In this groundbreaking interview with world expert Dermatologist Richard Weller, we discuss sunlight, skin cancer and the profound findings of large population-based studies that INCREASED ultraviolet (UV) light and greater sunlight is associated with LESS all cause mortality, less cardiovascular mortality and less cancer mortality, including skin cancer mortality K Biobank analysis, Stevenson et al. 2023 (pre-print)].
Professor Richard Weller is a UK dermatologist, researcher and world expert on the effect of ultraviolet (UV) light on systemic health. His discovery of nitric oxide (NO) release in the skin on UV-A exposure was pivotal in understanding the cardiovascular benefits of sunlight.
This interview is key in overturning the unreasonable sun-phobic narratives that disproportionately weight sun melanoma avoidance (misguided in causal model) while failing to appreciate the systemic and whole body, life extending benefits of UV light. Enjoy and share this episode!
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LINKS
Prof Weller bio - https://www.ed.ac.uk/inflammation-research/people/principal-investigators/professor-richard-weller
Higher ultraviolet light exposure is associated with lower mortality: an analysis of data from the UK Biobank cohort study - https://www.medrxiv.org/content/10.1101/2023.07.11.23292360v1
Avoidance of sun exposure is a risk factor for all-cause mortality: results from the Melanoma in Southern Sweden cohort - https://onlinelibrary.wiley.com/doi/10.1111/joim.12251
Follow DR MAX
Website: https://drmaxgulhane.com/
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Linktree: https://linktr.ee/maxgulhanemd
DISCLAIMER: The content in this podcast is purely for informational purposes and is not a substitute for professional medical advice, diagnosis, or treatment. Never disregard professional medical advice or delay in seeking it because of something you have heard on this podcast or YouTube channel. Do not make medication changes without first consulting your treating clinician.
#sun #sunlight #uvlight #ultravioletlight #circadianrhythm #circadianhealth #skincancerprevention #skincancer #skincancerawareness #melanoma #melanomaawareness #scc #bcc #squamouscellcarcinoma #cardiovascularfitness
In this groundbreaking interview with world expert Dermatologist Richard Weller, we discuss sunlight, skin cancer and the profound findings of large population-based studies that INCREASED ultraviolet (UV) light and greater sunlight is associated with LESS all cause mortality, less cardiovascular mortality and less cancer mortality, including skin cancer mortality K Biobank analysis, Stevenson et al. 2023 (pre-print)].
Professor Richard Weller is a UK dermatologist, researcher and world expert on the effect of ultraviolet (UV) light on systemic health. His discovery of nitric oxide (NO) release in the skin on UV-A exposure was pivotal in understanding the cardiovascular benefits of sunlight.
This interview is key in overturning the unreasonable sun-phobic narratives that disproportionately weight sun melanoma avoidance (misguided in causal model) while failing to appreciate the systemic and whole body, life extending benefits of UV light. Enjoy and share this episode!
--------------------------------------------------------------
LEARN how to GET HEALTHY SUN EXPOSURE - PRESALE Offer !
✅ Dr Max's Solar Callus Course 🌞
https://www.drmaxgulhane.com/offers/MbTx2Siw/checkout
See Dr Max, Dr Anthony Chaffee and more at the REGENERATE SUMMIT on April 21st in MELBOURNE, Australia
🎉 https://regenerateaus.com/
Join my private MEMBERS Q&A Group (USD20/month) to discuss this podcast with me
✅ https://www.skool.com/dr-maxs-circadian-reset
SUPPORT the Regenerative Health Podcast by purchasing through
✅ Bon Charge. Blue blockers, EMF laptop pads, circadian friendly lighting, and more.
Code DRMAX for 15% off. https://boncharge.com/?rfsn=7170569.687e6d
--------------------------------------------------------------
LINKS
Prof Weller bio - https://www.ed.ac.uk/inflammation-research/people/principal-investigators/professor-richard-weller
Higher ultraviolet light exposure is associated with lower mortality: an analysis of data from the UK Biobank cohort study - https://www.medrxiv.org/content/10.1101/2023.07.11.23292360v1
Avoidance of sun exposure is a risk factor for all-cause mortality: results from the Melanoma in Southern Sweden cohort - https://onlinelibrary.wiley.com/doi/10.1111/joim.12251
Follow DR MAX
Website: https://drmaxgulhane.com/
Private Group: https://www.skool.com/dr-maxs-circadian-reset
Courses: https://drmaxgulhane.com/collections/courses
Twitter: https://twitter.com/MaxGulhaneMD
Instagram: https://www.instagram.com/dr_max_gulhane/
Apple Podcasts: https://podcasts.apple.com/podcast/id1661751206
Spotify: https://open.spotify.com/show/6edRmG3IFafTYnwQiJjhwR
Linktree: https://linktr.ee/maxgulhanemd
DISCLAIMER: The content in this podcast is purely for informational purposes and is not a substitute for professional medical advice, diagnosis, or treatment. Never disregard professional medical advice or delay in seeking it because of something you have heard on this podcast or YouTube channel. Do not make medication changes without first consulting your treating clinician.
#sun #sunlight #uvlight #ultravioletlight #circadianrhythm #circadianhealth #skincancerprevention #skincancer #skincancerawareness #melanoma #melanomaawareness #scc #bcc #squamouscellcarcinoma #cardiovascularfitness
In one of the most important episodes of the Regenerative Health podcast, I'm speaking with dermatologist and researcher Professor Richard Weller from the UK. Now we discuss sunlight, skin cancer and the profound but clear and repeated findings from large population-based studies that increased ultraviolet light and sunlight is associated with less death, less cardiovascular death and less cancer death. I personally believe that sun avoidance narratives have been some of the most harmful of the public health messaging, given the critical role that all the wavelengths of natural sunlight have for optimal human health. Professor Weller is doing fantastic work in educating and researching these effects and adding nuance and balance to these narratives. If you want to learn how to harness the sun to reduce your risk of getting cardiovascular disease, cancer, autoimmune disease and your risk of dying, then check out my recently released Solar Calus Course. This is the most comprehensive course to date that puts together the theory, the preparation, the execution of getting sunlight in a way that is respecting your evolutionary biology. Now onto the podcast.
Speaker 1:Okay, I'm sitting down again with world-renowned dermatologist, professor Richard Weller. Now, professor Weller, you have released some very, very interesting research that we're going to get to, no doubt, in this podcast. But first I think it would very much benefit the listeners who don't have necessarily a background in medicine or dermatology to even understand some basic physiology of the skin, and that will really set us up for discussions about cancers of those different skin layers and how they're relevant to disease.
Speaker 2:The skin is great. It's where we meet the outside world. It's got, I suppose, a major role which is to keep the outside out and the inside in. It maintains moisture within the body. It keeps the environment and foreign organisms outside. It's that kind of envelope that wraps us up. So it's got quite a complex role. It also has to do things like sensation. It has to help us touch and feel. It has to do things like temperature control. So it's got a whole series of functions and it has to be self-healing.
Speaker 2:So it comes in layers and if the outermost layer strata and corneum is actually shed, we're continually shedding the skin from the outer surface of the skin. Below that you have the epidermis layer, the triple-layered structure of the epidermis. These skin cells, which we call keratinocytes, gradually move up and over the period of about three or four weeks, keratinocytes, which has started off on the bottom of the epidermis, move up the surface where they're shed, these corneocytes. Below that you have the dermis, which is the kind of permanent supporting structure of the skin, and that's where the blood vessels and sweat glands are embedded, and then sunlight. So that's the kind of layers of the skin and it varies in thickness depending on body site.
Speaker 2:Palms and soles are very thick. The face is much thinner. Skin Sunlight, uv, penetrates at different levels through the skin. So long long wavelength ultraviolet light, ultraviolet A, will actually penetrate through the epidermis down to the dermis Is the UVB raised. Shorter wavelength UV that makes vitamin D and causes burning doesn't penetrate as far, just goes into the epidermis. So yeah, and then so I suppose the other thing to add as well as the keratinocytes, the main skin cells, you've got other cells like melanocytes that produce melanin, causes skin pigmentation. You've got cells of the immune system that pick up infectious organisms or cancers coming in. You've got sensory cells. There's a number of other cell types, but the main type of cells are these keratinocytes, the skin cells.
Speaker 1:Great, and you mentioned that the UV light interacts and penetrates to different levels depending on its wavelength. What are the mechanisms that the skin has evolved to protect itself from what we're both acknowledging is the mutagenic effects of ultraviolet light?
Speaker 2:Yeah, so very interesting. The UVB hits us again, and particularly the UVB wavelengths will lead to DNA damage and mutations and actually the skin is continually facing that and the skin is continually having DNA mutations that might lead to cancer. So it's actually evolved lots of ways of handling that, because it's a constant thing. And I suppose the point to make about the skin meeting the environment, the skin meeting the outside world, is inevitably if you're meeting the outside world you're going to meet stuff that the body doesn't like and UV can cause mutations. So it's well set up to handle that.
Speaker 2:So there's a couple of things when DNA mutations occur which are caused by UV, there's a whole series of DNA repair enzymes. So the skin is continually detecting and correcting DNA mutations caused by UV. So that's the first thing. The second thing, of course, is actually where, continually it's a bit of a moving staircase.
Speaker 2:You form your keratinocytes at the bottom of the epidermis. They move up over a few weeks and are shared. That's actually a pretty useful process because any keratinocyte that might be heading down the route to a cancer is probably going to get shared. So you have this kind of shedding of the stuff that might cause problems. You then also have the technique called apoptosis, whereby keratinocytes that look like they're heading towards a cancer. If you haven't managed to repair that DNA, they will undergo a process called apoptosis. The body spots that and says ooh, and it kind of knocks off that skin cell so it can be harmlessly removed.
Speaker 2:So there's a lot of continual processes going on. I have to say what is really interesting is if you look at the number of DNA mutations in somebody with a keratinocyte skin cancer, a squamous cell skin cancer, and if you look at the number of DNA mutations with someone who's just got sunspots, you know active keratosis, something that every proper Australian has on their head beyond the age of 40, actually the mutation burden is about the same. So it is interesting that it's not the number of mutations that lead to skin cancer, it's mutations that escape surveillance and being removed at least a skin cancer. So yeah, yeah.
Speaker 1:And I want to make the point that the ingenious function of that continual shedding of those keratinocytes is in itself a form of protection against ultraviolet light, just like bark on a tree helps protect the living part of the tree.
Speaker 2:Yeah, indeed, and of course, the other thing is pigmentation. Melanin really counts, so melanocytes accrete melanin and melanin absorbs UV. It's a natural sunscreen and what's very interesting is you could have a cross section of the skin. What you see is you see a little cap of melanin, a little hat of melanin which sits over the nuclei in the lower part of the epidermis, giving protection against UV damage. And, of course, the real original Australians, aboriginal Australians, have dark skin to handle the high UV load. The problems we see are when white Europeans arrive on their convict ships 100 years ago and without that natural protection and that's where you see the UV and use skin cancer on the skin aging In people who. Basically, if you walk to Australia from Africa over 20,000 years, that gives you time for your skin to adapt to that changing UV environment. If you spend eight weeks on a ship from a British prison to an Australian to Australia, you don't get time to make those changes.
Speaker 1:I think that gets to the heart of the issue, which is the, the, the deviation or the problem with skin physiology that leads to cancer, and I think the key issue here is that underlying what's going on is a mismatch between skin pigmentation, genetic predisposition to having a certain skin pigmentation and latitude, and when that is mismatched, then we are more likely to get these types of malignancies.
Speaker 1:I want to make a point about melanin, because you mentioned that it absorbs ultraviolet light and, for those who have listened to my previous podcast that I've discussed melanin and it is essentially a black hole pigment. It's not only absorbing ultraviolet, but it's also absorbing visible light and basically everything on the electromagnetic spectrum. Dr Jaqruz, particularly, has talked about the role of melanin in actually splitting, using, having an ability to essentially derive energy from the, from the use of melanin. So I mean melanin is so key and the other fact, the fact is that it include heavy metal chelation, they include antioxidant ability. So, and I think what maybe isn't being emphasized as much is how multi-purpose and how useful melanin actually is in the skin.
Speaker 2:Yeah, I'm unaware of those other. I know nothing about these other post-laterals melanin, I mean it's a, you know it's, it's important in handling UV, which I know best. And of course there's two main types of melanin. There's U melanin and the black melanin and then there's FIO melanin, the red melanin I might say very usefully in Australia. Just last week in the Australian and New Zealand Journal of Public Health a superposition paper was published by a bunch of excellent in a distinguished Australian research is led by Rachel Neal at the Berghoffer in Queensland and they have looked at UV advice risk-benefit ratios in Australia and they've and they formally lay out how skin colour determines the risk-benefit ratio to UV and so you have to consider a constrictive skin colour or background skin colour when giving correct UV exposure advice.
Speaker 1:And that's particularly relevant in your country when you have, and in all the latitudes, when you have people from the equator who are migrated north, and to give them the same advice as someone with a Fitzpatrick one pale skin makes, you know, absolutely no sense at all. So I'm glad that that kind of nuances is being added into the narrative.
Speaker 2:Yes, absolutely right. Of course, the other interesting comparison to our two countries. So, first of all, absolutely right, somebody from a high UV environment coming to Low UV Scotland utterly different from a red-headed Scott in Australia. The other thing, of course, is how you get the UV. So in Australia you have high UV all the time, whereas here in the UK our UV exposure tends to come in short-shot burst in the two weeks in the med in summer. So it's not just the amount of UV but the pattern of UV which varies between the two countries and that it's interesting.
Speaker 2:At the moment in the UK we are also just reconsidering our advice to UV. So the research arm of the NHS, the National Institute of Health Research, is currently going through a big analysis of all the published data on UV benefits as well as hazards, and that's the important matter and they're going to be drawing up their conclusions, I think in around May of this year and I'm interested to see the decisions they make. I think I strongly suspect they'll be acknowledging the benefits as well as the risks. Their advice for what we should do, I hope, will take into account the nature of UV exposure in the UK no sunlight at all except for two weeks in your summer holidays.
Speaker 1:Yes, and this is a point that you made the last time we spoke, which is that melanoma, and we're going to explain the different types of skin cancers, but melanoma is a disease of sun burning, not of sunlight exposure.
Speaker 1:And again, people who have listened to my previous podcast, I've talked about this concept of a solar callus and what I have meant by that is the idea that gradual, small amounts of ultraviolet light that essentially cultivates melanin production such that we're not in a position to get a raging burn, and that is essentially what people who are doing, who are unprepared for sunlight and UV maybe they fly from Luton Airport down to Ibiza and with their friends and they'll absolutely roast to a crisp. The point here that I think the nuance that isn't in this narrative, in this dialogue, is that these people have essentially a trophic skin with regard to the UV yield that they're putting themselves in and the environment that they're exposing themselves to, and perhaps if they had acclimatized that area through a process of gradual but deliberate but gradual UVB and UVA exposure, then they wouldn't have been in the position of getting a sunburn, but they'd also have built up sufficient vitamin D levels, and we know that vitamin D deficiency is a very, very common finding in melanoma and non-melanoma skin cancers.
Speaker 2:Yeah, suddenly, and particularly people with low measured vitamin D levels have a worse prognosis for their melanoma. People who have high vitamin D levels when diagnosed have better outcomes. So the epidemiology of melanoma, as you say, is interesting and complex. So when I'm teaching my medical students I say right, is melanoma common in white Australians or white Scots? And they all say white Australians. The next question is in Australia, is melanoma common in outdoor workers or indoor workers? And actually the answer is indoor workers. And is melanoma common in the untanned or the tanned? And it's common in the untanned. So, and then you know why is this? Now that's different from squamous cell skin cancers, one of the other. So melanoma is a tumor of melanocytes. Squamous cell skin cancer is a tumor of the keratinocytes. Now it's much commoner than melanoma but it's got a lower mortality. And squamous cell skin cancer is a disease of chronic sun exposure, commoner in white Australians than white Scots, common in outdoor workers than indoor workers, common in the tanned and the untanned. So squamous cell skin cancers are going to proper old fashioned cancer. That's read the books. The more of you know smoking, the more you smoke, the more likely you are to drop dead of lung cancer. Dose dependently, you know, the more cancers you have, and it's the same with squamous cell skin cancer. The more UV you have, the greater your risk of dying, of developing and dying a bit.
Speaker 2:But melanoma is not just, is actually a family of diseases and they're all slightly different. So the ones that are most diagnosed now, the superficial spreading melanomas and the nodular melanomas, are the risk factor there appears to be intermittent sun exposure and sunburn, particularly in childhood. There's then what are called the acral melanomas, which occur on the palms of the souls. Those are the melanomas that occur in black people. They're rare in black people. They're rare in white people, probably about equally rare. They are unrelated to UV. So there is ultraviolet. It pays no part in their development. They've got a completely different pattern of DNA mutations than the UV induced one. So that's a non somewhat pays no part at all.
Speaker 2:And the final and least common probably least, maybe, you know or a very uncommon type of melanoma is what's called an antagonomalignant melanoma. Now, that's actually a melanoma of chronic sun exposure and it occurs on the face, which is chronically sun exposed. And it occurs in old people I don't think I've ever seen anyone less than 80 with one and so it occurs on the face of really old people and that is due to chronic sun exposure. But here in the UK it occurs in really old people who've had decades and decades and decades of sun exposure and interestingly it's often quite thin and often it's got pretty good prognosis because it's so thin. But yes, broadly the melanomas that we see, most of the super spreading and the nodular, are diseases of sunburn, not sunlight.
Speaker 1:It's a fascinating implication, and the reality or the questions that it raises in my mind are exactly what is going on here, and to what degree is it environmental changes that we are experiencing that are perhaps unrelated to ultraviolet light? And I want to highlight a couple of more pieces of this puzzle before we necessarily dive deeper into the exact what we think might be going on. You highlighted, too, that outcome in melanoma is also poorer with vitamin D deficiency, so there's a lot of papers that I've managed to find that have simply been retrospective cohort studies that are looking at people who've had melanoma and, as you say, and those with a lower vitamin D level have a higher tumor mitotic rate. They have deeper thickness. All these outcomes that really predict a worse and more likely to die are lower in people who have a higher and people have lower vitamin D, and it really makes me think that we need to be cultivating the vitamin D level in people who have melanoma diagnosis, which, paradoxically, would involve more UVB light, not less.
Speaker 2:Yeah, so we have. We've got a paper on review at the moment. We did a big study in the. I presented this at a couple of meetings so I can talk about it because we will meet abstracts but the paper review. So we look to the UK bar bank. 400,000 people in the UK followed. I'm in, recruited back in about 2000. I was one of the subjects and then they're being followed from then on and a mass of data collected and all those of us who were subjects in terms of behavioral factors, lifestyle factors, health and baseline, masses of measurements taken on people. We're then being followed up. And of course in the UK we have universal health records in the National Health Service and we've got universal death records, universal cancer records, so you can link each of those people and you know what their behaviors are at the start with what happens to them with time.
Speaker 2:And we've been looking at sunlight exposure and how does sunlight exposure correlate with death from any cause? And we use two main measures of sunlight exposure the date you have to use the data that was collected. We found the best measures of sunlight exposure were to. First of all, we looked actually at sunbed users, not so much because of sunbed use, as because of the fact that we know that some bed users are what we call some seekers, we know that if sunbathes more, they actually go out in the sun. There's very good data showing that, behaviorally, people that use sunbeds are different from those that don't. Now we had to correct for the fact that sunbed users are different in other ways they're younger, they're more female, they're less educated, they're more likely to smoke, they're more likely to come from Manchester, etc. Etc. So you correct for all of those factors and so you throw in the corrections for that. We're then able to measure their vitamin D levels, and measured vitamin D is a great biomarker for sunlight exposure. Vitamin D has a few narrow benefits it prevents rickets, it may prevent progression of some cancers. It could be relevant to this story mechanistically, but most of all, from my point of view, measured vitamin D is an excellent biomarker for sunlight exposure and we found that the sun seekers people who use sunbeds do indeed have higher measured vitamin D levels. And you correct the vitamin D for obesity.
Speaker 2:You put in lots of corrections to make sure it's an accurate measure and it's not ultimately confoundless, and what we found were that the sun seekers had a lower all cause mortality than non-sun seekers. They lived but they particularly they had about a 13% reduction in cardiovascular mortality. They had around a I think it was about a 10% reduction in cancer mortality, including skin cancer. So people that got more sun were less likely to have any cause, less likely to have heart disease, less likely to have cancer, less likely to die of skin cancer, and it's interesting that that actually kind of matches up to this data. We know that people with who have higher measured levels of vitamin D when they're diagnosed, are great by a market for some of that exposure, have a better prognosis for their vitamin D.
Speaker 2:Now that doesn't tell you the mechanism. I mean, if you want to find a mechanism, if it's vitamin D, you do clinical trials and you give people vitamin D and you have a control group. You know half get vitamin D, half don't, and those clinical trials have been done and vitamin D doesn't do very much. It stops people getting rickets. It may prevent progression of some cancers, but the effect is probably pretty small. It's nothing like as big as the observational size of effect If you look at someone who's got twice as high. A measured vitamin D level has a great reduced risk of cancer death, for instance. But when you give people vitamin D levels double the vitamin D level you don't see the same size of effect. So it suggests you know the point is. I think the data is very robust.
Speaker 2:For sunlight, I should say the other measure of sunlight we use for the first one was sun seekers. Our second measure of sunlight exposure was how far south people live. Now in the UK, unlike Australia, the further south you live, the closer you are to the equator and the more sun you get. And we found, dose-dependently, the further south you lived, the higher your vitamin D level. The straight line relationship, thus straight line increase sunlight exposure and the further south you lived, the reduced all-course mortality, reduced cardiovascular mortality, reduced cancer mortality. Just the same pattern that we saw with the sun seekers, the sun bit users.
Speaker 2:And again, we correct for confounders the further south you live, the better educated you are, the less likely to smoke, the younger, the more female you know, etc. So we correct for all of those factors. But the story is consistent and it's the same story that Pelle Lingqvist in Sweden showed. Can't remember if we discussed this in our previous conversation, but Pelle Lingqvist did another similar study in Sweden where he looked at, recruited 30,000 Swedish women back in 1990, how much sunlight you get, you know, our sorts of factors are corrective for all. The confounders thought of them 25 years and he, just as did we in the UK, showed that dose-dependently, the more sunlight people get, the reduced all-course mortality, reduced cardiovascular mortality, just the same as us. So what we have repeatedly is, when we look at North European cohorts, separate cohorts, separate countries, separate studies, the same answer coming out, which is that the more sunlight people have, dose-dependently, the longer they live.
Speaker 1:It's a remarkable finding and it is truly I mean groundbreaking, and the fact that you've repeated a finding that Lingqvist et al found in 2016 makes the strength of that association even more important, and that is the Bradford Hill criteria. Is our observed finding repeatable? Yes, it is. I want to make a point about the vitamin D and, to me, the fact that you mentioned that you can't get the same effect on cardiovascular mortality, on cancer outcome, by supplementing vitamin D.
Speaker 1:This makes so much sense to me because the difference is between refined and supplement and full spectrum sunlight. Is there no way equivalent? And the fact that the vitamin D generated by full UV in the presence of full spectrum sunlight, is sulfated, it creates other vitamin D metabolites. So there's chalk and cheese. So that makes a lot of sense to me. Maybe you can talk about how you controlled for and these confounders in your study, because epidemiology is a topic, especially in the nutrition world, that is fraught with confounders things like recall bias, things like food frequency questionnaires. There's a lot of confounding in there and a lot of association that isn't able to basically give us the strength of conclusion that you have managed to find. So maybe talk about how you were able to ensure more robust validity of your findings.
Speaker 2:So all observational studies, rather than interventional studies, are prone to confounding. So confounder is something associated with the exposure sunlight exposure in this case and the outcome death. So maybe, if you'll so do, people that spend, people that spend more time outside, do more exercise. Exercise reduces your risk of death. So you have to then correct for exercise. If you're outside, you're probably exercising exercise separately from sunlight, so that's a confounder. It's independently associated with exposure and outcome. So you need to correct for that.
Speaker 2:There is no to correct for confounders. You have to think what that confounder might be. You can't say to the data set tell me what the confounders are. It doesn't work like that. And actually it means you as a scientist and doctor need to spend time going out and looking at how the world works. Spending your whole life in the library will not do it. So you know I have been down to tanning parlours when I'm doing some previous research and just looked at who goes in, because you need to think to yourself what do I think might be different? You've got to go out and live life and think what that is confounders would be. So we do that and then, of course, in the data you then need to see. So, for instance, tanning bed users are younger and more female. You need to, and being female is very good for you and being young is very good for you, so both of those are very healthy things to have. You need to have that data collected in your database. So the UK Biobank collects gender, it collects age, it collects activity levels, it collects diet, it collects smoking habits. So the date you can only correct for confounders if you measured it in the first place.
Speaker 2:So when you're drawing up a study and this is one of the big things about doing these big prospective studies if you did a questionnaire with five gazillion questions that covered every single aspect in somebody's life, yes, you're undoubtedly going to be collecting stuff that may be a confounder, but nobody will ever complete study. So when you're drawing up one of these studies, there are lots of judgment calls. You need to ask enough questions to have robust data for later researchers to come along and be able to answer their questions. But you mustn't make the study so onerous that nobody goes into it. So actually drawing up these studies is harder than you would think. Every question needs to be considered. So that's the first thing how to handle those confounders.
Speaker 2:Well, there's two ways you can do it. You can either stratify it. So what that means is, say, gender, male or female you would look at all of the women that are in some beds and don't have some beds and see, you know, do the some bed user more or less death? And all of the men, and you'd see if the men some bed users and non-some. So you would handle them separately and see if the answer was the same in both cases. Now the fact that women tend to live longer than men doesn't matter, because you've looked at the women separately from the men, but you've looked for the some bed factors. So stratification is one way of dealing with it. The other means of dealing with it is you give a kind of mathematical waiting factor. You say that being female reduces your. You find, from doing you know complex statistics, you find that being female reduces your risk of dying by 5% or something. So you give a 5% correction factor to the men to make up for fact. They're not women. And that means, rather than just looking at men and just looking at women, just looking at smokers, just you know, if you stratify you've got to look at everything individually and go through it one at a stage. If you give a waiting factor to those separate confounders, you can do what's called multivariate analysis and you can sort of combine the whole lot and see what the overall effect is. So there's, I mean this is well established. I mean I'm not an epidemiologist. I work with epidemiologists. This is their bread and butter, so that's how you do with it.
Speaker 2:Look, the other thing I would throw in with our study and it's important is we had our two measures of sunlight exposure. We'd looked at other stuff that was in the bar bank. So people were asked in the UK bar bank, how much time do you think you spend outside? And the problem is everybody in summer said two hours. Everybody in 80% of people in summer said two hours in summer, one hour in winter. And that's because people think, oh, I go to work on the bus, you know, I walk whatever and I walk back. When we looked at their measured vitamin D levels, this great biomarker for sunlight exposure, it actually showed that that kind of self estimate of what you think you might do wasn't very accurate, whereas some bed users and latitude were markers no-transcript.
Speaker 2:Back to my point. The way the confounders moved with our sunbed users was different from how far south you lived. So, for instance, the further south you lived, the better educated, and the more sun you got because you live further south, the better educated, the less likely to smoke you were. The more sun you got from sunbed use, the less educated the more likely to be a smoker you were. All things moved together so some bed users and people who lived further south tended to be younger, tended to be more female, but other confounders moved in different directions.
Speaker 2:The point was these two measures. It wasn't as if all the confounders moved the same way. The more sun you got from living further south, the more sun from being inside. All the confounders moved in the same direction. Because then our concern is maybe there's a confounder we missed, maybe it turns out that, I don't know, having brown eyes makes you live longer and people with brown, you know, we never considered brown eye colour and lifespan and it turns out that brown eye people like that, you know, and it makes it less likely. There was an unmeasured confounder, something we didn't think about, because the confounders moved in different ways and it would be unusual for an unmeasured confounder to be moving in the same way.
Speaker 1:Yeah, thanks for that explanation. In when I was preparing for this interview, I also did a bit more research into the biobank and I found another study that I think really again gives us another piece of evidence or weight to back up the idea that yours is a very, very valid finding, and the title of the paper is Vitamin D status and risk of all cause and cause specific mortality. Results from the UK biobank. Higher 25 hydroxy vitamin D concentrations are non linearly associated with lower risk of all cause, cardiovascular disease and cancer mortality. So what that is telling me is that this is just a simply another way of looking at the data, which backs up that the more sunlight people get, and therefore the higher their vitamin D level, the lower their risk of the same all cause hard endpoint mortality measurements, as you found, richard, in your study.
Speaker 2:Yeah, and then the other important thing to throw into so that we got this great observational vitamin D, which I think is a bar mark of a sun like this many importance is. We then have the interventional studies. So the classic, the biggest one here. So you've done one in, well, new Zealand. So New Zealand is a different from Australians, I have to remember. So they've done a big study called the VITAD study in New Zealand and an even bigger study done in America called the vital study, and these were randomized, placebo controlled intervention studies. So the vital study in America 25,000 Americans, half were given vitamin D supplements for five years and they were middle aged, so middle aged people, you like, because they're more likely to start getting diseases and showing things up. So 25,000 Americans have got vitamin D supplements, half got placebo and basically did nothing. They did it for five years and the results are all coming out Absolutely no cardiovascular effects, no stroke effect.
Speaker 2:There's a whole list of negative findings and the New England Journal of Medicine, in July 2022, published an editorial attached to the latest negative study from the vital study and it said look a stop taking vitamin D supplements. It's not doing anything, it stops rickets. You've known that for a hundred years and it may prevent progression of some cancers. The rest of it is pretty negative, particularly bearing in mind the huge size of the observational differences. When you look at the effects on observational studies, that is a really powerful relationship. It's not some piddly little thing that you might just submit out in a trial. It is a big relationship on the observational studies.
Speaker 1:Yes, and not only in cardiovascular disease and cancer, but also in autoimmune disease, also in infectious susceptibility to respiratory viruses, whether that was influenza or the SARS-CoV virus. I want to make the point that unless clinicians realize and researchers realize that there is a difference between endogiously generated vitamin D from UVB sunlight and realize that there's a potential of improving health and vitamin D is simply the biomarker, as you've said, for how much sun someone has got.
Speaker 2:Yes, look, I think for me, I think we need to be stepping back to where we were a hundred years ago. I think the epidemiology powerfully is that sunlight has, I'm sure, systemic health benefits. Vitamin D, as proven by supplementation studies, accounts for some of those benefits, the rickets specifically. All we can say about the rest it is a sunlight-driven, I think, non-vitamin D effect Sometimes, but I don't know. It's sunlight-driven. I think the really interesting thing, and what I'm working on now, is what are those sunlight-driven non-vitamin D mechanisms? It's really exciting because there are all of these health outcomes which are worse in winter.
Speaker 1:Yes, let's talk about that. Two points I want to make before we jump into that topic. One is can you give a quick overview of what Pelley Lindquist found in Sweden, because I think the finding to do with smokers is incredibly accessible and hard-hitting for our listeners. The second point is to what degree can we generalize your findings and Pelley's findings to Northern Europeans, say, living in Australia?
Speaker 2:Yes, good questions. Pelley started it off. Pelley's great. He's actually an obstetrician in Sweden. I've been from inside the Dumptology fold saying the Emperor has no clothes. Pelley came along first as an outsider. I suppose it's easier for an outsider to say that the Emperor has no clothes.
Speaker 2:Pelley was looking at data on this study called the Melanoma in Southern Sweden study. The title tells you what they were thinking about. They were interested in how much UV do you need to cause melanoma? They were expecting to find more UV, more melanoma, more death overall. That was the expectation when they set the study up. The study was set up in 1990. They recruited 30,000 Swedish women in Southern Sweden. Melanoma is Southern Sweden study, which is sorry. Middle-aged Swedish women. Let's go for middle-aged people because they're closer to death. Death is a great endpoint. That was actually about a quarter of the population of middle-aged Swedish women in Southern Sweden.
Speaker 2:They were sent questionnaires and they were asked broadly four questions to assess sunlight exposure Do you sunbathe in summer? Do you sunbathe in winter? Odd people of Swedes, some of them do. Do you go on foreign holidays and do you sunbathe? There's obviously lots of confounders attached to that. If you go on foreign holidays you're better educated so you're probably less likely to smoke. But they corrected all of that. They corrected for social factors. They corrected for occupation income.
Speaker 2:In Sweden, everybody's tax return is published openly on the same day every year. If you want to find out what your boss earns, or your neighbor or the prime minister or your cleaner, you can look it up. America, I believe, is not the same. They looked at income, employment. They then looked at social factors like education level, things like that. Health factors, obesity, bmi, exercise all of these factors were looked for.
Speaker 2:They then followed them up for 25 years and went back to find well, actually, how many have got melanoma and how many have died? Their expectation was the more UV you got, the more melanoma and the more death was the expectation. The first half of that they satisfied. They found the more UV people had, the more melanoma was diagnosed. But they found that the more UV people had, the less likely they were to be dead. There was a straight line relationship With your UV exposure habits 0-4,. Those people that had the highest UV exposure were half as likely to be dead at 25 years as those goody two-shoes who followed the dump, told them to advice and lived in a cave.
Speaker 2:Maybe vitamin D supplements? Who knows this huge, great effect? The other interesting thing and to put, pelle went back and did a second analysis but to try and put this into perspective, how big the effect size was he found the worst thing you can do for your health until now has been smoking. Smoking is staggeringly bad for you. Pelle showed that people that got the most sun exposure and who smoked had the same risk of death at 25 years as non-smokers who avoided the sun altogether. Basically, the badness on your health of smoking is equally outweighed by the goodness of sunlight exposure. That is a powerful effect.
Speaker 1:The way society perceives people standing out outside a pub or a cafe chain smoking cigarettes and the way society looks down on that person. Then to think, the narratives around sun avoidance slip, slop, slap down. Here in Australia, as you said, live in a cave, take vitamin D supplements and God forbid you ever get a square centimeter exposed to natural sunlight. It's incredible to see that disconnect in public narratives. Yet the fact is those two behaviors, as Pelle discovered, are in a Swedish cohort. They're equally harmful sun avoidance and smoking.
Speaker 2:Now, of course, this was in Sweden Now I don't know what happens in Australia. Now. Where we have a problem here in Scotland is our sunlight advice is copied directly from your advice in Australia. These are very, very different UV environments. In Townsville, days of the year when the UV index exceeds 6, high is 365 out of 365, 366 this year. Anyway, the point is, every day is a high UV day in Australia. Today we're February, the 22nd. Today, for the first time for four months, the UV index here in Edinburgh tipped above zero. It hit one at midday today for the first time in four months. Completely, completely different UV environment.
Speaker 2:I think that what really matters and your Australian guidance takes this into account is skin color and where you live. I are advice here in Scotland where we have lifted the advice from Australia. Literally Scottish government advice is if you're outside between 11 and 3 at midday, you should slip, slap, slap. What Absolute madness. I live in Cairns and, believe me, cairns is different from Edinburgh. Perth, australia is different from Perth, scotland. It's not just the beer they drink either. We have very different environments. I don't think we have all the answers. What I'm saying is we need to be reconsidering the question and that when looking at sunlight, it's not just sunlight bad, it's sunlight has health benefits. What is my skin color? Where do I live? There is a much more interesting I say complex, but actually it's interesting. It's a much more interesting question that we need to be considering. The other thing I might quickly add in here, talking about this skin color, is going back to Pelle's work.
Speaker 2:Pelle then went back and he looked at his Swedish cohorts and their sunlight exposure. His cohort was scrutinized in 1990 before really immigration of any size happened to Sweden. It was a pretty much solidly white skin cohort. He was able to look at the red heads, pheomelonin and the non-red heads. Of course, red heads are the palest of the pale.
Speaker 2:He went and looked at sunlight and all caused mortality in white, red heads compared to white, non-red heads. What he found was that when he looked at Swedes who avoided the sun those people that got nought or one on their sunlight exposure scores red heads lived longer than non-red heads In a low light Swedes who avoid the sunlight. These are people who live in the gloom all their lives. Being the palest of the pale gives you a reduction in all cause mortality. It gives you a significant survival advantage. When, however, he looked at Swedes that go out and get more sunlight, those that get three and four that sunbathe and seek the sun, red heads lost their survival advantage. What this tells us is that the palest of the pale have a survival advantage, an evolutionary fitness advantage, in a really low light environment. So again, it confirms that skin colour is really important, for what amount of sunlight is optimal for us personally?
Speaker 1:Yeah, I mean, that makes a lot of sense to me. I think that this is a prelude to our next part of the discussion, which is what is mediating these non-vitamin D health benefits of sun exposure. And it's really pitting, essentially the, or putting things in perspective, because, as we talked about previously, as physicians, as medical doctors, it's our job to synthesize a clinical situation, understand risks and benefits of every intervention that we offer to patients and be able to present that in a coherent way so people can make an informed decision. And what I think we can think about sunlight is that is a medicine, because it has these different wavelengths of ultraviolet visible infrared and each of them are having a biological, biologically relevant effect.
Speaker 1:So the reason behind the Sun avoidance narrative in Australia and in your country too, richard, is that everyone is scared or has been scared and completely scared about metastatic melanoma, and I'm not diminishing the fact that that is a very, very scary illness. But if we're pitting metastatic melanoma mortality against all cause mortality, cancer mortality, cardiovascular mortality it's a shrew and an elephant. And we're still. We're scared of the shrew or the little mouse, which is again what Peli Lindquist found in Sweden, yet we're ignoring the massive elephant which is all cause and cardiovascular mortality, so maybe share some thoughts on that topic.
Speaker 2:Yeah, I mean it is interesting. I mean, what we do as physicians, I would say almost our core skill is risk benefit analysis. You know, whenever we do an intervention, when we prescribe a medicine to a patient, we don't even consciously do it. We subconsciously think benefits. You know why am I prescribing this medicine? Unit, you've got pneumonia. I'll give you an antibiotic because the benefits are it will cure your pneumonia and you won't die. The risks well, you might get a drug rash, you might have an advert, you might have an allergic reaction. You know, and we consider that risk benefit ratio and it's I would almost say it's our core skill.
Speaker 2:Handling is often quite complex equations in our head, in discussion with our patients. It's the core of what we do and for some reason, dermatologists have completely forgotten that when it comes to sunlight, they only consider risk, completely, forget the other, equally important side of the equation. And that is how, by concentrating on the true, we have missed the elephant. And you know you're about 100 times more likely to die of cardiovascular disease than melanoma In Britain. In Australia, you have half as much cardiovascular disease as us. So the equation is different. I wonder if it's with your sunlight. You know so. So we, you know, we actually have to keep things in proportion, as you say, and unfortunately dermatologists have dominated the debate on UV. It's interesting I'm now invited. I spoke at the European hypertension, the big European hypertension meeting last year talking about sunlight and hypertension, and it's very nice to be there with hypertension doctors and cardiologists who are a little bit surprised to hear from a dermatologist because you know why would a dermatologist be talking to them? And we have very we've had this rather compartmentalized approach Sunlight is for dermatologists who deal with skin cancer, blood pressure is for primary care doctors, clinical pharmacologists, cardiologists, multiple sclerosis is for neurologists, whereas actually it turns out that UV affects all of these things and we need to be considering all of it together.
Speaker 2:I mean, I would say one of the benefits of my training are that I started off doing internal medicine. I would say another big benefit is I also practiced in Australia for a year and that was that was hugely influential on me, just in the back of my mind. You know just I think I said this previously that you know Australians, you Australians live three years longer than us here in Scotland, twice the risk of skin cancer, three years longer life expectancy and always the story you've told us was it's because you're athletic gods. You spend your whole life running, surfing, doing things. And I discovered you're a bunch of bone idol, heavy drinking, hard living, smoking blooders, just the same as us in Britain, and you're not these godlike figures you pretend to be. So I can I can view your immensely good health with a degree of, I says, interest. Now how is it that these idle bloods are so healthy?
Speaker 1:Yeah, and that's why I respect your work and what you're doing so much, richard, because you're really the curiosity and the ability to see beyond the blinkers of your own specialty is what is enabled you to essentially make such important scientific discoveries that I think will rediscover these, because I think the health benefits of some of our ancient and big that essentially and bring this to some sanity, to a very, very one sided argument I think the point about the reduced cardiovascular mortality of Australians versus people of similar skin color in Scotland points to the fact that this UV light story is holding in in Australia and although we don't have the data, I would assume what you found, what peri-linkus found, is still going to be applicable and externally valid to an Australian cohort and therefore everywhere around the world.
Speaker 2:Yeah, I'm not gonna say I would, I really would strongly. Rachel Lill, this super. What is interesting to me actually is that probably the leading country in reconsideration of sunlight health benefits, not just harms has been Australia. So people like Robin Lucas, rachel Neal fantastic Prouheart, you know, shelley Gorman actually a lot of my closest collaborators and intellectual sparring partners, supporters have come from Australia and it's fascinating to me that you, from a country with lots of UV and a largely pale skinned population, are the ones reconsidering this. And I think everyone should go off and read this paper by Rachel Neal published this week in the Australian New Zealand Journal of Public Health, where you actually formally sit down and are really open to these discussions. So you know, advance Australia Fair, you're doing some great stuff there.
Speaker 1:Great. Well, I'll definitely include that in the show notes. Let's talk about these changes in and maybe one more point, because I don't want to let this go, because we have talked about melanoma again. What I believe and maybe you can give me your thoughts on this, richard what I believe is driving the rise in incidents of superficial spreading spreading melanoma in young people I think predominantly, in my opinion is the advent of artificial light, the fact that people are spending their time mostly under isolated blue, narrow wavelength, narrow band blue light without red, without infrared, and they've got disrupted circadian rhythms and they've got an ancestry inappropriate omega three to six ratio in their bodies, particularly in their skin. So that's a lot there and we don't necessarily need to go into each one of those points, but I just want to put that in this. Studies I can quote and I've talked about in previous podcasts, but I just wanted to put that there as a the thing.
Speaker 2:the thing I would, I would really like to turn here is over diagnosis. Now there's a difference in melanoma diagnosis and melanoma death. Melanoma death is a very robust end point. You've had a serious melanoma, you know they. Now there's some data from America.
Speaker 2:Here is tremendous, fantastic paper by Adawali Adamson, an American dermatologist down in Texas, and he had a paper actually in the New England Journal about two years ago where he looked at Melanoma diagnosis in America over the last 40 years. So the number of melanomas predominantly superficial spending melanomas diagnosed in America now are six times as many as the were 40 years ago, so a six fold rise. Now he points out in this paper that you know UV UV at most doubles your risk of developing melanoma. So say 40 years ago they all lived in caves. Say now everybody got sunburned, maximum UV, you would expect a doubling of melanoma at most. And if that has been a six fold rise. And he then shows that what determines your risk of being diagnosed with melanoma is not where you live in America. If it's driven by UV you'd expect Florida to have lots more than Alaska. He finds there is no correlation whatsoever between how much sunlight there is where you live and your risk of melanoma. But he finds there is an absolutely tight straight line relationship between access to a dermatologist, how many dermatologists there are, how many biopsies are done Basically it's over diagnosis. And he then shows that they took microscopes, slides from 40 years ago which had been some diagnosis melanoma, some diagnosed as funny mole, dysplastic nebis, not melanoma. Put them in front of pathologists today and a significant number of those biopsies that were diagnosed as not a melanoma 40 years ago are were diagnosed as melanoma when being looked at pathologists by now. Now the problem is the only only way of knowing if something's going to kill you is to take half of it out, sit there and see what happens. And you just can't get the volunteers, nor can you get the ethics committee, nor would you write to do it.
Speaker 2:But the problem with diagnosis of melanoma is its dermatologist looks at it, saying, yeah, it looks like a melanoma. That's it, pathologist. You do a biopsy, put it on the slide. Pathologist looks at it and goes, yeah, looks like a melanoma. So the whole thing is based on an impression. Now, if you're diagnosing a stroke, if you're diagnosing a heart attack, you do a blood test, you do the troponin levels. There is an unambiguous blood test which gives you a troponin level, which is a sensitive and highly specific indicator of a myocardial infarction.
Speaker 2:Melanoma diagnosis is always an impression and the other thing about melanoma diagnosis there are no prizes for missing one. If you say it looks like a funny mole and it turns out to be a melanoma and it kills them, that is the end of your career or it's a very expensive mistake. If you say and it harmless mole, oh, it's a melanoma, and you cut it out Not only, not only you then have an incredibly grateful patient. My God, I had a melanoma, my life has been saved, even if the reality of the matter is they never had a melanoma, it was just a mole. It was never going to do anything.
Speaker 2:So the whole diagnostic shift it's not malicious, but it's moving one way. Where it is wrong is in America. There's been a big commercial change in melanoma practice in the last 40 years. So in the US venture capitalists have bought up dermatology practices and they have bought up pathologists and they've said revenue maximization. Now the more biopsies. I want dermatologists to do more biopsies a chargeable event. To feed biopsies to pathologists a chargeable event. Who can feed diet. So there's been this financial pressure for dermatologists to do more, see more, do more biopsies and to halt this huge, great commercial drive.
Speaker 2:So they've repeated this study. They've looked again in Australia. It looks like there is a degree of overdiagnosis in Australia and I'm going to have to go and revise these papers. I'm at the moment trying to get the date of the last 40 years in Scotland and see if the same thing has happened here, because here and in Australia, just like in America, we've had a big rise in the number of melanomas diagnosed. Meaning dermatologist says yeah, I think it is. Pathologist says yeah, I think it is. That's the level I'm afraid to say, that's how it's diagnosed. There has been no change in deaths and I am suspicious of the dermatologist view that this is thank God we're there saving lives. If we haven't done it, I don't think dermatologists are chasing an epidemic. I think there is a strong chance here that dermatologists are creating an epidemic and I actually think that is. I think overdiagnosis to me strikes me as a much more likely than factors that we haven't considered leading to more melanoma. I don't think we've necessarily got more melanoma.
Speaker 2:That's my point, thank you.
Speaker 1:That's a very interesting perspective and one that I hadn't considered at all, but the same thing has happened in Australia with regard to the incentive system behind billing and skin biopsy, and they eventually had to tighten up some rules and you basically had to. You only got paid if what you biopsied, from a GP point of view, was actually here A suspicion Billing the government for it.
Speaker 2:I mean, this kind of thing actually has huge implications At the moment in Britain we are in. The NHS is just falling over. So I have been a dermatologist for 30 years now. So when I trained there were 300 dermatologists in Britain. There's now 700 dermatologists in Britain and are waiting this higher than when I trained 30 years ago. You know the pressure we're under is huge and yet we've got twice as many dermatologists and the terms of practice. We've got amazing new drugs. You treatex for fantastic new drugs. We no longer have hospital beds because we don't need them. It's got great new drugs.
Speaker 2:I think we're doing things wrong. I think we have created a problem. I think we are cycling faster and faster to go nowhere, because the more biopsies we do, the more skin checks we do, the more fake non-fake's word, the more artificial epidemic we're creating and I think we absolutely seriously need to look at this Again. You guys in Australia, yeah, I think we're doing things wrong. We're creating an epidemic and I think we absolutely seriously need to look at this Again. You guys in Australia. I love Australian dermatology research on UV In Australia over in the Burkaw in Queensland. That's a former care in Spoy, I'm very proud to say at Queensland Group, you're looking at this in fantastic detail and I'm keen that we should be doing it here.
Speaker 1:So let's talk about these non-vitamin D related illnesses or impacts, because to me, what I'm thinking that these are is all these are water immune disease, these cancer, this cardiovascular disease. This is a sunlight deficiency, this is a UV light deficiency. That's how I'm thinking about it.
Speaker 2:These are. We independently showed the first major non-vitamin D mechanism by which sunlight improves health. So we showed that. Or I showed that the skin contains large stores, storage forms or something called nitric oxide. No Big storage forms this in the skin. And we then showed Varsum, funky photochemistry, how sunlight hits the skin and it releases NO nitric oxide from these stores into the circulation. So nitric oxide Nobel Prize for medicine back in 1998, when the three Americans who discovered NO, actually a brick was there, but the Americans got the Nobel Prize Anyway.
Speaker 2:So and nitric oxide dilates blood vessels, lowest blood pressure and huge importance of stuff. And we show that stores fit in the skin. Sunlight releases it from the skin into the circulation where it loads the blood pressure. And I did studies, I had a number of studies. The most important studies were all done in man I speak about in my TED talk. And we show how sunlight lowers blood pressure by releasing nitric oxide from the skin into circulation. That, in terms of benefits from sunlight.
Speaker 2:Cardiovascular disease is the biggest killer in the world today. Not many people have rickets in the world today vitamin C, but cardiovascular disease is the biggie and that's my nitric oxide pathway and Kristoff's nitric oxide pathway. So that's the big one and that's really important. But I'm now I'm keen to get a second new route up, you see. So there's then a whole lot of gene regulatory stuff. So super paper by a chap called Doppicoe, who actually then studied in Edinburgh, was working, was doing his PhD in Cambridge and he did one of these great experiments where you do no active research yourself, you use other people's data, and he looked at studies where they'd measured whole blood transcriptome, so all the genes turned on and off in the blood. But he looked at it in a number of healthy volunteers done in about half a different studies where they were measuring gene transcription in the blood, half different studies done around the world, some in Australia, some in Europe, some in the Gambia. But he analysed the gene expression pattern in all of these healthy volunteers by the month of the year in which the blood was taken and he showed that about 30% of all the genes in your blood show seasonal variation 30%. A third of your in-char transcriptome has seasonal variation. Now we know about circadian rhythm, your 24-hour sleep-weight cycle really important, a key human, you know characteristic. There is then a seasonal variation and, broadly speaking, he showed that anti-inflammatory genes are up-regulated are turned on in summer and pro-inflammatory inflammation-driving genes turned on in winter. So that was this first. Really. I mean I think it sounded like 500 citations really important study.
Speaker 2:What I am doing now is I do my experiments in winter, is we are you can now do a technique called single cell sequencing. Rather than looking at the blood, you know all the cells in the blood and there's masses of different types of cells in the blood. There's red cells and white cells and platers, but then within the white cells there's hundreds of different subtypes, each of those cells doing different things. You can now do a technique where you look at every individual cell type and you can measure in every individual cell, every single gene, which the 30,000 genes humans have got, which are turned on, which are turned off, which are expressed and how they're expressed. So staggering amounts of detail and we're taking healthy volunteers midwinter or in winter.
Speaker 2:Now we're just coming to the end of the experimental season because I've got a UV index of one a midday to day. So we're moving out of no UV worth speaking of and we take blood from these subjects and we do single cells so we look at all of their gene expression and all of their white cells. We then give them two weeks of solar simulator lamps. These are actually old fashioned tanning lamps which have the same spectrum as the midsummer sun in Melbourne actually. So that's what we match it up to. So we give them the equivalent of two weeks sunshine in Melbourne and we then repeat the bloods to see which genes are turned on and off.
Speaker 1:Is that UV and visible, or is that infrared as well?
Speaker 2:Yeah, so, yeah, so it's UVA and B, because that's one of the Now, I think, visible. It's interesting. So we know from the Most of our measurements of lamp output is based on the spectrum of sunlight which leads to skin cancer. So when we use lamps for experiments, when we use lamps to treat patients with therapy, we look at the sunburn-inducing abilities of a lamp, because we know that the wavelengths that are most likely to cause sunburn are most likely to cause DNA damage and most likely to cause skin cancer. So when we measure the output of a lamp for use in experiments, we weight it for how many, how many short wavelength, how much 300 nanometers is 3, 5, 3, 6, weighted for how much light is called DNA dimension of the place. And when you do that, basically visible light and IR does causes no DNA damage, no, doesn't make you go red, doesn't cause skin cancer.
Speaker 2:So now of course, I don't know whether different wavelengths will have different biological effects. It may well be that visible light is having beneficial biological effects and that's you know. That's the next chapter. The point is this is the whole field is unexplored because we've just said sunlight bad, take vitamin D tablets. So for 100 years we've done nothing except avoid the sunlight and take vitamin D tablets, and absolutely right. So look that it visible kind of rolls, blue kind of rolls, I arc kind of rolls. I'm concentrating on UV because I know that UV has a lot of biological effects and when I'm spending a lot of my own experiments I'm I reckon I'm most likely to get results when I've got a big biological stimulus.
Speaker 1:Yeah, and my criticism of the use of narrow band UV, which is essentially what I understand. Most of the harm you know, uv light demarization and therefore extrapolated to the sun harm narrative is based on is narrow band UV which is emitted for a lamp. But the point is when we're in nature and UV is always balanced by red, it's always balanced by infrared and we have Dr Roger Schwelt, who's a US intensivist but is now branching into the light as medicine, and it shows that red specifically regenerates. It has a positive effect on mitochondria. That's known finding and essentially is preparing the skin for the later UV arrival.
Speaker 2:Yeah, I have said I'm always cautious about, you know, effects on mitochondria and skin. You know I just those things suggest mechanisms but you've got that then you can't use them until you've shown it in man and on my experience I've done my, I've done cell culture work. I've done my work. I do human work now because if it doesn't happen in man, you know what matters in man matters far more. The other thing I'd say about narrow band is that actually it's narrow band is remarkably safe. So the three 11 nanometers, the shorter the wavelengths when you're down at you know the shorter wavelengths, you know shorter end UVB. That's where you're tending to get the burning. What we know from experiments in man the best experimental model of all, classic experiments back in 1986 by Parrish at the Wellman Photobiology Institute at Harvard, the risk benefit ratio for so they were looking at different wavelengths of UV to treat cirrhosis and they showed the magic sweet spot where you get the most reduction in cirrhosis for the least chance of causing sunburn, dna damage, skin cancer is about 313 nanometers. So actually that particular wavelength you get the biggest benefit for risk. So from that they have developed three 11 nanometer lamps. My three 11 nanometer narrow band UVB lamps have been around now since the 1980s. We've got 30 or 40 years activity with them. Everybody getting narrow band UVB in Scotland is followed as the big database. There is no increased risk of skin cancer shown in 30 years of narrow band UVB.
Speaker 2:I think that narrow band UVB lamps should be available without seeing a doctor, without any medical intervention, without seeing a nurse. I think they should be available Open access. Tanning salons should stop them, I think, because there is no downside to them and at the moment when we treat eczema or we treat cirrhosis, we have a treatment, ascending treatment that does Dioprecipitants, emollients and topical steroids. If that fails, move on to narrow band phototherapy. If that fails, you move on to systemic agents, ethyl trachocytes like X-4, and if that fails you move on to expensive biologics. That is our ideal treatment regimen.
Speaker 2:The problem is it doesn't work because if your topical steroids topical dovernex, you know cathetrile fails for your cirrhosis or eczema, you are referred for a dermatologist. Well, in Britain that is a six month wait. I then refer you to my photodermatology department. Photobelgium says there is another six month wait. So you have got mild to modrotexma. It is not getting better with some topical steroids. You need the next step up.
Speaker 2:Well, it is a year before you get your phototherapy and so it doesn't work. So either you have dreadful eczema dreadful, or you know, not dreadful, not the worst, but just bloody, miserable eczema, cirrhosis going on for a year untreated, or by the time you get to see me, it has got worse and we have to move on to heavier weight drugs methotrexate we use these things really carefully, we really experience, we are brilliant at it. Nonetheless, these are heavy weight drugs, need lots of monitoring Before we move on to biologics hugely expensive, because we have utterly restricted and over-regulated this incredibly safe and effective narrow band UVB phototherapy and I think we should just remove medics altogether from this. Like paracetamol, when you get a headache If you wake up with a headache you don't get a referral to a neurologist six month weight referral pharmacist. Six or eight here have 500 milligrams of paracetamol. Of course we can hardly date.
Speaker 1:My criticism of narrow band is in the research setting, when that is ultraviolet and then that is used to justify or demonize natural sun exposure. In terms of narrow band phototherapy whether it's in the photobiomodulation red light, infrared and UV that makes complete sense to me. That again is being used like a medicine, has risk-based benefits and what you're describing for eczema sounds very, very justified To me. It would be cheaper and quicker if that patient took a flight again down to a more southern latitude, normalize their circadian rhythm and I believe their psoriasis and eczema probably improve much, much quicker than waiting for 12 months. I wanted to make a point about the cardiovascular benefits of sun, and you obviously you're the pioneer of elucidating this nitric oxide dependent pathway.
Speaker 1:I think that the sunlight touches cardiovascular disease in so many ways that we're just appreciating now, and ones that I've researched myself have been the presence of melanocortin receptors in the blood vessels and the fact that if you knock them out you get arteriosclerosis, stiffening, endothelial dysfunction. There's melanopsin, which you talked about, the circadian rhythm. There's non-visual photoreceptor melanopsin in the blood vessels, and blue light mediates photorealysation of the vessels. And then a biggest point that I don't think anyone is talking about, not in cardiology, and nor else is the work of Dr Geropolik, which showed that there's a biological water, a fourth phase water, inside the blood vessels, and exposure to infrared light essentially potentiates this formation of a biological surface inside the endothelium or above the endothelium, above the endothelial glycocalyx, and that is incredibly potent stimulus not only for blood flow but also to protect the underlying endothelial layer. So I think nitric oxide is one part of it, but there's all these other things that are mediating the natural sunlight to benefit on cardiovascular health.
Speaker 2:Yeah, look. So I mean there's different types of epidemiology mechanism. You know interventional trials, so the epidemiology to me is pretty robust, certainly those of us living in Northern Europe. The more sunlight we get, the longer we live, I think for whiteskin North Europeans in North Europe, that data to me looks pretty robust and it all has to add up. You know it's not no single instrument tells you the whole tune. You need an orchestra and you know all of these things have to play together.
Speaker 2:We've then been able very clearly in human studies in man, to show, you know, back to my animal model anything out there able to show that nitric oxide is certainly a really important causal pathway. Other mechanisms, you know. I almost think the key thing is we know that more sunlight, more sun, more sunlight. We know that more sunlight pretty robustly ties up with increased lifespan, reduced disease and sunlight is available for free to all of us and that you know we should be getting into use that. I think we need to refine the message based on skin color and where you live. Mechanistic stuff is important. I only feel comfortable really talking about with the mechanisms that I know, but almost mechanism plays second part to actually an effect. You know we have here a biological effect and we need to agonize too much over the mechanism. If we can show, the increased time in UV reduces risk of multiple sclerosis, cardiovascular events, stroke, blood pressure etc. Etc. Death from any cause.
Speaker 1:Yeah, and that's why your work is so important Really establishing that overall finding, which is those mortality findings. That is the hard outcome, and then I guess, yes, it's up to other researchers to work out there the minutiae, did you? I'm mindful of your time, richard, and I think we've had such a great discussion If you wanted to make mention about the effect of sun on immunity and disease susceptibility. But if you've got to go, then that's fine too, I'm going to have to take my son to football.
Speaker 2:So this is association, not Aussie rules, I should point out. So he's not wearing a single running around the freezing Scottish weather here, yeah, so I think seasonal disease is big. Is cardiovascular disease very clearly seasonal? Interesting infectious disease, pneumonia, a very seasonal disease. So I'm super at Prouheart out of Perth University of Western Australia, fantastic stuff doing that we're setting up some clinical trials that we're hoping to run in the United States using phototherapy to treat MS. There's a whole field of things out there, I think, more than we have time to go on for now, I'm afraid to say.
Speaker 1:Thank you so much, richard, and I can't wait to get this out to people and to share your very, very important message. So, yeah, thank you for your time and, yes, keep continue spreading the word, please.
Speaker 2:Okay, max, fantastic, we'll see you next time.