 Thank you everybody. Good morning It's great to be back at AHS this is the 6th AHS event that I've attended first one was at UCLA that Harvard, Atlanta Berkeley Seattle and now here and I always enjoy my time here. So it's good to be back Okay About a year ago, I gave a Ted talk at Marin entailed entitled how to optimize light for health. I Was planning on giving a slightly abbreviated or excuse me expanded version of that talk here today But I decided to go in a bit of a different direction yet still focusing on the effects of light and health so let me start off by actually giving you a more abbreviated Version of what that Ted talk was about to begin. I'd like to discuss humans relationship with light We can look to certain modern-day hundred gather communities to illustrate this In a study of some of these people by Jerry Siegel and Jerome Yiddish It was observed that they wake up about an hour before sunrise and They get peak light exposure between the hours of 9 a.m. And noon at which point They will seek shade during the midday heat After dark, they're exposed to light only in the forms of fire the moon and the stars now humans relationship with light had been constant for millennia all the way up until 1879 When Thomas Edison patented the incandescent light bulb Incandescent lamps emit a warm tone of light similar to that of sunset However, they consume a lot of energy Rightfully worrying policymakers about their contribution to global warming So in attempts to be more efficient humans invented compact fluorescent lighting now these bulbs are more efficient But they emit a unnatural Spectrum of light over-representing certain blues oranges and greens in their spectrum and they flicker causing eye strain and fatigue Literally nobody likes compact fluorescent lighting Then in 1992 the Japanese Invented light emitting diodes or LEDs They are bright. They are far more efficient and they can be dimmed And they can be used not only in lamps, but also in screens like TVs and tablets and smartphones And all this lighting technology has fundamentally changed the way that humans live Americans now spend 90% of our time indoors and According to a survey by the National Sleep Foundation nearly all US adults Have a screen in their bedroom and use that screen within an hour of going to bed So compared to our ancestors we now get longer periods of light within a 24-hour period Strange patterns of light for a given time of day for instance you could get a full spectrum bright light signal right before bed We experience less time with darkness And we get less sunshine and then in the time that talk I posed the question But does all this matter to our health? and then I spoke about the various ways like how strange lighting patterns and less darkness associate with and perhaps even evoke undesirable effects on the helpful functioning of the human body now today at this point this is where I will deviate considerably from that TEDx talk so for the rest of the day I'm going to focus exclusively on the health effects of sunlight Here's the agenda for the talk first I'll be discussing facts about sunshine as a primer Then I'll cover the negative aspects of sun exposure the positive aspects of sun exposure neither of those two parts of the talk will be comprehensive or exhaustive and Then I'll share some closing thoughts about This topic in general and I'll take some questions Okay So while this will not be a physics lecture, let's start by discussing some relevant information about sunlight But a quick side note if you haven't watched the series called one strange rock by National Geographic starring Will Smith and several us astronauts You should consider consider doing so. It's excellent and episode three Focuses entirely on Sun on the Sun Very very interesting and well-produced has anybody seen it. Oh My gosh, okay Right a note. Oh one person one person. Okay Okay sunlight is composed of three major wavelength bands from the smallest to largest We have ultraviolet light which has a wavelength of 100 to 400 nanometers Visible light which has a wavelength of 400 to 800 nanometers and infrared radiation which includes some wavelengths above 800 nanometers While red and infrared light is interesting a very interesting subject I will be focusing I will not be focusing on those frequencies for the for the talk Okay, now if we break down ultraviolet radiation further you have ultraviolet a b and c Let's go in reverse order from shortest wavelength to longest in the band UVC is Between 100 and 280 nanometers and it is prevented from reaching the earth by the ozone layer UVB is 280 to 315 nanometers and it comprises about 5% of UVA UV radiation that reaches the earth's surface and UVA is 315 to 400 nanometers and it comprises 95 percent of solar radiation that reaches the earth's surface So let's talk about the characteristics of UVA lights and more Exposure to UVA radiation Still occurs when the UV index is low including winter during cold climates in the morning hours and late afternoon And even through a window and by the way windows do block UVB from Block radiation from getting to you All right UVA does possess risks to human health because of its capacity to induce pro-inflammatory cytokine production in the skin and also it degrades vitamin D in the skin as well But it also may induce the release of nitric oxide from stores in the skin and this can Improve in lower blood pressure. We'll discuss nitric oxide more in a bit Okay, now the amount of UV radiation that reaches the earth's surface at any given Place and time is influenced by a variety of factors including time of day and season Geographic latitude and altitude and I have an interesting comment to make about latitude You see blood pressures rise linearly the farther you get from the equator and Cloud cover ends surface type so think of water or even better yet snow and how they reflect UV radiation Personal factors affecting a person's response to the solar radiation include things like genetics and age Exposure history and tan so tan being your more current exposure to Sun and Exposure history means how many sunburns did you get as a kid, etc It's the lifetime accumulation of your son relationship your relationship with the Sun and of course clothing and vitamin D status And then diet interestingly and sunblock Okay, so now let's transition and we'll talk about the negative health effects of sunlight which is primarily what we hear Certainly I did growing up by dermatologists, etc. The Sun this time will kill you, right? Okay So there are legitimate risks to sun exposure Excessive skin exposure can cause skin erythema or reddening of the skin. Oh edema or tissue swelling and inflammation and photo aging total UVR exposure and excessive exposure resulting in sunburns particularly in childhood and adolescence significantly increases the risk of developing certain cancers and there are ocular effects to including cataracts Now ultraviolet radiation can cause DNA damage in several ways first both UVA and UVB Wavelengths directly damage DNA through the formation of pyrimidine dimers Which are molecular lesions formed from thymine and cytosine bases in DNA? They are introduced when an ultraviolet photon causes two consecutive bases on a strand to stick together Which alters the structure and possibly the base pairing now DNA repair processes can often recognize the problem Remove the cross-links and restore it DNA back to the correct sequence But if they're not repaired they can interfere with DNA replication which leads to mutations and sometimes cancer In fact, pyrimidine dimers are the primary cause of melanomas in humans ultraviolet radiation Also damage damages DNA by inducing reactive oxygen species That cause oxidation of DNA bases and by activating Mac map kinase pathways And it can also promote tumor growth through immuno suppression. We'll talk more about immune responses in a bit Now UVA UVB excuse me is what causes you to get a tan It is also far more potent and carcinogenic than UVA at causing genetic mutations And suppressing immune responses at an equal dose But again the relative amounts of UVA versus UVB that reaches the sun's surface is vastly more right 95% of the solar radiation is UVA so UV Radiation's ability to cause genomic damage is likely the initiating factor in the pathogenesis of skin cancers Let's talk about cancer now cancers of the skin are by far the most common of all types of cancers Most people are die more people are diagnosed with skin cancer each year in the u.s than all other cancers combined This is all NIH data from sear which stands for surveillance epidemiology and results program And for melanoma of the skin there is a lifetime risk of 2.3 percent of Of men and women will be diagnosed with it at some point in their lifetimes Which represents 5.5 percent of all cancers And 1.2 percent of all cancer deaths For basal and squamous cell skin cancers There are about 3.3 million diagnosed with basal and squamous cell cancer each year Now 8 in 10 Of these diagnoses are basal cell cancers Uh now the exact number of people who develop or die from basal and squamous cell Skin cancers each year is not really known for sure But let's take a look Now so now we we've talked a little bit about Incidents and cancers it is a serious risk. We talked about some mechanisms about why it occurs For the remainder of the talk, I'll be discussing potential health benefits and mechanisms for sunlight exposure And I'll briefly discuss cancer and immunity and auto immunity But the primary focus of this section will be on fat regulation and metabolism And there's very interesting information there Let's start with Let's do a little survey of different types of cancers first Breast cancer The lifetime risk is approximately 12.8 percent of women will be diagnosed with female breast cancer at some point in their lifetimes Which represents 15.2 percent of all new cancers and 6.9 percent of all cancer deaths By the way for comparison on the next few slides I have put the statistics for melanoma as a reference at the bottom So you'll see that for every type of cancer that I show prostate cancer Approximately 11.6 percent of men will be diagnosed with prostate cancer at some point in their lifetimes Which represents 9.9 percent of all? Cancer cases and 5.2 percent of all cancer deaths For colorectal cancer the lifetime risk is 4.2 of men and women Will be diagnosed at some point in their life Which represents 8.3 percent of all new cancers and remarkably 8.4 percent of all cancer deaths So you can see that colorectal cancer is comparatively extra extra deadly And non-Hodgkins lymphoma lifetime risk is 2.2 percent of men and women will be diagnosed in their lifetime It represents 4.2 percent of all new cancer cases and 3.3 percent of all cancer deaths Now Why mention these different cancer statistics and accession that is about light and health? Because chronic but not acute exposure to uv radiation Associates with significant decreased incidence of breast cancer prostate cancer colorectal cancer and non-Hodgkins lymphoma Cancer survival Is also associated with better responses in patients who have higher cumulative sun exposure Or who are diagnosed in summer or autumn And the authors of this study had attributed this activity to increased circulating 25 hydroxy vitamin d which is the active form of vitamin d okay Sun exposure is inversely associated with some but not all infections including tuberculosis and acute respiratory tract infections an increased Sun or uv radiation exposure Is associated with decreased development and severity of immune driven Diseases including auto immune diseases such as arthritis inflammatory bowel disease and multiple sclerosis And the evidence in multiple sclerosis is particularly strong where increased sun exposure and serum 25 hydroxy vitamin d Associates with decreased risk of multiple sclerosis particularly in children and adolescents And allergic conditions such as asthma And anaphylaxis you see decreased risk for this or associations for it There are many pathways by which exposure to ultraviolet radiation suppresses immunity This occurs through multiple mediators and activation of multiple different cellular path networks And it occurs not just locally by the skin but also systemically And interestingly some of these mediators and immune network effects may be beneficial for the control of metabolic disorders, which we'll talk about a bit In fact, we'll talk about it now Okay, so now I'm going to be talking about white fat regulation and metabolism And the topics to be covered here are vitamin d Nitric oxide palm c which stands for pro-opio melanocortin and something called melanopsin Let's start with vitamin d It's a fat soluble hormone that is vital for maintaining human health It is needed for the homeostasis of plasma levels of calcium and phosphorus And when human skin is exposed to uvb radiation vitamin d3 is produced from seven Dihydroxycholesterol via pre vitamin d3 It's also obtained dietarily through vitamin d rich foods and supplements Although most people acquire most of their vitamin d through Sun exposure Okay, vitamin d deficiency is defined as 25 hydroxy vitamin d of less than 50 nanomoles per liter And low circulating Five hydroxy vitamin d levels are associated with obesity non-alcoholic fatty liver disease insulin resistance metabolic syndrome type 2 diabetes and cardiovascular disease but a meta analysis by otier Did I did not find support for a benefit of vitamin d supplementation for weight loss coronary artery disease hypertension or reducing signs of Metabolic risk such as glucose tolerance insulin sensitivity or circulating lipids Perhaps 25 hydroxy vitamin d levels are just a proxy for sun exposure and other Ultraviolet radiation inducing mediators like nitric oxide May be responsible for the positive health outcomes associated with increased circulating 25 hydroxy vitamin d levels Okay, so now let's talk about nitric oxide Skin exposure to ultraviolet radiation triggers nitric oxide release from dermal storage sites into the bloodstream And in a study by lewitt all whole body radiation of healthy adults volunteers with ultraviolet radiation a Decrease blood pressure and the effect was sustained for about 30 minutes And this effect associated with increased circulating nitrates So you see you get uva exposure your blood pressure drops It lasts for 30 minutes and that associates with circulating nitrite What does this have to do with that regulation and metabolism you ask? Well in a study published in 2014 in the journal of diabetes Researchers showed that ultraviolet radiation suppresses obesity and symptoms of meta box syndrome independently of vitamin d in mice fed a high fat diet And to test the hypothesis researchers also gave mice a nitric oxic donor So they wanted to then see is this effect happening from nitric oxide? So they gave them a nitric oxide donor separate from what the nitric oxide that is stimulated by ultraviolet radiation exposure And this decreased body weight and prevented the development of insulin resistance secondarily They challenged the idea further By adding nitric oxide a nitric oxide scavenger Which reversed some of the positive effects of ultraviolet radiation specifically the benefits seen with fasting glucose levels And also hepatic steatosis or fatty liver It has also been observed that dietary nitrate causes the browning of white adipose white adipose tissue And if you're unfamiliar with what that means it means that there is increased mitochondrial density that occurs in white adipose tissue And this basically turns white fat into an it's an anti-fat mechanism It can the brown fat will convert Triglycerides and circulating glucose into energy versus storing it as fuel and there's a lot of different Work that's now going on to see how we can stimulate the activity and also even perhaps Increase the amount of brown fat that we can we hold on our body So this information holds a mechanism. Oh, and there's one other thing by the way, um the increase nitrate also increased the expression of thermogenesis related genes in brown adipose tissue So what we see here now is a potential mechanism and a likely mechanism for why dietary nitrate has an anti-opicity effects Okay, so now we'll switch gears and we'll talk about palm c Palm c is a polypeptide. It is secreted by the pituitary gland by skin cells and also by neurons And it undergoes cleavage into several different peptides including alpha msh beta endorphin and adrenocorticotropin So alpha msh is quite interesting When you expose skin or the eye to ultraviolet a it increases serum levels of alpha Alpha msh in mice and this is important because alpha msh has an appetite suppressing effect There is also a surge in alpha msh and melanocortin for receptor expression So how many receptors there are that receive this signal in an area of the hypothalamus called the arcute nucleus Which is thought to be these Center that is controlling body fatness or one of the centers that is controlling the balance of body fatness Okay, now We'll move on and we're going to talk about melanopsin This is an interview that I did Or this is a person who I did an interview with for the podcast humanus radio His name is peter light And out of the 60 some op professors that I've interviewed now This definitely stands as one of the most interesting ones conversations that I've had Dr. Light is a chief and investigator at the light lab At the university of alberta and is the director of the university of alberta's diabetes institute He is a pharmacologist and a leader in the field of cellular electrical activity His research is focused on eyelid signaling and diabetes As well as developing therapies to treat diabetes and other metabolic diseases So How did this all get started? Well as the director of alberta's diabetes institute, dr. Light had an ongoing interest in diabetes research And about three years earlier He and his colleagues embarked on a project to engineer fat cells to secrete insulin One of the challenges of Islet cell transplantation is that they must come from a donor and that the immune system rejects them Much like they do with an organ transplant And this necessitates the use of immunosuppressant drugs So this research team came up with an idea to engineer a person's fat cells To produce insulin by inserting the insulin gene into fat cells And by adding an optogenetic sensor Channel rhodopsin which could then be used to activate insulin release In response to light now. This is absolute science fiction I started to hear Research presentations about this probably about 10 years ago. Maybe a little more So what they can do is they can introduce a viral vector. It inserts these channel rhodopsin Receptors into a variety of different cell tissue types like neurons and then you can activate Those neurons by shining a light on those neurons and it gives you great temporal specificity To be able to then turn them on and off very quickly So different than pharmacology, which might be affecting different receptors you have It's a very good research tool to understand Both both how different neuron systems might interact How what happens when you just turn those on and not at the whole network There's a lot of interesting things that occur here So to do this study, that's what they wanted to do They wanted to put these receptors into fat tissue and then turn make them insulin secreting by shining the light on them But first they needed to do a negative control experiment So just a flash of light, but without adding any light sensitive options. So that would be the control of five minutes. Okay To the q-net core So they exposed the control cells to blue light and expected to see Well, no response, right? This is just the control But instead The light elicited a reproducible small electrical current So they designed some experiments to figure out what was going on And after some deep research, they determined that the opn4 Gene that encodes melanopsin Is expressed in white subcutaneous adipose tissue Once their experiments confirmed that there were ops and receptors in fat tissue They contacted surgeons In the area to obtain skin and fat samples from cosmetic surgery patients And sure enough Light sensitive currents were detected within these human adipocytes So they stumbled upon this mechanism. They then got fat tissue from humans. They tested it and yes They actually when you put blue light on these on the fat tissue it causes the these electrical currents So they wanted to determine if there was a physiological relevance to this finding and What light intensity is required to activate these pathways And they had a variety of different questions So they exposed fat cells to a range of different light to light wavelengths and they found that fat cells were maximally responsive to blue light between 450 and 480 nanometers In order to activate these receptors you need a very bright light though Because only about 1 to 5 percent of blue light from sunlight actually penetrates the skin Uh, usually daylight is probably adequate Um, but blue light unlike uv can penetrate pretty well at different times of day So where uv exposure is going to have maximal benefits at peak solar times between let's say 10 and 2 When the sun is out blue light will get it will penetrate the skin Really when the sun is up Their next experiments were on a population of cells With longer term exposure to blue lights. They wanted to see okay What happens if we put these cells under the conditions of blue light more regularly? And they exposed the fat cells to blue light for 2 to 4 hours a day For 13 days to see how it affected the structure and the function of these adipocytes And after 13 days of light exposure fat cells were smaller They were few there were fewer cells retaining lipid droplets. In other words, they were not storing as much fat And this is a big deal because smaller fat cells are better able to accommodate excess lipids and are less inflammatory And generally they are associated with better metabolic health So larger fat cells equal higher information higher macrophage infiltration and cytokine secretion So this diminished lipid content also resulted in less secretion of adiponectin and leptin And these adipokines which Which means that they are hormones essentially that are secreted from fat tissue Are important for signaling. They're important signaling proteins And again, their higher levels are associated with inflammation and metabolic disease The researchers also found increased release of glycerol From the fat tissues which suggests that the higher rate of lipolysis or fat breakdown was occurring in response to blue light Overall, this suggests that blue light was changing the behavior of these fat tissue of the fat tissue And this is a great quote from him I think we may have come across a potential mechanism which feeds into the concept that We may have evolved to have a mechanism which tells Which which cells regulate Fat storage at different times of the year So imagine during winter months when the the tone and intensity of light changes Could that be a mechanism that tells the human body to store more fat for winter? Pretty interesting in light of the fact that we live Indoors mostly 90 percent of time indoors and are nearly always fully clothed Okay, so I've got one minute left Which is this timing actually worked out pretty well So we talked about the negative negative effects of sunshine And sun damage skin cancers ocular issues And some of the mechanisms so DNA damage occurs directly through pyrimidine dimers and also through activation of reactive oxygen species and we also talked about how Getting sun exposure Associates with a reduced risk for various cancers cancers that indeed are actually more deadly than skin cancers breast prostate colorectal non-Hodgkin's lymphoma Certain infections and also reduced immunity And then we talked about a variety of different mechanisms To regulate fat metabolism vitamin D nitric oxide palm c and melanopsin and there are there are more There's actually quite a lot. There's quite a bit more to say here Um, but that is that's the talk There's a lot of questions that remain and i'm happy to take some questions from the audience now But but i'll say a final point is that a lot of this is associational studies with mechanisms tested in animals And I think at this point what we need to do is to create interventional studies that give people a sensible Figure out what that is amount of light exposure over a period of time to see how that affects a variety of things particularly in fat fat metabolism and fat regulation And it wasn't just so we see also mechanisms that ultraviolet radiation are having positive effect, but it's also the blue light as well Could there be a product perhaps where you wear a blue light t-shirt under your clothing? That is able to then activate these blue the the fat receptors. I don't know it might not be strong enough But gosh, wouldn't that be interesting? Okay, so with that I will stop and I'm happy to take any questions and thank you for your attention All right, two things one just real quick. You mentioned Nanomoles per liter for vitamin d. We don't use that in the united states That's a metric in the united states is nanograms per milliliter, which is a totally different number Are you familiar with the work of john nash otte who did all this? You need to watch it's an old movie But it's all about how he exposed mice or rats to a number of different lights sunlight fluorescent light different types of fluorescent light Massive differences and somebody I mean maybe you or somebody else needs to reproduce What he did the movie is up on my website I think it's called into the light and john nash otte Reproduce his experiments adding another light source, which is our new one, which is leds Because he showed the tremendous benefit of sunlight the tremendous detriment of most fluorescence But not full spectrum fluorescence and leds didn't exist and we're all switching over to leds So we need some information we need some stuff done on benefits harm whatever of leds. Yeah, I'd love to see that movie and I think My opinion about leds and of course there's a lot more information that needs to be gathered on the totality of their effects I think that they have Great potential to both do good, but they're also harmful because they're more powerful So as technology becomes more powerful, we need to have a more sensible relationship with it So for instance in terms of light You can adjust the tone and intensity of leds with more fidelity than you can in condescence and of course compact fluorescence So you can imagine a smart lighting environment where the tone of light and this has more to do with my ted talk Changes across the day so that it's reflective or at least more representative of what a natural light signature is outside of that Given time that is a step in the right direction since we're spending so much time indoors But of course are there other effects that we need to know about as well. Yes And you know new technology is introduced into the world. There's very little You know quality control mechanisms are checking. It's it's not evaluated for 15 years before it's released to the public Like all like so many so much tech. It's just invented and released And we're not going to be able to stop that But hopefully with more information we can then sort of either control the power of these this technology So that we do better with it and we can identify potential harms faster as well But we need we need your research to come out because I mean I've reversed emotional issues By switching people over from regular lighting to either german or us made full spectrum fluorescence The chinese ones don't do that and now we need to find out about leds. Yeah, thank you. Thanks for the comment Really in presentation so there's a lot of concern about sunlight causing aging of the skin right and My interest is the omega-6 fats because they accumulate in our fat And when photons of light hit those they are going to potentially oxidize And wondering if you have evidence to or you believe that Those who consume higher proof of diets will have faster aging of their skin Yeah, that's a very interesting question. Thank you So one of the comments earlier that I Mentioned was what are the factors that affect a person's and individual's response to The solar radiation that they're exposed to and one of those factors Which could be an entirely different presentation is on dietary factors including supplementation of vitamin d So let me make a quick comment about what I would consider a very Regular common pattern of sun exposure We don't get much as an exposure when we do get sun exposure Because we've had so little we have little by circulating vitamin d 75 percent of the united states and over a billion people Worldwide have low vitamin d status that itself is protective of sun exposure So we get out there we get burns. We have this binge and purge relationship with sun Would it make sense to maintain a low level tan across the year even if it includes the use of some sun beds possibly and there is some evidence that Even the sensible use of sun beds could actually be beneficial for people in higher latitudes or people that just can't get full body sun exposure Now this might not be the type of it might be more therapeutic where you're just getting very little amount Five minutes a day or a couple times a week Versus going out, you know really trying to get it maximize your tan And then what kind what would make up a good solar bed? We know that uvb is what causes tanning a lot of the nitric oxide benefits however come from uva So again going back to the comment I made is that we need a lot more research here I think so much of it has been focused on the the preponderance has been around skin cancer But our rates of skin cancer might have a lot to do with the diet We're eating including the phytochemicals that we're taking in that help in that help shore up our DNA repair mechanisms and reduced Reduced the damage from oxidative stress If we're consuming if we have a lifestyle and diet that predisposes us to not be able to hand those types of stressors well then the stressor which might ordinarily be helpful might end up looking unhelpful in the context of The modern lifestyle So thank you for that comment. Thank you very very interesting. I do think that that is one area that I'd like to see more work on Thanks for your presentation I was just wondering as I see a lot of fatty liver disease in practice nowadays And it's my understanding that vitamin D production is is actually done in the liver And I'm just wondering what your thoughts might be on lack of vitamin D I mean you've stated that you think it's because we're indoors But I see a lot of patients that in the fall they spend a lot of time outdoors and yet in the fall I'll measure the vitamin D and it's deficient And I'm wondering if it's due to the fatty liver disease Yes That is entirely a possibility And it's one thesis that We consume vitamin D We either produce produce it less efficiently or we are consuming it in conditions that are high higher inflammatory conditions so That's a very interesting comment And I'll repeat what he said that there are people that are getting sun exposure, but there's still low vitamin D status So is it either under production or is it that we are perhaps consuming it more through some inflammatory processes? There one very interesting study that just came out gave People that were prebiotic diabetic very high dose five to ten times the recommended amount And it showed it slowed the progression of diabetes. So while we do see some the evidence for giving Vitamin D has been underwhelming in terms of meta analyses We are also seeing some positive signs there But then we also I do think that there are some positive effects from vitamin D But it also might be a marker for other for sun exposure Which then might be having other effects like nitric oxide, melanopsin, etc Thank you. Yeah Yeah, so a great question, um That is one of the dietary factors asked is the anthins Luteal and or lutein, excuse me, zeaxanthins NAD, nicotinamide precursors fenugreek A variety of rosminic acids from rosemary lots of things a lot of phytochemicals Will have an effect by increasing the our ability to handle oxidative stress interestingly Taking antioxidants directly in the forms of beta care team vitamin e and c They've had The data there is actually not very clear. In fact, if you were to pluck out What you think is happening is that direct antioxidants don't seem to be having a beneficial effect But rather inducing Your body to produce antioxidants through these small hormitic stressors of plant phytochemicals Seems to be a much better approach and there is evidence for this being in fact There are even some products out there that are considered oral sunblocks like firm block or heliocare And then there's a different combination of them, but I think you could sensibly Create a combination of different compounds that address different mechanisms That made the stress events of solar exposure Not not only not damaging, but you would prevent the damage and you'd get the benefits. That's my hope That's my hope. Thank you. Thank you. Thank you, Dan