In this episode, I’m back for the second part of my conversation with Dr. Mark Cronshaw, a highly respected expert in photobiomodulation (PBM), more commonly known as red light therapy.
The same warning applies to this episode as part 1! Again, this conversation is not a simple “how to” practical guide to photobiomodulation. It’s a continuation of going very deep into the scientific, technical, and even theoretical nuances of PBM based on Dr. Cronshaw’s vast research and clinical understanding of the topic.
Be prepared for lots of nerdy PBM science, along with a few practical pearls as our discussion unfolds.
Please listen to part 1 if you haven’t already, and leave any questions you have in the comments on YouTube…we’ll do our best to answer questions in future episodes.
Table of Contents
In this podcast, Dr. Cronshaw gets into some of the key controversial and contentious concepts in PBM science, as well as explore some of the leading edge progressive lines of thinking among PBM researchers. Topics include:
- The difference between what Dr. Cronshaw calls “evidence-based” vs “eminence-based” science, terms used to explain not just photobiomodulation science but scientific knowledge, generally
- 2 practical considerations about red light therapy dosing, the subject of Dr. Cronshaw’s recent dissertation
- Some history of why red light, versus blue, yellow, or other wavelengths, is the focus of health science research
- An in-depth explanation of light penetration depth (how deeply the light penetrates your tissues) and the healing properties of different wavelengths (colors)
- The fascinating way light interacts with your mitochondria
- Does photobiomodulation therapy have a whole-body effect? Or just a local one? Dr. Cronshaw provides a nuanced answer to these questions and why he believes our skin is a powerful part of the answer
- A simplified explanation of (the controversial topic of) irradiance—what it is and why it matters in photobiomodulation, especially when it comes to safety precautions
- Is heating tissues truly a problem with light therapy? Or could there be a therapeutic impact? How you can find a safe but effective device
- The difference between photobiostimulation and photobioinhibition…which is best for your specific issue?
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Transcript
Eminence-based versus evidence-based science
Ari: Yes. I think a great place to start, in reviewing some of my work, you made a distinction between– you used the distinction of eminence-based versus evidence-based. I thought that was really interesting. You basically were analyzing my work and saying, “Hey, this is the status quo. This is the existing perspective that is shared by most people out there.” You’re basically saying like, “Hey, but there’s all these emerging lines of research that challenged the status quo and represent the next generation of thinking that haven’t yet been incorporated into the mainstream lines of thinking and all the different papers that are being published.”
I see you as really representing this new generation of thinking, trying to challenge a lot of the status quo ideas that exist out there and the consensus that exists and saying like, “Hey, there’s these lines of evidence that suggest this and this, and maybe we should reevaluate our thinking here.” As people are hopefully getting a sense of, as I’ve published podcasts with different experts, different experts have different opinions. In some cases, people have a lot of certainty and confidence that their interpretation of the literature is the one true correct way to interpret things.
There’s all these areas of controversy, lasers versus LEDs, and what’s the appropriate irradiance, and should photobiomodulation be non-thermal or is some heating acceptable, and lots of different controversial topics that we’re going to get to. I would love for you to just explain better than I just did, this distinction between what you mean by evidence-based versus eminence-based thinking.
Dr. Cronshaw: In all fields of human activity, people tend to polarize towards key opinion formers and leaders. There is a tendency, even in science, where you’d think it would be cold, black and white for people to take received wisdom as if they were the commandments that Moses had brought down from the mountain. Whereas, in fact, these are just the perhaps well-founded or otherwise views of that particular individual, because of their preeminence and their authority and the fact that they’ve spent many years studying this, then these views are taken not just as the opinion and received wisdom of that person, but as being something which is irrefutable.
That’s something which I wouldn’t point a finger and accuse, but it’s just human nature. We look for leaders, and when we’re learning, there are those who learn and then repeat. Then there are those who are perhaps some disruptors like myself who think, “Hang on a bit, what about– have you thought about–,” and this is the beauty of science, because you can build up this magnificent edifice and then you get somebody comes along and looks at one of the foundation stones and gives it a pull and the whole house falls down.
Nobody gets hurt, and the better scientists who are having to accept that maybe there are issues in some of the earlier work which have now been identified because there’s new equipments and new thoughts, this isn’t a bad thing at all, it’s just the nature of things. Hence there’s this drive towards evidence-based science where it’s almost gone to the other extreme where to voice an opinion you have to be able to give sufficient gravitas to that opinion so they’re not just saying, “You can keep your opinion, but your opinion is just your opinion. I want to see some proof.”
This can get taken to a ridiculous extreme which was parodied beautifully some years ago with a mock scientific paper which was entitled A Randomized Controlled Trial of the Use of the Parachute.
Ari: Yes, skydiving without a parachute.
Dr. Cronshaw: Yes. Where they took the premise that any medical intervention, i.e. the use of the parachute, you have to have that trial and in the absence of a trial you shouldn’t be using it, and of course, common sense has to prevail unless you want to be part of that trial. It’s a great paper.
Ari: For people listening, basically this was taking– I think this would be considered a reductio ad absurdum type of argument, but basically taking this line of logic and argumentation to the idea that we can’t believe anything unless we have a study to show it, taking that to the extreme of saying, can you be sure that a parachute is useful if you’re skydiving if there’s no randomized controlled study to prove that it is. Because there isn’t, it’s never been tested. We don’t have a control group of skydivers who didn’t use a parachute so therefore, we don’t have the evidence to say a parachute really works.
Dr. Cronshaw: Yes, and by virtue of the intervention, sometimes it fails and people get killed, and things like this. There are rare instances where people haven’t used a parachute and they’ve survived, and so it was a hilarious paper, which just I think had great value, besides from amusing me, to make me appreciate a little more the necessary balance because I think it’s great to have opinions, and if anything the pendulum’s now swung far too far the other way whereas in the past you could quite easily publish, for instance, clinical trials and tests and a single case and you could get a decent journal to publish it.
These days if it’s not an ethically approved randomized controlled trial, forget it, they will just reject it even without taking it any further which is frankly a mistake because this can help stifle innovation because some of these randomized controlled trials are enormously expensive and very complicated to set up and getting things on ethics committee approvals can be a very slow and difficult process. The idea is not to stifle development, the idea is just to protect the public and so on.
It’s an ongoing debate, but in all areas of science this has been seen where it’s gone from one extreme maybe to the other, and it’d be nice if the pendulum would just swing back a little bit more towards the middle which I’m sure it will. Hence I do distinguish when I’m listening to people between people who put plenty of references there which subsequently I can look up and I can check the providence of what it is that they’re saying or people who are saying, “I’m the great white coat and I am saying this is what you must believe,” which is the other extreme.
I’m afraid I’m a man that thinks for myself and I just question everything, and by doing that I like to think that I can grow and learn, and that’s how I came into PBM. It was very much with an open mind and many, many questions.
The big areas of controversy within dosimetry in PBM
Ari: I have to say in starting to have these conversations with you both in podcast form as well as our private communication and you reviewing and making comments on my work, I have a mix of annoyance and excitement. One is the annoyance of, just as I was thinking I’m wrapping up my book and I’ve got everything dialed in, now I have this next generation thinker who’s saying, “This isn’t quite right, and this isn’t quite right,” and so I’m like, “Oh, more work to do. More correction. I’ve got to fix this and fix that and add more new layers of evidence and new perspectives here to maybe alter what I’m saying in this section or that section.”
I would say maybe it’s 80-20, it’s 80% excitement, 20% annoyance, but 80% is I’m deeply grateful to have met you and start this conversation to expand my own knowledge and to make sure that the information that’s going to be in my upcoming book is hopefully at least incorporates some layers of insight from the next generation of PBM researchers such as yourself. With that in mind, I know you’re considered one of the leading experts and researchers in the field of EM dosimetry, the dosing parameters, for people listening, around how this light is delivered.
This encompasses a few different– lots of different nuances and factors that go into this dosimetry, but I would say the two big ones that are at least historically regarded as the big factors in dosimetry are irradiance, which is the light intensity, and duration of time that you’re using it. I would like to ask you, before I introduce too much on my end, I would like to ask you to maybe give people an overview of this broad topic of dosimetry in PBM and maybe briefly mention, without getting too deep into it, briefly mention an overview of some of the big areas of controversy within dosimetry in PBM.
Dr. Cronshaw: Surely. It would be my pleasure. This is indeed a big topic. I spent the last five years doing a doctorate on the subject, and so there’s a lot that can be said about it. In short, in order to affect a change in a biological system using a photon, which is energy, there has to be some transformation of that energy into one form or another. This is being viewed as being primarily in PBM, photobiomodulation, as being a photochemical change, where the incoming photon has been absorbed and it’s kicked off a cascade which increases the amount of the energy, the fuel for the cell, which is ATP, and as a result, you’ve seen an increase in activity in the cell and things have happened.
The reality is that a photon is a little bundle of electromagnetic radiation, and there are different wavelengths of photons, so they carry different amounts of energy, and so how you package that energy, whether it’s in the individual photon or the way in which you deliver the photons, then can have a very marked effect on the outcome. If you’ve got a lot of photons and it’s really intense, you’re not going to be doing PBM, you’re going to be doing surgery. I do a lot of laser surgery, I’m a clinical dentist who uses lasers all the time to kill bacteria, cut tissues, and all the rest of it.
Ari: That’s basically the principle. I know this relates to lasers versus LEDs as well, but the main factor in that, correct me if I’m wrong, is essentially the irradiance, and once the irradiance gets to– the light intensity essentially gets so high, it becomes mostly something that heats and burns the tissues, rather than something that would be considered photobiomodulation.
Dr. Cronshaw: That’s one way in which we do surgery, and I know we’re not talking about surgery, but just to add to that concept, there are certain wavelengths of laser which have got a very high attraction to substances like water. I use some erbium lasers, which are mid-infrared lasers, and when the water molecules encounter one of those photons, in about some 2,780 to 2,940 nanometers, the water molecules turn more or less immediately from water into steam, and that steam has got a volume of 1,600 times the little water droplet, and it quite literally blows apart the tissues.
It’s an expansive explosive process, as opposed to it being something which is like James Bond, where you’re cutting through sheet metal on your way to cutting through poor old James. Although there’s indeed a thermal element, the difference there is you don’t get the buildup of heat inside of the tissues, as this happens inside of millionths of a second, and that tissue just fragments, which is great, because then as opposed to seriously cooking things, you’re doing it so that the amount of heat that’s left in the tissues is much less than if you use a conventional tool like a 250,000 rpm diamond tip dental drill. It’s a gentler tool on bone, on enamel, and other dental tissues because you’re not heating things up.
Coming back to the thread. Apart from photochemical reactions, there are many other aspects. We’ve already mentioned photothermal, but you can have these photoacoustic effects, which is this expansive explosive effect. With that type of laser, you can hear a popping sound, which is a shockwave it creates in the air, and you can create a similar shockwave inside the tissues. You can vibrate things and it can be a little bit if you’ve got enough energy there like an earthquake. You can start to break things up, and you can see cracks appearing and stuff. It can be a photoelectric effect.
Now, people tend to think that Einstein got his Nobel Prize for his theory of relativity. It wasn’t. It was because he got his work looking at the effects of bright light and aluminium to generate electricity. Really, he’s one of the fathers of solar PV. 17 years later, they gave him his Nobel Prize for that work. When a photon hits certain types of metal, then you can get an energy transfer, which results in a flow of electrons as well. That’s something that happens in biological substances, particularly ones that contain what are called transition metals, things like iron. Where do you find iron? Hemoglobin and lots of important enzymes contain iron. You can have a photoelectric effect and that can be important.
You can have a photomagnetic effect. We all know what a magnet does. It’s like attracts like or repels if it’s a magnet. If it’s iron, it’ll stick to your magnet. You can have photomagnetic effects as well. This is what we refer to as the dipole, which is the alignment of, say, the iron changes, and that can open up iron gates. You can have photomagnetic effects. You can even have photofluorescence. This is where you expose the light to the tissues and it glows in the dark. Sometimes you get fluorescence you see in the ocean, thanks to the activity of small marine creatures that absorb light, and then there’s phosphorescence and you can see this greenish glow that’s been released as the light which is stored inside of them is slowly released.
All of these effects are happening simultaneously. When you’re thinking about dissymmetry, you’re not just affecting one thing. You’re injecting this electromagnetic energy in, and according to how concentrated it is, which is what we refer to as the irradiance, you can start to produce effects ranging from doing very little through to having a biological influence through to cooking things, disrupting them and what have you. How you package that energy is a critical component. You’re quite right, irradiance is a very important element because you can have too much of a good thing or you can have too little. That’s this element of time.
At home, we have this thing called an AGA. It’s a cast iron one. I don’t know if you have AGAs in the States, but it’s a traditional cast iron oven. It’s wonderful, because it’s got this really hot oven where it cooks things really fast. There’s also a slow simmering one where it just feels warm and you can put a pot of food in there and all day it’ll be cooking slowly. It’s a slow cooker. It’s amazing, because low amounts of energy for a long time can cumulatively start to have an effect on the food. Whereas if you flash fry things, it’s a very different story. You can see things and it just changes some of the chemistry of what you’re doing, according to how you package the energy.
Ari: That’s a great analogy. As I was writing that section that corresponds to that and the Bunsen-Roscoe law of reciprocity is relevant here-
Dr. Cronshaw: Absolutely.
Ari: -which is that you can deliver the same dose with an extremely high irradiance for a very short period of time versus a very low irradiance for a very long period of time. It’s analogous to I think this picture you’re painting of a crock-pot, a slow cooker that simmers a beef stew over 12 hours versus taking a blowtorch and doing it in 5 seconds.
Dr. Cronshaw: Yes. Taking a magnifying glass and the sun’s rays and focus these onto a bit of newspaper. Hey, you’ve got a fire, or in PBM doing the opposite and taking a small point source and turning it into a big wide one, which is how we’ve managed to turn surgical lasers that we bought to do surgery with and turn them into devices you can use for photo medicine because when you get a big optic spot size by pulling the beam back, it becomes larger then you can then start to get down to the levels of energy per square centimeter at a rate, which is the watts per square centimeter, which is consistent with gently tickling the cells as opposed to clubbing them over the head and killing them.
These are two critical elements to do with the concentration of the energy as well as the amount of time. Then there are many other factors as well. There is a big choice of wavelengths. You can choose a really short wavelength, you can choose a really long wavelength, and what’s the best wavelength? That’s a big topic we could discuss. Then there’s some issues–
Ari: I think that’s the topic you said that you’re going to make me angry or challenge some of my views. I have the sense of where you’re– Now that we’ve had some private communication, I have a sense of this, and I’m intrigued to have that discussion when we get there.
Dr. Cronshaw: You entitled your book Red Light Therapy. Now, that’s because historically, PBM was all about red light. The first scientific studies on photobimodulation were conducted by a Hungarian scientist. He used a red laser, because that’s the only laser he had. Hence, he got some effects, which Enver Nestor, he’s a smart guy, and he said, “Hey, this is encouraging these mice to grow their hair faster. This is markable.” Out of that has come all this 50 years’ worth of studies since where we’ve been looking at this effect. Yet, although by heritage and also by availability, these were the only devices you could get your hands on, now we’ve got a huge variety.
You can get any wavelength of device, whether it’s an LED or a laser. These have got different properties as well. We’ve gone from having very few to choose from where most of the studies were done through to having this enormous choice of it. This is one of those areas where I would regard it as a sacred cow because people say no, no you have to use certain wavelengths of energy in order to produce the effects that you’re seeking.
That’s a heritage issue to do with the fact that most of the studies were done on those wavelengths. It’s not because the other wavelengths don’t work, it’s just that maybe the parameters were a little different when they did use those other wavelengths and because the amount of energy that’s associated with each wavelength is different, then the effect on the tissues is different. It starts to get increasingly more complex, but essentially, there’s a spectrum of light you can choose from. Some are undoubtedly better than others, there’s no doubt we will discuss.
Ari: I’m tempted to go there right now, but I suspect we might have to spend a full hour on that conversation alone.
Dr. Cronshaw: I promise I won’t, Ari. I’ll keep–
Ari: What’s that?
Dr. Cronshaw: I promise I won’t.
Ari: We might because I need to play– I’m going to be devil’s advocate and I’m going to play devil’s advocate there a little.
Dr. Cronshaw: Bring it on.
The effects of different wavelengths
Ari: There’s points where what you’re saying, certainly, it makes sense to me, but there’s points where it doesn’t make sense. Maybe we should just go straight into that, the topic of wavelengths right here, before we go into irradiance and some of the other aspects of dosimetry, because I’m so intrigued by this line of thinking. The general gist of your argument, as I currently understand it, with just– I’ve only seen a little bit of information from you here and there so far. Basically, you’re arguing, it sounds like, that some of our thinking– it sounds like maybe a lot of our thinking about the unique effects of red and near-infrared wavelengths are more this heritage issue of just what has been used and what’s been studied historically.
Again, I don’t want to put words in your mouth, but it sounds like you’re making the argument in the direction of, actually, there are lots of wavelengths that essentially will have similar effects, not only red in your infrared. Is that accurate? Please clarify.
Dr. Cronshaw: Yes, that is quite accurate. In fact, there is a study from Praveen Irani, who is, as you know, a recognized authority, where one of his students, Young, did a paper, I think it was two years ago, where they were looking at osteoblasts. Now, osteoblasts are the cells that form the inner core of teeth, dentine, and they expose those poor little osteoblasts. It’s tough when you’re in tissue culture, to either shorter wavelengths like blue wavelengths or longer wavelengths like red wavelengths or longer wavelengths still like near-infrared wavelengths, to look at the effects of those cells if they adjusted the dose according to the amount of power that each photon carried because there’s a concept which is a very important concept that the shorter the wavelength the more the energy.
This seems counterintuitive at first. You imagine that short wavelengths will have less energy but if you squash all the energy into a little small space, like you might get with ultraviolet or with blue wavelengths, then that’s a very intense source because that’s a very powerful thing. That photon it’s a rocket ship, it’s really going to fly. It’s got a lot of punch, whereas if you’ve got a longer wavelength, it’s more pedestrian. It’s more your slow-moving vehicle where it might not go so fast but it gets there, because the amount of energy packaged per photon is less.
Although we talk about dose in terms of the joule, which is the unit of energy, and here it gets complicated, isn’t it? The joule, this is where we’re referring to the amount of energy that’s necessary to heat up a little bit of water by 4.2 degrees centigrade. Now, I’d love to talk to you at length about this. Henry Joule and the history of the joule it’s a great story, but we’ll skip over that, we’ve got to cover this stuff. Basically, if it’s a certain amount of energy to heat up water, then it’s less to do with anything other than the amount of energy to heat the water, and so hence a joule is a joule.
If you take photons from say a shorter wavelength, then it’ll take basically less photons to be able to heat up that little bit of water because there’s so much more energy associated with it than if it’s a longer wavelength like a mid-infrared or something, where it’ll take an awful lot more of those photons to do the same thing because there’s less energy per photon, but both will effectively inside of a joule– If you get a little package of a joule of blue, or a big package of a joule of 2,780 nanometer, they will both heat up that water by 4.2 degrees centigrade. A joule is a joule, but a photon is not a photon.
If you think about the wavelengths between number of joules per nanometer, and that’s the measure of the wavelength, the length, 10 to the minus 9, whether it’s really short, very powerful, or very long, and you then scale down the amount of those photons that you deliver by basically turning down the joules, you’re turning down the power. With a blue wavelength, if you use essentially half the power for a 455-nanometer blue wavelength device to that you’d use with an 810-nanometer near-infrared device which is twice the wavelength, you’ll achieve exactly the same effect, and that’s what Young found with his odontoblast.
He could get exactly the same stimulation and production of ATP, and all the other positive effects we associate with photobiomodulation with shorter, intermediate, and longer wavelengths, simply by tooling down or up the number of photons he was delivering. This then changed totally the concept that it had to be a magic photon of a certain number. Now, there is an element in truth in that some photons are on the same resonance frequency as important molecules.
I mentioned earlier when I was talking about water how these wavelengths in the mid-infrared really do something to water. You can shine it for a glass full of water and the water just starts to bubble and boil if you use enough energy, and it’s because it’s creating this phase transition from water through to steam which has got this huge volume difference and it can be transmitted through the glass and it’s a very powerful effect and that’s because of the affinity for that wavelength for the water molecule. It’s not dissociating the water, otherwise, you boil the kettle once and there’d be a big bang, you’re not generating hydrogen, thank God.
What you are doing is you’re separating those weak ionic bonds between the water molecules, so it then turns to vapor, and that’s got a much bigger volume. It’s a playoff between the concept that you can transfer a certain amount of energy using any of these wavelengths to boost the effect that you want inside the cell, but then there are other things related to the absorption of those particular wavelengths in superficial tissues. Shorter wavelengths are very highly absorbed by stuff like collagen. Collagen is 70% of the subsurface of the skin.
There’s a lot of collagen also in keratin, which is basically the outer layer of your skin. You’re going to lose most of that energy in the superficial layers. How much of that stuff is actually going to get through down to that target, which might be some bone or nerve that you’re trying to stimulate to regenerate or to repair? The answer is not a lot, very little, so maybe that’s not the best wavelength to use. Maybe then you need to be using one of these less big guys, one of these little 810 nanometer ones which got less energy, which are very poorly absorbed in protein as well as in other elements such as water inside of the tissue and pigments like melanin or things like blood, which has got iron in it, which can be absorbed particularly by these shorter wavelengths.
Then it will then stand a chance. You can start to get to a centimeter or more deeper into the tissues. Hence your choice of wavelength really is– the issue is what have you got? Number one, because the best device is the one that you got. Next, what can I do with it? Is it superficial condition or is it something that’s subsurface? If it’s subsurface, these shorter wavelengths are not going to be maybe quite so useful as if I’ve got access to a longer wavelength. It’s not to say I can’t do it. It’s just then it’s much more difficult to do to achieve the effects that you’re seeking, as you have to turn the dose right down in order to avoid overheating superficial tissues.
That might not be practical, and it may take you hours in order to trickle through a few photons that just about managed to get down to that one-centimeter level. When we talk about optical penetration, this is the delivery of that magic bullet, if you want to call it that, which it isn’t, down to the depth. Then the amount of photons that are present, if you had a sensor that was sensitive enough, you probably pick up the odd photon on the surface of the moon.
If I was to point it out my window and fire it, that’s very few of them. By convention, we look at a cutoff point where there’s less than about 37%, which we regard as 1/e, which is this mathematical constant that engineers and scientists love, beyond which we say, “That’s it, guys, pack up shop. There’s nothing happening down there.” That’s not true. You still got photons down there. There’s still about a third of the package, and it will carry on going, as I say, to the depths of the deepest coal mine until there’s maybe one photon down there.
Ari: I just want to flag that as an important topic to come back to, because this relates to another controversy around the “penetration depth” of different wavelengths of light. This 1/e convention that you’re describing is a big source of widespread confusion about how deeply these photons of different wavelengths penetrate. We’ll come back to that later.
Dr. Cronshaw: We come back then to, “Marc, which one would you choose?” We’re talking to people out there thinking, “Oh, this sounds complicated. I don’t get it.” Can I just get any? Which one should I get? I said somewhere in the red to near infrared. That’s a good place. There are certain properties of shorter wavelengths, which can be really useful for certain things. Maybe you should be thinking about getting something that will give you a mixture of different wavelengths.
Some of the newer devices that we have available, they can simultaneously emit, maybe four or five different wavelengths at the same time. You can mix the colors, and produce different layered effects, which is potentially quite exciting, These are some stuff that you can already buy in the form of little LED torches. I had a paper published today, looking at these torches, but that’s a different story. When it comes to selecting wavelength, if you want to get down to depth, you need something that’s going to reach it.
There, the optimum wavelength, without doubt, is the near-infrared. If you’re asking for a sweet spot, I’d say around about 800 nanometers, 810 nanometers. If it’s 850, or if it’s 780, or if it’s 980, or 1064, or whatever, these will all reach subsurface targets. Some of them have got slightly different properties than others in regards to things like absorption of water. The 810 is very poorly absorbed in water. It’s one which can get through the tissues without getting scattered, which is an effect you might see with a pinball machine, where the photon keeps bouncing off everything else.
An 810, it just tends to keep going, Then you can start to get it deeper into layers of tissues where your object may be. As for more superficial things, without wanting to overheat things, which is always a concern with shorter wavelengths, then a red wavelength is always a good choice. Clinically, in my practice, when I’m using this for PBM, I’m typically mixing a red and a near-infrared through what we call a coaxial cable. I’m delivering it at the same time. It’s a little bit of PBM soup, a bit of this, and a little bit of that.
I’ve even got a device that let me mix in up to eight different wavelengths. You can really get carried away with this stuff, and I obviously have. That’s for horses for courses. If it’s superficial, red’s great. If it’s deeper, near-infrared. If you want to heat things up a bit, maybe a blue. Then why would you want to heat something up? That’s a clinical question. Maybe when we get past this principle stuff and we talk about the clinical applications of these things and how you go at managing different conditions, I can give you a philosophy of care, which will then rip off some of the mystique associated with all this stuff. I know it sounds complicated, but–
Ari: A philosophy of what? What did you say?
Dr. Cronshaw: There’s a philosophy of care in regards to how you approach clinical-
Ari: Of care, of C-A-R-E.
Dr. Cronshaw: Yes.
Ari: Okay. Got it.
Dr. Cronshaw: What are you trying to achieve? is it pain management? Are you trying to relieve inflammation? Are you trying to stimulate things so that they heal better, or both? That’s a separate conversation. No doubt, hopefully, we’ll get onto that later on. You can adopt a cookbook-like approach. Now, with a cookbook, it’s painting by numbers. Those little pictures you have as a child where you look to see what color number one is and you paint that. You do a little bit here and you end up with this nice-looking picture. Is that really art?
Whereas if you understand what it is that you’re doing, then as opposed to being a machine that’s just doing by rote what you’ve been told, you can then start to use your brain, and understand what it is that you’re looking at. Then you can work out why it’s working, why it’s not working, what you need to do about it. Then you’re driving the bus rather than bus driving you. That’s where the learning element of all this comes in. I teach this stuff. It’s a transferable skill. It’s definitely not wizardry and magic. This is science.
Ari: I’m reeling with questions, but I’m going to try to see if I can narrow this down. I want to– please interrupt me if anything I’m saying is objectionable or if you feel I’m putting words in your mouth or anything like that. I just want to paint a picture here and then go from there. I’m conceptualizing a spectrum of opinions here where let’s say on one extreme end of the spectrum, you might have people who are under the opinion that each individual wavelength, let’s say a 1064, a 980, a 904, or 5 or whatever, I forget which one that is, an 810, an 830, a 660, and so on.
Each individual wavelength has its own very precise, very unique effects that only apply to that wavelength. On the other extreme end of the spectrum, we might imagine someone who makes a very black-and-white argument where they say a photon is a photon. It’s all just light energy. Everything just acts the same. It sounds to me, again, correct me if I’m wrong, but it sounds to me like you’re more in the direction of a photon is a photon. Feel, jump in there and correct me if that’s if you would describe that as inaccurate. I know you’re not on the extreme end, but like more in that direction.
Dr. Cronshaw: I think the historical view was the former that you had to use a 632.5 helium neon. “I use a 1064 nanometer.” “No, no. You want to use an 810 nanometer.” These are what I would regard as manufacturers wars, where it’s like buying a car, you’re going to get a Ford or a Chrysler, or what are you going to buy, each is better than the other guy, They tout these various benefits associated with them, about blood absorption and melanin, and they have these absorption curves, and ours is definitely the best area.
When you rip the veneer off that, then actually, a car’s a car, and you can choose which car you want to drive to the supermarket. Some are better than others and got bigger boots and more space for your shopping, but there’s an element of consumer choice, and it’s not an absolute. Perhaps maybe, if you forgive the phrase overcooked it by saying, “Oh, no, no, yes, photons are photons,” because there is a sort of a happy medium along the middle, because of doubt.
Ari: That’s the territory that I want to try to clarify here. Am I interrupting? Do you want to complete?
Dr. Cronshaw: No. That’s absolutely fine.
Ari: Okay, so I think there’s two important aspects to address. One, you’ve already alluded to several times, which is the optical window, which is the idea that different wavelengths will penetrate into the tissue, either not very well, maybe not at all, or almost not at all. Then other wavelengths will penetrate quite deeply or much, much deeper, there’s a much higher amount of proportion of photons of what’s the from the light source that will actually go beneath the skin and penetrate into 1 centimeter, 2 centimeters, 3, 4 or 5 centimeters into the tissues.
I know you said a 10 nanometers in the near infrared as a sweet spot there for deep penetration. I think seeing things from that perspective, I think we could sort of have this perspective, let’s say, and I’m not saying this is your– what you’ve said, I’m just trying to paint a picture here. We could say a photon is a photon, let’s say they’re all acting the same, they all initiate the same mechanisms. It’s purely a difference of some will not make it past the skin.
They’ll hit the skin and either reflect off or be absorbed in the skin and nothing will penetrate deeper, whereas with other light wavelengths, you can deliver those photons to deeper depths into the tissue, but we’re still in the frame of a photon is a photon. It’s just a question of how deeply they’re penetrating into the tissue.
Dr. Cronshaw: I’m sorry, life is infinitely complicated. [crosstalk] the mid zone, which is where I sit, is there are certain affinities associated with specific wavelengths, which are important. For example, we know that with some of the erbium lasers, which are mid infrared lasers, they have a particular affinity to trigger the release by platelets of a growth factor, which is really important in the growth of bone. There is a really great for analgesia, which is pain relief.
Ari: You’re saying that’s occurring at relatively specific wavelengths.
Dr. Cronshaw: This isn’t something which will only occur at those wavelengths, but these are the ones which have been recognized as being the optimum for these effects. It’s to do with resonance. Now, you know when you get a soprano, singer, and she can just hit that right note, and then the glass shakes, the glass molecules vibrate and it breaks. This is the concept of resonance frequency. It’s the same with photons.
If there’s a photon which has got exactly the same resonance frequency as a molecule, then like the water with the mid infrared, then that water starts to vibrate and it turns to steam. That can be the same for other biological targets. For example, the 940 nanometer wavelengths got an affinity for glucose, and there are other wavelengths that are going to be different tissue constituencies, like the blue wavelengths have got a high affinity for proteins, as well as really dark pigments and things like this.
The choice of wavelength, you can, if you wish, tweak the dissymmetry in order to compensate for the excess or the under power, as it were, of that particular photon. There is definitely benefits in having a range of colors to choose from. If you’re painting a portrait, you don’t want to just do it in black and white. You want all the pastel shades and the colors. It’s the same when you’re looking at health care, whether it’s personal or professional, is that you choose which is the best tool for the job.
A painting is a painting. You can still paint. If you if you want to achieve the optimum effects, then you may choose, for instance, to use quite low powered, but some high affinity to water surgical lasers to do your cutting. Then you pick up afterwards an 810 nanometer near infrared device in order to treat the collateral tissues to improve this stress resistance to trauma because they’re not dead. They’re outside the zone of surgical damage caused by the high-powered laser, but also to encourage them so that they they’ve got some the best potential for the healing, repair and regeneration.
We have these concepts now in surgical care of a dual wavelength approach. It’s as I say, horses for courses, we can produce different effects going to each tool that we choose, just like going to a restaurant. You just don’t just have a meal. You decide I going to have the oysters today or whatever. You can pick your wavelength and all wavelengths, and the how you package that energy to produce some very selective effects.
When you’ve got to that level of skills levels, which is much of education, and you can then start to do some seriously quite exciting things. You can start to affect tendons which have been damaged, but without damaging the overlying tissues. You can start to help people who’ve got non-union. You can treat the brain and all manner of stuff. I’m getting ahead of myself.
Ari: Okay, so where you went with that is perfect. That’s exactly where I was trying to get to, is that starting from this idea that a photon is a photon. Really the only difference is how deeply they’re penetrating in the tissues. Let’s start to move in the direction of that other extreme argument of each wavelength has its own unique highly specific mechanism. I think we could start, you just gave a number of good examples of this, but I think some other clear examples are UV light creates, leads to a reaction that creates vitamin D synthesis in the body.
That is specific to ultraviolet light at specific wavelengths of ultraviolet light. It doesn’t even apply to the full spectrum of ultraviolet, let alone things like blue or red, or green, or near infrared and so on. We have a reaction starting in our eyes and in our part of our brain called the superchiasmatic nucleus that affects our circadian rhythm, that is dependent on very specific wavelengths, largely in the blue wavelengths.
Then we have, for example, blue, can also react with uniquely with porphyrins in certain bacteria in the skin, which makes it uniquely effective in combating the bacteria that is potentially as partly causal in acne. We also have a situation where melanin synthesis, the tanning of skin and the production of melanin in the skin is specific to certain wavelengths of light. Then there’s the whole issue of cytochrome c oxidase, which has been long theorized. I know you object to this view, but that, that’s historically been seen as the main mechanism of the effects of red in your infrared light and how they act in photo biomodulation.
There does seem to be some unique parts of the light spectrum that absorb well in cytochrome c oxidase, versus other wavelengths that don’t. You might correct me on that. Maybe there’s new information that shows something different. The broader point that I’m trying to make is there are many clear examples where specific biological reactions only take place in response to specific wavelength ranges, but not other wavelengths, where this idea that a photon is a photon is clearly not true.
Dr. Cronshaw: You’re doing great until that final sentence.
Ari: Okay. [laughs]
Dr. Cronshaw: The study that I mentioned from Arani’s group, they were able to see an increase in the amount of ATP generated, whether they’re using a blue wavelength or a red wavelength or a near-infrared wavelength. All they were doing was just tinkering with the dissymmetry. They produced this concept which is like a calibration scale, where they’re adjusting the dose according to the amount of energy of the photon.
As for what it’s doing inside of the mitochondrion, the air, there are specific elements inside of the structure of that enzyme chain that’s beautiful. Five little sections, each of which has got something which could be absorbed by different wavelengths. At unit one, which is coenzyme Q10, ubiquinol, that’s the first stage of electron transport chain. That’s basically where it’s starting to build up almost a pump across the inside of the mitochondrion. This little gap between the inner shell of the mitochondrion.
The outer shell of the mitochondrion, a bank of protons, which are hydrogen ions, which at unit four, then backflow like a hydrodynamic dam and drives the turbine, which then starts pumping at ATP, but ubiquinone has got a high affinity for blue wavelengths. As a dentist, I use blue LEDs to cure composite, which is dental resin, using something which is a catalyst called camphorquinone, while ubiquinone is a quinone. It’s the same group of chemical.
If you expose unit one, it increases the activity, unit one, the electron transport chain. At unit three, as well as at unit four, then there are cytochromes. The cytochrome, without getting boring about chemistry, contains iron and it contains copper. Iron and copper, what they referred to as transition metals, and these are high absorbers of photon energy, and they start spitting out electrons, so you can change the ionic status.
You can change the amount of electrons present in those groups, which then changes their chemical properties, and that then can start to change the activity of different enzymes. Then there are other effects as well. You could really, seriously get in deep when it comes to mitochondrial metabolism, but just to come to the point of why I went through all this, Ari.
Yes, there are certain photons which have got a specific affinity for certain elements of the chemistry of the cell. I just believe that there’s been an over-emphasis that it’s primarily a photochemical reaction because there’s a lot else happening. You’re looking at a three-dimensional very complicated thing. It’s not an amoeba. It’s not a single cell. You’re looking at a multicellular organism.
It’s got a nervous system. It’s got a hormone system, the endocrine system. It’s got all sorts of complex organs that interact with each other, and there are checks and balances at every place that from– the level of complexities that I can only describe as stunning. To think of it by looking just down the microscope at a single cell with a photon, maybe that’s the wrong perspective and maybe it’s just far too complicated. Do we really need to get so deep? I’m thinking about your poor listeners here.
There’s a different perspective to all of this stuff where essentially, a bit of light can be a really brilliant thing if you know how to apply it and how much to apply it in order to enhance your ability to heal and repair, and to mitigate pain, as well as to improve the resistance of your tissues to bad stuff, whether it’s a chemical like chemotherapy or radiation, as in radiotherapy, or alternatively, just the excess sunshine from UV where you can use red and near-infrared light at low doses in order to boost the stress resistance of the tissues to the mid-morning sun.
Ari: I think to try to summarize most of what we’ve talked about here, it sounds like you think that, generally speaking, there should be a shift more towards the idea that there’s actually a lot of these effects that we’re observing in the cells, in the tissues, in the body more broadly. There’s a lot of overlap between different wavelengths. It’s not so highly specific to these specific wavelength ranges. That aspect of things has been overemphasized and we should understand. We should move maybe a little bit in the direction of a photon is a photon. Would that be fair to say?
Dr. Cronshaw: Yes. I liked very much your mention earlier about the circadian rhythm and the effects of certain wavelengths, bluer wavelengths to set the internal clock, the body clock. Because you’re absolutely right, there’s some specialist receptors at the back of your retina and then a signal gets sent through to a nerve center, which is just above the pineal gland, which then suppresses the production of a chemical, which is melatonin, which then inhibits the body going into the parasympathetic cycle of metabolism as opposed to the sympathetic cycle of metabolism.
Now, this is terribly important to human health because basically you heal when you’re asleep. When the parasympathetic system is operational, when you’re asleep and that’s the time when my beard grows, and everything else grows, and when your immune system is most active, and when you can start to heal and to repair. Whereas during the day when your sympathetic nervous system is very active, it’s more about being bright and alert, and thinking and muscular action, the energy is diverted up there instead.
If you have this concept of entrainment, then this is where the light is then triggering off a global physiological response. Now, anybody who’s ever gone long haul knows how lousy they feel because of jet lag, that’s because their circadian rhythm hasn’t had time to adapt. They’re trying to give that important meeting when they’re still in the parasympathetic cycle, their body’s still half asleep and they’re trying to get their brain to work. I’ve been there, and maybe I’m sure you have too, Ari, you feel awful.
Similarly, you’re trying to get to sleep and you’re in that sympathetic cycle and you just can’t sleep, and it takes you the thick end of a week to get into it. Now, I love this idea of entrainment because I think when we’re talking about PBM, there’s an element of entrainment. As opposed to it being a specific receptor just in the back of your retina, when we’re doing phototherapies, I think we’re producing cascade effects, which can then start to have systemic effects as well as local effects.
You can then start to have multiple planes of action where, depending on how much area you expose and how long you do it for, you can start to affect very distant changes by triggering off some cascades that might be associated with the endocrine system, with hormones, or with the nervous system, or both. Which is why by doing PBM, you sometimes see distant effects, which are very hard to explain because how did the photon from this hand translate into the fact that happened in this hand? Stuff like this. It’s not a miracle. It’s just it’s a systemic effect.
Is PBM treatment only local?
Ari: This is something I think we touched on briefly in the last conversation. There’s a few lines of research, I think, one in humans from Dr. Arani’s group, and then there’s also a rodent study that was similar, where they looked at the effects on brain function and measures of brain health when either light was directly shined on the head or when no light was shined directly on the head, and they shined it on the legs or on the abdomen. In both the rodent and the human study, they showed similar benefits either way.
This speaks to this point of differentiation between local effects, where you’re expecting the photon of light to directly interact with that specific tissue that you’re trying to affect, versus systemic effects where the light has interacted with the blood or the skin, or other components of the body that then lead to different effects now presumably entering the circulation of the body and then affecting distant sites at that point. This distinction between systemic versus local is very interesting.
I’ve also been struck in my conversations with Dr. Hamblin that he almost seems to brush off. I don’t want to misrepresent his position, but there’s a number of conversations I’ve had with him where he almost seems to minimize the importance of the local effects. He’s more concerned when talking about dosing rather than joules per square centimeter, he’s more concerned with total joules delivered to the whole system, which makes me think that he’s much more of the opinion that the systemic effects matter more than the local effects.
What are your thoughts on all of that?
Dr. Cronshaw: Again, it’s a matter of what is it you’re hoping to achieve. Okay, so say you’ve got a sports injury, you’ve got some tendonitis. You’ve been playing too much tennis, and you’ve damaged the tendons in your elbow. Then your treatment objective there is to relieve the pain, improve the function, reduce any inflammation, as well as accelerate or promote the best quality healing you can get so you can get back to your game, all right?
Are you going to then go into a light pod, which is one of these machines where you’ve got a gazillion LEDs and you radiate your whole body, or are you going to pick up a more intense light source, say a therapeutic laser photobar modulation device, which can then really, as it were, jet hose in some photons to affect those tissues where there are all these inflammatory chemicals and there’s relatively poor circulation, and you want to have selectively a localized effect.
I think for specific conditions, and trauma is an obvious example, then it’s better to have a therapeutic approach which is directed at that target tissue, as opposed to dealing with the whole body. I see Mike Hamblin’s point in the sense that these systemic effects can be very powerful. However, when it comes to the mitigation, the relief of pain, if somebody’s got pain here, which they might have associated with, say, a jaw-related problem.
They clench and grind their teeth all night, and the muscle goes into spasm and, “Oh, they’re in so much pain. They’ve got toothache. They want to see me,” and I say, “It’s not a tooth. It’s a muscle.” It’s like you’ve gone to the gym all night, every night. that muscle’s gone into spasm. We treat that muscle, not the whole person. The idea of treating the whole person is maybe the reason they’re clenching their teeth is because they’re really stressed.
This is maybe whereby treating the whole person, you can start to affect their mood and other things. They want me to get them out of pain. I can get them out of the pain in the chair inside of three to five minutes by using a high-intensity photobar modulation laser source over that area. I think, again, it’s a polarization views, where we’ve moved from very small point applicator sources at very low output, which is the original devices used in PBM, to these great big machines, where you’ve got some full-body irradiation.
Don’t underestimate your skin
Ari: I think a good place to wrap up this episode is something you were alluding to a few minutes ago. You sent me a couple very interesting papers on this subject that I was reading this morning, talking about the skin. This relates to the systemic versus local effects. You basically were saying you feel what’s going on at the level of the skin is a hugely overlooked and historically under-emphasized area of what you think is mediating the effects of photobiomodulation.
Tell the listeners why you think that, and what are these layers of the story that are happening at the layer of the skin?
Dr. Cronshaw: I came into PBM from the direction of being a laser surgeon, as a dentist. I use lasers all the time, for treating gum disease and doing surgery of one form or another, and all the other horrible things that we dentists get up to as we’re trying to help our patients. I saw that things healed really well. To me, everything was all about lasers, and then I got interested in photobar modulation. Most of the literature was about lasers. Okay, you’re going to use laser for this.
Then I think probably more prominently in the last 5 to 10 years, there’s been an increasing amount of interest with non-coherent sources like LEDs. An LED is a much cheaper device. It’s less hazardous to your eyes. You’re less likely to burn your skin because it’s not such an intense source because of the difference in which the energy behaves.
Ari: This is another big area of controversy where you have the LED and the laser people who swear that laser has very unique effects that can’t be replicated by LED and other perspectives, as we argue.
Dr. Cronshaw: Absolutely.
Ari: [crosstalk] They’re mostly the same.
Dr. Cronshaw: I looked at the studies. I thought, well, LEDs cannot possibly work. Yet they do. I thought, well, how on earth can that be happening? I then had to put all my preconceptions to one side and go back to the drawing board. Then I realized that maybe there is another interface. I started looking outside of the PBM literature at some other sources of evidence base. I found some really interesting materials coming in from the dermatology community, as well as scientists who are interested in the physiology, biochemistry, and health of skin.
I discovered that they’d produced all this great work, and there’s quite a volume of literature on this, looking at what they referred to as the neuroendocrine axis. There’s an author who even put out a paper there calling skin like the brain on the outside. I thought, what? because I’d always seen skin just as being this protective layer, that’s to stop bacteria from getting in there and protect my innermost portions of the body from excessive exposure to dangerous wavelengths of light. I didn’t really think of it as being an organ.
Yet skin is a very sophisticated organ. It’s not just involved in the manufacture of vitamin D from the collision of ultraviolet light with some of the stuff that’s manufacturing the skin, which is a form of cholesterol. It’s also involved in the manufacture of all sorts of steroids, all sorts of hormones, and unbelievably, all sorts of really important neurotransmitters.
These are the chemicals that activate nerves, including important centers inside the brain, things like serotonin, which is the happy drug as it were, noradrenaline, which is the berserker drug as it were. It’s the thing where you really worked up and that’s very active. Other things like dopamine and dopamine is the feel good almost like addictive behavior drug. Along with things like Adrenocorticotropic hormone, luteinizing hormone and all sorts of other things. These are all manufactured in the skin. I thought that’s astounding.
Then there are pathways associated with the transmission of these materials into deeper structures. There’s a constant conversation between the skin and the nerves that are going to the central nervous system, not your brain and back. It’s not just a one-way messaging system. The nerves send signals back and forth. The skin is constantly monitoring the external environment in order to protect us as to, if it’s getting too hot, you start to sweat. That’s an obvious example, of that defensive reaction.
Skin is a highly complex organ with an interface where the cells that make up the skin, like keratinocytes, as well as melanocytes, are doing a lot more than you might think. By exposing skin to light, it’s not a question just of the skin protecting you. You’re actually producing some very profound biological effects in the skin, which can then start to have some systemic effects.
You know how it is on a nice, sunny day? You feel good, and there’s a reason for it. There’s no serotonin, you’re feeling happy. It’s a happy drug that’s been generated in your skin and exposure to light. This is key to health. Sun avoiders, people who hide from the sun, they’re at the same risk of premature death as people who smoke and some Swedish stuff. That’s not to say you should go out and overexpose yourself in the sun because it can be dangerous. You live in one of the sunshine capitals of the world in California and the midday sun, it’s got a lot of UV there. You’ll damage your skin, you could get skin cancers.
Ari: I spent most of the last four years in Costa Rica. It’s a totally different animal there compared to California.
Dr. Cronshaw: Okay. Costa Rica is beautiful. I don’t blame you. Let’s say that it’s the same issue of the amount of energy that you’re being exposed to. If you’ve got too little, it’s harmful. Too much, it can be harmful. The way in which skin’s there, it is in part a protective system, but there is a dynamic there. When you start to expose skin to light, you need a little bit more than you perhaps realize. It’s not just a matter of irradiating any materials in the blood, and you’re getting, say, like five to seven liters per minute of blood being pumped through the tissues.
When you start to expose large areas of skin, that’s a lot of blood that you’re irradiating, and that can have an effect on the immune system. It can affect how active the white blood cells are in combating infection. It can affect how competent platelets are in sticking together and clotting them, things like this.
It can affect all manner of other things, so much so that there’s a big literature where in the former Soviet Union, they had a lot of science studies where they were sticking a laser into a vein and they were irradiating the passing blood in order to start treating things like heart disease and diabetes, and all the rest of it, because they believed that this was a great way of producing a systemic anti-inflammatory effect.
The way in which this is mediated is very interesting. I’ve looked to see what the potential is, and in part, it’s due to the manufacture of these various chemicals, but also it can have an effect on the innervation. Now, nerves are present in skin. The other thing that’s present in skin are hair follicles, and hair follicles are hairs which go down to the hair follicle. The hair follicles have got a very rich innervation.
It’s possible that by feeding light onto nerves, well, nerves have got things called opsins as well as other iron gates which are photoreactive, and so this can then start to stimulate some nervous activity. These nerves, when activated, that’ll go through back to the spinal column and up to your brain, and all sorts of complex pathways can then be triggered.
There’s a lot that we don’t know. What we do know is what the safe limits are in regards to exposure, and the benefits that can be associated with it. We know some broad-sword aspects. For instance, if you’re doing transplant surgery, then if you irradiate people, expose people to blue wavelengths of light, their immune system’s much less active, and the transplant is much more likely to succeed, and things like this.
We’re starting to manipulate how we’re using light as an environmental factor in health. Inadvertently, there’s also adverse effects because at night people are doing stuff like looking at their tablets and their mobile phones, and this is quite blue white light, and that could be having a damaging effect, both in your eyes as well as affecting your circadian rhythms.
I wouldn’t say it’s an emergent area because we know a lot about it now, but when it comes to the therapeutic aspects of how best we drive this as a process, I describe this in PBM as something which is at most maybe a dawning awareness. Leading thinkers like Mike Hamblin are obviously very aware of it, and I guess Praveen will be too. So much in the PBM community at the moment is just so obsessed with the mitochondria. I think skin is terribly, terribly important.
Ari: Dr. Cronshaw, I think we ought to wrap this episode here, and we still have a ton to talk about. I feel like we can talk for probably 20 more hours. We still might be scratching the surface of your knowledge, but I feel like what you’ve done here is you’ve begun to paint a much more expansive picture for people of the interaction between light and human physiology.
You’ve start to rupture a lot of the constraints, the boxes that people tend to think in when it comes to photobiomodulation, seeing it as just a simple story of red and near-infrared wavelengths at particular wavelengths, having these unique interactions with, let’s say, cytochrome c oxidase in the mitochondria and nitric oxide. That’s the whole story of photobiomodulation.
I think what you’ve done here is really begun to paint this much more expansive picture where we start to see, well, actually, there’s a lot of wavelengths and a lot of layers of how these photons are interacting with human biology. I think some listeners might be frustrated maybe with a lack of practical take-home sort of, what should I do now? What device should I buy? How should I use it? This is just the reality of where this conversation has to go to first start to expand our understanding of what is actually going on between light and human biology.
Now with that more expansive picture, I think we can start to move into more specifics and more of the side that has more practical relevance. I think one interesting thing I can’t help but ask you before we wrap up is, I keep feeling like in many of the lines of logic that you’re presenting, that there is almost an argument towards– a naturalistic argument towards the idea that sunlight exposure is really, really important and that we maybe shouldn’t neglect that layer of the story in favor of this idea that a laser at 904 nanometers, a whole specific expansive evolutionary frame.
I’m curious if you have any thoughts on that before we conclude this one.
Dr. Cronshaw: The best time of day to expose yourself in the sun is when there isn’t too much UV around. A little bit of early morning sunshine, that’s when you get more of the red and near infrared wavelengths. That can precondition you. A little bit of 20 minutes to half an hour in the early morning sunshine, you’re unlikely to burn yourself. You could end up therapeutically achieving some benefits. It’ll improve your mood. You’ll be getting some exercise.
Also, along the way, physiologically, your tissues that have been exposed to those wavelengths will be a little bit more robust to stress and to trauma. It can be having some benefits. When it comes to sun, I certainly don’t recommend that you hide from the sun. At the same time, you have to be very, very aware that it’s a broadband. Although UV is only a small segment of what’s present, you need a tiny bit of UV. Some UV is carcinogenic. It can produce mutagenic change.
A little bit is really good for you. It’s good for generation of some very important hormones, like adrenocorticotrophic hormone, without which you’re not going to be so well. Then I’m primarily an office worker, particularly this time of year in the northern hemisphere, I go to work, and it’s still dark. I come home, and it’s still dark. I’m not getting enough light exposure. This is where some therapeutic lights, I think, can have some benefits.
Tissue heating is that a concern?
Ari: Dr. Cronshaw, so I want to get straight into some areas of controversy, important areas of controversy in this field of photobiomodulation. Also, I think there’s issues here, maybe areas of controversy within academic circles, and maybe different and somewhat overlapping areas of controversy within more of the general public, and then argumentation that goes on between different PBM device manufacturers. There’s probably some important distinctions there.
I think to start with, one of the key areas we need to get into is irradiance. There is quite a bit of controversy and argumentation that goes on within LED PBM circles around irradiance. I would say on one end of this spectrum, we have the people who are essentially of the view, and I would say this has been perpetuated by a lot of PBM device manufacturers, panel manufacturers in particular, who are generally promoting the idea that the higher irradiance, the better.
There has been a race within LED panel manufacturers that they’re all competing with each other for several years now of who has the highest irradiance panel. Over the last several years, everybody’s making more and more powerful panels, and everybody’s claiming that they have the most powerful panel. That’s all built around the assumption that higher irradiance means better, means better PBM effects.
On the other end of the spectrum, there are some people who argue that actually PBM should occur at fairly low irradiance. Some people who have even argued that over 50 milliwatts per square centimeter, anything significantly over that is excessive. This also relates to an issue of tissue heating. We need to address that as well as to what degree an irradiant starts to produce tissue heating, to what degree is tissue heating either acceptable or problematic or harmful.
What are your thoughts on the big controversy over irradiance and PBM?
Dr. Cronshaw: I think, first of all, it helps if you just discuss together a little of exactly what irradiance is, okay? Irradiance is essentially how you’ve packaged the energy in terms of delivery. The unit of energy is the joule, and the unit of irradiance, this is the number of joules per square centimeter you’ve delivered in a unit time, which we refer to as watts per square centimeter. That sounds awfully complicated. Let’s break that down a bit.
If you were to think of it a little bit like the gas tank in your car, the number of liters of petrol you stick in your car, that’s the joule, the number of joules that you’ve got available to go off for that long run to Vegas or whatever. Whereas the size of the engine, that’s the rate at which you’re going to burn it off. Do you have a little Fiat Cinquecento, which in this case is really low power, and you’re not going to be burning off much. You’re going to have loads of gas when you get to Vegas, or are you going to be driving a great big bus, like that nice Mercedes where halfway there, you’ve got to stop and fill up your gas tank?
The irradiance really is the rate at which you’re applying the energy to an area, which is a critical parameter. Now, by convention, when we’re talking about PBM, we look at a square centimeter because it’s a useful unit. This is where it really starts to get a little bit more complicated because people talk about power density as being the same as irradiance. Now, there’s a world of difference between the two. Power density is centimeters cubed, is the volume, not per square centimeter, all right?
Now, why is that important? If you’re a poor little fibroblast, a cell that produces collagen, and you’re sitting on the surface, and then you get delivered, say, five joules per square centimeter, hey, it’s a good day, you’re going to start producing lots of collagen. Whereas if you’re in a volume of tissue, maybe you’re not going to get exposed to that amount of energy because you’re beneath the superficial layers. When you think about irradiance, it’s a convention where we’re looking at the amount of energy delivered in a unit of time to a very superficial plane, like slices of a cake.
Having got that out of the way, then you have to think about, well, when you’re thinking about doing this, you can have a very small device like, say, a laser pointer, where the emission from that laser pointer is less than a single milliwatt. It’s a single thousandth of a watt. Yet, that is a very intense light source. Somebody points one at you, and you immediately blink if it’s in a visible range inside of 0.25 of a second to protect your eyes, because it’s a very intense source, because it’s a laser.
Even though it’s a very small spot size, because of the nature of the source, it’s having more impact on the tissues. The other aspect when you’re thinking about irradiance is what is the source? Is it a laser, or is it an LED? Because they will produce very different effects. The safety authorities have a concept of the maximum permitted exposure, which is the safe limit for hours of exposure to light of different sorts. That, for an LED, is very different to that for a laser.
When you’re thinking about irradiance, don’t just think about it as being the amount of energy you’re delivering per unit second to an area. What sort of sources are you using? Is it a laser, or is it an LED? Now, for the consumer, for normal people who aren’t clinicians, you’re not going to be able to get your hands on a laser. If you do, it’ll be a really weak, low-powered one because people like the USFDA, they don’t want you to damage yourself. They have all this protective legislation there, intended to make sure that untrained people don’t end up damaging themselves or their friends.
A lot of the stuff associated with lasers doesn’t really apply unless you’re clinicians, who are involved, in which case it’s a different story. When it comes to an LED, because of the difference in the way in which energy is packaged in an LED, as opposed to all the energy being concentrated where all the photons are in the same time and space, it’s scattered. There isn’t what we call temporal coherence. Say, a watt per square centimeter of LED is a very different story to a watt per square centimeter of laser energy. It’ll produce a very different biological effect.
One is you can sit beneath a one-watt bulb and you think, “Hey, that’s pleasant.” Whereas with a one-watt laser, you’ll jump, especially if it’s a small spot size. That’s going to get really hot. Think about source as well as, the spot size as well as the amount of energy. It starts to get even more complicated because then the issue is, well, is this a mathematical calculation or is this a reflection of the amount of energy that’s actually there? I can take a really small spot size device, say a 50-milliwatt output laser which is like a pen, a small pen device.
Because the optic spot, the size of the light that’s hitting the tissues is really small, I can start to get an irradiance of anything up to several watts per square centimeter. All right. How does that work? It’s because it’s a really weak source. It’s 0.05 of a watt. The spot size itself may be only, what, 2 millimeters in diameter. If you start doing your mathematics, 0.05 divided by 0.03, which is basically what it is, square centimeters, you’re then suddenly up to about one and a half to two watts per square centimeter.
Thinking, “Oh, hey, that’s dangerous.” No, it’s not because the amount of energy you’re actually delivering is very low. You’re only delivering 0.05 of a joule per second because a watt is a joule in a second. Look at the optics [crosstalk].
Ari: This very almost paradox thing where mathematically you’d arrive at an irradiance that seems like it’s this very high power light. Yet the total, if you were to look at it in total joules delivered, you’ve actually delivered a very minute amount of energy to the body.
Dr. Cronshaw: Absolutely. I think when you’re thinking about dissymmetry, it’s very useful to think how many joules have I actually delivered rather than just how many joules have I delivered per unit area because you might have pitched yourself that you’re delivering 5 joules per square centimeter, whereas with that 50 milliwatt device in 10 seconds, as opposed to having delivered 5 joules, in fact, you’ve only delivered maybe half a joule, 0.05. 50 milliwatts, that’s 0.05 of a watt, it would take you 20 seconds to deliver one joule and so it’s a really weak source.
Look at the power output and then look at the area, then you can start to make a rational decision about how relevant the calculation is for irradiance. If you’ve got a very small point applicator, then how useful is that in order for you to calculate your dissymmetry because you then start to get confused by the size of the mathematics and the size of the spot in relation to what you’re actually doing. Now, this has been very much an issue in some of the older scientific studies, where people didn’t realize this, and then they ended up with studies where they said, “No, this thing doesn’t work.”
I think now people are much more aware of this in the scientific community, but when you’re talking about irradiance, just think about what it actually represents. It’s the amount of energy in the amount of units of time you deliver to the unit area, and then get real about it. Think about, well, how big is the target? You’ve got that muscle you want to treat, how big is it? How many square centimeters is it? Then you can start to calculate how much energy you need to deliver in order to affect the change that you’re seeking to do, and then you have to then think about the rate at which you’re going to deliver it, and that’s the irradiance.
Now, the critical thing about irradiance is you don’t want to deliver it too slow because otherwise it’s going to take you forever. You might get there eventually, but life’s too short. We stood there for three or four hours, with this little pen thing waiting for finally, you got all the data, all the area. If you do it too quickly, then it’s going to get hot, really hot, and you can start to cause some damage, particularly if you package that energy into too small an area.
As opposed to using a 50-milliwatt laser pointer, you use a 200-milliwatt laser pointer. These are the sort of thing that idiots start pointing out at planes, and they start to dazzle pilots who are coming into land, at long distance because the irradiance is really high for that small spot size. When you come back to this safety question, it always comes back to the amount of energy you’re delivering and the rate at which you’re delivering it.
Rather than spitting out numbers and saying, “No, you mustn’t give more than 50 milliwatts per square centimeter,” think about, well, how much energy total am I delivering to what area? Then it’s a more rational thing. Now, with something like a flat panel LED, then that’s less of an issue than if it’s a small spot applicator because you’re less likely to underdose things, and then this issue then of higher irradiance becomes more relevant.
What happens if the irradiance is too high? Quite a substantial component of the energy, when it’s absorbed in the tissues, results in molecular vibration, and that generates heat. If you get too much heat, then you can start to cause some damage. What’s the level in which you start to cause damage? Then there’s a theoretical level, and then there’s a pragmatic and practical level, which we can return to later on. Essentially, you want to just gently tickle the cells, rather than suddenly sticking them in a bath of hot water because otherwise, you’re going to have a problem.
When you’re thinking about safe limits for irradiance, assuming that you’re not using some small spot size, assuming you’re not using a laser, and you’re looking at an LED, then the other issue then is which wavelength are you using? If you’re using some wavelengths, the amount of energy associated with that wavelength is much higher than it is with longer wavelengths.
Say you take a blue wavelength LED torch, and you decide that you’re going to look straight in at it, then it’s in the visible spectrum, and you’ll blink, but inside of that 2.25 of a second, which is your blimp reflex, there will be some energy will have reached the back of your retina. Blue wavelengths are ones which can cause what’s known as photobleaching, and they can cause some damage to the receptor cells, which are particularly sensitive to blue light, and that can then lead in later life, to age-related macular degeneration, as well as other associated permanent damage to the retina.
You need to be really careful with blue wavelengths, particularly if it’s a baby, or an elderly person, or somebody who’s maybe had some ophthalmic surgery. Blue wavelengths is a caution. Now, on a nice, beautiful, blue, sunny day, is it dangerous to stare at the blue sky? No. Your body has got good defensive reflexes, so if you’re getting an excess of energy, you blink, and you avert, and the aversion signal is sufficient for most purposes, but with some of the LEDs which are currently on sale, then you’ve got anything up to maybe 100 milliwatts of emission of that blue wavelength.
You certainly would not want to be looking directly at it. It’d be unpleasant for you anyway, and if you kept doing that, then you could end up damaging your eyes. That would be harmful and there are certain vulnerable groups you definitely wouldn’t recommend it. Some of the elderly people, and the other groups I previously mentioned.
As for the red to near-infrared, which is where most people end up looking when they’re thinking about buying a therapeutic PBM device, although there are these other multi-wavelength devices, which have got blue included in them, but what safe limits can you look at? If you then think, well, why is there a safe limit? It all revolves around the effects in terms of temperature on the tissue rather than anything else.
For the red to near-infrared, what you don’t want to do is to have an irradiance which is high enough to start to cause heating over and above the potential of the tissues to manage, to the extent where you start to see signs of tissue damage. Where does that rest? If you’re talking about an LED, you’re in pretty safe ground because it’s not such an intense light source as a laser. It’ll take you substantially longer at a higher radiance to start to get that thermal rise to the danger territory.
The danger territory we’re looking at here is sustained elevation of temperature above around about 45 degrees centigrade. That over a long period of time, eventually, you’ll start to see some damage which will manifest itself as some damage to proteins and fatty acid chains. You could, if you really, really worked at it. It’s a little bit like we were talking about earlier about my AGA, this cast iron oven, where you’ve just got that nice simmering oven, you put the food in there, and it’s maybe only maybe, I don’t know, something like 30, 35 degrees centigrade.
It feels nice and warm, but it’s not hot. You leave it there all day, and that cumulated energy progressively will then start to degrade protein to the extent that, that nice lamb shank is just falling off the bone. The issue then is the rate at which you’re delivering it. Now, if the rate from which you’re delivering it is relatively low, then you’re very unlikely to inadvertently damage tissues, so what is too high?
Assuming you’re dealing with red to near infrared wavelengths, you’ve got quite a lot of leeway when it comes to LEDs because you can start to go up to anything up to maybe a couple of a hundred milliwatts before you start to get a rapid thermal rise. Now, if you’re standing underneath a red or near infrared panel, which has got a very high irradiance, you’re going to feel heat, and you’ll feel heat when it reaches 43 degrees centigrade because you’ve got some sensors present which are called TRPVs.
There’s one, TRPV1, which is an iron gate which opens when it reaches 43 degrees centigrade. It’s both temperature as well as light-sensitive. When that gate opens, you go, “Oh, oh, that’s unpleasant, that’s hot, I’m moving.” When I’m doing my therapeutic PBM laser treatment with more intensive treatments for my patients, and my patient says, “It’s getting really quite warm,” I know I’m just getting to that threshold. That’s a safe threshold because above that level, this is where if I was to keep doing it, they’re not going to just sit there and let me overheat them. Macabrely patients don’t appreciate being barbecued. It just doesn’t happen. People pull away and say it’s too hot. I think the issue to do with irradiance with LEDs, there’s some flexibility there.
Generally, we like to administer a dose so that it’s gradual and it’s cumulative rather than shocking the cells, particularly if it’s a subsurface target. If you’ve got a superficial condition, then because you have these superficial sensors, you’re not going to cause some damage to the underlying tissues because they will fire long before you get to a point where you’re in the danger zone.
If you’re dealing with deeper tissues because of the difficulty to do with delivering the dose, because it takes a lot longer to start to deliver the photons to depth, then there is an ascending danger that you could end up overheating the overlying tissues. Then again, there is this natural protective system present, which will prevent you from damaging yourself.
I think when people start making pronouncements, that now you shouldn’t go above 50 milliwatts, I think this is, in my opinion, a little bit excessive, to say the least. A little bit like your kid’s first bike. They have stabilizers on them. You can go that way if you like, but it’s not something which is written in stone as an absolute far from it. If you look at the scientific literature on this, you’ll find that, for instance, the Multinational Association for Cancer Care and the International Society of Oral Oncology, who have an interest in phototherapies for treating cancer patients, they recommend not going above around about 150 milliwatts per square centimeter. That’s their international statement.
Ari: That’s with LED devices.
Dr. Cronshaw: Actually, that’s for a laser. When it comes to other authorities, people like Mike Hamblin, who did a paper with Randa Zain, who’s a former student of mine, and Wayne Selting, who’s a former mentor of mine, and all these people, they recommended for certain wavelengths not going above 750 milliwatts per square centimeter. It was wavelength-dependent.
Ari: This was, if you don’t mind me interjecting, I’m looking at this paper right now that you’re referring to. It’s called Review of Light Parameters and Biomodulation Efficacy: Dive into Complexity. They’re reviewing these parameters, and they say– This is a quote from this paper talking about the subject.
They say, “For instance, there exists a lower threshold, perhaps 0.5 milliwatts per centimeter squared, below which the illumination time could be infinite and would be no different from daylight. Similarly, the upper threshold is fixed by the possible photothermal effect–” That’s the heating of the tissues, “If the power density is too large. The irradiance values that produce unacceptable heating of the tissue are governed by the wavelength and are approximately 750 milliwatts per centimeter squared at 800 to 900 nanometers–” That’s the near-infrared, “And 300 milliwatts per centimeter squared at 600 to 700 nanometers, and as low as 100 milliwatts per centimeter squared at 400 to 500 nanometers.”
That’s the blue wavelengths of the spectrum. Actually, subsequently in conversation with Dr. Hamblin, he revised down the near-infrared safe parameters from about 750, as it states in this paper. He said he thinks it’s more around 500 milliwatts per centimeter squared.
Dr. Cronshaw: Absolutely. I would agree with that. I do disagree that 0.5 of a milliwatts would take an infinite amount of time. There’s actually a paper out there where somebody used some fiber-optic impregnated fabric with a really low irradiance. I think it’s 0.2 of a milliwatt over about five and a half to six hours. They were still able to biostimulate some tissue culture cells. Really low dose radiation can work. It just takes hours. Particularly, if it’s a subsurface target, it’s just not rational or reasonable.
Maybe you just wouldn’t get there. I think the pragmatic aspect to this is, do you have to be bound to only go for something which is a low irradiance? For red to near-infrared, I think if you’re, as a consumer, looking at the source, which in combination with all the different sources of light that are present in that device, because often you get multiple wavelengths present, a mixture of red and near-infrared of no more than about 500 milliwatts per square centimeter, you’re safe.
It’s not going to be so fast and so hot that you’re going to cause yourself a burn or a problem. You’ll know when it gets too warm because your body will tell you because it gets about 43 degrees centigrade and you will switch it off or leave. The other aspect to this, I guess, is this concept of area. Now, when you’re delivering dose, the bigger the area on the surface that you deliver it to, the more effect you’ll have on deeper subsurface targets, which is interesting.
I did a paper on this where I was actually looking at lasers, but I think this applies to LEDs as well. This is where I think Dr. Hamblin’s ideas of total dose start to come in because in order to start to treat appreciable volumes of tissue, you’ve got to stick enough energy in there to be able to produce the effect that you’re seeking which is, I think, a very brief approximation of where we are with that. Hopefully, that’s helped you with that rather complex discussion.
Ari: Yes. I want to just clarify a couple more points here. Let me do this layer first. There are some people who argue that photobiomodulation is by definition, non-thermal. That basically meaning that if we’re delivering, let’s say wavelengths in the red and near-infrared part of the spectrum, and there is, I guess maybe by this definition, any heating of the tissues, really, you don’t find a specific temperature associated with this argument.
The idea is that it should be non-thermal, which presumably applies, means no heating of the tissues. By this line of argumentation, anytime you’re applying photobiomodulation with using parameters that are causing, let’s say some degree of heating, let’s say a one or two or three or four degree rise in the tissue temperatures. Therefore, it means it’s not true photobiomodulation because it causes a normal effect. What do you think of this line of argumentation?
Dr. Cronshaw: It’s very pure thinking in the sense that trying to splice what photobiomodulation is into a certain pathway, which is related to a photochemical process, as opposed to the more intricate aspects of electromagnetic irradiation on biological tissues. In any chemical reaction, you get heat as a byproduct. You can’t have a chemical reaction without there being some spin-off in terms of heat. The 100% pure transfer of photonic energy into a photochemical one just doesn’t happen.
You always get heat and heat is very strictly regulated inside the cell. When they’re talking about heat, they’re talking about measurable heat in terms of tangible temperature increases, which then may be beyond the cell and into the tissues. This is where, indeed, there is a difference between photobiomodulation and its effects and heat. The two things inevitably go together. You always get some heat, even with a 50-milliwatt source.
If you were to get an ultra-sensitive temperature-sensitive fluorescent probe, which is the sort of stuff they’re using in laboratories now, where they’ve got some amazing microscopy and they can see the effects of little hotspots inside of the cell, then they can see that there are temperature gradients inside the cell. Actually, the mitochondria are much hotter than the rest of the cell. This is where, in terms of evolution, is one of the principal roles of mitochondria is not just to push out this really valuable energy currency, ATP, it’s also to generate heat.
There’s even one author who suggests that mitochondria look like radiators because they have these Christy plates like this, and they look just like radiators. That’s what they do. There is also endothermal heat, and that’s a byproduct of the chemical reactions associated with what we call oxidative phosphorylation, which is this fantastic process where sugars are broken down into the constituent energies in the control fashion. That energy is then used to fashion biological, useful little packets of energy, which the cell can then metabolize like ATP.
It’s biologically a nonsense to say that in photobiomodulation, there is no heat. It’s impossible. Either that or they belong to a different physical planet to the rest of us. It’s just not possible. I think where this argument gets conflated, if you’ll forgive the phrase, is when people start talking about the potential harmful effects of heat, where people say, well, if you heat up the cell beyond a couple of degrees centigrade, then you’re no longer seeing the stimulatory effects that you see in terms of metabolism.
Now, I’d dive fairly deep into this as part of my thesis. I found that the dermatology community have found that if you warm cells up a little bit, no more than two degrees centigrade, you get better skin healing. Beyond that, then as opposed to better skin healing, you see poorer skin healing. It just doesn’t heal as well as otherwise it might have done. The argument then is that photobiomodulation is all low dosimetry photobiomodulation below the threshold which heats the cells up above two degrees centigrade.
However, in that higher temperature range, when you’re starting to get up to round about 39.5 through to about 42 degrees centigrade, some very useful things clinically can happen because this coincides with what I would refer to as an analgesia zone, because then the cell, in order to protect itself, has got some very complex internal switching mechanisms, which allows itself to slow down the generation of heat to protect the cell from the damaging effects of excessive heat, because proteins, when they’re part manufactured, are very sensitive to temperature.
If it’s just a little bit too warm there, then you get damage to those proteins. This natural hormetic protective cascade kicks in, which then mothballs metabolism and everything shuts down until the stress is removed. Now, when things shut down, that can include nerves. If you’ve got pain and you can switch off the axon, you’ve not got pain anymore. That’s useful clinically. Maybe this is something which is a desirable effect. That again is photobiomodulation. As opposed to it being photobiostimulation, this is photobioinhibition.
Now, is that the same as photobiomodulation? I would say that it is. The purists would say, no, it’s only photobiostimulation. Otherwise, you’re looking at a heat-based one. They’re welcome to it. If there are patients seeking to get out of pain, I’m going to describe it as PBM that I’m doing, in order to help. It’s almost a semantic argument.
The range beyond which you don’t want to go is sustained increases of temperature above 45 degrees centigrade, where after a while, here you’re looking at some time, then you can start to see signs of tissue damage because then you’re starting to progressively overwhelm the capacity of the tissues to withstand the sustained insults of the temperature. The hotter it is, the shorter the duration the tissues can stand to exposure to heat.
You can have a sip of coffee or tea, which is maybe 55, not quite 60 degrees centigrade. You don’t burn your lips because it’s in present in contact with the tissues for less than a second. It’s spread over an area and you don’t burn yourself, just like you can lick your finger and touch the hot stove for a moment, without burning yourself. It’s the same. There’s a trade off between the temperature rise, the peak temperature that you achieve and the amount of damage you’re going to get.
Now, just to conclude what I’m saying, if you go up and above 60 degrees centigrade, inevitably, then that’s the level at which you are bound to coagulate proteins. This is where you’ve got your egg in your frying pan and you see it starting to go white because you’re denaturing the egg, which is where you don’t want to be.
Ari: [crosstalk] pretty far away from that point, though.
Dr. Cronshaw: Then that’s not really PBM. That’s the sort of thing I would be achieving when I’m doing laser surgery. When I’m doing laser surgery, I may intentionally heat tissues up so that they boil or alternatively that they fragment by the explosive, expansive power of steam so I can separate tissues to make my incisions and excisions and kill bacteria and things like this.
A little bit of superficial heat can be used selectively to kill pathogens like bacteria, viruses and fungi, which is why intense light sources like the blue wavelengths can be really useful as a superficial treatment because then they selectively absorb this very intense light source and it overheats those bugs and it kills them. This will work on things like MRSA, Methicillin Resistant Staph Aureus, which is a really wicked bug, which is multidrug-resistant, as well as some other of the heavy duty pathogens.
A little bit of heat can be useful therapeutically. For instance, physiotherapists do a type of treatment called diathermy where they heat up muscles where they have fasciculation. It’s a trigger point where you have that painful spot, which is just not resolving and the intention is slightly overheated. Then that triggers off remodeling. Similarly, dermatologists, when they’re doing facial aesthetics, they can do some treatments where they traumatize the surface of the tissue in order to trigger off an inflammatory response, in order to get remodeling of the tissues, to get rid of those acne points and to help give you nice collagen-rich, more useful tissues.
Ari: What temperatures roughly do you think would correspond to cause that sort of low damage that would induce remodeling?
Dr. Cronshaw: The equipment they’re using to do fractional dermatology, they’re actually using quite high temperatures, but they have a device which punches almost like tiny needle points, like a pinprick area of damage. That then triggers off remodeling and there it’ll be getting really hot. It may be as high as 100 degrees C-plus, but only for a very short duration of time. It’s very superficial damage. It’s something which has got very little collateral damage.
According to the wavelength from which they’re using it, it’s just enough just to get into the dermis, but without starting to cook and damage deep structures of collateral tissues. The parameters associated with this have been very carefully worked out, both scientifically, mathematically, as well as clinically by the dermatology communities. When you start to translate that pool of knowledge into PBM, you realize that the kit that we’re using, the apparatus we’re using, really doesn’t represent what you might refer to as a clear and present danger.
Ari: Let me present a couple of views to you, and this will speak to what you’ve already touched on here, but I just want to make sure we speak to this directly. Is the connection coming through okay at this point?
Dr. Cronshaw: Brilliant.
Ari: Okay. When I had Dr. Praveen Arany on my podcast, he seemed to mostly be arguing from the perspective that PBM should be non-thermal or mostly non-thermal. I think that was more of the camp that he was coming from. I think his exact words were something to the effect of, I think tissue heating has no place in PBM or something along those lines. When we dug into it further, he presented some research from his laboratory. I know you’re familiar with this study.
I think it was a mouse study or a rat study, where they showed that when the skin temperature got above 42 degrees Celsius, that it started to deactivate ROS, reactive oxygen species scavengers, and that this was indicative of harm starting to occur at 42 degrees Celsius. Then above 45 degrees Celsius, this is really when, I think, cellular damage starts to occur. That was Dr. Arany’s general take, is that he’s very concerned about tissue heating and then after some back and forth of clarifying whether PBM should be entirely non-thermal and whether heating of the skin temperature below 42 degrees Celsius is a problem, we had a back and forth there. Eventually, he clarified that he feels above 42 degrees Celsius is problematic. Overall, again, seems quite concerned about tissue heating.
Now, when I spoke to Dr. Hamblin about this same issue, he had quite a different perspective. His perspective was essentially almost like he was minimizing the importance of tissue heating. Number one, he said that the idea that PBM should be non-thermal, he said that’s rubbish. Those were his exact words, and that part of the mechanism of PBM is actually some degree of heating.
Now, when I asked him about irradiances that would lead to overheating of the tissue and at what degree is, what temperature would be considered problematic overheating, he seemed to mostly not be all that concerned with it because his position was basically, we’ve got sensors to detect when our tissues are overheating, and so we’re not just going to sit there and allow ourselves to be burned. Once we feel uncomfortably or painfully hot, we’re going to move that device or we’re going to stop the treatment. He almost felt like this is not even really an issue because nobody’s just going to sit there and harm themselves. What’s your take on those two perspectives?
Dr. Cronshaw: Of course, I’ve looked at the science and the study. I’m well acquainted with the study that Praveen did with Imran Khan and the Harvard group that did the study. In short, what they did was they took these poor little mice, and they shaved off the fur, and they took a laser, and I think it was a near-infrared 810 nanometer laser, so not an LED, but a laser, and they set it up at a distance from that poor little mouse’s leg. They set the output power of the laser to 3.2 watts to an area of 2 centimeters in diameter. That’s the equivalent of an area of 3.142, which is basically around about 1 watt per square centimeter, and that was their declared irradiance in that paper.
The problem with that is that some laser energy is inherently Gaussian. When you emit the energy from a laser, the energy doesn’t come out flat like that. It’s more like a traffic cone with a peak in the middle, and just short of 70% of the energy is in the mid-third of the beam. The periphery of the beam doesn’t get so much energy, but most of the energy is in the center. That basically means that that central zone, which is something which has got an area of around about 3 square centimeters, so around about that middle core of 1 centimeter squared, isn’t getting 1 watt, it’s actually getting 2 watts per square centimeter, which is really quite a lot of energy, especially from a laser.
It doesn’t stop there because in the middle of that 1 centimeter area, it carries on peaking as, as I say, it’s like a traffic cone. It comes to a peak, a spike in the middle of the beam. There, you’re getting up to 4 watts per square centimeter to an area around about 0.3 square centimeters. If you look at the histology of that study, you can see that there’s some localized photothermal-induced damage. That is a photothermal effect? All right. I contacted Praveen Irani, who is a scientist I’ve got great time for. I very much admire his work because there are many aspects of that study which are terrific.
I really like the work he did looking at the deactivation of the reactive oxygen species, and about 42 degrees centigrade, there’s catalyzed and the glutathione reductase and the potential toxic effects that could have. He did some very elegant tissue culture studies to confirm that, indeed, reactive oxygen species were an important element associated with the tissue damage that he said he was seeing in that if he basically neutralized those ROS, then he saw less tissue damage. He used that to argue that this is primarily an ROS-induced effect rather than photothermal effect.
However, in his tissue culture studies, he did exactly the same using a Gaussian source. I’m sorry, but I just don’t buy in. I am with Mike Hamblin, and I use high energy, large spot size laser devices, not LEDs, way beyond the capacity of the sort of stuff that you can buy on Amazon or eBay or whatever. I don’t go around burning patients. I’ve never had a patient with a burn, yet the level of energy that I’m using is at times really quite high. I might be putting 6.5 watts into something which has got a 12 1/2 square centimeter area, and all I’m doing there is I’m optically scanning to spread the beam in order to avoid overheating the energy in the middle of the beam, which is all you need to do.
In short, I think that there are strengths in Praveen’s study, which are really good, to do with the threshold beyond which certain key protective enzymes are deactivated. This association with it being an ROS. effect, I think it was a photothermal effect, not an ROS effect. I think it’s because he used a laser, I think, because the parameter in which he employed, then there was a lot of energy in the middle of the beam. If he was to repeat that, which maybe one day somebody will do with a different setup where it wasn’t a Gaussian beam and where they really were delivering 1 watt per square centimeter, I think you finally got a different effect.
Anyway, we wouldn’t use 1 watt per square centimetre in PBM. The maximum threshold we would use probably would be about 500 milliwatts per square centimeter, because we recognize that above that, certainly above 750 milliwatts per square centimeter, then there is an ascending risk of photothermal damage. I’m with Mike Hamblin, and so sorry, Praveen. We traded a couple of emails on this, and he says, “Well, we’ve got follow up studies.”
I very much respect the quality of his scientific work, but I did a paper myself all about photothermal aspects of photobiomodulation therapies. This is the sort of area where scientists differ. I don’t say Praveen’s wrong. I don’t think he would say that he’s right and I’m wrong. I think we could probably settle this sort of difference with some further tests and discussions. All this is telling me is that maybe we need to do some further studies before coming to a final position.
Ari: I suspect you’ll have some resistance to this question, but in the interest of, speaking to a [inaudible 00:48:04], who is using LED devices at home, whether we’re using LED panels or devices, more like neoprene pad style devices or things like this– this is a SunPowerLED Palm device from Tom Kerber, who I know. I have several other devices over here, LED devices. Speaking, I think, practically, taking everything that you’ve explained at this very high level of more scientific rigor that would be acceptable in an academic circle, practically speaking, what do you think are– what should be the level of concern that people have over the irradiance of LED-based devices and the degree to which there might be some warming or heating of the tissues?
Dr. Cronshaw: I think because there can be a multi-planar effect when you’re irradiating tissues, a little bit of warming is actually not a bad thing because the difficulty we have is in delivering photons to depth. Particularly, with a non-coherent source like an LED, if you’re doing a little bit of superficial warming, here I’m not talking about overheating in the sense of really heating things up, then you’re going to get what’s known as vasodilatation.
Then you’re going to get an enriched oxygenated blood supply quite deep into the tissues. You’ve got a sports injury, you’ve damaged your calf muscle, then that could be something which could then remove some of the lactic acid and some of the pro-inflammatory chemicals that are built up in that damaged area and offer you some relief. At the same time, the oxygenated blood supply could be beneficial.
Being more clinically oriented rather than some purists in regards to trying to activate some CCO and the electron transport chain, I can see that there could be multi planar effects in the sense of some, a little bit of warmth can actually be really helpful. As Dr. Hamblin says, there are these checks and balances within your own body, you’re very likely indeed with an LED to overdo it.
Devices like the one you showed, that neoprene pad or Tom Kerber’s SunPowerLED palm device, these are really good devices. I’ve got one myself. I have backache and it really helps me. It felt warm. That warmth wasn’t anything which was damaging me, it was actually helping because I got some vasodilatation of my deep back muscles, which really helps relieve some of the spasm that I was experiencing. Is this really a sort of an infrared heat therapy as opposed to PBM? I think here we’re splitting hairs because I’m just looking for therapeutic gain, and in terms of therapeutic benefits, I’m getting a combination effects.
PBM is not the same as heating. Heating is not the same as PBM. PBM and heating go hand in hand, you get a little bit of that no matter what low radiance you use. The issue then is there’s a little bit of warming, something which can be therapeutically beneficial. The answer is yes. What’s too much is when you’ve got a sustained elevated temperature above 45 degrees centigrade, because then as opposed to vasodilatation, what you get is vasoconstriction. The blood vessels close down, you then get containment of that heat, and that contained area, that can get hotter still. Then progressively, it can get to the level in which you’re going to get tissue damage, which is what you want to avoid.
Ari: To be clear, you said, I think, about 43 degrees Celsius is when we’re going to really start to feel subjectively the sense of pain?
Dr. Cronshaw: Absolutely. That’s when the TRPV channels open, TRPV1, and that’s when the axons get sensitized. That’s when you start to think, ow, that’s getting hot. Warming things up by two degrees centigrade above body temperature of 37.5 is a really useful thing if you want to induce analgesia. A little bit of warming then triggers off that protective mechanism inside the cell, which then switches off all the axonal activity and you see all manner of changes. It’s a fascinating area. I know that Juanita Anders at the Armed Forces University in the States has done a load of work on higher energy systems looking at managing chronic pain disorders, where with a single application of a higher intensity source, they’re seeing some long lasting relief from pain. It’s like resetting the axon so you can produce a temporary effect, but the more long lasting effects, that’s PBM. It isn’t just purely heat, but then there are aspects related to how this is working that we don’t as yet understand. Do you know it is an area of continued research? Short answer is a little bit of heat can be useful.
Ari: Okay. Last question to wrap up this, I think, this very important area of controversy within the PBM field. Using LED devices specifically, can you give a specific range of, and I think you’ve mentioned these numbers already in passing, but I just want to be clear about it. Is there a specific range of safe irradiance that we can say more generally this is going to keep us within the parameters that are not going to be a concern about overheating the tissues or causing damage to the tissues? Then, secondary to that is, is there an important distinction between photobiostimulation versus photobioinhibition and the irradiances that might correspond to one versus the other?
Dr. Cronshaw: For a start, I think more in terms of optic spot size rather than irradiance. Irradiance is the calculation that you’re looking to deliver a certain unit of power, which is the rate at which you’re delivering energy per square centimeter. Therefore, an NIR, an 800 nanometer wavelength device then, I think Mike Hamblin is quite right. I think keep it below 500 milliwatts per square centimeter. Then, I think you’re unlikely to find a device that’s got that amount of energy of it freely available to buy. When it comes to–
Ari: I think there’s one that I’ve seen that’s around that.
Dr. Cronshaw: There you go. There’s always going to be the guy that wants to buy the 5.6 liter rocket. Whatever. For my money, I’d rather drive safely around town. I don’t really want to have a hot rod where I might end up inadvertently overheating things. I think in the near infrared, that’s a good number to play. With the shorter wavelengths, with the red wavelengths, because there’s more energy associated with that photon, I suggest you put a lid on about 300 milliwatts per square centimeter as a maximum. Then when you start to get down to the shorter wavelengths, again, and I’d agree with Mike Hamblin, you want to be below 100 milliwatts because otherwise there is an appreciable possibility, because it’s such a hot wavelength, that you could start to cause some rapid heating with [unintelligible 00:56:01]
Ari: Milliwatts per wavelength, is that—
Dr. Cronshaw: The key decision is spot size. You want to go for a nice big applicator, something like that device you showed, that palm device, that’s really good, or one of these neoprene things with a larger area, because small devices like little torches and things, I just published a paper on it today, these can be useful but you’re only doing very small area. If you [unintelligible 00:56:31] large volumes of tissues, you’d be much more likely to produce the therapeutic effect that you’re seeking than if you use a larger device.
I would say go for a bigger optic spot size and then but there’s an element of ergonomics. If you’ve got something inside of your mouth, you’re not going fit Tom Kerber’s palm in there.
[laughter]
Dr. Cronshaw: That’d be a fine party trick. You can have some– maybe got a small glass optic probe and things like this and see how– This all comes into the considerations of the practicalities of the symmetry, which I’m hoping maybe we’ll have the opportunity to talk more about at length, maybe in one of your future podcasts.
The distinction between photobiostimulation and photobioinhibition
Ari: Excellent. Last thing is, is there an important distinction between photobiostimulation and photobioinhibition? You gave these parameters now, but is there further distinction between above, let’s say, 150 or 200 milliwatts? Now we started to get to get into an irradiance that’s more going to cause a photobioinhibition effect rather than a photobiostimulation effect? Is there any distinction along those lines?
Dr. Cronshaw: Ironically, I did a paper with Pravin called Feeling the Heat in 2019, which is all about PBM-associated analgesia. What I found, because this is a review paper that I wrote, which took an evolutionary perspective on the why mitochondria are incorporated in cells, the discovery I found from literature is that there are two dose windows. There’s a low dose window associated with stimulation. There’s a high dose window associated with analgesia, a safe zone from literature reviews of– since then we’ve conducted, as part of my research group, multiple systematic reviews and meta analysis.
The last paper we produced in ’22, I think it was, no, ’23, was looking at 143 different papers we included in the series, a huge study, which again just confirmed all the parameters that we decided that one window of opportunity to stimulate things, increase mitosis, increase production matrix, one dose in order to produce analgesia. How you go about delivering those joules, that’s related to the irradiance, which is the level at which you give it.
When I’m thinking about analgesia, I’m thinking more about dose, i.e. fluence, in other words, the radiant exposure, the number of joules per square centimeter I’ve actually delivered, rather than the rate at which I’m delivering it. Now, if I’m trying to deliver energy to a nerve, which is subsurface, as opposed to a superficial wound, I’m going to want to do that at a rate at which I don’t end up overheating the superficial layers of the tissues. There I may choose to go for something which is at a threshold below the area where I’m likely to end up overheating tissues, because the tissues are able to withstand a certain amount of thermal rise. If you do it too quickly, then they start to suffer from heat-induced stress, and it can start to produce some damage.
In short, the parameters that we discussed earlier, where you’ve got this upper limit with NIR 500 milliwatts per square centimeter, providing you’re using a decent-sized applicator of at least a centimeter or more in diameter, that’s fine. The only caveat to that is maybe scan the area, just move slowly in order to avoid overheating it. That’s particularly important if it’s a laser source. If it’s a really big applicator, and it’s an LED, you’re fine. You’re very unlikely to start to cause tissue damage because most of those devices are in the 100 to 200 milliwatts per square centimeter area.
Then, you just need to deliver sufficient joules in order to achieve the threshold, which is around about 10 to 15 joules per square centimeter at tissue level. This is where the maths start to get a little bit more complicated because you have to allow then for attenuation, which is loss of energy from the surface. As I say, that’s a great conversation to carry on if we talk more about dosimetry.
Ari: Yes, I think that one we need to get more into the layers of dosimetry of joules per square centimeter, as well as that also overlaps with discussions of [inaudible 01:01:30] and wavelength, and irradiance, tying a lot of different concepts, and spot size as well, tying a number of different concepts together there. Dr. Cronshaw, this has been wonderful. I continue to be in awe of the layers and bundles of knowledge that you have here, and loving this conversation, and excited to continue it. Thank you so much again for sharing all the wisdom and insights on these topics.
Dr. Cronshaw: It’s been very much my pleasure, and I look so much forward to continuing our discussions because then hopefully at the end of this long journey, your poor, long-suffering audience will actually know what to do.
[laughter]
Ari: Yes, we will get there. Probably in the next episode, maybe two more. There’s so much to cover here, but I think– I can see the PBM community, a lot of the PBM geeks, people like me who are not formal academics and researchers, like the people who are just trying to make sense of this landscape of PBM devices and how do we use them, these at-home devices, what are the proper dosing parameters. I think you’re doing critical work to cut through, to help clarify some really important areas of confusion. Very, very grateful to have this conversation.
Dr. Cronshaw: All right. Very much my pleasure. I’ll look forward to meeting you again.
Show Notes
00:00 – Intro
00:47 – Guest intro – Dr. Mark Cronshaw
04:32 – Eminence-based versus evidence-based science
12:34 – The big areas of controversy within dosimetry in PBM
26:45 – The effects of different wavelengths
1:02:07 – Is PBM treatment only local?
1:06:56 – Don’t underestimate your skin
1:24:42 – Tissue heating is that a concern?
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