When we talk about sunlight in the context of health, the picture is usually pretty negative. This is, of course, because of the well-established role of ultraviolet light as a carcinogen. Ultraviolet radiation penetrates deeply into the skin and generates DNA-damaging molecules. Over time, this can result in mutations and ultimately in cancer.
There is no doubt that excessive exposure to sunlight can be harmful. However, research increasingly suggests that too little sun may be nearly as detrimental, though the risks associated with this are a little harder to pin down.
A host of studies have shown, for instance, that living further from the equator, and consequently receiving less direct UV radiation, is associated with increased risk of multiple sclerosis. It was first reported in 1950 that deaths from MS were four times more prevalent at 40° from equator vs. 30° in the United States. Similar studies in Australia have replicated this latitudinal gradient, finding that the rate of MS is as much as seven times higher in Tasmania than in northern Queensland. Indeed, one study found that regional UV radiation levels closely predicted rates of multiple sclerosis in different parts of the country.
You might point out that all of this evidence is just correlational, and you’d be right! But there are plausible mechanisms that might explain this relationship. We’ll get to that shortly.
Before we get deeper into the molecular biology, it might be appropriate to step back and look at this from an evolutionary perspective. Humans evolved in equatorial Africa, under bright sunlight. So perhaps it shouldn’t be too surprising that we adapted to exposure to ultraviolet light, at least to some extent, and its relative absence may be costly to us.
Indeed, the wide variations in human skin color may be the most obvious evidence of our fundamental need for sunlight. As humans migrated to areas further from the equator, where ultraviolet levels were lower, natural selection favored lighter skin. This adaptation is thought to enable UV light to penetrate more readily, and generate essential vitamin D.
This, naturally, has led to intense interest in vitamin D supplementation. But trials that have tested this have been pretty disappointing, suggesting that some of the health effects associated with ultraviolet light are independent of vitamin D.
Some very clever researchers are beginning to tease out these hidden mechanisms, and in the process have uncovered some novel potential benefits of sun exposure.
And that brings me to our guest for this episode.
In this episode of humanOS Radio, Dan speaks with Scott Byrne. Scott is a professor at the University of Sydney School of Medicine. He is a cellular immunologist who is studying the molecular effects of sunlight on the body.
His work has focused particularly on how the ultraviolet part of the solar spectrum activates regulatory pathways that result in immune suppression and tolerance. This attribute of sunlight is important to understand, because it actually plays a key role in the development of skin cancer.
It’s well known that ultraviolet light damages DNA, causing mutations that eventually lead to cancer (typically many years down the road). But what makes UV light such an effective carcinogen is that it also suppresses the type of immune response that helps defend against cancer, seemingly by activating regulatory B cells. This is why immunotherapy has become an integral part of the standard of care for modern melanoma treatment.
But is this dampening effect on the immune system a wholly bad thing? Maybe not.
Think back to what I said earlier about MS rates and ultraviolet sun exposure. Using a rodent model of multiple sclerosis, Scott and his colleagues at the University of Sydney demonstrated that administration of low doses of ultraviolet light not only activated regulatory B cells, but also suppressed symptoms and progression of their autoimmune disease. And there was little doubt that it was indeed the B cells that were responsible here. Mice that were pharmacologically depleted of B cells showed no benefit from the UV light treatment. Findings like this, in combination with the aforementioned observational evidence, have spurred interest in how exposure to appropriate amounts of ultraviolet light might modulate the immune system, and potentially reduce the risk of autoimmunity.
But the health impact of sunlight may even extend beyond that. And here is where things get really interesting.
When Scott and his team were investigating skin cancer development in mice, they happened to notice that mice receiving ultraviolet radiation gained less weight than controls. At the same time, other researchers also pointed to compelling links between sunlight exposure and risk of cardiovascular disease (please check out this fascinating TED talk with Richard Weller to learn more about this!).
These observations inspired Scott and his team to perform a series of experiments examining how regular exposure to physiologically relevant doses of solar ultraviolet radiation (equivalent to about 30 minutes of summer sun per week) influences both weight gain and cardiovascular disease. And the findings were pretty remarkable, especially if you are one of the many people out there who routinely shrinks away from the sun. To learn what they found, and more about the far-reaching effects of sun exposure on human health, check out this interview!
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Scott Byrne - 00:00: If we gave the mice UV, they had significantly less atherosclerotic plaques. In some of the mice that had, we couldn't find any at all.
Dan Pardi - 00:08: We're generally encouraged to protect ourselves from sun exposure as much as possible by health organizations. This is due to the low understood link between UV light and skin cancer. Ultraviolet radiation penetrates deeply into the skin and generates DNA damaging molecules, which can result in mutations and cancer over time. There's little doubt that excessive sun exposure to sunlight can be harmful, but research increasingly suggests that too little sun exposure may be at least as detrimental. Studies have revealed, for instance, that living further from the equator is associated with increased risk for many other cancers like colon, breast, brain, leukemia, et cetera. Lack of sun exposure has also been linked to a greater risk for cardiovascular disease, type two diabetes, and obesity.
00:49: Humans evolved under bright sunlight in equatorial Africa, so perhaps it shouldn't be too surprising that ultraviolet light is an important health input. Indeed, the wide variations in human skin color may be the most obvious evidence of our fundamental need for sunlight.
01:03: As humans migrated to areas further from the equator where ultraviolet levels were lower, natural selection favored lighter skin. This adaptation is thought to enable UV light to penetrate more readily and generate essential vitamin D. Trials testing vitamin D supplementation have been largely disappointing, suggesting that the health effects of the ultraviolet light may be independent of vitamin D. Researchers are still trying to tease out these mechanisms.
01:27: One of these researchers is my guest today, Scott Byrne. Scott is a professor at the University of Sydney. He is a cellular immunologist who is studying the effects of sunlight on the body, particularly, the immune system. He recently published a study examining how solar ultraviolet radiation affects body fat and cardiovascular disease in mice. The results are pretty remarkable. Without further ado, Scott, welcome to the show.
Scott Byrne - 01:48: Thanks for having me, Dan.
Dan Pardi - 01:49: Tell us about your background, and how you became interested in the health effects of sunlight.
Scott Byrne - 01:54: I'm an immunologist. I'm fascinated by how the immune system works. My research started in the area of skin cancer, the effects of sunlight on the skin and the body, and how exposure to sunlight causes skin cancers.
02:06: It's well known, as you said in your introduction, Dan, that sunlight damages DNA, particularly the ultraviolet part of sunlight. This is a really important component to the development of skin cancers. What is perhaps less appreciated is that exposure to UV also suppresses our immune system, particularly the type of immune response that we need to fight off cancers. This is probably why sunlight is one of the most ubiquitous and most damaging of the carcinogens. It not only damages the DNA, it also suppresses immune system that is required to combat those cancers. This fascinated me as an immunologist. I wanted to know how does sunlight do this.
02:41: We started to investigate this in multiple models. We used animal models to dissect out mechanisms. We also do studies in human skin to work out whether the effects that we're seeing in our models can be replicated in humans. Remarkably, they can be. We can correlate some of the events that we see in our models to some of the events that we see in human population, as well.
Dan Pardi - 03:00: Is it UVA or UVB that is responsible for the observed effects on the immune system, or do both play a role?
Scott Byrne - 03:06: Traditionally, we've always thought that it's only been UVB that causes immune suppression. If you want to remember what UVB and UVA does what I always tell people is that B is for burning and A is for aging.
03:17: UVB is horribly immune suppressive and damaging to DNA. Some of the studies that we did, about 20 odd years ago now, show that UVA is also immune suppressive, but in different doses and via different mechanisms. Both UVB and UVA suppress our immune system.
Dan Pardi - 03:34: Could this immune suppression have other downsides aside from cancer? Does it increase susceptibility to infections or decrease effectiveness of vaccinations?
Scott Byrne - 03:41: That's another excellent question. To answer that the best way is give you a straight, quick introduction to the immune systems.
03:48: There are two types of immune responses that we make. One of them is what we call an innate response. It happens very quickly and very early. This type of response seems to be activated by UV, which is probably one of the reasons why we don't succumb to infections, bacterial infections, in particular, when we go out in the sun.
04:05: Over long periods of time, what we noticed is that the other type of immune response that we have, which is called the adaptive immune system, is suppressed. This is the type of immune response that we need to combat cancers. It's also the type of immune response that we target when we vaccinate to try and mount protection from infectious diseases. There is some very strong evidence to suggest that exposure to UV does have an effect on the success rates of vaccination.
Dan Pardi - 04:30: Okay. That's interesting. Epidemiological data suggests that immune disorders, like autoimmune and allergic disease, have been increasing over the last three decades in Western countries. Could reduced sun exposure due to spending more time indoors be a contributing factor?
Scott Byrne - 04:43: It could. We don't have any definitive evidence to show that that's actually the case. Certainly, there's been correlated evidence from epidemiological studies to suggest that could be a contributing factor. It is quite an alarming increase in autoimmunity and allergic responses over a very short period of time. What this tells us is that this is unlikely to be a genetic effect.
05:03: It's far more likely to be an environmental effect. It's not going to be just UV light or sunlight that is responsible for this. It's also likely to be diet. It's also likely to be activity. All of those things impact on our environment and our ability to respond to those and sorts.
Dan Pardi - 05:19: Sunlight causes skin cancer, but living closer to the equator seems to reduce the risk of many cancers. What do you think are some of the possible mechanisms there?
Scott Byrne - 05:27: I've looked at some of the data around the relationship between sunlight and latitude, which is what you're referring to about the equator and those other cancers, and we've got to review on that. The evidence is not that compelling that sunlight exposure and latitude is related to other cancers.
05:43: The evidence for autoimmunity is far more convincing, particularly, for multiple sclerosis. Some of the best studies I've seen in this area had been done in Australia. They've been done 30, 40 years ago. What that showed is that if you are born and bred in Tasmania, which for those who don't know, Tasmania is a part of Australia that's very far South, and therefore, a long way from the equator. If you're born in and bred in that part of Australia, you are six to seven times more likely to develop multiple sclerosis than if you're born in far North Queensland, which is much closer to the equator.
06:12: The evidence for autoimmunity is very strong in the correlation between the UV exposure and autoimmunity. The evidence for other cancers is not as compelling.
Dan Pardi - 06:20: Your recent study published earlier this year tested how solar radiation affects weight gain and cardio-metabolic markers. Before we go into that specifically, tell us about what previous research had shown regarding how ultraviolet light and the influence on body weight, cardiovascular disease, and glucose metabolism. What have we seen there previous to your work?
Scott Byrne - 06:38: Perhaps a little background as to why we started to investigate this. In our models, we use mice to dissect out the mechanisms responsible for skin cancer development. Part of those models involve exposing mice to longterm UV. This is very similar to the types of doses and UV exposures that a human would get throughout their life.
06:57: If you do that for long enough, little skin tumors will start to appear on the mouse's back. We can work out ways to stop that from happening and to develop new therapies.
07:04: What we noticed was that before the tumors started to develop, the mice that were receiving the UV radiation gained weight, but they gained weight far less than those who didn't get any of the UV.
07:15: What this suggested to us was that mechanisms, which we didn't understand, that if you've got some UV radiation, you didn't gain weight nearly as quickly. This was a fascinating observation to us. It turned out that others were also observing very similar things.
07:27: Shelley Gorman at the Telethon Kids Institute in Perth, Western Australia, who's a colleague and friend of mine, was also working on this aspect of UV and obesity and diabetes. She published a lovely paper before we did in a journal called Diabetes, where she showed very strong links between UV exposure and obesity, diabetes, and type two diabetes, in particular.
07:48: Also, other evidence in humans had suggested that exposure to UVA, in particular, was responsible for reductions in hypertension, that's blood pressure and vascular flow. This was done in humans. A dermatologist in the United Kingdom, called Richard Weller. Richard and his team showed, very convincingly, that if you gave the skin UVA, it lowered blood pressure and increased vascular flow, which is one of the major contributors to cardiovascular disease. There we were, we had evidence in both mice and humans that UV was having effect on obesity, diabetes, and cardiovascular disease.
Dan Pardi - 08:21: I've seen Weller's TedTalk. I'll link to that in the show notes so people can take a look at that. That was fascinating. What mechanisms might explain this relationship?
Scott Byrne - 08:29: What Shelley showed was that release of nitric oxide from the skin stores was responsible. For many years, we'd thought that UV-induced vitamin D would be responsible for this effect.
08:40: The reason we thought that was when you look at people who have diabetes, people who are suffering with cardiovascular disease, people with type one and type two diabetes, they have very low circulating levels of vitamin D. What it suggests is that vitamin D and these diseases might be linked.
08:56: It turns out, at least in their models, as well as in the humans exposed to UVA by Richard, that it doesn't appear to be vitamin D. There might be something else about UV that's causing this effect. Shelley suspected that nitric oxide might be involved, which she shared quite convincingly, that the nitric oxide was responsible, at least partly, for this effect.
Dan Pardi - 09:14: I saw in Gorman's study in 2014 that supplementing with vitamin D failed to show a lot of the benefits that we're seeing from sun exposure. Skin induction of nitric oxide produced a lot of the same benefits.
Scott Byrne - 09:24: This is consistent with the vitamin D supplementation trials being not as effective as we would like them to be. Again, it supports the idea that in addition to vitamin D, there's something else about UV that might be responsible for these health effects.
Dan Pardi - 09:37: Thank you for that background. I'd love to dive into your study now. Tell us what you did? There was a lot to this, so break it up in any fashion do you see as most beneficial.
Scott Byrne - 09:45: Following on from our observations in our skin cancer models, we decided that what we would do is we'd try to investigate how much UV is required to achieve this effect. This is important because if we want to be able to advise people more appropriately on sun exposure, we would need to work out how much is required to do this, what types of UV, and how frequently do we need to receive that type of UV.
10:09: What Shelley showed was that ultraviolet B radiation was responsible for this effect. It's unusual for us as humans to just be exposed to UVB. We're far more likely to be exposed to sunlight and the UVA in sunlight. Of course, sunlight is made up of both UVA and UVB. We have some sophisticated ways of mimicking the ultraviolet spectrum in sunlight in the lab, very expensive pieces of equipment that give a very good reproduction of the solar spectrum. We don't give any visible or infrared, so there's no heat that's given in our models. We expose the mice to various doses of solar simulated UV light at various times and various frequencies.
10:47: What we discovered, fortuitously perhaps, was that the types of UV that cause skin cancer, this is chronic low doses of UV over long periods of time, were not nearly as effective as more higher doses and less frequently. Once a week high doses were far more effective at placing limits on weight gain in our mouse models.
11:08: The mice were fed a Western style, high-fat, high-sugar diet, and they gained weight very quickly in this way. We were able to show that if you give a little bit of UV light once a week before we start the diet, or even if we start the UV after the mice have started eating their high-fat high-sugar diet, we could limit the amount of weight that they gained.
11:28: We can measure this by weighing the mice. There was at least a 10% reduction in weight gain. We also have sophisticated ways of measuring the amount of body fat that these mice put on. There was about a 30% reduction in body fat gain by the mice when they are exposed to UV.
Dan Pardi - 11:43: It appeared that you were attempting within the study to see if it prevented weight gain in normal wood mice, then also some mice that had gained weight over time to see if it limited it?
Scott Byrne - 11:52: This is important for translation because what it means is that, first of all, we need to develop ways of preventing weight gain, but also once people have started a high-fat, high-sugar diet, might play a role in helping to place limits on how much weight is gained.
Dan Pardi - 12:08: I did notice the effects of more punctuated, higher dose being more effective. We know that intermittent exposure to UV light is also thought to be a higher risk of exposure to melanoma.
Scott Byrne - 12:18: I am caught between a rock and a hard place here. My research focuses on both the carcinogenic effects of UV, but also the potentially health benefits of UV.
12:26: This is a conundrum because chronic low doses of UV will cause keratinocyte cancers, or what used to be called non-melanoma skin cancers. High intermittent doses, ones that are close to sun-burning doses, we know that they're the most dangerous for melanoma development. I think what we aim to do with our models is to understand how UV does this, so that we can either replicate or enhance that effect.
Dan Pardi - 12:50: The amount of exposure you were giving to these rodents, how much would that translate in terms of minutes of exposure, would you say?
Scott Byrne - 12:56: For the high-intermittent exposures, it depends on where you are on the planet. In Australia, our sun is relatively harsh compared to the Northern hemisphere because of the hole in the ozone layer just beneath us. In Sydney, Australia, that's roughly 20 to 30 minutes of sunlight exposure. In the Northern hemisphere it might be more like 30 to 40 minutes of sunlight exposure. We're still not talking about very, very high doses. We're just talking about doses that are very achievable by most people in the population when they're doing recreational activities outside.
Dan Pardi - 13:26: Did you acclimate the rodents to the higher dosage or were they burned?
Scott Byrne - 13:30: No. The doses we give are not sunburning doses and that's important because once you burn the skin, you start to get very, very different biological responses happening. We're very careful to make sure that we do not burn the skin because of that. The doses we give are definitely on the high side compared to what we would normally give for skin cancer, but they're definitely not sunburning doses.
Dan Pardi - 13:53: Do we see a threshold effect where the risk for melanoma begins at a certain level and then rises from there? I do know your history, so the amount of times you've been burned as a child and adolescent, that has an impact on your melanoma risk profile going forward. If you were to maintain a light tan across the year with moderate amounts of exposure consistently, generally speaking, because of course we have latitude, we have different genetic backgrounds
Scott Byrne - 14:16: We do know that the biggest predictor of whether you're going to get melanoma later in life is whether you had a sunburning event as a child. In Australia, nearly everyone has had a sun burning event as a child. In our country at least, it is a massive problem. The models former melanonin released, show that, unfortunately, even UV light later in life is also potentially dangerous.
14:39: The reason for that is that UV light continues to suppress our immune system, and therefore, it continues to suppress the antitumor immune response. Recently, it's been shown that exposure to UVA light after the development of melanomas can enhance melanoma metastasis. This is potentially lethal now. It's a really tricky problem, Dan, to say that there's any one point in your life where you can say this is the reason you have melanoma. I don't think we can say that. What we can say is that we need to continue to protect ourselves from what we know is a dangerous carcinogen.
15:11: What these studies that we're doing, Shelley, Richard, and others, and [inaudible 00:15:15] and others, are showing is that there are parts of the UV spectrum at different doses, different intermittencies that might have different effects on our health. How we balance that with the carcinogenic effects is a real challenge for everyone.
Dan Pardi - 15:29: We did see that these punctuated doses of UV, higher doses with more time in between, a powerful effect on suppressing weight gain in mice that were on a high-fat diet. What were you able to look at in terms of their energy intake and output?
Scott Byrne - 15:43: We suspected that what UV might be doing is it might be making them eat less food. Of course, that's a terrific way to place limits on weight gain. To test this, we used what's called a Promethian monitoring system. What this system allows us to do is to continually measure weight activity, distance traveled, food intake, all of the respiratory air measures, CO2 output, oxygen intake, of individual mice over a 24 to 48 hour period.
16:10: Surprisingly, what we found was UVA did not have any effect on the amount of food consumed. To some extent, the mice exposed UV ate a little more. We also found that there was no significant effect on the amount of movement, or the distance traveled by the mice over a 24 hour period. The mice who got UV traveled a little less. It looks ** you can eat, more, move less, and still place limits on weight gain. While there was no significant differences between the groups, what it does suggest is there's probably something else that explains the effect. That's where we started to look at some of the fat deposits. We started to look in the liver, as well. There was changes in the types of fat and the types of molecules that the fat produces that might explain why weight gain was being limited.
Dan Pardi - 17:00: You looked at brown fat and also liver cholesterol levels. Let's start with the brown fat. What did you find there?
Scott Byrne - 17:05: Normally, when you eat a high-fat, high-sugar diet, there's molecules get activated when we do this, when we eat these types of food. It's basically the body's way of responding to, essentially, a high-fat high-sugar diet. We noticed in our mouse models that, yes, as expected, mice being fed this type of diet had this activation phenotype.
17:22: It's called uncoupling protein number one. This was highly activated in response to the food intake. To our surprise, exposing the mice to UV prevented this from happening. It suggested to us that there was something that UV was doing to the brown fat that might explain the effects that we were seeing. It's from the cholesterol levels produced, triglyceride's produced by the liver. It turns out that, yes, there was some significant effects in the liver, as well. This is quite remarkable because ultraviolet radiation does not penetrate much more than a few micrometres underneath the skin. In terms of UVB, it doesn't penetrate much at all, and yet we were seeing these systemic effects in the liver and brown fat deposits. This suggests that there's something produced in the skin that is making its way to the liver to exert this type of effect.
Dan Pardi - 18:09: When I read the aspect about brown fat, and it having the paradoxical effect from what you might think, given what happened in terms of the weight loss, I would like to see more there to see if there's something else going on that is explaining this effect on brown fat.
Scott Byrne - 18:22: This is not what we hypothesized. It was definitely against what we had predicted. This is the nature of science. We have to be guided by the evidence that comes our way. We don't know what this means. We don't know how this is happening. Ongoing studies are trying to work out why this is happening and what it means for metabolism in the host.
Dan Pardi - 18:39: We have the nitric oxide release, which we've discussed, and also activation of regulatory immune cells and UV induced Interleukin-33. Is UV light making an inflammatory diet less inflammatory?
Scott Byrne - 18:52: A few years ago, we discovered that Interleukin-33 was significantly upregulated in the skin of both mice and humans exposed to UV. This is interesting for our current studies in that others have shown that this particular cytokine is involved in limiting obesity and diabetes, but also cardiovascular disease, particularly atherosclerosis.
19:10: This cytokine produced in the skin by UV could be responsible. We haven't proven that. We haven't been shown that that's the cytokine responsible for it. There could be other things, as well. Recently, after our paper was published, it was shown that the aryl hydrocarbon receptor, which we know is produced by the UV in the skin agonists to that receptor finding their way to the liver and to the gut. These UV-induced molecules are exerting effects distantly from the skin. The aryl hydrocarbon receptor agonists could also be involved, although we haven't explored that in this current study.
Dan Pardi - 19:42: You saw that liver triglyceride formation was increased. That might sound like a bad thing, but actually it's healthy.
Scott Byrne - 19:49: Yes, it's contentious. There is some evidence to suggest that increased triglycerides could be protective in the liver. Others have shown that increased triglycerides could be detrimental to the host. Clearly, what our studies have shown that, at least in response to UV, there is an immediate increase in triglycerides in the liver. We predict that that's responsible for protecting the liver and we know that UV can do this.
20:09: Shelley Gorman has shown that UV radiation can protect from liver steatosis, partly involving nitric oxide and partly involving vitamin D as well, in that particular aspect. Quite clearly, this was associated with protection from weight gain and signs of cardiovascular disease.
Dan Pardi - 20:26: Let's talk about atherosclerosis. This is pretty exciting. What did you find?
Scott Byrne - 20:30: As an immunologist, I find atherosclerosis a fascinating disease. Essentially, if you look at atherosclerotic plaques, there is massive immune infiltration. I would consider that to be a sign that modulating the immune system could be an effective way to treat this problem.
20:45: We thought we have limits on weight gain. Shelley has shown there's changes in glucose metabolism. We saw changes in the liver. We saw changes in brown fat. Could this be having an effect on real cardiovascular readouts?
21:01: We looked at a model of atherosclerosis. We know that if we feed our mice a high-fat, high-sugar diet for long enough, they will start to develop atherosclerotic plaques in the aortic arch, and various parts of the descending aorta, as well. Sure enough, in our control groups, they definitely developed significant atherosclerotic plaques.If we gave the mice UV, they had significantly less atherosclerotic plaques. In some of the mice that had, we couldn't find any at all. What this allows us do is to link those events, weight gain, obesity, diabetes, to actual cardiovascular outcomes.
21:34: I think this ties in very nicely with Richard's work on increased vascular flow and decrease in blood pressure. We can probably add to that, at least in animal models, effects on atherosclerotic plaques. What we don't understand is how UV is doing this. It could be because weight gain has been limited. It could be that glucose metabolism is being helped to be restored, could be that the liver is healthier, or it could be that the immune system is being altered by UV. I suspect it's the combination of all of those events, which is why exposure to UV is such a powerful health modulator.
Dan Pardi - 22:06: What types of work are you planning on doing next to follow up on what you found so far?
Scott Byrne - 22:12: There's a couple of things that we would really like to understand. We would like to understand whether we can replicate this effect with just UVA or just UVB. The reason for that is that Richard's work is showing us that UVA is particularly beneficial for releasing nitric oxide and for having effects on cardiovascular outcomes.
22:30: Question would be, in our models, does UVA alone achieve the same outcome, or do we need UVB to do this? The reason why this is an important question to ask is that dermatologists, within their repertoire of treatment options, have phototherapy devices, which can deliver just UVB or just UVA, or various types of either. Understanding which part of the UV spectrum is responsible for this could allow us to develop therapies at the dermatology clinics. We know this is important because giving just those types of UV means that we're less likely to get skin cancers. That's one aspect we're currently exploring.
23:05: The other aspect is to try to work out how could we work with epidemiologists and public health experts to find out exactly how much sunlight do we need to get skin cancer. Remarkably, we actually don't know how much sunlight we need to get skin cancers. We just know that sunlight causes skin cancer. We would need to work out that. We would need to work out what are the health benefits, and is it time for us to reconsider our guidance on UV exposure? I think we are having robust debates, particularly, with dermatologists who are rightfully concerned around the carcinogenic effects of UV.
23:39: The third area is, again, the focus of my group. By understanding the mechanisms by which UV drives these effects, can we actually develop ways to replicate and enhance those effects, so that we can get the benefits of sunlight without needing to go out and get exposed to carcinogenic UV.
23:57: I think this is a more long-term goal. We've alluded to some of those- Interleukin-33, the aryl hydrocarbon receptor agonists, activation of regulatory cells, the release of nitric oxide stores- can we do that in a therapeutic sense without having to get exposed to UV.
Dan Pardi - 24:13: I have to mention something that was casually mentioned to me at this conference that I was at last weekend, the Ancestral Health Symposium. I gave a talk on sunlight and health. Somebody came up to me and said, I went to Hawaii with my husband. I was on a ketogenic diet. I forgot to wear sunscreen, and I didn't burn. Then, I spent the week without any sunscreen on. Not only did I not tan, I didn't burn. Next time I went back to Hawaii, I'm on a low-carb diet, but not a ketogenic diet. She burned to a crisp. That's all I know. It does bring up the idea about diet and sun exposure.
Scott Byrne - 24:46: I know. Absolutely. I think this is a really important message that modulating our exposure to the sun is not going to be enough. We're going to need to alter our diet. We're going to need to alter our activity. We go to the gym to run on a treadmill, whereas, we used to run around an oval. We swim indoors. It's a consequence of a modern lifestyle. We play sports nighttime under lights because of our work habits. I think it's not just about sunlight. There are other things that have to change if we're going to combat these significant health problems.
25:17: It's very interesting you allude to diet in particular because in studies done here at Sydney by professor Diona Damian have shown that increasing nicotinamide, or vitamin B-3 is a terrific way to help combat the skin cancer problem. What her group has shown, and she published this in the New England Journal of Medicine a few years ago, very nicely, that supplementing people who are at high risk of developing non-melanoma skin cancers with vitamin B-3 significantly limited the number of new skin cancers that these patients got.
25:45: What that tells us is that there are things we can do with our diet that can have significant impacts on whether or not we get skin cancers, and whether or not we get the health benefits from UV.
Dan Pardi - 25:54: My son, who's now six years old, is at summer camp, so he's outside a lot. We do put sunscreen on him, but we also make sure he's got a phytonutrient rich diet every morning before he goes out there.
Scott Byrne - 26:05: That's right. I put sunscreen on my kids every day too when they go to school. It's very important, at least particularly in countries or sunny areas where the UV is quite intense, that we continue to protect our skin. It is exposed to some significant carcinogens. I think when we look at some of the co-carcinogens that are going to be significant, air pollution can have significant effects on whether or not we get skin cancers. Smoking cigarettes is also a contributing factor. There are going to be other environmental impacts that make it more or less likely to develop skin cancers.
Dan Pardi - 26:37: Scott, thank you for doing all the work that you've done, and also for coming on and talking about it.
26:43: As I alluded to in the beginning, we evolved on a planet where we had a lot of exposure to sunlight. We've underappreciated the impact that signal has on our health. How to create guidance to your average person about how much to get, given the fact that life is much different now. Avoiding the sun altogether doesn't feel intuitively right, and yet it's hard to give somebody something this descriptive about how much sun exposure to get. With the work you're doing and your colleagues, we'll continue to gain insights and come up with some clearer guidelines that help to negotiate this relationship that limits the downside and helps us benefit from the potential upside.
Scott Byrne - 27:17: Thanks, Dan. It's been a pleasure.