuff, you know, And I love what you said because you're bringing the heart into that as well, which you don't hear. I don't hear a lot in the thinking of this. It's like, we got the brain, we got the second brain, you know, And I love how you're thinking about bringing the heart into that equation as well.
And I love, I mean, just. What. And you mentioned HRV biofeedback. It just, I mean, one of the best documented, you know, uses of HRV biofeedback is for irritable bowel syndrome. So, you know, there. There's some really cool stuff, you know, going on there, you know, and again, I think to bring three complex systems, you know, or more together because you got the bare reflex in there and everything as well, is a really, I think, as you mentioned, a rich opportunity for future learning as well.
[00:39:43] Speaker C: Yes, yes.
[00:39:45] Speaker B: And I've got. I've gotta learn how to pronounce rumen. Okay.
[00:39:56] Speaker C: We can call it rumi.
[00:39:58] Speaker B: Okay. Rumi. Thank you for that. Because I. I tried.
I tried to pronounce that for about five minutes, and then I'm like, I don't think I'll ever get there. So. Yes, yes, I would love to dig into that more. Maybe a future episode, because I think it's. Again, it's. We're getting there with understanding the importance of the gut and how the stress response hits the gut as well.
And as you mentioned, we got a lot more room to grow with that as well.
[00:40:31] Speaker C: Yes, we have.
[00:40:33] Speaker B: Well, and I want to appreciate, I appreciate your papers so much. I've learned so much. And a good paper, I think, well, in my opinion, a good paper teaches you something.
A really good paper or a great paper teaches you something and then makes you think differently about things. And your paper. I was like, I'm an expert on allostatic load. And then after reading your paper, I realized maybe not, maybe not. And maybe everybody that thinks they're an expert on this.
There are so many open questions there that I'm excited to keep in touch with you and your research to learn what you discover.
Again, I just want to thank you so much for your work and joining us today.
[00:41:24] Speaker C: Thanks so much for the invitation.
[00:41:26] Speaker B: Absolutely. As always, you can find show notes. We'll put links to Anna's work in the articles in the show notes. And as always, thank you for joining us. You can find more information at optimalhrv. Com and we'll see you soon. Thank you so much.
