CytoLED: Hello Vlad, could you introduce yourself and tell us how you first got interested in Red Light Therapy?

Vladimir Heiskanen: I’m Vladimir Heiskanen, a dental student from the University of Helsinki in Finland; and now I’ve been studying dentistry for five years, but even a couple of years before that I used to read a lot of research related to medicine, and nutrition and health, and I also started a health blog which is nowadays quite popular in my country and followed by; even like, many professors and scientists and at first, I read a lot of research about like, diets and dietary supplements, and drugs and lifestyle interventions including like, those targeting circadian rhythm and, stuff like that but then, six years ago, I noticed that some people were writing about red light having effects on animals and humans and, how the cells work, especially like, there were some people claiming that, red light could improve the energy metabolism in cells, so I tried to find some evidence from that in pop med and surprisingly there were a lot of studies on that topic so, that’s how I originally got interested in this red light therapy or, as most researchers call it, photobiomodulation.

CytoLED: You’re well known online for creating a, database of red light therapy research, how did that come about?

Vladimir Heiskanen: Yeah, at first when I looked at the research related to red light therapy, I noticed that there is like, more than fifty different keywords for this one treatment, so if you used this search for the research articles, you could write, low-level laser therapy, or photobiomodulation, or soft laser or, light emitting diode therapy or, visible light irradiation so it’s kind of very clustered. If you want to find all of the papers about using red light for, for example of treating brain disease, you would have to find all these dozens of different keywords, so I was thinking that if I could make a, spreadsheet, it would make this data search much more convenient, and; in the beginning I thought that there was actually something like maybe two-thousand papers on the topic, so I thought that if I spent one or two years on the project, it would be finished, but then like nowadays the database or the spreadsheet has more than four-thousand studies and it was a really hard thing to finish, taking a lot of time, but that’s how I ended up doing it and nowadays it’s the best, like the best source for PBM research in the world; I think, because if you want to find any studies on any indication then, that’s the clearly fastest resource for that.

CytoLED: Can you tell us a bit more about the database, and where to find it?

Vladimir Heiskanen: The easiest way to find the database is to write the address, which is www.bitly.com/PBM-database. And the PBM should be with capital letters, but I guess you can include the link in the description of this podcast? And, basically the database nowadays, it has four different tabs, the first one is the most important and it has the collection of more than four-thousand studies, about photobiomodulation or red-light therapy research, and it’s separated by categories; so for example, if you are interested in applications of red-light therapy in, oral diseases or, in dentistry, there is this oral category, and there is a separate category for pain, separate category for joints, separate category for mechanisms, and so on. And from there you can like, for each study, the database also tells what was the journal that published it, when was the study published, where are the researchers from, and what are their main results, and there is some other information as well.
Then, in the database there are some other tabs, like the one listing all of the ongoing trials that have been registered to this clinical trials database. There you can see that nowadays there are almost one-hundred and fifty studies that are, being done all around the world with BPM devices. And then, there is also a tab in this database that is about, different websites related to the subject, like there you can find links to blog articles, and books, and news stories, and researcher interviews.

CytoLED: What do you consider your most promising findings that you discovered, while looking through the research to make your database?

Vladimir Heiskanen: I think the most interesting thing is that, there is so much research on PBM, and for example; if we look at the human data, there are like more than six-hundred randomised studies, which is a pretty huge amount of like, clinical research done. If you look at some other treatments or supplements, very few have been studied so intensively, and there were many meta-findings like approximately seventy different countries have published research related to this topic, and that there are something like seven-hundred different medical journals that have published papers related to photobiomodulation, and there are like, a lot of high quality journals as well that have published research related to this topic, as before I started reading about photobiomodulation I thought it’s a topic that hasn’t been studied, a topic that most scientists would find not very passable, but at least many papers have been published in very high-impact journals, like The Lancet or, PNAS or circulation or blood, or neurology and such high-impact journals, and the good news is also that, each year; more papers are being published so, this is kind of a hot topic in the scientific field right now.

CytoLED: What do you consider to be the most promising area of red-light therapy research?

Vladimir Heiskanen: One interest thing is that there are like scientific fields called for example, gerontology, which focuses on these findings that many age-related diseases have the same mechanisms. Like, if you compare heart disease, or diabetes, or eye diseases, or hair loss and many other things that are common when you get old, these very different diseases have similar underlying mechanisms and, so far it seems that red-light therapy probably improves some basic mechanisms that are very common in many different chronic diseases. If we look at the animal studies, red-light therapy has been beneficial for more than one-hundred different diseases, and in humans it has been investigated for dozens of different health problems, and there are some indications that are maybe a little bit more promising than the others.
Nowadays a lot of trials have been started that, are targeted to some brain diseases, especially in America for example, if we look at the Massachusetts General Hospital they have started some clinical trials on autism and depression, and anxiety, and traumatic brain injury, and many diseases that are related to brain function, and that’s probably like because for example, in Harvard University, they published recently a pilot trial, which showed very good results for the treatment of depression, and it’s a very common health problem, and so far the antidepressants haven’t been that effective. So I guess, one indication that I’m very interested in here is depression because, if the upcoming studies show beneficial results, that’s going to affect many people because; red-light therapy would be a treatment that is very easy to give to people, you don’t need a drug, you need just a proper light source, and then there is some very promising study on some diseases related to mouth; for example, this aphthous stomatitis, or cancer treatment related mouth inflammation.
Then like, there are many researchers that are very interested in the effect of red light on the eyes, because many old people get this age-related macular degeneration, and there are some pilot studies that show that, red light could improve visual acuity, contrast sensitivity, and also to decrease this harmful pigment called drusen that you find in the eyes of old people with this age-related macular degeneration. So right now, there is this one ongoing study that is going to address the possible beneficial effects on eye function, but basically there are a lot of potential indications that could possibly be treated with the photobiomodulation, and if we look at the existing human evidence, even if we only look at the systematic reviews there are like a lot of positive results for very different issues, like many painful conditions; like neck pain, or back pain, or some other diseases like hair loss, and in Brazil they also studied a lot for exercise performance because so far there have been many studies showing that red light could improve exercise performance, and maybe also make the recovery from exercise faster.

CytoLED: We notice that many of the studies on red light therapy are done in Brazil, why do you think this is?

Vladimir Heiskanen: First, Brazil is a very large country, so I guess they contribute to many different topics. I don’t really know; I don’t have any good reasons for that. I often ask other researchers what they think about Brazil, because it’s a country that I don’t know much about, and they kind of publish a lot of interesting papers. I have had this idea that maybe Brazil could be like a low-income country that produces low-quality research, but basically almost all of the researchers I have asked this question, they say that all of the research coming from Brazil is good quality and that they respect the country, so at least nowadays I view the country in a very positive way. And I was also going to say that, if we look at the photobiomodulation research coming from Brazil, the research is coming from many different cities and states within that country, or are they called provinces? Like, the whole country of Brazil, it’s kind of separated to many different parts and they have a lot of different cities that publish research about photobiomodulation so, I guess like within that country, the interest into photobiomodulation has spread very widely.

CytoLED: What do you think about the biphasic dose response? What do you think causes it, and is it always applicable?

Vladimir Heiskanen: There are, hundreds of animal studies and cell culture studies that show this biphasic dose response, so if you give a very high dose you see no benefits, and if you look at some review articles that try to address this effect, they often say that it could be related to excessive production of reactive oxygen in a species, within the mitochondria and, that’s what most of the researches tend to think, and some other researchers also claimed that the benefits of red light therapy, it could be a hermetic response like, this view implies that red light is a mild stressor to the cell and after the exposure, the cell kind of has this adaptive response that makes it stronger, and in this field of hormesis research, they often claim that like a small amount of this stressor is beneficial for the cell, but too much is not beneficial anymore, and exercise is one example of hormesis, if you do a little bit of sports, it can be very healthy but if you overdo it, then it can be harmful because then you have too much of the stress, and your body is not able to adapt to its effects.

CytoLED: What do you think about the research showing systemic effects, and do you think this is an important avenue for red light research to explore more in the future?

Vladimir Heiskanen: Yeah so, so far there have been like maybe twenty or thirty papers that have reported some kind of systemic effects, meaning that you can irradiate one body part but then, the beneficial effect also appears in some other body part. For example there is some research in sheep that, if you induce a heart attack then you can get some protective effects by irradiating their legs, and there is also some evidence from rodents that you can get some protection against Parkinson’s disease if you irradiate their bodies, but in those studies they kind of protected the head from the light rays, so they didn’t receive any light to their head, they irradiated only the body, but still they had these protective effects, and I’ve been very interested in this perspective because, for example; sunlight has been associated with decreased mortality and less multiple sclerosis and like, there are a lot of interesting associations between sunlight exposure and better health.
In the past, these associations were often explained by Vitamin D exposure, but nowadays we have a lot of data showing that Vitamin D is probably not that beneficial because so many randomised trials have failed to show the actual benefits, but if sunlight is associated with better health, I think that one possible explanation could be the red light and near infra-red that you receive, and it could somehow improve the function of your whole body, and the animal studies showing beneficial systemic effects, kind of support this view that you can get some kind of beneficial effects to the whole body when you get some irradiation, some red light on your skin. I think there was like, one animal study showing that, if you irradiate the ears of the rabbits, then you have like less calcification of the heart, like the largest artery in the body.

CytoLED: There is research showing effects; even when cytochrome c oxidase is knocked out, do you think that red light and NIR exert their effects through other mechanisms, and if so which?

Vladimir Heiskanen: Yeah like, most often when you ask somebody how does this red light therapy have its beneficial effects, the most common answer is that it has beneficial mitochondrial effects by activating mitochondrial cytochrome c oxidase, and that could lead to many effects within the cell. For example, the increased expression of some genes that are related to mitochondrial function and other important cell functions, but then very lately; a research group in Brazil published a cell culture study showing that you can get some benefits also even in cells that do not have cytochrome c oxidase. So it’s very likely that there are some other mechanisms in play as well, and there are some scientific review articles that list all the possible photo-acceptors that could mediate those beneficial effects, that include like for example some calcium channels within the cell, and one group of photo-acceptors that has this, that some researchers I do respect; find probably relevant, is those compounds that have bound some nitric oxide.
So, if you irradiate those compounds, they release nitric oxide, and nitric oxide also has some effects on the cell, but they are a little bit difficult to characterise. In some contexts, nitric oxide can be harmful and it can decrease the cellular metabolism but then; for example, if you ask some circulation researchers then they often say that nitric oxide is very important for blood circulation and artery function and, I guess some researchers have this idea that when you have this light irradiation, and you release some nitric oxide, it could improve the blood circulation in that part of the body. So, that’s one possible explanation, but there are some pretty good literature reviews that describe some other mechanisms as well. For example, Mike Hamblin published this review article with this Brazilian guy called Lucas Freitas de Freitas, a good review article on various mechanisms three years ago in 2016.

CytoLED: Do you think that red light exerts some, or perhaps all of its effects through hormetic mechanisms?

Vladimir Heiskanen: I guess, so far that’s mostly speculation this whole hormetic point of view. So far I guess there is a lack of cell-level research on PBM so, we need maybe some hormesis researchers to make some light research and maybe see if some pathways related to hormetic mechanisms are regulated from red light, and only after that can we kind of have better speculations about these hormetic mechanisms.

CytoLED: What do you think of some of the studies showing histological damage, and do you think they may have a hormetic effect, resulting in a net positive?

Vladimir Heiskanen: Umm, I have in this database that I have, including like four-thousand studies on red light therapy, I have a category called safety of PBM, and I’ve been trying to find harm from red light and basically, very few studies show any kind of injury from red light therapy, and maybe there are just like a couple of studies showing actual harm. For example, there was this one study where they irradiated testicles in, well I guess it was in rodents and it showed some harmful effects, and I don’t really have a clear opinion on what to think about that, I haven’t looked very carefully at those studies. In some cases, mild injury could maybe lead to an adaptive response, but yeah, I don’t know what to say about that specific case if you are referring to the single study that I referred to. There are also like some studies where they have caused injurious effects, with very high doses of light. For example, there was one rat study where they irradiated the ears and they used like more than seven-thousand joules. So, that’s quite logical, if you use extremely high doses that could probably cause some kind of not so beneficial effects, even harmful ones.

CytoLED: What are some of the claims you frequently see being made about red light therapy, that are not backed by strong evidence?

Vladimir Heiskanen: I think that, many companies are trying to market their own product as better than the other products, and the marketing claims are quite diverse. There’s this Swedish dentist Jan Tunér that has written about that in his book, but basically like for example, there are many companies that are selling a laser product and claiming that there is something special about lasers as light sources, but nowadays the research seems to suggest that like, LED’s are not worse than lasers for photobiomodulation, and some companies are claiming that they are selling a pulsed light source, but there is very contradictory research on pulsing, and I think it’s not very relevant whether the light is pulsed or not, and within the laser marketing field, some companies are trying to sell their super-pulsed lasers, claiming that there is something super about that, but I think there is no sufficient evidence for that as well. So basically, many marketing claims should be investigated carefully, and I think many of them are not very plausible.

CytoLED: Do you use red and NIR therapy yourself; and if so, what kind of lights do you use?

Vladimir Heiskanen: Yeah, quite recently I got myself an LED panel that is pretty similar to the smallest one that you are selling, the CytoLED One product and use it for basically one or two minutes a couple of times a week. I’m not that super regular with it, I’m pretty young and I don’t have any diseases so I think that there is like, not much reason to be super strict about this health improving intervention, but basically when I do the light treatment it feels somehow pretty good, it could be a placebo but that’s the kind of the reason I keep doing it.

CytoLED: What are you currently working on in the database, and what are your general plans for the future?

Vladimir Heiskanen: Right now, my database is mostly complete in that, in the past there was constantly this situation that it lacked many studies that had been published, but now it has almost everything in it. So, basically the main thing that I’m doing is just adding the new studies that keep being published, and also there is one Japanese journal called “Laser Therapy” and I should also add some articles that were published in that journal like, twenty years ago, that’s still on my to do list; but basically, I’m going to have a very intensive year at the University so I’m gonna just keep doing this basic housekeeping stuff, I mean adding new studies and I have one or two review articles on my to do list that I’m gonna probably finish before the Winter but, right now I’m not very active, not doing these photobiomodulation related things very actively. I think I will think about some new projects maybe next Summer, when I will hopefully have much more time.

CytoLED: Well thanks very much for talking to us Vlad, do you have any final words to sign off with?

Vladimir Heiskanen: Yeah, thank you it was nice talking to you, I don’t really have anything special to say, I can be contacted by internet if somebody has something more detailed to ask, and basically, I wish the best of luck for your company. I guess it’s a nice thing that you have decided to start working on PBM since I’ve known you for like many years before.