Dr. Pierre Capel on the Power of the Mind & the Science of Wim Hof
Posted on January 3rd 2016 (about 3 years)
Dr. Rhonda Patrick interviews Dr. Pierre Capel, professor emeritus in experimental immunology at the Utrecht University in the Netherlands where he researched a wide range of topics from genetic modification to cancer immunotherapy.
A special focus of this podcast, however, centers on Pierre's relationship with previous podcast guest Wim Hof, who is especially well-known for his extraordinary ability to withstand extreme cold, taking on many world records by doing so.
One such example: Wim once stayed in a tub with direct contact with ice for over an hour and fifty-three minutes.
What's especially interesting about Wim, however, is the fact that he's been able to reproduce some of the effects of his "technique" with a group of other people and the results of this has been published in a scientific journal.
- Study: Voluntary activation of the sympathetic nervous system and attenuation of the innate immune response in humans.
The Science of Wim Hof (as explained by Dr. Capel)
In this video, Pierre explains what he believes to be the reason why Wim Hof's technique, which involves breathing techniques that can kick off a gigantic release of catecholamines and induce a mild state of respiratory alkalosis. The latter of which causes a change in blood pH(something shown in the 2014 PNAS study)
The missing piece to the puzzle that Pierre brings to the table is the fact that pain receptors that are critical to feeling cold temperatures actually rely on what are known as "acid-sensing ion channels", which have been shown in other studies to become inactive within the pH ranges Wim and his trainees can increase their blood to.
Aside from just being able to better tolerate the cold, Wim has also demonstrated another interesting property of his method: in a 2012 study he showed he was able to suppress his response to bacterial endotoxin. As we learn in this video, this feat is most likely made possible by the enormous release of catecholamines he's able to achieve in even a lab environment through his breath.
In addition to talking about some of the thermo- and pain- receptor stuff, Pierre and Rhonda also discuss other literature he's familiar with, including:
- Good stress and bad stress and how meditation affects the expression your genes.
- Meditation and the speed with which it affects fMRI changes.
- How even loneliness can change gene expression, including some involved in metabolism, inflammation, and the endocrine system.
- The effect of social isolation in mice on cancer metastasis, and conversely how wound healing can be affected in mice just by changes in their environment.
- What affects the stress hormone cortisol has on gene expression.
- What the inflammasome is and how its activation can be linked to the central nervous system.
- How the limbic system regulates emotions (and this is not easily controlled) but meditation has been shown to help control the limbic system.
Learn more about Dr. Pierre Capel
WARNING: Breathing techniques should not be practiced when in water or before swimming. Shallow-water blackouts, which may be fatal, can occur.
- Rhonda: Hello, everyone. I'm sitting here in the wonderful city of Amsterdam, in Netherlands, with Professor Pierre Capel whom I met yesterday because we were both giving a talk at the Orthomolecular Medicine Congress in Bussum. We immediately hit it off and I found out that Pierre happens to be an acquaintance of Wim Hof, also known as the "Iceman," who many of you may know of through Tim Ferriss interview with Wim and also from the VICE documentary on Wim and his cold and breathing techniques. I am very honored to have Pierre here. He is an expert on many different subjects including the science behind meditation, how meditation changes our genes and our brain, and the science behind enjoying life in general. So I'd like to welcome Pierre and maybe if you want to tell us a little bit more about yourself.
- Pierre: Yes. Well, first of all, thank you that I can talk in this fantastic surrounding. My name is Pierre Capel and I'm…the official word is an emeritus professor, but I'm just a man who loves science and has now a little bit more time to do his little hobbies than only running a lab with more than 100 people. My hobbies are science, but science also connected to the joy of life as what you just said because it is incredibly important that we should not only be active and creative, but we also should be at ease that the creation we want to find really has a good background and not all this rush rush rush rush rush and ah ah ah ah. No, relax, and then the inspiration comes.
- Rhonda: I couldn't agree with you more on that, you know, I recently have been talking about some of the negative effects of the stress and the chronic stress response and how that literally ages your DNA, it ages your brain.
- Pierre: Oh, absolutely. Well, the point is that you have to make a definition between very functional stress, which is the natural stress, which has a very big influence in survival like animals do. So if there is a danger, you should not go to bed, and think about it, and write an article but you have to run, and fight, and do, and whatever. So this stress response, which people always know, it's linked to adrenaline, heartbeat, sweating, power, that stress response is very good. However, it's rather strong on your body. So if you do that for a too long time, it doesn't work. The other thing is the chronic stress, which is not related to danger but to stupid thoughts. "Oh, worry, what's tomorrow? Wow." That are all type of thoughts which can make you uneasy and give a stress response. However, there can also be a type of stress which is very real and chronic. For example, a disease in your family. If somebody has leukemia, you can't say, "Okay, relax or whatever." But if we're going to talk about meditation, which we will do in a moment, what is the very strong point is that it's chronic stress, which is outside your competence to cope with it, it is there, but what is the effect it really has on your body that you can influence? So the terrible disease is there, 24/7 but it should not devastate your life 24/7 but only 20 minutes, poof, and that we're going to talk about, or that we'll do.
- Rhonda: So what you're saying is, in a way, if you have an event that is out of your control, for example, if someone in your family gets critically ill, such as leukemia, obviously, you can't control that.
- Pierre: No.
- Rhonda: It's going to happen, and you are going to be affected emotionally by that event. But what you can control is how you emotionally respond to that event and whether or not you're going to ruminate, and continue to have these negative thoughts, and anxiety, and... - Well, the anxiety and negative thoughts you absolutely will have. It's supernatural to float off the real trouble, but that's not correct, but there should be a period in the day that you quit thinking, and start feeling, and don't think about tomorrow but go at this very moment and try to get rid of thoughts, breathing easily, quieting down and that's a fun thing, you hardly will believe it. But if you meditate 20 minutes a day, you will change the use of hundreds of genes in your body, and this change is a positive one, and we will explain that during this talk.
- Rhonda: So essentially, buffering the negative effects of the stress with something like meditation?
- Pierre: Yes. Also, physical exercise is also very important. So in a lot of psychiatric clinics, they just hang around drinking some coffee, smoking cigarettes, and doing absolutely nothing. But if you let them do some physical work, or walking, or swimming, or whatever, that has a direct effect on their psychological problems. So, you have to stay active, but you have to also contemplate proper moment to get your harmony back, which is disturbed by the outside stressor.
- Rhonda: Yeah, so both exercise and having that time to be mindful, and meditate and be in the present moment, they both serve important functions.
- Pierre: I would like to ask a question to your audience if you don't mind. Folks, you all have an agenda, you all are busy, you have all obligations, you have to bring this here, get that, do this and do that, and this whole exercise, we can summarize as your agenda. Where are you in your agenda? Where is your daily half-hour only for yourself and not being busy with whatever? If you really can answer that you have it, then you are okay. If not, you better think about it. You are worth half an hour a day for yourself. And that half hour, if you do that properly, really will have an effect.
- Rhonda: So I guess the answer, if you say, "When I sleep…" that doesn't count.
- Pierre: No. Sleeping is incredibly important. Without sleep seven days you'd die and sleep is a very active process in which the mind is really reprocessing, changing memory from this side to that side, cleaning up the hard-disk, so that's very important. But emotionally, you have to be awake to get rid of the negative thoughts, and come to harmony for 10, 15 minutes, and that active process changes the use of your DNA and your genes. The inactive, unconscious, sleeping is extremely important but that will not have this effect as meditation has.
- Rhonda: So if it can change the expression of over 100 genes, which means it can turn genes on, turn genes off.
- Pierre: You can do that yourself.
- Rhonda: How quickly does that happen? Is it immediate after meditating?
- Pierre: No, no, it's during. I will give a little example that there are a lot of measurements done with all type of medical instruments of brain scans in which you measure activity. And if you put somebody in such a surrounding, where you can measure brain function, blood flow, neurotransmitter production, and whatever, then you are on real time. And if these people start to meditate, electrical activity, and especially in this part of the brain, changes within 30 seconds, starts to change. Blood flow is changing within 5 to 10 minutes. And so even during meditation, you already are resetting a lot of basic functions. But if you don't mind, I would like to give a little example about because you said genes are changed, and DNA, and whatever. I would like to explain a little bit what it really is. People always think that DNA is something static, if we have our DNA passport, you know who you are. Well, forget about it. These 20,000 genes, which is not much, are used in a special way together, in a qualitative different way, in a dynamic way, and it is so complex that the description of the proteins you have to, which are the 200,000, isn't saying much but what are you using? The point is this, that there is a technique that you have a DNA chip in which you can measure which gene is switched on and which gene is switched off in a cell. That chip you can buy commercially and in an app, you can do the trick, and it is type of dipstick and then you'll see what is on and off. There was a fantastic research program in which they did this gene expression in white blood cells for people who were loners, socially isolated, had no friends, no contacts, and really felt lonely. So not a person who wants to be alone and is happy but the people who are really, "Hmm, I'm so alone." Compared to the same type of people with income, age, disease background etc., and these two types of white blood cells, you put a stick in this one, put a stick in that one, and then you have, heaven's sake, a good computer program and then they analyzed 10,000 genes and see what's different. In the case that somebody is lonely, in that article was at least 209 elementary functions in life were changed inside the immune system, inside metabolism, hormone levels, and whatever. So the feeling of unhappiness changes a whole use of hundreds of genes. But the other way around, happiness also changes an awful lot. So a lot of stress is related with unhappiness, or worry, and sorrow but if you actively try to be happy, enjoy your life, not continuously, it is not a burgundy type of living that only wine, women and singing in the German's, "Wein, Weib und Gesang," that is not what I am aiming at. But if you are eternally at ease with yourself, that switches on and off genes. It's not only with humans but a fantastic experiments with rats and this rat strain where the women are very susceptible to breast cancer. So after certain period of time, so many percent of the women have a breast cancer, and that is the way it is. Because rats are incredibly social animals, if you isolate them and give them the perfect room service, Hilton quality, but alone in a cage, they'll feel lonely. What you see is that the tumor incidence, which at the certain time is 20% in the population goes to 80%. The tumor size is 84 times bigger and it starts to spread out in the body, and metastasize. How is that possible? Only loneliness influences the effect how the tumor develops. Well, if the genes in the human is set into 200 to 9, in the rat, there's a similar setting going on. If a protein is expressed, which is absolutely a necessity for a tumor to get out of the tissue and to go into another tissue, then it is metastasizing, it's spreading. If the protein is not expressed, forget about it and leave. But if that protein is under control of the gene, which is under control of loneliness, you influence your disease. So having a harmonious life and really feeling okay, actively try to find the good things in life, not by being blindfolded but actively looking at it, really has a incredible effects of health.
- Rhonda: With a tumor loneliness study done in rats, that's incredible that they, you know, increase the tumor chance by 60% and the tumor growth and metastasized, was there any implications in terms of what caused the, you know, metastasis? So was there, you know, was there more cortisol or cortico releasing hormone that increased factors like VEGF or other angiogenic factors which are known to cause tumor and angiogenesis?
- Pierre: Yes. One of the explanations is that VEGF, which is the vascular endothelial growth factor, which is a necessity to form new blood vessels but also to do the maintenance. The point is that a tumor can actively produce VEGF that can be stimulated by this loneliness. So there is a much higher transcription factor which is the regulator of a gene. If that is up-regulated by loneliness, then the genes which follow this transcription factor will go up. In this loneliness, you see that a very important protein in DNA regulation is called NF-kB, which is a factor which switches on and off about 200 genes, very strongly involved in the immune response but also responsible for this vascular growth factor. So loneliness affects NF-kB, affects the growth factor, and if you go the other way around, then if you take away the growth factor by harmony then the VEGF goes down and a lot of tumors have lousy vessels, and start bleeding, and they become necrotic and they shrink. So it really is a funny effect.
- Rhonda: So there's really empirical evidence that social isolation, at least in the context of these animal studies, literally increases the inflammatory response via NF-kB. That's really very interesting and very important.
- Pierre: I will give you two funny examples. One about wound healing. If, in an animal situation, an animal is wounded then whether is he safe, or stressed, or whatever will affect the speed of the healing of its injury. And they did experiments with standardized incision which had to heal in animals. And depending, if they give extra nest material and extra content by which he was feeling better…
- Rhonda: Safe.
- Pierre: The wound healing…yes, feeling more safe, the wound healing increased incredibly, was much faster. But the other example is more in another effect which is coming not really into meditation but a little bit. There was a boy who was very often severely ill in his younger age, and he was laying in a room for days, and days, and a lot of pain, and trouble. But in the garland, was a beautiful tree which he could see through the window from his bed and it always gave him mental support, this tree. This tree was supporting his misery. Later on, this boy became a surgeon and started to work I guess it was in Chicago, I don't know which his town. But in the wards, there was a long corridor with rooms which patients were treated. But along this stretch of rooms, couple of them were looking to a concrete wall and a couple of them were looking into a park with trees. So then he started to analyze, for 12 years, all the documentation on surgeries, the outcome of it, how long, and how well did the patients perform. Guess what? The guys who were laying in the room looking at the tree had less pain medication, shorter hospitalization days, we're doing better and whatever. And the point is that, if you look at something beautiful, it's not only beautiful but it also really works.
- Rhonda: Yeah, there's a study that came out not too long ago, I didn't read the whole study I just read the press release, but it found that people that took walks in nature versus, you know, in a metropolitan city area, had less clinical symptoms of depression, anxiety. So they're both walking, they're both getting exercise which we know also has positive benefits on depression. However, something about being immersed in nature had a much more significant antidepressant effect which is a…
- Pierre: That's completely conceivable ways with everything you can see in this field.
- Rhonda: So I had a question in regards to the wound healing and feeling safe versus being stressed in the animal studies that you were referring to. I know that the stress response, at least in terms of cortisol, there's lots of things going on with the stress response but it dampens the immune response. So it actually, you know, your immune system doesn't get as activated. Does that have something to do with the delaying or prolonging the wound healing response?
- Pierre: Absolutely. So cortisol is an incredibly important hormone and it's fluctuating through the day. The official word is the circadian rhythm, and it fluctuates, and at night it's low and in day it's high, etc., and it regulates a lot. Every cell has a receptor on its membrane for cortisol, or almost every cell, and the complex of cortisol and receptor goes into the nucleus, and it's called a transcription factor and regulates 20% of our genome. So one in five genes is under control of cortisol. So if you are stressed, this rhythm is still there but this whole fluctuation is elevated. And genes are overexpressed in a stressful situation or underexpressed because cortisol can also switch these things off. So best way to say it's bringing things in this balance with strong effects. So the stress response is not only cortisol, is not only adrenaline, but it's far more complex. But the point is that this cortisol, adrenaline, and all these stress hormones do not only affect heartbeat, or sweating, or anxiety but also the immune system. The example is the wound healing, which is under influence of this stress response and changes whether you feel okay or not, but the immune system itself is making all type of factors and hundreds of them, who influence the central nervous system, who influence your mood, who influence depression, psychosis, and whatever. A very strong but sad example is that in the early '70s, when gamma-interferon was used as a therapeutic agent for a certain type of cancer, the only effect was that all these people who were treated ended up psychotic in a psychiatry ward because gamma-interferon influences the immune system but also influences the central nervous system. That is an incredibly complex interrelationship. And all type of factors from inflammatory reactions will affect your mind and vice versa, your mind will affect your immune system. And a very important immunological starting component, so the whole starting engine of the immune system is called the inflammasome. Inflammasome is a very old defense mechanism in every cell, what is living. And it is complex when there is a danger or stress. Individual proteins will come together, form a complex, and will start a defense reaction. In simple organisms, they will only make this, and that, and that factor, and in our system, we have the same as in plants and whatever, but you get a whole cascade of reactions. So if you trigger the inflammasome in the bowel, it will trigger all these inflammatory things which goes to the brain and your gut flora is directly linked through this inflammasome to depression. But if you are a very healthy, physically speaking and you are depressed, factors from the central nervous system go to the immune system. They will start the inflammatory response and you get a disease from psychological stress factor. So you cannot separate mind and body in this. And there are interlinking elements, many of them…and some are more important than others, but the cortisol levels influencing the immune system. The immune system influencing the central nervous system. The central nervous system influencing etc. So you cannot oversimplify it but you can really say mental problems will give physical diseases, physical diseases will give mental problems, and vice versa.
- Rhonda: Absolutely. I 100% agree. You mentioned the interferon causing psychosis when they're using it to treat cancer, I wasn't aware of that study, very interesting.
- Pierre: That was long ago when I was active.
- Rhonda: Oh, yeah. Well, you know, there was a little more contemporary study done where people were injected with interferon gamma, which is pro-inflammatory cytokine, induces an immune response, cause depression or depressive symptoms. But what was fascinating in that study is that there is a group that was given the interferon, and there was a group that was given interferon and the marine omega-3 fatty acid, eicosapentaenoic acid, EPA, which is also anti-inflammatory. They were given EPA with the interferon and they did not get the symptoms of depression. And of course, many different ways in which inflammation is affecting the brain through, you know, this inflammasome which is very interesting, I don't know much about it. I know about the inflammasome, but I don't know about the connection between…directly how it's influencing the brain. I do know that a lot of these pro-inflammatory molecules and cytokines can get into the brain and also the vagal nerve connecting the gut to the brain. But, you know, it's absolutely true people that are obese, for example, have type 2 diabetes. Lots of different inflammatory-related diseases are much more likely to also have depression, and depression also leads to, you know, there's cancer incidents that's more common and a whole host of diseases. But I kind of wanted to circle back and ask you about the meditation and how the meditation can specifically influence the way you will respond to a stressful event when it occurs. Let's say, if someone practices meditation for 20 minutes a day, and then something very stressful happens in their life, you know, will they release as much cortisol as someone who doesn't meditate or is that known?
- Pierre: Well, there are a lot of studies on all type effects of meditation and also, as long as we stay in the immune system, you can measure this pro-inflammatory cytokines IL-6 or whatever, and you directly influence IL-6 by meditation, it goes down. But before we go into the molecules and the things, I think it's more important to say what the real effect of meditation is. Meditation is not something hocus pocus or whatever, but the point is this, that all the stimuli, from the outside world, come into our life via our senses: our nose, eyes, and ears, but are handled by the limbic system in the brain. That is what popularly is between the ears, it's in the middle. That is a very effective complicated part of the brain which is almost, well, unconscious. It's reacting immediately and it's where your feelings and all type of things are. The conscious part what they cut is saying that is why we are, we think so, therefore as you see the cortex, but the cortex is developed in a very short period of time in evolution from normal cortex to little neocortex in the human being and so the hardware is not so good. So the emotional development of the brain, the limbic system, was a very slow process in which hundreds of different areas work together. One is for pain and fear, the amygdala, and the other one is for this and that for that. And so you have this whole complex system and you have this cortex where your motor neurons are, that you can move your hands consciously etc. However, the thinking is beautiful, and we can do fantastic things with our conscious thinking but the way back from the cortex to our feelings from…so our cognitive functions and our emotional functions the hardware is not so good. So if somebody is afraid of a spider, you can talk whatever you want but they are afraid. You cannot control the fear of spiders, if you have it, with thinking or talking. It doesn't work, a tiny bit but not really. So what we see is that emotions and conscious thinking are separate areas in the brain where the consciousness part has concerning for the neurological anatomy not a proper influence on the emotions. The emotions will dominate the thinking and not the vice versa. Well, selling cars is based on that every ad is going for the emotions and then you will stop thinking. Okay, but what is now the trick of meditation? Meditation is that you will come back to the activity of your limbic system, so where your emotions are, and disconnect it with thinking. And is disconnecting with thinking is incredibly important because the thinking almost always disturbs the balance of the emotions. If you think that tomorrow is a problem, in the amygdala there will be a reaction and the whole neural system will get fear and anxiety or whatever. However, there is no tomorrow, you are here. Perhaps tomorrow is not. It is your only invention that tomorrow will be devastating. You will make it devastating. Perhaps it's true but you can only say so if tomorrow becomes today, so we sit here. If we focus on our emotions here at this very moment and don't think what will happen or what has happened, then you've got the normal balance of all the neurotransmitters signaling inside the limbic system, and because it's such an old system, it's rather harmonious. You can lean on it. It's okay. But if we think about tomorrow, you get a disturbance. And the only thing what meditation is doing is not changing your life. It doesn't make it better but this tomorrow, and this space-time feeling but also the ego-feeling, I am afraid…if you disconnect that and that is a very simple way to do that because the connection between emotions and consciousness are rather weak. So multitasking they say you can do but how many things you really can multitask? If there is a lot of this, and that, and that, and that, you can only handle little thing. So if you concentrate on something which is not thinking, for example, breathing, you concentrate your airflow in the nose, calmed, out, and really concentrate on it, you don't have much base of solving a mathematical problem anymore because…and then if you concentrate where the airflow goes through the...and just close your eyes, and then have a little music, and then all of a sudden you stop thinking, and you stop losing the time-space feeling. You are…you get a function of being instead of going off whatever, and that is what meditation is doing. But as soon as this limbic system comes into the harmonious things, it really controls a lot of stress responses, a lot of hormones, a lot of cortisol, a lot of whatever, but also transcription factors including NF-kB. So if you meditate, your immune system is different. If you meditate, your stress response is different. And if you meditate regularly, then you have a very fundamental change, a positive one, which really becomes constant. So there are studies in which they measure activity in the left prefrontal cortex, that is this part of the brain. Normally, it's a 50-50 activity left and right. But with meditation, it shifts a little bit to the left, and the left part is more the harmonious, well-being, feeling okay instead of the troublesome on the right. And this shift and you'll make new neuronal connections, new nerve cells are being made, gives you a really constant feeling of emotional stability. And you can measure the number of brain activities at different levels after seven weeks of meditation and you'll see a fantastic change. It'd be positive.
- Rhonda: Wow. Yeah. I remember reading a study where people that had never meditated before were trained to meditate for eight weeks and they had changed, like, five regions of their brain. They had decreased the amygdala which is part of the limbic system. They decreased the activity of it and increased parts of the prefrontal cortex. Perhaps it was the left region, I don't remember.
- Pierre: Oh, that's hard details, but…
- Rhonda: Yeah.
- Pierre: No, it's true and so the amygdala, which is part of the fear, and pain, and trouble sensing organ, it's really changing in size and function.
- Rhonda: And you're saying that doing this long-term meditation has lasting effects and so then one would predict that then, you know, not only are you not going to continue to ruminate on the future the things you have to do. I mean, to a certain extent obviously setting goals and having goals you want to achieve is a good thing but when it becomes so overwhelming…
- Pierre: It becomes obsessive and 24/7, and you're absolutely wrong. A goal is fantastic but at this very moment, we are sitting here, I have zero goals. Only to be here, to enjoy your presence, to talk about the things I like, look at the flowers, that is my life now.
- Rhonda: Do you practice meditation?
- Pierre: Yes.
- Rhonda: Do you do it on a daily basis?
- Pierre: Yes.
- Rhonda: How long?
- Pierre: Well, about 20 minutes. I made some music compositions of a full type of meditative things and of about 20 minutes. And so, when the music stops, I stop. You always go along with it also five minutes later than you…oh, yeah.
- Rhonda: And does your meditation focus on the breathing aspects? - Well, the point is that with meditation a lot of people think that it is you really have to go into a zen mood, and your third eye, and chakra, this or the whatever, that's absolutely not necessary. Everybody should just do whatever…you do not have to sit in the lotus position. If you feel like it, you do it but you can walk, you can sit, you can lay down. And the only thing is you'll have to concentrate on something by which you do not think. I had very heavy times emotionally, by which I had a lot of stress. I turned gray in three months and from a slim boy, I changed into a fat belly person within half a year, with the same eating. So my whole metabolism was changed by stress which is called the metabolic syndrome. I didn't know exactly what it is but in those days, it was difficult to get grip on your life, people dying, and little children, and problems, and really heavy. So I went to a place which…if you have time you should do that. It's called the Kröller-Müller Museum in Holland, it is a national park in which there are hundreds of bikes for free. So you go in, you take a bike, you go through the forest, the fields, [inaudible] fields. You see deer walking. And then after this nature experience, you come in the most beautiful museum where Van Gogh is hanging, and beautiful Mondrian and whatever. And in those days when I really had some trouble, I went there, sitting in front of a picture, which I liked, and just looking at the picture for 20 minutes and then I could cope with it again. So, in very stressful situations, you really have to meditate. Now I have a happy life and I still like to meditate but the urge of it, especially if you are in trouble, is incredibly big you get a lot of power out of it.
- Rhonda: Yeah.
- Pierre: And how you do it, if you look at the picture, and look at nature, look into floating water, fireplace…
- Rhonda: Yeah. You called it my meditation moods. I've been wanting to meditate again and practice it on a daily basis. It's one part of my life that I'm really actively trying to incorporate something new, and I used to when I lived in San Diego many years ago before, about 10 years ago. I'm from San Diego but I grew up, you know, surfing and I was able to meditate while I was sitting on my surfboard looking at the waves coming in because I didn't care about anything else, because all I needed to think about was right now that wave coming. One, so it doesn't wipe me out and make me drowned, and two, because I wanted to catch one and have this fun ride in.
- Pierre: Yeah, so meditation is just coming to the current situation now, no time, just be. And that can be on a wave board, that can be on a bicycle, that can be on the top of a mountain, that can be anywhere, it can be in a museum, and it can…so there is not a strict rule in meditation and a lot of people make a lot of fuss about it how it should be, but it is stop thinking, start being.
- Rhonda: I really like that definition. I really like that definition of it. You were mentioning, when you're talking about the meditation and the breathing techniques, and it reminded me of some of Wim Hof's methods of, you know, breathing and there's some cold shock. I've been very interested in the effects of good types of stress on the body. So we've been talking about bad stress, chronic stress, but there's also youth stress, good stress.
- Pierre: Oh, absolutely.
- Rhonda: So maybe we could dive in a little bit because I know that you're very interested in some of the mechanisms and the science behind how cold and how these certain breathing techniques can change different hormones, you know, the endocrine system, immune system.
- Pierre: Oh, it changes a lot. The point is that first of all, Wim Hof is a very charming man with a lot of stamina and a lot of charisma, and he really know how to talk to people, to convince them that they have to do what they think they should not do, like, going into an ice bath. Everyone who just thinks, "I'm going into the ice," it's a little strange but he convinces, "Please do it." And the weird thing is that people like it, and get a positive effect, and they say, "Hey, how? Why?" Well, if you go unprepared into ice-cold water, zero degrees Celsius or whatever it's in Fahrenheit, you'll have a lot of pain. You'll get a lot of trouble, a lot of anxiety. It is terrible, don't do it. However, Wim is training people and they do it and they like it. What is the training? The training is…it has two components. First of all, a meditation type of things, so you really have to come at ease, and really try to get rid of all the surrounding stress, and then do this breathing technique. The breathing technique itself, you do about 20 minutes, it's a type of meditation in itself, but also a breathing technique. So why not have a double-edged sword? And this breathing technique, he really specialized in such a way that you change the content of carbon dioxide in your blood and you lower it. Carbon dioxide is acidic in water and if it's out of the bloodstream and the tissue or at least less then the pH is less acidic but more alkaline. In the normal situation the acid-alkaline balance, which is called pH, the strict balance is pH 7 and our body is 7.4, that is our regular situation. In the stomach, it's very acidic and intense, so there is a little difference in the body but let's say 7.4, that is our body equivalence of alkaline and acid. By this breathing technique and pumping out a lot of carbon dioxide, and having periods in not breathing, heavy breathing, and, well, he can tell people how to do it, you change your pH. And now comes a little trick, that in his training, that type of breathing raises the pH sometimes to 7.7, 7.8 and for biology that is a lot.
- Rhonda: Yeah, and this is published, and this...
- Pierre: And it is published. It's scientifically measured and whatever but we go now back to this terrible cold. If you go, you'll always have an ID of the temperature of your surrounding and for that, you have a whole family of receptors, thermal sensors, and there's a whole family. And for each temperature range you have a separate set of family members who are telling you what the temperature is. So if it is above 50 degrees Celsius, rather hot, you will burn. So if you touch something which is very hot, yah, immediately. You can't react differently, you can't keep it on and say, "Mmm, it smells." You don't. But if it is 37 degrees you say, "Mmh, nice." And so, for each temperature range, is a family of temperature sensors which are proteins, which are doing things, and they do not only measure temperature but also mechanical stress. And so if you feel something, this touch, you feel it's metal, it's colder, it's this, that is this whole family of things. One of the family members is effective beyond 17, Celsius, so cold. And because our body temperature doesn't want to be lowered, this cold surrounding is aggressive, we should avoid it. So you get a active stress response, "Get out of the cold and now." That is this receptor telling you. However, he is not alone because if you go in this cold water, it's painful. It's argh, it hurts, and you get a very strong anxiety response and, "I have to get out, ooh, aah," and that's so dominating that it really can cause you a lot of trouble, heart attack. So if you go into ice-cold water, you are really in trouble, the body is telling you that. However, pain, anxiety, and temperature, they are all combined in this skinny-dipping in the cold water. But biologically, they are separate units. And normally, the thermal sensor tells you it's cold and his job, of this thermal sensor, is telling you, "Hey, switch on the heat. Burn your brown fat. Generate calories like hell. Make energy, energy, energy, and temperature should not drop. So burn everything we have to keep your body temperature constant." That is the function of this receptor, but it is coupled to pain receptor. So you cannot just sit in the water and say, "Oh, nice. I'm changing my metabolism," you're in pain. But now we come to the pain receptor, which is another one, and there's also family of receptors and the trichocyst. It is a protein in the membrane and as a single protein it's doing nothing. But if three of these proteins combine into a trimer, so three proteins together in a certain conformation, then they will signal, and that signal is pain. Normal situation, like we are sitting here, let us say that 5% of our pain receptors are in an active state. So if I do this, well, I feel it but it doesn't hurt. However, if I have a big wound here and I do this, then we got trouble with the neighbors because I'd shout too loud, because then there's now 5% is on but everything is in the trimer position and generates a pain signal. So a pain signal has a volume switch, it can be low, it can be high but it is dependent on a lot of things, also inflammation, but also of pH. And at pH 7.7, the pain receptor is a monomer.
- Rhonda: So it's off.
- Pierre: It's out, so no pain, but the same receptor is also in the amygdalae giving fear and pain, but also in the spinal cord and all over your body. So all of a sudden, you don't feel pain, don't feel anxiety but the temperature receptor, which normally gives you pain and such, is doing now the job by himself only. Generates an incredible amount of adrenaline, gives you energy you won't believe, burns your fat like hell, and Wim Hof is able to sit for two hours, or 1 hour and 58 minutes, or something like that, to be precise, in ice-cold water without is a significant change in body temperature. Why? Because his thermal sensor is heating up and burning the brown fat, "Come on, boys," and afterwards, you're going change the white fat into brown fat, which is…the brown feathers in this area of your body and so you regenerate that. And so if you come into the cold, you get a fantastic amount of energy, you get this strong stress response without pain and fear, and then you can walk up a mountain in a short time.
- Rhonda: What's the name of the thermal receptor, do you know? [inaudible]
- Pierre: Yes, that is transient potential the TP...
- Rhonda: Oh, one of the TPV or RV?
- Pierre: Yeah, the TPV.
- Rhonda: Yeah, I know, it okay.
- Pierre: That's a whole family. I don't know, I always forget the name.
- Rhonda: So it's responding to the cold and…
- Pierre: And there are also receptors which is responding to heat and whatever.
- Rhonda: Right, yeah, I have so many questions, but one is the importance between coupling the breathing technique, which then decreases the carbon dioxide in the blood, and as a consequence raises…
- Pierre: Switches off the pain.
- Rhonda: Right, but it raises the blood pH to a little more alkaline, which by the way is not easy to do. Usually you can't just raise your pH in your blood but breathing techniques obviously it's working and that's been published, and that then switches off, the pain receptor, which needs to be trimerized. So it's now not able to do that because the pH is too high. So that's uncoupling now the pain receptor from the thermal receptor, which somehow, I know that UCP1, the uncoupling protein, which norepinephrine is called, releases norepinephrine and that activates uncoupling protein 1, which then uncouples your mitochondria. So your mitochondria usually are sensing, you know, the electrochemical gradient and when that becomes uncoupled, the mitochondria go, "Oh my God, I need to make energy." So they're basically burning all the energy, like you said, to generate heat and to also make energy.
- Pierre: ATP.
- Rhonda: ATP, so you end up burning fat like you said, and that this is all really cool because I was, for one, changing the pH of the blood, I was a little skeptical of that until I actually read the study and how, you know, carbon dioxide in the blood can do that. I think there's a term for it like "respiratory alkalosis" or something like that.
- Pierre: Yeah. You can name it whatever yeah, but the point is it's functional.
- Rhonda: Yeah, yeah. Have you tried any of the breathing techniques?
- Pierre: Well, no. Not in that sense but I have a little story. I know a guy who was doing this for the first time and he didn't take this breathing so serious. So I said, "Wow," I said, "Okay," and in the meantime wandering around and then hopped into the cold water that was extremely unpleasant. And then the second time, he really was aware. "Hey, I should take it serious," his breathing and then he had no trouble. So this is control in itself. So the breathing technique is really necessary to prepare for this cold and this cold will, after uncoupling of all the other effects, will have the positive stress response in metabolism, adrenaline, and etc.
- Rhonda: Without the pain?
- Pierre: Without the pain.
- Rhonda: So you can withstand the cold for longer.
- Pierre: Yes, yes.
- Rhonda: I've been very interested in the effects of temperature on the human physiology. I've talked a lot about the sauna and how the sauna is a good hormetic stress, it activates heat shock proteins which have a variety of positive effects. It also changes brain function as well. It changes the opioid system, endorphins, makes you more sensitive to them, so I became very interested in that. But cold more recently I became interested because there was a paper that was published in Nature last January, where researchers took mice and exposed them to about 4 degrees Celsius for 45 minutes, cased their core body temperature, so unlike Wim, their core body temperature dropped from, you know, 98.6 to about 65 degrees Fahrenheit, so very in hypothermia almost but what was very interesting is that the cold shock…there's a whole class of proteins called cold shock proteins that are activated by the cold and one of them specifically is in the brain and at the dendritic spine region of neurons, and it increases dramatically in the cold. And what's really interesting is that what the function of this protein is, is RBM3, is to regrow lost synapses. So hibernating animals, bears, for example, you know, some hibernating rodents, when they go into hibernation, they lose a significant amount of their synapses. I forgot, like, 30% or 40% or something like that. But when they come out of the hibernation, they regrow the synapses that they lost, which has huge implications, of course, for neurodegenerative disease, brain aging in general. So this is kind of what instigated the study because they found that what happens is upon hibernation they have this huge increase in this gene brain, RBM3, and that regulates re-growing the synapses. So that's when I became very interested in the cold, and then started reading about it, and all the effects on the endocrine system, or the nephron, burning of the metabolism. And now I'm very interested in some of the techniques that Wim's doing and the science behind what's going on. So I'm really excited to have you talk about it. But you wanted to talk about a couple of other interesting effects on the same family of receptors?
- Pierre: Yes, and then we don't go so bizarre as in the heat, or in the cold, or whatever but we just go to this family of receptors, which, the family name is TRP and then you have uncle M and aunty V and so the whole family is RTPV1 or M, etc. The question is that you have a measurement of each type of temperature by each family member, but now the question is why in the tropics people eat so spicy? A lot of hot peppers? The point is that a compound with a beautiful name in the red pepper, is binding to one of these family members which senses heat, not the extreme heat, not 50, but so around 40 degrees Celsius or so, around 100 Fahrenheit. What it's doing that pepper stimulates this receptor, so the receptor is saying, "You are too hot."
- Rhonda: Capsaicin, is that specifically what you mean?
- Pierre: Yes. That is the name but the receptor senses, "Hey, it's hot," and is reducing your body temperature to neutralize the effect of the outside temperature. So you lower your body temperature by spicy food. But if you're in the tropics, you will be heated up by the sun. And if I go, as a westerner not, well, I like spicy food, but I haven't done it, and I'm sweating and then you have this really white man's burden in the tropics. You know that? Well, sorry. But, yes, if you have spicy food, you lower your body temperature, the sun is raising it but to the normal level you want. You don't have to sweat to get rid of the extra temperature because you set your thermostat lower, so that is what the hot pepper is doing. Now the other way, the cold receptor, if you have a cold, you have all these type of things that you wrap your breast with menthol, or eucalyptus, etc. The point is that compounds from these plants binds to the cold receptor. So as soon as you wrap in your chest, it feels cold, because you sense cold, like the pepper, you feel hot, but that temperature receptor is not only making more energy and whatever but changing the blood flow. So the blood flow increases in this area where you put menthol or eucalyptus and you generate heat. So first it's cold and then it really gets you warm because you pump up the fire by this plant extract. And the trick with cold, why it's so good, and very simple and you don't need further medication because you can do it yourself is what is a common cold? If I'm for 10 minutes outside and unprotected and if you call tomorrow, I'm ill. How's it possible? The point is that this illness is already there, but I can cope with it. So you have a rhinovirus or whatever cause of my common cold and my immune system is coping with it. So let's say I have 100 units of immunity which have to fight to 80 units of a viral or whatever infection. So the immune system dominates the infectious agent and this is a continuous process. Now I go 10 minutes into the cold, the blood flow changes because the cold gives vasoconstriction, so you have less blood. So my 100 units per time can't reach that place and become 75. "Hey," says the virus, puff, and because that goes very fast, half a day or a day later, you have a common cold. So if you now put on some menthol or eucalyptus, by increasing the blood flow and giving a lot of energy, and raising the temperature, then the immune system comes back with much more units per time than the 100 and can cope with it, and so therefore these simple things from plants have a very strong effect.
- Rhonda: I never knew there was actually any validity behind putting menthol or eucalyptus oil.
- Pierre: But you feel cold, ah, cold, and puh, warm, and aah.
- Rhonda: I don't remember, like, you know, it's been so long. I was a kid. I think my mom put it on my chest when I was sick but, you know, just it's been decades since I've done it, so I don't remember feeling warm.
- Pierre: Well, you can do it now.
- Rhonda: I don't know, maybe. Yeah, kind of a burning feeling.
- Pierre: Yeah.
- Rhonda: So, okay, let me ask you this then why when you go out in the cold don't you have the same response? So, obviously, there's vasoconstriction occurring, how come there's not a response then also similarly to that increase the blood flow after or is there?
- Pierre: Well, the point is that if you go into the real cold, like Wim is doing, you switch on full-blown, all the engines to pump up the fire. But if I walk out here and I go from room temperature to a little lower, I don't have this family member which is reacting at minus 17. My throat is getting minus 24. So I don't activate the receptor Wim is using which pumps up the whole thing.
- Rhonda: Oh, I see.
- Pierre: And I do with menthol, I go to the low temperature receptor, which I pump up into activity. So a decrease in temperature from 37 to 28, so in your fingers, it's going to be 28 or so. That doesn't switch on the receptor which Wim is using in the cold bath, so you have to go much further. So if you go into the ice bath, you immediately trigger the subsequent response. If you just walk outside and you are just chilly or whatever, you do not have the proper family member of the receptor being activated.
- Rhonda: So we need to also be happy when we go outside, when it's cold, because being happy also regulates our response to this virus and whether or not we're going to fight it off?
- Pierre: Hopefully, yeah, and so it is really important to have a positive view on life. And there are a lot of studies of people who are optimistic or pessimistic and that really makes a difference statistically in how they cope with diseases, life expectancy, the number of days without disease, that is directly related to a positive or a negative attitude to life.
- Rhonda: Smell the flowers.
- Pierre: Beautiful.
- Rhonda: And look at them.
- Pierre: Oh, yeah, but if we talk about smell, what an effect that has?
- Rhonda: Oh, yeah.
- Pierre: You know, falling in love is based on smell.
- Rhonda: I didn't know that.
- Pierre: You didn't?
- Rhonda: No.
- Pierre: Oh, wow.
- Rhonda: Pheromones?
- Pierre: No. No, no, no. The point is that falling in love always has to do with sexuality and procreation from nature's side, let's say it that way. So if somebody wants a partner and wants children, they want to know if they are okay and if the genes are really properly fitting. A lot of genes are the same, so a gene for insulin-making is the same in all people but are also genes which are extremely different, polymorphic, and so many forms, polymorphic, which is especially in the immune system. Each individual has a different immune system. Each has an individual set. For that complexity, you have proteins which are the major histocompatibility complex MHC or HLA transportation antigens etc., they differ from person to person. And I am, for example, have a immunological setting, say, that I have no trouble with malaria, no trouble with yellow fever, but I cannot handle influenza. Now I meet…will encounter a woman who also can handle yellow fever, also malaria, and cannot cope with influenza. If we mate, that is a pity, that a child has nothing new. So I have to find someone who copes with influenza and I give a damn about yellow fever because that are my genes, so I want to know the gene passport. Animals are doing that, if you walk your dog they immediately sniff and the olfactory system in the nose is extremely fantastic and is highly polymorphic. So everybody has an odor smell perception, therefore you have all this racist things that the whole group of people smell. Well, no, my perception is genetically different from theirs, so I'm stinking for them and vice versa because each nose is different. Okay, back to the immunology. It is important to give the child as many defense possibilities as possible. For mathematical reasons, you cannot have a total immune system fighting everything because then you are included, and that includes autoimmunity. So the immune system is defense against the outside minus myself, and I should not turn to myself. But to make a long story short, these vital molecules, which are different in each individual, are being chopped up in little peptides and secreted by all type of body fluids which are in the armpits, and between the legs, and in all the sexual organs, and sweat, there they are secreted. And as soon as you smell them, you know, how the immune system of the other person is. And so, therefore, you come into the area that smell is an important thing for a genetic selection with whom you'll have to mate. Certain type of fish, all fish, doing that swimming together, exchanging smell. If that's okay then the wife…the woman puts her eggs down and can be fertilized by the man. If not, she's not putting any eggs down, he has to go. Dogs, and people, and mice, you name it, all type of studies. So therefore, smell is important and then you come to the thing and I don't know... The American population is always, you can't talk about things too much but let's talk about pubic hair. That's not there for protection or worm or whatever, holy bolly, it's warm enough. And the children don't have it because they are not sexually active. So as soon as you become sexually active, you have to distribute your smell, your little molecules, as much as possible. So you need a big surface. So therefore, in the areas where a lot of these molecules are secreted, you've got a lot of hair to increase the surface and to select. And it is impossible to make love from somebody whose smell you don't like. That doesn't mean that there is a strong smell, it can be stinky like hell, but you still like it. And if you don't like it, forget about it.
- Rhonda: That is really fascinating. First of all, I had no idea that you secreted the immuno-histocompatibility compounds.
- Pierre: You chopped it up. You chop them as little peptides.
- Rhonda: And you secrete them in your sweat and other bodily fluids.
- Pierre: Oh, I think we can go for a long time.
- Rhonda: I know. This has been a very interesting conversation, Pierre. I really, really enjoyed talking with you. We have a lot of common interests. If people are more interested in hearing or learning more about what you are researching, or the talks you give, or anything about you, is there a place where they can find you on the interwebs?
- Pierre: Well, I do have a website which is the first three Ws and then Meditation to Go, but in society I do not actively support so much, it's still okay. I'm now working at another one which will be pierrecapel.nl and there is my activity on meditation, but also on science, but also how you incorporate quantum mechanics into biology, and things like that. But that is now under construction so, please wait. But for your audience, I really want to say, why don't you take half an hour for yourself per day? What is so important in the outside world that you keep on running, "Oh, I have to do this. Oh, and..." Where are you in this situation? Please, make this choice for yourself, half an hour a day keeps more than only the doctor away.
Adenosine Triphosphate (ATP)
An energy-carrying molecule present in all cells. ATP fuels cellular processes, including biosynthetic reactions, motility, and cell division by transferring one or more of its phosphate groups to another molecule (a process called phosphorylation).
Two almond-shaped groups of nuclei located deep and medially within the temporal lobes of the brain in complex vertebrates, including humans. Shown in research to perform a primary role in the processing of memory, decision-making, and emotional reactions, the amygdalae are considered part of the limbic system.
Brown adipose tissues (BAT)
One of two types of fat, or adipose, tissue (the other being white adipose tissue, or white fat) found in mammals. The primary function of brown adipose tissue is to generate body heat. In contrast to white adipocytes (fat cells), which contain a single lipid droplet, brown adipocytes contain numerous smaller droplets and a much higher number of mitochondria, which make it brown. Brown fat also contains more capillaries than white fat, since it has a greater need for oxygen than most tissues.
Emotional pressure suffered for a prolonged period over which an individual perceives he or she has no control. It involves an endocrine system response in which occurs a release of corticosteroids.
Recurring naturally on a twenty-four-hour cycle, even in the absence of light fluctuations. Every cell in the human body follows a circadian rhythm, which governs when a cell is most metabolically active, when hormones are produced, when repair processes are activated, and more.
Cold shock proteins
Proteins that preserve cell viability at low temperatures by binding to nucleic acids and, subsequently, controlling gene expression. Cold shock proteins have what is known as a "cold-shock domain," a sequence of amino acids whose expression is associated with cold and is thought to help cells survive in lower than optimal temperatures.
A steroid hormone that participates in the body’s stress response. Cortisol is a glucocorticoid hormone produced in humans by the adrenal gland. It is released in response to stress and low blood glucose. Chronic elevated cortisol is associated with accelerated aging. It may damage the hippocampus and impair hippocampus-dependent learning and memory in humans.
A broad category of small proteins (~5-20 kDa) that are important in cell signaling. Cytokines are short-lived proteins that are released by cells to regulate the function of other cells. Sources of cytokines include macrophages, B lymphocytes, mast cells, endothelial cells, fibroblasts, and various stromal cells. Types of cytokines include chemokines, interferons, interleukins, lymphokines, and tumor necrosis factor.
A technique that enables scientists to measure the expression levels of thousands of genes simultaneously in order to study the effects of certain treatments, diseases, and developmental stages on gene expression. Also used for genotyping and sometimes referred to as a "DNA chip" or a "biochip."
System of glands regulating the body through the production of hormones. The endocrine system's effects are slow to initiate, and prolonged in their response, lasting from a few hours up to weeks. In contrast, the nervous system sends information very quickly, and responses are generally short lived.
Beneficial stress that can be psychological, physical (e.g. exercise), or biochemical (hormesis) in nature.
A component of the innate immune system. The inflammasome is expressed in the myeloid cells and promotes the maturation of the pro-inflammatory cytokines IL-1B and IL-18. It is responsible for activation of inflammatory processes.
A group of signaling proteins made and released by host cells in response to the presence of several pathogens, such as viruses, bacteria, parasites, and also tumor cells. In a typical scenario, a virus-infected cell will release interferons causing nearby cells to heighten their anti-viral defenses. Interferons are named for their ability to "interfere" with viral replication, and belong to a larger group of proteins involved in facilitating communication between cells for purposes of immune defense called "cytokines".
Interleukin 6 (IL-6)
A pro-inflammatory cytokine that plays an important role as a mediator of fever and the acute-phase response. IL-6 is rapidly induced in the context of infection, autoimmunity, or cancer and is produced by almost all stromal and immune cells. Many central homeostatic processes and immunological processes are influenced by IL-6, including the acute-phase response, glucose metabolism, hematopoiesis, regulation of the neuroendocrine system, hyperthermia, fatigue, and loss of appetite. IL-6 also plays a role as an anti-inflammatory cytokine through inhibition of TNF-alpha and IL-1 and activation of IL-1ra and IL-10.
Supports a variety of functions including epinephrine flow, emotion, behavior, motivation, long-term memory, and olfaction. Emotional life is largely housed in the limbic system, and it has a great del to do with the formation of memories.
Major histocompatibility complex (MHC)
A set of cell surface molecules encoded by a large gene family which controls a major part of the immune system in all vertebrates by determining histocompatibility. The main function of the MHC molecules is to bind to peptide fragments derived from pathogens and display them on the cell surface for recognition by the appropriate T-cells.
Associated with the risk of developing cardiovascular disease and diabetes, and defined as a clustering of at least three of five of the following medical conditions: abdominal (central) obesity, elevated blood pressure, elevated fasting plasma glucose, high serum triglycerides, and low high-density lipoprotein (HDL) levels. Some studies have shown the prevalence in the USA to be an estimated 34% of the adult population.
A rapid-acting transcription factor that responds to harmful cellular stimuli, such as reactive oxygen species, IL-1B, bacterial endotoxin (lipopolysaccharide or "LPS"), ionizing radiation, and oxidized LDL. Incorrect regulation of NF-kB has been linked to cancer, inflammatory and autoimmune diseases, septic shock, viral infection, and improper immune development. Several viruses, including the AIDS virus HIV, have binding sites for NF-kB. In the case of HIV, the presence of NF-kB is believed to be involved in switching the virus from a latent to an active state.
A substance produced in the brain. Norepinephrine acts as a hormone and neurotransmitter and is best known for its role in the body’s “fight or flight” response to stress. Its role as a neurotransmitter has been exploited as a molecular target for a class of drugs known as norepinephrine reuptake inhibitors, which were developed for the purpose of treating disorders ranging from ADHD to narcolepsy and depression. Norepinephrine also plays a role in converting white adipose tissue into brown adipose tissue via an uncoupling protein 1 (UCP-1) mediated mechanism.
RBM3 (RNA binding motif 3)
A cold-shock protein that is induced by exposure to low temperatures. RMB3 is induced in mammals during hibernation. In a cell model of Parkinson's disease, RBM3 provided neuroprotection, suggesting that RBM3 induction may be a suitable strategy for Parkinson's disease therapy.(https://www.frontiersin.org/articles/10.3389/fnins.2018.00298/full)
Increased respiration elevates the blood pH beyond the normal range (7.35-7.45) with a concurrent reduction in arterial levels of carbon dioxide. This condition is one of the four basic categories of disruption of acid-base homeostasis.
Single nucleotide polymorphism (SNP)
A change in one nucleotide DNA sequence in a gene that may or may not alter the function of the gene. SNPs, commonly called "snips," can affect phenotype such as hair and eye color, but they can also affect a person's disease risk, absorption and metabolism of nutrients, and much more. SNPs differ from mutations in terms of their frequency within a population: SNPs are detectable in >1 % of the population, while mutations are detectable in <1 %.
A protein that binds to specific DNA sequences, thereby controlling the rate of transcription of genetic information from DNA to messenger RNA. A defining feature of transcription factors is that they contain one or more DNA-binding domains (DBDs), which attach to specific sequences of DNA adjacent to the genes that they regulate.
Uncoupling protein 1 (UCP1)
A protein found in the mitochondria of brown adipose tissue, previously known as thermogenin. UCP1 is expressed only in brown adipose tissue, a specialized tissue which functions to produce heat via non-shivering thermogenesis.
Vascular Endothelial Growth Factor (VEGF)
Originally known as vascular permeability factor (VPF). VEGF's normal function is to create new blood vessels during embryonic development, after injury, in muscle following exercise, and new vessels (collateral circulation) to bypass blocked vessels. When VEGF is overexpressed, it can contribute to disease. Solid cancers cannot grow beyond a limited size without an adequate blood supply, and cancers that can express VEGF are able to grow and metastasize.
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